Case-control Study of the Effectiveness of Vaccination With Pentavalent Rotavirus Vaccine in Nicaragua

Merck Research Laboratories, North Wales, PA 19486, USA.
The Pediatric Infectious Disease Journal (Impact Factor: 2.72). 07/2011; 30(11):e209-15. DOI: 10.1097/INF.0b013e31822a8527
Source: PubMed


In 2006, Merck & Co., Inc., partnered with the Nicaraguan Ministry of Health to demonstrate the public health impact of routine universal vaccination by delivering more than 1.3 million doses of the oral, pentavalent rotavirus vaccine (RV5) in a 3-year period.
A matched case-control study evaluated the effectiveness of RV5 in reducing the risk for severe wild-type rotavirus gastroenteritis (RGE) resulting in hospitalizations and emergency department visits among children who completed the recommended 3-dose regimen as part of the routine national vaccine program. Cases were identified from 6 hospitals from February 2007 to October 2009 and were age-matched with hospital controls and community controls. Vaccine effectiveness was calculated using conditional logistic regression.
Three hundred RGE cases eligible for analysis were matched to 792 hospital and 851 community controls. Vaccine coverage of RV5 in the community reached 92%. Vaccine effectiveness during 2 years of follow-up against severe disease in children receiving 3 doses of RV5 was 87% (95% confidence interval [CI], 74-93) for community controls, 64% (95% CI, 44-78) for hospital controls, and 76% (95% CI, 63-84) when the groups were combined. For the combined groups, vaccine effectiveness was 85% (95% CI, 66-93) among children <12 months old at the time of RGE onset.
The Merck-Nicaragua Rotavirus Vaccine Partnership promoted rapid and widespread uptake of a novel vaccine in a developing country. Vaccine effectiveness was greatest for children younger than 12 months of age who were at the highest risk for severe rotavirus disease.

