# Presentation: 524749

## Mumps Outbreak, United States 2006

**Larry J. Anderson, MD**
**Division Viral Diseases**
**National Center for Immunizations and Respiratory Diseases**
**NVAC meeting, June 2006**

## Acknowledgements

**State and local health departments**
**CSTE, ACHA, AAP, other**
**CDC NCIRD **
**Division Viral Diseases – Jane Seward**
**Epidemiology branch – Umesh Parashar**
**Epi response team**
**MMR HV lab branch – Bill Bellini**
**Lab diagnostic team**
**Immunization Services Division**
**Division Bacterial Diseases**
**Global Immunization Division **
**Office Communications**
**OPER **
**CDC DEOC, BPRP, DGMQ, DHQP**

## Outline

**Background**
**Clinical, epi features**
**Mumps virus**
**Vaccination program, vaccine policy 1967 – 2005**
**Mumps Outbreak 2006**
**Changes to vaccine policy -- May 17****th****, 2006 ACIP **
**Issues/Challenges**

## Mumps:  Clinical features in unvaccination persons

**Incubation period: 16 - 18 days (range 12 – 26 days)**
**Symptoms:**
**Nonspecific prodrome of low-grade fever, headache, malaise, myalgias**
**Lower respiratory tract illness, especially preschool-aged children**
**Parotitis in 20% - 70%**
**Asymptomatic:  Up to 20% of infections**

**Notes:**
Mumps is generally a mild disease but may be severe with some unpleasant consequences.  The virus has a predeliction for glandular tissues (e.g. parotid glands, ovaries, testes, pancreas) and nerve tissue.

It has a 14-18 day incubation period and typically begins with a prodrome of nonspecific symptoms including low grade fever, headache, malaise and myalgias.

The typical swollen parotid glands (either unilateral or bilateral) occurs in 30-40% of cases.  Up to 20% of infections are asymptomatic while 40-50% of patients may have respiratory symptoms, particularly children younger than 5 years of age who may develop lower respiratory illnesses.

## Mumps Complications:Unvaccinated Persons

**Common**
**Meningitis – 5-15% of cases**
**Orchitis –  20%-30% of cases in post-pubertal males (rarely sterility)**
**Oophoritis, mastitis**
**Uncommon**
**Pancreatitis **
**Encephalitis with premanent sequelae**
**Deafness **
**Death**

## Mumps Epidemiology:Pre-vaccine Era

**Transmission**
**Route:  person-to-person (respiratory secretions, e.g. saliva), respiratory droplets, fomites**
**Communicability: 3 days before up to 9 days (>risk up to 3-4 days) after onset of illness (based on isolation data)**
**Risk of disease: ****> 50% reported cases 5-9 yrs but shift to younger children with child care**
**Seasonality:****	****Peak late winter and spring**
**Periodicity: ****~ 3 years**

**Notes:**
Humans are the only natural host for the mumps virus.  The virus is transmitted via direct contact (such as saliva or infected droplets on surfaces) or by respiratory droplets and enters through the nose and mouth. Asymptomatic or nonclassical infections can also transmit the virus. Mumps peaks in late winter and spring but can occur year round.  Patients are communicable 3 days before to 4 days after the onset of active disease. 

## Mumps Virus

**Non-segmented, enveloped, RNA virus**
**Member Rubulavirus genus, *****Paramyxoviridae family***
**Measles, HIPVs, RSV**
**One serotype, 12 genotypes**

**Notes:**
Mumps is a paramyxovirus and is related to parainfluenza, measles and RSV.  It is a single-stranded RNA virus with only one serotype.  It is rapidly inactivated by formalin, ether, chloroform, heat and UV light.

## Mumps in the USA,

- end-us45-**A**

- rubini-**A**

- sbl-swe69-**A**

- Jeryl-Lynn USA 63
**A**

- usa-80-**K**

- cna95-**F**

- cna96-**F**

- tay-uk50s-new

- lenin-3-vac-new

- l-zag-vac-new

- loug-uk97-**J**

- jnp94-**J**

- bf-uk75-**C**

- ed2-uk88-**E**

- bm1-uk90-**C**

**IA-USA 2006**

**KS-USA 2006**

- UK-2006

- Halifax-Canada

**NJ-USA  2005**

- Halifax-Canada

- Canada 2005

- Canada 2005

- UK2001-**G**

- glous-UK96-**G**

- Canada-2005

- UK2002-19-new

**NYS-2006 [Bulgaria]**

- manchs-UK1995-**H**

**NYS-2005**

- UK1988-**H**

- JPN2000-**L**

- JPN2001-**L**

- Korea1997-**I**

- odate-**I**

- miya-vaccine-**B**

- hoshino-vac-**B**

- mat-JPN84-**B**

**Urabe-B**

- Germany1977-**D**

- Islip-UK1997-**D**

- DMK1981-2001-**K**

- 5 changes

**Mumps in the USA,**
**2005-2006**
**Phylogenetic tree is based**
**on sequences of the**
**SH gene.**

**PA, IN, NM,**
**GA, WV, NYC,**
**MO [all 2006]**

## N

**N**

**P/V**

**M**

**F**

**HN**

**L**

**SH**

**Mumps Viral Genome**** **

_**S**_**mall **_**H**_**ydrophobic gene**
**Most variable part of mumps genome**
**6-8% variability between genotypes**
**Used for analysis in determination of genotype**
**Target for real time PCR**

