Evaluating ATSBs for Malaria Reduction in Kenya

NCT ID: NCT05219565

Last Updated: 2024-06-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 2962 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-03-07
• Study Completion Date: 2024-04-24

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.

Conditions

Malaria

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Attractive Targeted Sugar Bait (ATSB)

Intervention Type: 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.

Control

Clusters within the control arm will not receive ATSBs.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Attractive Targeted Sugar Bait (ATSB)

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.

Intervention Type: DEVICE

Other Intervention Names

Attractive Toxic Sugar Bait

Eligibility Criteria

Inclusion Criteria

• A grouping of contiguous rural villages in Alego-Usonga and Rarieda sub-counties of Siaya County
• A minimum of 200 households

• 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

--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

• 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

• 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

• 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

• Serving as an ATSB monitoring assistant with experience installing ATSBs and monitoring the deployment Eighteen years of age or older

Exclusion Criteria

• Hard to reach in the rainy season
• Refusal to participate by village elders

• 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

• Refusal of consent by the head-of-household to deploy ATSB on the outer walls (intervention villages only)
• Vacated compounds

• 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

--Unable to provide consent

• Less than one month experience (i.e. is new to the job)
• Unable to provide consent

• Minimum Eligible Age: 1 Year
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Kenya Medical Research Institute

OTHER

Sponsor Role: collaborator

Centers for Disease Control and Prevention

FED

Sponsor Role: collaborator

PATH

OTHER

Sponsor Role: collaborator

Kenya Ministry of Health

OTHER_GOV

Sponsor Role: collaborator

Liverpool School of Tropical Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Aaron Samuels, MD, MHS

Role: PRINCIPAL_INVESTIGATOR

Centers for Disease Control and Prevention

Eric Ochomo

Role: PRINCIPAL_INVESTIGATOR

Kenya Medical Research Institute

Locations

Naya Health Centre

Siaya, Siaya County, Kenya

Benga Dispensary

Siaya, Siaya County, Kenya

Boro Dispensary

Siaya, Siaya County, Kenya

Manyuanda Health Centre

Siaya, Siaya County, Kenya

Nyadhi Dispensary

Siaya, Siaya County, Kenya

Ong'ielo Model Health Centre

Siaya, Siaya County, Kenya

Rabar Dispensary

Siaya, Siaya County, Kenya

Rageng'ni Dispensary

Siaya, Siaya County, Kenya

Rambugu Dispensary

Siaya, Siaya County, Kenya

Countries

Kenya

References

Huho B, Briet O, Seyoum A, Sikaala C, Bayoh N, Gimnig J, Okumu F, Diallo D, Abdulla S, Smith T, Killeen G. Consistently high estimates for the proportion of human exposure to malaria vector populations occurring indoors in rural Africa. Int J Epidemiol. 2013 Feb;42(1):235-47. doi: 10.1093/ije/dys214. Epub 2013 Feb 9.

Reference Type: BACKGROUND

PMID: 23396849 (View on PubMed)

Amek N, Bayoh N, Hamel M, Lindblade KA, Gimnig JE, Odhiambo F, Laserson KF, Slutsker L, Smith T, Vounatsou P. Spatial and temporal dynamics of malaria transmission in rural Western Kenya. Parasit Vectors. 2012 Apr 28;5:86. doi: 10.1186/1756-3305-5-86.

Reference Type: BACKGROUND

PMID: 22541138 (View on PubMed)

Moiroux N, Damien GB, Egrot M, Djenontin A, Chandre F, Corbel V, Killeen GF, Pennetier C. Human exposure to early morning Anopheles funestus biting behavior and personal protection provided by long-lasting insecticidal nets. PLoS One. 2014 Aug 12;9(8):e104967. doi: 10.1371/journal.pone.0104967. eCollection 2014.

Reference Type: BACKGROUND

PMID: 25115830 (View on PubMed)

Sougoufara S, Diedhiou SM, Doucoure S, Diagne N, Sembene PM, Harry M, Trape JF, Sokhna C, Ndiath MO. Biting by Anopheles funestus in broad daylight after use of long-lasting insecticidal nets: a new challenge to malaria elimination. Malar J. 2014 Mar 28;13:125. doi: 10.1186/1475-2875-13-125.

Reference Type: BACKGROUND

PMID: 24678587 (View on PubMed)

Killeen GF. Characterizing, controlling and eliminating residual malaria transmission. Malar J. 2014 Aug 23;13:330. doi: 10.1186/1475-2875-13-330.

Reference Type: BACKGROUND

PMID: 25149656 (View on PubMed)

Killeen GF, Marshall JM, Kiware SS, South AB, Tusting LS, Chaki PP, Govella NJ. Measuring, manipulating and exploiting behaviours of adult mosquitoes to optimise malaria vector control impact. BMJ Glob Health. 2017 Apr 26;2(2):e000212. doi: 10.1136/bmjgh-2016-000212. eCollection 2017.

Reference Type: BACKGROUND

PMID: 28589023 (View on PubMed)

Zhu L, Muller GC, Marshall JM, Arheart KL, Qualls WA, Hlaing WM, Schlein Y, Traore SF, Doumbia S, Beier JC. Is outdoor vector control needed for malaria elimination? An individual-based modelling study. Malar J. 2017 Jul 3;16(1):266. doi: 10.1186/s12936-017-1920-y.

