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

Abstract

Background The introduction of Wolbachia (wMel strain) into Aedes aegypti mosquitoes reduces their capacity to transmit dengue and other arboviruses. Randomised and non-randomised studies in multiple countries have shown significant reductions in dengue incidence following field releases of wMel-infected Ae. aegypti. We report the public health outcomes from phased, large-scale releases of wMel-Ae. aegypti mosquitoes throughout three contiguous cities in the Aburrá Valley, Colombia. Methodology/Principal findings Following pilot releases in 2015–2016, staged city-wide wMel-Ae. aegypti deployments were undertaken in the cities of Bello, Medellín and Itagüí (3.3 million people) between October 2016 and April 2022. The impact of the Wolbachia intervention on dengue incidence was evaluated in two parallel studies. A quasi-experimental study using interrupted time series analysis showed notified dengue case incidence was reduced by 95% in Bello and Medellín and 97% in Itagüí, following establishment of wMel at ≥60% prevalence, compared to the pre-intervention period and after adjusting for seasonal trends. A concurrent clinic-based case-control study with a test-negative design was unable to attain the target sample size of 63 enrolled virologically-confirmed dengue (VCD) cases between May 2019 and December 2021, consistent with low dengue incidence throughout the Aburrá Valley following wMel deployments. Nevertheless, VCD incidence was 45% lower (OR 0.55 [95% CI 0.25, 1.17]) and combined VCD/presumptive dengue incidence was 47% lower (OR 0.53 [95% CI 0.30, 0.93]) among participants resident in wMel-treated versus untreated neighbourhoods. Conclusions/Significance Stable introduction of wMel into local Ae. aegypti populations was associated with a significant and sustained reduction in dengue incidence across three Colombian cities. These results from the largest contiguous Wolbachia releases to-date demonstrate the real-world effectiveness of the method across large urban populations and, alongside previously published results, support the reproducibility of this effectiveness across different ecological settings. Trial registration NCT03631719.

Rapid host switching of Wolbachia and even more rapid turnover of their phages and incompatibility-causing loci

“…While wMel introductions into Ae. aegypti have been very effective in locations where they have spread to high, stable frequencies (Hoffmann et al 2011;Utarini et al 2021;Lenharo 2023;Velez et al 2023)…”

“…CI facilitates the establishment of wMel in natural Ae. aegypti populations and successful biocontrol of dengue (Walker et al 2011;Utarini et al 2021;Lenharo 2023;Velez et al 2023) Here we focus on determining the timescale of divergence and evolution of Wolbachia closely related to wMel (Martinez et al 2021) and observed in holometabolous host species diverged about 350 MY. We present a new temporal calibration of Wolbachia divergence using cladogenically inherited Wolbachia.…”

“…CI kills Wolbachiafree embryos fertilized by Wolbachia-carrying males, often driving the endosymbiont to high frequencies in natural populations (Yen and Barr 1973;Hoffmann et al 1990). CI also enables successful biocontrol of human diseases by facilitating the establishment in vector populations of pathogen-blocking Wolbachia like wMel from Drosophila melanogaster (Walker et al 2011;Utarini et al 2021;Lenharo 2023;Velez et al 2023). Using published and new data, our goal is to elucidate the timescale of Wolbachia movements among host species and the rapid turnover and evolution of genes (cifs) that can cause (cifB and cifA) and rescue (cifA) CI (…”

Dengue: A review of laboratory diagnostics in the vaccine age

“…Control and mitigation measures for DENV may impact the need for laboratory diagnostics. Control measures have had some recent successes, including the deployment of Wolbachia -infected mosquitos (which has significantly decreased infection rates in release areas) [17–23], and the development of vaccines [24–27]. Due to the risk of subsequent severe DENV infection related to ADE [28], vaccination is only recommended for those who have confirmed prior DENV infection, unless there is high local seroprevalence in the target age group for vaccination [27, 29].…”

DENV-1 Titer Impacts Viral Blocking in wMel Aedes aegypti with Brazilian Genetic Background

“…In North Queensland, Australia, dengue incidence reduced nearly 65% during w Mel releases for 28 months between 2014 and 2017 and >95% 24 months after releases [ 27 ]. Another recent study in Colombia has shown that the Wolbachia deployments occurring since 2015 achieved an impressive dengue incidence decrease of 94–97%, with two out of the three cities that received the program being considered fully treated (60% of the local mosquitoes with Wolbachia [ 28 , 29 ]).…”