Epidemiologic Characteristics of Recent Measles Outbreaks in ROK

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1 Epidemiologic Characteristics of Recent Measles Outbreaks in ROK Park Ok Director, Division of VPD control and NIP, KCDC

Immunization History for MMR Vaccine 1980 MMR was introduced 1983 MMR was included in NIP 1997 2 dose MMR was recommended by NIP 2000-2001 Nationwide huge measles outbreak 2001 MR

2 Immunization History for MMR Vaccine 1980 MMR was introduced 1983 MMR was included in NIP dose MMR was recommended by NIP Nationwide huge measles outbreak 2001 MR Supplementary immunization activity 2002 Immunization registry 2005 Web based immunization registry Routine MMR vaccine schedule - MMR 1 at 12-15mo, MMR 2 at 4-6 yr * MMR Vaccine used in Korea

3 Reported Cases of Measles ( Jul) in Korea Cases Imported Import-linked Imported-virus Unknown Under investigation Year Measles incidence: 8.2 cases per 1M population Annual median number: cases [range, cases]

4 Measles Cases in Korea, by Import Status, Jan-July 2014 Cases Epidemiological week Under investigation Imported Import-linked Imported virus Unknown Jul 18, Total Imported Import-associated Endemic Unknown 46 (under investigation) n % Under investigation Imported Import-linked Imported virus Unknown Total

5 Details of Imported measles cases Country Cases No. Details The Philippines 6 Multicultural family Korean returning from international travel Foreign worker International student, Korean China 5 Multicultural family Korean returning from international travel International student, Korean International student, Chinese International worker, Chinese Vietnam 3 Multicultural family Korean returning from international travel Singapore 1 Foreign visitor 1

Measles Cases in Korea, by Genotype, Jan-July 2014 Cases 250 200 150 100 50 0 B3 D8 H1 Unknown Genotype Genotype n B3 209 D8 7

6 Measles Cases in Korea, by Genotype, Jan-July 2014 Cases B3 D8 H1 Unknown Genotype Genotype n B3 209 D8 7 H1 5 Unknown* 198 Total 419 * Unknown: includes cases under investigation WHO Measles-Rubella Bulletin, Vol 8 Issue 6 (June 2014)

7 Measles Cases in Korea by Age, Jan-July 2014 Cases Age (yr)

8 Measles Cases in Korea by Age Group, Jan-July 2014 Cases Age (yr) Age Group Cases (no.) % ~1yr unvaccinted 1-3yr day care 4-6yr kidergarten 7-12yr yr elementary schooler middle schooler 16-18yr high schooler 19-29yr yr~ college students

9 Measles Cases in Korea, by Age Group and Vaccination History, Jan-July % Never 38% 1 dose Cases % 9% 2 doses Unknown Vaccination History Unknown Age (yr) Vaccination History Unknown Total ~ ~ ~ ~ Subtotal ~3 4~6 7~19 20~ Age (yr)

10 Measles Cases in Korea by Region, Jan-July 2014 Region Confirmed New cases in recent 2 weeks Imported cases Genotype B3 D8 H1 Total Seoul Incheon North Gyeonggi South Gyeonggi Gangwon Daejeon Chungbuk Chungnam Gwangju Jeonbuk Jeonnam Daegu Ulsan Gyeongbuk Busan Gyeongnam Jeju

classic manifestations of measles [OR=3.656 (p <0.000)](among 330 measles cases with available data).

11 Clinical Manifestations of Measles Cases in Korea, Jan-July 2014 Classic measles (F+R+3C) Non-classic measles Vaccinated Unvaccinated * Unvaccinated cases were more likely to present classic manifestations of measles [OR=3.656 (p <0.000)](among 330 measles cases with available data). Rash: mild, atypical H-F-M dz?, acne?, varicella? Hospitalization rate: 34.8% Pneumonia, encephalitis, death : not reported so far

12 Epidemiological curve of Measles Cases in Korea by Outbreaks, Jan-July 2014 Cases 70 K 대학교 H 중학교 B 중고교 대전, 파주 B 병원 D 고교 가족병원어린이집지역사회학교학원회사 Epidemiological week Daejeon, Mokpo, Gyeonggi(Paju,Bundang,Bucheong) hospital

13 Transmission Chain of Outbreaks in Mokpo and Jeonnam Province F (2) A (48) C (38) G (19) J (19)? B Hospital A Hospital B (31) D (1) M (17 ) E (2) H (6m) I (13m ) C Hospital L (10m ) O (1 ) K (13) 12 persons (12~13) D Mid. School? Family N P (33 ) (6m ) Feb. Mar. Apr. May

14 Transmission Chain of Outbreaks in Health Care Workers of a Hospital Apr May Jun A: 33 B: 32 C: 33 D: 27 Phillippines (Cebu) Deteted during Epi. investigation R/O Mycoplasma infection, R/O Viral infection Worked at emergency room when A pt visited E: 2M F: 30 R/O Sepsis, R/O Meningitis Nurse of the ward where E pt admitted Infective period Hospital visit Exposure Rash onset

