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Twelve patients were treated with three dose levels of minocycline for 30 days, primarily to detect the dose-related effects on Mycobacterium leprae viability, followed by another 5 months of daily minocycline for overall efficacy and persistence of clinical and antibacterial effects. Subsequently, the patients were given standard WHO/MDT chemotherapy for multibacillary leprosy. Clinical improvement was recognizable during the first month, occurring much earlier among those on minocycline 200 mg daily than those who received minocycline 100 mg daily. A similar change also was observed in one patient 11 days after three daily doses of 100 mg of minocycline. At the end of 6 months, all patients were clinically improved with a slight reduction in the average bacterial index (BI) and logarithmic index of bacilli in biopsy (LIB). The effects of minocycline on viability by mouse foot pad inoculation and palmitic acid oxidation assays were noted beginning at 10 to 14 days of daily dosing and becoming more definite after 30 days of treatment. Both tests correlated fairly well. Doses of 200 mg daily did not appear to be more efficient than minocycline 100 daily. Phenolic glycolipid-I (PGL-I) antigen determinations done on some patients during the first month remained positive and did not correlate with changes in viability results. At the end of 6 months, after 5 months of 100 mg of minocycline monotherapy, no viable organisms could be demonstrated by mouse foot pad inoculation and palmitic acid oxidation assays; assays for PGL-I antigen were all negative.(ABSTRACT TRUNCATED AT 250 WORDS)

An indirect enzyme-linked immunosorbent assay (ELISA) using natural disaccharide octyl bovine serum albumin (ND-O-BSA) as antigen was used in testing leprosy patients, contacts and a normal population in Cebu, The Philippines, from 1985 to 1989. A total of 1413 persons were studied. The results suggested that ELISA reactivity and the bacterial index (BI) correlate in a general way. In multibacillary (MB) leprosy, positivity ranges from 54.2% to 92.3% among patients with a BI of2+ to4+ on the Ridley scale, with an overall average of 84.5%. Paucibacillary (PB) leprosy patients have a low degree of reactivity, with only 15.0% ELISA positive. The test is more efficient in detecting MB than PB leprosy. The contacts of MB leprosy showed 6.5% positivity; contacts of PB leprosy, 7.0% positivity. The normal population showed 1.7% positive ELISA or 17 per thousand population, which is very much less than that of the household contacts. However, because the normal population is a much larger population than the household contact population in a community, more new leprosy cases would emanate from it. Leprosy workers are concerned about the transmission of the disease to household contacts. However, for the reason stated above, we should be more concerned with the silent spread of the disease to the normal population in the community.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy specimens were obtained from 102 leprosy patients before chemotherapy and examined by polymerase chain reaction (PCR) using the primers amplifying the 372-bp DNA of a repetitive sequence of Mycobacterium leprae. The PCR results were then compared with bacterial indices (BI) of slit-skin smears and biopsy specimens. The intensities of DNA bands were in general correlated with the numbers of acid-fast bacilli, and even a sample with only one organism gave a PCR positive result. Ten 5-micron sections from each frozen tissue sample were pooled and processed for DNA preparation. PCR was positive for 11 (73.3%) of 15 biopsy specimens with BI of 0 determined for the paraffin sections from the same biopsy samples. PCR also gave positive results for 84 (96.6%) of 87 BI positive biopsy samples. Although the difference in overall results between the two methods was not statistically significant, PCR seemed to have an advantage over microscopic examination in detecting M. leprae in biopsy specimens negative for acid-fast bacilli. Further evaluation of PCR using more specimens from leprosy patients who are bacteriologically negative is warranted to ensure PCR's advantage over the conventional microscopic examination for the diagnosis of leprosy.

Since phenolic glycolipid-I (PGL-I) is an unequivocal marker of Mycobacterium leprae, the antigen has been a good candidate for the serodiagnosis and monitoring the effectiveness of leprosy chemotherapy. As an effort to define the kinetics of the PGL-I antigen and its antibodies in leprosy patients, this study was initiated to examine the serum specimens obtained serially from lepromatous patients under chemotherapy trials. PGL-I was detectable in 64 (94.1%) of 68 new lepromatous (bacterial index, BI = 3.2 to 5.8) and in 26 (78.8%) of 33 relapsed lepromatous patients (BI = 3.0 to 5.3). Meanwhile, virtually all of the new and relapsed patients were strongly seropositive to PGL-I. PGL-I was not detectable in any of the patients about 18 months after chemotherapy was initiated; however, anti-PGL-I reactivity declined by 50% at 2 years and by about 70% at 5 years after chemotherapy regardless of the drug regimens under study. Considering the rapid disappearance of the PGL-I antigen and steady decrease in anti-PGL-I IgM antibodies following chemotherapy, the PGL-I-based serology may be useful for monitoring the effectiveness of treatment, at both the early and late stages, in leprosy patients whose initial sera contain a significant level of PGL-I antigen or antibodies.

Chemotherapy trials in lepromatous leprosy using various combinations of existing antileprosy drugs were conducted jointly by Korea, The Philippines, and Thailand. The general objective of these trials was to determine the most effective and practicable regimen or regimens for field application. Lepromatous patients were divided into two groups: Group I was comprised of new, untreated patients infected with dapsone-sensitive Mycobacterium leprae and Group II consisted of relapsed patients with dapsone-resistant disease. Four different regimens were administered to each group for 5 years. Comparison among the regimens was based on antileprotic efficacy, drug safety, acceptability, field practicability, and economic feasibility. No significant differences were noted among the various regimens as judged by the reduction in the bacterial index (BI), clinical response, and change in biopsy index. Toxicity was seen only in the regimens containing prothionamide and rifampin. The regimens were acceptable to the patients and all were found practical for field use. Clofazimine, even in low doses, was found to suppress the frequency and severity of erythema nodosum leprosum. A multidrug regimen effective against both new and relapsed cases of lepromatous leprosy, whether dapsone sensitive or dapsone resistant, is recommended for field use. Given priority, the cost of the regimens is affordable in the three countries.

Because of the recent spate of reports of primary resistance to dapsone among patients with lepromatous leprosy, largely to small concentrations of the drug, a survey was made of the results of dapsone-susceptibility testing of strains of Mycobacterium leprae isolated before 1977 among six laboratories which employed the mouse foot pad technique for this work prior to that time. Data have been found for strains that had been isolated from 73 patients, representing 19 countries and dependencies, with previously untreated lepromatous leprosy; all 73 strains were inhibited from multiplication by dapsone administered to mice in a concentration of 0.0001 g per 100 g mouse diet. These data suggest that the properties of M. leprae isolated from previously untreated patients with respect to susceptibility to dapsone have changed since the years preceding 1977.