A Review: The Current In Vivo Models for the Discovery and Utility of New Anti-leishmanial Drugs Targeting Cutaneous Leishmaniasis

Abstract

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.

Antiviral screening identifies adenosine analogs targeting the endogenous dsRNA Leishmania RNA virus 1 (LRV1) pathogenicity factor

“…Thus far there are no data available in humans permitting tests of the association of LRV1 with L. braziliensis parasite burden nor the severity of cutaneous leishmaniasis (CL), which can show a range of presentations (14,15). In lieu of such information, studies have focused on the association of LRV1 with MCL vs. CL, which is thought to reflect primarily immunopathology rather than parasite numbers (2,6,(14)(15)(16). Although in some studies LRV1 was not correlated with MCL clinical manifestations (17,18), in others there was a strong association (6,19,20).…”

Antiulcer Activity after Oral Administration of the Wormwood Ethanol Extract on Lesions due to <I>Leishmania major</I> Parasites in BALB/C Mice

“…According to recent reports 10,26 , the BALB/c mouse -L. major model has extensively been used in drug discovery studies but it is an exceptionally rigorous non-cure model in which the most active drugs have any efficacy and absolute cure is scarce. The treatment of CL is difficult due to the intracellular (within macrophages) location and replication of the infectious Leishmania amastigote parasites.…”

Leishmania antimony resistance/ susceptibility in Algerian foci

“…Several animal species served as experimental hosts especially for CL: BALB/c mice and Syrian golden hamster, dogs and monkeys [71,72]. The choice of convenient animal models depends on Leishmania species under study.…”

“…For instance, the most suitable animal models are C57BL/6 mice (or vervet-monkeys, or rhesus-monkeys) for L. major and CsS-16 mice for L. tropica. CBA mice are convenient to study physiopathological effects caused by the infection with L. amazonensis and CBA and golden hamsters or rhesus-monkeys can be used for L. braziliensis 71 . We have recently established a murine model for Leishmania killicki cutaneous infections and probed its suitability for pharmacological purposes [73].…”