| Summary: | <p>Abstract</p> <p>Background</p> <p>When ingested in a blood meal, ivermectin has been shown to reduce the survivorship of <it>Anopheles gambiae</it> in the laboratory and field. Furthermore, ivermectin mass drug administrations in Senegal have been shown to reduce the proportion of <it>Plasmodium falciparum</it>-sporozoite-containing <it>An. gambiae</it>. This study addresses whether ivermectin inhibits sporogony of <it>P. falciparum</it> in <it>An. gambiae.</it></p> <p>Methods</p> <p><it>Anophele gambiae</it> s.s. G3 strain were fed two concentrations of ivermectin (LC<sub>25</sub> and LC<sub>5</sub>) along with <it>P. falciparum</it> 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 <it>P. falciparum</it> sporozoite-containing <it>An. gambiae</it> were more susceptible to ivermectin than uninfected controls, survivorship was recorded for mosquitoes which ingested <it>P. falciparum</it> or control blood meal on DPI 0 and then a second blood meal containing ivermectin (LC<sub>25</sub>) on DPI 14.</p> <p>Results</p> <p>Ivermectin (LC<sub>25</sub>) co-ingested (DPI 0) with parasites reduced the proportion of <it>An. gambiae</it> that developed oocysts (<it>χ</it><sup>2</sup> = 15.4842, <it>P</it> = 0.0002) and sporozoites (<it>χ</it><sup>2</sup> = 19.9643, <it>P</it> < 0.0001). Ivermectin (LC<sub>25</sub>) ingested DPI 6 (<it>χ</it><sup>2</sup> = 8.5103, <it>P</it> = 0.0044) and 9 (<it>χ</it><sup>2</sup> = 14.7998, <it>P</it> < 0.0001) reduced the proportion of <it>An. gambiae</it> that developed sporozoites but not when ingested DPI 3 (<it>χ</it><sup>2</sup> = 0.0113, <it>P</it> = 1). Ivermectin (LC<sub>5</sub>) co-ingested (DPI 0) with parasites did not reduce the proportion of <it>An. gambiae</it> that developed oocysts (<it>χ</it><sup>2</sup> = 4.2518, <it>P</it> = 0.0577) or sporozoites (<it>χ</it><sup>2</sup> = 2.3636, <it>P</it> = 0.1540), however, when ingested DPI −3 the proportion of <it>An. gambiae</it> that developed sporozoites was reduced (<it>χ</it><sup>2</sup> = 8.4806, <it>P</it> = 0.0047). <it>Plasmodium falciparum</it> infection significantly reduced the survivorship of <it>An. gambiae</it> that ingested ivermectin (LC<sub>25</sub>) on DPI 14 compared to control mosquitoes that ingested a primary blood meal without parasites (<it>χ</it><sup>2</sup> = 4.97, <it>P</it> = 0.0257).</p> <p>Conclusions</p> <p>Ivermectin at sub-lethal concentrations inhibits the sporogony of <it>P. falciparum</it> in <it>An. gambiae</it>. These findings support the utility of ivermectin for <it>P. falciparum</it> transmission control.</p>
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