1. Validation of measles & rubella elimination, challenges in Ecuador and Haiti Carlos Castillo-Solórzano Katri Kontio Eleventh Annual Meeting The Measles and Rubella Initiative September 18-19, 2012

2. Presentation Outline Issues in documentation and validation process  Virus importations from other regions  Sustained outbreaks - Ecuador  Maintaining elimination - Haiti How to maintain the Regional measles/rubella elimination?

3. Last Endemic Measles, Rubella and CRS Cases MEASLES: Venezuela / NOV 16, 2002 CRS: Brazil/ AGO 26, 2009 RUBELLA Argentina/ FEB, 2009 > 12 years without endemic MEASLES virus transmission > 3 years without RUBELLA endemic virus transmission Source: Country reports to PAHO/WHO.

4. Impact of measles resurgence to the Region In 2011 an eightfold increase over the previous annual average of 156 cases between 2003 and 2010. Most common genotypes identified were D4 and B3 174 measles virus importations were detected in the Region in 2011

5. Rate: 1.37 X 1,000,000 pop. Confirmed Cases N=119 N=108 N=1374 N=85 N=226 N=176N=207 N=253 N=89 Distribution of Confirmed Measles Cases Following the Interruption of Endemic Transmission, the Americas, 2003-2012* Source: Country reports to PAHO/WHO. * Data as of EW 36/2012. N=129

6. The role of the laboratory in a context of low incidence  Pregnant women  Post-vaccine  False positives or cross-reaction  False negatives: is it a problem in this stage of elimination? –These cases should be investigated on a case- by-case basis taking the epidemiological information into account –A second blood sample –Additional tests may be required

7. ALGORITHM FOR SPECIMENS : IgM positive and indeterminate results IgG test YESI IgG Positive There first serum sample available for further investigation? IgG Negative Collect second blood specimen Second serum sample collected Resultados IgG de sueros pareados (primera y segunda muestra) Results IgG, second sample Avidity testing IgG test NO Collect second serum sample IgG NegativaIgG Positiva Te case discarded YESI RT-PCR /VIRAS isolation Sequencing and genotyping Positive Respiratory or urine sample exist?* Indeterminate results (cannot be confirmed nor discard)) Report as RT-PCR negative Negative IgG titers permanently stable IgG titers increased four times or more IgG titers increased less than 4 times DISCASRD ED CONFIRM RECENT CONTACTS Indeterminate results (revise tiempo de recolección muestras) IgG Negative IgG Positive CASE DISCARDE D CONFIRM RECENT CONTACT Low avidity High avidity Confirm contacts <3 months Evidence of contacts> 3 meses Report as RT- PCR positive with identified genotype

8. Efforts maintaining the elimination of endemic disease is more expensive than eliminating the disease Health care-associated measles outbreak in the United States after an importation: challenges and economic impact An infected Swiss traveler visited hospital A in Tucson, Arizona, and initiated a predominantly health care-associated measles outbreak involving 14 cases in 2008. The 2 hospitals spent US$799,136 responding to and containing 7 cases in these facilities. community partners. J Infect Dis. 2011 Jun 1;203(11):1517-25. J Infect Dis. The Cost of Containing One Case of Measles: The Economic Impact on the Public Health Infrastructure—Iowa, 2004 The containment costs of 1 measles case in this outbreak were high. The costs to the Iowa public health infrastructure of preventing the spread of disease from these cases were $140 000. Pediatrics 2005;116:1--4.

9. Containment costs for a measles outbreak in Indiana, USA - 2005 Costs itemUnitary cost (USD) Cost per patient4,932 Wages and salaries108,592 Overhead30,431 MMR vaccine and immune globulin 21,692 Mileage1,610 Other5,360 TOTAL167,685 Source : Parker A, Staggs W, Dayan G et all. Implications of a 2005 measles outbreak in Indiana for sustained elimination of measles in the United States. The New England Journal of Medicine, Vol 355, No 5, August 3, 2006 Total number of cases was 34; the majority was among 5-19 years old and 32 lacked evidence of measles vaccination.

