DEPARTMENT OF HEALTH AND HUMAN SERVICES 

CENTERS FOR DISEASE CONTROL AND PREVENTION
 

Advisory Committee on 

Immunization Practices (ACIP)
 

Summary Report

February 24-25, 2010 

Atlanta, Georgia
 

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Advisory Committee on Immunization Practices (ACIP) Summary Report February 24-25, 2010 

Table of Contents Page 

Acronyms 4-6

Agenda 7-9

Wednesday, February 24 

Welcome and Introductions 10-13

Dr. Frieden’s Opening Remarks 14 

Human Papillomavirus (HPV) Vaccines 

Introduction

 Quadrivalent HPV Vaccine for Adult Women: Efficacy, Epidemiology, Natural History, Cost-Effectiveness 

 Quadrivalent HPV Vaccine in Males: Efficacy in Prevention of Anal Precancers 

 Summary of Future Plans 

15-38

13-Valent Pneumococcal Conjugate Vaccine (PCV13)

Introduction

Recommendation for Use of PCV13 and Immunization Schedules

VFC Vote

Program Implementation: Transition from PCV7 to PCV13

39-58

Hepatitis Vaccines

 Update on Hepatitis Vaccines Work Group

 Diabetes and Liver Disease 

58-64

Influenza Vaccines

 Introduction and Work Group Discussions 

 2009-2010 Season Review 

 Influenza Epidemiology 

 Virology 

 2009 H1N1 Immunization Program Update

 High Dose Influenza Vaccine for Persons 65 and Older

 Work Group Discussions 

 Annual Influenza Prevention and Control Recommendations 

65-105

Public Comments Day ! 106 

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Advisory Committee on Immunization Practices (ACIP) Summary Report February 24-25, 2010 

Thursday, February 25 

Unfinished Business 106 

Agency Updates

 CDC 

 Center for Medicare and Medicaid Services (CMS) 

 Department of Defense (DoD) 

 Department of Veteran’s Affairs (DVA)

 Food and Drug Administration (FDA) 

 Heath Resources and Services Administration (HRSA) 

 Indian Health Services (I HS)

 Immunization Safety Office (ISO) 

 National Institutes for Health (NIH) 

 National Vaccine Advisory Committee (NVAC) 

 National Vaccine Program Office (NVPO) 

106 - 111 

Liaison Updates

 National Medical Association (NMA) 

 American College of Physicians (ACP) 

 American Medical Association (AMA) 

 Department of Health, United Kingdom (UK)

 Healthcare Infection Control Practices Advisory Committee (HICPAC) 

112-113 

Update 

National Vaccine Plan 

113-116 

Meningococcal Vaccine 

Introduction

 Cost-Effectiveness Analysis of Infant Meningococcal Vaccines 

 Considerations in the Use of Meningococcal Vaccines in Infants 

Public Comment 

116-137 

On-Going Mumps Outbreaks: Northeastern United States July 2009 to Present 137-141 

Rotavirus Vaccines

 Severe Combined Immunodeficiency (SCID) and Rotavirus Vaccine 

141-143 

Vaccine Supply 143-144 

Evidence-Based Recommendations Work Group 

Introduction

 Methodological Standards for Clinical Practice Guidelines 

Guidelines for Grading the Quality of Evidence

 Guidelines for Synthesizing and Presenting Recommendations 

145-159 

Public Comment Day 2 159-160 

Certification 161 

Participant Roster 162-169 

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Advisory Committee on Immunization Practices (ACIP) Summary Report February 24-25, 2010 

Acronyms 

AAAAI American Academy of Allergy, Asthma, and Immunology 

AAFP American Academy of Family Physicians 

AAP American Academy of Pediatrics 

ABCs Active Bacterial Core surveillance system 

ACHDNC Advisory Committee for Heritable Disorders in Newborns and Children 

ACHA American College Health Association 

ACP American College of Physicians 

ACS American Cancer Society 

ACIP Advisory Committee on Immunization Practices 

AEs Adverse Events 

AGS American Geriatrics Society 

AHIP America’s Health Insurance Plans 

AIN Anal Intraepithelial Neoplasia 

APA American Pharmacists Association 

AMA American Medical Association 

AOM Acute Otitis Media 

ARRA American Recovery and Reinvestment Act 

ATP According to Protocol 

ASTHO Association of State and Territorial Health Officials 

BARDA Biomedical Advance Research and Development Authority 

BLA Biologics License Application 

BOI Burden of Illness 

BRFSS Behavioral Risk Factor Surveillance System 

CBER Center for Biologics Evaluation and Research 

CDC Centers for Disease Control and Prevention 

CIN Cervical Intraephithelial Neoplasia 

CMS Centers for Medicare and Medicaid Services 

COI Conflict of Interest 

COPD Chronic Obstructive Pulmonary Disease 

CSTE Council of State and Territorial Epidemiologists 

CVD Cardiovascular Disease 

DoD Department of Defense 

DSMB Data Safety Monitoring Board 

DSTDP Division of Sexually Transmitted Diseases Prevention [of NCHHSTP] 

DtaP-IPV Diphtheria, tetanus, and pertussis with inactivated poliovirus vaccine 

DVA Department of Veterans Affairs 

DVD Division of Viral Diseases (of NCIRD) 

DVH Division of Viral Hepatitis (of NCIRD) 

EUA Emergency Use Authorization 

EGL External Genital Lesion 

EIA enzyme immunoassay 

EIP Emerging Infections Program 

EIS Epidemic Intelligence Service 

EMR Electronic Medical Records 

ESSENCE Electronic Surveillance System for Early Notification of Community-Based Epidemics 

EUA Emergency Use Authorization 

FDA Food and Drug Administration 

FQHC Federally Qualified Health Center 

GBS Guillain Barré Syndrome 

GDP Gross Domestic Product 

GISN Global Influenza Surveillance Network 

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Advisory Committee on Immunization Practices (ACIP) Summary Report February 24-25, 2010 

GMCs Geometric Mean Concentrations 

GMTs Geometric Mean Titers 

GSK GlaxoSmithKline 

HCC Hepatocellular Carcinoma 

HCP Health Care Personnel 

HI Hemagglutination Inhibition 

HICPAC Healthcare Infection Control Practices Advisory Committee 

HepA Hepatitis A 

HepB Hepatitis B 

HHS Department of Health and Human Services 

Hib Haemophilus influenzae B 

HM Heterosexual Men 

HPV Human Papillomavirus 

HRSA Health Resources and Services Administration 

ICD-9 International Classification of Diseases, Ninth Revision 

ID Influenza Division (of NCIRD) 

IDSA Infectious Disease Society of America 

IgG Immunoglobulin G 

IgM Immunoglobulin M 

IHS Indian Health Services 

ILI Influenza-Like Illness 

ILINet Influenza-Like Illness Surveillance Network 

IM intramuscular 

IOM Institute of Medicine 

IPD Invasive Pneumococcal Disease 

IRB Institutional Review Board 

ISD Immunization Services Division (of NCIRD) 

ITT Intent to Treat 

JE Japanese Encephalitis 

JORRP Juvenile Onset Recurrent Respiratory Papillomatosis 

LEEP Loop Electrosurgical Excision Procedure 

LYS Life Years Saved 

MenACYWCRM Meningococcal Conjugate Vaccine 

MCV4 Quadrivalent Meningococcal Conjugate Vaccine 

MMR Measles, Mumps, Rubella 

MMWR Morbidity and Mortality Weekly Report 

MSM Men Who Have Sex With Men 

NACCHO National Association of County and City Health Officials 

NAFLD Non-Alcoholic Fatty Liver Disease 

NASH Non-Alcoholic Steatohepatitis 

NCHHSTP National Center for HIV, Hepatitis, STD, and TB Prevention (of CDC/CCID) 

NCIRD National Center for Immunization and Respiratory Diseases (of CDC/CCID) 

NHANES National Health and Nutrition Examination Survey 

NHFS National 2009 H1N1 Flu Survey 

NICE National Institute Clinical Excellence 

NICU Neonatal Intensive Care Unit 

NIH National Institutes of Health 

NIS National Immunization Survey 

NNDSS National Notifiable Diseases Surveillance System 

NORC National Opinion Research Center 

NSFG National Survey of Family Growth 

NVAC National Vaccine Advisory Committee 

NVP National Vaccine Plan 

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Advisory Committee on Immunization Practices (ACIP) Summary Report February 24-25, 2010 

NVPO National Vaccine Program Office 

NYSDH New York State Department of Health 

OAH Office of Adolescent Health (NVPO / HHS) 

OBS Observational Study 

OD Office of the Director (of CDC) 

PAHO Pan American Health Organization 

PCP Pneumocystis Jirovecii 

PCR Polymerase Chain Reaction 

PCV Pneumococcal Conjugate Vaccine 

PEP Post-Exposure Prophylaxis 

QALY Quality-Adjusted Life Year 

RCT Randomized Controlled Trial 

RDD Random-Digit-Dialed 

RRP Recurrent Respiratory Papillomatosis 

RSV Respiratory Syncytial Virus Immunoprophylaxis 

SAEs Serious Adverse Events 

SAM Society for Adolescent Health and Medicine 

sBLA Supplemental Biologics License Application 

SCID Severe Combined Immunodeficiency 

SEER Surveillance, Epidemiology, and End Results Program 

SES Socioeconomic Status 

Tdap Tetanus and Reduced Diphtheria Toxoids 

UK United Kingdom 

US United States 

VAERS Vaccine Adverse Event Reporting System 

VFC Vaccines for Children 

VRBPAC Vaccines and Related Biological Products Advisory Committee 

VSD Vaccine Safety Datalink 

VSSN Vaccine Safety Surveillance Network (DoD) 

VSRAWG Vaccine Safety Risk Assessment Working Group 

VZV Varicella-Zoster Virus 

WG Work Group 

WHO World Health Organization 

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Advisory Committee on Immunization Practices (ACIP) Summary Report February 24-25, 2010 

FINAL – February 18, 2010

MEETING OF THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP) 

Centers for Disease Control and Prevention
 

1600 Clifton Road, NE, Tom Harkin Global Communications Center (Building 19), Atlanta, Georgia 

AGENDA ITEM 

Wednesday, February 24,

8:00 

PURPOSE 

 2010 

Welcome & Introductions 

PRESIDER/PRESENTER(s) 

Dr. Carol Baker (Chair, ACIP) 

Dr. Larry Pickering 

(Executive Secretary, ACIP; CDC) 

8:30 Human Papillomavirus 

(HPV) Vaccine 

Introduction 

Quadrivalent HPV 

vaccine for adult women 

Efficacy in women 24 

through 45 years of age 

Epidemiology and natural 

history 

Cost effectiveness 

Quadrivalent HPV 

vaccine in males 

Efficacy in the prevention 

of anal precancers 

Summary and future 

plans 

Information 

& 

Discussion 

Information 

& 

Discussion 

Dr. Janet Englund (ACIP, WG Chair) 

Dr. Richard Haupt (Merck) 

Dr. Eileen Dunne (CDC/NCHHSTP) 

Dr. Harrell Chesson (CDC/NCHHSTP) 

Dr. Richard Haupt (Merck) 

Dr. Lauri Markowitz (CDC/NCHHSTP) 

10 :15 Break 

10:45 13-Valent Pneumococcal 

Conjugate Vaccine 

(PCV13) 

Introduction 

Recommendation for 

use of PCV13 and 

immunization schedules 

VFC vote 

Program 

implementation - transition 

from PCV7 to PCV13 

Information 

Discussion 

Vote 

VFC 

Information 

Dr. Kathy Neuzil (ACIP, member)

Dr. Pekka Nuorti (CDC/NCIRD) 

Dr. Jeanne Santoli 

(CDC/ NCIRD) 

Dr. Jeanne Santoli (CDC/ NCIRD) 

12:15 Lunch 


 

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Advisory Committee on Immunization Practices (ACIP) Summary Report February 24-25, 2010 

1:15 Hepatitis Vaccines 

Update on Hepatitis Vaccines Work Group 

Diabetes and liver disease 

1:45 Influenza Vaccines 

Introduction 

2009-10 Season review 

Influenza epidemiology

Virology 

2009 H1N1 

Immunization Program 

Update 

Information

& 

Discussion 

3:45 Break 

4:00 Influenza Vaccines (cont’d) 

High dose influenza 

vaccine for persons 65 and 

older 

Work Group discussion 

Annual influenza 

prevention and control 

recommendations 

VFC vote 

Information 

& 

Discussion 

Vote 

VFC 

5:50 

6:05 

8:45 

8:55 

Thursday, February 25, 2010 

8:00 

8:30 

Unfinished Business 

Agency Updates (CDC, 

CMS, DOD, DVA, FDA, 

HRSA, IHS, NIH, NVAC, 

NVPO) 

Update: National Vaccine 

Plan 

Meningococcal Vaccine 

Introduction 

Cost-effectiveness 

analysis of infant 

meningococcal 

vaccines 

Considerations for use 

of meningococcal vaccines 

in 

infants 

Public Comment 

Adjourn 

Information 

Information 

Information 

Information 

& 

Discussion 

10:10 Break 

Dr. Mark Sawyer (ACIP, WG Chair) 

Dr. John W.Ward (CDC/NCHHSTP)
 

Dr. Kathy Neuzil (Chair, WG ACIP) 

Dr. Anthony Fiore (CDC/NCIRD) 

Dr. Lyn Finelli (CDC/NCIRD)
 

Dr. Nancy Cox (CDC/NCIRD) 

Dr. Anthony Fiore (CDC/NCIRD) 

Dr. James Singleton (CDC/NCIRD) 

Dr. Pascale Wortley (CDC/NCIRD)
 

Dr. David Greenberg (sanofi) 

Dr. Neuzil and Dr. Fiore 

Dr. Fiore (CDC/NCIRD) 

Dr. Jeanne Santoli (CDC/NCIRD)
 

Dr. Carol Baker (Chair, ACIP) 

ACIP Ex Officio Members
 

Dr. Ray Strikas (HHS/OS) 

Dr. Cody Meissner (ACIP, WG Chair) 

Dr. Ismael Ortega-Sanchez 
 

(CDC/NCIRD)
 

Dr. Amanda Cohn (CDC/NCIRD) 

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Advisory Committee on Immunization Practices (ACIP) Summary Report February 24-25, 2010 

10:25 Ongoing Mumps 

Outbreaks, Northeastern 

United States, July 2009 -

present 

10:35 Rotavirus Vaccines 

Severe Combined 

Immunodeficiency (SCID) 

and rotavirus vaccine 

10:50 Vaccine Supply 

Update on vaccine 

supply 

11:05 Evidence Based 

Recommendations Work 

Group 

Introduction 

Methodological 

standards for clinical 

practice 

guidelines 

Guidelines for grading 

the quality of evidence 

Guidelines for 

synthesizing and 

presenting 

recommendations 

12:20 

Information 

Information 

Discussion 

Information 

Discussion 

Information 

Information 

Discussion 

Public Comment 

Dr. Kathleen Gallagher 

(CDC/NCIRD) 

Dr. Catherine Yen 

(CDC/NCIRD) 

Dr. Jeanne Santoli 

(CDC/ NCIRD) 

Dr. Jonathon Temte 

(ACIP, WG Chair) 

Dr. Faruque Ahmed 

(CDC/NCIRD) 

Dr. Craig Umscheid 

(University of 

Pennsylvania) 

Dr. Faruque Ahmed 

(CDC/NCIRD) 

12:35 Adjourn 

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Discussion

Advisory Committee on Immunization Practices (ACIP) Summary Report February 24-25, 2010 

February 24, 2010 

Welcome and Introductions 

Dr. Carol Baker 

Chair, ACIP 

Dr. Larry Pickering 

Executive Secretary, ACIP / CDC 

Dr. Baker called the meeting to order, welcoming those present. She then introduced Dr. 

Pickering who delivered the administrative announcements. 

Dr. Pickering welcomed everyone to the February 2010 Advisory Committee on Immunization 

Practices (ACIP) meeting. He indicated that the proceedings of this meeting would be 

accessible to people not in attendance via the World Wide Web. He also welcomed those who 

could not attend the meeting in person. 

Noting that Natalie Greene would not be in attendance during this meeting due to the birth of 

her baby, Dr. Pickering recognized several others in the room who were to be present 

throughout the duration of the ACIP meeting to assist with various meeting functions: Antonette 

Hill, Committee Management Specialist for ACIP; Tamara Miller; Tanya Lennon; and John 

Rawlinson. He also recognized that their hard work very much contributes to the success of 

each meeting. Those with any questions were instructed to see him, any of these individuals, or 

Dr. Baker. He indicated that boxed lunches would be provided for a charge during the two days 

of the meeting in the hallway outside of the auditorium, and that coffee and tea would be 

available in the hallway for the duration of the meeting. 

Handouts of the presentations were distributed to the ACIP members and were made available 

for others on the tables outside of the auditorium. Slides presented at this meeting will be 

posted on the ACIP website, generally within one to two weeks after the meeting concludes, 

while meeting minutes will be available on the website within 90 days of the termination of the 

meeting. 

Members of the press interested in conducting interviews with various ACIP members were 

instructed to contact Tom Skinner for assistance in arranging the interviews. 

Dr. Pickering welcomed the following international visitors, noting that they were attending the 

ACIP meeting to observe the process of immunization policy development in the United States: 

 Dr. Barbara Jauregui, Technical Officer, Pan American Health Organization (PAHO) 

 Dr. Carla Vizotti, EPI Manager, Ministry of Health, Argentina 

 Dr. Elizabeth Ferdinand, EPI Manager, Ministry of Health, Barbados 

 Dr. Suarez Castaneda Eduardo, Director of Infectious Diseases, Ministry of Health, El 

Salvador 

 Dr. Hassan Foad Moises, Pediatric Hospital of Nicaragua 

 Dr. Nobuhiko Okabe, Director, Infectious Disease Surveillance Center, National Institute of 

Infectious Diseases, Tokyo, Japan 

 Dr. Hajime Kamiya, Medical Officer, National Institute of Infectious Diseases, Tokyo, Japan 

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Advisory Committee on Immunization Practices (ACIP) Summary Report February 24-25, 2010 

Those unable to attend this ACIP meeting for either or both days included the following: 

ACIP Members 

 Dr. Michael Marcy 

Ex Officio Members 

 Dr. Bruce Gellin, National Vaccine Program Office (NVPO) attended the first day; Dr. Mark 

Grabowsky attended on his behalf the second day. 

 Dr. Linda Kinsinger from the Department of Veterans Affairs (DVA) was unable to attend 

either day; Dr. Terri Murphy attended on her behalf the second day. 

 Dr. George Curlin has been the ACIP ex officio member from the National Institutes for 

Health (NIH) for 12 years. With his retirement, ACIP lost not only an exceptional person 

from the committee, but also a friend. Dr. Curlin will be replaced by Dr. Richard Gorman 

beginning with the June 2010 ACIP meeting. 

Liaison Representatives 

 Dr. Greg Poland from the American College of Physicians (ACP) was present the first day; 

Dr. Sandra Fryhofer attended on his behalf the second day. 

 Dr. Christine Hahn from the Council of State and Territorial Epidemiologists (CSTE) was 

unable to attend; Dr. Dale Morse attended on her behalf. 

 Dr. James Cheek from the Indian Health Services (IHS) was unable to attend; Dr. John 

Redd attended on his behalf. 

 Ms. Patricia Stinchfield from the National Association of Pediatric Nurse Practitioners 

(NAPNAP) was unable to attend; Ms. Tammy Tempfer attended on her behalf. 

To avoid disruptions during the meeting, those present were instructed to turn off all cell phones 

or place them in the vibrate mode. Given that the meeting could not begin unless a quorum of 

members was present, all appointed members were asked to return from breaks and lunch in a 

timely manner to participate in the meeting. 

Topics presented during the ACIP meeting include open discussion with time reserved for public 

comment. During this meeting, a time for public comment was scheduled following the 

afternoon sessions during both meeting days. In certain circumstances, a formal comment 

period may be scheduled during the deliberations of a specific agenda item rather than at the 

end of the day in order to be considered before a vote is taken. Those who planned to make 

public comments were instructed to visit the registration desk in the rear of the room to have 

Antonette Hill record their name and provide information on the process. Those who registered 

to make public comments prior to the meeting were instructed to see Ms. Hill to verify that their 

names were listed and to receive any additional information. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report February 24-25, 2010 

With regard to disclosure, the goal in appointing members to the ACIP is to achieve the greatest 

level of expertise, while minimizing the potential for actual or perceived conflicts of interest. To 

summarize conflict of interest provisions applicable to the ACIP, as noted in the ACIP policies 

and procedures manual, members of the ACIP agree to forego participation in certain activities 

related to vaccines during their tenure on the committee. For certain other interests that 

potentially enhance the members’ expertise while serving on the committee, CDC has issued 

limited conflict of interest (COI) waivers. Members who conduct vaccine clinical trials or who 

serve on data safety monitoring boards (DSMBs) may serve as consultants to present to the 

committee on matters related to those specific vaccines; however, they are prohibited from 

participating in deliberations or committee votes on issues related to those specific vaccines. 

Regarding other vaccines of the affected company, a member may participate in a discussion 

with a proviso that he or she abstains on all votes related to that vaccine company. 

The following information was shared pertaining to ACIP: 

E-mail: acip@cdc.gov Web homepage: www.cdc.gov/vaccines/recs/acip/ 

Nominations: http://www.cdc.gov/vaccines/recs/acip/req-nominate.htm 

The ACIP Secretariat solicits applications throughout the year for candidates to serve on ACIP. 

Detailed instructions for submissions of name of potential candidates may be found on the ACIP 

website. Applications may be submitted at any time of the year. Materials in support of the next 

cycle of applications for ACIP membership are due no later than November 15, 2010 for the 

term beginning July 2011. Interested parties were encouraged to complete an application and 

submit it by the deadline. 

Next ACIP meeting: June 23-24, 2010 

Registration Deadlines: Non-U.S. Citizens 6/4/2010 – U.S. Citizens 6/11/2010 

Vaccine Safety: www.cdc.gov/vaccinesafety/ 

Vaccine Abbreviations: 

http://www.cdc.gov/vaccines/recs/acip/vac-abbrev.htm 

Vaccine Schedules: 

http://www.cdc.gov/vaccines/recs/schedules/default.htm 

Adult Vaccine Scheduler: 

http://www.cdc.gov/vaccines/recs/Scheduler/AdultScheduler.htm 

This scheduler was developed by National Center for Immunization and Respiratory Diseases 

(NCIRD) of CDC and Georgia Tech. This is very similar to the Pediatric Scheduler, which has 

been published for a couple of years. The Adult Vaccine Scheduler is an interactive, web-based 

scheduler that can be downloaded to people’s computers so that adults can keep track of the 

vaccines they have received and prognosticate what vaccines they need in the future. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report February 24-25, 2010 

Vaccine Toolkit: 

http://www.cdc.gov/vaccines/spec-grps/hcp/conversations.htm 

The Vaccine Toolkit was also developed by NCIRD / CDC in conjunction with the American 

Academy of Family Physicians (AAFP) and the American Academy of Pediatrics (AAP). This is 

a providers’ resource for vaccine conversations with parents. 

Dr. Baker requested that Dr. Pickering comment on the timeline from ACIP recommendations to 

publication in the Morbidity and Mortality Weekly Report (MMWR), given the number of 

questions raised regarding this issue. Dr. Pickering responded that they recognize that there 

has been a delay that has lengthened over the past couple of years between ACIP 

recommendations and publication of these recommendations. A document was prepared to 

address this subject, which was currently being reviewed by the NCIRD leadership for 

comments, followed by which it would be submitted to the ACIP Steering Committee. The three 

areas this document approaches include: 1) more liberal use of the policy notes in the MMWR 

(e.g., the shortened versions of publications of the recommendations), which would cut the 

timeframe down to a couple of months following the vote; 2) streamline of the process for 

publication of the recommendations and reports, which are the longer versions; and 3) more 

frequent use of electronic publishing. One way this will be done is if there are updates or 

contraindications to any of the recommendations, they will be published in the MMWR and the 

base document will include notifications of links that include new recommendations and 

updates. 

Dr. Baker welcomed and introduced new ACIP member, Attorney Sara Rosenbaum, to ACIP. 

Professor Rosenbaum is a Harold and Jane Hirsch Professor of Health Law Policy and Chair of 

the Department of Health Policy at George Washington University School of Public Health and 

Health Services in Washington, DC. She is also the Director of the Center for Health Services 

Research and Policy and the Director of the Hirsch Health Law and Policy Program at George 

Washington University. Her commitment to strengthening access to care for middle income 

minority and medically under-served populations has had a transforming effect on the lives of 

many Americans, particularly children. Her representation of consumers will be of tremendous 

value to ACIP. 

The following conflicts of interest were declared: 

Dr. Janet Englund: Research support for clinical trials from MedImmune, sanofi pasteur, and 

Novartis 

Dr. Wendy Keitel: Clinical trial support from Novartis 

Dr. Cody Meissner: Payments made to Tufts Medical Center by MedImmune and Wyeth for 

participation in multi-vent clinical trials for Prevnar® and RSV-related vaccines 

The remainder of the ACIP members declared no conflicts. 

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Discussion

 

Advisory Committee on Immunization Practices (ACIP) Summary Report February 24-25, 2010 

Director’s Remarks 

Thomas R. Frieden, MD, MPH 

Director, Centers for Disease Control and Prevention 

Administrator, Agency for Toxic Substances and Disease Registry 

Dr. Frieden thanked the ACIP members and liaisons for their work, pointing out that ACIP is a 

great example of not only evidence-based public health practice, but also evidence-based public 

health practice that can make a major difference in peoples’ lives. He stressed that the 

information presented during this meeting illustrated the important results of their work. For 

example, with H1N1 ACIP made extremely important contributions and played a significant role 

in making policy based on the best evidence that was available at the time that decisions had to 

be made. ACIP’s recommendations were flexible, recognized local concerns, and were 

available just in time to contribute to the response. ACIP’s recommendations are really a key 

part of the decision making science base that affects national policy and maximizes the public 

health impact of vaccination. With the VFC program, a reduction has been observed in health 

disparities or disparities in access to health care in children that has not been observed in 

adults. Not only can evidence-based practices improve health generally, but also evidencebased practices tied to effective programs like the VFC program can significantly reduce 

disparities in health care access and ultimately health outcomes. Dr. Frieden cited 

pneumococcal vaccination as another great example of just in time intergovernmental work. 

CDC has a wonderful relationship with the FDA, and Dr. Frieden expressed his pleasure to be 

working again with his longtime friend and colleague Dr. Margaret A. Hamburg, Commissioner 

of Food and Drugs, who is doing a terrific job there. He thought CDC and FDA were illustrating 

that when two agencies work together well, there really is synergy. Similarly with ACIP’s terrific 

work, he thought there was a synergy in CDC receiving their input for good analyses that 

change the way children grown up and live and the way doctors practice. He stressed that they 

must continue to be rigorous in assessing the science of vaccination, as well as the costeffectiveness, to fully understand what is being recommended and what the implications are. 

Public health is a best buy and vaccination is a great example of that. As they examine the 

large number of vaccinations that could be added, they must also be diligent in assessing the 

costs. That is a decision that must ultimately be shared with society in terms of how much 

health the public is willing to pay for. Certainly, vaccines are one of the great triumphs of the 

past century. In closing, Dr. Frieden emphasized his gratitude to ACIP and its liaisons for the 

work they are doing and for continued significant progress. 

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Discussion

Advisory Committee on Immunization Practices (ACIP) Summary Report February 24-25, 2010 

Human Papillomavirus (HPV) Vaccine 

Introduction 

Janet Englund, MD 

Chair, ACIP HPV Vaccine Work Group 

Dr. Englund reported that there had been new information on HPV vaccine, specifically with 

regard to the quadrivalent vaccine for females age 27 through 45 years of age and quadrivalent 

HPV vaccine for males. Quadrivalent HPV Vaccine for women over 26 years of age was first 

considered by ACIP in 2008. Merck submitted a supplementary application to the FDA in 

November 2009 for quadrivalent HPV vaccine for women over 26 years of age, for which a FDA 

decision is expected before June 2010. The HPV Vaccine Work Group is preparing ACIP for a 

possible vote during the June 2010 ACIP meeting. Work on quadrivalent HPV vaccine in males 

has also been a topic of discussion among the HPV Vaccine Work Group. In October 2009, the 

FDA licensed the vaccine for males ages 9 through 26 years for prevention of HPV 6/11-related 

genital warts. At that time, ACIP made a permissive recommendation for use of vaccine in 

males. Data are now available on efficacy for prevention of anal intraepithelial neoplasia in 

males, although these data have not been submitted to the FDA 

[http://www.fda.gov/BiologicsBloodVaccines/ 

Vaccines/ApprovedProducts/ucm094042.htm]. 

HPV Vaccine Work Group discussions throughout the past several months pertaining to 

quadrivalent HPV vaccine for females 27 through 45 years of age have focused on HPV 

epidemiology and natural history, cost-effectiveness analyses, end-of-study efficacy data from 

the vaccine trial, recommendation options, and new diagnostic tests for HPV that are available 

clinically. In terms of quadrivalent HPV vaccine in males, discussions have focused on vaccine 

efficacy for prevention of anal intraepithelial neoplasia and policy issues. 

GARDASIL® Update 

Richard M. Haupt, MD, MPH 

Clinical Research 

Infectious Diseases & Vaccines 

Merck Research Laboratories 

Dr. Haupt presented data from the end-of-study analyses regarding the efficacy of GARDASIL® 

in adult women 24 through 45 years old (e.g., Protocol 019). He explained that Merck’s studies 

are designed with pre-specified endpoint-driven tests of efficacy hypotheses. The first analyses 

were conducted in late 2007, data from which were presented during the February 2008 ACIP 

meeting. During this session, Dr. Haupt presented the end-of-study data, which now includes 

the completion of nearly 4 years of follow-up for the women who participated in Protocol 019. 

With regard to the study design, Protocol 019 was a randomized, placebo-controlled, doubleblind study. This was an international, multi-center study with a fixed event design that was 48 

months in duration. The study included 3,800 healthy women enrolled from 24 to 45 years of 

age at time of first vaccination, with a 1:1 stratification by age: 24 to 34 years of age and 35 to 

45 years of age. Subjects were randomized (1:1) to receive either 3 intramuscular (IM) 

injections of quadrivalent HPV vaccine or a placebo at Day 1, Month 2, and Month 6. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report February 24-25, 2010 

The key exclusion criteria for Protocol 19 were a history of a Loop Electrosurgical Excision 

Procedure (LEEP) or hysterectomy; history of biopsy-diagnosed cervical HPV disease in the 

past 5 years; and prior history of genital warts, VIN, or VaIN. Different from Merck’s studies in 

younger populations, no limitations were placed on number of lifetime sexual partners. These 

exclusion criteria were defined to try to identify women who were less likely to have on-going or 

active disease due to infection with HPV types, particularly vaccine type, at enrollment. 

As in all Merck studies, the primary analysis is known as the per-protocol efficacy population. 

This consists of women are HPV DNA negative and seronegative at baseline, and HPV DNA 

negative at Month 7 for the relevant HPV type. Case counting began after Month 7. That is, the 

women completed the vaccine series and were without any protocol violations. There were 

several pre-specified objectives, including two co-primary endpoints. The first co-primary 

endpoint was combined incidence of HPV 6/11/16/18-related persistent infection, CIN, AIS, 

cervical cancer and external genital lesions (EGLs: genital warts, VIN, VaIN, vulvar cancer, 

vaginal cancer). The second co-primary was combined incidence of HPV 16/18-related 

persistent infection, CIN, AIS, and cervical cancer and EGLs. The secondary endpoint was 

combined incidence of HPV 6/11-related persistent infection, CIN, AIS, and cervical cancer and 

EGLs. The tertiary endpoint was reduction in HPV 6/11/16/18-related abnormal Pap tests. In 

previous studies of women, Merck designed studies that were powered to assess disease 

endpoints and to define efficacy against CIN 2/3. Protocol 019 was not designed to be a 

standalone study to assess disease endpoints. A composite endpoint of persistent infection and 

disease as a bridge to the efficacy already demonstrated in Merck’s studies of young adult 

women. The majority of the endpoints accrued in Protocol 019 are persistent infection rather 

than disease endpoints. 

Before reporting on the efficacy analyses, Dr. Haupt reviewed some of the natural history data 

that can be evaluated from Merck’s clinical trials. Regarding Day 1 or HPV baseline status for 

four vaccine types (HPV 6, 11, 16 and / or 18), roughly 8% of study participants had evidence of 

HPV DNA detection to one or more of these vaccine types. About a third were positive by 

either DNA or serology to one or more of these vaccine types. Therefore, of the study subjects, 

67% were negative by both HPV DNA and serology to all 4 vaccine HPV types at baseline. It 

was concluded that 90% of subjects would potentially benefit from protection against 3 or 4 

vaccine HPV types. Similar to other populations, most individuals who are positive by either 

DNA or serology to a vaccine type are typically positive to only one type. Many women are still 

negative to 3 or 4 types. 

Analyses were conducted to understand which subject characteristics were associated with the 

risk of being infected with a vaccine HPV type at study entry. In a cross-sectional analysis at 

Day 1 of all women who participated in the trial, a subgroup was selected from within three 

categories (e.g., lifetime number of sexual partners, number of new sexual partners, marital 

status) who had the lowest risk as the referent population and the odds ratio was calculated 

against that referent population to reflect the odds of having a prevalent HPV DNA detection at 

baseline. Not surprisingly, women who had more lifetime sex partners or who had more new 

lifetime sex partners had higher odd of having prevalent HPV DNA detection. Also observed 

was that other than being in a first marriage, all of the other relationships statuses defined also 

increased the odds of having a prevalent HPV infection. In addition, a longitudinal analysis for 

new incident infections in the placebo arm of subjects HPV DNA negative and seronegative at 

baseline was conducted. Based on this analysis, the same subject characteristics that 

predicted prevalent infection predicted the risk of developing a new infection in a woman who is 

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negative at baseline [Velicer C, Zhu X, Vuocolo S, Liaw KL, Saah A. Prevalence and incidence 

of HPV genital infection in women. Sex Transm Dis. 2009 Nov;36(11):696—703]. 

In summary, most women who had evidence of past or current vaccine HPV type infection were 

infected with only one type. Few women had evidence of past or current infection with 3 or 4 

vaccine HPV types. Subject characteristics that predicted baseline vaccine HPV type infection 

were the same characteristics that predicted incident infections, which makes the identification 

of a risk demographic difficult to identify. 

Dr. Haupt then reported on efficacy in the pre-specified population and pre-specified endpoints 

(e.g., the vaccine type related endpoints). Based on the end-of-study data for the first coprimary endpoint (HPV 6/11/16/18-Related Persistent Infection, CIN, or EGL), there were 10 

cases in the GARDASIL® arm and 86 cases in the placebo arm, and the observed efficacy is 

88.7% (78, 95 CI). Most of the end points were persistent infection endpoints. Because there 

was a stratified enrollment, Dr. Haupt also provided data for efficacy based on the stratified age 

group populations. The efficacy by age strata was also high and statistically significant. For 24 

to 34 year-olds, there were 5 cases in the GARDASIL® arm and 56 cases in the placebo arm, 

with an observed efficacy of 91.3% (78, 97 CI). In the 35 to 45 year-olds, there were 5 cases in 

the GARDASIL® arm and 30 cases in the placebo arm, and the observed efficacy was 83.8% 

(58, 95 CI). Given that vaccine efficacy is a calculation based on a relative risk reduction, 

having lower event rates in the older age group will lower the calculated vaccine efficacy. 

Vaccine efficacy in the older age strata is numerically lower, although not statistically so based 

on the confidence intervals. Because there are equal numbers of women in these groups, the 

30 events in the placebo arm of the older age group and 56 in the younger age group reflects 

the lower event rates in the older age strata. 

In terms of the co-primary endpoint by disease severity, because the study was powered on the 

composite endpoint, there are limitations of power particularly for the CIN 2/3 endpoint. Most of 

the endpoints were persistent infection. There were 9 events of persistent infection, 7 of which 

were related to type 16 and 2 of which were related to type 6. There was 1 disease event in the 

GARDASIL® arm, which was a CIN 2 attributed to type 16 in a woman in whom that lesion was 

also confounded with HPV type 51. There was very high efficacy against CIN (94.1%) and 

external genital lesions (100%). Regarding the co-primary endpoint by HPV type, there were 2 

events of HPV 6 (35 in the placebo arm), 0 events of HPV 11 (4 in the placebo arm), 8 events of 

HPV 16 (39 in the placebo arm, and 0 cases of HPV 18 (13 in the placebo arm). The observed 

efficacy was 94.4% (78, 99 CI) for HPV 6, 100% (-52, 100 CI) for HPV 11, 79.9% (56, 92 CI) for 

HPV 16, and 100% (67, 100) for HPV 18. 

For women to have been evaluated in the full analysis set population (e.g., intention-to-treat 

population), they had to have been enrolled and have received at least one dose of either 

vaccine or placebo, to have had at least one follow-up visit, and they did not have to complete 

the vaccine series. Case counting began right after Day 1, so this reflects a lot of prevalent 

infection or disease at study entry. Even in the intent-to-treat populations, there was close to 

50% efficacy (47.2%) against the composite endpoint due to vaccine types which was 

statistically significant. Assessing that by disease severity, there is significant efficacy for some 

of the endpoints, but power is limited for the CIN 2/3 endpoint.: persistent infection 49.0% (36, 

60 CI), any grade CIN 47.5% (16, 68 CI), CIN 2/3 or worse 22.4% (-43, 58 CI), external genital 

lesions 8.5% (-127, 63 CI), condyloma 41.8% (-60, 81CI), and for VIN 2/3 or VaIN 2/3 there 

were too few endpoints for meaningful analysis. 

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With 1 or more AEs 1645 87.0 1535 81.3 

With injection-site AEs 1450 76.7 1213 64.2 

With systemic AEs 1121 59.3 1135 60.1 

With serious AEs 14 0.7 16 0.8 

With serious vaccine-related AEs* 0 0.0 0 0.0 

Who died† 7 0.4 1 0.1 

Discontinued due to an AE 7 0.4 2 0.1 

Discontinued due to a serious AE 2 0.1 0 0.0 

Discontinued due to a serious vaccine-related AE 0 0.0 0 0.0 

 

 

 

 

 

 

Advisory Committee on Immunization Practices (ACIP) Summary Report February 24-25, 2010 

In terms of the co-primary and secondary endpoints across all ages, efficacy for HPV 16/18­

related persistent infection, CIN, or EGL was 84.7% (68, 94 CI); and efficacy for HPV 6/11­

related persistent infection, CIN, or EGL was 94.8% (80, 99 CI). Regarding co-primary and 

secondary endpoints by age strata for HPV 16/18-related persistent infection, CIN, or EGL, 

efficacy was 86.0% (64, 96 CI) in 24 to 34 year-olds and 81.8% (36, 97 CI) in 35 to 45 yearolds. Efficacy for HPV 6/11-related persistent infection, CIN, or EGL was 100% (83, 100 CI) in 

24 to 34 year-olds and 86.2% (40, 99 CI) in 35 to 45 year-olds. The same trend is reflected 

here as well, with high efficacy in both age strata, but numerically lower efficacy in the older age 

strata driven primarily by the lower event rates observed in that group. 

Regarding the tertiary endpoint of the impact of GARDASIL® on incidence of HPV 6/11/16/18­

related Pap diagnoses, in the per protocol efficacy population, there was very high efficacy of 

97.4% (85, 100 CI). Efficacy was equally high in both age groups in this analysis. There was 

only one case in the GARDASIL® group, which was HPV 16-related. Of the 38 placebo cases, 

12 were HPV 6-related, 4 were HPV 11-related, 21 were HPV 16-related, and 6 were HPV 18­

related. In the intention-to-treat population (e.g., full analysis set), observed efficacy overall was 

50.1% (24, 68 CI). Efficacy in 24-34 year-olds was 52.6% (21, 72 CI) and in 35-45 year-olds 

was 42.0% (-25, 74 CI). This intention-to-treat analysis includes subjects with prevalent vaccine 

HPV type infection. No impact was observed in an intention-to-treat analysis that was 

irrespective of any HPV type, which assessed the prevention of abnormal Paps of all women 

who entered the study regardless of causative HPV type, regardless of prevalent versus 

incident occurrence. This illustrates that a tremendous amount of prevalent infection by nonvaccine types occurred in this population, which were already present at baseline before women 

were enrolled into the study. 

Observed fairly consistently across all populations studied, GARDASIL® is a generally welltolerated vaccine. The most common adverse event observed is local injection site reactions 

(e.g., injection site pain, swelling, redness). That by far drives the adverse event profile. 

Serious adverse events are uncommonly observed. No vaccine-related serious adverse events 

were observed in this study population. It is uncommon for women to discontinue from Merck’s 

clinical trials at all, and it is certainly uncommon due to an adverse event. The following table 

illustrates clinical adverse events: 

Clinical Adverse Experience Summary 

Gardasil 

(N=1890) 

n % 

Placebo 

(N=1888) 

n % 

Number (%) of subjects: 

*Determined by the investigator to be possibly, probably, or definitely related to the vaccine. †All deaths in the study were determined by the investigator to be "definitely not" related to the 

vaccine. Vaccine: hypertensive heart disease, nasopharyngeal cancer, breast cancer, 

pulmonary tuberculosis, cardiac failure from hyperthyroidism, post-operative PE, pericarditis 

secondary to SLE. Placebo: Acute lymphoblastic Leukemia 

N = number of subjects with follow-up 

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Advisory Committee on Immunization Practices (ACIP) Summary Report February 24-25, 2010 

In summary, women aged 24 to 45 are susceptible to HPV 6/11/16/18 infection and disease. 

Women aged 24 to 45 are at continued risk for acquiring infection and disease lesions from 

these HPV types. GARDASIL® is highly efficacious against HPV 6/11/16/18-related persistent 

infection, CIN or EGL in adult women negative to the relevant HPV type. Efficacy is supported 

by significant efficacy for the primary endpoint in the intention-to-treat population analyses. 

GARDASIL® is generally safe and well tolerated in women aged 24 to 45 years old. 

HPV Epidemiology in Adult Women 27 Through 45 Years 

Eileen Dunne MD, MPH 

Division of STD Prevention, CDC 

Dr. Dunne presented updated information on the epidemiology of HPV infection, with a focus on 

women 27 through 45 years of age. HPV epidemiology is one of several considerations for 

policy decisions for use of HPV vaccine in women 27 through 45 years of age. Other 

considerations include vaccine efficacy, safety, immunogenicity, programmatic considerations, 

and cost-effectiveness. To put this policy consideration in perspective, Dr. Dunne reviewed 

ACIP’s current recommendations for use of the HPV vaccine, which is as follows 

[http://www.cdc.gov/vaccines/recs/provisional/downloads/hpv-vac-dec2009-508.pdf]: 

Routine vaccination is recommended by ACIP with either the bivalent or quadrivalent 

HPV vaccine for 11 or 12 year old girls. Catch-up vaccination is recommended through 

age 26 years. Benefit is greatest before sexual debut. 

Based on data previously shown to ACIP from the National Survey of Family Growth on the 

percentage of adolescents who have had vaginal sex, for both females and males there is an 

increasing prevalence of ever having vaginal sex with increasing age. By age 15 years, 26% of 

girls have had vaginal sex [Mosher et al. 2005; Vital and Health Statistics: No. 362]. Thus, 

increasing age presents more opportunities for acquiring HPV infection, which may reduce the 

opportunities for the full benefit of prophylactic HPV vaccines. HPV prevalence peaks in the 

20s, and tends to decline with age. Smaller secondary peaks in prevalence among older 

women have been observed in some geographic regions outside the United States (US). A 

variety of sexual behaviors are risk factors for prevalent and incident HPV infection (e.g., lifetime 

sex partners, recent sexual partners). 

Some of the best data on incident infection in adult women is data from the clinical trials and 

cohorts outside the US. Based on data regarding incidence from the quadrivalent vaccine 

clinical trials, which provides information on acquisition of vaccine-type infection during the trial, 

with increasing age the incidence of infection with HPV 6, 11, 16 or 18 decreased from 7.4 

infections per 100 person years in 24 through 29 year olds to 1.9 per 100 person years in the 40 

through 45 year olds [Haupt R, Merck presentation to ACIP, Feb 2008]. A study of women 

attending cervical cancer screening centers in Bogota, Colombia similarly demonstrates 

decreased incidence of infection with age. In terms of the incidence of infection with HPV 16, 

18, 6 or 11 by age in this study, the highest rate of infections occurred among the women in 

their late teens and early 20s and decreased with age. 

When considering incident infection in women over 26 years of age, it is important to note that it 

is unclear if these are first infections, re-infections, or re-activations from a previous infection 

acquired earlier. There may be a contribution of each of these. In studies of younger women, 

especially virgins, incident infection is often implied to be new infection, but this same 

conclusion cannot be made with older women who may have had more sexual experiences. 

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There is evidence that at least a proportion of incident infections in this age group is due to 

transmission from a partner. 

Regarding HPV infection from a partner in adult women, epidemiologic data that suggests HPV 

infection is transmitted from and between sex partners are from a myriad of studies in younger 

women, showing that sexual behaviors are risks for incident infection. However, there are fewer 

studies of adult women over 25 years of age. Sex behavior is clearly linked to incident infection 

in studies of younger women. Based on the few studies of adult women over 25 years of age, 

adult women dating online were more likely to have prevalent oncogenic HPV with increasing 

number of male sex partners, concurrent partnerships, and recent relationship [Winer R, et al. 

IPV Conference 2009 P-30.18]. Additional data are available from the quadrivalent HPV 

vaccine clinical trials on risk factors for incident HPV 6, 11, 16 or 18 infection. In terms of the 

risk factors for incident infection, incident infection HPV 6, 11, 16, or 18 infection is associated 

with increasing lifetime sex partners, increasing number of new partners, and marital status 

[Velicer C, Zhu X, Vuocolo S, Liaw KL, Saah A,Sex Transm Dis. 2009 Nov;36(11):696—703]. 

Given that the risk of incident HPV infection is related to sexual behavior, it is important to 

summarize sexual behavior data from the US. The National Survey of Family Growth found that 

between 7.1% and 15.1% of adult women, depending on age, had two or more sex partners in 

the past 12 months. 

Despite clear risk factors for incident infection, it is challenging to identify specific groups of 

adult women who might benefit from vaccination. Data available from the placebo month of the 

vaccine trial found that although there were clear sexual risk factors for incident infection, these 

risk factors were the same risk factors for finding baseline prevalent infection. This means that 

identifying women at risk of incident infection who could possibly benefit from vaccination may 

also identify women who were more likely to already have been infected who possibly would not 

benefit from vaccination. In addition, there are programmatic challenges to implementing a 

“targeted” approach for adult woman, especially using sexual behavior risk factors. For both of 

these reasons, the opportunity to identify specific groups of adult women who would benefit 

from vaccination is not feasible. 

There are other important considerations about preventing “incident” infection in adult women 

through vaccination. Questions remain with regard to the natural history of incident infection in 

women over the age of 25 years. For example, it is not clear whether incident infection in 

women over 26 years of age is more aggressive than that in younger women. That is, do these 

infections contribute to more persistent infection or disease? If this is the case, there might be a 

stronger reason to prevent even few incident infections. One study evaluated incident infections 

prospectively. This study enrolled women who had low grade abnormalities or normal findings 

on Pap screening and evaluated women for incident infection. Women with incident infection 

were followed to find what percentage of these infections persisted and for how long. Different 

age groups were evaluated, and essentially a similar pattern was found in the women aged 30 

years and older compared to younger women. This implies that the natural history of incident 

HPV infection is not more aggressive in older women than younger women [MourcourtBoulch,et al. Int J Cancer 2010]. Another study, a cohort study in Guanacaste, Costa Rica, 

evaluated development of CIN 2/3, and CIN3 after incident infection and found that older 

women with incident infection had a similar risk of CIN 2/3 and CIN3 as younger women 

[Rodriguez AC, et al. J Nat Cancer Inst. 2010]. 

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-

Advisory Committee on Immunization Practices (ACIP) Summary Report February 24-25, 2010 

The following graphic reminds us about the natural history of HPV infection and the 

development of cervical pre-cancers and cancer, and is a reminder that infection occurs years 

to decades before development of disease, and that persistent infection is the most important 

risk factor for development of pre-cancers and cancers: 

Within 1 Year 1 5 Years Decades 

Initial 

HPV 

Infection 

Persistent 

Infection 

CIN 

2/3 

Cervical 

Cancer 

CIN 1 

Cleared HPV Infection 

Background: Natural History 

Cervical Precancers/Cancers 

The peak in diagnoses of CIN 2/3, or cervical pre-cancers, in the US is among women in their 

late 20s to 30s. infection often occurs years earlier before development of these disease 

outcomes [Insigna RP, et al. Am J Ob Gyn 2004]. 

In conclusion, as women age from their mid 20s, HPV prevalence and HPV incidence decrease. 

The likelihood of having acquired HPV infection increases. Given that disease outcomes (e.g., 

genital warts, CIN 2/3) peak among women in their mid to late 20s, the potential benefit of 

vaccinating women in their late 20s to early 40s would be minimal. Questions remain with 

regard to the natural history of incident infections in adult women. The greatest benefit would 

be from vaccinating females in early adolescence. 

Cost-Effectiveness of Quadrivalent HPV Vaccination of Adult Women 

Harrell Chesson, PhD 

NCHHSTP 

Centers for Disease Control and Prevention 

The routine vaccination of 12-year-old females in the US is a cost-effective use of public health 

resources. Cost-effective estimates are consistent across a wide range of studies. However, 

there is more uncertainty and less precision in the cost-effectiveness estimates for HPV 

vaccination of adult women and HPV vaccination of males. With that in mind, Dr. Chesson 

focused this presentation on an update of data pertaining to vaccination of adult women that 

was presented to ACIP in February and June 2008, a review of cost-effectiveness ratios and 

quality adjusted life years (QALYs) for other vaccines and other health interventions, which was 

specifically requested by several ACIP members; and a summary of three cost-effectiveness 

models for adult women in the US: Kim & Goldie (N Engl J Med 2008), Merck (based on 

Elbasha et al., Emerg Inf Dis 2007); and Chesson et al. (based on Emerg Inf Dis 2008). 

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______________________________________________________________________ 

 

Vaccine Cost per outcome gained 

(compared to no vaccine) 

Source 

DTaP, Hib, MMR, Polio, 

Varicella 

<$0 per QALY (cost-saving) 

Individually and as a group 

Ekwueme (2000), 

Zhou (2004, 2005, 2008), Cochi (1985), 

White (1985), Thompson (2006), 

Preblud (1985) 

Influenza (LAIV) § $10,000 per QALY Prosser (2006) 

Hepatitis A § $10,000 to $30,000 per QALY Das (1999), Rein (2007) 

Meningococcal § $120,000 per QALY Shepard (2005) 

Advisory Committee on Immunization Practices (ACIP) Summary Report February 24-25, 2010 

Vaccination cost-effectiveness is often expressed in terms of the cost per QALY gained. The 

cost per QALY gained by adding HPV vaccination to cervical cancer screening can be 

expressed as follows: 

(Vaccine cost + administration cost) – (cost of illness averted by vaccination) 

Number of QALYs gained by vaccination 

QALYs can be used to measure the health impacts of interventions, such as vaccination. 

QALYs also take into account reductions in morbidity and mortality by taking into account quality 

and length of life. One year in perfect health = 1 QALY, Death = 0 QALY, and one year of life in 

less than perfect health is assigned a value between 0 and 1 QALY depending upon the 

severity of the health issues. 

Currently, there is no consensus on the appropriate cost-per-QALY threshold for determining 

cost-effectiveness of public health interventions in the US. Likewise, there is no official ACIP 

threshold for determining the cost-effectiveness of vaccination. In the US, a threshold of 

$50,000 to $100,000 is often cited. However, this threshold has been described as arbitrary 

and lacking in empirical or theoretical justification [Grosse (2008). See also Weinstein et al. 

(2010) for additional incremental QALY threshold interpretation]. Globally, the World Health 

Organization (WHO) suggests using per-capita Gross Domestic Product (GDP) [Grosse (2008). 

See also Weinstein et al. (2010) for additional incremental QALY threshold interpretation] in 

which a cost per QALY of less than per-capita GDP would very cost-effective, and less than 3 

times per-capita GDP would still be considered cost-effective. Under this guideline, the US percapita GDP of approximately $50,000 per person would correspond to a cost-effectiveness 

threshold of about $50,000 to $150,000. However, the WHO threshold has also been described 

as lacking a theoretical rationale [Grosse (2008). See also Weinstein et al. (2010) for additional 

incremental QALY threshold interpretation]. 

Another way to think about cost-effectiveness thresholds for vaccination is to assess the costeffectiveness of recommended vaccines. The following chart shows the cost per outcome 

gained for selected childhood vaccines in the US: 

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Pneumococcal § $10,000 to $105,000 per LYS Ray (2006, 2009) and Lieu (2000) 

Rotavirus § $135,000 to $225,000 per LYS Cortese (2009) and Widdowson (2007) 

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These results are shown in terms of cost per QALY except for pneumococcal and rotavirus 

vaccine, which are shown in terms of cost per life year saved. The first five vaccines (DTaP, 

Hib, MMR, polio, varicella) have been found to be cost saving whether considered individually or 

as a group. That is, each one of these vaccines pays for itself in terms of offset medical costs. 

Other vaccines such as meningococcal have a relatively high cost per QALY at $120,000. 

