International Center for Clinical Research in Malaria, Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazil.
Escola Superior de Ciências da Saúde, Universidade do Estado do Amazonas, Manaus, Brazil.
PLoS Negl Trop Dis. 2018 Feb 14;12(2):e0006221. doi: 10.1371/journal.pntd.0006221. eCollection 2018 Feb.
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.
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.
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.
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.
蚊子对杀虫剂的抗药性威胁着疟疾控制工作，可能成为一个主要的公共卫生问题。向人类施用伊维菌素 (IVM) 等替代方法已被提议作为一种可能的病媒控制方法，以减少疟原虫的传播。按蚊aquasalis 和按蚊 darlingi 是间日疟原虫的有效传播媒介，它们曾导致巴西沿海和南美洲亚马逊地区的各种疟疾爆发。
为了确定伊维菌素对按蚊 aquasalis 和按蚊 darlingi 中间日疟原虫的敏感性，将伊维菌素混入间日疟原虫感染的血液中：(1) 粉末状伊维菌素浓度为 4 个浓度 (0、5、10、20 或 40ng/mL)。(2) 健康志愿者给予伊维菌素单口服剂量 (200μg/kg) 后，采集血浆 (0 小时、4 小时、1 天、5、10 和 14 天)。(3) 用伊维菌素血浆处理感染间日疟原虫的蚊子，4 小时后提供收集的伊维菌素血浆。(4) 用各种伊维菌素、氯喹和伯氨喹组合治疗间日疟原虫感染患者，并在 4 小时采集血浆或全血。在感染性血餐 7 天后，解剖蚊子以评估卵囊的存在。此外，还评估了伊维菌素对体外无性血期间日疟原虫的作用。
伊维菌素显著降低了按蚊 aquasalis 中卵囊发育的流行率，浓度为 10 至 40ng/mL 的 pIVM 和血浆 4 小时、1 天和 5 天。在按蚊 darlingi 中为 4 小时和 1 天。按蚊 aquasalis 的死亡率在 pIVM(40ng/mL)和血浆 4 小时、1、5、10 和 14 天摄入药物后显著增加，在按蚊 darlingi 中仅在 4 小时和 1 天增加。双餐喂养的蚊子用 mIVM 对感染蚊子的比例产生了相当大的影响，持续了 7 天。当蚊子摄入接受伊维菌素+CQ、PQ+CQ 和 IVM+PQ+CQ 治疗的疟疾病人的血液时，卵囊感染的流行率和强度显著降低。间日疟原虫无性发育在 mIVM 的四倍稀释下受到明显抑制。
总之，全血中加入伊维菌素可降低按蚊 aquasalis 和按蚊 darlingi 中的间日疟原虫感染率，并增加蚊子的死亡率。伊维菌素给药后健康志愿者的血浆会影响间日疟原虫无性发育。这些发现支持伊维菌素可用于减少间日疟原虫的传播。
