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Biomedical subjects

Sreevatsa

Publications and source records attributed to Sreevatsa.

At least 19 recordsLinked to original sources
PubMed2004

10-12 years follow-up of highly bacillated BL/LL leprosy patients on combined chemotherapy and immunotherapy.

This study reports the follow-up results of 36 highly bacillated untreated BL/LL cases who were serially allocated to three treatment groups. Group I patients received a modified WHO regimen (Rifampicin 600 mg once a month supervised, 50 mg of Clofazimine and 100 mg of Dapsone daily unsupervised) and BCG 0.1 mg per dose 6 monthly; group II patients received the same multi-drug treatment (MDT) and Mw (2 x 10(8) killed bacilli per dose) 6 monthly: group III patients received the same MDT with 0.1 ml of distilled water 6 monthly and acted as a control. Treatment was continued till smear negativity. All these three groups were comparable by their initial clinical score, bacteriological index (BI), viable bacilli as assessed by the mouse foot pad (MFP), bacillary adenosine triphosphate (ATP) content and also histologically at the time of starting treatment. All these parameters were evaluated every 6 months. The vaccines were well tolerated. All the patients in group I became smear negative by 3.5 years, in group II in 3 years whereas those in group III took 5 years. The incidence of reactions was the same in all the groups during the first 2 years, however, patients of group III (MDT + placebo) continued to have reactions up to 3 years. No viable bacilli could be detected in the local and distal sites as estimated by MFP and bacillary ATP after 12 months in both the immunotherapy groups. These could be detected in patients on MDT alone up to 24 months of therapy. Histologically patients in both the immunotherapy groups (groups I and II) showed accelerated granuloma clearance, histological upgrading and non-specific healing without granuloma formation both at the local and distal sites and this was achieved much earlier compared to the MDT + placebo group. Thus, by the addition of immunotherapy the effective treatment period of achieving bacteriological negativity could be reduced by about 40%, time period of reactions reduced by 33% and there were no reactions and/or relapses in the 10-12 years post-treatment follow-up.

Adenosine Triphosphate↗
PubMed1995

Treatment of bacilliferous BL/LL cases with combined chemotherapy and immunotherapy.

Thirty-six, untreated borderline lepromatous/lepromatous (BL/LL) leprosy patients with an initial bacterial index (BI) of 4+ to 6+ were serially allocated to three treatment groups. Group I patients received a slightly modified WHO regimen (rifampin once a month, clofazimine and dapsone daily) and BCG intradermally (i.d.) (0.1 mg/per dose). Group II patients were administered the same MDT and Mycobacterium w (2 x 10(8)) killed bacilli/dose i.d., and Group III received the same MDT with 0.1 ml of distilled water i.d. Vaccination was repeated every 6 months. Biopsies were taken from the local site of vaccination and from a distant site, i.e., the back. The progress was monitored periodically by clinical, histopathological and bacterial (BI, mouse foot pad, ATP) parameters. Twenty-five patients had completed a follow up of more than 2 years. These included: 7 in Group I, 10 in Group II, and 8 in Group III. One patient of the MDT + BCG group who was progressing well dropped out after 28 months. In cases on combined chemotherapy and immunotherapy, no viable bacilli were demonstrable by mouse foot pad and ATP measurement after 6 months (at 12 months or afterward). However, in come of the control cases on MDT alone, viable bacilli could be detected even up to 18 months (by mouse foot pad) and 2 years (by ATP estimation). With 36 months of treatment, the mean BI decreased from 4.64+ to 1.66+ in the group on MDT alone (controls), 4.9+ to 0.08+ in the MDT + BCG group, and 4.75+ to 0 in the MDT+Mycobacterium w group. Compared with the MDT and MDT + BCG groups, the fall in the BI was significantly more in the MDT + Mycobacterium w group at 12, 18, and 24 months. While all of the cases in the Mycobacterium w groups became smear negative by 36 months, it took 42 months for all of the BCG group to achieve negativity. Immunotherapy appears to have a significant effect on the killing and clearance of bacilli and should be considered as an adjunct to chemotherapy, especially in bacilliferous lepromatous cases.

