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Competent and Sustainable Global Laboratory Surveillance for Measles and Rubella is Provided by the WHO Global Measles and Rubella Laboratory Network Jim Goodson, Paul Rota, David Featherstone 11th Annual Measles & Rubella Initiative Meeting Washington D.C. September 19, 2012 A global partnership to stop measles & rubella A global partnership to stop measles & rubella Quick Quiz… A global partnership to stop measles & rubella What's causing these fever Measles and rash cases? HHV-6 Rubella A global partnership to stop measles & rubella Countries Conducting Measles Case-Based Surveillance with Laboratory Testing in 2011 Case-based measles surveillance implementation status at national level Yes (181 countries or 94%) No (12 countries or 6%) A global partnership to stop measles & rubella 6 WHO Global Measles and Rubella Laboratory Network (LabNet): 2012 N= 690 labs 10 Sub-National Labs 2012 N= 690 labs 31 Prov. Labs + 331 Prefect. Labs 184/194 countries served by proficient labs National Laboratories Regional Reference Labs Global Specialised Labs Provincial Labs China Sub-National Labs Russia A global partnership to stop measles & rubella LabNet Plays a Critical Role in Measles and Rubella Control Programs •Laboratory confirmation of suspected cases of measles and rubella •Detection of measles/rubella specific IgM in a serum or oral fluid sample taken at first contact with patient •Detection of viral RNA in an appropriately collected clinical sample •Isolation of virus in cell culture •Genetic characterization of circulating strains for molecular epidemiology analysis •Measurement of population immunity A global partnership to stop measles & rubella Structure of the WHO Global Measles and Rubella Laboratory Network (LabNet) •Multiple layers (similar to polio lab network) Global Specialized Labs (CDC-Atlanta, HPA-London, NIID-Japan) Regional Reference Labs (molecular biology, cell culture, sequencing) National Labs and sub national networks (sample collection, EIA, some molecular testing and cell culture) Management and supervision Lab Coordinator at WHO Geneva (annual meeting) GSL Regional Lab Coordinators at WHO Regional Offices Financial support Host country/institute RRL NL WHO, CDC, MR Initiative, Others A global partnership to stop measles & rubella Strengths of the LabNet Structure Standardized testing and reporting structure Excellent quality control at all levels High quality data reported with stringent timeliness requirements Use of lab data linked with epi data to drive public health decisions Local ownership and alignment with national public health priorities National laboratories are nominated by MOH in collaboration with WHO Integrated surveillance for measles and rubella and other VPDs (e,g, Yellow Fever and Japanese Encephalitis) A global partnership to stop measles & rubella Major Activities of the Measles and Rubella LabNet • Serologic testing for detection of measles and rubella IgM • Training and Capacity Building • Standardization • Quality Control • Verification of Elimination • Virologic Surveillance A global partnership to stop measles & rubella Activity: Serologic Testing: IgM test results as reported to WHO HQ by WHO region, 2010 & 2011 Measles375,012 and Rubella tests 2010-11 (N= tests) 70000 60000 Rubella results No. of test results 50000 Rub Pos 40000 Rub Equiv 30000 Measles Rub Neg results Meas Pos Meas Equiv Meas Neg 20000 10000 0 2010 2011 AFR 2010 2011 AMR 2010 2011 EMR 2010 2011 EUR 2010 2011 SEAR 2010 2011 WPR As of May 31, 2012: N= 74,504 tests Activity: Training and Capacity Building • • • Training workshops Multifunctional • Measles, Rubella, YF, JE • Serological, molecular, data analysis Continual process: • Staff attrition • New methods • QA processes • Molecular techniques • Data management • Laboratory management A global