A Cluster Randomized Trial of the Efficacy of a Spatial Repellent (the Envelope) on Plasmodium Falciparum Malaria Incidence as Measured by Time to First Infection in Western Kenya
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- University of Notre Dame
- Enrollment
- 5,984
- Locations
- 2
- Primary Endpoint
- First-time malaria infection in core zones during intervention period.
Study Overview
Brief Summary
Spatial repellents are chemical-based devices that when placed in a room, make that room non-conducive for mosquitoes. These tools can be used to help in the fight against vector borne diseases such as malaria and dengue. However, their efficacy in reducing mosquito biting and therefore malaria transmission has never been evaluated in Africa. This study will evaluate the efficacy of a spatial repellent in reducing mosquito biting on human beings and measure the impact any reduced biting will have on malaria transmission. The investigators will recruit and follow-up 5,984 children between 6 months and <10 years of age in Busia County to determine how many times they will be infected with malaria in villages where the investigators will have distributed spatial repellents and compare the rate of infection to villages where the investigators will not have distributed the repellent devices. Additionally, the investigators will measure whether the distribution of spatial repellents in one village will drive mosquitoes to their neighboring houses thereby increasing malaria transmission in those areas. The children participating in the study will be divided into 3 groups (cohorts). The first group will be followed up during the first 4 months before any intervention is distributed and the purpose here will be to determine that the villages are comparable. After this, the investigators will recruit the next group of participants and follow them up for 1 year and repeat this again for another year. During the follow-up, the children will be asked to come to the health facility where they will be tested for malaria using RDT or blood slide for microscopy. Every two weeks, a member of the study team will come to the participant's house and ask them if they had any history of fever. If the participants had fever, they will be tested for malaria. All children who turn out to be positive for malaria by RDT will be treated free of charge. At the same time, the investigators shall also perform mosquito collections to determine the impact of spatial repellents on the density of Anopheles mosquitoes.
Detailed Description
Spatial repellents (SRs) have been widely used for the prevention of mosquito bites but their protective efficacy (PE) in reducing mosquito-borne diseases has never been evaluated in Africa. To address this knowledge gap, western Kenya was selected as a site to estimate the impact of a transfluthrin-based spatial repellent on malaria-related outcomes in Busia County, where baseline malaria transmission ranges from 2.5 to 4.1 new infections per person per year.
A total of 5,984 children between 6 months and <10 years of age will be enrolled in three separate cohorts (baseline, cohort 1 and cohort 2). A total of 2,040 children from among 60 clusters will be enrolled for a four-month baseline prior to placement of the SR intervention. After baseline, a total of 1,972 participants from among 58 clusters, will be enrolled into cohort 1 and followed for one year. Cohort 2, consisting of a total of 1,972 children, will be enrolled from among 58 clusters to provide a total of two years of follow up. Children who have been selected for inclusion in the baseline cohort will be eligible for selection to cohort 1 or 2 but not both.
Cohort 1 and Cohort 2 during intervention will be split into two groups, one to estimate the direct effect of the SR (total of 1,624 children, 812 per follow up year) and a second to estimate the degree of diversion (or mass effect) of mosquitoes and malaria transmission from persons protected by the SR to persons who are unprotected (total of 2,320 children, 1,160 per follow up year). All cohorts will be followed once every two weeks with finger prick blood samples taken once every 4 weeks to test for malaria or whenever a participant reports a recent (within 48 hours) history of fever.
The incidence of malaria in the baseline cohort will be used to validate underlying assumptions prior to intervention. The incidence of malaria in each cohort followed with intervention will be estimated and compared to determine the benefit of using an SR in an area with high, year-round transmission of malaria. Monthly collections of mosquitoes using CDC light traps will be conducted to determine if there are entomological correlates of SR efficacy that may be useful for the evaluation of new SR products. Quarterly human landing catches will be done to assess the behavioral effects of the SR. The primary hypothesis on PE against the first-time malaria infection will be estimated by comparing the hazard rates of first-time malaria infection between SR and placebo upon the completion of the study in the ITT population.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Prevention
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 6 Months to 10 Years (Child)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Children aged 6 months to <10 years
- •Hb > 5mg/dl
- •Sleeps in cluster >90% of nights during any given month
- •No plans for extended travel (>1month) outside of home during study
- •Not participating in another clinical trial investigating a vaccine, drug, medical device, or a medical procedure during the Trial
- •Provision of informed consent form signed by the parent(s) or guardian
- •Children not on regular malaria prophylaxis° such as Proguanil
- •Willingness to take AL and no history of hypersensitivity to AL
Exclusion Criteria
- •Children < 6 months or ≥ 10 years
- •Hb ≤ 5 mg/dL, or Hb < 6mg/dL with signs of clinical decompensation
- •Sleeps in cluster <90% of nights during any given month
- •Plans for extended travel (>1month) outside of home during study
- •Participating or planned participation in another clinical trial investigating a vaccine, drug, medical device, or a medical procedure during the trial
- •No provision of informed consent form signed by the parent(s) or guardian
- •Children on regular malaria prophylaxis° such as Proguanil
- •Unwillingness or refusal to take AL and history of AL hypersensitivity
- •Other malaria prophylaxis medicines: Mefloquine, Atavaquone/Proguanil (Malarone), Doxycycline, Tafenoquine, Sulfadoxine-Pyrimethamine (Fansidar), Amodiaquine and Co-trimoxazole (Septrin)
Outcomes
Primary Outcomes
First-time malaria infection in core zones during intervention period.
Time Frame: 12 months
Measured by microscopy in children aged between 6 months to 10 years.
Secondary Outcomes
- Overall new malaria infections in core zones during intervention period.(12 months)
- Parasite-species-specific overall malaria infections in the core zones.(12 months)
- Anopheline parity rate as an indicator of population age structure for all anophelines and by anopheline species.(12 months)
- Overall new malaria infections in buffer zones during intervention period.(12 months)
- The first-time malaria infections in buffer zones during intervention period.(12 months)
- The first time malaria infections by two age groups (≤ 59 months old; 5 years to 10 years old).(12 months)
- Anopheline infectivity using EIR as an indicator for all anophelines and by anopheline species.(12 months)
- Insecticide resistance.(28 months)
- Parasite-species-specific first-time malaria infections in the core zones.(12 months)
- Anopheline infectivity using sporozoite rate as an indicator for all anophelines and by anopheline species.(12 months)
- CDC-light trap indoor density for all anophelines and by anopheline species.(12 months)
- Overall malaria infections by two age groups (≤ 59 months old; 5 years to 10 years old).(12 months)
- Anopheline-human contact (indoor and outdoor) using human biting rate (HBR) as an indicator for all anophelines and by anopheline species.(12 months)
- Adverse Events and Serious Adverse Events.(28 months)