Sulfadoxine-pyrimethamine impairs Plasmodium falciparum gametocyte infectivity and Anopheles mosquito survival
Sulfadoxine-pyrimethamine impairs Plasmodium falciparum gametocyte infectivity and Anopheles mosquito survival
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DOI：
10.1016/j.ijpara.2010.05.004
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发表时间：
2010-08-15
影响因子：
4
通讯作者：
Djimde, Abdoulaye A.
中科院分区：
文献类型：
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作者：
Kone, Aminatou;van de Vegte-Bolmer, Marga;Djimde, Abdoulaye A.
磺胺多辛(SP)是目前用于孕期和婴儿期恶性疟原虫间歇预防治疗的首选药物。DHFR和DHPS突变导致的寄生虫清除时间延长被认为是SP处理个体配子体患病率增加的原因。然而，使用马里的直接喂养试验，我们发现SP治疗后外周静脉血中存在的配子细胞降低了对严格感按蚊(SS)的感染性。我们研究了dhfr和dhps五重突变体NF-135和单个dhps 437突变体nF-54的可能机制。在SP处理后的第3天(S=61mU g/ml，P=154.7 ng/ml)、第7天(S=33.8mU g/ml，P=66.6 ng/ml)和第14天(S=14.2mU g/ml，P=15.7 ng/ml)浓度相当于上述药物血清浓度的磺胺多辛(5)和乙胺嘧啶(P=15.7 ng/ml)，研究了人工膜对斯氏按蚊配子细胞发生、配子成熟和感染性的影响。这些药物很容易在突变的NF-135菌株中诱导配子细胞生成，但有效地杀死野生型NF-54。然而，这两种药物都会损害配子体成熟，产生形状奇特的非脱节成熟配子体。与对照组相比，同时摄入S和磷以及配子体血粉显著降低了卵囊阳性率和卵囊密度(P<；0.001)。此外，第三天的SP浓度降低了蚊子存活率高达65%(P<；0.001)。这项研究表明，SP在体外对配子体的感染性和蚊子的生存都是有害的。(C)2010年澳大利亚寄生虫学学会。爱思唯尔有限公司出版。保留所有权利。
Sulfadoxine-pyrimethamine (SP) is currently the drug of choice for intermittent preventive treatment of Plasmodium falciparum both in pregnancy and infancy. A prolonged parasite clearance time conferred by dhfr and dhps mutations is believed to be responsible for increased gametocyte prevalence in SP treated individuals. However, using a direct feeding assay in Mali, we showed that gametocytes present in peripheral venous blood post-SP treatment had reduced infectivity for Anopheles gambiae sensu stricto (ss) mosquitoes. We investigated the potential mechanisms involved in the dhfr and dhps quintuple mutant NF-135 and the single dhps 437 mutant NF-54. Concentrations of sulfadoxine (5) and pyrimethamine (P) equivalent to the serum levels of the respective drugs on day 3 (S = 61 mu g/ml, P = 154.7 ng/ml) day 7 (S = 33.8 mu g/ml, P = 66.6 ng/ml) and day 14 (S = 14.2 mu g/ml, P = 15.7 ng/ml) post-SP treatment were used to study the effect on gametocytogenesis, gametocyte maturation and infectivity to Anopheles stephensi mosquitoes fed through an artificial membrane. The drugs readily induced gametocytogenesis in the mutant NF-135 strain but effectively killed the wild-type NF-54. However, both drugs impaired gametocyte maturation yielding odd-shaped non-exflagellating mature gametocytes. The concomitant ingestion of both S and P together with gametocytemic blood-meal significantly reduced the prevalence of oocyst positivity as well as oocyst density when compared to controls (P < 0.001). In addition, day 3 concentrations of SP decreased mosquito survival by up to 65% (P < 0.001). This study demonstrates that SP is deleterious in vitro for gametocyte infectivity as well as mosquito survival. (C) 2010 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.