1. Jane Seward, MBBS, MPH Acting Deputy Director, Division Viral Diseases Centers for Disease Control and Prevention FDA BPAC Meeting Bethesda, August 16 th, 2007 Measles Epidemiology United States, 2006

2. Measles Highly contagious viral illnessHighly contagious viral illness Near universal childhood infection in the pre-vaccine eraNear universal childhood infection in the pre-vaccine era Morbidity and mortality 1950s, United StatesMorbidity and mortality 1950s, United States 450 deaths annually450 deaths annually 48,000 hospitalizations48,000 hospitalizations 4,000 cases encephalitis4,000 cases encephalitis

3. Measles 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 ≥ 12 months: 95%One dose ≥ 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 studentsCollege students Health care workersHealth care workers International travelersInternational travelers

4. Strategies to Control and Eliminate Measles, 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 childrenIncrease second dose coverage in school children Vaccinate high risk adultsVaccinate high risk adults Assure adequate surveillanceAssure adequate surveillance Respond rapidly to outbreaksRespond rapidly to outbreaks Work to improve global controlWork to improve global control

5. Reported Measles Cases by Year, United States, 1950-2006 Vaccine licensed School immunization laws started in all states Second dose strategy and school laws Improved first dose preschool coverage

6. Reported Measles Incidence United States, 1992-2006* 1 case/million *provisional 2006 data Measles elimination declared

7. Measles Cases by Age Group United States, 1976-2006

9. Age Specific Incidence of Measles, 1996-2006

10. Largest Measles Outbreaks United States, 1999-2006 12LOCATIONIndiana Boston, MA Cases3418Year20052006 Age Group AdultAdultOriginImportedImported 3 Bedford Co, VA 151999 Preschool /Adult Imported 45Multi-state Multnomah Co, OR 141320011999 Preschool /Adult ImportedUnknown 67 Lee County, AL South King Co, WA 131220022001 Infant/ Daycare Preschool/AdultImportedImported 8910 Delaware County, PA Oswego, NY Multi-state11109200320042000SchoolInfant/AdopteesSchoolImportedImportedUnknown 11 Brooklyn, NY 92000PreschoolImported

11. Age Distribution of Measles Cases US, 2001-2006 * Provisional

12. Vaccination Status Measles Cases US, 2001-2006 * From NNDSS

13. Internationally Imported Measles Cases, 1985 – 2006

14. Measles Genotypes and Measles Cases USA: 1980-2005 97 Measles Cases 80818283848586 87 88899091929394 0 5,000 10,000 15,000 20,000 25,000 30,000 9596 Interruption in transmission 999800 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) 010102020303

15. Imported Measles Cases 1996-2005* Total Cases Imported - 348 Japan - 50 cases China - 36 cases Germany - 26 cases India - 23 cases Philippines - 19 cases Italy - 17 cases Pakistan - 15 cases Greece, United Kingdom – 11 cases each 54 other countries – 140 cases *2005 provisional data through Oct 29

16. Measles in the U.S.—2006* 55 cases reported by 16 states55 cases reported by 16 states States reporting largest number of cases: MA (18), NY (10), CA (6) & FL (4)States reporting largest number of cases: MA (18), NY (10), CA (6) & FL (4) 52 cases (95%) were imported-associated cases : 52 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

17. Source Countries for 2006 Imported Measles Cases (N=31) India 6 Ukraine 6 China 5 U.K. 3 Pakistan 2 Australia 2 Italy 1 Hong Kong 1 Thailand 1 Kenya 1 Ethiopia 1 Uganda 1 Yemen 1

18. 2006 Measles Outbreaks 4 outbreaks:4 outbreaks: MA (18 cases) resulting from single import from India -- Office Building(s)MA (18 cases) resulting from single import from India -- Office Building(s) FL (3 cases) among cruise ship employees, source UkraineFL (3 cases) among cruise ship employees, source Ukraine NYS (3 cases) among Immigrants living in a Yemen communityNYS (3 cases) among Immigrants living in a Yemen community CA (1 case) WA (1 case) MO (1 case) - 3 mothers exposed in China during adoptionsCA (1 case) WA (1 case) MO (1 case) - 3 mothers exposed in China during adoptions

19. Indiana 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] Oregon Cases 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’l travel Australia] 1 case: B3 [UK] 1 case: H1 [China]

20. 33 34 case outbreak: D4 [Romania] Indiana 1 Illinois 1 case: D9 Indonesia] & 1 case: D8 [India] 1 1 case: D6 [Armenia] Arizona 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] Texas Washington Wisconsin 2 1 Michigan New Jersey New York Cases in US in 2005 with genotype associated with case(s) or outbreaks

21. Evidence 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 associatedMajority of cases are internationally imported or import associated 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

22. Adequate Surveillance to Detect Endemic 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 measlesHigh level of investigative effort for measles Molecular typing consistent with elimination of indigenous genotype of measles virusMolecular typing consistent with elimination of indigenous genotype of measles virus

23. High Population Immunity First dose coverage > 90% since 1996 for 19-35 month-old childrenFirst dose coverage > 90% since 1996 for 19-35 month-old children First dose coverage > 97% for school-age childrenFirst dose coverage > 97% for school-age children Second dose required for 82% of school children as of 2001Second dose required for 82% of school children as of 2001 Seroprevalence 1999-2004 shows 96% immunity (EIA) ages 6-49 yearsSeroprevalence 1999-2004 shows 96% immunity (EIA) ages 6-49 years

24. Prevalence of Measles Antibodies U.S Population, 1988-1994 Hutchins SS et al, JID 2004 93% ≥ 6 years Born < 1957 99% Born >= 1957 87% Born 1967-76 81%

25. Duration of Vaccine Induced Immunity?  US has used measles vaccine since 1963  Some vaccine recipients received measles vaccine 40 years ago  Younger cohorts are not being exposed to wild measles virus  Important to monitor population immunity including whether immunity remains above the protective level

26. Persistence of Measles Antibodies After 2 Doses of 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

27. Projected Measles Antibody Levels following MMR2 Vaccination at Kindergarten Age A, Titers in the kindergarten group B, Percentage potentially susceptible in the kindergarten group.

28. Persistence of Vaccine-Induced Measles Antibody Small long term follow up study of persons from vaccine trial in 1971Small long term follow up study of persons from vaccine trial in 1971 Participants 26-33 years after last measles vaccine doseParticipants 26-33 years after last measles vaccine dose No known exposures to measlesNo known exposures to measles All 56 participants had PRN antibody ≥ 1:8All 56 participants had PRN antibody ≥ 1:8 9% had PRN titer ≤ 1209% had PRN titer ≤ 120 (not considered protective) (not considered protective) Cellular immunity?Cellular immunity? Dine MS, Hutchins SS et al JID 2004

29. Conclusions Measles no longer endemically transmitted in U.S.Measles no longer endemically transmitted in U.S. Almost 100% cases are import associatedAlmost 100% cases are import associated Importations continue to challenge population immunityImportations continue to challenge population immunity Extremely limited spread from importations due to high population immunityExtremely limited spread from importations due to high population immunity No indication of immunity waning to “susceptibility” from epidemiological dataNo indication of immunity waning to “susceptibility” from epidemiological data Continue long term monitoring of vaccine- induced immunityContinue long term monitoring of vaccine- induced immunity

30. Thank You