1. Rotavirus: advocacy slides These slides are intended to support your advocacy efforts. Please incorporate those that may be useful to you in your presentations. For questions, please contact jen.farber@gmmb.com.jen.farber@gmmb.com Special thanks to the ROTA Council’s Partners: Johns Hopkins University, PATH, US Centers for Disease Control and Prevention and Bill & Melinda Gates Foundation for their technical guidance and expertise in developing these slides.

2. Rotavirus Vaccines

3. Rotavirus vaccines: provide best protection benefits saves lives improves health cost effective A comprehensive approach to fighting diarrhea, including rotavirus vaccines and other proven preventions and treatments, can significantly reduce child illnesses and deaths.

4. Two vaccines licensed for global use RotaTeq (Merck)Rotarix (GSK) FormulationPentavalent, bovine-human reassortant Monovalent, human Orally administered, doses32 Safety: clinical trials (intussusception risk) No difference 1 Safety: post-introduction (intussusception risk) Low-level risk in some countries, not others 2,4,5,6 Low-level risk in some countries, not others 2,3 Efficacy: against severe rotavirus diarrhea in children < 1 (developed countries) 98% 7 85%-96% 8,9 Efficacy: against severe rotavirus diarrhea in children < 1 (developing countries) 51%-64% 10,11 59% 13 1 Soares-Weiser, Cochrane Review, 2012 2 Buttery, PID, 2011 3 Patel, NEJM, 2011 4 Shui, JAMA, 2012 5 Cortese, PID, 2010 6 Haber, Pediatrics, 2008 Shown to be safe and effective in large-scale clinical studies and real-world use 7 Vesikari, NEJM, 2006 8 Ruiz-Palacios, NEJM, 2006 9 Vesikari, Lancet, 2007 10 Armah, Lancet, 2010 11 Zaman, Lancet, 2010 13 Mahdi and Cunliffe, NEJM, 2010

5. Rotavirus vaccines: recommended by WHO  WHO recommends rotavirus vaccines in all national immunization programs (NIPs), particularly in south and south- eastern Asia and sub-Saharan Africa  Should be part of a comprehensive approach to control diarrhea  Vaccination age restriction may be relaxed in countries where delays in immunizations and deaths from rotavirus are common WHO. Rotavirus vaccines: WHO position paper – January 2013 NIP status as of August 2013 But only 47 countries have introduced rotavirus vaccines into their NIPs 5

6. 47 countries have introduced rotavirus vaccines into their NIPs

7. Rotavirus vaccine: introduction status 47 countries have introduced rotavirus vaccines into their national immunization programs as of August 2013 WHO, 2013 AfricaBotswana, Ghana, Malawi, Rwanda, South Africa, Tanzania, The Gambia AmericasBolivia, Brazil, Cayman Islands, Colombia, Dominican Republic, Ecuador, El Salvador, Guatemala, Guyana, Haiti, Honduras, Mexico, Nicaragua, Panama, Paraguay, Peru, USA, Venezuela Eastern Mediterranean Bahrain, Iraq, Morocco, Qatar, Saudi Arabia, Sudan, Yemen EuropeArmenia, Austria, Belgium, Finland, Georgia, Israel, Luxembourg, Moldova, United Kingdom Southeast AsiaPhilippines Western PacificAustralia, Fiji, Marshall Islands, Micronesia, Palau *Canada, Thailand, United Arab Emirates, Zambia have introduced regionally

9. Diarrhea: comprehensive approach Rotavirus vaccines are key to a comprehensive approach to fighting diarrheal disease Protect Exclusive Breastfeeding Appropriate complementary feeding Treat Rehydration therapy (oral rehydration solution [ORS], home available or IV fluids) Zinc supplementation Prevent Rotavirus vaccines Improved drinking water, hygiene, sanitation

10. Major reductions in hospitalizations for children under 5 observed within 2 years of rotavirus vaccine introduction  Hospital admissions for rotavirus reduced by half or more (49-89%)  Significant declines (17- 55%) in hospitalizations for all causes of diarrhea Impact: reductions in hospitalizations Patel, Lancet, 2012

11. Impact: reduction in rotavirus hospitalizations Country (Nationwide) Vaccine UsedAge Group Eligible to Receive Vaccine Yearly Reductions in Hospitalizations (Across Studies and Age Groups) AustraliaRotaTeq & Rotarix0-1 years old87% AustriaRotaTeq & Rotarix0-2 years old74-79% BelgiumRotaTeq & Rotarix0-2 years old50-77% BoliviaRotarix0-1 years old~70% USRotaTeq0-2 years old66-86% Note: table derived from Table 2 from: Patel MM, Glass R, Desai R, Tate JE, Parashar UD. Fulfilling the Promise of Rotavirus Vaccines: How Far Have We Come Since Licensure? The Lancet Infectious Diseases. 2012;12(7):561-570. Patel, British Medical Journal, 2013. Hospitalizations: documented reductions of 50% or more

