With the Visceral Leishmaniasis/Kala-azar Elimination Program in South Asia in its consolidation phase, the focus is mainly on case detection, vector control, and identifying potential sources of infection. Accordingly, emphasis is presently on curbing transmission, which is potentially achievable by identification and elimination of potential reservoirs. The strongest contenders for being the disease reservoir are cases of Post Kala-azar Dermal Leishmaniasis (PKDL) which occurs in a minor proportion of individuals apparently cured of Visceral Leishmaniasis (VL). The demonstration of parasites in tissue aspirates despite being a risky and invasive process is the gold standard for diagnosis of VL, but is now being replaced by serological tests e.g., rK39 strip test and direct agglutination test. However, these antibody based tests are limited in their ability to diagnose relapses, detect cases of PKDL, and monitor effectiveness of treatment. Accordingly, detection of antigen or nucleic acids by polymerase chain reaction has been successfully applied for monitoring of parasite kinetics. This review article provides updated information on recent developments regarding the available antibody or antigen/nucleic acid based biomarkers for longitudinal monitoring of patients with VL or PKDL and emphasizes the need for availability of studies pertaining to quantification of treatment response or relapse.
Background The assessment of chemotherapeutic responses in Post Kala-azar Dermal Leishmaniasis (PKDL), especially its macular form is challenging, emphasizing the necessity for ‘test of cure’ tools. This study explored the diagnostic and prognostic potential of IgG subclasses and associated cytokines for monitoring the effectiveness of chemotherapy in PKDL. Methods Participants included PKDL cases at (a) disease presentation, (b) immediately at the end of treatment (12 weeks for Miltefosine or 3 weeks for Liposomal Amphotericin B, LAmB and (c) at any time point 6 months later, for estimating anti-leishmanial immunoglobulin (Ig, IgG, IgM, IgG1, IgG2 and IgG3) and cytokines (IL-10, IL-6). Results In PKDL, Ig levels were elevated, with IgG3 and IL-10 being the major contributors. Miltefosine decreased both markers substantially and this decrease was sustained for at least six months. In contrast, LAmB failed to decrease IgG3 and IL-10, as even after six months, their levels remained unchanged or even increased. Conclusions In PKDL, IgG3 and IL-10 proved to be effective predictors of responsiveness to chemotherapy and may be considered as a non invasive alternative for longitudinal monitoring.
Kala-azar, commonly known as visceral leishmaniasis (VL), is a neglected tropical disease that has been targeted in South Asia for elimination by 2020. Presently, the Kala-azar Elimination Programme is aimed at identifying new low-endemic foci by active case detection, consolidating vector control measures, and decreasing potential reservoirs, of which Post Kala-azar Dermal Leishmaniasis (PKDL) is considered as the most important. PKDL is a skin condition that occurs after apparently successful treatment of VL and is characterized by hypopigmented patches (macular) or a mixture of papules, nodules, and/or macules (polymorphic). To achieve this goal of elimination, it is important to delineate the pathophysiology so that informed decisions can be made regarding the most appropriate and cost-effective approach. We reviewed the literature with regard to PKDL in Asia and Africa and interpreted the findings in establishing a potential correlation between the immune responses and pathophysiology. The overall histopathology indicated the presence of a dense, inflammatory cellular infiltrate, characterized by increased expression of alternatively activated CD68+ macrophages, CD8+ T cells showing features of exhaustion, CD20+ B cells, along with decreased CD1a+ dendritic cells. Accordingly, this review is an update on the overall immunopathology of PKDL, so as to provide a better understanding of host-parasite interactions and the immune responses generated which could translate into availability of markers that can be harnessed for assessment of disease progression and improvement of existing treatment modalities.
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