Jane Seward, MBBS, MPHJane Seward, MBBS, MPH

Acting Deputy Director, Division Viral Diseases Acting Deputy Director, Division Viral Diseases

Centers for Disease Control and PreventionCenters for Disease Control and Prevention

FDA BPAC Meeting FDA BPAC Meeting Bethesda, August 16Bethesda, August 16thth, 2007, 2007

Measles EpidemiologyMeasles EpidemiologyUnited States, 2006United States, 2006

MeaslesMeasles

• Highly contagious viral illnessHighly contagious viral illness• Near universal childhood infection in Near universal childhood infection in

the pre-vaccine erathe pre-vaccine era• Morbidity and mortality 1950s, United Morbidity and mortality 1950s, United

StatesStates• 450 deaths annually450 deaths annually• 48,000 hospitalizations48,000 hospitalizations• 4,000 cases encephalitis4,000 cases encephalitis

Measles PreventionMeasles Prevention

• Live, attenuated measles vaccine licensed 1963Live, attenuated measles vaccine licensed 1963• Almost all administered as MMR vaccineAlmost all administered as MMR vaccine

• EfficacyEfficacy• One dose One dose ≥ 12 months: 95%≥ 12 months: 95%• Two doses at least 4 weeks apart ≥ 12 months: 99%Two doses at least 4 weeks apart ≥ 12 months: 99%

• Schedule: 2 dosesSchedule: 2 doses• Children 4-6 years (school students)Children 4-6 years (school students)• College students College students • Health care workersHealth care workers• International travelersInternational travelers

Strategies to Control and Eliminate Strategies to Control and Eliminate Measles, USMeasles, US

• Maximize population immunity to measlesMaximize population immunity to measles• Deliver the first dose on timeDeliver the first dose on time• Increase second dose coverage in school Increase second dose coverage in school

childrenchildren• Vaccinate high risk adultsVaccinate high risk adults

• Assure adequate surveillanceAssure adequate surveillance

• Respond rapidly to outbreaksRespond rapidly to outbreaks

• Work to improve global control Work to improve global control

Reported Measles CasesReported Measles Casesby Year, United States, 1950-2006by Year, United States, 1950-2006

0.01

0.1

1

10

100

1000

50

56

62

68

74

80

86

92

98

04Year

Rep

ort

ed

case

s -1

00

0s Vaccine

licensed

School immunization laws started in all states

Second dose strategy and school laws

Improved first dose preschool coverage

Reported Measles IncidenceUnited States, 1992-2006*

0

2

4

6

8

10

Year

Cases/million

1 case/million1 case/million

*provisional 2006 data

Measles elimination declaredMeasles elimination declared

Measles Cases by Age GroupMeasles Cases by Age GroupUnited States, 1976-2006United States, 1976-2006

0

10

20

30

40

50

60

Cas

es (

thou

san

ds)

0- 4 yrs

5-19 yrs

20+ yrs

age unk

Total

Measles Cases by Age GroupMeasles Cases by Age GroupUnited States, 1976-2006United States, 1976-2006

0

5

10

15

20

25

30

35

40

1976

1978

1980

1982

1984

1986

1988

1990

1992

1994

1996

1998

2000

2002

2004

2006

Cas

es (

thou

sand

s)

0- 4 yrs

5-19 yrs

20+ yrs

age unk

Age Specific Incidence of Age Specific Incidence of Measles, 1996-2006Measles, 1996-2006

0.00

0.25

0.50

1996 1997 1998 1999 2000 2001 2002 2003 2004 2005

Incid

en

ce p

er

100,0

00

< 15 yrs 15 yrs +

Largest Measles OutbreaksLargest Measles OutbreaksUnited States, 1999-2006United States, 1999-2006

11

22

LOCATIONLOCATION

IndianaIndiana

Boston, MABoston, MA

CasesCases

3434

1818

YearYear

20052005

20062006

Age GroupAge Group

AdultAdult

AdultAdult

OriginOrigin

ImportedImported

ImportedImported

33 Bedford Co, VABedford Co, VA 1515 19991999 Preschool /AdultPreschool /Adult ImportedImported

44

55

Multi-stateMulti-state

Multnomah Co, ORMultnomah Co, OR

1414

1313

20012001

19991999

Preschool /AdultPreschool /Adult

Preschool /AdultPreschool /Adult

ImportedImported

UnknownUnknown

66

77

Lee County, ALLee County, AL

South King Co, WASouth King Co, WA

1313

1212

20022002

20012001

Infant/ DaycareInfant/ Daycare

Preschool/AdultPreschool/Adult

ImportedImported

ImportedImported

88

99

1010

Delaware County, PADelaware County, PA

Oswego, NYOswego, NY

Multi-stateMulti-state

1111

1010

99

20032003

20042004

20002000

SchoolSchool

Infant/AdopteesInfant/Adoptees

SchoolSchool

ImportedImported

ImportedImported

UnknownUnknown

1111 Brooklyn, NYBrooklyn, NY 99 20002000 PreschoolPreschool ImportedImported

Age Distribution of Measles CasesAge Distribution of Measles CasesUS, 2001-2006US, 2001-2006

