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

The objective of this trial is evaluate the efficacy of Targeted Indoor Residual Spraying (TIRS) in preventing symptomatic disease caused by Aedes-borne diseases (ABDs) in children 2 to 15 years of age in the city of Merida, Yucatan State, Mexico.

Study Overview

• Status: Completed
• Conditions: Dengue; Chikungunya; Zika; Aedes-borne Diseases
• Intervention / Treatment: Other: Targeted Indoor Residual Spraying (TIRS)

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 Type: Interventional
• Enrollment (Actual): 4461
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Mexico
  • Yucatán
    • Mérida, Yucatán, Mexico, 97203
      • Universidad Autonoma de Yucatan

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

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

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 (for children in TIRS cluster)

Exclusion Criteria:

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 7days a week outside the home)
• Inability for a resident to provide informed consent
• Non-residential places (e.g., businesses, schools, markets, etc.)

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 (for children in TIRS cluster)
• Having a medical condition that prevents implementation of study procedures
• Temporary visitor to household
• Plans to leave study area within next 12 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Targeted Indoor Residual Spraying (TIRS); All households in Targeted Indoor Residual Spraying (TIRS) clusters will be offered the intervention, and children in households that consent to TIRS will be recruited into this study arm.	Other: Targeted Indoor Residual Spraying (TIRS); Spraying of insecticide Actellic 300CS will start in May or June extending for 1 to 2 months. Residents will be asked to temporarily leave the house during treatment and wait half an hour to one hour for the product to dry before re-entering the house. Insecticide application will follow strict protocol developed by the Centers for Disease Control and Prevention (CDC), Emory University, and the Universidad Autónoma de Yucatán.; Other Names: Actellic 300CS
No Intervention: Routine Aedes-borne Virus (ABV) Prevention and Control; Households in the control clusters receive routine Aedes-borne virus (ABV) prevention and control, without Targeted Indoor Residual Spraying (TIRS). Children in the control households will be recruited into this study arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Symptomatic Participants Testing Positive for Aedes-borne Virus Infections That Are Laboratory Confirmed or Serologically	The number of symptomatic children with laboratory confirmed, by reverse transcription-polymerase chain reaction (RT-PCR) or immunoglobulin M/ immunoglobulin G (IgM/IgG) enzyme-linked immunosorbent assay (ELISA), Aedes-borne Viruses infections. The number of any Aedes-borne virus infection during three seasons of high transmission is described, as well as the number of Dengue virus (DENV), Chikungunya virus (CHIKV), Zika virus (ZIKV) and coinfections.	18 months of active surveillance during high transmission seasons (each 6 months in duration) during 3 years (July through December in 2021, 2022, and 2023)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number Positive Tests of Laboratory Confirmed Aedes-borne Viruses Infections By Season	Number of laboratory confirmed (IgG ELISA and neutralization testing) Aedes-borne Viruses (DENV, CHIKV and ZIKV) in annual surveillance samples.	Up to 36 months, during serosurvey seasons 2021-2022, 2022-2023, and 2023-2024
Ae. Aegypti Mosquito Infection Rate With Aedes-borne Viruses (DENV, CHIKV and ZIKV)	Ae. aegypti mosquito infection rate with Aedes-borne Viruses (DENV, CHIKV and ZIKV) assessed by the number of positive RT-PCR tests. Infection is mosquitoes is analyzed by collecting binary data (a mosquito pool is either infected or not) and transforming that into minimum infection rates (MIR) with the calculation: (1/number of mosquitoes in the pool) times 1000. Households were randomly selected for testing; houses were eligible for testing if they were located within the central blocks and had at least one child enrolled in the study.	Up to 6 months (mosquito pools were collected during the 6 months post TIRS spraying samplings in 2021)
Ae. Aegypti Indoor Entomological Index of Adult Mosquito Abundance	The Ae. aegypti indoor entomological index of adult mosquito presence/abundance is calculated as the number of adult mosquitoes per house. Higher values mean that more mosquitoes are found within houses.	Up to 36 months starting at the first TIRS application
Ae. Aegypti Indoor Entomological Index of Female Mosquito Abundance	The Ae. aegypti indoor entomological index of female mosquito presence/abundance is calculated as the number of female mosquitoes per house. Higher values mean that more mosquitoes are found within houses.	Up to 36 months starting at first TIRS application
Ae. Aegypti Indoor Entomological Index of Bloodfed Female Mosquito Abundance	The Ae. aegypti indoor entomological index of bloodfed female mosquito presence/abundance is calculated as the number of bloodfed female mosquitoes per house. Higher values mean that more mosquitoes are found within houses.	Up to 36 months starting at first TIRS application
Number of Households Where the Head of Household Would Recommend the Intervention	Acceptability of the intervention is determined through household surveys, for households that received the intervention. Acceptability is assessed as the number of households where the head of that household would recommend the intervention to others.	Post-intervention (up to 41 months and 26 days after the start of the intervention)
Number of Households With a Resident That Had a Reaction to the Insecticide	Safety of the intervention is assessed as the number of households receiving the TIRS intervention that had evidence of a household resident having a reaction possibly related to the insecticide, which was assessed and confirmed by study doctors.	Post-intervention (up to 41 months and 26 days after the start of the intervention)

Collaborators and Investigators

• Sponsor: Emory University
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Principal Investigator: Gonzalo Vazquez Prokopec, MD, Emory University

Publications and helpful links

General 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.

Helpful Links

• link to project website

Study record dates

Study Major Dates

• Study Start (Actual): November 3, 2020
• Primary Completion (Actual): April 28, 2024
• Study Completion (Actual): April 28, 2024

Study Registration Dates

• First Submitted: April 9, 2020
• First Submitted That Met QC Criteria: April 9, 2020
• First Posted (Actual): April 13, 2020

Study Record Updates

• Last Update Posted (Estimated): September 18, 2025
• Last Update Submitted That Met QC Criteria: August 29, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Children; Targeted Indoor Residual Spraying; Ae. aegypti mosquito; Dengue virus (DENV); Chikungunya virus (CHIKV); Zika virus (ZIKV)
• Additional Relevant MeSH Terms: Vector Borne Diseases; Infections; RNA Virus Infections; Virus Diseases; Arbovirus Infections; Flavivirus Infections; Flaviviridae Infections; Hemorrhagic Fevers, Viral; Alphavirus Infections; Togaviridae Infections; Zika Virus Infection; Mosquito-Borne Diseases; Dengue; Chikungunya Fever
• Other Study ID Numbers: IRB00108666; 1U01AI148069-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Deidentified individual participant data that underlie the results reported in publications of this study will be available for sharing with other researchers.
• IPD Sharing Time Frame: Data will be made available for sharing starting one year following conclusion of the trial, with no end date.
• IPD Sharing Access Criteria: Investigators wanting to share data from this study should provide a methodologically sound proposal. Data will be shared with other researchers in order for them 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No