10. Estimated costs of containing measles outbreaks in selected LAC countries Studies suggests that economic analyses may need to go beyond the costs of individual illness to account for the costs of protecting society, particularly when countries are close to elimination. Country# of cases Scope of outbreak control activities Cost (USD)* Chile (2009)1Limited to 1 municipality12,400 Peru (2009)1 1 municipality in Peru and 1 in Ecuador 20,300 Ecuador (2011-2012) 266Nationwide 8.5 million *Estimated costs include outbreak investigation, follow-up of contacts and vaccination activities Source: Country reports to FCH/IM

11. Last confirmed case EW 28/2012 (7/10/2012) Source: Ministry of Health, Ecuador. Preliminary data by EW 36/2012 Ecuador outbreak All confirmed cases = 329 (EW 24/2011 to EW 37/2012) Sustained outbreak with low incidence First cases were not notified on time

12. Measles attack rate by age group, Ecuador 2012* Fuente: PAI, Ministerio de Salud Pública de Ecuador * Datos preliminares a la SE 12/2012 Attack rate per 100.000 population = 1,78

13. Fuente: Reporte de país a Septiembre 2008 Age groups 16-39 years Both sexes: 98% Year: 2004 Recent measles outbreak suggest over-estimation of routine and SIAs coverage in Ecuador? Cohort Analysis protected MR by year of birth and vaccination strategies. Ecuador 1965-2010 Introduction MMR in the routine program, 1999

14. Coverage range <80% 80-94% ≥95% Source: PAHO-WHO/UNICEF Joint Reporting Form, 2012. Administrative coverage 2011: MMR1 = 94% MMR2 = 92% Heterogeneity in coverage Ecuador 2011

15. Characterization of the affected population Other factors Over crowded inpatient wards High risk groups: unvaccinated persons (religious groups or other groups that reject vaccination) or in specific geographic areas, such as in indigenous communities, in large cities (especially on the peripheries), and in rural and border areas with limited access to health care.

16. Laboratory analysis of measles / rubella in serum samples of the dengue IgM-negative cases with presence of fever and rash in three stages during the outbreak: 1. Analysis before the detection of the first measles case to see previous circulation of measles virus 2. Analysis during the outbreak in provinces, which have not reported confirmed cases; 3. In order to provide evidence of not having measles virus circulation, collected specimens should be collected also within the last three months after detection of the last case. Outbreak response: dengue analysis

17. Fuente: Base de Datos Guayas :MESSS-ISIS Challenges  Communications between epidemiology and laboratory teams - the regular meeting of the EPI teams, surveillance and laboratory is recommended to conduct the analysis of the cases, especially the last cases reported  Private sector participation – involvement of the private clinics and the laboratories in detecting and notifying the suspected and confirmed cases

18. Haiti: Epidemiology of measles/rubella  Introduction of the MCV (≈ 1982) + campaigns  Last epidemic situation in 2000  Last measles case: September 2001  Last rubella case: November 2006

19. 200520062007200820092010 # of suspected cases 468246319 Population862145788661639117815937660996427499916443 Rate0.16230.76690.26350.06390.03110.1916 Reporting rate of suspected case Haiti 2005-2010 Source: MSPP Haiti Quality of surveillance

20. Age group: 1-19 years Men and Women** 94% Coverage Year: 2007-2008 Analysis of cohorts protected against measles and rubella by birth year and vaccination strategy, Haiti 1980-2010

21. Status of the documentation/verification of measles, rubella and CRS elimination in Haiti ComponentsStatus  Active case search for measles and rubella in hospitals and the community  Retrospective search of CRS Measles/rubella: Confirmed cases by lab :0; Compatible cases: 0 CRS: Detected CRS suspect cases: 273. Confirmed cases and Compatible cases: 0  Vaccinated Population Cohorts Immunization campaign is accomplished Seroprevalence study of measles and rubella: Test for measles/rubella IgG antibody in random sample of 740 sera is ongoing  Sustainability of Measles, Rubella, and CRS Elimination The process of strengthen the routine immunization is ongoing including funding with involvement of all the partners