Other vaccines such as pneumococcal ($10,000 to $105,000 per LYS) and rotavirus ($135,000 

to $225,000 per LYS) have relatively high costs per outcome gained. The meningococcal 

estimate is for vaccination at age 1 year. This table shows a collection of point estimates; the 

ranges shown for hepatitis A, pneumococcal, and rotavirus vaccination reflect base case results 

of more than one study. For each vaccine, the actual range of plausible cost-effectiveness 

estimates varies (not shown). See source studies for details. 

The cost per QALY gained for selected adolescent vaccines in the US, with HPV shown in bold: 

Vaccine Target group Cost per QALY gained 

(compared to no vaccination) 

Hepatitis B College freshmen <$0 (cost-saving) to § $10,000 

Hepatitis A College freshmen <$0 (cost-saving) to § $15,000 

HPV 12-year-old females § $3,000 to $45,000 

Influenza (LAIV) 12- to 17-year olds, high risk § $10,000 

Tdap All 11-year-olds § $25,000 

Meningococcal (MCV4) All 11- to 17-year-olds § $105,000 

Influenza (LAIV) 12- to 17-year olds, healthy § $140,000 

Meningococcal (MCV4) All 11-year-olds, routine § $140,000 

Source: Ortega-Sanchez et al. Pediatrics (2008), except HPV 

HPV vaccination compares relatively favorably to the other vaccines. Again, meningococcal 

has a relatively high cost per QALY gained as does influenza for healthy 12- to 17-year olds. 

For HPV, lower and upper bound estimates were obtained from Elbasha (2007) and Kim (2008), 

respectively. This table shows a collection of point estimates; the range shown for HPV reflects 

base case results of two studies; and the ranges shown for hepatitis A & B reflect base case 

results from two perspectives. For each vaccine, the actual range of plausible costeffectiveness estimates varies (not shown). See source studies for details. 

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Cost per QALY gained for selected health interventions in the US is shown in the following 

table: 

Vaccine Cost per QALY gained 

Chlamydia screening § $3,000 to $40,000 

Cervical cancer screening

 Every 2 years vs. never § $25,000

 Annual vs. every 2 years § $725,000 

Breast cancer screening

 Every 2 years vs. never § $40,000

 Annual vs. every 2 years § $65,000 to $160,000 

All of these screening activities have the potential to cost less than $40,000 per QALY gained, 

but the cost-effectiveness of screening depends upon the frequency of screening. For example, 

cervical cancer screening every two years as compared to never screening costs about $25,000 

per QALY gained. However, if the frequency was increased to every year, the cost per QALY is 

estimated to be $725,000 or greater. Chlamydia screening shown is annual (compared to no 

screening), for sexually active women aged 15-24 years (Hu 2004, lower bound estimate) and 

for women aged 15 to 34 years (Gift 2008, upper bound estimate). Cervical cancer screening 

estimates were extrapolated from Goldhaber (2008) and consistent with other estimates [Tengs 

1995; Goldie 2004,2006; Kulasingam 2006; and Kim 2002]. Breast cancer screening (every 

year vs. every 2 years, and every 2 years vs. every year) was estimated to cost approximately: 

$40,000 and $160,000, respectively, by Ahern (2009)(extrapolated), for combined 

mammography and clinical breast exam for ages 40 to 79 years; and $40,000 to $65,000, 

respectively, by Stout (2006)(extrapolated), for mammography for ages 40 to 80 years, per 

QALY. Ranges (where given) reflect point estimates from more than one study. For each 

intervention, the actual range of plausible cost-effectiveness estimates varies (not shown). See 

the source studies for more details. 

While there is a great deal of confidence that HPV vaccine for 12-year old females is fairly costeffective compared to other vaccines and health interventions, one of the remaining issues 

regards the cost-effectiveness of vaccinating adult women. Dr. Chesson summarized the three 

models that address this issue: Kim & Goldie, Merck, and Chesson et al. All three models 

examined female only vaccination and assumed a lifelong duration of vaccine protection. The 

Merck model used a $400 cost per vaccine series, while the Kim & Goldie and Chesson et al 

models used $500. All models examined a wide range of outcomes (e.g., cervical cancer, CIN, 

genital warts, non-cervical cancers, recurrent respiratory papillomatosis (RRP)); however, not all 

of these outcomes were included in every scenario examined. The published results by Kim & 

Goldie did not include the reductions in HPV-associated health outcomes in men that might be 

achieved by vaccinating women, nor did they assume that CIN would have an impact on quality 

of life. All models included indirect effects, although the Chesson model used a relatively simple 

approach to do so. All models examine the addition of HPV to cervical cancer screening, 

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although the Chesson model did not model cervical cancer screening directly and instead 

assumed that it was reflected in the rates of cervical cancer observed in the US. All models 

assumed a relatively similar impact of genital warts on the quality of life, but the duration of this 

reduction in quality of life was greater in the Merck model. 

All of the models assumed that there would be no vaccine protection against HPV types 

acquired prior to vaccination, and that there would be lifelong natural immunity following 

clearance of HPV, although the degree of this immunity varied across the models. All models 

examined a relative long time horizon at 100 years for the Merck and Chesson models and 

lifetimes of relevant birth cohorts for the Kim & Goldie model. With respect to the results of the 

Kim & Goldie model when cervical outcomes and genital warts were included, as older age 

groups were added incrementally the cost per QALY increased as follows: 12 years of age 

$34,900; 13-18 $81,000; 19-21 $101,300; and 22-26 $133,600. This increase in the cost per 

QALY as the age at vaccination increases is to be expected because the probability of being 

previously exposed to the vaccine types increases and incidence of HPV decreases. Although 

this model did not address the cost effectiveness of vaccinating women over age 26, some 

information on the cost-effectiveness of vaccinating women over age 26 can be derived from 

this model. Based on the increasing costs per QALY for the ages included, it is reasonable to 

assume that the cost per QALY of vaccinating women over age 26 would be at least $133,000. 

When Kim & Goldie focused on the effect of inclusion of other health conditions on the costeffectiveness of female vaccination strategies, the cost effectiveness of vaccine appears to be 

more favorable. 

In this model for age 26, the cost per QALY exceeded $100,000 in all of these scenarios except 

the most optimistic scenario of 100% vaccine efficacy against a wide range of health outcomes. 

In another application of their model, Kim et al focused on women 35 to 45 years old. The 

results were fairly consistent with what would be expected based on their previous study. 

Compared with current screening, HPV vaccination was less cost-effective than other wellaccepted interventions in US. 

With regard to the Merck model results of the cost-effectiveness of female vaccination by age 

when including cervical, vulvar, and vaginal outcomes in women and genital warts in males and 

females, incremental ages added resulted in the following cost per QALY: 9-26 years of age 

$7,800; 27-34 $51,900; and 35-44 $142,000. As with the Kim & Goldie model, when more 

health outcomes were included, the cost per QALY was reduced as shown in the following 

table: 

Incremental cost-effectiveness ratios by
 

HPV disease prevented
 Merck model results: Base case cost per QALY estimates
 

HPV Diseases Femaleonly 926 

+ 2734 

females 

+ 3544 

females 

Cervical $17,500 $84,000 $224,000 

+ Vulvar and vaginal $16,000 $77,000 $205,200 

+ Genital warts $7,800 $51,900 $142,000 

Evidence of vaccine efficacy in females 

+ Anal $6,200 $41,600 $113,400 

+ Head & neck $4,300 $31,700 $87,800 

+ Penile $4,200 $30,900 $85,700 

+ RRP $2,300 $28,900 $83,300 

QALY: quality-adjusted life year 

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Ages 

vaccinated 

Incremental

ages added 

Cost per QALY 

Cervical, warts All outcomes 

12 12 $8,000 $3,000 

12-18 13-18 $26,000 $17,000 

12-2 19-21 $55,000 $38,000 

12-26 21-26 $119,000 $85,000 

12-29 27-29 $254,000 $179,000 

12-34 30-34 $449,000 $305,000 

Cost per QALY (quality-adjusted life year) of each strategy is the incremental cost-effectiveness ratio of the 

strategy compared to the preceding strategy. Cost per QALY of vaccinating 12-year-olds is as compared to 

no vaccination (screening only). All strategies include cervical cancer screening. Results preliminary. 

 

 

 

Advisory Committee on Immunization Practices (ACIP) Summary Report February 24-25, 2010 

This chart shows how the cost per QALY gained by vaccination decreases as more health 

outcomes are included in the analyses. The top row shows the cost per QALY when including 

only cervical outcomes, while the bottom row shows the cost per QALY when all health 

outcomes are included. In the most optimistic scenario shown by the bottom row, the cost per 

QALY was about $28,000 for vaccination 27 to 34 year olds and about $83,000 for vaccinating 

35 to 44 year olds. If the analysis is limited to just those outcomes for which there is evidence 

of vaccine efficacy in females, the cost per QALY in 27 to 34 year olds is about $50,000 and for 

35 to 44 year olds is about $142,000. 

The Chesson model includes results for two scenarios, one in which cervical outcomes and 

genital warts were included and one in which all outcomes were included. As with the other 

models, as the age of vaccination increases, the cost per QALY increases as well as shown in 

the following table: 

Chesson et al. model results: Cost-effectiveness

of female vaccination by age 

1

The following chart summarizes the results of all three models by showing the age group at 

which female vaccination exceeds an arbitrary threshold of $100,000 per QALY: 

19 21 22 23 25 27 29 31 33 35 37 39 41 43 45 47 49 

Age group at which female vaccination 

exceeds $100,000 per QALY 

Kim & Goldie model (except w/ high efficacy against all health outcomes) 

Chesson et al. model (when limited to cervical outcomes, genital warts) 

Chesson et al. model (when including all health outcomes) 

Merck model (when limited to cervical, vaginal, vulvar, anal outcomes and genital warts) 

AGE 

Merck model 

does not exceed $100,000 

er QALY for ages 35 to 44 

when including all health 

outcomes 

p

In the Kim & Goldie model, the cost per QALY exceeded $100,000 in the early to mid 20s 

except when they included all health outcomes at 100% vaccine efficacy. In the Chesson 

model, the cost per QALY exceeded $100,000 in the 22 to 26 age group when focusing only on 

cervical outcomes and genital warts. When Chesson et al included all health outcomes, the 

cost per QALY exceeded $100,000 somewhere in the 27 to 29 year age group. In the Merck 

model, the cost per QALY exceeded $100,000 for ages 35 to 44 when the analysis was limited 

to cervical, vaginal, vulvar, and anal outcomes and genital warts. However, when all outcomes 

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were included in the Merck model, the cost per QALY never exceeded $100,000 even at ages 

35 to 44. 

Regarding factors that contribute to differences in model results, compared to the Kim & Goldie 

model, the Merck model uses a lower cost per vaccine series, assumes a greater quality of life 

impact of CIN and genital warts, and includes more health outcomes (outcomes in males; adultonset RRP). There are also differences in how screening is modeled, which may affect the 

calculation of the marginal benefits of adding vaccination to screening. The model structures 

also differ, which may make it difficult to compare how each model simulates the changing 

dynamics of HPV in the population after the introduction of a vaccine. 

The actual change in costs and benefits when expanding the cut-off age of vaccination age from 

26 to 44 years were presented for the Merck and Chesson models. As would be expected, 

when more people are included in a vaccination program, vaccination costs will increase, 

(approximately 20% in each model). The increase in the net cost of vaccination, however, is 

relatively more pronounced. This is because the net cost of vaccination includes the cost of the 

vaccine as well as the medical costs offset by the vaccination. On average, vaccinating a 27 to 

44 year old will offset less future medical costs than will vaccinating a 12 to 26 year old, so the 

net costs increase relatively more rapidly than vaccination costs when expanding vaccination to 

include 27 to 44 year olds (~70% to 80%). The increase in QALY gained was less than 5% in 

both models. Thus, expanding vaccination to include 27 to 44 years olds has a notable 

increase in cost with a relatively smaller increase in health improvements as measured by the 

gain in QALYs. 

In conclusion, routine HPV vaccination of 12-year-old girls is cost-effective. For adult women, 

vaccination is less cost-effective as age at vaccination increases due to the fact that HPV 

incidence decreases, and the probability of previous exposure increases. Extending vaccination 

beyond age 26 years would account for small percentage of total vaccine benefits. The precise 

age at which vaccine is no longer cost-effective is uncertain. This depends on many factors 

such as the health outcomes included in the analysis, screening assumptions, other modeling 

assumptions, et cetera. Results can vary within and across models due to uncertainties in the 

natural history of HPV that the models must address, other uncertainties such as the cost and 

impact on quality of life of HPV-related outcomes, and differences in model structure. 

Quadrivalent HPV Vaccine Recommendation 

Options for Adult Women 27-45 Years 

Dr. Lauri Markowitz 

CDC / NCHHSTP 

Dr. Markowitz reported that in 2008 when the HPV Vaccine Work Group first considered adult 

women and again more recently, the group has considered a variety of options for women in 

this age group including a permissive recommendation only; a targeted catch-up 

recommendation, which may be risk-based; and extending catch-up recommendations to 

females in all or part of this age group. 

Some of the key points presented during this session today, and which were considered by the 

work group when reviewing options, are that HPV vaccine is prophylactic and would have the 

greatest impact and be most cost-effective when administered before exposure to HPV. 

Infections do occur in females over the age of 26, but incidence decreases with increasing age. 

It is difficult to target by behavioral risk factors. Risk factors for prevalent infection and past 

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exposure are similar to those associated with incident infection. Models show decreasing costeffectiveness with age at vaccination for adult women, although the age at which vaccine is not 

cost-effective differs by model and within models. 

If the vaccine is licensed by the Food and Drug Administration (FDA) for use in women over 26 

years of age, it is unclear what the indications will be. There were few CIN 2/3 cases in the trial 

and there were no cases of VIN / VaIN 2/3, which is part of the indication for 9 to 26 year olds. 

As noted earlier, there is very high efficacy against the combined endpoint, but few CIN 2/3 

endpoints, which was the primary outcome in the pivotal trial, or VIN / VaIN 2/3. 

Based on this information, the quadrivalent HPV vaccine recommendation to be proposed by 

the ACIP HPV Work Group for women 27-45 years during the June 2010 ACIP meeting will be a 

permissive recommendation. The rationale for this is that there would be a relatively small 

impact of vaccination in adult women, the models show potential for high cost per QALY in this 

age range, and that the main focus of the vaccination program should be adolescents. The 

ACIP HPV Vaccine Work Group plans are to further review of data on adult women, prepare for 

a vote during the June 2010 ACIP meeting in the event that the vaccine is licensed for this age 

group by FDA before that time, and to draft a “Policy Note” for an MMWR (publication pending 

ACIP vote), which would state the efficacy observed in this age group; that vaccine may be 

given to women age 27-45 years but that there is no extension of the catch-up recommendation; 

and that cervical cancer screening should be the primary focus of cervical cancer prevention in 

this age group. 

Discussion 

Regarding larger social questions pertaining to vaccination, Dr. Rosenbaum inquired about the 

extent that something like HPV becomes understood as routine for all women beginning prior to 

sexual activity and through their adult years, and whether there was any energy at the crucial 

pre-puberty ages by having the vaccine understood as something people should receive 

universally. That is, she would be inclined to worry less about the cost implication in older ages 

if there was a rollover effect on the younger populations (e.g., understanding that this is routine). 

Dr. Markowitz responded that the HPV Vaccine Work Group’s feeling was that ACIP should 

emphasize that the focus of the HPV immunization program is on adolescents. If anything, 

having an extended recommendation would likely dilute that emphasis. Thus, she thought the 

focus should be on targeting the vaccine to adolescents before sexual activity. 

Dr. Temte pointed out that there is good evidence that the decision by mothers to immunize 

their daughters is dependent upon two things: their knowledge of HPV causing cervical cancer 

and their own behavior regarding Pap smears. This also fits into ACIP’s duty to enhance 

coverage for HPV in the younger age group. HPV, and especially cervical cancer, are highly 

disparate illness that tends to affect minority communities, the poor, and lower educated 

individuals. He thought this was where ACIP’s focus should be. 

Regarding Dr. Haupt’s presentation showing that the number of lesions in 27 to 45 year old 

women is not changed overall by the vaccine (e.g., those who have received the vaccine do not 

have more lesions overall for all HPV types than those who are in the control group), Dr. Chilton 

said that this implied to him that there was some replacement of 16 and 18 by other viruses. He 

wondered whether this was also Dr. Haupt’s interpretation. 

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Dr. Haupt replied that it was not. His interpretation was that they were assessing a study 

population of about 3,800 women, which is a relatively small sample size to examine intent-totreat analyses across all HPV types. In terms of non-vaccines types, Merck observed an 

imbalance in the number of cases due to non-vaccine types. However, this reflects an 

imbalance of the same non-vaccine types that occur at baseline. These women were not 

randomized across those non-vaccine types, so there is an imbalance by type-specific nonvaccine type at baseline which then contribute to the development of disease endpoints by 

those same non-vaccine later. 

It seemed to Dr. Cieslak that when considering the cohort of women 27 and older, they were 

really addressing all women rather than any subgroups. He wondered if there was enough 

information to determine whether certain subgroups of these women may be more likely to 

benefit from the vaccine (e.g., women who present at STD clinics; women who are less likely to 

obtain regular Pap smears), while others would be less likely to benefit (e.g., married women in 

stable relationships). 

Dr. Dunne responded that that the findings from the clinical trial suggest that sexual behavior 

factors that make incident infection likely also make prevalent infection likely. However, there 

would be a number of challenges in terms of a venue-based or Pap screening findings-based 

approach. At this time, it is unknown whether there would be a benefit to focusing on certain 

subgroups. 

Noting that Dr. Haupt did not discuss a booster dose in his presentation, Dr. Meissner noted that 

there is some evidence that there is loss of antibody a number of years after administration of 

GARDASIL®, particularly Type 18. He requested that Dr. Haupt comment on the issue of 

equating loss of antibody to susceptibility to infection, and whether the cost of booster doses 

should be factored in. 

Dr. Haupt responded that they have observed loss of seropositivity in women who they have 

followed for a while. There continues to be virtually 100% efficacy in women who become 

seronegative. At this point, it does not appear that the loss of antibody is associated with loss of 

protection. Particularly for type 18, they are measuring a very specific neutralizing antibody 

against one known neutralizing epitope. They know it is not the immunodominant epitope, and 

it is very likely that the amount of antibody women need for protection is substantially lower than 

what is being measured. The data thus far suggest that no booster is going to be required, and 

using immunogenicity as a measure of that is probably not the right approach. 

In terms of long-term immunologic memory, Dr. Judson inquired as to whether at this point this 

seemed analogous to hepatitis B. 

Dr. Haupt responded that this was a fair comparison. Much like hepatitis B, HPV vaccine is a 

subunit protein vaccine with a prime boost immunological response, so it behaves similarly. It is 

important to remember that there is evidence from 5 years of GARDASIL® and about 9.5 years 

from the monovalent HPV 16 study in which 100% efficacy has been observed against infection 

and disease. Some of those women are seronegative as well. Long-term surveillance projects 

are in place that will continue to assess this. An important study in the Scandinavian countries 

will come out in 2010, which will continue to address long-term protection. 

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Dr. Sumaya said he was agreeable to the potential language to be used by the work group for 

the recommendation. He has sometimes had difficulty with the disconnect of expanding to other 

groups in which vaccine may not have major impact, while the principal age group that will have 

the greatest impact is often left with deficiencies in implementation. He supported the focus of 

the potential recommendation on immunizing the younger age group, and wondered whether 

the work group had discussed any specific steps that might be taken to increase the impact in 

that age group. 

Dr. Markowitz replied that they would need to work on this in conjunction with the Immunization 

Services Division (ISD) of NCIRD. Everyone realizes that uptake needs to be increased in the 

target age group. 

Dr. Baker stressed the importance of focusing on the age group before sexual debut because, 

especially for the medically underinsured or uninsured, this is the age at which there is the 

greatest likelihood of capturing them while they are still socially engaged in school and other 

venues. There is a great deal of emphasis in many states on the medical home for 

underinsured and uninsured individuals. 

Dr. Rodewald (ISD / NCIRD / CDC) added that the National Vaccine Advisory Committee 

(NVAC) has had a major focus on improving vaccination of adolescents. For the three 

adolescent vaccines that are currently front and center in terms of the best programmatic way to 

improve coverage, a key issue is making the vaccine and financing available. This has been 

done quite well for the HPV vaccine. Also important is to measure coverage at the state level. 

For the first time ever, there has been coverage measurement at the state level for the 

population. They should now be able to see what the performance is and what needs to be 

improved. This is a much longer conversation, but there is a considerable amount of interest in 

making sure that this vaccine and the other adolescent vaccines help to establish a platform for 

vaccination. 

Dr. Baker inquired as to what the state level coverage is for the Vaccines for Children (VFC) 

program. 

Dr. Rodewald (ISD / NCIRD / CDC) replied that very quickly after ACIP passed the VFC 

resolution and the contract was in place, within less than two months all states were ordering 

HPV vaccine using the VFC program. This has been somewhat slow on the Section 317 side 

Dr. Sawyer said that he was always sobered by the difference in outcome in the intent-to-treat 

population compared to the per protocol population. He inquired as to what vaccine efficacy 

was used in the summary numbers provided for the models Dr. Chesson presented on, and / or 

how they responded in sensitivity analyses to lower efficacy more like what is observed in the 

intent-to-treat group. 

Dr. Chesson replied that the Merck model used the efficacies observed in the according to 

protocol population because the model can actually know who has been exposed and who has 

not, takes into account what happens after exposure, and assumes that there will be no 

protection against an HPV vaccine type for vaccination after exposure to that HPV type. The 

Kim & Goldie model used a range of efficacies from 75% to 100%. Those have not been 

updated yet, but they still capture the range of probable vaccine efficacies. The Chesson model 

used vaccine efficacies that were similar to Merck’s. 

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Dr. Sawyer inquired as to whether he was right that at least the Merck data reported during this 

session showed an intent-to-treat efficacy of about 50%. 

Dr. Chesson responded that this would be taken that into account because the models would 

apply no vaccine efficacy for those who were exposed to the HPV types already. In effect, the 

models should reflect that same finding. 

Regarding the cost per outcome gained for selected childhood vaccines and the use of two 

different units (e.g., QALY and LYS), Dr. Turner (ACHA) wondered what would happen to the 

figures for which LYS was used if they were converted to QALYs, in terms of whether they 

would be higher or lower and what the order of magnitude would be. 

Dr. Chesson responded that while it was difficult to determine for sure, most of the time when 

cost-effectiveness is expressed in terms of cost per QALY rather than cost per LYS, , the costeffectiveness ratio is lower. For example, when influenza vaccine is expressed in terms of cost 

per LYS, it can be much higher than it is in terms of cost per QALY because of the substantial 

reductions in non-fatal outcomes. It is difficult to speculate regarding the difference in cost per 

life year and cost per QALY for a given vaccine. The percentage of the benefits that pertain to 

mortality and the percentage that pertain to morbidity would have to be taken into account. The 

potential is there for it to be an order of magnitude difference for some vaccines, but not 

necessarily. 

Dr. Neuzil added that for PCV13 vaccine that is more expensive in an older age group, QALYs 

are in the $25,000 range or lower. 

Dr. Schaffner (NFID) very much favored the emphasis on pre-adolescent and adolescent 

immunization, but was still interested in adult women. In terms of behavioral characteristics, he 

wondered how much was really known about incident infection in women by socioeconomic 

status (SES) and perhaps race / ethnicity, and whether it is possible that there are subsets of 

the population defined in those ways who have higher risk of incident infections. 

Dr. Markowitz responded that there are national data from the National Health and Nutrition 

Examination Survey (NHANES) on prevalence of different HPV type infections by SES and 

race / ethnicity, but there are not any good incidence data in this age group. It is difficult to 

conduct these studies. Some of the best data there are have come from the placebo arm of the 

vaccine trial. The work group has been reluctant to assess / target specific risk groups, so she 

expressed interest in knowing whether ACIP would like for the work group to pursue this 

direction. 

Given that these vaccines never would have been developed if there was not a belief that they 

would prevent cervical cancer, Dr. Judson wondered whether there was a more direct way to 

answer this question merely by assessing rates of cervical cancer by race / ethnicity that can be 

assumed as proxies for SES. 

Dr. Markowitz replied that there are data on rates that cervical cancer, and part of that is due to 

differences in screening. The risk of infection is different from the risk of cervical cancer. These 

data can be provided to the full ACIP. However, the work group has not gone down the path of 

a risk-based recommendation. 

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As the Chair of the work group, Dr. Englund emphasized that the group had discussed multiple 

scenarios with multiple experts, particularly some of the adolescent experts on the committee, 

about the use of target- or risk-based use of this vaccine. The work group felt that it would be a 

major disservice to the use of this vaccine in the adolescent population if it became stigmatized 

to be used for certain risk-based socioeconomic persons when they are potentially more at risk 

because of the inequalities in health care delivery systems and screening. The majority of the 

work group members believe that a targeted strategy is not suitable. However, she agreed that 

if the full ACIP was interested in further consideration of this issue, the work group could further 

assess it. 

Dr. Baker noted that the ACIP had a history of observing how ineffective risk-based 

recommendations are, even if there is lack of stigma in risk-based recommendations. 

Dr. Salisbury (DOH UK) reported that at the time they were making decisions about the age 

groups to consider for inclusion in their program, cost effectiveness was a very important 

component of that consideration. According to the criteria they used, it was not going to be 

cost-effective to vaccinate beyond the age of 18. They have revisited this a number of times, 

and the situations remains the same. The point is that those considerations were being taken 

forward a couple of years ago. Since then, the girls within the catch-up program up to 18 years 

of age are now moving through into the over 18 cohort. That reduces any possible costeffectiveness of having a recommendation for those over 18 as each of those who is highly 

protected moves into that group. This is not a static consideration. They break down their 

coverage data by locality. When they assess the immunization coverage now observed in the 

12 year old girls, some of the highest reports (e.g., 98% third dose coverage) come from the 

most deprived and most multi-ethnic parts of the country. Dr. Salisbury believes that it is 

delivery of the program that is following forth rather than targeting, which creates new 

inequalities. 

Dr. Schuchat pointed out that an important difference between the UK program and the US is 

the role of schools as a site for vaccination. 

Dr. Rosenbaum said that rather than thinking about this incrementally in terms of risk groups 

and sub-risk groups, she was mindful of the cost issues and was also very focused on how the 

strength of messaging around the universality of this vaccine for women beginning early in their 

lives and proceeding up through life could serve as a boost to the earliest vaccinations. The 

benefits are profound in the earliest vaccinations, and as the consumer representative, she 

wished that her daughter had had the benefit of this vaccine at a time when she would have 

truly benefited. She expressed her hope that as they deliberated, they would give consideration 

to what position on specific cohorts would get them to the point where the American public could 

understand that this is something that really must happen for women generally. 

Dr. Neuzil responded that this spoke to the fact that there is a lot that is not understood about 

vaccine acceptance. This arises frequently with influenza vaccine when they try to understand 

why coverage rates have plateaued and they cannot get beyond certain levels She made a 

more general plea that this is an understudied area, and that it would help ACIP in many of their 

deliberations to better understand what does affect consumer opinion and uptake of vaccines. 

Representing college health which people believe to be a highly insured, affluent, and fairly welleducated population, Dr. Turner (ACHA) reported that as of last fall, only 39% of women they 

surveyed had even received one dose of HPV vaccine. They are pretty discouraged by this. 

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Some of their focus groups have suggested that cost is an issue, but beyond that he did not 

have any ideas about why there was not more success in getting these women vaccinated. 

Dr. Chilton said it sounded as though some of the discussion they had had in the last few 

minutes had laid the low immunization rate of teenagers at the feet of the teenagers themselves 

or their families. He expressed his hope that it was clear to most people that much of the lack of 

good immunization rates in this country as a whole, and not just regarding this vaccine, was 

really at the discretion of providers in that providers are not doing a very good job of getting 

vaccines into adolescents. Vaccines must be promoted not only to the public, but also to 

providers. 

Dr. Baker added that in certain, probably at risk, communities there was also a knowledge 

problem in terms of parents not reaching out to acquire the vaccines that their adolescents 

should receive. 

GARDASIL® Update: Efficacy Against 

Intra-Anal Infections and Disease 

Richard M. Haupt, MD, MPH 

Clinical Research 

Infectious Diseases & Vaccines 

Merck Research Laboratories 

Dr. Haupt reported on the end-of-study results for Protocol 20, which assessed GARDASIL® 

efficacy against intra-anal infections and disease. Given that HPV-related cancers affect a 

significant number of US men each year, Merck was pleasantly surprised by the results of this 

exploratory study against intra-anal endpoints. 

Estimates were calculated using 2007 data from the American Cancer Society (ACS) on the 

annual incidence (N=12,383) and mortality (N=2,595) from anal cancer, penile cancer, oral 

cavity cancer, oropharyngeal cancer, and laryngeal cancer [Based on American Cancer Society. 

Cancer Facts and Figures 2008]. The fraction of these cases attributable to HPV was then 

calculated using published estimates of HPV prevalence in the relevant cancers [1. Based on 

American Cancer Society. Cancer Facts and Figures 2008. 2. Daling JR et al. Cancer. 

2004;101:270–280. 3. Ryan DP et al. N Engl J Med. 2000;342:792–800. 4. Kreimer AR et al. 

Cancer Epidemiol Biomarkers Prev. 2005;14:467–475]. There are cancers caused by HPV in 

men as well. When added together, they are similar in terms of total incidence to cervical 

cancer in women. 

Up to 90% of anal cancers, the rate of which has been steadily increasing in men, are 

HPV-related. In the US, the annual incidence of anal cancer in males is approximately 2,020 

cases [American Cancer Society. Cancer Facts and Figures 2008]. Approximately 80% to 90% 

of these cases are HPV-related [International Agency for Research on Cancer. IARC 

Monographs on the Evaluation of Carcinogenic Risks to Humans. 2007;90]. In one study of 

patients in the United States, 88% of anal cancers were positive for HPV. HPV 16 was the most 

common HPV type detected among men and women, found in 73% of tumors. HPV 18 was the 

next most common type identified, found in 7% of tumors [Daling JR et al. Cancer. 

2004;101:270–280]. Evidence indicates that the incidence of anal cancer is increasing, 

particularly among men [Partridge JM et al. Lancet Infect Dis. 2006;6:21–31]. An analysis of 

data from the Surveillance, Epidemiology, and End Results (SEER) Program from 1973 to 2000 

found that anal cancer incidence was lower for males (1.06/100,000) than for females 

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(1.39/100,000) between 1973 and 1979, but it was similar for males (2.04/100,000) and females 

(2.06/100,000) between 1994 and 2000. Other estimates have suggested that the incidence of 

anal cancer in US men has increased almost 3-fold in 3 decades. However, the incidence of 

anal cancer in men who have sex with men, even before the HIV epidemic, was considerably 

higher (35/100,000). This is roughly equivalent to the incidence of cervical cancer in women in 

the US prior to routine cervical cancer screening. 

Protocol 20 was a randomized, double-blind, placebo-controlled, international, multi-center 

study. Subjects received 3 doses of GARDASIL® or placebo at 0, 2, and 6 months. Follow-up 

was designed to be 36 months for each subject. Enrolled subjects included heterosexual men 

(HM) ages 16 to 23 (N=3463) and men having sex with men (MSM) ages 16 to 26 (N=602). 

Subjects were seen every 6 months over the course of the 3-year follow-up period. Swabs were 

obtained for HPV DNA testing (e.g., penile, scrotal, and perineal / perianal swabs were obtained 

from all subjects, and intra-anal from MSM only); and anal Pap smears were done for cytology 

in MSM only. Any disease lesion that was determined by the investigators that could potentially 

be HPV-related was biopsied, so all of these endpoints are based on biopsies with adjudication 

by the Consensus Pathology Panel and HPV testing. All of the external genital endpoints come 

from both populations of heterosexual and MSM, while the intra-anal biopsies were done in 

MSM only. 

The primary objective of Protocol 20 was to demonstrate the safety and tolerability of 

GARDASIL® in young men. There were two efficacy objectives. The primary efficacy objective 

was to demonstrate reduction in primary-combined incidence of HPV 6/11/16/18-related 

external genital lesions (e.g., external genital warts, as well as penile, perineal / perianal 

intraepithial neoplasia) in heterosexual and MSM subjects. The second efficacy objective was 

efficacy against anal intraepithelial neoplasia (AIN) in MSM only. The secondary efficacy 

endpoints evaluated 6/11/16/18 persistent infection (6-month definition) and any-time HPV 

6/11/16/18 DNA detection. The immunogenicity endpoint evaluated vaccine-induced serum 

anti-HPV 6/11/16/18 responses. 

In terms of the baseline status of HPV types across the entire study set, by serology about 7.6% 

of the men were seropositive to one or more of the four vaccine types, 12.2% were HPV DNA 

positive, and 17.3% were positive by either PCR or serology, which means that approximately 

83% of the men studied were negative for all four types. As observed with the adult women, 

most men infected with a vaccine type were infected with only one type. Dr. Haupt also 

examined this data stratified by the two different sexual orientation groups. There was a lifetime 

sexual partner exclusion criteria for this study, so men had to have had 5 or fewer lifetime sex 

partners. That was true for the MSM subgroup as well. One of the reasons that the age range 

went to 26 in the MSM was because there were difficulties enrolling MSM with that few a 

number of lifetime sex partners. Despite that their baseline positivity by PCR and serology is 

substantially higher than the MSM, which reflects two things. First, there was additional swab 

with the intra-anal swab that was done in the MSM, so there was greater opportunity to capture 

HPV DNA. Second, even though these men may have reported fewer lifetime sex partners, 

there is no limit to how many lifetime sexual partners their partners had. Of the 602 MSM who 

were positive to one or more HPV 6/11/16/18, 22.8% were positive by serology, 30.5% by PCR, 

and 39.1% by PCR or serology. 

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In previous presentations which represented the first EGL analyses, there were case counts of 3 

(vaccine) and 31 (placebo) with an efficacy of about 90%. At the end-of-study there are still 3 

GARDASIL® cases and 32 cases in the placebo arm, for a highly statistically significant efficacy 

for external genital lesions. Most of these endpoints are external genital warts, with 3 

GARDASIL® cases and 28 placebo arm cases, for an efficacy of 89.3% (65, 98 CI). The 

additional case that occurred in this study against external genital lesions was a PIN 2/3 in the 

placebo arm that occurred in one of the MSM subjects. At the end-of-study there are now 4 

endpoints of PIN where there were 3 previously. 

Procedures were performed in addition to genital procedures for evaluation of anal endpoints in 

the MSM substudy. Rectal examinations were conducted at Day 1 and Months 7, 12, 18, 24, 

30, and 36. High resolution anoscopy was performed if an abnormality was noted in the rectal 

examination or a subject had an abnormal anal Pap test, and a mandatory high resolution 

anoscopy was done on all subjects at the close of the study. It was recommended by their Data 

Safety Monitoring Board (DSMB) to end the study early based on the early high efficacy and 

safety demonstrated. Thus, completion of the study was accelerated so that they could begin 

vaccinating placebo recipients and a high resolution anoscopy was done in all subjects at the 

close of the study. In order to be an endpoint, subjects had to have a consensus diagnosis 

made by the Pathology Panel of AIN1, AIN2, AIN3, anal cancer and detection of HPV 6/11/16 or 

18 DNA by Thinsection PCR in an adjacent section in the same tissue block. Pathology Panel 

consensus diagnosis of condyloma acuminatum in an intra-anal biopsy specimen are grouped 

under AIN1 (acuminate and non-acuminate), which was advised by Merck’s Scientific Advisory 

Committee. 

Dr. Haupt reminded everyone that in October 2009, he cautioned everyone that he may not be 

able to present anal disease endpoints. Given the number of case counts, he was concerned 

that they may not reach the number needed to show efficacy. In fact, there were 29 endpoints, 

which was quite remarkable for the MSM per protocol efficacy population. There were 5 

GARDASIL® HPV 6/11/16/18-related AIN endpoints and 24 placebo cases, with an observed 

efficacy of 77.5% (40, 93 CI). This study was powered for any grade AIN, but was not powered 

for AIN 2/3. Thus, they were very surprised to have 16 endpoints for AIN 2/3 (3 GARDASIL® 

and 13 placebo), reflecting 74.9% observed efficacy (9, 95 CI). Stratification of AIN 1 was very 

good in terms of identifying condyloma, with 100% observed efficacy due to intra-anal 

condyloma, which are typically HPV 6 /11. 

Two of Merck’s analyses support this efficacy against AIN 2/3. The high risk types associated 

with AIN 2/3 were assessed for the 3 GARDASIL® and 13 placebo subjects. For overall HPV 

16/18-related AIN 2/3, there was 1 GARDASIL® case and there were 8 placebo cases for 

86.6% efficacy (0.013, 100 CI). For HPV 16 there was 1 GARDASIL® case for 82.8% efficacy 

(-41, 100 CI), and for HPV 18 there were no GARDASIL® cases and there were 2 placebo 

cases for 100% efficacy (-501, 100 CI). By lesion type, for AIN 2 there were no GARDASIL® 

cases and 6 placebo cases for 100% efficacy (9, 100 CI). For AIN 3 there was 1 GARDASIL® 

case and 4 placebo cases for 73.0% efficacy (-173, 100 CI). There were no cases of anal 

cancer in either group. The one case of HPV 16-related was an AIN 3 that was a co-infected 

lesion with Type 39. The subject had persistent infection with Type 39 from Day 1 throughout 

the entire study period until this lesion was identified. This was the only time that Type 16 was 

actually found in that subject. The other compelling analysis for the potential of GARDASIL® for 

preventing intra-anal disease is the efficacy against persistent infection. There was very high 

efficacy for the vaccine types of 94.9% (80, 99 CI), with 2 cases in the GARDASIL® group and 

39 in the placebo group. 

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End-of-study safety data are consistent with previous data. No new vaccine-related severe 

adverse events (SAEs) were observed. There were 25 SAEs in 21 subjects, none of which 

were vaccine-related. The proportion of subjects reporting new medical conditions was 

comparable between the vaccine and placebo groups (28% versus 30% respectively). The 

most common conditions included upper respiratory infections and pharyngitis. The proportion 

of subjects reporting conditions potentially consistent with autoimmune phenomena was 

comparable between vaccine and placebo groups (0.7% versus 1.1% respectively). 

The conclusions are that GARDASIL® has high efficacy against 6/11/16/18-related intra-anal 

persistent infection, AIN, and AIN 2/3, as well as 16/18-related AIN 2/3. High efficacy against 

HPV vaccine type persistent infection and disease (including high-grade) is now demonstrated 

at another anogenital site (CIN, VIN, VaIN, AIN, genital warts). High efficacy is observed in both 

keratinized and mucosal epithelial surfaces in both women and men, which provides a strong 

picture of the overall benefit of GARDASIL® against vaccine type HPV-related infections and 

diseases. 

Quadrivalent HPV Vaccine For 

Males: Future Considerations 

Lauri Markowitz, MD 

NCHHSTP / CDC 

Dr. Markowitz reminded everyone that in October 2009, the FDA licensed the quadrivalent 

vaccine for males 9 through 26 years of age for prevention of HPV types 6/11-related genital 

warts [http://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm094042.htm]. 

During the October 2009 ACIP meeting, after considering various options, ACIP made a 

permissive recommendation for use in males. Data are now available on some additional 

endpoints in terms of efficacy for prevention of anal intraepithelial neoplasia in males. 

With regard to the projected timeline for review of the new data, submission of the AIN sBLA by 

Merck to FDA is expected in 2010, and the FDA review will take approximately 6 to 10 months. 

The data were presented during this session to update ACIP, but there is no projected timeline 

yet for when there would be a possible vote. 

In terms of the current status of the recommendations and availability of quadrivalent HPV 

vaccine for males, there is a permissive ACIP recommendation and HPV vaccine for males was 

also included in the VFC program. Merck has also included HPV vaccine for males in their 

Vaccine Patient Assistance Program, which provides vaccines free of charge to males 19 to 26 

years of age who are uninsured and meet the program criteria. The specific wording of the 

October 2009 ACIP recommendation and VFC resolution are as follows: 

ACIP Recommendation 

The 3-dose series of quadrivalent HPV vaccine may be given to males aged 9 through 26 years 

of age to reduce their likelihood of acquiring genital warts. Ideally, vaccine should be 

administered before potential exposure to HPV through sexual contact. 

Vaccines for Children (VFC)
 

Quadrivalent HPV vaccine for males approved to be included in VFC enabling VFC providers to 

provide VFC HPV vaccine to eligible males, age 9 through 18 years of age. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report February 24-25, 2010 

Further information may be found at the following urls: 

http://www.cdc.gov/vaccines/recs/provisional/default.htm#acip 

http://www.cdc.gov/vaccines/programs/vfc/downloads/resolutions/1009hpv-508.pdf 

When considering a recommendation for males during the October 2009 ACIP meeting, the 

work group and the full ACIP reviewed a variety of data including vaccine efficacy and 

immunogenicity available at that time, epidemiology and burden of disease, programmatic 

issues, and cost-effectiveness. The cost-effectiveness of HPV vaccine in males depends upon 

a variety of assumptions in models. The models show that male vaccination is most costeffective when coverage among females is low, when all potential health outcomes are 

included, and when vaccine efficacy is high in males. Results from one efficacy model (Kim & 

Goldie) were shown. In this model, vaccine efficacy was assumed to be 100% in females in the 

Kim & Goldie model and vaccine coverage was assumed to be 75% in males and females. In 

this model, efficacy for prevention of outcomes in males was 75%, which is similar to the results 

from the efficacy trial in males that were presented during this session. Of note, some costeffectiveness analyses to date, including the Kim & Goldie model, have included prevention of 

anal cancers as well as other HPV-associated cancers for which there are not yet data. While 

male vaccination did not appear cost effective in Kim & Goldie analysis, using coverage 

estimates that reflect current coverage in the US would result in more favorable costeffectiveness analyses for male vaccination. 

Because of the importance of coverage in these models of male vaccination, and also because 

questions had arisen during the course of this ACIP session, Dr. Markowitz presented some 

data on current coverage in adolescent girls in the US. These were data pertaining to vaccine 

initiation (e.g., 1 or more doses, not complete coverage) from the National Immunization Survey 

(NIS) in 2007 and 2008 showing coverage in 13 to 17 year old adolescent females. Coverage 

increased between these two years from 25% in 2007 to 37% in 2008. Coverage with 3 doses 

was lower at about 18%, although this is probably an underestimate because not everyone in 

this survey had an opportunity to complete their series. The following map reflects the 

considerable variation in vaccine initiation by state from 55% in some states in the Northeast to 

the lowest coverage of just 16% in some states in the South: 

Estimated 1+ Dose HPV Vaccination 

Coverage, Females 13-17 Years 

National Immunization Survey, 2008 

National Coverage = 37% 

Source: CDC. National, state, and local area vaccination coverage among 

adolescents aged 13-17 years---United States, 2008. 

40-49% 

30-39% 

20-29% 

50-59% 

10-19% 

D.C. 

NA 

In terms of the ACIP HPV Vaccine Work Group’s plans to address the new data for quadrivalent 

vaccine in males, vaccine trial data in males will be further reviewed. The cost-effectiveness 

analyses will be refined with the vaccine trial data endpoints and different coverage 

assumptions. The work group will also review the epidemiology and develop cost-effectiveness 

models for HPV vaccine in MSM, and will consider the feasibility of reaching MSM when they 

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would most benefit from vaccination. Further consideration and discussion of these issues will 

occur during the June 2010 and subsequent ACIP meetings. 

Discussion 

Dr. Keitel inquired as to whether subjects in the MSM group were screened for HIV infection 

before enrollment, and if so whether the investigators monitored incident HIV infections and 

whether there was any association between the acquisition of the two types of viruses. That is, 

was acquisition of HIV associated with more advanced lesions. 

Dr. Haupt responded that men had HIV assessment at enrollment, as well as yearly serology or 

more frequent serology depending upon potential risks. He clarified that the data shown were in 

the per protocol efficacy population, so any subject who became HIV positive at any point during 

the clinical trial would have been considered a protocol violator, so there are no HIV positive 

subjects included in those analyses. While there were HIV seroconversions, no association with 

the vaccination was observed. There are not enough cases to show anything significant or 

robust in an analysis of whether acquisition of HIV was associated with more advanced lesions. 

None of the subjects represented in his data shown during this session would have been HIV 

positive. 

Dr. Keitel indicated that she was having difficulty understanding the difference in all of the 

denominators in the different categories of lesions in the MSM group. 

Dr. Haupt replied that all of the denominators are based on type analysis, so the denominators 

change depending upon which type a subject had. A subject can be in a per protocol efficacy 

analysis for a specific type because he was naïve or negative to that type, so he could qualify 

for one per protocol analysis but they may not for another. Someone could have an AIN 1 or 

AIN 2, so the numbers in the rows do not always add up to the composite number because 

subjects could have more than one disease lesion. 

Dr. Temte inquired as to whether anything was known about the uptake in males in the October 

2009 ACIP vote. 

Dr. Markowitz responded that while there are no data at this time, there will be data about this 

because these questions were added to the NIS and other surveys. 

Dr. Haupt said that his understanding was that insurance coverage for boys was actually quite 

high. In addition to the VFC coverage, a majority of health plans appear to be covering the 

vaccine for boys in the indicated age group. 

Dr. Turner (ACHA) added that on the ACHA national survey, even before the ACIP 

recommendation last fall, 15% of males reported that they had received one or more doses of 

HPV vaccine. They will conduct the survey again in 2010 to determine whether that has 

increased. They were surprised because they made no specific effort to vaccinate males. 

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Discussion

Advisory Committee on Immunization Practices (ACIP) Summary Report February 24-25, 2010 

13-Valent Pneumococcal Conjugate Vaccine (PCV13) 

Introduction 

Dr. Kathy Neuzil 

ACIP Member 

Dr. Neuzil thanked the very hardworking members of the Pneumococcal Work Group. She also 

reminded everyone that they had engaged in significant discussion pertaining to PCV13 during 

the June and October 2010 ACIP meetings. Thus, they were very pleased to have the licensure 

and to be able to vote during this meeting. 

Proposed Recommendation and Immunization Schedules 

Pekka Nuorti, MD, DSc 

Respiratory Diseases Branch 

Centers for Disease Control and Prevention 

Dr. Nuorti reminded everyone that PCV13 (Prevnar 13®) contains the seven PCV7 serotypes 

(e.g., 4, 6B, 9V, 14, 18C, 19F, 23F) and the additional serotypes 1, 3, 5, 6A, 7F, 19A. Prevnar 

13® was licensed by the FDA in February 2010 and was approved for use in children 6 weeks 

through 5 years (71 months) of age for prevention of invasive pneumococcal disease (IPD) 

caused by the 13 serotypes, and prevention of otitis media caused by PCV7 serotypes. The 

latter is because there is no efficacy data for the other serotypes. 

The PCV13 information previously presented to the ACIP members in June 2009 included 

immunogenicity and safety (Wyeth); estimated vaccine-preventable IPD burden and options for 

catch-up immunization; and the economic and public health impact of a routine program and 

supplemental immunization (Wyeth). In October 2009, PCV13 information was presented on 

immunogenicity and safety with regard to transition and supplemental immunization (Wyeth); 

cost-effectiveness for routine and supplemental vaccination (CDC); and draft recommendations 

and immunization schedules. PCV13 is recommended for all children ages 2 through 59 

months of age; and children 60 through 71 months who have underlying medical conditions that 

increase their risk of pneumococcal disease or complications. 

The recommendation was divided into 5 distinct parts, and the votes were structured in the 

same manner, as follows: 

1. Routine recommendation 

•	 Infants and children who have not previously received PCV7 or PCV13 

2. Transition recommendation 

•	 Children incompletely vaccinated with PCV7 or PCV13 

3. Supplemental PCV13 dose recommendation (referred to previously as “catch-up” but 

changed by the work group to “supplemental” because these children have not actually 

missed doses) 

•	 Children completely vaccinated with PCV7 

4. High risk children >6 years of age (new since the October 2009 meeting) 

5. PPSV23 after PCV13 

• Children >2 years with underlying medical conditions 

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Regarding the routine recommendation, for children <59 months who have not previously 

received PCV7 or PCV13,,the proposed recommendation and immunization schedules for 

PCV13 vaccination are the same as currently recommended for PCV7 [1. MMWR 2008;57: 

343-4; 2. MMWR 2000;49 (RR-9)]. PCV13 replaces PCV7 for all doses. For routine infant 

immunization, PCV13 is recommended as a 4-dose series at 2, 4, 6, and 12 through 15 months. 

The following table (Table 2) reflects the recommended routine schedule for PCV13 for 

unvaccinated infants and children by age at the time of their first dose of vaccine. This table is 

identical to the PCV7 schedule: 

Considerations for the transition recommendation from PCV7 to PCV13 are that they have 

shared serotypes and similar vaccine formulations, and comparable safety profiles and immune 

responses [PCV13 – package insert, February 2010]. A schedule of 3 PCV7 doses followed by 

1 PCV13 dose vs. 4 PCV13 doses may result in lower IgG antibody levels for 6 additional 

serotypes; however, the functional OPA responses are comparable for these groups after the 4th 

dose2 [Paradiso P, Pfizer. ACIP October 2009]. The product insert for PCV13 states that the 

clinical relevance for this is unknown. Program implementation and logistic considerations 

include interchangeability of vaccine doses. Table 3 summarizes the recommendations for 

children who previously received doses of PCV7 or PCV13. The primary point is that children 

who have received one or more doses of PCV7 should complete their immunization series with 

PCV13: 

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Table 9a is intended to provide the detailed schedules for providers for the number of doses and 

dosing intervals by the age of the child at examination, and the vaccination history of either 

PCV7 or PCV13: 

The proposed recommendation for children >24 months who are incompletely vaccinated with 

PCV7 or PCV13 is that healthy children 24 through 59 months with any incomplete PCV 

schedule (PCV7 or PCV13) should received a single dose of PCV13. Children 24 through 71 

months with underlying medical conditions who have received an incomplete schedule of <3 

doses of PCV (PCV7 or PCV13), 2 doses of PCV13 are recommended. If 3 doses of PCV have 

been received (PCV7 or PCV13), a single dose of PCV13 is recommended. 

In terms of the supplemental recommendation for children who have been completely 

vaccinated, a supplemental PCV13 dose appears to be safe. The data suggest that the local 

and systemic adverse reactions after one supplemental dose are similar to those after a 4-dose 

PCV13 series. Based on the available data, the additional dose is no more reactogenic than a 

4-dose series. In addition, one dose of PCV13 elicits antibodies against 6 additional serotypes 

in children >12 months [1. PCV13 package insert, February 2010; 2. Paradiso, P Pfizer. ACIP 

June and October 2009]. Two independent cost-effectiveness analyses have been presented to 

the committee, the first of which was presented during the June 2009 ACIP meeting. In that 

analysis, the supplemental dose was found to be cost saving under the assumption that it would 

accelerate the indirect effects by 6 months or more. Even if the indirect effects in this Wyeth 

study were removed, the supplemental dose was still found to be cost-effective [Strutton D, 

Pfizer. ACIP June 2009]. The second cost-effectiveness study was conducted by CDC and was 

presented to the committee during the October 2009 ACIP meeting. Although the methods and 

some of the assumptions of that analysis were different from the Wyeth analysis, the 

conclusions were largely consistent. The CDC analysis found that the supplemental dose was 

not cost saving when indirect effects were not considered, but it was found to be reasonable 

with about $28,000 per discounted QALY saved in a cohort model that did not take into account 

the indirect effects. This analysis was conducted with a base case scenario with an 

approximate vaccine price of about $100 average between the public and private sectors 

[Messonnier M, CDC, ACIP October 2009]. In terms of the potentially preventable disease 

burden that was also discussed during the October 2009 ACIP meeting, it is true that the rates 

of invasive disease are quite low in that age group and they decrease rapidly; however, there is 

a substantial burden of pneumococcal pneumonia, otitis media, and antibiotic-resistant disease 

in that age group, particularly of serotype 19A. There have been multiple reports on multi-drug 

resistant 19A disease causing meningitis or severe invasive disease. The supplemental 

recommendation that the work group is proposing is not only based on the invasive disease 

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rates, but also other potentially preventable pneumococcal syndromes. It was felt that this 

approach would be programmatically feasible with a limited implementation time period of one 

year. This proposal does not include active recall of children. Instead, this vaccine should be 

given during the next routine medical visit. 

The proposed recommendation for the supplemental dose is that children 14 through 59 months 

of age who have been completely vaccinated with PCV7 who have received 4 doses of PCV7 or 

other age-appropriate, complete PCV7 schedules are recommended to receive a single 

supplemental dose of PCV13. For children who have underlying medical conditions, the 

supplemental dose is recommended through 71 months of age. This includes children who 

have previously received PPSV23. The reason for the somewhat awkward age of 14 months 

has to do with the minimum interval between doses, which is at least last 8 weeks after the last 

PCV7 dose, at the next medical visit. Age 14 months is the first opportunity to receive 

supplemental PCV13 according to the schedule. Tables 9a and 9b shown earlier reflect this 

information, and the footnotes for Table 9 are as follows: 

The need for a statement about children >6 years of age who have a high risk condition was 

also raised during the October 2009 ACIP meeting. While the work group discussed this at 

length between that meeting and this, Dr. Nuorti emphasized that PCV13 is not licensed for this 

indication, so this would be an off-label recommendation. PCV7 is licensed by the FDA up to 

age 9 years. The current ACIP recommendations for PCV7 are as follows [MMWR 2000;49 

(RR-9); ACIP, June 2008]: 

x	 

x	 

x	 

Administering PCV7 to older children [>5 years] with high risk conditions is not 

contraindicated. 

