Closing MR Immunity Gaps Experiences from the Regions Sri Lanka

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Closing MR Immunity Gaps Experiences from the Regions Sri Lanka Dr. Paba Palihawadana Chief Epidemiologist Epidemiology Unit Ministry of Health Sri Lanka

Background of the National Immunization Programme National Immunization Programme & Communicable disease surveillance : implemented by National Epidemiology Unit, Ministry of Health Provincial level authority (9 provinces ) District level : Regional Epidemiologist (26 districts) Divisional level : In charge Medical Officer of Health (342) Medical Officer of Health : Public Health staff working at field level Field level Maternal and Child Health clinics & hospital Immunization clinics provide Immunization services

Overview of Measles and Rubella (MR) Data Collection and Reporting System Organizational structure Measles Rubella surveillance Central level: Ministry of Health/Epidemiology Unit Virology Laboratory, investigation: Lab confirmation Provincial level: Provincial Director of Health Services/ Provincial Community Physicians District level : Regional Director Regional Epidemiologist Health care Institutions : Hospitals Field Level : Medical Officer of Health, Public Health Nursing Sister Public Health Inspector, Public Health Midwife

Feed back (weekly/quarterly/annually) Data Flow : Organization of surveillance, outbreak detection & response Health Institution s Medical Officer of Health (Field) Regional Epidemiolo gist District level Routine notification (included all VPD) to Medical officer of Health: patient s residence Active surveillance of VPD : [AFP,Measles,Rubella,CRS, NNT] Investigate the case at the field Weekly compile & Notify to district level and central level case based investigation: special investigation Detect outbreaks, notify and investigate Active surveillance of sentinel site hospitals for VPD Detect and respond outbreaks Compiled monthly Each case & weekly Each case Weekly aggregate & case based JRF Epidemiology Unit (central level) /MoH WER, QEB

Susceptibility Profiles by Age Necessary to understand who remains susceptible Guides timing for Supplementary Immunization Activities(SIAs) Surveillance data : disease burden- incidence rates, mortality rates Coverage data : MMR 1 and MMR 2 coverage at district level Sero-surveys : selected districts / samples, different age categories, different population categories Special studies : vaccine effectiveness (Field level vaccine efficacy) Risk or susceptibility profile assessment : WHO tools

51 53 55 57 59 61 63 65 67 69 71 73 75 77 79 81 83 85 87 89 91 93 95 97 99 01 03 05 07 09 11 13 14 15 Rate per 100,000 population Coverage(%) Incidence of Measles and immunization coverage, 1951-2015 100 100 90 90 80 80 70 70 60 60 50 50 40 40 30 30 20 20 10 10 0 0 Year Incidence rate Measles Coverage MR MMR

Measles seroprevalence survey-sri Lanka : 2014 Sero prevalence study : carried out by the Epidemiology Unit and the MRI in 2014 Rationale to conduct seroprevalence study: Country with high immunization coverage for both Measles containing vaccine (MCV) 1 (at 1 year of age) and 2 (at 3 years of age) Catch up programmes only in 2003 & 2004 in 10-15 year and 16-20 year age groups (coverage 95% and 72%) Measles outbreak situation in 2013-2014 : majority < 1 year Reported cases were from all age groups but all were not tested at the laboratory Regional and country plans for elimination by 2020 To assess seroprevalence of measles IgG antibody levels in Sri Lanka to assess the population level immunity at different age groups

Methodology Descriptive cross sectional study, Cluster sampling from randomly selected 4 districts Age groups selected : 7 age groups 6-8months 9-11 months 2 years 5 years 15-16 years 20-29 years 30-39 years Sample size : total sample 800 (each age group selected at expected prevalence of 90% for all age groups except 50% for 30-39 years, expected precession 7%, design effect 1.5 )

Laboratory investigation (MRI) : IgG antibody titer detection Anti - Measles IgG antibody levels were measured by using commercial ELISA kit (Serion Immundiagnostica GmbH) Optical density values were converted to antibody titers Sero-positivity was based on cut-off levels given by manufacturer measles >200 miu/ml Border line range measles 150-200 miu/ml Measles Laboratory/ MRI

