Browsing by Author "Sundar, S."
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PublicationArticle A microculture technique for isolating live Leishmania parasites from peripheral blood of visceral leishmaniasis patients(2007) Hide, M.; Singh, R.; Kumar, B.; Bañuls, A.L.; Sundar, S.Current procedures for diagnosing Leishmania parasites from patients involve invasive and dangerous tissue aspiration. We have developed a non-invasive and highly sensitive microculture method that can isolate parasites from the buffy coat of the patient's peripheral blood. The parasites were cultured in 96-well culture plates. Nineteen parasitologically proven visceral leishmaniasis (VL) patients were included in the study. Using this technique, we were able to isolate parasites from 16 (84%) samples. However, all 19 (100%) samples were positive on culture of splenic aspirates. We conclude that this technique is useful for the isolation and cryoconservation of parasites from patients' blood. This simple method could be tried as a first-instance alternative before other more sensitive procedures such as splenic aspirate; however, negative results should be confirmed by tests with higher sensitivity. © 2007 Elsevier B.V. All rights reserved.PublicationArticle A simple and inexpensive "cell dissociation sieve-tissue grinder" apparatus(2001) Pai, K.; Sundar, S.A simple and inexpensive cell dissociation sieve-tissue grinder apparatus consisting essentially of stainless steel sieve (the one popularly used for sieving tea leaves) and a glass syringe plunger acting as pestle, is described for making single cell suspension.PublicationArticle A simple and sensitive test for field diagnosis of Post Kala-azar Dermal Leishmaniasis(Blackwell Publishing Ltd., 2001) Salotra, P.; Sreenivas, G.; Ramesh, V.; Sundar, S.Background: Current methods for diagnosis of post kala-azar dermal leishmaniasis (PKDL) do not offer adequate sensitivity and specificity. Objectives To develop a simple and sensitive test for field diagnosis of PKDL. Methods: Immunochromatographic nitrocellulose strips precoated with recombinant k39 antigen were evaluated for the detection of circulating antibodies to leishmanial k39 in PKDL sera. A drop of serum applied to the strip followed by buffer led to the development of two visible bands indicating the presence of anti-k39 IgG. Results: The strip test was able to detect cases of PKDL with 91% sensitivity. The specificity of the test was evaluated using controls with other skin diseases, other common infections and healthy persons from endemic and non-endemic regions. Of 125 controls examined, all were negative on the strip test, indicating 100% specificity of the test. Conclusions: The immunochromatographic nitrocellulose strips provide a non-invasive, rapid and accurate method for diagnosing PKDL. © 2001 British Association of Dermatologists.PublicationArticle Alteration of Fas and Fas ligand expression during human visceral leishmaniasis(2002) Eidsmo, L.; Wolday, D.; Berhe, N.; Sabri, F.; Satti, I.; El Hassan, A.M.; Sundar, S.; Chiodi, F.; Akuffo, H.Several studies in murine systems have suggested a role of apoptosis in the pathogenesis of leishmaniasis. However, the role of apoptosis in visceral leishmaniasis in man has not been explored. In this study, we show that patients with visceral leishmaniasis demonstrate significant dysregulation of Fas and Fas ligand. Levels of soluble Fas (sFas) and soluble Fas ligand (sFasL) were elevated in plasma of patients with active visceral leishmaniasis (VL) and individuals co-infected with VL-HIV-1 compared to healthy controls. The levels of sFas and sFasL were normalized 6 months after successful treatment. In VL patients, the expression of membrane bound Fas, and to a lower extent FasL, were up-regulated on Leishmania donovani-infected spleen cells, the site of parasite multiplication. Expression of Fas and FasL on peripheral blood mononuclear cells was within normal range, probably reflecting that the blood is not a normal site of L. donovani infection. Furthermore, this is suggested by the finding that in vitro infection of macrophages with L. donovani up-regulated Fas expression on the surface of infected cells and enhanced the levels of sFasL in supernatants from infected cultures. How this dysregulation may affect the pathogenesis of human visceral leishmaniasis is discussed.PublicationArticle Amphotericin B Lipid Complex in the Management of