[Bacteriology and human and experimental pathology of ulcers caused by Mycobacterium ulcerans].
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Biomedical subjects
Publications and source records attributed to S R Pattyn.
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Mycobacteria were cultivated from 16 out of 32 samples of tissues from armadillos inoculated with Mycobacterium leprae. Three out of 7 samples from non-inoculated armadillos held in captivity were also positive for cultivable mycobacteria. Some isolated strains belonged to the M. avium-intracellulare-scrofulaceum complex, while others were identified as M. gordonae and M. terrae. Unclassified mycobacteria were isolated from M. leprae-inoculated armadillos only. Taxonomic studies confirmed that these new armadillo-derived mycobacteria (ADM) are different from all presently known species of mycobacteria, including M. leprae. The same new species were isolated from different armadillo colonies and were never found in non-inoculated animals. Different factors influence the isolation of these ADM in primary culture. Analysis of some specific markers of these ADM has been suggested in order to quantitatively determine the proportion of these ADM to M. leprae in armadillo tissues. No mycobacteria were cultivated from Nude mouse footpads infected with M. leprae.
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Quinacrine administered in 100 mg per kg body weight to mice had a bacteriostatic activity on M. leprae in the mouse, chloroquine at 15 mg per kg and primaquine at 0.25 mg per kg were without activity. These findings could point to the presence of a functioning direct oxidative pathway of glucose catabolism in M. leprae.
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Three enzymes of aerobic pathways (cytochrome c oxidase, peroxidase and catalase) and one key enzyme of the tricarboxylic acid cycle (succinate dehydrogenase) were investigated for their ultrastructural localization in M. lepraemurium in infected mouse liver and in cultures of M. fortuitum as a control. All four enzymes were localized in M. fortuitum. To M. lepraemurium only cytochrome c oxidase and peroxidatic activity were detected. The localization of the latter enzyme activity was different compared with M. fortuitum. Succinate dehydrogenase was not detected in M. lepraemurium but rather surprisingly was found in the membrane of the phagosomes containing the bacteria. It is concluded that M. lepraemurium can function aerobically and has either a glyoxalate pathway or is an obligate autotroph.
Ten patients infected with mouse proven DDS-resistant bacilli were treated with the following combined regimen: RMP 600 2/7 6 months, ETH 500 7/7 6 months and DDS 100 7/7 12 months. Follow up was for 27-54 months, without relapses. Added to patients from previous study (Int. J. Lepr. 1984, 52, 297-303) the 95% confidence limit decreases from 12 to 9%.
Between 1980 et 1983 all PB patients presenting at the Institut Marchoux, Bamako, took part in a prospective randomized therapeutic trial and were allocated to one of the following regimens: DDS 100 mg 7/7 3 years, RMP 900 mg 1/7 8 doses, RMP 900 mg 7/7 12 doses. At this moment 24, 29 and 22 patients respectively have been followed for periods of 24 to 56 months. With the exception of some irregular drug intake in the DDS patients followed either by relapse or delay in improvement, the efficacity as judged by histopathological examinations did not reveal any difference between the regimens. The study continues.
Treatment of PB leprosy patients with 10 weekly doses of RMP 600 mg gave a cure rate of 88% or more at 3 years as judged by histopathology. There were no severe neurological complications. The future will show if this regimen also prevents relapses. In MB leprosy a 2 months regimen of daily RMP, ETH, DDS followed by 10 months of daily ETH, DDS with weekly RMP gave excellent clinical and bacteriological results. There were no relapses during 2 and 3 years after the end of therapy among 111 newly diagnosed and previously treated patients (95% confidence interval 3.3%) of whom 67 were new patients (95% confidence interval 5.3%). The hepatotoxicity of this regimen has to be followed closely. The results illustrate the possibility to cure MB leprosy by a treatment of finite duration.
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Among a population of over 500 PB patients treated with different regimens, 6 multibacillary relapses were detected: 5 in patients erroneously classified as PB but in reality MB with a low bacterial load, one patient was PB at the start. Treatment regimens had been: 10 weekly doses of RMP either 600 mg (1 case) or 900 mg (1 case) two successive doses of RMP 1500 mg (1 case) a single dose of RMP 40 mg/K (3 cases). Four MB patients with proven DDS-R relapsed after a single dose of RMP either 20 mg/K (1 case) or 40 mg/K (3 cases). The two strains isolated were RMP sensitive. Seven of the 10 relapses appeared within 24 months after start of treatment.
Histopathological examination of skin biopsies from PB patients during the first 12-18 months of treatment did not reveal any significant difference in the time necessary for disappearance of the lesions. The regimens studied were: DDS 100 mg 7/7, RMP 600 mg 1/30 6x, RMP 600 mg 6/6 6x, RMP 900 mg 1/7 8x and 12x, RMP 1500 mg 1x and 1 year of DDS, RMP 4 mg/K 1x.
Behind the story of one paucibacillary patient treated by dapsone monotherapy, the authors discussed on the possibility of relapse. But the therapy course, observed by DDS/Urine examination shows a default of the patient. The problems of follow up and attendance of the patient are discussed.
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Subcultures of strain HI-75 of Skinsnes leprosy bacillus received in Antwerp and London have been studied bacteriologically and compared. Both contained moderately large acid-fast bacilli readily subcultured and maintained on ordinary mycobacteriologic media. These organisms were found to be a variety of Mycobacterium marianum (syn. serofulaceum) and were considered likely to be a laboratory contaminant. The earlier subculture studied also contained numbers of a much smaller mycobacterium (of a similar size to M. leprae) which appeared to be dead and which did not grow on the ordinary media. Skin tests and immunodiffusion analyses performed with extracts of the earlier subculture failed to demonstrate the presence of the specific antigens of leprosy bacilli. Similar studies on other cultures of Skinsnes bacillus must be performed to confirm or refute its identity as M. leprae.
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