Phase III, Open-label, Community-based, Cluster Randomised Controlled Trial to Evaluate the Efficacy, Cost-effectiveness, and Acceptability of Attractive Targeted Sugar Baits (ATSB) for Malaria Burden Reduction in Western Kenya
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Enrollment
- 2,962
- Locations
- 9
- Primary Endpoint
- Clinical malaria
Study Overview
Brief Summary
The effectiveness of long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) in western Kenya are threatened by insecticide resistance and vector behaviour changes toward early evening and outdoor biting malaria vectors. New tools to control malaria are needed to reduce and even interrupt malaria transmission. Attractive Targeted Sugar Bait (ATSB) is a promising new intervention designed to attract and kill mosquitoes, including those that IRS and LLINs do not effectively target. The ATSB 'bait stations' are A4-sized panels containing thickened fruit syrup laced with a neonicotinoid insecticide, dinotefuran, to attract and kill the foraging vectors. Entomological field trials in western Mali showed that ATSBs successfully reduce mosquito densities and longevity and thus have the potential to reduce malaria transmission. In Kenya, the investigators will conduct an open-label cluster-randomized controlled trial in 80 village clusters (40 per arm) to evaluate the effect of ATSBs on the burden of malaria. During two years, households in half of these village clusters will receive two or three ATSB bait stations per household structure on exterior walls approximately 1.8 meters above the ground. ATSBs will be replaced every six months. The primary outcome will be the incidence of clinical malaria in children aged 1-<15 years enrolled in a prospective cohort followed monthly for about six months each during a 2-year period. Secondary outcomes include malaria infection prevalence assessed by rapid diagnostic tests through household surveys and the case burden of clinical malaria assessed by passive facility-based and community-based surveillance. The study includes entomological monitoring and nested acceptability, feasibility, and health economics studies. The stand-alone trial in western Kenya is a part of a multi-country ATSB consortium conducting similar trials in Zambia and Mali.
Detailed Description
The current malaria vector control tools, long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) are critically important and have saved many lives. However, their effectiveness in western Kenya is threatened by insecticide resistance and vector behaviour changes toward more early evening and outdoor biting malaria vectors. LLINs and IRS specifically target indoor-biting and indoor-resting mosquitoes. Malaria vectors exhibit different behavioural characteristics that mitigate the effectiveness of vector control strategies. For example, traditionally, An. gambiae s.s. has been regarded as human-biting with late-night indoor-feeding and indoor-resting behaviours, while An. Arabiensis is found more often in drier environments and is more zoophagic with outdoor biting and resting behaviours. Following LLINs and IRS's widespread scale-up, the dominant African vectors' distributions and behaviours changed with An. gambiae s.s. and An. Funestus (also an indoor human biter) diminishing in abundance relative to An. arabiensis. Subsequently, shifts towards earlier evening biting by An. Gambiae s.s. (before people enter houses to sleep under LLINs) and later biting by An. Funestus (biting in the morning after sunrise) are examples of behavioural plasticity enabling these species to avoid contact with the LLIN and IRS insecticides.
There is a need for interventions that supplement and complement LLINs and IRS by killing mosquitoes outside houses using other biologic mechanisms (e.g., targeting sugar feeding behaviour). Furthermore, insecticides are required with novel modes of action that may restore sensitivity to pyrethroids by killing both pyrethroid-resistant and sensitive mosquitoes. Attractive Targeted Sugar Bait (ATSB) (the name was recently changed from Attractive Toxic Sugar Bait to highlight that it targets malaria vectors) is a promising new intervention that potentially fills the need for outdoor interventions with novel killing effects.
ATSB 'bait stations' are A4-sized panels containing thickened fruit syrup laced with a neonicotinoid insecticide (dinotefuran) to attract and kill the foraging vectors. Entomological field trials in Mali showed that ATSBs successfully reduce mosquito densities and longevity and thus have the potential to reduce malaria transmission. Large scale efficacy studies are now needed to establish the efficacy of ATSB for controlling malaria transmission.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Prevention
- Masking
- None
Eligibility Criteria
- Ages
- 1 Year to — (Child, Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Eligibility criteria for clusters: Inclusion criteria
- •A grouping of contiguous rural villages in Alego-Usonga and Rarieda sub-counties of Siaya County
- •A minimum of 200 households
- •Eligibility criteria for clusters:
Exclusion Criteria
- •Hard to reach in the rainy season
- •Refusal to participate by village elders
- •Eligibility criteria for participants in the cohort study: Inclusion criteria
- •A resident of a household within the core area of a study cluster, defined as living in the household in the recent four months and planning to live in the same household for the next 6.5 months
- •Aged ≥ 1 year and < 15 years at the time of enrollment
- •Written informed consent and/or assent
- •Eligibility criteria for participants in the cohort study: Exclusion criteria
- •A confirmed or suspected pregnancy. Pregnant women are excluded because they are eligible for intermittent preventive treatment of malaria in pregnancy (IPTp).
