1. Rotavirus vaccine impact

2. Introduction. Rotavirus vaccines lead to significant reductions in severe and fatal diarrhea in both vaccinated and unvaccinated children Rotavirus vaccines are saving lives and improving health in countries where children have access to them. Swift and significant declines in hospitalization and deaths due to rotavirus and all-cause diarrhea have been observed in many of the countries that have introduced rotavirus vaccines into their national immunization programs. Researchers also have found that use of rotavirus vaccines may protect unvaccinated children and adults by reducing transmission of rotavirus from the vaccinated population to unvaccinated members of the community (called “indirect effects” to those unvaccinated and sometimes referred to as “herd immunity” effects). These remarkable results underscore the incredible potential for rotavirus vaccines to improve child health and save children’s lives. Note: The results for reductions in hospitalizations or deaths in these tables are not generally directly comparable. This is because the different studies vary by study methodology and setting, including ages studied and/or eligible for vaccination, location, vaccine coverage, and years since vaccine implementation. Nonetheless, the results provide evidence of consistent reductions in a variety of settings where rotavirus vaccines have been introduced.

3. Table 1. Impact of rotavirus vaccines on hospitalizations for rotavirus gastroenteritis among children <5 years old *Pre- and post-vaccine data time periods have been approximated for those studies that did not indicate specific months of data used to estimate the yearly reduction. Ɨ Reductions that includes a range of percentages reflect results for multiple years.

4. Table 1 references 1.Paulke-Korinek M, Rendi-Wagner P, Kundi M, Kronik R, Kollaritsch H. Universal mass vaccination against rotavirus gastroenteritis: impact on hospitalization rates in Austrian children. Pediatric Infectious Disease Journal. 2010;29:319–323. 2.Paulke-Korinek M, Kundi M, Rendi-Wagner P, et al. Herd immunity after two years of the universal mass vaccination program against rotavirus gastroenteritis in Austria. Vaccine. 2011;29:2791–2796. 3.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. 4.Pendleton A, Galic M, Clarke C, et al. Impact of rotavirus vaccination in Australian children below 5 years of age. Human Vaccines & Immunotherapeutics 2013;9(8):1-9. 5.Braeckman T, Van Herck K, Raes M, Vergison A, Sabbe M, Van Damme P. Rotavirus vaccines in Belgium: policy and impact. Pediatric Infectious Disease Journal. 2011;30(suppl 1):S21–S24. 6.Raes M, Strens D, Vergison A, Verghote M, Standaert B. Reduction in pediatric rotavirus-related hospitalizations after universal rotavirus vaccination in Belgium. Pediatric Infectious Disease Journal. 2011;30: e120–e25.9 7.Standaert B, Gomez JA, Raes M, et al. Impact of rotavirus vaccination on hospitalisations in Belgium : Comparing model predictions with observed data. PLoS One 2013;8(1):e53864. 8.Yen C, Armero Guardado JA, Alberto P, Rodriguez Araujo DS, Mena C, Cuellar E, Nolasco JB, De Oliveira LH, Pastor D, Tate JE, Parashar UD, Patel MM 2011a. Decline in rotavirus hospitalizations and health care visits for childhood diarrhoea following rotavirus vac­cination in El Salvador. Pediatr Infect Dis J 30 (Suppl. 1): S6-S10. 9.Vesikari T, Uhari M, Renko M, et al. Impact and Effectiveness of Rotateq Vaccine Based on Three Years of Surveillance Following Introduction of a Rotavirus Immunization Program in Finland. Pediatric Infectious Disease Journal 2013 [epub ahead of print]. 10.Yen C, Tate JE, Wenk JD, Harris JM 2nd, Parashar UD. Diarrhea-associated hospitalizations among US children over 2 rotavirus seasons after vaccine introduction. Pediatrics. 2011;127:e9–e15. 11.Payne DC, Staat MA, Edwards KM, et al. Direct and indirect effects of rotavirus vaccination upon childhood hospitalizations in 3 US counties, 2006-2009. Clinical Infectious Diseases. 2011;53(3):245-253. 12.Tate JE, Hanes A, Payne DC, et al. Trends in national rotavirus activity before and after introduction of rotavirus vaccine into the national immunization program in the United States, 2000 to 2012. Pediatric Infectious Disease Journal 2013;32(7):741-744.

