Updates from the Regional Measles and Rubella Laboratory Network.

1. Updates from the Regional Measles and Rubella Laboratory Network. Accelerating Progress towards Measles and rubella Elimination Gloria Rey-Benito PAHO, Regional Advisor FGL/IM Geneva, Switzerland. 21-24 June 2016

2. Outline • Status of Regional measles and rubella elimination • Measles and rubella regional lab network: virological surveillance, lab performance, strengthen technical capacities • Main activities from Canada and USA labs • Summary and Recommendations

3. Impact of Measles and Rubella Elimination Strategies in the Americas Impact of measles and rubella elimination strategies: The Americas, 1980-2016* Catch up campaign for measles Speed-up campaigns for Rubella Follow-up campaigns for measles % Vaccination Coverage Last endemic measles case Confirmed cases Last endemic rubella case The Comprehensive Family Immunization Unit (FGL/IM) – Pan American Health Organization, data as of June 8, 2015 Source: Country reports to FGL/IM - PAHO * Data as of 17 June 2016

4. Bye-bye, rubella! ¡Adiós rubéola! Media coverage on rubella elimination | April 29-30, 2015 Cobertura de prensa sobre la eliminación de la rubéola | 29-30 de abril de 2015

5. Measles-Rubella Surveillance Indicators, The Americas, 2011-2016* Source: ISIS, MESS systems and country reports *Data as of epidemiological week 23, 2016.

6. Rate of suspected measles and rubella casesThe Americas, 2003 -2015 Rate per 100,000 population Source: ISIS, MESSS and country reports to FGL-IM/PAHO.

7. Confirmed measles cases by second administrative level The Americas, 2014 and 2015 2015 N=611 cases 2014 N=1,966 cases Brazil= 876 Canada= 418 Mexico= 3 United States= 667 Others = 2 Total (2014)= 1966 Brazil= 214 Canada= 196 Colombia=1 Chile=9 Mexico= 1 United States= 186 Peru=4 Total (2015)= 611 Source: Country reports to FGL-IM/PAHO. *Data as of epidemiological week 23, 2016

8. First Outbreak in Post Elimination Era with More Than 12 Months of Transmission Confirmed Measles Cases by Epidemiological Week, Selected States Brazil, 2013-2015 Number of Cases 2014 2013 2015 The Comprehensive Family Immunization Unit (FGL/IM) – Pan American Health Organization, as of June 8, 2015epidemiological week 21, 2015 by second administrative level

9. Distribution of confirmed measles cases by ageThe Americas, 2015 N=568 confirmed cases Source: Country reports to FGL/IM

10. Virologic surveillance and molecular epi

11. 2 Regional Reference Lab Measles and Rubella laboratory network Region of the Americas, 1995 – 2016 Global Specialized Lab (CDC) 141 Sub-natlLab Argentina (21), Brasil (27), Canada (26), Colombia (11), México (31), Venezuela (25) 21 National Labs 1 Global Specialized Lab Regional MR Labnet= 165 Labs

12. Distribution of imported rubella cases after interruption of endemic transmission The Americas, 2010-2016* A total of 65 rubella and 8 CRS* imported cases were reported. Number of rubella cases Fuente: ISIS, MESS e informe de los países a FGL-IM/OPS. *Datos de semana epidemiológica 23, 2016.

13. Rubellagenotypes in theAmericas, 2012 - 2015 Canada 2013: 2B 2014: 1J, 2015: 2B 1J, 2B USA 2013: 1E, 2B 2014: 2B 2015: 1J, 2B 1E, 1J, 2B • Mexico • 2012: 2B 2B 2B • Colombia • 2012:2B 2B • Argentina • 2014: 2B *Datos hasta la SE 2/2016 Fuente: Reporte de países a OPS/OMS

14. Distribution of confirmed measles cases following the interruption of endemic transmission. The Americas, 2003-2016* N=1,966 Rate= 1.9 x 1,000,000 population N=1,369 Number of confirmed Cases Rate per 1,000,000 population N=473 N=611 N=143 N=27 Source: ISIS, MESSS and country reports to FGL-IM/PAHO. *Data as of epidemiological week 23, 2016.

15. Measlesoutbreakwithgenotypeidentification. LAC, 2010-2015 (a) Mismo brote B3 (b) Mismo brote, D8 NA – No disponible

16. Confirmed measles cases by second administrative level The Americas, 2014, 2015, and 2016* 2015 N=611 cases 2014 N=1,966 cases Brazil= 876 Canada= 418 Mexico= 3 United States= 667 Others = 2 Total (2014)= 1966 Brazil= 214 Canada= 196 Colombia= 1 Chile= 9 Mexico= 1 United States= 186 Peru= 4 Total (2015)= 611 2016* N=27 cases Canada= 7 Ecuador= 1 United States= 19 Total (2016)= 27 Source: Country reports to FGL-IM/PAHO. *Data as of epidemiological week 23, 2016

17. Distribution of measles genotypes in the Americas, 2014-2016* CAN = 108 USA = 176 CAN = 80 CAN = 7 USA = 156 USA = 12 BRA = 77 2014 COL = 1 ECU = 1 2016* BRA= 27 Color code: 2015 B3 D3 D4 D6 D8 D9 H1 CHI = 1 Source: MeaNS, N and H gene sequences. *Data as of 17Jun2016.

