Reeder J C, Rieckmann K H, Genton B, Lorry K, Wines B, Cowman A F
Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.
Am J Trop Med Hyg. 1996 Aug;55(2):209-13. doi: 10.4269/ajtmh.1996.55.209.
Plasmodium falciparum isolates from 24 Papua New Guinean patients with symptomatic malaria were tested for susceptibility to pyrimethamine and cycloguanil. Thirteen isolates were sensitive to both agents and the remainder exhibited varying degrees of resistance. No isolates were found to be resistant to one agent yet sensitive to the other and a positive correlation suggesting cross-resistance was found. Parasite DNA extracted from the patients' stained blood slides was amplified and sequenced to examine point mutations in the dihydrofolate reductase (DHFR) and dihydropteroate synthetase genes (DHPS) associated with antifolate resistance. All resistant isolates possessed mutations in the DHFR gene at codon 108, the majority changing from Ser to Asn, but one isolate from Ser to Thr, a change not previously reported in field isolates. A second mutation of the DHFR gene at Cys-59 to Arg was present in isolates with higher level resistance, but not exclusively so. Sequencing the DHPS gene, as a predictor of sulfadoxine resistance, revealed only one example that was different from DHPS alleles of sensitive isolates.
对来自24名巴布亚新几内亚有症状疟疾患者的恶性疟原虫分离株进行了乙胺嘧啶和环氯胍敏感性测试。13个分离株对这两种药物均敏感，其余分离株表现出不同程度的耐药性。未发现对一种药物耐药而对另一种药物敏感的分离株，且发现存在提示交叉耐药性的正相关关系。从患者染色血涂片提取的寄生虫DNA进行扩增和测序，以检查与抗叶酸耐药性相关的二氢叶酸还原酶（DHFR）和二氢蝶酸合酶基因（DHPS）中的点突变。所有耐药分离株的DHFR基因第108密码子均有突变，大多数从Ser变为Asn，但有一个分离株从Ser变为Thr，这一变化在野外分离株中此前未见报道。DHFR基因在Cys-59处的第二个突变变为Arg存在于耐药性较高的分离株中，但并非所有此类分离株都有该突变。对DHPS基因进行测序作为磺胺多辛耐药性的预测指标，仅发现一个与敏感分离株的DHPS等位基因不同的例子。
