Abstract
BackgroundWhile bed nets and insecticide spraying have had significant impact on malaria burden in many endemic regions, outdoor vector feeding and insecticide resistance may ultimately limit their contribution to elimination and control campaigns. Complementary vector control methods such as endectocides or systemic insecticides, where humans or animals are treated with drugs that kill mosquitoes upon ingestion via blood meal, are therefore generating much interest. This work explores the conditions under which long-lasting systemic insecticides would have a substantial impact on transmission and burden.MethodsHypothetical long-lasting systemic insecticides with effective durations ranging from 14 to 90 days are simulated using an individual-based mathematical model of malaria transmission. The impact of systemic insecticides when used to complement existing vector control and drug campaigns is evaluated in three settings—a highly seasonal high-transmission setting, a near-elimination setting with seasonal travel to a high-risk area, and a near-elimination setting in southern Africa.ResultsAt 60% coverage, a single round of long-lasting systemic insecticide with effective duration of at least 60 days, distributed at the start of the season alongside a seasonal malaria chemoprevention campaign in a high-transmission setting, results in further burden reduction of 30–90% depending on the sub-populations targeted. In a near-elimination setting where transmission is sustained by seasonal travel to a high-risk area, targeting high-risk travellers with systemic insecticide with effective duration of at least 30 days can result in likely elimination even if intervention coverage is as low as 50%. In near-elimination settings with robust vector control, the addition of a 14-day systemic insecticide alongside an anti-malarial in mass drug administration (MDA) campaigns can decrease the necessary MDA coverage from about 85% to the more easily achievable 65%.ConclusionsWhile further research into the safety profile of systemic insecticides is necessary before deployment, models predict that long-lasting systemic insecticides can play a critical role in reducing burden or eliminating malaria in a range of contexts with different target populations, existing malaria control methods, and transmission intensities. Continued investment in lengthening the duration of systemic insecticides and improving their safety profile is needed for this intervention to achieve its fullest potential.
Highlights
While bed nets and insecticide spraying have had significant impact on malaria burden in many endemic regions, outdoor vector feeding and insecticide resistance may limit their contribution to elimination and control campaigns
Ivermectin has been distributed in mass drug administrations (MDA) for onchocerciasis and lymphatic filariasis [6], and is lethal to mosquitoes upon ingestion during blood feeding on humans or animals [6,7,8,9]
Pharmacokinetics of systemic insecticides are modelled as constant efficacy of duration over 14, 30, 60, or 90 days, subsequently referred to as systemic insecticide with 14-day duration (SI-14), systemic insecticide with 30-day duration (SI-30), systemic insecticide with 60-day duration (SI-60), and systemic insecticide with 90-day duration (SI-90) respectively
Summary
While bed nets and insecticide spraying have had significant impact on malaria burden in many endemic regions, outdoor vector feeding and insecticide resistance may limit their contribution to elimination and control campaigns. There has been recent interest in developing longer-lasting systemic insecticide formulations for malaria control and potential elimination, including slow release formulations [8, 12] and high-dose ivermectin, which has been observed to reduce mosquito survival 28 days post-treatment in a study of outpatients at a hospital in Kenya [15]. A recent study in Burkina Faso observed a 20% reduction in clinical incidence in an intervention group receiving ivermectin 6 times over 18 weeks at 3 week intervals, with young children, pregnant women, and women nursing newborns excluded from MDA eligibility [16] Another drug class, isoxazolines, shows promise to maintain mosquitocidal activity up to 50–90 days based on allometric scaling of preclinical pharmacokinetic data [17], safety concerns still need to be addressed [18]
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