22. RMC Coverage 9m-9 y Administrative Coverage 9m-9 y RMC Coverage 1-4 y Administrative Coverage 1-4 y Immunization RR Coverage (9m-9 y) and (1-4 y) by Department, Haiti 03-08-12 Référence: SIVAC < 80 % 80-94 % 95 a + % Référence: MRC Nord Nord Est Centre Ouest Sud Est Nord Ouest Grand’Anse Artibonite Sud Nippes A. Metropol Ouest Nord Nord Est Centre Ouest Sud Est Nord Ouest Grand’Anse Artibonite Sud Nippes A. Metropol Ouest Nord Nord Est Centre Ouest Sud Est Nord Ouest Grand’Anse Artibonite Sud Nippes A. Metropol Ouest Nord Nord Est Centre Ouest Sud Est Nord Ouest Grand’Anse Artibonite Sud Nippes A. Metropol Ouest Haiti= 96.0 % Haiti= 100 % Haiti= 95.0 %Haiti= 100 %

23. Maintain the achieved results: Development of plans with partners and Multi-annual plan for the Expanded Program on Immunization 2011–2015 Strategies implementation Phase 1: Maintain and strengthen the achievements of AISE with short-term activities such as the introduction of new vaccines, increased immunization coverage and strengthening epidemiological surveillance Phase 2: Focuses on improving and sustaining the performance of routine immunization program

24. Maintain high-quality, elimination-standard surveillance, including full compliance with indicators, and ensure timely and effective outbreak response measures to any wild virus importation  Implement external rapid assessments of measles, rubella, and CRS surveillance systems to increase robustness and quality of case detection and reporting and strengthen registries of congenital anomalies;  Conduct active case searches and review the sensitivity of surveillance systems in epidemiologically silent areas;  Involve the private sector in disease surveillance with a special focus on inclusion of private laboratories in the Regional Measles and Rubella Laboratory Network;  Enhance collaboration between epidemiological and laboratory teams to improve measles and rubella surveillance and the final classification of suspected cases;  Improve molecular genotyping of the confirmed cases throughout outbreaks

25. Maintain high population immunization coverage against measles and rubella (>95%)  Implement rapid coverage monitoring to identify populations susceptible to measles and rubella, focusing particularly on localities of high-risk populations: live in high-traffic border areas, live in densely populated areas such as urban fringe settlements, live in areas with low vaccination coverage or high vaccination dropout rates, live in areas not reporting suspected cases (epidemiologically silent), live in areas of high population density that also receive a large influx of tourists and other visitors, especially workers related to the tourism industry (such as those related to airports, seaports, hotels and hospitality sector, tour guides) as well as those in low density or isolated areas (ecotourism destinations), are geographically, culturally, or socioeconomically difficult to reach, and are engaged in commerce/trade (such as through fairs, markets) or live in highly industrialized areas;  Implement high-quality follow-up vaccination campaigns.

26. THANK YOU! www.paho.org/immunization

27. –Plan of Action to maintain the Regional elimination of endemic measles and rubella was approved in the 28 th Pan American Sanitary Conference How to maintain the regional measles/rubella elimination?

28. Improved access to IM service delivery Integrating immunization services with other health services Organizing the network of service providers Improving access to immunization services Organizing Immunization service delivery Identify the best ways to increase uptake and the vaccination coverage

29. Regional Documentation and Verification Process Status: Regional report with the plan of action was presented to the Governing Bodies of the Pan American Health Organization on progress made in the implementation of Resolution CSP27.R2 18 th of September 2012 Conclusion: After careful analysis of the reports submitted by the National Commissions and Subregional Commission: –It appears that the interruption of endemic measles and rubella virus transmission has been achieved –The Region of the Americas continues to be exposed to high risk of virus importations -the countries have reported weaknesses and failures in their national surveillance systems and routine immunization programs, which make them particularly vulnerable to the risk of reintroduction of viruses that can cause outbreaks.

