The Malta Project--a country freed itself of leprosy. A 27-year progress study (1972-1999) of the first successful eradication of leprosy.

The successful conclusion of the first leprosy eradication program carried out with combination therapy is reported. This program started in Malta in June 1972. It was based on extensive experimental and clinical studies and was formally concluded on 31 December 1999. No new infections occurred after the start of this 27-year progress report. The youngest patient was 16, and the eldest 83 years old. Of the total of 261 cases in the project, 201 had already received pretreatment [mainly with diaminodiphenylsulfone (DDS)] at the start. Sixty-one cases had no pretreatment. These were predominantly elderly patients who were late in deciding to have treatment. The very long follow-up period totaling 27 years was consistently maintained in order to be able to refute all potential objections empirically, e.g. with regard to relapses at a late stage. Besides the overall symptoms which are typical for the broad picture of leprosy, the involvement of the eyes was very striking (at least 50%). The therapeutic effect was of very rapid onset in these cases without surgery. Rifampicin (RMP) + isoniazid + prothionamide + DDS (trade name Isoprodian-RMP) was used as medication in a fixed combination. This fixed combination had already proved to be highly effective in the treatments during the course of the project, surprising therapy results (including lifesaving effects) were also noticed in other diseases.

Cotrifazid--an agent against malaria.

Following the brief information on a new malaria treatment with the fixed multiple combination Cotrifazid (rifampicin+isoniazid+sulfamethoxazole+trimethoprim) in Chemotherapy [1995;41:396-398], very good results are reported for the treatment of 61 patients with various forms of malaria. The tolerance was found to be good. Some relevant fundamental considerations (chemoresistance, synergism/antagonism, fixed multiple combination, switching from monotherapy to combination therapy) and the implementation of the principle of a "multidisease therapy' are discussed.

Malaria therapy and prophylaxis with cotrifazid, a multiple complex combination consisting of rifampicin + isoniazid + sulfamethoxazole + trimethoprim.

This report contains the first therapeutic results with the multiple combination rifampicin + isoniazid + sulfamethoxazole + trimethoprim in the treatment of malaria. Clinical symptoms declined rapidly and parasites were cleared from the erythrocytes. Tolerance was excellent. This fixed combination is outstandingly practicable, with few problems with compliance.

Critical comments on the treatment of leprosy and other mycobacterial infections with clofazimine.

The usefulness of clofazimine (CLO, CAS 2030-63-9) in the treatment of mycobacterial infections with special emphasis on treatment of leprosy is critically discussed. Skin discolouration which decreases compliance, placenta passage, excretion in mother's milk which endanger the embryo or baby respectively, saturation kinetics in absorption and difficulties to determine free drug concentration are severe problems. The observed antagonism in the combination of CLO with other drugs, especially with dapsone, is another argument against its application in the therapy of mycobacterial infections. In Germany CLO has not been approved by the Bundesgesundheitsamt.

[Short-term chemotherapy of leprosy using the combination rifampicin + cotrimoxazole + isoniazid]. / Kurzzeitchemotherapie der Lepra mit der Kombination Rifampicin + Cotrimoxazol + Isoniazid.

With the fixed combination RMP + SXT + INH an objective and subjective improvement was obtained within two months, even in severe LL-cases. Treatment resulted in final and relapse-free cure. In the majority of patients the typical erythematous infiltrative oedematous skin processes disappeared within the two months of treatment, in some of them (three of 21) within the six-month follow-up period. Lepromas (15 cases) disappeared in two patients within the two months of treatment. In the sixth month of the follow-up period nine patients were free from lepromas. In another six cases they subsided in the course of the following months. Reactions occurred in 13 patients, in part during treatment, in part during the follow-up period. Three of them were reversal reactions. Chemotherapy was not interrupted. When required, corticosteroids or thalidomide were given in addition. Erythema nodosum leprosum (17 cases) quickly subsided under treatment. Tolerance and compliance were excellent. The subjective minor "side effects" were not specific and cannot clearly be attributed to the medication. The major advantage of the combination RMP + INH + SXT described in this paper lies in the considerably reduced treatment duration (two to four months instead of two years), the rapid disappearance of the symptoms typical of leprosy, the high tolerance, the ease of application as fixed combination and the absence of relapses. So far the patients have been followed up for two years. Through the short treatment duration the cost of treatment is considerably reduced. The new combination allows outpatient treatment and is universally applicable. The patient can maintain his social and professional habits.

A new short-term combination therapy of leprosy.

Report on the results with a new therapy with a complex combination (rifampicin + co-trimoxazole + isoniazid) for the treatment of leprosy. High tolerance. Duration of treatment 2 months.

[Chemotherapy of opportunistic infections in AIDS]. / Chemotherapie opportunistischer Infektionen bei AIDS.

Proposal for therapy and prophylaxis of opportunistic infections in AIDS using complex combinations consisting of four substances (Rifampicin + Sulfamethoxazol + Trimethoprim + Isoniazide or Rifampicin + Sulfamethoxazol + Trimethoprim + Protionamide) in a fixed combination.

New forms of multidrug therapy for the treatment of leprosy. First report for the practice on rifampicin + sulfamethoxazole-trimethoprim + protionamide and rifampicin + sulfamethoxazole-trimethoprim + isoniazid.

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.

Integrated complex combinations for the treatment of opportunistic infections in AIDS.

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.

[Occurrence of Mycobacterium shimoidei in West Germany]. / Vorkommen von Mycobacterium shimoidei in der Bundesrepublik Deutschland.

In the Federal Republic of Germany Mycobacterium shimoidei has been isolated from a patient with a pulmonary infection. This strain is different from all other slowly growing mycobacteria. It seems that Mycobacterium shimoidei has been isolated in Germany for the first time.