Antimony Unresponsive Indian Visceral Leishmaniasis(1999) Sundar, S.; Goyal, A.K.; Mandal, A.K.; Makharia, M.K.; Singh, V.P.; Murray, H.W.Fifty-eight Indian patients with visceral leishmaniasis who did not respond or relapsed after 30 days of consecutive sodium stibogluconate therapy were randomised to treatment with amphotericin B lipid complex (ABLC) using a total dose of 7.5 or 10 mg/kg. Treatment induced a prompt clinical response n all patients with resolution of fever and regression in spleen size. Fever and chills developed during ABLC infusion, but it diminished with successive infusions. Fourteen days after treatment, 26 of 28 (93%) patients in the 7.5 mg/kg group and all 30 (100%) in the 10 mg/kg group had splenic aspirate parasite density scores of 0 and were considered apparent clinical and parasitologic responders. Four and three patients in the 7.5 and 10 mg/kg groups respectively relapsed during six months of followup; thus, overall 22 of 28 (79%) patients treated with 7.5 mg/kg and 27 of 30 (90%) treated with 10 mg/kg were definitive cures. All initial non-responders and relapses were retreated successfully with higher dose of ABLC. These results confirm the efficacy of short-course ABLC therapy for antimony-unresponsive Indian patients with visceral leishmaniasis. Since treatment with a total dose of 7.5 mg/kg did not appear to increase efficacy (79% vs. 84% induced by 5 mg/kg in a prior study), initial treatment with a total dose of 5 mg/kg followed by retreatment of any non-responders represents a potentially less costly approach in patients who fail antimony therapy. Though high cure rates are achieved with ≥ 10 mg/kg total dose of ABLC, treatment using lower doses with retreatment of non-responders or relapses with higher dose can result in considerable savings.PublicationArticle Anthropometrically derived dosing and drug costing calculations for treating visceral leishmaniasis in Bihar, India(2009) Olliaro, P.; Sundar, S.Objective and method To estimate drug costs of treating visceral leishmaniasis (VL) based on data on the VL population structure from the high-burden, antimony-resistant area of Northern Bihar, India. Results Paromomycin is the cheapest option ($7450 to treat 1000 patients). Treating 1000 patients with oral miltefosine would cost $119 250 at the current private market price or $64 383-$75 129 at preferential public sector price depending on the size of the order. With AmBisome ® it would be $163 600 or $229 500 depending on the dose (10 or 15 mg/kg total). These costs are without considering other direct costs (daily intramuscular injections for 3 weeks for paromomycin; intravenous devices and hospitalization for AmBisome®; directly observed treatment if applied for miltefosine) and indirect costs. Conclusion These calculations provide useful basic information for projections. © 2008 Blackwell Publishing Ltd.PublicationArticle Antithrombin III in liver disorders.(1991) Sundar, S.; Mall, R.K.; Dube, B.; Singh, V.P.Biological and immunological antithrombin III was studied in 26 patients of viral hepatitis including 6 with encephalopathy, and in 11 patients with cirrhosis of liver. There was a significant reduction in both biological and immunological activity of antithrombin III in all the groups of liver disorders studied. There was a good correlation between biological and immunological activity of antithrombin III (P less than 0.05). Further, there was a significant inverse correlation between immunological activity of antithrombin III and SGOT/SGPT (P less than 0.01) as well as serum bilirubin (P less than 0.001), signifying the prognostic value of antithrombin III in hepatitis. Biological activity on the other hand did not show any relation with the hepatic enzymes or bilirubin elevation. The antithrombin III levels appeared to decline in direct proportion to the degree of hepatic necrosis, probably due to reduced synthesis.PublicationArticle Atypical mucocutaneous involvement with Leishmania donovani(2012) Pulimood, S.A.; Rupali, P.; Ajjampur, S.S.R.; Thomas, M.; Mehrotra, S.; Sundar, S.Mucocutaneous leishmaniasis has rarely been reported from India. The usual causative organisms of this infection are Leishmania braziliensis and L. tropica. Another species, L. donovani, which usually causes visceral leishmaniasis, has recently been reported to cause mucocutaneous disease in a few patients from Sri Lanka. We report two patients who had undiagnosed chronic skin lesions for several years. Skin biopsies revealed Leishmania and the species was characterized as L. donovani in both patients. There was considerable improvement in the skin lesions following treatment with liposomal amphotericin B. © The National Medical Journal of India 2012.PublicationArticle Clinicoepidemiological study of drug resistance in Indian kala - azar(1994) Sundar, S.; Thakur, B.B.; Tandon, A.K.; Agrawal, N.R.; Mishra, C.P.; Mahaptra, T.M.; Singh, V.P.