Enosse S, Butcher G A, Margos G, Mendoza J, Sinden R E, Høgh B
Department of Blood Parasitology, National Institute of Health, Maputo, Mozambique.
Trans R Soc Trop Med Hyg. 2000 Jan-Feb;94(1):77-82. doi: 10.1016/s0035-9203(00)90447-4.
Despite its recognized importance, the prevention of patients with malaria from continuing to infect mosquitoes after treatment is not always achieved in practice. An inevitable consequence of the prolonged life-span and relative metabolic stasis of the mature gametocytes of Plasmodium falciparum is that they are not cleared by most antimalarials, and few antimalarials block infection in the mosquito vector. Previous research on the constituents of Malarone, a new 'combined antimalarial', suggested that the active components, atovaquone and proguanil, might inhibit infectivity of gametocytes to mosquitoes. We contrast here the impact of atovaquone-proguanil and chloroquine on the transmission of P. falciparum and P. berghei. While chloroquine enhanced infectivity of P. falciparum, atovaquone-proguanil caused a significant reduction. Surprisingly, sporontocidal activity against the rodent parasite persisted long after the levels of the constituent drugs would have been expected to have fallen below effective plasma concentrations on the basis of the established pharmacokinetics of atovaquone and proguanil. The P. berghei model may thus have provided a sensitive bioassay, detecting drug(s) at levels below that normally found with the usual chemical assays.
尽管疟疾预防具有公认的重要性，但在实际操作中，治疗后的疟疾患者继续感染蚊子的情况并非总能得到预防。恶性疟原虫成熟配子体寿命延长和相对代谢停滞的一个必然结果是，大多数抗疟药无法清除它们，而且很少有抗疟药能阻断在蚊媒中的感染。此前对新型“联合抗疟药”玛拉氧喹成分的研究表明，其活性成分阿托伐醌和氯胍可能会抑制配子体对蚊子的感染性。我们在此对比了阿托伐醌-氯胍和氯喹对恶性疟原虫和伯氏疟原虫传播的影响。氯喹增强了恶性疟原虫的感染性，而阿托伐醌-氯胍则使其显著降低。令人惊讶的是，基于阿托伐醌和氯胍已确定的药代动力学，在组成药物的水平预计已降至有效血浆浓度以下很久之后，对啮齿动物寄生虫的杀孢子活性仍持续存在。因此，伯氏疟原虫模型可能提供了一种灵敏的生物测定方法，能检测到低于常规化学测定法通常所能检测到水平的药物。
