The impact of city-wide deployment of Wolbachia-carrying mosquitoes on arboviral disease incidence in Medellín and Bello, Colombia: study protocol for an interrupted time-series analysis and a test-negative design study

Abstract

Background: Dengue, chikungunya and Zika are viral infections transmitted by Aedes aegypti mosquitoes, and present major public health challenges in tropical regions. Traditional vector control methods have been ineffective at halting disease transmission. The World Mosquito Program has developed a novel approach to arbovirus control using Ae. aegypti stably transfected with the Wolbachia bacterium, which have significantly reduced ability to transmit dengue, Zika and chikungunya in laboratory experiments. Field releases in eight countries have demonstrated Wolbachia establishment in local Ae. aegypti populations. Methods: We describe a pragmatic approach to measuring the epidemiological impact of city-wide Wolbachia deployments in Bello and Medellín, Colombia. First, an interrupted time-series analysis will compare the incidence of dengue, chikungunya and Zika case notifications before and after Wolbachia releases, across the two municipalities. Second, a prospective case-control study using a test-negative design will be conducted in one quadrant of Medellín. Three of the six contiguous release zones in the case-control area were allocated to receive the first Wolbachia deployments in the city and three to be treated last, approximating a parallel two-arm trial for the >12-month period during which Wolbachia exposure remains discordant. Allocation, although non-random, aimed to maximise balance between arms in historical dengue incidence and demographics. Arboviral disease cases and arbovirus-negative controls will be enrolled concurrently from febrile patients presenting to primary care, with case/control status classified retrospectively following laboratory diagnostic testing. Intervention effect is estimated from an aggregate odds ratio comparing Wolbachia-exposure odds among test-positive cases versus test-negative controls. Discussion: The study findings will add to an accumulating body of evidence from global field sites on the efficacy of the Wolbachia method in reducing arboviral disease incidence, and can inform decisions on wider public health implementation of this intervention in the Americas and beyond. Trial registration: ClinicalTrials.gov: NCT03631719. Registered on 15 August 2018.

Intrinsic factors driving mosquito vector competence and viral evolution: a review

“…Similar field trials have seen successful Ae. aegypti population replacement in other parts of Australia, Brazil, Colombia, Malaysia, Indonesia, and Vietnam, with some reporting a reduction in endemic arbovirus transmission (CHIKV and DENV in Brazil, DENV in Australia, Indonesia, and Malaysia) (O'Neill et al, 2018;Nazni et al, 2019;Velez et al, 2019;Tantowijoyo et al, 2020;Pinto et al, 2021;Utarini et al, 2021). A current criticism against population replacement, is that it may prevent future deployment of population suppression in the same area.…”

A tangled threesome: understanding arbovirus infection in Aedes spp. and the effect of the mosquito microbiota

“…The use of Wolbachia (wMel) is a successful and promising strategy for reducing arbovirus transmission (Aliota et al, 2016 ; Flores and O'Neill, 2018 ; Velez et al, 2020 ). However, it is important to characterize the interference mechanism with arbovirus development, as well as the fitness costs of the bacteria in their new host, interaction with the mosquito microbiota at the local level, the effect of local climatic conditions on Wolbachia infection, and interaction with other components of the mosquito microbiota.…”

Reduced dengue incidence following city-wide wMel Wolbachia mosquito releases throughout three Colombian cities: Interrupted time series analysis and a prospective case-control study

“…In Colombia, pilot Wolbachia deployments were undertaken in several neighbourhoods in the municipality of Bello in 2015–2016. The declaration of Zika as a public health emergency by the WHO in early 2016 [ 21 ] accelerated the planned expansion of pilot releases to city-scale, with the aim of optimising methods for scaled deployment under operational conditions while also evaluating the epidemiological effectiveness against Aedes- borne viruses [ 22 ]. We report here the public health outcomes of city-wide deployments of w Mel-infected Ae .…”