Reference Type: BACKGROUND

PMID: 28673298 (View on PubMed)

Traore MM, Junnila A, Traore SF, Doumbia S, Revay EE, Kravchenko VD, Schlein Y, Arheart KL, Gergely P, Xue RD, Hausmann A, Beck R, Prozorov A, Diarra RA, Kone AS, Majambere S, Bradley J, Vontas J, Beier JC, Muller GC. Large-scale field trial of attractive toxic sugar baits (ATSB) for the control of malaria vector mosquitoes in Mali, West Africa. Malar J. 2020 Feb 14;19(1):72. doi: 10.1186/s12936-020-3132-0.

Reference Type: BACKGROUND

PMID: 32059671 (View on PubMed)

Beier JC, Muller GC, Gu W, Arheart KL, Schlein Y. Attractive toxic sugar bait (ATSB) methods decimate populations of Anopheles malaria vectors in arid environments regardless of the local availability of favoured sugar-source blossoms. Malar J. 2012 Feb 1;11:31. doi: 10.1186/1475-2875-11-31.

Reference Type: BACKGROUND

PMID: 22297155 (View on PubMed)

Fiorenzano JM, Koehler PG, Xue RD. Attractive Toxic Sugar Bait (ATSB) For Control of Mosquitoes and Its Impact on Non-Target Organisms: A Review. Int J Environ Res Public Health. 2017 Apr 10;14(4):398. doi: 10.3390/ijerph14040398.

Reference Type: BACKGROUND

PMID: 28394284 (View on PubMed)

Marshall JM, White MT, Ghani AC, Schlein Y, Muller GC, Beier JC. Quantifying the mosquito's sweet tooth: modelling the effectiveness of attractive toxic sugar baits (ATSB) for malaria vector control. Malar J. 2013 Aug 23;12:291. doi: 10.1186/1475-2875-12-291.

Reference Type: BACKGROUND

PMID: 23968494 (View on PubMed)

Pocock SJ. When (not) to stop a clinical trial for benefit. JAMA. 2005 Nov 2;294(17):2228-30. doi: 10.1001/jama.294.17.2228. No abstract available.

Reference Type: BACKGROUND

PMID: 16264167 (View on PubMed)

Protopopoff N, Mosha JF, Lukole E, Charlwood JD, Wright A, Mwalimu CD, Manjurano A, Mosha FW, Kisinza W, Kleinschmidt I, Rowland M. Effectiveness of a long-lasting piperonyl butoxide-treated insecticidal net and indoor residual spray interventions, separately and together, against malaria transmitted by pyrethroid-resistant mosquitoes: a cluster, randomised controlled, two-by-two factorial design trial. Lancet. 2018 Apr 21;391(10130):1577-1588. doi: 10.1016/S0140-6736(18)30427-6. Epub 2018 Apr 11.

Reference Type: BACKGROUND

PMID: 29655496 (View on PubMed)

Gimnig JE, Walker ED, Otieno P, Kosgei J, Olang G, Ombok M, Williamson J, Marwanga D, Abong'o D, Desai M, Kariuki S, Hamel MJ, Lobo NF, Vulule J, Bayoh MN. Incidence of malaria among mosquito collectors conducting human landing catches in western Kenya. Am J Trop Med Hyg. 2013 Feb;88(2):301-8. doi: 10.4269/ajtmh.2012.12-0209. Epub 2012 Dec 18.

Reference Type: BACKGROUND

PMID: 23249685 (View on PubMed)

Ogwang C, Samuels AM, McDermott DP, Kamau A, Lesosky M, Obiet K, Janssen JM, Odongo W, Gimnig JE, Gutman JR, Schultz JS, Towett O, Seda B, Chepkirui M, Muchoki M, Omondi S, Kosgei J, Polo B, Aduwo F, Otieno K, Donnelly MJ, Kariuki S, Ochomo E, Kuile FT, Staedke SG. Attractive targeted sugar baits for malaria control in western Kenya (ATSB-Kenya) - Effect of ATSBs on epidemiologic and entomologic indicators: A Phase III, open-label, cluster-randomised, controlled trial. PLOS Glob Public Health. 2025 Jun 26;5(6):e0004230. doi: 10.1371/journal.pgph.0004230. eCollection 2025.

Reference Type: DERIVED

PMID: 40570028 (View on PubMed)

Kamau A, Obiet K, Ogwang C, McDermott DP, Lesosky M, Janssen J, Odongo W, Gutman JR, Schultz JS, Nicholas W, Seda B, Chepkirui M, Aduwo F, Towett O, Otieno K, Donnelly MJ, Ochomo E, Kariuki S, Samuels AM, O Ter Kuile F, Staedke SG. Attractive targeted sugar baits for malaria control in western Kenya (ATSB-Kenya): enrolment characteristics of cohort children and households. Malar J. 2024 Dec 30;23(1):403. doi: 10.1186/s12936-024-05234-0.

Reference Type: DERIVED

PMID: 39736740 (View on PubMed)

Attractive Targeted Sugar Bait Phase III Trial Group. Attractive targeted sugar bait phase III trials in Kenya, Mali, and Zambia. Trials. 2022 Aug 9;23(1):640. doi: 10.1186/s13063-022-06555-8.

Reference Type: DERIVED

PMID: 35945599 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

21-027

Identifier Type: -

Identifier Source: org_study_id