Serum Activity Determination as Connecting Link between Experiment and Clinic

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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...

Section: Discussion and Comments To Our Proceduresmentioning

confidence: 99%

“…be the most effective ones [13,22,23,26,32], In this sense, therefore, the obtained treatment results can also serve as indicator of the efficacy of these therapy forms and their excellent compatibility even in cases of continuous administration over several years.…”

Section: General Aspectsmentioning

confidence: 99%

Leprosy Eradication Project of Malta

Freerksen¹,

Rosenfeld²

1977

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“…It provides an insight into the expected therapeutic effect of the substance or medication to be tested. Although this connecting link [13] between experimental and clinical findings may also be of major relevance for clinical studies, it is often misjudged or underestimated, and only rarely used. There is of course no scope for a detailed discussion of the respective methods in this paper.…”

Section: Serum Activitymentioning

confidence: 99%

The Malta Project – A Country Freed Itself of Leprosy

Freerksen

Rosenfeld²,

Depasquale³

et al. 2001

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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.

“…From the results ob tained, the therapeutic action to be ex pected of the substances or medications under test can be largely estimated. Al though this connecting link between experiment and clinic [11,29] could be of great help for clinical work, it is often not correctly understood or is underrated. Discussions on this subject have been con tinuing since the end of the forties [5,6,14,16,20,25,34,35,36], Of course, a detailed discussion of methodology is not possible here.…”

Section: Determination Of Serum Activitymentioning

confidence: 99%

Integrated Complex Combinations for the Treatment of Opportunistic Infections in AIDS

Freerksen¹,

Rosenfeld²,

Spannuth³

1989

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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.