Mycobacterium leprae: aspectos da resistência aos fármacos na poliquimioterapia / Drug resistance in multidrug therapy for Mycobacterium leprae

Introdução: O diagnóstico da hanseníase possui números significativos que causam preocupação à saúde pública. Os casos de resistência medicamentosa nessa doença se iniciaram em meados dos anos 60 e diante do problema, a Organização Mundial da Saúde instituiu em 1981 a poliquimioterapia, associação dos antibióticos rifampicina, dapsona e clofazimina, tratamento atual de escolha. A resistência aos fármacos na hanseníase é reportada pela literatura, desvelando um obstáculo à sua eliminação. Apresentamos nessa revisão os principais aspectos da resistência medicamentosa no tratamento para hanseníase e seus impactos. Metodologia: Revisão sistemática sobre os aspectos da resistência medicamentosa utilizando a pesquisa exploratória como metodologia de abordagem. Foram pesquisados os termos resistência medicamentosa, hanseníase, recidiva, alterações genéticas e os operadores booleanos "and" e "or" na busca. Resultados e discussão: A dificuldade de tomar a medicação corretamente foi um dos principais fatores que acarretaram resistência do bacilo Mycobacterium leprae aos fármacos. Homens de países norte e sul-americanos e asiáticos foram os mais atingidos por episódios de resistência. A resistência medicamentosa é uma das principais causas de recidivas em hanseníase. O principal fármaco causador de resistência medicamentosa descrito nos trabalhos foi a dapsona (46,6%) e a maioria das alterações genéticas encontradas estão no gene rpoB; 23,2% dos registros relatados foram de resistência secundária aos fármacos e, também, sete casos de resistência múltipla a esses medicamentos. Conclusão: Os principais aspectos da resistência medicamentosa na hanseníase são os equívocos ao ingerir os medicamentos e as alterações genéticas na bactéria. Os impactos causados estão na dificuldade de refazer o tratamento, a possibilidade de nova transmissão e o aparecimento de sintomas mais graves.

Introduction: The diagnosis of leprosy has significant numbers causing public health concern. Reports of drug resistance in this disease begun in the mid-1960s and due to this problem, the World Health Organization instituted a multidrug therapy with rifampicin, dapsone, and clofazimine antibiotic association in 1981, which is currently the first-choice treatment for leprosy. Cases of drug resistance have been reported in literature, revealing an obstacle to the eradication of the disease. This paper has the purpose of presenting the key aspects and impacts of drug resistance in the treatment for leprosy. Methods: Systematic review of the drug resistance aspects using exploratory research as an approach methodology. The authors searched the terms drug resistance, leprosy, recurrence, genetic alterations, and the Boolean operators "and" and "or" between them. Results and discussion: The difficulty in taking the medication correctly was one of the key factors that led to drug resistance for Mycobacterium leprae. Men from North and South American, as well as from Asian countries, were the most affected by episodes of resistance. Drug resistance is one of the main causes of leprosy recurrences. Dapsone was the most frequently identified drug resistance in the studies (46.6%), while most of the genetic alterations were found in the rpoB gene; 23.2% of the cases were from secondary resistance episodes, and seven cases of multiple resistance were reported. Conclusion: The misconceptions when taking the treatment and the Mycobacterium leprae genetic alterations have been described as the key aspects of drugs resistance in leprosy and the impacts caused are the difficulty in redoing the treatment, the possibility of new transmission, and the appearance of more severe symptoms.

Ofloxacin-Containing Multidrug Therapy in Ambulatory Leprosy Patients: A Case Series.

BACKGROUND: Standard dapsone and clofazimine-containing multidrug therapy (MDT) for leprosy is limited by drug tolerability, which poses treatment adherence barriers. Although ofloxacin-based regimens are promising alternatives, current efficacy and safety data are limited, particularly outside of endemic areas. We evaluated treatment outcomes in patients with leprosy receiving ofloxacin-containing MDT (OMDT) at our center. METHODS: We performed a retrospective chart review of patients treated for leprosy at our center over an 8-year period (2011-2019). Primary outcomes evaluated were clinical cure rate, occurrence of leprosy reactions, antibiotic-related adverse events, and treatment adherence. Analyses were descriptive; however, data were stratified by age, sex, spectrum of disease, region of origin, and treatment regimen, and odds ratios were reported to assess associations with adverse outcomes. RESULTS: Over the enrolment period, 26 patients were treated with OMDT (n = 19 multibacillary, n = 7 paucibacillary), and none were treated with clofazimine-based standard MDT. At the time of analysis, 23 patients (88%) had completed their course of treatment, and all were clinically cured, while 3 (12%) were still on treatment. Eighteen patients (69%) experienced either ENL (n = 7, 27%), type 1 reactions (n = 7, 27%), or both (n = 4, 15%). No patients stopped ofloxacin due to adverse drug effects, and there were no cases of allergic hypersensitivity, tendinopathy or rupture, or C. difficile colitis. CONCLUSIONS: We demonstrate a high cure rate and tolerability of OMDT in this small case series over an 8-year period, suggesting its viability as an alternative to standard clofazimine-containing MDT.