For HIV infected children aged 5-17 years on HAART who have not been 

previously immunized with PCV7, practitioners may consider administering 2 

doses of PCV7 followed by PPSV23. 

Current AAP / COID recommendation for PCV7 [AAP COID Red Book, 28th edition, 2009] are 

as follows: 

Administration of a single dose of PCV7 to children of any age who are at high 

risk of IPD, is not contraindicated 

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While studies of PCV13 among healthy children >6 years and children with HIV infection and 

SCD are currently underway to evaluate safety and the optimal number of doses, there are no 

data available at this point. The proposed wording for high risk children >6 years of age is as 

follows: 

•	 Vaccination with a single dose of PCV13 may be appropriate for children 6 

through 18 years of age who are at increased risk for IPD because of sickle cell 

disease, HIV-infection, or other immunocompromising condition, regardless of 

whether they have previously received PCV7 or PPSV23. 

•	 Routine use of PCV13 is not recommended for healthy children >5 years of age. 

Limited safety data are available for PPSV23 after PCV7. There are some immunogenicity data 

showing that this induces a nice booster response to those serotypes that are shared with the 

vaccine. No safety or immunogenicity data available for PPSV23 given after (or before) PCV13, 

and the clinical effectiveness of this sequence is unknown. CDC surveillance data suggest that 

the opportunity to provide additional serotype coverage with PPSV23 when PCV13 is 

implemented may become limited since the serotypes in PPSV23 that are not in PCV13 caused 

about 16% of the IPD cases in children 24 through 59 months with medical conditions over a 

three-year period [CDC, Active Bacterial Core surveillance 2006-2008, unpublished]. PCV13 

types cause about 45%. With that information , the proposed recommendation is that in 

addition to PCV13, children with underlying medical conditions should receive PPSV23 at age 

>2 years. The recommended doses of PCV13 should be completed before PPSV23 is given. 

However, children who have previously received PPSV23 should also receive the 

recommended PCV13 doses. Table 11 reflects the schedule for vaccination with PPSV23 after 

PCV13 for children >2 years of age with underlying medical conditions: 

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Table 1 defines the underlying medical conditions that are indications for pneumococcal 

vaccination among the children to whom the recommendation applies: 

Discussion 

Dr. Englund noted that for children with underlying conditions, Table 9a indicates that those who 

have had 4 doses of PCV7 should receive 1 supplemental dose, while the proposed 

recommendation stated that children 24 through 71 months with underlying medical conditions 

who received 3 doses of PCV (PCV7 or PCV13) should receive a single dose of PCV13. 

Dr. Nuorti responded that this was for children who were incompletely vaccinated with PCV7 

versus the supplemental dose, which is for children who have completed their vaccinations. 

Dr. Englund said she wanted this to be absolutely clear because she was sent there from her 

Transplant Unit to determine whether they could give the extra dose of PCV13. 

Dr. Nuorti responded that the recommendation for children 24 months and older who are 

incompletely vaccinated is similar to what has been previously recommended for PCV7. 

Dr. Chilton pointed out that this year, practitioners have had to deal with the discrepancy 

between 9 and 10 years of age for a second dose of influenza vaccine. He wondered whether it 

was really necessary to have a difference between 5 and 6 years of age for children with no 

underlying conditions versus those who do have underlying conditions. There did not seem to 

be a natural break point in either of those ages. 

Dr. Nuorti responded that this point was discussed by the work group. The reason the decision 

was made to break the recommendation down in this way was because that is how PCV7 is 

recommended. PCV7 is not recommended for healthy children 5 years and older. The work 

group felt that since the vaccine is approved through 5 years of age, it should at least be 

recommended for those children who are at increased risk. The other consideration was that it 

was the work group’s understanding that the manufacturers intends to apply for an expanded 

indication for the vaccine once all of the data are in such that the upper age limit would be 18 

years. At that point, it would be easier to extend the high risk recommendation up to age 18 

years. 

Dr. Baker wondered whether there were any data on the duration of protection (functional or 

immunoantibody) for high risk children who have been vaccinated appropriately with PCV7 and 

at 2 or more years have received PPSV23. 

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Dr. Nuorti responded that he was unaware of any data that have assessed this specific 

situation. Limited immunogenicity data are available for PCV7, and it is difficult to study now. 

Dr. Baker wondered whether such data would become available as they moved forward. 

Dr. Nuorti deferred to the manufacturer to discuss the types of studies they have planned. 

Dr. Whitney added that there are really no data pertaining to duration of protection with PCV7. 

There was a study regarding PCV9 in South Africa that examined direction of protection among 

healthy children and children with HIV. Those children received a 3-dose primary series without 

a booster. The healthy children had significant protection 4 years later, but the HIV children did 

not. Given that this was without a booster, it is difficult to compare to the US schedule. 

Dr. Paradiso added that when the South African children were given a dose of vaccine at 4 

years of age, the induced response was higher in the children who had received the 3 doses in 

infancy than those who had not. That was true for HIV positive children as well, although by the 

time the HIV positive children reach 5 years of age, they had similar antibodies to the 

unvaccinated children. 

In terms of the supplemental dose, Dr. Neuzil reported that the work group spent a significant 

amount of time discussing the issues and were quite persuaded by the cost data. The amount 

of $28,000 per QALY was congruous with some of the other outcomes gained for other selected 

childhood vaccines. The HPV models discussed earlier by Dr. Chesson, for example, all 

included indirect effects. For PCV13, the figure was $28,000 with no indirect effects included. 

These data were presented to the full ACIP in more detail in October 2009. The work group 

also felt that high risk children should receive that dose at an early age. It would be nice to say 

“high risk children >5” but because of the licensure language, between 5 and 6 years of age, the 

work group is stating that it is recommended. For over the age of 6, since it is not yet licensed, 

the group is suggesting that it “may be given.” The discrepancy in age does not really pertain to 

healthy versus high risk children. It is because of the age of licensure currently. 

Ms. Rosenbaum requested that someone explain to her the range of possible votes that could 

be cast. 

Dr. Nuorti responded that the work group prepared five separate votes, and that if the 

committee wanted to package some of those, it would be fine. 

Ms. Rosenbaum clarified that she did not mean the specific votes. She assumed that for any 

topics upon which ACIP voted, there would be possible votes that could be taken. For example: 

a recommendation without any limitation, a permissive recommendation, et cetera. She 

requested that someone walk her through the possible range of voting could be. 

Dr. Pickering replied that the possible range was that a recommendation would be made for 

general use for the population for that age group, as licensed by the FDA. 

Ms. Rosenbaum inquired as to whether ACIP always voted for routine use as opposed to 

permissive use, and requested further information between these two types of votes. 

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Dr. Pickering explained that votes vary based upon what work groups propose. Work groups 

make proposals about what they feel the recommendations should be. Sometimes there are 

options, in which case they will state the options in order of preference. There are cases in 

which there is permissive use, which means that the vaccine can be given to an individual who 

requests the vaccine or to a person for whom the physician feels the vaccine is needed after 

discussion with that person.. It is considered by some to be a weaker recommendation. 

Dr. Gellin indicated that they are in a transition period, which allows them to take a step back to 

think about where they have been and where they are going. He expressed gratitude to the 

FDA for giving them a just-in-time indication, which is for a 3 + 1 schedule. He also 

acknowledged that throughout the world, not everyone has a 3 + 1 schedule. In Europe, it is 

about split. It is complicated because of the schedule that has been licensed, but he wondered 

whether there had been any discussion regarding 2 + 1 versus 3 + 1 and what this country gets 

for what it buys, particularly in light of Dr. Frieden’s comments. 

Dr. Neuzil responded that the work group has discussed this, but not extensively. There is 

some difficulty within the committee when dealing with the US’s package insert and country 

experience of 3 + 1. It is not that the work group is not willing to consider other countries, but it 

difficult because they do not know what plans the manufacturer has for further studies of the 

schedule and perhaps requesting a license change. Moving forward, she thought that if there 

was interest, they could systematically review the schedules of other countries. However, the 

position in the past has been that they would be stepping fairly far from US licensure, which 

makes the work group members somewhat uncomfortable. 

Dr. Whitney responded that they reviewed this extensively for PCV7 as some of the data began 

to show that a 2 + 1 schedule had been used effectively in other situations. Until there is 

licensure in this country suggesting that this is okay for providers, the work group is hesitant to 

recommend a primary schedule that is off label. This is complicated and it was raised with the 

National Vaccine Advisory Committee (NVAC), where it also did not receive much traction. 

Dr. Baker added that providers have been accustomed to using this schedule for nearly a 

decade with PCV7. To re-educate them would be quite a major task. 

VOTE 1 

For Vote 1, ACIP members voted on the routine vaccination for infants 2 through 6 months of 

age and catch-up vaccination for unvaccinated children 7 months of age and older, the exact 

wording for which is as follows: 

Infants 2 through 6 months of age: 

•	 The primary infant series consists of 3 doses of PCV13. Infants receiving their first dose 

at age <6 months should receive 3 doses of PCV13 at intervals of approximately 8 

weeks (the minimum interval is 4 weeks). 

•	 Minimum age for administration of first dose is 6 weeks. 

•	 The fourth (booster) dose is recommended at age 12 through 15 months and should be 

given at least 8 weeks after the third dose (Table 8). 

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Unvaccinated children 7 months of age and older–catch-up: 

• Infants 7 through 11 months of age 

Three doses are recommended. The first 2 doses should be given with an interval of at 

least 4 weeks between doses. The third dose should be give at age 12 through 15 

months, at least 8 weeks after the second PCV13 dose. 

• Children 12 through 23 months of age 

Two doses are recommended, with an interval of at least 8 weeks between doses. 

• Children 24 months of age and older 

Unvaccinated healthy children 24 through 59 months of age should receive a single 

dose of PCV13. Unvaccinated children 24 through 71 months of age with underlying 

medical conditions (Table 2) should receive 2 doses of PCV13 with an interval of at least 

8 weeks between doses (Tables 8 and 9). 

Vote 1 Motion: Routine and Catch-Up Recommendations 

Dr. Sawyer made a motion to approve the routine and catch-up recommendations as stated. 

Ms. Ehresmann seconded the motion. The motion carried with 13 affirmative votes, 1 

abstention, and 0 negative votes. 

VOTE 2 

For Vote 2, ACIP members voted on the transition recommendation for children incompletely 

vaccinated with PCV7 or PCV13, the exact wording for which is as follows: 

Children <24 months incompletely vaccinated with PCV7 or PCV13 

•	 Infants and children <24 months of age who have received one or more doses of PCV7 

should complete the 4-dose immunization series with PCV13 (Tables 9 and 10). 

•	 For children 12 through 23 months of age who have received 3 doses of PCV7 before 

age 12 months, 1 dose of PCV13 is recommended given at least 8 weeks after the last 

dose of PCV7 (Tables 9 and 10). 

Children ൒24 months incompletely vaccinated with PCV7 or PCV13 

•	 A single dose of PCV13 is recommended for all healthy children 24 through 59 months 

of age with any incomplete PCV schedule (PCV7 or PCV13). 

•	 For children 24 through 71 months of age with underlying medical conditions who have 

received any incomplete schedule of <3 doses of PCV (PCV7 or PCV13), 2 doses of 

PCV13 are recommended (Table 9). 

•	 For children with underlying medical conditions who have received 3 doses of PCV 

(PCV7 or PCV13), a single dose of PCV13 is recommended through 71 months of age. 

•	 The minimum interval between doses is 8 weeks. 

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Discussion 

Dr. Nuorti noted that “4-dose” should be removed so that the first bullet would read: Infants and 

children <24 months of age who have received one or more doses of PCV7 should complete 

the immunization series with PCV13 (Tables 9 and 10). 

To better harmonize, Dr. Lett inquired as to whether it would be acceptable to state “children 

with underlying medical conditions through 9 years of age?” This is included in the original 

label. 

Dr. Nuorti responded that based on the work group discussions, there was hesitancy to 

recommend beyond the label. Vote 4 addresses the older high risk children, so that would be a 

separate permissive statement. 

Dr. Cieslak was not clear what the second bullet added to the first. 

Dr. Nuorti explained that it was to emphasize that children who had received the full infant 

series with PCV7 could receive a booster dose of PCV13. This could be removed because it is 

covered in the first bullet. 

For physicians who have a refrigerator full of PCV7 vaccine, Dr. Temte inquired as to whether 

there were plans to institute a buy-back or exchange program. 

Dr. Garrett (Pfizer) responded that Pfizer plans to take returns of Prevnar® and will amend the 

return policy to accept in-date Prevnar® as well as partial packages through the end of 2010. 

Dr. Judson inquired as to whether he was correct in understanding that there is no evidence 

showing that 3 + 1 is superior to 2 + 1. 

Dr. Whitney responded that for PCV7 there is a fair amount of data. There are some subtle 

differences with a couple of the serotypes in that there is not quite as good protection in 

between the primary series and the booster dose. Some breakthrough cases have been 

observed early on until herd immunity occurs, which seems to protect most children. While 

there are subtle differences, they are very similar in terms of the impact studies that have been 

conducted and the quality of those. 

Dr. Richardson (NACCHO) reported that Mexico uses a 2 + 1 schedule. They do not have 

serologic evidence thus far, but preliminary data show a significant decrease in mortality from 

pneumonias and bacterial meningitis as of 2007, which is when the vaccine was introduced. 

She will forward these data to Dr. Whitney. 

Vote 2 Motion: Transition Recommendation 

Dr. Sawyer made a motion to approve the transition recommendations as written, with the 

removal of “4-dose” and removal of the second bullet for Children <24 months incompletely 

vaccinated with PCV7 or PCV13. Dr. Keitel seconded the motion. The motion carried with 13 

affirmative votes, 1 abstention, and 0 negative votes. 

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VOTE 3 

For Vote 3, ACIP members voted on the supplemental PCV13 dose recommendation for 

children completely vaccinated with PCV7, the wording for which is as follows: 

Children >14 months of age who are completely vaccinated with PCV7 

•	 A single supplemental dose of PCV13 is recommended for all children 14 through 59 

months of age who have received 4 doses of PCV7 or other age-appropriate, complete 

PCV7 schedule (fully vaccinated with PCV7). 

•	 For children who have underlying medical conditions, a single supplemental PCV13 

dose is recommended through 71 months of age. This includes children who have 

previously received PPSV23. 

•	 PCV13 should be given at least 8 weeks after the last dose of PCV7 or PPSV23. This 

will constitute the final dose of PCV for these children (Tables 9 and 10). 

Discussion 

Dr. Meissner indicated that he and Dr. Neuzil had been discussing the issue of cost of the 

vaccine because this will be an additional dose to what is currently being done. He requested 

comments on this. 

Dr. Garrett (Pfizer) responded that the private market price would be $108 plus .75 cents for 

Federal Excise tax. The VFC contract is not yet completed, given that it is awaiting a vote. The 

expected price of the VFC price with the private price will bring the average weighted price just 

under the $100 that was used in all of the economic studies. 

Ms. Ehresmann pointed out that this is really a time-limited recommendation in that it is a catchup for children, so even if there is a cost factor it will not be on-going throughout the duration of 

using this product. 

Dr. Baker clarified that this would be true for healthy children, and that in the future they would 

likely be considering those with underlying risk factors in terms of age limits when more data 

become available. 

In view of recurring or intermittent shortages or lack of availability of vaccine, Dr. Keitel inquired 

as to whether it would be beneficial to include verbiage in the background materials indicating 

that there are data available that suggest that the 2 + 1 schedule can be implemented. 

Dr. Nuorti replied that there would later be an implementation presentation, and he requested 

that the manufacturer to comment on the current supply situation in terms of the availability of 

PCV13. 

Dr. Baker indicated that the scenario of children not being fully vaccinated exists in practice. 

Dr. Garrett (Pfizer) responded that currently there are 8.3 million doses of product already filled 

for the US market. They are in the process of final packaging now that the final labeling is 

approved. Pfizer expects to begin shipping these doses the week of March 15, 2010. That 

represents approximately 6 months of supply for the US market based on Prevnar® usage. 

There are over 20 million doses already filled for global demand, so Pfizer is ahead of supplies 

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normally anticipated for a launch supply-wise. They also anticipate exiting 2010 with a global 

inventory of filled product of over 6 months of inventory. 

To address Dr. Keitel’s question, Dr. Pickering reported that there is a very active group which 

considers vaccine supply and limitations, which meets by teleconference on a weekly basis and 

is composed of private professional and state organizations, many of which were represented in 

the room. When a vaccine is known to be in short supply the manufacturers inform this group, 

at which time plans are made in terms of dosing recommendations for the future depending 

upon the manufacturers’ provision of information about supply. Therefore, this includes a 

specific recommendation about supply in the statement may be somewhat limiting. 

Vote 3 Motion: Supplemental PCV13 

Recommendation for Completely Vaccinated Children 

Dr. Neuzil made a motion to approve the supplemental PCV13 recommendation for completely 

vaccinated children as stated. Dr. Chilton seconded the motion. The motion carried with 13 

affirmative votes, 1 abstention, and 0 negative votes. 

VOTE 4 

For Vote 4, ACIP members voted on the recommendation for children 6 through 18 years of age 

with SCD, HIV, or other immunocompromising condition, the exact wording for which is as 

follows: 

Children 6 through 18 years of age 

•	 A single dose of PCV13 may be administered for children 6 through 18 years of age 

who are at increased risk for invasive pneumococcal disease because of sickle cell 

disease, HIV-infection, or other immunocompromising condition, regardless of whether 

they have previously received PCV7 or PPSV23. 

Discussion 

Dr. Baker inquired as to whether this was a recommendation for permissive use. 

Dr. Nuorti responded that this is not an approved indication for the vaccine, so it would be for 

permissive use. 

Ms. Rosenbaum requested that someone explain to her the impact of a permissive use 

recommendation versus a recommendation on VFC coverage and the standard response by the 

insurance industry. 

Dr. Nuorti replied that this age group is listed under the eligible groups that are included in the 

proposed VFC recommendation that Dr. Santoli would be showing. In terms of the impact of a 

permissive recommendation versus a recommendation, in this case it is included in the VFC. 

Dr. Santoli added that the ACIP would have the opportunity to decide whether to include a 

permissive recommendation just like any other recommendation in the VFC resolution. This 

would be included in the VFC vote. 

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Dr. Netoskie (AHIP) indicated that generally speaking, routine vaccinations would be covered by 

practically all insurers. There is more variability with a permissive vaccine; however, something 

like this would most likely also be covered based on the discrete population for which the 

permissive vaccine is being indicated. 

Dr. Nuorti added that this is fairly small group of children. 

Dr. Neuzil commented that sometimes the work group, and certainly it is true in this case, is 

persuaded by whether there will be more information in the future to help answer questions. For 

example, ACIP recommends influenza vaccine for pregnant women even though it is not 

licensed because they do not believe that this indication is likely to change and there is a very 

strong rationale for that recommendation. In this case, the work group opted to select “may be 

administered” because this is done for PCV7 and they do believe that this group of high risk 

children needs the protection. There are on-going studies that will offer further information in 

the future with respect to what the exact recommendation and perhaps what the exact number 

of doses should be. 

Dr. Ceislak pointed out that the end of the recommendation states “regardless of whether they 

have previously received PCV7 or PPSV23.” A year from now there will be 5-year olds who 

have received a dose of PCV13, and he wondered whether a dose would be appropriate for 

them at 6 to 18 years of age. 

Dr. Nuorti responded that his interpretation was that if they have received a single dose prior to 

that, they would not receive another dose. 

Dr. Baker agreed that this was her interpretation as well. As Dr. Neuzil emphasized, they would 

receive additional information to inform future recommendations in high risk children. 

As a practicing pediatrician, Dr. Englund found the recommendation to be very helpful. The 

permissive recommendation is beneficial because there are children whose conditions change. 

She appreciated the inclusion of “other immunocompromising condition” because there are 

children who have conditions that were not in the text. However, she expressed concern about 

Table 2 which stated “underlying medical conditions that are indications for pneumococcal 

vaccination” because she wanted to insure that they were not limited to those underlying 

medical conditions (e.g., diseases associated with immunosuppressive chemotherapy because 

it could be steroids). She like the wording for Vote 4 and commended the work group for 

making it a broad condition, but wanted that philosophy continued in the text. 

Dr. Duchin (NACCHO) encouraged the committee to include language that would educate 

clinicians about the real intent to immunize children who have underlying risk conditions. “May 

be administered” might not convey the language discussed here about the importance of 

vaccinating that group. 

Dr. Baker responded that this could be dealt with at the professional society level. 

Regarding the wording of the draft statement presented to ACIP members, Dr. Sawyer pointed 

out that beginning on line 546 referring to the immunization of premature infants, the first 

statement is that “Premature infants should receive PCV13 at the recommended chronologic 

age” but then the next sentence is “For infants with prolonged nursery stays, vaccination should 

begin during discharge planning,” which would not necessarily be the chronologic age. The 

General Recommendations, as they currently stand, suggest that premature infants should be 

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immunized based on chronologic age. Thus, he wondered why the second sentence was 

included and whether someone could clarify this. 

Dr. Nuorti responded that this point has already been revised to be consistent with the General 

Recommendations and the sentence about discharge planning has been deleted. 

Dr. Pickering complimented the work group for getting this policy note to the members so that 

they could review it. He requested that any changes or suggestions regarding the wording 

should be submitted to the work group immediately for incorporation as appropriate so that they 

could submit it to the MMWR as soon as possible. 

Ms. Rosenbaum voted affirmatively, with significant reservations about the wording, given the 

potential spillover effects on financing. 

Vote 4 Motion: Children 6 through 18 Years of Age with 

SCD, HIV, or Other Immunocompromising Condition
 

Dr. Sawyer made a motion to approve the recommendation for children 6 through 18 years of 

age with SCD, HIV, or other immunocompromising condition as stated. Ms. Ehresmann 

seconded the motion. The motion carried with 13 affirmative votes, 1 abstention, and 0 

negative votes. 

VOTE 5 

For Vote 5, ACIP members voted on the recommendation for PPSV23 after PCV13 for children 

>2 years with underlying medical conditions, the exact wording for which is as follows: 

Use of PPSV23 among children 2 through 18 years of age at increased risk for IPD 

•	 In addition to receiving PCV13, children with underlying medical conditions (Table 2) 

should receive PPSV23 at age 2 years or as soon as possible after the diagnosis of 

chronic illness is made in children >2 years. 

•	 Doses of PCV13 should be completed before PPSV23 is given. 

•	 However, children who have previously received PPSV23 should also receive 

recommended PCV13 doses.
 

•	 Minimum interval: at least 8 weeks after the last dose of PCV13 (Table 11). 

Vote 5 Motion: PPSV23 after PCV13 for Children >2 

Years with Underlying Medical Conditions
 

Dr. Judson made a motion to approve the recommendation for PPSV23 after PCV13 for 

Children >2 years with underlying medical conditions as stated. Dr. Englund seconded the 

motion. The motion carried with 13 affirmative votes, 1 abstention, and 0 negative votes. 

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VFC Vote 

Dr. Jeanne M. Santoli 

Immunization Services Division 

National Center for Immunization and Respiratory Diseases 

Dr. Santoli indicated that the PCV component of the VFC Resolution was intended to mirror the 

vote just made by the ACIP. The pneumococcal resolution has two components: the conjugate 

component and the polysaccharide component. 

For the conjugate component, the current wording for eligible groups is: Includes all infants and 

children at least six weeks of age through 59 months old. The proposed wording extends that to 

include the following language: 

All infants and children at least six weeks through 59 months of age and children 60 

through 71 months with certain underlying medical conditions listed in the table below. 

Children 6 through 18 years of age who are at increased risk for invasive 

pneumococcoal disease because of sickle cell disease, HIV-infection, or other 

immunocompromising condition. 

The following will be labeled as Table 1 in the VFC Resolution: 

PCV component of the VFC Resolution will include the following Recommended Schedule and 

Dosage Intervals, which will be labeled as Table 2 in the VFC resolution and includes the 

supplemental doses for the age groups where that is appropriate: 

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Table 2

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The footnotes will be as follows for Table 2: 

The Recommended Schedule and Dosage Intervals will also include the following statement 

about the permissive use of the vaccine in children 6 through 18 years of age: 

A single dose of PCV13 may be administered for children 6 through 18 years of age who 

are at increased risk for invasive pneumococcal disease because of sickle cell disease, 

HIV-infection, or other immunocompromising condition, regardless of whether they have 

previously received PCV7 or PPSV23. 

For the recommended dosage, the VFC Resolution will refer to the product package inserts as 

is done on all VFC Resolutions. The following contraindications and precautions will be 

included: 

Vaccination with PCV13 is contraindicated among persons known to have severe 

allergic reactions (e.g., anaphylaxis) to any component of PCV13 or PCV7, or any 

diphtheria toxoid-containing vaccine. 

For the PPV23 component of the VFC Resolution, the current wording pertaining to eligible 

groups is: 

Children and adolescents aged 2-18 years who have functional or anatomical asplenia, 

immunocompromising illness or medications, chronic illness (as specified above), who 

are Alaska Native or American Indian, or who have received a bone marrow transplant. 

The proposed wording is: 

Children and adolescents 2 through 18 years with certain underlying medical conditions 

listed in Table 1 above or children 2 through 18 years who are Alaska Native or 

American Indian. 

For the Recommended Schedule and Dosage Intervals, the following table and footnote that 

follows it will be labeled as Table 3 in the VFC Resolution: 

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Note: Doses of PCV13 should be completed before PPSV23 is given. 

No more than two PPSV23 doses are recommended. 

For the recommended dosage, again there will be a referral to the product package inserts. 

Contraindications and precautions refers to the current statement, given that those are 

unchanged and can be found at the following site: 

http://www.cdc.gov/mmwr/preview/mmwrhtml/rr4909a1.htm 

Where published links can be used, they are. When recommendations are new and are 

appearing in writing for the first time, the wording and tables are included. When there are 

published documents, tables are changed to links so that a single source can be referred to. 

There is also a statement regarding coverage of PCV7 during the transition period, which reads 

as follows: 

Until the transition between seven valent pneumococcal conjugate vaccine (PCV7) and 

thirteen valent pneumococcal conjugate vaccine (PCV13) is complete and providers 

have sufficient supplies of thirteen valent pneumococcal conjugate vaccine in their 

offices to meet demand among VFC eligible children, the VFC program will continue to 

include seven valent pneumococcal conjugate vaccine and the schedule provided in 

VFC resolution 2/09-1 should be followed for administration of PCV7 during that time. 

In addition, a statement regarding updates based on published documents is included, which 

reads as follows: 

If an ACIP recommendation regarding pneumococcal vaccination is published within 12 

months following this resolution, the relevant language above (except in the eligible 

groups sections) will be replaced with the language in the recommendation and 

incorporated by reference to the publication URL. 

Discussion 

Dr. Keitel commented that Table 2 lists underlying medical conditions, but does not include 

Alaska Natives / Native Americans. While she understood that they could not list everything, 

she suggested including these groups on the table. 

Dr. Santoli responded that the ACIP specifically voted these groups of children in the PPV23 

component, which is why they were added to the eligible groups, which is why the wording 

states “those in the table or those who are Alaska Native / American Indian.” This differed from 

the recommendation, but was a conscious decision. They would not have been included in the 

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table of immunocompromising conditions necessarily, but this is the way that the ACIP can state 

that they want these specific children covered in the VFC program. 

Ms. Rosenbaum requested clarification regarding whether, if they say a vaccine “may be 

appropriate” versus “may be administered” or some other language, the vote they were about to 

make would make clear that in those situations where the vaccine is appropriate, VFC will fully 

cover the vaccine. When ACIP members express their views on VFC, she wondered whether 

the committee would explain the framework for the determination. That is, she assumed that 

what they would be signaling to the world was that ACIP considers the issue of appropriateness 

to be an issue of clinical judgment, and in those situation where clinical judgment needs to be 

exercised, they expect that the vaccine will be readily available. She emphasized that it is very 

important to say what they mean, even if it takes extra words or a note, because whatever they 

have to say within the VFC vote will have spillover effects into how insurers understand what 

ACIP is recommending. Based on the answer from the AHIP representative, if they elaborated 

on what they meant by saying that something was “clinically appropriate,” they would be 

sending a strong signal to private insurers by how recommendations are dealt with within the 

VFC. 

Dr. Santoli requested that Ms. Rosenbaum submit a specific suggestion. 

Dr. Chilton thought the recommendations seemed more complex than necessary, given that 

under the age of 5 years to 59 months all children receive PCV13. Between 5 and 6 years of 

age, all children in Dr. Nuorti’s Table 2 receive the vaccine, and between 6 and 18 years of age, 

all of the people in Table 2 minus those who are immunocompetent receive the vaccine. He 

wondered if there was a way to simplify the recommendation somewhat. 

Dr. Santoli inquired as to whether he was talking about the recommendations or the VFC 

resolution. 

Dr. Chilton responded that he meant both. 

Dr. Santoli replied that the tricky thing about the resolution was that in two days, this would be 

the first item published. Due to the components required by law, there must be significantly 

more information in a resolution than is really needed just to say that it is covered in the 

program. All of the changes and suggestions about simplifying really need to go into the 

recommendations. This was simply an opportunity to say “yes” for the VFC resolution, except 

sometimes there may be some additional groups who should be covered. This is not really a 

chance to make any changes to the recommendations sections because this is not the final 

reference document. 

Dr. Baker pointed out that they had already voted on the recommendations, which would remain 

as they stood following the vote. 

Dr. Schuchat indicated that the ability to simplify and enhance uptake was an implementation 

issue that CDC’s education and communication staff and their health professional partners 

could assist with. 

Dr. Sumaya thought this tied to the issue that Ms. Rosenbaum raised. While he understood that 

while they had language such as “may be appropriate” or a permissive recommendation, he 

thought it would behoove them as an advisory group to understand that first the provider may be 

making that judgment. In addition, someone has to pay for it. The VFC provides a structure for 

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that. He thought it would be beneficial to have further information how permissive ACIP 

language has impacted the private insurance world, such as: How are these recommendations 

utilized? Who is making the determinations? Are the communities ACIP is targeting being 

reached? 

John Redd (IHS) indicated that IHS supported the verbiage of the VFC resolution as stated. 

Given the complexity of the schedule, Dr. Whitley-Williams thought this supported the use of 

immunization registries. In addition, she pointed out that pediatric providers are caring for an 

aging group, particularly of HIV-infected patients and youth who are transitioning. While these 

recommendations address individual through 18 years of age, she thought consideration should 

be given to that population moving forward so that they could benefit from this as well. 

Motion: VFC Resolution 

Dr. Judson made a motion to approve the VFC Resolution as stated. Dr. Neuzil seconded the 

motion. The motion carried with 13 affirmative votes, 1 abstention, and 0 negative votes. 

Program Implementation: 

Transition from PCV7 to PCV13 

Dr. Santoli then reported upon an implementation plan that has been discussed in-house at 

CDC and with partner groups with regard to PCV13 replacing PCV7 in terms of challenges, 

plans for educational materials, and evaluation plans for the use of this vaccine. 

As commented upon by the manufacturer, PCV13 supply is currently sufficient to vaccinate 

children according to the routine schedule and to provide the supplemental dose as indicated. 

When PCV13 is available in the office, unvaccinated and incompletely vaccinated children 

should receive PCV13 not PCV7. That is the spirit of the recommendation and is being crafted 

for an MMWR that will be published sooner than the recommendation. CDC anticipates 

publishing this MMWR in mid-March. If only PCV7 is available in the office, also covered in the 

planned MMWR, unvaccinated and incompletely vaccinated children should receive PCV7 and 

should complete the series with PCV13 at subsequent visits. Children for whom the 

supplemental PCV13 dose is recommended should receive it at their next medical visit. Active 

recall is not recommended. 

With respect to some of the logistics of implementation at the practice level, CDC is currently 

preparing to add this vaccine to its vaccine contracts. Work has been done on the back end to 

try to facilitate this. Now that there is a vote, they will move forward. The guidance to providers 

is that they should contact state and local immunization programs to determine when PCV13 

available to order. It is anticipated that state programs will be able to begin ordering at the end 

of March. However, programs have different timeframes by which they make vaccines available 

to their providers because of changes that they need to make. Thus, the direction is that 

providers should reach out to their state programs. During the transition period, providers are 

encouraged to maintain their unused doses of PCV7. In terms of returning unused PCV7, for 

private supplies, Pfizer is offering a credit for returns of unused PCV7 vaccine. For public 

supplies, providers should work with their state VFC program. 

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Discussion

Advisory Committee on Immunization Practices (ACIP) Summary Report February 24-25, 2010 

There are some challenges in making this transition. As often occurs, private supplies of 

PCV13 will be available before public supplies. However, CDC has done as much work in 

advance as possible so that the contract does not delay the process of making this vaccine 

available in the VFC program. The challenge of administering a supplemental dose of PCV13 is 

somewhat minimized by having that vaccine recommended at the next rather than during an 

additional medical visit. 

In terms of communication and educational materials, the provisional recommendations will be 

posted online ahead of the official recommendation and will be available at the following site: 

http://www.cdc.gov/vaccines/recs/provisional/default.htm 

The MMWR, with an anticipated March 12, 2010 publication date, will highlight the information 

discussed during the presentations. A Provider Q & A and Parent Q & A are under 

development. The plan is to post the Provider Q & A in early March, with the Parent Q & A to 

follow. 

With respect to future evaluation plans, there are two short-term evaluations planned in addition 

to including this vaccine and its coverage in the National Immunization Survey (NIS). The first is 

a registry sentinel site for which an immunization information sentinel site analysis will take 

place 6 months after the transition to assess uptake by provider type, VFC status of the child, 

and other factors. In addition, a provider survey is being planned that will use sentinel networks 

of physicians (e.g., pediatricians and family practitioners), which will assess knowledge, 

attitudes, practices, and barriers related to the transition from PCV7 to PCV13. 

At the conclusion of this session, Dr. Pickering noted that Dr. Stanley Plotkin had not been able 

to attend the last few ACIP meetings. While his presence was truly missed, Dr. Pickering 

indicated that luckily Dr. Plotkin was present during this meeting and that they looked forward to 

his insight. 

Hepatitis Vaccines 

Update on Hepatitis Vaccines Work Group 

Mark Sawyer, MD 

Chairman, ACIP Hepatitis Vaccines Work Group 

Dr. Sawyer reported that the Hepatitis Vaccine Work Group had been meeting to deliberate the 

term of reference to review data from recent hepatitis B outbreaks among diabetics in 

institutional care to determine whether vaccination is appropriate. Topics reviewed and 

discussed by the work group regarding this matter included modes of hepatitis B virus 

transmission during diabetes care; outbreaks and the morbidity of acute hepatitis B among 

persons with diabetes; long-term care and infection control; current prevention 

recommendations; the epidemiology of diabetes and blood glucose monitoring practices; 

hepatitis B vaccine immunogenicity relative to age, diabetes status, obesity, and specific 

vaccine type / dose; hepatitis B vaccine coverage estimates among persons with diabetes; 

diabetes and liver disease; and seroprevalence of hepatitis B virus infection among persons 

with diabetes versus persons without diabetes. 

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The Hepatitis Work Group is currently considering three major options to bring forward to the full 

ACIP. The work group’s timeline has been delayed slightly, but the intent is to deliver additional 

presentations during the June 2010 ACIP meeting, as well as a proposal for consideration. A 

vote is anticipated in October 2010. The three major options are as follows: 

A: Prevent hepatitis B virus infection among persons with diabetes using three approaches 

Æ

Æ

Æ

Improve infection control practices, uptake of prevention recommendations 

(HICPAC, ADA, etc) 

Improve devices used to manage diabetes (FDA, manufacturers) 

Recommend hepatitis B vaccine at diagnosis of diabetes 

B: Obtain additional data needed to establish incident risk of hepatitis B virus infection among 

persons with diabetes 

C: Expand hepatitis B vaccine recommendation to the entire US adult population 

Tentative future Hepatitis Work Group topics before bringing the recommendation to the full 

ACIP include estimates of risk for hepatitis B infection among persons with diabetes; vaccination 

schedules and dosages; pre / post-vaccination serological testing; “catch-up;” cost-effectiveness 

analysis; and implementation. 

Diabetes and Liver Disease: 

Implications for Hepatitis B Vaccination 

John W. Ward, MD
 

Division of Viral Hepatitis (DVH) 

National Center for HIV / AIDS, Viral Hepatitis,
 

STD and TB Prevention (NCHHSTP)
 

Centers for Disease Control and Prevention 

Dr. Ward discussed trends in diabetes; the adult hepatitis B immunization schedule; acute 

hepatitis B outbreaks among persons with diabetes; and offered an overview of diabetes and 

liver disease with respect to acute liver failure and chronic liver disease in terms of non-alcoholic 

fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and cirrhosis and 

hepatocellular carcinoma (HCC). 

The number of persons living with person in the US has increased over the last several 

decades, particularly over the last 10 to 15 years. The most recent estimate is that 17.7 million 

persons are living with diagnosed diabetes in the US. That represents about 7.8% of the US 

population [CDC’s Division of Diabetes Translation. National Diabetes Surveillance System 

available at http://www.cdc.gov/diabetes/statistics from NHIS].. The average age at diagnosis is 

approximately 50 years, with a large increase in prevalence between the 20 to 39 year old age 

group (2.6%) and the 40 to 59 year old age group (10.8%), with the prevalence approaching 1 in 

4 for persons 60 years of age and older (23.1%) [Cowie et al., Diabetes Care 2009;32:287-94. 

CDC available at http://www.cdc.gov/diabetes/statistics/prev/national/tprevage.htm]. 

Monitoring blood glucose is a recommended intervention for self-management of diabetes. This 

is a 2010 Healthy People objective that is monitored through the Behavioral Risk Factor 

Surveillance System (BRFSS). The question included on the BRFSS is: About how often do 

you check your blood for glucose or sugar? The responses to this question indicate that the 

majority of people with diabetes do self-monitor their blood glucose at least one time per day: 

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 % (95% CI)
 

 

 

 

Advisory Committee on Immunization Practices (ACIP) Summary Report February 24-25, 2010 

Rates of monitoring blood glucose >1 time/day by type of medication 

Medication 

None 

 All persons with diabetes 64 (62-66) 

Insulin and oral medication 84 (80-88)

Insulin only 91 (88-93)
 

Oral medication only 63 (59-66)
 

35 (31-39)

The prevalence of self-monitoring is highest for those who are receiving medication, oral or 

insulin. Blood glucose monitoring also has implications for risks of blood-borne transmission in 

settings where good infection control is not practiced by the individual or by the person who may 

be monitoring glucose for that individual in a setting such as a residential care facility [Adults 

18+ yrs. Behavioral Risk Factor Surveillance System MMWR 2007;56:1133-1137]. 

The relationship between hepatitis causing morbidity among persons with diabetes has also 

been examined. According to a dataset from the National Hospital Discharge Dataset (1987­

1991), though quite old and in need of updating, the ratio of the rates for discharge diagnoses in 

persons without diabetes for hepatitis and cirrhosis was more common than for those without 

diabetes [Everhart JE. Digestive Diseases and Diabetes (Table 21.3, Figure 21.2) 

Diabetes in America 2nd edition 1995]. 

The current US adult immunization schedule, published in January 2010, is as follows: 

Recommended Adult Immunization 

Schedule - United States, 2010 

The yellow bars in the adult schedule indicate vaccine recommendations for particular and 

specific patient categories. Hepatitis A and B vaccine are recommended for persons with 

chronic liver disease, which is how this is stated in the 2006 ACIP statement, which was the first 

time for the hepatitis B recommendations to include a recommendation for vaccination of 

persons with chronic liver disease. Persons with diabetes are on this schedule and are 

recommended for the receipt of other vaccines; however, the recommendation does not 

currently include a recommendation for hepatitis A and B vaccine. The rationale for placing 

chronic liver disease on the immunization schedule for hepatitis A and B vaccine was that 

hepatitis A superimposed on chronic hepatitis C (HCV) infection and other chronic liver disease 

increases the risk of acute liver failure and death; acute hepatitis B (HBV) infection morbidity 

can be more severe among persons with chronic HCV than without chronic HCV; and chronic 

infection with both HCV and HBV increases incidence of cirrhosis and liver cancer [Datta D, et 

al. Antiviral Ther. 2000. Keeffe EB. Am J Med. 2005, Bell B. Acta Gastroenterol Belgica 2000, 

Reiss G,Aliment Pharmacol Ther. 2004. Sagnelli E. Hepatology. 2002, Benvegnu L, Cancer. 

1994]. 

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With that as a backdrop, the work group felt that it was important, as they consider the rationale 

for hepatitis B vaccine for persons with diabetes to assess acute hepatitis B virus infection, 

acute liver disease among persons with diabetes, and the risk for chronic liver disease among 

persons with diabetes. The following graphic depicts the timeline of outbreaks of hepatitis B 

virus infection associated with blood glucose monitoring that have been reported to CDC: 

Since 2007, about 9 (39%) of the 23 outbreaks that have been identified are recent outbreaks in 

nursing homes and 21 were in some type of elder care facility. On-going investigations are 

being conducted for the most recent outbreaks, shown by the red stars in the graphic. 

When the 21 outbreaks in persons with diabetes in long term care facilities are examined more 

closely, 136 / 151 (90%) of the cases reported in these settings were among persons with 

diabetes who were having their blood glucose monitored, and 15 / 151 (10%) cases among 

roommates, family members, and staff suggests secondary transmission of infection in longterm care facilities. The median age was 76.5 years (range 42–92) for the outbreaks that 

included that information (age information was available for 14 of 21 outbreaks) [CDC. In terms 

of the clinical picture of the cases among the 151 persons with acute hepatitis B (positive for 

anti-HBc and anti-HBc IgM), 56 (37%) had symptoms, 21 (38%) were hospitalized, and 10 

(18%) died from acute hepatitis B (median age 88 years; range 64 to 92) [CDC. Unpublished 

Data 2009]. 

For 13 of the outbreaks, a serologic survey was done to identify all cases of acute hepatitis B 

among residents with and without diabetes (n=1278) [CDC. Unpublished Data 2010]. The 

following table reflects the comparison of the serologic results for persons with diabetes versus 

persons with no diabetes: 

Hepatitis B No Diabetes (n=940) Diabetes 

(n=338) 

Acute Infection 01.0% (9/940) 30.5% (103/338) 

Chronic

 Infection** 

0.4% (3/818) 6.3% (19/300) 

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This shows that the prevalence of both acute and chronic disease was higher for persons with 

diabetes in these settings where outbreaks were identified and investigated. The 6.3% 

prevalence of chronic infection suggests a persistence of hepatitis B infection after a 

transmission that is higher than what is typically observed among adults. It has been reported 

in the literature that persons with diabetes have an increased likelihood of persistent or chronic 

hepatitis B infection after transmission The risk for developing chronic hepatitis B in young, 

healthy adults is < 5% -10%; in persons with diabetes is ~ 45%; in older adults (mean age 74 

yrs) is ~ 59%, and in those undergoing hemodialysis is 40% - 45%. [Shepard CW, Epidemiol 

Rev 2006; Hyams Clin Infect Dis 1995, Polish LB. N Engl J Med 1992, Kondo K . Hepatology 

1993]. This study is referenced in the current ACIP statement. 

Some investigators have also examined the risk of acute liver failure among persons with 

diabetes. In a study based on the National VA Medical Record System, patients ages 20+ 

years with a discharge diagnosis diabetes between 1985 to 1990 were followed up through 

2000. Medical records were reviewed for this group to identify ICD-9 codes indicative of acute 

liver failure and diabetes. A control group was identified and comparisons were made regarding 

the rate of acute liver failure and its causes. Patients were excluded who had previous liver 

disease (e.g., HCV, HBV, ETOH, cirrhosis, et cetera). Patients eligible for observation included 

173,643 with diabetes (1,494,995 person-years) and 650,620 without diabetes (6,556,350 

person-years) [El-Serag HB, Gastroenterology 2002]. 

In terms of the cumulative risk of acute liver failure by diabetes status in the US from 1985 to 

2000, was 0.30% for persons with diabetes (versus the comparison group (no diabetes; 0.19% 

showing that persons with diabetes were increased risk of acute liver failure and that that risk 

increased over the observation period [El-Serag HB, Gastroenterology 2002]. In the Cox 

proportional hazard model (adjusted for demographic, military service, HCV, HBV, other liver 

disease), diabetes was retained as a risk for acute liver failure, with the strongest risk for acute 

liver failure being some evidence of underlying liver disease: Diabetes HRR 1.4 (1.3-1.6), Older 

Age (per decade) HRR 1.9 (1.4-2.5), and Chronic Liver Disease HRR 14.3 (12.5-16.3). The 

causes were uncertain, although the investigators mentioned that they looked for evidence of 

hepatitis B as a cause of acute liver failure, but that investigation was not quantified. They went 

on to speculate that hepatotoxic drugs could have been the culprit because of increased 

exposure or increased susceptibility [El-Serag HB, Gastroenterology 2002]. 

It is important to note that diabetes can be a consequence of chronic liver disease as well as a 

cause of chronic liver disease. Regarding diabetes as a consequence of liver disease, cirrhosis 

is associated with dysregulation of glycemic control. With on-going fibrosis leading to cirrhosis, 

glycemic control becomes compromised, and insulin resistance increases, leading to chronic 

diabetes. At least one report suggests that this occurs in 1 in 5 persons. 

Hepatitis C infection also increases the risk for diabetes because of direct biologic activity, host 

response, or the increasing fibrosis phenomenon [Tolman, Diabetes Care 2007, Mehta SH. 

Ann Intern Med 2000, White J. Hepatology 2008]. Studies have found that persons with 

hepatitis C have a 1.7 to 3.8 fold greater risk of diabetes than those without. This must be taken 

into account when reviewing these studies and trying to determine whether diabetes itself is a 

risk for progression to chronic liver disease and cancer. The investigations of diabetes and 

chronic liver disease have found that the association is linked most closely with non-alcoholic 

fatty liver disease (NAFLD). NAFLD in and of itself is a metabolic disorder with a basis in insulin 

resistance similar to Type 2 diabetes, leading to an imbalance in lipid metabolism and fatty acid 

accumulation in the liver. Risks include obesity (central), diabetes, and hypertriglyceridemia. 

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NAFLD is estimated to affect 40% to 69% of persons with diabetes. At a minimum, about 1 in 

10 persons with diabetes in that group will have non-alcoholic steatohepatitis (NASH), and 

about 10% to 20% may progress to cirrhosis over a 10-year period [Moscatiello, Nut Metab and 

Cardio Disease 2007; Tolman, Diabetes Care 2007; Lazo, Sem Liver Dis 2008]. NAFLD 

represents a broad spectrum of fatty liver disorders, ranging from very mild-hepatitis steatosis to 

the severe outcome of NASH (e.g., inflammation, cell death, fibrosis; cirrhosis; hepatocellular 

carcinoma) [Moscatiello, Nut Metab and Cardio Disease 2007; Tolman, Diabetes Care 2007]. 

Dr. Ward presented a few representative studies pertaining to the question of diabetes 

associated with liver disease, and highlighted those that also included assessment of viral 

hepatitis B and C. A study of Taiwanese Patients with chronic hepatitis B of 500 adults aged 42 

± 15 years with chronic hepatitis B who were attending a liver clinic followed these subjects for 

an average of 5.8 years. The study excluded those with a history of alcoholism, IDU, MSM, 

HIV, et cetera. Of the 500 patients, 71 developed cirrhosis during the study timeframe. Among 

the 71 cases of cirrhosis, 15 (21%) had diabetes mellitus. That group was then compared to 

102 controls without cirrhosis who were age and sex-matched. Factors were examined to 

determine what increased the risk of developing cirrhosis. One of the risks was diabetes. Thus, 

in the group of persons with chronic hepatitis B, diabetes was an independent and additional 

risk for cirrhosis [Huo T-L. J Clin Gastroenterol 2000]. 

Returning to the national VA medical record study for risk of chronic liver disease and 

hepatocellular carcinoma (1985 to 2000), the risk of chronic liver disease for persons with 

diabetes was about twice that for persons without diabetes (18.3 versus 9.6/10,000 patient 

years), and there was about a 2.75 increase risk for development of liver cancer versus those 

persons without diabetes. This study also found that over the period of observation this risk 

increased, demonstrating that it was not just the capture of a person with diabetes about to be 

diagnosed with cirrhosis, but rather that it was persons with pre-existing diabetes for whom the 

increased presence of diabetes led to increased risk for progressive liver disease [El-Serag HB 

Gastroenterology 2004]. 

An interesting population-based, case-control study of Medicare linked databases examined 

diabetes and risk for hepatocellular carcinoma (HCC) in the US for the years 1994 through 

1999. The study identified 2061 cases with HCC ages > 65+ years and developed a control 

group of 6183 without HCC. The study looked for potential risk factors (e.g., hepatitis B, 

hepatitis C, HIV, alcoholic liver disease, and hemochromatosis) and placed those into a model 

to identify their relative risk . In this study, alcoholic liver disease was by far the risk factor that 

was most strongly associated with development of HCC: OR 69.6 (44.9-107.9) followed by 

HCV: OR 24.4 (17.5-34.1), HBV: OR 23.9 (13.7-42.0), Hemochromatosis: OR 8.9 ( 5.2-15.1), 

and diabetes: OR 2.9 ( 2.5-3.3) [Davila JA. Gut 2005]. 

In 2009, a study was published that examined diabetes and the risk for HCC in Taiwan, which 

was based on data from 1997 to 2004. This was a community-based cohort among 5929 

persons drawn from community recognized to have a high incidence of HCC. Of these, 4115 

were seronegative for HBV and HCV; 696 were hepatitis B surface antigen positive (HBsAg +); 

982 were anti-hepatitis C positive (HCV+); 134 were co-infected with hepatitis B and C; and 546 

had diabetes at baseline. The cohort data were matched with the national cancer registry to 

assure more complete ascertainment of liver cancer, and found 111 diagnoses of hepatocellular 

carcinoma. The multivariate Cox hazards model (95% CI) adjusted for demographic factors, 

health behaviors, BMI, hepatitis status, and diabetes status found that co-infection before the 

study with hepatitis B and C conferred the greatest risk: HR 25.9 (11.8-57.0; P < 0.01) followed 

by anti-HCV+ before study: HR18.8 (10.3-34.2; P < 0.01); HBsAg+ (chronic hepatitis B virus 

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infection) before study: HR12.6 (6.4-25.0; P < 0.01); age > 65 years: HR 3.8 ( 2.6- 5.6; P < 

0.01); male gender: HR 3.3 ( 2.0- 5.0; P < 0.01); diabetes before study: HR 2.7 ( 1.7- 4.3; P < 

0.01); and BMI > 30: HR 1.7 (1.0- 2.8; P <0.05). In this area with a high prevalence of HBV 

and HCV, diabetes remained an independent risk factor for liver cancer [Wang C-H. Cancer 

Epidemiol Biomarker Prev 2009]. 

In summary, it appears that persons with diabetes have multiple possible insults to the liver that 

they have either already experienced or have the potential to experience (e.g., hepatitis C, 

hepatitis B, hepatitis A, medication, NASH, and others) that can confer liver disease. This body 

of work reveals that an estimated 17.7 million persons are diagnosed with diabetes in the US 

who tend to be older and who are either monitoring blood glucose on their own or have 

someone monitoring it for them. Outbreaks of hepatitis B virus infection and related morbidity 

and mortality continue to occur among persons with diabetes. Diabetes can increase the risk 

for chronic hepatitis B after acute HBV infection, posing on-going health risks for the individual 

with diabetes and posing a risk for on-going transmission. Diabetes is an independent risk 

factor for chronic liver disease and hepatocellular carcinoma. 

Discussion 

Dr. Plotkin expressed his hope that the work group would assess immunization in this group 

with respect to two factors. The first is the relationship of age to response. There are data 

showing poorer response with age to hepatitis B. If a vaccine recommendations is going to be 

made in this group, it will probably have to be similar to the way in which a dialysis patient would 

be vaccinated with higher doses or with some of the new adjuvanted vaccines that are now in 

development. The second point regards juvenile diabetics who may have been immunized 

when they were children. The current doctrine is that people who are vaccinated when young 

do not need boosters. However, this population should be examined more closely. By 

examining B-cell memory a determination can be made regarding whether these individuals will 

need booster immunizations. 

Dr. Ward responded that questions pertaining to immunogenicity have been a major focus of the 

work group’s discussions, and they hope to further discuss this issue in more detail when they 

have more time during the June 2010 meeting. Most of the focus has been on the older 

diabetic, which is where over 99% of Type 2 diabetes is found. Consideration will have to be 

given to what can be brought to bear in terms of the immune response for Type 1 diabetes. 

Dr. Baker emphasized that the explosion / epidemic of juvenile onset Type 2 diabetes is a logrhythmic. Pediatric studies should examine both Type 1 and the increasing number of Type 2 

diabetic children. 

