Quantifying the Epidemiological Impact of Targeted Indoor Residual Spraying on Aedes-borne Diseases

• ClinicalTrials.gov Identifier: NCT04343521
• Recruitment Status: Active, not recruiting
• First Posted: April 13, 2020
• Last Update Posted: February 14, 2023
• Sponsor: Emory University
• Collaborator: National Institute of Allergy and Infectious Diseases (NIAID)
• Information provided by (Responsible Party): Gonzalo Vazquez-Prokopec, Emory University

Study Description

Brief Summary:

The trial will be conducted in the city of Merida extending ongoing longitudinal cohort to follow a population of 4,600 children 2-15 years old randomly allocated to receive either TIRS treatment or not. If efficacious, TIRS will drive a paradigm shift in Aedes control by: considering Ae. aegypti behavior to rationally guide insecticide applications; the change to preventive control (pre- ABD transmission season rather than in response to symptomatic cases); the use of third generation insecticides to which Ae. Aegypti is susceptible.

Condition or disease	Intervention/treatment	Phase
Aedes-borne Diseases; Dengue; Chikungunya; Zika	Biological: Targeted Indoor Residual Spraying (TIRS)	Phase 3

Detailed Description:

Contemporaneous urban vector control (truck-mounted ultra-low volume spraying, thermal fogging, larviciding) has failed to contain dengue epidemics and to prevent the global range expansion of Aedes-borne diseases (ABDs: dengue, chikungunya, zika). Part of the challenge in sustaining effective ABD control emerges from the remarkable paucity of evidence about the epidemiological impact of any vector control method. Furthermore, the classic deployment of interventions in response to clinical cases fails to account for the important contribution of out-of-home human mobility and asymptomatic infections.

The trial will be conducted in the city of Merida extending ongoing longitudinal cohort to follow a population of 4,600 children 2-15 years old randomly allocated to receive either TIRS treatment or not. If efficacious, TIRS will drive a paradigm shift in Aedes control by: considering Ae. aegypti behavior to rationally guide insecticide applications; the change to preventive control (pre- ABD transmission season rather than in response to symptomatic cases); the use of third generation insecticides to which Ae. Aegypti is susceptible.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 4702 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Quantifying the Epidemiological Impact of Targeted Indoor Residual Spraying on Aedes-borne Diseases
• Actual Study Start Date: November 3, 2020
• Estimated Primary Completion Date: December 1, 2024
• Estimated Study Completion Date: December 31, 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Targeted Indoor Residual Spraying (TIRS); All households in Targeted Indoor Residual Spraying (TIRS) clusters will be offered the intervention, epidemiological and entomological evaluation will occur in the center of each cluster	Biological: Targeted Indoor Residual Spraying (TIRS); Spraying of insecticide Actellic 300CS will start May-June and extend for 1-2 months. Residents will be asked to temporarily leave the house during treatment and wait 0.5-1 h for the product to dry before re-entering the house. Insecticide application will follow strict protocol developed in CDC-Emory-UADY collaboration.; Other Name: Actellic 300CS
No Intervention: Control; Routine Aedes-borne virus (ABV) prevention and control, no Targeted Indoor Residual Spraying (TIRS)

Outcome Measures

Primary Outcome Measures :

1. Number of laboratory confirmed (RT-PCR or IgM/IgG ELISA) symptomatic Aedes-borne Viruses in paired acute and convalescent samples living in the core 3x3 city blocks of each cluster. [ Time Frame: Up to 5 years ]
   Number of laboratory confirmed (RT-PCR or IgM/IgG ELISA) symptomatic Aedes-borne Viruses (DENV, CHIKV and ZIKV) in paired acute and convalescent samples for a subset of children living in the core 3x3 city blocks of the cluster.

Secondary Outcome Measures :

1. Number of laboratory confirmed (IgG ELISA and neutralization testing) Aedes-borne Viruses cases in annual surveillance samples [ Time Frame: Up to 5 years ]
   Number of laboratory confirmed (IgG ELISA and neutralization testing) Aedes-borne Viruses (DENV, CHIKV and ZIKV) in annual surveillance samples
2. Ae. aegypti mosquito infection rate with Aedes-borne Viruses (DENV, CHIKV and ZIKV) [ Time Frame: Up to 5 years ]
   Ae. aegypti mosquito infection rate with Aedes-borne Viruses (DENV, CHIKV and ZIKV) assessed by RT-PCR
3. Ae. aegypti indoor entomological index adult presence/abundance [ Time Frame: Up to 5 years ]
   Ae. aegypti indoor entomological index adult presence/abundance will be calculated. Presence of mosquitoes/house. The higher the value, the worst the outcome.
4. Ae. aegypti indoor entomological index female presence/abundance [ Time Frame: Up to 5 years ]
   Ae. aegypti indoor entomological index female presence/abundance will be calculated. Number of mosquitoes/house. The higher the value, the worst the outcome.
5. Ae. aegypti indoor entomological index bloodfed female presence/abundance. Number of bloodfed females per house. The higher the value, the works the outcome. [ Time Frame: Up to 5 years ]
   Ae. aegypti indoor entomological index bloodfed female presence/abundance will be calculated
6. Number of laboratory confirmed (RT-PCR or IgM/IgG ELISA) symptomatic Aedes-borne Viruses in paired acute and convalescent samples living in the entire cluster. [ Time Frame: Up to 5 years ]
   Number of laboratory confirmed (RT-PCR or IgM/IgG ELISA) symptomatic Aedes-borne Viruses (DENV, CHIKV and ZIKV) in paired acute and convalescent samples for a subset of children living in the entire cluster.

