Dorsey G, Kamya M R, Singh A, Rosenthal P J
Department of Medicine, San Francisco General Hospital, University of California, San Francisco, CA 94143-0811, USA.
J Infect Dis. 2001 May 1;183(9):1417-20. doi: 10.1086/319865. Epub 2001 Mar 27.
The molecular mechanism of chloroquine resistance in Plasmodium falciparum remains uncertain. Polymorphisms in the pfcrt and pfmdr-1 genes have been associated with chloroquine resistance in vitro, although field studies are limited. In evaluations of known polymorphisms in parasites from patients with uncomplicated malaria in Kampala, Uganda, the presence of 8 pfcrt mutations and 2 pfmdr-1 mutations did not correlate with clinical response to therapy with chloroquine. Most notably, the pfcrt lysine-->threonine mutation at position 76, which recently correlated fully with chloroquine resistance in vitro, was present in 100% of 114 isolates, of which about half were from patients who recovered clinically after chloroquine therapy. These results suggest that, although key pfcrt polymorphisms may be necessary for the elaboration of resistance to chloroquine in areas with high levels of chloroquine resistance, other factors, such as host immunity, may contribute to clinical outcomes.
恶性疟原虫对氯喹耐药的分子机制仍不明确。尽管现场研究有限，但pfcrt和pfmdr - 1基因的多态性已与体外氯喹耐药相关。在对乌干达坎帕拉单纯性疟疾患者体内寄生虫已知多态性的评估中，8个pfcrt突变和2个pfmdr - 1突变的存在与氯喹治疗的临床反应并无关联。最值得注意的是，第76位的pfcrt赖氨酸→苏氨酸突变，最近在体外与氯喹耐药完全相关，在114株分离株中100%存在，其中约一半来自氯喹治疗后临床康复的患者。这些结果表明，尽管关键的pfcrt多态性可能是氯喹高耐药地区产生氯喹耐药所必需的，但其他因素，如宿主免疫力，可能影响临床结果。