Adenosine Triphosphate↗
PubMed1995

Extended studies on the viability of Mycobacterium leprae outside the human body.

Very little is known in leprosy regarding the transmission of the infection from the source to the susceptible host. One of the important factors which governs the transmission of the disease is the viability of Mycobacterium leprae outside the human body. In this study M. leprae obtained from untreated patients have been subjected to several adverse conditions. Their viability was verified by their multiplication in the footpads of normal mice. After drying in the shade the organisms were viable up to 5 months. On wet soil, they remained alive for 46 days. Kept in saline at room temperature, the organisms lived for 60 days. Surprisingly on exposure to direct sunlight for 3 hours a day the bacteria survived for 7 days. On refrigeration at 4 degrees C, the bacteria could be preserved for 60 days. On the other hand, keeping at -70 degrees C, the bacteria could be maintained in a living condition for only 28 days. On exposure to antiseptics like Savlon (R) and alcohol, the bacteria were rapidly killed. These results indicate the survival outside the human body of M. leprae under different environmental conditions in India where the disease is endemic. Transmission of infection by indirect contact and occurrence of new cases in the absences of any known source, are consistent with M. leprae being viable outside the human body for varying periods of time. The findings could also be pointers to understand the epidemiology of leprosy.

Animals↗
PubMed1991

Nasal myiasis in leprosy.

Infestation of the nose with larvae of certain files can occur in leprosy patients. This results in severe distress and agony and can cause extensive tissue damage. The predisposing factors, clinical presentation and treatment is described.

Humans↗
PubMed1991

Antigens of Mycobacterium leprae in the cerebrospinal fluid of leprosy patients: detection by monoclonal-antibody-based sandwich immunoradiometric assay and avidin/biotin immunoblotting.

Mycobacterium leprae antigens could be detected in the cerebrospinal fluid (CSF) of patients with leprosy, using a monoclonal-antibody-based sandwich immunoradiometric assay (SIRMA). Antigens of 12 kD, 35 kD and 30-40 kD were detected using ML06, ML04, and ML34 monoclonal antibodies, respectively. The 30-40-kD polysaccharide antigen, although present in larger amounts in M. leprae than the 12-kD and 35-kD protein antigens, was found in the CSF of comparatively fewer subjects. The antigen capture assay has been found sensitive to the level of nanograms. Avidin-biotin-based immunoblotting using pooled leprosy sera detected a larger number of antigens than using anti-M. leprae antisera raised in rabbits. The immunoblotting of CSF samples revealed about three antigens in the region of 100-160 kD and three more in the region of 45-60 kD as probed by leprosy sera. This study has for the first time revealed the presence of M. leprae antigens in the CSF of leprosy patients and the probable involvement of the central nervous system in leprosy.

Antibodies, Monoclonal↗
PubMed1990

Preliminary observations on myiasis in leprosy patients.

Out of 3350 leprosy patients attending the surgical outpatient department for various ulcerative lesions, 18 patients had typical symptoms of myiasis. Maggots were collected in 5 cases from the nose, in 3 cases from ulcers of the hand and in 10 cases from ulcers of the foot. It was possible to rear the maggots into flies in 8 out of 18 cases. The flies were identified as Sarcophaga ruficornis and Chrysomyia bezziana.

Adolescent↗
PubMed1989

Results of a modified WHO regimen in highly bacilliferous BL/LL patients.

A regimen consisting of 600 mg of rifampin once a month, 100 mg of clofazimine on alternate days, and 100 mg of dapsone daily was used in 56 untreated, highly bacillated borderline lepromatous/lepromatous (BL/LL) patients with an average bacterial index (BI) of 4.45. Treatment was continued until skin-smear negativity. After 2 years of therapy, none of the patients had become smear negative and the average BI was 2.56. There was no growth on inoculation of skin-tissue biopsies in the normal mouse foot pad after 6 months of therapy. Bacillemia was still detectable in 11/50 patients, and significant ATP levels were detected in Mycobacterium leprae from skin-tissue biopsies in 16% of the cases. After 3 years of therapy, three patients had become smear negative. The average BI was 1.30. None of the patients had detectable bacillemia, and 5% of the cases showed detectable ATP levels in M. leprae from tissue biopsies. After 4 years of therapy, 41.7% of the patients had become smear negative. The average BI was 0.66, and no ATP was detected in any of the purified bacillary suspensions. The fall in BI was accelerated, and more patients on continued treatment became negative earlier compared to those having treatment for a limited duration, as reported by others.

