Perfil clínico-epidemiológico de pacientes com hanseníase atendidos em hospital universitário no Rio de Janeiro entre 2008 e 2017 / Clinical and epidemiological profile of leprosy patients admitted to a university hospital in Rio de Janeiro between 2008 and 2017

Modelo do estudo: Estudo observacional, longitudinal, retrospectivo e descritivo de uma coorte de pacientes. Objetivo: Descrever o perfil clínico e epidemiológico dos pacientes com diagnóstico de hanseníase, atendidos em um centro de referência no estado do Rio de Janeiro. Metodologia: Foram incluídos todos os pacientes com diagnóstico de hanseníase atendidos no Hospital Universitário Gaffrée e Guinle entre os anos de 2008 a 2017. Os dados foram coletados através da revisão de prontuários e analisados através de estatística descritiva, utilizando-se o software SPSS 22.0 database. Resultados: Um total de 112 pacientes foi incluído no estudo, sendo que 54,5% eram do sexo masculino. A média de idade foi de 49,9 anos, 62,4% eram moradores do município do Rio de Janeiro e 69,9% apresentaram formas clínicas multibacilares da hanseníase. Foi possível avaliar o grau de incapacidade inicial de 36 (32,1%) dos pacientes incluídos. Desses, 25% apresentaram grau de incapacidade inicial II. Durante o tratamento poliquimioterápico, 21 (18,8%) pacientes apresentaram algum efeito colateral, sendo o mais comum a anemia relacionada à dapsona. Cinquenta e nove (52,7%) pacientes apresentaram algum tipo de estado reacional da hanseníase e 10 (8,9%) apresentaram complicações sistêmicas graves durante o acompanhamento. Conclusões: O presente estudo evidenciou um perfil clínico-epidemiológico diferente do descrito na literatura, com uma grande porcentagem de pacientes com grau de incapacidade inicial II, uma alta frequência de estados reacionais e de complicações advindas do curso clínico da doença ou dos tratamentos implementados.(AU)

Introduction: This was an observational, longitudinal, retrospective and descriptive study of a cohort of patients. Objectives: To describe the clinical and epidemiological profile of the patients diagnosed with leprosy admitted to a reference medical center in the State of Rio de Janeiro. Methods: All leprosy patients admitted to the dermatology clinic from the Hospital Universitário Gaffrée and Guinle between 2008 and 2017 were included. Pertinent patients' data were collected through medical charts review. Data were then analyzed through descriptive statistics using SPSS 22.0 software. Results:a total of 112 patients were included in the study. Among them, 54.5% were male, the median age was 49.9 years old, 62.4% were residents in the city of Rio de Janeiro and 69.9% presented multibacillary leprosy clinical forms. We evaluated the initial disability grade of 36 from the 112 included patients, and out of them, 25% had grade II disability. During multidrug therapy, 21 (18.8%) patients presented an adverse effect, which the most common was anemia related to dapsone. Fifty-nine (52.7%) patients presented leprosy reaction and 10 (8.9%) patients presented severe systemic complications during the follow-up. Conclusions: In the present study, it was observed a distinctive clinical and epidemiological leprosy profile. There was a high frequency of grade II initial disability, leprosy reaction and severe clinical complications due to the progression of the disease or as adverse effects of leprosy treatment. (AU)

Corticosteroid therapy in borderline tuberculoid leprosy patients co-infected with HIV undergoing reversal reaction: a clinical study.

Background: Mycobacterium leprae and HIV cause infectious diseases of great concern for the public health care sector worldwide. Both are especially worrisome diseases when patients become co-infected and exhibit the expected clinical exuberance. The objective of this study was to evaluate episodes of reversal reaction (RR) and the effect of the use of corticosteroids on the treatment of borderline tuberculoid leprosy patients co-infected with the human immunodeficiency virus (HIV). Methods: This is a retrospective cohort study in which the clinical manifestations of the patients and their responses to corticosteroid therapy were observed. Variables were analysed during and after multidrug therapy between the first and last days of prednisone, which occurred up to a maximum of 6 months after initiating corticosteroid therapy. Results: A total of 22 HIV-positive and 28 HIV-negative cases were included. Loss of sensitivity and neural thickening were statistically significant while clinically ulcerated lesions were only observed in the co-infected group. Most patients were diagnosed with leprosy in the presence of RR and six patients manifested RR as an immune reconstitution inflammatory syndrome. On average, both groups received similar doses of corticosteroids (difference of 0·1 mg/kg/day).

Role of CD8(+) T cells in triggering reversal reaction in HIV/leprosy patients.

