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.

Summary A report is presented of a fo llow-up examination of 116 multibacillary leprosy patients who had received multidrug therapy (MDT) as part of a leprosy eradication programme known as the Malta-Project, inaugurated in 1972. Length of treatment varied between 5 and 89 months, and side-effects were mostly mild. No signs of clinical relapse were found at fo llow-up, and 36 patients had positive skin smears; 26 had granular bacilli alone, and 10 had scanty 'solids'. It is proposed that these 'solids' are 'persisters', and their significance will be known after long-term fo llow-up of these 10 patients.The objective of this fo llow-up investigation, carried out in April 1983, was to examine the bacilliferous patients who had been given multidrug therapy (MDT) in Malta since 1972. The particular objectives were the following: 1, to look for signs of clinical relapse; 2, to discover if any leprosy bacilli, whether granular or solid-staining, were present in skin smears; and 3, to study the incidence of side-effects.Professor E Freerksen's design of the Malta-Projectl was to treat by MDT all leprosy patients whose names appeared on the registration lists of the Ministry of Health, and similarly to treat all new patients diagnosed in subsequent years, with the objective of eradicating leprosy fr om Malta by rapidly rendering the patients non-infectious. It should be noted that he never intended that this should be looked upon as therapeutic research:'The Malta-Project is not meant to be a trial with the objective to assess anti-leprosy drugs, but an eradication programme which is exclusively based on antimycobacterial chemotherapy.'l 0305-751 8/84/055247 + 07 S01 .00

This report is based on data obtained from 64 lepromatous cases. Despite many years of DDS monotherapy, the homogenates from biopsies of these patients revealed 10⁴ or more bacteria. From the beginning of combination therapy with synergisticacting substances (rifampicin + isoprodian (INH + PTH + DDS) the logarithms of the number of bacteria in the homogenates decreased, both during treatment period and during treatment-free observation period (Figs. 3–8). During the whole time biopsies were taken almost monthly. A considerable regression of the bacterial mass or even «negativity» could be observed within a relatively short time. Once started, the process of reduction of bacteria continued also after termination of therapy. To be able to evaluate a medication, therapy-free observation periods (for a minimum of 5 years) are indispensable.

Malta is the largest of a group of small islands situated in the middle of the Mediterranean. The aggregate area of the whole group is 121.8 square miles and the population is 314,369, with a density of 2,624 per square mile, one of the highest, if not the highest, in the world. The latitude is 350 N. and the longitude 140 E. The group of islands lies 60 miles south of Sicily and about 180 miles north of Africa and forms part of Europe. They enjoy temperate climate with an average annual rainfall of 21 .5 inches. Malta is the largest and most important of the islands. It is 17 miles long, 9 miles wide, with an area of 96 square miles. In its capital, Valetta, is the seat of the Government, and there is also the centre of the social, economic and industrial life of the Maltese archipela go. Gozo, which is the second largest island, is 9 miles l ong, 4i miles wide, and covers an area of 26 square miles. Comino, the smallest island of the group, is It miles long and