Abstract
BackgroundThe prospect of eliminating malaria is challenged by emerging insecticide resistance and vectors with outdoor and/or crepuscular activity. Ivermectin can simultaneously tackle these issues by killing mosquitoes feeding on treated animals and humans. A single oral dose, however, confers only short-lived mosquitocidal plasma levels.MethodsThree different slow-release formulations of ivermectin were screened for their capacity to sustain mosquito-killing levels of ivermectin for months. Thirty rabbits received a dose of one, two or three silicone implants containing different proportions of ivermectin, deoxycholate and sucrose. Animals were checked for toxicity and ivermectin was quantified periodically in blood. Potential impact of corresponding long-lasting formulation was mathematically modelled.ResultsAll combinations of formulation and dose released ivermectin for more than 12 weeks; four combinations sustained plasma levels capable of killing 50% of Anopheles gambiae feeding on a treated subject for up to 24 weeks. No major adverse effects attributable to the drug were found. Modelling predicts a 98% reduction in infectious vector density by using an ivermectin formulation with a 12-week duration.ConclusionsThese results indicate that relatively stable mosquitocidal plasma levels of ivermectin can be safely sustained in rabbits for up to six months using a silicone-based subcutaneous formulation. Modifying the formulation of ivermectin promises to be a suitable strategy for malaria vector control.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-015-0618-2) contains supplementary material, which is available to authorized users.
Highlights
The prospect of eliminating malaria is challenged by emerging insecticide resistance and vectors with outdoor and/or crepuscular activity
Increased funding and political commitment have led to outstanding worldwide achievements in malaria control over the last 14 years
The estimated malaria mortality rate in children under five has almost been halved worldwide since 2000 and it is projected to decrease by 61% by 2015 [1]
Summary
The prospect of eliminating malaria is challenged by emerging insecticide resistance and vectors with outdoor and/or crepuscular activity. There has been a renewed interest for malaria elimination [2], and the general mood is that of ‘impatient optimism’ [3]. The malERA consultative group on vector control identified three main challenges to eradication [9]: 1) the emergence of insecticide resistance affecting all major vector species and all classes of insecticides in twothirds of endemic countries [7]; 2) the presence of outdoor-biting/resting mosquitoes, not readily targeted by insecticide-treated nets (ITNs) and indoor-residual spraying (IRS) [10,11]; and, 3) the need for new approaches to achieve elimination in areas where vectors exhibit a high vectorial capacity. Additional problems include the selection of vectors with early or Chaccour et al Malaria Journal (2015) 14:102 crepuscular activity in areas with good ITN coverage [12,13], vector biodiversity and environmental change [14]
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