Abstract Background The diagnosis of Hansen disease (HD) can be difficult when acid-fast bacilli are not detected in the patient's skin sample. Objective To demonstrate that detailed morphological analysis of nonspecific inflammatory and/or noninflammatory alterations in dermal nerves as well as skin adnexa in leprosy-suspected biopsy samples could improve the efficacy of histopathological diagnosis. Methods Patients with one to five skin lesions were enrolled in the study and classified into three groups by skin histopathology findings: Hansen disease (HD, n = 13), other diseases (OD, n = 11), and inconclusive cases (INC, n = 11). We quantified dermal nerve damage via the nerve lesion index (NLI) and PGP9.5-immunoreactive axon quantitative index in dermal nerves (AQI). We also measured inflammatory involvement of adnexa in cutaneous samples as indirect evidence of HD. Results We observed a higher median endoneurial inflammatory infiltrate NLI (HD = 0.5; INC = 0; OD = 0; p < 0.001) and more frequent inflammatory involvement of skin adnexa in samples of the HD group compared with those of the INC and OD groups (HD = 7; INC = 1; OD = 0). However, samples from the INC and OD groups also showed inflammatory and noninflammatory damage of dermal nerves, with 2 or more kinds of alterations in nerves in the same sample (respectively: INC = in 1 and 2 samples; OD = in 3 and 5 respectively). The quantification of PGP9.5-immunoreactive axons in dermal nerves revealed no difference between the groups. Conclusion A detailed morphological analysis of cutaneous nerves in lesions with a suspicion of HD enabled us to select patients with nonspecific inflammatory or non-inflammatory lesions in the dermal nerves in the INC and OD groups, so they may be clinically monitored aiming at a possible future diagnosis of the disease. These INC and OD patients cannot have the HD diagnosis definitely excluded, and HD may coexist with another disease as a comorbidity. acidfast acid fast patient s andor leprosysuspected leprosy suspected findings HD, 13, 13 , 13) OD, (OD 11, 11 11) INC, (INC 11. . (NLI PGP9.5immunoreactive PGP95immunoreactive PGPimmunoreactive PGP9.5 immunoreactive PGP9 PGP AQI. AQI (AQI) 0.5 05 0 0.001 0001 001 7 0. 0) However respectively (respectively respectively. respectively) non excluded comorbidity 5immunoreactive PGP95 PGP9. (AQI 0.00 000 00 0.0

Resumo Antecedentes A hanseníase pode ter o seu diagnóstico histopatológico dificultado quando bacilos álcool-ácido resistentes não são encontrados nas amostras de pele dos pacientes. Objetivo Demonstrar que uma análise morfológica detalhada de alterações histopatológicas dos nervos dérmicos pode aumentar a eficácia diagnóstica. Métodos Foram selecionadas amostras de pele de pacientes com uma a cinco lesões suspeitas de hanseníase. Os casos selecionados foram classificados conforme achados histopatológicos: hanseníase (HD, n = 13), casos inconclusivos (INC, n = 11), e outras doenças (OD, n = 11). Quantificamos as lesões dos nervos cutâneos por meio do índice de lesão de nervos (nerve lesion index, NLI, em inglês) e do índice quantitativo de axônios (axon quantitative index, AQI, em inglês) imunorreativos a PGP9.5 nos nervos cutâneos. Também medimos o envolvimento inflamatório dos anexos em amostras de pele como evidência indireta de hanseníase. Resultados Foram observadas no grupo HD medianas mais altas do NLI com relação a infiltrados inflamatórios endoneurais (HD = 0,5; INC = 0; OD = 0; p < 0,001) e mais alta frequência de acometimento inflamatório de anexos cutâneos (HD = 7; INC = 1; OD = 0). Entretanto, as amostras dos grupos INC e OD também mostraram comprometimento inflamatório e não inflamatório dos nervos cutâneos, com 2 ou mais tipos de alterações de nervos na mesma amostra (respectivamente: INC = 1 e 2; OD = 3 e 5). Não houve diferença significativa na quantidade de axônios endoneurais imunorreativos a PGP9.5 entre os grupos. Conclusão A análise morfológica detalhada dos nervos cutâneos em lesões suspeitas de hanseníase permitiu selecionar pacientes com lesões inespecíficas inflamatórias ou não inflamatórias nos nervos dérmicos nos grupos INC e OD, para que sejam monitorados clinicamente visando um possível diagnóstico futuro da doença. Esses pacientes INC e OD não podem ter o diagnóstico de HD definitivamente excluído, e a hanseníase pode coexistir com outra doença como uma comorbidade. álcoolácido álcool ácido diagnóstica histopatológicos HD, 13, 13 , 13) INC, (INC 11, 11 11) (OD 11. . nerve index inglês axon AQI PGP95 PGP PGP9 5 PGP9. 0,5 05 0 0,001 0001 001 7 0. 0) Entretanto respectivamente (respectivamente 5. 5) excluído comorbidade 0, 0,00 000 00 0,0