Eligibility Criteria

• Ages Eligible for Study: 2 Years to 15 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Household Level Inclusion Criteria:

   • Household is located within the bounds of a study cluster (5x5 city-block clusters).
   • City block has at least 60% premises that are residential.

2. Individual Level Inclusion Criteria:

   • 2 or more and up to 15 years of age at the time of initial enrollment
   • Living in a house that consented to TIRS.

Exclusion Criteria:

1. Household Level Exclusion Criteria:

   • Households where study personnel identify a security risk (i.e., site where drugs are sold, residents are always drunk or hostile)
   • Sites where no residents spend time during the day (i.e. work 7d a week outside the home).Inability for a resident to provide informed consent.
   • Non-residential places (e.g., businesses, schools, markets, etc.).

2. Individual Level Exclusion Criteria:

   • Less than 2 years of age or more than 15 years of age at the time of enrollment.
   • Not living in a house that consented to TIRS.
   • Having a medical condition that prevents implementation of study procedures.
   • Temporary visitor to household
   • Plans to leave study area within next 12 months

Contacts and Locations

Locations

Mexico

Universidad Autonoma de Yucatan

Merida, Yucatan, Mexico, 97203

Sponsors and Collaborators

Emory University

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

• Principal Investigator: Gonzalo Vazquez Prokopec, MD; Emory University

More Information

Additional Information:

link to project website 

Publications:

Manrique-Saide P, Dean NE, Halloran ME, Longini IM, Collins MH, Waller LA, Gomez-Dantes H, Lenhart A, Hladish TJ, Che-Mendoza A, Kirstein OD, Romer Y, Correa-Morales F, Palacio-Vargas J, Mendez-Vales R, Perez PG, Pavia-Ruz N, Ayora-Talavera G, Vazquez-Prokopec GM. The TIRS trial: protocol for a cluster randomized controlled trial assessing the efficacy of preventive targeted indoor residual spraying to reduce Aedes-borne viral illnesses in Merida, Mexico. Trials. 2020 Oct 8;21(1):839. doi: 10.1186/s13063-020-04780-7.

Che-Mendoza A, Gonzalez-Olvera G, Medina-Barreiro A, Arisqueta-Chable C, Bibiano-Marin W, Correa-Morales F, Kirstein OD, Manrique-Saide P, Vazquez-Prokopec GM. Efficacy of targeted indoor residual spraying with the pyrrole insecticide chlorfenapyr against pyrethroid-resistant Aedes aegypti. PLoS Negl Trop Dis. 2021 Oct 4;15(10):e0009822. doi: 10.1371/journal.pntd.0009822. eCollection 2021 Oct.

Dzul-Manzanilla F, Correa-Morales F, Che-Mendoza A, Palacio-Vargas J, Sanchez-Tejeda G, Gonzalez-Roldan JF, Lopez-Gatell H, Flores-Suarez AE, Gomez-Dantes H, Coelho GE, da Silva Bezerra HS, Pavia-Ruz N, Lenhart A, Manrique-Saide P, Vazquez-Prokopec GM. Identifying urban hotspots of dengue, chikungunya, and Zika transmission in Mexico to support risk stratification efforts: a spatial analysis. Lancet Planet Health. 2021 May;5(5):e277-e285. doi: 10.1016/S2542-5196(21)00030-9.

Kirstein OD, Ayora-Talavera G, Koyoc-Cardena E, Chan Espinoza D, Che-Mendoza A, Cohuo-Rodriguez A, Granja-Perez P, Puerta-Guardo H, Pavia-Ruz N, Dunbar MW, Manrique-Saide P, Vazquez-Prokopec GM. Natural arbovirus infection rate and detectability of indoor female Aedes aegypti from Merida, Yucatan, Mexico. PLoS Negl Trop Dis. 2021 Jan 4;15(1):e0008972. doi: 10.1371/journal.pntd.0008972. eCollection 2021 Jan.

Dzib-Florez S, Ponce-Garcia G, Medina-Barreiro A, Gonzalez-Olvera G, Contreras-Perera Y, Del Castillo-Centeno F, Ahmed AMM, Che-Mendoza A, McCall PJ, Vazquez-Prokopec G, Manrique-Saide P. Evaluating Over-the-Counter Household Insecticide Aerosols for Rapid Vector Control of Pyrethroid-Resistant Aedes aegypti. Am J Trop Med Hyg. 2020 Nov;103(5):2108-2112. doi: 10.4269/ajtmh.20-0515.

• Responsible Party: Gonzalo Vazquez-Prokopec, Associate Professor, Emory University
• ClinicalTrials.gov Identifier: NCT04343521
• Other Study ID Numbers: IRB00108666; 1U01AI148069-01 ( U.S. NIH Grant/Contract )
• First Posted: April 13, 2020
• Last Update Posted: February 14, 2023
• Last Verified: February 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, and appendices), will be shared.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP)
• Time Frame: Starting one year following conclusion of the trial. No end date.
• Access Criteria: Investigators who provide a methodologically sound proposal will get access to achieve aims in the approved proposal. Proposals should be directed to lwaller@emory.edu. To gain access, data requesters will need to sign a data access agreement.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Gonzalo Vazquez-Prokopec, Emory University:

Targeted Indoor Residual Spraying; Children; DENV; CHIKV; ZIKV; Ae. aegypti mosquito