30. * It does not include clinical cases reported. ** Five cases have been notified in the island of Saint Martin (1 import and 4 import-related). Data as of EW 52 NUMBER OF IMPORTED MEASLES CASES BY COUNTRY 2011 CountryImport Import relatedUnknownSource of Infection Argentina120 2 cases: D4 ( exposure to French and/or German tourists); 1 case (travel history to Italy) Brazil9249 D4 (unknown source; recent travel to US); D4 (France), D4, source unknown Chile330 D4 (outbreak < 1 case) recent travel to NY and 1 case with a travel history to Thailand and Malaysia, genotype D9. Canada*274772 India (D8) and D4, France (D4), England (D9); D4 and D9 (unknown source) Colombia150 1 case with travel history to Brazil Dominican Rep.200 1 case with travel history to Italy D4 / 1 case among a French tourist, it was confirmed by epidemical link. Ecuador12620 No travel history, B3 genotype identified Guadalupe**761 France French Guiana230 France Martinique201 Mexico300 France Panama400 France, Mexico with a travel history to London); Mexico with travel history to NYC and Niagara falls, date of rash-onset. D4 United States1118923 Travel history to Israel and Polonia; genotype D4, strain MVs/Wroclaw.POL/28.09/ ; China, Dominican Republic, France, France/UK (D4), France/Italy/Spain/Germany, India, Indonesia, Italy, Kenya (B3), Nigeria, Pakistan, Philippines; Philippines/Vietnam/Singapore/Malaysia; Poland (D4), Romania, United Kingdom, D4(unknown source) Total174398805

31. * It does not include clinical cases reported. ** Five cases have been notified in the island of Saint Martin (1 import and 4 import-related). Data as of EW 52 Number of import/imported related measles cases per country, The Americas - 2012 MEASLES CountryImportImport relatedUnknownSource of Infection Argentina100D4 Italy Brazil109D4 Portugal,Spain Canada300 D4 from India, Uganda, Pakistan B3, Pakistan Colombia100Madrid Ecuador0690B3 United States23244 The outbreaks >1 case 3 cases, Romania; 14 cases, Ethiopia (B3), 6 cases Ethiopia (B3); 4 cases, UK D4) Total299313

32. Reported MMR1 and MMR2 coverage Latin America, US and Canada, 2011 * Haiti coverage for MR vaccine in children<1 year of age Source: Country reports through the PAHO-WHO/UNICEF Joint Reporting Form (JRF), 2012 95%

33. Background of the Ecuadorian measles outbreak In EW 24, 2011, the surveillance system caught in the parish Latacunga Canton Latacunga, Cotopaxi province, a suspected case of 2-year-old, who was later confirmed with genotype D4. No source of infection identified. In EW 28-29 two cases from the parish Atahualpa, Canton Ambato, Tungurahua province were identified (11 months and 2 years old), confirmed with genotype B3. No source of infection identified 327 confirmed measles cases (263 in 2011 and 69 in 2012) have been reported (EW28/2011 to EW37/2012) In EW 24, 2011, the surveillance system caught in the parish Latacunga Canton Latacunga, Cotopaxi province, a suspected case of 2-year-old, who was later confirmed with genotype D4. No source of infection identified. In EW 28-29 two cases from the parish Atahualpa, Canton Ambato, Tungurahua province were identified (11 months and 2 years old), confirmed with genotype B3. No source of infection identified 327 confirmed measles cases (263 in 2011 and 69 in 2012) have been reported (EW28/2011 to EW37/2012)

