Determinants of Inapparent and Symptomatic Dengue Infection in a Prospective Study of Primary School Children in Kamphaeng Phet, Thailand

Timothy P Endy,Robert V Gibbons,Daniel H Libraty,Richard G Jarman,Ananda Nisalak,Sharone Green,Stephen J Thomas,Alan L Rothman,Kathryn B Anderson,In-Kyu Yoon,Eva Harris

doi:10.1371/journal.pntd.0000975

Abstract

BackgroundDengue viruses are a major cause of morbidity in tropical and subtropical regions of the world. Inapparent dengue is an important component of the overall burden of dengue infection. It provides a source of infection for mosquito transmission during the course of an epidemic, yet by definition is undetected by health care providers. Previous studies of inapparent or subclinical infection have reported varying ratios of symptomatic to inapparent dengue infection.Methodology/Principal FindingsIn a prospective study of school children in Northern Thailand, we describe the spatial and temporal variation of the symptomatic to inapparent (S:I) dengue illness ratio. Our findings indicate that there is a wide fluctuation in this ratio between and among schools in a given year and within schools over several dengue seasons. The most important determinants of this S:I ratio for a given school were the incidence of dengue infection in a given year and the incidence of infection in the preceding year. We found no association between the S:I ratio and age in our population.Conclusions/SignificanceOur findings point to an important aspect of virus-host interactions at either a population or individual level possibly due to an effect of heterotypic cross-reactive immunity to reduce dengue disease severity. These findings have important implications for future dengue vaccines.

Highlights

Dengue virus infection can manifest as a clinically inapparent infection, an undifferentiated febrile illness, classic dengue fever (DF), or its more severe form, dengue hemorrhagic fever (DHF) [1]
Inapparent dengue infection is defined as a dengue virus infection that results in no clinical manifestations or an illness that is mild and is not associated with a visit to a health care provider or an absence from school or work due to illness
Dengue viruses are a major cause of illness and hospitalizations in tropical and subtropical regions of the world

Summary

Introduction

Dengue virus infection can manifest as a clinically inapparent infection, an undifferentiated febrile illness, classic dengue fever (DF), or its more severe form, dengue hemorrhagic fever (DHF) [1]. Determining the incidence of inapparent dengue infection requires detailed prospective cohort studies of populations in dengue endemic areas that can detect dengue infection by paired dengue antibody serology without an associated clinical illness during the time of seroconversion. Few studies of this scope have been performed and our knowledge on the full burden of dengue infection is limited. Inapparent dengue is an important component of the overall burden of dengue infection It provides a source of infection for mosquito transmission during the course of an epidemic, yet by definition is undetected by health care providers. Previous studies of inapparent or subclinical infection have reported varying ratios of symptomatic to inapparent dengue infection

Methods

Results

Discussion

Conclusion