Late leprosy reaction presenting as erythema multiforme-like erythema nodosum leprosum with underlying rifampicin resistance and its potential implications.

Erythema multiforme (EM)-like erythema nodosum leprosum (ENL) is a rare atypical presentation, and its late appearance after the completion of multidrug therapy (MDT) is unusual. We describe the case of a lepromatous leprosy patient who after the completion of MDT presented to us with late EM-like ENL and was found to be resistant to rifampicin. We discuss the implications of this finding and the potential role of resistant bacilli in causing reactions with atypical presentations.

World Health Organization (WHO) antibiotic regimen against other regimens for the treatment of leprosy: a systematic review and meta-analysis.

BACKGROUND: To evaluate the effectiveness and safety of the World Health Organization antibiotic regimen for the treatment of paucibacillary (PB) and multibacillary (MB) leprosy compared to other available regimens. METHODS: We performed a search from 1982 to July 2018 without language restriction. We included randomized controlled trials, quasi-randomized trials, and comparative observational studies (cohorts and case-control studies) that enrolled patients of any age with PB or MB leprosy that were treated with any of the leprosy antibiotic regimens established by the WHO in 1982 and used any other antimicrobial regimen as a controller. Primary efficacy outcomes included: complete clinical cure, clinical improvement of the lesions, relapse rate, treatment failure. Data were pooled using a random effects model to estimate the treatment effects reported as relative risk (RR) with 95% confidence intervals (CI). RESULTS: We found 25 eligible studies, 11 evaluated patients with paucibacillary leprosy, while 13 evaluated patients with MB leprosy and 1 evaluated patients of both groups. Diverse regimen treatments and outcomes were studied. Complete cure at 6 months of multidrug therapy (MDT) in comparison to rifampin-ofloxacin-minocycline (ROM) found RR of 1.06 (95% CI 0.88-1.27) in five studies. Whereas six studies compare the same outcome at different follow up periods between 6 months and 5 years, according to the analysis ROM was not better than MDT (RR of 1.01 (95% CI 0.78-1.31)) in PB leprosy. CONCLUSION: Not better treatment than the implemented by the WHO was found. Diverse outcome and treatment regimens were studied, more statements to standardized the measurements of outcomes are needed.

Leprosy in elderly people and the profile of a retrospective cohort in an endemic region of the Brazilian Amazon.

BACKGROUND: Leprosy has a global presence; more than 180 thousand new cases were registered in 2013, 15% of which were found in the Americas. The elderly are a very susceptible demographic in terms of developing illnesses, mainly because of characteristics natural to the senescence of the human organism. This study's goals were to analyze leprosy in an elderly population from a hyperendemic region of the Brazilian Amazon in a historical series from 2004 to 2013 and to determine the clinical and epidemiological profile of a series of leprosy cases of elderly people in the period spanning from 2009 to 2013. METHODS: To achieve these goals, an observational, longitudinal, retrospective and descriptive study was put together to analyze leprosy in elderly people from data acquired from the Notification Aggravations Information System. Furthermore, a profile of the disease from a retrospective cohort based on data collected from medical records was developed. RESULTS: The number of new cases and the leprosy detection rate decreased across the observed period but remained stable among the elderly. The trend for the next ten years indicates decreases in the number of cases and in the detection rate in the general population and an increase in only the elderly. The overall profile was characterized by a predominance of males (64.32%), the multibacillary clinical form (87.57%), Type 1 reaction episodes (37.50%) and some physical incapacity at diagnosis (49.19%). The risk of reaction was greater in the first six months of multidrug therapy, and the positive result from the skin smear was associated with the greater chance of reactional condition development. CONCLUSIONS: The resulting data demonstrate that leprosy amongst the elderly deserves attention because of the increased susceptibility to disability in this age group, with their higher risk of reaction and their greater level of co-morbidity.