0

20

40

60

80

100

120

140

2001 2002 2003 2004 2005 2006*

Year

Nu

mb

er o

f C

ases

20+ yrs

5-19 yrs

<5 yrs

* Provisional

Vaccination Status Measles CasesVaccination Status Measles CasesUS, 2001-2006US, 2001-2006

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

2001 2002 2003 2004 2005 2006*

Unv/Unk

2 Doses

1 Dose

* From NNDSS

Internationally Imported Internationally Imported Measles Cases, 1985 – 2006Measles Cases, 1985 – 2006

050

100150200250300350

1985 1991 1997 2003 '06

Imp

ort

ed c

ases

0

20

40

60

80

100

%

Imported Cases % Imported % Import associated

Measles Genotypes and Measles Cases USA: Measles Genotypes and Measles Cases USA: 1980-20051980-2005

97

Mea

sles

Cas

es

80 81 82 83 84 85 8687 88 89 90 91 92 93 94 0

5,000

10,000

15,000

20,000

25,000

30,000

95 96

Interruption in transmission

9998 00

Viral Genotypes

G1

(2 strains in 1983)

D3

(30 isolations)

A, C2, B2, B3, D2, D4, D3, D5, D6, D7, D8, G2, H1, H2

(>100 isolations)

01 02 03

Imported Measles CasesImported Measles Cases1996-2005*1996-2005*

Total Cases Imported - 348Total Cases Imported - 348

Japan - 50 casesJapan - 50 cases

China - 36 casesChina - 36 cases

Germany - 26 casesGermany - 26 cases

India - 23 casesIndia - 23 cases

Philippines - 19 casesPhilippines - 19 cases

Italy - 17 casesItaly - 17 cases

Pakistan - 15 casesPakistan - 15 cases

Greece, United Kingdom – 11 cases eachGreece, United Kingdom – 11 cases each

54 other countries – 140 cases54 other countries – 140 cases

*2005 provisional data through Oct 29

Measles in the U.S.—2006*Measles in the U.S.—2006*• 55 cases reported by 16 states55 cases reported by 16 states

• States reporting largest number of cases: MA States reporting largest number of cases: MA (18), NY (10), CA (6) & FL (4)(18), NY (10), CA (6) & FL (4)

• 52 cases (95%) were imported-associated cases52 cases (95%) were imported-associated cases: : • 31 imports31 imports• 20 epi-linked to imported cases20 epi-linked to imported cases• 1 virus only case1 virus only case

• 3 cases were unknown source cases3 cases were unknown source cases

*CDC data, unpublished

Source Countries for 2006 Source Countries for 2006 Imported Measles Cases (N=31)Imported Measles Cases (N=31)

India India 6 6 Ukraine Ukraine 6 6 China China 5 5 U.K. U.K. 3 3 Pakistan Pakistan 2 2 Australia Australia 2 2 Italy Italy 1 1 Hong Kong Hong Kong 1 1 Thailand Thailand 1 1 Kenya Kenya 11Ethiopia Ethiopia 11Uganda Uganda 11Yemen Yemen 11

2006 Measles Outbreaks2006 Measles Outbreaks

• 4 outbreaks:4 outbreaks:• MA (18 cases) resulting from single import from MA (18 cases) resulting from single import from

India -- Office Building(s)India -- Office Building(s)

• FL (3 cases) among cruise ship employees, FL (3 cases) among cruise ship employees, source Ukrainesource Ukraine

• NYS (3 cases) among Immigrants living in a NYS (3 cases) among Immigrants living in a Yemen communityYemen community

• CA (1 case) WA (1 case) MO (1 case) - 3 CA (1 case) WA (1 case) MO (1 case) - 3 mothers exposed in China during adoptionsmothers exposed in China during adoptions

Ind

ian

a

New York City

17 cases: D8 [India]

Boston

1 case: D6 [Ukraine]

1 case:D8 [India]

1 case:D6 [Ukraine]

1 case : H1 [Hong Kong]

Ore

go

n

Cases in US in 2006 with genotype associated with case(s) or outbreaksCases in US in 2006 with genotype associated with case(s) or outbreaks

1 case: B3 [inter’l travel, UK]

2 cases: B3[travel: Disneyworld]

3 cases: B3[Yemen]

1 case: D4[Pakistan]

1 case:D8 [inter’ltravelAustralia]

1 case:B3 [UK]

1 case: H1[China]

33

34 case outbreak: D4 [Romania]

Ind

ian

a

1

Illin

ois

1 case: D9 Indonesia] & 1 case: D8 [India]