**Nucleoprotein**
**Gene**
**Purified Viral Nucleoprotein**
**utilized as the antigen **
**in CDC’s IgM assay**

## Mumps – United States, 1968- 2005*

**Mumps – United States, 1968- 2005***

***2005 provisional data**

**Mumps Vaccine licensed 1967**

**Routine childhood recommendation 1977**

**2 dose MMR**

**MMR1 Vaccine licensed 1971**
**MMR2 Vaccine licensed 1978**

**Notes:**
Mumps became a nationally reportable disease in 1968.  Since the live attenuated mumps vaccine was licensed in 1967, there has been more than a 99% decline in the annual incidence of mumps.

## Mumps Resurgence 1986-90

**Outbreaks in high schools, colleges and workplace among young adults**
**Largest outbreaks in states without school requirements for vaccination**
**1986-87 -- ~20,000 cases and 15 states without requirements 14-fold higher incidence than in states with requirements***
**Outbreaks in highly 1-dose vaccinated (95%) schools**
**Attack rates of 6-18% **
**Conclusion**
**Incomplete coverage of adolescents and young adults***
**1-dose insufficient for control**

- *Cochi SL, Preblud SR, Orenstein WA. AJDC 1988;142:499-507

## Mumps Vaccination Program Goal

**Healthy People 2010 – ****Elimination of indigenous mumps transmission in the U.S.**
**Status ****(before 2006 outbreak)**
**<300 cases/year since 2001**
**2-3 epi-linked cases**
**Import-associated outbreak NY summer camp 2005 – 31 cases**

## Slide 13

## Slide 14

## CDC’s Outbreak Response Activities

**National surveillance and Epidemiological investigations**
**Vaccine efficacy**
**Transmission and risk factors for infection, disease**
**Laboratory support and investigations**
**Control measures**
**Isolation**
**Vaccination – coverage and supply**
**Communications- media, web documents**

## Mumps Outbreak United States 2006

Provisional Number of Cases by State as of May 30, 2006

**Mumps Outbreak United States 2006**
**Provisional Number of Cases by State as of May 30, 2006**

**1,889**

**4**

**131**

**633**

**13***

**405**

**126**

**324**

**3**

**707**

**2**

**Reported cases as of May 30th, 2006, although numbers not up to date in all states. **
**In PA, 13 of 65 total cases are outbreak related**

**1**

**1**

**Total reported cases 4,283**

**Notes:**
Orange – cases linked to Iowa; red – subsequent transmission; AR in Iowa = 64/100K other 0.6-25/100K

## *  Of 3067 cases reported, 1868 (61%) are confirmed and 1199 (39%) are probable.

- ** Event week : 2771 (90.4%) represent the date of symptom onset, 19 (0.6%)  represent the date of diagnosis, 224 (7.3%)  the date of laboratory result,
-    21 (0.7%)  the date of the first report to the community health system, and 32 (1.0%)  the state/MMWR report date.
- *** The 8 states include: IA, NE, KS, IL, WI,  MO, PA, and SD.				5/252006 11:00 am

**Notes:**
Clinical case definition -- An illness with acute onset of unilateral or bilateral tender, self-limited swelling of the parotid or other salivary gland, lasting 2 or more days, and without other apparent cause.  Probable -- only clinical defn; Confirmed: clinical defn + epi link or Lab + (+/- clinical defn)
CSTE CASE CLASSIFICATION 
Probable: A case that meets the clinical case definition, has noncontributory or no serologic or virologic testing, and is not epidemiologically linked to a confirmed or probable case.
Confirmed: A case that is laboratory confirmed or that meets the clinical case definition and is epidemiologically linked to a confirmed or probable case. A laboratory-confirmed case does not need to meet the clinical case definition.

## Age-Specific Incidence of Mumps in the 8 Outbreak-Associated States1 , 1 January – 29 April, 2006 (n=2073)2

**Age-Specific Incidence of Mumps in the 8 Outbreak-Associated States****1**** , 1 January – 29 April, 2006 (n=2073)****2**

- 1 IA, IL, KS, MO,NE, PA, SD, WI
- 2 Age unknown for 6 of the 2073 cases.