RESUMO OBJETIVO Descrever o processo de adaptação transcultural da “Explanatory Model Interview Catalogue – Stigma Scale” para pessoas afetadas por hanseníase no Brasil. MÉTODOS Após a autorização do autor da escala para seu uso no contexto nacional, deu-se início aos cinco passos do processo de adaptação transcultural: (1) tradução, (2) reunião de síntese, (3) retrotradução, (4) comitê de peritos e (5) pré-teste. A consistência interna da escala foi avaliada utilizando o coeficiente alfa de Cronbach. RESULTADOS Os 15 itens da versão original da escala foram traduzidos para a língua portuguesa do Brasil. A escala adaptada apresentou evidência de boa compreensão de seu conteúdo, atestada tanto por peritos como por membros da população alvo. Sua consistência interna foi de 0,64. CONCLUSÕES O instrumento adaptado apresenta consistência interna satisfatória. Pode ser útil em estudos futuros que intencionem viabilizar ampla análise situacional que sustente programas sólidos de saúde pública com enfoque na efetiva redução de estigma. Em estudo ulterior será avaliada a validade de constructo, critério e reprodutibilidade.

ABSTRACT OBJECTIVE Describe the process of cross-cultural adaptation of the “Explanatory Model Interview Catalog – Stigma Scale” for people affected by leprosy in Brazil. METHODS After being authorized by the author of the scale to use it in the national context, we initiated the five steps process of cross-cultural adaptation: (1) translation, (2) synthesis meeting, (3) back-translation, (4) committee of experts and (5) pre-test. The internal consistency of the scale was evaluated using Cronbach’s alpha coefficient. RESULTS The 15 items of the scale’s original version were translated into Brazilian Portuguese. The adapted scale showed evidence of a good understanding of its content, attested both by experts and members of the target population. Its internal consistency was 0.64. CONCLUSIONS The adapted instrument shows satisfactory internal consistency. It may be useful in future studies that intend to provide broad situational analysis that supports solid public health programs with a focus on effective stigma reduction. In a later study, the construct’s validity, criterion, and reproducibility will be evaluated.

RESUMO OBJETIVO Descrever o processo de adaptação transcultural da “Explanatory Model Interview Catalogue – Stigma Scale” para pessoas afetadas por hanseníase no Brasil. MÉTODOS Após a autorização do autor da escala para seu uso no contexto nacional, deu-se início aos cinco passos do processo de adaptação transcultural: (1) tradução, (2) reunião de síntese, (3) retrotradução, (4) comitê de peritos e (5) pré-teste. A consistência interna da escala foi avaliada utilizando o coeficiente alfa de Cronbach. RESULTADOS Os 15 itens da versão original da escala foram traduzidos para a língua portuguesa do Brasil. A escala adaptada apresentou evidência de boa compreensão de seu conteúdo, atestada tanto por peritos como por membros da população alvo. Sua consistência interna foi de 0,64. CONCLUSÕES O instrumento adaptado apresenta consistência interna satisfatória. Pode ser útil em estudos futuros que intencionem viabilizar ampla análise situacional que sustente programas sólidos de saúde pública com enfoque na efetiva redução de estigma. Em estudo ulterior será avaliada a validade de constructo, critério e reprodutibilidade.

ABSTRACT OBJECTIVE Describe the process of cross-cultural adaptation of the “Explanatory Model Interview Catalog – Stigma Scale” for people affected by leprosy in Brazil. METHODS After being authorized by the author of the scale to use it in the national context, we initiated the five steps process of cross-cultural adaptation: (1) translation, (2) synthesis meeting, (3) back-translation, (4) committee of experts and (5) pre-test. The internal consistency of the scale was evaluated using Cronbach’s alpha coefficient. RESULTS The 15 items of the scale’s original version were translated into Brazilian Portuguese. The adapted scale showed evidence of a good understanding of its content, attested both by experts and members of the target population. Its internal consistency was 0.64. CONCLUSIONS The adapted instrument shows satisfactory internal consistency. It may be useful in future studies that intend to provide broad situational analysis that supports solid public health programs with a focus on effective stigma reduction. In a later study, the construct’s validity, criterion, and reproducibility will be evaluated.