15 Transmission Chain of Outbreaks in North Gyeonggi Province C Hospital F (25) G (11m) O (10m) L (14m) P (1) From Philippine C (9m) B Hospital K (13m) M (1) N (10m) A (12) E (11m) B (22m) D (18m) F (9m) G (11m) H (12m) L (13m) H (8m) I (12m) A Hospital Feb. Mar. Apr. May

16 Measles Outbreaks in Health Care Setting, Korea, 2014 Outbreak Name Region Cases No. Import State Genotype Rash onset Duration Age range S Hospital Daejeon 6 Imported virus B days 11M - 31 M Children s hospital J Hospital M Children s hospital N. Gyeonggi (Paju) S. Gyeonggi (Bundang) Jeonnam (Mokpo) 7 Imported (Philippines) B days 8M 12 5 Imported virus B days 10M 1 5 Imported virus B days 6M 1 S ENT clinic Chungbuk 4 Unknown days D Hospital G Hospital S children s hospital N. Gyeonggi (Ilsan) Jeonnam (Mokpo) S. Gyeonggi (Pucheon) 6 Imported (Philippines) B days 9M Imported virus B days Imported virus B ongoing (7.13) 5M 1 G Hospital Incheon 16 Imported virus B days 7M - 30 H Hospital S Hospital S Hospital Jeonnam (Mokpo) Gyeongnam (Andong) S. Gyeonggi (Pucheon) B Hospital Busan 7 Imported (Philippines) /Imported virus * Outbreak: cluster of more than two cases 5 Imported virus B days Imported virus B3 5.1 ongoing (6.28) 5M Imported virus B days 2M - 47 B days 11M - 33

Measles Outbreaks in other than Health Care Setting, in Korea, Jan-July 2014 Outbreak Name G Residence Academy H Middle school Region Cases No. Import State S.

17 Measles Outbreaks in other than Health Care Setting, in Korea, Jan-July 2014 Outbreak Name G Residence Academy H Middle school Region Cases No. Import State S. Gyeonggi (Kwangmyeog) Jeonnam (Mokpo) 9 Imported virus 15 Imported virus K Univ Seoul 85 Imported virus Genotype Setting Rash onset B3 Boarding school Duration Age range days B3 School days B3 University days G Company Chungnam 3 Imported D8 Office days B Upper school Seoul 17 Imported virus Y High school Seoul 4 Imported virus S High school Daegu 3 Imported (China) D High school Daegu 4 Imported (China) B3 School days B3 School days H1 School days H1 School 6.16 Ongoing (7.4) # Outbreaks in Korea, Jan-July 2014 Total 21 measles outbreaks Hospital(13), School(7), and Office(1) Average size: 12 cases [ranges, 3-85 cases] Average duration: 31 days [ranges, 3-58 days] * Outbreak: cluster of more than two cases

18 An Outbreak in K University and Catch Up Campaign 50 Cases Catch-up( ) Week

19 Summary of Surveillance Data of Measles Cases in Korea, Jan-July 2014 There are bimodal peaks; aged <1 year and aged years. The main outbreak settings were hospitals and schools. Significant proportion of measles cases in Korea, Jan-July 2014 was vaccinee (40.0%). Among 419 confirmed measles cases, there were 15 (3.6%) imported cases; 14 (93.9%) occurred in Korean residents returning from international travel, and 1 (6.1%) occurred in foreign visitor. Measles importation were associated with travel from 4 countries: the Philippines, China, Vietnam, and Singapore. Outbreak-related cases comprised 265 (63.2%) of total measles cases. Predominant measles genotype was B3.

20 Characteristics of the Recent Measles Outbreaks in Korea Continuous import from abroad Hospital infections among infants Outbreaks in previously vaccinated youth Overseas travels during vacations (students for language course in abroad, international students from abroad, multicultural families) Diagnosis failure due to atypical symptoms at the first visit to clinics Delayed notice of outbreaks after transmissions of several generations through hospitals, families, and schools Imports from abroad hospital infection through contacts to imported cases transmission among family members and in community transmission through infections at schools

21 Huge Outbreaks in Neighbor Countries WHO Measles-Rubella Bulletin, Vol 8 Issue 6 (June 2014)

22 Continuous Imports from Abroad Huge outbreaks in neighbor countries transmission by travellers

23 2ndary Transmission in Children s Hospital (57.0%) Transmission routes of measles cases in 2013 Hospital Day care Family School Overseas travel Community Total (37.5%) Transmission routes of measles cases in 2014 as of Jul 18 Hospital Day care Family School Overseas travel Community Total

Decrease of Passive Immunity in infants 7% of neonates have no measles Ab, 90% of infants have no measles Ab at 6 months of age in USA J Infect Dis 2004;190:83, J Infect Dis

24 Decrease of Passive Immunity in infants 7% of neonates have no measles Ab, 90% of infants have no measles Ab at 6 months of age in USA J Infect Dis 2004;190:83, J Infect Dis 2007;196:1459 Measles Sero-positive Rates under 2 years olds in Korea Kim SS et al. Vaccine23(2004) Measles Sero-positive Rates In infants under 1 year old Kim KH, 2009

more likely to present classic manifestations of measles [OR=3.656 (p <0.000)](among 330 measles cases with available data).

