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S Sundar

Publications and source records attributed to S Sundar.

At least 73 records · Page 4Linked to original sources
PubMed2000

Failure of pentavalent antimony in visceral leishmaniasis in India: report from the center of the Indian epidemic.

In India, 320 patients with visceral leishmaniasis (209 in the state of Bihar and 11 in the neighboring state of Uttar Pradesh) received identical pentavalent antimony (Sb) treatment. Sb induced long-term cure in 35% (95% confidence interval [CI], 28%-42%) of those in Bihar versus 86% (95% CI, 79%-93%) of those in Uttar Pradesh. In Bihar, the center of the Indian epidemic, traditional Sb treatment should be abandoned.

Adolescent↗
PubMed2000

Short-course of oral miltefosine for treatment of visceral leishmaniasis.

A total of 54 Indian patients with visceral leishmaniasis were treated with oral miltefosine, 50 mg given twice daily, for 14 days (18 patients; group A), 21 days (18; group B), or 28 days (18; group C). Cure was achieved in 89% of group A, 100% of group B, and 100% of group C. Adverse reactions were self-limited and primarily mild. The 21-day miltefosine regimen combines high-level efficacy, convenient dosing, and a relatively short duration.

Administration, Oral↗
PubMed1999

Miltefosine, an oral agent, for the treatment of Indian visceral leishmaniasis.

BACKGROUND: There is no effective orally administered medication for any leishmania infection. We investigated miltefosine, which can be taken orally, for the treatment of Indian visceral leishmaniasis. Miltefosine is a phosphocholine analogue that affects cell-signaling pathways and membrane synthesis. METHODS: The study was an open-label, multicenter, phase 2 trial in which four 30-person cohorts received 50, 100, or 150 mg of miltefosine per day for four or six weeks. The 120 patients, who ranged in age from 12 to 50 years, had anorexia, fever, and splenomegaly with at least moderate (2+) leishmania in a splenic aspirate. A parasitologic cure was defined by the absence of parasites in a splenic aspirate obtained two weeks after completion of treatment. The clinical response was assessed at six months. RESULTS: In all 120 patients there was an initial parasitologic cure. Six patients had clinical and parasitologic relapses; the remaining 114 patients had not relapsed by six months after treatment, for a cure rate of 95 percent (95 percent confidence interval, 89 to 98 percent). With the regimen of 100 mg of miltefosine per day (approximately 2.5 mg per kilogram of body weight per day) for four weeks, 29 of 30 patients (97 percent) were cured. Gastrointestinal side effects were frequent (occurring in 62 percent of patients) but mild to moderate in severity, and no patient discontinued therapy because of gastrointestinal side effects. In two patients, treatment was discontinued because of elevated levels of aspartate aminotransferase or creatinine; in both patients the levels rapidly returned to normal. In 12 other patients, the level of aspartate aminotransferase increased to 100 to 150 U per liter during treatment. CONCLUSIONS: Orally administered miltefosine appears to be an effective treatment for Indian visceral leishmaniasis.

Administration, Oral↗
PubMed1999

Diagnostic PCR with Leishmania donovani specificity using sequences from the variable region of kinetoplast minicircle DNA.

Kala azar or visceral leishmaniasis, a parasitic disease caused by Leishmania donovani, is presently causing an epidemic in the eastern region of India. Diagnosis of kala azar is often complicated. We developed a pair of oligonucleotides suitable as primers from the variable region of a predominant sequence class of minicircles of L. donovani. These primers were used in a nonisotopic polymerase chain reaction and found to be highly specific for the parasites of L. donovani complex. Using these primers, amplification of L. donovani kinetoplast DNA minicircle from the peripheral blood of kala azar patients results in a product of 204 bp. The patient group was comprised of individuals from a highly endemic region of India. We feel that PCR could assess the efficacy of new leishmanicidal drugs under investigation in these patients. PCR could also predict response to therapy which would be useful for both clinical and research applications.

Adolescent↗
PubMed1999

Oral treatment of visceral leishmaniasis with miltefosine.