12. Impact: reduction in rotavirus hospitalizations Belgium 50-77% RotaTeq & Rotarix US 66-86% RotaTeq Bolivia 70% Rotarix Austria 74-79% RotaTeq & Rotarix Australia 87% RotaTeq & Rotarix Note: data derived from Table 2 from: Patel MM, Glass R, Desai R, Tate JE, Parashar UD. Fulfilling the Promise of Rotavirus Vaccines: How Far Have We Come Since Licensure? The Lancet Infectious Diseases. 2012;12(7):561-570. Hospitalizations: documented reductions of 50% or more in children 0-2 years old following rotavirus vaccination

13. Impact: reduction in all causes of diarrhea hospitalizations Country (Nationwide) Vaccine UsedAge Group Eligible to Receive Vaccine Yearly Reductions in Hospitalizations (Across Studies and Age Groups) MexicoRotarix0-2 years old40% BelgiumRotaTeq & Rotarix0-2 years old33% USARotaTeq0-2 years old29-52% El SalvadorRotarix0-2 years old28-37% BrazilRotarix0-2 years old17-48% Hospitalizations: documented reductions of nearly 20% or more Note: table derived from Table 2 from: Patel MM, Glass R, Desai R, Tate JE, Parashar UD. Fulfilling the Promise of Rotavirus Vaccines: How Far Have We Come Since Licensure? The Lancet Infectious Diseases. 2012;12(7):561-570.

14. Impact: reduction in all causes of diarrhea hospitalizations Brazil 17-48% Rotarix El Salvador 28-37% Rotarix USA 29-52% RotaTeq Belgium 33% RotaTeq & Rotarix Mexico 40% Rotarix Note: data derived from Table 2 from: Patel MM, Glass R, Desai R, Tate JE, Parashar UD. Fulfilling the Promise of Rotavirus Vaccines: How Far Have We Come Since Licensure? The Lancet Infectious Diseases. 2012;12(7):561-570. Patel, British Medical Journal, 2013. Hospitalizations: documented reductions of nearly 20% or more in children 0-2 years old following rotavirus vaccination

15. Impact: herd immunity/indirect benefits of vaccination Rotavirus related hospitalizations reduced Country (nationwide) Children age-eligible for vaccine Children NOT age-eligible for vaccine El Salvador79-86%41-81% Austria76-79%35% USA74-85%41-80% Belgium65-80%20-64% Country (regional) Sao Paulo, Brazil56-69%24% Queensland, Australia50-70%30-70% Significant reductions in hospitalization observed for non-vaccinated children Note: table derived from Table 2 from: Patel MM, Glass R, Desai R, Tate JE, Parashar UD. Fulfilling the Promise of Rotavirus Vaccines: How Far Have We Come Since Licensure? The Lancet Infectious Diseases. 2012;12(7):561-570.

16. Impact: herd immunity/indirect benefits of vaccination Belgium 65-80% USA 74-85% Austria 76-79% El Salvador 79-86% Note: data derived from Table 2 from: Patel MM, Glass R, Desai R, Tate JE, Parashar UD. Fulfilling the Promise of Rotavirus Vaccines: How Far Have We Come Since Licensure? The Lancet Infectious Diseases. 2012;12(7):561-570. Belgium 20-64% USA 41-80% Austria 35% El Salvador 41-81% Hospitalizations: documented reductions of more than 50% in children eligible for vaccination Hospitalizations: documented reductions of more than 20% in children NOT eligible for vaccination

17. Rotavirus vaccines: cross-strain protection Rotavirus vaccines provide broad protection against rotavirus–even against strains of the virus not included in the vaccine. Rotarix Efficacy Against Vaccine and Non-Vaccine Type Rotavirus Vaccine TypeEfficacyNon-Vaccine TypeEfficacy G164.1%G1255.5% G864.6% P859.1%P[4]70.9% P[6]55.2% Steele, BMCID, 2012

18. Real world impact: Mexico and Brazil 1 Richardson V, et al. 3 Lanzieri, IJID, 2011 4 Carmo, PLOS, 2011 Post-introduction impact in Mexico and Brazil comparable to phase 3 clinical trial efficacy data Mexico Widespread introduction in 2007 In 2008, diarrhea deaths declined by 35% 1 In 2009, diarrhea deaths declined by more than 65% Brazil Widespread introduction in 2006 In 2007, diarrhea deaths declined by 30% 3 In 2008, diarrhea deaths declined by 39% 3 Sustained reduction of 22% over 3 years (2007-2009) 4 Hospitalizations for rotavirus and all-cause diarrhea decline

