Scholarly Publications
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This community showcases the academic contributions of faculty and researchers at Banaras Hindu University (BHU) and provides a year-wise compilation of publications across disciplines. Institutional Repository BHU
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PublicationArticle Identification of antibodies directed against O-acetylated sialic acids in visceral leishmaniasis: Its diagnostic and prognostic role(1998) Mitali Chatterjee; Vineeta Sharma; Chitra Mandal; Shyam Sundar; Sandeep SenA significantly increased O-acetylated sialic acid (O-AcSA) binding fraction was purified from serum of visceral leishmaniasis (VL) patients by affinity chromatography on immobilized bovine submaxillary mucin (BSM) and found to be immunoglobulin in origin. The serodiagnostic and prognostic potential of BSM as a capture antigen was established by ELISA with no cross reactivity with coendemic diseases like malaria, tuberculosis, leprosy, chagas disease and cutaneous leishmaniasis; however, a strong cross reactivity was present with trypanosomiasis patients. In 56 clinically diagnosed VL patients, the BSM-ELISA was compared with diagnosis by microscopy using Giemsa stained tissue smears and direct ELISA using crude parasite antigen (parasite-ELISA); 49/56(87.5%) and 5/56(9.0%) were positive and negative respectively by all 3 methods. The BSM-ELISA failed to diagnose 2/56(3.5%) patients which were biopsy and parasite-ELISA positive. The prognostic potential of the BSM-ELISA in 18 longitudinally monitored VL patients before and after conventional antimonial treatment showed a significant decrease in anti O-AcSA titres in drug responsive patients whereas anti O-AcSA levels persisted in drug unresponsive patients. The IgG subclass distribution of antibodies directed against O-AcSA showed increased lgG2 levels in VL patients as compared to healthy controls. The BSM-based ELISA holds great promise as a serodiagnostic and prognostic assay for VL.PublicationArticle Monitoring of Leishmania transmission in the postelimination phase: The potential of serological surveys(Elsevier B.V., 2024) Kristien Cloots; Om Prakash Singh; Abhishek Kumar Singh; Tulika Kumari Rai; Vishwa Deepak Tiwari; Aziza Neyaz; Sundaram Pandey; Vivek Kumar Scholar; Paritosh Malaviya; Epco Hasker; Shyam SundarObjectives: Monitoring of Leishmania transmission is considered a strategic priority for sustaining elimination of visceral leishmaniasis as a public health problem in the Indian subcontinent. The objective of this study was to evaluate whether serological surveys can distinguish between communities with and without Leishmania transmission, and to assess which serological marker performs best. Methods: Seven villages were selected from Bihar and Uttar Pradesh state, India, and categorized as either currently endemic (CE), previously endemic (PE) or nonendemic (NE). Blood samples were analyzed with the rK39 RDT, direct agglutination test (DAT), and rK39 ELISA. Results: Contrary to the rK39 RDT and DAT, the rK39 ELISA showed a significant difference between all three categories of endemicity, with a seroprevalence of 5.21% in CE villages, 1.55% in PE villages, and 0.13% in NE villages. Even when only looking at the seroprevalence among children aged <10 years, the rK39 ELISA was still able to differentiate between villages with and without ongoing transmission. Conclusion: Our findings suggest the rK39 ELISA to be the most promising marker for monitoring of Leishmania transmission. Further validation is required, and practical, context-adapted recommendations need to be formulated in order to guide policymakers toward meaningful and sustainable surveillance strategies in the post-elimination phase. © 2024 The Author(s)PublicationReview Visceral leishmaniasis elimination in India: progress and the road ahead(Taylor and Francis Ltd., 2022) Om Prakash Singh; Shyam SundarIntroduction: As of 2021, visceral leishmaniasis (VL) elimination program has met with success in reducing the rate of VL to target levels in many locales, but there is persistence of low-level disease and sporadic outbreaks, sometimes in new locations. Thus, there is an urgent need to identify knowledge gaps and factors that impede total VL elimination. Area