Impact of Rotavirus Vaccination in Latin America Manish Patel Viral Gastroenteritis Team Epidemiology Branch Division of Viral Diseases National Center for Immunizations and Respiratory Diseases CDC * The findings and conclusions in this presentation are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention (CDC).

Rotavirus causes half a million childhood deaths annually under 5 1 dot = 1000 deaths Parashar et al. EIDJ 2005

Rotavirus Causes of a Third of the Diarrhea Hospitalizations Among Children <5 Industrialized Countries Developing Countries Unknown Unknown Rotavirus Rotavirus Other Bacterial Bacterial Other A. Kapikian, Fields Virology 2003

Rotavirus Vaccines: RV5 & RV1 RV1 Rotarix (GSK) RV5 RotaTeq (Merck & Co.) G1 G3 G2 G4 P[8] Bovine rotavirus with single human rotavirus gene substitution G1P[8] Human rotavirus

RV1 RV5 Tested against severe rotavirus disease Efficacy in industrialized countries: 85%-96% Efficacy in developing countries: 50-77% RV5

2006: WHO recommends rotavirus vaccination in Latin America and Eastern Europe 2009: WHO expanded rotavirus immunization recommendation globally

Rotavirus Vaccination in the Americas United States – Feb 2006 and Jun 2008 Mexico: May 2007 Venezuela: Apr 2006 ELS: Oct 2006 Panama: Mar 2006 Nicaragua: Oct 2006 Ecuador, Oct 2007 Brazil: Mar 2006 Bolivia, Aug 2008 Slide – L Oliveira, PAHO 7 7

Postlicensure Issues of Priority Vaccine performance in routine use Effectiveness in low income settings Impact on diarrhea mortality Not assessed in trials 8

El Salvador & Nicaragua

Comparison of Countries El Salvador Nicaragua Birth cohort 150,000 GNI ~2,800 US$ Low-middle ~980 US$ Low income Vaccine RV1 RV5 Year introduced October, 2006 October 2006 Age 2, 4 months 2, 4, 6 months Concomitant vaccines OPV, DTP, HiB, Hepatitis B

Case-control Vaccine Effectiveness Evaluation—ELS & NIC Active surveillance for diarrhea Cases: overnight hospitalization for lab-confirmed rotavirus diarrhea 323 (ELS) and 285 (NIC) Controls: 3 per case, matched on date of birth (+/- 4 weeks) Card-confirmed vaccination status

Vaccine Effectiveness (95% CI) Vaccine Effectiveness against Rotavirus Diarrhea Requiring Admission Differed by Country No. of doses Vaccine Effectiveness (95% CI) El Salvador* (RV1) Nicaragua** (RV5) Full series 76% (63, 84) 44% (15, 63) *De palma et al BMJ, in press **Patel et al JAMA,2009

Vaccine Effectiveness (95% CI) Vesikari* ≥ 15 (MOST severe) Disease Severity: Effectiveness was Comparable against the MOST Severe Rotavirus Diarrhea Severity Score Vaccine Effectiveness (95% CI) El Salvador (RV1) Nicaragua (RV5) Vesikari* ≥ 15 (MOST severe) 83% (52, 94) 77% (39, 92) *Vesikari score is a 20-point clinical severity scoring system

Vaccine Coverage: Rapid Uptake in Both Countries* Proportion of children 6-12 months of age receiving 2 doses of rotavirus vaccination in El Salvador* *per Ministry of Health vaccine administration data

Rotavirus Trends: Large Reduction in Lab Confirmed Rotavirus Admissions among children < 5, El Salvador 70-80% reduction in rotavirus hospitalizations children < 5 years

Will Vaccination Impact Diarrhea Mortality? Not assessed in clinical trials Difficult to evaluate

Mexico Pre-vaccine, annual median of ~1800 diarrhea deaths are reported among children < 5 years RV1 introduction in 2006 & 2007 By December 2007, 74% of children under 1 year of age received 1 dose Compared diarrhea mortality before and after vaccination Richardson, V et al. NEJM 2010: 362; 299-305

What happened to Total Diarrhea Deaths after Vaccination, 2008-2009? Vaccine Introduction (May 2007) 2008 2009

Summary Rotavirus vaccination is making a substantial real-world impact against diarrhea hospitalizations and deaths in the Americas Gradient of protection that correlates with socioeconomic status—reasons remain unclear Impact data from the Americas provide promise and highlight challenges for Asia & Africa

Acknowledgements CDC Viral Gastro Group RVP Team – PATH PanAmerican Health Organization/WHO Nicaragua Ministry of Health El Salvador, Ministry of Health IMIP, Recife Brazil Mexico Ministry of Health GAVI