Epidemiological, clinical and immune factors that influence the persistence of antiphospholipid antibodies in leprosy

Abstract Introduction: Antiphospholipid antibodies (aPL) are described in individuals with leprosy without the clinical features of antiphospholipid antibody syndrome (APS), a condition involving thromboembolic phenomena. We have described the persistence of these antibodies for over 5 years in patients with leprosy after specific treatment. Objectives: To determine whether epidemiological, clinical and immunological factors played a role in the longterm persistence of aPL antibodies in leprosy patients after multidrug therapy (MDT) had finished. Methods: The study sample consisted of 38 patients with a diagnosis of leprosy being followed up at the Dermatology and Venereology Outpatient Department at the Alfredo da Matta Foundation (FUAM) in Manaus, AM. ELISA was used to detect anticardiolipin (aCL) and anti-β2 glycoprotein I (anti-β2GPI) antibodies. Patients were reassessed on average of 5 years after specific treatment for the disease (MDT) had been completed. Results: Persistence of aPL antibodies among the 38 leprosy patients was 84% (32/38), and all had the IgM isotype. Mean age was 48.1 ± 15.9 years, and 23 (72.0%) were male. The lepromatous form (LL) of leprosy was the most common (n = 16, 50%). Reactional episodes were observed in three patients (9.4%). Eighteen (47.37%) were still taking medication (prednisone and/or thalidomide). Mean IgM levels were 64 U/mL for aCL and 62 U/mL for anti-β2GPI. In the multivariate binary logistic regression the following variables showed a significant association: age (p = 0.045, OR = 0.91 and CI 95% 0.82-0.98), LL clinical presention (p = 0.034; OR = 0.02 and CI 95% = 0.0-0.76) and bacterial index (p = 0.044; OR = 2.74 and CI 95% = 1.03-7.33). We did not find association between prednisone or thalidomide doses and positivity for aPL (p = 0.504 and p = 0.670, respectively). No differences in the variables vascular thrombosis, pregnancy morbidity, diabetes, smoking and alcoholism were found between aPL-positive and aPL-negative patients. Conclusion: Persistence of positivity for aPL antibodies was influenced by age, clinical presentation and bacterial index. However, further studies are needed to elucidate the reason for this persistence, the role played by aPL antibodies in the disease and the B cell lineages responsible for generation of these antibodies.

Efectos colaterales de antibacilares en pacientes con enfermedad de Hansen / No disponible

Introducción: La Organización Mundial de la Salud (OMS) recomendó el uso de la poliquimioterapia (PQT) desde 1981, y desde 1998 esta pauta de tratamiento fue introducida en Paraguay. Desde ese entonces y hasta la actualidad el esquema Multibacilar (MB) comprende tres drogas: rifampicina, clofazimina y dapsona, y, el esquema Paucibacilar (PB), dos drogas: rifampicina y dapsona. Todas ellas relacionadas en mayor o menor medida a efectos colaterales. A pesar de ello, hay pocos estudios a nivel mundial, y ningún estudio en el Paraguay. Métodos: Estudio retrospectivo, observacional, de corte transversal con componente analítico, llevado a cabo en la Cátedra de Dermatología del Hospital de Clínicas - Universidad Nacional de Asunción, en San Lorenzo, Paraguay. En el periodo de enero de 2013 a octubre de 2017. Resultados: Fueron incluidos en el estudio 58 pacientes con enfermedad de Hansen, de los cuales 45 (78%) presentaron al menos un efecto colateral a la PQT, 3 pacientes presentaron más de un efecto colateral. De los 45, 25 (56%) fueron del sexo masculino y 20 (44%) del sexo femenino. En cuanto a la distribución por rango de edad: Dos (4%) en menores de 18 años, 8 (18%) de 19 a 30 años, 27 (18%) de 31 a 59 años y 8 (18%) 60 y más años. Seis (3%) pacientes de procedencia rural y 39 (87%) de procedencia urbana. Cuarenta y siete (98%) casos de efectos colaterales hematológicos (Anemia: 45; leucopenia: 1 y trombocitopenia: 1) y 1 (2%) caso de efecto colateral gastrointestinal (hepatitis). La conducta en casos de anemia: suplementación con hierro y ácido fólico: 40, suspensión de dapsona: 10 y ninguna conducta: 6 suspensión de la dapsona en 1 caso de leucopenia, suspensión de la dapsona en 1 caso de trombocitopenia y suspensión de la rifampicina en 1 caso de hepatitis. En 26 (58%) pacientes los efectos colaterales se presentaron al mes del inicio de la PQT, en 15 (33%) pacientes entre 2 y 5 meses del inicio y en 4 (9%) pacientes a los 6 y más meses del inicio. En 14 (31%) de los pacientes con efectos colaterales existía comorbilidad y en 31 (69%) casos, eran pacientes sanos. De los 45 pacientes, 41 (91%) estaban en tratamiento MB, 4 (9%) en tratamiento PB. Conclusión: La mayoría de los pacientes incluidos en el estudio presentaron efectos colaterales. Los hombres fueron los más afectados, el rango etario en el cual se presentaron con mayor frecuencia fue entre los 31 y 59 años. La mayoría procedían del medio urbano. Los efectos colaterales más frecuentes fueron los hematológicos y, de entre ellos, la anemia. Ante tal situación la medida más frecuentemente adoptada fue la suplementación con hierro y ácido fólico. En la mayoría de los casos los efectos colaterales aparecieron en el primer mes de recibir la medicación. Aquellos pacientes que recibieron PQT MB presentaron la mayor frecuencia de efectos colaterales