5. Table 2. Impact of rotavirus vaccines on hospitalizations for all- cause acute gastroenteritis among children <5 years old *Pre- and post-vaccine data time periods have been approximated for those studies that did not indicate specific months of data used to estimate the yearly reduction. Ɨ Reductions that includes a range of percentages reflect results for multiple years.

6. Table 2 references 1.Raes M, Strens D, Vergison A, Verghote M, Standaert B. Reduction in pediatric rotavirus-related hospitalizations after universal rotavirus vaccination in Belgium. Pediatric Infectious Disease Journal. 2011;30: e120–e25. 2.De Oliveira LH, Giglio N, Ciapponi A, et al. Temporal trends in diarrhea-related hospitalizations and deaths in children under age 5 before and after the introduction of the rotavirus vaccine in four Latin American countries. Vaccine 2013 ;31 :C99-C108. 3.Lanzieri TM, Costa I, Shafi FA, et al. Trends in hospitalizations from all-cause gastroenteritis in children younger than 5 years of age in Brazil before and after human rotavirus vaccine introduction, 1998–2007. Pediatric Infectious Disease Journal. 2010 ;29 :673–675. 4.do Carmo GM, Yen C, Cortes J, Siqueira AA, de Oliveira WK, Cortez-Escalante JJ, et al. Decline in diarrhea mortality and admissions after routine childhood rotavirus immunization in Brazil: a time-series analysis. PloS Medicine. 2011 ;8(4) :e1001024. 5.Yen C, Armero Guardado JA, Alberto P, et al. Decline in rotavirus hospitalizations and health care visits for childhood diarrhea following rotavirus vaccination in El Salvador. Pediatric Infectious Disease Journal. 2011;30 (suppl 1):S6–S10. 6.Quintanar-Solares M, Yen C, Richardson V, Esparza-Aguilar M, Parashar UD, Patel MM. Impact of rotavirus vaccination on diarrhea- related hospitalizations among children <5 years of age in Mexico. Pediatric Infectious Disease Journal. 2011;30(suppl 1):S11–S15. 7.Becker-Dreps S, Melendez M, Liu L, et al. Community diarrhea incidence before and after rotavirus vaccine introduction in Nicaragua. American Journal of Tropical Medicine and Hygiene 2013;89(2):246-250. 8.Bayard V, DeAntonio R, Contreras R, et al. Impact of rotavirus vaccination on childhood gastroenteritis-related mortality and hospital discharges in Panama. International Journal of Infectious Diseases 2012 ;16 :e94-e98. 9.Molto Y, Cortes JE, de Oliveira LH, et al. Reduction of diarrhea-associated hospitalizations among children aged <5 years in Panama following the introduction of rotavirus vaccine. Pediatr Infect Dis. 2011;30:S16 –S20. 10.Curns AT, Steiner CA, Barrett M, Hunter K, Wilson E, Parashar UD. Reduction in acute gastroenteritis hospitalizations among US children after introduction of rotavirus vaccine: analysis of hospital discharge data from 18 US states. Journal of Infectious Disease. 2010; 201:1617–1624. 11.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. 12.Yen C, Tate JE, Wenk JD, Harris JM 2nd, Parashar UD. Diarrhea-associated hospitalizations among US children over 2 rotavirus seasons after vaccine introduction. Pediatrics. 2011 ;127 :e9–e15. 13.Desai R, Haberling D, Holman RC, et al. Impact of rotavirus vaccine on diarrhea-associated disease burden among American Indian and Alaska Native children. Pediatrics 2012;129(4):e907-e913.