Basic characteristics of the study sample Sample size & age category Age Category 6-8 9-11 15-16 20-29 30-39 month month 2 years 5 years years years years Total District Colombo 25 25 25 25 25 25 49 199 Monerag ala 25 25 25 25 25 25 50 200 Kegalle 25 25 25 25 25 25 51 201 Vavuniya 25 25 25 25 25 25 50 200 Total 100 100 100 100 100 100 200 800 Sample size by district and ethnicity Ethnicity Sinhala Tamil Muslim Total District Colombo 101 13 35 149 67.8% 8.7% 23.5% 100.0% Moneragala 149 1 0 150 99.3%.7% 0.0% 100.0% Kegalle 310 3 38 351 88.3%.9% 10.8% 100.0% Vavuniya 0 148 2 150 0.0% 98.7% 1.3% 100.0% Total 560 165 75 800 70.0% 20.6% 9.4% 100.0%

Protective measles antibody levels by age category Age category IgG antibody protective level positive negative equivocal total 6-8 months 2 (2%) 94 (94%) 4 (4%) 100 9-11 months 1(1%) 99 (99%) 0 (0%) 100 2 years 100 (100%) 0 (0%) 0 (0%) 100 5 years 98 (98%) 0 (0%) 2 (2%) 100 15-16 years 84 (84%) 11 (11%) 5 (5%) 100 20-29 years 94 (94%) 3 (3%) 3 (3%) 100 30-39 years 195 (97.5%) 5 (2.5%) 0 (0%) 200 IgG protective level among vaccinated 571 (95.2%) 95% CI 93-96.7%) 212 (26.5%) 14 (1.8%) 800

Measles Seroprevalence status

Measles seroprevalence status by district

Mean and median antibody titers for each age group Age category Number tested Median titer IU Mean titer IU 6-8 months 100 19.9 35.6 9-11 months 100 11.6 24.7 2 years 100 1018.5 1276.5 5 years 100 822.9 997.4 15-16 years 100 388.9 599.7 20-29 years 100 713.2 948.3 30-39 years 200 1463.2 1650.9 Protective level Total (all) 800 622 miu/ml (IQR 105.5-1361.2 miu/ml) Total mean population immunity (vaccinatio n due age groups) 600 735 miu/ml (IQR 462.9-1667.8 miu/ml) 1094.6

Conclusions of sero survey Population level immunity is high among vaccinated age groups Observed reduction of population immunity among 15-16 year age group is probably due to waning of antibodies with advancing age Infants of 6 months to 1 year : not adequately protected for measles due to inadequate maternal antibodies (MMR 1 given at 1 year at the time of the study) Majority of mothers are measles immunized mothers: waning of antibodies in infancy among babies of immunized mothers are earlier than the antibodies of the babies of naturally infected mothers : infants are susceptible

Field level vaccine efficacy (Effectiveness) Vaccine effectiveness - ability of the vaccine to prevent outcomes of interest in the real world During the outbreak in 2013-2014 assessed the field level vaccine effectiveness by determining the percentage reduction in the incidence rate of disease among vaccinated persons compared to unvaccinated persons Proportionate reduction of disease attack rates among vaccinated to unvaccinated age group *ARU Attack Rate for Unvaccinated / ARV Attack Rate for Vaccinated / VE Vaccine Efficacy

Presented in Annual Scientific Sessions 2015 College of Community Physicians of Sri Lanka

2013-2014 outbreak : Vaccine effectiveness (field level vaccine efficacy) 2013 2014 Age group ARV ARU VE % (ARU-ARV/ARU) x100 ARV ARU VE% 1-2 years 0.010 1.205 99.2% 0.007 3.378 99.8% 3-15 years 0.001 0.027 95.6% 0.001 0.009 94.7% 16-28 years 0.003 0.037 89.2% 0.002 0.026 92.3%

MR vaccination schedule and schedule changes - Sri Lanka Year Vaccine Target 1984 Measles 9 months 1996 EPI Rubella Women aged 16-44 years 2001 EPI MR All children aged 3 years 2002 EPI MR 14 years (girls first and all after 2 years) school based programme for Rubella prevention 2003 Catch-up campaign MR 10-15 years (95% coverage) 2004 Catch-up campaign MR 16-20 years (72% coverage) 2011 EPI MMR (replacing Measles at 9 months and MR at 3 years MMR1 advanced to 1 year age in 2011 and re-scheduled to 9 months in 2015; MMR2 at 3 years of age 2014: during outbreak- Measles vaccination- SIA: 6-11 months infants high risk categories: Prisoners, University students, Healthcare staff

Current situation - Measles 01 st January 2016 30 th April 2016 Measles No. Suspected Cases 195 Lab confirmed 57 Clinical 28 Rubella Confirmed 4 Discarded 110 Non Measles Non Rubella Rate 2 / 100,000

Current situation High political commitment for programme sustainability Outbreak situation is waning, but if returns will plan for SIA but need to decide at the ACCD(NITAG)?wide age range?approaches/ feasibility