# Presentation: 453787

## Influenza and Influenza Vaccine

**Epidemiology and Prevention of Vaccine-Preventable Diseases**
**National Center for Immunization and Respiratory Diseases**
**Centers for Disease Control and Prevention**

**Revised March 2008**

## Note to presenters:

**Images of vaccine-preventable diseases are available from the Immunization Action Coalition website at ****http://www.vaccineinformation.org/photos/index.asp**

## Influenza

**Highly infectious viral illness**
**First pandemic in 1580 **
**At least 4 pandemics in 19th century**
**Estimated 21 million deaths worldwide in pandemic of 1918-1919**
**Virus first isolated in 1933**

## Influenza Virus

**Single-stranded RNA virus**
**Orthomyxoviridae family**
**3 types: A, B, C**
**Subtypes of type A determined by hemagglutinin and neuraminidase**

## Influenza Virus Strains

**Type A****	****- moderate to severe illness****	****	****	****- all age groups****	****	****	****- humans and other animals**** **
**Type B****	****- milder disease****	****	****	****- primarily affects children****	****	****	****- humans only**** **
**Type C****	****- rarely reported in humans****	****	****	****	****- no epidemics****	****	****	****	****	****	****	**

## Influenza Virus

## Influenza Antigenic Changes

**Hemagglutinin and neuraminidase antigens change with time**
**Changes occur as a result of point mutations in the virus gene, or due to exchange of a gene segment with another subtype of influenza virus**
**Impact of antigenic changes depend on extent of change (more change usually means larger impact)**

## Influenza Antigenic Changes

**Antigenic Shift**
**major change, new subtype**
**caused by exchange of gene segments**
**may result in pandemic**
**Example of antigenic shift**
**H2N2 virus circulated in 1957-1967**
**H3N2 virus appeared in 1968 and completely replaced H2N2 virus**

## Influenza Antigenic Changes

**Antigenic Drift**
**minor change, same subtype**
**caused by point mutations in gene**
**may result in epidemic**
**Example of antigenic drift**
**in 2002-2003, A/Panama/2007/99 (H3N2) virus was dominant**
**A/Fujian/411/2002 (H3N2) appeared in late 2003 and caused widespread illness in 2003-2004**

## Influenza Type A Antigenic Shifts

_**Year**_
**1889**
**1918**
**1957**
**1968**
**1977**

_**Subtype**_
**H3N2**
**H1N1**
**H2N2**
**H3N2**
**H1N1**

**Severity of**
_**Pandemic**_
**  ****Moderate**
**  ****Severe**
**  ****Severe**
**  ****Moderate**
**  ****Mild**

## Impact of Pandemic Influenza

**200 million people could be affected**
**Up to 40 million require outpatient visits**
**Up to 700,000 hospitalized**
**89,000 - 200,000 deaths**

## Influenza Pathogenesis

**Respiratory transmission of virus**
**Replication in respiratory epithelium with subsequent destruction of cells**
**Viremia rarely documented**
**Viral shedding in respiratory secretions for 5-10 days**

##  Influenza Clinical Features

**Incubation period 2 days ****(range 1-4 days)**
**Abrupt onset of fever, myalgia, sore throat, nonproductive cough, headache**
**Severity of illness depends on prior experience with related variants**

## Influenza Complications

**Pneumonia**
**secondary bacterial**
**primary influenza viral **
**Reye syndrome**
**Myocarditis**
**Death 0.5-1 per 1,000 cases**

## Impact of Influenza-United States, 1990-1999

**Approximately 36,000 influenza-associated deaths during each influenza season**
**Persons 65 years of age and older account for more than 90% of deaths**
**Higher mortality during seasons when influenza type A (H3N2) viruses predominate**

## Highest rates of complications and hospitalization among young children and person 65 years and older
Average of more than 200,000 influenza-related excess hospitalizations 
57% of hospitalizations among persons younger than 65 years of age
Greater number of hospitalizations during type A (H3N2) epidemics

**Average of more than 200,000 influenza-related excess hospitalizations **
**57% of hospitalizations among persons younger than 65 years of age**
**Greater number of hospitalizations during type A (H3N2) epidemics**

**Impact of Influenza-United States, 1990-1999**

## Impact of Influenza

**Rates of hospitalization among children 2 years and younger are similar to those of persons 65 and older with high-risk medical conditions**
**Children 24 through 59 months of age are at increased risk for influenza-related clinic and emergency department visits**

## Hospitalization Rates for Influenza By Age and Risk Group*

_**Age Group**_
**0-11 mos**
**1-2 yrs**
**3-4 yrs**
**5-14 yrs**
**15-44 yrs**
**45-64 yrs**
_**>**_**65 yrs**

