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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PublicationLetter Ketoconazole in visceral leishmaniasis(1990) Shyam Sundar; Kailash Kumar; V.P. Singh[No abstract available]PublicationArticle Evaluation of the direct agglutination test as an immunodiagnostic tool for kala-azar in India(1993) V.K. Vinayak; Neena Singla; G.S. Singh; Shyam SundarThe direct agglutination test (DAT) has been assessed as a diagnostic procedure for visceral leishmaniasis. Fifty-six of 58 sera (96·5%) from confirmed cases of visceral leishmaniasis, whose bone marrow aspirates contained Leishmania donovani amastigotes, had agglutinating antibodies above the cut-off titre of 1:800. None of the sera from healthy control subjects from non-endemic or endemic areas had anti-leishmanial antibodies. Similarly, none of the sera obtained from cases of malaria or tuberculosis had agglutinating antibodies above the cut-off titre. A significant decline in agglutinating antibody titre in 3 cases following anti-leishmanial chemotherapy appeared to correlate with regression of clinical symptoms and the absence of amastigotes from bone marrow aspirates. One of 3 cases developed post-kala-azar dermal lesions and sera from this subject had an elevated agglutinating antibody titre. It is concluded that the DAT is a sensitive and specific test to confirm visceral leishmaniasis. As the formalin-fixed promastigotes, stained with Coomassie blue, which are used as antigen could be stored at 4 °C for 6 months without any loss of ability to detect anti-leishmanial antibodies, the DAT is recommended for use under field conditions. © 1993 Oxford University Press.PublicationArticle Successful treatment of refractory visceral leishmaniasis in india using antimony plus interferon-γ(1994) Shyam Sundar; Frank Rosenkaimer; Henry W. MurrayFifteen Indian patients with relapsing or drug-refractory visceral leishmaniasis were retreated for 30 days with antimony plus interferon-γ (IFN- γ). All 15 had failure of an initial course of antimony and at least one additional course of antimony or pentamidine; 7 patients had failure of three or four prior courses of therapy. During the study, treatment was discontinued in 2 patients because of anemia and congestive heart failure in 1 and intractable vomiting in the other; both subsequently died. In the remaining 13 patients, IFN-γ plus antimony treatment was associated with daily fever but no other adverse reactions. After 30 days of therapy, 9 (69%) of the 13 patients were apparently cured. Six months after treatment, all 9 were healthy, had parasite-free bone marrow aspirate smears, and were considered cured. None have relapsed during a mean follow-up of 15.9 1.7 months. These results support the use of antimony plus IFN-γ as an immunochemotherapeutic alternative for kala-azar patients who have repeated failures of conventional treatment. © 1994 by The University of Chicago.PublicationArticle Immunochemotherapy for a systemic intracellular infection: Accelerated response using interferon-γ in visceral leishmaniasis(1995) Shyam Sundar; Frank Rosenkaimer; Martin L. Lesser; Henry W. MurrayTo determine if cytokine immunotherapy accelerates the response to conventional treatment in visceral leishmaniasis (kala-azar), previously untreated Indian patients were given antimony for 30 days (n = 15) or antimony plus interferon-v (IFN-γ n = 16). After 10 days, 10 (63%) of 16 patients treated with antimony plus IFN-γ versus 1 (7%) of 15 randomized to antimony alone were considered cured of parasites (P <.005). On day 20, 14 (93%) of 15 versus 6 (40%) of 15 patients, respectively, were apparent clinical cures (P <.006), and treatment was discontinued early in the 14 IFN-γ-treated responders. Day 30 apparent cure rates (100% vs. 73%) and 6-month ultimate cure responses (87% vs. 60%) were higher in IFN-γ-treated patients but not statistically different from controls (P>.05). All 13 IFN-γ-treated subjects who were cured (12 of whom received therapy for 20 days) have remained healthy with follow-up of 14-24 months (mean, 18.9). These results