Arbovirus Infections
Conditions
Keywords
Dengue, Zika, Chikungunya, Spatial Repellent, Transfluthrin, Vector-borne diseases, Mosquito vectors, Incidence
Brief summary
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
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.
Interventions
DEVICETransfluthrin
Passive emanator with formulated transfluthrin
DEVICEPlacebo
Passive emanator with formulated inert ingredients
Sponsors
S.C. Johnson & Son, Inc.
fhiClinical
Ministry of Health, Sri Lanka
University of Sri Jayewardenepura, Sri Lanka
University of Washington
RemediumOne
University of Notre Dame
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
6 Months to No maximum
Healthy volunteers
Yes
Inclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Aedes-borne virus (ABV) infection in the 'longitudinal cohort'. | 24 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinically apparent cases of Aedes-borne virus (ABV) disease. | 24 months | 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. |
| Adult female Aedes aegypti indoor abundance. | 24 months | 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. |
| Adult female Aedes aegypti blood fed rate. | 24 months | 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. |
| Diversion of Aedes aegypti mosquitoes into untreated houses. | 24 months | 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. |
| Overall incidence of Aedes-borne virus (ABV) infection. | 24 months | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Aedes-borne virus (ABV) infection in subjects residing in households within treatment clusters but without SR product. | 24 months | Measured by comparing Aedes-borne virus infection rates between subjects residing in households with SR product in treatment clusters and subjects from the same clusters who did not agree to the SR application in their households but are receiving standard entomological surveillance and control procedures by the local ministry of health, as an indicator of community effect due to effect of product. |
| Clinically apparent cases of Aedes-borne virus (ABV) disease in subjects residing in households within treatment clusters but without SR product. | 24 months | Measured by comparing Aedes-borne virus disease case rates between subjects residing in households with SR product in households in treatment clusters and individuals from the same clusters who did not agree to the SR application in their households but are receiving standard entomological surveillance and control procedures by the local ministry of health, as an indicator of community effect due to effect of product. |
| Adult female Aedes aegypti indoor abundance using Procopak mosquito aspiration in households within treatment clusters but without SR product. | 24 months | Measured by comparing adult female Aedes aegypti indoor abundance in households with SR product in treatment clusters and households from the same clusters who did not agree to the SR application but are receiving standard entomological surveillance and control procedures by the local ministry of health, as an indicator of community effect to effect of product. Indoor mosquito collections in enrolled households once every 28 days during intervention |
| Adult female Aedes aegypti blood fed rate using Procopak mosquito aspiration in households within treatment clusters but without SR product. | 24 months | Measured by comparing adult female Aedes aegypti blood fed rate in households with SR product in treatment clusters and households from the same clusters who did not agree to the SR application but are receiving standard entomological surveillance and control procedures by the local ministry of health, as an indicator of community effect to effect of product. Samples from indoor mosquito collections in enrolled households once every 28 days during intervention. |
| Adverse Events (AEs) and Serious Adverse Events (SAEs). | 24 months | Measured by solicited and unsolicited reports from both the longitudinal cohort and febrile surveillance cohort during the trial period. Mean, minimum and maximum frequency and percentage of AEs and SAEs across clusters among enrolled subjects will be summarized by treatment arm. |
Countries
Sri Lanka
Outcome results
None listed