Francisco Amanda F, Jayawardhana Shiromani, Lewis Michael D, Taylor Martin C, Kelly John M
Department of Pathogen Molecular Biology,London School of Hygiene and Tropical Medicine,Keppel Street,London WC1E 7HT,UK.
Parasitology. 2017 Dec;144(14):1871-1880. doi: 10.1017/S0031182017001469. Epub 2017 Aug 23.
Chagas disease is caused by infection with the insect-transmitted protozoan Trypanosoma cruzi, and is the most important parasitic infection in Latin America. The current drugs, benznidazole and nifurtimox, are characterized by limited efficacy and toxic side-effects, and treatment failures are frequently observed. The urgent need for new therapeutic approaches is being met by a combined effort from the academic and commercial sectors, together with major input from not-for-profit drug development consortia. With the disappointing outcomes of recent clinical trials against chronic Chagas disease, it has become clear that an incomplete understanding of parasite biology and disease pathogenesis is impacting negatively on the development of more effective drugs. In addition, technical issues, including difficulties in establishing parasitological cure in both human patients and animal models, have greatly complicated the assessment of drug efficacy. Here, we outline the major questions that need to be addressed and discuss technical innovations that can be exploited to accelerate the drug development pipeline.
恰加斯病由昆虫传播的原生动物克氏锥虫感染引起，是拉丁美洲最重要的寄生虫感染。目前的药物苯硝唑和硝呋莫司疗效有限且有毒副作用，治疗失败屡见不鲜。学术界和商业界共同努力，非营利性药物开发联盟也大力投入，以满足对新治疗方法的迫切需求。鉴于近期针对慢性恰加斯病的临床试验结果令人失望，显然对寄生虫生物学和疾病发病机制的不完全理解对更有效药物的开发产生了负面影响。此外，技术问题，包括在人类患者和动物模型中确定寄生虫学治愈的困难，极大地复杂化了药物疗效的评估。在此，我们概述了需要解决的主要问题，并讨论了可用于加速药物开发进程的技术创新。
