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 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? Last Endemic Measles, Rubella and CRS Cases MEASLES: Venezuela / NOV 16, 2002 > 12 years without endemic MEASLES virus transmission CRS: Brazil/ AGO 26, 2009 > 3 years without RUBELLA endemic virus transmission RUBELLA Argentina/ FEB, 2009 Source: Country reports to PAHO/WHO. 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 Distribution of Confirmed Measles Cases Following the Interruption of Endemic Transmission, the Americas, 2003-2012* Rate: 1.37 X 1,000,000 pop. Confirmed Cases 1400 1.6 N=1374 1200 1.4 1000 1.2 1 800 0.8 600 400 N=226 N=119 N=108 N=253 N=176 N=85 0.6 N=207 N=129 N=89 200 0.4 0.2 0 0 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 Regional rate Brazil Canada Mexico USA Venezuela * Data as of EW 36/2012. Source: Country reports to PAHO/WHO. Others Regional rate 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 caseby-case basis taking the epidemiological information into account – A second blood sample – Additional tests may be required ALGORITHM FOR SPECIMENS : IgM positive and indeterminate results There first serum sample available for further investigation? YESI NO Respiratory or urine sample exist?* Collect second serum sample IgG test IgG test YESI IgG Negative IgG Positive IgG Positiva Second serum sample collected Collect second blood specimen Results IgG, second sample Resultados IgG de sueros pareados (primera y segunda muestra) IgG Negativa Te case discarded Indeterminate results (cannot be confirmed nor discard)) Avidity testing IgG Negative IgG Positive CASE DISCARDE D CONFIRM RECENT CONTACT 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) Low avidity Confirm contacts <3 months RT-PCR /VIRAS isolation High avidity Evidence of contacts> 3 meses Positive Negative Sequencing and genotyping Report as RT-PCR negative Report as RTPCR positive with identified genotype 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. 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. Containment costs for a measles outbreak in Indiana, USA - 2005 Costs item Total number of cases was 34; the majority was among 5-19 years old and 32 lacked evidence of measles vaccination. Cost per patient Unitary cost (USD) 4,932 Wages and salaries 108,592 Overhead 30,431 MMR vaccine and immune globulin 21,692 Mileage 1,610 Other 5,360 TOTAL 167,685 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 Estimated costs of containing measles outbreaks in selected LAC countries Country # of cases Scope of outbreak control activities Cost (USD)* Chile (2009) 1 Limited to 1 municipality 12,400 Peru (2009) 1 1 municipality in Peru and 1 in Ecuador 20,300 Ecuador (2011-2012) 266 Nationwide 8.5 million 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. *Estimated costs include outbreak investigation, follow-up of contacts and vaccination activities Source: Country reports to FCH/IM Ecuador outbreak 50 45 40 35 30 25 20 15 10 5 0 Last confirmed case EW 28/2012 (7/10/2012) First cases were not notified on time Sustained outbreak with low incidence 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 32 33 34 35 36 37 Nº casos All confirmed cases = 329 (EW 24/2011 to EW 37/2012) Semana Epidemiológica Tungurahua Pastaza Pichincha Morona S Guayas Manabi Cotopaxi Sto. Domingo Chimborazo Source: Ministry of Health, Ecuador. Preliminary data by EW 36/2012 Measles attack rate by age group, Ecuador 2012* Attack rate per 100.000 population = 1,78 30 27.7 Tasa de ataque 25 23.8 20 15 10 7.7 5 1.6 2.4 0.9 0.2 0.09 0 <6 meses 6-11 meses 1-4 años 5-9 años 10-14 años 15-19 años Fuente: PAI, Ministerio de Salud Pública de Ecuador * Datos preliminares a la SE 12/2012 20-39 años >40 años Recent measles outbreak suggest over-estimation of routine and SIAs coverage in Ecuador? 