In a pilot trial, 28 days of oral treatment with 100-200 mg miltefosine (hexadecylphosphocholine) per day cured 14 of 15 patients with Indian visceral leishmaniasis (VL). To extend the testing of this regimen, 45 additional subjects with VL, of whom 17 had failed previous antimony therapy, were treated with 100 (N = 17), 150 (N = 18) or 200 (N = 10) mg/day. Enrollment at 200 mg/day was stopped after three subjects in this treatment arm developed reversible but serious (grade-3) adverse reactions. The overall clinical and parasitological responses to miltefosine were rapid, with 40 [89%; 95% confidence interval (CI) = 76%-96%] and 44 (98%; CI = 88%-100%) of the patients apparently cured on days 14 and 28, respectively. The one 'treatment failure' recorded on day 28 (and at 6 months) was a subject lost to follow-up. Those apparently cured by day 28 included six patients (one on 100 mg, two on 150 mg and three on 200 mg/day) removed from treatment on days 7-17 because of grade-3 diarrhoea (two cases), vomiting (two cases), diarrhoea and hepatotoxicity (one case) or nephrotoxicity (one case). Transient, mild-moderate vomiting and/or diarrhoea were common during weeks 1-2 and about 25% of the patients also developed primarily mild, self-limited increases in concentrations of aspartate aminotransferase and creatinine and/or blood urea nitrogen. At a 6-month follow-up, all 44 patients apparently cured at day 28 were considered complete responders (definitive cures), including the six treated for only 7-17 days. These results indicate that 100 mg miltefosine/day for 28 days is a promising oral-treatment regimen for VL cases, including those with antimony-unresponsive infections.

Administration, Oral↗
PubMed1999

Evidence that the high incidence of treatment failures in Indian kala-azar is due to the emergence of antimony-resistant strains of Leishmania donovani.

The possibility that the high frequency of treatment failures in Indian kala-azar might be due to infection with antimony-resistant strains of Leishmania donovani has not been experimentally addressed. L. donovani isolates were obtained from splenic aspiration smears of 24 patients in Bihar, India, who either did not respond (15) or did respond (9) to 1 or more full courses of treatment with sodium antimony gluconate (SAG). A strong correlation (P<.001) between clinical response and SAG sensitivity in vitro was observed only when strains were assayed as intracellular amastigotes: responsive isolates ED50=2.4+/-2.6, ED90=6.4+/-7.8 microgram SAG/mL; unresponsive isolates ED50=7.4+/-3.7 microgram SAG/mL, ED90=29.1+/-11.1 SAG/mL. No correlation with clinical response was found by use of extracellular promastigotes (ED50=48+/-22 vs. 52+/-29 microgram/mL). The emergence of antimony-resistant L. donovani strains appears to be a cause of treatment failures in India.

Adolescent↗
PubMed1999

Diagnostic and prognostic potential of a competitive enzyme-linked immunosorbent assay for leishmaniasis in India.

A Leishmania donovani species-specific monoclonal antibody (monoclonal antibody D2) was evaluated for its diagnostic and prognostic potential by a competitive enzyme-linked immunosorbent assay (C-ELISA) in sera from Indian patients with visceral leishmaniasis (VL) and seven patients with post-kala-azar dermal leishmaniasis (PKDL). These results were compared with those obtained by microscopy with Giemsa-stained tissue smears and a direct enzyme-linked immunosorbent assay (direct ELISA) with crude parasite antigen. Of 121 patients with clinically diagnosed VL examined, 103 (85.1%) were positive and 11 (9.1%) were negative by all three methods. An additional 7 (5.8%) who were negative by microscopy were positive by both C-ELISA and direct ELISA. Seven PKDL patients were also examined and were found to be positive by all three methods. Analysis of the chemotherapeutic response to sodium antimony gluconate of these 110 serologically positive VL patients showed that 57 (51.8%) were drug responsive and 53 (48.2%) were drug resistant. The C-ELISA with sera from 20 longitudinally monitored VL patients before and after chemotherapy showed a significant decrease in percent inhibition of monoclonal antibody D2 in drug-responsive patients. However, in drug-unresponsive patients, the percent inhibition of D2 was unchanged or was slightly increased. Our results therefore indicate (i) the applicability of L. donovani species-specific monoclonal antibody D2 for sensitive and specific serodiagnosis by C-ELISA, (ii) that the C-ELISA is more sensitive than microscopy, especially for early diagnosis, (iii) that L. donovani is still the main causative agent of VL, irrespective of the chemotherapeutic response, and (iv) that the C-ELISA can be used to evaluate the success of drug treatment.

Animals↗
PubMed1999

Kala-azar epidemic in Varanasi district, India.

Reports at the Sir Sunder Lal Hospital, Banaras Hindu University, of a large number of kala-azar cases from one particular village in Varanasi district, Uttar Pradesh, led us to carry out an epidemiological study of the situation using standard techniques. The overall prevalence and case fatality of the disease were 12.9% and 10.5%, respectively. A history of fever and hepatosplenomegaly was noted for all the cases. The case definition was the presence of parasites in bone marrow or splenic aspirate smears. The disease was more prevalent among adults, but occurred also among children. However, there was no clear linear relationship between the prevalence of the disease and age group. Kala-azar occurred among males and females, and its prevalence did not correlate significantly with income. Since the disease vector continues to be present in the study area, the health authorities should take strong steps to control the disease.

Adolescent↗
PubMed1999

Amphotericin B lipid complex in the management of antimony unresponsive Indian visceral leishmaniasis.

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 in 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 > or = 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.

