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Ivermectin inhibits the sporogony of Plasmodium falciparum in Anopheles gambiae

BACKGROUND: When 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. g...

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Autores principales: Kobylinski, Kevin C, Foy, Brian D, Richardson, Jason H
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3519548/
https://www.ncbi.nlm.nih.gov/pubmed/23171202
http://dx.doi.org/10.1186/1475-2875-11-381
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author Kobylinski, Kevin C
Foy, Brian D
Richardson, Jason H
author_facet Kobylinski, Kevin C
Foy, Brian D
Richardson, Jason H
author_sort Kobylinski, Kevin C
collection PubMed
description BACKGROUND: When 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. METHODS: Anophele gambiae s.s. G3 strain were fed two concentrations of ivermectin (LC(25) and LC(5)) 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 (LC(25)) on DPI 14. RESULTS: Ivermectin (LC(25)) co-ingested (DPI 0) with parasites reduced the proportion of An. gambiae that developed oocysts (χ(2) = 15.4842, P = 0.0002) and sporozoites (χ(2) = 19.9643, P < 0.0001). Ivermectin (LC(25)) ingested DPI 6 (χ(2) = 8.5103, P = 0.0044) and 9 (χ(2) = 14.7998, P < 0.0001) reduced the proportion of An. gambiae that developed sporozoites but not when ingested DPI 3 (χ(2) = 0.0113, P = 1). Ivermectin (LC(5)) co-ingested (DPI 0) with parasites did not reduce the proportion of An. gambiae that developed oocysts (χ(2) = 4.2518, P = 0.0577) or sporozoites (χ(2) = 2.3636, P = 0.1540), however, when ingested DPI −3 the proportion of An. gambiae that developed sporozoites was reduced (χ(2) = 8.4806, P = 0.0047). Plasmodium falciparum infection significantly reduced the survivorship of An. gambiae that ingested ivermectin (LC(25)) on DPI 14 compared to control mosquitoes that ingested a primary blood meal without parasites (χ(2) = 4.97, P = 0.0257). CONCLUSIONS: Ivermectin 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.
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spelling pubmed-35195482012-12-12 Ivermectin inhibits the sporogony of Plasmodium falciparum in Anopheles gambiae Kobylinski, Kevin C Foy, Brian D Richardson, Jason H Malar J Research BACKGROUND: When 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. METHODS: Anophele gambiae s.s. G3 strain were fed two concentrations of ivermectin (LC(25) and LC(5)) 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 (LC(25)) on DPI 14. RESULTS: Ivermectin (LC(25)) co-ingested (DPI 0) with parasites reduced the proportion of An. gambiae that developed oocysts (χ(2) = 15.4842, P = 0.0002) and sporozoites (χ(2) = 19.9643, P < 0.0001). Ivermectin (LC(25)) ingested DPI 6 (χ(2) = 8.5103, P = 0.0044) and 9 (χ(2) = 14.7998, P < 0.0001) reduced the proportion of An. gambiae that developed sporozoites but not when ingested DPI 3 (χ(2) = 0.0113, P = 1). Ivermectin (LC(5)) co-ingested (DPI 0) with parasites did not reduce the proportion of An. gambiae that developed oocysts (χ(2) = 4.2518, P = 0.0577) or sporozoites (χ(2) = 2.3636, P = 0.1540), however, when ingested DPI −3 the proportion of An. gambiae that developed sporozoites was reduced (χ(2) = 8.4806, P = 0.0047). Plasmodium falciparum infection significantly reduced the survivorship of An. gambiae that ingested ivermectin (LC(25)) on DPI 14 compared to control mosquitoes that ingested a primary blood meal without parasites (χ(2) = 4.97, P = 0.0257). CONCLUSIONS: Ivermectin 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. BioMed Central 2012-11-21 /pmc/articles/PMC3519548/ /pubmed/23171202 http://dx.doi.org/10.1186/1475-2875-11-381 Text en Copyright ©2012 Kobylinski et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Kobylinski, Kevin C
Foy, Brian D
Richardson, Jason H
Ivermectin inhibits the sporogony of Plasmodium falciparum in Anopheles gambiae
title Ivermectin inhibits the sporogony of Plasmodium falciparum in Anopheles gambiae
title_full Ivermectin inhibits the sporogony of Plasmodium falciparum in Anopheles gambiae
title_fullStr Ivermectin inhibits the sporogony of Plasmodium falciparum in Anopheles gambiae
title_full_unstemmed Ivermectin inhibits the sporogony of Plasmodium falciparum in Anopheles gambiae
title_short Ivermectin inhibits the sporogony of Plasmodium falciparum in Anopheles gambiae
title_sort ivermectin inhibits the sporogony of plasmodium falciparum in anopheles gambiae
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3519548/
https://www.ncbi.nlm.nih.gov/pubmed/23171202
http://dx.doi.org/10.1186/1475-2875-11-381
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