Adenosine Triphosphate↗
PubMed1989

Evaluation of two multidrug regimen in hospitalised multibacillary cases.

Fifty three multibacillary leprosy cases were treated with two regimens of MDT L1 consisting of Rifampicin, Dapsone and Ethionamide and L2 consisting of Rifampicin, Dapsone and clofazimine. The results were compared at regular intervals and at the end of the study (24 months). Clinical inactivity, bacteriological negativity, ENL reactions, upgrading reactions were seen in L1 group in 65%, 4.54%, 50% and 41% of cases respectively while 65%, 25.8%, 30% and 45% respectively in L2 regimen group. Zero percent morphological Index was achieved in all cases in L1 regimen 90% in L2 regimen cases. No viability was found on mouse foot pad inoculation after 6 months in L1 while after 18 months in L2 cases.

Clofazimine↗
PubMed1988

Pyrazinamide as a part of combination therapy for BL and LL patients--a preliminary report.

Pyrazinamide in a dose of 1500 mg was given to 63 borderline lepromatous (BL) and lepromatous (LL) leprosy patients on different drug regimens for the initial 2 months of therapy. Fifty-one BL and LL patients were put on the same drug regimens without pyrazinamide. There was a rapid and good clinical improvement in the patients in both of the groups. At the end of 2 years, the patients who received pyrazinamide had a morphological index (MI) of zero as compared to those patients who did not receive pyrazinamide, some of whom still had solidly staining bacilli. One out of 20 (5%) scrotal (smooth muscle) biopsies of the patients who received pyrazinamide had growth in the mouse foot pad as compared to 9 out of 38 (23.7%) smooth muscle biopsies of the patients who did not receive pyrazinamide. At the end of 5 years, the patients who received pyrazinamide had slightly better results compared with the non-pyrazinamide group. Pyrazinamide appears to have some effect against persisters in multibacillary leprosy. A well-controlled, randomized trial with longer duration of pyrazinamide therapy in a larger group of patients needs to be carried out to unequivocally determine the exact role of pyrazinamide in leprosy.

Adolescent↗
PubMed1988

Evaluation of the efficacy of candidate vaccines against M. leprae infection in mice.

Delayed-typed hypersensitivity (DTH) response and protection value of some of the candidate vaccines alone and in combination with BCG has been investigated. It was observed that both M.w. and BCG gave heightened DTH and good protection. On the other hand both M. leprae and ICRC evoked moderate DTH and gave poor protection. However on combining any of these candidate vaccines with live BCG, the lowering of DTH and poor protection was observed except in the M. leprae combination which in spite of low DTH gave better protection.

Animals↗
PubMed1987

Comparative study of immunizing and delayed hypersensitivity eliciting antigens of Mycobacterium leprae, M. tuberculosis, M. vaccae, and M. bovis (BCG).

A variety of mycobacterial antigens have been associated with the delayed-type hypersensitivity (DTH) reactions in human beings and animals. An attempt has been made in the present study to identify the major antigen fractions of Mycobacterium leprae and M. tuberculosis responsible for the elicitation of DTH and to evaluate their specificity by a comparison with the antigens of two closely related mycobacteria, BCG and M. vaccae. Guinea pigs and mice were sensitized with native or heat-killed M. leprae, M. tuberculosis, M. vaccae, and BCG. Four fractions each of the latter three mycobacteria, obtained by preparatory polyacrylamide slab gel electrophoresis, were used for elicitation of DTH. Three fractions of M. leprae (MY1, MY2, and MLSE) were obtained by affinity chromatography using monoclonal antibodies. Heat-killed M. leprae and M. vaccae proved to be better sensitizers for DTH compared to their native counterparts, whereas there were no significant differences between the efficacies of autoclaved and unautoclaved M. tuberculosis or BCG. The best DTH responses were recorded with a 16-24 kD fraction of M. tuberculosis, a 20-27 kD fraction of BCG, and MLSE of M. leprae. The purified molecules of M. leprae, MY1 (12 kD) and MY2 (35 kD), did not elicit a DTH reaction. Although none of the fractions of M. tuberculosis or BCG exhibited species specificity, fraction II (15-24 kD) of M. vaccae and MLSE might be comprised of species-specific determinants.

