Abstract
BackgroundWhen ingested in a blood meal, ivermectin has been shown to reduce the survivorship of Anopheles gambiae in the laboratory and field. Furthermore, ivermectin mass drug administrations in Senegal have been shown to reduce the proportion of Plasmodium falciparum-sporozoite-containing An. gambiae. This study addresses whether ivermectin inhibits sporogony of P. falciparum in An. gambiae.MethodsAnophele gambiae s.s. G3 strain were fed two concentrations of ivermectin (LC25 and LC5) along with P. falciparum NF54 in human blood meals at staggered intervals. Mosquitoes ingested ivermectin concurrent with parasites (DPI 0), or at three (DPI 3), six (DPI 6), and nine (DPI 9) days post parasite ingestion, or three days prior (DPI −3) to parasite ingestion. Mosquitoes were dissected at seven, twelve or fourteen days post parasite ingestion and either oocyst or sporozoite prevalence was recorded. To determine if P. falciparum sporozoite-containing An. gambiae were more susceptible to ivermectin than uninfected controls, survivorship was recorded for mosquitoes which ingested P. falciparum or control blood meal on DPI 0 and then a second blood meal containing ivermectin (LC25) on DPI 14.ResultsIvermectin (LC25) co-ingested (DPI 0) with parasites reduced the proportion of An. gambiae that developed oocysts (χ2 = 15.4842, P = 0.0002) and sporozoites (χ2 = 19.9643, P < 0.0001). Ivermectin (LC25) ingested DPI 6 (χ2 = 8.5103, P = 0.0044) and 9 (χ2 = 14.7998, P < 0.0001) reduced the proportion of An. gambiae that developed sporozoites but not when ingested DPI 3 (χ2 = 0.0113, P = 1). Ivermectin (LC5) co-ingested (DPI 0) with parasites did not reduce the proportion of An. gambiae that developed oocysts (χ2 = 4.2518, P = 0.0577) or sporozoites (χ2 = 2.3636, P = 0.1540), however, when ingested DPI −3 the proportion of An. gambiae that developed sporozoites was reduced (χ2 = 8.4806, P = 0.0047). Plasmodium falciparum infection significantly reduced the survivorship of An. gambiae that ingested ivermectin (LC25) on DPI 14 compared to control mosquitoes that ingested a primary blood meal without parasites (χ2 = 4.97, P = 0.0257).ConclusionsIvermectin at sub-lethal concentrations inhibits the sporogony of P. falciparum in An. gambiae. These findings support the utility of ivermectin for P. falciparum transmission control.
Highlights
When ingested in a blood meal, ivermectin has been shown to reduce the survivorship of Anopheles gambiae in the laboratory and field
When ivermectin (LC25) was ingested on days after (post) the infectious (DPI) 3, it did not reduce the proportion of An. gambiae that contained sporozoites at dissected on day post infection (DDPI) 12 (χ2 = 4.3718, P = 0.0556, n = 112) or at DDPI 14 (χ2 = 0.0113, P = 1, n = 145) (Figure 2)
Ivermectin (LC25) ingested on DPI 6 and DPI 9 reduced the proportion of An. gambiae that contained sporozoites at DDPI 12 and DDPI 14 [DPI 6 at DDPI 12 (χ2 = 12.4919, P = 0.0006, n = 95) and DPI 6 at DDPI 14 (χ2 = 8.5103, P = 0.0044, n = 135); DPI 9 at DDPI 12 (χ2 = 16.2056, P < 0.0001, n = 132) and DPI 9 at DDPI 14 (χ2 = 14.7998, P < 0.0001, n = 161)] (Figure 2)
Summary
When ingested in a blood meal, ivermectin has been shown to reduce the survivorship of Anopheles gambiae in the laboratory and field. Ivermectin mass drug administrations in Senegal have been shown to reduce the proportion of Plasmodium falciparum-sporozoite-containing An. gambiae. Novel Anopheles vector control methods are needed for current malaria elimination and eradication efforts [1]. Ivermectin mass drug administration (MDA) to humans has been suggested as a possible vector control method to reduce Plasmodium transmission [2,3,4,5,6,7,8]. The vectorial capacity equation provides a framework that defines the factors that regulate Plasmodium transmission by Anopheles vectors [12]. There are several other variables in the vectorial capacity equation that vector control methods could impact which would reduce Plasmodium transmission
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