**Median age 22 years (range <1-85 yrs)**

## Mumps Outbreak 2006*

**Mumps G genotype (12 specimens)  - ****source unknown ?UK**
**Vaccination status cases (Iowa)**
**6% unvaccinated**
**12% 1 dose**
**51% 2 doses**
**31% unknown vaccination status (adults)**

## Mumps Outbreak 2006

**College students especially in Iowa (25% cases)**
**Health care workers (Iowa reports > 100 cases) **
**Reported complications (incomplete)* **
**27 orchitis**
**11 meningitis**
**4 encephalitis**
**4 deafness**
**Oophoritis, mastitis**
**Hospitalizations, no deaths**

- *As of May 2, 2006

## Why?

**Vaccine failure**
**Failure to vaccinate**
**Waning immunity**
**Accumulation of susceptibles**
**Setting, high risk for transmission**
**Characteristics of mumps infection of immunity**
**Misdiagnosis of mumps**

## Vaccine Coverage and Requirements

**Coverage**
**MMR1 93% in 2004 among 19 – 35 month old children**
**MMR2 median 97% school entry and 98% middle school entry**
**Likely lower among college students **
**Entry requirements**
**Child care (all states)**
**Schools (all states)**
**College: 25 states report requirement, implementation?**

## Preliminary Data:  Vaccine Efficacy

**Attack rates in 2 highly affected college campuses **
**2.0% (97% students 2 vaccine doses) **
**3.8% (77% students 2 vaccine doses) **
**Vaccine failure rate (college room mate contact study)**
**1 dose recipients ~ 10% (1/10)**
**2 dose recipients ~ 8% (7/84)**
**Historical 1-dose failure rates 6%-18% (schools and colleges)**
**Mumps IgG by EIA among 2 dose vaccinated college students non outbreak state ~ 93.8%**

## MMR Effectiveness

**1- Dose VE efficacy - ~80% efficacy**
**2- Dose VE efficacy - ~90% efficacy with limited data**
**5 times lower attack rate outbreak 2 versus 1 dose KS 1986 (Hersh et al)**
**91% outbreak in NY state 2005 (unpublished)**
**88% study in UK (2 MMR vaccines)**
**90%+ in current UK outbreak (unpublished)**
**Mumps elimination in Finland with high and sustained 2 dose MMR coverage **

## United Kingdom Mumps Outbreak2004-05

**72,757 cases reported  **
**Highest incidence in persons 15-24 years old **
**Vaccination status:**
**67% cases unvaccinated**
**30% 1 dose MMR**
**3% 2 doses MMR**

## Mumps Diagnosis

**Clinical**
**Clinician expertise**
**Vaccinated population**
**Laboratory ****(validation)**
**Isolation**
**PCR**
**Serologic**
**IgG**
**IgM**

## CAPTURE IgM EIA

- Goat anti-human IgM

- capture antibody

- Serum IgM antibody
- diluted 1:200

- Viral Antigen: Nucleoprotein (NP)
- 		(Enders strain)

- MAb (mouse) to viral antigen* *

- Peroxidase-labeled goat anti-mouse IgG

## Isolation of Mumps Virus from Oral/Buccal Swabs:Iowa Hygienic Laboratory, Iowa 2006

**N=119: isolation positive=20; isolation negative=99**

## Updated ACIP Recommendations

- Changes in evidence of immunity (vaccination not needed)
- 1 dose children 1-4 years and low risk adults
- 2 doses school aged children, students in post high school educational facilities and workers in health care facilities
- Health facility workers
- Birth after 1957 - 2 doses routinely
- Birth before 1957 - without other evidence of immunity –1 dose in non- outbreak setting and strongly consider 2 doses during outbreak
- Outbreak control recommendations
- 2nd dose for children 1-4 years and low risk adults if affected by outbreak

## Comments

**Understand clinical and epi features**
**Better laboratory diagnostics**
**Understand relative roles of vaccine failure, failure to vaccinate, waning immunity, accumulation of susceptibles, and setting**
**2-dose vaccination**
**Refine control and prevention strategies**

## Thank You

## United Kingdom Mumps Cases

**Increase in cases mostly in persons 15-24 years old who were too old to be eligible for routine MMR vaccination**
**Vaccination status:**
**67% cases unvaccinated**
**3% 2 doses MMR**
**30% 1 dose MMR**
**UK Policy:  MMR at 12-15 months (1988) **
**	****MR catch up campaign in 1994 (5 – 16 years)**
**	****Second dose of MMR at 3.5-5 years (1996) **
**2004 – 16,367 cases reported, and 8,128 lab-confirmed cases**
**2005 – 56,390 reported, high rate of lab- confirmed until halted in February 2005**

## Mumps Notifications, U.K, 1990-2005*