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Discussion

Advisory Committee on Immunization Practices (ACIP) Summary Report February 24-25, 2010 

Influenza Vaccines 

Introduction 

Anthony Fiore, MD, MPH 

Medical Officer, Influenza Division 

National Center for Immunization and Respiratory Diseases 

Centers for Disease Control and Prevention 

Dr. Fiore indicated that this session would consist of presentations regarding the following 

topics: 

 U.S. epidemiology update (Dr. Lyn Finelli, CDC) 

 Virology and immunology (Dr. Nancy Cox, CDC) 

 Influenza vaccine coverage update (Mr. James Singleton, CDC) 

 2009 H1N1 vaccine program implementation (Dr. Pascale Wortley, CDC) 

 Higher dose inactivated vaccine for persons 65 years (Dr. David Greenberg, SanofiPasteur Vaccines) 

 ACIP influenza workgroup discussions (Dr. Anthony Fiore, CDC) 

Æ 2010 influenza vaccine recommendations 

Lyn Finelli, DrPH 

Epidemiologist / Team Lead, Influenza Division 

National Center for Immunization and Respiratory Diseases 

Centers for Disease Control and Prevention 

Dr. Finelli reported on data from the US Outpatient Influenza-Like Illness Surveillance Network 

(ILINet), of about 3000 to 4000 sentinel providers in the US, covering about half of the 

geographic area of the US. Data from June 27th, the peak of the Spring / Summer pH1N1 wave 

that occurred during the June ACIP meeting, disease was very focal and only a few areas were 

two or three standards of deviation above their non-influenza season baseline. In September 

12th, the beginning of the Fall pH1N1 wave, disease was largely concentrated in the Southeast 

where the outbreak began in the Fall and in the West. October 24th, during the last ACIP 

meeting, the peak of the Fall pH1N1 wave occurred. By February 13th, there was a low level of 

ILI, with focal outbreaks in a variety of areas scattered across the US. 

Based on the traditional ILINet trends time series pertaining to the percentage of visits for 

influenza-like illness (ILI) from October 1, 2006 through February 13, 2010, in February 2009 

there was a peak of influenza that declined. That was followed by a peak in May 2009 that 

declined again under baseline in June and July 2009. There was a major peak in October 2009 

of about 7.8% ILI of all people presenting to the sentinel provider offices. This is the largest 

peak ever observed in ILI since surveillance began. At the time of this ACIP meeting, ILI was at 

about 2.1%, which is slightly below the 2.4% baseline. Assessing this regionally, regions 1, 2, 

and 3 were below their baseline at this time; Region 4, which includes Georgia, was slightly 

above its baseline though not too critical; Region 7 was slightly above its baseline with nothing 

dramatic; and Region 9 was somewhat more above its baseline than any other region, and was 

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being monitored closely because it was somewhat unstable. About half of individual providers 

were over their baseline in October 2009, while by February 2010 only about 30 to 40 providers 

were over their baseline rather than half of all providers reporting. 

CDC has been following ACHA surveillance of the college population very closely, given that the 

college age population is one of the primary risk groups. Based on data provided by Jim Turner 

of ACHA, their peak occurred at about the same time as the ILINet peak. They have had over 

91,000 cases reported to their surveillance system, with 169 hospitalizations and 4 deaths in 

this age group (primarily 18 to 24 year olds). At the time of this ACIP meeting, there was a low 

level of ILI in the college / university population [Courtesy of Jim Turner and Randol Doyle 

ACHA. American College Health Association Influenza Like Illnesses (ILI) Surveillance in 

Colleges and Universities 2009-2010: Weekly College ILI cases reported. Linthicum, MD: 

American College Health Association; 2010]. 

Based on data from the BRFSS, overall reports of ILI among adults in households for the first 

part of February 2010 was 7.6%. This is a fairly dramatic decline from the 10% to 11% 

observed in October 2009, and it is slightly elevated from about 4% observed at baseline. 

During the October 2009 ACIP meeting, 49 of 50 states were experiencing widespread ILI; 

whereas, by the time of the February 2010 ACIP meeting, 3 states had regional ILI activity, 8 

states had local activity, most of the remaining states had sporadic activity, and 2 states had no 

activity. It is very unusual to see the map look like this in mid-February. 

CDC has aggregate reporting from 35 health departments for influenza positive, laboratory 

confirmed hospitalizations and deaths. As of February 13, 2010 there were very low rates of 

hospitalizations for all age groups over the preceding several weeks. In terms of the overall 

cases reported, 39% were in the 0 to 18 age group, 52% in the 19 to 64 age group, and only 9% 

of those found to be hospitalized in this surveillance system were over 65 years of age. The 

rates of hospitalization were highest in 0 to 4 year olds, but then decline and nearly flatline for all 

of the other age groups. There was a slight increase in 5 to 24 year olds, a decline until 49 

years old, a slight increase between 49 and 64, and then a decrease over 65 years of age. 

From the Emerging Infections Program (EIP) data, which were vital to CDC during the outbreak, 

Dr. Finelli described data from 4 influenza seasons. 2007-2008 was an influenza A (H3N2)­

predominant season, as was 2003-2004 (data only on children). For 5 to 17 year olds, 18 to 49 

year olds, and 50 to 60 year olds, H1N1 represents the most severe season that has occurred 

during surveillance. For those over 65 years old, the H3N2 season in 2007-2008 was far more 

severe than the 2009 H1N1 pandemic. However, for younger children ages 0 to 4, the 2003­

2004 season was much worse than the H1N1 pandemic. In terms of hospitalization rates by 

age group, for children 0 to 4 years of age, the 2003-2004 influenza season represented much 

higher hospitalization rates that the current season. However, this season these rates were 

much higher than most influenza seasons. In the 5 to 17 year old age group, there was a high 

magnitude of hospitalizations, with worse rates than any other influenza season under 

surveillance. However, the rates in this age group remained lower than those in the 0 to 4 year 

old age group. There were also higher hospitalization rates in the 18 to 49 year old and 60 to 

64 year old age groups than in any other season under surveillance in this system. For the over 

65 year old age group, there were lower rates than the 2005-2006 and 2007-2008 H3N2 

seasons, which were much worse for this age group. 

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Based on the 122 Cities Mortality Reporting System, this influenza exceeded the epidemic 

threshold in the Fall, and currently was fluctuating at the epidemic threshold. Most of the deaths 

reported through this system have been in people over 65 years of age, and additional 

investigation has shown that most reported in recent weeks have been in people with various 

types of pneumonia that is not influenza-related. From the pediatric mortality data, the take 

away message is that there have thankfully been many fewer deaths in children less than 18 

since January 1, 2010. From the aggregate reporting system from 35 states, the peak number 

of deaths reported was in the Fall around October 31st. By the time of the February 2010 ACIP 

meeting, influenza deaths due to laboratory-confirmed influenza were low for all age groups. 

Rates among 50 to 64 year olds have remained elevated above all others. By age groups, as of 

February 13th, about 12% of deaths were in the 0 to 18 year old age group, 74% in the 19 to 64 

age group, and in the 65+ age group 14%. Note that the proportion of the US population that is 

over 65 years of age is about 13%. The lowest death rates have been in young children 0 to 4 

years of age and 5 to 24 year olds, rates increase with age until 50 to 64 years old, and then 

decrease again in those 65+ years of age. 

The risk groups have not changed since the Spring wave, with children and adolescents 

remaining at the highest risk for acquisition. Hospitalizations are highest in young children and 

decline with age, and deaths increase with age up to 50 to 64 year olds, but then decline again 

in the 65+ age group. The majority of those who die and who are hospitalized with influenza 

remain those with underlying conditions, including pregnancy. Based on EIP data, about 30% 

of people admitted with influenza have asthma, 23% have diabetes, 20% have cardiovascular 

disease (CVD), and 14% have chronic pulmonary lung disease (COPD). Neurodevelopmental 

conditions and neuromuscular disorders are much less prominent than they are in children, and 

about 9% overall of these cases were pregnant. Note that pregnant women comprise only 

about 1% of the US population at any time. 

Based on the pediatric data, among children who are hospitalized with laboratory-confirmed 

influenza, the frequency of asthma is very similar in children compared to adults at 33%, 11% 

have neurodevelopment disorders, 8% have moderate to severe development delay, 6% have 

seizures, 3% have CP, 5% have chronic lung disease excluding asthma (mostly BPD), 5% have 

hemoglobinopathy (majority sickle cell), 1% have diabetes, and 1% are pregnant. From the 

Influenza Associated Pediatric Mortality Surveillance System, among pediatric H1N1 deaths, 

65% of children had an underlying condition. Neurological and developmental disorders are 

extremely common among children who died from 2009 pandemic influenza (42%), with 

moderate to severe developmental delay being most common at 31%, other neurologic 

disorders (including CP) 31%, seizure disorders 22%, and other neurologic disorders 2%. 

Chronic pulmonary disease (excluding asthma) has a frequency of 20% among children who 

have died from influenza, and cardiac disease has a frequency of 13%. Different from the 

cardiac disease in adults, this cardiac disease is almost all congenital. These diseases and 

disorders are not mutually exclusive. Many children have several conditions simultaneously 

such as CP, seizures, and developmental delay. 

With respect to race / ethnicity, data were presented in October 2009. However, during the 

February 2010 meeting, Dr. Finelli was able to present more robust numbers. The following 

table reflects the findings from the self-reported ILI during the month preceding interview by 

adults and ILI related health care-seeking behavior by race and ethnicity from the September 

through December 2009 BRFSS data: 

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Race/Ethnicity Influenza Season 

2009 2009-10 

White, non-Hispanic 3.0 16.3 

Black, non-Hispanic 10.9 29.7 

Hispanic 8.2 30.7 

Asian/Pacific Islander 8.1 12.5 

American Indian/Alaska Native 4.1 32.7 

 

Advisory Committee on Immunization Practices (ACIP) Summary Report February 24-25, 2010 

Race and Ethnicity % Reporting ILI 

(weighted) 

(95% CI) 

% Reporting 

Seeking Health 

Care for ILI 

(weighted) 

(95% CI) 

White, non-Hispanic 8 (7.6, 8.4) 41 (38.6, 

43.4) 

Black, non-Hispanic 8 (6.7, 9.6) 48 (38.0, 

57.5) 

Hispanic 7 (6.0,8.2) 36 (29.1, 

43.5) 

American 

Indian/Alaska Native 

16 (11.6, 22.3) 37 (22.6, 

54.3) 

Total 8 (7.8, 8.5) 41 (38.3, 

42.9) 

As shown in the above table, ILI reporting is about equal for White, non-Hispanic and Black nonHispanic groups, but appears to be about double for American Indian / Alaska Natives. All 

races / ethnicities reported about an equal rate of health care seeking behavior. 

However, there is a disparity between race / ethnicity in terms of hospitalization as reflected in 

the age-adjusted and season-specific pH1N1 influenza-related hospitalization rates (per 

100,000) by race /ethnicity from EIP (2009-2010) shown as follows: 

In conclusion, H1N1 was widespread over most of the US but incidence has declined in recent 

weeks. ILINet rates were higher in October 2009 than they have been in any influenza season 

since surveillance began. According to BRFSS data, 10% of adults and >20% children reported 

ILI in October 2009. Hospitalizations are highest in the youngest children and decline with age, 

while excess hospitalizations are highest in the 5-17 year old age group. Deaths are lowest in 

the youngest children and increase with age, but only up to 50-64 year old age group. Deaths 

decline in the 65+ age group. The majority of those hospitalized during the 2009 H1N1 

pandemic have underlying medical conditions. Asthma is common among those hospitalized. 

Neurologic disorders are common among children dying from influenza. Pregnant women are 

at higher risk for severe outcome. Racial ethnic disparities in severe outcomes persist and are 

under investigation. 

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Nancy J. Cox, Ph.D. 

Director, Influenza Division 

National Center for Immunization and Respiratory Diseases 

Centers for Disease Control and Prevention 

Dr. Cox reported on the updated global influenza virology and recommendations for the vaccine 

composition for next season, including a summary of both the WHO’s vaccine recommendations 

and those of FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC), 

which met on February 22, 2010. 

Percentage of influenza viruses reported to the Global Influenza Surveillance Network (GISN) 

by Types / Subtypes (From 1st September 2009 to 30th January 2010) are reflected in the 

following pie chart: 

Clearly, pandemic H1N1 viruses predominated globally. Seasonal H1N1 viruses circulated in 

very low numbers globally. H3N2 viruses circulated in greater numbers than seasonal H1N1 

and actually caused some significant disease in some locations. There was a group of viruses 

that were not sub-typed, but were reported to this network as influenza A. Some of those were 

not able to be sub-typed using PCR and others were simply run through a rapid influenza 

diagnostic test. Influenza B viruses also circulated globally, though at a rather low level, but 

there was an interesting resurgence of influenza B in China during the last month or so. CDC 

was inundated by samples beginning in May 2009. The majority of those samples were the 

pandemic H1N1 virus. Thus, there were numerous samples and very rich data to examine. 

A major accomplishment of the Global Influenza Surveillance Network is that CDC has been 

able to fill in many of the gaps in surveillance, particularly in Central America, some countries in 

South America, and most countries in Africa, which have been able to detect and report to WHO 

pandemic A(H1N1) occurrence. 

In terms of a global summary, pandemic A(H1N1) 2009 viruses pose a public health risk in the 

coming 2010-2011 Northern Hemisphere influenza season. Currently circulating pandemic 

A(H1N1) 2009 viruses remain similar to the WHO-recommended vaccine virus. The 

recommendation was that A/California/7/2009-like virus remains suitable for use in influenza 

virus vaccines for the Northern Hemisphere for the 2010-2011 influenza season. 

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Almost all 2009 H1N1 viruses characterized globally were antigenically and genetically similar to 

the A/California/07/2009 vaccine virus. Only a few viruses (7 analyzed by CDC’s WHO 

Collaborating Center) have > 8-fold reduced titers to the A/California/07/2009 vaccine virus. 

Since September 1, 2009 WHO Collaborating Centers have characterized > 8,000 virus isolates 

and clinical specimens. Very little genetic variation has been detected, complete genomes have 

been sequenced for over a hundred viruses, and there is no evidence of reassortment. Almost 

all 2009 H1N1 viruses are resistant to M2 blockers. All 2009 H1N1 viruses are sensitive to 

zanamivir and most are sensitive to oseltamivir. A total of approximately 100 oseltamivirresistant viruses have been reported to WHO. Most patients with resistant viruses have taken 

oseltamivir in the recent past or are taking it at the time the oseltamivir-resistant virus is isolated. 

Antigenic cartography, done using data from the hemagglutination inhibition (HI) assay, shows 

little change in antigenicity as reflected in the following graphic: 

The vast majority of H1N1 viruses were antigenically homologous to the A/California/07/2009 

vaccine virus. A minority of viruses (<1%) had reduced titers against serum to A/CA/7/09 

vaccine virus. Examination of clinical samples from the “low reactor group” indicated that 

isolation substrate (eggs and cell line) affected the antigenicity of the virus isolates, and the 

mutations that confer low reactivity are not present in the original clinical sample. No molecular 

markers for increased virulence were detected. 

The following is an amino acid tree, which reflects only those changes that confer amino acid 

changes in the hemagglutin gene. There are just a few amino acid changes and much more 

homogeneity then would normally be observed for seasonal influenza viruses. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report February 24-25, 2010 

Limited sequence diversity 

Oseltamivir resistance 

falling throughout the tree 

H1N1 pandemic viruses- Sequence analysis of HA gene 

While there have been some amino acid changes among some viruses compared to the 

vaccine virus, this particular amino acid change does not confer any change in antigenicity. 

There was also a lot of discussion in the media and among scientists about changes at an 

amino acid designated 222, which is near the receptor binding pocket of the hemagglutin. The 

question regarded whether this change really conferred a difference in virulence. The particular 

change that was being discussed is neither necessary nor sufficient for severe disease. 

With regard to seasonal A(H1N1) viruses globally, seasonal A(H1N1) viruses show little 

evidence of circulation, and are most likely pose a low risk for the Northern Hemisphere 2010­

2011 influenza season in the view of WHO and FDA experts. Therefore, WHO and FDA did not 

recommend a seasonal A(H1N1) virus as a component for vaccines for the Northern 

Hemisphere 2010-2011. 

Influenza A(H3N2) have continued to circulate globally, but at remarkably reduced levels 

compared with previous years. H3N2 viruses likely pose a risk in the coming 2010-2011 

Northern Hemisphere influenza season due to evolution of a new variant. Antigenic, genetic, 

and drug resistance assays were carried out, and the majority of viruses tested were resistant to 

M2 blockers and all were sensitive to neuraminidase inhibitor drus. The H3N2 viruses analyzed 

are antigenically closely related to the vaccine virus recommended by WHO in September 2009 

for the Southern Hemisphere 2010 season: A/Perth/16/2009. This emerged after the vaccine 

recommendations were made in February 2010. In a few countries in Africa, H3N2 viruses 

were isolated and were causing significant outbreaks. In the early part of the influenza season, 

H3N2 viruses predominated in China. Thus, it is believed that these viruses will not disappear. 

Based on the antigenic cartography of A(H3N2), they are clustering around the A/Perth/16/09 

virus, which is the recommended strain for the Southern Hemisphere, and have swarmed 

Southeast away from the A/Brisbane/10/07 vaccine virus that was previously recommended. 

This is reflected in the following graphic: 

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Advisory Committee on Immunization Practices (ACIP) Summary Report February 24-25, 2010 

Influenza B viruses of both the B/Victoria and B/Yamagata lineages continued to circulate at low 

levels globally. As noted, there was a resurgence of influenza B activity reported by China with 

B/Victoria lineage viruses predominating in January and February 2010. Influenza B viruses 

likely pose a continuing risk in the coming 2010-2011 Northern Hemisphere influenza season. 

Antigenic, genetic, and drug resistance assays have been carried out, and there appears to be 

no resistance to NIs. The WHO and FDA recommendation is for the B/Victoria lineage only and 

to retain B/Brisbane/60/2008. 

B Victoria antigenic cartography is illustrated as follows: 

In summary, the WHO recommendations for the 2010-11 Northern Hemisphere influenza 

season are as follows: 

It is recommended that vaccines for use in the 2010-10 influenza 

season contain the following: 

– 

– 

– 

an A/California/7/2009 (H1N1)-like virus 

an A/Perth/16/2009 (H3N2)-like virus 

a B/Brisbane/60/2008-like virus 

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Advisory Committee on Immunization Practices (ACIP) Summary Report February 24-25, 2010 

Discussion 

Dr. Schaffner (NFID) inquired as to whether Dr. Cox could speculate about why in January and 

February there had not been more conventional seasonal Influenza A or B viral activities in the 

US, particularly since pandemic H1N1 seemed to have “given up the field.” 

Dr. Cox replied that everyone is somewhat puzzled by this, particularly since a resurgence of 

influenza B has been observed in China during the same period. At this point, there is no 

explanation. It is a matter of watching and waiting to see what will happen since influenza is 

difficult to predict. 

Dr. Temte inquired as to whether there was an estimate of the existing immunity for H1N1 either 

by infection or vaccine, especially considering the age group of the spreaders. 

Dr. Cox responded that while there are on-going seroprevalence studies in the US, there are no 

data ready to report. The UK has reported seroprevalence data, which indicate that about 30% 

of the population has been infected. As more data are accumulated, CDC will publish it as soon 

as possible. Seroprevalence data should be coming out from some European countries and 

China as well. 

Dr. Keitel requested a follow-up from Dr. Finelli on obesity as a risk factor. 

Dr. Finelli replied that there has been some follow-up and inclusion of more cases in the study 

that Morgan et al conducted in the Fall on adults. The analysis could not be done on children. 

Using H1N1 cases who were both hospitalized and died, and comparing people who were 

hospitalized and died of H1N1 without underlying conditions to those in NHANES without 

underlying conditions, there is about a 4-fold increase in hospitalization and death in people who 

are morbidity obese (BMI 40). It is hoped that these data will be finalized and published soon. 

Dr. Meissner noted that while current influenza surveillance data shows that activity had 

decreased, mortality due to pneumonia and influenza were still high between the seasonal and 

epidemic thresholds, which seemed contradictory. He thought influenza was the major cause of 

death. 

Dr. Finelli responded that the deaths in the 122 cities were the proportion of deaths attributed to 

pneumonia or influenza among of all deaths. CDC also receives data on whether deaths are 

attributed to pneumonia only or influenza only. At this time of year, normally there is some 

proportion of influenza deaths and pneumonia deaths. Typically, about half are due to 

influenza, or there is slightly more pneumonia, especially in the elderly and influenza. Those 

deaths were all pneumonia in almost all people over 65 years of age. Even though these are 

7.7% of pneumonia / influenza deaths over all, very few influenza deaths were reported. That is 

typical of every season. In influenza seasons that are H3N2 or B predominant, a large 

proportion of the deaths are from influenza. In seasons that are seasonal H1N1 predominant, 

the proportion of deaths from influenza are reduced among the elderly, and the total number of 

deaths is less. 

Dr. Schuchat clarified that Dr. Finelli was reporting on the excess deaths, and that the vast 

majority of the excess were considered to be pneumonia deaths, not necessarily influenza 

related. The vast majority of influenza and pneumonia deaths do not receive a specific etiologic 

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Advisory Committee on Immunization Practices (ACIP) Summary Report February 24-25, 2010 

diagnosis. There was much more laboratory testing being done during the past year than 

several years ago, but a lot of these are clinical definitions. 

Dr. Cieslak noted that based on the numbers circulating, seasonally influenza kills 

approximately 36,000 people. This season there was a pandemic, and for the most part 

vaccine was not available before the peak of the pandemic, making the US essentially an 

unvaccinated population. The number published recently is that 11,000 people died of influenza 

during this pandemic. While he was aware of where these numbers come from and the different 

methodologies that generated them, he requested Dr. Finelli’s reaction to those numbers. 

Dr. Finelli replied that in a season from which those numbers are modeled, there are 8,000 to 

9,000 influenza-specific attributable deaths and the remainder of the 36,000 is from underlying 

all-cause mortality such as CVD, pulmonary disease, et cetera. During this influenza season, 

there have been more than 11,000 influenza-specific deaths, which exceeds the influenzaspecific deaths in a typical season. If CVD and pulmonary disease were added, there would 

likely be more than 36,000. However, those data are not yet available to analyze. 

Dr. Neuzil said she was intrigued by the impact of H3N2 in 2003 for 0 to 4 year olds compared 

to this season. If memory of deaths from 2003 was correct, there were 153 total while during 

this season there were 71 just in 0 to 4 year olds. She wondered whether Dr. Finelli thought 

that was a function of 2003 being the first year that the deaths were reportable and now a better 

job was being done, or whether there was some discrepancy between the deaths and 

hospitalization rates in the two years. She emphasized that this was a record number of 

pediatric deaths, which should be noted. 

Dr. Finelli responded that she thought they had more deaths during the current season, with a 

higher proportion of deaths in school age children over 5 years of age than in 2003. That may 

add to the excess deaths, although she did not know the exact number in each of the age 

groups. She also thought a better job was being done of testing and reporting during this 

season, so there may be some deaths that are just a function of that. There is no question that 

older children had the highest attack rates and were at the highest risk for acquisition, so there 

are more deaths in that age group. 

Dr. Turner (ACHA) reported that ACHA released data that morning that shows that for the first 

time in 10 weeks, their flat curve and increased. The rate has been running about 2.7 since 

early December, but was up to 4.2 per 10,000. Interestingly, the cases are highest in the 

Southeast and somewhat in the Midwest as well. 

Dr. Finelli indicated that she would review these data, particularly in the state-specific data. 

Regional spread has been observed more in the Southeastern states, especially in Alabama, 

Georgia, and Tennessee. 

Regarding the comparative death issue from seasonal influenza to the pandemic numbers, Dr. 

Schuchat pointed out that there are numerous ways to measure these. The key issue is age. 

With seasonal influenza, regardless of whether primary to influenza or secondary to respiratory 

or circulatory collapse, 90% of the deaths are occurring in people 65 and older. Therefore, of 

the 36,000 number being reported, 32,000 are in those over 65 years of age. Based on 

modeling that has been done, CDC is estimating that the deaths in children are probably 5-fold 

higher at least compared to what would be observed with seasonal influenza. Deaths in people 

65 years of age and older are about one-fifth of what is usually observed. There is complexity in 

a summary number, even when apples are compared to apples, because this was a very bad 

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year for people under 65 and a wonderfully good year (relatively) for people 65 and over. 

However, the strains are still circulating and vaccination remains a good idea for seniors and 

others. 

Dr. Kimberlin (AAP) requested that someone comment on Peramivir’s susceptibility to pandemic 

H1N1, seasonal H3N2, and seasonal B viruses. 

Dr. Cox replied that the overwhelming number of viruses are sensitive to Peramivir. 

Dr. Sumaya inquired as to whether the data on racial / ethnic stratification of hospitalizations 

and deaths were in adults only or included children. Deaths were disproportionately higher in 

various racial / ethnic minorities. He wondered what the denominator was: Were these 

percentages of the group that was hospitalized and died, or population-specific numbers of the 

racial ethnic groups. 

Dr. Finelli responded that the data she showed included all ages. The denominator of patients 

upon which the rates were calculated was approximately 7,000 patients (3,000 children and 

4,000 adults). The racial / ethnic distribution was the denominator. 

With regard to infant and child morbidity and mortality, Dr. Katz (IDSA) pointed out that there 

were some reports of myocarditis detected in infants who died. He wondered whether there 

were any data to suggest whether this was an isolated event, or if there was a different tropism 

that H1N1 has demonstrated for organ specificity. 

Dr. Finelli replied that she conducted some analyses for an IDSA talk in which she assessed 

myocarditis, and remembered that it was very infrequent. However, she did not have any data 

on the underlying pathology. 

Dr. Temte requested that someone comment on the contribution of schools, school-aged 

children, and the school year in the termination of the first wave and the resurgence of the 

second wave. 

Dr. Finelli indicated that CDC has been very attentive to those data in school age children. She 

did not believe that by chance alone termination / resurgence occurred. There was a fair 

amount of transmission in schools that abated when schools adjourned in May and June. H1N1 

continued to smolder, and there were a number of camp outbreaks in the summer. In the fall, 

there were widespread outbreaks in many places with the commencement of the school year. 

Some analyses are being completed by some of CDC’s colleagues to assess this issue and 

offer more insight into community transmission from school outbreaks. 

Dr. Baker commented that because schools begin / end at different times in different regions, an 

analysis by region may make that association even more robust. 

Dr. Meissner asked whether there were any results pertaining to Peramivir, which was made 

available under an Emergency Use Authorization (EUA). 

Dr. Schuchat replied that the Peramivir intravenous formulation has been made available under 

an EUA. CDC runs that program, providing the medication to doctors who order it. There is 

mandatory adverse event monitoring and surveys are being conducted through which some 

follow-up data can be obtained. However, she did not want people’s expectations to be raised 

about the completeness and ability of those data to offer effectiveness information. They are 

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not really suitable for that, so CDC is working with FDA on ways to better determine the efficacy 

of medications made available under EUAs in the future. 

Dr. Whitley-Williams inquired as to whether there were any morbidity and mortality data for the 

youngest age group, those too young to be vaccinated (0 to 4 years of age), in terms of how 

many cases occurred in infants less than 6 months of age. This age group is always lumped in 

with the less than age 4 group, but she thought it was important to acquire PK data, particularly 

in the youngest children. She also wondered about the mortality data by race / ethnicity. 

Dr. Finelli responded that CDC does have these data for a proportion of children less than 6 

months of age for both those who were hospitalized and those who died. However, because 

she did not have those data with her, she preferred not to speculate. In terms of the mortality 

data by race / ethnicity, only the BRFSS system and Emerging Infections Hospitalization 

Program collect these data. CDC does not systematically collect mortality data by race or 

ethnicity, just by aggregate number by age group. 

Dr. Chilton noted that the other drug that was used under an EUA was oseltamivir for children 

younger than 1 year. He wondered whether that EUA would persist into the next influenza 

season and / or what might be done for young children who are exposed or infected during the 

coming season. 

Dr. Sun (FDA) said that he preferred to defer that question since it pertained to the drug side of 

FDA and he was from the biological side. In general, an EUA can last no longer than one year, 

at which time it must be renewed. 

Dr. Schuchat added that the EUA is tied to the emergency declarations. She did not believe 

they should assume that these would be good for the next season. 

Based on the way in which data were presented during this ACIP meeting, Dr. Dekker gained 

the impression that it was viewed by the experts that there is a vaccine for the upcoming season 

that contains no seasonal H1, but because there were no strong seasonal candidates, it 

contains the pandemic H1. He wondered at what point they would begin saying that 

A/California/07/2009 is just another H1N1 that is competing with all of the rest for the chance to 

be in a seasonal vaccine. 

Dr. Cox responded that this point had almost been reached; however it would be premature to 

state that the pandemic was completely over. There was an increase in activity in some 

countries such as Africa, and they had yet to see what would occur in the Southern 

Hemisphere. It is believed that this will become a seasonal strain and will continue to circulate 

just as the previous H1N1 did, but certain parts of the world and certain communities were being 

affected by the pandemic virus for the first time. 

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H1N1 Vaccination Coverage: Updated Interim Results February 24, 2010 

James A. Singleton, MS

H1N1 Vaccination Coverage Monitoring Team 

Immunization Services Division 

Centers for Disease Control and Prevention 

Dr. Singleton presented an update on vaccination rates with H1N1. These results were based 

on CDC’s National 2009 H1N1 Flu Survey (NHFS) results published in the MMWR in January 

2010 and interviews conducted by February 13, 2010. 

The NHFS has provided CDC with weekly estimates of H1N1 and seasonal coverage, including 

some behavioral data associated with vaccination. The NHFS is a random-digit-dialed (RDD) 

telephone survey of about 6,000 households per month, which includes land line and cell phone 

samples, conducted from October 2009 through June 2010. It is supplemented by a sample of 

children from the National Immunization Survey (NIS) sampling frame. Information from other 

surveys and data systems used for surveillance of influenza vaccination this season will be 

reported later, including state-level estimates using data from the BRFSS. 

By February 13, 2010 an estimated 97 million doses of H1N1 vaccine (95% CI 81 million to 112 

million) had been administered to 86 million persons. This number of doses administered 

represents about 78% of doses shipped (95% CI 65% to 90%). An estimated 37 million doses 

had been administered to 27 million children (95% CI 23 to 31). The proportion of estimated 

cumulative doses received by persons in the initial target group was over 85%, and had 

declined to 72% by February 13. By December 19, 2009 39 programs had expanded their 

H1N1 vaccination effort to the general population. Based on NHFS interviews from December 

27 through January 30, 2010 an estimated 166 million persons (95% CI 158 to 174) were in the 

initial target group, or 56% (95% CI 53% to 58%) of the US civilian, non-institutionalized 

population aged 6 months or older. In terms of cumulative H1N1 vaccination rate by week, by 

the second week of February, estimated coverage was 28.8% (95% CI 25.2% to 32.4%) overall. 

Based on a cumulative total of about 126 million doses distributed by February 13, 2010, less 

than 42% of the population could have been vaccinated, 28.8% of the total population had been 

vaccinated, and most of those who definitely intended to get an H1N1 vaccination had done so. 

Data were accumulated from December 27 to January 30 to have more stable estimates for 

different sub-groups. By mid-January, overall about 24% had been vaccinated. Coverage rates 

in children were higher than in adults (about 1/3 of children compared to about 1/5 of adults). 

Coverage by mid-January in the initial target group was 30% higher than the overall population. 

The highest rate was in healthcare practitioners at 39%. Pregnant women were included in 

initial target group estimate, but there were not enough (n=43) for separate estimate. As 

reported in the January 15, 2010 MMWR article, based on BRFSS December 1-27 preliminary 

data, estimated H1N1 coverage before mid-December was 38.0% (24.3-51.7) for pregnant 

women. Complete BRFSS data for January are not yet available to provide an updated estimate 

for pregnant women. Based on the BRFSS estimated reported in the MMWR for coverage 

before mid-December, coverage was 11.6% (9.9-13.3) for high risk adults aged 25-64, and 

22.3% (19.6-25.0) for HCP. NHFS December estimates of coverage by mid-December for 

these groups were 18.5% (14.5-22.5) for high risk adults aged 25-64 and 30.7% (25.0-36.4) for 

HCP. 

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With respect to weekly NHFS estimates of the percent of children aged 6 months through 9 

years receiving at least one dose of H1N1 vaccination, confidence intervals are wide, but these 

data indicate an increasing trend in receipt of a second dose among those with at least one 

dose. At least one third and possibly up to two thirds of children with at least one dose may 

have received a second dose. This rate may increase as children initially vaccinated in January 

have more time to get their second dose. By comparison, from the NIS estimates for children 6­

23 months, 2007-08 season, 23.4% were fully vaccinated and 40.7% had at least dose of 

seasonal vaccination, a ratio of 57%. Children were more likely than adults to get both H1N1 

and seasonal vaccination by mid-January, while adults were more likely to get seasonal 

vaccination only. Overall, 51% of children and 47% of adults had received an influenza 

vaccination of either type. 

Racial and ethnic disparities in H1N1 vaccination coverage were also assessed. As is observed 

for seasonal influenza vaccination, some racial and ethnic disparities in coverage occurred with 

H1N1. These differences were significant among adults but not children, and these differences 

were of lower magnitude than for seasonal vaccination. Significant disparities were also 

observed by levels of income and education, with higher coverage among persons living above 

the poverty threshold with annual incomes of over $75,000, and for college graduates. The 

sample size is not sufficient in NHFS monthly samples to reliably estimate disparities among HR 

25-64 or HCP. January BRFSS data are not complete yet to allow update of disparity estimates 

based on December BRFSS data published in the MMWR. 

With respect to the limitations of the survey, vaccination status and identification of target 

groups were based on self- or parental-report. Non-response bias may remain after weighing 

adjustments. The RDD response rate was relatively low at 34% for the landline sample and 

26% for the cellular telephone sample; however, this was on par with telephone studies 

currently. Survey estimates of coverage are consistent with vaccination patterns observed with 

SDI data. 

In summary, by mid-February, 86 million people had been vaccinated with about 97 million 

doses. Most doses were administered to the target groups. Coverage was higher in children 

than adults. An estimated 39% of health care workers were vaccinated. Of children less than 

10 years who were vaccinated, as many as 60% had received their second dose. H1N1 

vaccine coverage in adults was significantly higher in Whites than Blacks or Hispanics. H1N1 

coverage did not differ significantly by race or ethnicity among children. 

The next steps are to publish state-level H1N1 and seasonal estimates in the MMWR, continue 

to monitor through June, conduct post-season evaluation using all data sources to determine 

lessons learned for future seasons, and enhance the influenza vaccination surveillance system 

for the 2010-11 season. 

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H1N1 Vaccine: Implementation Update February 24, 2010 

Pascale Wortley, MD, MPH 

Immunization Services Division 

Centers for Disease Control and Prevention 

Dr. Wortley reported that as of a few days prior to this meeting, about 126 million doses of 

vaccine had been ordered by states. As a comparison, for the VFC program that uses the same 

system, about 80 million doses of vaccine are distributed each year. Of course, all of that 

activity continued while the intense H1N1 effort took place over 3.5 months. There were over 

70,000 unique “ship-to” sites, although vaccine found its way to a lot more than 70,000 sites 

because states engaged in a fair amount of redistribution using their own resources. The 

greatest increase in distribution was up through the first half of December 2009. There was a 

very marked slowing in the ordering pattern beginning the second half of January 2010. 

With respect to some of the challenges encountered, influenza vaccine is not generally handled 

as a “just-in-time” inventory as occurred during the first period. What normally is a fairly invisible 

process was under a magnifying lens to the point that even a delayed shipment due to weather 

conditions did not go unnoticed. Sometimes plans had to change because vaccine did not 

arrive on time for whatever reason. Managing allocations when demand varied across states 

also posed challenges. During October, everybody wanted more vaccine than there was and 

things were very straightforward. By mid-November, changes in patterns started to occur. 

Demand began to decrease in some parts of the country, while it remained strong in other parts. 

Also important was not to have a situation in which vaccine sat unused in warehouses, because 

there was always somewhat of a lag between ordering and shipping. 

A system was devised that allowed states to order against their future allocations, and the 

vaccine that was used was that cushion. Of course, that had to be done very carefully so that a 

back ordering situation did not occur. That system worked well and allowed for addressing the 

needs of states that were experiencing their ILI peak later than others and had higher demand 

for the vaccine. Managing allocations was complex for Dr. Santoli’s group. Also challenging 

was the provision of ancillary supplies. Complaints were received from providers who did not 

like the supplies they received. Part of the challenge was that in order to have enough supplies, 

HHS purchased 8 different types of supplies. Given that providers could not select what they 

were going to receive, they often received products they were not familiar with, which created 

some challenges that CDC tried to overcome with some training. 

The current issue pertains to ramping down of the system. By the end of April, CDC will be 

reducing the amount of vaccine that is available in the warehouses, but will retain the capacity 

to use it. All viable vaccine will be stored for use. Most of the vaccine will be expired by the end 

of June 2010, but there are some sanofi pasteur multi-dose vials that have expiration dates in 

2011. Decisions must be made about how that can be used. Because it is unknown what the 

Spring, Summer, and Fall might hold with regard to influenza activity and vaccine demand, this 

will be a useful asset upon which to draw if necessary. 

With respect to financing, the topic that seemed to have consumed so much of CDC’s time over 

the summer, the NVAC H1N1 vaccine financing recommendations involved all key stakeholders 

in a consensus on important recommendations. They were able to draw upon work that they 

had already done for vaccination of children and adolescents. The VFC served as a very good 

model of a free government vaccine program, and it helped to address a number of the policy 

issues that had to be dealt with throughout the summer. Most private plans covered H1N1 

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vaccine administration. At some point later in the summer, a decision was made to allow public 

health to bill in public clinic settings, though they could not charge cash. The impact of the 

ability to bill in public clinic settings needs to be evaluated. 

Providers who were to receive the H1N1 vaccine had to sign a provider agreement. There were 

minimal federal requirements, and states could add requirements as well. States were asked 

on a periodic basis to report to CDC how many provider agreements had been signed, which 

reached a maximum of about 120,000. That is three times the number of VFC providers of 

45,000. The make-up of providers varied across states. CDC is in the process of obtaining 

better information about that, but suspects that it varied somewhat in relation to how states went 

about recruiting providers, differences in provider interests, and decisions that states or local 

areas made in terms of whether vaccine was directed to a variety of types of providers or was 

more specifically directed to specific providers (e.g., pediatric providers, school vaccination, et 

cetera). A considerable amount of work was done around October 2009 in terms of registering 

providers. 

In terms of where children and adults were vaccinated, H1N1 vaccine (58.6%) was administered 

primarily in medical settings (e.g., doctor’s office, clinic or health center, hospital, other medical 

related location) just as seasonal vaccine is (64.5%). Other settings included health 

departments, pharmacies / drug stores, workplaces, schools, and other non-medical settings. 

Seasonal influenza vaccine is administered in these settings at 32.6%, and H1N1 at 39%. To 

some extent, that is a reflection of the large amount of school-based vaccination that occurred 

this past fall. About 40 of the 54 grantees reported some school vaccination activity. In some, it 

was a statewide activity that was coordinated at the state level, or it may have been a state and 

local responsibility, but generally was coordinated state-wide. For another 30 areas, it varied 

county by county, in that counties were responsible for deciding whether they were going to 

conduct a school-based program. 

There was a wide range in vaccination rates by state among children 6 months to 17 years of 

age, which is typically observed for seasonal influenza vaccination in children as well. For 

example, in a recent year for 6 to 23 month olds, seasonal influenza vaccination ranged from 

about 15% to 50%. A number of factors affect influenza vaccination rates. This season, some 

of the factors likely included the timeframe during which ILI peaked by state, the population the 

state was focusing on for vaccination, and whether state-wide school vaccination programs 

coincided with their ILI peak. 

Only a few weeks after states were wrestling with what to do with limited vaccine supply, they 

had to turn their attention to determining the point at which it was appropriate to open 

vaccination up to the general public. One state started a couple of weeks before Thanksgiving. 

The week of Thanksgiving, nothing happened. Then there was an increase over the next three 

weeks. By Christmas, most states had expanded H1N1 vaccination to the general public. A 

few states did not expand until the latter part of December or early January. 

As noted earlier, the proportion of estimated cumulative doses received by persons in the initial 

target group was over 85%, and had declined to 72% by February 13. 2010. Based on NHFS 

interviews from December 27 to January 30, an estimated 166 million persons (95% CI 158 to 

174) were in the initial target group, or 56% (95% CI 53% to 58%) of the US civilian, noninstitutionalized population aged 6 months or older. For the immunization program veterans 

who recalled the challenges of vaccine shortages in 2004, the major challenge was starting 

soon enough that there would still be demand once they expanded the target groups, but not 

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 “ l t t fl i ti . 

 t i ill t/ ill l t/ t 

i t i ”

t

The “Main Reason” for not getting an H1N1 vaccination 

among all unvaccinated, by month of interview, NHFS 

Percen age reporting reason 

Responses are to the question There are many reasons why peop e don’ ge u vacc na ons 

What is he ma n reason you [w not ge w probab y no ge have no yet gotten] an H1N1 flu 

vacc nation h s flu season? 

Advisory Committee on Immunization Practices (ACIP) Summary Report February 24-25, 2010 

expanding too soon creating demand that could not be met. Generally, the ACIP 

recommendations, which were designed for exactly this type of flexibility, worked well. 

The purpose of the retail pharmacy initiative that occurred at the end of December was to 

extend the reach of public health. This was a deviation from the pro rata allocation of vaccine to 

states. The vaccine was allocated directly to 10 participating retail pharmacies that 

subsequently distributed doses across their systems as they wished. All but three states 

participated. A number of states already were directing vaccine to retail pharmacies before this 

initiative, but the idea was to allow public health to focus on other populations and to send more 

vaccine out. This was the same principle as the advanced allocation in order to use vaccine 

that was in the cushion that was sitting unordered. In all, vaccine was distributed to over 10,000 

locations. The first direct shipment of vaccine to retailers was sent on December 24, 2009. To 

date, these pharmacies and clinics have received over 5.4 million doses of 2009 H1N1 vaccine 

directly from CDC. 

The following graphic depicts the reasons stated for not getting vaccinated: 

The contract in turquoise and light turquoise are data from January and December. Notably in 

December is that “vaccine is not needed” and “vaccine is not available” were the two leading 

reasons. By January, few people were saying vaccine was not available and the focus was that 

it was not needed. A potential barrier not listed on this graphic was “cost of the vaccine,” which 

fewer than 3% of people reported. An important concern over the summer was that it would be 

confusing to people that vaccine could be obtained in different places, but they would have to 

pay for it in some places and not in others. In the end, this did not end up being a barrier at all. 

In summary, there were a number of key accomplishments. Public health coordinated 

distribution of a large amount of vaccine as quickly as it became available. Much experience 

was gained in large-scale clinics and school-located vaccination. Experience was also gained 

in managing a scarce resource and addressing vaccine safety and supply concerns. There was 

a tripling in providers receiving vaccine from public health. New partnerships were forged with 

health care, community groups, and education which can be built upon in the future. 

Key evaluation areas upon which CDC is focusing include approaches to allocation and 

distribution (state and local), school vaccination best practices, provider involvement best 

practices, provider perspectives, and billing by public health. Moving forward, consideration 

must be given to building upon the momentum that was acquired during this past influenza 

season in terms of partnerships, new capacities that were acquired, and prospective evaluation. 

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Discussion 

It was Dr. Baker’s understanding that there has been great reluctance by the AAP to move any 

kind of vaccines out of the medical home. This season provides some lessons that there can be 

both school-based immunizations and immunizations in the medical home depending upon the 

ages of children and other factors. She requested that Dr. Bocchini comment on this, and 

emphasized that if they were ever going to increase rates, they must diversify their efforts. 

Dr. Bocchini (AAP) replied that this subject certainly has been discussed extensively. He 

thought that the important point was that better vaccine registries must be developed so that the 

medical home knows what is occurring. Some of the issues in the medical home involve trying 

to vaccinate all children within a brief period of time for one or two doses of vaccine and making 

sure that there is adequate supply for that. Planning for patient visits and adequate vaccine 

supplies placed a great deal of stress and strain on practitioners, but also made them realize 

that school-based immunization may be a better method on an annual basis for influenza 

immunization. 

Dr. Keitel requested an estimate of how many doses remain in warehouses and what efforts are 

being undertaken to ensure that those are distributed, particularly given the uncertainty about 

what will occur in the Fall. 

Dr. Wortley responded that there were recently about 28 million doses in the warehouses. CDC 

is in the process of gradually bringing this number down because by the end of April, they will 

have half of that. The reason there is so much vaccine in the warehouses is because the 

ordering has slowed down so much. In terms of distributing these doses, states and local areas 

are still holding clinics. The demand from providers has slowed down significantly. Most of the 

states originally were in a mode of pushing vaccine out to providers and then switched to an 

ordering mode. 

Dr. Sawyer noted that clearly, they are still not doing a very good job of immunizing health care 

workers. In his community, a number of hospitals developed much more aggressive policies for 

immunization of their workers that had great effect. He inquired as to whether Dr. Singleton 

could tell them what percent of the healthcare workers surveyed were employed in hospitals as 

opposed to clinic settings, and whether the survey asked whether there were changes in policy 

such as a mandatory policy for immunization. 

Dr. Singleton responded that while they will be able to examine occupation type later, they do 

not currently have these data. CDC contracted with RAND and Knowledge Networks, Inc. to 

conduct internet surveys of healthcare workers and there are some preliminary results; 

however, these results have not yet been released yet. They should be published in an MMWR 

article by early April. Surveys are conducted monthly that include occupation type and policies 

that were implemented for this season. Data from the National Epidemiology Center from past 

seasonal show differences in location. Healthcare workers in hospitals tend to have higher 

rates than those in long-term care facilities. 

Reflecting on Dr. Singleton’s comments that there were not differences by race and ethnicity for 

children receiving vaccine in terms of seasonal and H1N1 but there were for the adults, Ms. 

Ehresmann hypothesized that the reason for that may be because there is such a strong 

childhood vaccination program with the VFC. For adults, there were less barriers for H1N1 

vaccination than for seasonal vaccination. This supports the fact that the lack of an adult 

immunization program is quite significant problem. 

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Dr. Lett shared that Massachusetts is still administering about 60,000 doses a week of H1N1 

vaccine. However, they are concerned about using all of the doses available to them and are 

seeking any possible epidemiologic support they can share with people. For example, spring 

break may mean that children may be going to Mexico. This could be a reason to have an 

initiative. 

Dr. Baker pointed out that they also need to know whether there is going to be a third wave. 

Dr. Fiore responded that CDC is certainly keeping an eye on activity in the US and abroad. 

There is not a clear hint that something is brewing, but certainly there continues to be activity in 

the US and other areas. There is always the potential for people to travel to areas where there 

might be more activity and bring it back to their own community that might not have been hit so 

hard by the second wave, which could start a new chain of transmission. There are many 

reasons to continue to promote H1N1 vaccination. 

Referring to the two NHFS surveys, Dr. Duchin (NACCHO) noted that the percent vaccinated for 

adults ages 25 through 64 with high risk health conditions was very different from 11.6% to 

almost 30%. He wondered what Dr. Singleton’s interpretation was of that jump in terms of 

whether it meant that these people were vaccinated later, and that they were not vaccinated at 

the time the initial survey was conducted. 

Dr. Singleton explained that the number published in the MMWR was from the BRFSS from 

December data, which represented cumulative coverage sometime before mid-December. The 

number he presented during this session was from the NHFS. There were two different 

surveys. They were similar in methodology in terms of being telephone surveys, but one major 

difference was that with data from a month later, they should expect to see an increased uptake. 

They have compared results from the two surveys using comparable time periods and generally 

are matching it fairly well, but a few differences are observed. Most of the difference is probably 

due to it being more up to date with the recent estimates. The NHFS was a little higher than the 

BRFSS back in December. It was 18% in mid-December and he was showing 29% in midJanuary from the same data source. 

Dr. Duchin (NACCHO) said that because these are the people at highest risk of death, he 

thought the timing during which they were immunized was of some significance in the context of 

informing policy making about how prioritization is done. The timing of immunization for the 

different subgroups would be useful to know in future reports. 

Dr. Singleton replied that they are collecting the month of vaccination, and numerous analyses 

are being conducted on vaccination timing in different subgroups. 

Reflecting on Dr. Sawyer’s comments about breaking out where health care providers are 

vaccinated, Dr. Foster (APA) reported that most of their healthcare professionals were not 

hesitant to acquire the vaccine. However, they are primarily healthcare professionals versus 

food service workers, housekeeping staff, et cetera so it would be interesting to understand 

what is included in the healthcare worker category. 

Dr. Singleton responded that the question asked in the surveys is: Do you work in a healthcare 

facility? This is followed by some examples. Another question asks: Do you provide direct 

patient care as part of your routine? If someone responded “yes” to either of those questions, 

they were included. They will be able to assess occupation type later when the data are coded. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report February 24-25, 2010 

Dr. Foster (APA) pointed out that every state is different in terms of the state laws that govern 

what pharmacists can do. Currently, in all 50 states pharmacists can administer immunizations 

in some manner. Pharmacists are probably the least threat to pediatrics because they usually 

do not administer pediatric vaccines in pharmacies. However, states will allow them to 

vaccinate down to age 12 to 14. It was very difficult for APA this year because they did have a 

lot of patients present to pharmacies requesting the vaccine. They had to defer people until the 

season was almost over, and by that point, no one wanted it. Pharmacists have access to 

many patient records, so they can easily identify those with chronic diseases. Therefore, he 

advocated that pharmacies be considered to receive vaccine early on because typically in a 

season, pharmacies administer more vaccines than health departments. 

Dr. Sumaya was struck the primary reason for not getting an H1N1 vaccine being “not needed.” 

He thought this needed further investigation, scrutiny, analysis, et cetera. 

Ms. Ehresmann pointed out that as they moved forward to build on the successes of this 

influenza season, it was important to keep in mind that there were some additional funds made 

available for those efforts. Without those funds, it is not clear how feasible it will be for folks to 

continue such efforts in the future. 

Regarding health care workers, Dr. Morse (CSTE) noted that New York had enacted regulations 

requiring health care workers to be immunized, but this effort had to be suspended due to a 

shortage of vaccine. They conducted a brief survey that compared to the previous year when 

only 43% of healthcare workers were immunized, During this season, it reached approximately 

71%. While they need to follow-up on this, it appears to be a successful program that will go 

forward as a regulation for the coming year. In terms of sustainability, obviously there were a 

number of good practices developed as a result of the pandemic influenza vaccine campaign. 

He wondered how that could be translated to seasonal influenza vaccine and what progress 

was being made to garner funding to support that. It would be a shame to lose the momentum if 

there is no funding to translate these efforts. 

Dr. Wortley responded that clearly, school vaccination requires both operations and vaccine 

funds for non-VFC children. 

Dr. Schuchat added that currently, there are no more resources to support school-associated 

vaccination, with the exception of the economic stimulus ARRA funds that the states have been 

programming. There was about a $300 million, two-year program that included substantial 

funds for vaccine purchase, so the states still have some discretion regarding how to program 

their remaining vaccine purchase dollars. The operations funds included in that also were at 

their discretion. This past year, an enormous amount of emergency funds were allocated to 

support states. Most of the funds that went to the states were for vaccine administration. 

Dr. Sun (FDA) said that although there are a lot of successes associated with the response to 

this pandemic, there might still be a lot of challenges. One of those will be assessment of safety 

profiles and the effectiveness of these vaccines on their pandemic circumstances. Because in 

the future there will probably be different vaccines made with more varied technologies, it would 

be especially important to examine issues of safety and effectiveness, and to be able to track 

particular manufacturers of vaccines. 

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Regarding how to promote vaccination, Dr. Plotkin said he had read the paper that states that 

the transmission of H1N1 was lower than might have been expected. Guinea pig data suggest 

that this is not the case. He thought that calculating the reproductive number would be 

important because this is the first time this much vaccination has been given to children, who 

are the main transmitters of influenza. If they believe that vaccinating children is going to have 

an impact on an epidemic, he wondered whether there were any data regarding reproductive 

number which would allow calculations to tell them whether the percentage of children who 

were vaccinated could have actually had an impact on the epidemic. It may be too optimistic to 

say that that this is what stopped the transmission at the end of last year, but he though such 

calculations would be extremely important to determine whether, in fact, vaccination of children 

is having an impact. He also wondered whether there were any effectiveness data from either 

American or European experience that would tell them about the effectiveness of the H1N1 

vaccine. 

Dr. Fiore responded that in terms of the reproductive, certainly CDC is working on this with a 

number of others throughout the world. Other investigators have done their own calculations of 

this. However, he did not have a number to provide at this moment. A number of studies are 

underway to examine vaccine effectiveness. Some preliminary estimates are available, but 

CDC is hampered by the fact that the pandemic wave in many of the areas where these studies 

were set up beforehand proceeded the time before there was a lot a vaccination. He thought 

they would soon have this information and that other countries would also have vaccine 

effectiveness data available. 

Dr. Judson said he thought a study was published just recently that spoke to the issue of 

transmissibility when there was a primary case within the household, and then assessed spread 

to other household members. He thought some of that was examined before vaccine was 

widespread. 

Dr. Fiore replied that there are some studies, but he was not prepared to quote them at this 

point. He indicated that he would review these and provide them to the members. 

Fluzone® High-Dose Vaccine: High-dose Influenza 

Virus Vaccine for Persons 65 Years of Age and Older 

David Greenberg, MD 

sanofi pasteur 

Dr. Greenberg thanked Dr. Fiore, Dr. Neuzil, and the Influenza Work Group for giving him the 

opportunity to present data from sanofi pasteur’s Fluzone® High-Dose clinical trial during this 

session. Before discussing the clinical trial data, he briefly reviewed the burden of disease in 

the older adult population and the rationale for developing this vaccine. 

Based on a retrospective analysis of some 25 years of influenza seasons (1976–2000) 

demonstrating the influenza-related hospitalizations and death rates among the older 

population, hospitalization and death rates increase quite dramatically in the oldest age groups 

as reflected in the following graphic [Thompson WW, et al. J Infect Dis. 2006;194(suppl 2):S82­

S91Thompson WW, et al. J Infect Dis. 2006;194(suppl 2):S82-S91]: 

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CDC: Influenza-associated hospitalization 

and death rates, by age group, 1976–2000 

3 

19 33 65 

358 

190 

321 

431 

686 

1195 

129 

0 

200 

400 

600 

800 

1000 

1200 

1400 

65-69 70-74 75-79 80-84 >85 

Age Group, years 

Per 100,000 Population 

Annual influenza-related deaths 

Annual influenza-related hospitalizations 

Thompson WW, et al. J Infect Dis. 2006;194(suppl 2):S82-S91. 

