Platteeuw J J
Avivia, Boxtel, The Netherlands.
Trop Med Int Health. 2006 Jun;11(6):804-8. doi: 10.1111/j.1365-3156.2006.01646.x.
Sulphadrug treatment failure in malaria therapy cannot solely be ascribed to the build-up of genetic resistance within the parasitic genome. Although numerous in vitro studies have tried to determine the exact genetic markers that could predict treatment outcome in patients, this research has not been conclusive. Sulphadrugs work by competitive inhibition with pABA at one point of the pathway to de novo folate synthesis. However, evidence suggests that the malaria parasite is capable of overcoming this competitive inhibition by switching over to other metabolic pathways, like direct folate salvage from a person's bloodstream. In other words, increased folic acid administration, via diet or supplementation, may have reduced the effectiveness of sulphadrugs more than genetic mutations. Although in vitro studies are valuable for understanding disease mechanisms, we should not forget that the human being is infinitely more complex than any laboratory model.
疟疾治疗中磺胺类药物治疗失败不能仅仅归因于寄生虫基因组内遗传抗性的积累。尽管许多体外研究试图确定能够预测患者治疗结果的精确遗传标记，但这项研究尚无定论。磺胺类药物通过在从头合成叶酸途径的某一点上与对氨基苯甲酸竞争性抑制起作用。然而，有证据表明疟原虫能够通过切换到其他代谢途径，如直接从人的血液中挽救叶酸，来克服这种竞争性抑制。换句话说，通过饮食或补充剂增加叶酸的摄入量，可能比基因突变更能降低磺胺类药物的有效性。虽然体外研究对于理解疾病机制很有价值，但我们不应忘记，人类比任何实验室模型都要复杂得多。