indicate that IFN-γ successfully accelerates the parasitologic and clinical response to antimony treatment, an effect that should permit shortening the duration of conventional therapy in previously untreated kala-azar. © 1995, by The University of Chicago.PublicationArticle Effect of treatment with interferon-γ alone in visceral leishmaniasis(1995) Shyam Sundar; Henry W. MurrayInterferon-γ (IFN-γ) enhances the therapeutic response to pentavalent antimony in patients with visceral leishmaniasis. To determine the effect of cytokine immunotherapy alone, 9 patients with kala-azar were treated with IFN-γ before receiving antimony. After 20 days of IFN-γ therapy, 4 patients showed no parasitologic response; in the remaining 5 patients, however, splenic aspirate parasite scores declined from 4.2 ± 0.2 to 1.2 ± 0.5 (mean ± SE). These results indicate that treatment with IFN-γ alone can induce visceral antileishmanial activity. However, the limited efficacy in this uncontrolled pilot trial suggests that the therapeutic role of IFN-γ in kala-azar is that of an adjunct to conventional antimony treatment. © 1995 The University of Chicago press.PublicationArticle Cure of antimony-unresponsive Indian visceral leishmaniasis with amphotericin B lipid complex(Oxford University Press, 1996) Shyam Sundar; Henry W. MurrayTwenty-one Indian patients with visceral leishmaniasis who did not respond to or relapsed after 28-60 days of pentavalent antimony therapy were treated with amphotericin B lipid complex (ABLC). Five infusions (3 mg/kg each) given every second day over 9 days (total dose, 15 mg/kg) resulted in a 100% apparent cure response. In 4 other patients who had not responded to antimony, apparent cure was also induced by ABLC given at 3 mg/kg a day for 5 consecutive days (total dose, 15 mg/kg). Fever and chills developed routinely during the initial 2-h infusions; these reactions were tolerated and diminished with successive infusions. Six months after treatment, all 25 patients were healthy, had parasite-free bone marrow aspirates, and were considered cured. ABLC is effective short-course therapy for kala-azar patients who do not respond to conventional antimony treatment.PublicationArticle Molecular typing of HLA class I and class II antigens in indian kala- azar patients(Blackwell Publishing Ltd, 1997) Neeloo Singh; Shyam Sundar; Fionnuala Williams; Martin D. Curran; Anil Rastogi; Suraksha Agrawal; Derek MiddletonHLA has been shown to be associated with many diseases. To find out whether host genetic factors like the HLA are involved in susceptibility to kala-azar (visceral leishmaniasis) in India, we formulated an association study with genetically related controls. All samples were typed by PCR SSOP (sequence specific oligonucleotide probes) for HLA class I (A and B) and class II (DR) antigens. The test of association we used was the transmission disequilibrium test (TDT). No significant evidence for association with any of the three HLA loci was obtained.PublicationArticle Antibody response against a Leishmania donovani amastigote-stage-specific protein in patients with visceral leishmaniasis(American Society for Microbiology, 1997) Elodie Ghedin; Wen Wei Zhang; Hugues Charest; Shyam Sundar; Rick T. Kenney; Greg MatlashewskiThe antibody response against an amastigote-specific protein (A2) from Leishmania donovani was investigated. Sera from patients with trypanosomiasis and various forms of leishmaniasis were screened for anti-A2 antibodies. Sera from patients infected only with L. donovani or Leishmania mexicana specifically recognized the A2 recombinant protein. These results were consistent with karyotype analyses which revealed that the A2 gene is conserved in L. donovani and L. mexicana strains. The potential of this antigen in diagnosis was further explored by screening a series of sera obtained from patients in regions of the Sudan and India where L. donovani is endemic. The prevalence of anti-A2 antibodies was determined by Western blotting for all samples. Enzyme-linked immunosorbent assay (ELISA) and an immunoprecipitation assay were also performed on