Frequent In-Migration and Highly Focal Transmission of Dengue Viruses among Children in Kamphaeng Phet, Thailand

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.

Improving Dengue Virus Capture Rates in Humans and Vectors in Kamphaeng Phet Province, Thailand, Using an Enhanced Spatiotemporal Surveillance Strategy

“…This finding supports the concept that DENV transmission is focal and serotype-conserved in space and time. 17,24 The authors' acknowledge that the assumption that each initiating case represents the true index (i.e., first) infection in each spatiotemporal group may be incorrect. Because most DENV infections are asymptomatic or not clinically severe enough to drive health-care-seeking behavior, it is possible the initiating case simply represents the first clinically overt infection in that defined geographic area.…”

Estimating infectious disease transmission distances using the overall distribution of cases

“…Further, if there exists an intermediary vector or reservoir (such as the case of dengue, chikungunya or cholera), sequential cases in a transmission chain may never have been in contact with each other. Phylogeographic methods have been developed to estimate rates of viral movement across countries or continents under these conditions (Faye et al, 2015; Rabaa et al, 2013). However, these approaches have not yet been able to reliably capture micro-scale dynamics except in isolated settings such as hospital-based outbreaks (Cotten et al, 2013; Iles et al, 2014; Pybus et al, 2012; Rabaa et al, 2010), and may be impossible where genome mutation rates are particularly low or high relative to the generation time.…”

Retrospective screening of acute undifferentiated fever serum samples with universal flavivirus primers

“…The importation of DENV lineages to Thailand from different countries has been observed previously [16].…”

“…As the samples were all collected between July 2011 and December 2012, it can be assumed that these three viruses were circulating simultaneously in Thailand, consistent with the known hyper-endemic nature of DENV in Thailand [16]. While no case of DENV 4 was detected, this might be a reflection of the total number of DENV positive samples, and it cannot be concluded that DENV 4 was not circulating during the study period.…”