100% 100 90% 90 80% 80 70% 70 60% 50% 40% 30% Age groups 16-39 years Both sexes: 98% Year: 2004 60 50 40 30 20% 20 10% 10 % Vaccinated % Vaccinated Cohort Analysis protected MR by year of birth and vaccination strategies. Ecuador 1965-2010 Introduction MMR in the routine program, 1999 0% 0 1965 1968 1971 1974 1977 1980 1983 1986 1989 1992 1995 1998 2001 2004 2007 2010 Routine Program-ASA Año de nacimiento Routine Program MMR Follow-up 1998 (1-4)-ASA-99% Follow-up 2002 (6m-14)-SR-99% Follow up 2008 (1-6) SR-98% Follow up 2011 The results of the susceptible population cohorts calculated at the national level in many cases do not reflect the reality of the coverage in the provinces, due to heterogeneity in coverage Fuente: Reporte de país a Septiembre 2008 Heterogeneity in coverage Ecuador 2011 Administrative coverage 2011: MMR1 = 94% MMR2 = 92% Coverage range <80% 80-94% ≥95% Source: PAHO-WHO/UNICEF Joint Reporting Form, 2012. Characterization of the affected population Affected population Affected areas • 90% of the affected population is indigenous • Groups with high mobility (staff time, customs) • Rural zones • Areas inhabited by indigenous people who have migrated to the city • Street vendors and food vendors in markets • Overcrowding Social conditions • Access to culturally sensitive health services is limited Over crowded inpatient wards Other factors 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. Outbreak response: dengue analysis 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. 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 Fuente: Base de Datos Guayas :MESSS-ISIS 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 Quality of surveillance Reporting rate of suspected case Haiti 2005-2010 2005 2006 2007 2008 2009 2010 # of suspected cases 4 68 24 6 3 19 Population 8621457 8866163 9117815 9376609 9642749 9916443 0.1623 0.7669 0.2635 0.0639 0.0311 0.1916 Rate Source: MSPP Haiti Analysis of cohorts protected against measles and rubella by birth year and vaccination strategy, Haiti 1980-2010 Age group: 1-19 years Men and Women** 94% Coverage Year: 2007-2008 Status of the documentation/verification of measles, rubella and CRS elimination in Haiti Components Status 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, The process of strengthen the Rubella, and CRS Elimination routine immunization is ongoing including funding with involvement of all the partners Immunization RR Coverage (9m-9 y) and (1-4 y) by Department, Haiti 03-08-12 < 80 % 80-94 % 95 a + % Administrative Coverage 9m-9 y Haiti= 100 % RMC Coverage 9m-9 y Haiti= 96.0 % Nord Ouest Nord Ouest Nord Nord Nord Est Nord Est Artibonite Artibonite Centre Centre A. Metropol Grand’Anse A. Metropol Ouest Ouest Nippes Grand’Anse Sud Est Sud Nippes Sud Est Sud Administrative Coverage 1-4 y Haiti= 100 % Ouest Ouest RMC Coverage 1-4 y Haiti= 95.0 % Nord Ouest Nord Ouest Nord Nord Nord Est Artibonite Artibonite Centre Centre A. Metropol Grand’Anse Sud Référence: SIVAC Nippes A. Metropol Ouest Ouest Nord Est Grand’Anse Sud Est Sud Référence: MRC Nippes Ouest Ouest Sud Est 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 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 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. THANK YOU! www.paho.org/immunization How to maintain the regional measles/rubella elimination? – Plan of Action to maintain the Regional elimination of endemic measles and rubella was approved in the 28th Pan American Sanitary Conference Improving access to immunization services Organizing Immunization service delivery Organizing the network of service providers Improved access to IM service delivery Identify the best ways to increase uptake and the vaccination coverage Integrating immunization services with other health services 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 18th 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. NUMBER OF IMPORTED