Introduction: The World Health Organization (WHO) recommends the implementation of multidrug (MDT) since 1981, and this régimen was introduced in Paraguay in 1998. The MDT administrate three drugs: rifampicin, clofazimine and dapsone to multibacillary patients (MB) and only two: rifampicina and dapsone to paucibacillary patients (PB). All the drugs have some adverse effects. But very few statistics have been carried out in the world on this matter and none at all in Paraguay. Methods: The work is a retrospective, observational, cross-sectional and analytical study carried out at Catedra de Dermatología del Hospital de Clínicas-Universidad Nacional de Asunción, San Lorenzo, Paraguay between January 2013 and October 2017. Results: Fifty eight leprosy patients were registered in the study and 45 (78%) presented at least one adverse effect to the MDT and 3 patients presented more tan one. 25/45 were men and 20 (44%) women. The age distributions were: Two (4%) less than 18 years old, 8 (18%) between 19-30 years old, 27(18%) 31-59 years old and 8 (18%) 60 and older. Six (3%) lived in rural setting and 39 (87%) urban. Forty seven (98%) presented adverse hematological effects (anemia: 45, leucopenia: 1 and thrombocytopenia:1) and 1 (2%) presented a gastrointestinal effect. Forty patients with anemia received iron and folic acid supplements and 6 cases with no modifications. There was 1 case leucopenia, 1 thrombocytopenia, and 1 hepatitis due to rifampicine. In 26 patients (58%) adverse effects were detected during first month of MDT, in 15 (33%) between 2-5 of treatment and in 4 (9%) patients after 6 or more months of treatment. Fourteen (31%) patients had comorbility and 31 (69%) were healthy patients. Forty one (91%) patients were receiving MB MDT and 4 (9%) PB MDT. Conclusions: The mayority of the patients in the study presented adverse effects. Men were the most affected and the mayority were in the 31-59 years age group and from urban settings. Most of the effects were hematological and among them, anemia the most frequent. These cases were supplemented with iron and folic acid. Most adverse effects appeared during the first month of treatment and MB MDT group was the most affected

Clinical trial for uniform multidrug therapy for leprosy patients in Brazil (U-MDT/CT-BR): adverse effects approach.

BACKGROUND: The Clinical Trial for Uniform Multidrug Therapy for Leprosy Patients in Brazil (U-MDT/CT-BR), designed to evaluate the effectiveness of a six-months regimen, assessed the adverse effects caused by the drugs. OBJECTIVE: Describe adverse effects due to MDT in U-MDT/CT-BR, comparing the uniform regimen (U-MDT) to the current WHO regimen (R-MDT). PATIENTS AND METHODS: After operational classification, patients were randomly allocated to the study groups. U-MDT PB and U-MDT MB groups, received the U-MDT regimen, six doses of MB-MDT (rifampicin, dapsone and clofazimine). R-MDT PB and R-MDT MB groups, received the WHO regimens: six doses (rifampicin and dapsone) for PB and 12 doses (rifampicin, dapsone and clofazimine) for MB. During treatment, patients returned monthly for clinical and laboratorial evaluation. Patients with single lesion were not included in this trial. RESULTS: Skin pigmentation (21.7%) and xerosis (16.9%) were the most frequent complaints among 753 patients. Laboratory exams showed hemoglobin concentration lower than 10g/dL in 23.3% of the patients, glutamic oxaloacetic transaminase (GOT) above 40U/L in 29.5% and glutamic pyruvic transaminase (GPT) above 40U/L in 28.5%. Twenty-four patients (3.2%) stopped dapsone intake due to adverse effects, of whom 16.6% due to severe anemia. One case of sulfone syndrome was reported. STUDY LIMITATIONS: Loss of some monthly laboratory sample collection. CONCLUSIONS: There was no statistical difference regarding adverse effects in the R-MDT and U-MDT groups but anemia was greater in patients from R-MDT/MB group, therefore adverse effects do not represent a constraint to recommend the six-month uniform regimen of treatment for all leprosy patients.

