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

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 Overview

• Status: Active, not recruiting
• Conditions: Dengue; Chikungunya; Zika; Aedes-borne Diseases
• Intervention / Treatment: Biological: 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): 4702
• Phase: Phase 3

Contacts and Locations

Study Locations

• Mexico
  • Yucatan
    • Merida, Yucatan, Mexico, 97203
      • Universidad Autónoma de Yucatán

Participation Criteria

Eligibility Criteria

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

Description

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

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, 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 Names: Actellic 300CS
No Intervention: Control; Routine Aedes-borne virus (ABV) prevention and control, no Targeted Indoor Residual Spraying (TIRS)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of laboratory confirmed (IgG ELISA and neutralization testing) Aedes-borne Viruses cases in annual surveillance samples	Number of laboratory confirmed (IgG ELISA and neutralization testing) Aedes-borne Viruses (DENV, CHIKV and ZIKV) in annual surveillance samples	Up to 5 years
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 RT-PCR	Up to 5 years
Ae. aegypti indoor entomological index adult presence/abundance	Ae. aegypti indoor entomological index adult presence/abundance will be calculated. Presence of mosquitoes/house. The higher the value, the worst the outcome.	Up to 5 years
Ae. aegypti indoor entomological index female presence/abundance	Ae. aegypti indoor entomological index female presence/abundance will be calculated. Number of mosquitoes/house. The higher the value, the worst the outcome.	Up to 5 years
Ae. aegypti indoor entomological index bloodfed female presence/abundance. Number of bloodfed females per house. The higher the value, the works the outcome.	Ae. aegypti indoor entomological index bloodfed female presence/abundance will be calculated	Up to 5 years
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.	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.	Up to 5 years

Collaborators and Investigators

• Sponsor: Emory University
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID)

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 (Anticipated): December 1, 2024
• Study Completion (Anticipated): December 31, 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 (Actual): May 3, 2023
• Last Update Submitted That Met QC Criteria: April 28, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Children; CHIKV; DENV; ZIKV; Targeted Indoor Residual Spraying; Ae. aegypti mosquito
• 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: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, and appendices), will be shared.
• IPD Sharing Time Frame: Starting one year following conclusion of the trial. No end date.
• IPD Sharing 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.
• 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