**  ****Rate****
_**(high-risk)**_
**1900**
**800**
**320**
**92**
**56-110**
**392-635**
**399-518**

** ****Rate****
_** **__**(not high-risk)**_
**496-1038**
**186**
**86**
**41**
**23-25**
**13-23**
**125-228**

** ***** Data from several studies 1972 - 1995**
**** Hospitalizations per 100,000 population**

## Influenza Diagnosis

**Clinical and epidemiological characteristics**
**Isolation of influenza virus from clinical specimen (e.g., nasopharynx, throat, sputum)**
**Significant rise in influenza IgG by serologic assay**
**Direct antigen testing for type A virus**

## Influenza Epidemiology

**Reservoir****	****Human, animals ****	****(type A**
**	****	****only)**
**Transmission****	****Respiratory****	****Probably airborne**
**Temporal pattern  ****	****Peak December – March ****	****in temperate climate****	****May occur earlier or later**
**Communicability****	****1 day before to 5 days ****	****after onset (adults)****	**

## Month of Peak Influenza Activity United States, 1976-2006

**13%**

**19%**

**45%**

**13%**

**3%**

**3%**

***MMWR***** 2007;55(RR-6):5**

## Influenza Vaccines

**Inactivated subunit (TIV)**
**intramuscular**
**trivalent**
**split virus and subunit types**
**duration of immunity 1 year or less**
**Live attenuated vaccine (LAIV)**
**intranasal**
**trivalent**
**duration of immunity at least 1 year****	**

## Composition of the 2008-2009 Influenza Vaccine* 

**A/Brisbane/59/2007 (H1N1)**
**A/Brisbane/10/2007 (H3N2)**
**B/Florida/4/2006**

***manufacturers may use strains that are antigenically identical to the selected strains**

## Inactivated Influenza Vaccines Available in 2007-2008

| Vaccine | Package | Dose | Age |
| --- | --- | --- | --- |
| Fluzone
(sanofi pasteur) | Multi-dose vial*+ | Age-dependent | >6 mos |
|    | Single dose syringe* | 0.25 mL | 6-35 mos |
|    | Single dose syringe* | 0.5 mL | >36 mos |
|    | Single dose vial* | 0.5 mL | >36 mos |

***vaccines approved for children younger than 4 years**
**+all multi-dose vials contain thimerosal as a preservative **

## Inactivated Influenza Vaccines Available in 2007-2008

| Vaccine | Package | Dose | Age |
| --- | --- | --- | --- |
| Fluvirin
(Novartis) | Multi-dose vial+ | 0.5 mL | >4 yrs |
| Fluarix
(GSK) | Single dose syringe | 0.5 mL | >18 yrs |
| FluLaval
(GSK) | Multi-dose vial+ | 0.5 mL | >18 yrs |
| Afluria
(CSL) | Single dose syringe | 0.5 mL | >18 yrs |
|  | Multi-dose vial+ | 0.5 mL | >18 yrs |

**+all multi-dose vials contain thimerosal as a preservative **

## Transmission of LAIV Virus

**Transmission of LAIV Virus**

**LAIV replicates in the nasopharyngeal  mucosa**
**Mean shedding of virus 7.6 days – longer in children**
**One instance of transmission of vaccine virus documented in a child care setting**
**Transmitted virus retained attenuated, cold-adapted, temperature-sensitive characteristics**
**No transmission of LAIV reported in the U.S. **

## Inactivated Influenza Vaccine Efficacy

**70%-90% effective among healthy persons younger than 65 years of age**
**30%-40% effective among frail elderly persons**
**50%-60% effective in preventing hospitalization**
**80% effective in preventing death**

## Influenza and Complications Among Nursing Home Residents

**Influenza and Complications Among Nursing Home Residents**

**RR=1.9**

**RR=2.0**

**RR=2.5**

**RR=4.2**

***Inactivated influenza vaccine. Genesee County, MI, 1982-1983**

## LAIV Efficacy in Healthy Children

**LAIV Efficacy in Healthy Children**

**87% effective against culture-confirmed influenza in children ****5-7 years old**
**27% reduction in febrile otitis media (OM)**
**28% reduction in OM with accompanying antibiotic use**
**Decreased fever and OM in vaccine recipients who developed influenza**

## LAIV Efficacy in Healthy Adults

**LAIV Efficacy in Healthy Adults**

**20% fewer severe febrile illness episodes**
**24% fewer febrile upper respiratory illness episodes**
**27% fewer lost work days due to febrile upper respiratory illness**
**18%-37% fewer days of healthcare provider visits due to febrile illness**
**41%-45% fewer days of antibiotic use **

## Timing of Influenza Vaccine Programs

**Influenza activity can occur as early as October**
**In more than 80% of seasons since 1976, peak influenza activity has not occurred until January or later**
**In more than 60% of seasons the peak was in February or later **

