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Mumps Outbreak, United States 2006Mumps 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
22
AcknowledgementsAcknowledgements• 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
33
OutlineOutline
• Background
– Clinical, epi features
– Mumps virus
– Vaccination program, vaccine policy 1967 – 2005
• Mumps Outbreak 2006
• Changes to vaccine policy -- May 17th, 2006 ACIP
• Issues/Challenges
• Background
– Clinical, epi features
– Mumps virus
– Vaccination program, vaccine policy 1967 – 2005
• Mumps Outbreak 2006
• Changes to vaccine policy -- May 17th, 2006 ACIP
• Issues/Challenges
44
Mumps: Clinical features in unvaccination persons
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
55
Mumps Complications:Unvaccinated PersonsMumps Complications:Unvaccinated Persons
• CommonMeningitis – 5-15% of casesOrchitis – 20%-30% of cases in post-pubertal
males (rarely sterility)Oophoritis, mastitis
• UncommonPancreatitis Encephalitis with premanent sequelaeDeafness Death
• CommonMeningitis – 5-15% of casesOrchitis – 20%-30% of cases in post-pubertal
males (rarely sterility)Oophoritis, mastitis
• UncommonPancreatitis Encephalitis with premanent sequelaeDeafness Death
66
Mumps Epidemiology:Pre-vaccine Era
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
77
Mumps VirusMumps 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
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end-us45-Arubini-A
sbl-swe69-AJeryl-Lynn USA 63Ausa-80-K
cna95-Fcna96-F
tay-uk50s-newlenin-3-vac-new
l-zag-vac-newloug-uk97-J
jnp94-Jbf-uk75-C
ed2-uk88-Ebm1-uk90-C
IA-USA 2006KS-USA 2006UK-2006Halifax-CanadaNJ-USA 2005
Halifax-Canada Canada 2005
Canada 2005UK2001-G
glous-UK96-GCanada-2005
UK2002-19-newNYS-2006 [Bulgaria]
manchs-UK1995-HNYS-2005
UK1988-HJPN2000-L
JPN2001-LKorea1997-I
odate-Imiya-vaccine-B
hoshino-vac-Bmat-JPN84-BUrabe-B
Germany1977-DIslip-UK1997-D
DMK1981-2001-K5 changes
Mumps in the USA,2005-2006
Phylogenetic tree is basedon sequences of theSH gene.
PA, IN, NM,GA, WV, NYC,MO [all 2006]
99
N P/V M F HN LSH
Mumps Viral Genome
Small Hydrophobic gene
Most variable part of mumps genome6-8% variability between genotypes
Used for analysis in determination of genotypeTarget for real time PCR
NucleoproteinGene
Purified Viral Nucleoproteinutilized as the antigen in CDC’s IgM assay
1010
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1968 1972 1976 1980 1984 1988 1992 1996 2000 2004
Cas
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tho
usa
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1968 1972 1976 1980 1984 1988 1992 1996 2000 2004
Cas
es (
tho
usa
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s)Mumps – United States, 1968- 2005*Mumps – United States, 1968- 2005*
*2005 provisional data*2005 provisional data
Mumps Vaccine licensed 1967
Routine childhood recommendation 1977
2 dose MMR
MMR1 Vaccine licensed 1971
MMR2 Vaccine licensed 1978
1111
Mumps Resurgence 1986-90Mumps 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
1212
Mumps Vaccination Program GoalMumps Vaccination Program Goal
• Healthy People 2010 – Elimination of indigenous mumps transmission in the U.S.
• Status (before 2006 outbreak)<300 cases/year since 20012-3 epi-linked casesImport-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 20012-3 epi-linked casesImport-associated outbreak NY summer
camp 2005 – 31 cases
1313
1414
1515
CDC’s Outbreak Response ActivitiesCDC’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
1616
Mumps Outbreak United States 2006Provisional Number of Cases by State as of May 30, 2006
1,8891,889
44
131131
633633
13*13*405405
126126
324324
33707707
22
•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
11
11
Total reported cases 4,283Total reported cases 4,283
1717
Provisional Number of Confirmed or Probable Cases* of Mumps by Event** Week in the 8** Outbreak States, 2006,
Reported to NNDSS of May 24, 2006
0
100
200
300
400
Jan1-7
2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 May11-17
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)
Iowa
Other
Provisional Number of Confirmed or Probable Cases* of Mumps by Event** Week in the 8** Outbreak States, 2006,
Reported to NNDSS of May 24, 2006
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100
200
300
400
Jan1-7
2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 May11-17
Week
Mu
mp
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as
es
(n
)
Iowa
Other
* 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
1818
Age-Specific Incidence of Mumps in the 8 Outbreak-Associated States1 , 1 January – 29 April, 2006 (n=2073)2
1 IA, IL, KS, MO,NE, PA, SD, WI2 Age unknown for 6 of the 2073 cases.
Median age 22 years (range <1-85 yrs)
1919
Mumps Outbreak 2006*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)
2020
Mumps Outbreak 2006Mumps 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*As of May 2, 2006
2121
Why?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
2222
Vaccine Coverage and RequirementsVaccine 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?
2323
Preliminary Data: Vaccine EfficacyPreliminary 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%
2424
MMR EffectivenessMMR 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
2525
United Kingdom Mumps Outbreak2004-05
United Kingdom Mumps Outbreak2004-05
• 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
2626
Mumps DiagnosisMumps Diagnosis
• ClinicalClinician expertiseVaccinated population
• Laboratory (validation)
IsolationPCRSerologic
– IgG
– IgM
• ClinicalClinician expertiseVaccinated population
• Laboratory (validation)
IsolationPCRSerologic
– IgG
– IgM
2727
CAPTURE IgM EIACAPTURE IgM EIA
Goat anti-human IgMcapture antibody
Serum IgM antibodydiluted 1:200
Viral Antigen: Nucleoprotein (NP)(Enders strain)
MAb (mouse) to viral antigen
Peroxidase-labeled goat anti-mouse IgG
2828
Isolation of Mumps Virus from Oral/Buccal Swabs:Iowa Hygienic Laboratory, Iowa 2006
Isolation of Mumps Virus from Oral/Buccal Swabs:Iowa Hygienic Laboratory, Iowa 2006
0
10
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30
40
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30
Days since symptom onset
No
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d Virus Isolated Virus Not Isolated
N=119: isolation positive=20; isolation negative=99
2929
Updated ACIP RecommendationsUpdated 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
• 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
3030
CommentsComments
• 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
3131
Thank YouThank You
3232
United Kingdom Mumps CasesUnited 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
3333
Mumps Notifications, U.K, 1990-2005*Mumps Notifications, U.K, 1990-2005*
0
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