Delayed resolution versus treatment failure in paucibacillary leprosy patients under six months fixed duration multidrug therapy.

Thirty paucibacillary (PB) patients were given multidrug therapy (MDT) PB regimen for six months and were examined clinically and histopathologically before therapy, at six months and 12 months after therapy; and in four patients, at 18 to 23 months after MDT. Histopathological activity was present in 50% and 25% of patients after six months and 12 months respectively after MDT. At 18 to 23 months, the four patients continued to have active lesions both clinically and histopathologically. On the basis of this study it is found that fixed duration of MDT is effective in a large majority of patients especially those with indeterminate leprosy. However, there is "delayed resolution" in a significant number of patients which in a few instances may turn out to be "treatment failures". Therefore, a regular follow up of high risk patients for at least two years and if possible, five years, with freedom to intervene with additional anti-inflammatory or antileprosy therapy as desired, is recommended.

Viability of Mycobacterium leprae in lepromatous patients after five years of dapsone monotherapy supplemented with two years of multidrug therapy.

Eleven lepromatous leprosy (LL) patients with a bacterial index (BI) of three and above who had undergone two years of multidrug therapy (MDT) and yet had positive skin smears at the end of treatment were chosen for this study. Biopsies from the skin and lymphnodes were histopathologically evaluated for the presence of granulomas and M. leprae. M. leprae isolated from the skin and lymphnodes were inoculated into the foot-pads of normal mice to test their viability. On histopathological examination of the biopsy specimens, it was found that granulomas and M. leprae were present in the skin and lymphnode biopsies of all patients except two, in whom, although granulomas persisted, M. leprae were not found in skin biopsy specimens. No growth was obtained in the foot-pads of mice inoculated with organisms isolated from skin and lymphnode biopsies of all 11 patients indicating a near complete bacterial kill. That would account for the extremely low relapse rates reported until now in LL patients who had undergne two years of MDT.

Influence of acetylator phenotype of the leprosy patient on the emergence of dapsone resistant leprosy.

The half time of disappearance of dapsone and monoacetyl dapsone and the acetylator phenotype of the leprosy patients who harboured dapsone sensitive and dapsone resistant M. leprae was assessed in 27 subjects. Sixteen patients were rapid acetylators, five were slow and six were intermediate acetylators. The mean T 1 1/2 lives of dapsone (30.26 +/- 11.0) and monoacetyl dapsone (31.11 +/- 12.0) were also studied in the above patients. The percentage of different acetylators in both resistant and sensitive groups were similar showing no correlation between the emergence of drug resistance and the phenotype of the patient. The mean time of disappearance of DDS and MAD in the different acetylators did not show significant difference. The ratios of MAD/DDS in an individual at 3, 6 or 24 hours after the dose were similar. The mean T 1 1/2 lives of DDS and MAD in resistant and sensitive patients also showed no difference. Neither T 1 1/2 lives of DDS or MAD nor the acetylator phenotype seem to influence the emergence of dapsone resistance.

Certain aspects of dapsone metabolism in leprosy patients as studied by high performance liquid chromatography (HPLC) and qualitative screening tests.

Dapsone (DDS) in urine of 250 leprosy patients collected on surprise visits were screened by simple paper spot, tile tests and sensitive Enzyme linked immunosorbent assay (ELISA) and Haemagglutination inhibition (HI) tests. The urinary DDS concentration as well as DDS/C ratios were also studied. Simultaneously, 50 microliter of blood was collected from each of these patients and its dapsone content was estimated by HPLC. Urine samples with means of 25 to 30 micrograms/ml DDS and 55-64 micrograms/mg DDS/C ratios were found to give positive tests by any of the above screening procedures, while their mean blood DDS concentration was found to be 0.91 microgram/ml. The corresponding values for those specimens giving negative tests were 3.8 to 5.7 micrograms DDS per ml and 9 to 13 micrograms/mg DDS/C ratio. The blood DDS concentration in this group was ranging from 0.16 to 0.18 micrograms/ml. The findings are discussed in relation to their metabolic significance and their application in a leprosy control programme.

Secondary and primary dapsone resistant leprosy: an analysis of 199 patients from St. Thomas Hospital and leprosy project, Chettupattu, South India.

The occurrence of secondary and primary dapsone resistance in 199 patients in our control area and the influence of certain variables such as age, initial bacteriological and morphological indices, duration of regular dapsone monotherapy, on the emergence of dapsone resistance was investigated. Ninety one of 122 patients and 29 out of 77 showed secondary (SDR) and primary (PDR) resistance to dapsone respectively. Very low BI (BI:2.5) group also showed both SDR (60%) and PDR (40%). Low or high MI group exhibited the same degree of resistance. Multiplication of M. leprae was obtained even when the MI of the inocula was zero. Even in the group who had 1 to 5 years duration of regular dapsone treatment, 85% patients showed SDR. Significance of such results are discussed in relation to chemotherapy. The overall minimum prevalence of SDR was found to be 5.6% and 21% in the case of PDR in our control area.