Background: Dengue virus infection is a major public health problem. A hypothesis put forward for severe dengue is the cytokine storm, a sudden increase in cytokines that induces vascular permeability. Previous studies and our recent meta-analysis showed that IL-6, IL-8, IFNγ, TNFα, VEGF-A and VCAM-1 are associated with dengue shock syndrome. Therefore, in this study we aim to validate the association of these cytokines with severe dengue. Methods & Findings: In a hospital based-case control study in Vietnam, children with dengue fever, other febrile illness and healthy controls were recruited. Dengue virus infection was confirmed by several diagnostic tests. Multiplex immunoassay using Luminex technology was used to measure cytokines simultaneously. A positive association with dengue shock syndrome was found for VCAM-1, whereas a negative association was found for IFNγ. Furthermore, multivariate logistic analysis also showed that VCAM-1 and IFNγ were independently correlated with dengue shock syndrome. Conclusion: IFNγ and VCAM-1 were associated with dengue shock syndrome, although their role in the severe dengue pathogenesis remains unclear. Additional studies are required to shed further light on the function of these cytokines in severe dengue.

Background: Mortality in tropical countries varies considerably from season to season. As many of these countries have seen mortality moving from child to old-age mortality, we have studied seasonal variation in child and old-age mortality in a rural area in Ghana that currently undergoes an epidemiologic transition. Methods:In an annual survey from 2002 through to 2011, we followed 29 642 individuals and obtained the cause and month of death from 1406 deceased individuals by making use of verbal autopsies.Results: When comparing the seasons, we observed a trend for higher mortality during the wet season. When comparing separate months, we observed 34% more deaths than expected in September (95% CI 1.04-1.69; p¼0.024) at the end of the wet season and 43% more deaths in April (95% CI 1.13-1.80; p¼0.004) at the end of the dry season, while there were 42% less deaths than expected in December (95% CI 0.52-0.70; p¼0.003), shortly after the wet season. Cause-specific analysis indicated that the peak at the end of the wet season was due to excess mortality from infectious diseases in children and older people alike, whereas the peak in old-age mortality at the end of the dry season was due to non-infectious causes in older people only.Conclusions: Taken together, our data suggest that during the epidemiologic transition, mortality not only shifts from child to old-age and from infectious to non-infectious, but also from the wet to the dry season.