Association Between Pentavalent Rotavirus Vaccine and Severe Rotavirus Diarrhea Among Children in Nicaragua

CONTEXT: Pentavalent rotavirus vaccine (RV5), a live, oral attenuated vaccine, prevented 98% of severe rotavirus diarrhea in a trial conducted mainly in Finland and the United States. Nicaragua introduced RV5 in 2006, providing the first opportunity to assess the association between vaccination and rotavirus disease in a developing country. OBJECTIVE: To assess the association between RV5 vaccination and subsequent rotavirus diarrhea requiring overnight admission or intravenous hydration. DESIGN, SETTING, AND PARTICIPANTS: Case-control evaluation in 4 hospitals in Nicaragua from June 2007 to June 2008. Cases were children age-eligible to receive RV5 who were admitted or required intravenous hydration for laboratory-confirmed rotavirus diarrhea. For each case (n = 285), 1 to 3 neighborhood (n = 840) and hospital (n = 690) controls were selected. MAIN OUTCOME MEASURES: Primary outcome was the association of RV5 and rotavirus diarrhea requiring overnight admission or intravenous hydration in the emergency department. Secondary analysis further classified disease as severe and very severe. We computed the matched odds ratio of vaccination in cases vs controls. Vaccine effectiveness was estimated using the formula 1 - matched odds ratio x 100%. RESULTS: Of the 285 rotavirus cases, 265 (93%) required hospitalization; 251 (88%) received intravenous hydration. A single rotavirus strain (G2P4) was identified in 88% of the cases. Among cases and controls, respectively, 18% and 12% were unvaccinated, 12% and 15% received 1 dose of RV5, 15% and 17% received 2 doses, and 55% and 57% received 3 doses. Vaccination with 3 doses was associated with a lower risk of rotavirus diarrhea requiring overnight admission or intravenous hydration (odds ratio OR, 0.54; 95% confidence interval CI, 0.36-0.82). Of the 285 rotavirus cases, 191 (67%) were severe and 54 (19%) were very severe. A progressively lower risk of severe (OR, 0.42; 95% CI, 0.26-0.70) and very severe rotavirus diarrhea (OR, 0.23; 95% CI, 0.08-0.61) was observed after RV5 vaccination. Thus, effectiveness of 3 doses of RV5 against rotavirus disease requiring admission or treatment with intravenous hydration was 46% (95% CI, 18%-64%); against severe rotavirus diarrhea, 58% (95% CI, 30%-74%); and against very severe rotavirus diarrhea, 77% (95% CI, 39%-92%). CONCLUSION: Vaccination with RV5 was associated with a lower risk of severe rotavirus diarrhea in children younger than 2 years in Nicaragua but to a lesser extent than that seen in clinical trials in industrialized countries.