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Mouse foot pad testing for primary dapsone resistant leprosy was performed in 15 patients. 13 were resistant (87%). Two patients below 10 years were living with lepromatous leprosy mothers, one male aged 21, was born in Kokana leprosarium and ten others gave no history of known contact of leprosy.
Between 1980-1982, 56 patients suspected of developing dapsone resistant leprosy were seen at the skin clinic of Anandaban Leprosy Hospital and Kokana Leprosarium. Out of 56, 16 control mice had no growth. 29 patients (72.5%) were proved resistant by Mouse foot pad tests.
Two cohorts of bacterio-positive cases registered and started on treatment during 1960-62 and 1968-70 were studied for differences in their response to DDS monotherapy. Proportion of male and female cases, mean Bacteriological Index (B.I.) and the distribution of cases according to the initial BI did not differ between the two cohorts. 49.7% of the patients in the II cohort were taking regular treatment against 27.4% in the I cohort. At the end of 7 years of treatment, proportion of the cases that were bacteriologically negative were 68.6% and 83.0% in I and II cohorts respectively. Relapse rates in I and II cohorts were 14.3% and 7.9% respectively, over a period of 7 years. The findings showed that Dapsone continued to be an effective antileprosy drug and must be included in all multidrug regimens in the therapy of leprosy.
Disseminated granuloma faciale developed in a 38-year-old man following radiation therapy. A dramatic response to dapsone therapy is noted and the possible role of radiation in the pathophysiology of the disease is presented.
Oral zinc was tried in 15 cases of multibacillary leprosy as an immunostimulant in addition to conventional antileprosy drugs. Results were compared with those in ten similar cases treated with dapsone alone. Cases treated with zinc showed faster clinical improvement, regrowth of eyebrows, rapid fall in the bacterial index (BI) and in the bacterial index in the granuloma (BIG), early and greater influx in lymphocytes in the granuloma, and neovascularization. Upgrading occurred in 6 out of 15 patients taking zinc, but in only 1 out of 10 patients in the control group. Five out of six patients who showed upgrading in the treated group became lepromin positive. Only one patient (BL) showed lepromin conversion in the control group.
T and B cell counts and their response to PHA and lepromin were studied in 46 patients of polar tuberculoid leprosy (TT), divided into two age and sex matched groups. Twenty five normal healthy controls were similarly investigated. While one group consisted of 26 untreated TT patients, the other included 20 individuals who had taken dapsone, 50 mg daily, for 12 to 14 months. There was significant decrease in the number of T-lymphocytes and their response to PHA and lepromin was lower in the treated, as compared to the untreated patients and normal persons. No significant change was found in the number of B-lymphocytes in any of the groups.
Enthusiasm in the use of dapsome for acne conglobata and other severe acne has created an increase in the use of this drug by dermatologists. We describe three patients in whom jaundice developed during dapsome therapy of 3 to 36 weeks' duration. Jaundice was due to cholestasis in two cases and to hemolysis in the third. These significant side effects call for careful observation by the physician if dapsone is to be used with safety.
In a stable rural population of South India, 18 consecutive untreated persons newly discovered to have leprosy with a Bacterial Index (BI) greater than or equal to 2+ were tested for Mycobacterium leprae resistant to dapsone (DDS) by the mouse foot pad test. Of 12 successful tests, five detected resistant M. leprae. Known contact with a treated patient in the ten years preceding the diagnosis of leprosy was not found to increase the risk of DDS-resistant M. leprae occurring in an untreated, newly diagnosed patient. This data is consistent with the bulk of evidence in the field of bacteriology, which makes it seem unlikely that treated patients are the only source, or even the major source, of resistant M. leprae in untreated patients. Bacterial mutants resistant to a drug have been shown to precede initial use of the drug. Tests for drug-resistant bacteria in untreated patients before a drug is widely used in a community are likely to be important for subsequent evaluation of resistance to the drug in that community.
At the Schieffelin Leprosy Research and Training Centre, Karagiri, India, 148 lepromatous (LL) and borderline lepromatous (BL) leprosy patients registered for treatment in the years 1971 to 1973 were found to respond as well to dapsone (DDS) monotherapy as 391 LL and BL patients registered in 1964 to 1966, as indicated by clearance of Mycobacterium leprae from skin smears during the initial seven years of therapy in each patient. Apparently, the efficacy of DDS monotherapy has not been progressively diminishing since the introduction of DDS monotherapy into the area.
At the Schieffelin Leprosy Research and Training Centre, Karigiri, India, an analysis of "relapse" rates was undertaken on all the 1293 residents of Guidyatham Taluk who were known to have lepromatous (LL) or borderline lepromatous (BL) leprosy and had attained "smear negative" status. "Relapse" was defined as the reappearance of acid-fast bacilli (AFB) in skin smears, whether by reinfection from other patients or from the patient's own persisting organisms. The "relapse" rate decreased steadily with the time elapsed after the attainment of smear negativity: 2.8% (2.8 per 100 patients per year) in the initial two years; 1.1% from the third year onwards; and 0.9% from the ninth year onwards. Of the 1293 patients, 694 (53.7%) had taken greater than or equal to 80% regular dapsone (DDS) treatment during smear negativity. In this group, the "relapse" rate from the third year onwards was only 0.7% per year. The vast majority (90.9%) of LL and BL patients on DDS monotherapy in the area had at some point attained smear negative status. It appears important to study whether a limited period of DDS monotherapy after the attainment of negative skin smears would be an effective alternative to life-long DDS treatment in LL and BL patients.
