Spatial Repellents for Aedes-borne Virus Control in Sri Lanka

Study Overview
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Brief Summary
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The primary objective of the study is to demonstrate and quantify the protective efficacy (PE) of a single SR product, in reducing DENV infection and active Aedes-borne virus (ABV) disease in human cohorts. The study design will be a prospective, cluster randomized controlled trial (cRCT). Although not a specific objective of this project, an overall goal is to allow for official recommendations (or not) from the World Health Organization (WHO) for the use of SRs in public health. A WHO global policy recommendation will establish evaluation systems of SR products to regulate efficacy evaluations, thereby increasing quality, overall use and a consequent reduction in disease.

Detailed Description
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The study will be a prospective, cRCT, participant and observer-blinded, placebo-controlled trial in a site endemic for ABV to measure the impact of a SR product on new ABV virus infections. Clusters of households, each cluster containing 110-120 residents testing negative for antibodies against DENV (seronegative) or positive to a single DENV infection (monotypic), will be selected from three MOH areas in the district of Gampaha: Negambo, Wattala, Kelaniya. All participating houses in each cluster will be monitored entomologically for adult Aedes aegypti surveys for 3 months before deployment of the SR intervention and monthly after the intervention is in place. Entomological surveys will include monitoring of indoor Ae. aegypti adult population densities and blood-fed status. DENV infection in study participants will be assessed by serologic testing of scheduled longitudinal blood samples (primary outcome) and passively by monitoring febrile persons for acute Dengue illness (secondary outcome). Seroconversion to DENV from baseline (pre-intervention) and follow-up (post-intervention) samples as well as ABV active disease rates will be compared between active intervention and placebo (control) clusters. Testing and confirmation of Zika virus (ZIKV) and Chikungunya virus (CHIKV) infection at baseline and during the intervention phase of the trial will be dependent on circulation history/detection in study area during study period. The spatial repellent (SR) will be a new formulation of transfluthrin. This active ingredient (AI) is widely used in mosquito coils and other household pest control products worldwide. The new formulation is a passive emanator that will release the AI over a period of up to four weeks, Mosquito ShieldTM. The emanator will consist of a pre-treated piece of cellulose acetate or other medium, which will be positioned within consenting households according to manufacturer specifications of 2 units/9m2. A placebo product of matched design with inert ingredients will be applied similarly. The Mosquito ShieldTM and placebo products for this study will be designed and provided by S.C. Johnson, INC. A Family Company.

Official Title
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A Cluster Randomized, Placebo Control Trial to Evaluate the Efficacy of a Spatial Repellent (Mosquito ShieldTM) Against Aedes-borne Virus Infection Among Children ≥ 4-16 Years of Age in the Gampaha District, Sri Lanka

Conditions
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Arbovirus Infections

Intervention / Treatment
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* Device: Transfluthrin
* Device: Placebo


Participation Criteria
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Eligibility Criteria
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LONGITUDINAL SEROCONVERSION Individual Level Inclusion Criteria: ≥ 4 - 16 years of age Plans to stay in residence and/or study area for a minimum of 24 months Resident of household or frequent visitor ( 20% of day hours in house / month) Exclusion Criteria: < 4 and > 16 years of age Plans to leave residence and/or study area within next 24 months Temporary visitor to household (<20% of day hours in house/ month) FEBRILE SURVEILLANCE Household Level Inclusion Criteria: Adult head of households agrees to census, health visits and logging resident symptoms when febrile (or in the case of suspected Zika in the absence of fever, presenting with rash, arthralgia, arthritis or non-purulent conjunctivitis). Individuals spend a minimum of 4hrs per week during the daytime hours or sleep in the house. Exclusion Criteria: Adult head of households does not agree to census, health visits or logging symptoms of residents. 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). FEBRILE SURVEILLANCE Individual Level Inclusion Criteria: ≥ 6mo of age. Fever at the time of presentation or report of feverishness within the previous 24 hours or presenting with a rash, arthralgia, arthritis or non-purulent conjunctivitis (suspicion of ZIKA determined by project physician) Individual who spends a minimum of 4 hours per week within the household or sleeps in the house. Exclusion Criteria: < 6mo of age. No fever at time of presentation or report of feverishness within the previous 24 hours or not reporting with a rash, arthralgia, arthritis or non-purulent conjunctivitis Individuals who have spent less than 4 hours in the household during the week prior to illness. ENTOMOLOGICAL MONITORING Household Level Inclusion Criteria: Adult head of household agrees to surveys. Properties where study personnel do not identify a security risk (i.e., site where drugs are sold, residents are always drunk or hostile). Exclusion Criteria: Adult head of household does not agree to surveys. Properties where study personnel identify a security risk (i.e., site where drugs are sold, residents are always drunk or hostile). SPATIAL REPELLENT INTERVENTION Household Level Inclusion Criteria: Adult head of households agrees to have intervention applied inside the home and to provide access to team member at 4-week intervals to change products. Properties where study personnel do not identify a security risk (i.e., site where drugs are sold, residents are always drunk or hostile). Exclusion Criteria: Adult head of household does not agree to Mosquito ShieldTM deployment or study team access. Properties where study personnel identify a security risk (i.e., site where drugs are sold, residents are always drunk or hostile).

