Drug resistance to sulphadoxine-pyrimethamine in Plasmodium falciparum malaria in Mlimba, Tanzania.
Drug resistance to sulphadoxine-pyrimethamine in Plasmodium falciparum malaria in Mlimba, Tanzania.
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DOI：
10.1186/1475-2875-5-94
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发表时间：
2006-10-31
期刊：
影响因子：
3
通讯作者：
Mshinda H
中科院分区：
文献类型：
--
作者：
Mbugi EV;Mutayoba BM;Malisa AL;Balthazary ST;Nyambo TB;Mshinda H
在许多非洲国家，磺胺多辛-乙胺嘧啶 (SP) 已经且目前用于治疗无并发症的恶性疟原虫疟疾。然而，寄生虫对 SP 治疗的反应在个体之间表现出显着差异。以二氢叶酸还原酶 (dhfr) 和二氢叶酸合成酶 (dhps) 基因为标记，研究了 141 名 5 岁以下儿童对 SP 的寄生虫抗性。采用 Chelex 法从收集并保存在滤纸上的血液样本中提取寄生虫 DNA。随后，应用聚合酶链反应（PCR）和限制性片段长度多态性（PCR-RFLP）检测dhfr和dhps上与SP抗性相关的点突变。检查了 dhfr 中密码子 51、59、108 和 164 以及 dhps 域中密码子 437、540 和 581 处常见报道的点突变。感染带有一系列单至五重 dhfr/dhps 突变的寄生虫的儿童无法通过 SP 治愈。然而，五重 dhfr/dhps 突变基因型大多与治疗失败有关。本研究中检测到高比例的 SP 耐药相关点突变，但在随访第 14 天临床观察到的足够的临床反应 (89.4%) 反映了半免疫保护和寄生虫清除在人群中的作用。在监测 SP 耐药性时，应考虑对与恶性疟疾耐药性发展相关的可能混杂因素进行同时研究。本研究中检测到的 SP 抗药性潜力对其作为坦桑尼亚和其他疟疾流行国家的疟疾临时一线药物的有效治疗寿命提出了警告。
Sulphadoxine-pyrimethamine (SP) has been and is currently used for treatment of uncomplicated Plasmodium falciparum malaria in many African countries. Nevertheless, the response of parasites to SP treatment has shown significant variation between individuals. The genes for dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) were used as markers, to investigate parasite resistance to SP in 141 children aged less than 5 years. Parasite DNA was extracted by Chelex method from blood samples collected and preserved on filter papers. Subsequently, polymerase chain reaction (PCR) and restriction fragment length polymorphism (PCR-RFLP) were applied to detect the SP resistance-associated point mutations on dhfr and dhps. Commonly reported point mutations at codons 51, 59, 108 and 164 in the dhfr and codons 437, 540 and 581 in the dhps domains were examined. Children infected with parasites harbouring a range of single to quintuple dhfr/dhps mutations were erratically cured with SP. However, the quintuple dhfr/dhps mutant genotypes were mostly associated with treatment failures. High proportion of SP resistance-associated point mutations was detected in this study but the adequate clinical response (89.4%) observed clinically at day 14 of follow up reflects the role of semi-immunity protection and parasite clearance in the population. In monitoring drug resistance to SP, concurrent studies on possible confounding factors pertaining to development of resistance in falciparum malaria should be considered. The SP resistance potential detected in this study, cautions on its useful therapeutic life as an interim first-line drug against malaria in Tanzania and other malaria-endemic countries.
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影响因子：
2.9
作者：
Danis, M;Bricaire, F
通讯作者：
Bricaire, F
影响因子：
4.9
作者：
Ahmed, A;Bararia, D;Sharma, YD
通讯作者：
Sharma, YD
DOI：
10.1016/s0035-9203(02)90349-4
发表时间：
2002-11-01
影响因子：
2.2
作者：
Hastings, MD;Bates, SJ;Sibley, CH
通讯作者：
Sibley, CH
影响因子：
2.1
作者：
DEPECOULAS, PE;BASCO, LK;MAZABRAUD, A
通讯作者：
MAZABRAUD, A
影响因子：
2.9
作者：
Le Bras, J;Durand, R
通讯作者：
Durand, R