[No abstract available]PublicationArticle Clinicopathological profile and therapeutic appraisals in lymphoma in eastern Uttar Pradesh(1997) Singh, V.P.; Sundar, S.; Gupta, S.; Rastogi, B.L.; Kumar, M.; Pant, G.C.; Jain, A.; Gera, N.Ninety-four patients of lymphoma (55 of Non-Hodgkin's and 39 of Hodgkin's) were evaluated for clinical profile, histological subtypes and therapeutic outcome. Out of 94, 'B' symptoms were present in 66, lymphadenopathy in 82 and anaemia in 50 patients. Forty-three patients presented in stage IV. Mixed cellularity (53.8%) was the most common histologic subtype in Hodgkin's disease and diffuse mixed (30.5%) in non-Hodgkin's lymphoma. Initial complete remission rates as seen with chemotherapeutic regimes were 74.1% with COPP in Hodgkin's disease and 58.3% with CVP and 75% with CHOP in non-Hodgkin's lymphoma.PublicationArticle Comparative evaluation of parasitology and serological tests in the diagnosis of visceral leishmaniasis in India: A phase III diagnostic accuracy study(2007) Sundar, S.; Singh, R.K.; Bimal, S.K.; Gidwani, K.; Mishra, A.; Maurya, R.; Singh, S.K.; Manandhar, K.D.; Boelaert, M.; Rai, M.In this phase III trial for diagnostics for visceral leishmaniasis (VL) in India, we compared parasitological diagnosis with several serological tests: direct agglutination test (freeze dried; DAT-FD), rK-39 strip test, rK-26 strip test and a latex agglutination test for antigen detection in urine (KAtex) in 452 subjects from the endemic regions of Bihar, India. The subjects were segregated into four categories: 230 confirmed patients, 52 probable cases, 70 non-cases and 100 healthy endemic controls. The first two groups were used for estimating sensitivity, the latter two for specificity. Sensitivity of DAT-FD was 98.9%, rK-39: 98.9%, KAtex: 67.0% and rK-26: 21.3%. Sensitivity of DAT-FD on blood taken on filter paper (DAT-FDF) was 99.3%, which was comparable with that using serum. Specificity of serological tests was comparable and high (DAT-FD and DAT-FDF: 94%, rK-39 strip test: 97%, KAtex: 99% and rK-26 strip test: 100%). The classical 'gold standard' parasitological demonstration in splenic smear performed poorly as it missed 18.4% of cases that benefited from VL treatment. Reproducibility of the serological tests between field and central laboratories was excellent (κ = 1.0, 0.99, 0.96 and 0.94 respectively for microscopy, DAT-FD, rK-39 strip test and rK-26 strip test). A high degree of agreement was observed between DAT-FD and rK-39 strip test (κ = 0.986). Although DAT-FD and rK-39 strip test were highly sensitive with excellent specificity, the ease of use of the latter makes it most suitable for the diagnosis of VL in the field conditions. © 2007 Blackwell Publishing Ltd.PublicationArticle Correlation between clinical features and degree of immunosuppression in HIV infected children(2008) Agarwal, D.; Chakravarty, J.; Sundar, S.; Gupta, V.; Bhatia, B.D.We conducted this study to find out correlation of CD4% with clinical status in 102 HIV infected antiretroviral naïve children. Mean age of presentation was 4.8 years. Perinatal transmission was the commonest mode of transmission (94%). Fever (53%), chronic diarrhea (36%), and cough (29%) were the commonest presenting symptoms. Protein energy malnutrition was seen in 56.7% of children. 33.3% children were asymptomatic, whereas 45.1% were in WHO clinical stages III and IV at the time of presentation. The most common opportunistic infection was tuberculosis. CD4% correlated significantly with the deterioration of the WHO clinical stages (P<0.01) and increasing grades of protein energy malnutrition (P<0.05).PublicationArticle Danazol in Indian haemophiliacs.