Animals↗
PubMed1983

Evaluation of drug regimen in lepromatous leprosy--II.

A 2 year follow-up study of 4 drug regimen in 45 cases is reported; whereas the combination of Rifampicin and Dapsone had been found to effect clearance of bacteraemia within a week and effect negativity of nasal smears in a shorter period of time, at 2 years the clinical and bacteriological results in the DDS, DDS + Rifampicin, DDS + Thiacetazone + INH, and DDS + Clofazimine regimen were similar. However, on inoculating bacilli obtained from the dartos muscle into the foot-pads of mice, multiplication was found in 1 out of 11 cases on Rifampicin and DDS, whereas 2 out of 9 cases on DDS + Thiacetazone + INH; 2 out of 10 cases on DDS + Clofazimine and 4 out of 8 cases on DDS alone showed multiplication. Therefore at the end of 2 years there was no significant difference in the results of treatment with any of the drug combinations used in the trial. However, the drug combinations have been found to be better than monotherapy with dapsone alone.

Adult↗
PubMed1982

Rapid, radiolabeled macrophage culture method for detection of dapsone-resistant Mycobacterium leprae.

Mycobacterium leprae cells extracted from the skin biopsies of 14 bacilliferous lepromatous patients were maintained in human-murine macrophage cultures for 3 weeks in the presence of [3H]thymidine and DDS (4,4'-diaminodiphenyl sulfone). All cultures except one containing freshly extracted viable bacilli showed significant incorporation of [3H]thymidine as compared to control cultures containing heat-killed bacilli of the corresponding strain. Six susceptible strains of M. leprae obtained from untreated, freshly diagnosed patients showed significant inhibition of the uptake of the radiolabel in the presence of 3 and 10 ng of DDS per ml per culture. Eight strains of M. leprae obtained from patients clinically suspected of DDS resistance were tested in a similar manner. These strains were also concurrently inoculated in the footpads of mice given orally 10(-2), 10(-3), and 10(-4) g of DDS per 100 g of body weight for 9 months. Concordant results were obtained by both methods: five strains were found to be resistant, one was susceptible, and one was partially resistant. Strain VIII did not incorporate [3H]thymidine in the macrophage cultures and proved to be resistant in the mouse footpad. The macrophage culture system provides a sensitive, rapid screening method for the early diagnosis of DDS resistance.

Adult↗
PubMed1982

Disposition of dapsone in protein deficiency--an experimental study in mice.

With an aim to evaluate the metabolic disposition of Dapsone (DDS) in protein malnutrition, a study was undertaken to determine DDS content of blood and tissues of protein deficient mice in comparison to the levels in ad-libitum and pair-fed mice. Three groups of Rockfeller's strain mice of same sex (roughly weighing 25 gm) were fed on low protein diet and high protein diet (for pair-fed and ad-libitum groups). After one month feeding DDS was administered by oral intubation daily for 7 days at a dose of 0.01 mg per g body weight. On 7th day animals were sacrificed 3 hours after DDS administration. Heparinised blood was collected from ocular plexus. Tissues (liver and kidney) were taken out for DDS estimations. DDS levels were determined by the method of Simpson (1949) and tissue protein content was assayed by the method of Lowry et al (1951). Hypoproteinemic mice presented higher values for blood and tissue DDS as compared to their pair-fed and ad-libitum fed groups. Our observations indicate that in hypoproteinemic mice, on account of the possible diminished binding of DDS to plasma albumin, the concentration of free DDS in blood and in tissues is higher.

Animals↗