Advisory Committee on Immunization Practices (ACIP) Summary Report February 24-25, 2010 

To put this into context, the rates for healthy adults under age 65 are a fraction of what is shown 

here. Adults t 65 years of age comprise 15% of the US population, but account for 65% of 

hospitalizations and 90% of deaths attributable to influenza and its complications each year. 

Among older adults, influenza causes an estimated 3.2 million illnesses, 136,000 

hospitalizations, and 36,000 deaths per year, with annual direct medical costs of $4.2 billion and 

total economic burden of $56.1 billion. Influenza vaccines provide substantial protection, but 

older adults respond less well to standard-dose influenza vaccines compared with younger 

adults. Lower antibody titers leave older adults more vulnerable to serious infection and severe 

complications [Thompson WW, et al. J Infect Dis. 2006;194(Suppl. 2):S82-S91. Zheng B, et al. 

J Immunol. 2007;179(9):6153-6159. Molinari NM, et al. Vaccine 2007;25(27):5086-96]. 

In terms of standard influenza vaccine and geometric mean titers (GMT) high in responses from 

one of sanofi pasteur’s recent annual Fluzone® release studies, there were remarkably lower 

antibody responses for adults over age 65 compared to the younger adult population [sanofi 

pasteur annual release study GRC41]. 

Decreased immunity against influenza is a result of aging and immunosenescence. Declining 

humoral and cellular immunity, a result of aging, increases susceptibility of older adults to 

infection. Older adults have decreased immunologic responses to vaccines due to 

immunosenescence. Age-related changes in T-cell subsets and in cytokine production profiles 

affect the magnitude, quality, and persistence of antibody responses to vaccines [Zheng B, et al. 

J Immunol. 2007;179(9):6153-6159. Doria G, et al. Mech Ageing Dev. 1997;96(1-3):1-13. 

Siegrist CA. The immunology of vaccination. In: Plotkin SA, Orenstein WA, Offit PA, eds. 

Vaccines. 5th ed. Saunders; 2008]. 

In response to the increase in calls for vaccines to improve immune responses in this older adult 

population and to help prevent influenza to a greater degree, sanofi pasteur developed the 

Fluzone® High-Dose vaccine. The genesis of Fluzone® High-Dose began about a decade ago 

in discussions between and CDC, National Institute of Health (NIH), sanofi pasteur, and 

investigators at Baylor and elsewhere. This led to the initiation of sanofi pasteur’s Phase I and 

Phase II trials. In the interest of time, these two trials were not discussed. 

During this session, Dr. Greenberg reported on the Fluzone® High-Dose Vaccine Study FIM05 

Phase III multicenter, randomized double-blind study of 3876 participants 65 years of age and 

older. Participants were randomized 2:1 to receive either High-Dose (HD; 60μg HA per strain) 

or Standard-Dose (SD; 15μg HA per strain). Participants in the High-Dose group were further 

randomized to receive 1 of 3 different lots of the vaccine. Blood specimens were obtained pre86 

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- =

 

 

Solicited Systemic Reactions, 

Study FIM05 (Phase III) 

11 

High Dose (N 2573) Standard-dose (N=1260) 

Reaction % 95% CI % 95% CI 

Any Myalgia 21.4 (19.8; 23.0) 18.3 (16.2; 20.5) 

Grade III 1.6 (1.2; 2.2) 0.2 (0.0; 0.7) 

Any Malaise 18.0 (16.5; 19.5) 14.0 (12.1; 16.0) 

Grade III 1.6 (1.1; 2.2) 0.6 (0.2; 1.1) 

Any Headache 16.8 (15.3; 18.3) 14.4 (12.5; 16.5) 

Grade III 1.1 (0.7; 1.6) 0.3 (0.1; 0.8) 

Any Fever 3.6 (2.9; 4.4) 2.3 (1.5; 3.3) 

Grade III 0.0 (0.0; 0.2) 0.1 (0.0; 0.4) 

Intensity of Systemic Reactions Day 0 to Day 7 Postvaccination 

Sanofi Pasteur, Study FIM05. Falsey AR, et al. J Infect Dis 2009;200:172-180. 

Advisory Committee on Immunization Practices (ACIP) Summary Report February 24-25, 2010 

vaccine and on Day 28 for evaluation of influenza antibodies. Safety data were collected by 

diary card (1 week), visits (4 weeks), and telephone calls (up to 6 months) post-vaccination. 

Primary endpoints included the following: 

Immunogenicity for lot consistency 

Immunogenicity for superiority 

 GMTs 

4-fold rise rates 

Secondary endpoints included the following: 

Immunogenicity for seroprotection rates 

Solicited safety and reactogenicity 

Unsolicited adverse events (AEs) and serious adverse events (SAEs) 

With regard to safety data from this trial, injection site pain, erythema, and swelling were 

reported at higher frequencies for High-Dose High-Dose (N = 2573) compared to StandardDose recipients (N = 1260). The vast majority of these were Grade I and II, and were mild to 

moderate. The proportion of Grade III, or severe reactions, was quite low for both groups. 

Their reactions, for the most part, resolved within three days after vaccination. In terms of the 

solicited systemic reactions, myalgia, malaise, and headache were reported at about 3 to 4 

percentage points higher in the High-Dose compared to Standard-Dose recipients. Fever was 

just slightly higher. Again, the vast majority of these were mild to moderate and resolved within 

three days [Sanofi Pasteur, Study FIM05. Falsey AR, et al. J Infect Dis 2009;200:172-180]. 

Solicited injection site and systemic reactions are shown in the following tables: 

10 

High Dose 

(N = 2573) 

Standard dose 

(N = 1260) 

Intensity % 95% CI % 95% CI 

Pain 

Any 35.6 (33.7; 37.5) 24.3 (21.9; 26.8) 

Grade III 0.3 (0.2; 0.7) 0.2 (0.0; 0.6) 

Erythema 

Any 14.9 (13.6; 16.4) 10.8 (9.1; 12.6) 

Grade III 1.8 (1.3; 2.4) 0.6 (0.2; 1.1) 

Swelling 

Any 8.9 (7.9; 10.1) 5.8 (4.6; 7.2) 

Grade III 1.5 (1.1; 2.1) 0.6 (0.3; 1.2) 

Intensity of Injection-site Reactions Day 0 to Day 7 Postvaccination 

Solicited Injection Site Reactions, 

Study FIM05 (Phase III) 

Sanofi Pasteur, Study FIM05. Falsey AR, et al. J Infect Dis 2009;200:172-180. 

The other safety parameters included immediate reactions within 30 minutes, which occurred at 

a low rate and were equal between the two groups. Unsolicited adverse events within the first 

28 days were the same in both groups at 22%. Rates of SAEs were 6.1% in the High-Dose 

group and 7.4% in the Standard-Dose group. Only two SAEs were reported by investigators as 

being vaccine-related. One case of an exacerbation of Crohn’s disease occurring two days 

after vaccination with high-dose and one case of a new diagnosis of myasthenia gravis 

occurring a month after standard-dose vaccine. There were no deaths within the first 28 days 

after vaccination in either group and the 23 deaths that were reported through 6 months of 

follow up, the rates of deaths were the same in the two groups, 0.6%, and they were all 

considered unrelated to vaccination. 

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Adverse events occurring in the 30 minutes following vaccination were comparable at 0.3% in 

both groups. Rates of unsolicited adverse events within 28 days post-vaccination were 

comparable at 22% in both group. Rates of SAEs were comparable at 6.1% with High-Dose 

vaccine and 7.4% Standard-Dose vaccine. Only two SAEs were reported by investigators as 

being vaccine-related: an exacerbation of Crohn's Disease 2 days after vaccination with HighDose vaccine, and a new diagnosis of myasthenia gravis 1 month after vaccination with 

Standard-Dose vaccine. No deaths occurred between Day 0 and Day 28, and 23 deaths were 

reported after Day 28 (0.6% in both groups). All deaths were deemed unrelated to vaccination. 

A rigorous approach was applied for superiority assessments. For Fluzone® High-Dose to be 

considered superior to Fluzone® Standard-Dose, demonstration of superiority for at least two of 

the three vaccine strains without inferiority of the third strain was required. In most studies, 

superiority criteria would be met when the lower bound of the 95% confidence interval is greater 

than 1.0 for GMT ratio or greater than 0% for the difference in 4-fold rise rates. In discussions 

with the FDA, it was agreed that for this trial, the superiority criteria would require that the lower 

bound of the 95% CI be greater than 1.5 for the GMT ratio and greater than 10% for the 

difference in 4-fold rise rates. These substantial margins would not only guarantee statistical 

superiority, but also would ensure clinical superiority. The GMTs were significantly higher in the 

High-Dose recipients compared to the Standard-Dose recipients for all three strains. Superiority 

was achieved for the H1N1 and the H3N2 strains, with non-inferiority for the B strain. 

Perhaps the most vulnerable of the elderly populations to influenza and its complications would 

be those entering the season with negative baseline titers. In a subset of the population in this 

study who had negative baseline titers (e.g., titers less and 1:10), the GMTs generated by the 

High-Dose vaccine were statistically significantly higher with the High-Dose compared to the 

Standard-Dose group for all three strains. In terms of GMT by age, higher GMTs were found for 

all three age groups in the High-Dose versus Standard-Dose recipients. When the subjects 

were enrolled, they were asked about history of cardiovascular or respiratory disease. The 

increased antibody responses with High-Dose vaccine were maintained even in those with a 

history of cardiovascular or respiratory disease. Based on the FDA criteria, the immunogenicity 

of Fluzone® High-Dose vaccine was superior to Fluzone® Standard-Dose. The GMT ratios of 

1.7, 1.8, and 1.3 demonstrate that High-Dose induced 70%, 80%, and 30% higher antibody 

titers compared to Standard-Dose for H1N1, H3N2, and B strains. In addition, the High-Dose 

vaccine induced 4-fold rise rates more often than Standard-Dose vaccine by differences of 25%, 

18%, and 12%. The pre-defined endpoints for superiority were met for the two A strains and 

non-inferiority for the B strain. For that B strain, the GMT ratio of 1.3 and the difference in 4-fold 

rise rates of 12% were statistically significant [Sanofi Pasteur, Study FIM05. Falsey AR, et al. J 

Infect Dis 2009;200:172-180]. 

In summary, rates of solicited injection-site and systemic reactions were more frequent with 

High-Dose vaccine, but were transient and well-tolerated. Fluzone® High-Dose vaccine was 

significantly more immunogenic than Standard-Dose vaccine against all 3 strains as measured 

by GMTs, 4-fold rise rates, and seroprotection rates. Benefit were maintained across age, 

underlying condition, and gender. Fluzone® High-Dose vaccine met the pre-specified FDAdefined superiority criteria. Fluzone® High-Dose vaccine induced superior antibody responses 

compared with Standard-Dose vaccine against H1N1 and H3N2 strains (70% and 80% higher), 

and was non-inferior against B strain (30% higher). 

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Regarding licensure and next steps, the Center for Biologics Evaluation and Research (CBER) 

licensed Fluzone® High-Dose vaccine on December 23, 2009. This vaccine will available for 

the upcoming 2010-2011 season. A post-licensure efficacy trial was begun in September 2009. 

This is a study of approximately 30,000 subjects, all 65 years of age and older. It is a three-year 

study. Subjects are randomized 2:1 to High-Dose or Standard-Dose vaccines, double blind. 

Post-vaccination blood draws are being obtained from about one-third of the subjects. There is 

active surveillance for influenza-like illness (ILI) and respiratory specimens collected for culture 

and PCR. Safety will be monitored for 6 months after vaccination at a minimum, through the 

following influenza season. The superiority criterion for this study is the lower bound of the 95% 

confidence interval for the relative vaccine efficacy of Fluzone® High-Dose compared with 

Standard-Dose greater than 9.1%. The first subject was enrolled September 22, 2009 and the 

enrollment for the first year completed in early November 2009 with over 9000 subjects enrolled 

across the US. Surveillance for ILI and collection of respiratory specimens for culture and PCR 

are on-going. An independent data monitoring committee will review the safety and efficacy trial 

as it progresses. As noted, Fluzone® High-Dose vaccine will be available for the upcoming 

season in preservative-free, non-adjuvanted, 0.5mL pre-filled syringes. sanofi pasteur began 

accepting reservations for this vaccine on February 15, 2010. Medicare Part B coverage is 

expected. 

Discussion 

Dr. Baker inquired as to whether there were plans to use High-Dose vaccine exclusively for the 

65 and older age group with the licensure. In other words, will the supply of 60μg for the older 

persons affect the supply for those persons under 65 years of age? 

Dr. Greenberg responded that because this is the launch year for the vaccine, he did not think 

that supply would be an issue. 

Dr. Hosbach (sanofi pasteur) added that in terms of the overall influenza supply, sanofi pasteur 

anticipates providing more vaccine than provided last year. That will be dependent upon the 

reservations accepted as well as the performance and yield of the strains. They fully anticipate 

being able to supply more of the regular vaccine as well as, including this additional vaccine. 

Dr. Baker noted that the motivation behind her questions was that it was hypothesized that 

running out of preservative-free pediatric vaccine was due to the redirection of sanofi pasteur’s 

efforts toward H1N1. 

Dr. Hosbach responded that he did not believe this was the case, and that sanofi pasteur 

achieved all of its numbers in terms of commitments for influenza vaccine supply in the US last 

year. He did not think they ran out. There was probably greater demand for some of the 0.5mL 

product than anticipated. He thought they still had 0.25mL pediatric left over. 

Dr. Baker replied that this was very bad. 

Dr. Sawyer pointed out that they now had the wonderful problem of yet another influenza 

preparation. Given that there are now at least 15 products, there will inevitable confusion in the 

refrigerator. As they learned this season, some people received 2 doses of H1N1 and no doses 

of seasonal and vice versa. With that in mind, he wondered whether sanofi pasteur had any 

experience with the High-Dose product in younger individuals, including children, in terms of 

what might happen to someone with a more robust immune system if they receive this vaccine. 

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Dr. Greenberg responded that High-Dose vaccine has not been administered to individuals 

under 65 years of age, but he reflected on what happened with other seasonal and pandemic 

H1N1 vaccines in younger individuals. For all manufacturers, there was a very robust antibody 

response to the California 7 H1N1 vaccine antigen. In fact, in the clinical trials that were 

conducted, higher doses (30 μg) were administered to children and young adults. To his 

knowledge, there has never been any evidence increased adverse reactions with a robust 

antibody response. 

Dr. Keitel noted that while this specific High-Dose vaccine has not been studied in younger 

people, there certainly are a number of clinical trials assessing high dose influenza vaccines. 

Doses up to 425 μg of HA have a higher injection site reaction, but have been well-tolerated. 

She asked whether there were any data regarding how many of the people in the study were 

vaccinated previously and if so whether they were they stratified according to prior receipt of 

vaccine before randomization, and whether the endpoints were analyzed according to prior 

receipt of vaccine. 

Dr. Greenberg replied that analyses were not the analyses were not stratified by vaccination 

background information. This was done in-season, so prior vaccinations would have been 

received a full year or longer before the study. Some studies have shown decreased response 

when an individual had been vaccinated within a few months prior to their vaccination. 

Dr. Meissner inquired as to how much more the High-Dose Fluzone® would cost than regular 

Fluzone ®. 

Dr. Hosbach replied that the list price for High-Dose Fluzone® will be $25 for the single dose, 

non-preserved syringe. This is about twice the amount of the syringe-based product, with 4 

times the amount of antigen. Percentagewise, the cost is about double. 

Dr. Meissner found this to be significant, but Dr. Baker pointed out that part of this is due to the 

use of prefilled syringes. 

In the absence of any efficacy data, Dr. Meissner wondered whether sanofi pasteur had any 

assays of functional antibody. He also wondered whether there were any data on decay of 

antibody, given that adults tend to lose their antibodies more rapidly. 

Dr. Greenberg responded that for the Phase III clinical trial, they used the hemagglutinin 

inhibition (HI) antibody assay. Neutralization tests were done in the early Phase I study, which 

neutralization assay results showed significantly higher responses with High-Dose compared to 

Standard-Dose. They did not collect long-term antibody data. Blood was not collected beyond 

one month post-vaccination. Based on what is known with Standard-Dose vaccines, protection 

is provided throughout the season. Certainly, he would expect no less from this vaccine. If 

antibodies decay at a similar rate, there would likely be a season of higher titers with High-Dose 

than with Standard-Dose, but that is speculation since there are no specific antibody data. 

Thinking about the rapid increase in mortality in those over 80 years of age, Dr. Judson inquired 

as to the overall goals in terms of quality of life and worthwhile life expectancy in simply 

preventing influenza. 

Dr. Plotkin protested the question. 

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Regarding efficacy or functional antibody, Dr. Dubin (GSK) reported that GSK is developing an 

adjuvanted vaccine, which is a different approach to try to improve efficacy in individuals over 

65 years of age. Because there is no accepted correlate of protection in the 2008 / 2009 

season, GSK initiated an efficacy study that has enrolled over 43,000 subjects who are now 

being followed through two influenza seasons. GSK looks forward to being able to share the 

results of that trial, once they are analyzed, hopefully in the near future. 

Dr. Foster (APhA) wondered whether, if ACIP made a full recommendation, there would be 

ample supply to cover all elderly people. 

Dr. Hosbach (sanofi pasteur) Replied that in terms of their supply, he did not believe they were 

anticipating some sort of preference for this vaccine. However, if that were to occur, they would 

have to adjust their thinking and report back to ACIP whatever they believe they can 

accomplish. 

Dr. Schmader (AGS) noted that most elders, even when demented, would not like to have 

influenza. Routine immunization programs are used in nursing homes throughout the country. 

Along that line, it is known that the health of older adults is quite heterogeneous. He assumed 

that in the immunogenicity studies, most of the individuals were community-dwelling elders who 

are independent and are not frail or functionally impaired. 

Dr. Greenberg responded that this was correct. These studies were all conducted in physicians’ 

offices. While the participants could have had a host of underlying medical conditions, they 

were ambulatory. 

With that in mind, Dr. Schmader (AGS) suggested that it would be important to know the 

performance of the High-Dose vaccine in a large segment of older adults who are frail and 

complex. 

Dr. Greenberg replied that the studies were not targeted in long-term care facilities or nursing 

homes, but this is an area that sanofi pasteur is interested in and would like to explore. 

Having spent a great deal of her career working on a vaccine that will never come to fruition, 

and understanding GMCs, GMTs, and the data this hides, Dr. Baker asked what percent of 

these individuals had titers less than 1:40 post-immunization with the 60 μg dose. She was 

thinking that this would be a heterogeneous group and that age would not necessarily tell them 

who has true senescence. 

Dr. Greenberg responded that 10% had titers less than 1:40 against H1N1, 1% for H3N2 , and 

21% for the B strain one month after immunization. 

Following up on Dr. Sawyer’s earlier remarks about potential medical errors, Dr. Lett inquired as 

to how different the labeling and packaging would be for the High-Dose. She wondered if FDA 

was more mindful about this after H1N1, given the difficultly in differentiating between the 

seasonal and the H1N1 formulations of a manufacturer. 

Dr. Greenberg replied that the packaging is distinct and that the plunger is a different color for 

the High-Dose. Dr. Hosbach added that 65+ is shown in very large font on the front. 

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Dr. Temte inquired as to whether CMS would consider High-Dose to be a routine influenza 

vaccine that would be covered under Medicare in the same way that seasonal vaccine is 

covered. 

Ms. Murphy (CMS) responded that she works in Medicaid and could not speak for Medicare. 

She indicated that if someone would email the question to her, she would be happy to find an 

answer. 

Dr. Hosbach (sanofi pasteur) added that they have been engaged in conversations with CMS 

and have provided them with all of the information they need. It is fully anticipated that the 

High-Dose vaccine will be covered under Medicare. 

Dr. Schaffner (NFID) asked what the age distribution was of the people in this trial. 

Dr. Greenberg responded that the GMTs are stratified by age. Of 65 through 74 year olds there 

were 1648 in the High-Dose group; in the 75 through 84 years of age group there were 779 in 

the High-Dose group; and in the 85 years of age group there were 117 in the High-Dose 

group. 

Dr. Schaffner (NFID) inquired as to whether there were any plans to investigate this vaccine in 

those younger than age 65 who might also have immunocomprising conditions. 

Dr. Greenberg indicated that the licensure request just came a couple of months ago, so sanofi 

pasteur is currently highly invested in and spending a lot of time on the efficacy trial. However, 

they are open to and would be interested in studying populations under 65 who are 

immunocompromised. They welcome investigator proposals, and will review them to determine 

whether they could support them. 

Influenza Vaccine Workgroup Discussions and 

Recommendations November 2009-February 2010 

Anthony Fiore, MD, MPH 

Influenza Division, NCIRD, CDC 

Dr. Fiore began by thanking the members of the work group, particularly given that this past 

season has been an enormous challenge. Everybody stepped up and attended the much more 

frequent calls, engaged in numerous telephone discussions, and addressed many emails. He 

especially expressed gratitude to his Chairperson, Dr. Neuzil. 

The Influenza Work Group engaged discussions during scheduled teleconferences twice per 

month, and through on-going e-mails and ad hoc discussions in between the teleconferences. 

The major topics this group addressed over the past several months pertained to updates on 

and the response to the pandemic, with a focus on the implications of the pandemic for the 

upcoming seasonal influenza vaccine recommendations. The group discussed vaccine 

coverage, the immunization program, and the safety and immunogenicity of the 2009 H1N1 

vaccines. Their second major topic regarded vaccine recommendations for the upcoming 

influenza season. In the proposed 2010–2011 season recommendations, there are new 

vaccine strains in the vaccine as determined by WHO and FDA over the past few days. There 

are new age indications and formulations for some of the currently licensed vaccines, which is 

good news. There is also the newly licensed vaccine, Fluzone® High-Dose trivalent inactivated 

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Advisory Committee on Immunization Practices (ACIP) Summary Report February 24-25, 2010 

vaccine. The work group has particularly focused on which children should receive two doses, 

and whether there should be a universal recommendation for adults. 

The overall objectives for 2009 H1N1 vaccine safety monitoring that were developed before the 

vaccine was rolled out were as follows: 

Identify clinically significant adverse events following receipt of 2009 HINI vaccine in a timely 

manner 

Rapidly evaluate serious adverse events following receipt of 2009 H1N1 vaccine and 

determine public health importance 

Evaluate if there is a risk of Guillain-Barré syndrome (GBS) associated with the 2009 H1N1 

vaccine 

Communicate vaccine safety information in a clear and transparent manner to healthcare 

providers, public health officials, and the public 

As part of this, the H1N1 VSRAWG was formed and reported to NVAC. Its purpose was to 

conduct independent, rapid reviews of available federal immunization safety monitoring data for 

the 2009 H1N1 influenza vaccines. It was comprised of 8 members from various federal 

advisory committees, the IOM, and the public. VSRAWG met every two weeks and reported to 

NVAC. Other federal agencies (e.g., BARDA, CDC, DoD, FDA, HIS,VA and NVPO) contribute 

scientific expertise and data, and NVPO coordinates these activities [Acknowledgment: Claudia 

Vellozzi and colleagues Immunization Safety Office]. 

Reports have been submitted to NVAC approximately every month. The last report available is 

from January 20, 2010 from which Dr. Fiore shared the following quote: 

“Working Group concluded that the data are adequate to assess the presence or 

absence of a signal. Additionally, the Working Group concluded that the data do not 

favor a signal between the outcomes examined and the H1N1 vaccines. A signal is 

defined as an event that could be temporally occurring more often after vaccine receipt 

than anticipated by chance alone.” 

This is good news, and additional good news is anticipated in the next report to the NVAC due 

to be submitted within the week or two following this ACIP meeting [January 20, 2010 (next 

update available Feb 26, 2010); available at http://www.hhs.gov/nvpo/nvac/reports/ 

2010vaccinesafetyreport.html. Acknowledgment: Claudia Vellozzi and colleagues Immunization 

Safety Office]. 

In terms of the immunogenicity of influenza A(H1N1) 2009 monovalent vaccines, after 1 dose, 

hemagglutinin inhibition (HI) titers considered to be protective (40) develop in 93% to 98% of 

older children and adults; 72% to 93% of children 3 years through 9 years of age; and 45% to 

92% of children ages 6 months through 35 months. After 2 doses, >90% of infants and young 

children develop antibody response considered to be protective [Data sources: Greenberg N 

Engl J Med 2009; Nolan JAMA 2009; Plennevaux Lancet 2009; Arguedas NEJM 2010]. The 

work group concluded that the safety profile appears to be similar to seasonal vaccine based on 

the data thus far, and that the immunogenicity is similar to or better than the seasonal vaccine in 

all age groups. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report February 24-25, 2010 

The second the work group addressed was the recommendations for the upcoming influenza 

season. As reported earlier, the vaccine strain recommendations for 2010-2011 seasonal 

influenza vaccines is as follows [FDA. Vaccines and Related Biological Products Advisory 

Committee meeting, February 24, 2010]: 

An A/California/7 2009 (H1N1)-like virus 

Æ

Æ

Æ

Æ

Æ

Æ

Æ

Æ

Same strain as in the 2009 H1N1 monovalent vaccine 

An A/Perth/16/2009 (H3N2)-like virus 

New strain for N Hemisphere vaccine 

Same strain as 2010 S hemisphere seasonal vaccine 

A B/Brisbane/60/2008-like virus 

No change from last season 

New seasonal influenza vaccines and age indications include the following: 

Newly licensed standard dose vaccine 

Novartis: Agriflu (18 years and older) 

New age indications 

CSL: Afluria (6 months and older) 

GSK: Fluarix (36 months and older) 

New higher dose inactivated vaccine 

Sanofi: Fluzone High Dose (65 years and older) 

With regard to the new Fluzone® High-Dose by sanofi pasteur, the Influenza Vaccine Work 

Group agrees that compared to standard dose inactivated vaccine, Fluzone® High-Dose has 

equal or superior immunogenicity. While there was a slight increase in local reactogenicity 

among seniors, these reactions were mild and self-limited. Licensure expands options for 

adults 65 or older. Persons 65 years or older and their providers can choose any of the 

currently licensed inactivated vaccines, including Fluzone® High-Dose. A pivotal vaccine 

effectiveness trial of High-Dose versus Standard-Dose is underway. 

So for the 2010 – 2011 vaccine recommendations for young children, Dr. Fiore described some 

of the discussions held by the influenza vaccine workgroup regarding vaccination of children 

ages 6 months through 8 years. 

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Æ

Æ

Æ

Æ

Æ

Æ

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Advisory Committee on Immunization Practices (ACIP) Summary Report February 24-25, 2010 

No changes are proposed for the 2010-2011 influenza vaccine recommendations for children 

ages 6 months through 8 years. These currently are as follows: 

All children aged 6 months through 18 years should be vaccinated annually 

Children and adolescents at higher risk for influenza complications should continue to be a 

focus of vaccination efforts, including those: 

aged 6 months through 4 years; 

who have chronic pulmonary (including asthma), cardiovascular (except 

hypertension), renal, hepatic, cognitive, neurological, neuromuscular, hematological 

or metabolic disorders (including diabetes mellitus); 

who are immunosuppressed (including immunosuppression caused by medications 

or by human immunodeficiency virus); 

who have any condition (e.g., cognitive dysfunction, spinal cord injuries, seizure 

disorders, or other neuromuscular disorders) that can compromise respiratory 

function or the handling of respiratory secretions or that can increase the risk for 

aspiration; 

who are receiving long-term aspirin therapy who therefore might be at risk for 

experiencing Reye syndrome after influenza virus infection; 

who are residents of chronic-care facilities; and 

who will be pregnant during the influenza season. 

Note: Children aged <6 months cannot receive influenza vaccination. Household and 

other close contacts (e.g., daycare providers) of children aged <6 months, including 

older children and adolescents, should be vaccinated. 

With respect to the number of vaccine doses for children ages 6 months through 8 years old, 

previous studies indicate that children <9 years old should receive 2 doses in the current 

season if they have never received trivalent vaccine before; or if they only received 1 dose last 

season and it was the first time they had ever been vaccinated. Children <9 years old who have 

been vaccinated in a year before last season (e.g., 2008-09 or before) receive 1 dose annually. 

The need for two doses is believed to be due to the need for a priming dose followed by a 

booster. Many children <9 years old lack previous experience with influenza or influenza 

vaccine. Seasonal vaccine coverage among young children is low (<25%). Many, perhaps 

most, young children enter each season recommended for 2 doses because they have never 

been vaccinated. 

For the upcoming influenza season, the 2009 H1N1-like virus is expected to continue to 

circulate. Thus, the question remains with respect to how many doses of the 2010-2011 

seasonal vaccine a child should receive who did not receive any of the monovalent vaccine 

doses. Following considerable discussion over the past few weeks, the work group concluded 

that at this point, they do not recommend a changed in the current recommendations. The 

reason for this decision is that it is not urgent to make a decision at this time. Most children are 

not affected because they are either due for two doses anyway or received monovalent 

vaccine(s). More data to inform the decision likely to be available within 3 months include 

additional analyses from the immunogenicity studies, updated monovalent and seasonal 

vaccine coverage data, the potential for additional seroprevalence and epidemiologic data, and 

the potential for a decision analysis approach. This allows more time for additional work group 

discussion and, if needed, a vote during the June 2010 ACIP meeting and to harmonize these 

issues with CDC’s partners. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report February 24-25, 2010 

Regarding the 2010-2011 influenza vaccine recommendations for healthy adults 19 through 49 

years old, an estimated 50% already have an indication for annual vaccination, including the 

following: 

Women who will be pregnant during influenza season and their contacts 

Persons who are contacts of 

Children younger than 5 years old 

Adults 50 and older 

Children and adults with chronic medical conditions that confer higher risk of influenza 

complications 

 Healthcare workers 

There has been a longstanding permissive recommendation for “Anyone who wants to be 

vaccinated.” Nevertheless, there has been low coverage among 19 through 49 year olds 

regardless of their indication for vaccination. Healthcare worker coverage has also been low. 

There is some evidence that coverage is low among persons who are contacts of high risk 

persons, and coverage of pregnant women has been notoriously low in the 15% to 20% range 

for many years. At this point, only about 15% of the population does not have an annual 

indication for vaccination. Conversely, 85% of the population has an annual indication. 

Over the past several months, the work group has considered a number of critical factors 

regarding expanding the annual vaccination recommendations to include all adults ages 19 

through 49 that were raised during the October 2009 ACIP meeting, including: vaccine supply 

(excess vaccines in recent seasons), vaccine safety (severe adverse events are rare in young 

healthy adults), vaccine effectiveness (50% to 90%, depending on match / season), disease 

burden (lower burden of hospitalizations and deaths compared with older adults / young 

children; similar to adolescents; estimated 0.5 to 2.5 days work lost per illness), costeffectiveness (unlikely to be cost-saving; $/QALY and $/illness averted are influenced by 

vaccination cost / administration venue—most expensive in physician offices, work loss 

estimate; similar to costs for older adolescents), feasibility (no VFC equivalent; potential for 

workplace interest), acceptability, and implementation [Source: Workgroup Discussions May 

through September 2008]. 

Acceptability continues to be a poorly understood factor of why people in this age group do not 

get vaccinated. Studies indicate that lack of concern about influenza risk and excessive 

concern about vaccine safety are primary reasons for adults not getting vaccinated among 

those currently recommended for vaccination, including health care workers. More information 

is needed on what could better inform adults who are reluctant to be vaccinated. Many adults 

with a vaccine indication do not know they should be vaccinated. With respect to timing, there 

were some rapid recommendations changes (including the childhood universal indication voted 

in that year) and persistent low coverage in all recommended groups except the elderly. There 

was some concern that focus might be lost on those at higher risk for complications. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report February 24-25, 2010 

The work group was also looking forward to some preliminary evaluation of expansion to 

school-aged children needed. No change was proposed in the recommendations for healthy 

adults ages 19 through 49 in October 2008, which were as follows: 

No change in recommendations for healthy adults ages 19 through 49 year old at that time 

Continued support for routine vaccination of contacts of persons at risk for influenza 

complications, including healthy adult contacts of: 

Persons 50 years old or older 

Persons younger than 5 years old 

Pregnant women 

Persons with chronic medical conditions 

Continued support for permissive recommendation: any healthy adult who wants to be 

vaccinated should be vaccinated 

With regard to why the work group was raising the issue of vaccination recommendations for 

healthy adults ages 19 through 49, the primary impetus was the issues raised by the 2009 

H1N1 pandemic. During the 2009 H1N1 pandemic, an estimated 87% of hospitalizations and 

deaths were among those <65 years old, including many among 19 through 49 year olds. 

There was an unprecedented demand for seasonal and 2009 H1N1 monovalent vaccines. 

Many new immunization programs were instituted that vaccinated adults. The 2009 H1N1 

vaccination was targeted for 19 through 24 year olds during the time of limited vaccine 

availability. The 2009 H1N1-like virus is likely to continue circulation in the 2010-2011 season. 

The proportion of healthy adults now immune to the 2009 H1N1 pandemic virus is unknown. 

The 2009 H1N1-like virus will now be in 2010-11 seasonal vaccines. There is a possible new or 

newly recognized medical risk factor for influenza complications of obesity / morbid obesity. 

There were a disproportionate number of obese, particularly morbidly obese, patients among 

the severely ill during the 2009 H1N1 pandemic. This was found to be an independent risk 

factor for severe illness in one unpublished analysis. Most (60-80%) obese or morbidly obese 

with influenza complications (hospitalization or death) had chronic medical condition(s). In the 

US adult population, 28% of adults are obese and 5% are morbidly obese. 

Another observation was that influenza-related complications differed by race / ethnicity AfricanAmericans and Hispanics experienced higher hospitalization rates. American Indians and 

Alaska Natives had a four-fold increased mortality compared with other racial and ethnic groups 

during 2009 pandemic in 1 study [MMWR Dec 2009]. The reasons for the differences are 

uncertain but might include differences in prevalence of underlying medical conditions and 

obesity, differences in medical care, and / or race / ethnicity based differences in influenza 

pathogenesis. These differences require further study. 

Based on the information available and the work group discussions, the work group considered 

the following 5 options for the influenza vaccine recommendations for adults 19 through 49 

years old: 

1. No change 

2. Add new possible risk factor indications 

3. Provisional new risk factor indication(s) for 2010-11 season; re-evaluate later 

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4. Provisional universal recommendation for 2010-11 season; re-evaluate later 

5. Universal recommendation: Two sub-options 

a) Full implementation immediately in 2010-11, or 

b) Phase-in: 2 stage as was done for universal childhood recommendation 

1) Begin vaccinating all adults in 2010-11 season where feasible, with special efforts to 

reach adults with newly recognized risk factors 

2) Full implementation 2011-12 season 

The work group discussed this on several calls and voted amongst themselves to determine 

where they stood. No one favored the status quo (e.g., no change), incremental addition of new 

risk factor indications, or provisional recommendations. All favored advancing to a universal 

recommendation, with the discussion focused on immediate implementation versus phased in 

implementation over two influenza seasons. The rationale for a recommendation to vaccinate 

all people ages 6 months or older included several considerations. Annual influenza vaccination 

is a safe and effective prevention measure that provides a potential benefit for people in all age 

groups. Morbidity and mortality occurs in all age groups, including among adults aged 19 

through 49. Some persons who have influenza complications have no previously identified risk 

factors, or have risk factors but are unaware that they should be vaccinated. A recommendation 

that all people ages 6 months or older receive an annual influenza vaccination eliminates the 

need to determine whether each person has an indication for vaccination; emphasizes the 

importance of preventing influenza across the population spectrum; and reduces potential 

barriers to increasing the number of persons protected from influenza, including lack of 

awareness about vaccine indications among persons at higher risk for influenza complications 

and their close contacts. 

While a universal vaccination recommendation for adults would be proposed, in order to 

maintain emphasis on those at higher risk for influenza complications, the work group also 

proposed to include last season’s recommendation for those at higher risk of complications from 

influenza, which reads as follows: 

 Certain people should continue to be a focus of vaccination efforts, because they are at 

higher risk for influenza complications, or are close contacts of persons at higher risk, 

including: 

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children aged 6 months through 4 years 

adults aged >50 years; 

women who will be pregnant during the influenza season; 

persons who have chronic pulmonary, cardiovascular, renal, hepatic, neurological, 

neuromuscular, hematological or metabolic disorders; 

persons who have immunosuppression (including immunosuppression caused by 

medications or by human immunodeficiency virus); 

residents of nursing homes and other chronic-care facilities; 

health-care personnel; 

household contacts and caregivers of children aged <5 years and adults aged >50 

years, with particular emphasis on vaccinating contacts of children aged <6 months; and, 

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Emphasis will also be placed on possible new risk factors for influenza complications, with the 

following language proposed: 

 Preliminary data indicates that certain persons had higher rates of influenza-related 

complications such as hospitalizations or deaths during the 2009 pandemic. The cause(s) 

of this increased risk for influenza complications is under investigation, but likely includes an 

increased prevalence of medical risk factors in these persons. Medical risk factors might be 

present but not known to the patient or provider. Immunization providers and programs 

should emphasize vaccination for these persons as well as those with known medical risk 

factors: 

Æ Adults who are obese (BMI30), particularly those who are morbidly obese (BMI40) 

Æ Adults who are African American, Hispanic, American Indian, or Alaskan Native 

The following options were proposed for a vote for a universal recommendation: 

 Option 1: Vaccinate all adults beginning with the 2010-11 season. 

 Option 2: Annual vaccination of all adults should begin in September or as soon as vaccine 

is available for the 2010-11 influenza season, if feasible, but annual vaccination of all adults 

should begin no later than during the 2011-12 influenza season. 

Work group members who favored phased in approach believed the approach was effective for 

the childhood universal recommendation. They were concerned that immediate implementation 

would create new additional demands on programs with insufficient notice. They were also 

concerned that vaccine pre-booking had already occurred and might lead to demand exceeding 

supply for some providers and programs. Those who favored immediate implementation 

believed that because 2009 H1N1-like viruses would likely continue to circulate in 2010-11, they 

would continue to cause increased morbidity among young adults, including those who do not 

currently have a vaccine indication. They were troubled by the phase-in approach because it 

does not fully address the problem that persons at risk may not self-identify until 2011-12. They 

were also concerned that such an approach would add complexity, and that it would not fully 

take advantage of opportunities created by programs developed during the pandemic, and new 

interest in vaccination among younger adults. 

Discussion 

Dr. Baker inquired as to whether Dr. Fiore had information regarding how many people ages 19 

through 49, either by occupation or parenting, are around infants less than 6 months of age and 

how many obtain influenza vaccine. A cocoon has been recommended for years for those 

babies who cannot be vaccinated. Many of the parents are in this age group, but it is not clear 

that they even know that they should be immunized for influenza. 

Dr. Fiore replied that it would be somewhat hard, particularly before this season, to identify 

some of the contact indications. As he recalled, Dr. Singleton’s data showed coverage of 20% 

to 25%, which is striking because that was a sub-prioritization group that was recommended for 

vaccination from the outset. 

With regard to communications if a universal recommendation is made, Dr. Baker suggested 

that this those in this age group who are around infants under 6 months of age should be 

targeted to motivate them to get vaccinated to help protect these young children. 

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Dr. Lett reported that the Association of Immunization Program Managers (AIPM) conducted a 

survey to determine Program Managers’ beliefs about these options. Though not unanimous, 

there was fairly overwhelming support for Option 2 (75%). A number of Program Managers 

submitted comments about their concerns. There has been a lot of success with H1N1, but 

there was a lot of infrastructure funding available to support that success in terms of payment 

for vaccine administration and the vaccine itself being free. This type of funding will not be 

available in the future, and if there is not support in the private sector for this beyond what can 

be reimbursed, it is going to place burdens on the public sector. Many state and county health 

departments purchase and provide a lot of influenza vaccine for adults. Pre-booking has 

occurred, and most Program Mangers are concerned that the supply will not be sufficient to 

meet the demand. They are skeptical that if supplies are not sufficient to meet the demand or 

that there is another delay, ACIP should at least have a back-up of prioritization should that 

occur. A number of groups have plans to use what resources they do have to purchase vaccine 

for school-based immunization efforts this season. However, a considerable amount of support 

will still be needed for training and vaccine administration. 

Ms. Ehresmann added that in an ideal world in which an adult vaccine infrastructure already 

existed, implementing a universal vaccine could be done immediately and likely with few 

challenges. However, because it is not an ideal world, she thought they needed to make the 

decision to move forward on universal vaccination in the absence of that, but her hope was that 

with this type of recommendation and in light of all of the other recommendations that ACIP has 

made for adults, that this will start to drive funding and emphasis for formal adult vaccination 

programs. One of the questions in their background documents was: We have made these 

recommendations for adults. Why are they not happening? While she did not think federal and 

state programs were a panacea, some they are the glue that is needed to coordinate these 

programs. In the absence of that, it is difficult to be successful. She wanted to acknowledge 

what Program Managers have said, but also wanted to use this as a platform to promote the 

idea of moving toward a stronger adult program once the vote is made. Some Program 

Managers did believe that universal vaccination could move forward immediately. In some 

ways, with H1N1, they had a painful but good year in which they reached out to providers they 

had not worked with in the past. They should build on that going forward. 

Dr. Judson took the other side for Option 1. He thought they had practiced creeping and 

staging for the last 10 to 15 years, and if there was any evidence that enhancing or enlarging 

the group for whom vaccines were recommended detracted from achieving other goals of 

previously recommended target groups, then it would be a reasonable argument to select 

Option 2. Or, if there were any evidence that clearly and consistently demand was exceeding 

supply, they would have to consider Option 2. There are now a large number of suppliers with 

ample capacity to produce a large number of vaccines; therefore, supply is not likely to be a 

long-term, consistent problem. There are only 15% of people for whom influenza vaccine is not 

recommended. From an administrative standpoint, it is often more costly and difficult to try to 

sort out the 15% for whom the vaccine is not recommended than to simply offer it to everyone. 

In speaking to people at Kaiser, this is the way they view it. H1N1 was great because they had 

an excess supply and they offered to everyone who came through their doors. 

Dr. Baker clarified that her question about the percent of those 19 to 49 years of age who are 

around young children was to try to tease out what proportion of those people should be getting 

vaccinated. 

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Dr. Meissner reminded everyone that when ACIP made the phase-in recommendation for 

children, similar wording was utilized. There was very consistent feedback from pediatricians 

who had no idea how to interpret that sort of recommendation. Thus, they waited until the next 

year. Therefore, he favored Option 1. 

Dr. Neuzil said she also strongly favored Option 1. She did not believe that waiting a year 

would solve the adult immunization problem. Therefore, they should move ahead. In 

recognition of the very practical challenge raised about pre-booking, she suggested to the 

manufacturers that they consider extending the pre-booking period. This has been a very 

exceptional year from which people are still reeling. The hope is that providers are still 

administering monovalent pandemic vaccine. That would be a wonderful gesture as they herald 

universal influenza immunization in this country to extend the pre-booking period. 

Dr. Englund reported that their pediatricians welcomed the fact that they had a year to plan. 

Their hospital worked with community practitioners to set up evening and Saturday clinics. 

They got buy-in from practitioners to administer vaccination in the hospital away from the 

primary medical home. That helped them very much to prepare for the H1N1 outbreak. Given 

the administrative logistical issues, she favored Option 2. 

Dr. Neuzil added that in adults this is already done. She got her vaccine at Safeway, and her 

oldest son got it in O’Hare Airport. Adults are much more comfortable with that already. 

Dr. Pickering read Dr. Poland’s (ACP) comments into the record, given that he was unable to 

attend. They were as follows: Our vote today is both historic and personally gratifying! Historic 

in that a universal recommendation for flu vaccine in all adults brings this into line with all other 

vaccines for respiratory viruses—that of universal use! Historic too in that we have moved over 

the many decades we have had this vaccine from very limited use, through the latest period of 

creeping incrementalism where nearly every year brought another indication, to finally 

recognizing the need for and simplicity of a universal recommendation. Personally gratifying in 

that I first began advocating for this 26 years ago! In these nearly 3 decades, I’ve given 

hundreds of talks on the topic and published these views in the peer-reviewed literature. An 

Olympic effort! All this reached a “tipping point” in the late 1990s and early 2000s when I was 

an ACIP member. At that time I introduced the idea, and called for a vote. There was mostly 

solid support for the recommendation, but concerns over vaccine supply. Over those 

intervening years, use of the flu vaccine in younger adults did not increase, and every year tens 

of millions of doses of vaccine went unused and wasted. Most of these concerns I would 

characterize as “trying to drive into the future by looking through the rear view mirror.” I raised 

the issue again during Dale Morse’s 2006-2009 tenure as Chair of ACIP, this time garnering 

more support as more recognized the significant morbidity of influenza in younger adults, 

significant loss of schools and work time and productivity, an adequate vaccine supply, and the 

desire by clinicians for a simpler and more practical approach. Dale vowed to get this passed 

before the end of his tenure. No one can easily recall the 20-some odd current indications that 

ironically cover all but 15% of the population already! So thank you! Thank you on behalf of the 

physicians and professional societies who take care of and who advocate for the health of 

adults. Now the word needs to go out—without ambivalence—that influenza is a serious 

infection, it can be prevented safely and effectively by vaccine, and the vaccine is 

recommended for ALL! FINALLY! 

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Dr. Foster (APhA) reported that when pharmacies first began administering vaccines about 

three years ago, the statistics were that pharmacies administered about 7% of the vaccines. 

This year they administered 10% even though they did not receive vaccine until late in the 

season. He thought if pharmacy had access, they already have the infrastructure to increase 

adult immunization. Most of the adults in this age group do not present to physicians anyway. 

Most of them are seen in emergency departments (ED), so if they could increase the rates of 

vaccines administered there, that would be beneficial as well. When pharmacies turned people 

away this season because they did not have vaccine, they did not return later to acquire the 

vaccine. They could not give the vaccine away after that point. He knew of one facility that 

would soon be throwing away 300 doses because it would expire March 1. Therefore, he highly 

encouraged voting for Option 1. 

As Co-Chair for the Vaccine National Influenza Summit, which is an organization that represents 

about 130 national partners in influenza, Dr. Tan (AMA) reported for the record that in 2005 the 

Summit voted on this and urged that ACIP move toward a universal recommendation as soon 

as possible. 

Dr. Sawyer commented that he is the ACIP member who sits on the NVAC Safety Committee 

that is reviewing H1N1 safety. As reported earlier, there has been absolutely no signal to data 

to raise any concern. They should take this opportunity to assure the public that in the coming 

season that at least that component of the vaccine is very safe. He also supported Option 1 for 

this and all of the other reasons stated in favor of this option. 

Dr. Fryhofer (ACP) also agreed with Option 1 for the reasons that had been mentioned. She is 

also a practicing physician, and she thought this would be much simpler. With Option 1, 

physicians will not have to figure out who can receive vaccine now, who has to come back later, 

et cetera and there is typically vaccine left over. By voting for Option 1, they can protect 

everybody. 

Dr. Turner (ACHA) also expressed support for Option 1. He thought it tragic that for the last 

couple of years millions of doses of unused influenza vaccine have been thrown away. He 

heard earlier that 21 million doses of H1N1 vaccine were sitting in a warehouse currently. He 

pointed out that the manufacturers had “stepped up to the plate” and delivered supply, and that 

they needed to create demand. In due respect to the providers worried about not having the 

infrastructure, the way to build infrastructure is to create demand. If there was unmet demand, 

they could probably argue with their financial supporters that more infrastructure is needed. 

Ms. Ehresmann inquired as to whether there were any data regarding how much of the 

seasonal influenza vaccine was utilized. With the universal recommendation, she wondered if 

they would continue in a shortage situation to revert to using priority groups from the past or 

maintain a universal recommendation. 

Dr. Baker replied that all of the seasonal vaccine was utilized. 

Dr. Fiore responded that they could describe how much vaccine was distributed, but they lose 

track of the ability to know whether vaccine was actually all utilized once it was out. Certainly, 

seasonal vaccine supply was tight at one point in the Fall due to the demand generated by the 

pandemic. He heard of vaccine availability in the last month or two that he assumed would go 

unused. He thought less would be thrown away this season than in the past. In terms of what 

would occur in a shortage, Dr. Fiore thought they would probably revert to the priority groups 

discussed during the 2004-2005 shortage. However, this would depend upon the formulations 

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for which there were shortages and would have to be addressed at the time they became aware 

of a shortage. 

Dr. Schuchat added that they are basically virtually out of seasonal influenza vaccine. 

Dr. Baker reminded everyone that in the shortage year, high demand was created, but millions 

of doses were ultimately thrown away. 

Dr. Morse stated that approximately four years ago as a rookie or novice ACIP member, he had 

the humbling experience of being on the wrong but arguably the right side of Greg Poland who 

made an unexpected, unscripted, but passionate motion to by-pass a phase-in approach and go 

directly to a universal recommendation for influenza recommendation. As he recalled, Dr. 

Morse was sitting where Dr. Sumaya was sitting today when the vote reached him 6 to 2 or 7 to 

1 in favor and he felt obligated to vote “no” and there ended up being a 7 to 8 vote against the 

motion. Dr. Morse voted “no” not because he did not support the concept, but because he was 

concerned that there had not been an adequate scientific base vetting of the proposal. Coming 

on the heels of the vaccine shortage of 2004-2005, he also felt that without careful planning 

there could be unintended consequences of vaccinating health individuals creating an iatrogenic 

shortage among high risk populations with accompanying increased morbidity and mortality. 

That day was the wrong place, the wrong day, the wrong time. However, the goal was the right 

one. Since then, ACIP has used scientific evidence to systematically inch closer to a universal 

recommendation. Based on that progress, two years ago in February 2008, as Chair Dr. Morse 

urged the ACIP Influenza Work Group to speed up the original proposed time table that 

stretched out until 2013 by continuing discussions and bringing back recommendations with a 

vote within a year, hoping that the phased-in approach for universal vaccine, which began in 

early 2000 would be accomplished during his tenure and by the end of the decade similar to the 

US’s previous success to reach the moon. The work group delivered the review as requested 

and provided sufficient science-based evidence to support such a recommendation as Dr. Fiore 

outlined earlier, but stopped short of a universal recommendation because of remaining 

feasibility and implementation questions. Dr. Morse’s personal opinion was that during this 

session, a strong case for a universal influenza vaccination had been made stronger based on 

more complete science-based evidence and increased feasibility that came from the 

implantation experience during the 2009 H1N1 pandemic. While they still have not reached the 

levels of immunization that they would like, ACIP has the opportunity to build upon the 

momentum gained over the past year. They must remember that this is a marathon—not a 

sprint. As with smoking cessation programs, it will take persistent to make progress. If they 

could not make the case for universal influenza immunization now, when could they? Either 

Option 1 or 2 would get them to where they needed to be, but he favored Option 1 because it 

would get them there quicker. He initially leaned toward Option 2, but this would seem to ignore 

the potential for 2009 H1N1’s return. The evidence for increased risk among certain 

populations (e.g., obese / morbidly obese; racial / ethnic groups) also warrants a stronger 

recommendation for the upcoming year. It would seem that Option 2 would first need to make a 

strong recommendation to add these high risk groups and phased-in encouragement for the 

rest, which would again add complexity to an already confusing picture. This is further 

complicated by what to do with the 19 to 24 year old age group. H1N1 is still circulating and a 

number of individuals in this age group are still not covered. When all of these groups are 

added together, the picture is almost completed anyway. Why not go for the gold instead of 

settling for the bronze. From his perspective, this was the right place, the right day, and the 

right time. It’s Poland time. While such an accomplishment did not occur within his or Dr. 

Poland’s ACIP tenure, given that the first expansion occurred in 2000 and this was 2010, on a 

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technicality the recommendation could still be successfully adapted within a decade. Dr. Morse 

concluded that “The goal and the moon are still within our reach. Let’s grab it.” 

John Redd (IHS) indicated that the IHS supports universal adult recommendation and plans to 

implement it with great vigor. However, they wanted to point out that with either option, they 

would like American Indians / Alaska Natives included as a general high risk group which has 

great impact in settings of vaccine scarcity and for priority. He wanted to get this on the record 

because they have observed disparate impact for influenza in American Indians / Alaska 

Natives through the entire spectrum of disease (e.g., outpatient illness to death). In an MMWR 

report in December 2009, 12 states were discussed that are American Indian / Alaska heavy. 

These states included more than 50% of the American Indian / Alaska Native population in the 

country, so those data were considered to be very helpful. The disparities observed in the 

entire range of influenza illness have occurred in this past season despite quite good 

vaccination coverage through IHS. Their coverage ranged from approximately 23% to 24% for 

H1N1 for the monovalent vaccine to over 40% in the pediatric population (6 to 59 months). The 

disparity that impacted Native Americans / Alaska Natives is partially accounted for by the 

presence of risk factors for morbidity and mortality. However, there are no models in which 

disparities have been entirely accounted for by risk factors. 

Regarding the percentage of people in the 19 to 49 year old age group, Lt. Col. (Dr.) Philip 

Gould (Office of the Air Force Surgeon General) reported that the Air Force has been tracking 

high risk groups for the last three years. This past season, seasonal influenza coverage as of 

the week before the ACIP meeting was approximately 30% for this with children and slightly 

higher at 40% for pregnant women. H1N1 was slightly higher by about 5% in both of those 

groups. Regarding whether they are in the 19 to 49 year old age group, these could also be 

family members in attendance of those small children as well. He can supply that breakdown to 

ACIP. 