MEASLES CASES BY COUNTRY 2011 Country Import Import related Argentina Brazil 1 9 2 24 Unknown 0 9 Chile 3 3 0 Canada* Colombia 27 1 4 5 772 0 Dominican Rep. 2 Ecuador 1 Guadalupe** 7 French Guiana 2 0 262 6 3 0 0 1 0 Martinique Mexico 0 0 1 0 Panama 2 3 4 0 0 United States 111 89 23 Total 398 805 174 Source of Infection 2 cases: D4 ( exposure to French and/or German tourists); 1 case (travel history to Italy) D4 (unknown source; recent travel to US); D4 (France), D4, source unknown D4 (outbreak < 1 case) recent travel to NY and 1 case with a travel history to Thailand and Malaysia, genotype D9. India (D8) and D4, France (D4), England (D9); D4 and D9 (unknown source) 1 case with travel history to Brazil 1 case with travel history to Italy D4 / 1 case among a French tourist, it was confirmed by epidemical link. No travel history, B3 genotype identified France France France France, Mexico with a travel history to London); Mexico with travel history to NYC and Niagara falls, date of rash-onset. D4 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) * 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 Country Import Import related Unknown Argentina 1 0 0 Brazil 1 0 9 Canada 3 Colombia 1 Ecuador 0 0 0 69 0 0 0 United States 23 24 4 Total 29 93 13 Source of Infection D4 Italy D4 Portugal,Spain D4 from India, Uganda, Pakistan B3, Pakistan Madrid B3 The outbreaks >1 case 3 cases, Romania; 14 cases, Ethiopia (B3), 6 cases Ethiopia (B3); 4 cases , UK D4) * 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 Reported MMR1 and MMR2 coverage Latin America, US and Canada, 2011 100 95% Coverage (%) 80 60 40 20 0 ARG BOL BRA CAN CHI COL COR CUB DOR ECU ELS GTM HAI HND MEX NIC PAN PAR PER URU USA VEN MMR1 * Haiti coverage for MR vaccine in children<1 year of age Source: Country reports through the PAHO-WHO/UNICEF Joint Reporting Form (JRF), 2012 MMR2 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) Evolution of the outbreak: Confirmed cases of measles by EW and province, Ecuador 2011-2012 * 8 Santo Domingo EW 49/2011 (1 caso) EW 12-13/2012 (3 casos) 3 1 9 ManabÍ EW 11/2012 (1 caso) Pichincha EW 30-51 (34 casos) EW 3-9/2012 (14 casos) Cotopaxi EW 24: 1 caso EW 41-51 (7 casos) EW 3-26/2012 (4 casos) W Tungurahua 2 E 28-48 (163 casos) EW 3/2012 (1 caso) 6 5 4 Guayas EW 40-52 (23 casos) EW 1-3/2012 (14 casos) Fuente: PAI, Ministerio de Salud Pública de Ecuador. * Datos a la SE 30/2012 Chimborazo EW 46-46 (4 casos) 7 Morona Santiago E W 2-24/2012 (28 casos) Pastaza EW 46-52 (25 casos) EW 2-8/2012 (5 casos) Confirmed cases: age groups and attack rates 2011-2012 Age Year 2012 Total <6 months 31 16 47 15.39 10 6 a 11 months 43 18 61 20 8.46 1 a 4 years 83 14 97 6.74 0.91 5 a 9 years 34 2 36 1.57 0.07 10 a 14 years 44 2 46 2.4 0.13 15 a 19 years 7 7 14 0.63 0.21 20 a 39 years 13 10 23 0.22 0.11 >40 years 5 0 5 0.12 0 260 69 329 Total * Per 100,000 populations Attack rate 2011* Attack rate 2012* Year 2011 Source: Ministry of Health, Ecuador 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 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 Immunization Administrative RR Coverage by Department, 9-11m, 1-4 y and 5-9 y, Haiti 03-08-2012 100 100 100 100 100.0 100 100 100 100 100 100 100 100 100 100 100 100 100 98.0 100 100 97.0 100 100 96.0 100 100 96.0 90.0 100 100 100 100 100 100 95.0 84.0 80.0 pourcentage 70.0 60.0 50.0 40.0 30.0 20.0 10.0 0.0 Départements Référence: SIVAC- DEPT Haiti RR (9-11 m ) = 100. % RR (1-4 a ) = 100 % RR (5-9 a ) = 100 % 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 . 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. 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, ...) Measles Sequences from Ecuador and Columbia, 2011. Genotype D4 Sequences 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 “Manchester Lineage” from Europe 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