Research Article: Relationship between Transmission Intensity and Incidence of Dengue Hemorrhagic Fever in Thailand

Date Published: July 16, 2008

Publisher: Public Library of Science

Author(s): Suwich Thammapalo, Yoshiro Nagao, Wataru Sakamoto, Seeviga Saengtharatip, Masaaki Tsujitani, Yasuhide Nakamura, Paul G. Coleman, Clive Davies, Mercedes Pascual

Abstract: BackgroundDengue is the most prevalent mosquito-borne virus, and potentially fatal dengue hemorrhagic fever (DHF) occurs mainly in secondary infections. It recently was hypothesized that, due to the presence of cross-immunity, the relationship between the incidence of DHF and transmission intensity may be negative at areas of intense transmission. We tested this hypothesis empirically, using vector abundance as a surrogate of transmission intensity.Methodology/Principal FindingsHouse Index (HI), which is defined as the percentage of households infested with vector larvae/pupae, was obtained from surveys conducted on one million houses in Thailand, between 2002 and 2004. First, the utility of HI as a surrogate of transmission intensity was confirmed because HI was correlated negatively with mean age of DHF in the population. Next, the relationship between DHF incidence and HI was investigated. DHF incidence increased only up to an HI of about 30, but declined thereafter. Reduction of HI from the currently maximal level to 30 would increase the incidence by more than 40%. Simulations, which implemented a recently proposed model for cross-immunity, generated results that resembled actual epidemiological data. It was predicted that cross-immunity generates a wide variation in incidence, thereby obscuring the relationship between incidence and transmission intensity. The relationship would become obvious only if data collected over a long duration (e.g., >10 years) was averaged.ConclusionThe negative relationship between DHF incidence and dengue transmission intensity implies that in regions of intense transmission, insufficient reduction of vector abundance may increase long-term DHF incidence. Further studies of a duration much longer than the present study, are warranted.

Partial Text: Dengue is the most prevalent vector-borne viral disease, the distribution of which has been expanding continually [1]. Dengue virus is transmitted by Aedes mosquitoes [2]–[4], which breed predominantly in water-holding containers within human habitats. Infections with dengue virus may manifest as dengue fever (DF), or the potentially more fatal dengue hemorrhagic fever (DHF). There are four serotypes of dengue virus, among which transient cross-protection exists [5]. Dengue virus is unique in that viral amplification in a primate host is enhanced dramatically in the presence of pre-existing immunity to a heterogeneous dengue serotype(s). This phenomenon, called antibody-dependent enhancement (ADE), had been reported initially in other arthropod-borne virus infections [6],[7]. In terms of dengue, ADE was demonstrated both by in vitro[8] and animal experiments [9]. Subsequently, pre-existing hetero-serotypic antibodies were shown to be associated with elevated risk for development of DHF [10].

Our analysis demonstrates that HI is a reliable indicator of transmission intensity, at least at the district level. The usefulness of HI is evident by its highly significant, inverse relationship to mean age, otherwise equivalent to a positive correlation between HI and transmission intensity. Our findings are consistent with observations from Singapore, where an increase in the mean age of patients with dengue infection was preceded by a substantial reduction in HI [13],[14].



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