Leishmaniasis, classified as a neglected tropical disease, exerts its impact on millions globally. Its clinical spectrum encompasses diverse forms, from benign self-resolving skin lesions (cutaneous leishmaniasis) to life-threatening visceral infections (visceral leishmaniasis or kala-azar). This review aims to comprehensively explore the spectrum of the disease as an outcome of often-overlooked parasite variants. Additionally, it addresses the emerging challenges faced in the pursuit towards disease elimination. The evolving landscape of leishmaniasis demands the development of molecular surveillance tools to detect the heterogeneous parasite strains that contribute to the emergence of new endemic foci. Such surveillance poses formidable challenges to current elimination strategies. As the disease landscape continues to evolve, understanding the molecular intricacies of causative parasite strains becomes paramount. This knowledge not only aids the understanding of the basis of emerging/shifting endemic areas but also facilitates the search for and the design of targeted interventions. In this context, this review will navigate through the dynamic terrain of leishmaniasis, the various causative species of Leishmania parasites emphasising the urgency for the development of robust surveillance mechanisms and innovative approaches to confront the evolving challenges in our quest for global disease elimination.

The present studies on infections with Leishmania (Viannia) braziliensis in rhesus macaques were made to characterize the evolution of different parasite strains and the immune responses they elicited in this experimental host. A standardized inoculum of promastigotes was injected intradermally either above the eyelid or on the forearm of each monkey. Sixteen infected monkeys developed longstanding infections which lasted until the end of the observation period (33 months). The time required for lesion development was very variable, not only for the isolates showing molecular differences but also for individual animals in groups infected with the same parasite strain. The inocula produced lesions of variable severity, ranging from localized cutaneous leishmaniasis (CL) with a tendency to spontaneous healing to non-healing disease. One infected animal developed persistent metastatic skin and mucosal lesions. Anti-Leishmania antibodies and parasite-specific T-cell responses were induced by the experimental infections. As the granulomatous inflammatory response found at the lesions in L. (V.) braziliensis-infected M. mulatta was similar to that in patients with CL, this primate model could be useful for studying the pathophysiology and immunoregulatory events associated with disease evolution, as well as for the evaluation of new drugs or candidate vaccines.