Efficacy and risk of harms of repeat ivermectin mass drug administrations for control of malaria (RIMDAMAL): a cluster-randomised trial

Autor: Hannah C Slater, Florence Fournet, André B. Sagna, François Drabo, Roch K. Dabiré, Martina Wade, Sangeeta Rao, Sunil Parikh, Jonathan A. Seaman, Brian D. Foy, Roland W Bougma, Dieudonné Diloma Soma, Tereza Magalhaes, Noel Rouamba, Abdoulaye Diabaté, A Gafar V Coulidiaty, Haoues Alout
Přispěvatelé: Department of Microbiology, Immunology, and Pathology, Arthropod-borne and Infectious Diseases Laboratory, Colorado State University [Fort Collins] (CSU), Animal, Santé, Territoires, Risques et Ecosystèmes (UMR ASTRE), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA), Department of Clinical Sciences [Fort Collins, CO, USA] (Orthopaedic Research Center), Department of Epidemiology of Microbial Diseases [New Haven], Yale School of Public Health (YSPH), Institut de Recherche en Sciences de la Santé Bobo Dioulasso (INSSA), Université Polytechnique Nazi Boni Bobo-Dioulasso (UNB), International Mixed Laboratory on Vector Diseases, Partenaires INRAE, Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Diversity, ecology, evolution & Adaptation of arthropod vectors (MIVEGEC-DEEVA), Evolution des Systèmes Vectoriels (ESV), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Imperial College London, Ministère de la Santé [Burkina Faso], Institut de Recherche en Sciences de la Santé (IRSS), CNRST, Centre Muraz [Bobo-Dioulasso, Burkina Faso], Bill & Melinda Gates Foundation, Foy, Brian D., MRC Centre for Global Infectious Disease Analysis (MRC-GIDA), Imperial College London
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: The Lancet
The Lancet, 2019, 393 (10180), pp.1517-1526. ⟨10.1016/S0140-6736(18)32321-3⟩
The Lancet, . (2019)
The Lancet, Elsevier, 2019, 393 (10180), pp.1517-1526. ⟨10.1016/S0140-6736(18)32321-3⟩
ISSN: 0140-6736
1474-547X
0923-7577
DOI: 10.1016/S0140-6736(18)32321-3⟩
Popis: Summary Background Ivermectin is widely used in mass drug administrations for controlling neglected parasitic diseases, and can be lethal to malaria vectors that bite treated humans. Therefore, it could be a new tool to reduce plasmodium transmission. We tested the hypothesis that frequently repeated mass administrations of ivermectin to village residents would reduce clinical malaria episodes in children and would be well tolerated with minimal harms. Methods We invited villages (clusters) in Burkina Faso to participate in a single-blind (outcomes assessor), parallel-assignment, two-arm, cluster-randomised trial over the 2015 rainy season. Villages were assigned (1:1) by random draw to either the intervention group or the control group. In both groups, all eligible participants who consented to the treatment and were at least 90 cm in height received single oral doses of ivermectin (150–200 μg/kg) and albendazole (400 mg), and those in the intervention group received five further doses of ivermectin alone at 3-week intervals thereafter over the 18-week treatment phase. The primary outcome was cumulative incidence of uncomplicated malaria episodes over 18 weeks (analysed on a cluster intention-to-treat basis) in an active case detection cohort of children aged 5 years or younger living in the study villages. This trial is registered with ClinicalTrials.gov, number NCT02509481. Findings Eight villages agreed to participate, and four were randomly assigned to each group. 2712 participants (1333 [49%] males and 1379 [51%] females; median age 15 years [IQR 6–34]), including 590 children aged 5 years or younger, provided consent and were enrolled between May 22 and July 20, 2015 (except for 77 participants enrolled after these dates because of unavailability before the first mass drug administration, travel into the village during the trial, or birth), with 1447 enrolled into the intervention group and 1265 into the control group. 330 (23%) participants in the intervention group and 233 (18%) in the control group met the exclusion criteria for mass drug administration. Most children in the active case detection cohort were not treated because of height restrictions. 14 (4%) children in the intervention group and 10 (4%) in the control group were lost to follow-up. Cumulative malaria incidence was reduced in the intervention group (648 episodes among 327 children; estimated mean 2·00 episodes per child) compared with the control group (647 episodes among 263 children; 2·49 episodes per child; risk difference −0·49 [95% CI −0·79 to −0·21], p=0·0009, adjusted for sex and clustering). The risk of adverse events among all participants did not differ between groups (45 events [3%] among 1447 participants in the intervention group vs 24 events [2%] among 1265 in the control group; risk ratio 1·63 [1·01 to 2·67]; risk difference 1·21 [0·04 to 2·38], p=0·060), and no adverse reactions were reported. Interpretation Frequently repeated mass administrations of ivermectin during the malaria transmission season can reduce malaria episodes among children without significantly increasing harms in the populace. Funding Bill & Melinda Gates Foundation.
Databáze: OpenAIRE
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