Abstract
Revealing the patterns and determinants of the spread of dengue virus (DENV) at local scales is central to understanding the epidemiology and evolution of this major human pathogen. We performed a phylogenetic analysis of the envelope (E) genes of DENV-1, -2, -3, and -4 isolates (involving 97, 23, 5, and 74 newly collected sequences, respectively) sampled from school-based cohort and village-based cluster studies in Kamphaeng Phet, Thailand, between 2004 and 2007. With these data, we sought to describe the spatial and temporal patterns of DENV spread within a rural population where a future vaccine efficacy trial is planned. Our analysis revealed considerable genetic diversity within the study population, with multiple lineages within each serotype circulating for various lengths of time during the study period. These results suggest that DENV is frequently introduced into both semi-urban and rural areas in Kamphaeng Phet from other populations. In contrast, the persistence of viral lineages across sampling years was observed less frequently. Analysis of phylogenetic clustering indicated that DENV transmission was highly spatially and temporally focal, and that it occurred in homes rather than at school. Overall, the strength of temporal clustering suggests that seasonal bottlenecks in local DENV populations facilitate the invasion and establishment of viruses from outside of the study area, in turn reducing the extent of lineage persistence.
Highlights
Dengue is the leading cause of mosquito-borne viral disease worldwide, and dengue fever (DF) and dengue hemorrhagic fever (DHF) continue to increase in both incidence and geographic range
To investigate the genetic diversity and structure of dengue virus (DENV) populations circulating in Kamphaeng Phet (Figure 1) from 2004 to 2007, we sequenced and analyzed the E genes of viruses collected during school-based surveillance and geographicallybased community cluster studies
This pattern generally reflects the relative proportions of DENV isolated through passive surveillance across the region during the period of sampling, passive surveillance data from the Kamphaeng Phet Provincial Hospital detected all four serotypes circulating each year (Figure 2)
Summary
Dengue is the leading cause of mosquito-borne viral disease worldwide, and dengue fever (DF) and dengue hemorrhagic fever (DHF) continue to increase in both incidence and geographic range. Recent estimates are that over 50 million DENV infections occur each year, including 500,000 hospitalizations for DHF, primarily among children [1,2]. Dengue viruses (DENV) are single-stranded, positive-sense RNA viruses (family Flaviviridae, genus Flavivirus) that are comprised of four antigenically distinct serotypes (or viruses; DENV-1, DENV-2, DENV-3, and DENV-4) that co-circulate in many endemic areas in the tropics and sub-tropics. The phenomenon of co-circulation of multiple DENV serotypes is referred to as hyperendemicity and is believed to increase the risk of severe disease in a population [3,4,5]. Molecular epidemiological studies of global DENV populations play a key role in understanding the Author Summary
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