Decline in Diarrhea Mortality and Admissions after Routine Childhood Rotavirus Immunization in Brazil: A Time-Series Analysis

Greice Madeleine Ikeda Do Carmo,Wanderson Kleber De Oliveira,Catherine Yen,Alessandra Araújo Siqueira,Eduardo Hage Carmo,Lucia Helena De Oliveira,Brendan Flannery,Manish Patel,Juan José Cortez-Escalante,Jennifer Cortes,Ben Lopman,Lorenz Von Seidlein

doi:10.1371/journal.pmed.1001024

Abstract

In 2006, Brazil began routine immunization of infants <15 wk of age with a single-strain rotavirus vaccine. We evaluated whether the rotavirus vaccination program was associated with declines in childhood diarrhea deaths and hospital admissions by monitoring disease trends before and after vaccine introduction in all five regions of Brazil with varying disease burden and distinct socioeconomic and health indicators. National data were analyzed with an interrupted time-series analysis that used diarrhea-related mortality or hospitalization rates as the main outcomes. Monthly mortality and admission rates estimated for the years after rotavirus vaccination (2007-2009) were compared with expected rates calculated from pre-vaccine years (2002-2005), adjusting for secular and seasonal trends. During the three years following rotavirus vaccination in Brazil, rates for diarrhea-related mortality and admissions among children <5 y of age were 22% (95% confidence interval 6%-44%) and 17% (95% confidence interval 5%-27%) lower than expected, respectively. A cumulative total of ~1,500 fewer diarrhea deaths and 130,000 fewer admissions were observed among children <5 y during the three years after rotavirus vaccination. The largest reductions in deaths (22%-28%) and admissions (21%-25%) were among children younger than 2 y, who had the highest rates of vaccination. In contrast, lower reductions in deaths (4%) and admissions (7%) were noted among children two years of age and older, who were not age-eligible for vaccination during the study period. After the introduction of rotavirus vaccination for infants, significant declines for three full years were observed in under-5-y diarrhea-related mortality and hospital admissions for diarrhea in Brazil. The largest reductions in diarrhea-related mortality and hospital admissions for diarrhea were among children younger than 2 y, who were eligible for vaccination as infants, which suggests that the reduced diarrhea burden in this age group was associated with introduction of the rotavirus vaccine. These real-world data are consistent with evidence obtained from clinical trials and strengthen the evidence base for the introduction of rotavirus vaccination as an effective measure for controlling severe and fatal childhood diarrhea.

Highlights

In July 2009, the World Health Organization recommended introduction of rotavirus vaccines into national immunization programs of all countries worldwide for controlling severe rotavirus disease, which accounts for approximately one-third of the 1.34 million diarrhea deaths and 9 million hospital admissions worldwide among children younger than 5 y of age [1,2,3]
After the introduction of rotavirus vaccination for infants, significant declines for three full years were observed in under-5-y diarrhea-related mortality and hospital admissions for diarrhea in Brazil
The largest reductions in diarrhea-related mortality and hospital admissions for diarrhea were among children younger than 2 y, who were eligible for vaccination as infants, which suggests that the reduced diarrhea burden in this age group was associated with introduction of the rotavirus vaccine

Summary

Introduction

In July 2009, the World Health Organization recommended introduction of rotavirus vaccines into national immunization programs of all countries worldwide for controlling severe rotavirus disease, which accounts for approximately one-third of the 1.34 million diarrhea deaths and 9 million hospital admissions worldwide among children younger than 5 y of age [1,2,3]. Not replacing the urgent need to provide access to clean water and improved sanitation for all, vaccination programs that protect young children against some infections that cause diarrhea, such as rotavirus, which accounts for one-third of all child deaths caused by diarrhea, are a pragmatic way forward. As large clinical trials have shown the safety and efficacy of rotavirus vaccines in population settings, in July 2009, the World Health Organization recommended including rotavirus vaccines into every country’s national immunization programs

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