Dengue diversity across spatial and temporal scales: Local structure and the effect of host population size

Abstract

A fundamental mystery for dengue and other infectious pathogens is how observed patterns of cases relate to actual chains of individual transmission events. These pathways are intimately tied to how strains interact and compete across spatial scales. Phylogeographic methods have been used to characterize pathogen dispersal at global and regional scales, but have yielded few insights into the local spatio-temporal structure of endemic transmission. Using geolocated genotype (N=800) and serotype (N=17,291) data, we show that in Bangkok, Thailand, 60% of cases living <200m apart come from the same transmission chain, versus 3% of cases separated by 1–5km. At distances <200m from a case (enclosing an average of 1,300 people in Bangkok) the effective number of chains is 1.7. This increases by 7-fold for each 10-fold increase in enclosed population, whether due to density or increased area; though increases in density over 7,000 people per km2 do not lead to additional chains. Within Thailand these chains quickly mix, and by the next dengue season viral lineages are no longer highly spatially structured within the country. In contrast, viral flow to neighboring countries is limited. These findings are consistent with local, density dependent transmission; and implicate densely populated communities as key sources of viral diversity with home location the focal point of transmission. These findings have important implications for targeted vector control and active surveillance.

Reconstruction of antibody dynamics and infection histories to evaluate dengue risk

“…This provides strong support of our modeling framework by suggesting that the model can correctly identify spatio-temporal clustering of otherwise undetected infections. These findings also support focal transmission, irrespective of disease outcome 13,30,31 . The approach presented here will be applicable across disease systems where longitudinal titer data exists, allowing a wide range of insights into fundamental questions of disease ecology and risk.…”

“…These findings are consistent with a reduced risk of disease from DENV-4 compared to other serotypes resulting in a largely silent DENV-4 epidemic. This is supported by a phylogenetic analysis that found DENV-4 was widespread in Thailand throughout this period (Figure S4 in Salje et al , 13 ). This suggests the serotype distributions from hospital-based or community-based surveillance may not be representative of infections in the population and supports previous evidence that the transmissibility of a serotype can be delinked from the propensity to cause symptomatic and/or severe disease 14,15 .…”

Route of inoculation and mosquito vector exposure modulate dengue virus replication kinetics and immune responses in rhesus macaques

“…Vero passage-2 stocks, following the original isolation in C6/36 cells, were used for infection of NHP and mosquitoes. The stocks were sequenced using DENV1 and DENV2 specific primers, respectively, on the Illumina MiSeq platform as described in [78] to authenticate contents. The genomes were assembled using an in-house developed reference mapping pipeline, ngs_mapper (https://github.com/ VDBWRAIR/ngs_mapper).…”

Codon adaptation biases among sylvatic and urban genotypes of Dengue virus type 2

“…Differential selection pressures exerted by the complex interplay of distinct virus factors, such as infection efficiency, population density and herd immunity (Plowright et al, 2017;Salazar et al, 2010). For example, a recent study reported by Salje et al (2017) demonstrated the association between population density and the establishment of transmission chains. The increase in mosquito populations has also been identified as a potential determinant of the emergence and increased transmission of arbovirus, particularly in immunologically naïve human populations (Dudas et al, 2018;Pettersson et al, 2016).…”