Kelly Moore (Tennessee Immunization Program) strongly supported Option 1. They would like 

to continue to sustain the momentum gained from 2009 H1N1, knowing that many in that age 

group were not vaccinated against 2009 H1N1 and remain at risk in the coming season from the 

same virus that has disproportionately affected them. They also understand that other states 

feel a greater degree responsibility than Tennessee does for covering adults, but many states’ 

immunization programs are focused on the VFC-eligible population and are not in public health 

primarily responsible for meeting the needs of adults. Until Option 1 is vote on, there is nothing 

to present to legislators to argue for funding and infrastructure to meet those needs. These 

adults are unlikely to be vaccinated with an optional recommendation, unlikely to be seen in 

doctors’ offices, and are still at risk from 2009 H1N1. With that in mind, Tennessee supports 

Option 1. 

Steve Allred (GetAFluShot.com) added that another reason to favor Option 1 is that a major 

obstacle to increasing vaccinations in the US is insurance coverage. Many insurance 

companies have high deductibles, exclusions, or co-payments that apply vaccinations. 

GetAFluShot.com administers tens of thousands of influenza vaccinations in worksites every 

year. When influenza vaccination is covered by the insurance company, 2 to 4 times as many 

people participate in vaccinations than if people have to reach into their own pockets to pay for 

vaccine. A universal vaccination may not be a panacea, but it will put pressure on insurance 

companies, hopefully supported by other means as well, to eliminate this very important barrier 

to vaccination. 

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Dr. Baker said she thought that CDC and its many partners had done a wonderful job of 

communication this season with H1N1. The public is much better informed, and can continue to 

be much more informed about how serious influenza is, especially in young, seemingly healthy 

people. The previous week, she cared for a 140 kilo 12-year old who needed an MRI and could 

not fit in their machine. She was told by the child’s mother that she was “just a big girl.” 

Calculating BMI and helping people to understand this is another communication issue that 

could be very useful in a positive way. Dr. Baker congratulated CDC for the improved 

communication efforts, and emphasized the importance of building upon that. 

Dr. Keitel inquired as to whether there could be any emphasis placed on encouraging 

monovalent vaccine, given that there is still in the warehouses. 

Dr. Baker replied that this would probably not be a component of the vote, but they could 

discuss it further subsequent to the vote. 

Motion: Universal Adult Influenza Vaccination 

Dr. Sumaya made a motion to approve Option 1: Vaccinate all adults beginning with the 2010­

11 season. Ms. Ehresmann seconded the motion. The motion carried with 12 affirmative votes, 

1 abstention, 0 negative votes, and thunderous applause. 

Discussion 

Given the vote for universal influenza vaccination, Dr. Fiore indicated that Dr. Santoli’s 

presentation and a VFC vote would not be necessary. 

Regarding Dr. Keitel’s suggestion pertaining to the vaccine remaining in the warehouses, Dr. 

Baker did not believe a vote was needed. The messaging from all partners and CDC has been 

to encourage / recommend continued H1N1 immunization. During the 1968 pandemic, Dr. 

Baker was infected and was quite ill during the third wave. Therefore, she thought it was too 

soon to know whether there would be more disease. That has been a very clear communization 

message from partner organizations, liaison organizations, and CDC. 

Dr. Schuchat responded that CDC has been working with state health departments the CDC 

communications team to sort through the best way to message how vaccine should continue to 

be used. Key points are that the virus continues to circulate and illness, hospitalizations, and 

deaths continue although the rates of disease are lower than observed in the Fall of 2009. A lot 

is now known about the vaccine in terms of safety, which CDC believes will be reassuring to 

many. Continuing to make vaccine available and accessible to people makes a lot of sense. 

These are the components of CDC’s key package of messaging they are trying to communicate. 

Dr. Baker reminded everyone that work group meetings would begin at 6 PM. With no further 

business posed, she officially adjourned the first day of the meeting. 

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Discussion

Discussion

Advisory Committee on Immunization Practices (ACIP) Summary Report February 24-25, 2010 

Day 1 : Public Comments 

No public comments were offered during the first day of the meeting. 

February 25, 2010 

Welcome / Unfinished Business 

Dr. Carol Baker 

Chair, ACIP 

Dr. Baker called the meeting to order and welcomed those present. She indicated that there 

was no unfinished business carried over from the previous day, and that while no public 

comment session was held during the first day because no one signed up, there would be a 

public comment session at the end of the presentations for the second day. 

Agency Updates 

Centers for Disease Control and Prevention (CDC) 

Dr. Anne Schuchat indicated that the next National Immunization Conference will be convened 

in Atlanta on April 19-22, 2010. She welcomed everyone to register for and attend that meeting. 

With regard to the stimulus program, the American Recovery and Reinvestment Act (ARRA), 

$300 million was designated for immunization strengthening. An innovative component of that 

funding is focused on strengthening the laboratory detection of vaccine preventable diseases. A 

series of training courses for public health laboratories have been on-going, with recent training 

for mumps and pertussis diagnostics. These courses have been extremely popular, wellreceived, and a great use of the one-time ARRA resources to help improve capacity. In 

addition, she noted that the members were provided with a small card at their tables. For years 

there have been discussions regarding challenges with provider / parent interactions pertaining 

to vaccines in terms of trying to better address parents’ concerns and improve the office visit 

experience. CDC has been working with the American Academy of Family Physicians (AAFP), 

the American Academy of Pediatrics (AAP), and communication experts to develop a suite of 

materials that have been posted on the web and continue to be rolled out. She expressed her 

hope that everyone would offer feedback, and that they would make these tools known so that 

providers can address this important gap. 

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Centers for Medicare and Medicaid Services (CMS) 

Linda Murphy reported on the status of the administration rates. The rates are under review, 

and had made it to the highest level at the time of this ACIP meeting. She expressed her hope 

that they would soon be published in the Federal Register. 

Discussion 

Dr. Chilton requested information regarding progress with respect to reimbursement for multiple 

component vaccines. The American Academy of Pediatrics (AAP) news included an article a 

few months ago stating that as of January 1, 2010 reimbursement will be based on the number 

of individual components in vaccines rather than on the number of vaccines per se. 

Ms. Murphy responded that CMS did not make this determination; however, some individual 

states have determined that they are going to have a sliding scale of administration fees based 

on the number of antigens in the immunization. CMS has permitted this. The new schedule will 

still allow for this, but there is going to be more flexibility for states. CMS only states that if it is 

medically feasible to administer all antigens in one shot, they must do so. If providers are 

charging for three separate shots (MMR for example), they cannot do this. They can only 

charge for the one shot. Some of the states have said that single antigen is one amount, two 

antigens are $2 more, and three antigens are $3. CMS has also allowed this. 

In response to Miss Murphy’s comments, Dr. Katz indicated that he checked with Dr. Feinberg 

to be certain and learned that Merck no longer manufactures monovalent MMR. 

Dr. Murphy thanked Dr. Katz for the update, clarifying that MMR was just an example that they 

had used for years. 

LJ Tan, AMA announced that effective in 2011, there will be new Current Procedural 

Terminology (CPT) codes that will be based on the antigen content of the vaccine. 

Department of Defense (DoD) 

Dr. Wayne Hachey reported on the policy of mandatory immunization for all active duty 

members for both seasonal and pandemic flu vaccines. As of the previous week, the seasonal 

influenza coverage was 92% of DoD’s population. For novel H1N1, their coverage rate was 

82% and climbing. The DoD’s Vaccine Safety Surveillance Network (VSSN) now has well over 

a million people enrolled. Like CDC, they have identified no increased signals. The Naval 

Health Research Center in San Diego, which was the first to identify the novel H1N1 virus, also 

has provided seed strain for next year’s seasonal H1N1 vaccine component. Like their 

university colleagues, they had also noted, at least in the previous week or so, an increase in 

Influenza-Like Illness (ILI), although it was still well below the seasonal influenza threshold. It 

could be adenovirus or the predicted third wave of novel H1N1. 

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Department of Veterans Affairs (DVA) 

Terri Murphy reported that the DVA’s primary biosurveillance for tracking ILI is known as the 

Electronic Surveillance System for Early Notification of Community-Based Epidemics 

(ESSENCE). ESSENCE calculates the percent of all visits seen for ILI and compares the VA 

numbers to the CDC ILI-Net. In general, the VA trends have been comparable to those 

reported by CDC, except that they did not observe the large bump this past fall that was seen by 

the ILI-Net providers. For the 2009 H1N1 vaccine, the VA expanded its availability beyond the 

initial target groups to all patients and employees on December 23, 2009. As of February 15, 

2010, they received approximately 1.6 million doses and vaccinated over 600,000 patients and 

about 132,000 employees. For seasonal influenza vaccine, their goals for 2010 are to vaccinate 

75% of their patients over 50 years of age and 70% of their employees. Last year they 

succeeded in vaccinating about 69% of the patients age 50 to 64, 83% of those 65 and older, 

and about 64% of their employees without mandatory declination or mandatory vaccination. 

Food and Drug Administration (FDA) 

Dr. Wellington Sun offered brief highlights of the FDA’s major approvals for 2009. There were 

18 approvals, 10 of which were related to influenza. There were four original BLAs approved: 

one for Japanese Encephalitis (JE) vaccine, one for a booster dose of Hib (HIBERIX®), the new 

influenza vaccine from Novartis, and the second licensed HPV vaccine in the US with a new 

adjuvant (Cervarix®). There were also 4 concomitant Administration Efficacy Supplements, 

three of which were infant vaccinations and one of which was for the elderly. The FDA 

approved the pneumococcal conjugate vaccine, Prevnar 13TM, for two indications: 1) invasive 

pneumococcal disease for all 13 serotypes; and 2) otitis media for the 7 common serotypes with 

Prevnar® for vaccination of infants 6 weeks to 5 years of age. 

Heath Resources and Services Administration (HRSA) 

Dr. Geoffrey Evans from HRSA was unable to attend due to inclement weather. However, he 

submitted a written report for the record, which was provided to ACIP members and read as 

follows: 

National Vaccine Injury Compensation Program (VICP)
 

Summary of Current Issues 

February 2010 

VICP Thimerosal/MMRvaccine/Autism Litigation 

In 2002, the Chief Special Master of the U. S. Court of Federal Claims ordered a process for 

adjudicating petitions filed with the National Vaccine Injury Compensation Program (VICP) 

alleging autism or autism spectrum disorder (ASD) from either the MMR vaccine, thimerosalcontaining vaccines, or a combination of both. Most of these cases have been consolidated 

into the Omnibus Autism Proceeding (OAP). 

As of February 1, over 5,600 autism claims have been filed with the VICP, although the trend 

in filed claims has significantly decreased over the past year. Only 8 autism claims have been 

filed in FY 2010 versus 108 autism claims filed in FY 2009. 

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Nearly 5,000 pending cases have been divided among the three presiding special masters. 

The remaining cases were either dismissed at the request of petitioners or dismissed by the 

Court because of jurisdictional issues. 

In 2007, Petitioners’ Steering Committee (PSC) and the respondent presented testimony 

concerning the “general causation issue” for the first theory (a combined theory that both MMR 

vaccines and thimerosal-containing vaccines cause autism or ASD). The parties also presented 

evidence on the specific causation issue in three test cases for the combined theory. 

On February 12, 2009, three special masters issued decisions in the three test cases under the 

first combined theory. In each test case, the special master ruled in favor of respondent, 

concluding that petitioners failed to demonstrate that the combination of thimerosal-containing 

vaccines and MMR vaccines cause autism. Petitioners appealed all three test cases to a judge of 

the US Court of Federal Claims. On 7/24, Judge Wiese ruled in favor of HHS in Hazelhurst, 

Judge Wheeler ruled similarly in Cedillo on 8/6, as did Judge Sweeney, in Snyder, on 8/12. 

Notices of appeal to the US Court of Appeals for the Federal Circuit have been filed in Hazelhurst 

and Cedillo. The time period for filing a similar notice in Snyder expired. Federal Circuit decisions 

in the two test cases are not expected until late 2010 or 2011. 

In 2008, the Court heard testimony on the general causation issues for the second theory, that 

thimerosal-containing vaccines cause autism or ASD. Evidence in three test cases for the 

second theory was also presented. Decisions on theory two are expected in 2010. 

Petitioners are no longer pursuing the third theory (i.e., MMR vaccine alone causes autism or 

ASD). 

Institute of Medicine Meeting 

The Institute of Medicine Committee to Review Adverse Effects of Vaccines continues work 

on assessing adverse events for varicella, influenza, hepatitis A, hepatitis B, meningococcal, 

human papilliomavirus vaccines and DTaP and MMR vaccines (in various combination). 

The latter four vaccines were added to the contract in the fall of 2009, and the working list of 

adverse events for the second four vaccines was posted on the IOM website and an 

announcement on the project listserv on December 2, 2009. The last public workshop was 

in August 2009, and additional open workshops will be scheduled later this year. The 

Committee’s final report is expected in 2011. 

Advisory Commission on Childhood Vaccines 

On December 3-4, the Advisory Commission on Childhood Vaccines held its 74th quarterly 

meeting in Rockville. Agenda items included reports from HRSA’s Division of Vaccine Injury 

Compensation and the Department of Justice; reports from the Causation, Petitioners 

Payment and Outreach Workgroups; reports on the VICP outreach contract; reports from 

ACCV ex-officio members; and consideration of a Departmental proposal to add hepatitis A, 

trivalent influenza, meningococcal and human papillomavirus vaccines as separate 

categories in the Vaccine Injury Table. The ACCV voted unanimously in favor of the 

proposal. 

The ACCV will hold its next quarterly meeting on March 4-5. 

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Indian Health Services (IHS) 

Dr. John Redd presented the report for IHS. He reported that most of their activity has 

pertained to novel H1N1. Early in the outbreak, they developed a system known as the IHS 

Influenza Awareness System, which is a new real-time data collection methodology. IHS is 

quite a widely distributed system. They are now receiving data, most of which are uploaded and 

updated on a daily basis, from over 500 sites around the county covering more than 60% of the 

visits to IHS. The first component assessed with this system is ILI. From that, they developed 

an ICD-9 (International Classification of Diseases, Ninth Revision) and temperature-based 

system for detecting ILI, which worked quite well. The data are generally completed for the 

previous influenza week ending Saturday at midnight by the close of business on the following 

Tuesday, so it is a rapid system. IHS observed a peak in the second wave around Halloween. 

Their general trends were very similar to the rest of the country in terms of the temporal 

associations. Also as part of that system, continuously updated data are collected on vaccine 

delivery for both seasonal and novel H1N1. They are approaching 250,000 doses of nH1N1. 

Approximately 70% of those doses have been documented to be delivered to people who are in 

one of the traditional high risk groups for novel H1N1. A very exciting effort in which IHS is 

involved is an active collaboration with the FDA. IHS is part of the Vaccine Safety Risk 

Assessment Working Group (VSRAWG) and have been collecting adverse events data 

following H1N1 and seasonal influenza vaccine administration. They have detected no signals 

to date. They are also receiving coverage data, including risk factor group data on novel H1N1 

coverage. 

National Institutes of Health (NIH) 

No update provided. 

National Vaccine Program Office (NVPO) 

Dr. Mark Grabowski discussed two relevant new initiatives from the Secretary of Health, Howard 

Koh, who is also the Director of the National Vaccine Program Office (NVPO). Dr. Koh has 

created a new Office of Adolescent Health (OAH) with Evelyn Kappeler serving as the Acting 

Director. NVPO will be working with that office to assure that adolescent vaccination is on their 

agenda. Dr. Koh has also convened a new Viral Hepatitis Inter-Agency Working Group. John 

Ward of CDC is going to Washington to help with the start-up of that group. At this point, NVPO 

is completing an inventory of agency assets and activities involving hepatitis and, over the 

coming months, will develop a new HHS strategic plan on viral hepatitis prevention and care. 

With regard to vaccine finance, a supplement on financing on childhood and adolescent and 

vaccines was published in the Journal of Pediatrics in December 2009, which arose out of an 

NVAC working group, with financial and technical support from CDC. This supplement contains 

original research, NVAC recommendations, and stakeholder comments. Dr. Grabowski shared 

a few copies of this publication. 

NVAC also put forth a recommendation for all health insurance plans to voluntarily eliminate 

cost sharing with the administration of vaccines and requested the recommendation to be 

costed. NVPO has contracted with the National Opinion Research Center (NORC) to provide a 

comprehensive policy brief that will include a literature review, expert interviews, and a cost 

estimate. The cost estimate will be derived from combining National Immunization Survey (NIS) 

coverage data with the market scan database containing employer sponsored claims data. Also, 

providers have long voiced concerns over low reimbursement rates for purchasing 

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administration of vaccines. NVPO has contracted with Surveillance Data Incorporated to 

examine payment and reimbursement practices of providers who purchase and administer 

vaccines. Essentially, they will assess third party electronic claims data and identify billing 

trends such as time frame to be reimbursed; percent of claims that were paid, denied, or 

modified; and reasons for modified claims. This contract will produce a report and list by 

different variables such as geography and specialty type. 

With regard to vaccine safety, the H1N1 Vaccine Safety Risk Assessment Working Group, the 

VSRAWG, has completed three reports to the NVAC. They have concluded that there are 

enough data to assess that no signals have been detected for H1N1. The NVAC Safety 

Working Group is writing a White Paper pertaining to what the optimal safety system ought to 

include to detect adverse events in a timely manner when they occur, and to improve public 

confidence. The first informational gathering meeting was convened in July 2009. Additional 

stakeholder meetings are being planned and a report is anticipated in September 2010. 

In terms of communications, throughout the H1N1 pandemic, NVPO has convened weekly calls 

with agency communicators to discuss vaccine safety communications. Building on these 

lessons learned from flu.gov, this Interagency Communications Working Group will become the 

steering committee for a new cross-departmental website called vaccines.gov. In its first phase, 

vaccines.gov will be a consumer portal for HHS-related vaccines and immunization content. 

The site is scheduled to launch in the summer of 2010. 

National Vaccine Advisory Committee (NVAC) 

Dr. Gus Birkhead was unable to attend due to inclement weather. However, he submitted a 

written summary report of his slides for the record, which was provided to ACIP members and 

read as follows: 

The National Vaccine Advisory Committee (NVAC) approved its 2009 State of the National 

Vaccine Program Report on February 4, 2010. This report reviewed recent activities of the 

National Vaccine Program Office and NVAC, as well as provided a framework of priorities for 

the NVAC in 2010. Following review of the most recent draft of the National Vaccine Plan 

currently under revision, as well as Institute of Medicine recommendations on the draft Plan, the 

NVAC provided a series of recommendations for the draft Plan. Regarding H1N1 influenza, 

NVAC continues to hold monthly meetings by teleconference to receive updates as necessary 

and to consider and vote on recommendations of the NVAC H1N1 Vaccine Safety Risk 

Assessment Working Group related to the ongoing Federal H1N1 vaccine safety monitoring 

programs. 

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Liaison Member Updates 

National Medical Association (NMA) 

Dr. Whitley-Williams reported that prior to the ACIP meeting, she was informed by her Executive 

Director that the NMA will be convening a consensus panel to assess management of infants 

with RSV in terms of RSV prophylaxis. 

American College of Physicians (ACP) 

Dr. Fryhofer reported that ACP is in the process of developing an adult immunization manual, 

about which they are very excited. 

Dr. Poland was unable to attend. However, he submitted a written report for the record, which 

was provided to ACIP members and read as follows: 

Our vote today is both historic and personally gratifying! Historic in that a universal 

recommendation for flu vaccine in all adults brings this into line with all other vaccines for 

respiratory viruses—that of universal use! Historic too in that we have moved over the 7 

decades we have had this vaccine from very limited use, through the latest period of creeping 

incrementalism where nearly every year brought another indication, to finally recognizing the 

need for and simplicity of a universal recommendation. Personally gratifying in that I first began 

advocating for this 26 years ago! In these nearly 3 decades, I’ve given hundreds of talks on the 

topic and published these views in the peer-reviewed literature. An Olympic effort! 

All this reached a “tipping point” in the late 1990s and early 2000s when I was an ACIP member. 

At that time I introduced the idea, and called for a vote. There was mostly solid support for the 

recommendation, but concerns over vaccine supply. Over those intervening years, use of the 

flu vaccine in younger adults did not increase, and every year tens of millions of doses of 

vaccine went unused and wasted. Most of these concerns I would characterize as “trying to 

drive into the future by looking through the rear view mirror.” 

I raised the issue again during Dale Morse’s 2006-2009 tenure as Chair of ACIP, this time 

garnering more support as more recognized the significant morbidity of influenza in younger 

adults, significant loss of schools and work time and productivity, an adequate vaccine supply, 

and the desire by clinicians for a simpler and more practical approach. Dale vowed to get this 

passed before the end of his tenure. No one can easily recall the 20-some odd current 

indications that ironically cover all but 15% of the population already! 

So thank you! Thank you on behalf of the physicians and professional societies who take care 

of and who advocate for the health of adults. Now the word needs to go out—without 

ambivalence—that influenza is a serious infection, it can be prevented safely and effectively by 

vaccine, and the vaccine is recommended for ALL! FINALLY! 

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Discussion

Advisory Committee on Immunization Practices (ACIP) Summary Report February 24-25, 2010 

American Medical Association (AMA) 

Dr. Tan reported that the AMA has been working with state medical societies to conduct a 

vaccine safety state level program to educate physicians regarding vaccine safety issues along 

the lines of the card that Dr. Schuchat distributed. The next program will be in Portland, Oregon 

on March 8-9, 2010. They are already engaged with the regional chapter of AAP there as well. 

AMA conducts about four to five of these programs per year. The last program was in 

Tennessee. Kelly Moore was very involved in that. Dr. Tan also reminded everyone that CDC 

and AMA co-host the National Influenza Vaccine Summit, which will be held May 17-19, 2010 in 

Scottsdale, Arizona. The registration website is now live for those who are invited to attend. 

Department of Health, United Kingdom (UK) 

Dr. Salisbury mentioned that as a follow-up to a discussion the previous day, the UK will be 

switching from 7- to 13-valent pneumococcal conjugate vaccine as of the beginning of April 

2010. They will do this as a seamless change from one product to the other. As the stocks of 

one expire, they will supply 13-valent. They are not changing the schedule or recommending 

any sort of catch-up program. These children will be switched during the course of 

immunization, apart from those who are in risk groups for pneumococcal disease, for those for 

whom they have recommended one additional dose at the first opportunity of a medical visit . 

They will also continue with a 2 + 1 schedule, given that the vaccine is licensed in Europe in that 

manner. 

Healthcare Infection Control Practices Advisory Committee (HICPAC) 

Dr. Elward reported that HICPAC is updating the Occupational Health Guidelines and will be 

harmonizing with the Health Care Personnel Immunization Work Group to coordinate that with 

ACIP. 

National Vaccine Plan Update 

Raymond A. Strikas, MD 

Immunization Services Division 

National Immunization Program 

Coordinating Center for Infectious Diseases 

Centers for Disease Control and Prevention 

Dr. Strikas said he was pleased on behalf of NVPO and many other colleagues in the federal 

government to discuss the National Vaccine Plan (NVP). NVPO commissioned an Institute of 

Medicine (IOM) report titled Priorities for the National Vaccine Plan that was published 

December 11, 2009. His office was authorized to develop an NVP in the original legislation in 

1986. That plan was issued in 1994. The original legislation called for annual updates to the 

plan; however, because this did not occur, the legislation was revised such that annual updates 

are not required. They began working on a revised plan in 2007. The first draft of that plan was 

issued for public comment in November 2008. They soon hope to have a second draft out. 

They envision a 10-year plan that extends through 2020 to be in concert with Healthy People 

2020 objectives for the nation, which will include a number of immunization infectious disease 

objectives. 

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National Vaccine Plan Revision Timeline 2010 Current Activities 

OCT NOV DEC JAN FEB MAR APR MAY JUN JULY AUG SEP 

Complete Strategic Plan 

Version 2 with 

Priorities 

OCT NOV 

Public Comment 

RAND stakeholder 

Interviews on roles 

Complete Implementation Plan 

Feb 3-4, 26 

NVAC mtg, call 

On priorities 

Complete Final 

Strategic Plan 

HHS/Federal 

Activities 

Advisory 

Committee 

Activities 

External 

Activities/ 

Stakeholders Dec 11 

IOM Report 

Jan-April, 2009 

HHS received, 

addressed 466 public 

comments; 

Hosted 3 public 

meetings 

Advisory Committee on Immunization Practices (ACIP) Summary Report February 24-25, 2010 

The following reflects the conceptual framework that has been developed for the National 

Vaccine Plan: 

Conceptual Framework for the National Vaccine Plan 

Vaccine 

Research 

Vaccine 

Development 

Vaccine 

Licensure 

Vaccine 

Manufacture 

Vaccine Sales/ 

Purchase 

Vaccine 

Distribution 

Vaccination 

(Adult, 

Adolescent and 

Childhood) 

High Vaccination 

Rates 

Disease 

Surveillance

Population health 

protection against 

infectious disease 

in the U.S. and 

Globally 

Reduced 

Morbidity and 

Mortality from 

infectious disease 

in the U.S. and 

Globally 

Adverse Event 

Monitoring 

Vaccine

Coverage

Surveillance 

Access/ 

Payment for 

Vaccination / 

Reimbursement 

Vaccine 

Effectiveness 

Attitudes 

about 

vaccination 

Communication 

and Education 

Strategies Recognition of 

public health 

priorities 

Develop vaccine 

recommendations 

Translational research 

for diffusion of 

innovation 

Vaccine Injury Compensation 

The 2008 Draft Strategic National Vaccine Plan includes the following goals: 1) develop new 

and improved vaccines; 2) enhance the safety of vaccines and vaccination practices; 3) support 

informed vaccine decision-making by the public, providers, and policy-makers; 4) ensure a 

stable supply of recommended vaccines and achieve better use of existing vaccines to prevent 

disease, disability, and death in the US; and 5) Increase global prevention of death and disease 

through safe and effective vaccination. The fifth goal was not included in the 1994 plan. 

The following is a truncated timeline: 

Not shown in the timeline is that the draft was issued in November 2008. Also not shown is 

NVAC’s stakeholder meeting convened in February 2008, which led to work on the vision for the 

plan. NVAC is reviewing the IOM Expert Committee report. There are 5 goals, 36 objectives, 

and about 130 strategies. Consideration must be given to the most important achievements 

that must be made by 2020. Once NVAC is finished considering those achievements, or 

priorities, NVPO hopes to issue the plan publicly in early April 2010 for public comment, and 

then to subsequently complete the final strategic plan. The implementation plan must still be 

developed to include action steps, time tables, roles and responsibilities, et cetera. Work on the 

implementation plan is expected to begin in the summer of 2010 and to end by the end of the 

year. That will be done in concert with all of the stakeholders. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report February 24-25, 2010 

IOM worked on the plan beginning in 2008 through the end of 2009. They convened a series of 

public meetings beginning in 2008 to address each of the goals, which were as follows: Goal 4 

(July 24, 2008), Goal 1 (December 1, 2008), Goal 3 (February 2, 2009), Goal 2 (April 14, 2009), 

and Goal 5 (June 4, 2009). As noted, the final report was issued on December 11, 2009 and 

can be found at the following site: http://www.iom.edu/Activities/PublicHealth/NatVaxPlan.aspx 

The IOM reported 20 priorities, of which 19 related to the existing Goals and Objectives in the 

draft strategic plan. Goal 6, regarding coordination in general, is an overarching 

recommendation. Selected recommendations from 12/11/09 IOM Report on Priorities for the 

National Vaccine Plan include the following: 

Goal 1 – Vaccine Development 

 Vaccine prioritization 

 Address non-infectious diseases’ vaccines (not a priority for this office, but important 

to do) 

Goal 2 – Vaccine Safety 

 Develop prioritized research agenda for all federal agencies and stakeholders 

Goal 3 – Communications / Informed Decision-Making 

 Develop national communications strategy 

Goal 4 – Vaccine Supply and Use 

 Assure a stable vaccines’ supply 

 Eliminate financial barriers to vaccination 

 Assume active role in national health information initiative 

 Assess national health reform outcomes’ role in the Plan 

Goal 5 – Global Vaccine Issues 

 Support low-middle income countries’ capacity building to implement new vaccines 

 Provide expertise and resources to incorporate new vaccines, strengthen 

infrastructure, and achieve higher vaccination levels 

Recommendation 6-1: The Secretary of HHS should actively demonstrate the Department’s 

support for the National Vaccine Plan by: 

 (1) clarifying its primacy as the strategic planning tool applicable to all federal 

agencies with roles in the National Vaccine Program, and 

 (2) allocating the resources necessary to assure robust planning and 

implementation, with coordination by the National Vaccine Program office. 

NVAC’s criteria to recommend priorities for the draft strategic National Vaccine Plan include the 

following: 

Feasibility (financial and technical) 

Potential impact on morbidity and mortality 

Strategic opportunity (likely to require, motivate multi-stakeholder involvement) 

Public salience (derived from public engagement meetings’ priority areas) 

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Discussion







Advisory Committee on Immunization Practices (ACIP) Summary Report February 24-25, 2010 

Discussion 

Dr. Duchin (NACCHO) noted that the desire to have an adult immunization program analogous 

to the VFC program has been stated on numerous occasions. He wondered how that fit into the 

NVP. 

Dr. Strikas replied that while he did not know how this would play out in terms of the top 

priorities, objective 4.2 addresses eliminating financial and non-financial barriers to 

immunization for all age groups. Several strategies deal with the public health infrastructure for 

adult immunization and improving vaccination rates for all groups. So this issue is generally 

addressed. Action steps will be addressed in the implementation plan: Are we going to 

recommend a vaccine program for uninsured adults? Can we do that with some confidence that 

there are resources to support such an effort? NVPO hopes to host a meeting in the summer 

with all of the partners they can think of to determine who is willing to put forth resources to 

move this plan forward. 

Meningococcal Vaccine 

Introduction 

H. Cody Meissner, MD 

Meningococcal Work Group Chair 

Advisory Committee on Immunization Practices 

Dr. Meissner began by acknowledging the work group members and expressing his 

appreciation for all of their efforts in the many discussions they had regarding meningococcal 

issues. 

Currently, meningococcal vaccination is recommended for all children 11 through 18 years of 

age. Routine vaccination of persons 2 through 55 years of age who are at increased risk of 

meningococcal disease is also recommended. Following FDA licensure the previous Friday of 

the Novartis vaccine, either of the following two conjugate meningococcal vaccines may be 

used for immunization of persons 11 through 55 years of age: 

MCV4-D (Sanofi) licensed for persons 2 through55 years of age 

 MenACWY-CRM197 (Novartis) licensed 2/19/2010 for persons aged 11 through55 years of 

age 

For use in infants and toddlers, three investigational conjugate meningococcal vaccines are 

under consideration. These three vaccines are likely to be licensed by the FDA for use in 

children less than 2 years of age in either 2010 or 2011: 

HibMenCY is manufactured by GlaxoSmithKline (GSK). This vaccine contains 

polysaccharides from groups C and Y and haemophilus influenza Type B conjugated to 

tetanus toxoid. GSK has submitted a BLA for this meningococcal vaccine. The vaccine 

would be administered as a 4-dose series at 2, 4, 6 months of age, with a booster dose at 

12 to 15 months. 

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 MenACWY-CRM197 is manufactured by Novartis. This is a tetravalent meningococcal ACY 

W135 vaccine. This vaccine contains polysaccharide from four groups that are conjugated 

to CRM197, a naturally occurring mutant diphtheria toxin. This vaccine would also be 

administered as a 4-dose series at 2, 4, and 6 months of age, with a booster dose at 12 to 

15 months. 

 MCV4-D is a tetravalent meningococcal vaccine containing capsulate polysaccharide from 

serogroups A, C, Y, and W135 conjugated to a chemically altered diphtheria toxoid. This 

vaccine is manufactured by sanofi Pasteur, and was licensed in January 2005 for use 

among persons 11 through 55 years. Presently, it is licensed for children as young as 2 

years of age. The new indication for this vaccine would extend the use of this vaccine to 

toddlers as a 2-dose series starting at 9 months, with a booster dose at 12 to 15 months. 

During the October 2009 ACIP, three presentations were delivered regarding meningococcal 

vaccine. GSK presented data for a phase III non-inferiority immunogenicity and safety trial with 

the combination Hib and Neisseria meningitidis serogroup C and Y conjugate vaccine. 

Immunogenicity and antibody persistence data from two other trials were also presented. The 

second presentation reviewed the epidemiology of meningococcal disease in infants and young 

children less than 5 years of age. Surveillance data from the Active Bacterial Core Surveillance 

system (ABCs) and the National Notifiable Diseases Surveillance System (NNDSS) were 

presented. Two conclusions were established. First, rates of meningococcal disease are 

presently at historically low levels—levels that are approximately half the lowest rates ever 

recorded. Second, the epidemiology of meningococcal disease is dynamic and will need careful 

monitoring for change in disease patterns among infants and children, as well as among 

adolescents and adults. The third presentation was an overview of considerations by the work 

group in regard to a possible recommendation for the use of meningococcal conjugate vaccine 

in infants and toddlers. The work group conclusion was that the amount of meningococcal 

disease that can be prevented with infant and toddler vaccination is low based on the present 

epidemiology of meningococcal disease as well as the investigational vaccines under 

consideration, which do not offer protection against serogroup B. 

During the ACIP discussions that followed, there was general agreement that a 

recommendation for routine vaccination of infants and toddlers is not appropriate at the present 

time, and not vote was taken. This conclusion was based on a number of considerations. The 

current incidence of meningococcal is 0.3 cases per 100,000 population. While several theories 

have been proposed, it is not clear why the rates have fallen to historically low levels; therefore, 

it is not possible to predict whether this is a permanent decline perhaps due to societal changes 

and that rates will continue to fall. Perhaps rates will rise in the years ahead. It is also not clear 

if changes in serogroup predominance may occur. 

In addition, serogroup b is not included in any of the three investigational vaccinations under 

consideration. Overall, serogroup B accounts for about 35% to 40% of meningococcal disease 

in the US, but among children less than 5 years of age, serogroup B is the most important 

cause of disease, accounting for 231 of the 381 average number of meningococcal cases 

occurring during the first 5 years of life. Thus, more than 60% of all meningococcal cases in this 

age group would not be prevented even with 100% update and 100% efficacy of these 

vaccines. Moreover, case fatality rates and complications are lower in the first year of life than 

later in life. Nonetheless, it is important to remember that an estimated 8 deaths occur in the 

first 5 years of life due to serogroup C and Y, which might be prevented by these vaccines. 

While the duration of immunity following infant immunization is not known, it is unlikely that 

protection will last until the time of the first 11-year meningococcal dose. This means that an 

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Advisory Committee on Immunization Practices (ACIP) Summary Report February 24-25, 2010 

unknown number of booster doses will be required to maintain protection through the first 

decade of life. Finally, vaccination of infants will likely have little impact on overall 

meningococcal carriage rates. However, with maturation of the adolescent immunization 

program, as increasing numbers of teenagers and young adults in their early twenties become 

vaccinated, a benefit among infants and young children from herd immunity may be observed. 

Since the last ACIP meeting, work group discussions have focused on three areas. First, a cost 

effectiveness analysis was presented. Second, data were reviewed on provider attitudes 

toward infant immunization. Data were presented from a University of Colorado survey and 

from a GSK market survey regarding HibMenCY vaccine. Third, the work group has spent a 

considerable amount of time considering the possibility of a recommendation for permissive use 

of any of the three infant meningococcal vaccines. Specifically, the following question was 

addressed: In the absence of a recommendation for routine use, would a permissive 

recommendation be appropriate? The answer will come with the understanding that a vaccine 

which does not receive a recommendation for routine use and which is not recommended for 

permissive use will not be covered by the VFC program. The work group discussions also 

included the option that the HibMenCY vaccine might be considered as a Hib vaccine. 

The challenges presented by the three infant meningococcal conjugate vaccines are extremely 

complex, and work group members have struggled with these issues. The consequences of 

meningococcal disease are often tragic. They are well known by physicians on the work group 

through personal experience with their patients. However, the amount of disease prevented 

must be balanced as objectively as possible against ACIP’s role for responsible stewardship of 

limited resources. A recommendation for either routine use or permissive use of a 

meningococcal vaccine must be weighed thoughtfully against the benefits derived. 

The work group had a number of concerns about either a routine recommendation or a 

permissive recommendation for any of the three investigational meningococcal conjugate 

vaccines. At this time, these concerns appear to override the benefit of either recommendation. 

As noted, 60% of the meningococcal disease in the first year of life is due to serogroup B and 

therefore will not be prevented. Disease due to serogroup C and Y peaks at 4 to 5 months of 

age, which is too soon to be protected by three doses of vaccine administered at 2, 4, and 6 

months of age. An infant vaccine program will prevent an estimated 80 to 120 cases, only 

about one-third of the approximately 381 cases of meningococcal disease in the first 5 years of 

life. The duration of immunity is likely to be short-term, meaning a gap in protection will occur 

before the 11-year dose. This means at least one additional booster dose after the 12- to 15­

month dose and before the 11-year dose will be necessary to maintain protection. The need for 

the 11-year dose is unlikely to be eliminated. Finally, the impact of adolescent immunization on 

herd immunity is presently unknown, but it is possible that as more adolescents are vaccinated, 

less transmission from adolescents and young adults to infants and young children will occur. 

In addition, concerns were raised about considering the HibMenCY vaccine as a Hib vaccine. 

This combination vaccine would be more expensive than a monovalent vaccine. Even if the 

cost of the HibMenCY vaccine were the same as monovalent Hib, the benefit from the 

meningococcal serogroup CY component would be low for reasons just articulated. 

The goals of this session were to present a cost-effectiveness analysis of infant meningococcal 

vaccines; review the rationale for not recommending routine use of infant vaccines; and discuss 

language options for permissive use of these vaccines and then discuss issues surrounding the 

HibMenCY vaccine. No vote was taken during this session. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report February 24-25, 2010 

Changes in the Cost-Effectiveness of Meningococcal 

Vaccination Strategies in the United States 

Ismael Ortega-Sanchez, PhD 

National Center for Immunization and Respiratory Diseases (NCIRD) 

Dr. Ortega-Sanchez discussed the changes in the cost-effectiveness of the meningococcal 

vaccination in the US. He thanked his collaborators from NCIRD, and noted that this 

presentation followed the ACIP Guidance for Health Economics Studies. 

The objective of this study was to analyze the effectiveness and cost-effectiveness of 

meningococcal vaccination program in infants and toddlers in the US under the changing 

epidemiology, using the societal perspective. For this purpose, the following model was utilized: 

This model was utilized to compare four strategies: three with vaccination for each age group 

and one without vaccination. To calculate the number of cases as well as the number of dates 

or number of survivors with sequelae, the model includes notes that describe meningococcal 

disease infection rates and probabilities of specific outcomes. 

With respect to the design, Monte Carlo simulation analysis was utilized. This simulation allows 

for the calculation of the most likely or base case estimates for health benefits and costs. 

Two hypothetical populations of equal size were used: 4 million birth cohort and 4 million 

adolescent cohort (11-years old). A 22-year timeframe was used, but the benefits of vaccination 

are estimated using age-specific life expectancy (e.g., analytic horizon). The typical discount 

rate was used for both cost and benefits: 3% (0%-5%). Once the core of the model was set, it 

was filled with the base data and physical assumptions. The investigators also consulted with 

the work group and many other experts. At first, they needed to include the base available data 

and to have an unbiased model. Inputs included epidemiologic data, resource utilization, 

indirect costs, vaccine characteristics, quality of life after meningococcal disease, and other 

parameters. Three important components of the epidemiology data include age-, year-, and 

C+Y+W135 serogroup-specific incidence rates (1991-2007); age- and serogroup-specific case 

fatality ratios; and the proportion of survivors with sequelae by condition. 

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The following table illustrates shows market changes in the annual incidence in vaccine 

serogroups CYW135 by age group per 100,000 (95% CI) [Active Bacterial Core Surveillance in 

Cohn et al CID 2010]: 

8 

Changes in the Annual Incidence in Vaccine 

Serogroups CYW135 by Age Group 

per 100,000 (95% CI) 

Source: Active Bacterial Core Surveillance in Cohn et al CID 2010 

One fifth One fourth >Two fifths 

In particular, children aged less than one year showed the largest reduction. The 2006-2007 

rates were one-fifth what they were in 1998-1999. The other groups also experienced 

reductions; however, to keep the variability of the data in the model, a wider range of years data 

were used from the ABCs for each age group. Nevertheless, more weight was given to the 

most recent data. 

In terms of fitting probabilities in case fatality ratios for Serogroups C-Y-W135, as in previous 

analyses, proportions of survivor cases with specific sequelae reported in the literature were 

used. The most common, long-term sequelae for most survivors with meningococcal disease 

for which reliable data exists are skin scarring, single amputation, multiple amputations, and 

hearing loss [Edwards et al. Complications and sequelae of meningococcal infections in 

children. J Pediatrics 1981; 99:540-5], and significant long-term neurological disability [Baraff et 

al. Outcomes of Bacterial meningitis in children: a meta-analysis PIDJ 1993;12:389-94]. 

With respect to vaccine characteristics, in relation to the already established one dose of 

adolescent vaccination strategy, two additional studies were modeled on the birth cohort: 1) A 

toddler strategy with two doses given and 9 and 12 months of age; and 2) An infant strategy 

with four doses given at 2, 4, 6, and 12 to 15 months of age. For the birth cohort, year one 

begins at birth. Since vaccination occurs part way to year one, age-specific incidence data were 

used. For effectiveness, it was assumed that the first dose of the toddler and infant schedules 

had a vaccine efficacy equal to zero. Two scenarios were modeled for efficacy duration, one 

with 10 years of duration and one with 5 years. For the base case analysis, a 10-year duration 

was used [Pichichero et al., Pediatr Infect Dis J 2005; Shepard et al., Pediatrics 2005; Snape et 

al., JAMA. 2008; Sanofi Pasteur 2-10y-MCV4 Insert 2007]. 

Vaccine coverage rates were used in the model from the national coverage data acquired for 

vaccines currently and routinely administered to infant, toddlers, and adolescents. The rates of 

coverage are specific to the doses for infants and toddlers. Coverage rates for adolescents are 

based on 2008 Tdap vaccine for 11 year olds, given that the uptake of the meningococcal 

vaccine seems to be lower than that. 

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Cost of Illness 

*** 

* Includes caregivers' work time loss and public health response in outbreaks
 

** Includes special education for neurologic disability, prosthesis &
 

rehabilitation for amputations, etc.
 

*** Annual medical costs for significant neurologic disability
 

Sources: Shepard et al., Pediatrics 2005, 16 

O’Brian et al., Value in Health 2007 

Ortega-Sanchez et al., CID 2008 

Advisory Committee on Immunization Practices (ACIP) Summary Report February 24-25, 2010 

To adjust the incidence rates and vaccination, a formula was applied that weighted vaccine 

coverage and vaccine effectiveness. This adjusted rate was then multiplied by the population 

denominator to generate the number of expected cases of meningococcal disease with 

vaccination. To cost incidence burden, one-time costs related to the acute phase of 

meningococcal disease and lifetime costs based on the recurring charges for caring for 

sequelae were used. 

For each age group and for each strategy the following formula was utilized: 

MDIvacc = MDIno vacc * [1-(Vcov * Veff)] 

Where: 

• MDIvacc = Meningococcal disease incidence under vaccination 

• MDIno vacc = Meningococcal disease incidence without vaccination 

• Vcov = Vaccination coverage 

• Veff = Vaccine efficacy 

In the model, all meningococcal cases were hospitalized and included medical and indirect 

costs during the acute phase of the disease. Those included in the model who suffered 

sequelae incurred specific medical costs in addition to costs related to acute meningococcal 

disease, as illustrated in the following: 

Given that the analysis is from a societal perspective, costs associated with productivity losses 

were included for death (labor market earnings + household production), neurologic sequelae 

(labor market earnings), multiple amputations (30% of labor market earnings), and hearing loss 

(33% of labor market earnings) [Haddix AC et al., Prevention Effectiveness: A Guide to 

Decision Analysis and Economic Evaluation. 2nd ed. 2003 Oxford University Press, New York. 

Age-specific values, US population, 3% discount rate]. 

Differences in quality of life among survivors of meningococcal disease with long-term sequelae 

were accounted for. Because there are no published measurements of loss of quality of life 

specific to meningococcal disease, published health-related QALY scores were used for 

conditions closely resembling each of the meningococcal-related long-term sequelae. Note that 

because meningococcal disease follows a very rapid clinical course, decreases in quality of life 

associated with this acute phase were not estimated [Several sources cited in: Shepard et al., 

Pediatrics 2005; Ortega-Sanchez et al., CID 2008]. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report February 24-25, 2010 

Since each strategy uses a different vaccine, vaccine costs are differentiated. For infants, the 

only cost is the meningococcal component of the combo vaccine, in this case, the HibMenCY. 

This was assumed to be $2 per dose (range $15-$60) + $AEs. For toddlers, $20 per dose 

(range $15-$60) +$AEs* +$Adm was assumed for the meningococcal conjugate MCV4 that is 

recommended for toddlers at 9 to 15 months of age. For adolescents, the 2009 public and 

private sector prices were used for MCV4 of $90 per dose (range $80-$103) +$AEs* +$Adm. In 

each one of these cases, the cost of adverse events was included, which were taken from the 

adverse event rates from the UK experience with MCC [Trotter et al., BMJ 2002; OrtegaSanchez et al., CID 2008]. Importantly, the infant vaccination strategy does not include any 

vaccine administration costs; whereas, the toddler and adolescent vaccination strategies include 

administration costs. 

Using the recommendations by the United States Panel on Cost-Effectiveness in Health and 

Medicine, incremental cost-effectiveness ratios can be calculated as difference in the net costs 

divided by the difference in the health benefits: 

Incremental cost-effectiveness ratio, ICE 

NC  NC ICE vacc unvacc

HOvacc  HOunvacc

Where: 

• NCvacc = Net cost of vaccination strategy * 

• NCunvacc = Net cost of no vaccination * 

• HOvacc = Health outcome of vaccination strategy * 

• HOunvacc = Health outcome of no vaccination strategy* 

*Net costs and health outcomes were discounted 

With regard to the preliminary results, the mean baseline estimates for the 4 million cohort and 

no vaccination with the 5th and 95th percentiles are presented in the following table: 

Baseline per 4M Cohort 

No vaccination: Mean (5th,95th Percentile)* 

Adolescent Cohort Birth Cohort 

Cases 395 (246-605) 559 (385-805) 

Deaths 52 (33-79) 59 (42-84) 

Life years lost ** 1,056 (643-1,648) 1,258 (935-1,731) 

QALY’s lost ** 4,159 (1,550-9,160) 4,054 (2,084-7,733) 

(in Millions $ ** 

Total cost of illness 

) $184 ($111-$290) $231 ($157-$334) 

* Estimates from Monte Carlo Simulation 22 

** Discounted at 3% 

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These baseline estimates are the consequences of the epidemiology data, bearing in mind that 

the investigators used a very wide span of incidence data with significant weight on the recent 

data. To these estimates, the three vaccination programs were applied. 

In terms of the new number of cases prevented for the three strategies (e.g., adolescents, 

toddlers, and infants), in the base case scenario, meningococcal vaccination would prevent 

approximately 195 cases if the infant strategy was adopted for the 4 million cohort, 160 cases in 

the toddler strategy, and 176 cases in the adolescent-based strategy. Vaccination in 

adolescents prevents approximately 176 cases. Two additional scenarios were compared with 

the base case scenario: 1) changes in vaccine efficacy duration from 10 years (the base case) 

to 5 years; and 2) changes in vaccine efficacy on the first dose from 0% (base case) to 50% in 

the infant and toddler strategies. Compared to the base case estimates, with only 5 years 

duration, an adolescent strategy would prevent only 106 cases as opposed to 176 cases of the 

base case scenario. The infant strategy would prevent 67 fewer cases; whereas, the toddler 

strategy would prevent 65 fewer cases. Conversely, always making a comparison to the base 

case scenario with a 50% vaccine efficacy in the first dose, the toddler strategy would prevent 

22 more cases and the infant strategy would prevent 10 more cases. All results are for the 4 

million cohort. The first dose vaccine efficacy for the adolescents was not changed because 

only one dose is scheduled for that strategy. 

For deaths, the analyses are similar. In the base case scenario, meningococcal vaccination 

would prevent approximately 13 deaths in the infant strategy, 12 deaths in the toddler strategy, 

and 21 deaths in the adolescent strategy. For the two alternative scenarios compared to the 

base case scenario, with only 5 years duration, an adolescent strategy would prevent 8 fewer 

deaths, and the toddler and infant strategies would prevent 5 fewer deaths each. In contrast, 

with a 50% vaccine efficacy on the first dose, the toddler strategy would prevent one more death 

and the infant strategy would prevent 2 more deaths. Along with the base case scenario, 

estimates for life years saved were calculated for the two alternative scenarios in comparison 

with the base case. Estimates for QALYs saved are for the two alternate scenarios in 

comparison with the base case increase when vaccine efficacy for the first dose is assumed to 

be 50% as opposed to 0%, and decreases when the duration of vaccine efficacy is only 5 years 

as opposed to 10 years. 

In terms of the cost-effectiveness estimate for cost per life year saved and cost per QALY 

saved, the average costs per life year saved were $707,000 for the infant strategy; $786,000 for 

the toddler strategy; and $390,000 for the adolescent strategy. This relationship changed 

somewhat when another measure, the cost per QALY, was used. The average costs per QALY 

saved were $139,000 for the infant strategy; $229,000 for the toddler strategy; and $145,000 for 

the adolescent strategy. 

The medical costs of acute meningococcal disease and the lifetime costs of long-term sequelae 

did not result in large changes on the societal cost per QALY saved in either direction. That 

was not the case for when the cost per dose of vaccination was changed. Overall, the 

strategies show higher sensitivity to variations in vaccine price. In particular, when the vaccine 

price per dose was $15 in toddlers and infants, the cost per QALY was approximately $65,000 

for toddlers and $85,000 for infants. When the vaccine price was $60, which is four times what 

was assumed in the previous scenario, the cost per QALY ratios increased to $387,000 for 

toddlers and $425,000 for infants. 

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A number of sensitivity analyses were performed, most of which were probabilistic. With regard 

to the sensitivity analyses for the toddler and the infant strategies using a specific methodology, 

the sensitivity of cost per QALY ratio to variable analysis is measured to the standardized 

coefficient b. Vaccine cost per dose is regulated first, which means that positive changes in the 

vaccine cost, with increments in the vaccine cost per dose, will increase the cost per QALY. 

This makes the strategy for toddlers less cost-effective; whereas, increases in the incidence of 

the disease will decrease the cost per QALY. The infant and toddler vaccination strategies 

show higher sensitivity to variations in vaccine costs. 

The strengths of the model are that complex modeling is utilized to uncover the uncertainties 

and to objectively and explicitly show them; and incidence and CFR surveillance data for MCV4 

vaccine-containing serogroups are explicitly used. Limitations are that data on vaccine 

effectiveness are from clinical trials, and quality of life during the acute phase of the disease is 

not assessed. 

In conclusion, disease incidence and cost of vaccine drive the analyses (more doses => more 

expensive => less cost-effective). Although additional cases could be prevented by either an 

infant or toddler vaccination strategy, they do so at higher cost. Using the last 10 years of 

epidemiology data increases the cost of all strategies compared to previous analyses. 

Considerations for Use of Meningococcal Conjugate Vaccines in Infants 

Amanda Cohn, MD 

National Center for Immunization and Respiratory Diseases 

Centers for Disease Control and Prevention 

Dr. Cohn expanded upon some of the issues Dr. Meissner raised, and discussed the working 

group’s current thinking and struggles regarding the use of infant meningococcal vaccines. This 

vaccine is not yet licensed; therefore, the work group did not propose specific recommendations 

or call for a vote during this ACIP meeting. 

During the October 2009 ACIP meeting, GSK presented on the safety and immunogenicity of 

HibMenCY vaccine. The four dose series is highly immunogenic, with 82% (y) and 94% (c) of 

subjects having a seroresponse after two doses to serogroup Y and C respectively, and 96 % 

(y) and 99% (c) of subjects having a seroresponse after dose 3. The Hib response was noninferior to monovalent Hib vaccine. Mild and local systemic reactions were similar to 

monovalent Hib vaccine, and there were no serious adverse events. Duration of protection of 

the serogroup Y and C components is unknown, but 84% and 97% of subjects had persistence 

of bactericidal response for serogroups Y and C respectively, one year after the fourth dose. 

The work group interpretation of the immunogenicity and safety data is that HibMenCY is a safe 

and effective vaccine for Hib and serogroups C and Y meningococcal disease after either the 

second or third dose, and for one year after the fourth dose. Evidence of waning immunity, 

especially for serogroup Y, indicates that the vaccine is unlikely to provide protection against 

meningococcal disease until 11 to 12 years of age, and boosting may be required to maintain 

immunity throughout childhood. 

Meningococcal disease has always been a rare, but serious infectious disease. With regard to 

the incidence of meningococcal disease in the US from 1970 to 2008, rates of disease have 

been declining for the last 10 years. The US is currently at a historic nadir of disease incidence. 

It is not known why disease incidence has continued to remain so low, but it is unlikely to be due 

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Advisory Committee on Immunization Practices (ACIP) Summary Report February 24-25, 2010 

to the introduction of MCV4. This decrease is observed in all age groups—not just in 

adolescents, occurs for serogroup B as well as for serogroups C and Y, and the most significant 

declines occurred prior to introduction of MCV4 [1921-1996 NNDSS data, 1997-2008 ABCs 

data projected to U.S. population]. 