18. Laboratory Performance

19. Results EQA for Measles-IgM Region of the Americas, 2013-2015 2013 2015 2014 2015 = new scoring system 19 of 24 with results >= 93.2 Source: Country reports to FGL-IM/PAHO * Data as of epidemiological week 52, 2015

20. Results EQA for Rubella-IgM Region of the Americas, 2013-2015 2013 2015 2014 2015 = new scoring system 19 of 24 with results >= 91.7

21. Results molecular PT for Measles and Rubella Region of the Americas, 2015 Canada USA Mexico Colombia Peru Brazil Chile Argentina Source: CDC reports.

22. Accreditation of Measles and Rubella Laboratories Region of the Americas, 2015 Main findings Timely report EQAP participation QC On-site visits 2015 CAN, DOR y HND

23. Support the development of technical capacities

24. Support at national level with kits for serology and supplies for molecular assays. Regional MR Laboratory Network of the Americas, 2015. 17 of 21 National labs supported with Measles and Rubella IgM and IgG kits Supplies for 8 National Laboratories: micropipettes set, tips, RNA extraction and enzymes kits

25. Meeting of the Regional Measles and Rubella Laboratory Network of the Region of the Americas, Quito – Ecuador, February 2016. The Regional LabNetisdoingwell and supportingtheelimination of rubella and theverification of theelimination of measles. There are however, someissuesthatshould be improved in order to provide a better and timelierresponse in thecontext of a lowincidence of diseaseand new events of significantimpact in publichealth.

26. Main activities from Canada and USA laboratories

27. Measles Activity in Canada, June 2015 – June 2016 1Preliminary data2≥2 cases 3 1 case unknown source Courtesy Joanne Hiebert, NML - Canada

28. MVi/Harare.ZWE/38.09 JF973033.1 MVs/Alberta.CAN/10.16 (ex:PAK) MVs/Ontario.CAN/9.16 (ex:PAK) MVs/Ontario.CAN/1.16 ex:PAK MVs/British Columbia.CAN/9.16 (ex:PAK) MVs/Quebec.CAN/42.15 (ex:TUN) B3 MVi/Ibadan.NGA/0.97/1 AJ232203 B3 MVi/New York.USA/0.94 L46753 D8 MVi/Manchester.GBR/30.94 AF280803 MVs/Ontario.CAN/19.16 MVs/Ontario.CAN/11.16 (ex:IND) MVi/Hulu Langat.MYS/26.11 JX486001.1 MVs/British Columbia.CAN/3.16 (ex:WPR) 5 Measles Activity in Canada, June 2015 – June 2016 N-450 Genotypes: B3 (n=5) D8 (n=3)

29. Rapid measles vaccine RT-PCR screening (MeVA) • During measles outbreaks, we frequently get requests for STAT genotyping for cases recently vaccinated to rule out wild type and direct the response • Genotyping can take several days • NML developed a rapid, real-time RT-PCR (MeVA) to quickly identify measles genotype A (vaccine) • In the last 12 months MeVA RT-PCR was used to rapidly screen 17 cases: • 15 were identified as post-vaccine cases • Method will be described by Alberto Severini in Laboratory Session 4

30. CRS case report • Baby born in December of 2015 with respiratory distress, congenital cataracts & microphthalmia • Rubella RT-PCR on NPS & urine @ 2.5 weeks of age NEGATIVE • Mother an immigrant with no documented travel or known exposures • Rubella seropositive on prenatal screen • Rubella RT-PCR POSITIVE (genotype 2B) on lens fluid & eye swab @ 5 weeks of age (late January 2016) • Retrospective rubella serology on blood collected ~1 week of age: (Feb 2016) • IgM positive; IgG positive; low avidity IgG • Follow up investigation: mother travelled to India very early in pregnancy • Follow up NPS & Urine collected until 4 months of age (3 sets) • Inconclusive NPS at 2 months of age • 2 subsequent sets: Negative

