Inoculum effect leads to overestimation of in vitro resistance for artemisinin derivatives and standard antimalarials:: a Gambian field study
Inoculum effect leads to overestimation of in vitro resistance for artemisinin derivatives and standard antimalarials:: a Gambian field study
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DOI：
10.1017/s0031182099004953
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发表时间：
1999-11-01
期刊：
影响因子：
2.4
通讯作者：
Warhurst, DC
中科院分区：
文献类型：
--
作者：
Duraisingh, MT;Jones, P;Warhurst, DC
青蒿素(QHS)及其衍生物是一种新型的抗疟疾药物，对氯喹(CQ)耐药的恶性疟原虫有较好的疗效。随着这些药物的引入，监测耐药性是当务之急。在本文中，我们证明了体外试验中使用的接种量影响了在WHO体外微量试验中常规使用的寄生虫范围内对QHS及其衍生物双氢青蒿素(DHA)、甲氟喹(MEF)和CQ的体外敏感性。寄生虫血症和/或红细胞压积的增加伴随着两个实验室菌株测量灵敏度的下降。在冈比亚法贾拉一项实地研究的背景下，我们测试了来自无并发症疟疾患者的寄生虫分离株的体外敏感性，我们证明，未能控制接种量大大高估了对QHS和DHA以及MEF、卤代喹(HAL)和奎宁(Quin)的耐药性水平。当控制接种效应时，观察到QHS、MEF和HAL之间存在交叉耐药，表明存在类似多药耐药的机制。这些研究强调了接种量在体外药敏试验中的重要性。
Artemisinin (QHS) and its derivatives are new antimalarials which are effective against Plasmodium falciparum parasites resistant to chloroquine (CQ). As these drugs are introduced it is imperative that resistance is monitored. In this paper we demonstrate that the inoculum size used in in vitro testing influences the measured in vitro susceptibility to QHS and its derivative dihydroartemisinin (DHA) and to mefloquine (MEF) and CQ over the range of parasitaemias routinely used in testing with the WHO in vitro microtest. An increase in parasitaemia and/or haematocrit was accompanied by a decrease in the measured sensitivity of 2 laboratory lines. In the context of a field study testing in vitro susceptibility of parasite isolates from patients with uncomplicated malaria in Fajara, The Gambia we demonstrate that failure to control for inoculum size significantly overestimates the level of resistance to QHS and DHA as well as MEF, halofantrine (HAL) and quinine (QUIN). When controlling for the inoculum effect, cross-resistance mas observed between QHS, MEF and HAL suggesting the presence of a multidrug resistance-like mechanism. These studies underline the importance of inoculum size in in vitro susceptibility testing.