Multidrug Therapy Regimens Research Articles

Ultrastructural study of the dermal nerves in the cutaneous macular lesions of patients with early leprosy

Thirteen biopsies of macular lesions of early leprosy patients were studied ultrastructurally with transmission electron microscopy (TEM). All of the biopsies displayed at least one dermal nerve partially or completely encircled by mononuclear cells in the conventional histopathological study with light microscopy The patients'diagnosis varied from indeterminate leprosy to borderline tuberculoide (BT). In the ultrastructural study,twenty-seven dermal nerve branches were found in the thirteen biopsies. Twenty dermal nerve branches in eleven biopsies were found to display no inflammatory involvement Seven nerves in seven biopsies were morphologically associated with mononuclear leukocytic cells. Four biopsies exhibited nerves with and without inflammatory involvement concomitantly. Three nerves showed morphological evidence of endoneurial fibrosis, not morphologically associated with the inflammatory process at least in the sections examined. No detectable axional andSchwann cell ultra strutural changes even in the twenty-seven nerveswere found. The sensorial loss exhibited by the patients before the institution of treatment was completely reversed in eight patients after the end of multidrug therapy regimen. These findings suggest that sensory loss in the early stages of leprosy may be caused by reversible pathological mechanisms, rather than anatomical damage. It is also possible, concerning the mechanisms of nerve damage in leprosy, to speculate on the existence of a pathological process which may precede the inflammation.

Leprosy in the tropics and Australia.

Leprosy is no longer the feared disease of the past, but it still causes significant morbidity in countries where it is endemic, and it is estimated that up to 2500 million people are at risk of contracting the disease. Control with dapsone monotherapy over the past 20-30 years has been effective in some countries but secondary and, more recently, primary drug resistance is now widespread. This situation prompted the development of multidrug therapy regimens which are proving highly effective. Here the natural history and clinical features are described, as well as the history and impact of leprosy in Australia. Early diagnosis and the current multidrug regimens offer hope for long-term control of the disease.

1. Chemotherapy of leprosy—current status and future prospects

The introduction of multi-drug therapy (MDT) by the World Health Organization in 1982 has proved to be the most important advance in the management and control of leprosy since the first use of the sulphone drugs 40 years earlier. For the first time, the number of registered leprosy cases has shown a decline from a peak of 5 · 37 million in 1985 to 3 · 1 million in February 1992. The 2 standard MDT regimens have proved simple to apply in most parts of the world, are relatively cheap, generally acceptable, and have shown remarkably few toxic side-effects. Nevertheless, difficulties have arisen in distinguishing between multibacillary and paucibacillary leprosy, especially when skin smears are of poor quality. Relapses in paucibacillary leprosy have proved difficult to distinguish from late reversal reactions. In multibacillary leprosy, the duration of treatment, 2–10 years in lepromatous leprosy, is a source of difficulty, and in addition light-skinned patients dislike the skin discolouration caused by clofazimine, for fear that their diagnosis might be discovered. The discovery that 3 different groups of drugs are highly bactericidal for the leprosy bacillus, although not so rapidly bactericidal as rifampicin, raises the possibility of having simplified, shorter, or better supervised regimens in the future as second generation MDT. These drugs include the 4-fluoroquinolones, pefloxacin, ofloxacin and sparfloxacin, the tetracycline minocycline, and the macrolide clarithromycin. Finally, in low-prevalence areas it is opportune to consider chemoprophylaxis and immunoprophylaxis for child contacts of lepromatous patients.

In-vitro activity of three new fluoroquinolones and synergy with ansamycins against Mycobacterium leprae.

The efficacy of three fluorinated quinolones, clinafloxacin (PD 127391), sparfloxacin (PD 131501) and PD 131628, either alone or in combination with rifampicin/rifabutin, against Mycobacterium leprae was evaluated in vitro using two biochemical parameters to measure the metabolic activity of the organism. Clinafloxacin was found to be most effective with an MIC of 0.75 mg/L, followed by sparfloxacin (MIC 1.5 mg/L) and PD131628 (MIC 3.0 mg/L). When combined with rifampicin each of the three quinolones were additive to the activity. However, when combined with rifabutin, both clinafloxacin and sparfloxacin demonstrated pronounced synergic activity. Incorporation of clinafloxacin and rifabutin in a multi-drug therapy regimen is suggested.

Bacillaemia in leprosy and effect of multidrug therapy

Twenty-five patients of bacilliferous leprosy (17 LL, 8 BL) were studied by the modified haemolysis method for occurrence of bacillaemia and its clearance after two multidrug therapy regimens. Acid-fast bacilli were found in 76% of all patients and in 88.2% LL and 50% BL patients. Bacillaemia occurred with significantly reduced frequency in patients with type II reaction. Acid-fast bacilli were demonstrable in peripheral blood after 1 month in one patient on MDT of an Indian Working Group and 3 lepromatous patients on WHO multidrug therapy. However, bacillaemia could not be demonstrated in any patients after 2 and 3 months of treatment with both regimens.

Relapses after multidrug therapy for leprosy: a preliminary report of 22 cases in west Nepal.

The WHO recommended multidrug therapy regimens for leprosy patients were implemented in Nepal from 1982. Therefore a considerable number of both paucibacillary (PB) and multibacillary (MB) patients have been on observation after release from MDT, for as long as 4-5 years. A retrospective study was done considering the patients who relapsed during this period and who were registered at the Out-patients Department of Green Pastures Hospital in Pokhara, Nepal. A total of 22 patients relapsed out of 927 who were released from MDT.