Abstract
Background: Post Kala Azar Dermal Leishmaniasis (PKDL) is a non-fatal dermal sequel of Visceral Leishmaniasis (VL), affecting individuals worldwide. Available diagnostic tools lack sensitivity and specificity toward identifying macular (MAC) PKDL patients, due to low parasite load in patients' sample. Confirmatory test like punch biopsy are invasive and painful. Considering the rural nature of this disease and the prevailing situation of diagnostic scenario, PKDL patients mostly remains unattended from receiving proper medical care. They in turn act as “mobile parasite reservoir,” responsible for VL transmission among healthy individuals (HI). This study aims to identify PKDL disease specific glycated protein biomarkers, utilizing the powerful LC-MS/MS technology, which is the tool of choice to efficiently identify and quantify disease specific protein biomarkers. These identified PKDL disease specific novel glycoproteins could be developed in future as immunochromatographic based assay for efficient case detection.Methodology: Previously our lab had identified importance of glycated (Circulating Immune Complexes) CICs, among PKDL patients. This study aims to further characterize disease specific glycated protein biomarkers, among MAC PKDL patients for both diagnostic and prognostic evaluation of the disease. LC-MS/MS based comparative spectral count analysis of MAC PKDL to polymorphic (POLY) PKDL, HI, and Cured (CR) individuals were performed. Proteins level alterations among all study groups were confirmed by Western blot and enzyme-linked immunosorbant Assay (ELISA).Results: Among MAC PKDL patients 43, 60, 90 proteins were altered compared to POLY PKDL, HI, and CR groups, respectively. Filtering for the most significant proteins, Plasminogen (PLG) and Vitronectin (VTN) were identified which promisingly identified MAC PKDL cases. Active surveillance results from endemic districts of West Bengal revealed drastic rise of MAC PKDL cases, alarming the urgency for field adaptive efficient biomarker.Conclusion: This current study aims to establish PLG and VTN as novel diagnostic and prognostic protein biomarker for MAC and POLY PKDL cases management.
Highlights
Post Kala Azar Dermal Leishmaniasis (PKDL) is a non-fatal dermal sequel of Visceral Leishmaniasis (VL), caused by protozoan parasite Leishmania donovani
Among MAC PKDL patients 43, 60, 90 proteins were altered compared to POLY PKDL, healthy individuals (HI), and CR groups, respectively
The predominance of PKDL patients suffering with MAC lesions varies among different regions; for example in Sudan, PKDL patients suffering with MAC lesions were reported to be 9% whereas in Indian scenario the percentage of PKDL patients suffering with MAC lesions ranges from 15 to 31%
Summary
PKDL is a non-fatal dermal sequel of VL, caused by protozoan parasite Leishmania donovani. PKDL patients suffering with MAC lesions, have comparatively lower parasitic load, and lack detection sensitivity with standard techniques like rK39 (73% sensitivity) (Salotra et al, 2001) Leishmanin skin test (54% sensitivity), histopathological studies with patients’ skin biopsy sample (7–33% sensitivity) (WHO, 2015) and is often misdiagnosed as Vitiligo cases (Domínguez and Toraño, 1999; Jaiswal et al, 2018). Considering the rural nature of this disease and the prevailing situation of diagnostic scenario, PKDL patients mostly remains unattended from receiving proper medical care. They in turn act as “mobile parasite reservoir,” responsible for VL transmission among healthy individuals (HI). These identified PKDL disease specific novel glycoproteins could be developed in future as immunochromatographic based assay for efficient case detection
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