The World Health Organization advocates 2 leprosy treatment regimens on the basis of disease classification (as multibacillary or paucibacillary) by skin lesion count. This method, which, in the Philippines, results in a high prevalence (78%) of patients with multibacillary leprosy, was directly compared with classification using standard histopathological and microbiological criteria in 264 currently untreated patients with leprosy. Of those whose leprosy was classified as paucibacillary, 38%-51% of patients had multibacillary leprosy according to classic criteria and were thus at risk of undertreatment according to World Health Organization recommendations.

Abstract. The objective of this study was to ascertain risk factors for complications (reactions or neuritis) in leprosy patients at the time of diagnosis in three leprosy-endemic countries. Newly diagnosed patients were enrolled in Brazil, the Philippines, and Nepal, and risk factors for reactions and neuritis were assessed using a case-control approach: "cases" were patients with these complications, and controls were patients without complications. Of 1,972 patients enrolled in this study, 22% had complications before treatment. Type 1 reaction was diagnosed in 13.7% of patients, neuritis alone in 6.9.%, and type 2 reaction in 1.4%. The frequency of these complications was higher in Nepal, in lepromatous patients, in males, and in adults versus children. Reactions and neuritis were seen in patients at diagnosis, before treatment was started. Reactions were seen in adults and children, even in patients with only a single lesion. Neuritis was often present without other signs of reaction. Reactions and neuritis were more likely to occur in lepromatous patients, and were more likely to be seen in adults than in children.

In a clinical trial of moxifloxacin in eight multibacillary leprosy patients, moxifloxacin proved highly effective. In all trial patients, a single 400-mg dose of moxifloxacin resulted in significant killing (P < 0.006) of Mycobacterium leprae, ranging from 82% to 99%, with a mean of 91%. In all instances, no viable bacilli were detected with an additional 3 weeks of daily therapy, this observed rapid bactericidal activity being matched previously only by rifampin. On moxifloxacin therapy, skin lesions cleared exceedingly rapidly with definite improvement observed consistently after eight doses and progressive resolution continuing for the 56 days of the trial. Side effects, toxicities, and laboratory abnormalities were mild, not requiring discontinuation of therapy.Fluoroquinolones have proven to be active against Mycobacterium leprae in rodents (10,13,18,20,31) and in clinical trials (9,19,26) in leprosy patients. The first studies of fluoroquinolones in M. leprae-infected mice found that ciprofloxacin was inactive while pefloxacin and ofloxacin were bactericidal (18,20). We (13) tested several fluoroquinolones against M. leprae in mice, finding some, namely WIN5727, temafloxacin, and particularly sparfloxacin, to be superior to pefloxacin and ofloxacin. Furthermore, in the heavily infected, neonatally thymectomized Lewis rat, the combination of rifampin and ofloxacin was more regularly sterilizing than the combinations of both rifampin plus dapsone and rifampin plus clofazimine (10), rifampin, dapsone, and clofazimine being the three components of the widely implemented WHO-recommended regimens for treatment of multibacillary (MB) leprosy (36, 37). Clinical trials of pefloxacin and ofloxacin treatments in leprosy have demonstrated encouraging clinical responses and the clearance of viable M. leprae within 2 months (9,19,26), this rate of clearance being higher than those with dapsone and clofazimine (several months [32]), similar to those with minocycline (8, 12) and clarithromycin (3), but much lower than that with rifampin (29,32,34).Moxifloxacin against Mycobacterium tuberculosis (6, 14, 23, 25) has been found to be more bactericidal in vitro than other quinolones and similar in bactericidal activity to rifampin. Also, moxifloxacin has been demonstrated in a murine model of tuberculosis to add to the sterilizing activities of isoniazid, rifampin, and pyrazinamide (27) and to provide significant bactericidal activity in the first few days of treatment of human tuberculosis, both as monotherapy (17,24,28) and as multidrug therapy (2, 15). As a result, trials with moxifloxacin treatment of active pulmonary tuberculosis are currently in progress, using it to both replace established agents and shorten the course of effective therapy of active pulmonary tuberculosis.In a murine model of leprosy, moxifloxacin has been demonstrated to be more bactericidal than ofloxacin and, in that regard, as potent as rifampin (5). Because the 1-year WHO regimen (37) for MB leprosy is still quite lengthy, some studies have foun...

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As a participant in a multicenter trial, we evaluated the relapse rate in 189 multibacillary (MB) leprosy patients treated with four different regimens and followed-up for as many as 12 years after the initiation of treatment. Treatment regimens included 1 year of WHO MDT (a regimen including dapsone, clofazimine, and rifampin), 2 years of WHO MDT, 1 month of daily rifampin and daily ofloxacin, and 1 year of WHO MDT plus an initial 1 month of daily rifampin and daily ofloxacin. Relapse rates after 9 and 12 years from the initiation of therapy in the three regimens that included WHO MDT were 0-3%, whereas relapses occurred in those treated with the 1-month regimen alone at a significantly greater rate (P < 0.05): 11% at 9 years and 25% at 12 years. Relapses occurred late, beginning at 5 years after the initiation of therapy, and were confined to those patients histopathologically borderline lepromatous and polar lepromatous having a high bacterial burden. Prospects for an alternative effective short-course therapy of leprosy are presented.