- •Taking daily cotrimoxazole prophylaxis (because this has antimalarial effects)
- •Known sickle cell disease (because they received antimalarial prophylaxis)
- •Contraindication to artemether-lumefantrine, the medication used for parasite clearance
- •Eligibility criteria for households for ATSB deployment: Inclusion criteria
- •-Households located within one of the 40 clusters (core or buffer area) randomly allocated to the trial intervention arm with a least one permanent resident
- •Eligibility criteria for households for ATSB deployment: Exclusion criteria
- •Refusal of consent by the head-of-household to deploy ATSB on the outer walls (intervention villages only)
- •Vacated compounds
- •Eligibility criteria for households for entomological monitoring: Inclusion criteria
- •Household located within the core area of the cluster
- •Head of household or his/her representative is at least 18 years of age
- •Written informed consent for the collection of entomological data by the head of household or representative
- •Eligibility criteria for households for entomological monitoring: Exclusion criteria --No residents sleeping in the household during the planned night of monitoring
- •Eligibility criteria for human landing catches: Inclusion criteria
- •Men aged 18 to 49 years
- •Willingness and ability to work late at night for up to 7 hours at a time
- •Willingness to take and tolerate a treatment regimen of the appropriate Kenya Ministry of Health (MoH) recommended antimalarial and chemoprophylaxis with 250 mg of mefloquine weekly to prevent malaria starting two weeks before the start of and until four weeks after completing HLCs
- •Written informed consent
- •Eligibility criteria for human landing catches: Exclusion criteria
- •Refusal/inability to work late at night for up to 7 hours at a time
- •Unwillingness to take or intolerance/allergy to appropriate MoH treatment regimen or chemoprophylaxis
- •Eligibility criteria for participants in rapid ethnographic methods evaluation (community members): Inclusion criteria
- •A resident of a household within an intervention area defined as an ATSB area during the main trial or an ASB area during any preliminary studies
- •Resides in a household at the time of ASB/ATSB deployment, where the ASB/ATSB was installed for at least one month.
- •18 years of age or older if participating in focus group discussions; 15 years of age or older if participating in in-depth interviews
- •Eligibility criteria for participants in rapid ethnographic methods evaluation (community members): Exclusion criteria
- •-Unable to provide consent
- •Eligibility criteria for participants in rapid ethnographic methods evaluation (ATSB monitoring assistants): Inclusion criteria
- •Inclusion criteria ethnographic evaluation (ATSB monitoring assistants)
- •Serving as an ATSB monitoring assistant with experience installing ATSBs and monitoring the deployment Eighteen years of age or older
- •Eligibility criteria for participants in rapid ethnographic methods evaluation (ATSB monitoring assistants): Exclusion criteria
- •Less than one month experience (i.e. is new to the job)
- •Unable to provide consent
Arms & Interventions
Attractive Targeted Sugar Bait (ATSB)
Clusters within the ATSB arm will have 2 ATSBs hung on all eligible structures in the cluster where consent from the corresponding compound has been given.
Intervention: Attractive Targeted Sugar Bait (ATSB) (Device)
Control
Clusters within the control arm will not receive ATSBs.
Outcomes
Primary Outcomes
Clinical malaria
Time Frame: Two years
The incidence rate of clinical malaria defined as current fever (axillary temperature of ≥37.5°C) or history of fever in last 48 hours and a positive rapid diagnostic test (RDT, pLDH or HRP2), in children aged 1-\<15 years enrolled in the cohort study
Secondary Outcomes
- AEs(Two years)
- Perceptions of ATSBs(Two years)
- Complexity of infection (COI)(Two years)
- Incidence of non-malaria illness (cohort)(Two years)
- Incidence of non-malaria illness (passive surveillance)(Two years)
- Prevalence of non-malaria illness(Two years)
- Sporozoite rate(Two years)
- Markers of insecticide resistance (deltamethrin)(Two years)
- Time to first malaria infection by PCR(Two years)
- Malaria infection incidence by RDT (pLDH)(Two years)
- Incidence of malaria illness (passive surveillance)(Two years)
- Entomological Inoculation Rate (EIR)(Two years)
- Non-Target Organisms (NTOs) attracted to ATSBs(Two years)
- Household care seeking behavior in the setting of ATSBs(Two years)
- Markers of insecticide resistance (dinotefuran)(Two years)
- Markers of insecticide resistance (permethrin)(Two years)
- Antibody concentrations against malaria antigen MSP-1(Two years)
- Antibody concentrations against malaria antigen CSP(Two years)
- Malaria vector density(Two years)
- Malaria infection prevalence by RDT (pLDH)(Two years)
- Proportion of female anopheles mosquitoes older than three gonotrophic cycles,(Two years)
- Mosquito salivary antigens(Two years)
- ATSB removal rate(Two years)
- Household use of LLINs in the setting of ATSBs(Two years)
- Cost-effectiveness(Two years)