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几内亚比绍与氯喹和氨酚喹耐药性相关的恶性疟原虫基因型

Plasmodium falciparum genotypes associated with chloroquine and amodiaquine resistance in Guinea-Bissau.

作者信息

Ursing Johan, Kofoed Poul-Erik, Rodrigues Amabelia, Rombo Lars, Gil José Pedro

机构信息

Malaria Research Unit, Department of Infectious Diseases, Division of Medicine, Karolinska Hospital, Karolinska Institutet, Stockholm, Sweden.

出版信息

Am J Trop Med Hyg. 2007 May;76(5):844-8.

Abstract

Chloroquine is the most commonly used antimalarial in Guinea-Bissau and high doses are routinely prescribed. Blood from 497 patients treated with different doses of chloroquine or amodiaquine were genotyped. Pfcrt and pfmdr1 polymorphisms were identified. Pfmsp2 analysis identified recrudescent infections. The pfcrt 72-76 haplotypes were CVIET and CVMNK. The pfcrt 76T prevalence was 23% at day 0 and 96%, 83% and 100% at recrudescence following treatment with 25 mg/kg and 50 mg/kg of chloroquine and 15 mg/kg of amodiaquine respectively. When treating pfcrt 76T carrying P. falciparum the efficacy of 50 mg/kg and 25 mg/kg of chloroquine was 78% and 34% respectively (P = 0.007). The genetic basis of chloroquine resistance is probably the same in Guinea-Bissau as in the rest of Africa. The low pfcrt 76T prevalence suggests that resistance to normal dose chloroquine does not confer a major advantage to falciparum in Bissau and could be a result of treatment with high-dose chloroquine.

摘要

氯喹是几内亚比绍最常用的抗疟药,通常会开具高剂量处方。对497名接受不同剂量氯喹或阿莫地喹治疗的患者的血液进行了基因分型。鉴定了Pfcrt和pfmdr1基因多态性。Pfmsp2分析确定了复燃感染情况。Pfcrt 72 - 76单倍型为CVIET和CVMNK。Pfcrt 76T在第0天的流行率为23%,在用25mg/kg和50mg/kg氯喹以及15mg/kg阿莫地喹治疗后复燃时分别为96%、83%和100%。当治疗携带Pfcrt 76T的恶性疟原虫时,50mg/kg和25mg/kg氯喹的疗效分别为78%和34%(P = 0.007)。几内亚比绍氯喹耐药的遗传基础可能与非洲其他地区相同。Pfcrt 76T的低流行率表明,对正常剂量氯喹的耐药性并未给比绍的恶性疟原虫带来主要优势,这可能是高剂量氯喹治疗的结果。

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