Multidrug Therapy for Leprosy Can Cure Patients with Lobomycosis in Acre State, Brazil: A Proof of Therapy Study.

Lobomycosis, also referred to as lacaziosis, is an endemic cutaneous and subcutaneous fungal disease that mainly affects Amazonian forest dwellers in Brazil. There is no disease control program in place in Brazil, and antifungal therapy failures are common, and the therapy is inaccessible to most patients. We performed a randomized, unblinded clinical trial testing the cure rate of multiple drug therapy (MDT) for leprosy with surgical excision, with or without itraconazole. A control arm consisted of patients who did not adhere to either therapeutic regimens but continued to be followed up. Multiple drug therapy consisted of monthly supervised doses of 600 mg rifampicin, 300 mg clofazimine, and 100 mg dapsone, in addition to daily doses of 50 mg clofazimine and 100 mg dapsone. The patients in the MDT plus itraconazole arm also received itraconazole 100 mg twice daily. We followed up 54 patients from the MDT group and 26 patients from the MDT plus itraconazole group for an average of 4 years and 9 months. The 23 controls were followed up for 6 months on average. The following endpoints were observed: 1) unchanged (no apparent improvement), 2) improved (reduction in lesion size and/or pruritus), and 3) cured (complete remission of the lesions, no viable fungi, and no relapse for 2 years after the end of the drug treatment). The results indicated a significantly greater likelihood of cure associated with the use of multidrug therapy for leprosy with or without itraconazole when compared with the control group. The addition of itraconazole to MDT was not associated with improved outcomes, suggesting that MDT alone is effective.

Mid borderline leprosy in type Bα Blaschko linear pattern: a rare phenomenon.

INTRODUCTION: Leprosy is a chronic granulomatous disease caused by M. leprae. It is a great imitator as it can manifest in different unusual and atypical ways. Mid borderline leprosy (BB) is an unstable form representing the immunologic midpoint in the clinical spectrum. CASE REPORT: Here, we report a case of BB leprosy having classical inverted saucer-shaped lesions elsewhere on the body with a linear psoriasiform lesion over the left forearm following the lines of Blaschko. Biopsy from this lesion revealed granulomas consisting of equal admixture of epithelioid cells and macrophages without multinucleate giant cells suggesting mid borderline leprosy. CONCLUSION: Occurrence of lesions in a Blaschko linear pattern supports the role of genetic susceptibility to leprosy. The genetically vulnerable cells along the lines of Blaschko were infected while the surrounding cells remained unaffected. This explains the concept of locus minoris resistentiae due to cutaneous mosaicism.

Uniform multidrug therapy for leprosy patients in Brazil (U-MDT/CT-BR): Results of an open label, randomized and controlled clinical trial, among multibacillary patients.

BACKGROUND: Leprosy control is based on early diagnosis and multidrug therapy. For treatment purposes, leprosy patients can be classified as paucibacillary (PB) or multibacillary (MB), according to the number of skin lesions. Studies regarding a uniform treatment regimen (U-MDT) for all leprosy patients have been encouraged by the WHO, rendering disease classification unnecessary. METHODOLOGY AND FINDINGS: An independent, randomized, controlled clinical trial conducted from 2007 to 2015 in Brazil, compared main outcomes (frequency of reactions, bacilloscopic index trend, disability progression and relapse rates) among MB patients treated with a uniform regimen/U-MDT (dapsone+rifampicin+clofazimine for six months) versus WHO regular-MDT/R-MDT (dapsone+rifampicin+clofazimine for 12 months). A total of 613 newly diagnosed, untreated MB patients with high bacterial load were included. There was no statistically significant difference in Kaplan-Meyer survival function regarding reaction or disability progression among patients in the U-MDT and R-MDT groups, with more than 25% disability progression in both groups. The full mixed effects model adjusted for the bacilloscopic index average trend in time showed no statistically significant difference for the regression coefficient in both groups and for interaction variables that included treatment group. During active follow up, four patients in U-MDT group relapsed representing a relapse rate of 2.6 per 1000 patients per year of active follow up (95% CI [0·81, 6·2] per 1000). During passive follow up three patients relapsed in U-MDT and one in R-MTD. As this period corresponds to passive follow up, sensitivity analysis estimated the relapse rate for the entire follow up period between 2·9- and 4·5 per 1000 people per year. CONCLUSION: Our results on the first randomized and controlled study on U-MDT together with the results from three previous studies performed in China, India and Bangladesh, support the hypothesis that UMDT is an acceptable option to be adopted in endemic countries to treat leprosy patients in the field worldwide. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00669643.

Multidrug therapy for leprosy: a game changer on the path to elimination.

