Comparison of three regimens containing rifampin for treatment of paucibacillary leprosy patients

Three regimens containing rifampin have been tried in paucibacillary leprosy patients. The patients were selected according to the criteria laid down by the World Health Organization (WHO). In Regimen I, rifampin 600 mg is given once a month for 6 months with dapsone 100 mg daily. Treatment is stopped at the end of 6 months. Regimen II is the same as Regimen I, and is supplemented with an additional 6 months' treatment with dapsone 100 mg daily. Regimen III is the same as Regimen II, except that rifampin is administered daily for the first 7 days. At the end of the scheduled treatment period, 72.2% of the patients in Regimen I, 94.9% of the patients in Regimen II, and 97.1% in Regimen III became inactive. Eighteen out of the 25 active cases at the time Regimen I treatment was stopped had to be restarted on drug therapy since they showed a worsening of their disease, as indicated by an increase in their bacterial index, the appearance of new lesions, renewed activity in old lesions, an increase in the size of old lesions, or development of nerve abscesses. The remaining seven cases regressed without further treatment. All four Regimen II patients and two Regimen III patients who had evidence of activity at the time treatment was stopped did not require any further treatment. On follow-up for 1 1/2 years, three Regimen I patients and none of the Regimen II or Regimen III patients showed relapses. It is thus apparent that rifampin helps to shorten the time duration and to increase the cost effectiveness of treatment of paucibacillary leprosy cases.(ABSTRACT TRUNCATED AT 250 WORDS)     

Histological progression of paucibacillary leprosy during treatment with various therapeutic regimens

Histopathological examination of skin biopsies from PB patients during the first 12-18 months of treatment did not reveal any significant difference in the time necessary for disappearance of the lesions. The regimens studied were: DDS 100 mg 7/7, RMP 600 mg 1/30 6x, RMP 600 mg 6/6 6x, RMP 900 mg 1/7 8x and 12x, RMP 1500 mg 1x and 1 year of DDS, RMP 4 mg/K 1x.     

Relapses in paucibacillary leprosy after MDT--a clinical study

A study was undertaken in a field-based project to assess the incidence and clinical profile of relapses occurring in paucibacillary leprosy patients after adequate doses of multidrug therapy (MDT). Of the 1509 paucibacillary patients who had received not less than 6 doses of MDT (WHO regimen), 85 relapsed; a relapse rate of 5.63% (17.5/1000 person years at risk). These relapses included 12 cases with features of reversal reaction. Seventy-nine percent of the patients relapsed with skin lesions. The relapse rate was higher in borderline cases and in those with more lesions, and it was lower in those who had received dapsone for at least 6 months after cessation of MDT. Seventy-four percent of the relapses were detected between 7 and 24 months of follow up. We feel that uniform clinical criteria should be formulated for the diagnosis of relapse. Individualization of therapy, rather than adhering to a fixed duration of MDT, would be likely to achieve satisfactory cure rates and fewer relapses.     

Risk of paucibacillary leprosy patients released from control relapsing with multibacillary leprosy

We studied 51 paucibacillary patients who had relapsed after cessation of dapsone monotherapy. Among the 51 relapses, the lepromin-negative group had a significantly higher risk of relapsing with multibacillary leprosy compared with the lepromin-positive group of patients. The significance of these findings is discussed.     

Histopathological activity in paucibacillary leprosy patients after ROM therapy

Histopathological activity was assessed in the skin tissue of 13 skin-smear negative, borderline tuberculoid leprosy patients after administration of a single dose of ROM (rifampin 600 mg, ofloxacin 400 mg and minocycline 100 mg) therapy. Biopsies taken just before therapy showed Mycobacterium leprae to be present in eight cases. After 6 months, only three showed granulomatous lesions and others showed only resolving or inactive lesions. Acid-fast bacilli (AFB) persisted in the nerves of three cases. At the end of 12 months, granulomas persisted in 2 out of 13 (15%) patients. No bacilli, however, were detected in any of them at the end of 12 months. This study demonstrated that 12 months after a single dose of ROM granuloma cleared in 85% of the patients and AFB were absent in all of them.     

