Shoklo Malaria Research Unit, Mahidol Oxford Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Ramat, Tak, Thailand.
Nuffield Department of Medicine, Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, England, United Kingdom.
Antimicrob Agents Chemother. 2024 Sep 4;68(9):e0085324. doi: 10.1128/aac.00853-24. Epub 2024 Jul 26.
is now the main cause of malaria outside Africa. The gametocytocidal effects of antimalarial drugs are important to reduce malaria transmissibility, particularly in low-transmission settings, but they are not well characterized for . The transmission-blocking effects of chloroquine, artesunate, and methylene blue on gametocytes were assessed. Blood specimens were collected from patients presenting with vivax malaria, incubated with or without the tested drugs, and then fed to mosquitos from a laboratory-adapted colony of (a major malaria vector in Southeast Asia). The effects on oocyst and sporozoite development were analyzed under a multi-level Bayesian model accounting for assay variability and the heterogeneity of mosquito infection. Artesunate and methylene blue, but not chloroquine, exhibited potent transmission-blocking effects. Gametocyte exposures to artesunate and methylene blue reduced the mean oocyst count 469-fold (95% CI: 345 to 650) and 1,438-fold (95% CI: 970 to 2,064), respectively. The corresponding estimates for the sporozoite stage were a 148-fold reduction (95% CI: 61 to 470) and a 536-fold reduction (95% CI: 246 to 1,311) in the mean counts, respectively. In contrast, high chloroquine exposures reduced the mean oocyst count only 1.40-fold (95% CI: 1.20 to 1.64) and the mean sporozoite count 1.34-fold (95% CI: 1.12 to 1.66). This suggests that patients with vivax malaria often remain infectious to anopheline mosquitos after treatment with chloroquine. Use of artemisinin combination therapies or immediate initiation of primaquine radical cure should reduce the transmissibility of infections.
现在是非洲以外地区疟疾的主要病因。抗疟药物的配子体杀伤作用对于降低疟疾的传染性很重要,特别是在低传播地区,但目前对 的配子体杀伤作用还没有很好的描述。评估了氯喹、青蒿琥酯和亚甲蓝对 配子体的阻断作用。从患有 vivax 疟疾的患者中采集血液标本,在有或没有测试药物的情况下孵育,然后用来自实验室适应的 (东南亚主要疟疾媒介)蚊群进行喂食。在一个多水平贝叶斯模型中分析了对卵囊和孢子发育的影响,该模型考虑了测定变异性和蚊子感染的异质性。青蒿琥酯和亚甲蓝,但不是氯喹,表现出强大的阻断作用。配子体暴露于青蒿琥酯和亚甲蓝分别使平均卵囊数减少 469 倍(95%CI:345 至 650)和 1,438 倍(95%CI:970 至 2,064)。对于孢子阶段,平均计数分别减少 148 倍(95%CI:61 至 470)和 536 倍(95%CI:246 至 1,311)。相比之下,高氯喹暴露仅使平均卵囊数减少 1.40 倍(95%CI:1.20 至 1.64),平均孢子数减少 1.34 倍(95%CI:1.12 至 1.66)。这表明患有 vivax 疟疾的患者在接受氯喹治疗后往往仍然对按蚊具有传染性。使用青蒿素联合疗法或立即开始使用伯氨喹根治治疗应降低 感染的传播性。