Adolescent↗
PubMed1998

Trial of oral miltefosine for visceral leishmaniasis.

BACKGROUND: There is no effective oral treatment for visceral leishmaniasis (kala-azar), a disseminated intracellular protozoal infection that occurs worldwide. Miltefosine, an alkyl phospholipid developed as an oral antineoplastic agent, is active against visceral infection in animal models. We tested safety, tolerance, and efficacy of miltefosine in kala-azar. METHODS: Oral doses of miltefosine were given to six groups of five Indian men for 28 days: 50 mg every second day (group 1), 100 mg every second day (group 2), 100 mg/day (group 3), 150 mg/day (group 4), 200 mg/day (group 5), and 250 mg/day (group 6). Assessment for apparent cure--taken as an afebrile state with decreased spleen size and a splenic-aspirate parasite-density score of 0--was done on days 14 and 28. Definitive cure at 8 months required a parasite-free bone-marrow aspirate and no clinical evidence of relapse. FINDINGS: 21 of 30 patients were apparently cured on day 14. Transient episodes of vomiting and diarrhoea, were common during weeks 1-2 and were seen in 22 patients. Four other patients in groups 5 and 6 had miltefosine withdrawn after 7-10 days because of vomiting. One patient in group 6 developed renal insufficiency and severe diarrhoea and died on day 21. On day 28, all 29 remaining patients were apparently cured. By 8 months, seven of ten patients in groups 1 and 2 had relapsed; however, 18 of 19 patients treated daily (groups 3-6) appeared to be cured. Among the 21 definitive cures were the four patients treated for 10 days or less and 12 for whom previous therapy with pentavalent antimony had failed. INTERPRETATION: Treatment with miltefosine at 100-150 mg/day for 4 weeks has promise as an effective oral treatment of visceral leishmaniasis including antimony-resistant infection.

Administration, Oral↗
PubMed1998

Rapid accurate field diagnosis of Indian visceral leishmaniasis.

BACKGROUND: A firm diagnosis of visceral leishmaniasis (kala-azar) requires demonstration of the parasite in organ aspirates or tissue biopsy samples. The aim of this prospective study was to assess the diagnostic usefulness of non-invasive testing for antibody to the leishmanial antigen K39 by means of antigen-impregnated nitrocellulose paper strips adapted for use under field conditions. METHODS: One drop of peripheral blood is applied to the hitrocellulose strip. Three drops of test buffer (phosphate-buffered saline plus bovine serum albumin) are added to the dried blood. The development of two visible bands indicates presence of IgG anti-K39. 323 consecutive patients with suspected kala-azar referred to two specialist units in India, and 25 healthy controls, provided fingerstick blood samples for the test. Spleen aspirates were taken from 250 patients. FINDINGS: Kala-azar was confirmed by microscopy of spleen-aspirate smears in 127 patients. The K39 strip test was positive in all 127; the estimated sensitivity was therefore 100% (95% CI 98-100). Four patients had positive strip tests but negative aspirate smears; all four responded to treatment for leishmaniasis. 217 individuals, including the 25 healthy controls, 73 patients with malaria or tuberculosis, and 119 spleen-aspirate-negative patients who had presumed malaria or cirrhosis (79) or no final diagnosis (40), had negative strip-test results. None of the 119 aspirate-negative patients developed evidence of kala-azar during 3-6 months of follow-up. The estimated specificity of the strip test was 98% (95-100; 217/221). INTERPRETATION: Detection of anti-K39 by immunochromatographic strip testing is a rapid and non-invasive method of diagnosing kala-azar, which has good sensitivity and specificity and is well suited for use in field conditions.

Adolescent↗
PubMed1998

Identification of antibodies directed against O-acetylated sialic acids in visceral leishmaniasis: its diagnostic and prognostic role.

A 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 IgG2 levels in VL patients as compared to healthy controls. The BSM-based ELISA holds great promise as a serodiagnostic and prognostic assay for VL.

Acetylation↗
PubMed1998

Treatment of antimony-unresponsive Indian visceral leishmaniasis with ultra-short courses of amphotericin-B-lipid complex.

