Molecular assessment of drug resistance in Plasmodium falciparum from Bahr El Gazal Province, Sudan
Molecular assessment of drug resistance in Plasmodium falciparum from Bahr El Gazal Province, Sudan
复制标题
DOI：
10.1046/j.1360-2276.2003.01144.x
复制
发表时间：
2003-12-01
影响因子：
3.3
通讯作者：
Balkan, S
中科院分区：
文献类型：
--
作者：
Anderson, TJC;Nair, S;Balkan, S
目的 评估苏丹寄生虫群体对氯喹 (CQ) 和磺胺多辛/乙胺嘧啶 (SP) 的耐药性。方法 苏丹阿库姆反复出现的安全问题使我们无法进行经典的体内治疗效果研究。相反，我们对氯喹耐药转运蛋白 (pfcrt)、多药耐药基因 (pfmdr1)、二氢叶酸还原酶 (dhfr) 和二氢叶酸合成酶 (dhps) 中的关键突变进行了基因分型。我们通过限制性消化荧光末端标记的聚合酶链反应（PCR）产物对pfcrt中的K76T突变和（pfmdr）中的N86Y突变进行基因分型，同时通过引物对dhfr中的密码子16、51、59、108和164以及dhps中的密码子436、437、540、581和613进行基因分型结果 63% 的寄生虫在 pfcrt 处携带对 CQ 抗性至关重要的 76T 突变，而 31% 的寄生虫在 pfmdr 处携带 86Y 突变，该突变与 CQ 抗性相关，但不是必需的。我们发现了 5 个 dhfr 等位基因：60% 的感染者含有野生型 dhfr 等位基因，3% 有 1 个突变，34% 有 2 个突变，3% 有 3 个突变。我们发现了三种 dhps 等位基因：47% 为野生型，44% 有一种突变，而 9% 有两种突变。 结论 我们预计 CQ 治疗失败率 (RI-RIII) 较高（20-40%），并预测 SP 治疗有效。然而，存在具有三个突变（51I、59R、108N）的 dhfr 等位基因以及具有两个突变（437G、540E）的 dhps 等位基因。因此，SP 的成功治疗可能是短暂的。
AIMS To assess resistance to chloroquine (CQ) and sulphadoxine/pyrimethamine (SP) in a Sudanese parasite population.METHODS Recurrent security problems in Akuem, Sudan, prevented us from conducting a classical in vivo treatment efficacy study. Instead we genotyped key mutations in the chloroquine resistance transporter (pfcrt), the multidrug resistance gene (pfmdr1), dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps). We genotyped the K76T mutation in pfcrt and the N86Y mutation in (pfmdr) by restriction digestion of fluorescent end-labelled polymerase chain reaction (PCR) products, while we genotyped codons 16, 51, 59, 108 and 164 in dhfr and codons 436, 437, 540, 581 and 613 in dhps by primer extension in 100 blood samples.RESULTS Sixty-three percent of parasites carried the 76T mutation at pfcrt critical for CQ resistance, while 31% carried the 86Y mutation at pfmdr that is associated with, although not essential, for CQ resistance. We found five dhfr alleles: 60% of infections contained wild-type dhfr alleles, 3% had one mutation, 34% had two mutations, while 3% had three mutations. We found three dhps alleles: 47% were wild type, 44% had one mutation, while 9% had two mutations.CONCLUSIONS We expect high levels of treatment failure (RI-RIII) with CQ (20-40%) and predict efficient treatment with SP. However, dhfr alleles with three mutations (51I, 59R, 108N) are present as are dhps alleles with two mutations (437G, 540E). Successful treatment with SP is therefore likely to be short-lived.