1. 8 th Global Measles and Rubella LabNet Meeting, Sept 2010 Key Recommendations GLOBAL MEASLES AND RUBELLA MANAGEMENT MEETING 15-17 March 2011 Salle B, WHO Headquarters, Geneva, Switzerland David Featherstone EPI / IVB WHO Geneva

2. Outline What are the challenges for the LabNet? –Implications for achieving Elimination Quality Indicators –Reporting data –Quality Assurance –New Laboratory Procedures –Funding –Summary WHO Vaccine Preventable Disease Lab Network 2

3. 3 33 3 Global LabNet Meeting Participants

4. Implications for LabNet in achieving Elimination Indicators (WER No 49, 2010, 85, 490-495) ELISA IgM testing: – ≥ 2/100,000 (non-measles rash/fever cases) per year & ≥ 80% serum samples collected Workload increase estimated extra ~50,000 cases / yr Workload increase estimated extra ~50,000 cases / yr Mainly Pakistan and India moving to case based surveillance Mainly Pakistan and India moving to case based surveillance India planning 3 new labs 2011 (~$100,000) India planning 3 new labs 2011 (~$100,000) LabNet has proven surge capacity LabNet has proven surge capacity –Measles IgM cost ~ $ 3 -11 per sample (depending on batch size) –Rubella IgM cost ~ $ 4.50 -17 per sample WHO Vaccine Preventable Disease Lab Network 4

5. Implications for LabNet in achieving Elimination Indicators (WER No 49, 2010, 85, 490-495) Virus detection: –Measles elimination: The absence of endemic measles cases: –Re-establishment of endemicity: continuous transmission of indigenous measles virus for a period of > 12 months: –>80% of laboratory-confirmed measles outbreaks have adequate samples for virus characterization in an accredited lab WHO Vaccine Preventable Disease Lab Network 5

6. Current challenges for improving molecular surveillance African region: –Building molecular capacity in Uganda and CIV Molecular surveillance gaps: –Sequencing capacity available but limited sample collection for virus detection –Enhanced molecular surveillance using Oral fluid Trials in India, Benin, CIV, Kenya, Malawi and Zimbabwe Trials in India, Benin, CIV, Kenya, Malawi and Zimbabwe WHO Vaccine Preventable Disease Lab Network 6

7. Molecular surveillance recommendations Reference and sequencing laboratories –determine their capacity to reach surveillance indicators –determine the additional resources needed Laboratory and field surveillance programmes –collaborate to enhance molecular surveillance Greater molecular capacity needed with documented accuracy –training programmes –molecular proficiency programme established

8. Data Reporting

9. WHO Vaccine Preventable Diseases Lab Network 9 Member states reporting (expected) Specimens received Measles 2010 Rubella 2010 WHO regionTestedPositiveTestedPositive AFR31(46)18,151 6,75712,6051,963 AMR30(35)11,5825,347225,678134 EMR21(21)12,24211,6153,8739,7601,042 EUR46(53)27,11022,3254,99421,590936 SEAR11(11)5,2844,9681,6973,5241,547 WPR12(27)16,89715,6584,14113,6173,606 Total153(193)91,26678,06421,48466,7749,228 * As of Jan 2011 Data Issues: Measles and Rubella Laboratory Tested Cases Reported to WHO HQ 2010* Data source: surveillance DEF file Data in HQ as of 8 Jan 2011

10. WHO Vaccine Preventable Diseases Lab Network 10 Member states reporting (expected) Specimens received Measles 2010 Rubella 2010 WHO regionTestedPositiveTestedPositive AFR31(46)18,151 6,75712,6051,963 AMR30(35)11,5825,347225,678134 EMR21(21)12,24211,6153,8739,7601,042 EUR46(53)27,11022,3254,99421,590936 SEAR11(11)5,2844,9681,6973,5241,547 WPR12(27)16,89715,6584,14113,6173,606 Total153(193)91,26678,06421,48466,7749,228 * As of Jan 2011 Data Issues: Measles and Rubella Laboratory Tested Cases Reported to WHO HQ 2010* Data source: surveillance DEF file Data in HQ as of 8 Jan 2011 South Africa outbreak 18,359 laboratory confirmed 2010 ~ 50,000 / year (2008)China not reporting 22,037 from Country reports

11. Data reporting: Recommendations LabNet encouraged to work with their national surveillance programmes to reconcile laboratory and field surveillance data Data sent to WHO according to agreed upon reporting requirements

