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Glycoproteins in circulating immune complexes are biomarkers of patients with Indian PKDL: A study from endemic districts of West Bengal, India.

ABSTRACT: Post Kala Azar Dermal Leishmaniasis (PKDL) occurs as dermal consequence of previous Visceral Leishmaniasis (VL) infection and serves as an important reservoir for transmission of VL. Diagnosis of PKDL is often challenging for its symptomatic resemblance to other co-endemic diseases like Leprosy or Vitiligo. Parasitological examination by slit-skin smear and culture are the standard methods but lack high sensitivity. Thus, for efficient control of VL, reliable diagnostic and prognostic assay of PKDL are required.Previously, glycoproteins (9-OAcSA) have been reported as promising biomarkers of Indian VL patients. However, till date, the status of glycans in Indian PKDL patients remains unexplored. Accordingly, in this study, the glyco-profile of PKDL Circulating Immune Complexes (CICs) as compared to other cross diseases like Vitiligo and Leprosyhas been investigated. Further, a novel Glyco CIC assay has been developed for efficient Indian PKDL patient diagnosis.In the present study, 90 PKDL patients were enrolled from 3 VL endemic districts of West Bengal during 2015-16. Glycosylation profile of isolated CICs from sera of PKDL patients were initially analyzed through gradient SDS gel electrophoresis followed by PAS silver double staining, which revealed the presence of several glycan rich PKDL specific proteins of varying molecular weights. To further characterize the glyco-profile of acid dissociated affinity purified immuno-reactive antigens present in the CICs, glycosylation was demonstrated in these purified CIC antigens by DIG glycan differentiation kit with or without glycosidase as well as neuraminidase treatment. Diagnostic evaluation of the newly developed colorimetric Glyco CIC assay through Receiver Operating Characteristic (ROC) curve analysis revealed excellent (0.99) AUC value as compared to other conventional serodiagnostic assays like PEG CIC, Parasite ELISA (IgG and IgM). Additionally, longitudinal monitoring of 18 PKDL patients further revealed its good prognostic utility.These results highlight the glycosylation status of CICs among Indian PKDL patients present in all the studied endemic districts of West Bengal. These PKDL biomarkers were completely absent in cross diseases like Vitiligo and Leprosy. Further, the newly developed Glyco CIC assay had an improved sensitivity of 95.6%, specificity of 99.3%, NPV of 97.1% and PPV of 98.9%.

SUBMITTER: Jaiswal P

PROVIDER: S-EPMC5805291 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Glycoproteins in circulating immune complexes are biomarkers of patients with Indian PKDL: A study from endemic districts of West Bengal, India.

Jaiswal Priyank P Datta Souvik S Sardar Bikash B Chaudhuri Surya Jyoti SJ Maji Dipankar D Ghosh Manab M Saha Bibhuti B Mukhopadhyay Sumi S

PloS one 20180208 2

<h4>Background</h4>Post Kala Azar Dermal Leishmaniasis (PKDL) occurs as dermal consequence of previous Visceral Leishmaniasis (VL) infection and serves as an important reservoir for transmission of VL. Diagnosis of PKDL is often challenging for its symptomatic resemblance to other co-endemic diseases like Leprosy or Vitiligo. Parasitological examination by slit-skin smear and culture are the standard methods but lack high sensitivity. Thus, for efficient control of VL, reliable diagnostic and pr ...[more]

PMID: 29420575

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Project description:BACKGROUND:Mosquitoes belonging to genus Aedes are the prime vectors of several arboviral diseases such as Dengue, Zika and Chikungunya worldwide. Every year numerous cases of dengue infections occur throughout the world, proper control of which depends on efficient vector control. However the onset of insecticide resistance has resulted in failure of vector control approaches. PRINCIPAL FINDINGS:This study was carried out to unveil the degree of prevailing insecticide resistance along with its underlying mechanisms among the primary dengue vector in dengue endemic districts of West Bengal, India through standard WHO protocol. It was observed that, the majority of the tested populations were found to possess resistance to more than one insecticide. In adult bioassay, the toxicity levels of the six tested insecticides was found to decrease in the following order: deltamethrin > lambdacyhalothrin > malathion > propoxur > permethrin > DDT. In larval bioassay, one of the tested populations was found to possess moderate resistance against temephos, mortality percentage 92.5% and 79.8% for WHO (0.0200 ppm) and National Vector Borne disease Programme, India recommended dose (0.0125 ppm) respectively. Carboxylesterases were found to be involved in conferring resistance as revealed in synergistic and quantitative assay against temephos in North Dinajpur (NDP) population and malathion in Alipurduar (APD) and Darjeeling (DAR) populations. Similar correlations were also observed in the majority of the tested populations between reduced susceptibilities against pyrethroid insecticides and Cytochrome P450s activity. CONCLUSION:Efficient disease management in this region can only be achieved through proper integrated vector management along with tools to minimize insecticide resistance. This study may help the concerned authorities in the formulation of an effective vector control strategy throughout this region incorporating the knowledge gained through this study.

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Glycoproteins in circulating immune complexes are biomarkers of patients with Indian PKDL: A study from endemic districts of West Bengal, India.

Publications

Glycoproteins in circulating immune complexes are biomarkers of patients with Indian PKDL: A study from endemic districts of West Bengal, India.

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