Conclusions and Recommendations of the Experts Meeting on Rotavirus Genotypes in the Region of the Americas

Transcription

1 Conclusions and Recommendations of the Experts Meeting on Rotavirus Genotypes in the Region of the Americas Eyal Leshem December 9, 2013 National Center for Immunization & Respiratory Diseases Division of Viral Diseases

2 Objectives What have we learned about the ecology rotavirus strains after vaccine introduction? What critical questions remain unanswered? How can we answer these questions utilizing rotavirus surveillance? Protocol modifications

3 Rotavirus Strain Typing

4 Rotavirus Strain Typing Rotavirus genomes can recombine through genetic reassortment (like flu virus)

5 Surveillance Before Rotavirus Vaccine Introduction What is rotavirus strain distribution? Match with vaccine antigens

6 Pre-vaccine Rotavirus Strains, G1P8 G2P4 G3P8 G4P8 G9P8 Number of samples = 73,811 Banyai Vaccine 2012

7 Post-vaccine Rotavirus Strains, G3P8 8% G4P8 2% G9P8 9% G1P8 29% G2P4 52% Number of samples = % Brazil 22% US 24% Australia Leshem, Unpublished

8 Post Vaccine Strain Distribution Strain distribution changed Are observed changes related to vaccine introduction or just natural variation over time?

9 Rotavirus Vaccines Rotarix (RV1) Human Rotavirus G1P[8] RotaTeq (RV5) Human-Bovine WC3 Rotavirus Reassortant G1,G2,G3,G4,P[8]

10 Efficacy Against Heterotypic Strains G2P4? G3P8? Rotarix (RV1) Human Rotavirus G1P[8] RotaTeq (RV5) Human-Bovine WC3 Rotavirus Reassortant G1,G2,G3,G4,P[8]

11 Rotavirus Genotyping Results from NVSN 2006 to 2008 Strain Prevalence: 2006 (n=225) G1 P[4] 0.4% G2 P[4] 4.9% G2 P[8] 0.4% G9 P[6] 0.4% G12 P[8] 0.4% G12 P[6] 3.6% GM P[8] 0.9% Strain Prevalence: (n=28) G1 P[6] 1.8% G1 P[M] 3.1% G1 P[8] 84.0% GNT P[NT] 7.1% Strain Prevalence: (n=273) G12 P[M] 0.4% GM P[8] 1.5% GM P[M] 0.4% GNT P[8] 1.1% GNT P[NT] 0.4% G3 P[8] 10.7% G1 P[8] 82.1% G9 P[8] 0.4% G4 P[8] 0.4% G12 P[8] 27.5% G1 P[8] 44.7% G1 P[M] 0.4% G3 P[8] 2.2% G2 P[M] 1.1% G2 P[8] 7.7% G2 P[6] 0.7% G2 P[4] 10.3% G1 P[NT] 1.1% Bowen, CDC

12 Genotype Prevalence USA, NVSN n= Bowen, Unpublished

13 Strains by Year and Vaccine, Australia, RV1 100% 50% 0% N= G9P8 G4P8 G3P9 G2P4 G1P8 RV5 100% 50% 0% N= G9P8 G4P8 G3P9 G2P4 G1P8 Leshem, Unpublished

14 Strains by Vaccine, Australia, G4P8, 5% G3P8, 13% G9P8, 2% G1P8, 32% G4P8, 1% G3P8, 7% G9P8, 7% G1P8, 37% G2P4, 48% G2P4, 48% RV5 N=519 RV1 N=769 Leshem, Unpublished

15 Conclusion 1: Post Vaccine Strain Distribution Changes in strain distribution: Do not appear to be consistent over several years No particular patters is associated with either vaccine

16 Post Vaccine Strain Distribution How effective are rotavirus vaccines against specific strains in real life? Vaccine status Age Severity

17 RV1 Strain Specific Effectiveness Middle Income Countries Author/Year Country Strain Vaccine Effectiveness (95% CI) De Palma 2010 El Salvador* G1P8 (92%) 76% (64,84) Gurgel 2009 Brazil G2P4 89% (87,92) Corriera 2010** Brazil G2P4 77% (43,90) Justino 2011 Brazil G2P4 75% (57,86) Patel 2013 Bolivia* G2P4 71% (19,90) Patel 2013 Bolivia* G3P8 92% (60,98) Yen 2011 Mexico G9P4 94% (16,100) Patel 2013 Bolivia* G9P6 87% (-10,98) Patel 2013 Bolivia* G9P8 84% (64,92) *Low middle income ** 6-11 month olds Leshem, Unpublished

18 RV5 Genotype-Specific Vaccine Effectiveness NVSN Data, % VE Payne Clin Infect Dis 2013

19 Conclusion 2: Vaccine Effectiveness All data indicate good heterotypic protection from vaccines to date

20 Additional Questions Significance of events detected by surveillance: Outbreaks Rotavirus affecting older children, adults and elderly Circulating vaccine reassontant strains Circulating animal related strains Non-typeable strains Vaccine failures

21

22 Rose EID 2013

23 Objectives What have we learned about the ecology rotavirus strains after vaccine introduction? What critical questions remain unanswered? How can we answer these questions utilizing rotavirus surveillance? Protocol modifications

24 Recommendations: Country Rotavirus Surveillance Prioritization of data quality over quantity of samples Emphasis on linkage of strain and epidemiology data Patient age, disease severity, vaccine status Enhanced surveillance sites

25 Recommendations: Country Rotavirus Surveillance Capacity building in country rotavirus reference laboratories G,P Strain typing Specimen archive What proportion of cases do we need to save and genotype?