partnership to stop measles & rubella Activity: Capacity Building for 2012 Region Focus Planned quarter AFR YF, M&R, Mol IgM/QA 1st -3rd quarters W&C, E&S AMR Molecular 3rd NLs EMR Molecular 2nd Mol Labs EUR IgM 2nd TUR EUR Molecular 3rd Mol Labs WPR Molecular 4th Mol labs WHO Vaccine Preventable Disease Lab Network Participants Activity: Standardization 2012 WER nomenclature articles published – Measles virus: published 2 March 2012 • Genotype D11 was verified • Decisions were made on subgenotypes • 6 genotypes not detected since 2000 • 5 genotypes not detected since 2006 • Protocols were made accessible on WHO genotype database – Mumps virus: published 1 June 2012 • Nomenclature and genotype classification • Reference strains revised • Global distribution of genotypes reported, including map – Rubella virus Nomenclature update • planned for late 2012 - early 2013 A global partnership to stop measles & rubella Activity: Quality Assurance A proficiency testing (PT) panel for serology is sent annually from VIDRL, in Melbourne – 180 laboratories participating with excellent results A PT for molecular techniques is being planned Regular laboratory accreditation processes including site visits A global partnership to stop measles & rubella 15 Meeting the Need for Enhanced Surveillance Oral fluid samples (OF) – AFR • 5 country trial: Zimbabwe, Malawi, Kenya, Benin, CIV – SEAR • India and Sri Lanka good correlation with serum but highlighted need for adequate training of surveillance staff – EUR • France tested >3500 OFs in recent measles outbreak Point of care – Refinements of sample type and field testing is underway WHO Vaccine Preventable Disease Lab Network Activity: Verification of Elimination of Measles and Rubella • Monitoring of surveillance performance indicators • ≥80% of confirmed outbreaks with a sample for virus detection and genotyping • Determining population immunity using serosurveys to validate reported vaccination coverage A global partnership to stop measles & rubella Activity: Virologic Surveillance for Measles and Rubella Molecular epidemiology is a key component of the verification process for measles and rubella elimination A criterion for elimination is the absence of an endemic genotype for one year Genetic data in conjunction with standard epidemiologic information can be used to track transmission patterns and identify sources of infection A global partnership to stop measles & rubella Measles D4 (Enfield strain) distribution Mar 2007–Dec 2011 As of 01 July 2012 Aug 07 Dec 08 (MA) Jun 08 (CA) Jan 09 (CA) Mar 07Dec 11 Apr 07 Jan 08 Feb 08 Oct 08 Nov 07 Feb 08 Apr 08 x3 Jun-Jul 08 Dec 08 Aug 08 Mar-May 08 Aug 08 XX 08 (JAM) Dec 08 (IL) May 2010 Acknowledgements: WHO Measles LabNet esp HPA, Lux, RKI & CDC Measles Surveillance Programmes The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. WHO 2008. All rights reserved LabNet Genetic Sequence Data as of July 2012 Viruses submitted dating from 1954 to 2012 WHO Databases (started 2006) No. of viruses Genotypes Countries and Territories Proportion with GenBank entries Measles 13,312 All 24 135 32% Rubella 1,302 All 9 + 4 prov. 49 22% MeaNS database (HPA/WHO, started 2008) N – 450bp – 9632 sequences N – full – 3 sequences H – full – 592 sequences A global partnership to stop measles & rubella 13192_MVs/Sgor.MYS/21.11/_15 95.8% 13190_MVs/Kuala_Lumpur.MYS/21.11/_14 14162_MVs/Klumpur.MYS/21.11/_13 2562_MVs/New_York.USA/1.05/_14 1529_MVs/VEN/02/_13 2547_MVi/Santander.COL/31.02/_13 87.4% 8811_MVs/PHL/0.08/7/D9_13 30_MVs/Bristol.GBR/15.05/_13 0% G3 200 B2 D6 150 D5 D9 100 D8 H1 50 2857_MVs/Halifax.GBR/33.04/_16 2022_MVi/Yamagata.JPN/3.04/_15 2023_MVi/Yamagata.JPN/5.04/_15 2024_MVs/Yamagata.JPN/7.04/_15 2025_MVs/Yamagata.JPN/7.04/2_15 2026_MVs/Yamagata.JPN/7.04/3_15 10271_MVs/Saitama.JPN/5.11/_15 18754_MVs/Tokyo.JPN/03.11/2_15 18799_MVs/Tokyo.JPN/05.11/_15 