Evaluation of the protective efficacy of a spatial repellent to reduce malaria incidence in children in Mali compared to placebo: study protocol for a cluster-randomized double-blinded control trial (the AEGIS program)

Suzanne Van Hulle, Issaka Sagara, Momar Mbodji, Ghislain Ismael Nana, Mamadou Coulibaly, Alassane Dicko, Mamady Kone, Ismaila Thera, Daman Sylla, Mamadou Diango Traore, Fang Liu, John P Grieco, Nicole L Achee, Suzanne Van Hulle, Issaka Sagara, Momar Mbodji, Ghislain Ismael Nana, Mamadou Coulibaly, Alassane Dicko, Mamady Kone, Ismaila Thera, Daman Sylla, Mamadou Diango Traore, Fang Liu, John P Grieco, Nicole L Achee

Abstract

Background: Spatial repellents have been widely used for the prevention of mosquito bites but their efficacy in reducing mosquito-borne diseases has never been evaluated in Africa. Additionally, spatial repellents have the potential of being critical tools in the prevention of mosquito-borne diseases in contexts where typical vectors control efforts such as insecticide-treated nets (ITNs) and indoor residual spray (IRS) are inaccessible or underutilized such as among displaced populations or in emergency relief settings. To address this knowledge gap, Kolondieba District, Sikasso Region, Mali was selected as a site to estimate the impact of the Mosquito Shield™, a spatial repellent that incorporates transfluthrin on a plastic sheet, on malaria-related outcomes. Over the past decade, the Region of Sikasso, Health districts of Kadiolo, Yorosso, and Kolondieba have remained among the most afflicted, characterized by an annual parasite incidence of more than 116 cases per 1000 population [1] and a Plasmodium falciparum prevalence rate of 29.7% [2].

Methods: Cluster-randomized, placebo-controlled, double-blinded clinical trial, whereby children ≥ 6 months to < 10 years old will be enrolled and followed to determine the time to malaria infection with monthly blood samples for microscopic diagnosis. A total of 1920 subjects (HHs) will be enrolled in 60 clusters (30 spatial repellent, 30 placebo). Malaria incidence will be estimated and compared to demonstrate and quantify the protective efficacy (PE) of a spatial repellent, in reducing malaria infection. Monthly mosquito collections using CDC light traps will be conducted to determine if there are entomological correlates of spatial repellent efficacy that may be useful for the evaluation of new spatial repellents. Quarterly human landing catches (HLC) will assess the behavioral effects of the intervention.

Discussion: Findings will serve as an efficacy trial of spatial repellent products for sub-Saharan Africa. Findings will be submitted to the World Health Organization Vector Control Advisory Group (WHO VCAG) for assessment of whether spatial repellents have "public health value." Entomological outcomes will also be measured as proxies of malaria transmission to help develop guidelines for the evaluation of future spatial repellent products.

Trial registration: ClinicalTrials.gov NCT04795648 . Registered on March 12, 2021.

Keywords: Cluster randomized controlled trial; Malaria; Mali; Spatial repellent; Transfluthrin.

Conflict of interest statement

The authors declare that they have no competing interests.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Distribution of clusters and location of health facilities in the study area