Leprosy is present in more than 100 countries, where it remains a major cause of peripheral neuropathy and disability. Attempts to eliminate the disease have faced various obstacles, including characteristics of the causative bacillus Mycobacterium leprae: the long incubation period, limited knowledge about its mode of transmission, and its poor growth on culture media. Fortunately, the leprosy bacillus is sensitive to several antibiotics. The first antibiotic to be widely used for leprosy treatment was dapsone in the 1950s, which had to be taken over several years and was associated with increasing bacterial resistance. Therefore, in 1981, WHO recommended that all registered patients with leprosy should receive combination therapy with three antibiotics: rifampicin, clofazimine, and dapsone. Global implementation of this highly effective multidrug therapy took about 15 years. In 1985, 5·3 million patients were receiving multidrug therapy; by 1991, this figure had decreased to 3·1 million (a decrease of 42%) and, by 2000, to 597 232 (a decrease of almost 90%). This reduction in the number of patients registered for treatment was due to shortening of the treatment regimen and achievement of 100% coverage with multidrug therapy. This achievement, which owed much to WHO and the donors of the multidrug therapy components, prompted WHO in 1991 to set a global target of less than one case per 10 000 population by 2000 to eliminate the disease as a public health problem. All but 15 countries achieved this target. Since 2000, about 250 000 new cases of leprosy have been detected every year. We believe an all-out campaign by a global leprosy coalition is needed to bring that figure down to zero.

Multidrug therapy for leprosy: a game changer on the path to elimination

Leprosy is present in more than 100 countries, where it remains a major cause of peripheral neuropathy and disability. Attempts to eliminate the disease have faced various obstacles, including characteristics of the causative bacillus Mycobacterium leprae: the long incubation period, limited knowledge about its mode of transmission, and its poor growth on culture media. Fortunately, the leprosy bacillus is sensitive to several antibiotics. The first antibiotic to be widely used for leprosy treatment was dapsone in the 1950s, which had to be taken over several years and was associated with increasing bacterial resistance. Therefore, in 1981, WHO recommended that all registered patients with leprosy should receive combination therapy with three antibiotics: rifampicin, clofazimine, and dapsone. Global implementation of this highly effective multidrug therapy took about 15 years. In 1985, 5·3 million patients were receiving multidrug therapy; by 1991, this figure had decreased to 3·1 million (a decrease of 42%) and, by 2000, to 597 232 (a decrease of almost 90%). This reduction in the number of patients registered for treatment was due to shortening of the treatment regimen and achievement of 100% coverage with multidrug therapy. This achievement, which owed much to WHO and the donors of the multidrug therapy components, prompted WHO in 1991 to set a global target of less than one case per 10 000 population by 2000 to eliminate the disease as a public health problem. All but 15 countries achieved this target. Since 2000, about 250 000 new cases of leprosy have been detected every year. We believe an all-out campaign by a global leprosy coalition is needed to bring that figure down to zero.

Uniform multidrug therapy for leprosy patients in Brazil (U-MDT/CT-BR): results of an open label, randomized and controlled clinical trial, among multibacillary patients

BACKGROUND: Leprosy control is based on early diagnosis and multidrug therapy. For treatment purposes, leprosy patients can be classified as paucibacillary (PB) or multibacillary (MB), according to the number of skin lesions. Studies regarding a uniform treatment regimen (U-MDT) for all leprosy patients have been encouraged by the WHO, rendering disease classification unnecessary. METHODOLOGY AND FINDINGS: An independent, randomized, controlled clinical trial conducted from 2007 to 2015 in Brazil, compared main outcomes (frequency of reactions, bacilloscopic index trend, disability progression and relapse rates) among MB patients treated with a uniform regimen/U-MDT (dapsone+rifampicin+clofazimine for six months) versus WHO regular-MDT/R-MDT (dapsone+rifampicin+clofazimine for 12 months). A total of 613 newly diagnosed, untreated MB patients with high bacterial load were included. There was no statistically significant difference in Kaplan-Meyer survival function regarding reaction or disability progression among patients in the U-MDT and R-MDT groups, with more than 25% disability progression in both groups. The full mixed effects model adjusted for the bacilloscopic index average trend in time showed no statistically significant difference for the regression coefficient in both groups and for interaction variables that included treatment group. During active follow up, four patients in U-MDT group relapsed representing a relapse rate of 2.6 per 1000 patients per year of active follow up (95% CI [0·81, 6·2] per 1000). During passive follow up three patients relapsed in U-MDT and one in R-MTD. As this period corresponds to passive follow up, sensitivity analysis estimated the relapse rate for the entire follow up period between 2·9- and 4·5 per 1000 people per year. CONCLUSION: Our results on the first randomized and controlled study on U-MDT together with the results from three previous studies performed in China, India and Bangladesh, support the hypothesis that UMDT is an acceptable option to be adopted in endemic countries to treat leprosy patients in the field worldwide.