covered: We reviewed the progress and current status of VL elimination program. We discuss the knowledge gaps influencing the success of elimination program and strategies to be required to ensure VL elimination as a public health problem is achieved and sustained. Expert opinion: VL elimination is considered technically possible and operationally feasible owing to focal nature of transmission, absence of an animal reservoir, single vector, availability of an effective diagnostic test, use of a single dose of liposomal amphotericin B along with a strong political commitment. Substantial progress has been made in the reduction of VL incidence rates in the country. However, there are many challenges remain that need to be addressed if the elimination goal is to be reached and sustained. These are increasing relapse, outbreaks in new foci and increasing number of PKDL and HIV-VL co-infections. © 2022 Informa UK Limited, trading as Taylor & Francis Group.PublicationArticle Diagnosis of Visceral Leishmaniasis in an Elimination Setting: A Validation Study of the Diagnostic Algorithm in India(Multidisciplinary Digital Publishing Institute (MDPI), 2022) Kristien Cloots; Om Prakash Singh; Abhishek Kumar Singh; Anurag Kumar Kushwaha; Paritosh Malaviya; Sangeeta Kansal; Epco Hasker; Shyam SundarVisceral leishmaniasis (VL) is on the verge of elimination on the Indian subcontinent. Nonetheless, the currently low VL-incidence setting brings along new challenges, one of which is the validity of the diagnostic algorithm, based on a combination of suggestive clinical symptoms in combination with a positive rK39 Rapid Diagnostic Test (RDT). With this study, we aimed to assess the positive predictive value of the diagnostic algorithm in the current low-endemic setting in India by re-assessing newly diagnosed VL patients with a qPCR analysis on venous blood as the reference test. In addition, we evaluated the specificity of the rK39 RDT by testing non-VL cases with the rK39 RDT. Participants were recruited in Bihar and Uttar Pradesh, India. VL patients diagnosed based on the diagnostic algorithm were recruited through six primary health care centers (PHCs); non-VL cases were identified through a door-to-door survey in currently endemic, previously endemic, and non-endemic clusters, and tested with rK39 RDT, as well as—if positive—with qPCR on peripheral blood. We found that 95% (70/74; 95% CI 87–99%) of incident VL cases diagnosed at the PHC level using the current diagnostic algorithm were confirmed by qPCR. Among 15,422 non-VL cases, 39 were rK39 RDT positive, reflecting a specificity of the test of 99.7% (95% CI 99.7–99.8%). The current diagnostic algorithm combining suggestive clinical features with a positive rK39 RDT still seems valid in the current low-endemic setting in India. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.PublicationArticle Carboxymethyl chitosan modified lipid nanoformulations as a highly efficacious and biocompatible oral anti-leishmanial drug carrier system(Elsevier B.V., 2022) Aakriti Singh; Ganesh Yadagiri; Manorma Negi; Anurag Kumar Kushwaha; Om Prakash Singh; Shyam Sundar; Shyam Lal MudavathHerein, carboxymethyl chitosan (CMC) grafted lipid nanoformulations were facilely prepared by thin-film hydration method as a highly efficient biocompatible anti-leishmanial carrier encapsulating amphotericin B (AmB). Nanoformulations were characterized for their physicochemical characteristics wherein TEM analysis confirmed the spherical structure, whereas FTIR analysis revealed the conjugation of CMC onto nanoformulations and confirmed the free state of AmB. Furthermore, the wettability study confirmed the presence of CMC on the surface of nanoformulations attributed to the enhanced hydrophilicity. Surface hydrophilicity additionally contributes towards consistent mucin retention ability for up to 6 h, superior mucoadhesiveness, and hence enhanced bioavailability. The proposed nanoformulations with high encapsulation and drug loading properties displayed controlled drug release in the physiological microenvironment. In vitro, antileishmanial results showed an astounding 97% inhibition in amastigote growth. Additionally, in vivo studies showed that treatment with nanoformulations significantly reduced the liver parasitic burden (93.5%) without causing any toxicity when given orally. © 2022 Elsevier B.V.PublicationArticle Febrifugine dihydrochloride as a new oral chemotherapeutic agent against visceral leishmaniasis infection(Academic Press Inc., 2022) Rajan Kumar Pandey; Rupal Ojha; Moodu Devender; Prince Sebastian; Madhulika Namdeo; Bajarang Vasant Kumbhar; Shyam Sundar; Radheshyam Maurya; Vijay Kumar PrajapatiVisceral leishmaniasis (VL) is the deadliest form of leishmaniasis without a safer treatment option. This study implies drug repurposing to find a novel antileishmanial compound, namely febrifugine dihydrochloride (FFG) targeting Leishmania antioxidant system. Starting with virtual screening revealed the high binding affinity and lead likeness of FFG against the trypanothione reductase (TR) enzyme of Leishmania donovani, followed by experimental validation. The promastigotes inhibition assay gave the IC50 concentration of FFG and Miltefosine (positive control) as 7.16 ± 1.39 nM and 11.41 ± 0.29 μM, respectively. Their CC50 was found as 451 ± 12.73 nM and 135.9 ± 5.94 μM, respectively. FFG has been shown to increase the reactive oxygen species (ROS), leading to apoptosis-like cell death among L. donovani promastigotes. Spleen touch biopsy resulted in 62% and 55% decreased parasite load with FFG and miltefosine treatment, respectively. Cytokine profiling has shown an increased proinflammatory cytokine response post-FFG treatment. Moreover, FFG is safe on the liver toxicity parameter in mice post-treatment. © 2022 Elsevier Inc.PublicationArticle IFN-γ+ CD4+T cell-driven prophylactic potential of recombinant LDBPK_252400 hypothetical protein of Leishmania donovani against visceral leishmaniasis(Academic Press Inc., 2021) Sunita Yadav; Jay Prakash; Om Prakash Singh; Mallikarjuna Rao Gedda; Shashi Bhushan Chauhan; Shyam Sundar; Vikash Kumar DubeyVisceral leishmaniasis (VL) is a potentially fatal parasitic disease causing high morbidity and mortality in developing countries. Vaccination is considered the most effective and powerful tool for blocking transmission and control of diseases. However, no vaccine is available so far in the market for humans. In the present study, we characterized the hypothetical protein LDBPK_252400 of Leishmania donovani (LdHyP) and explored its prophylactic behavior as a potential vaccine candidate against VL. We found reduced hepato-splenomegaly along with more than 50% parasite reduction in spleen and liver after vaccination in mice. Protection in vaccinated mice after the antigen challenge correlated with the stimulation of antigen specific IFN-γ expressing CD4+T cell (~4.6 fold) and CD8+T cells (~2.1 fold) in vaccinated mice in compared to infected mice, even after 2–3 months of immunization. Importantly, antigen-mediated humoral immunity correlated with high antigen specific IgG2/IgG1 responses in vaccinated mice. In vitro re-stimulation of splenocytes with LdHyP enhances the expression of TNF-α, IFN-γ, IL-12 and IL-10 cytokines along with lower IL-4 cytokine and IL-10/IFN-γ ratio in vaccinated mice. Importantly, we observed ~3.5 fold high NO production through activated macrophages validates antigen mediated cellular immunity induction, which is critical in controlling infection progression. These findings suggest that immunization with LdHyP mount a very robust immunity (from IL-10 towards TFN-γ mediated responses) against L. donovani infection and could be explored further as a putative vaccine candidate against VL. © 2020 Elsevier Inc.PublicationArticle Visceral leishmaniasis (Kalazar)(Indian Medical Association, 2020) Shyam Sundar; Eram NahidVisceral leishmaniasis (VL, also known as kala-azar) a neglected tropical and fatal parasitic disease caused by a parasite belonging to the Leishmania donovani complex and transmitted by infected female Phlebotomusargentipes sand flies. The main target of parasite is reticuloendothelial system, with infiltration of the spleen, liver, bone marrow and lymph nodes causing organomegaly and pancytopenia. Confirmation of diagnosis relies on invasive procedures like spleen or bone marrow aspirate, but most cases, having typical clinical fearures, can be detected using serological testing. Treatment of VL is very challenging because of few treatment options, long duration of treatment and drug toxicity.Treatment