In vitro monitoring of Plasmodium falciparum drug resistance in French Guiana:: a synopsis of continuous assessment from 1994 to 2005
In vitro monitoring of Plasmodium falciparum drug resistance in French Guiana:: a synopsis of continuous assessment from 1994 to 2005
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DOI：
10.1128/aac.00263-07
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发表时间：
2008-01-01
影响因子：
4.9
通讯作者：
Esterre, Philippe
中科院分区：
文献类型：
--
作者：
Legrand, Eric;Volney, Beatrice;Esterre, Philippe
作为20世纪90年代初在法属圭亚那实施的疟疾控制计划的一个分支，我们的实验室已经建立了寄生虫对一组8种抗疟药的体外药物敏感性谱，用于从感染患者中分离出1,000多株恶性疟原虫。1995年采用奎宁-多西环素复方制剂，取代氯喹，作为治疗无并发症恶性疟原虫疟疾的一线药物，2002年，一线药物复方制剂改为蒿甲醚-苯芴醇复方制剂。在1995年不再将氯喹作为一线药物后5年，对氯喹的耐药性有所下降，但与非洲的类似情况不同，这种下降迅速停止。从2002年到2005年，多西环素敏感性大幅下降，表明寄生虫选择奎宁-多西环素药物压力下。自1997年起，甲氟喹的敏感性下降。在整个1994年至2005年期间，大多数菌株在体外对奎宁，阿莫地喹和阿托伐醌敏感。阿莫地喹的敏感性与氯喹的敏感性密切相关，与甲氟喹和卤泛群的敏感性在较小程度上相关。甲氟喹和卤泛群的敏感性也密切相关。2002 - 2003年和2005年分别发布了两次体外蒿甲醚耐药警报，这两次警报均与肌质/内质网钙ATP酶（SERCA）型恶性疟原虫ATP酶6（PfATP酶6）基因中存在S769 N多态性有关。2005年首次进行的本芴醇敏感性分析表明，50%抑制浓度的升高速度令人震惊。应进行寄生虫药物敏感性的体外监测，以进一步记录具体药物政策对当地寄生虫种群的影响，特别是确定对药物组合中个别成分的敏感性概况，以提供寄生虫抗药性出现的预警信号。
Implemented as one arm of the malaria control program in French Guiana in the early 1990s, our laboratory has since established in vitro profiles for parasite drug susceptibility to a panel of eight antimalarials for more than 1,000 Plasmodium falciparum isolates from infected patients. The quinine-doxycycline combination was introduced in 1995 as the first-line drug treatment against uncomplicated P. falciparum malaria, replacing chloroquine, and the first-line drug combination was changed to the artemether-lumefantrine combination in 2002. Resistance to chloroquine declined 5 years after it was dropped in 1995 as the first-line drug, but unlike similar situations in Africa, there was a rapid halt to this decline. Doxycycline susceptibility substantially decreased from 2002 to 2005, suggesting parasite selection under quinine-doxycycline drug pressure. Susceptibility to mefloquine decreased from 1997 onward. Throughout the period from 1994 to 2005, most isolates were sensitive in vitro to quinine, amodiaquine, and atovaquone. Susceptibility to amodiaquine was strongly correlated with that to chloroquine and to a lesser extent with that to mefloquine and halofantrine. Susceptibilities to mefloquine and to halofantrine were also strongly correlated. There were two alerts issued for in vitro artemether resistance in the period from 2002 to 2003 and again in 2005, both of which could be associated with the presence of an S769N polymorphism in the sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA)-type P. falciparum ATPase6 (PfATPase6) gene. Analysis of susceptibility to lumefantrine, conducted for the first time in 2005, indicates an alarming rate of elevated 50% inhibitory concentrations. In vitro monitoring of parasite drug susceptibility should be pursued to further document the consequences of specific drug policies on the local parasite population and, in particular, to establish profiles of susceptibility to individual components of drug combinations to provide early warning signs of emerging parasite resistance.