Glomerulonefritis por inmunocomplejos en un paciente con lepra / Immune-complex glomerulonephritis in a patient with leprosy

La lepra es una enfermedad cuyas manifestaciones se dan a nivel cutáneo y neurológico periférico. Es conocida desde siglos atrás y continúa siendo un problema de salud pública a nivel mundial. La prevalencia ha disminuido después de la instauración de esquemas de tratamiento poliquimioterápicos. En Colombia no está considerada como un problema de salud pública por su baja prevalencia. El compromiso multisistémico es común, especialmente en las formas multibacilares. Los sistemas articular y renal son frecuentemente afectados, aunque estas afectaciones son en muchas ocasiones pasadas por alto. Se reporta el caso de un paciente con lepra lepromatosa que presentó glomerulonefritis mediada por inmunocomplejos y, además, compromiso poliarticular secundario a una reacción leprosa del tipo eritema nudoso lepromatoso. No hay conciencia por parte del personal de salud sobre las características de la enfermedad, ya que en muchos casos se cree erradicada. Este caso ilustra la importancia del reconocimiento y tratamiento oportunos para prevenir la discapacidad asociada.

Leprosy is a disease whose manifestations are seen in the skin and at the peripheral neurological level. It has been known for centuries and remains a public health problem worldwide; however its prevalence has declined after the introduction of multidrug treatment schemes. In Colombia leprosy is not considered a public health problem because of its low incidence. Multisystem compromise is common, especially in multibacillary forms, with the articular and renal systems commonly affected; although these effects are often overlooked. We report a patient with lepromatous leprosy who presented immune-mediated glomerulonephritis and polyarticular impairment secondary to erythaema nodosum leprosum. There is no awareness on the part of health personnel on the characteristics of the disease and in many cases are believed eradicated. This case illustrates the importance of early recognition and timely treatment to prevent disability associated.

Epidemiología de la lepra en la región del Norte Araguaia, MT, Brasil, en el período entre 2001 y 2012 (parte III) / No disponible

No disponible

Leprosy New Case Detection Trends and the Future Effect of Preventive Interventions in Pará State, Brazil: A Modelling Study.

BACKGROUND: Leprosy remains a public health problem in Brazil. Although the overall number of new cases is declining, there are still areas with a high disease burden, such as Pará State in the north of the country. We aim to predict future trends in new case detection rate (NCDR) and explore the potential impact of contact tracing and chemoprophylaxis on NCDR in Pará State. METHODS: We used SIMCOLEP, an existing individual-based model for the transmission and control of M. leprae, in a population structured by households. The model was quantified to simulate the population and observed NCDR of leprosy in Pará State for the period 1990 to 2014. The baseline scenario was the current control program, consisting of multidrug therapy, passive case detection, and active case detection from 2003 onwards. Future projections of the NCDR were made until 2050 given the continuation of the current control program (i.e. baseline). We further investigated the potential impact of two scenarios for future control of leprosy: 1) discontinuation of contact tracing; and 2) continuation of current control in combination with chemoprophylaxis. Both scenarios started in 2015 and were projected until 2050. RESULTS: The modelled NCDR in Pará State after 2014 shows a continuous downward trend, reaching the official elimination target of 10 cases per 100,000 population by 2030. The cessation of systematic contact tracing would not result in a higher NCDR in the long run. Systematic contact tracing in combination with chemoprophylaxis for contacts would reduce the NCDR by 40% and bring attainment of the elimination target two years forward to 2028. CONCLUSION: The NCDR of leprosy continues to decrease in Pará State. Elimination of leprosy as a public health problem could possibly be achieved around 2030, if the current control program is maintained. Providing chemoprophylaxis would decrease the NCDR further and would bring elimination forward by two years.

Global elimination of leprosy by 2020: are we on track?

