1. 1 1 Mumps Outbreak, United States 2006 Larry J. Anderson, MD Division Viral Diseases National Center for Immunizations and Respiratory Diseases NVAC meeting, June 2006 Larry J. Anderson, MD Division Viral Diseases National Center for Immunizations and Respiratory Diseases NVAC meeting, June 2006

2. 2 2 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 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

3. 3 3 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 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

4. 4 4 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 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

5. 5 5 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 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

6. 6 6 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 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

7. 7 7 Mumps Virus Non-segmented, enveloped, RNA virus Member Rubulavirus genus, Paramyxoviridae family  Measles, HIPVs, RSV One serotype, 12 genotypes Non-segmented, enveloped, RNA virus Member Rubulavirus genus, Paramyxoviridae family  Measles, HIPVs, RSV One serotype, 12 genotypes

8. 8 8 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 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]

9. 9 9 NP/VMFHNL SH Mumps Viral Genome Small Hydrophobic 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

10. 10 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

11. 11 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 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

12. 12 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 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

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15. 15 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 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

16. 16 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.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 relatedIn PA, 13 of 65 total cases are outbreak related 1 1 Total reported cases 4,283

17. 17 * 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

18. 18 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)

19. 19 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 G genotype (12 specimens) - source unknown ?UK Vaccination status cases (Iowa) –6% unvaccinated –12% 1 dose –51% 2 doses –31% unknown vaccination status (adults)

20. 20 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 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

21. 21 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 failure Failure to vaccinate Waning immunity Accumulation of susceptibles Setting, high risk for transmission Characteristics of mumps infection of immunity Misdiagnosis of mumps

22. 22 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? 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?

23. 23 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% 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%

24. 24 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 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

25. 25 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 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

26. 26 Mumps Diagnosis Clinical  Clinician expertise  Vaccinated population Laboratory (validation)  Isolation  PCR  Serologic –IgG –IgM Clinical  Clinician expertise  Vaccinated population Laboratory (validation)  Isolation  PCR  Serologic –IgG –IgM

27. 27 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

28. 28 Isolation of Mumps Virus from Oral/Buccal Swabs: Iowa Hygienic Laboratory, Iowa 2006 N=119: isolation positive=20; isolation negative=99

29. 29 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 –2 nd dose for children 1-4 years and low risk adults if affected by outbreak 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 –2 nd dose for children 1-4 years and low risk adults if affected by outbreak

30. 30 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 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

31. 31 Thank You

32. 32 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 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

33. 33 Mumps Notifications, U.K, 1990-2005*