Mass Drug Administration of Ivermectin and Dihydroartemisinin-piperaquine as an Additional Intervention for Malaria Elimination

Summary

This is a community-based cluster-randomized trial in which a novel approach to interrupt residual malaria transmission by mass drug administration (MDA) with ivermectin (IVM) combined with dihydroartemisinin-piperaquine (DP) will be tested. This cluster-randomized trial will involve 32 villages in the Upper River Region of The Gambia that will be randomized to MDA with IVM and DP or to standard of care in a ratio 1:1. This trial aims at establishing whether MDA with IVM and DP can reduce or interrupt malaria transmission in medium to low transmission settings by reducing vector survival and the human reservoir of infection. MDA with IVM and DP will be implemented in the intervention villages and all human settlements in the buffer zone, with the aim of minimizing spillover effects. Control clusters will receive standard malaria control interventions as implemented by the National Malaria Control Program. The primary outcomes will be the prevalence of malaria infection determined by molecular methods in all age groups at the peak of the second transmission season (November-December 2019) and the vector's parous rate 7-14 days after MDA.

Timeline

Start

2018-08-11

Primary completion

2019-12-31

Completion

2021-07-31

Outcome

Mixed primary results

paper Primary outcomes were malaria prevalence by qPCR at the end of the second intervention year in November 2019, and Anopheles gambiae (s l) parous rate PMID 34919831 ↗

paper In November 2019, malaria prevalence was 12·8% (324 of 2529) in the control group and 5·1% (140 of 2722) in the intervention group PMID 34919831 ↗

paper (odds ratio [OR] 0·30, 95% CI 0·16-0·59; p<0·001). PMID 34919831 ↗

paper A gambiae (s l) parous rate was 83·1% (552 of 664) in the control group and 81·7% (441 of 540) in the intervention group (0·90, 0·66-1·25; p=0·537). PMID 34919831 ↗

Publications

• Kositz C, Vasileva H, Mohammed N, Achan J, Dabira ED, D'Alessandro U, Bradley J, Marks M. Risk factors for non-participation in ivermectin and dihydroartemisinin-piperaquine mass drug administration for malaria control in the MASSIV trial. Malar J. 2024 Feb 22;23(1):54. doi: 10.1186/s12936-024-04878-2.
• Fehr A, Nieto-Sanchez C, Muela J, Manneh E, Baldeh D, Ceesay O, D'Alessandro U, Dabira E, Kingori P, Peeters Grietens K, Bardaji A, Bunders-Aelen J, Zuiderent-Jerak T. Doing 'reciprocity work': The role of fieldworkers in a mass drug administration trial in the Gambia. Glob Public Health. 2022 Dec;17(12):4116-4128. doi: 10.1080/17441692.2022.2125998. Epub 2022 Oct 2.
• Dabira ED, Soumare HM, Conteh B, Ceesay F, Ndiath MO, Bradley J, Mohammed N, Kandeh B, Smit MR, Slater H, Peeters Grietens K, Broekhuizen H, Bousema T, Drakeley C, Lindsay SW, Achan J, D'Alessandro U. Mass drug administration of ivermectin and dihydroartemisinin-piperaquine against malaria in settings with high coverage of standard control interventions: a cluster-randomised controlled trial in The Gambia. Lancet Infect Dis. 2022 Apr;22(4):519-528. doi: 10.1016/S1473-3099(21)00557-0. Epub 2021 Dec 15.
• Dabira ED, Soumare HM, Lindsay SW, Conteh B, Ceesay F, Bradley J, Kositz C, Broekhuizen H, Kandeh B, Fehr AE, Nieto-Sanchez C, Ribera JM, Peeters Grietens K, Smit MR, Drakeley C, Bousema T, Achan J, D'Alessandro U. Mass Drug Administration With High-Dose Ivermectin and Dihydroartemisinin-Piperaquine for Malaria Elimination in an Area of Low Transmission With High Coverage of Malaria Control Interventions: Protocol for the MASSIV Cluster Randomized Clinical Trial. JMIR Res Protoc. 2020 Nov 19;9(11):e20904. doi: 10.2196/20904.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	ARTENIMOL	Small molecule	20 mg	Oral
Subject	ARTENIMOL	Small molecule	40 mg	Oral
Subject	Ivermectin	Small molecule	300 ug/kg	Oral
Subject	Ivermectin	Small molecule	400 ug/kg	Oral
Subject	piperaquine	Small molecule	160 mg	Oral
Subject	piperaquine	Small molecule	320 mg	Oral

Indications