BACKGROUND: Every year more than 200,000 new leprosy cases are registered globally. This number has been fairly stable over the past 8 years. WHO has set a target to interrupt the transmission of leprosy globally by 2020. The aim of this study is to investigate whether this target, interpreted as global elimination, is feasible given the current control strategy. We focus on the three most important endemic countries, India, Brazil and Indonesia, which together account for more than 80 % of all newly registered leprosy cases. METHODS: We used the existing individual-based model SIMCOLEP to predict future trends of leprosy incidence given the current control strategy in each country. SIMCOLEP simulates the spread of M. leprae in a population that is structured in households. Current control consists of passive and active case detection, and multidrug therapy (MDT). Predictions of leprosy incidence were made for each country as well as for one high-endemic region within each country: Chhattisgarh (India), Pará State (Brazil) and Madura (Indonesia). Data for model quantification came from: National Leprosy Elimination Program (India), SINAN database (Brazil), and Netherlands Leprosy Relief (Indonesia). RESULTS: Our projections of future leprosy incidence all show a downward trend. In 2020, the country-level leprosy incidence has decreased to 6.2, 6.1 and 3.3 per 100,000 in India, Brazil and Indonesia, respectively, meeting the elimination target of less than 10 per 100,000. However, elimination may not be achieved in time for the high-endemic regions. The leprosy incidence in 2020 is predicted to be 16.2, 21.1 and 19.3 per 100,000 in Chhattisgarh, Pará and Madura, respectively, and the target may only be achieved in another 5 to 10 years. CONCLUSIONS: Our predictions show that although country-level elimination is reached by 2020, leprosy is likely to remain a problem in the high-endemic regions (i.e. states, districts and provinces with multimillion populations), which account for most of the cases in a country.

It is time to review concepts on renal involvement in leprosy: pre- and post-treatment evaluation of 189 patients.

BACKGROUND: Functional and morphological renal lesions have been widely described in leprosy for decades. Nevertheless few studies have assessed renal function pre- and during treatment after the advent of multidrug therapy (MDT). METHODS: This is a prospective study involving 189 consecutive patients, with all forms of leprosy (Ridley-Jopling scale). Laboratory (serum urea and creatinine, estimated GFR, urinalysis, microalbuminuria, urinary RBP) and clinical features of renal disease were evaluated previously and after onset (3 and 8 months later) of MDT. RESULTS: One hundred and eighty-nine patients (M 1.8: F 1; mean age 44 ± 16 years) were included just after diagnosis of leprosy and before the introduction of MDT. Mean time until manifestation of symptoms and/or signs of leprosy was 29 ± 56 months (25 days-480 months). Microhematuria and microalbuminuria were detected in 7.5% and 9.6% of the cases, respectively. Elevated serum creatinine was detected in 34% pre-MDT; this was statistically more frequent in males, hypertensive and frequent users of non-steroidal anti-inflammatory drugs (NSAID), as well as in patients with erythema nodosum lepromatosum, 45.5% by the time of diagnosis, 18% after 3 months and 9% after 8 months of MDT (p = 0.039). CONCLUSIONS: Our results suggest that functional renal lesions in leprosy are currently mild and predominantly of glomerular origin, in opposition to the severe involvement described in the past. This improved outcome of renal disease secondary to leprosy is possibly due to the advent of MDT and effective treatment of episodes of reaction, leading to shorter periods of active infectious disease.

Enfermedad de Hansen y ginecomastia / No disponible

La lepra es una de las causas de ginecotelia, sin embargo poco se ha publicado sobre este signo común y generalmente ignorado. La prevalencia de ginecomastia, una complicación bien conocida de la lepra en pacientes varones adultos, es poco reportada. El tratamiento temprano tiene un efecto notable en la reducción de la misma. Presentamos el caso de un varón con lepra multibacilar con ginecotelia y ginecomastia, en el curso de la enfermedad

Leprosy is one of the causes of gynaecothelia, however little has been published on this common and generally ignored sign. The prevalence of gynecomastia, a well known leprosy complication in adult male patients, is little reported. Early treatment has a marked effect in reducing it. Here we present the case of a man with multibacillary leprosy who had been associated gynaecothelia and gynecomastia in the course of the disease

Six years' follow-up of multibacillary leprosy patients treated with uniform multi-drug therapy in China.

OBJECTIVE: This study was conducted to evaluate the effectiveness of uniform multi-drug therapy (UMDT) in patients with multibacillary (MB) leprosy. METHODS: Newly detected MB leprosy patients were treated with six months of UMDT as recommended by the World Health Organization (WHO). The effectiveness of treatment was evaluated by clinical status and skin smear tests. RESULTS: At the start, 114 patients were recruited, examined, and treated. These patients were re-examined and followed annually for up to six years. A total of 75 (65.8%) patients completed six years of follow-up. Dropouts were attributable to death, severe drug reactions, and other reasons. The mean ± standard deviation bacteriological index (BI) of all patients decreased from 3.01 ± 1.50 before treatment to 0.02 ± 1.84 at the end of year 6, reflecting a mean annual decrease of 0.50. The rate of smear negativity in all patients was 98.7% at the end of year 6 of follow-up. A total of 53 leprosy reactions were observed. One patient relapsed 13 months after the cessation of treatment. CONCLUSIONS: A 6-month administration of UMDT is effective in MB leprosy patients. The changes in BI values and the frequency of leprosy reactions were similar to those cited in reports in the literature of patients treated with 1- or 2-year regimens of MDT. However, further research should be conducted to confirm the present results.