Rotavirus: advocacy slidesThese 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.

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.

Rotavirus Vaccines

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.

Two vaccines licensed for global useRotaTeq (Merck) Rotarix (GSK)

Formulation Pentavalent, bovine-human reassortant

Monovalent, human

Orally administered, doses 3 2Safety: clinical trials (intussusception risk)

No difference1 No difference1

Safety: post-introduction(intussusception risk)

Low-level risk in some countries, not others2,4,5,6

Low-level risk in some countries, not others2,3

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

1Soares-Weiser, Cochrane Review, 20122Buttery, PID, 20113Patel, NEJM, 20114Shui, JAMA, 20125Cortese, PID, 20106Haber, Pediatrics, 2008

Shown to be safe and effective in large-scale clinical studies and real-world use

7Vesikari, NEJM, 20068Ruiz-Palacios, NEJM, 20069Vesikari, Lancet, 2007

10Armah, Lancet, 201011Zaman, Lancet, 201013Mahdi and Cunliffe, NEJM, 2010

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 2013NIP status as of August 2013

But only 47

countries have

introduced

rotavirus vaccines

into their NIPs

5

47 countries have introduced rotavirus vaccines into their NIPs

Rotavirus vaccine: introduction status47 countries have introduced rotavirus vaccines into their

national immunization programs as of August 2013

WHO, 2013

Africa Botswana, Ghana, Malawi, Rwanda, South Africa, Tanzania, The Gambia

Americas Bolivia, 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

Europe Armenia, Austria, Belgium, Finland, Georgia, Israel, Luxembourg, Moldova, United Kingdom

Southeast Asia Philippines

Western Pacific Australia, Fiji, Marshall Islands, Micronesia, Palau

*Canada, Thailand, United Arab Emirates, Zambia have introduced regionally

Diarrhea: comprehensive approachRotavirus 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

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

Impact: reduction in rotavirus hospitalizations

Country (Nationwide)

Vaccine Used Age Group Eligible to Receive Vaccine

Yearly Reductions in Hospitalizations(Across Studies and Age Groups)

Australia RotaTeq & Rotarix 0-1 years old 87%

Austria RotaTeq & Rotarix 0-2 years old 74-79%

Belgium RotaTeq & Rotarix 0-2 years old 50-77%

Bolivia Rotarix 0-1 years old ~70%US RotaTeq 0-2 years old 66-86%

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

Impact: reduction in rotavirus hospitalizations

Belgium50-77%

RotaTeq & Rotarix

US66-86%RotaTeq

Bolivia70%

RotarixAustria 74-79%RotaTeq & Rotarix

Australia87%

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

Impact: reduction in all causes of diarrhea hospitalizations

Country (Nationwide)

Vaccine Used Age Group Eligible to Receive Vaccine

Yearly Reductions in Hospitalizations(Across Studies and Age Groups)

Mexico Rotarix 0-2 years old 40%

Belgium RotaTeq & Rotarix 0-2 years old 33%

USA RotaTeq 0-2 years old 29-52%

El Salvador Rotarix 0-2 years old 28-37%

Brazil Rotarix 0-2 years old 17-48%

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.

Impact: reduction in all causes of diarrhea hospitalizations

Brazil17-48%

Rotarix

El Salvador28-37%RotarixUSA

29-52%RotaTeq Belgium

33% RotaTeq & Rotarix

Mexico40%

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

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 Salvador 79-86% 41-81%

Austria 76-79% 35%

USA 74-85% 41-80%

Belgium 65-80% 20-64%

Country (regional)

Sao Paulo, Brazil 56-69% 24%

Queensland, Australia 50-70% 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.

Impact: herd immunity/indirect benefits of vaccination

Belgium65-80%

USA74-85%

Austria 76-79%

El Salvador79-86%

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.

Belgium20-64%

USA41-80%

Austria 35%

El Salvador41-81%

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

Rotavirus vaccines: cross-strain protectionRotavirus 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 Type Efficacy Non-Vaccine Type Efficacy

G1 64.1% G12 55.5%

G8 64.6%

P8 59.1% P[4] 70.9%

P[6] 55.2%

Steele, BMCID, 2012

Real world impact: Mexico and Brazil

1Richardson V, et al.3Lanzieri, IJID, 20114Carmo, 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

Impact: Mexico

1Gastañaduy, Pediatrics, 20132Richardson, NEJM, 2010

Reduction in deaths of more than 50% realized and sustained (2009-2011) across all regions1

Reduction in deaths of 35% seen in just the first year.2

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

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

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)

Rotavirus vaccines: cost effectiveCost 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.

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

Rotavirus vaccines: benefits outweigh risksIf 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

Real world observations: intussusception risk

Post-licensure StudiesAustralia• Low-level risk• 5-6 excess cases of

intussusception/100,000 children vaccinated

Mexico• Low-level risk• 1st dose: 2 excess cases of

intussusception/100,000 children vaccinated

• 2nd dose: no excess risk observed so far

Brazil • Low-level risk• 1st dose: no excess risk

observed so far• 2nd 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, 2011Patel, NEJM, 2011CDC, 2013FDA, 2013

Benefits outweigh risk, but surveillance remains essential

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.

• 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.

• 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.

• FDA. Risk of intussusception after rotavirus vaccination: results of a PRISM study. http://www.cdc.gov/vaccines/acip/meetings/downloads/slides-jun-2013/04-Rotavirus-Yih.pdf. Published 2013. Accessed 29 July 2013.

