![]() aegypti compared to areas that did not receive wMel deployments 23. In a recent randomized controlled trial in Yogyakarta, Indonesia, (the ‘Applying Wolbachia to Eliminate Dengue’ trial), the incidence of virologically-confirmed dengue cases was 77% lower in neighbourhoods where wMel was successfully introgressed into local Ae. ![]() Accumulating field evidence from randomized and non-randomized wMel deployments demonstrates a significant reduction in the incidence of dengue and other Aedes-borne diseases in communities where wMel has been established at a high level 19, 20, 21, 22, 23. aegypti have resulted in successful introgression of wMel into Ae. aegypti has been shown in the laboratory to reduce their transmission potential for dengue, chikungunya, Zika and Yellow fever viruses 14, 15, 16, 17, 18 and releases of wMel- Ae. Wolbachia ( wMel-strain) infection of Ae. A lack of evidence for the efficacy and optimal implementation of conventional approaches to Aedes control 11, 12 together with the challenge of sustaining these activities at scale and over the long term 13, helps explain the ongoing occurrence of dengue outbreaks worldwide in spite of the efforts of vector control programs.Īn alternative approach to the control of Aedes-borne diseases uses Wolbachia, a naturally occurring bacterium that is common in insect species but absent from Ae. The temporal scale of focal dengue transmission is important here, however, with some studies finding serological evidence for clustering of recent DENV infections but no excess of acute, prospectively-detected DENV infections 10, suggesting limited opportunity for reactive efforts to interrupt chains of transmission after detection of an index case. Peridomestic space spraying of insecticide is a mainstay of dengue control efforts in endemic settings, and the observed focal clustering of dengue cases provides a rationale for the common approach of targeted reactive insecticide spraying around the immediate neighbourhood of one or more notified dengue cases. Local mosquito population dynamics, and human population density, immunity and mobility 7, 8, 9 are understood to be key determinants of these patterns. A retrospective analysis of serotyped dengue cases in Bangkok 5 showed spatial dependence in both homotypic (same serotype) and heterotypic (different serotype) dengue cases at different time scales, reflecting complex interactions between local population immune profiles and dengue transmission. ![]() A prospective index-cluster study in rural Thailand 2 demonstrated highly focal DENV transmission among children residing within 100 m and 15 days of an index case. The temporal and spatial scale at which dengue case clustering occurs is informative about both the underlying transmission dynamics and the opportunity to intervene and interrupt transmission. These bionomic factors make households a primary location for DENV transmission risk and the focal nature of DENV transmission has been well observed 2, 3, 4, 5, 6. The four serotypes of dengue virus (DENV) are transmitted between humans primarily by the Aedes aegypti mosquito, a species that thrives in urban settings where breeding sites and human blood sources co-exist in close proximity. The disease burden is growing in both case load and countries affected 1. Introgression of wMel Wolbachia into Aedes aegypti mosquito populations interrupts focal dengue virus transmission leading to reduced case incidence the true intervention effect may be greater than the 77% efficacy measured in the primary analysis of the Yogyakarta trial.ĭengue places seasonal pressure on healthcare systems and public health resources throughout the tropical and subtropical world, with an estimated 100 million cases globally each year. In contrast, we find no evidence of spatiotemporal clustering among the 53 dengue cases (2838 controls) resident in the wMel-treated arm. potentially transmission-related) as compared to pairs occurring at any distance. Participant pairs enrolled within 30 days and 50 m had a 4.7-fold increase (compared to 95% CI on permutation-based null distribution: 0.1, 1.2) in the odds of being homotypic (i.e. We find evidence of spatial clustering up to 300 m among the 265 dengue cases (3083 controls) in the untreated trial arm. We analysed 318 serotyped and geolocated dengue cases (and 5921 test-negative controls) from a randomized controlled trial in Yogyakarta, Indonesia of wMel deployments. We tested the hypothesis that spatiotemporal clustering of homotypic dengue cases is disrupted by introduction of the arbovirus-blocking bacterium Wolbachia ( wMel-strain) into the Aedes aegypti mosquito population. Dengue exhibits focal clustering in households and neighborhoods, driven by local mosquito population dynamics, human population immunity, and fine scale human and mosquito movement.
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