## Timing of Influenza Vaccine Programs

**Providers should begin offering vaccine soon after it becomes available, if possible by October**
**To avoid missed opportunities for vaccination, providers should offer vaccine during routine healthcare visits or during hospitalizations whenever vaccine is available **

## Timing of Influenza Vaccine Programs

**Persons planning organized vaccination campaigns should consider scheduling these events after at least mid-October**
**Scheduling campaigns after mid-October will minimize the need for cancellations because vaccine is unavailable **
**Continue to offer influenza vaccine in December**
**Providers should continue to vaccinate throughout influenza season**

## Inactivated Influenza Vaccine Schedule

**Age**
_**Group**_
**6-35 mos**
**3-8 yrs**
_**>**_**9 yrs**

_**Dose**_
**0.25 mL**
**0.50 mL**
**0.50 mL**

**No.**
_**Doses**_
**1* or 2**
**1* or 2**
**1**

***Only one dose is needed if the child received 2 doses of  influenza vaccine during the previous influenza season**

## Influenza Vaccination of Children

**Children 6 months through 8 years of age who did not receive the recommended second dose of influenza vaccine in the initial year that they received influenza vaccine should receive 2 doses during the next influenza season***
**Children 6 months through 8 years of age who are being vaccinated two or more seasons after receiving an influenza vaccine for the first time should receive a single annual dose, regardless of the number of doses administered previously **

***applies only to the influenza season that follows the first season that a child younger than 9 years receives influenza vaccine **

## Influenza Vaccination of Children 6 Months Through 8 Years Of Age*

_**Previous vaccination**_
**One dose last year**
**One dose in each of the last 2 years**
**One dose 3 years ago**
**One dose in each of the last 3 years**

_**Vaccine THIS year**_
**Two doses**
**One dose**
**One dose**
**One dose**

***children 9 years and older should receive only one dose of influenza vaccine per year regardless of the number of doses in previous years**

## Inactivated Influenza Vaccine Recommendations

**All persons 50 years of age or older**
**Children 6-59 months of age**
**Residents of long-term care facilities**
**Pregnant women**
**Persons 6 months to 18 years receiving chronic aspirin therapy**
**Persons 6 months of age or older with chronic illness**

## Inactivated Influenza Vaccine Recommendations

**Persons with the following chronic illnesses should be considered for inactivated influenza vaccine:**
**pulmonary (e.g., asthma, COPD)**
**cardiovascular (e.g., CHF)**
**metabolic (e.g., diabetes)**
**renal dysfunction**
**hemoglobinopathy**
**immunosuppression, including HIV infection**
**any condition that can compromise respiratory function or the handling of respiratory secretions **

## Pregnancy and Inactivated Influenza Vaccine

**Risk of hospitalization 4 times higher than nonpregnant women**
**Risk of complications comparable to nonpregnant women with high-risk medical conditions**
**Vaccination (with TIV) recommended if pregnant during influenza season**
**Vaccination can occur during any trimester **

## HIV Infection and Inactivated Influenza Vaccine

**Persons with HIV at increased risk of complications of influenza**
**TIV induces protective antibody titers in many HIV infected persons**
**TIV will benefit many HIV-infected persons**
**Do not administer LAIV to persons with HIV infection**

## Influenza Vaccine Recommendations

**Healthcare providers, including home care***
**Employees of long-term care facilities**
**Household contacts of high-risk persons**

***LAIV should not be administered to healthcare workers who have contact with severely immunosuppressed persons who require hospitalization and care in a protective environment**

## Influenza Vaccine Recommendations*

**Providers of essential community services**
**Persons traveling outside the U.S.**
**Persons in institutional settings (e.g., students who reside in a dormitory; persons in a correctional facility)**
**Anyone who wishes to reduce the likelihood of becoming ill from influenza**

***these groups may receive TIV, and some may be **
** ****eligible for LAIV**

## Influenza Vaccination of Children

**Children 6-59 months at increased risk of hospitalization and physician visits**
**Inactivated influenza vaccination of healthy children 6-59 months is recommended**
**Vaccination of household contacts and other caregivers of children younger than 59 months is encouraged**

## In the 2004 National Health Interview Survey, only 40% of healthcare personnel reported receiving influenza vaccine in the previous 12 months.

