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Clin Infect Dis. 2015 Feb 1;60(3):357-65. doi: 10.1093/cid/ciu797. Epub 2014 Nov 19.

Efficacy and safety of the mosquitocidal drug ivermectin to prevent malaria transmission after treatment: a double-blind, randomized, clinical trial.

Author information

1
Department of Biomedical Sciences, Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso.
2
Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands.
3
Entomology Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland Entomology Department, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.
4
College of Pharmacy, The University of Iowa, Iowa City.
5
MRC Centre for Outbreak Analysis and Modelling, Infectious Disease Epidemiology, Imperial College London.
6
Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, United Kingdom.
7
Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, United Kingdom.

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:

falciparum; gametocyte; sporogony; survivorship; transmission

PMID:
25414262
DOI:
10.1093/cid/ciu797
[Indexed for MEDLINE]

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