34. Cotopaxi EW 24: 1 caso EW 41-51 (7 casos) EW 3-26/2012 (4 casos) Cotopaxi EW 24: 1 caso EW 41-51 (7 casos) EW 3-26/2012 (4 casos) 1 W Tungurahua E 28-48 (163 casos) EW 3/2012 (1 caso) W Tungurahua E 28-48 (163 casos) EW 3/2012 (1 caso) 2 Pichincha EW 30-51 (34 casos) EW 3-9/2012 (14 casos) Pichincha EW 30-51 (34 casos) EW 3-9/2012 (14 casos) 3 Guayas EW 40-52 (23 casos) EW 1-3/2012 (14 casos) Guayas EW 40-52 (23 casos) EW 1-3/2012 (14 casos) 4 Chimborazo EW 46-46 (4 casos) Chimborazo EW 46-46 (4 casos) 5 Fuente: PAI, Ministerio de Salud Pública de Ecuador. * Datos a la SE 30/2012 Evolution of the outbreak: Confirmed cases of measles by EW and province, Ecuador 2011-2012 * Pastaza EW 46-52 (25 casos) EW 2-8/2012 (5 casos) Pastaza EW 46-52 (25 casos) EW 2-8/2012 (5 casos) 6 Morona Santiago E W 2-24/2012 (28 casos) Morona Santiago E W 2-24/2012 (28 casos) 7 ManabÍ EW 11/2012 (1 caso) ManabÍ EW 11/2012 (1 caso) 9 Santo Domingo EW 49/2011 (1 caso) EW 12-13/2012 (3 casos) Santo Domingo EW 49/2011 (1 caso) EW 12-13/2012 (3 casos) 8

35. Confirmed cases: age groups and attack rates 2011-2012 AgeYear 2011Year 2012TotalAttack rate 2011* Attack rate 2012* <6 months 31164715.3910 6 a 11 months 431861208.46 1 a 4 years 8314976.740.91 5 a 9 years 342361.570.07 10 a 14 years 442462.40.13 15 a 19 years 77140.630.21 20 a 39 years 1310230.220.11 >40 years 5050.120 Total 26069329 * Per 100,000 populations Source: Ministry of Health, Ecuador

36. Outbreak response  Enhanced surveillance in public and private sector  Active search of suspected cases in institutions and in communities  Investigation of suspected cases (contact tracing and monitoring)  Community interventions (sampling, MRC, active case search, vaccination )  Adaptation of health services (triage, isolation rooms)  National vaccination campaign (6 months to 14 years olds)  RCM  Vaccinations at night and in early mornings in specific areas  Enhanced surveillance in public and private sector  Active search of suspected cases in institutions and in communities  Investigation of suspected cases (contact tracing and monitoring)  Community interventions (sampling, MRC, active case search, vaccination )  Adaptation of health services (triage, isolation rooms)  National vaccination campaign (6 months to 14 years olds)  RCM  Vaccinations at night and in early mornings in specific areas

37. Implemented activities in Haiti COMPONENT  Sero-prevelance survey  National MR: intensified vaccination project; Independent coverage survey  Active case search for measles and rubella in hospitals  Active case search measles and rubella at the community level  Retrospective search of CRS (specialized institutions) STATUS  Serum specimens collected for 2012 antenatal clinic (ANC) sentinel survey for HIV, syphilis  RCM: coverage >95%  Initial results from the survey? M&R: Investigated cases : 113  Confirmed cases by lab :0; Compatible cases : 0 CRS:  Detected CRS suspect cases : 273  Investigated cases : 113  Investigated cases (<1 year old) with blood specimen : 12  Confirmed cases by lab :0  Compatible cases : 0

38. Référence: SIVAC- DEPT Immunization Administrative RR Coverage by Department, 9-11m, 1-4 y and 5-9 y, Haiti 03-08-2012 pourcentage Départements 100 RR (9-11 m ) = 100. % Haiti RR (1-4 a ) = 100 % RR (5-9 a ) = 100 % 100

39. Haiti: Sustainability The intensification activities are planned in a way that build upon what already exists and with the aim of leaving a routine vaccination program strengthened: Political commitment: Visibility of the routine program, and the coordination between national and international partners Micro-planning: Staff trained in micro-planning, planning tools, areas of responsibility, well-defined target population, maps available Training: pool of trained people, training of trainers, training materials.