• Haber P, Patel M, Izurieta HS, Baggs J, Gargiullo P, Weintraub E, Cortese M, Braun MM, Belongia EA, Miller E, Ball R, Iskander J, Parashar UD. Postlicensure monitoring of intussusception after RotaTeq vaccination in the United States, February 1, 2006, to September 25, 2007. Pediatrics; 2008:121(6):1206-12.

• Kotloff KL, Nataro JP, Blackwelder WC, Nasrin D, Farag TH, Panchalingam S, et al. Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): a prospective, case-control study. Lancet. 2013.

• Liu L, Johnson HL, Cousens S, Perin J, Scott S, Lawn JE, et al. Global, regional, and national causes of child mortality: an updated systematic analysis for 2010 with time trends since 2000. Lancet. 2012; 379(9832): 2151-61.

• Madhi S, Cunliffe N, Steele D et al. Effect of human rotavirus vaccine on severe diarrhea in African infants. The New England Journal of Medicine. 2010;362(4):289-298.

• Parashar U, Hummelman E, Bresee J, et al. Global illness and deaths caused by rotavirus disease in children. Emerging Infectious Diseases. 2003 May; 9(5):565–572.

References

References • Parashar UD, Gibson CJ, Bresse JS, et al. Rotavirus and severe childhood diarrhea. Emerging Infectious Diseases.

2006;12:304–306.• Patel MM, Glass R, Desai R, Tate J, Parashar UD. Fulfilling the promise of rotavirus vaccines: how far have we come since

licensure? Lancet Infect Dis 2012; 12; 561-70• Patel M, Richardson V, et al. Intussusception risk and health benefits of rotavirus vaccination in Mexico and Brazil. The New

England Journal of Medicine. 2011;364(24):2283- 2292.• Patel MM, Patzi M, Pastor D, Nina A, Roca Y, Alvarez L, et al. Effectiveness of monovalent rotavirus vaccine in Bolivia: case-

control study. BMJ. 2013;346:f3726• Patel MM, Santosham M, Tate, J. Preventing Rotavirus Disease in the Developing World: Issues, Opportunities, and

Challenges. Medscape, December 2012. http://www.medscape.org/viewarticle/776009 • Richardson V, Hernandez-Pichardo J, Quintanar-Solares M, et al. Effect of rotavirus vaccination on death from childhood

diarrhea in Mexico. The New England Journal of Medicine. 2010;362(4):299–305.• Rheingans RD, Antil L, Dreibelbis R, et al. Economic costs of rotavirus gastroenteritis and cost-effectiveness of vaccination in

developing countries. JID 2009;200 (Supplement 1):S16–S27.• Ruiz-Palacios GM, Perez-Schael I, Velazquez FR, Abate H, Breuer T, Clemens SC, et al. Safety and efficacy of an attenuated

vaccine against severe rotavirus gastroenteritis. N Engl J Med. 2006; 354(1): 11-22.• Santosham M, Chandran A, Fitzwater S, et al. Progress and barriers for the control of diarrhoeal disease. The Lancet. 2010;

376: 63–67.• Shui IM, Baggs J, Patel M, Parashar UD, Rett M, Belongia EA, Hambidge SJ, Glanz JM, Klein NP, Weintraub E. Risk of

intussusception following administration of a pentavalent rotavirus vaccine in US infants. JAMA; 2012: 307(6):598-604.

References • Soares-Weiser K, Maclehose H, Bergman H, Ben-Aharon I, Nagpal S, Goldberg E, Pitan F, Cunliffe N. Vaccines for preventing

rotavirus diarrhoea: vaccines in use. Cochrane Database Syst Rev.; 2012:11:CD008521.• Steele AD, Neuzil KM, Cunliffe NA, Madhi SA, Bos P, Ngwira B, et al. Human rotavirus vaccine Rotarix provides protection

against diverse circulating rotavirus strains in African infants: a randomized controlled trial. BMC Infect Dis. 2012; 12: 213.• Tate JE, Burton AH, Boschi-Pinto C, Steele D, et al. 2008 estimate of worldwide rotavirus-associated mortality in children

younger than 5 years before the introduction of universal rotavirus vaccination programmes: a systematic review and meta-analysis. The Lancet. Published online October 25, 2011.

• Vesikari T, Matson DO, Dennehy P, Van Damme P, Santosham M, Rodriguez Z, et al. Safety and efficacy of a pentavalent human-bovine (WC3) reassortant rotavirus vaccine. N Engl J Med. 2006; 354(1): 23-33.

• WHO. Diarrhoeal disease. 2009 [cited 2011 September 28]; Available from: http://www.who.int/mediacentre/factsheets/fs330/en/index.html

• WHO. Meeting of the immunization Strategic Advisory Group of Experts, April 2009 – conclusions and recommendations. Weekly Epidemiological Record. 2009; 84(23):232-236.

• WHO. Rotavirus vaccines: WHO position paper – January 2013. Wkly Epidemiol Rec. 2009; 88(50): 49-64.• WHO: Rotavirus vaccine update 2012. Available from: http://www.sabin.org/sites/sabin.org/files/Fatima%20Serhan.pdf • WHO. Estimated rotavirus deaths for children under 5 years of age. Available from:

http://www.who.int/immunization_monitoring/burden/rotavirus_estimates/en/• Zaman K, Dang DA, Victor J, et al. Efficacy of pentavalent rotavirus vaccine against severe rotavirus gastroenteritis in infants

in developing countries in Asia: a randomised, double-blind, placebo-controlled trial. The Lancet. 2010;376(9741):615-623.