Interactions between serotypes of dengue highlight epidemiological impact of cross-immunity

Abstract

Dengue, a mosquito-borne virus of humans, infects over 50 million people annually. Infection with any of the four dengue serotypes induces protective immunity to that serotype, but does not confer long-term protection against infection by other serotypes. The immunological interactions between serotypes are of central importance in understanding epidemiological dynamics and anticipating the impact of dengue vaccines. We analysed a 38-year time series with 12 197 serotyped dengue infections from a hospital in Bangkok, Thailand. Using novel mechanistic models to represent different hypothesized immune interactions between serotypes, we found strong evidence that infection with dengue provides substantial short-term cross-protection against other serotypes (approx. 1–3 years). This is the first quantitative evidence that short-term cross-protection exists since human experimental infection studies performed in the 1950s. These findings will impact strategies for designing dengue vaccine studies, future multi-strain modelling efforts, and our understanding of evolutionary pressures in multi-strain disease systems.

Impact of human mobility on the emergence of dengue epidemics in Pakistan

“…In the absence of serotype information, for example, we chose not to include immunological covariates in our model. As Pakistan moves toward an endemic transmission setting in the northeast of the country, however, serotype data will be increasingly important to determine how strain dynamics are likely to affect the likelihood of outbreaks (28). Indeed, we believe that the substantial lag time in Lahore we observed was probably due to the recent large outbreak in 2011, which may have generated substantial immunity and delayed the 2013 epidemic (16,29).…”

Quantifying the added value of climate information in a spatio-temporal dengue model

“…Consequently, the relative risk of clinical dengue 4-6 months later is reduced because of a reduced susceptible population, despite conditions propitious for dengue transmission. This may occur irrespective of the circulating serotype as homotypic immunity is believed to be life-long (Sabin, 1952) and heterotypic immunity is estimated to last from 3 months to a year (Reich et al, 2013;Sabin, 1952). The latter may not prevent infection, but rather reduce clinical disease (Endy et al, 2011;Grange et al, 2014;Sabin, 1952).…”

Assessing dengue vaccination impact: Model challenges and future directions

“…That is, ambiguities still exist relating to the various factors affecting dengue virus transmission and immunity, which mostly revolve around the short and long-term effects of a primary dengue virus infection on the immuno-epidemiology and pathology of subsequent infections. For example, it is commonly assumed that following an infection the host remains fully protected against reinfection by all other serotypes for a certain length of time (between 6 months and 2 years) [22][23][24] and that due to the phenomenon of antibody-dependent enhancement, severe infection outcomes are not only much more likely during secondary, heterologous infections but also much more transmissible. This view has recently been challenged, however [25]; and with the majority of dengue infections going unreported and much of the available epidemiological data based on clinical cases only, robust empirical evidence that conclusively relate age, prior exposure, infection pathology and viral transmission is still lacking.…”