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

NCT ID: NCT06595745

Last Updated: 2024-09-19

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 15243 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-05-28
• Study Completion Date: 2026-09-30

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Release sites

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.

Group Type: EXPERIMENTAL

Wolbachia induced incompatible mating

Intervention Type: 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.

Standard traditional chemical mosquito control

Intervention Type: COMBINATION_PRODUCT

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

Control sites with traditional mosquito control only

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

Group Type: ACTIVE_COMPARATOR

Standard traditional chemical mosquito control

Intervention Type: COMBINATION_PRODUCT

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

Interventions

Wolbachia induced incompatible mating

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.

Intervention Type: GENETIC

Standard traditional chemical mosquito control

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

Intervention Type: COMBINATION_PRODUCT

Other Intervention Names

Incompatible insect technique; Sterile insect technique

Eligibility Criteria

Inclusion Criteria

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

Exclusion Criteria

• No exclusion will be performed.

• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Universidad Autónoma de Yucatán

OTHER

Sponsor Role: collaborator

Emory University

OTHER

Sponsor Role: collaborator

Michigan State University

OTHER

Sponsor Role: lead

Responsible Party

Zhiyong Xi

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Gonzalo Vazquez Professor Prokopec, PhD

Role: STUDY_CHAIR

Emory University

Locations

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

Mérida, Yucatán, Mexico

Countries

Mexico

References

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.

Reference Type: BACKGROUND

PMID: 36714832 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 38342109 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 35471983 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 31316207 (View on PubMed)

Other Identifiers

7200AA23FA00021

Identifier Type: OTHER

Identifier Source: secondary_id

STUDY00010509

Identifier Type: -

Identifier Source: org_study_id