26 Recommendations: Regional Reference Laboratory Support country rotavirus surveillance Training and capacity building Quality assurance, resolution of problems

27 Recommendations: Regional Reference Laboratory Hypothesis driven research Strain characterization by advanced molecular techniques: Emerging; outbreak; vaccine reassortant; animal related; non-typeable; vaccine failures Characterize vaccine failures detect co-infection with other diarrheal pathogens

28 Recommendations: Regional Reference Laboratory Hypothesis driven research Serologic studies: waning immunity; population studies Studies of rotavirus circulation in older children, adult and elderly

29 Conclusion

30 Conclusion

31 Acknowledgments Roger Glass NIH Dioselina Pelaez Instituto Nacional de Colombia Michael Bowen CDC Martha Elizabeth Melendez Quevedo Laboratorio Nacional de Referencia MOH El Salvador Duncan Steele BMGF Dina Castro Laboratorio Nacional de Virologia Honduras John Gentsh CDC Herlinda Garcia Lozano Jose Paulo Leite Oswaldo Cruz Institute-FIOCRUZ Brazil Instituto Evandro Chagas, MOH Brazil Fatima Serhan Instituto de Diagnotico de Referencia Mexico WHO Alexandre da Costa Linhares Gloria Rey-Benito PAHO - Costa Rica Manish Patel CDC Lúcia de Oliveira PAHO - WDC Cuauhtemoc Ruiz PAHO - WDC Jennifer Sanwogou PAHO - WDC Matus

32 Discussion Points Improving data linking epi and lab Case sensitive ID numbers Vaccine data photocopy of vaccine card Improving timeliness and quality of data at all levels Challenges of sentinel, national and regional laboratories Ensure compliance with rules and responsibilities of sentinel laboratories Improve communication and feedback between actors in sentinel surveillance

33 Summary Rotavirus Surveillance Before Introduction Question What is strain distribution? Data collected Strains After introduction How does strain distribution change? What is the impact of strain changes on vaccine effectiveness? How to interpret detection of unusual strains? Strains Vaccine status Age Clinical severity (hospitalized?)

34 RV1 Proportion of samples by strain and year, post rotavirus vaccine introduction, published worldwide, % 50% 0% N= G9P8 G4P8 G3P9 G2P4 G1P8 RV5 100% 50% 0% G9P8 G4P8 G3P9 G2P4 G1P8 N=

35 Visits / 10,000 PY Diarrhea-Associated Hospitalizations Vaccinated Vs. Unvaccinated Children<5, US, Rotavirus-Coded 0.4 Unvaccinated RV5 RV1

36 Visits / 10,000 PY Diarrhea-Associated Hospitalizations Vaccinated Vs. Unvaccinated Children<5, US, RV5 92% (87-96) RV1 96% (74-100) 1 Rotavirus-Coded 0.4 Unvaccinated RV5 RV1

37 Visits / 10,000 PY Diarrhea-Associated Hospitalizations Vaccinated Vs. Unvaccinated Children<5, US, Unvaccinated RV5 RV Any-Diarrhea

38 Visits / 10,000 PY Diarrhea-Associated Hospitalizations Vaccinated Vs. Unvaccinated Children<5, US, RV5 55% (46-62) RV1 53% (36-66) Unvaccinated RV5 RV Any-Diarrhea

39 Visits / 10,000 PY Diarrhea-Associated Hospitalizations Children<5, United States RV All diarrhea Rotavirus-coded diarrhea Leshem, Unpublished

40 Real-World Decline in Childhood Diarrhea Deaths after Rotavirus Vaccination in Mexico Vaccine Introduction (May 2007) 2011 *Gastanaduy Pediatrics

41 Reduction % RV5 Provided Good Efficacy against Common Rotavirus Strains 0 % G1 G2 G3 G4 G9 100% 95% CI 95%* [92,97] 88% [<0,99] 93%[ 49,99] 89%* [52,98] 100%* [67,100] Vesikari NEJM

42 Vaccine efficacy (%) RV1: Potential lower efficacy against G2P[4] strains in Latin America 92% G1 P[8] 91% 88% In Europe, efficacy against G2P4 was 86% 41 [-79.2; 82.4] G9 P[8] G3 P[8] G2 P[4] Ruiz-Palacios NEJM 2006