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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Aedes-borne Diseases, Dengue, Chikungunya, Zika

Intervention / Treatment
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* Biological: Targeted Indoor Residual Spraying (TIRS)


Participation Criteria
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Eligibility Criteria
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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. 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 7d 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. Having a medical condition that prevents implementation of study procedures. Temporary visitor to household Plans to leave study area within next 12 months

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 15 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Targeted Indoor Residual Spraying (TIRS)<br>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)<br>* 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.<br>* Other names: Actellic 300CS;|
| No Intervention: Control<br>Routine Aedes-borne virus (ABV) prevention and control, no Targeted Indoor Residual Spraying (TIRS) | |

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Targeted Indoor Residual Spraying, Children, DENV, CHIKV, ZIKV, Ae. aegypti mosquito