Testing Combined IIT-SIT to Control Mosquito-Borne Diseases At Scale

NCT06595745 | Terminated

• 2 other identifiers: STUDY000105097200AA23FA00021
• Study Type: interventional
• Target: 15,243
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Dengue; Zika; Chikungunya

Keywords

Wolbachia; IIT; SIT; Aedes aegypti; Dengue; Zika; Chikungunya

Outcome Measures

Primary Outcomes (1)

• Epidemiological impact of combined IIT-SIT

  Incidence of symptomatic Aedes-borne virus (dengue, chikungunya, Zika) confirmed by laboratory testing by the Yucatan Ministry of Health.

  Up to 19 months

Secondary Outcomes (1)

• Entomological impact of combined IIT-SIT

  Up to 19 months

Study Arms (2)

Release sites

EXPERIMENTAL

Traditional mosquito control will be applied, followed by weekly release of Wolbachia wAlbB-infected Aedes aegypti males to induce sterile mating with wild female mosquitoes.

Genetic: Wolbachia induced incompatible mating; Combination Product: Standard traditional chemical mosquito control

Control sites with traditional mosquito control only

ACTIVE COMPARATOR

Traditional mosquito control will be applied but no mosquito release will occur in the control sites

Interventions

Wolbachia induced incompatible mating GENETIC

The intervention will be performed by weekly release of male Aedes aegypti carrying Wolbachia (wAlbB strain) to mate with wild females, resulting in the death of their eggs for birth control. Before release, these males will be irradiated with X-rays to minimize the chance of any residual fertile female releases. The intervention will lead to Ae. aegypti population suppression or even elimination and preventing dengue transmission in release sites.

Also known as: Incompatible insect technique, Sterile insect technique

Release sites

Standard traditional chemical mosquito control COMBINATION_PRODUCT

Traditional and commonly used chemical insecticide will be applied to reduce the mosquito population

Release sites

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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

Sponsors & Collaborators

• Michigan State University: lead
• Universidad Autónoma de Yucatán: collaborator
• Emory University: collaborator

Study Sites (1)

Laboratorio para el Control Biolo´gico de Aedes aegypti (LCB-UADY), Universidad Autónoma de Yucatán

Mérida, Yucatán, 97160, Mexico

Location

Related Publications (4)

• Liang X, Tan CH, Sun Q, Zhang M, Wong PSJ, Li MI, Mak KW, Martin-Park A, Contreras-Perera Y, Puerta-Guardo H, Manrique-Saide P, Ng LC, Xi Z. Wolbachia wAlbB remains stable in Aedes aegypti over 15 years but exhibits genetic background-dependent variation in virus blocking. PNAS Nexus. 2022 Sep 22;1(4):pgac203. doi: 10.1093/pnasnexus/pgac203. eCollection 2022 Sep.

  PMID: 36714832 BACKGROUND

• Lim JT, Bansal S, Chong CS, Dickens B, Ng Y, Deng L, Lee C, Tan LY, Chain G, Ma P, Sim S, Tan CH, Cook AR, Ng LC. Efficacy of Wolbachia-mediated sterility to reduce the incidence of dengue: a synthetic control study in Singapore. Lancet Microbe. 2024 May;5(5):e422-e432. doi: 10.1016/S2666-5247(23)00397-X. Epub 2024 Feb 8.

  PMID: 38342109 BACKGROUND

• Martin-Park A, Che-Mendoza A, Contreras-Perera Y, Perez-Carrillo S, Puerta-Guardo H, Villegas-Chim J, Guillermo-May G, Medina-Barreiro A, Delfin-Gonzalez H, Mendez-Vales R, Vazquez-Narvaez S, Palacio-Vargas J, Correa-Morales F, Ayora-Talavera G, Pavia-Ruz N, Liang X, Fu P, Zhang D, Wang X, Toledo-Romani ME, Xi Z, Vazquez-Prokopec G, Manrique-Saide P. Pilot trial using mass field-releases of sterile males produced with the incompatible and sterile insect techniques as part of integrated Aedes aegypti control in Mexico. PLoS Negl Trop Dis. 2022 Apr 26;16(4):e0010324. doi: 10.1371/journal.pntd.0010324. eCollection 2022 Apr.

  PMID: 35471983 BACKGROUND

• Zheng X, Zhang D, Li Y, Yang C, Wu Y, Liang X, Liang Y, Pan X, Hu L, Sun Q, Wang X, Wei Y, Zhu J, Qian W, Yan Z, Parker AG, Gilles JRL, Bourtzis K, Bouyer J, Tang M, Zheng B, Yu J, Liu J, Zhuang J, Hu Z, Zhang M, Gong JT, Hong XY, Zhang Z, Lin L, Liu Q, Hu Z, Wu Z, Baton LA, Hoffmann AA, Xi Z. Incompatible and sterile insect techniques combined eliminate mosquitoes. Nature. 2019 Aug;572(7767):56-61. doi: 10.1038/s41586-019-1407-9. Epub 2019 Jul 17.

  PMID: 31316207 BACKGROUND

MeSH Terms

Conditions

Dengue; Zika Virus Infection; Chikungunya Fever

Condition Hierarchy (Ancestors)

Mosquito-Borne Diseases; Vector Borne Diseases; Infections; Arbovirus Infections; Virus Diseases; Flavivirus Infections; Flaviviridae Infections; RNA Virus Infections; Hemorrhagic Fevers, Viral; Alphavirus Infections; Togaviridae Infections

Study Officials

• Gonzalo Vazquez Professor Prokopec, PhD

  Emory University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 9, 2024
• First Posted: September 19, 2024
• Study Start: May 28, 2024
• Primary Completion: January 31, 2025
• Study Completion: January 31, 2025
• Last Updated: March 19, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

ME (1)