Clinical trial for uniform multidrug therapy for leprosy patients in Brazil (U-MDT/CT-BR): adverse effects approach

Abstract: BACKGROUND: The Clinical Trial for Uniform Multidrug Therapy for Leprosy Patients in Brazil (U-MDT/CT-BR), designed to evaluate the effectiveness of a six-months regimen, assessed the adverse effects caused by the drugs. OBJECTIVE: Describe adverse effects due to MDT in U-MDT/CT-BR, comparing the uniform regimen (U-MDT) to the current WHO regimen (R-MDT). Patients and methods: After operational classification, patients were randomly allocated to the study groups. U-MDT PB and U-MDT MB groups, received the U-MDT regimen, six doses of MB-MDT (rifampicin, dapsone and clofazimine). R-MDT PB and R-MDT MB groups, received the WHO regimens: six doses (rifampicin and dapsone) for PB and 12 doses (rifampicin, dapsone and clofazimine) for MB. During treatment, patients returned monthly for clinical and laboratorial evaluation. Patients with single lesion were not included in this trial. RESULTS: Skin pigmentation (21.7%) and xerosis (16.9%) were the most frequent complaints among 753 patients. Laboratory exams showed hemoglobin concentration lower than 10g/dL in 23.3% of the patients, glutamic oxaloacetic transaminase (GOT) above 40U/L in 29.5% and glutamic pyruvic transaminase (GPT) above 40U/L in 28.5%. Twenty-four patients (3.2%) stopped dapsone intake due to adverse effects, of whom 16.6% due to severe anemia. One case of sulfone syndrome was reported. STUDY LIMITATIONS: Loss of some monthly laboratory sample collection. CONCLUSIONS: There was no statistical difference regarding adverse effects in the R-MDT and U-MDT groups but anemia was greater in patients from R-MDT/MB group, therefore adverse effects do not represent a constraint to recommend the six-month uniform regimen of treatment for all leprosy patients.

Reacción lepromatosa tipo I, a propósito de un caso / Type I lepra reaction: a case report

La lepra es una infección crónica, granulomatosa, producida por Mycobacterium leprae, que afecta piel y nervios periféricos. Se describen dos tipos de reacciones leprosas: tipo I y tipo II, las que corresponden a cuadros agudos que exacerban la enfermedad. Estas leproreacciones pueden ocurrir antes, durante o después del tratamiento. Se presenta el caso de un paciente masculino que acude a consultar con lesiones cutáneas y resultado de biopsia de piel con diagnóstico de lepra. Se inicia tratamiento multidroga OMS-MB1. Posteriormente presenta una leproreacción tipo I, por lo que se le realiza tratamiento con prednisona.

Leprosy is a chronic granulomatous infection of the skin and peripheral nervous system produced by Mycobacterium leprae. Two types of acute leprosy reactions have been described: type I and type II. These reactions can occur before, during or after treatment. We present the case of an adult male patient presenting with skin lesions and skin biopsy diagnostic for leprosy. A multidrug WHO-MB 1 treatment was initiated, after which he presents with type I lepra reaction requiring corticosteroids.

Efeitos adversos da poliquimioterapia para hanseníase: utilização de doses alternativas e avaliação pós alta / Adverse effects of multidrug therapy for leprosy: use of alternative doses and post discharge evaluation

O tratamento da hanseníase pode causar efeitos adversos relacionados à Rifampicina (RMP) ou Dapsona (DDS) levando à mudança no esquema terapêutico. Objetivou-se determinar as causas da mudança do tratamento e avaliar as condições clínicas dermatológicas dos pacientes que fizeram uso da terapêutica alternativa. De 182 pacientes tratados entre 1997-2008, 34 (18,7%) fizeram doses alternativas e 21 foram entrevistados. O perfil foi constituído por casados, de 40 à 59 anos, baixa condição socioeconômica e escolaridade. Os pacientes paucibacilares (PB) e multibacilares (MB) sem o uso de DDS e de RMP tiveram as últimas baciloscopias (BAAR) negativas (>50%), e os resultados positivos dos outros mostrou involução lenta. A forma clínica mais incidente foi a virchowiana nos intolerantes à DDS, e a dimorfa nos sem a RMP. Os efeitos adversos acometeram mais os MB. Nos intolerantes à DDS, a mudança do esquema terapêutico foi relacionada às causas hematológicas (48,5%) e os à RMP, as hepáticas (50%). Na avaliação as placas e nódulos desapareceram. As manchas, dor geral ou localizada em membros, diminuição da sensibilidade e da força muscular com aparecimento de garra móvel foram significativas. A evolução das incapacidades revelou a necessidade de monitorar atentamente a função neural nos casos de alta.