40. Haiti: Sustainability Information System: Pool of trained data managers, experience in using software, promoting the data organization, flow, analysis and quality Supervision: Supervision plan for the regular program, pool supervisors trained and with experience on on-site training Logistics: Distribution system, new equipment installed, pool of trained technicians, more efficient distribution and better wastage management Epidemiological surveillance: Strengthening the national epidemiological surveillance, pool of field epidemiologists, an expanded network of reporting sites, national laboratories capable of testing for multiple diseases, RMC.

41. Maintain the role of the laboratory in a context of low incidence Occurrence of sporadic positive IgM: False positive or true positive? The correct classification of the case depends on the review of laboratory results and clinical and epidemiological data (last vaccination, contact with international visitors, travel history within 21 or 23 days of rash onset). Probability of false negative IgM results: First blood sample collected <= 3 days of rash onset Strongly suspected measles or rubella: recent travel, exposure and vaccination history. Additional tests may be required: Viral detection (RT-PCR) or viral isolation Second blood sample (IgM, IgG) Avidity Test Differential Diagnosis: (dengue, Parvo B19, HHV-6,...)

42. MVs/Barranquilla.COL/37.11/1 2011725332 MVs/Barranquilla.COL/37.11/2 2011725335 MVs/Barranquilla.COL/38.11 2011725337 MVs/Cotopaxi.ECU/26.11 2012721966 MVs/Barranquilla.COL/35.11 2011725331 MVs/Barranquilla.COL/33.11 2011725279 MVs/Barranquilla.COL/34.11 2011725281 Measles Sequences from Ecuador and Columbia, 2011. Genotype D4 Sequences “Manchester Lineage” from Europe

43. MVs/Ambato.ECU/38.11/2 2011725344 MVs/Pichincha.Ecuador/43.12/1 2012721961 MVs/Ambato.ECU/36.11 2011725341 MVs/Pichincha.Ecuador/43.12/4 2012721960 MVs/Tungurahua.ECU/42.11/2 2012721918 MVs/Ambato.ECU/38.11/1 2011725343 MVs/Ambato.ECU/29.11 2011725283 MVs/Tungurahua.Ecuador/40.11 20212721967 MVs/Guayas.Ecuador/49.12 2012731964 MVs/Pichincha.Ecuador/45.12/1 2012721962 MVs/Pichincha.Ecuador/43.12/2 2012721958 MVs/Guayas.Ecuador/45.12/2 2012721963 MVs/Tungurahua.ECU/39.11/4 2012721908 MVs/Ambato.ECU/30.11 2011725285 MVs/Tungurahua.ECU/42.11/1 2012721916 MVs/Tungurahua.ECU/39.11/2 2012721906 MVs/Tungurahua.Ecuador/40.12/1 201272... MVs/Tungurahua.ECU/39.11/5 2012721909 MVs/Guayas.ECU/45.11 2012721917 MVs/Pichincha.Ecuador/43.12/3 2012721959 MVs/Tungurahua.Ecuador/41.12/2 201272... MVs/Tungurahua.Ecuador/40.12/2 201272... MVs/Tungurahua.ECU/39.11/3 2012721907 MVs/Tungurahua.Ecuador/39.12 2012721951 MVs/Latacunga.ECU/45.11 2012721920 MVs/Tungurahua.Ecuador/43.12 2012721957 MVs/Tungurahua.Ecuador/41.12/3 201272... MVs/Pichincha.ECU/45.11 2012721912 MVs/Tungurahua.ECU/39.11/1 2012721904 MVs/Tungurahua.ECU/45.11 2012721914 MVs/Guayas.Ecuador/45.11 2012721965 5 Measles Sequences from Ecuador and Columbia, 2011. Genotype B3 Sequences