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 June 2016

Outline 1.Status of Regional measles and rubella elimination 2.Measles and rubella regional lab network: virological surveillance, lab performance, strengthen technical capacities 3.Main activities from Canada and USA labs 4.Summary and Recommendations

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

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

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

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

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

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

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

Virologic surveillance and molecular epi

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

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

*Datos hasta la SE 2/2016 Fuente: Reporte de países a OPS/OMS Rubella genotypes in the Americas, Argentina 2014: 2B

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

Measles outbreak with genotype identification. LAC, AñoBrotes con 1 caso Brotes con 2-5 casos Brotes con 6-20 casos Brotes con >20 casos 2010FRG – 2 (D4)BRA – 1 (B3)ARG – 1 (B3) BRA – 1 (B3) 2011ARG – 1 (D4) BRA – 5 (D4) CHI – 1 (D9) JAM – 1 (B3) MEX – 3 (D4) BRA – 2 (NA) ARG – 1 (D4) BRA – 6 (D4) CHI – 2 (D4) DOR – 1 (D4) PAN – 1 (D4) COL – 1 (D4) FRG – 1 (D4) GLP – 1 (D4) BRA – 1 (D4) ECU – 1 (B3) (a) 2012ARG – 1 (D4) COL – 1 (D4) VEN – 1 (D4) BRA – 1 (NA)BRA – 1 (D8)ECU – 1 (B3) (a) 2013BRA – 2 (D8) BRA – 1 (D4) BRA – 2 (NA) COL – 1 (NA) BRA – 2 (D8)BRA – 1 (D8) (b) 2014ARG – 1 (D8) BRA – 1 (B3) BRA – 1 (NA) BRA – 2 (D8)BRA – 1 (D8) (b) 2015COL – 1 (B3) BRA – 2 (NA) MEX – 1 (NA) PER – 1 (D8)CHI – 1 (H1)BRA – 1 (D8) (b) TOTAL Oubreaks – (% with genotype info) 31– (71%)18 – (94%)7– (100%)4– (100%) (a) Mismo brote B3 (b) Mismo brote, D8 NA – No disponible

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

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

Laboratory Performance

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

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

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

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

Support the development of technical capacities

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 Support at national level with kits for serology and supplies for molecular assays. Regional MR Laboratory Network of the Americas, 2015.

Meeting of the Regional Measles and Rubella Laboratory Network of the Region of the Americas, Quito – Ecuador, February The Regional LabNet is doing well and supporting the elimination of rubella and the verification of the elimination of measles. There are however, some issues that should be improved in order to provide a better and timelier response in the context of a low incidence of disease and new events of significant impact in public health.

Main activities from Canada and USA laboratories

Measles Activity in Canada, June 2015 – June Total Confirmed cases 1 Sporadic cases Outbreaks (cases) 2 Number of cases imported Total Cases genotyped Preliminary data 2 ≥2 cases 3 1 case unknown source Courtesy Joanne Hiebert, NML - Canada

Measles Activity in Canada, June 2015 – June N-450 Genotypes: B3 (n=5) D8 (n=3) MVi/Harare.ZWE/38.09 JF 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 AJ B3 MVi/New York.USA/0.94 L46753 D8 MVi/Manchester.GBR/30.94 AF MVs/Ontario.CAN/19.16 MVs/Ontario.CAN/11.16 (ex:IND) MVi/Hulu Langat.MYS/26.11 JX MVs/British Columbia.CAN/3.16 (ex:WPR) 5

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 29

CRS case report Baby born in December of 2015 with respiratory distress, congenital cataracts & microphthalmia –Rubella RT-PCR on NPS & 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 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 30

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. Measles USA 2015 (Provisional) Courtesy Paul Rota, CDC - Atlanta

1 st onsetlatest rash 2015 Measles OUTBREAKS State(s) # cases Ages Range from SourceGeno 04/02/201504/21/2015 Florida (St. Lucie and Indian River Co) FL 56 yrs to 23 yrsIndiaD8 12/28/20143/2/2015 Disneyland, CA* (*multiple counties/7 states) CA 131, AZ 7, CO 1, NE 2, OR 1, UT 3, WA wks to 70 yrs (median 22 y) UnkB3 9 mos to 44 yrs (median 28 y) 1/10/20152/25/2015 Clark Co., NV 2015 (Las Vegas) NV 9Unk B3 1/16/20152/19/2015 Cook Co., IL 2015 (day- care) IL15 3 mos to 41 yrs (median 9 m) UnkB3 5 yrs to 52 yrs 1/30/20153/4/2015Clallam Co., WA 2015WA6UnkD9 Measles Outbreaks (defined as 3 or more linked cases) were reported during 2015

Phylogenetic tree based on the N-450 gene sequences of measles viruses detected in the US in B3 H1 D8 D4

Named lineages of Measles in the USA: 2015 GenotypeMeasles Representative Strain2015MeaNS Match B3MVs/Illinois.USA/7.15/5 ( )+ 103 identical strainsMVi/Harare.ZWE/38.09/ B3MVs/Hawaii.USA/1.15 ( )+ 2 identical strainsMVs/Allada.BEN/3.10 B3MVs/California.USA/5.15/10 ( ) NEM B3MVs/Minnesota.USA/19.15 (CDC RC ) NEM B3MVs/Arizona.USA/5/15/ (CDC RC ) NEM B3MVs/Nevada.USA/7.15 (CDC RC )+ 3 identical strainsNEM H1MVs/Oklahoma.USA/11.15 ( )+ 1 identical strainNEM H1MVs/New Jersey.USA/20.15 ( )+ 3 identical strainsMVs/Hong Kong.CHN/49.12 H1MVs/California.USA/15.15/2 (CDC RC ) NEM H1MVs/California.USA/15.15 (CDC RC ) NEM H1MVs/Washington.USA/17.15/ (CDC RC )+ 1 identicalMVs/Hong Kong.CHN/49.12 D8MVs/Florida.USA/12.15 ( )+ 1 identical strainMVs/RostovonDon.RUS/47.13/2 D8MVs/Georgia.USA/5.15 ( ) MVs/London.GBR/6.15/4 D8MVs/California.USA/6.15 (CDC RC ) NEM D8MVs/Arizona.USA/2.15 ( )+ 4 identical strainsNEM D4MVs/New York.USA/2.15 (CDC RC )+ 1 identicalMVs/Ontario.CAN/3.15 (17) D4MVs/California.USA/8.15 (CDC RC ) MVs/Brussels.BEL/14.15/ NEM=No exact match indicates a named lineage

SummarySummary o Regional laboratory network is doing well and supporting the elimination of rubella and the verification of the elimination of measles. o 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 – o Several importations of measles and some of rubella virus still as the main risk to maintain the elimination. o 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.

o 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. o Improve the capacity and capability to perform molecular assays: RNA detection and genotyping (training, reagents, supplies) o Laboratories of the network are requested to ensure timely reporting of sequence data to the WHO sequence databases o Improve a real time communication between Epi and Lab staff o Maintain the commitment of Member States with the elimination in a context of new diseases of public health concern Recommendations

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