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喀麦隆当地居民中的氯喹耐药恶性疟原虫

Chloroquine resistant Plasmodium falciparum in indigenous residents of Cameroon.

作者信息

Oduola A M, Moyou-Somo R S, Kyle D E, Martin S K, Gerena L, Milhous W K

机构信息

Department of Parasitology, Walter Reed Army Institute of Research, Washington, DC 20307-5100.

出版信息

Trans R Soc Trop Med Hyg. 1989 May-Jun;83(3):308-10. doi: 10.1016/0035-9203(89)90482-3.

Abstract

Thirty-nine percent (36 of 92) of children in Limbe, Cameroon, treated with chloroquine (10 mg/kg body weight on days 1 and 2, and 5 mg/kg on day 3) for falciparum malaria failed to respond within 7 d of treatment. Twenty-two of these children with chloroquine-resistant malaria were successfully treated with Fansidar [one-half tablet (250 mg sulfadoxine and 25 mg pyrimethamine) per 10 kg body weight], while the other 14 children were cured with mefloquine (25 mg/kg body weight). In vitro, a combination of verapamil at 1.0 x 10(-6) M with chloroquine or desethylchloroquine reversed resistance to the antimalarial drug and its primary metabolite in each of the 2 isolates successfully adapted and maintained in continuous culture. Similar combinations had no effect on susceptibilities of a sensitive reference clone, D6, used as control. Both chloroquine-resistant isolates from Cameroon were significantly more susceptible to mefloquine and halofantrine in vitro than the chloroquine-sensitive reference clone. Clinical observation, and in vitro confirmation, of chloroquine-resistant falciparum malaria in these indigenous children from Cameroon, and the current socio-economic condition in West Africa, underscore the need for pragmatic health management policies for efficient use of alternative antimalarial drugs in controlling drug resistant Plasmodium falciparum in the region. This observation of reversal of chloroquine resistance in isolates of P. falciparum obtained from West Africa, and a previous report on clones obtained from south-east Asia and South America, suggest that the mechanism(s) of resistance to chloroquine may be identical in resistant parasites from the 3 continents.

摘要

在喀麦隆林贝,92名接受氯喹(第1天和第2天10毫克/千克体重,第3天5毫克/千克体重)治疗恶性疟原虫疟疾的儿童中,39%(92名中的36名)在治疗7天内没有反应。这22名对氯喹耐药的儿童用Fansidar[每10千克体重半片(250毫克周效磺胺和25毫克乙胺嘧啶)]成功治疗,而另外14名儿童用甲氟喹(25毫克/千克体重)治愈。在体外,1.0×10⁻⁶ M的维拉帕米与氯喹或去乙基氯喹联合使用,在2株成功适应并维持连续培养的分离株中,逆转了对该抗疟药物及其主要代谢物的耐药性。类似的联合用药对用作对照的敏感参考克隆D6的敏感性没有影响。来自喀麦隆的2株氯喹耐药分离株在体外对甲氟喹和卤泛群的敏感性明显高于氯喹敏感参考克隆。对这些喀麦隆本地儿童中氯喹耐药恶性疟原虫疟疾的临床观察和体外确认,以及西非目前的社会经济状况,强调需要制定务实的卫生管理政策,以便有效使用替代抗疟药物来控制该地区耐药性恶性疟原虫。对从西非获得的恶性疟原虫分离株中氯喹耐药性逆转的这一观察结果,以及先前关于从东南亚和南美洲获得的克隆的报告,表明来自这3个大陆的耐药寄生虫对氯喹的耐药机制可能相同。

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