12. Sequencing data reporting

13. WHO Vaccine Preventable Disease Lab Network WHO Global genotype databases: Current Status Viruses submitted dating from 1954 to 2011 WHO Database No. of viruses GenotypesCountries and Territories WHO Regions Proportion with GenBank entries Measles891223 + 1 prov. 131637% Rubella7739 + 4 prov. 44636% Data as of 28 Feb 2011 13 N – 450bp – 5542 sequences N – full – 5 sequences H – full – 503 sequences MeaNS database (HPA/WHO)

14. Measles Genotype data submitted to WHO Database WHO Vaccine Preventable Disease Lab Network 6 4 17 3 24 8 4 2 22 12 2 9 10 3 20 10 9 3 11 3 13 9 2 19 9 4 21 10 17 3 Number of countries submitting virus data per region Year of onset 26 31 30 39 58 55 57 64 10 Total number of countries submitting virus data per year Number of viruses submitted 14

15. 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. 2010 incidence

16. China: Measles isolates and genotyping results, 2009 D4 (1 case) D9 (1 case) d11 (17 cases) Yunnan 2009: 270 cases H1a measles virus reported to database Unpublished data provided by Xu Wenbo

17. 17 Recognition of new genotypes d11 MVi/Menglian.Yunnan.CHN/47.09/1. Virus to be provided by China CDC. Genotype B3 sequences from Libya, Tunisia and Sudan should be considered as a third cluster in genotype B3. Virus to be provided by Institut Pasteur de Tunis. Reference viruses for Rubella genotypes 1h, 1i, and 1j have been identified. These viruses to deposited in the WHO rubella virus strain banks The recent changes in the list of recognized rubella and measles genotypes should be published in the WER A steering committee to be formed to review and refine the protocols for accepting and distributing sequence information via MeaNS and the WHO Database WHO should develop a mechanism for rapidly notifying LabNet of important developments such as detection of a new lineage or genotype WHO Vaccine Preventable Disease Lab Network 17

18. Higher resolution sequencing

19. D6 strains in Germany and Belarus 1 month 6 months N geneNPH gene UKR BEL Data Provided by Luxemburg Laboratory Recommendation: Select laboratories to evaluate and identify when appropriate to implement

20. 20 Quality Assurance

21. LabNet Proficiency test performance- Measles IgM Panels Panel No. ≥ 90% correct (Pass) 00801 n=46 (2001) 96% 00702 n=17 (2002) 88% 01002 n=66 (2003) 95% 00703 n=99 (2004) 90% 00704 n=115 (2005) 94% 00508 n=142 (2006) 98% 00607 n=164 (2007) 98% 00705 n=173 (2008) 99% 00805 n= 171 (2009) 98% 00905 n= 220 (2010) 99%

22. Quality Assurance Recommendations More comprehensive analysis of IgM proficiency testing and reporting Introduction of proficiency test for molecular techniques More comprehensive training & post training assessments WHO Vaccine Preventable Disease Lab Network 22

23. New Procedures

24. 24 Point of care rapid measles assay The measles rapid point of care (POC) shows promising sensitivity and specificity compared with detection of IgM in serum WHO Vaccine Preventable Disease Lab Network 24 POC to be further validated using oral fluid samples collected under routine field conditions

25. Documentation of new procedures WHO Vaccine Preventable Disease Lab Network Alternative samples to serum for measles and rubella New sequencing primers for measles and rubella Real time PCR; M & R Validated and in process of implementation In process of validation Rapid Point of care assays M & R PCR QC programme Standards for measles serosurvey 25 QC for Oral fluid

26. Funding

27. Current LabNet Estimated Costs WHO Vaccine Preventable Disease Lab Network 27 Estimated shortfall $1,300,000

28. Funding recommendations LabNet should endeavour to find additional resources and new partners Countries encouraged to include laboratory support in their surveillance budgets Additional funds for training, to: –Maintain the current high level of LabNet performance –Strengthen sequencing capacity

29. Summary LabNet has capability to meet increased surveillance needs –Some capacity will need to be developed Capacity building and extra testing comes at a cost, not all of which is realised

30. Thank you to all our LabNet Supporters WHO Vaccine Preventable Disease Lab Network CDC WHO Korean CDC National MsOH IFFIM Luxemburg Gov't Merck Measles Initiative HPA Labs belonging to LabNet 30 Programmes sharing resources Polio JE YF