Mears Emily Rose, Modabber Farrokh, Don Robert, Johnson George E
College of Medicine, Swansea University, Swansea, United Kingdom; School of Biological Sciences, The University of Auckland, Auckland, New Zealand.
Drugs for Neglected Diseases initiative, Geneva, Switzerland; Center for Research and Training on Skin Diseases and Leprosy (CRTSDL), Tehran University Medical Sciences, Tehran, Iran.
PLoS Negl Trop Dis. 2015 Sep 3;9(9):e0003889. doi: 10.1371/journal.pntd.0003889. eCollection 2015.
The current in vivo models for the utility and discovery of new potential anti-leishmanial drugs targeting Cutaneous Leishmaniasis (CL) differ vastly in their immunological responses to the disease and clinical presentation of symptoms. Animal models that show similarities to the human form of CL after infection with Leishmania should be more representative as to the effect of the parasite within a human. Thus, these models are used to evaluate the efficacy of new anti-leishmanial compounds before human clinical trials. Current animal models aim to investigate (i) host-parasite interactions, (ii) pathogenesis, (iii) biochemical changes/pathways, (iv) in vivo maintenance of parasites, and (v) clinical evaluation of drug candidates. This review focuses on the trends of infection observed between Leishmania parasites, the predictability of different strains, and the determination of parasite load. These factors were used to investigate the overall effectiveness of the current animal models. The main aim was to assess the efficacy and limitations of the various CL models and their potential for drug discovery and evaluation. In conclusion, we found that the following models are the most suitable for the assessment of anti-leishmanial drugs: L. major-C57BL/6 mice (or-vervet monkey, or-rhesus monkeys), L. tropica-CsS-16 mice, L. amazonensis-CBA mice, L. braziliensis-golden hamster (or-rhesus monkey). We also provide in-depth guidance for which models are not suitable for these investigations.
目前用于发现和评估针对皮肤利什曼病(CL)的新型潜在抗利什曼药物的体内模型,在对该疾病的免疫反应和症状临床表现方面存在巨大差异。感染利什曼原虫后与人类CL形式表现出相似性的动物模型,对于寄生虫在人体内的作用应该更具代表性。因此,这些模型用于在人体临床试验之前评估新型抗利什曼化合物的疗效。当前的动物模型旨在研究(i)宿主-寄生虫相互作用,(ii)发病机制,(iii)生化变化/途径,(iv)寄生虫的体内维持,以及(v)候选药物的临床评估。本综述重点关注利什曼原虫之间观察到的感染趋势、不同菌株的可预测性以及寄生虫负荷的测定。这些因素用于研究当前动物模型的整体有效性。主要目的是评估各种CL模型的疗效和局限性及其在药物发现和评估方面的潜力。总之,我们发现以下模型最适合评估抗利什曼药物:硕大利什曼原虫-C57BL/6小鼠(或-绿猴,或-恒河猴)、热带利什曼原虫-CsS-16小鼠、亚马逊利什曼原虫-CBA小鼠、巴西利什曼原虫-金黄仓鼠(或-恒河猴)。我们还针对哪些模型不适合这些研究提供了深入指导。