Post-kala-azar dermal leishmaniasis: insights into underlying pathogenic mechanisms and genetic landscape

Post-apparently successful treatment visceral leishmaniasis (VL), caused by protozoan parasite <i>Leishmania donovani</i>, is often followed by a dermal manifestation among patients known as post-kala-azar dermal leishmaniasis (PKDL). Although non-fatal disorder PKDL manifests itself clinically with a spectrum of cutaneous lesions, including macular, papular, nodular, or polymorphic types, that appear following apparent cure from VL. The absence of reliable non-invasive diagnostic techniques contributes to the underreporting of PKDL, particularly in rural regions. Individuals affected by PKDL may act as reservoirs of <i>Leishmania</i>, posing a significant challenge to ongoing VL elimination initiatives. The transition from VL to PKDL is governed by a complex interplay between host immune mechanisms and parasite-specific genetic polymorphisms. Investigations into the molecular dialog between host and parasite employing both <i>in-vitro</i> and <i>in-silico</i> methodologies are currently underway to elucidate the underlying biological processes. A key objective of these efforts is the identification of reliable biomarkers associated with PKDL, which would facilitate a comprehensive understanding of disease progression and enable the development of improved diagnostic tools for early detection. In this context, genome sequencing has emerged as a critical tool for uncovering genetic variants of <i>L. donovani</i> that contribute to parasite persistence in a subset of individuals, even after effective VL therapy. Insights gained from genomic studies may also reveal novel therapeutic targets and inform vaccine development strategies, thereby opening new avenues for disease control and eradication. This review aims to examine the molecular strategies being employed to investigate the pathophysiology of PKDL, with an emphasis on portraying the mechanistic differences between VL and PKDL. A nuanced understanding of these distinctions is essential for effective disease management, early diagnostic intervention, and interruption of transmission cycles in endemic regions.