Chloroquine resistant Plasmodium vivax: in vitro characterisation and association with molecular polymorphisms.
Chloroquine resistant Plasmodium vivax: in vitro characterisation and association with molecular polymorphisms.
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DOI：
10.1371/journal.pone.0001089
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发表时间：
2007-10-31
期刊：
影响因子：
3.7
通讯作者：
Price RN
中科院分区：
文献类型：
--
作者：
Suwanarusk R;Russell B;Chavchich M;Chalfein F;Kenangalem E;Kosaisavee V;Prasetyorini B;Piera KA;Barends M;Brockman A;Lek-Uthai U;Anstey NM;Tjitra E;Nosten F;Cheng Q;Price RN
在印度尼西亚东部省份，氯喹对间日疟原虫感染的治疗失败已经达到很高的水平，然而，氯喹耐药性的体外特征及其相关的分子图谱尚未确定。我们使用一种改进的裂殖子成熟试验研究了来自印度尼西亚巴布亚和泰国的间日疟原虫分离株的氯喹敏感性谱和分子多态。在巴布亚，临床上氯喹治疗失败的报道很高，在泰国，氯喹治疗通常有效。来自巴布亚(n = 145)的间日疟原虫分离株的几何平均氯喹IC_(50)为312nM[95%CI：237411 nM]，而来自泰国(n = 81)的分离株的氯喹几何平均IC50值为46.8nM[95%CI：34.763.1nM]；p<；0.001。与该地区已知的临床疗效相关，氯喹耐药性的界限被定义为220 nm，超过该水平的泰国分离株和巴布亚分离株分别为13.6%(11/81)和65%(94/0.001)。发现了pvcrt-o和pvmdr1的几个序列多态，以及pvmdr1拷贝数的差异。Pvmdr1基因Y976F突变存在于96%的巴布亚分离株和25%(17/69)的泰国分离株中；P<；0.001。总体而言，Y976F突变菌株的几何平均氯喹IC50为283nM[95%CI211-379]，而野生型菌株为44.5nM[95%CI31.363.4]；p<；0.001。在泰国分离株中有23%(15/66)出现了pvmdr1扩增，而在印度尼西亚分离株(p<；0.001)中没有出现扩增，但在控制地理位置后与氯喹耐药性的增加无关。间日疟原虫的体外药敏试验区分了氯喹临床疗效不同的人群。Y976F的pvmdr1多态可能提供了一个有用的工具来强调新出现的氯喹耐药区域，尽管需要进一步研究确定其临床相关性。
Treatment failure of chloroquine for P. vivax infections has reached high levels in the eastern provinces of Indonesia, however, in vitro characterization of chloroquine resistance and its associated molecular profile have yet to be determined. Using a modified schizont maturation assay we investigated the in vitro chloroquine susceptibility profile and molecular polymorphisms of P. vivax isolates collected from Papua, Indonesia, where high levels of clinical chloroquine treatment failure have been reported, and from Thailand, where chloroquine treatment is generally effective. The geometric mean chloroquine IC50 for P. vivax isolates from Papua (n = 145) was 312 nM [95%CI: 237–411 nM] compared to 46.8 nM [95%CI: 34.7–63.1 nM] from Thailand (n = 81); p<0.001. Correlating with the known clinical efficacy of the area, a cut off for chloroquine resistance was defined as 220nM, a level exceeded in 13.6% (11/81) of Thai isolates and 65% (94/145) of Papuan isolates; p<0.001. Several sequence polymorphisms in pvcrt-o and pvmdr1, and difference in pvmdr1 copy number were identified. A Y976F mutation in pvmdr1 was present in 96% (123/128) of Papuan isolates and 25% (17/69) of Thai isolates; p<0.001. Overall, the geometric mean chloroquine IC50 in isolates with the Y976F mutation was 283 nM [95%CI: 211–379], compared to 44.5 nM [95%CI: 31.3–63.4] in isolates with the wild type; p< 0.001. Pvmdr1 amplification occurred in 23% (15/66) of Thai isolates compared to none (0/104) of Indonesian isolates (p<0.001), but was not associated with increased chloroquine resistance after controlling for geographical location. In vitro susceptibility testing of P. vivax discriminates between populations with differing levels of clinical efficacy of chloroquine. The pvmdr1 polymorphism at Y976F may provide a useful tool to highlight areas of emerging chloroquine resistance, although further studies defining its clinical correlates are needed.
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影响因子：
3.3
作者：
Phan, GT;de Vries, PJ;Kager, PA
通讯作者：
Kager, PA
影响因子：
4.9
作者：
Price, RN;Cassar, C;Krishna, S
通讯作者：
Krishna, S
影响因子：
11.8
作者：
Phillips, EJ;Keystone, JS;Kain, KC
通讯作者：
Kain, KC
DOI：
10.4269/ajtmh.2001.64.97
发表时间：
2001-01-01
影响因子：
3.3
作者：
Mendis, K;Sina, BJ;Carter, R
通讯作者：
Carter, R
DOI：
10.1016/s0035-9203(96)90526-x
发表时间：
1996-07-01
影响因子：
2.2
作者：
Baird, JK;Nalim, MFS;Wignall, FS
通讯作者：
Wignall, FS