The USAID fund sponsoring this trial was terminated in February 2025.

Mosquito-borne diseases cause suffering for hundreds of millions of people and claim more than 700,000 lives yearly. Diseases such as dengue, Zika, and chikungunya cause symptoms similar to malaria and are endemic in many parts of the world, yet there are no treatments for them nor vaccines for Zika and chikungunya. Mosquito control, particularly of the Aedes aegypti species, is seen as a potentially effective solution to slow or stop the spread of these diseases but has not yet demonstrated significant, sustainable impacts on disease transmission. The investigators will aim to significantly control or eliminate local foci (hot-spots) of dengue, chikungunya and Zika transmission and significantly reduce disease transmission by implementing a combined incompatible and sterile insect technique (IIT-SIT) program based on the release of male Aedes aegypti carrying Wolbachia (wAlbB strain) that have been previously irradiated with X-rays (to minimize the chance of fertile female releases). The investigators will implement a two-arm cluster randomized controlled trial to evaluate the epidemiological and entomological impact of population suppression via IIT-SIT on Aedes-borne diseases in the city of Merida, Mexico. Primary endpoint of the trial is the incidence of laboratory Aedes-borne viruses detected by the passive surveillance system of Mexico. Secondary endpoints will allow estimating the level of suppression of Ae. aegypti populations. This trial design will allow establishing a link between epidemiologic, entomo-virological and entomological indicators to determine the effectiveness of IIT-SIT in real world conditions. The approach is novel because it effectively eliminate vectors, such as urban, outdoor, daytime biting mosquitoes, which are not susceptible to standard vector control approaches, by targeting cryptic and inaccessible mosquito habitats. In addition, the intervention has the below advantages comparing to existing alternatives: (i) highly competitive males are used for release as Wolbachia-infected males have the mating competitiveness equal to wild-type males; (ii) release can continue until population elimination is reached as a low dose of radiation is used to sterilize females for preventing risk of population replacement; (iii) any residual females contaminated in released male pools is resistant to pathogens; (iv) public acceptance of release of Wolbachia-infected males can be easily achieved, because Wolbachia are bacteria naturally presenting in ~50 percent of insect species, and male mosquitoes neither bite nor transmit diseases and can be self-limiting post release; (v) it will not impact non-target species. Successful findings from this study will pave the way for future expansions of the combined IIT-SIT to the entire city and nationwide using a rolling-carpet strategy, which has been successfully demonstrated for area-wide control of screwworm and medfly in Latin America.

Inclusion Criteria:

• All residents in the release sites will be included in the studies

Exclusion Criteria:

• No exclusion will be performed.