High cost is the principal drawback of treating visceral leishmaniasis (VL; kala-azar) with any of the new lipid formulations of amphotericin B. The aim of the present study was to see if the costs of treatment with such drugs could be reduced by using ultra-short courses. Amphotericin-B-lipid complex (ABLC) was given to 77 Indian patients with antimony-unresponsive VL, either as a single infusion of 5 mg/kg (Group A) or two infusions, each of 5 mg/kg, given 5 days apart (Group B) or on consecutive days (Group C). Other than the anticipated higher fever and chills, treatment was well-tolerated. On day 19 after first infusion, 72 patients were considered apparent cures: 24 (89%) of the 27 in Group A; all 24 (100%) in Group B; and 24 (92%) of the 26 patients in Group C. Six months after treatment, 19 (70%) of 27 in Group A, 19 (79%) of 24 in Group B, and 21 (81%) of 26 in Group C were healthy, relapse-free and considered definitive cures. These cure rates were not statistically different. All 18 treatment failures (five initial non-responders and 13 relapses) were cured after treatment with a 5-day course of ABLC at a higher dose (10-15 mg/kg.day). In a related analysis of hospital plus drug costs for treating antimony-unresponsive VL, short-course ABLC (1-5 days) was compared with conventional amphotericin B (0.75-1.0 mg/kg on alternate days over 30-34 days). This analysis, which included the cost of re-treatment, identified one short-course ABLC regimen with an overall estimated expense which was only modestly higher than that of amphotericin B. Together, the present results provide further support for the use of ABLC in the management of VL patients who fail antimony therapy.

Adolescent↗
PubMed1998

Splenic cytokine responses in Indian kala-azar before and after treatment.

Cytokine mRNA levels were measured in serial splenic aspirates from 27 patients with visceral leishmaniasis during monotherapy with interferon-gamma (IFN-gamma; n = 9), sodium antimony gluconate (SAG; n = 8), or amphotericin B lipid complex (ABLC; n = 10). At baseline, mRNA for IFN-gamma was detected in 18 (86%) of 21 patients, and mRNA for interleukin (IL)-10 and IL-4 was detected in 21 (100%) and 10 (48%) of 21 patients, respectively. With IFN-gamma treatment alone, levels of IFN-gamma mRNA decreased by day 10 and then returned to baseline levels; IL-10 mRNA levels were high throughout treatment. In the SAG and ABLC groups, levels of IFN-gamma and IL-10 mRNA decreased significantly. Polarized Th2 cell type responses do not appear to develop in Indian kala-azar; instead, there is an initial mixed Th1-Th2 cell picture. With successful treatment and resolution of infection, both components of the immune response appear to involute.

Adolescent↗
PubMed1998

A cluster of cases of severe cardiotoxicity among kala-azar patients treated with a high-osmolarity lot of sodium antimony gluconate.

In India, sodium antimony gluconate is the drug of choice for kala-azar. Due to increasing unresponsiveness to this drug in the current epidemic that began in the early 1970s, daily doses of 20 mg/kg/day for 30 days or more is recommended as opposed to the 10 mg/kg/day dose for 6-10 days used in the past. Of the 130-150 patients treated annually at our center with locally made sodium antimony gluconate, serious cardiotoxicity has occurred in less than 10%. During April 1995 at the University Hospital in Varanasi, we encountered life-threatening cardiotoxicity after 3-28 days of therapy in each of the eight patients being treated with a new lot of this drug made by a different manufacturer. Of the eight patients, six each developed congestive heart failure and/or prolongation of the corrected QT interval (QTc), and three died as a direct consequence of drug-induced toxicities. In three instances, the life-threatening complications occurred with a cumulative dose of less than 300 mg/kg. In patients with prolonged QTc, ventricular premature beats and ventricular tachycardia were recorded; in one patient, the ventricular tachycardia progressed to torsade de pointes, culminating in ventricular fibrillation and death. Since switching to different lots of this drug, we have not seen further clustering of dangerous cardiotoxicity. The antimony content of the implicated drug was comparable with that in lots from other manufacturers that did not show overt toxicity, but the osmolarity was approximately 300 mOsm/L higher. The simple technique of measuring of osmolarity may help identify inappropriately manufactured drug.

Adult↗
PubMed1998

Pediatric renal transplantation--Indian experience.

OBJECTIVE: To analyze our experience with renal transplantation in children with end-stage renal disease (ESRD) in India. DESIGN: Retrospective study. METHODS: Over the last 7.5 years, 27 renal transplants were performed on children below 12 years of age, 8 children were less than 6 years old, 19 were between 6 and 12 years of age. Sixteen children had underlying glomerular disease while eleven had tubulointerstitial renal disease. Transperitoneal approach was used in smaller recipients weighing less than 12 kg. Extraperitoneal approach was used in the remainder. Triple immunosuppression with Cyclosporine, Azathioprine and Steroids was used in all cases. RESULTS: Follow-up period ranged from 6 months to 7.5 years (mean 3.7 years). There were 10 episodes of acute rejection. Three cases of acute rejection failed to respond to therapy. No surgical complications were encountered. Graft survival was 73.2% at one year and 71% at two years. Satisfactory rehabilitation was achieved in children with functioning grafts. CONCLUSIONS: Renal transplantation in children in India offers an acceptable choice in ESRD as anywhere in the world.

Child↗
PubMed1997

Short-course, low-dose amphotericin B lipid complex therapy for visceral leishmaniasis unresponsive to antimony.

BACKGROUND: Visceral leishmaniasis (kala-azar) is a worldwide, 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.

Adolescent↗