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Adjunctive ivermectin mass drug administration for malaria control on the Bijagos Archipelago of Guinea-Bissau (MATAMAL): a quadruple-blinded, cluster-randomised, placebo-controlled trial - 15/11/24

Doi : 10.1016/S1473-3099(24)00580-2 
Harry Hutchins, MSc a, Elizabeth Pretorius, MSc b, John Bradley, PhD c, Eunice Teixeira da Silva, RN e, f, Hristina Vasileva, MSc a, d, Mamadou Ousmane Ndiath, PhD g, Robert T Jones, PhD b, Harouna dit Massire Soumare, PharmD g, Haddy Nyang, MSc g, Aurelia Prom, BSc g, Sarata Sambou, BSc g, Fatima Ceesay, MSc g, Sainey Ceesay, BSc g, Sophie Moss, MSc a, David Mabey, ProfDM a, Paulo Djata, MD h, Jose Ernesto Nante, MSc h, Cesario Martins, PhD e, James G Logan, ProfPhD b, i, Hannah Slater, PhD j, Kevin Tetteh, PhD d, k, Chris Drakeley, ProfPhD d, Umberto D’Alessandro, ProfPhD g, Amabelia Rodrigues, PhD e, f, Anna Last, PhD a,
a Clinical Research Department, London School of Hygiene & Tropical Medicine, London, UK 
b Department of Disease Control, London School of Hygiene & Tropical Medicine, London, UK 
c Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK 
d Department of Infection Biology, London School of Hygiene & Tropical Medicine, London, UK 
e Projecto de Saúde Bandim, Bissau, Guinea-Bissau 
f Instituto Nacional da Saúde Pública, Ministério de Saúde Pública, Bissau, Guinea-Bissau 
g Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, Fajara, The Gambia 
h Programa Nacional de Luta Contra o Paludismo, Ministério de Saúde, Bissau, Guinea-Bissau 
i Arctech Innovation, London, UK 
j PATH, Seattle, USA 
k FIND, Geneva, Switzerland 

* Correspondence to: Dr Anna Last, Clinical Research Department, London School of Hygiene & Tropical Medicine, London WC1 E7HT, UK Clinical Research Department London School of Hygiene & Tropical Medicine London WC1 E7HT UK
Sous presse. Épreuves corrigées par l'auteur. Disponible en ligne depuis le Friday 15 November 2024

Summary

Background

Arthropod vectors feeding on the blood of individuals treated with ivermectin have substantially increased mortality. Whether this effect will translate into a useful tool for reducing malaria burden at scale is not clear. Our trial aimed to assess whether using ivermectin as an adjunct to mass drug administration (MDA) with dihydroartemisinin–piperaquine would further reduce malaria prevalence.

Methods

MATAMAL was a quadruple-blinded, cluster-randomised, placebo-controlled trial, conducted on the Bijagos Archipelago, Guinea-Bissau, an area of seasonal malaria transmission. All residents were invited to participate, with exclusions for drug safety. 24 clusters were randomised in a 1:1 ratio, using restriction randomisation, to either MDA with three daily oral doses of dihydroartemisinin–piperaquine and ivermectin (300 μg/kg per day) in three sequential months during the transmission season in 2021 and 2022, or MDA with dihydroartemisinin–piperaquine and placebo in the same schedule. The primary outcome was quantitative PCR prevalence of Plasmodium falciparum parasitaemia in all age groups, during peak transmission, after the second year of intervention. The primary entomological outcome was anopheline parity rate. The trial is registered with ClinicalTrials.gov (NCT04844905).

Findings

Participants were recruited between June 7, 2021 and Sept 21, 2022. The baseline population was 25 882 (12 634 [50·6%] were female individuals and 12 317 [49·4%] were male individuals): 13 832 were in the intervention group and 12 050 in the control group. Cluster-level coverage for dihydroartemisinin–piperaquine ranged from 60·4% to 78·7%, and for ivermectin or ivermectin–placebo from 58·1 to 77·1%. Following the intervention, the prevalence of P falciparum infection was 118 (5·05%) of 2300 in the control group and 141 (6·64%) of 2083 in the intervention group. The adjusted risk difference was 1·67% (95% CI –1·44 to 4·78; p=0·28). There were 124 adverse events in the control group (1·0% of participants) and 267 in the intervention group (1·9% of participants). Two serious adverse events were reported, neither related to the intervention, and no treatment-related deaths. The anopheline parity rate was 1679 (67·8%) of 2475 in control clusters and 1740 (72·3%) of 2414 in intervention clusters. The adjusted risk difference was –1·32 (95% CI –14·77 to 12·12; p=0·84).

Interpretation

Adding ivermectin to dihydroartemisinin–piperaquine MDA had no additional effect on reducing malaria prevalence or vector parity in this setting. The intervention was well tolerated. To our knowledge, this trial is the first to be designed to assess whether ivermectin has an additive effect on malaria when coadministered with dihydroartemisinin–piperaquine MDA.

Funding

The National Institute for Health and Care Research, Medical Research Council, Wellcome, and Foreign, Commonwealth & Development Office.

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© 2024  The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Publié par Elsevier Masson SAS. Tous droits réservés.
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