Leprosy treatment can cause adverse effects related to rifampin (RMP) or dapsone (DDS) leading to changes of the therapeutic regimen. The objective was to determine the causes of changes in the treatment and to evaluate the clinical dermatological conditions of patients who underwent alternative therapy. Out of 182 patients treated between 1997- 2008, 34 (18.7%) underwent alternative doses, and 21 were interviewed. The profile of the patients was: married, 40 to 59 years, low socioeconomic and educational status. The latest bacilloscopic index (BI) of paucibacillary (PB) and multibacillary (MB) patients that did not use DDS and RMP was negative (> 50%), and the positive results observed in the other patients evidenced slow recovery. The most frequent clinical form was lepromatous in patients intolerant to DDS and borderline leprosy in those without RMP. Adverse effects were most commonin MB patients. Intolerance to DDS was related to hematological causes (48.5%), and intolerance to RMP was due to hepatic conditions (50%). Upon evaluation nodules and plaques disappeared. Plaques, generalor localized pain in limbs, reduced sensitivity and muscular strength with the appearance of claw were significant findings. The development of disabilities revealed the need of careful monitoring of the neural function in cases discharged from treatment.

Borderline tuberculoid leprosy and type 1 leprosy reaction in a hepatitis C patient during treatment with interferon and ribavirin.

Hepatitis C is an inflammatory disease of the liver caused by a single-stranded RNA virus belonging to the Hepacivirus genus in the Flaviviridae family, called the hepatitis C virus. After initial infection, 70% to 85% of the patients develop chronic hepatitis C with hepatic fibrosis. In addition to specific liver changes, various extrahepatic manifestations have been associated with the hepatitis C virus infection or with medications used to treat the condition. We report the case of a patient with chronic hepatitis C who presented with the signs and symptoms of borderline tuberculoid leprosy and type 1 reaction four months after the start of treatment with a pegylated interferon/ribavirin combination.

Borderline tuberculoid leprosy and type 1 leprosy reaction in a hepatitis C patient during treatment with interferon and ribavirin / Hanseniase boderline tuberculoide e reacao hansenica do tipo 1 em paciente com hepatite C durante tratamento com interferon e ribavirina

Hepatitis C is an inflammatory disease of the liver caused by a single-stranded RNA virus belonging to the Hepacivirus genus in the Flaviviridae family, called the hepatitis C virus. After initial infection, 70% to 85% of the patients develop chronic hepatitis C with hepatic fibrosis. In addition to specific liver changes, various extrahepatic manifestations have been associated with the hepatitis C virus infection or with medications used to treat the condition. We report the case of a patient with chronic hepatitis C who presented with the signs and symptoms of borderline tuberculoid leprosy and type 1 reaction four months after the start of treatment with a pegylated interferon/ribavirin combination.

A hepatite C é uma doença inflamatória fígado causada por um vírus RNA de fita simples, pertencente ao gênero Hepacivirus e à família Flaviviridae, denominado de vírus da hepatite C. Após infecção inicial 70 a 85% dos pacientes infectados evoluem para hepatite C crônica, com fibrose progressiva. Além das alterações hepáticas específicas, várias manifestações extra-hepáticas têm sido relacionadas à infecção pelo vírus da hepatite C ou às medicações utilizadas no seu tratamento. Nesse trabalho, apresenta-se caso de paciente portador de hepatite C crônica, que manifestou um quadro hanseníase boderline tuberculóide e reação hansênica do tipo I, quatro meses após início do tratamento com interferon peguilado associado à ribavirina.

Adverse effects of alternative therapy (minocycline, ofloxacin, and clofazimine) in multibacillary leprosy patients in a recognized health care unit in Manaus, Amazonas, Brazil.

BACKGROUND: After the introduction of the multidrug therapy, there was a decline in the coefficients of prevalence and detection of new cases of leprosy. However, the records of drug resistance and relapses are threatening factors in leprosy control. Hence, new alternative schemes and monitoring of adverse effects to avoid treatment abandonment are important considerations. OBJECTIVE: Describe the side effects of a multidrug regimen containing minocycline, ofloxacin, and clofazimine in multibacillary leprosy patients. METHODS: We conducted a prospective, descriptive, and observational study with multibacillary patients, including cases of intolerance to standard MDT and relapses. The study was carried out at Fundação Alfredo da Matta (Alfredo da Matta Foundation), in Manaus, Amazonas, from April 2010 to January 2012. The patients received alternative therapy, which consisted of daily self-administered doses of 100mg of minocycline, 400 mg of ofloxacin, and 50mg of clofazimine and a supervised monthly dose of 300mg of clofazimine for six months, followed by eighteen months of daily doses of ofloxacin 400mg, clofazimine 50mg, and a supervised monthly dose of clofazimine 300mg. RESULTS: Twenty-one cases were included. Mild and transitory side effects occurred in 33.3% of patients. Of the total episodes, 45.9% were attributed to ofloxacin and they included abdominal pain, nausea, vomiting, headache, and insomnia; 21.6% were due to clofazimine, with 100% of patients presenting skin pigmentation. The mean time for the development of adverse effects after beginning the therapy was 15.2 days. CONCLUSION: All patients tolerated the drugs well, and compliance was satisfactory, with no serious events. Unlike other standard MDT studies had shown, no treatment was stopped due to side effects. Nevertheless, patient follow-up and studies with bigger samples are necessary to guarantee the efficacy and safety of the alternative regimen as a second-line scheme in multi-drug therapy.