(1993) Sundar, S.; Moorleedhur-Singh, G.S.; Dube, B.; Singh, V.P.; Kumar, K.Danazol, 10 mg/kg/day (maximum 600 mg/day) was given in two divided doses for 14 days in 30 patients with haemophilia-A. Rise in factor-VIII level was observed in all the patients after one week of danazol therapy, irrespective of initial factor-VIII Levels. In haemophiliacs with less than 1% factor VIII level, rise was maximum (3-6 folds); mean factor-VIII level at 7th and 14th day of danazol therapy was 2.3 +/- 0.6% and 4.8 +/- 1.1%, respectively. Only marginal increase in factor-VIII was noted in haemophiliacs with initial factor-VII levels more than 3%. The raised level of factor-VIII persisted after stopping the therapy during the observation period of 2 more weeks, irrespective of initial levels. No adverse effect was observed during or after.PublicationArticle Determinants of bednet ownership and use in visceral leishmaniasis-endemic areas of the Indian subcontinent(2010) Vanlerberghe, V.; Singh, S.P.; Paudel, I.S.; Ostyn, B.; Picado, A.; Sánchez, A.; Rijal, S.; Sundar, S.; Davies, C.; Boelaert, M.Objective To document ownership and use of bednets with its determinants in the visceral leishmaniasis (VL)-endemic region where mainly non-insecticide impregnated nets are available through commercial channels, and bednets are being considered as a leishmaniasis vector control measure. Methods In August-September 2006, semi-structured household (HH) questionnaires and observation guides were used in a random sample of 1330 HHs in VL-endemic districts of India and Nepal to collect data on VL knowledge, HH socio-economic status, bednet ownership and use patterns. An asset index was constructed to allow wealth ranking of the HH. A binary logistic response General Estimating Equations model was fitted to evaluate the determinants of bednet ownership and use. Results The proportion of HHs with at least one bednet purchased on the commercial market was 81.5% in India and 70.2% in Nepal. The bednets were used in all seasons by 50.6% and 54.1% of the Indian and Nepalese HH owning a bed net. There was striking inequity in bednet ownership: only 38.3% of the poorest quintile in Nepal owned at least one net, compared to 89.7% of the wealthiest quintile. In India, the same trend was observed though somewhat less pronounced (73.6%vs. 93.7%). Multivariate analysis showed that poverty was an important independent predictor for not having a bednet in the HH [OR 5.39 (2.90-10.03)]. Conclusion Given the inequity in commercial bednet ownership, free distribution of insecticide-treated bednets to the general population seems imperative to achieve a mass effect on vector density. © 2009 Blackwell Publishing Ltd.PublicationArticle Development and performance evaluation of amphotericin B transfersomes against resistant and sensitive clinical isolates of visceral leishmaniasis(2010) Singodia, D.; Gupta, G.K.; Verma, A.; Singh, V.; Shukla, P.; Misra, P.; Sundar, S.; Dube, A.; Mishra, P.R.The present study was aimed to assess the efficacy of developed transfersome (TF-3) formulation bearing amphotericin B (AmB) against sensitive and resistant clinical isolates of L donovani and compared with conventional liposomal formulation (F-2) and free AmB (F-1). The skin permeation of AmB from TF-3 was performed using Franz diffusion cell using rat skin which showed fickian diffusion across the skin. When tested against L. donovani (intramacrophagic amastigotes), it has been observed that TF was more effective than F-1 and F-2 formulation in sensitive and resistant clinical isolates. The data provides evidences that the TF formulation owing to its fluidized behaviour imparted by sodium deoxycholate, enables to penetrate well in the infected cells and thus provide enhanced activity. The permeation study also supports this data as the flux value of AmB through TF formulation was 1.5 fold higher compared to conventional liposomes suggesting improved penetration and better partitioning in skin layers. Implicit to this preliminary data it is evident that the AmB loaded TF formulation has potential as alternate chemotherapeutic approach to control of VL. Potential utilities of novel formulation as a transdermal delivery of AmB for leishmaniasis necessitates further elaborated investigations which is underway in our laboratory. Copyright © 2010 American Scientific Publishers All rights reserved.PublicationArticle Diagnostic tests for kala-azar: a multi-centre study of the freeze-dried DAT, rK39 strip test and KAtex in East Africa and the Indian subcontinent(2008) Boelaert, M.; El-Safi, S.; Hailu, A.; Mukhtar, M.; Rijal, S.; Sundar, S.; Wasunna, M.; Aseffa, A.; Mbui, J.; Menten, J.; Desjeux, P.; Peeling, R.W.Three