11192_MVs/Arizona.USA/06.11/_15 9614_MVs/Ontario.CAN/49.10/D9_17 76.6% 9705_MVs/Ontario.CAN/52.10/D9_17 9741_MVs/Ontario.CAN/01.11/D9_17 9897_MVs/Aichi.JPN/46.10/_16 9916_MVs/Christchurch.NZL/6.11/3_18 82% 9983_MVs/Christchurch.NZL/8.11/D9_18 10127_MVs/Ontario.CAN/7.11/1_18 18609_MVs/Newsouthwales.AUS/9.11/_17 18611_MVs/Newsouthwales.AUS/10.11/_17 18612_MVs/Newsouthwales.AUS/11.11/_17 18613_MVs/Newsouthwales.AUS/11.11/2_17 18614_MVs/Newsouthwales.AUS/11.11/3_17 18615_MVs/Newsouthwales.AUS/12.11/2_17 18616_MVs/Newsouthwales.AUS/12.11/3_17 18617_MVs/Newsouthwales.AUS/12.11/_17 2012 2010 2008 2006 2004 2002 78.9% 2000 0 1998 93.1% 250 1996 53.7% 2621_MVs/London.GBR/22.08/9_18 3033_MVs/Reading.GBR/24.08/_18 1994 91.8% 3364_MVs/Alkmaar.NLD/09.09/_341 3251_MVs/Nis.SRB/45.08/_15 85.8% 3548_MVi/Lopburi.THA/8.08/_15 3549_MVi/Lopburi.THA/8.08/7_15 3551_MVi/Khonkaen.THA/9.08/4_15 3826_MVs/London.GBR/1.09/_16 3860_MVs/London.GBR/4.09/_16 0%3918_MVs/Ipswich.GBR/12.09/_16 3980_MVi/Yamagata.JPN/12.09/_15 4032_MVi/Moscow.RUS/12.09/3_15 4035_MVi/Moscow.RUS/11.09/3_15 4036_MVi/Moscow.RUS/11.09/4_15 4037_MVi/Moscow.RUS/11.09/5_15 4038_MVi/Moscow.RUS/10.09/_15 4041_MVs/Moscow.RUS/41.08/_15 4044_MVs/Irkutsk.RUS/12.09/_15 4045_MVs/Irkutsk.RUS/13.09/_15 4046_MVi/Krasnoyarsk.RUS/13.09/_15 4047_MVs/Krasnoyarsk.RUS/15.09/_15 4048_MVs/Krasnoyarsk.RUS/17.09/_15 15052_MVs/Bremerhaven.DEU/35.08/_16 15059_MVs/Muenchen.DEU/13.09/_16 19806_MVs/London.GBR/11.12/2_16 20230_MVs/Medway.GBR/14.12/_16 20692_MVs/Medway.GBR/14.12/2_16 20923_MVs/Watford.GBR/15.12/_16 20926_MVs/Medway.GBR/14.12/3_16 20934_MVs/Medway.GBR/15.12/_16 21889_MVs/Samut-Prakan.THA/8.11/_16 22268_MVi/Yunnan.CHN/2.12/_15 MVi/Yangon.MMR/1.12/1D9 MVi/Yangon.MMR/8.12/1D9 MVi/Yangon.MMR/8.12/2D9 MVi/Yangon.MMR/11.12/2D9 2572_MVi/Sarawak.MYS/2.05/_13 2573_MVs/Victoria.AUS/14.04/_13 4707_MVs/Manila.PHL/19.07/2_13 13411_MVs/California.USA/17.10/_13 0%22275_MVi/California.USA/20.10/_14 1992 88.3% 3822_MVs/Colchester.GBR/4.09/_16 3830_MVs/Colchester.GBR/3.09/_16 3855_MVs/Colchester.GBR/10.09/_16 3896_MVs/Cambridge.GBR/7.09/_16 4305_MVs/Newcastle_upon_Tyne.GBR/22.09/_16 3373_MVs/Granada.ESP/25.08/_15 3552_MVi/Phare.THA/27.08/_14 3558_MVs/Maastricht.NLD/22.08/_14 84.3% 5067_MVs/Villeneuve.FRA/28.08/_14 6168_MVs/Villeneuve-stGeorges.FRA/26.08/_14 6171_MVs/Nice.FRA/18.08/_14 6173_MVi/Nice.FRA/20.08/_14 6174_MVi/Nice.FRA/20.08/2_14 90% 3550_MVi/Khonkaen.THA/9.08/2_15 12324_MVs/Hiroshima.JPN/14.11/_16 0% MVi/Yangon.MMR/7.12/1D9 12464_MVs/Osaka.JPN/14.11/_16 51.1% 65.2% 1990 .11/3_12 MeaNS: Global Measles Sequence Database Allows Real Time Reporting and Analysis of Sequence Data MeaNS: Circulating genotypes A 1980 1981 1982 1983 1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 B1 B2 B3 C1 C2 D1 D2 D3 D4 D5 D6 D7 D8 D9 D10 D11 E F G1 G2 G3 H1 H2 0 0 0 0 1 0 0 0 0 0 0 0 2 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 1 0 1 0 0 0 0 0 0 0 0 0 0 0 0 2 0 0 0 0 0 0 7 0 3 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 3 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 1 0 0 0 0 2 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 1 0 0 0 0 1 0 0 0 0 0 0 1 0 0 0 0 0 0 2 1 0 0 0 2 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 1 2 3 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 3 0 0 2 1 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 5 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 4 0 0 2 0 0 0 0 0 0 0 0 0 0 0 0 0 5 0 1 0 0 4 0 2 0 0 0 0 2 0 0 0 0 0 0 0 0 0 0 0 9 0 0 0 0 2 0 2 0 0 2 3 4 2 0 2 0 0 0 0 1 0 0 0 10 2 1 0 0 0 0 0 0 0 0 9 0 0 0 0 0 0 0 0 0 0 0 0 3 0 2 0 0 0 0 11 0 0 0 0 1 4 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 22 0 3 0 0 11 6 8 23 0 2 0 0 0 0 0 0 6 0 4 1 0 0 0 49 0 6 0 0 11 8 9 10 0 2 0 0 0 0 0 0 1 0 2 2 1 0 0 8 0 5 0 0 13 9 1 3 1 7 3 0 0 0 0 0 1 3 15 0 0 0 4 28 0 3 0 1 5 6 21 7 5 0 0 14 0 0 0 0 5 0 37 1 1 0 0 84 0 0 0 