of choice is chemotherapy with single dose of Liposomal amphotericin B (LAmB) ormultidrug therapy (LAmB + miltefosine, LAmB + paromomycin (PM), or miltefosine + PM) for patients of VL in the Indian sub-continent.About 5-15% develop skin eruptions as sequelae of VL, known as Post Kala-azar Dermal Leishmaniasis, and ~5% have HIV-VL coinfection. Both these conditions do not have satisfactory treatment regimens. © 2020, Indian Medical Association. All rights reserved.PublicationArticle Formulation, characterization and in vitro anti-leishmanial evaluation of amphotericin B loaded solid lipid nanoparticles coated with vitamin B12-stearic acid conjugate(Elsevier Ltd, 2020) Aakriti Singh; Ganesh Yadagiri; Shabi Parvez; Om Prakash Singh; Anurag Verma; Shyam Sundar; Shyam Lal MudavathDespite the advancement of new anti-leishmanials, amphotericin B (AmB) prevails as one of the most potent agent in the treatment of visceral leishmaniasis (VL), a neglected tropical disease affecting mostly poverty ridden and underdeveloped regions of the globe. Nonetheless, many patients display intolerance to parenteral AmB, notably at higher dosages. Also, conventional AmB presents an apparently poor absorption. Therefore, to improve AmB bioavailability and overcome multiple barriers for oral delivery of AmB, we fabricated a promising vitamin B12-stearic acid (VBS) conjugate coated solid lipid nanoparticles (SLNs) encapsulated with AmB (VBS-AmB-SLNs) by a combination of double emulsion solvent evaporation and thermal sensitive hydrogel techniques. VBS-AmB-SLNs showed a particle size of 306.66 ± 3.35 nm with polydispersity index of 0.335 ± 0.08 while the encapsulation efficiency and drug loading was observed to be 97.99 ± 1.6% and 38.5 ± 5.6% respectively. In vitro drug release showed a biphasic release pattern and chemical stability of AmB was ensured against simulated gastrointestinal fluids. Cellular uptake studies confirmed complete internalization of the formulation. Anti-leishmanial evaluation against intramacrophage amastigotes showed an enhanced efficacy of 94% which was significantly (P < 0.01) higher than conventional AmB without showing any toxic effects on J774A.1 cells. VBS-AmB-SLNs could serve as a potential therapeutic strategy against VL. © 2020 Elsevier B.V.PublicationArticle Immunogenicity and Protective Efficacy of T-Cell Epitopes Derived from Potential Th1 Stimulatory Proteins of Leishmania (Leishmania) donovani(Frontiers Media S.A., 2019) Sumit Joshi; Narendra Kumar Yadav; Keerti Rawat; Vikash Kumar; Rafat Ali; Amogh Anant Sahasrabuddhe; Mohammad Imran Siddiqi; Wahajul Haq; Shyam Sundar; Anuradha DubeDevelopment of a suitable vaccine against visceral leishmaniasis (VL), a fatal parasitic disease, is considered to be vital for maintaining the success of kala-azar control programs. The fact that Leishmania-infected individuals generate life-long immunity offers a viable proposition in this direction. Our prior studies demonstrated that T-helper1 (Th1) type of cellular response was generated by six potential recombinant proteins viz. elongation factor-2 (elF-2), enolase, aldolase, triose phosphate isomerase (TPI), protein disulfide isomerase (PDI) and p45, derived from a soluble antigenic fraction (89.9-97.1 kDa) of Leishmania (Leishmania) donovani promastigote, in treated Leishmania patients and golden hamsters and showed significant prophylactic potential against experimental VL. Moreover, since, it is well-known that our immune system, in general, triggers production of specific protective immunity in response to a small number of amino acids (peptide), this led to the identification of antigenic epitopes of the above-stated proteins utilizing immunoinformatics. Out of thirty-six, three peptides-P-10 (enolase), P-14, and P-15 (TPI) elicited common significant lymphoproliferative as well as Th1-biased cytokine responses both in golden hamsters and human subjects. Further, immunization with these peptides plus BCG offered 75% prophylactic efficacy with boosted cellular immune response in golden hamsters against Leishmania challenge which is indicative of their candidature as potential vaccine candidates. Copyright © 2019 Joshi, Yadav, Rawat, Kumar, Ali, Sahasrabuddhe, Siddiqi, Haq, Sundar and Dube. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.