25 Atypical Measles Manifestations in Pts with Vaccination history 홍역발생상황평가 : 청소년 / 성인백신접종자중심집단적인홍역발생 Classic measles (F+R+3C) Typical measles rash Non-classic measles Vaccinated Unvaccinated * Unvaccinated cases were more likely to present classic manifestations of measles [OR=3.656 (p <0.000)](among 330 measles cases with available data). *Atypical mild measles clinical features & low measles incidence Difficulty in diagnosis Atypical rash of a recent measles case

26 Delayed Notice Lead Wide Transmission Early detection and notification from clinics are important for control Index case

27 Delayed Notice Lead Wide Transmission Early detection and notification from clinics are important for control Index case

Vaccine Failure : Primary vs 2ndary 22% Never 38% 1 dose 2 doses Unknown 31% 9% Reported measles cases, Jan-July 2014, KCDC * A study in USA (2014.1.1-5.

28 Vaccine Failure : Primary vs 2ndary 22% Never 38% 1 dose 2 doses Unknown 31% 9% Reported measles cases, Jan-July 2014, KCDC * A study in USA ( )(n: 288) : unvaccinated : 200(69%), unknown : 58(20%), vaccinated : 30(10%) * A study in Japan ( )(n: 183) : unknown or unvaccinated : 146(80%), vaccinated : 37(20%)

29 Waning Immunity after Vaccination Vaccination Natural infection P.O.Viana et al. J C linimmunol 2010 Davidkin I et al. JID 2008:197

30 Secondary Vaccine Failure Measles Outbreak in a Vaccinated School Population: Epidemiology, Chains of Transmission and the Role of Vaccine Failures Nkowane et al. Am J Public Health 1987 Outbreak of measles among persons with prior evidence of immunity, New York A Limited Measles Outbreak in a Highly Vaccinated US Boarding School Rosen et al. CID 2014 Yeung et al. Pediatrics, 2005 In case the level of neutralizing Ab is not enough, measles infection is possible. The present neutralizing Ab can t prevent atypical measles. (continuum of clinical illness) JID 1990 Chen RT et al. Based on the large cohort study(n=763) in U.S., 8.9% of vaccinees at 7.4 years after 2-dose MMR have Ab level < 210mIU/mL (protective threshold). There was no difference between ethnic groups Haralambieva IH et al. Vaccine 2011 Genetic factors(hla class I, II genotype, SNP polymorphism) may determine the response to Measles containing vaccine Haralambieva IH et al Expert Rev. Vaccines 2013

31 Utility of PCR for Measles Case Confirmation Classification Clinical IgM IgG PCR Vaccine reaction Fever/Rash P P or N Positive and Sequence indicates vaccine strain Measles Meets CCD* P P or N Positive PCR can confirm IgM Secondary vaccine Failure CCD or Modified # P or N P Positive PCR can confirm case *=clinical case definition (CCD) Presented by Paul Rota, Meeting at Korea CDC, March #=modified or mild presentation does not meet CCD In patients with vaccination history, Mild symptoms IgM may be negative in acute serum Characterized by rapid and robust IgG response If a second serum sample collected 5-10 days later remains IgM negative, then the paired serum samples can be tested in a PRN assay or quantitative or semiquantitative IgG EIA CDC VPD Surveillance Manual, 6 th Edition, 2013 Measles: Chapter 7-9

32 Vaccination is the most important Protective Measure Vaccine effectiveness (2014) No. of Hospitalized No. of infected Incidence Total % With vaccination hx % No vaccination hx % No. of hospitalized : All the hospitalized patients during the infective period of the index case of a hospital in Kyeonggi province No. of Hospitalized No. of infected Incidence Total % With vaccination hx No vaccination hx % No. of hospitalized : All the hospitalized patients during the infective period of the index case at the same ward of a hospital in Daejeon city

33 Latest Data of Measles Vaccine Efficacy/Effectiveness * Measles vaccine efficacy: Proportion of Vaccinee with measles specific Ab level (protective threshold) 15 years later after vaccination : 91.1% (Vaccine, 2011) * Measles vaccine effectiveness: 1 st dose measles vaccine: 9-11mo: 77.0% (IQR, 62%-91%) 12mo: 92.5% (IQR, 84.8%-97.0%) 2 nd dose measles vaccine: 94.1% (IQR, 88.3%-98.3%) (JID, 2013)

34 Acknowledgements

국내소아무균성뇌막염의전국적발생양상 정해관박수경기모란이관 B3 3 [14], 1995 B3 7 [13,15], 1996 B1[13], A24 9[16], 1997 B5 Echo 30[17,18], [19] [1-4]. . - [10].

원저 국내소아무균성뇌막염의전국적발생양상 정해관박수경기모란이관 성균관대학교의과대학사회의학교실을지대학교의과대학예방의학교실 서울대학교의과대학예방의학교실동국대학교의과대학예방의학교실 [1-4] 서론 1994 B3 3 [14] 199 B3 7 [13] 199 B1[13] A24 9[1] B Echo 3[1718] 1998 [19] enterovirus adenovirus