10 9 6 80 40 13 2 0 13 1 0 0 0 4 0 76 1 2 0 0 22 0 1 0 4 7 38 41 2 12 5 2 1 0 0 0 0 0 2 69 1 4 0 0 37 0 11 0 4 7 53 6 11 62 115 1 34 0 0 0 0 0 0 80 6 10 0 1 27 0 14 0 0 3 105 16 14 3 16 7 0 1 0 0 0 1 2 57 0 3 0 27 36 0 0 0 1 0 46 12 20 0 56 4 2 0 0 0 0 0 0 139 0 6 0 21 364 0 0 0 0 0 149 34 108 0 58 2 0 0 0 0 0 0 3 195 0 3 0 0 9 0 1 0 0 0 550 132 18 1 59 1 0 0 0 0 0 0 4 175 0 5 0 1 9 0 0 0 0 0 422 113 0 0 72 21 0 0 0 0 0 0 0 157 0 1 0 10 79 0 0 0 0 0 294 13 0 0 39 23 0 5 0 0 0 0 0 32 0 3 0 52 335 0 0 0 0 3 533 0 0 0 75 39 0 0 0 0 0 0 24 56 0 7 0 7 224 0 0 0 0 0 1777 0 0 0 220 171 0 0 0 0 0 0 51 5 0 1 0 0 258 0 0 0 0 0 0 0 0 74 49 0 0 0 0 0 0 0 0 0 284 1 - 10 10 - 100 > 100 Distributionof ofmeasles measles genotypes, 2012. Data as of 2012 Distribution genotypes, 2011. Data as19 ofJune 1919 June 2012 Distribution of measles genotypes, 2011. Data as of June 2012 Viruses =2946 Genotypes = 8 Countries = 74 West Africa inset West Europe Genotypes: Incidence: (per 100'000) B2 <0.1 B3 ≥0.1 - <1 D4 ≥1 - <5 D8 ≥5 D9 No data reported D11 G3 H1 Chart proportional to number of genotypes 5 1 0 2'500 5'000 Kilometers A global partnership to stop measles & rubella Acknowledgement: WHO Measles LabNet. The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. ©WHO 2011. All rights reserved. Distribution of reported rubella genotypes, 2011. Data as of 3 August 2012 West Europe 2011 120 countries reporting laboratory confirmed rubella 12 countries reporting genotype information Legend 1a 1E Pie slice size proportional to the number of years each genotype was reported 2005-2011. 1j 5 1 2B 0 2'500 5'000 Kilometers A global partnership to stop measles & rubella Acknowledgement: WHO LabNet. The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. ©WHO 2011. All rights reserved. Measles and Rubella LabNet Challenges (1) Financial support to maintain laboratory activities Financial support to expand case based surveillance for measles and rubella (especially GAVI countries) Staff turnover (RLCs, GLC) and training needs Need to maintain and expand sequence databases Better use of date by linking epi and lab data in Africa Expansion in India Introduction of new methods (Molecular) Maintain and expand QC/QA Program Integration with surveillance for other VPDs Development of testing strategies for low incidence settings A global partnership to stop measles & rubella 26 Measles and Rubella LabNet Challenges (2) Molecular surveillance plays a vital role in monitoring progress with rubella control and in verification of elimination Large gaps in surveillance for rubella virus Baseline data should be collected well before acceleration of activities for control Global rubella sequence database (RubeNS) under development Enhance laboratory capacity in GAVI eligible countries A global partnership to stop measles & rubella Global Measles and Rubella LabNet Estimated Costs 2011 $1,600,000 $1,400,000 Estimated shortfall shortfall Estimated $1,300,000 $1,300,000 $1,200,000 Shortfall Funds Identified 2011 Shortfall met $1,000,000 $800,000 $600,000 $400,000 $200,000 $0 Lab Support Meetings Consumables Kits WHO Vaccine Preventable Disease Lab Network Training Travel Equipment Global Measles and Rubella LabNet Projected Budget, 2012 Total : $4,376,000 Shortfall : $900,000 Summary Strong capacity: >200,000 IgM tests, 3,000 measles sequences and 330 rubella sequences annually Proficiency high -- closely monitored and maintained Molecular surveillance is becoming increasingly important for monitoring progress of elimination and verification Still gaps in molecular surveillance, especially for rubella Financial support for the LabNet is tenuous Search for new coordinator is ongoing A global partnership to stop measles & rubella Summary 10th Annual Measles and Rubella LabNet Meeting: 2012 30 Anne Ray Charitable Trust A global partnership to stop measles & rubella 31