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Biomedical subjects

S Sundar

Publications and source records attributed to S Sundar.

At least 91 records · Page 5Linked to original sources
PubMed1997

Response to interferon-gamma plus pentavalent antimony in Indian visceral leishmaniasis.

One hundred fifty-six previously untreated Indian patients with visceral leishmaniasis were treated with pentavalent antimony (Sb) alone for 30 days (group A), Sb plus interferon-gamma (IFN-gamma) for 30 days (group B), or Sb plus IFN-gamma for 15 days (group C). The purpose was to show that IFN-gamma would increase the response to 30 days of Sb treatment and that short-course (15 days) combination therapy was as effective as 30 days of Sb alone. Six months after treatment, 36% of group A, 49% of group B, and 42% of group C patients were designated as definitively cured. The success rates for long-term responses to Sb alone (36%) and Sb plus IFN-gamma (49%) were unexpectedly low, and responses in groups A, B, and C were not significantly different. These results suggest that the beneficial effects of adjunctive IFN-gamma in visceral leishmaniasis may be limited in regions where this disseminated intracellular infection shows high-level resistance to Sb.

Adolescent↗
PubMed1997

Antibody response against a Leishmania donovani amastigote-stage-specific protein in patients with visceral leishmaniasis.

The 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.

Animals↗
PubMed1997

Circulating T helper 1 (Th1) cell- and Th2 cell-associated cytokines in Indian patients with visceral leishmaniasis.

Sera from 61 Indian patients with visceral leishmaniasis caused by infection with Leishmania donovani were tested for the presence of T helper 1 (Th1) cell-(interferon-gamma [IFN-gamma]) and Th2 cell-associated cytokines (interleukin-4 [IL-4] and IL-10). The IFN-gamma activity was detected in 53%. IL-4 in 84%, and IL-10 in 56% of patient samples. Sera from 10 healthy Indian controls showed detectable IFN-gamma in 90%. IL-4 in 10%, and IL-10 in 20%; corresponding percentages for sera 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 IFN-gamma, but three- and 13-fold increases in IL-10 and IL-4, respectively. Undetectable IFN-gamma 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-gamma 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.

Adult↗
PubMed1997

Molecular typing of HLA class I and class II antigens in Indian kala-azar patients.

HLA 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.

Disease Susceptibility↗
PubMed1996

Cure of antimony-unresponsive Indian visceral leishmaniasis with amphotericin B lipid complex.

Twenty-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 3 mg/kg a day 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.

Adolescent↗
PubMed1995

Immunochemotherapy for a systemic intracellular infection: accelerated response using interferon-gamma in visceral leishmaniasis.

To 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-gamma (IFN-gamma; n = 16). After 10 days, 10 (63%) of 16 patients treated with antimony plus IFN-gamma 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-gamma treated responders. Day 30 apparent cure rates (100% vs. 73%) and 6-month ultimate cure responses (87% vs. 60%) were higher in IFN-gamma-treated patients but not statistically different from controls (P > .05). All 13 IFN-gamma-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-gamma 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.

Adolescent↗
PubMed1995

Effect of treatment with interferon-gamma alone in visceral leishmaniasis.

Interferon-gamma (IFN-gamma) 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-gamma before receiving antimony. After 20 days of IFN-gamma 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-gamma alone can induce visceral antileishmanial activity. However, the limited efficacy in this uncontrolled pilot trial suggests that the therapeutic role of IFN-gamma in kala-azar is that of an adjunct to conventional antimony treatment.

Adult↗
PubMed1995

Platelet function studies in Indian kala-azar.

Platelet function studies were conducted on 25 parasitologically positive cases of Indian kala-azar and 25 age and sex matched healthy controls. Ninety-two per cent of patients had thrombocytopenia of variable degree; in 44% of patients, platelets were less than 60,000 mm-3. The platelet adhesive index was less than 30% in 70% of patients with kala-azar (normal 31-60%). Platelet aggregation time with ADP and adrenaline was abnormally prolonged compared to the controls. Platelet factor III availability was poor in 40% of cases. There was a fair degree of correlation between platelet adhesiveness and platelet factor III availability in these patients: 50% of patients with poor platelet adhesiveness showed reduced platelet factor III availability.

Blood Platelets↗
PubMed1994

Successful treatment of refractory visceral leishmaniasis in India using antimony plus interferon-gamma.

Fifteen Indian patients with relapsing or drug-refractory visceral leishmaniasis were retreated for 30 days with antimony plus interferon-gamma (IFN-gamma). 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-gamma 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-gamma as an immunochemotherapeutic alternative for kala-azar patients who have repeated failures of conventional treatment.

Adolescent↗