It has been reported that the initiation of highly active anti-retroviral therapy (HAART) is associated with the development of reversal reaction (RR) in co-infected HIV/leprosy patients. Nevertheless, the impact of HIV and HAART on the cellular immune response to Mycobacterium leprae (ML) remains unknown. In the present study, we observed that ex vivo peripheral blood mononuclear cells (PBMCs) of both RR and RR/HIV patients presented increased percentages of activated CD4(+) T cells when compared with the healthy individuals (HC) group. The frequency of CD8(+)  CD38(+) cells increased in the PBMCs of RR/HIV patients but not in RR patients when compared with the HC group. Both RR and RR/HIV skin lesion cells presented similar percentages of activated CD4(+) cells, but the numbers of activated CD8(+) cells were higher in RR/HIV in comparison to the RR group. The frequency of interferon-γ-producing cells was high in response to ML regardless of HIV co-infection. In ML-stimulated cells, there was an increase in central memory CD4(+) T-cell frequencies in the RR and RR/HIV groups, but an increase in central memory CD8(+) T-cell frequency was only observed in the RR/HIV group. ML increased granzyme B(+) effector memory CD8(+) T-cell frequencies in the RR/HIV PBMCs, but not in the HC and RR groups. Our data suggest that the increased expression of effector memory CD8(+) T cells, together with greater perforin/granzyme B production, could be an additional mechanism leading to the advent of RR in co-infected patients. Moreoever, this increased expression may explain the severity of RR occurring in these patients.

Superposition of leprosy and other neglected tropical diseases in the state of Rio de Janeiro: a case series report.

This is a report on eight non-HIV infected leprosy patients presenting unusual co-infection with other, often neglected, tropical diseases, namely: American tegumentary leishmaniasis (ATL), sporotrichosis, and cryptococcosis. To the best of our knowledge, there have been very few ATL-leprosy co-infection reports in the literature to date and only one previous description of the coexistence of leprosy-cryptococcosis and leprosy-sporotricosis.

Avaliação dos aspectos epidemiológicos, clínicos e imunopatológicos da reação tipo 1 em pacientes coinfectados pelo vírus da imunodeficiência humana e o Mycobacterium leprae / The epidemiological, clinical and immunopathological reaction of type 1 evaluation in patients co-infected with human immunodeficiency virus and Mycobacterium leprae

Introdução: Na última década, diversas publicações sobre a associação entre o início de terapia antirretroviral e o desenvolvimento de reação reversa foram publicadas. [...] Objetivo: Avaliar a influência da infecção pelo HIV na epidemiologia, apresentação clínica e mecanismos imunopatológicos envolvidos na reação tipo 1. Material e método: Estudo I: Estudo de série de casos, onde foi realizada uma descrição das características clínicas e epidemiológicas de todos os pacientes coinfectados pelo HIV/ M. leprae no momento do diagnóstico de hanseníase no ASA entre 1989 e 2011. Uma análise multivariada dos fatores associados à presença de reação reversa foi realizada. Os dados foram coletados pelo banco de registros dos pacientes no ASA e complementados por revisão de prontuários. Mapas temáticos sobre a distribuição geográfica dos pacientes foram construídos através do programa ArcMap. Estudo II: estudo de coorte retrospectiva, onde foram incluídos todos os pacientes borderline tuberculoide , maiores de 15 anos de idade e atendidos no ASA entre 1997 a 2008. Os pacientes foram comparados de acordo com a sorologia para infecção pelo HIV. Os dados foram coletados através de revisão de prontuários. A densidade de incidência de reação reversa foi calculada para cada grupo. Os fatores de risco para reação reversa foram avaliados através de análise multivariada por regressão de Poisson. Comparou- se as características clínicas da reação. Em soro de pacientes com reação reversa, foi avaliada a expressão de citocinas por Luminex e de proteína C reativa por ELISA. A detecção de IgM anti-PGL1 no diagnóstico de hanseníase foi avaliada através de ELISA.

