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Completed

NCT Number: NCT05219565

Evaluating ATSBs for Malaria Reduction in Kenya

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.

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Key information

Age range

1 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Benga Dispensary, Siaya, Siaya County, Kenya

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About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Attractive Targeted Sugar Bait (ATSB)

Device

An ATSB is a A4-sized panel containing thickened fruit syrup laced with a neonicotinoid insecticide, dinotefuran. The syrup-insecticide mixture is covered with a protective membrane that allows mosquitoes to feed through the membrane while preventing non-target organisms from feeding. This device is designed to attract and kill mosquitoes.

Other names: Attractive Toxic Sugar Bait

Primary outcomes

  1. 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

  1. Time to first malaria infection by PCR

    Time frame: Two years

    The time to first malaria infection assessed by PCR in children aged 1-<15 years enrolled in a cohort study

  2. Malaria infection incidence by RDT (pLDH)

    Time frame: Two years

    The incidence rate of malaria infection detected by RDT (pLDH) in children aged 1-<15 years enrolled in a cohort study

  3. Malaria infection prevalence by RDT (pLDH)

    Time frame: Two years

    The prevalence of malaria infection detected by RDT (pLDH) in cross-sectional household surveys

  4. Incidence of malaria illness (passive surveillance)

    Time frame: Two years

    The incidence rate of malaria illness (sick-visit with a positive malaria rapid diagnostic test or microscopy) assessed by health-facility and community-based surveillance

  5. Incidence of non-malaria illness (cohort)

    Time frame: Two years

    The incidence rate of non-malaria illness in children aged 1-<15 years enrolled in a cohort study

  6. Incidence of non-malaria illness (passive surveillance)

    Time frame: Two years

    The incidence rate of non-malaria illness assessed by health-facility and community-based surveillance

  7. Prevalence of non-malaria illness

    Time frame: Two years

    The prevalence of non-malaria illness in cross-sectional household surveys

  8. Malaria vector density

    Time frame: Two years

    Entomological outcome: Malaria vector densities

  9. Proportion of female anopheles mosquitoes older than three gonotrophic cycles,

    Time frame: Two years

    Entomological outcome: The proportion of female anopheles mosquitoes older than three gonotrophic cycles.

  10. Sporozoite rate

    Time frame: Two years

    Entomological outcomes: Sporozoite rate

  11. Entomological Inoculation Rate (EIR)

    Time frame: Two years

    Entomological outcome: Entomological Inoculation Rate (EIR)

  12. Non-Target Organisms (NTOs) attracted to ATSBs

    Time frame: Two years

    Entomological outcome: Proportion of monitoring visits where NTOs were observed on bait stations

  13. Markers of insecticide resistance (dinotefuran)

    Time frame: Two years

    Entomological outcome: Proportion of mosquitoes with resistance to dinotefuran among total mosquitoes collected in 4 WHO mosquito tubes in the trial area

  14. Markers of insecticide resistance (permethrin)

    Time frame: Two years

    Entomological outcome: Proportion of mosquitoes with resistance to permethrin among total mosquitoes collected in 4 WHO mosquito tubes in the trial area

  15. Markers of insecticide resistance (deltamethrin)

    Time frame: Two years

    Entomological outcome: Proportion of mosquitoes with resistance to deltamethrin among total mosquitoes collected in 4 WHO mosquito tubes in the trial area

  16. Antibody concentrations against malaria antigen MSP-1

    Time frame: Two years

    Antibody concentration against merozoite surface protein-1 (MSP-1) among cohort participants

  17. Antibody concentrations against malaria antigen CSP

    Time frame: Two years

    Antibody concentration against circumsporozoite proteins (CSP) among cohort participants

  18. Complexity of infection (COI)

    Time frame: Two years

    The complexity of (malaria) infection assessed by molecular markers, including, but not limited to, 24-single-nucleotide polymorphisms (24-SNP) barcodes

  19. Mosquito salivary antigens

    Time frame: Two years

    Presence of mosquito salivary antigens in human blood as a measure for mosquito biting rates among cohort participants

  20. AEs

    Time frame: Two years

    Number of adverse events associated with misuse of ATSBs.

  21. ATSB removal rate

    Time frame: Two years

    The proportion of ATSBs that have been moved/removed

  22. Perceptions of ATSBs

    Time frame: Two years

    The proportion of household heads who perceive ATSBs as safe and effective out of all household head who consented to ATSB deployment on their household structures.

  23. Household use of LLINs in the setting of ATSBs

    Time frame: Two years

    The proportion of children aged 1-<15 years enrolled in a cohort study who used an LLIN the night prior

  24. Household care seeking behavior in the setting of ATSBs

    Time frame: Two years

    The proportion of children aged 1-<15 years enrolled in a cohort study who sought care for febrile illness

  25. Cost-effectiveness

    Time frame: Two years

    Incremental cost-effectiveness of ATSB above the standard of care measured through costing of intervention and efficacy outcomes

Sponsors and collaborators

Lead sponsor

Liverpool School of Tropical Medicine

Other

Collaborators

  • Centers for Disease Control and Prevention
  • Kenya Medical Research Institute
  • Kenya Ministry of Health
  • PATH

Registry information

Official study title

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

Important dates

Study start
2022
Primary completion
2024
Study completion
2024
First posted
Feb 2, 2022
Registry last updated
Jun 10, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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