Even with very low incidence, there are cases of meningococcal disease in young children 

every year. Regarding the average number of cases of meningococcal disease annually in 

children less than 5 years based on data from 1999 to 2008, there are approximately 221 cases 

of serogroup B and 139 cases of serogroups C and Y combined annually. However, a large 

proportion of cases are in children less than 6 months of age, most of whom will be too young to 

be protected by this vaccine. In children 6 months to 4 years of age, there are approximately 89 

cases of serogroup C and Y disease annually. With respect to the nadir in incidence, in 2008, 

the number of cases of serogroup C and Y disease decreases to approximately 50 or 60 cases 

[ABCs cases from 1999-2008 and projected to the U.S. population]. 

The working group has reviewed the epidemiology of meningococcal disease in infants, and has 

come to the conclusion that the low burden of potential vaccine-preventable disease does not 

justify addition of HibMenCY to the routine infant vaccination program. The working group 

recognizes that the epidemiology of meningococcal disease is dynamic and rates of disease 

may increase, but rates may also continue to decline, especially if there is an indirect impact of 

adolescent immunization on infant disease. The working group cannot say what magic number 

or rate of increase would be the trigger point for vaccination, but is committed to regularly 

reevaluate this issue. 

Programmatic considerations were also addressed during the October 2009 ACIP meeting. 

Over the last several months, the working group has reviewed programmatic considerations for 

HibMenCY specifically. Beginning with the MenCY component of this vaccine, depending on 

the other products used, HibMenCY may add no additional shots. However, two standalone 

vaccines are likely to be licensed in the next 12 to 18 months, which will require additional 

shots. Regardless, there will have to be adjustments to the infant schedule. Additionally, given 

that the burden of disease in infants occurs primarily in infants less than 6 months of age, the 

need to attain high coverage early in an infant’s life to prevent a majority of the disease would 

be a programmatic challenge. 

There are also programmatic considerations for the Hib component of HibMenCY vaccine. 

Supply of Hib vaccine was discussed in the working group. These discussions occurred during 

and shortly after a major Hib vaccine shortage. There are currently 3 monovalent Hib vaccine 

products available, and Hib supply is stable. The working group does not think concerns about 

Hib vaccine supply should influence a recommendation for meningococcal vaccines, but having 

an additional Hib vaccine is a benefit of HibMenCY. On the other hand, a routine 

recommendation for HibMenCY would have the opposite effect and would limit the use of other 

available combination vaccines containing the Hib component, especially during the period of 

time with no standalone infant meningococcal vaccines. 

The working group concluded that if the burden of disease justified use of this vaccine, 

programmatic complexities would not prevent a recommendation. But in this setting of very low 

disease incidence, the working group felt strongly there should be a judicious approach to 

adding vaccines to the infant schedule. Achieving programmatic balance and high coverage 

with an increasing number of vaccines in the infant schedule is challenging. Adding HibMenCY 

or any meningococcal vaccine to the infant schedule would have an impact on society, health 

departments, providers, and parents. 

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The working group has known that an infant meningococcal vaccine would not be cost-effective, 

as presented earlier by Dr. Ortega-Sanchez. The incremental cost of HibMenCY over 

monovalent Hib vaccine would have to be under $20 to be comparable with the adolescent 

meningococcal vaccine effectiveness. This analysis also used the best case scenario 

assumptions, including a 10-year duration of protection with no waning, and a long time-span of 

epidemiological data to include both sides of the peak of disease observed in the late 1990s. 

Finally, the working group understands that this price of $20 does not include any administration 

fees because it was assumed that HibMenCY would not add any additional injections. With the 

stand-alone vaccines, a price of $20 is impossible because of the added $15 to $20 

administration costs. 

Once again, if the burden of disease justified use of this vaccine, the cost-effectiveness analysis 

would not impact the working group decision to make a routine recommendation. However, in 

the setting of low disease burden, there was a strong consensus to not recommend vaccine 

regardless of price. Even if HibMenCY vaccine is the same price as the monovalent Hib 

vaccine, the opportunity costs of adding this vaccine to the infant schedule are immeasurable, 

but important. Additionally, the price of vaccine is not fixed over time. 

Dr. Cohn then offered a summary of some of the data presented on a working group call from a 

provider survey conducted by Allison Kempe at the University of Colorado. Beginning in 

December 2009, physicians were surveyed who are in an existing sentinel network recruited 

from random samples of American Academy of Pediatrics (AAP) and American Academy of 

Family Physicians (AAFP). Questions were asked about MCV4 practices among adolescents 

and knowledge and attitudes about infant meningococcal vaccination. The response rate was 

72%, with 59% response for family practitioners and 85% response from pediatricians. 

Regarding the strength of providers’ recommendation for infant meningococcal vaccination 

under different scenarios if an infant meningococcal vaccine is recommended by ACIP, AAP, 

and AAFP, approximately 90% of providers would recommend infant meningococcal vaccine in 

the setting of a recommendation if there are no additional injections. Among pediatricians, only 

52% would strongly recommend if there were 4 additional injections, and only 39% would 

strongly recommend if it required a change to different vaccine products than what the provider 

is currently using. The same pattern holds true for family medicine physicians. If ACIP, AAP, 

and AAFP do not recommend infant vaccination for routine use, the proportion of providers who 

would recommend this vaccine decreases to about 40% and 32% among pediatricians and 

family medicine providers, respectively. If there were no additional injections, 19% of 

pediatricians and 17% of family practitioners would strongly recommend this vaccine. The 

working group took from this presentation that most providers will use meningococcal vaccines 

in infants only if recommended by ACIP, AAP, and AAFP. Additional injections and the need to 

change their current use of products would impact acceptability. The working group is acutely 

aware of the impact their proposed recommendations would have on the use and uptake of 

infant meningococcal vaccines. 

Many working group calls have started with the question: How can we not recommend a 

vaccine we know will prevent 4 to 8 deaths in 10 to 15 children from having long-term disability 

a year? But when the working group works through their rationale using a societal, not an 

individual perspective, the discussion returns to a strong consensus that the best public health 

decision is to not recommend routine infant vaccination at this time. The primary rationale is the 

current low burden of meningococcal disease combined with the high proportion of serogroup B 

cases in infants that are not prevented by this vaccine. But an additional important reason is 

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that if infants are vaccinated, booster doses will likely be required to maintain immunity. The 

working group is uncomfortable with the potential for a child to be protected through 5 years old, 

but then to lose protection, given that this course would likely commit them to a booster dose at 

4 to 6 years old. High-risk infants would be recommended for vaccination. 

In terms of some of the complicated discussions pertaining to the language for the use of 

HibMenCY, the working group is thinking through permissive language about the use of 

HibMenCY to prevent Hib disease, and the implications this language has in relation to the 

inclusion of HibMenCY in the VFC program. The working group discussed language about the 

use of HibMenCY as a Hib vaccine. This vaccine can definitely be used as a Hib vaccine. The 

work group does do not think there is an increase in risk from the additional antigens, but there 

is a benefit from the meningococcal components, which is limited. The working group 

discussed indicating a preference for HibMenCY as a Hib product, especially if the vaccine were 

priced competitively with other Hib vaccine products, but determined that even if the price of this 

vaccine is equivalent, stating a preference is not very different from making a routine 

recommendation. Providers can have preferences, but from a societal perspective, there is not 

sufficient public health benefit to have ACIP state a preference. There was consensus to 

acknowledge the added benefit of MenCY component of HibMenCY without stating a 

preference. An example of the kind of language being considered is as follows: 

HibMenCY may be used in infants for routine vaccination against Hib. At the current 

time, the additional benefit of the serogroup C and Y meningococcal component of this 

vaccine is limited; serogroup B meningococcal disease not prevented by this vaccine. 

Protection from the MenCY component may be of short duration (4-5 years) and booster 

doses are likely needed to maintain protection until the 11-12 year-old dose. 

The working group recognizes that permissive use recommendations are confusing to providers 

and the question of what exactly a permissive recommendation is has been debated. An FDA 

approved vaccine means it is safe and effective, and several working group members believe 

licensure indicates permission to use. The working group grappled quite a bit with how 

permissive language translates into a VFC resolution, and is taking the approach that decisions 

about permissive language should be independent of considerations for VFC inclusion. 

The working group has discussed three options from no language to broader language. First, 

there could be no language about permissive use of vaccine, and there would only be language 

around recommendations for high-risk infants, including use during community outbreaks. In 

the middle is language to communicate that this is a safe and effective licensed vaccine, and 

can be used. The more broad language option is to add after HibMenCY is a safe and 

immunogenic vaccine that Parents and providers may vaccinate infants with HibMenCY for 

protection against meningococcal disease... 

The working group discussed these language options extensively. There is a preference from 

some working group members to limit permissive language, with the understanding that 

licensure allows for use of the vaccine and that permissive language may be more broadly 

interpreted than intended. It is not the intention of the working group to discourage use of this 

vaccine, and understanding the nuances of how permissive language impacts health 

departments, providers, and parents is still being worked through. If the working group does 

propose permissive language, it should reflect the conviction of the working group that the risk 

of disease is low and vaccination is not recommended. In other words, it should be clear that 

the working group is not waffling. 

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There are various scenarios for inclusion of HibMenCY in VFC if ACIP does not recommend 

routine vaccination. The first would be to have permissive use of infant meningococcal vaccines 

added to the meningococcal VFC resolution. Another scenario would be to add HibMenCY to 

the Hib vaccine resolution as an additional Hib vaccine choice. The final scenario is to include 

only high-risk infants in the meningococcal VFC resolution, and infants who are not high-risk 

would not be eligible for HibMenCY or any meningococcal vaccine. 

The working group has had complex discussions around inclusion of this vaccine in the VFC 

program. These discussions have raised issues of public health stewardship, desire for this 

vaccine to be available, use of limited resources, and consistency with ACIP recommendations. 

The working group is continuing to be educated about the VFC program and understands that 

the direct and indirect implications of this decision are important. 

In conclusion, the epidemiology of meningococcal disease is dynamic, and there is currently a 

historic nadir. The current low burden of disease is the primary rationale for no routine 

vaccination for infants at this time. The working group is committed to frequently evaluating 

changes in the burden of disease and to recognizing increases rapidly. What the working group 

also understands if that if they do not recommend this vaccine now, there may be a delay in 

getting the vaccine back quickly if it is needed. The working group is in agreement with this 

conclusion, but has been through tough conversations. The members are committed to disease 

prevention and have struggled with the implications of this decision. The working group 

recognizes the incredible impact this disease has on children and families, and anticipates that 

one day vaccinating infants against meningococcal disease will be the right public health 

decision. For all of the reasons outlined, they feel that even more so than usual, communicating 

the rationale for these recommendations needs to be clear and consistent. 

Discussion 

Dr. Baker reiterated that the new vaccine, Menveo®, that was licensed recently for ages 11 

through 55 will automatically go into the adolescent program as a second vaccine. That was not 

up for discussion during this session. She also reminded everyone that this information would 

not lead to a vote during this session. 

Dr. Keitel requested comments on the epidemiology of the disease in other countries, 

particularly those which do not have an adolescent immunization strategy. 

Dr. Cohn replied that meningococcal disease is very different throughout the world. In Europe 

specifically, many countries had very high rates, higher rates than the US, of MenC disease. 

However, they do not have any MenY disease. Many countries in Europe have introduced 

meningococcal C conjugate vaccines. Currently, those countries still have a burden of 

meningococcal B disease, which is still higher than in the US. There are other countries in 

which it is believed that the burden of meningococcal disease has been reduced similarly to the 

US. In Sub-Saharan Africa, MenA disease occurs at much higher rates than in the US. 

Dr. Judson pointed out that, in terms of tracking the long-term secular incidence trends in 

meningococcal disease, it seems that things develop very slowly over multiple years. Thus, 

there does not seem to be any evidence to suggest that there will be a radical increase in the 

next year or two. Regarding the concerns raised about forcing a huge increase in costs on the 

VFC, if this is a permissive recommendation, it seems that the use of the HibMenCY as a Hib 

vaccine could create a situation in which anybody could request that preferentially with the 

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rationale that, “It’s all free. Why not just get a little extra protection no matter how small it may 

be for meningococcal disease?” 

Dr. Santoli emphasized that being able to use this vaccine would depend upon the decision that 

ACIP ultimately makes about including it in the VFC program. When there is a licensed product, 

that will come up as a vote. It might be a vote about including it as a Hib vaccine or it might be 

a vote about including it as a meningococcal, but if there is not a recommendation, ACIP 

members would have to decide if they want to put this forward as a VFC resolution. There is an 

opportunity to do things different in the VFC program, but it is really the thinking of this group 

that would decide if this vaccine should be included in the VFC program. 

Dr. Meissner said that in terms of the declining incidence, he thought they were very close to 

observing some impact from the adolescent immunization program, because meningococcal 

disease is acquired primarily from individuals in their late teens and early twenties. As that 

program matures and there are more individuals who are immunized, hopefully there will be 

fewer carriers and there will be less disease in younger children as has been observed with Hib 

and pneumococcal disease. One of the reservations about a permissive use, which would 

include coverage of this vaccine by VFC, is that if they believe meningococcal disease should 

be prevented and that it is a serious / extensive enough problem in the US, they should move 

forward with that recommendation. He was uncomfortable with the concept of telling people 

they could prevent meningococcal disease if they wanted to, but that it would be only a few 

cases. 

With regard to the modeling, Dr. Temte asked Dr. Ortega to clarify whether inherent in the 

toddler and infant programs they were you still looking at maintaining an adolescent program or 

would replace an adolescent program. He wondered whether the costs of an adolescent 

program were reflected in the infant and the toddler data or the analyses. 

Dr. Ortega-Sanchez replied that the comparisons made for a vaccination program were that it 

gains no vaccination so it is not a replacement. The reason for this is that they assumed only 

10 years duration of vaccine efficacy. Because of the timeframe during which infants and 

toddlers are vaccinated, they will need to be vaccinated at 11 years old. The comparisons are 

made against no vaccination. They followed the cohort 22 years to determine the impact of the 

intervention. The birth cohort was followed from Day 1 to 22 years of age, and a number of 

cases were calculated that would come out of this vaccination program with and without the 

vaccination program. 

Dr. Temte asked if the infant program would involve just the vaccination costs associated with 

the infant program, but not presumably as that infant ages to 11 or 12 years old and would 

received an additional meningococcal vaccine. If the adolescent program was included, the 

cost per QALY would balloon. 

Dr. Ortega-Sanchez replied that the vaccination of the infants has been included in the strategy 

for the infants. Including adolescents would be a different strategy, with a booster dose at 11 

years old. It is not an infant study with only the four doses at one-year old. 

Dr. Cohn pointed out that because the adolescent program already exists, it was not included 

the cost of the adolescent program. Because they would then be preventing a similar number of 

cases if they used the QALYs of the adolescent program, it would work out to be pretty similar 

because costs would be added, but more disease would also be prevented. It would probably 

not balloon the cost per QALY. 

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Dr. Cieslak inquired as to whether any analyses were conducted in the model for serogroup B 

vaccine. 

Dr. Ortega-Sanchez replied that he is trying to do this. 

Dr. Chilton inquired about the other three serotypes that are not in the MenCY vaccine, and said 

he assumed that the A and W135 are not current contributors. He also wondered how close 

they were to a serogroup B vaccine. 

Dr. Cohn responded that serogroup A disease in the US is extremely rare, and in the past 10 to 

15 years, there have been no identified cases of serogroup A disease among infants based on 

10% of the US population that has been under active surveillance. There has been one 

serogroup W135 case, so the burden of W135 disease definitely exists in infants. There are 

probably a few cases per year, but it is not to the same extent as serogroup C and Y. In terms 

of when there will be a serogroup B vaccine, there have been extensive discussions with some 

of the pharmaceutical companies. She requested that the companies comment on this. 

Dr. Howe (GSK) responded that this was discussed during the October 2009 ACIP meeting. 

GSK has a serogroup B vaccine under development, but it is in the very early phases of 

development, so it is a number of years away. 

Dr. Dull (Novartis) replied that Novartis has phase III studies on-going in Europe with its multicomponent MenB vaccine. They are striving to bring that to the US for phase III studies, but 

have not yet begun phase III studies in the US. He could not put a timeframe on this. 

Dr. Paradiso (Pfizer) indicated that Pfizer is currently testing a meningococcal B vaccine 

formulation in adolescents, which will be followed up in infants as well. 

Dr. Dekker (sanofi pasteur) indicated that sanofi pasteur is also working on the development of 

a meningococcal B vaccine. 

Dr. Katz reported that he was recently attending a meeting in Buenos Aires and was very 

impressed that group B meningococcal disease is highly prevalent in many Latin American 

countries. He thought that cast another aspect to the epidemiology in terms of what should be 

considered as they think optimistically about the inclusion of group B. Group B is prevalent in 

infants, older children, and adults. 

Regarding the continual comments that it is not understood why the incidence of meningococcal 

disease has been decreasing since 2000, Dr. Turner (ACHA) pointed out that one way to 

protect infants is to vaccinate adolescents and young adults. ACHA has been conducting 

surveys of its students about vaccines for a number of years. In the year 2000, shortly after the 

first recommendation was made for meningococcal vaccines in college students, ACHA had 

achieved 24% uptake of polysaccharide. By the spring of 2005, before conjugate was available, 

they had already achieved 55% uptake. Since conjugate has become available, they have been 

at about 60% uptake. While he realized that serotype B had fallen during the same period, Dr. 

Turner submitted that vaccinating over half of the college students in America since the year 

2000 had perhaps had an impact on the decline of incidence. He thought they should 

emphasize adolescent and young adult vaccine to prevent the disease among infants. 

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Ms. Murphy (CMS) mention that as the CMS representative for the VFC program, she does not 

care for permissive used in the votes for the VFC, although she did understand the need for 

doing so. When the word “permissive” is going to be used, she suggested that they be very 

careful to spell out that they mean “permissive for parents and providers” so that no one else 

can interpret this as their ability to determine whether they are going to cover the vaccine within 

the state or region. 

Dr. Baker pointed out that upon FDA licensure, providers may purchase vaccine and parents 

may request it. The permissive language for VFC is a different “kettle of fish.” 

Dr. Salisbury (DOH, UK) said he thought the UK experience was worth mentioning because 

there are some similarities and some considerable differences. Regarding the epidemiology in 

the UK, in the mid to late 1990s, they observed about 3 cases per 100,000 total population of 

meningococcal C disease, which would relate to something on the order of 7,500 US cases, and 

750 deaths. The scale of what the UK is now facing differs from the current US scale. The UK 

introduced meningococcal C conjugate vaccine for infants at 2, 3, and 4 months. A catch-up 

campaign was conducted for the remainder of the population up to 18 years of age for one 

dose. In the catch up campaign, there was about 85% coverage and approximately 90% to 

93% coverage with three doses in the infant program. Meningococcal C disease has virtually 

disappeared. However, vaccine efficacy is short-lived in the infants, and it was clear that 

vaccinating at 2, 3, and 4 months did not offer long-lasting protection. Thus, they changed the 

schedule, dropping one infant dose. They now vaccinate with meningococcal C conjugate at 3 

months and 4 months and give a HibMenC combined conjugate boost at 12 months. The 

consequence of that is that there are nearly 0 levels of MenC extending through the ages. The 

result of the catch-up program administered at a very high coverage rate has been enormous, 

and has lasted at least a decade. Clearly, they are assessing carefully to ensure that there is 

no adolescent resurgence of disease, but thus far there has been absolutely none. In 2008 and 

2009, there was not a single death from meningococcal C in the under 18 age group in the UK. 

However, all of that is predicated on very different epidemiology in which the burden of the 

disease was of the order of log differences compared with American disease. 

Dr. Baker inquired as to what happened to group B disease in the UK during this interval. 

Dr. Salisbury responded that group B disease has fallen somewhat, but to the low levels 

observed in the US. The UK still experiences about 1,000 cases, which would be on the order 

of 5,000 US cases of group B disease per year. 

Dr. Langley (NACI) reported that Canada’s experience was a variation of the UK experience. 

Canada had large outbreaks in 2001. Immunization campaigns were conducted using a 

bivalent product and a MenC product. Infant programs were introduced as well. Initially, they 

were introduced according to the schedule that Dr. Salisbury mentioned. As they learned that 

not having a dose after one year of age led to waning immunity, they had fewer infant doses. 

Most provinces use a single dose at 1-year, which is given at the same time as the MMR visit. 

Now the adolescent dose is a booster dose. The result of that is that C disease is now about 

.25 per 100,000 and the most common serotype is B at .3 per 100,000. 

Dr. Judson inquired as to whether, from a general perspective, they should revisit the use of the 

“permissive” category and whether it was leading to unhelpful confusion, increased costs, and 

unintended VFC entitlements. 

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Dr. Baker replied that there has been some concern, but that they would unlikely be able to 

solve that particular question during this session. 

Dr. Sawyer said he thought that a permissive recommendation would lead to a great deal of 

confusion. Most physicians are not aware of the change in epidemiology and would likely have 

the general reaction that the workgroup had: How can we not immunize? It is likely that they 

will not understand a permissive recommendation from ACIP. He supported the work group’s 

effort to be very clear, but would not favor a permissive recommendation. 

Dr. Englund said she thought their group needed to support the work group in defining who is at 

high risk. There are certainly high risk children, and that needs to be covered by the VFC 

program. The work group has already made some inroads in that, which she would totally 

support. 

Dr. Pickering inquired as to whether the number of high risk infants who have disease impact 

the total disease rate and if so, how that impacts the economic analysis. 

Dr. Cohn responded that they cannot answer that question. It is known that the number of high 

risk children in the US is very low. Most infants will not have complement deficiencies 

recognized. Very few children have functional asplenia. Even children with sickle cell disease 

sometimes as infants still have their spleens. There are probably not many infants traveling to 

endemic countries where meningococcal disease is hyper endemic, such as the Sub-Saharan 

meningitis belt. Fewer children are believed to be in the high risk age group compared to the 2-

to 10-year olds. Because there are so few high risk children, most cases of meningococcal 

disease in infants are not occurring in high risk infants. There would certainly be some, but 

there is no way of knowing that. The definition of “high risk” that they would want to include, 

which a couple of work group members have strongly encouraged, is used during local 

community outbreaks of C and Y disease for which vaccination is recommended. This would be 

a really great option, and previously there has not been a good option for vaccination of less 

than 2-year olds in community outbreaks. This language would be included in the VFC 

resolution. 

Dr. Baker noted that most states have a sickle cell disease screening program even though they 

are not functionally asplenic as young as two months. She assumed that all of these individuals 

would be considered high risk. 

Dr. Cohn replied that the language could be made clear about this point as well, perhaps even 

suggesting that giving these children a full 4-dose series would be better than giving them a 

single dose at 2 years. 

Dr. Baker thought this should be considered before they came to a vote, because the newborn 

screening programs will identify those infants early. Some of them will acquire disease before 

they are two years of age with CY-containing serogroups. 

Dr. Judson inquired as to how common screening is for C3, C4 complement deficiency in 

infants. 

Dr. Baker responded that most of those children show up in the 2- to 10-year old and 

adolescent age groups. 

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Dr. Howe (GSK) stated that GSK is committed to bringing products of value to the market. They 

believe their candidate HibMenCY vaccine is an excellent Hib vaccine, which was also 

developed to address an important non-medical need for vaccination in infants and toddlers. 

Despite the observed recent historic low rate, meningococcal disease remains a serious illness 

and the impact of the disease can be devastating. Meningococcal disease is known to have a 

cyclical nature, which means that the low rates may not be sustained long-term. As reported 

earlier in this session, vaccines to prevent serogroup B disease are in earlier stages of 

development, so they will not be available in the short-term. Therefore, GSK believes in the 

value of HibCY vaccine, as approximately 40% of infant disease is caused by serogroups C and 

Y. Now ACIP has implemented recommendations that address the risk of disease in 

adolescents. HibCY vaccine was developed to address vaccine preventable meningococcal 

disease in infants and toddlers, for whom the risk is even higher. Based on the health outcomes 

data presented during this session, infants and adolescents can be immunized at a similar level 

of cost-effectiveness, and that does not consider the additional value of the Hib component, 

which is highly cost-effective if not cost saving. In October 2009, ACIP heard about the clinical 

trials involving more than 9,000 infants and toddlers conducted over 7 years with HibMenCY in 

which the HibCY vaccine was shown to be safe and immunogenic, with a large majority of 

children maintaining protection through the highest period of risk. This product was developed 

specifically for the US to fit within the existing pediatric schedule without additional shots, office 

visits, or administrative fees, and it will be priced at an appropriate value to enable equitable 

patient access. We believe our product would be a valuable addition to infant immunization. If 

licensed and with a recommendation with VFC resolution, which one would expect to be justified 

based on the Hib component, GSK’s HibCY vaccine would broaden provider choices and give 

parents access to a vaccine to prevent these serious diseases. 

Dr. Katz noted that aside from Dr. Plotkin, he may be the only one old enough to remember the 

history of meningococcal vaccines in the ACIP. Meningococcal vaccines were originally used 

by the Armed Forces for their recruits. ACIP has repeatedly discussed meningococcal vaccines 

and made no recommendation until one day during the public comment session, parents 

brought in their children in with the amputations, scarring, et cetera. That changed the attitude 

of ACIP members. He wondered what might happen with the parents of children who have 

been damaged by C and Y, even thought the numbers are small. 

Dr. Ehresmann stressed that this has been a really challenging discussion for all members of 

the work group, and that they have all wrestled with the issues. She thought the presenters did 

an excellent job of conveying the challenges faced by the work group members and the method 

by which they came to their decisions. 

Dr. Keitel asked whether the countries that have had experience implementing immunization 

against MenC intend for that vaccine to remain in the schedule though they now have on-going 

low levels of disease. 

Dr. Salisbury (DOH, UK) replied that the UK dropped one of its infant doses. They include a 

HibMenC at one year of age. Their disease rates remain exceptionally low. He thought it would 

be a very brave step to assume that that success is just due to natural variation and the 

prevalence of meningococci. 

Dr. Langley (NACI) responded that their committee has increasingly seen control of 

meningococcal disease on the population level rather than the individual protection level. In 

terms of indirect effects from immunizing adolescents and how that affects children, Canada 

believes that control is only as good as the re-immunization program and that on-going 

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immunization is needed to control disease. She could not imagine that they would stop a 

toddler or infant program. Given that they address this on a population level, they also take into 

consideration the effects on public health. When there is a case of meningococcal, public 

health resources are totally diverted to the communication of difficulties, fear in the community, 

and the effect of that fear on confidence in vaccine programs in general. Those are also issues 

of concern for infant vaccine programs. 

Dr. Meissner acknowledged the very thoughtful comments by Dr. Katz, and noted that most of 

the members of the work group committee are pediatricians who have dealt with the devastating 

consequences of meningococcal disease. Making public health policy decisions necessitates 

an inherent tension between what is best for society and the individual perspective they all feel 

as advocates for patients as physicians. It is not by any means an easy issue to resolve, but he 

thought they must maintain a balanced perspective. In this era of increasingly limited 

resources, a societal rather than individual perspective must be taken as difficult and painful as 

that is. 

Dr. Paradiso (Pfizer) pointed out that obviously, Pfizer is watching with great interest the 

thinking and recommendations of ACIP related to meningococcal disease as Pfizer makes 

decisions about making fairly substantial investments in the phase III programs for 

meningococcal B vaccine. The implications of these discussions are beyond the HibCY 

vaccine, and they all must make decisions about how to proceed. 

Dr. Lewin (Novartis) reiterated Dr. Paradiso’s comments from Novartis’s perspective. While it is 

premature to speculate, Novartis also develops vaccines to meet unmet public health needs in 

the US. They, too, carefully and closely watch ACIP decisions and continually re-evaluate their 

programs in light of these decisions. 

Dr. Plotkin thought it would be useful for the industry to hear from the work group what kind of 

incidence would lead to general recommendations. 

Dr. Meissner responded that it is extremely difficult to answer that question. It is a critical 

question, and everyone on the work group and ACIP is also concerned about the ramifications 

that this sort of decision has on the pharmaceutical industry. However, he did not believe it 

would be possible to cite specific incidence figures that would determine what decisions might 

be made in the future, given that this is simply too complex an issue. 

Dr. Cohn added that the work group would consider not only the level of incidence, but also the 

rate of rise of incidence. These discussions have taken place among the work group members, 

and they do not believe this can be done currently. 

Frankie Milley (Meningitis Angels) indicated that Meningitis Angels represents over 600 families 

across the US, and is the mother of an only child who died with meningococcal meningitis at the 

age of 18. Given that Meningitis Angels is seeing more and more meningococcal disease 

among children under 5 years of age, it concerned her the data presented were three years old. 

Dr. Cohn responded that the reason they present data that are a couple of years old is because 

that is the best data they have that can separate which serogroups are causing disease. C and 

Y versus B data come from a different surveillance system than the national surveillance 

system. Reports from state health departments to CDC in 2008 and 2009 both showed 

decreases each year compared to 2007. In 2008, in total for B, C, and Y combined, there were 

137 cases of meningococcal disease in 6 month olds to 5 year olds. Although the reporting is 

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not completely closed, there may be a couple more in 2009, there were 104 cases. That 

includes both serogroups, and CDC thinks that about 45% of those are likely to be serogroup C 

or Y. A decrease is still being observed in the nationally reported data. 

Dr. Baker clarified that the data pertaining to the epidemiology were through December 2008, so 

the data are only about a year old. 

Public Comment: Meningococcal Vaccine 

Frankie Milley 

Meningitis Angels 

This is my son. I would like to remind everybody—I think the thing that really burns me the most 

is that we all need to realize that meningococcal does not stop at the dorm room door. It 

doesn’t stop. It doesn’t just affect kids living in dorms. It affects kids living outside the dorm, 

and it affects teenagers and tweens. We recently did a survey among some of our people. We 

took 17 of those interviews, and out of the 17 people that were interviewed, 9 of those children 

died and they were under the age of 5. The ones who died, if you want to look at economic 

impact, out of the 9 who died, 5 were under three years old. Just the medical bills for them, 

from the time they went to the hospital to the time of death, were over half a million dollars. To 

bury those children cost those families almost $200,000. The 8 that survived have lost limbs, 

have severe seizure disorders, kidney transplants, blindness, deafness, and their medical bills 

are into the millions of dollars and continue. I can’t tell you how hard this is. We had 8 parents 

lined up to come here today, but we only have 5. One of them, 8 years later after their son had 

meningitis, he’s been in the hospital three times this year already for severe seizure disorders, 

and his mom told me the other day is her greatest fear is she will go in to wake her baby up and 

he will be gone. 

The economic and social impact is horrendous. You guys have done an amazing job by 

recommending it for college freshmen. You’ve done an amazing job doing it for adolescents. I 

know because I’ve been there every step of the way. You know, it’s like if you have a cruise 

ship and you only have 40 life rafts. Are you going not let as many people on the life raft as you 

can or are you going to let everybody sink with the ship? We’ve got to save as many kids as we 

have. If you look at us, you can’t tell a parent who’s lost a child or who lives with a child so 

severely debilitated that is draining them financially, draining them emotionally, you can’t tell 

them their one child is not worth a recommendation. I thank you and commend you for the job 

you do, but I am begging you with all of my heart, please consider this carefully. Please take 

into account the lives that are affected. Please take into account some of the lives you are 

going to hear about today. Please understand that with meningitis, once children come out of 

the hospital is not over. It goes on for a lifetime. Thank you. 

Chris Boone 

Meningitis Angels 

I’m Chris Boone. This is my wife, Heather, and my son, Ethan. Ethan contracted meningitis or 

meningococcal at seven months old. He lost both legs, both arms, and has major facial 

scarring. He has many more surgeries to go to help his face. His nose practically fell off of his 

face. Please recommend this vaccine. Thank you. 

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Aida D'Antona 

Meningitis Angels 

Hi, my name is Aida D’Antona and I’m from New York. At the age of 3, my son John contracted 

meningococcal meningitis. As a result, he lost the top of an ear and three fingertips. They had 

to amputate both of his legs above the knee, and it affected his brain in 5 places. He has shortterm memory loss and he is learning disabled now. He was in the hospital for 5 1⁄2 months. It’s 

12 years later. He had 20 surgeries by the time he was 7 years old and he’s still not done. He 

suffers every day of his life. I beg you to please recommend this vaccine so that no child has to 

endure what my child does every day. Thank you. 

Jennifer Bax 

Meningitis Angels 

My name is Jennifer Bax and this Riley, my little boy. He contracted meningococcal when he 

was 3. He has severe hearing loss and is learning disabled now as well. We beg you to please 

recommend this vaccine so that no other parent or child ever has to see this. Thank you. 

Wendy Meigs 

Meningitis Angels 

My name is Wendy Meigs and this is my daughter Leslie. She contracted meningococcal 

meningitis in 1998. She was 8 years old. This is a picture of her before she got sick. She 

spent two months in the hospital—a month in ICU, and three weeks on a ventilator. She has 

extensive nerve damage, scarring, and poor circulation. We go in periodically because she has 

to have part of her bone removed as it dies off. Although she was 8, the situation is the same. I 

believe the vaccine was not available. The other thing that she left with was dialysis. She was 

in kidney failure, which I didn’t see mentioned. Three months after we left the hospital, 

Medicare called me to tell me that she was now Medicare Primary. But it was an unusual week. 

It turned out that her kidneys had begun working again and she was able to get her catheter 

removed. We dealt with kidney failure for 12 years. At 11 years old last April, she received a 

kidney transplant. She’s doing better, but she still has all of the issues that are associated with 

renal failure. So what I’m asking you is to please, please approve this vaccine and allow this 

vaccination to take place so that children do not have to suffer illnesses that are life-long and 

will continue. You have the opportunity to save these infants and protect them, so I ask you to 

please save the babies. Thank you. 

Lisa Nauman 

National Meningitis Association 

Hi, my name is Lisa and you’re going to see a video of my daughter Sarah [Video was played 

and then Ms. Neuman offered her comments]. My daughter suffered more than the physical 

devastation you just watched. She also had neurological complications from the meningococcal 

disease. Her condition has left her dependent on others, and her cognitive level will never be 

that of an adult. Sarah just turned 15 this month, and she has received physical therapy weekly 

for the past 14 years. She’s endured multiple facial and surgical procedures to reconstruct her 

nose and lip. Being confined to the wheelchair, she has developed severe scoliosis, which will 

require surgery in the near future. As a parent, I urge you to make the vaccine available to 

infants. Parents need to have information to make decisions about the disease, and no child 

should be lost or suffer from a vaccine preventable disease. Here’s Sarah today [photograph 

shown]. 

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Dr.Baker thanked everyone for their public comments about meningococcal disease. Speaking 

on behalf of the committee and CDC staff, she emphasized that they care about parents and 

their children and are sorry for these consequences. 

Kathleen Gallagher, DSc, MPH 

Division of Viral Diseases, NCIRD, CDC 

Dr. Gallagher provided an update on the status on the on-going mumps outbreak in the 

Northeastern US that began in June 2009. This outbreak began when an 11 year old boy 

returned to a Jewish summer camp in upstate New York (NY) in June 2009 after a visit to the 

United Kingdom (UK). This location is depicted on the following map by the red star: 

The child subsequently developed parotitis and infected additional campers, who subsequently 

developed disease. When the camp ended in August, the children, some of whom were 

incubating mumps, returned to their homes in Brooklyn and Rockland County where additional 

cases occurred. Further spread to Ocean County, New Jersey (NJ) and Orange County, NY 

occurred in the fall. In the past few weeks, additional cases have been reported from 

Connecticut (CT) and Northern NJ. The green dots on the above map represent the locations 

where outbreaks of mumps are currently occurring in the US. This outbreak was also exported 

to Quebec and Israel. 

This is the largest outbreak of mumps in the US since 2006. A total of 2,336 cases were 

reported to CDC through February 19, 2010. The median age of cases is 15, with a range in 

age from 3 months to 90 years. Of the cases, 74% are in males. The majority of cases are 

reporting typical clinical presentations, with most patients reporting either unilateral or bilateral 

parotitis. 84 persons (about 4%) have reported complications, the majority of which have been 

Orchitis (70). Other complications have included pancreatitis(6), meningitis(5), oophorotis (1), 

mastitis (1), deafness (1), Bell’s Palsy (1), and meningoencephalitis (1). Cases continue to be 

reported. Of the case patients, more than 98% thus far belong to the Hasidic Jewish 

community. Of the 45 cases that have been reported outside of these, almost all of them have 

had some sort of contact with the community through either employment in their community or 

in a surrounding community. For the most part, this Jewish community has limited interaction 

with other surrounding communities. The children, for the most part, attend private Jewish 

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Discussion On-Going Mumps Outbreaks Northeast United States June 2009 to Present 

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religious schools. The average household size is relatively large. It is not unusual for a family 

to have 10 or more children. 

For the 1,565 (67%) cases for whom measles, mumps, rubella (MMR) vaccination status is 

known, 76% had 2 doses, 13% had one dose, and 8% had zero doses. Unknown vaccination 

status is most commonly noted in adults who frequently were not in possession of their 

immunization records. 

There have been several factors in common that contributed both to this outbreak and the 

mumps outbreak in 2006. Both outbreaks were initiated by importation of the type G genotype 

from endemic areas outside of the US. For this outbreak, it is known that the importation is from 

the UK, and it is suspected that this is also true for 2006. Previous studies have estimated that 

vaccine effectiveness is approximately 73% to 91% after a single dose of mumps vaccine and 

79% to 95% after 2 doses. Thus, if mumps is introduced into a highly dense living or 

educational environment, as is the case currently and was the case in 2006, transmission of 

mumps might be expected to occur. 

In the Jewish community, particularly for boys, long hours are spent at school 5 days per week. 

Unlike girls, who study in more traditional settings, boys will spend many hours of their day 

focusing on their religious studies in crowded study halls. 

A third dose of MMR vaccine is not currently recommended for mumps outbreak control or postexposure prophylaxis. However, in Orange County, New York, schools had high 2-dose MMR 

coverage and still reported on-going mumps transmission in their schools, presumably 

facilitated by these crowded conditions. Because social distancing measures were not thought 

to be feasible and because virtually all children in this one community attend one of three 

religious schools, in collaboration with the county and state health departments and support of 

the community, CDC chose to offer a third dose of MMR to all fully vaccinated 6 to 12 graders, 

which was the most affected age group in this community. In addition, a protocol which allows 

for the receipt of a third dose of MMR vaccine within 5 days of mumps exposure in a household 

has also just been initiated. These two protocols were submitted to and approved by 

institutional review boards (IRBs) at CDC and the New York State Department of Health 

(NYSDH). 

Over the next several months, CDC will continue to conduct on-going surveillance for mumps 

throughout the US, particularly to monitor for changing epidemiology or spread to other 

geographic locations or communities. As always, CDC continues to promote early recognition, 

diagnosis, and public health intervention, as well as timely vaccination with 2 doses of MMR 

vaccine. There are also plans to evaluate the impact of the administration of a third dose of 

MMR in Orange County to determine if this might be a possible intervention in future outbreaks 

of mumps. 

Discussion 

Dr. Baker inquired as to whether the genotype in this outbreak is the same as that in the 2006 

outbreak, and whether there was anything special about that strain in terms of transmissibility or 

virulence compared to other strains. 

Dr. Gallagher confirmed that it is the same genotype. CDC has addressed the question of 

transmissibility and virulence numerous times over the last several months. Thus far, there is 

no evidence to suggest there is any particular difference. 

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In terms of duration of immunity, Dr. Cieslak inquired as to whether CDC had assessed case 

status versus time since vaccination, and whether there was increased incidence with time 

since vaccination. 

Dr. Gallagher responded that they had examined this. The median duration of protection is 

about 10 years. Some cases have received vaccine more recently. She examined whether 

there was increased incidence with time since vaccination. It peaks at 10 years and beyond 

that drops off again. It is a bell-shaped curve. She thought this was in part because the nature 

of this outbreak is very much focused in religious schools that only certain age groups attend. 

Dr. Katz (IDSA) asked whether any serologic or virologic studies had been conducted. 

Dr. Gallagher responded that while such studies have not yet been conducted, they are under 

discussion. A meeting was planned that afternoon to discuss further research. Given that these 

cases continue, there are opportunities for additional studies. 

Dr. Middleman (SAM) inquired as to whether CDC observed a difference in complication rates 

among those who had 2 doses versus 1 dose versus 0 doses. 

Dr. Gallagher replied that they did. The most common complication was Orchitis by far. There 

is a statistically significant difference between the Orchitis rate in people who have had 1 dose 

versus 2 doses. It is lower in people who have had 2 doses. 

Dr. Lett noted that they would very much be looking forward to the data from the third dose 

studies. State and local health departments are trying to cope with what to do when they have 

cases. She wondered whether there were any national plans to communicate to religious 

groups to encourage people to be vaccinated before the upcoming religious holidays. While 

most children are vaccinated, a number of people are not or have unknown vaccination status. 

Dr. Gallagher indicated that CDC has begun to have these discussions, starting with some of 

the communities that are affected, given that the Passover holidays were approaching. Jewish 

boys attend schools called Yeshivas where frequently there is a mix of day students and boys 

who board there who may be from other parts of the country. During the Jewish holidays, the 

boys who are boarding will likely return home where they may introduce mumps into a new 

Orthodox Jewish Community, resulting in further spread. CDC has considered ways to send 

information home with Yeshiva students, and to disseminate messages to other Orthodox 

communities within the US that have not been affected so that they will be on heightened alert. 

Consideration is also being given to potentially sending out a message about being up to date 

on two doses so that these communities are prepared for potential imports. 

Dr. Salisbury (DOH, UK) reported that the UK has experienced measles problems in North 

London with this same community, particularly in 2007 and 2008. This was not because of any 

resistance to vaccination amongst this group. It was entirely to do with access. These are 

families with many children who simply were not availing themselves of the services offered. 

Working with the local communities certainly helped. Once these families knew the facilities 

were there for them to be immunized, they made more effort to get their children vaccinated. It 

was not a resistance to vaccines. It was simply being overwhelmed by the number of children. 

He alerted everyone that not only was mumps an issue in this community, but also measles can 

be spread very easily by this group due to their numerous international connections. 

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Dr. Meissner commented that the mumps component of the MMR does not work as well as the 

measles and the rubella components. With that in mind, he wondered whether Dr. Katz or Dr. 

Plotkin would comment on the need for improvement of the mumps strain in the vaccine. 

Dr. Katz said that in the absence of poor Dr. Hilleman who died several years ago, he was 

loathe to make any comments. He suggested that Dr. Offit may be able to comment more 

knowledgably on the Hilleman family. He also thought it would be interesting to hear from their 

Japanese visitors. Japan used the Urabe strain for a number of years, which was more 

reactogenic and produced aseptic meningitis among some of the recipients, so they abandoned 

it. One wonders if there is that much of a difference in the antigenicity or the immunogenicity of 

the strains that have been studied. As far as Dr. Katz was aware, the US outbreaks in 2006 and 

currently suggest that there is not long-lasting immunity for some individuals. For mumps, it is 

T-cell mediated immunity more than it is B-cell. 

Dr. Plotkin agreed that based on the range of efficacy presented, it was clear that the efficacy of 

a single dose certainly is less than one would wish, and less than the other two components. 

Japan no longer uses mumps vaccines, and they do have a mumps problem that has been wellwritten about. For whatever reason, they do not import measles, mumps, and rubella vaccine. 

As far as the relative safety and efficacy, the Jeryl Lynn strain and the GSK derivative of the 

Jeryl Lynn strain are the only two strains that are not associated with aseptic meningitis. 

However, there are comparative data that suggest that the Urabe strain in particular is 

somewhat more effective than the Jeryl Lynn strain. It also depends upon the duration of 

immunity—the time since vaccination. It is a complex situation, but he does believe that a better 

mumps vaccine strain is needed. There are several strains, but none of them is perfect. 

Dr. Temte noted that presumably, all of these individuals are being immunized within a limited 

set of clinics. With that in mind, he wondered whether anything was known about the storage 

and handling of vaccine at those sites. 

Dr. Gallagher responded that they are all being immunized within a limited set of clinics. Within 

one community that has received the third dose, there are basically four pediatric providers 

currently and probably over the last 20 or 30 years. Those who have lived in the community 

during that timeframe would have received vaccine from one of these providers. CDC has not 

conducted an assessment of the vaccine storage issues in these particular clinics. Many people 

have moved into this community who probably lived in New York City and may have received 

their vaccine there. There are many providers in various counties in New York and New Jersey 

who would have been providing vaccine to this group. 

Dr. Jane Zucker (NYCDHMH) reported that NYCDHMH examined the risk of Orchitis with 

vaccination, finding that there is a 4-fold higher risk of Orchitis in post-pubertal males who did 

not have any vaccine compared to those who had 2 doses (8% versus 2%, respectively). They 

conducted assessments and made VFC storage and handling visits to limited providers in the 

Brooklyn community. There appeared to be no problems with vaccine storage and handling. 

Among their initial cases, they collected rubella serology as a comparison to determine whether 

children really had been vaccinated or if records were being falsified for school for some reason 

(e.g., religious or philosophic exemptions; concerns about vaccination). This was not found to 

be an issue. In addition to the Passover holidays, there is Purim during which there are many 

parties and numerous children are gathering together. Last year, New York had a measles 

outbreak right after Purim, so they conducted numerous vaccination activities in the past few 

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Discussion Rotavirus Vaccines in Infants with Severe Combined Immunodeficiency 

Advisory Committee on Immunization Practices (ACIP) Summary Report February 24-25, 2010 

weeks. They anticipated the holidays and began preparing in advance for uptake in mumps and 

/ or measles cases. They also had an outbreak after the Jewish holidays in September. 

Catherine Yen, MD MPH
 

Epidemic Intelligence Service Officer
 

National Center for Immunization and Respiratory Diseases (NCIRD) 

Division of Viral Diseases (DVD) 

Dr. Yen provided background information regarding severe combined immunodeficiency (SCID) 

and discussed rotavirus vaccination in infants with SCID. 

SCID is a rare, heritable primary immunodeficiency characterized by impaired humoral and cellmediated immunity which is secondary to a lack of T-lymphocytes and low immunoglobulin 

levels, resulting in an inability to fight off infections of all types. At least 15 single gene disorders 

associated with SCID have been identified to date. The estimated incidence of SCID is about 1 

per 60,000 to 100,000 live births per year, for a total of about 100 infants in the US per year. 

The median age at diagnosis ranges from 4 to 7 months. 

Infants with SCID commonly present with chronic diarrhea, failure to thrive, early onset 

respiratory infections, and / or other infections that may include rotavirus. Diagnosis is usually 

made at the time of hospitalization with presentation of more severe disease or infection. 

However, prenatal diagnosis is available for those with a family history of SCID, though it is 

important to note that the majority of infants do not have a family history of SCID. Newborn 

screening techniques are also available, although they are not widely implemented. Currently, 

pilot newborn screening programs have been implemented in two states. A few other locations 

are planning to implement such pilot programs as well. 

The prevention and treatment of infectious diseases and hematopoietic stem cell transplantation 

offer the best chance of survival for infants with SCID. More specifically, early diagnosis and 

transplant before the occurrence of any severe infection offer the greatest chance of cure. 

Without transplant, death in early childhood due to infection will occur, with the majority of 

deaths occurring by 1 year of age. One possible exception is for those infants with adenosine 

deaminase deficiency. These children may survive longer with enzyme replacement therapy 

while awaiting transplant. Infants with SCID who acquire wild type rotavirus infection may 

develop chronic infection, which may manifest as prolonged diarrhea and prolonged fecal 

shedding of rotavirus. 

With regard to rotavirus vaccine infection in infants with SCID, in March 2009, a report of 2 

infants with diagnoses of SCID and infection with pentavalent vaccine-type rotavirus (RV5) was 

presented at the American Academy of Allergy, Asthma, and Immunology (AAAAI) Annual 

Meeting. Since then, 4 additional cases have been identified in the US, two of which have been 

published and reported to the Vaccine Adverse Event Reporting System (VAERS) and two of 

which we were notified through personal communication and were subsequently reported to 

VAERS. Another case from Australia was published in the Journal of Allergy and Clinical 

Immunology in September 2009. 

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i l l l 

 

 i f f i

i i i 

 I

 

li

Advisory Committee on Immunization Practices (ACIP) Summary Report February 24-25, 2010 

The following tables provide a summary of what is known about these 7 infants with SCID and 

rotavirus vaccine infection: 

Summary of Confirmed Cases 

Case 

Age at 

presentat on 

(months) 

Sex 

Doses of 

RV5 

received 

Past medica history C inica presentation 

1* 3 M 1 Milk protein allergy, 

chronic diarrhea 

Fever, vomiting, diarrhea, 

weight loss 

2* 4 M 2 None Diarrhea, dehydration, 

failure to thrive 

3* 4 F 2 Admission for respiratory 

distress at 1 week of age 

Fever, respiratory distress, 

diarrhea, dehydration, 

failure to thrive 

4* 4 F 3 Chronic diarrhea, 

faltering growth 

Vomiting, diarrhea, 

poor weight gain 

5 4 F 1 Hypothyroidism, 

failure to thrive 

Diarrhea, dehydration, 

failure to thrive 

6* 5 M 2 Chronic diarrhea Diarrhea, dehydration, 

failure to thrive 

7 6 F 2† Chronic diarrhea; ex-36 

week gestation 

Intermittent fevers, cough, 

diarrhea, periorbital cellulitis 

*Published case 

† Confirmation pending regard ng the number o doses o RV5 rece ved 

9 

Summary of Confirmed Cases 

Case Cl nical course Durat on of rotav rus 

shedding by E A 

1* Coinfection: Pneumocystis jirovecii; 

Treatment: transplant 11 months 

2* Coinfections: Pneumocystis jirovecii, rhinovirus, adenovirus, Giardia; 

Treatment: transplant 4 months 

3* Coinfection: Pseudomonas aeruginosa (respiratory); 

Treatment: transplant 5 months 

4* Treatment: transplant 7.5 months 

5 Coinfections: Escherichia coli (urine), Pneumocystis jirovecii; 

Treatment: transplant 8 months 

6* Coinfections: Salmonella (blood and stool), Pneumocystis jirovecii; 

Treatment: awaiting transplant >1 month 

7 Coinfections: rhinovirus, Pneumocystis jirovecii; 

Treatment: receiving PEG ADA, awaiting transplant <1 week 

*Pub shed case 

10 

Information was obtained through publications, VAERS reports, and in some cases, medical 

records that were sent to the VAERS team. The age at time of presentation of symptoms 

ranged from 3 to 6 months, and most infants had received either 1 or 2 doses of RV5 prior to 

presentation. For case number 4, the Australian case, this infant began to experience chronic 

diarrhea and poor growth at age 4 months, but was not actually diagnosed with SCID until the 

age of 9 months and had received 3 doses of rotavirus vaccine. Many of the infants had past 

medical histories significant for chronic diarrhea. All of the infants presented with diarrhea 

around the time of diagnosis of SCID. For case number 7, where it says confirmation pending 

regarding the number of doses of RV5 received, it has been confirmed that this infant received 2 

doses of vaccine. 

The majority of infants who were eventually diagnosed with SCID presented with co-infections, 

including fungal infection with Pneumocystis jirovecii (otherwise known as PCP), viral infections 

such as rhinovirus and adenovirus, parasitic infection with Giardia, and bacterial infections with 

Pseudomonas aeruginosa, E. coli, and Salmonella. At the time of CDC’s follow-up of these 

cases, 5 infants had undergone hematopoietic stem cell transplantation and 2 were awaiting 

transplant. The duration of rotavirus shedding by enzyme immunoassay (EIA) for these infants, 

defined as the period between the initial positive rotavirus EIA test and the first negative EIA 

test, was from less than 1 week to 11 months. This could be a minimum duration of shedding 

depending on when that first positive test was performed. Additionally, 5 of the infants had 

multiple stool samples positive for vaccine-type rotavirus. 

Given these reports of rotavirus vaccine infection in infants with SCID, Merck and Company 

requested to add SCID as a contraindication to the RotaTeqTM product label. This request was 

approved by the FDA on December 23, 2009. Given the change in the RotaTeqTM product 

label, CDC initiated a discussion regarding this topic with members of the former ACIP 

Rotavirus Working Group. After discussion and at this time, CDC recommends the addition of 

SCID as a contraindication for both licensed vaccines, RV5 and the RV1 monovalent vaccine. 

Though at this time CDC is not aware of an RV1 infection in a US infant with SCID, RV1 will be 

included in the contraindication given the biological plausibility for RV1 infection in infants with 

SCID. CDC also recommends the publication of an MMWR Policy Note regarding the addition 

of this contraindication to the current recommendations for rotavirus vaccination. Additionally, 

CDC will continue to monitor reports of rotavirus vaccine infection in infants with SCID. 

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Discussion

Advisory Committee on Immunization Practices (ACIP) Summary Report February 24-25, 2010 

Given the importance of early diagnosis of SCID in terms of survival, on January 21, 2010, the 

Advisory Committee for Heritable Disorders in Newborns and Children (ACHDNC) unanimously 

voted to recommend the addition of SCID to the core panel of the recommended uniform 

screening panel for newborns. This recommendation is awaiting approval by the Department of 

Health and Human Services (DHHS). If approved, this likely will lead to more widespread 

implementation of newborn screening and earlier diagnosis of SCID for affected infants. 

Discussion 

Dr. Cieslak said he understood the manufacturer’s choice, but rotavirus is essentially universal 

in unvaccinated children. He inquired as to what occurs when SCID children contract a wild 

virus as opposed to an attenuated virus. 