Comparison of 3 therapeutic regimens in paucibacillary leprosy. Preliminary note

Between 1980 et 1983 all PB patients presenting at the Institut Marchoux, Bamako, took part in a prospective randomized therapeutic trial and were allocated to one of the following regimens: DDS 100 mg 7/7 3 years, RMP 900 mg 1/7 8 doses, RMP 900 mg 7/7 12 doses. At this moment 24, 29 and 22 patients respectively have been followed for periods of 24 to 56 months. With the exception of some irregular drug intake in the DDS patients followed either by relapse or delay in improvement, the efficacity as judged by histopathological examinations did not reveal any difference between the regimens. The study continues.     

Suspicion of paucibacillary leprosy resistant to dapsone: importance of follow-up

Behind the story of one paucibacillary patient treated by dapsone monotherapy, the authors discussed on the possibility of relapse. But the therapy course, observed by DDS/Urine examination shows a default of the patient. The problems of follow up and attendance of the patient are discussed.     

Supervised bimonthly quadruple chemotherapy in 72 paucibacillary leprosy patients in French Guyana

In French Guyana we have treated 72 paucibacillary leprosy with an association of Rifadine + Lamprene + Trecator + Disulone given twice monthly under supervision during 6 months. Results have been satisfying and side effects rare. The sequential character of treatment shows a substantial advantage on the operational side but may appear to be favorable to bacterial resistance.     

Indeterminate leprosy: histopathologic and histochemical predictive parameters involved in its possible change to paucibacillary or multibacillary leprosy

In an attempt to find clinical, bacteriological, histopathological, and immunohistochemical parameters to predict the progress of indeterminate leprosy patients to either paucibacillary (PB) or multibacillary (MB) leprosy, skin biopsies from 51 patients with indeterminate leprosy were retrieved from the files of the S?o Paulo Health Institute (Brazil). All of these patients had progressed to either PB or MB leprosy over a period of time which varied from 2 months to 24 years. Clinical records were examined, and new sections were cut from the paraffin blocks and stained by hematoxylin-eosin and Fite-Faraco stains; the avidin-biotin peroxidase technique was used with primary antibodies to detect bacillary antigens (anti-BCG serum) and nerve branches (anti-S-100 protein anti-serum). A moderate (++) or strongly positive ( ) Mitsuda skin test was observed in some patients progressing to PB leprosy. Noteworthy is that even patients initially Mitsuda negative may evolve to PB leprosy. a) A 2+ bacterial index and/or the presence of bacilli, even though few in number, in various dermal structures; b) multiple positive antigen sites as detected by anti-BCG anti-serum; and c) dermal nerve involvement, when evaluated as single parameters, correlated with a progression indeterminate to MB leprosy. An index resulting from the summation of the above three parameters identified 13 (72%) of 18 of these cases which progressed to MB leprosy.     

Single lesion paucibacillary leprosy: baseline profile of the Brazilian Multicenter Cohort Study

In Brazil, there is little information about the clinical and epidemiological characteristics of paucibacillary, single skin lesion leprosy patients (SSL-PB). Only recently has the official notification system distinguished leprosy patients with a single lesion as a clinical entity, for whom the single-dose ROM (rifampin, ofloxacin and minocycline) regimen has been recommended. In this paper, we describe the baseline clinical features and the immunological background of a multicenter cohort of SSL-PB leprosy cases enrolled between December 1997-1998. Patients were recruited at health centers located in the following regions: Southeast = Rio de Janeiro; North = Amazon and Rond?nia states and Center-West = Goiás state. Eligible cases were newly detected, untreated single-lesion leprosy patients without thickened nerve involvement, and were assessed by clinical, bacilloscopic and histopathological exams. The Mitsuda skin test and anti-PGL-I serology (ELISA) were also performed. Of the 299 SSL-PB leprosy patients, 259 (86.6%) fulfilled the criteria for single-dose ROM intervention. Our results showed that patients recruited from different sites had similar features, considering the clinical and immunological profiles. There was a predominance of adults (mean age 32.4; S.D. = 16.0), and a BCG scar was detected in 76.7% of the children (< or = 15 years old). Only 7 cases were diagnosed as the multibacillary type, representing less than 3% of the patients being misclassified. Our data indicate that in Brazil SSL-PB case ascertainment based on clinical and bacilloscopic criteria can be accurately defined under a routine control program; 75.0% of SSL-PB cases were Mitsuda positive (> or = 5 mm) and seropositivity for anti-PGL-I was detected in 17.3% of the patients. These data are compatible with effective cell-mediated immunity and low bacillary load, suggesting favorable clinical outcomes for most SSL-PB participants of this cohort.     

