Introduction of Aedes aegypti mosquitoes carrying wAlbB Wolbachia sharply decreases dengue incidence in disease hotspots.

Partial replacement of resident Aedes aegypti mosquitoes with introduced mosquitoes carrying certain strains of inherited Wolbachia symbionts can result in transmission blocking of dengue and other viruses of public health importance. Wolbachia strain wAlbB is an effective transmission blocker and stable at high temperatures, making it particularly suitable for hot tropical climates. Following trial field releases in Malaysia, releases using wAlbB Ae. aegypti have become operationalized by the Malaysian health authorities. We report here on an average reduction in dengue fever of 62.4% (confidence intervals 50-71%) in 20 releases sites when compared to 76 control sites in high-rise residential areas. Importantly the level of dengue reduction increased with Wolbachia frequency, with 75.8% reduction (61-87%) estimated at 100% Wolbachia frequency. These findings indicate large impacts of wAlbB Wolbachia invasions on dengue fever incidence in an operational setting, with incidence expected to further decrease as wider areas are invaded.

Characterization of Sodium Channel Mutations in the Dengue Vector Mosquitoes Aedes aegypti and Aedes albopictus within the Context of Ongoing Wolbachia Releases in Kuala Lumpur, Malaysia.

Specific sodium channel gene mutations confer target site resistance to pyrethroid insecticides in mosquitoes and other insects. In Aedes mosquito species, multiple mutations that contribute to resistance vary in their importance around the world. Here, we characterize voltage sensitive sodium channel (Vssc) mutations in populations of Aedesaegypti from Kuala Lumpur, Malaysia, and look at their persistence in populations affected by ongoing Wolbachia releases (a dengue control measure). We also describe a Vssc mutation in Aedesalbopictus (F1534L) found for the first time in Malaysia. We show that there are three predominant Vssc haplotypes in Aedesaegypti in this region, which all persist with regular backcrossing, thereby maintaining the original genetic composition of the populations. We identify changes in genotype frequency in closed populations of Ae. aegypti maintained for multiple generations in laboratory culture, suggesting different fitness costs associated with the genotypes, some of which may be associated with the sex of the mosquito. Following population replacement of Ae. aegypti by Wolbachia in the target area, however, we find that the Vssc mutations have persisted at pre-release levels. Mosquitoes in two genotype classes demonstrate a type I pyrethroid resistance advantage over wildtype mosquitoes when exposed to 0.25% permethrin. This resistance advantage is even more pronounced with a type II pyrethroid, deltamethrin (0.03%). The results point to the importance of these mutations in pyrethroid resistance in mosquito populations and the need for regular backcrossing with male mosquitoes from the field to maintain similarity of genetic background and population integrity during Wolbachia releases.