Abstract
Accurate estimates of rotavirus incidence in infants are crucial given disparities in rotavirus vaccine effectiveness from low-income settings. Sero-surveys are a pragmatic means of estimating incidence however serological data is prone to misclassification. This study used mixture models to estimate incidence of rotavirus infection from anti-rotavirus immunoglobulin A (IgA) titres in infants from Vellore, India, and Karonga, Malawi. IgA titres were measured using serum samples collected at 6 month intervals for 36 months from 373 infants from Vellore and 12 months from 66 infants from Karonga. Mixture models (two component Gaussian mixture distributions) were fit to the difference in titres between time points to estimate risk of sero-positivity and derive incidence estimates. A peak incidence of 1.05(95% confidence interval [CI]: 0.64, 1.64) infections per child-year was observed in the first 6 months of life in Vellore. This declined incrementally with each subsequent time interval. Contrastingly in Karonga incidence was greatest in the second 6 months of life (1.41 infections per child year [95% CI: 0.79, 2.29]). This study demonstrates that infants from Vellore experience peak rotavirus incidence earlier than those from Karonga. Identifying such differences in transmission patterns is important in informing vaccine strategy, particularly where vaccine effectiveness is modest.
Highlights
Prior to wide-spread rotavirus vaccination, rotavirus was responsible for over 450 000 deaths in young children, with 95% of these deaths occurring in low income, GAVI-the Vaccine Alliance (GAVI)-eligible countries[1]
Rotavirus-specific immunoglobulin A (IgA) titres were quantitated against a standard curve and positive, negative and uninfected cell lysate controls were added to each plate
Mixture models fit to the Vellore data set over 3 years showed an initial high frequency of rotavirus infection, with a risk of seroconversion of 0.41 (95% confidence interval [confidence intervals (CI)]: 0.27, 0.56) between birth and 6 months, which declined with each subsequent time interval (Fig 2 and Table 1)
Summary
Prior to wide-spread rotavirus vaccination, rotavirus was responsible for over 450 000 deaths in young children, with 95% of these deaths occurring in low income, GAVI-the Vaccine Alliance (GAVI)-eligible countries[1]. Two live oral vaccines are currently globally licenced for the prevention of severe rotavirus gastroenteritis, a monovalent and a pentavalent formulation.
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