## Influenza Vaccination of HCPs

**Educate HCWs about the benefits of vaccination for themselves, their families,  and their patients**
**Educate staff about vaccine adverse reactions**
**Provide free vaccine at the work site to all employees, including night and weekend staff**

## Age Group
2 - 8 years, no previous influenza vaccine

2 - 8 years, previous influenza vaccine *

9 - 49 years

_**Age Group**_
**2 - 8 years, no previous influenza vaccine**
**2 - 8 years, previous influenza vaccine ***
**9 - 49 years**

_**Number of Doses**_
**2 **
**(separated by 4 weeks)**
**1**
**1**

**   ****Live Attenuated Influenza Vaccine****Schedule**

##    Live Attenuated Influenza VaccineIndications

**Healthy*, nonpregnant persons 2-49 years of age **
**healthy children**
**healthcare personnel**
**persons in close contact with high-risk groups**
**persons who want to reduce their risk of influenza**

***Persons who do not have medical conditions that increase their risk for complications of influenza**

## Simultaneous Administration of LAIV and Other Vaccines

**Inactivated vaccines can be administered either simultaneously or at any time before or after LAIV**
**Other live vaccines can be administered on the same day as LAIV**
**Live vaccines not administered on the same day should be administered at least 4 weeks apart**

## Inactivated Influenza Vaccine Adverse Reactions

**	****Local reactions****	****	****15%-20%**
**	****Fever, malaise****	****	****	****not common**
**	****Allergic reactions****	****	****rare**
**	****Neurological****	****	****	****very rare reactions**

## Live Attenuated Influenza VaccineAdverse Reactions

**Children**
**no significant increase in URI symptoms, fever, or other systemic symptoms**
**significantly increased risk of asthma or reactive airways disease in children 12-59 months of age **
**Adults**
**significantly increased rate of cough, runny nose, nasal congestion, sore throat, and chills reported among vaccine recipients**
**no increase in the occurrence of fever**
**No serious adverse reactions identified **

**Notes:**
These symptoms were reported in 10 to 40 percent of both vaccine and placebo recipients. LAIV not licensed for children <60 months of age.

## Inactivated Influenza VaccineContraindications and Precautions

**Severe allergic reaction to a vaccine component (e.g., egg) or following a prior dose of vaccine**
**Moderate or severe acute illness**
**History of Guillian Barre’ syndrome within 6 weeks following a previous dose of TIV (precaution) **

## Live Attenuated Influenza VaccineContraindications and Precautions

**Children younger than 2 years of age***
**Persons 50 years of age or older***
**Persons with chronic medical conditions***
**Children and adolescents receiving long-term aspirin therapy***

***These persons should receive inactivated influenza vaccine**

## Live Attenuated Influenza VaccineContraindications and Precautions

**Immunosuppression from any cause***
**Pregnant women***
**Severe (anaphylactic) allergy to egg or other vaccine components**
**History of Guillian-Barré syndrome**
**Children younger than 5 years with recurrent wheezing***
**Moderate or severe acute illness  **

***These persons should receive inactivated influenza vaccine**

## Live Attenuated Influenza Vaccination of Children 2-4 Years of Age

**Clinicians and immunization programs should avoid use of LAIV in children with asthma or a recent wheezing episode**
**Consult the medical record, when available, to identify children 2 through 4 years of age with asthma or recurrent wheezing that might indicate asthma **

## Live Attenuated Influenza Vaccination of Children 2-4 Years of Age

**Parents or caregivers of children 2-4 years should be asked:**
** “****In the past 12 months, has a healthcare provider ever told you that your child had wheezing or asthma?” **
**Children whose parents or caregivers answer "yes" to this question, or whose medical record notes asthma or a wheezing episode within the past 12 months, should not receive LAIV**
**Inactivated influenza vaccine should be administered to children with asthma or possible reactive airways diseases **

## Influenza VaccineStorage and Handling

**Both types of influenza vaccine must be stored at refrigerator temperature (35°-46°F,  2°-8°C)**
**Neither vaccine should be frozen**
**If LAIV is inadvertently frozen the vaccine should be placed at refrigerator temperature and used as soon as possible **

## Influenza VaccineStrategies to Improve Coverage

**Ensure systematic and automatic offering of TIV to high-risk groups**
**Educate healthcare providers and patients**
**Address concerns about adverse events**
**Emphasize physician recommendation**

## Influenza Antiviral Agents*

**Amantadine and rimantadine**
**Not recommended because of documented resistance in U.S. influenza isolates **
**Zanamivir and oseltamivir**
**neuraminidase inhibitors**
**effective against influenza A and B**
**should be used if an influenza antiviral drug is indicated for chemoprophylaxis or treatment**

***see influenza ACIP statement or CDC influenza website for details**

## Influenza Surveillance

**Monitor prevalence of circulating strains and detect new strains**
**Estimate influenza-related morbidity, mortality and economic loss**
**Rapidly detect outbreaks**
**Assist disease control through rapid preventive action**

## CDC Vaccines and ImmunizationContact Information  

**Telephone     800.CDC.INFO**** **
**Email****	****	****    nipinfo@cdc.gov**** **
**Website****	****    www.cdc.gov/vaccines**