[Physical disabilities in leprosy patients after discharge from multidrug therapy in Northern Brazil]. / Incapacidades físicas em pessoas acometidas pela hanseníase no período pós-alta da poliquimioterapia em um município no Norte do Brasil.

Chronic sequelae and disabilities are one of the main problems in leprosy. The current study aimed to estimate the prevalence of disabilities in leprosy patients after successfully completing multidrug therapy in Araguaína, Tocantins State, Brazil. This was a cross-sectional study including 282 cases diagnosed from 2004 to 2009. The degrees of disability at diagnosis and at discharge from treatment were collected from medical records and the National Information System for Notifiable Diseases (SINAN). A simplified neurological workup was performed after discharge from treatment. The prevalence of disabilities at diagnosis was 29.4%, and 8.9% of then was grade II. Between diagnosis and discharge, the degree of physical disability worsened in 25% of cases. At diagnosis, the proportion of deformities was significantly higher in men (RR = 1.7; 95%CI: 1.23-2.37). There was a significant association between disability and multibacillary disease (p < 0.001) and occurrence of reactions (p < 0.001). The data show that after discharge from multidrug therapy, in order to prevent chronic sequelae and functional limitations, continuous monitoring is still needed for individuals that have been recorded as cured and thus deleted from the records.

Incapacidades físicas em pessoas acometidas pela hanseníase no período pós-alta da poliquimioterapia em um município no Norte do Brasil / Physical disabilities in leprosy patients after discharge from multidrug therapy in Northern Brazil / Incapacidades físicas en personas afectadas por la hanseniasis en el período post alta de la poliquimioterapia en un municipio en el norte de Brasil

Chronic sequelae and disabilities are one of the main problems in leprosy. The current study aimed to estimate the prevalence of disabilities in leprosy patients after successfully completing multidrug therapy in Araguaína, Tocantins State, Brazil. This was a cross-sectional study including 282 cases diagnosed from 2004 to 2009. The degrees of disability at diagnosis and at discharge from treatment were collected from medical records and the National Information System for Notifiable Diseases (SINAN). A simplified neurological workup was performed after discharge from treatment. The prevalence of disabilities at diagnosis was 29.4%, and 8.9% of then was grade II. Between diagnosis and discharge, the degree of physical disability worsened in 25% of cases. At diagnosis, the proportion of deformities was significantly higher in men (RR = 1.7; 95%CI: 1.23-2.37). There was a significant association between disability and multibacillary disease (p < 0.001) and occurrence of reactions (p < 0.001). The data show that after discharge from multidrug therapy, in order to prevent chronic sequelae and functional limitations, continuous monitoring is still needed for individuals that have been recorded as cured and thus deleted from the records.

Danos neurais contribuem para a incapacidade física na hanseníase. O objetivo foi estimar a prevalência de indivíduos com incapacidade física após a alta de poliquimioterapia da hanseníase em Araguaína, Tocantins, Brasil. Estudo transversal com 282 casos novos de 2004 a 2009. O grau de incapacidade no diagnóstico e na cura foi coletado de prontuários e do Sistema de Informação de Agravos de Notificação. No pós-alta usou-se o formulário de avaliação neurológica simplificada. A prevalência de incapacidade foi de 29,4%, sendo 8,9% grau 2. Houve associação entre incapacidades físicas com multibacilares (p < 0,001) e com episódios reacionais (p < 0,001). No diagnóstico, a ocorrência de deformidades foi 1,7 vez maior nos homens (IC95%: 1,23-2,37). Entre o diagnóstico e a alta houve piora do grau de incapacidade e esta piora foi maior após a alta: 25%. A piora do grau de incapacidade foi mais expressiva após a alta, apresentando associação com multibacilares e episódios reacionais. É preciso monitoramento contínuo de casos em alta, para prevenir sequelas e limitação funcional.