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    • "Yen, 2011 33 Mexico 2010 Hospital Healthy, neighbourhood-matched G9P[4] Middle-income countries, RV5 Mast, 2011 34 Nicaragua 2007–09 Hospital or emergency department, and Vesikari score ≥11 Acute gastroenteritis, rotavirus negative, hospital or emergency department; acute non-diarrhoeal infection, hospital or emergency department; healthy, neighbourhood-matched G1, G2, G3, G4, G9, P[4], P[6], P[8], P[5] "
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    ABSTRACT: Background Concerns exist about whether monovalent (RV1) and pentavalent (RV5) rotavirus vaccines provide adequate protection against diverse strains and whether vaccine introduction will lead to selective pressure. We aimed to investigate the distribution of rotavirus strains and strain-specific rotavirus vaccine effectiveness after vaccine introduction. Methods We did a systematic review of published work to assess the strain-specific effectiveness of RV1 and RV5 rotavirus vaccines. We classified strains as homotypic, partly heterotypic, and fully heterotypic based on the amount of antigen-matching between strain and vaccine. When studies reported vaccine effectiveness against single antigens (G-type or P-type), we categorised them as either single-antigen vaccine type or single-antigen non-vaccine type. Our primary outcome was strain-specific vaccine effectiveness, comparing effectiveness of homotypic strains with fully or partly heterotypic strains. A secondary outcome was the prevalence of rotavirus strains after vaccine introduction. We estimated pooled odds ratios using random-effect regression models, stratified by country income level and vaccine type, and tested for differences in strain-specific vaccine effectiveness. We assessed strain distribution trends from surveillance reports. Findings In high-income countries, RV1 pooled vaccine effectiveness was 94% (95% CI 80–98) against homotypic strains, 71% (39–86) against partly heterotypic strains, and 87% (76–93) against fully heterotypic strains. In middle-income settings, respective pooled data were 59% (36–73), 72% (58–81), and 47% (28–61). In high-income countries, RV5 vaccine effectiveness was 83% (78–87) against homotypic strains, 82% (70–89) against single-antigen vaccine type strains, 82% (70–89) against partly heterotypic strains, and 75% (47–88) against single-antigen non-vaccine type strains. In middle-income settings, RV5 vaccine effectiveness was 70% (58–78) against single-antigen vaccine type strains, 37% (10–56) against partly heterotypic strains, and 87% (38–97) against single-antigen non-vaccine type strains. No difference was noted in vaccine effectiveness for either RV1 or RV5 in any setting (all p>0·05). Prevalent strains in countries using RV1 were G2P[4] (2198 of 4428, 50%) and G1P[8] (953, 22%), and those in countries using RV5 were G1P[8] (1280 of 3875, 33%) and G2P[4] (1169, 30%). Sustained predominance of a single strain was not recorded. Interpretation RV1 and RV5 exert similar effectiveness against homotypic and heterotypic rotavirus strains. Persistence of specific strains was not recorded, suggesting vaccine-induced selective pressure did not occur. Expansion of rotavirus surveillance efforts to low-income countries and ongoing surveillance are crucial to identify emergence of new strains and to assess strain-specific vaccine effectiveness in various settings. Funding None.
    Full-text · Article · Sep 2014 · The Lancet Infectious Diseases
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    • "Moreover, in hospital wastewater, NoV was detected in 46.4%, whereas RV was only detected in 7.1% of the samples. This suggests a low frequency of severe hospital-requiring RV infections in the community as recently reported [30]. Furthermore, differences were not only observed in virus prevalence, but also in virus concentration; in average RV concentrations were lower as compared to NoV concentrations, both in hospital and in community wastewater. "
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    ABSTRACT: Rotavirus (RV) and norovirus (NoV) are major causes of pediatric diarrhea and are altogether associated with approximately 800,000 deaths in young children every year. In Nicaragua, national RV vaccination program using the pentavalent RV5 vaccine from Merck was implemented in October 2006. To determine whether RV vaccination decreased the overall number of RV infections, we investigated the occurrence of RV and NoV in wastewater in the city of León from July 2007 to July 2008 and compared these data with pre-vaccination data. The major finding was the low prevalence of RV compared to NoV in all sampling points (11% vs 44%, p<0.05), and that RV concentration was lower as compared to NoV. RV was observed mainly during the rainy season (July-September), and the majority of all RV detected (6/9) belonged to subgroup (SG) I. The partial VP7-gene obtained from one RV positive sample was similar (99% nt identity) to a G6 VP7-gene of bovine origin and similar to the corresponding gene of the vaccine strain (98%). Furthermore RV G-types 2 and 4 were found in the incoming wastewater. NoV strains were detected throughout the year, of which a majority (20/21) were of genotype GII.4. We conclude that the introduction of RV vaccination reduced the transmission of RV in the community in Nicaragua. However, the burden of diarrhea in the country remains high, and the high prevalence of NoVs in hospital and municipal wastewater is noteworthy. This study highlights the need for further assessment of NoV following RV vaccine introduction.
    Full-text · Article · Oct 2011 · PLoS ONE
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    ABSTRACT: Rotavirus infection is the most common cause of severe diarrhea disease in infants and young children worldwide and continues to have a major global impact on childhood morbidity and mortality. Two effective rotavirus vaccines are available and recommended for routine immunization of all infants. These vaccines have been introduced in both developed and developing countries. As rotavirus vaccines are implemented, studies have been undertaken that assess the effects of vaccination on rotavirus disease in children. This review summarizes the results of these studies. Studies that assess health impact, indirect benefits, and strain changes after the introduction of rotavirus vaccine have been reported. In industrialized countries, rotavirus vaccination has led to dramatic drops in severe rotavirus-related hospitalizations and has reduced emergency room visits. Data from clinical trials in developing counties in Asia and Africa have demonstrated that rotavirus vaccines significantly reduce severe diarrhea episodes due to rotavirus. Herd (community) immunity has also been noted after routine rotavirus immunization in several countries. There have been no significant strain shifts or escape mutants noted since the introduction of rotavirus vaccines. Two well tolerated and effective rotavirus vaccines have reduced the health burden of rotavirus gastroenteritis in both developed and developing countries.
    No preview · Article · Dec 2011 · Current opinion in pediatrics
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