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Background While 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. Methods Hypothetical 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. Results At 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%. Conclusions While 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.

Background In Niger, malaria transmission is markedly seasonal with most of the disease burden occurring in children during the rainy season. Seasonal malaria chemoprevention (SMC) with amodiaquine plus sulfadoxine– pyrimethamine (AQ + SP) is recommended in the country to be administered monthly just before and during the rainy season. Moreover, clinical decisions on use of SP for intermittent preventive treatment in pregnancy (IPTp) now depend upon the validated molecular markers for SP resistance in Plasmodium falciparum observed in the local parasite population. However, little is known about molecular markers of resistance for either SP or AQ in the south of Niger. To address this question, clinical samples which met clinical and biological criteria, were collected in Gabi, Madarounfa district, Maradi region, Niger in 2011–2012 (before SMC implementation). Molecular markers of resistance to pyrimethamine (pfdhfr), sulfadoxine (pfdhps) and amodiaquine (pfmdr1) were assessed by DNA sequencing. Results Prior to SMC implementation, the samples showed a high proportion of clinical samples that carried the pfdhfr 51I/59R/108N haplotype associated with resistance to pyrimethamine and pfdhps 436A/F/H and 437G mutations associated with reduced susceptibility to sulfadoxine. In contrast mutations in codons 581G, and 613S in the pfdhps gene, and in pfmdr1, 86Y, 184Y, 1042D and 1246Y associated with resistance to amodiaquine, were less frequently observed. Importantly, pfdhfr I164L and pfdhps K540E mutations shown to be the most clinically relevant markers for high level clinical resistance to SP were not detected in Gabi. Conclusion Although parasites with genotypes associated with the highest levels of resistance to AQ + SP are not yet common in this setting, their importance for deployment of SMC and IPTp dictates that monitoring of these markers of resistance should accompany these interventions. This study also highlights the parasite heterogeneity within a small spatial area and the need to use caution when extrapolating results from surveys of molecular markers of resistance in a single site to inform regional policy decisions.