Daños neurales contribuyen a la incapacidad física en la hanseniasis. El objetivo fue estimar la prevalencia de individuos con incapacidad física, tras el alta de poliquimioterapia de la hanseniasis en Araguaína, Tocantins, Brasil. Estudio transversal con 282 casos nuevos de 2004 a 2009. El grado de incapacidad en el diagnóstico y en la cura se recogió de historiales médicos y del sistema de información de quejas por notificación. En el post alta se usó el formulario de evaluación neurológica simplificada. La prevalencia de incapacidad fue de un 29,4%, siendo un 8,9% grado 2. Hubo asociación entre incapacidades físicas con multibacilares (p < 0,001) y con episodios reaccionales (p < 0,001). En el diagnóstico, la ocurrencia de deformidades fue un 1,7 veces mayor en los hombres (IC95%: 1,23-2,37). Entre el diagnóstico y el alta hubo un empeoramiento del grado de incapacidad y ese empeoramiento fue mayor tras el alta: un 25%. El empeoramiento del grado de incapacidad fue más expresivo tras el alta, presentando asociación con multibacilares y episodios reaccionales. Es preciso el monitoreo continuo de casos en alta, para prevenir secuelas y limitación funcional.

Adverse effects of alternative therapy (minocycline, ofloxacin, and clofazimine) in multibacillary leprosy patients in a recognized health care unit in Manaus, Amazonas, Brazil / Efeitos adversos das drogas (minociclina, ofloxacina e clofazimina) utilizadas no esquema alternativo para pacientes com hanseníase multibacilar, em unidade de referência, Manaus, Amazonas, Brasil

BACKGROUND: After the introduction of the multidrug therapy, there was a decline in the coefficients of prevalence and detection of new cases of leprosy. However, the records of drug resistance and relapses are threatening factors in leprosy control. Hence, new alternative schemes and monitoring of adverse effects to avoid treatment abandonment are important considerations. OBJECTIVE: Describe the side effects of a multidrug regimen containing minocycline, ofloxacin, and clofazimine in multibacillary leprosy patients. METHODS: We conducted a prospective, descriptive, and observational study with multibacillary patients, including cases of intolerance to standard MDT and relapses. The study was carried out at Fundação Alfredo da Matta (Alfredo da Matta Foundation), in Manaus, Amazonas, from April 2010 to January 2012. The patients received alternative therapy, which consisted of daily self-administered doses of 100mg of minocycline, 400 mg of ofloxacin, and 50mg of clofazimine and a supervised monthly dose of 300mg of clofazimine for six months, followed by eighteen months of daily doses of ofloxacin 400mg, clofazimine 50mg, and a supervised monthly dose of clofazimine 300mg. Results: Twenty-one cases were included. Mild and transitory side effects occurred in 33.3% of patients. Of the total episodes, 45.9% were attributed to ofloxacin and they included abdominal pain, nausea, vomiting, headache, and insomnia; 21.6% were due to clofazimine, with 100% of patients presenting skin pigmentation. The mean time for the development of adverse effects after beginning the therapy was 15.2 days. CONCLUSION: All patients tolerated the drugs well, and compliance was satisfactory, with no serious events. Unlike other standard MDT studies ...

FUNDAMENTOS: Após introdução do esquema poliquimioterápico padrão, houve declínio nos coeficientes de prevalência e detecção de casos novos; entretanto, os registros de resistência medicamentosa e recidivas representam ameaça para o controle da hanseníase. Dessa forma, a proposição de novos esquemas alternativos e a necessidade de monitorar efeitos adversos são importantes para evitar o abandono do tratamento. OBJETIVO: Descrever efeitos adversos do esquema alternativo contendo clofazimina, ofloxacina e minociclina em pacientes com hanseníase multibacilar. MÉTODOS: Estudo prospectivo, descritivo e observacional de casos multibacilares, incluindo recidivas ou intolerância à poliquimioterapia padrão, realizado na Fundação Alfredo da Matta, Manaus, Amazonas, de abril de 2010 a janeiro de 2012. Os indivíduos receberam a terapia composta de doses diárias auto-administradas de 100mg de minociclina, 400mg de ofloxacina e 50mg de clofazimina e mensais supervisionadas de 300mg de clofazimina por seis meses, seguidas de 18 meses de doses diárias de ofloxacina 400mg, clofazimina 50 mg e supervisionadas mensais de clofazimina 300mg. Resultados: 21 pacientes foram incluídos. Efeitos adversos leves e transitórios foram observados em 33,3% dos pacientes; 45,9% foram atribuídos à ofloxacina, como dor abdominal, náuseas, vômitos, cefaléia e insônia; 21,6% foram associados à clofazimina, com relatos e observação em 100% dos pacientes de hiperpigmentação cutânea. O tempo médio de desenvolvimento das reações adversas a partir do início do esquema foi de 15,2 dias. ...