1 1 Mumps Outbreak, United States 2006 Larry J. Anderson, MD Division Viral Diseases National Center...

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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

88

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

0

20

40

60

80

100

120

140

160

1968 1972 1976 1980 1984 1988 1992 1996 2000 2004

Cas

es (

tho

usa

nd

s)

0

20

40

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80

100

120

140

160

1968 1972 1976 1980 1984 1988 1992 1996 2000 2004

Cas

es (

tho

usa

nd

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

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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

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

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•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

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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

Week

Mu

mp

s C

as

es

(n

)

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

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

Week

Mu

mp

s C

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)

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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)


• Vaccine failure rate (college room mate contact study)

– 1 dose recipients ~ 10% (1/10)


• 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



• Vaccine failure rate (college room mate contact study)



• 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%

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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



– 30% 1 dose MMR

– 3% 2 doses MMR

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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

20

30

40

0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30

Days since symptom onset

No

. o

f sp

ecim

ens

coll

ecte

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



– 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



– 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

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

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