Recovery of chloroquine sensitivity and low prevalence of the Plasmodium falciparum chloroquine resistance transporter gene mutation K76T following the discontinuance of chloroquine use in Malawi
Recovery of chloroquine sensitivity and low prevalence of the Plasmodium falciparum chloroquine resistance transporter gene mutation K76T following the discontinuance of chloroquine use in Malawi
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DOI：
10.4269/ajtmh.2003.68.413
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发表时间：
2003-04-01
影响因子：
3.3
通讯作者：
Björkman, A
中科院分区：
文献类型：
--
作者：
Mita, T;Kaneko, A;Björkman, A
1993年，马拉维因治疗失败率较高（58%）而停止使用氯喹治疗恶性疟原虫疟疾患者。 1998年，马拉维萨利马地区氯喹体外耐药率为3%； 2000年，体内耐药率为9%。我们在 1998 年和 2000 年研究期间收集的 82 株恶性疟原虫分离株中，检测了与氯喹耐药性有关的两个基因突变（恶性疟原虫多重耐药基因 1 中的 N86Y 和恶性疟原虫氯喹耐药转运蛋白基因中的 K76T）。N86Y 的流行率与继续使用氯喹的邻国非洲国家相似。相比之下，K76T的患病率明显低于邻国，从1998年的17%显着下降至2000年的2%（P < 0.02）。然而，这两种突变均与体内或体外耐药性没有显着相关性（P > 0.29）。停止使用氯喹似乎可以恢复氯喹疗效并降低 K76T 患病率。然而，其他多态性预计也会导致耐药性。
In 1993, Malawi stopped treating patients with chloroquine for Plasmodium falciparum malaria because of a high treatment failure rate (58%). In 1998, the in vitro resistance rate to chloroquine was 3% in the Salima District of Malawi; in 2000, the in vivo resistance rate was 9%. We assayed two genetic mutations implicated in chloroquine resistance (N86Y in the P. falciparum multiple drug resistance gene 1 and K76T in the P. falciparum chloroquine resistance transporter gene) in 82 P. falciparum isolates collected during studies in 1998 and 2000. The prevalence of N86Y remained similar to that in neighboring African countries that continued to use chloroquine. In contrast, the prevalence of K76T was substantially lower than in neighboring countries, decreasing significantly from 17% in 1998 to 2% in 2000 (P < 0.02). However, neither mutation was significantly associated with in vivo or in vitro resistance (P > 0.29). Withdrawal of the use of chloroquine appears to have resulted in the recovery of chloroquine efficacy and a reduction in the prevalence of K76T. However, other polymorphisms are also expected to contribute to resistance.