Dr. Yen replied that the same symptoms could occur. 

Dr. Baker pointed out that rotavirus has been seen in these children for a number of years. 

They are not particularly ill, but they shed for a very long time with intermittent, fairly easy to 

control diarrhea. They may need hydration, for example. 

Vaccine Supply Update 

Jeanne M. Santoli, MD, MPH 

Vaccine Supply and Assurance Branch 

Dr. Santoli presented an update for Hib, Hepatitis B, Hepatitis A, Rotavirus, MMRV, and Zoster 

vaccines, and reported on supply constraints. 

Merck received FDA approval for distribution of monovalent Hib vaccine, PedvaxHIB®, on 

January 14, 2010. The product became available for order the following week. PedvaxHIB® is 

one of a number of products currently available for Hib vaccination. Other products available for 

Hib include monovalent Hib vaccine from sanofi; monovalent Hib from GSK, which is currently 

licensed for the booster dose only; and the combination Pentacel vaccine from sanofi pasteur. 

There are two combination Hib vaccines, one from Merck (Comvax) and one from sanofi 

(TriHIBit) that are not currently available. 

CDC is updating website Hib postings to emphasize the recommendation for active recall of 

children in need of a booster dose based on current supply. The initial discussions about recall 

were limited to the next medical visit. Next, they were limited to when feasible and when supply 

permits, but at this point, active recall of these children is recommended to get them caught up. 

Both manufacturers are back to full supply of their monovalent pediatric hepatitis B vaccines. 

There were some doses borrowed from the stockpile last year, which are in the process of being 

repaid. CDC had been managing orders through allocation to states, which was discontinued 

on January 1, 2010. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report February 24-25, 2010 

In terms of Hepatitis B vaccines for adults, Merck is not currently distributing its adult or dialysis 

hepatitis B vaccines. The dialysis formulation is anticipated to return sometime in the third 

quarter of 2010. The adult formulation will not be available from Merck for the first half of 2010, 

but there will be an update during the first half to provide information regarding when that 

vaccine will be available again. Following backorders (> 1 month) in the late fall for both 

formulations, GSK now has product available and has cleared backorders. GSK expects to 

have at least one presentation of adult monovalent product continuously available (vials). The 

combination product, Hep A-Hep B vaccine, is available as an alternative. 

There were some product outages of GSK’s pediatric hepatitis A vaccines in the second half of 

2009. Both manufacturers are currently making vaccine available to the market and utilizing 

doses from the pediatric stockpiles to fill in gaps as needed. 

For adult Hepatitis A vaccine, Merck announced it would not be distributing adult Hepatitis A 

vaccine for the rest of 2010; however, GSK's production and supply of their monovalent and 

combination adult vaccines are in adequate supply to meet demand for 2010. 

With regard to rotavirus vaccines, GSK experienced some intermittent product outages in 

November and December 2009, but supply became available in late December and GSK has 

been able to clear back orders for that product. GSK anticipates that there may be some 

intermittent backorders until mid-March 2010, but both manufacturers anticipate being able to 

meet demand for their customers for the two rotavirus products. 

Merck had recently delayed the re-launch of MMR-V that was originally set for mid-February. 

That delay reflects varicella manufacturing prioritizations for 2010 due to a less than expected 

yield of bulk product. Varicella vaccine remains the first priority for varicella bulk, followed by 

zoster vaccine, and then MMR-V. Limited doses of the MMRV will be available later this year 

and Merck will provide more information as it becomes available. Importantly, the supply of 

varicella and MMR vaccines is sufficient to support current recommendations. 

Zoster vaccine is currently available to order, but Merck anticipates that customers will likely 

experience backorders throughout the year, given that bulk varicella product is prioritized for 

use in manufacturing the varicella vaccine. 

Regarding supply constraints of specific presentations, GSK anticipates intermittent supply 

constraints during the first half of 2010, including Havrix® pediatric syringes and KinrixTM 

syringes; however, alternative presentations (vials) and other brands are available to address 

these constraints. 

CDC’s Vaccine Supply / Shortage Webpage can be found at the following url: 

http://www.cdc.gov/vaccines/vac-gen/shortages/default.htm 

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Advisory Committee on Immunization Practices (ACIP) Summary Report February 24-25, 2010 

Evidence Based Recommendations Work Group 

Introduction 

Jonathon Temte, MD, PhD, Chair 

Evidence Based Recommendations Work Group 

Dr. Temte noted that ACIP is constantly being asked to translate complex information into 

meaningful and implementable recommendations. The comments from Dr. Frieden the 

previous day and from the last time he spoke during an ACIP meeting got to the heart of using 

very good evidence for this process. 

The Evidence Based Recommendations Work Group’s charge is to develop a uniform approach 

to making explicit the evidence base for ACIP recommendations. This is fairly straightforward, 

at least on the surface. This work group was reactivated in November 2007. When Dr. Temte 

first joined ACIP as an American Academy of Family Physicians (AAFP) liaison in 2004, this 

group had some activity, but it faded out for a while. He expressed his hope that they would 

reach a point of bringing some activities to a conclusion. The work group has convened 

monthly conference calls since January 2008, and has been working on guiding principles and 

reviewing several evidence-based systems for developing guidelines used by other 

organizations. For example, the work group has assessed the methods of the following groups 

and systems: 

 US Preventive Services Task Force, 

www.ahrq.gov/clinic/uspstf08/methods/procmanual5.htm 

 Guide to Community Preventive Services, www.thecommunityguide.org/about/methods.html 

 GRADE: Grading the quality of evidence and the strength of recommendations, which we 

will be talking much more through this discussion. www.gradeworkinggroup.org/intro.htm 

 National Advisory Committee on Immunization from Canada, www.phacaspc.gc.ca/publicat/ccdr-rmtc/09pdf/acs-1.pdf 

 American Academy of Pediatrics 

The work group’s guiding principles are to focus on transparency; use evidence of varying 

strengths; consider individual and community health; adopt / adapt an existing system rather 

than re-creating something that may already exist; continually strive to improve the process; and 

first apply the proposed process to new vaccines and new indications or restrictions of existing 

vaccines. The components of evidence-based vaccine recommendations include key elements 

for consideration (e.g., safety, efficacy, and burden of illness); an assessment method for 

existing evidence; standardized format for recommendations; and a means for reporting of 

elements and evidence in a clear and transparent manner. 

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Overview of Evidence Assessment 

External assessment 

of recommendations 

Methodological 

Evidence Grading Standards 

Quality of AGREE 

Research studies Evidence 

RCT 

method 

method 

GRADE Case-control 

Cross sectional Recommendation 

Expert opinion 

 

 

 

 

Advisory Committee on Immunization Practices (ACIP) Summary Report February 24-25, 2010 

The work group proposed to adopt the Grades of Recommendation Assessment, Development 

and Evaluation (GRADE) framework for rating quality of evidence, and to adapt the GRADE 

system for moving from evidence to recommendations. The GRADE system has had wide 

uptake from a number of sister groups, such as the following: 

 Agency for Health Care Research and Quality (AHRQ) 

 American College of Chest Physicians 

 American College of Physicians 

 American Thoracic Society 

 Allergic Rhinitis in Asthma Guidelines 

 CDC Healthcare Infection Control Practices Advisory Committee 

 Infectious Diseases Society of America 

 UpToDate 

 British Medical Journal 

 Canadian Cardiovascular Society 

 Clinical Evidence 

 Cochrane Collaboration 

 European Society of Thoracic Surgeons 

 National Institute Clinical Excellence (NICE) 

 Scottish Intercollegiate Guideline Network (SIGN) 

 World Health Organization (WHO) 

 Over 20 other major organizations 

Dr. Temte indicated that during this session, presentations would be offered regarding 

methodological standards for clinical practice guidelines, grading the quality of evidence, and 

synthesizing and presenting recommendations. He noted that Dr. Craig Umscheid from the 

University of Pennsylvania, who would present information on the GRADE system, is one of the 

members of the working group for GRADE. 

Dr. Temte clarified how GRADE differs from AGREE: 

Appraisal of Guidelines for Research and Evaluation (AGREE) is an external process by which 

recommendations can be evaluated. There are two different processes: 1) moving from 

evidence to a recommendation (GRADE); and 2) external assessment of that recommendation 

of the guidelines (AGREE). 

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Advisory Committee on Immunization Practices (ACIP) Summary Report February 24-25, 2010 

Methodological Standards for Clinical Practice Guidelines 

Faruque Ahmed, PhD 

National Center for Immunization and Respiratory Diseases 

Centers for Disease Control and Prevention 

Dr. Ahmed pointed out that major organizations in the US, Canada, and Europe are increasingly 

using evidence-based methods to develop clinical practice guidelines. Methodological 

standards have been developed to direct the development of guidelines. Clinical practice 

guidelines are systematically developed statements to assist practitioner decisions about 

appropriate health care for specific clinical circumstances. “Quality of guidelines” means the 

confidence that the potential biases of guideline development have been addressed adequately. 

AGREE is an international collaboration of researchers and policy makers who seek to improve 

the quality and effectiveness of clinical practice guidelines. The AGREE collaboration 

developed the AGREE instrument to provide a systematic framework for assessing key 

components of guideline development. The AGREE instrument includes 23 items grouped into 

6 domains: scope and purpose, stakeholder involvement, rigor of development, clarity and 

presentation, applicability, and editorial independence. 

The rigor of development domain, for example, includes the following components: 

 Systematic methods were used to search for evidence 

 The criteria for selecting the evidence are clearly defined 

 The methods used for formulating the recommendations are clearly described 

 The health benefits, side effects and risks have been considered in formulating the 

recommendations 

 There is an explicit link between the recommendations and the supporting evidence 

 The guideline has been externally reviewed by experts prior to its publication 

 A procedure for updating the guideline is provided 

Alonso-Coello et al used the AGREE instrument to assist in the quality of 626 guidelines 

published from 1988 through 2007. These guidelines are published primarily in North America 

and Europe by medical societies and governments on a variety of healthcare topics. The 

number of each is reflected in the following table: 

Characteristics Number 

Continent of published guidelines 

 North America 

Europe

 Other 

264 

264

 97 

Type of organization responsible for guideline 

Medical society

 Government

 Other 

373 

121 

110 

Healthcare topic 

Internal medicine / critical care / geriatrics 

 Musculoskeletal 

 Oncology 

 Other 

173 

136 

127 

184 

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The mean scores for the 626 guidelines for the AGREE domains were: applicability 22%, 

editorial independence 30%, stakeholder involvement 35%, rigor of development 43%, clarity 

and presentation 60%, and scope and purpose 64%. While the mean scores have increased 

slowly over the last 20 years, there is substantial room for improvement. The mean scores over 

time for the 6 AGREE domains are depicted in the following graphic: 

Use of evidence-based systems such as GRADE can improve the quality of guidelines. As 

noted, GRADE has two components: assessing the quality of evidence and a process for 

moving from evidence to recommendations. The quality of evidence is rated as high, moderate, 

low, or very low. The strength of recommendation is graded as strong or weak. Guideline 

developers need to incorporate structured and rigorous methodologies to improve the 

methodological quality of guidelines. 

Grading Quality of Evidence; the GRADE approach 

Craig A Umscheid, MD, MSCE 

Assistant Professor of Medicine 

Co-Director, Center for Evidence-based Practice 

University of Pennsylvania 

Dr. Umscheid indicated that he is a hospitalist clinically and an epidemiologist at the University 

of Pennsylvania. He explained that one of the reasons he was invited to speak during this ACIP 

meeting was because he and the center he co-directs at the University of Pennsylvania, the 

Center for Evidence Based Practice, worked closely with CDC’s HICPAC committee to update 

their guideline methodology. The first guideline using that methodology was recently published 

in Infection Control and Hospital Epidemiology, and is titled Guideline for Prevention of 

Catheter-Associated Urinary Tract Infections 2009. 

During this session, Dr. Umscheid focused on how the GRADE system helps to grade the 

quality of evidence in a guideline, the guideline development processes from higher than a 

30,000 foot view, the GRADE approach, and grading of evidence quality. 

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The following illustrates the general guideline development process: 

Prioritise Problems, establish panel, questions 

È

Systematic Review 

È

Evidence Profile 

È

Relative importance of outcomes 

È

Overall quality of evidence 

È

Benefit – downside evaluation 

È

Strength of recommendation 

È

Implementation and evaluation of guidelines 

Guideline development process

3

Dr. Umscheid emphasized that arguably the most important step in the guideline development 

process is developing the right key question. Guidelines are a way of answering questions 

about clinical, communication, and organizational or policy interventions in the hope of 

improving health care or health policy. It is, therefore, helpful to structure a guideline in terms of 

answerable questions. If the right question is not posed, a guideline will result that does not 

address the questions that are on the minds of practicing providers. For ACIP, Dr. Umscheid 

thought that process might be relatively easy in that the questions would be largely 

circumscribed around the efficacy and safety of particular vaccines. For other groups, question 

development can be very challenging. 

There is information about how Dr. Umscheid’s group helped HICPAC update their guideline 

methodology on the HICPAC website and in a March 2010 in the American Journal of Infection 

Control. He also recommended reading an article by the GRADE Working Group about the 

GRADE approach published in the British Medical Journal in April 2008, which is a very general 

article about the approach. 

To illustrate how to grade the quality of evidence in a guideline, Dr. Umscheid walked through 

one of many questions that were posed for the HICPAC guideline: Do Texas catheters impact 

UTI outcomes differently than Foley catheters? A systematic review of the evidence was 

conducted to determine the answer to this question. The GRADE process was then used to 

judge the overall quality of the evidence and weigh the risks and benefits in order to make a 

recommendation. Obviously, GRADE uptake is pretty broad and deep. Probably the most 

important organizations to emphasize for ACIP that use GRADE are the World Health 

Organization (WHO), the National Institute Clinical Excellence (NICE), the Infectious Diseases 

Society of America (IDSA), and most recently HICPAC. 

The following table outlines the clinical question asked in the guideline regarding Texas versus 

Foley catheters in terms of outcomes, quantity and type of evidence, and findings: 

Comparison Outcome Quantity and Type of Evidence Findings 

Texas vs. Foley Symptomatic UTI 1 RCT Decreased risk 

catheter 

Bacteriuria 1 RCT No difference 

Bacteremia 1 OBS No difference 

Patient Satisfaction 

1 RCT 

1 OBS Increased satisfaction 

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Once the systematic review of the literature for the key question done and all of the outcomes 

available in the literature are determined, consideration must be given to which outcomes are 

most important in terms of making a decision about how to answer the key question. The 

importance of the outcome, with the following categories used: critical for decision making, 

important but not critical for decision making, and of low importance. For this particular 

question, outcomes that are critical for decision making might be symptomatic UTI - the 

difference between incidence of symptomatic UTI between the two catheters, and patient 

satisfaction between the two catheters. An outcome that may be important but not necessarily 

critical for decision making might be bacteremia. An outcome of low importance might be 

asymptomatic UTI or bacteriuria. The guideline committee basically agreed with this 

assessment. 

In terms of understanding how the quality of evidence is judged for each of outcome available in 

the literature, evidence that includes RCTs are considered to be of the highest quality, while 

OBS [observational studies] are considered to be of low quality evidence. There are 5 factors 

that can lower the quality of evidence and 3 factors that can increase the quality of evidence. 

For example, the outcome of symptomatic UTI has an RCT informing it. The initial grade of the 

evidence is going to be high, but 5 criteria can decrease that grade. One of those criteria is 

study quality limitations. For each guideline, the specific criteria that will be used to understand 

whether the quality of the study is limited have to be developed a priori. For example, a study 

quality might be limited if the randomization in it is incorrect or if there is no blinding. 

Inconsistency is the next criterion that could decrease the grade of quality for an individual 

outcome. Basically, inconsistency means that results are not consistent across studies that are 

informing that outcome. For example, two RCTs assessing symptomatic UTI for Texas versus 

Foley catheters may differ. One the RCTs might suggest that there is decreased UTI with 

Texas catheters, while the other might suggest that there is increased UTI with Texas catheters. 

If these inconsistent results cannot be explained, a point is taken off. Indirectness is another 

criterion for which a point may be taken off (e.g., no data on male Texas catheters, the study 

question; but information is available on female Texas catheters versus Foley catheters). 

Imprecision simply means that there are very few events in the studies that are informing the 

outcome. Either there are very few studies, or confidence intervals in the studies are very large. 

Publication bias simply means that perhaps there are just one or two small studies that show a 

very large magnitude of effect for condom catheters, but both are published by the manufacturer 

of Texas catheters. Conversely, beginning with an OBS that is informing one of the outcomes, 

the grade may start out low, but there are criteria that can be used to increase the quality grade, 

one of which is strength of association. Dose response is another criterion that could increase 

the grade. Inclusion of unmeasured confounders would increase the magnitude of effect. 

In terms of what these outcomes actually mean, a high overall quality grade means that further 

research is very unlikely to change confidence in the estimate of effect. Moderate grade means 

that further research is likely to impact confidence in the estimate of effect, and it may change 

the estimate. A low quality grade means that further research is very likely to impact confidence 

in the estimate of effect and is likely to change the estimate. Very low quality means that any 

estimate of effect is very uncertain. 

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Specific to symptomatic UTI in the example, because RCTs informed this particular outcome, 

the quality of the evidence for that outcome started out as high, but one point was taken off for 

imprecision because there is just one study, so the grade went down to moderate. One RCT 

informed the outcome of bacteriuria, so the outcome started out as high quality. Again one 

point was taken off because there was just one RCT. Thus, the grade went down to moderate. 

Only one OBS informed the bacteremia outcome, so that outcome started out as low quality but 

one point was taken off for imprecision. Therefore, this outcome dropped to very low. Two 

studies informed the patient satisfaction outcome (one RCT and one OBS). Because there was 

an RCT informing this outcome, the quality for the outcome started out as high. No points were 

taken off for any of the other criteria (e.g., inconsistency, individual study quality, or 

indirectness) so the quality for that outcome remained high. To obtain a quality for the overall 

evidence base answering this question, the lowest quality grade for the outcomes deemed 

critical is used. Symptomatic UTI and patient satisfaction were deemed to be critical, so the 

lower of these two grades was used for an overall grade of evidence for that outcome was 

moderate. 

In conclusion, GRADE provides a structured approach to assess the quality of evidence across 

guideline questions and outcomes. Although judgments are involved, as long as those 

judgments are systematically applied and they are transparent, it is reasonable to make them. 

Guidelines for Synthesizing and Presenting Recommendations 

Faruque Ahmed, PhD 

National Center for Immunization and Respiratory Diseases 

Centers for Disease Control and Prevention 

Dr. Ahmed presented the guidelines for formulating and presenting recommendations, 

discussing the GRADE approach for going from evidence to recommendations; describing how 

WHO and ACP are using GRADE for the development of recommendations for non-vaccine 

topics; and discussing how the GRADE approach could be adapted for vaccine 

recommendations. 

GRADE has two components: rating the quality of evidence and grading the strength of the 

recommendation. GRADE suggests using two grades for the strength of recommendation: 

strong and weak. Guideline panels may prefer to use the word “conditional” rather than “weak.” 

Strong or weak recommendations can be either for or against a recommended course of action. 

That is, a recommendation for a course of action can be strong or weak and a recommendation 

against a course of action can be strong or weak. Quality of evidence is only one factor in 

determining the strength of a recommendation. 

GRADE deliberately separates judgments regarding the quality of evidence from judgments 

about the strength of recommendation. Quality of evidence is linked to strength of 

recommendation, but there is no automatic one-to-one connection. High quality evidence does 

not necessarily imply strong recommendations, and strong recommendations can arise from low 

quality evidence. For example, the question may be asked: Should patients with deep vein 

thrombosis continue to take Warfarin long-term? High quality RCTs show that continuing 

Warfarin will decrease the risk of recurrent thrombosis, but at a cost of increased risk of 

bleeding and inconvenience. Because patients with varying values and preferences will make 

different choices, a weak recommendation becomes appropriate despite the high quality 

evidence. Guideline panels may offer a weak recommendation in this case [Guyatt et al. BMJ 

2008; 336:924-926]. 

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There may be instances where a strong recommendation based on lower quality evidence is 

appropriate. It will not always be possible or ethical to conduct RCTs. Examples include 

emergency or emerging situations such as the pharmacological management of avian influenza 

(H5N1) patients and management of individuals exposed to anthrax. An evidence-based 

approach entails transparency concerning the evidence that was considered and transparency 

in how judgments regarding the quality of evidence were made. 

As noted, key factors that can weaken the strength of recommendation are lower quality 

evidence, uncertainty about the balance of benefits versus harms and burdens, uncertainty or 

differences in values, and uncertainty about whether the net benefits are worth the costs. For 

example, the ACIP recommendation for use of HPV vaccine in males is a permissive or 

conditional recommendation because of cost and other factors. Additional factors that can 

affect recommendations include the burden of disease, equity, and potential for improvement in 

quality of care. In general, the higher the burden of disease, the higher the magnitude of the 

benefit of an intervention. 

With regard to the implications of strong and weak recommendations for clinicians, a strong 

recommendation implies that most patients should receive the recommended course of action. 

A weak recommendation implies that clinicians should be prepared to help each patient arrive at 

a decision that is consistent with his or her values and preferences. It is important to note that 

clinicians, patients, insurers, review committees, other stakeholders, and / or the courts should 

never view recommendations as dictates. Even strong recommendations based on high-quality 

evidence will not apply to all circumstances and all patients.
 

Dr. Ahmed presented information about WHO’s use of the GRADE method for developing 

guidelines for the pharmacological management of avian influenza, which was published in The
 

Lancet in 2007. Clinical questions were initially identified by clinicians managing patients with 

avian influenza and refined by the members of the guideline panel. One of the clinical questions 

was: Should oseltamivir be used for treatment of avian influenza A (H5N1) patients? The 

outcomes of interest included mortality, hospitalizations, resource use, adverse outcomes, and 

antimicrobial resistance. In terms of the summary of the evidence, there are no randomized 

trials of oseltamivir for treatment of avian influenza. There are 4 systematic reviews and health 

technology assessments that assessed the effectiveness of oseltamivir in seasonal influenza. 

According to the GRADE framework, these studies provide indirect evidence of the 

effectiveness of oseltamivir in avian influenza A (H5N1). There are 3 published case series 

describing H5N1 patients treated with oseltamivir. There are many in vitro and animal studies
 

of the effects of oseltamivir on the H5N1 virus, which provide indirect evidence. There is no 

alternative that is more promising at present, and the cost of oseltamivir is about $40 per 

treatment course. 

The judgments of the WHO guideline panel on the 4 key factors that determine the strength of 

the recommendation are reflected in the following comments they made:
 

“The benefits are uncertain, but potentially large.” 

“The quality of the evidence is very low.” 

“All patients and care providers would accept treatment for H5N1 disease.” No alternative. 

“The cost is not high for treatment of sporadic cases.” 

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W.H.O. Recommendation on Use of 

Oseltamivir for Avian Influenza 

Recommendation: In patients with confirmed or 

strongly suspected infection with avian influenza A 

(H5N1) virus, clinicians should administer oseltamivir 

treatment as soon as possible (strong recommendation, 

very low quality evidence). 

Re mar k s 

Thi s r ecommendat i on pl aces a hi gh val ue on t he pr event i on 

of deat h i n an i l l ness wi t h a hi gh case f at al i t y. It 

pl aces r el at i vel y l ow val ues on adver se r eact i ons, t he 

devel opment of r esi st ance and cost s of t r eat ment . Despi t e 

t he l ack of cont r ol l ed t r eat ment dat a f or H5N1, t hi s i s a 

st r ong r ecommendat i on, i n par t , because t her e i s a l ack of 

known ef f ect i ve al t er nat i ve phar macol ogi cal i nt er vent i ons 

at t hi s t i me. Schunemann et al., The Lancet ID, 2007 

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The American College of Physicians' Guideline Grading System

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Advisory Committee on Immunization Practices (ACIP) Summary Report February 24-25, 2010 

The WHO panel made a strong recommendation for using oseltamivir. Please note the format 

for presenting the recommendation. The word “should” is used for strong recommendations. 

The strength of the recommendation and the quality of evidence are shown in parentheses. 

The remarks section indicates the key considerations underlying the recommendation. This 

section also explains why this is a strong recommendation, despite the fact that the quality of 

evidence is low: 

The format makes the strength of recommendation, the quality of evidence, and the thought 

process underlying the recommendation very transparent. 

The following table illustrates the ACP’s guideline grading system, which is based on the 

GRADE approach. The quality of evidence is rated as high, moderate, or low. The strength of 

recommendation is graded as strong or weak. There is also a category of insufficient evidence 

to make a recommendation: 

16 

Qaseem A e a Ann Intern Med 2008;148:680 684 

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Advisory Committee on Immunization Practices (ACIP) Summary Report February 24-25, 2010 

The current ACIP wording of recommendations is illustrated in the following recommendations 

extracted from the ACIP website: 

17 

Current ACIP Wording of Recommendations* 

FOR: ACIP recommends vaccination; ACIP recommends 

routine vaccination; Should receive; Vaccination is 

indicated; Should be considered; Can be considered; May 

be considered; Consider vaccination; Should receive 

special consideration; May elect vaccination; May be 

offered on a voluntary basis; Any person who wishes. 

AGAINST: Vaccination is not recommended; Not routinely 

indicated; Should avoid use; Should not be provided; Not 

usually recommended; Is not indicated; Is not necessary; 

Data are insufficient to recommend vaccination. 

*The word “routine” is often used in the context of age-based recommendations 

There is a wide range of wording used for recommendations for vaccination and 

recommendations against vaccination. The word “routine” is often used in the context of agebased recommendations. For example, the ACIP recommends routine HPV vaccination of girls 

aged 11 or 12 years. 

Given that categorizing recommendations as strong or weak may not be most appropriate for 

vaccine recommendations, the Evidence Based Recommendations Work Group proposed the 

following categories for ACIP recommendations: 

 Recommendation for or against (Category I) 

 Optional use (Category II), which is similar to what is currently referred to as a “permissive 

recommendation;” other suggested terms are “options” and “conditional recommendation” 

 No recommendation/unresolved issue 

Key factors for ACIP to make an optional use recommendation include: 

 Uncertainty about the balance between desirable and undesirable effects 

 Lower quality of evidence 

 Uncertainty or variability in values and preferences 

 Uncertainty about whether the net benefits are worth the costs (cost-effectiveness) 

These are the same key factors that GRADE suggests for determining the strength of a 

recommendation. 

Examples of desirable effects that are relevant for vaccine recommendations include mortality 

reduction, reduction in disease, fewer hospitalizations, fewer emergency department visits, and 

improvement in quality of life. Examples of undesirable effects include deleterious impact on 

morbidity, mortality, or quality of life. Other factors for formulating vaccine recommendations 

include burden of disease (the higher the burden of disease, the higher the magnitude of 

benefit, acceptability of vaccine, vaccine supply, feasibility of implementation, equity, and other 

ethical considerations. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report February 24-25, 2010 

The work group wrestled with wording for recommendations because this is critical to provide 

adequate guidance to clinicians. The work group proposed the following wording: 

 For category I, use words like “recommend,” “recommend against,” “should,” and “should 

not.” 

 For category II, use words like “may.” For example: HPV vaccine may be given to males 

aged 9 through 26 years. 

The proposed format for presenting ACIP recommendations is as follows: 

• Recommendation 

– ACIP recommends/does not recommend ... (Category, quality of evidence) 

• Remarks 

–	 Explicit consideration of the quality of evidence, benefits, harms, burdens, costs, 

values and preferences, and other factors for formulating each recommendation 

should be described here 

The ACIP recommendation should be followed in parentheses by the recommendation category 

and the quality of evidence. The remarks section should describe the key considerations and 

the thought process underlying the recommendation. 

The labels for the recommendation categories and the evidence grades are illustrated as 

follows: 

24 

Labels for ACIP Recommendation 

Categories and Evidence Grades 

Evidence Grade* Label 

High A 

Moderate B 

Low C 

Very Low D 

*For vacc ine safety and efficacy 

Recommendation for or recommendation against are to be labeled Category I. Optional use 

recommendations are to be labeled Category II. The evidence grades are to be labeled A, B, C, 

or D. Please note that the evidence grades refer to the quality of evidence for vaccine safety 

and vaccine efficacy. For cost-effectiveness the guidance for health economic studies 

published by the ACIP Work Group on Economic Analysis should be used. The guidance 

enhances the transparency and quality of economic materials presented to ACIP. The 

Evidence Based Recommendations Work Group is not proposing to grade the quality of costeffectiveness studies. 

In summary, the Evidence Based Recommendations Work Group proposed that ACIP adopt the 

GRADE framework for assessing quality of evidence and for going from evidence to 

recommendations. The advantages of adopting GRADE include explicit, comprehensive criteria 

for downgrading and upgrading quality of evidence ratings; a transparent process of going from 

evidence to recommendations; explicit acknowledgment of values and preferences; balance 

155 

Recommendation Category Label 

Recommendation for or against Category I 

Optional use Category II 

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Advisory Committee on Immunization Practices (ACIP) Summary Report February 24-25, 2010 

between simplicity and methodological rigor; and use by many other organizations, which 

unifies the meaning of recommendations across organizations. 

Discussion 

Dr. Pickering pointed out that ACIP now has 14 work groups, some of which will need to learn 

how to use the GRADE framework if ACIP votes to adopt this system. New work groups will be 

formed in the future, so there will need to be a continual educational process. He wondered 

how they would recommend educating people in a simple manner who have various 

backgrounds with regard to evidence-based medicine so that this system can be applied to 

future ACIP recommendations. 

Dr. Umscheid responded that HICPAC decided to consult with methodologists and provide 

content experts who worked with his group to produce their guidelines. Another way might be to 

develop a cadre of methodologists at CDC, perhaps specifically for ACIP, who know how to use 

this process and who could act as consultants to the content experts for each of the guidelines 

to be developed. He recommended that the cadre of methodologic experts work with a group 

that has used this method at least once in the past, in order to prepare to guide others on their 

own. 

Dr. Ahmed reminded everyone that there are two components of GRADE: 1) the quality of 

evidence, which is more technical and requires expertise; and 2) recommendations, which is not 

as technical, so ACIP work group members can be trained for this. For the first component, at 

least one person is needed who is trained in the GRADE method at CDC who would work with 

the ACIP work group. This could be the CDC lead on that work group. Not all work group 

members need to know the statistical details of the evidence grading. Perhaps a one- or twohour presentation would be sufficient to understand the framework. 

Dr. Morse congratulated the work group on significant progress in the development of a more 

uniform evidence-based system to help ACIP make recommendations. This shows great 

promise as they continue to improve the science-based criteria that ACIP is so dependent upon. 

However, he reminded everyone that while this is a necessary and important tool to assist ACIP 

in making complex and difficult decisions, it alone, like cost-benefit analyses, is not sufficient to 

do so. If it were, there would be computers rather than ACIP members sitting at the inner circle 

to make decisions. It is critical that the tool does not become the policy. Also, acceptability of 

the tool is directly related to the ability to understand its use and to explain that to ACIP’s 

customers—the public who is affected by its use. Today’s presentation was a great first step, 

but as ACIP utilizes this tool, it will require continuing education, as Dr. Pickering mentioned, as 

well as assessment. With that preamble in mind, Dr. Morse inquired as to whether there were 

plans to pilot test this approach and further improve it before implementation. 

Dr. Umscheid responded that this approach and process is really not a “plug and chug process.” 

This is a process which requires a group of methodologists who understand how to conduct 

systematic reviews and the nuances of that; who understand how to grade the quality of an 

evidence base and that is going to change depending upon the question being asked; and who 

understand how to translate that evidence into recommendations and incorporate the values, 

preferences, risk benefits, and costs. In addition, this process has been used successfully in 

many different areas across medicine and beyond, not just in infection control (e.g., cardiology, 

pulmonary critical care, et cetera). In that respect, it has been tested. The strength of the 

recommendations and the quality of evidence that have come out of these processes have had 

good validity to support this framework. 

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Dr. Temte emphasized that what is important is clarity and transparency. What they want to 

end up with eventually is recommendations that include a remarks section. The values placed 

on the meningococcal vote from 4 or 5 years ago were very important. A lot of value was 

placed on the quality of life and individual suffering that went into that decision. He thought of 

the methodology not as the end, but as the appropriate tool to get from the questions and the 

evidence to what ACIP is voting on. One thing the work group proposes is run this process on 

one or two fairly recent previous recommendations as an example. 

Dr. Ahmed mentioned that the second component of GRADE, going from evidence to 

recommendations, is done by ACIP anyway. The concepts are very similar. Using GRADE will 

simply put a structure around recommendations that is transparent to everyone. The only 

addition being made with the GRADE framework is assessing the quality of the evidence as 

high, moderate, low, and very low. 

Dr. Baker agreed that they basically use this process anyway. For vaccines, they have the 

advantage of always having a very robust RCT, which is not always true with other guidelines. 

The reason they had a Pregnancy Work Group was because the language from vaccine to 

vaccine differed widely in terms of cautions, recommendations, or no recommendations. She 

thought that standardization of language from vaccine to vaccine would be a benefit of this 

framework. 

Dr. Langley (NACI) pointed out that there is a culture change that is moving toward this 

framework. NACI published their method in January 2009. Thought some individual members 

felt uncomfortable if they did not have a Masters in Clinical Epidemiology, overall using such a 

framework aids in the decision making process. NACI does not use the GRADE framework, but 

does use a lot of the same components. They begin with the knowledge synthesis, which is the 

individual construction of tables of evidence and harm in which each study is listed. The next 

step is to synthesize that into a recommendation. They considered GRADE when they were 

developing their construct, but found it difficult how the weighting of plusses and minuses really 

reflected the domain they were trying to capture. Is a plus really equal to a minus in terms of 

the weight of how important that factor is? Instead, they assess the evidence itself, but then in 

summarative text list other factors that were important, like burden of illness and so on. It is a 

little different, but so far it seems to be working for them. The main effect is that although many 

people can carry around evidence in their heads, most people are simple folk who really look at 

it differently when it is objectively listed in a table. NACI posts their tables and literature 

syntheses on the website, separate from the statement, so anybody can review it. Though they 

might make a different decision, at least they know how NACI came to their decision. 

Dr. Chilton thought this would be very helpful to ACIP as they develop guidelines. He expressed 

his hope that the RSV immunoprophylaxis workgroup, with which he is associated, will be one 

of the first adopters of the GRADE framework. When he grades medical students who pass 

through their rotation, he constantly rails against few choices: outstanding, good, fair, or poor. 

He keeps wanting a “very good” category. Similarly with GRADE, this is a relatively small 

number of categories of strength of recommendation, one of which disappeared in the course of 

Dr. Ahmed’s presentation—the middle grade, which is not sufficient information to offer even a 

weak recommendation. There will likely be cases when either the evidence is poor or the 

evidence is balanced plus and minus, so there should be a category for time when a 

recommendation simply cannot be made. 

Dr. Ahmed clarified that this category does exist, but is not assigned a label (Category III). 

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Dr. Sumaya said that he was very favorable to this process, even knowing that it is something 

else they are going to have to learn and that will require a change in culture. He thought it 

would strike at a core number of the issue, particularly in terms of the language in the actual 

recommendations. He wondered whether the GRADE framework was one size fits all or if 

some adaptations would have to be made to address ACIP’s needs. 

Dr. Umscheid replied that one of the strengths of the GRADE process is that even though there 

are a lot of details to learn, the process itself is relatively flexible. This was why he believed 

there was uptake by so many different types of organizations. When they worked on the 

HICPAC guidelines, one of the first things they were asked was to keep the recommendation 

scheme that HICPAC used in tact and to modify GRADE to fit that scheme. They have 1a, b, 

and c and 2. The GRADE approach was modified to fit that scheme. There are benefits and 

harms in doing that. The HICPAC committee thought the benefits outweighed the harms. The 

benefits were essentially that the users of HICPAC guidelines over years and decades were 

very familiar with what a category 1a versus 1b versus 1c versus 2 meant, so it was very 

important to maintain that scheme. That said, he would probably recommend sticking with the 

very broad GRADE approach as presented. He would also recommend utilizing the criteria 

presented to increase or decrease the quality of the individual outcomes, although ACIP would 

have to define what “inconsistent” or “study limitation” means based on each of the guideline 

reviews conducted. It is key to define criteria and apply standards consistently across all of the 

studies being evaluated. There is judgment involved in creating some of the schemes, defining 

criteria to increase or decrease the grade, and in defining values or preferences. However, as 

long as they are systematic in the application of those judgments, their results will be 

reasonable. 

Peter Briss indicated that he was asked to attend the ACIP meeting because he was an original 

co-developer of GRADE. He said he anticipated that ACIP would have to develop a cadre of 

people, internally or externally, who are able to develop and apply these judgments. He 

expressed skepticism personally about whether this framework could just be pulled off the shelf 

to meet all of ACIP’s needs. Safety and harms are typically difficult to apply. Often, the best 

conceivable data scores low quality, so ACIP may have to fiddle with the system to figure out 

how to adapt to that. Although it is argued that people have applied the GRADE system to 

actual public health interventions, all of the examples to date have been very individual efforts 

such as anthrax prophylaxis. There are not any population-based examples of which he was 

aware, and he personally did not believe this system would work very well in population-based 

interventions where randomized trials are not feasible. To the extent that ACIP has to deal with 

safety and more population-based questions, they may have adapting to do. While he would be 

delighted to be wrong about that and it may be that ACIP’s first few examples settle such 

issues, there may be some predictable issues that will be sticky. 

Dr. Cieslak said that he also had some skepticism; however, his skepticism regard how much 

ACIP needed this framework and whether they needed to solve their issues with such an 

involved process. While he agreed that they need a better standardization of language, he 

thought they could set some standards without fully adopting this process. He feared that the 

amount of work it entail to try to fit recommendations into these formats would be considerable. 

ACIP already does a pretty good job of explaining its rationale in the MMWR statements that are 

published. ACIP recommendations are usually based on randomized clinical trials. When they 

are not, as with the rabies vaccine or harmonizing the rotavirus vaccine schedules, the 

rationales for those recommendations were made clear in the statements. He also feared that 

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Discussion

Advisory Committee on Immunization Practices (ACIP) Summary Report February 24-25, 2010 

the costs in bureaucracy would be significant. They would have to have lengthened time to 

produce the statements in order to get them into these formats. 

Based on recent experiences in the MMRV Safety Work Group, Dr. Temte observed how many 

of the GRADE components would fit directly. What they strive for in that work group is to be 

very clear, very transparent, and relate the information. It would have been enhanced if they 

had a framework to put this into that was recognized by everybody, and that when they 

presented, it would be in a meaningful way that captures all of those elements (e.g., safety, 

efficacy, et cetera). Some elements were of critical importance (safety), some were less 

important, and others were not important. To be able to express this clearly, succinctly, and 

transparently is of very high importance. He did not perceive that as being a cost or time 

problem. Instead, he saw it as building efficiency into the process. In terms of language, he 

said he cringed every time he heard the word “permissive” used, and invited everyone to look 

the word up in the dictionary. As a parent, he does not like his children to visit the permissive 

parents’ house. 

Dr. Umscheid indicated that they were asked to work with HICPAC to update their guideline 

methodology because they were experiencing a number of challenges, one of which was the 

inefficiency of their guideline development process. He acknowledged that the area HICPAC 

address differs from the area that ACIP addresses. By using the GRADE process with 

HICPAC, they were able to develop guidelines much faster than they had been completed in the 

past. HICPAC did make an investment in using his group to produce those guidelines, so that is 

one downside. 

Dr. Ahmed clarified that the proposal was for the GRADE framework to be used for new vaccine 

recommendations or new indications of vaccines. For these situations, the number of studies 

would be 4 or 5 versus 50 if applied it to existing recommendations. 

It was noted that consideration should be given to staffing needs in terms of literature reviews, 

because they can be daunting. 

Dr. Baker noted that at least they were beginning with an internal expert in Peter Briss. While 

there would be a learning curve, she was personally happy with the framework and hoped that 

other ACIP members would be as well. 

Public Comments Day 2 

Kari Hinton Judson 

Parent Advocate 

While you all are speaking about evidenced-based medicine and recommendations for certain 

diseases, I would like to advocate for other parents, because the scientific and medical 

evidence that you publish has our children’s lives at stake. 

My name is Kari Judson. This is my son, Alexander. Five days before his first birthday, he 

died. At the same time, his identical twin brother, Dominic, spent 11 days at Children’s 

Healthcare of Atlanta and survived. They did not have a rare disease. They had Respiratory 

Syncytial Virus (RSV). Because my twins did not go to the neonatal intensive care unit (NICU) 

when they were born at 36 weeks, I was never told about RSV. 

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When any illness, including RSV, affects almost every child before their third birthday, parents 

have a right to know about it. It seems that only the parents of premature or sickly infants are 

informed of the signs and symptoms of RSV. Because I do have a large network of friends and 

acquaintances, I believe that knowing Alexander’s story has saved several lives. What about 

the parents who don’t know about Alexander or this virus? What about Madison Byrd, the 

healthy two-year old in Blue Ridge, Georgia, who died two weeks ago due to RSV? Why did 

her mom know about it? Why didn’t this little girl have a chance? 

This virus is so common and so contagious, why hasn’t every parent in America been told about 

it? I am doing everything I can to spread the word about RSV, but I’m only one mom who’s had 

a devastating loss. I believe it is up to all of you, the CDC and medical professionals, to do a 

better job informing parents of the dangers of RSV through education, the development of a 

vaccine, or more readily and widely available antibodies. Please know that I think every parent 

needs to know about this potentially fatal virus so more of our children don’t die, like my 

Alexander did. 

Dr. Baker thanked Mrs. Judson and expressed everyone’s sympathy for her loss. 

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_____________________ 

 

Advisory Committee on Immunization Practices (ACIP) Summary Report February 24-25, 2010 

I hereby certify that to the best of my 

knowledge, the foregoing Minutes of the 

February 24-25, 2010 ACIP Meeting are 

accurate and complete. 

Date ________________________________ 

 Dr. Carol Baker, Chair 

 Advisory Committee on 

 Immunization Practices (ACIP) 

161 

 

 hereby certify that to the best of my knowledge, the foregoing Minutes of the October 21-22, 

2009 ACIP Meeting are accurate and complete. Certification 

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Discussion

 

 

 

 

 

 

 

 

 

 

 

 

 

Advisory Committee on Immunization Practices (ACIP) Summary Report February 24-25, 2010 

List of Attendees 

Last Name First Name Citizenship 

Abu-Elyazeed Remon Egypt 

Akhter Farzana Bangladesh 

Barker Janine South Africa 

BOGAERTS Hugues Belgium 

Boseila Abeer Egypt 

Bryson Maggie Canada 

Butt Tausif United Kingdom 

Castaneda Eduardo MD Suárez El Salvador 

DasGupta Joy Canada 

Edelman Laurel Canada 

Ferdinand Elizabeth Barbados 

Florez Jorge Colombia 

Franka Richard Slovakia 

Hassan Foad Nicaragua 

HENDRICKX Bernadette France 

HTUN-MYINT Latt Burma 

Ismail Shainoor Canada 

Jauregui Barbara Argentina 

Kamiya Hajime Japan 

Kim Yeu-Chun South Korea 

Langley Joanne Canada 

Lucidi Bruno France 

MAHAMAN LAWAN ISSOUFOU Niger 

Matias Gonçalo Portugal 

Merengwa Enyinnaya Saint Kitts and Nevis 

Misurski Derek Canada 

MONTEYNE Philippe Belgium 

Okabe Nobuhiko Japan 

Omer Saad Pakistan 

ORIOL VALERIE France 

Rappuoli Rino Italy 

Reynolds Donna Canada 

ROCHA CRISANTA Nicaragua 

Saddier Patricia France 

Saito Tomoya Japan 

Salisbury David United Kingdom 

Schodel Florian Germany 

Seet Bruce T. Canada 

Tan Litjen (L.J) Singapore 

Tsuzuki Daisuke Japan 

Van Brackel Esthel Belgium 

Verstraeten Thomas Belgium 

VILLAFANIA RUBY Philippines 

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Vizotti Carla Argentina 

York Laura Canada 

Abramson Allison United States 

Akinsanya-Beysolow Iyabode United States 

Alexa Pam United States 

Allen Woodruff Jennifer United States 

Allen-Sherrod Deborah United States 

Allred Stephen United States 

Ambrose Karita United States 

ARMSTRONG JENNIFER United States 

Arthur Phyllis United States 

Ashley Donald United States 

Atkins Jennean United States 

Ault Kevin United States 

Baker Carol J. United States 

Bandell Allyn United States 

Bargatze Robert United States 

Basket Michelle United States 

Bauer Christine United States 

Bax Jennifer United States 

Bax Riley United States 

Baylor Norman United States 

Bianchi Paul United States 

Bibila Theodora United States 

Billings Pamela United States 

Birkhead Guthrie United States 

Blalack Gary United States 

Bocchini, Jr. Joseph United States 

Bolanos Brenda United States 

Boone Chris United States 

Boone Heather United States 

Boone Ethan United States 

Boone Maggie United States 

Bozio Catherine United States 

Bozof Lynn United States 

Bradley Kimberly United States 

Brady Michael United States 

Bresnitz Eddy United States 

Brooks Dennis United States 

Bugenske Erin United States 

Bush Kim United States 

Campos-Outcalt Doug United States 

Caporizzo John United States 

Cary Donna United States 

Center Kimberly United States 

Chadalawada Rekha United States 

Chaney Mike United States 

Chattopadhyay Sanat United States 

Chavez Carol United States 

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Chilton Lance United States 

Cieslak Ted United States 

Cieslak Paul United States 

Claxton Isabelle United States 

Clippard Jessie United States 

Clover Richard United States 

Coelingh Kathleen United States 

Coit Henry United States 

Collins Heather United States 

Colquitt-hall Karen United States 

Colwell Chris United States 

Constantino Salvatore United States 

Cooley Brendan United States 

Cooper Brian United States 

Corsino Cynthia United States 

Counard Catherine United States 

Creed Carlisle United States 

Crumlich Brittani United States 

Cullison Mark United States 

Curlin George United States 

Dalrymple Donald "Dack" United States 

Dana Adrian United States 

D’'Anthony Mike United States 

D’'Antona Aida United States 

D’'Antona John United States 

Decker Michael United States 

DeLong Lynn United States 

DeNoon Daniel United States 

Dinovitz Richard United States 

Donnelly Jessica United States 

Dormitzer Philip United States 

Dougherty Kelley United States 

Dubin Gary United States 

Duchin Jeffrey United States 

Duke Lynn United States 

Dull Peter United States 

DuPont Lisa United States 

Ehresmann Kristen United States 

Eiden Joseph United States 

Ekhtiar Rum United States 

Elbasha Elamin United States 

Elward Alexis United States 

Englund Janet United States 

Evans Jim United States 

Evans Geoffrey United States 

Faulconer Brian United States 

Feinberg Mark United States 

Fisher Gwen United States 

Foster Stephan United States 

Friedland Leonard United States 

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Fryhofer Sandra United States 

Fuller Yvonne United States 

Fye Jessica United States 

Gaffoglio Diane United States 

Gall Stanley A United States 

Gargano Lisa United States 

Garrett Matt United States 

Gaskins Diana United States 

Geddes Cathy United States 

Gellin Bruce United States 

Gensheimer Kathleen United States 

Gery Laurie United States 

Gesser Richard United States 

Giolli Chris United States 

Glode Mary United States 

Goldstein Mitch United States 

Gordon Lili United States 

Gordon-Evans Jill United States 

Gorham Millicent United States 

Goveia Michelle United States 

Grabenstein John United States 

Grabowsky Mark United States 

Greenberg David United States 

Greenspan Joel United States 

Grogg Stanley United States 

Gromyko Natalya United States 

Groom Amy United States 

Groothuis Jessie United States 

Hachey Wayne United States 

Hahn Christine United States 

Halsey Neal United States 

Hammer Sandra United States 

Hannan Claire United States 

Harriman Kathleen United States 

Haupt Richard United States 

Hazelwood Kimberley United States 

Henry Stephanie United States 

Hering David United States 

Heyward William United States 

Higgins Jacqueline United States 

Hightower Dwan United States 

Hogan Cathy United States 

Hogrefe Wayne United States 

Hosbach Phil United States 

Howe Barbara United States 

Hughes Jim United States 

Hull Harry United States 

Humphrey-Franklin Donelle United States 

Iconis Rosemary United States 

Jackson Grant Melonie United States 

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Jain Varsha United States 

James Chuntiel United States 

Janssen Alan P. United States 

Johnson David United States 

Johnson Amy United States 

Jones Eric United States 

Jones Abbey United States 

Judson Kari United States 

Judson Franklyn N United States 

Kagan Stephen United States 

Kanesa-thasan Niranjan United States 

Kaslow David C. United States 

Kates Jesse United States 

Katz Samuel United States 

Kauffman Richard United States 

Kaye Bronwen United States 

Keane Margaret United States 

Keitel Wendy United States 

Keyserling Harry United States 

Kimberlin David United States 

Kinsinger Linda United States 

Kitchen Chester United States 

Kondos Leeza United States 

Kudis Amanda United States 

Kuter Barbara United States 

Laird Susan United States 

Lake Fred United States 

Lammers Peter United States 

Landry Sarah United States 

Lawson Herschel United States 

Lee Lucia United States 

Leger Marie-Michele United States 

Leroy Zanie United States 

Lett Susan United States 

Lewin Clement United States 

Lewis Tamara United States 

Link-Gelles Ruth United States 

Lorick Suchita United States 

Mahadevia Parthiv United States 

Makari Doris United States 

Malhame Melissa United States 

Malone Robert United States 

Mansoura Monique United States 

Masaquel Anthony United States 

Mason Dean United States 

Mazur Marie United States 

McCauley Mary United States 

McCubbins Tom United States 

MCLAUGHLIN JEFFREY United States 

McLoughlin Sean United States 

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Medea William United States 

Meehan Judith United States 

Mehrdady Rosemina United States 

Meigs Wendy United States 

Meissner Cody United States 

Mendenhall Heather United States 

Mergler Michelle United States 

Middleman Amy United States 

Miller Sarah United States 

Miller Jacqueline United States 

Milley Frankie United States 

Modi Raken United States 

Moline Heidi United States 

Moore Kelly United States 

Morgan Devon United States 

Muhammad Riyadh United States 

Mullette Michael United States 

Mulligan Mark United States 

Murphy Linda United States 

Murphy Ann T. United States 

Myers Martin United States 

Narasimhan Vasant United States 

Naumann Lisa United States 

Neal John United States 

Netoskie Mark United States 

Neuman William United States 

Neuzil Kathleen United States 

Norman James United States 

Offit Paul United States 

Owens Jack United States 

Paradiso Peter United States 

Patel Jaymin United States 

Penrod Deborah United States 

Peters Martin United States 

Peterson Diane United States 

Petrucelli Michael United States 

Pina Liza Miriam United States 

Pisani Amy United States 

Poland Gregory United States 

Polino Pamela United States 

Porter Cathy United States 

Powell Delories United States 

Pugh Pearl United States 

Quandelacy Talia United States 

Quinn Jane United States 

Rai Saroj United States 

Rall Kristen United States 

Randall Lisa United States 

Ray Jill United States 

Redd John United States 

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Rennels Margaret United States 

Richards Steve United States 

Richardson Vesta United States 

Richmond Heather United States 

Roark Jill B United States 

Robertson Jeff United States 

Roche Corleen United States 

Rosenbaum Sara United States 

Ross David United States 

Rousculp Matthew United States 

Ryan Kellie United States 

Ryan Nessa United States 

Saah Alfred United States 

Sanders Courtney United States 

Sawyer Mark United States 

Schaffner William United States 

Schechter David United States 

Schmader Kenneth United States 

Schuchat Anne United States 

Scott Laura United States 

Scott Daniel United States 

Seifert Harry United States 

Shawen Elizabeth United States 

Shelton Jerry United States 

Sievert Alan United States 

Silsbee Jeffrey United States 

Silverstein Leonard United States 

Singer Andy United States 

Skjeveland Eric United States 

Smalling Delores United States 

Smith Stephen United States 

Smith Parker United States 

So Phillip United States 

Sorrells Keira United States 

Stanley Jennifer United States 

Steinberg Nina United States 

Stephens David United States 

Stewart Lorrie United States 

Stinchfield Patsy United States 

Stobbe Mike United States 

Stoddard Jeffrey United States 

Strikas Raymond United States 

Strutton David United States 

Stuerke Stacy United States 

Suárez Castaneda Eduardo United States 

Sumaya Ciro United States 

Sun Wellington United States 

Swain Chris United States 

Sylvester Gregg C. United States 

Talarico John United States 

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Talkington Kathy United States 

Tedesco Francesca United States 

Temte Jonathan United States 

TenEyck Carolyn United States 

Thomas Lonnie United States 

Thomas Shannon United States 

Thompson Bradley United States 

Toyer Sheryl Ann United States 

Tsai Theoldore United States 

Tucker Miriam E. United States 

Turner James United States 

Umscheid Craig United States 

Vaupel Christine United States 

Via Christina United States 

Vigliarolo Peter United States 

Waldapfel Christopher United States 

Wallace Fred United States 

Walters Jean United States 

Wassil James United States 

Welch Verna United States 

Werzberger Alan United States 

Wexler Deborah United States 

Whitley-Williams Patricia United States 

Whitney Ellen United States 

Wighton Timothy United States 

Wolfe Antoinette United States 

Wood Laurel United States 

Wu Lauren United States 

Wyble Lance United States 

Xu Fujie United States 

Zimmerman Richard United States 

This document can be found on the CDC website at: 

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