Resultados: Estudo I: Houve um aumento no número de pacientes diagnosticados com hanseníase e HIV nos últimos anos, em um centro de referência. A maioria dos pacientes apresentava a forma paucibacilar da hanseníase e o uso de TARV foi único fator associado ao desenvolvimento de reação. A maioria dos pacientes eram moradores da região metropolitana e da região norte da cidade do Rio de Janeiro. Estudo II: A incidência de reação reversa foi significantemente maior entre pacientes coinfectados pelo HIV. A presença de BAAR nas lesões cutâneas, a infecção pelo HIV e o teste de Mitsuda negativo foram fatores de risco para a reação reversa. Uma maior proporção de pacientes coinfectados apresentou lesões cutâneas ulceradas, porém todos os pacientes responderam bem ao tratamento para reação com prednisona. Houve uma maior frequência de citocinas de perfil Th1 em pacientes sem HIV e de perfil Th2 em pacientes coinfectados na reação reversa. Nenhum paciente coinfectado apresentou positividade no exame de ELISA anti- PGL1. Conclusões: A maioria dos pacientes coinfectados foi proveniente de regiões com grande densidade populacional. A reação reversa é mais frequente em pacientes coinfectados. A infecção pelo HIV, o teste de Mitsuda negativo e a presença de BAAR em lesões cutâneas são fatores de risco para reação reversa. A reação reversa não parece ser mais grave em indivíduos coinfectados pelo HIV.

Introduction: In the last decade, Leprosy and HIV coinfection gained the attention of thescientific community due to the relation of type 1 reaction and the initiation of antiretroviraltherapy. [...] Objective: To evaluate the interaction of the HIV infection with the epidemiological, clinicaland immune pathological features of type 1 reaction.Subjects and Methods: Study I: A case series description of the geographical distributionand demographic characteristics of HIV/ M. leprae co-infected patients at the moment ofleprosy diagnosis in a Brazilian Leprosy referral center from 1989 - 2011. A multivariateanalysis was performed in order to establish clinical factors associated with type 1 reaction.Study II: We have conducted a retrospective longitudinal study of all BT leprosy patients older than 15 years of age attended at the FIOCRUZ Clinic from 1st January 1997 to 31th December 2008. Data retrieved from patients chart were compared according to the status of HIVinfection. The incidence rate of type 1 reaction and recurrent reaction was calculated. Riskfactors for type 1 reaction were evaluated by multivariate Poison regression model. In serumsamples from patients under type 1 reaction before prednisone treatment, cytokine levels wereanalyzed by Luminex and reactive C protein levels by ELISA. The presence of IgM antiPGL1was determinate by ELISA at leprosy diagnosis.

Results: Study I: There were an increasing number of patients diagnosed with leprosy andHIV over the last years at a referral center. Most patients presented paucibacillary leprosyclinical form and the use of ART was the only independent factor associated with type 1reaction. The majority of the patients were living in the metropolitan region and in the northsubarea of Rio de Janeiro city. Study II: The incidence per 100 person-years of type 1reaction was significantly greater in the HIV positive group. The presence of AFB in the skinlesion, a negative lepromin test and HIV infection were independent risk factors for type 1reaction. A greater proportion of coinfected patients presented ulcerated skin lesion, howeverall patients had a favorable evolution after treatment with corticosteroid. There was a greaterfrequency of type 1 cytokines among HIV negative patients and type 2 cytokines among HIVpositive patients. No coinfected patients responded for the detection of anti- PGL1.Conclusions: Patients living with both HIV and leprosy are likely to live in regionscharacterized by a high density impoverished population. The incidence rate of type 1 isgreater in HIV coinfected individuals under TARV. The HIV infection, a lepromin negativetest and the presence of AFB in the skin lesion are risk factor for type 1 reaction. Type 1reaction did not seem to be more severe in this group of individuals.

Leprosy reaction as a manifestation of immune reconstitution inflammatory syndrome: a case series of a Brazilian cohort.

Several case reports have demonstrated that the immune reconstitution inflammatory syndrome induces reversal reaction in HIV and leprosy-coinfected patients. The present study describes 10 cases of immune reconstitution inflammatory-associated reversal reaction. The patients evolved satisfactorily despite presenting a more severe form of the disease and the fact that three required an additional use of corticoids. The present study, the largest case series published to date, demonstrates that leprosy reaction is a manifestation of immune reconstitution.

Novos Rumos para a Educação Médica / New Directions for Medical Education

Resumo: Por várias décadas, o ensino médico ficou estagnado naquele que deveria ser o ponto de partida para mudanças continuas. Nos últimos anos, as escolas médicas de todo o mundo têm se deparado com a crescente demanda por reformas curriculares e pedagógicas, dando origem a diferentes estratégias de ensino. Descrevem-se aqui as principais estratégias didático-pedagógicas da atualidade, enfatizando suas vantagens e desvantagens, com o objetivo de proporcionar elementos para formar uma visão crítica a seu respeito.

Summary Medical education has remained stagnant for decades, when it should be the starting point for continuous changes. During recent years, medical schools worldwide have faced an increasing demand for curricular and pedagogical reforms, this giving rise to different educational strategies. This paper describes the main current didactic-pedagogical strategies, focusing on their advantages and disadvantages, with the objective of identifying elements for a critical analysis.