Ages Eligible for Study
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Minimum Age: 6 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Spatial Repellent<br>Transfluthrin | Device: Transfluthrin<br>* Passive emanator with formulated transfluthrin<br>|
| Placebo Comparator: Placebo<br>Inert ingredients | Device: Placebo<br>* Passive emanator with formulated inert ingredients<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Aedes-borne virus (ABV) infection in the 'longitudinal cohort'. | The primary endpoint is the fraction of monotypic or seronegative individuals in the 'longitudinal cohort' who seroconvert to an arbovirus during the follow-up period post randomization with intervention. Here, the intervention follow-up period is 2 years after initial deployment of SR or placebo. There will be 3 blood samplings from longitudinal cohort participants for measure of seroconversion: one for baseline serostatus characterization (T0), a second at 12 months (T1) and a third at 24 months (T2) from time of initial placement of intervention. | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinically apparent cases of Aedes-borne virus (ABV) disease. | Clinically apparent is defined as an acute infection that causes overt symptoms (fever, rash, etc.) indicating virus circulation in the blood. For the longitudinal cohort participants, acute and convalescent blood sampling based on time of health facility visit when febrile throughout the intervention period. For other household members participating in febrile surveillance, case definition measured and reported whenever they visit designated health facilities throughout the intervention period. | 24 months | 
| Adult female Aedes aegypti indoor abundance. | Measured by comparing adult female Aedes aegypti indoor abundance in households using Procopak mosquito aspiration with active and placebo product receiving standard entomological surveillance and control procedures by the local Ministry of Health, as an indicator for reduced mosquito house entry due to effect of product. Indoor mosquito collections in enrolled households once every 28 days during intervention. | 24 months | 
| Adult female Aedes aegypti blood fed rate. | Measured by comparing adult female Aedes aegypti blood fed rate in households with active and placebo product receiving standard entomological surveillance and control procedures by the local Ministry of Health, as an indicator for reduced mosquito human contact due to effect of product. Direct mosquito abdominal observation by microscopy from samples taken by Procopak aspiration during indoor mosquito collections in enrolled households once every 28 days during intervention. | 24 months | 
| Diversion of Aedes aegypti mosquitoes into untreated houses. | Measured by comparing adult female Aedes aegypti abundance using Procopak mosquito aspiration in untreated households adjacent to treatment clusters (with active product) to untreated households adjacent to placebo clusters as an indicator for mosquito diversion due to effect of product. Indoor mosquito collections in enrolled households once every 28 days during intervention. | 24 months | 
| Overall incidence of Aedes-borne virus (ABV) infection. | Measured by the seroconversion rates of all children enrolled in the trial, independent of order of infection (i.e., including tertiary and quaternary infections). Based on blood samples taken for longitudinal seroconversion and febrile surveillance from time of initial placement of intervention. | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Zika, Chikungunya, Spatial Repellent, Transfluthrin, Incidence, Dengue, Vector-borne diseases, Mosquito vectors