diagnostic tests for visceral leishmaniasis (VL), the freeze-dried direct agglutination test (FD-DAT), the rK39 dipstick and a urine latex antigen test (KAtex), were evaluated for use in primary care in East Africa and the Indian subcontinent. Clinical suspects were prospectively recruited and tissue, blood and urine samples were taken. Direct microscopic examination of tissue smear, and FD-DAT, rK39 and KAtex were performed. Sensitivity and specificity with 95% credible intervals were estimated using Bayesian latent class analysis. On the Indian subcontinent both the FD-DAT and the rK39 strip test exceeded the 95% sensitivity and 90% specificity target, but not so in East Africa. Sensitivity of the FD-DAT was high in Ethiopia and Kenya but lower in Sudan, while its specificity was below 90% in Kenya. Sensitivity of the rK39 was below 80% in the three countries, and its specificity was only 70% in Ethiopia. KAtex showed moderate to very low sensitivity in all countries. FD-DAT and rK39 can be recommended for clinical practice on the Indian subcontinent. In East Africa, their clinical use should be carefully monitored. More work is needed to improve existing formats, and to develop better VL diagnostics. © 2007 Royal Society of Tropical Medicine and Hygiene.PublicationArticle Differential gene expression analysis in antimony-unresponsive Indian kala azar (visceral leishmaniasis) clinical isolates by DNA microarray(2007) Singh, N.; Almeida, R.; Kothari, H.; Kumar, P.; Mandal, G.; Chatterjee, M.; Venkatachalam, S.; Govind, M.K.; Mandal, S.K.; Sundar, S.In this study, cDNA microarray analysis of a closely related species, Leishmania major, was used as a screening tool to compare antimonial-resistant and susceptible clinical isolates of Leishmania donovani in order to to identify candidate genes on the basis of antimony resistance. Clinically confirmed resistant isolate 39 and sensitive isolate 2001 were used in this study. Many differentially regulated genes were identified whose expression levels differ in sodium antimony gluconate (SAG)-treated patients. Interestingly, genes on the array, showing changes in expression of over 2-fold revealed the identity of ABC transporters, which are known determinants of drug resistance in laboratory mutants. The functionality of the transporters was validated by flow cytometry which, being biologically informative, provides direct clues to gene function. The results suggest that isolate 39 could have developed resistance by an increased multidrug resistance protein (MRP)-like pump. This study provides preliminary clues to the role of a thiol-dependent efflux system in antimonial resistant clinical isolates of Leishmania donovani. © 2007 Cambridge University Press.PublicationArticle Digoxin toxicity and electrolytes: A correlative study(1983) Sundar, S.; Burma, D.P.; Vaish, S.K.Serum levels of sodium, potassium, calcium, magnesium and digoxin were studied in 67 patients on maintenance dose of digoxin, 42 with digitoxicity and 25 without. The mean serum digoxin level of toxic group was significantly higher (p < 0.001) than non-toxic group. The mean serum potassium was significantly lower in toxic group (p < 0.05) as compared to the non-toxic group. Of the toxic patients, 23.8% had hypokalemia. Hypokalemia resulted by significantly higher (p < 0.005) dose of diuretic use in toxic group. The mean serum digoxin level of hypokalemic toxic group was significantly lower as compared to the normokalemic toxic group (p < 0.001) and it was interesting to note that all hypokalemic toxic patients had their serum digoxin levels below 3 ng/ml (3.84 n mol/ml) and well within therapeutic range. There was a positive correlation between serum digoxin and potassium level amongst toxic patients (p < 0.001). Thus, in patients on maintenance dose of digoxin therapy, use of large dosage of diuretics may result in hypokalemia, causing digitalis toxicity even at low serum digoxin levels. Serum digoxin level alone may fail as an independent guide in diagnosis of digoxin toxicity in presence of hypokalemia.PublicationArticle Down's syndrome with acute myeloid leukemia.(1994) Singh, V.P.; Sundar, S.; Kumar, K.; Shukla, J.; Dube, B.[No abstract available]PublicationArticle Effect of smoking on blood pressure, body weight, electrocardiogram and serum cholesterol in young hypertensive and normotensive subjects(1985) Sinha, A.K.; Sundar, S.; Vaish, S.K.[No abstract available]