7. Table 3. Impact of rotavirus vaccines on deaths for all-cause acute gastroenteritis among children <5 years old *Pre- and post-vaccine data time periods have been approximated for those studies that did not indicate specific months of data used to estimate the yearly reduction. Ɨ Reductions that includes a range of percentages reflect results for multiple years.

8. Table 3 references 1.De Oliveira LH, Giglio N, Ciapponi A, et al. Temporal trends in diarrhea-related hospitalizations and deaths in children under age 5 before and after the introduction of the rotavirus vaccine in four Latin American countries. Vaccine 2013 ;31 :C99-C108. 2.Lanzieri TM, Linhares AC, Costa I, et al. Impact of rotavirus vaccination on childhood deaths from diarrhea in Brazil. International Journal of Infectious Diseases. 2011;15(3):e206-e210. 3.do Carmo GM, Yen C, Cortes J, Siqueira AA, de Oliveira WK, Cortez-Escalante JJ, et al. Decline in diarrhea mortality and admissions after routine childhood rotavirus immunization in Brazil: a time-series analysis. PloS Medicine. 2011;8(4):e1001024. 4.Richardson V, Hernandez-Pichardo J, Quintanar-Solares M, Esparza-Aguilar M, Johnson B, Gomez-Altamirano CM, et al. Effect of rotavirus vaccination on death from childhood diarrhea in Mexico. The New England Journal of Medicine. 2010;362(4):299-305. 5.Richardson V, Parashar U, Patel M. Childhood diarrhea deaths after rotavirus vaccination in Mexico. The New England Journal of Medicine. 2011;365(8):772-773. 6.Gastanaduy PA, Sanchez-Uribe E, Esparza-Aguilar M, et al. Effect of Rotavirus Vaccine on Diarrhea Mortality in Different Socioeconomic Regions of Mexico. Pediatrics 2013 ;131(4) :e1115-20. 7.Bayard V, DeAntonio R, Contreras R, et al. Impact of rotavirus vaccination on childhood gastroenteritis-related mortality and hospital discharges in Panama. International Journal of Infectious Diseases 2012;16:e94-e98.

9. Table 4. Indirect benefits of rotavirus vaccination *Reductions that include a range of percentages reflect results for multiple years.

10. Table 4 references 1.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. 2.Yen C, Tate JE, Wenk JD, Harris JM 2nd, Parashar UD. Diarrhea-associated hospitalizations among US children over 2 rotavirus seasons after vaccine introduction. Pediatrics. 2011;127:e9–e15. 3.Payne DC, Staat MA, Edwards KM, et al. Direct and indirect effects of rotavirus vaccination upon childhood hospitalizations in 3 US counties, 2006-2009. Clinical Infectious Diseases. 2011;53(3):245-253. 4.Field EJ, Vally H, Grimwood K, Lambert SB. Pentavalent rotavirus vaccine and prevention of gastroenteritis hospitalizations in Australia. Pediatrics. 2010;126:e506–512. 5.Raes M, Strens D, Vergison A, Verghote M, Standaert B. Reduction in pediatric rotavirus-related hospitalizations after universal rotavirus vaccination in Belgium. Pediatric Infectious Disease Journal. 2011;30: e120–e25. 6.Paulke-Korinek M, Kundi M, Rendi-Wagner P, et al. Herd immunity after two years of the universal mass vaccination program against rotavirus gastroenteritis in Austria. Vaccine. 2011;29:2791–2796. 7.Safadi MA, Berezin EN, Munford V, et al. Hospital-based surveillance to evaluate the impact of rotavirus vaccination in São Paulo, Brazil. Pediatric Infectious Disease Journal. 2010;29:1019–1022. 8.Yen C, Armero Guardado JA, Alberto P, et al. Decline in rotavirus hospitalizations and health care visits for childhood diarrhea following rotavirus vaccination in El Salvador. Pediatric Infectious Disease Journal. 2011;30 (suppl 1):S6–S10. 9.Pendleton A, Galic M, Clarke C, et al. Impact of rotavirus vaccination in Australian children below 5 years of age. Human Vaccines & Immunotherapeutics 2013;9(8):1-9.