19. Impact: Mexico 1 Gastañaduy, Pediatrics, 2013 2 Richardson, NEJM, 2010  Reduction in deaths of more than 50% realized and sustained (2009-2011) across all regions 1  Reduction in deaths of 35% seen in just the first year. 2

20. Impact: Bolivia  Bolivia, first high-mortality country to introduce Rotarix® in 2008, with GAVI support  Study found vaccinated children 70% less likely to be hospitalized for rotavirus compared to unvaccinated children  Protection sustained through first 2 years of a child’s life, when risk of infection is greatest  Vaccination protected against wide variety of rotavirus strains, including those not found in the vaccine  Findings applicable to many other GAVI-eligible countries in Africa and Asia, especially those using Rotarix BMJ, 2013

21. Rotavirus vaccines: cost effective Atherly, Vaccine, 2012 If used in all GAVI- eligible countries, rotavirus vaccines could… Prevent an estimated 180,000 deaths annually Avert 6 million clinic and hospital visits annually Save US $68 million annually

22. Cost-effectiveness: GAVI countries Slide from Debbie Atherly Source: GAVI Investment Case Cost per DALY averted, 2011-2030 Compared to GDP per capita (Very cost effective when cost per DALY averted < 1x GDP )

23. Rotavirus vaccines: cost effective Cost effectiveness is about more than the price of the vaccine. We must also consider:  Hospitalizations  Loss of income/productivity when taking care of a sick child  Child suffering Patel, Santosham, & Tate, Medscape, 2012.

24. Rotavirus vaccination: benefits outweigh risks Benefits of rotavirus vaccination are substantial and include prevention of hospitalization and death Benefits far outweigh possible low-level risk of intussusception associated with the vaccine

25. Rotavirus vaccines: benefits outweigh risks If introduced into all national immunization programs at the same coverage levels of other routine vaccines administered by 15 weeks of age Benefit: 156,000 deaths related to rotavirus averted WHO, 2012 Risk: 288 potential deaths from vaccine-associated intussusception, an intestinal obstruction

26. Real world observations: intussusception risk Post-licensure Studies Australia Low-level risk 5-6 excess cases of intussusception/100,000 children vaccinated Mexico Low-level risk 1 st dose: 2 excess cases of intussusception/100,000 children vaccinated 2nd dose: no excess risk observed so far Brazil Low-level risk 1 st dose: no excess risk observed so far 2 nd dose: 1-2 excess cases of intussusception/ 100,000 children vaccinated US Low-level risk 1-5 excess cases of intussusception/100,000 children vaccinated Buttery, Vaccine, 2011 Patel, NEJM, 2011 CDC, 2013 FDA, 2013 Benefits outweigh risk, but surveillance remains essential

27. References Ansari SA, Springthorpe VS, Sattar SA. Survival and vehicular spread of human rotaviruses: possible relation to seasonality of outbreaks. Reviews of infectious diseases. 1991; 13(3): 448-61. Atherly D, Lewis K, Tate J et al. Projected health and economic impact of rotavirus vaccination in GAVI-eligible countries: 2011–2030. Vaccine. 30S (2012) A7– A14. Armah G, Sow S, Breiman R, et al. Efficacy of pentavalent human-bovine reassortant rotavirus vaccine against severe rotavirus gastroenteritis in sub-Saharan Africa: a randomized, double-blind, placebo-controlled trial. The Lancet. 2010;376(9741):606-614. Buttery JP, Lambert SB, Grimwood K, et al. Reduction in rotavirus-associated acute gastroenteritis following introduction of rotavirus vaccine into Australia’s National Childhood vaccine schedule. Pediatric Infectious Disease Journal. 2011;30(suppl 1):S25–S29. Buttery JP, Danchin MH, Lee KJ, Carlin JB, McIntyre PB, Elliott EJ, et al. Intussusception following rotavirus vaccine administration: post-marketing surveillance in the National Immunization Program in Australia. Vaccine. 2011;29(16):3061- 3066. CDC. Rotavirus vaccines and intussusception in the Vaccien Safety Datalink (VSD). http://www.cdc.gov/vaccines/acip/meetings/downloads/slides-jun-2013/02-Rotavirus-Weintraub.pdf. Published 2013. Accessed 29 July 2013. http://www.cdc.gov/vaccines/acip/meetings/downloads/slides-jun-2013/02-Rotavirus-Weintraub.pdf Cortese MM, Tate JE, Simonsen L, Edelman L, Parashar UD. Reduction in gastroenteritis in United States children and correlation with early rotavirus vaccine uptake from national medical claims databases. Pediatric Infectious Disease Journal. 2010;29:489–494.

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