some of the samples. Anti-A2 antibodies were detected by ELISA in 82 and 60% of the samples from individuals with active visceral leishmaniasis (kala-azar) from the Sudan and India, respectively, while the immunoprecipitation assay detected the antibodies in 92% of the samples from India. These data suggest that the A2 protein may be a useful diagnostic antigen for visceral leishmaniasis.PublicationArticle Circulating T helper 1 (Th1) cell- and Th2 cell-associated cytokines in Indian patients with visceral leishmaniasis(American Society of Tropical Medicine and Hygiene, 1997) Shyam Sundar; Steven G. Reed; Sashi Sharma; Amit Mehrotra; Henry W. MurraySera from 61 Indian patients with visceral leishmaniasis caused by infection with Leishmania donovani were tested for the presence of T helper 1 (Th 1) cell-(interferon-γ [IFN-γ]) and Th2 cell-associated cytokines (inteleukin-4 [IL-4] and IL-10). The IFNΥ activity was detected in 53%, IL- 4 in 84%, and IL-10 in 56% of patient samples. Sere from 10 healthy Indian controls showed detectable IFN-γ in 90%, IL-4 in 10%, and IL-10 in 20%; corresponding percentages for sere from eight healthy American controls were 100%, 12%, and 0%, respectively. Quantitative data for the 61 patients compared with the 10 Indian controls indicated comparable mean levels of IFNΥ, but three- and 13-fold increases in IL-10 and IL-4, respectively. Undetectable IFN-γ activity, observed in 47% of patients, was associated with the presence IL-4 alone or in combination with IL-10 but not with IL-10 alone. In patients who had failed prior therapy (n = 29) compared with previously untreated patients (n = 32). IFN-γ levels were 67% lower and IL- 4 levels were two-fold higher; IL-10 activity was comparable. These results using peripheral blood support the presence of a suppressive Th2 cell- associated immune response in symptomatic Indian kala-azar and point to a possible role for IL-4.PublicationArticle Short-course, low-dose amphotericin B lipid complex therapy for visceral leishmaniasis unresponsive to antimony(American College of Physicians, 1997) Shyam Sundar; Nutan K. Agrawal; Prabhat R. Sinha; Gary S. Horwith; Henry W. MurrayBackground: Visceral leishmaniasis (kala-azar) is a world-wide, disseminated intracellular protozoal infection for which prolonged, conventional therapy with pentavalent antimony has become increasingly less effective. Objective: To determine the efficacy and minimal effective dose of short-course therapy with amphotericin B lipid complex in visceral leishmaniasis. Design: A randomized, open-label study. Setting: Inpatient kala-azar treatment unit in the state of Bihar in northeast India, where visceral leishmaniasis is endemic. Patients: 60 patients with active infection who had not responded to or who had relapse after receiving conventional (>30 days) treatment with pentavalent antimony. Intervention: Intravenous amphotericin B lipid complex was given once daily for 5 consecutive days by 2-hour infusion. Patients were randomly assigned to receive 1, 2, or 3 mg/kg of body weight per day (total doses of 5, 10, or 15 mg/kg, respectively). Measurements: Clinical and parasitologic responses (the latter were measured by parasite density score of the splenic aspirate) were determined 14 days after treatment. Definitive responses were assessed 6 months after treatment according to clinical outcomes and findings on examination of bone marrow aspirate. Results: All 60 patients responded to 5 days of treatment. Fourteen days after therapy, all patients had parasite- free splenic aspirates and were considered to have an apparent clinical and parasitologic response. Six months after therapy, definitive responses were documented in 16 of 19 (84% [95% Cl, 60% to 97%]), 18 of 20 (90% [Cl, 68% to 99%]), and 21 of 21 (100% [Cl, 84% to 100%]) patients who received total doses of 5, 10, and 15 mg/kg, respectively. Conclusion: Short-course therapy with low-dose amphotericin B lipid complex is effective for visceral leishmaniasis and is an important therapeutic alternative in the management of this serious intracellular protozoal infection.