31. Measles USA 2015 (Provisional) • 189 cases of measles were reported by 24 states and DC: AK (1), AZ (7), CA (108), CO (1), DE (1), DC (2), FL (5), GA (1), IL (17), MA (1), MI (1), MN (2), MO (1), NE (2), NV (9), NJ (3), NYS (1), NYC (7), OH (1), OK (1), PA (1), SD (2), TX (1), UT (2), VA (1) & WA (10). • 178 (94%) of the cases were import-associated which includes: 25 imports, 5 import-linked, 66 IV cases (Imported Virus), and 82 linked to IV case(s) or IV chains. • Travel countries for the 25 imported cases were: Afghanistan (1) Azerbaijan (1), China (5), United Arab Emirates/India (1), France (2), Belgium/France (1), Germany (2), India (4), Indonesia (1), Kyrgyzstan (1), Pakistan (1), Qatar (1), Singapore/Indonesia (1), Mongolia (2), Republic of Djibouti (1). • Of the 24 imported cases where country of residence was known; 14 were US residents and 10 were foreign visitors • 189 cases reported, 30 (16%) were vaccinated and 159 (84%) were unvaccinated or vaccination status was unknown. Courtesy Paul Rota, CDC - Atlanta

32. Measles Outbreaks (defined as 3 or more linked cases) were reported during 2015

33. MVs/Minnesota.USA/19.15/ (CDC RC-2015-162) MVs/Nevada.USA/7.15/ (CDC RC-2015-67) + 3 identical strains MVs/Arizona.USA/5.15/ (CDC RC-2015-59) MVs/Illinois.USA/7.15/5 (3000375772) + 103 identical strains MVs/Hawaii.USA/1.15 (3000373195-96) + 2 identical strains MVs/California.USA/5.15/10 (3000373477) MVi/Ibadan.NGE/0.97/1 (B3) MVi/New York.USA/0.94 (B3) MVi/Yaounde.CMR/12.83 (B1) MVi/Libreville.GAB/0.84 (B2) MVi/Goettingen.DEU/0.71 (E) MVi/Maryland.USA/0.54 (A) Phylogenetic tree based on the N-450 gene sequences of measles viruses detected in the US in 2015. MVs/Madrid.ESP/0.94 (F)(SSPE) MVi/Tokyo.JPN/0.84 (C1) MVi/Maryland.USA/0.77 (C2) MVi/Erlangen.DEU0.90 (C2) MVi/Amsterdam.NLD/49.97 (G2) MVi/Gresid.IDN/17.02 (G3) MVi/Berkeley.USA/0.83 (G1) MVi/Beijing.CHN/0.94/1 (H2) MVi/Hunan.CHN/0.93/7 (H1) MVs/California.USA/15.15/2 (CDC RC-2015-140) MVs/Washington.USA/17.15/ (CDC RC-2015-153) +1 identical strain MVs/California.USA/15.15/ (CDC RC-2015-139) MVs/Oklahoma.USA/11.15 (3000375494) +1 identical strain MVs/New Jersey.USA/20.15/ (3000403856) +3 identical strains MVi/Bristol.GBR/0.74 (D1) MVi/New Jersey.USA/0.94/1 (D6) MVi/Johannesburg.ZAF/0.88/1 (D2) MVi/Kampala.UGA/51.01/1 (D10) MVs/NewYork.USA/2.15/ (CDC RC-2015-81) +1 identical strain MVs/California.USA/8.15/3 (CDC RC-2015-101) MVi/Montreal.CAN0.89 (D4) MVi/Victoria.AUS/12.99 (D9) MVi/Bangkok.THA/0.93/1 (D5) MVi/Palau.PLW/0.93 (D5) MVi/Illinois.USA/0.89/1 (D3) MVi/Victoria.AUS/16.85 (D7) MVi/Illinois.USA/50.99 (D7) MVi/Menglian.Yunnan.CHN/47.09 (D11) MVi/Manchester.GBR/30.94 (D8) MVs/California.USA/6.15/ (CDC RC-2015-71) MVs/Georgia.USA/5.15 (3000374882) MVs/Florida.USA/12.15 (3000358809) + 1 identical strain MVs/Arizona.USA/2.15 (3000375779) +4 identical strains 5 B3 H1 D8 D4

34. Named lineages of Measles in the USA: 2015

35. Summary • Regional laboratorynetworkisdoingwell and supportingtheelimination of rubellaand theverification of theelimination of measles. • The Molecular epidemiologic data has documented the lack of measles endemic genotype in the Americas between 2003 and 2013 and rubella endemic genotype between 2010 – 2015. • Several importations of measles and some of rubella virus still as the main risk to maintain the elimination. • In April 2015, the Region of the Americas was certified as free of rubella and Brazil was able to stop ongoing endemic measles transmission in July 2015.

36. Recommendations • MR laboratories of the Region should maintain the good performance and reach the surveillance indicators in order to support the verification of measles elimination and maintain rubella elimination. • Improve the capacity and capability to perform molecular assays: RNA detection and genotyping (training, reagents, supplies) • Laboratories of the network are requested to ensure timely reporting of sequence data to the WHO sequence databases • Improve a real time communication between Epi and Lab staff • Maintain the commitment of Member States with the elimination in a context of new diseases of public health concern

37. Thanks! RRLs NLs Partners reyglori@paho.org