Preliminary appraisal of a WHO-recommended multiple drug regimen in paucibacillary leprosy patients in Malawi

A study was undertaken within the framework of the LEPRA Evaluation Project and the LEPRA Control Project in Malawi (Central Africa) to study the incidence rates of type 1 reactions and of relapses in paucibacillary leprosy patients treated with the current World Health Organization-recommended multiple drug regimen (WHO/MDT). Of 503 patients recruited into the study, 488 were reviewed at the end of treatment and 480 have now been followed for 1 year after completion of treatment. At the end of treatment the skin lesions had completely disappeared in 27.4%, but were judged to be still active in 4.3%. During the follow-up period two patients were found with new active skin lesions, giving a relapse rate of 4.17 (2 of 480) per 1000 person years during the first year after completion of WHO/MDT (95% confidence interval 1.14 to 15.06 per 1000 person years). The incidence rate of marked type 1 reaction (renewed inflammation in previously inactive lesions) during the first year after completion of WHO/MDT was 47.8 per 1000 person years in self-reporting patients but zero in patients identified by active case finding. Data are presented which suggest that the incidence rate of late type 1 reactions is closely related to the classification and stage of the disease at detection.     

Efficacy of single-dose ROM therapy plus low-dose convit vaccine as an adjuvant for treatment of paucibacillary leprosy patients with a single skin lesion

The recent World Health Organization multicentric field study on the treatment of paucibacillary (PB) leprosy patients with single skin lesion (SSL) and a single dose of rifampin-ofloxacin-minocycline (ROM) brought new hope to those who are engaged in the eradication of leprosy from India. Being encouraged by the WHO report, we undertook the present hospital-based study and found that PB leprosy patients with SSL were morphologically and histopathologically heterogeneous. The histological spectrum of SSL ranged from indeterminate through tuberculoid (TT) to borderline tuberculoid (BT) leprosy, and most patients had active BT leprosy. Ninety new, untreated PB leprosy patients with SSL were included in the present study for comparative assessment of the efficacies of ROM and ROM plus Convit vaccine therapies. Children, pregnant women, lactating mothers and patients with any thickening of nerves were excluded. All patients were bacteriologically negative (skin-smear test) but lepromin reactive. The patients were divided into two groups after proper matching for morphological and histological status of SSL: a) The test group included 60 patients and the control group included 30 patients. The test group was given a single dose of ROM initially and two injections of low-dose Convit vaccine, one initially and the other at the end of 3 months. b) The control group was given only a single dose of ROM initially. Both groups were followed clinically every 2 weeks for 6 months and retested for histological, bacteriological and lepromin status at the end of 6 months. Thereafter, they were followed clinically every month for another 6 months. In the test group, the SSL resolved in 33.3%, regressed in 48.3%, and remained active in 18.3% of the patients, while the granuloma disappeared in 70% of the cases. Only one patient developed neuritis, and in another patient the disease relapsed on the eighth month. On the other hand, the SSL in the control patients resolved, regressed and remained active in 13.3%, 63.3% and 23.3% of the cases, respectively, while the granuloma disappeared in 53.3% of the cases. In the seven patients who remained active, the disease course was progressive, and two of them developed neuritis. The clinical outcome of the patients treated with ROM plus low-dose Convit vaccine was statistically superior to those treated with single-dose ROM therapy alone.     

Four-year follow-up results of a WHO-recommended multiple-drug regimen in paucibacillary leprosy patients in Malawi

An evaluation of a World Health Organization-recommended multidrug therapy (WHO/MDT) in 499 paucibacillary leprosy patients is described. Patients were followed for 48 months after completion of treatment. Overall relapse rates after treatment were found to be 6.5 per 1000 person years (95% confidence interval 3.4-11.4). There were 12 relapses. A relative lack of cell-mediated immunity, as suggested by number of lesions, clinical classification and lepromin test results, and poor compliance with the dapsone component of WHO/MDT, appeared to be associated with a marginally increased risk of relapse. Severe type 1 reactions after completion of treatment occurred in 17 (3.5%) patients, 15/17 during the first 12 months of follow-up. Overall, 12 (2.5%) patients developed new disabilities during or after WHO/MDT.