Effect of mono treatment and combined treatment on the morphology of Myco. leprae in the skin

Abstract

A study is made of the effect of clofazimine, of rifampicin, of a combination of rifampicin with isoniazid and sulphamethoxy pyrazinamide and of a combination of rifampicin with tri methoprim sulphonamide and prothionamide, on the morphology of Myco. leprae in foamy cells, in arrectores pilorum muscles, in blood vessel walls, and in nerves in the skin of patients with lepromatous leprosy. The method of assessment was by blind examination of serial biopsies, taken each time from the same lesion. At the onset of the trial the percentage of granular bacilli was, on the average, 14.3% lower in blood vessel walls, 8.3% lower in arrector pilorum muscle and 8.1% lower in nerves, than it was in foamy cell infiltrates. Occasionally higher percentages of granular bacilli were found in muscle or nerve, and this was related to previous treatment. After 1-3 mth of treatment, with all drug regimens, the percentages of granular bacilli increased markedly, not only in the foamy cell infiltrates, but also proportionally in smooth muscle and nerve. The effect of clofazimine was slower than of the other drug regimens. No significant difference was found between the group of patients treated with rifampicin and those treated with a combination of rifampicin with other drugs. The finding of 99% granular bacilli in several patients treated for 1-2 yr indicates that none of the drug regimens had produced complete clearance of viable bacilli. Even if only 1% of the non granular bacilli is viable, in a lepromatous patient with a load of bacilli of 1010, a granularity index of 99% means that 106 viable bacilli are still present. The method used is not regarded as sufficiently sensitive for excluding the possibility that even in patients with counts of 100% granular bacilli complete clearance of viable bacilli has been achieved. The rapid and good response of bacilli in muscle and nerve in the skin to all drug regimens suggests that these sites are not the only or the most important sites of therapy resistant bacilli. Other sites, e.g. large peripheral nerves, bone marrow and internal organs should be investigated. One patient treated with the combination supposed to have the highest bacteriocidal activity (rifampicin eusaprim ethionamide), absconded after 4 mth of treatment and relapsed after a period of 2 years without treatment, indicating that not all viable bacilli were eliminated. In this patient in a biopsy of an old lesion large numbers of bacilli were present, but all bacilli were granular, whereas in the new relapse lesions a high percentage of non granular bacilli was found. This suggests that the relapse was not due to survival of bacilli in old skin lesions, but to therapy resistant bacilli at other sites.