Open AccessPromising approach to reducing Malaria transmission by ivermectin: Sporontocidal effect against Plasmodium vivax in the South American vectors Anopheles aquasalis and Anopheles darlingi
Author(s) -
Yudi T. Pinilla,
Stefanie Costa Pinto Lopes,
Vanderson de Souza Sampaio,
Francy's Sayara Andrade,
Gisely Cardoso de Melo,
Alessandra S Orfanó,
Nágila F. C. Secundino,
Maria Graças V.B. Guerra,
Marcus Vinícius Guimarães Lacerda,
Kevin C. Kobylinski,
Karin Escobedo-Vargas,
Victor M. López-Sifuentes,
Craig A. Stoops,
G. Christian Baldeviano,
Joel Tärning,
Gissella M. Vásquez,
Paulo Pimenta
Publication year - 2018
Publication title -
plos neglected tropical diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.99
H-Index - 135
eISSN - 1935-2735
pISSN - 1935-2727
DOI - 10.1371/journal.pntd.0006221
Subject(s) - malaria , plasmodium vivax , primaquine , anopheles , biology , ivermectin , plasmodium falciparum , veterinary medicine , virology , chloroquine , immunology , medicine , zoology
Background The mosquito resistance to the insecticides threatens malaria control efforts, potentially becoming a major public health issue. Alternative methods like ivermectin (IVM) administration to humans has been suggested as a possible vector control to reduce Plasmodium transmission. Anopheles aquasalis and Anopheles darlingi are competent vectors for Plasmodium vivax , and they have been responsible for various malaria outbreaks in the coast of Brazil and the Amazon Region of South America. Methods To determine the IVM susceptibility against P . vivax in An . aquasalis and An . darlingi , ivermectin were mixed in P . vivax infected blood: ( 1) Powdered IVM at four concentrations (0, 5, 10, 20 or 40 ng/mL). ( 2 ) Plasma (0 hours, 4 hours, 1 day, 5, 10 and 14 days) was collected from healthy volunteers after to administer a single oral dose of IVM (200 μg/kg) ( 3 ) Mosquitoes infected with P . vivax and after 4 days was provided with IVM plasma collected 4 hours post-treatment ( 4 ) P . vivax -infected patients were treated with various combinations of IVM, chloroquine, and primaquine and plasma or whole blood was collected at 4 hours. Seven days after the infective blood meal, mosquitoes were dissected to evaluate oocyst presence. Additionally, the ex vivo effects of IVM against asexual blood-stage P . vivax was evaluated. Results IVM significantly reduced the prevalence of An . aquasalis that developed oocysts in 10 to 40 ng/mL pIVM concentrations and plasma 4 hours, 1 day and 5 days. In An . darlingi to 4 hours and 1 day. The An . aquasalis mortality was expressively increased in pIVM (40ng/mL) and plasma 4 hours, 1, 5 10 and 14 days post-intake drug and in An . darlingi only to 4 hours and 1 day. The double fed meal with mIVM by the mosquitoes has a considerable impact on the proportion of infected mosquitoes for 7 days post-feeding. The oocyst infection prevalence and intensity were notably reduced when mosquitoes ingested blood from P . vivax patients that ingested IVM+CQ, PQ+CQ and IVM+PQ+CQ. P . vivax asexual development was considerably inhibited by mIVM at four-fold dilutions. Conclusion In conclusion, whole blood spiked with IVM reduced the infection rate of P . vivax in An . aquasalis and An . darlingi , and increased the mortality of mosquitoes. Plasma from healthy volunteers after IVM administration affect asexual P . vivax development. These findings support that ivermectin may be used to decrease P . vivax transmission.