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Since 1970, when the lifelong monotherapy with dapsone (DDS) in leprosy could be replaced by short-term combination therapy with rifampicin + isoniazid + protionamide-!-DDS (Isoprodian-RMP), chemotherapeutic research was faced with two problems: (1) to find alternative treatment regimens for cases of intolerance, and (2) to work out forms of therapy allowing a further reduction of the average treatment time of 2 years. The present paper describes the attempts made to find solutions to these problems. With two new combinations, alternatives have become available, and the average treatment time is shortened to 6 months. Both combinations are also effective in tuberculosis.

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In the present paper the ‘serial combinations’ (components of the combination offered separately), as used in conventional combination therapy, are compared with the ‘integrated complex combination’ (offered as fixed combinations). So far, three combinations have been worked out on the basis of this concept (RMP + SMZ + TMP + INH; RMP + SMZ + TMP + PTH; RMP + INH + PTH + DDS). They allow successful treatment of almost all mycobacterial infections and diseases (including tuberculosis and leprosy) and a number of infections caused by gram-negative and gram-positive microorganisms and by Pneumocystis carinii.

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This is the first publication of the initial 5-year-period of the eradication programme since its introduction in the Maltese Islands in the second half of 1972. All patients were treated with a combined drug regimen, its chief components being rifampicin (RMP), prothionamide (PTH), isoniazid (INH) and diaminodiphenyl-sulfone (DDS). To simplify the therapeutic technique, PTH, INH and DDS were given as a fixed combination. Other medications, such as DDS-free regimens, were whenever possible also given as fixed combinations. Fixed combinations not only make treatment simpler, but also guarantee a more reliable acceptance of the medication and the adherence to the dosage proportions which play an important role with regard to the effectiveness. For an eradication programme the classification into the different leprosy types plays not a too important role. It was rather our goal to cure each single patient so as to eliminate him as a possible source of infection. Whether or not this goal has been reached was as far as possible related to the results of the bacteriological assessment. Of the originally recorded 210 patients 206 were included in the first part of the programme (groups I–III). By the end of 5 years, a total of 20 patients had left the programme (death or emigration) so that 186 patients remained registered per June, 1977. In 180 cases treatment has been discontinued; 6 patients are still under therapy. The relapse-free observation periods are more than 2 years in 160 patients, more than 3 years in 120 patients, and more than 4 years in 12 patients. 31 patients joined the programme when it was already under way, namely 11 patients in 1973, 9 patients in 1974, 6 patients in 1975, and 5 patients in 1976. These newly registered cases were grouped separately (group IV). 27 patients were found to be bacteriologically positive; 10 of them are meanwhile negative, 11 are still being treated. Under observation without therapy are 19. One patient died of nonspecific disease in 1976. In continuation of the programme we are aiming at (a) conclusive treatment of the rest of the patients who are still under therapy, (b) conclusive treatment of the patients according to group IV, (c) regular observation of all cases for the absence of relapses, and (d) search for new cases and inclusion of such eventually newly identified cases in the programme. Further scientific evaluation of the material, chiefly in the bacteriological, clinical, pathological and genetic field, will require lengthy investigations which we are working at. A larger quantity of well-examined and well-classified material has accumulated since the start of the programme. The material is at the disposal also of all colleagues outside Borstel Institute. Up to the present, we have collected approximately 30,000 histological slides, representing all stages of leprosy, i.e. from the period before, during and after treatment (about 5000 biopsies). The article explains the prerequisites for an eradication programme which in principle can serve as a model for si...

Bacterial growth kinetics and checkerboard titration experiments have been performed to determine the inhibitory power of metioprim (I) and brodimoprim (II) alone and in combination with diaminodiphenylsulfone (DDS) using Escherichia coli and mycobacteria as test organisms. The evaluated potency of the new TMP derivatives alone and in combination is compared to TMP and other derivatives. A strongly synergistic activity of I and II in combination with DDS against E. coli and various mycobacteria is observed which is also operative in case of highly DDS-resistant mycobacterial strains. The implication of these findings for the development of a combined chemotherapy with these drugs against atypical mycobacterial infections – especially leprosy -is discussed.

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