ABSTRACT
The current drive by the Government of India to eliminate Leishmaniasis has pinpointed
post-kala azar dermal leishmaniasis (PKDL) as the strongest contender for the disease
reservoir. This emphasizes the necessity to consider the eradication of PKDL as top
priority, and hinges on its early diagnosis and management. We undertook this challenge
and have provided insights into Leishmania biology, by focusing our efforts in (i) delineating the immunopathogenesis of PKDL,
a disease unique to South Asia (ii) developing diagnostic/prognostic tools for monitoring
antileishmanial treatment in patients with visceral leishmaniasis and PKDL. In order
to delineate the immunopathogenesis of PKDL, it was established that the parasite
adopts multiple approaches to deviously manipulate host monocytes/macrophages, and
thus facilitate parasite survival and disease progression. The parasite adopts a multipronged
approach that includes attenuation of the oxidative burst within phagocytes, polarization
of monocytes/ macrophages towards alternate activation, enhancement of CD8 T-cell
exhaustion and a decreased presence of Langerhans cells. Identification of these immunological
changes have allowed for development of biomarkers that have been exploited to develop
diagnostic and prognostic markers for monitoring the disease progression, either in
terms of antibody based markers, or quantification of the parasite load, the latter
being the most definitive approach. Measurement of parasite load has proved to be
an effective tool for monitoring the effectiveness of chemotherapy. Taken together,
the identification of biomarkers and new chemotherapeutic modalities has helped in
improved management and potential elimination of leishmaniasis.
Keywords
Leishmania biology - post-kala azar dermal leishmaniasis (PKDL) - visceral leishmaniasis
- Th-associated cytokines - Toll-like receptors - antimonials - miltefosine