Lymphocytes from peripheral blood were isolated from leprosy patients and healthy contacts (HC) of leprosy patients and stimulated in vitro with: Mycobacterium leprae and a M. leprae cell wall antigen, MLW 1; tuberculin purified protein derivative (PPD); antigens prepared from Candida albicans, Entamoeba histolytica, Leishmania aethiopica, and parotitis virus; the non-specific mitogens phytohemagglutinin (PHA) and concanavalin A (Con-A). Lymphocytes from patients with untreated lepromatous leprosy failed to respond to the M. leprae antigens, and the median response to PPD was also significantly (p less than 0.005) lower than in the HC group. They responded almost as well as the other groups to non-mycobacterial antigens, PHA, and Con-A. In LL patients who had been treated with dapsone for several (median 10) years, the failure to respond to M. leprae antigens remained, but the depression of the PPD response and the slight non-specific depression of the lymphocyte stimulation test (LST) responsiveness had been reversed. Our results confirm that the major defect in the cell-mediated immune response of LL patients is M. leprae-specific and permanent. The possibility that the defect may be due to a continuous, antigen-induced suppression of the immune response is discussed. That the defect also affected the response to PPD is important since it points to a clear antigenic relationship between M. leprae and BCG/M. tuberculosis. Evidence is presented suggesting that an antigen induced suppressor mechanism may be operating in vitro with cells from patients with borderline tuberculoid leprosy.
Methemoglobinemia and hemolysis are well-known side effects after using high doses of dapsone (4,4'-diaminodiphenylsulfone). Their occurrence after low doses of the drug, and subsequent investigation, revealed the presence of hemoglobin Hasharon, and low content of NADH-dependent methemoglobin reductase in five members of an East European ashkenazic Jewish family.
Dapsone sensitivity was tested on Loewenstein-Jensen medium on 164 mycobacterial strains belonging to 32 different species. A minimum inhibitory concentration as low as that of M. leprae, as determined "in vivo" was never observed. The most sensitive strains belong to the species M. kansasii, M. ulcerans, M. gordonae, M. szulgai and M. gastri with minimal inhibitory concentrations varying between 0.3 and 0.1 microgram/ml, still approximately 10 times the value known for wild strains of M. leprae.
The effect of leprosy and dapsone (DDS) on the basal levels of blood lactic and pyruvic acids has been studied. In untreated tuberculoid and lepromatous leprosy patients both of the acids were found to be significantly raised. The rise in lactic acid was relatively more in tuberculoid patients; whereas pyruvic was relatively more elevated in lepromatous cases. Both the acids showed a tendency to increase with the duration of the disease in lepromatous leprosy. Statistically no significant differences were observed in lactic acid levels between untreated and treated cases of both forms of leprosy, suggesting that DDS was not effective in controlling the conditions responsible for the increased lactic acid. On the other hand, pyruvic acid showed a further increase in cases who were on DDS therapy, particularly in lepromatous cases. This indicated that DDS affects pyruvic acid metabolism. Whether DDS disturbs the normal degradative pathway of pyruvic acid or affects pathways of pyruvic acid production is not clear.
Neonatally thymectomized Lewis rats (NTLR) were shown to be highly susceptible to infection with Mycobacterium leprae. We have used them in chemotherapeutic studies as models of human lepromatous leprosy. NTLR chronically infected with M. leprae were treated with various regimens combining a background of the minimal effective dose (MED) of dapsone (4,4'-diaminodiphenylsulfone, DDS) or 100 times this dose in the diet with one to ten doses of rifampin (RMP) of 10 mg/kg. To test for persisting viable M. leprae passage of 5 X 19(3) organisms was made to intact mice, and 10(5) to 10(7) acid-fast bacilli were passaged to NTLR. The only regimen that appeared to be completely effective in eliminating infectivity for intact mice was ten doses of RMP given on the background of the MED of DDS. No viable organisms were detected in any passage mice, but multiplication of M. leprae was detected in 12 of 16 passage NTLR, representing three of the four groups in which passage was made. In no instance did we fail to detect organisms in passage of NTLR when we detected them in passage mice, and multiplication was demonstrated in passage NTLR in 14 instances in which M. leprae failed to multiply in passage mice. Because of its high degree of immunosuppression, the NTLR was able to detect a small population of viable M. leprae in inocula containing up to 5000 times the number of organisms that can be inoculated into intact mice. The NTLR appears to provide a model for the study of microbial persistence in leprosy.
In this controlled trial in 35 patients with lepromatous leprosy the therapeutic effects of adding rifampin 450 mg daily (Regimen A) or 1200 mg once a month (Regimen B) to a standard dapsone regimen of 50 mg daily were practically identical. Moderate to marked clinical improvement was observed in 88% and 83% of the patients treated with Regimens A and B respectively. The average rates of decrease in the MI of the skin smears and nose-blow smears were similar. The average decreases in the BI of the skin smears were 0.7 and 0.6 in patients on the Regimen A and B respectively. Following 6 months' treatment with Regimens A and B the average decreases in the Logarithmic Bacterial Indexes of Biopsies were 4.7% and 7% respectively. The once-monthly rifampin schedule was well tolerated and did not lead to "flu" syndrome, anuria, oliguria, hemolytic anemia, thrombocytopenia, or anaphylactic shock. This trial revealed the satisfactory efficacy, good tolerability, and practicability of a supervised once-monthly 1200 mg single oral dose rifampin schedule as a component of combination regimes for the initial treatment of patients with lepromatous (LLs and LLp) leprosy.
For the early recognition of dapsone resistance, it is essential to regularly examine patients at risk for suspicious new lesions, backed by regular clinical treatment records including smear results. The earlier the recognition and starting on alternative treatment, the better is the response. However, it is not advisable to change treatment without attempting at least clinical confirmation, and endorsing the chart so that the problem is not missed on subsequent occasions.
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.