1

1 case: D6[Armenia]

Ari

zona

1 case:D8 [India]

2 cases: D4[inter’l travel, Germany]

3

1 case: D4 [Yemen]

1 case: D4[inter’l meeting, France]

1 case: B3[Kenya]

New York City

& 1 case: D4[Romania]

2

3

3 cases: B3[inter’l travel, Mexico]

Texa

s

Washington

Wisconsin

2

1

Mic

higa

n

New Jersey

New York

Cases in US in 2005 with genotype associated with case(s) or outbreaksCases in US in 2005 with genotype associated with case(s) or outbreaks

Evidence for EliminationEvidence for Elimination of Endemic Measles in the U.S.of Endemic Measles in the U.S.

• Extremely low incidenceExtremely low incidence

• Majority of cases are internationally imported or import Majority of cases are internationally imported or import associatedassociated

• Surveillance system is adequateSurveillance system is adequate

• Population immunity is very highPopulation immunity is very high

• No endemic strain of measles virusNo endemic strain of measles virus

Adequate Surveillance to Detect Adequate Surveillance to Detect Endemic MeaslesEndemic Measles

• Consistent detection of imported measles casesConsistent detection of imported measles cases

• Detection of isolated cases and small outbreaksDetection of isolated cases and small outbreaks

• High level of investigative effort for measles High level of investigative effort for measles

• Molecular typing consistent with elimination of Molecular typing consistent with elimination of indigenous genotype of measles virusindigenous genotype of measles virus

High Population ImmunityHigh Population Immunity

• First dose coverage > 90% since 1996 for 19-35 First dose coverage > 90% since 1996 for 19-35 month-old childrenmonth-old children

• First dose coverage > 97% for school-age First dose coverage > 97% for school-age childrenchildren

• Second dose required for 82% of school children Second dose required for 82% of school children as of 2001as of 2001

• Seroprevalence 1999-2004 shows 96% immunity Seroprevalence 1999-2004 shows 96% immunity (EIA) ages 6-49 years(EIA) ages 6-49 years

Prevalence of Measles AntibodiesPrevalence of Measles AntibodiesU.S Population, 1988-1994U.S Population, 1988-1994

Hutchins SS et al, JID 2004

93% ≥ 6 years

Born < 1957 99%Born >= 1957 87%Born 1967-76 81%

Duration of Vaccine Induced Duration of Vaccine Induced Immunity? Immunity?

US has used measles vaccine since 1963US has used measles vaccine since 1963 Some vaccine recipients received measles Some vaccine recipients received measles

vaccine 40 years agovaccine 40 years ago Younger cohorts are not being exposed to Younger cohorts are not being exposed to

wild measles viruswild measles virus Important to monitor population immunity Important to monitor population immunity

including whether immunity remains above including whether immunity remains above the protective levelthe protective level

Persistence of Measles Antibodies After 2 DosesPersistence of Measles Antibodies After 2 Dosesof Measles Vaccine in a Postelimination Environmentof Measles Vaccine in a Postelimination Environment

LeBaron CW, Beeler J, Sullivan BJ et al. LeBaron CW, Beeler J, Sullivan BJ et al. Arch Pediatr Adolesc Med. 2007;161:294-301

Projected Measles Antibody Levels following Projected Measles Antibody Levels following MMR2 Vaccination at Kindergarten AgeMMR2 Vaccination at Kindergarten Age

A, Titers in the kindergarten groupB, Percentage potentially susceptible in the kindergarten group.

Persistence of Vaccine-Induced Persistence of Vaccine-Induced Measles Antibody Measles Antibody

• Small long term follow up study of persons Small long term follow up study of persons from vaccine trial in 1971from vaccine trial in 1971

• Participants 26-33 years after last measles Participants 26-33 years after last measles vaccine dose vaccine dose

• No known exposures to measlesNo known exposures to measles• All 56 participants had PRN antibody All 56 participants had PRN antibody ≥ 1:8≥ 1:8• 9% had PRN titer ≤ 120 9% had PRN titer ≤ 120 (not considered protective)(not considered protective)• Cellular immunity?Cellular immunity?

Dine MS, Hutchins SS et al JID 2004

ConclusionsConclusions

• Measles no longer endemically transmitted Measles no longer endemically transmitted in U.S.in U.S.

• Almost 100% cases are import associated Almost 100% cases are import associated • Importations continue to challenge Importations continue to challenge

population immunitypopulation immunity• Extremely limited spread from importations Extremely limited spread from importations

due to high population immunitydue to high population immunity• No indication of immunity waning to No indication of immunity waning to

“susceptibility” from epidemiological data“susceptibility” from epidemiological data• Continue long term monitoring of vaccine-Continue long term monitoring of vaccine-

induced immunityinduced immunity

Thank YouThank You