Efficacy and Safety of the Mosquitocidal Drug Ivermectin to Prevent Malaria Transmission After Treatment: A Double-Blind, Randomized, Clinical Trial
Open Access
- 19 November 2014
- journal article
- research article
- Published by Oxford University Press (OUP) in Clinical Infectious Diseases
- Vol. 60 (3), 357-365
- https://doi.org/10.1093/cid/ciu797
Abstract
Background. Artemisinin combination therapy effectively clears asexual malaria parasites and immature gametocytes but does not prevent posttreatment malaria transmission. Ivermectin (IVM) may reduce malaria transmission by killing mosquitoes that take blood meals from IVM-treated humans. Methods. In this double-blind, placebo-controlled trial, 120 asymptomatic Plasmodium falciparum parasite carriers were randomized to receive artemether-lumefantrine (AL) plus placebo or AL plus a single or repeated dose (200 µg/kg) of ivermectin (AL-IVM1 and AL-IVM2, respectively). Mosquito membrane feeding was performed 1, 3, and 7 days after initiation of treatment to determine Anopheles gambiae and Anopheles funestus survival and infection rates. Results. The AL-IVM combination was well tolerated. IVM resulted in a 4- to 7-fold increased mortality in mosquitoes feeding 1 day after IVM (P < .001). Day 7 IVM plasma levels were positively associated with body mass index (r = 0.57, P < .001) and were higher in female participants (P = .003), for whom An. gambiae mosquito mortality was increased until 7 days after a single dose of IVM (hazard rate ratio, 1.34 [95% confidence interval, 1.07–1.69]; P = .012). Although we found no evidence that IVM reduced Plasmodium infection rates among surviving mosquitoes, the mosquitocidal effect of AL-IVM1 and AL-IVM2 resulted in 27% and 35% reductions, respectively, in estimated malaria transmission potential during the first week after initiation of treatment. Conclusions. We conclude that IVM can be safely given in combination with AL and can reduce the likelihood of malaria transmission by reducing the life span of feeding mosquitoes. Clinical Trials Registration. NCT0160325.Keywords
This publication has 23 references indexed in Scilit:
- Ivermectin to reduce malaria transmission: a research agenda for a promising new tool for eliminationMalaria Journal, 2013
- Primaquine to prevent transmission of falciparum malariaThe Lancet Infectious Diseases, 2013
- Mosquito Feeding Assays to Determine the Infectiousness of Naturally Infected Plasmodium falciparum Gametocyte CarriersPLOS ONE, 2012
- The Threat of Artemisinin-Resistant MalariaNew England Journal of Medicine, 2011
- Ivermectin Mass Drug Administration to Humans Disrupts Malaria Parasite Transmission in Senegalese VillagesThe American Journal of Tropical Medicine and Hygiene, 2011
- Mass drug administration of ivermectin in south-eastern Senegal reduces the survivorship of wild-caught, blood fed malaria vectorsMalaria Journal, 2010
- Effect of Ivermectin onAnopheles gambiaeMosquitoes Fed on Humans: The Potential of Oral Insecticides in Malaria ControlThe Journal of Infectious Diseases, 2010
- Artemisinin Resistance inPlasmodium falciparumMalariaNew England Journal of Medicine, 2009
- Strong Gametocytocidal Effect of Methylene Blue-Based Combination Therapy against Falciparum Malaria: A Randomised Controlled TrialPLOS ONE, 2009
- Liquid chromatographic assay of ivermectin in human plasma for application to clinical pharmacokinetic studiesJournal of Pharmaceutical and Biomedical Analysis, 2006