Dept. of Microbiology, School of Genetics & Microbiology, Moyne Institute, Trinity College, Dublin, Ireland.
Curr Pharm Des. 2013;19(2):300-6. doi: 10.2174/138161213804070366.
Antimalarial drugs have in the past fallen prey to resistance and this problem is likely to continue in the future. One approach to developing drugs that might be less prone to resistance might be to target the disease rather than the parasite itself. The rationale for this idea, which has been somewhat developed in antibacterial chemotherapy, is that drugs that can alleviate disease pathogenesis while not compromising the survival, growth or transmission of the pathogen should not exert selective pressure that would encourage the emergence and spread of resistance. This review considers (concentrating on possible interventions at the parasite level) whether such 'anti-disease' therapy could be developed for severe Plasmodium falciparum malaria, and if so whether it might be less prone to resistance. Several anti-adhesive treatments, aiming to reduce the tissue sequestration of P. falciparum-parasitised erythrocytes that is associated with cerebral malaria and other complications, have been investigated as 'adjunctive' therapies. These therapies are however unlikely to be 'resistance proof' because sequestration appears to enhance parasite survival in the host. Severe malarial anaemia is another potentially fatal complication of malaria that results not only from lysis of host erythrocytes by intracellular parasites but to a greater extent from lysis of unparasitised erythrocytes and impaired erythropoiesis. The possibility of therapy interfering with the last of these processes, which may be more 'resistance proof', is discussed in detail.
过去，抗疟药物曾因耐药性而失效，而这个问题在未来可能还会继续存在。一种可能不太容易产生耐药性的药物研发方法是针对疾病本身，而不是寄生虫。这种想法的基本原理在抗菌化疗中已经得到了一定的发展，即那些既能缓解疾病发病机制，又不会影响病原体的生存、生长或传播的药物，不应施加选择性压力，从而鼓励耐药性的出现和传播。这篇综述考虑了（主要集中在寄生虫水平上的可能干预措施）这种“抗疾病”疗法是否可以用于严重的恶性疟原虫疟疾，如果可以，它是否可能不太容易产生耐药性。几种旨在减少与脑型疟疾和其他并发症相关的恶性疟原虫寄生红细胞在组织中的黏附的抗黏附治疗方法已被作为“辅助”疗法进行了研究。然而，这些疗法不太可能具有“耐药性证明”，因为黏附似乎会增强寄生虫在宿主中的生存能力。严重的疟疾性贫血是疟疾的另一种潜在致命并发症，不仅是由于宿主红细胞被细胞内寄生虫溶解，而且在更大程度上是由于未寄生的红细胞溶解和红细胞生成受损所致。本文详细讨论了治疗方法干扰最后一个过程的可能性，这可能更具“耐药性证明”。