References

    1. Système Local d’Information Sanitaire, (SLIS) Annuaire Statistique 2018 du Système Local d'Information Sanitaire du Mali. Bamako: Ministere de la Sante et du Developpement Social; 2019. p. 195.
    1. Institut National de la Statistique-, INSTAT, Santé-Développement Cellule de Planification et de Statistique SecteurCellule de Planification et de Statistique Secteur Santé-Développement Social et Promotion de la Famille . Mali Demographic and Health Survey 2018. Bamako: THe Demographic and Health Surveys; 2019.
    1. WHO . World Malaria Report 2020. Geneva: World Health Organization; 2020. p. 299.
    1. Achee NL, Bangs MJ, Farlow R, Killeen GF, Lindsay S, Logan JG, et al. Spatial Repellents: from Discovery and Development to Evidence-Based Validation. Malar J. 2012;11:164.
    1. WHO. Guidelines for Efficacy Testing of Spatial Repellents. WHO; 2013.
    1. Hill N, Zhou HN, Wang P, Guo X, Carneiro I, Moore SJ. A household randomized, controlled trial of the efficacy of 0.03% transfluthrin coils alone and in combination with long-lasting insecticidal nets on the incidence of Plasmodium falciparum and Plasmodium vivax malaria in Western Yunnan Province, China. Malar J. 2014;13(1):208. doi: 10.1186/1475-2875-13-208.
    1. Syafruddin D, Asih PBS, Rozi IE, Permana DH, Nur Hidayati AP, Syahrani L, Zubaidah S, Sidik D, Bangs MJ, Bøgh C, Liu F, Eugenio EC, Hendrickson J, Burton T, Baird JK, Collins F, Grieco JP, Lobo NF, Achee NL. Efficacy of a Spatial Repellent for Control of Malaria in Indonesia: A Cluster-Randomized Controlled Trial. Am J Trop Med Hyg. 2020;103(1):344–358. doi: 10.4269/ajtmh.19-0554.
    1. Morrison AC, Reiner RC, Elson WH, Astete H, Guevara C, del Aguila C, Bazan I, Siles C, Barrera P, Kawiecki AB, Barker CM et al. Efficacy of a spatial repellent for control of Aedes-borne virus transmission: a cluster randomized trial in Iquitos, Peru. medRxiv. 2021. 10.1101/2021.03.03.21252148.
    1. Programme National de Lutte contre le Paludisme (PNLP), Institut National de la Statistique (INSTAT), INFO-STAT, Institut National de la Recherche en Santé Publique (INRSP) et ICF International, 2016. Enquête sur les Indicateurs du Paludisme au Mali (EIPM) 2015. Rockville: INSTAT, INFO-STAT et ICF International. .
    1. District Health Information Software, 2 (DHIS2). Health Management Information System. 2018. . Accessed 19 July 2021.
    1. Cisse MBM, Keita C, Dicko A, Dengela D, Coleman J, Lucas B, Mihigo J, Sadou A, Belemvire A, George K, Fornadel C, Beach R. Characterizing the Insecticide Resistance of Anopheles gambiae in Mali. Malar J. 2015;14(1):327. doi: 10.1186/s12936-015-0847-4.
    1. Keita M, Traoré S, Sogoba N, Dicko AM, Coulibaly B, Sacko A, et al. Susceptibility status of Anopheles gambiae sensu lato to insecticides commonly used for malaria control in Mali. Bull Soc Pathol Exot. 2016;109(1):39–45. doi: 10.1007/s13149-015-0461-2.
    1. Fanello C, Petrarca V. della Torre A, Santolamazza F, Dolo G, Coulibaly M, et al. The Pyrethroid Knock-Down Resistance Gene in the Anopheles gambiae Complex in Mali and Further Indication of Incipient Speciation within An. gambiae s.s. Insect Mol Biol. 2003;12(3):241–245. doi: 10.1046/j.1365-2583.2003.00407.x.
    1. Tripet F, Wright J, Cornel A, Fofana A, McAbee R, Meneses C, et al. Longitudinal Survey of Knockdown Resistance to Pyrethroid (Kdr) In Mali, West Africa, and Evidence of its Emergence in the Bamako Form of Anopheles gambiae s.s. Am J Trop Med Hyg. 2007;76(1):81–87. doi: 10.4269/ajtmh.2007.76.81.
    1. WHO-Department of Control of Neglected Tropical Diseases . Guidance on Phase III Vector Control Field Trial Design. Geneva: World Health Organization; 2017. How to Design Vector Control Efficacy Trials; p. 62.
    1. Millum J, Grady C. The ethics of placebo-controlled trials: Methodological justifications. Contemp Clin Trials. 2013;36(2):514. doi: 10.1016/j.cct.2013.09.003.
    1. Syafruddin D, Bangs MJ, Sidik D, Elyazar I, Asih PBS, Chan K, et al. Impact of a Spatial Repellent on Malaria Incidence in Two Villages in Sumba, Indonesia. Am J Trop Med Hyg. 2014;91(6):1079–1087. doi: 10.4269/ajtmh.13-0735.
    1. Choi DB, Grieco JP, Apperson CS, Schal C, Ponnusamy L, Wesson DM, Achee NL. Effect of Spatial Repellent Exposure on Dengue Vector Attraction to Oviposition Sites. PLoS Negl Trop Dis. 2016;10(7):e0004850. doi: 10.1371/journal.pntd.0004850.
    1. Horstmann S, Sonneck R. Contact Bioassays with Phenoxybenzyl and Tetrafluorobenzyl Pyrethroids against Target-Site and Metabolic Resistant Mosquitoes. PloS one. 2016;11(3):e0149738. doi: 10.1371/journal.pone.0149738.
    1. Institut National de la Statistique, (INSTAT) Recensement General de la Population et de l’Habitat du Mali. Bamako: INSTAT; 2009.
    1. Benjamini Y, Hochberg Y. Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing. J R Stat Soc. 1995;57(1):289–300.
    1. Norris E, Coats J. Current and Future Repellent Technologies: The Potential of Spatial Repellents and Their Place in Mosquito-Borne Disease Control. Int J Environ Res Public Health. 2017;14(2):124. doi: 10.3390/ijerph14020124.
    1. WHO . Seventh Meeting of the Vector Control Advisory Group (VCAG) Geneva: World Health Organization; 2017.

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