Chloroquine Resistant Plasmodium falciparum in Nigeria: Relationship between pfcrt and pfmdr1 Polymorphisms, In-Vitro Resistance and Treatment Outcome.
Chloroquine Resistant Plasmodium falciparum in Nigeria: Relationship between pfcrt and pfmdr1 Polymorphisms, In-Vitro Resistance and Treatment Outcome.
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DOI：
10.2174/1874315300801010074
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发表时间：
2008-01-01
期刊：
影响因子：
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通讯作者：
Happi, T C
中科院分区：
文献类型：
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作者：
Folarin, O A;Gbotosho, G O;Happi, T C
本研究旨在评估恶性疟原虫新鲜分离株中pfcrt和pfmdr1基因的多态性与体外氯喹敏感性和患者治疗结果的关系。采用改良裂殖体抑制法测定恶性疟原虫的体外敏感性。应用套式聚合酶链式反应和限制性片段长度多态性技术检测84株恶性疟原虫的pfcrt和pfmdr1基因多态性，其中85%(71/84)和15%(13/84)的恶性疟原虫对环丙沙星耐药和敏感。分子检测显示，突变型pfcrtT76、pfmdr1Y86和pfmdr1F184分别在60%、33%和14%的分离株中存在。恶性疟原虫体外和体内CQ耐药性之间存在显著的相关性(p=0.029)，突变的pfcrtT76+pfmdr1 Y86-Y184单倍型与体外(p=0.013)和体内CQ耐药性(p=0.024)之间也存在显著的相关性。
This study was designed to evaluate the association between polymorphisms in pfcrt and pfmdr1 genes and in-vitro chloroquine (CQ) sensitivity in fresh isolates of P. falciparum and patients' treatment outcome. The modified schizont inhibition assay was used to determine in-vitro sensitivity of P. falciparum. Polymorphisms in pfcrt and pfmdr1 genes were detected using nested PCR and RFLP techniques in 84 P. falciparum isolates obtained from patients with acute uncomplicated malaria.Eighty five percent (71/84) and 15% (13/84) of the parasites were resistant and sensitive in-vitro to CQ respectively. Molecular analysis showed presence of mutant pfcrtT76, pfmdr1Y86 and pfmdr1F184 alleles in 60%, 33% and 14% of the isolates respectively. There was a significant association between in-vitro and in-vivo CQ resistance (p=0.029) and also between the presence of mutant pfcrtT76+pfmdr1 Y86-Y184 haplotype and in-vitro (p=0.013) or in-vivo CQ resistance (p=0.024).Overall results from this study demonstrates that the presence of pfcrtT76+ pfmdr1 Y86-Y184 haplotype in Nigerian isolates of Plasmodium falciparum is predictive of in-vitro and in-vivo CQ resistance and therefore may be useful for monitoring resistance to this drug.