A Review: The Current In Vivo Models for the Discovery and Utility of New Anti-leishmanial Drugs Targeting Cutaneous Leishmaniasis.
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.
College of Medicine, Swansea University, Swansea, United Kingdom; School of Biological Sciences, The University of Auckland, Auckland, New Zealand.
Emily Rose
ER
Mears
Drugs for Neglected Diseases initiative, Geneva, Switzerland; Center for Research and Training on Skin Diseases and Leprosy (CRTSDL), Tehran University Medical Sciences, Tehran, Iran.
Farrokh
F
Modabber
Drugs for Neglected Diseases initiative, Geneva, Switzerland.
Robert
R
Don
College of Medicine, Swansea University, Swansea, United Kingdom.
George E
GE
Johnson
D000818:Animals; D000981:Antiprotozoal Agents / Q000302:isolation & purification* / Q000627:therapeutic use; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D055808:Drug Discovery / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy*; D008253:Macaca mulatta; D008647:Mesocricetus; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA
D000981:Antiprotozoal Agents