Projecting the effectiveness of RotaTeq® against rotavirus-related hospitalisations in Brazil

Abstract

RotaTeq® (Merck & Company, Inc, Whitehouse Station, NJ, USA) is an oral pentavalent rotavirus vaccine (RV5) that has shown high and consistent efficacy in preventing rotavirus gastroenteritis (RGE) in randomised clinical trials previously conducted in industrialised countries with high medical care resources. To date, the efficacy and effectiveness data for RV5 are available in some Latin American countries, but not Brazil. In this analysis, we projected the effectiveness of RV5 in terms of the percentage reduction in RGE-related hospitalisations among children less than five years of age in four regions of Brazil, using a previously validated mathematical model. The model inputs included hospital-based rotavirus surveillance data from Goiânia, Porto Alegre, Salvador and São Paulo from 2005-2006, which provided the proportions of rotavirus attributable to serotypes G1, G2, G3, G4 and G9, and published rotavirus serotype-specific efficacy from the Rotavirus Efficacy and Safety Trial. The model projected an overall percentage reduction of 93% in RGE-related hospitalisations, with an estimated annual reduction in RGE-related hospitalisations between 42,991-77,383 in the four combined regions of Brazil. These results suggest that RV5 could substantially prevent RGE-related hospitalisations in Brazil

The use of an adequate mathematical model is crucial to evaluate vaccine effectiveness

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A recent paper by El Khoury et al (2011) reported estimates of effectiveness of the RotaTeq ® vaccine against rotavirus-related hospitalisations in Brazil of 93%. After carefully examination of the data presented in this paper, it appears that there are important limitations on this study leading to a potential overestimation of the reported vaccine effectiveness.

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“…Indeed, differences in access to health care services and differences in health seeking behaviour between locations in Brazil may alter the disease severity presentation of hospitalised children with rotavirus diarrhoea and therefore impact the estimated vaccine efficacy. Thus, it is a daring assumption to conclude that the "true" rotavirus strain distribution in Brazil is equivalent to a weighted average of the strain distributions observed in the four cities studied given the known dynamics of rotavirus strain circulation profile in Brazil (Leite et al 2008).El Khoury et al (2011) acknowledged that although the model utilized was developed to estimate projected efficacy, they used the term "projected effectiveness" throughout the paper because their objective was to project the real-life impact of RotaTeq ® vaccine on the reduction of rotavirus-related hospitalisations. This is an important shortcoming of the El Khoury el al.…”

“…In summary, we agree the estimated type-adjusted vaccine efficacy of RotaTeq ® vaccine (93%) may be closer to the real life value for Brazil, than the original value observed in the REST study for Latin American countries (50.2%; 95% CI: < 0-99.1%) (Vesikari et al 2007). However, it is important to highlight that the model utilized by El Khoury et al (2011) was not intended to estimate real-life vaccine effectiveness, but rather efficacy estimates extrapolated from data obtained in a very controlled setting (clinical randomized controlled trial) covering mainly study sites located outside Latin America. When mathematical models are used, it is always valuable to clearly understand the goals the model was developed for.…”

“…The model used was developed to project expected rotavirus vaccine efficacy in settings where applying unadjusted efficacy data could overestimate the benefits of immunisation. To generate a weighted efficacy estimate for Brazil, El Khoury et al (2011) used serotype-specific vaccine efficacy estimates against hospitalised rotavirus gastroenteritis (RGE) from the Rotavirus Efficacy and Safety Trial (REST) (Vesikari et al 2006) and the distribution of rotavirus types observed in four cities of Brazil (Goiânia, Porto Alegre, Salvador and São Paulo) from [2005][2006]. It is difficult to determine whether the strain-specific vaccine efficacy against hospitalised RGE observed in the REST study would be obtained if that study were performed in Brazil.…”

“…El Khoury et al (2011) acknowledged that although the model utilized was developed to estimate projected efficacy, they used the term "projected effectiveness" throughout the paper because their objective was to project the real-life impact of RotaTeq ® vaccine on the reduction of rotavirus-related hospitalisations. This is an important shortcoming of the El Khoury el al.…”