The diagnosis of single-lesion paucibacillary leprosy remains a challenge. Reviews by expert dermatopathologists and quantitative polymerase chain reaction (qPCR) results obtained from 66 single-plaque biopsy samples were compared. Histological findings were graded as high (HP), medium (MP) or low (LP) probability of leprosy or other dermatopathy (OD). Mycobacterium leprae-specific genes were detected using qPCR. The biopsies of 47 out of 57 clinically diagnosed patients who received multidrug therapy were classified as HP/MP, eight of which were qPCR negative. In the LP/OD (n = 19), two out of eight untreated patients showed positive qPCR results. In the absence of typical histopathological features, qPCR may be utilised to aid in final patient diagnosis, thus reducing overtreatment and delay in diagnosis.

It is important to understand the mechanisms that enable peripheral neurons to regenerate after nerve injury in order to identify methods of improving this regeneration. Therefore, we studied nerve regeneration and sensory impairment recovery in the cutaneous lesions of leprosy patients (LPs) before and after treatment with multidrug therapy (MDT). The skin lesion sensory test results were compared to the histopathological and immunohistochemical protein gene product (PGP) 9.5 and the p75 nerve growth factor receptors (NGFr) findings. The cutaneous neural occupation ratio (CNOR) was evaluated for both neural markers. Thermal and pain sensations were the most frequently affected functions at the first visit and the most frequently recovered functions after MDT. The presence of a high cutaneous nerve damage index did not prevent the recovery of any type of sensory function. The CNOR was calculated for each biopsy, according to the presence of PGP and NGFr-immunostained fibres and it was not significantly different before or after the MDT. We observed a variable influence of MDT in the recovery from sensory impairment in the cutaneous lesions of LPs. Nociception and cold thermosensation were the most recovered sensations. The recovery of sensation in the skin lesions appeared to be associated with subsiding inflammation rather than with the regenerative activity of nerve fibres.

OBJECTIVE: To analyze a profile of patients treated at a national leprosy outpatient referral clinic in metropolitan Rio de Janeiro, Brazil, over a period of more than two decades, and the subgroup of nationally registered leprosy cases from the same residential area, as well as all registered cases statewide. METHODS: An observational, descriptive analysis was carried out for patients treated from 1986 to 2007 at the Souza Araújo Outpatient Clinic (Ambulatório Souza Araújo, ASA), a national referral center for the diagnosis and treatment of leprosy at the Oswaldo Cruz Foundation (Fiocruz) that serves clients from the city of Rio de Janeiro and other municipalities in the metropolitan area of Rio de Janeiro State. Demographic and clinical data for the subgroup of leprosy cases registered with Brazil's National Disease Notification System (Sistema Nacional de Informação de Agravos de Notificação, SINAN) between 2001 and 2007 and residing in the same municipalities as the ASA patients, and for all registered cases statewide, were also analyzed. RESULTS: Among the ASA patients, there was a decrease in average family income (from 3.9 to 2.7 times the minimum salary between the periods 1998-2002 and 2003-2007); the proportion of multibacillary (MB) patients (from 52.7% to 46.9%); and the proportion of patients younger than 15 years old (from 12.8% to 8.7%). Among the MB patients, the average initial and final bacilloscopic indices were significantly higher in 2003-2007. Compared with the SINAN cases, more ASA cases involved disability and were younger than 15 years old. CONCLUSIONS: Patients living with leprosy in the metropolitan area of the state of Rio de Janeiro belong to the most deprived social strata and have not benefited from the overall improvement in socioeconomic conditions in Brazil.

OBJETIVO: Analizar el perfil de los enfermos tratados en un servicio nacional de remisión de pacientes ambulatorios con lepra ubicado en la zona metropolitana de Río de Janeiro, Brasil, durante más de dos decenios, y el subgrupo de casos de lepra registrados a nivel nacional de la misma zona de residencia, así como todos los casos registrados a nivel estatal. MÉTODOS: Se llevó a cabo un análisis observacional y descriptivo de los pacientes tratados desde 1986 a 2007 en el servicio ambulatorio Souza Araújo (ASA), un centro de remisión nacional para el diagnóstico y el tratamiento de la lepra en la Fundación Oswaldo Cruz, que atiende a pacientes de la ciudad de Río de Janeiro y de otros municipios de la zona metropolitana del Estado de Río de Janeiro. También se analizaron los datos demográficos y clínicos del subgrupo de casos de lepra registrados con el Sistema Nacional de Notificación de Enfermedades del Brasil (SINAN) entre el 2001 y el 2007 residentes en los mismos municipios que los pacientes atendidos en el ASA, y de todos los casos registrados a nivel estatal. RESULTADOS: En los pacientes atendidos en el ASA hubo una disminución en los ingresos familiares promedio (de 3,9 a 2,7 veces el sueldo mínimo entre los períodos 1998-2002 y 2003-2007), en la proporción de pacientes multibacilares (de 52,7% a 46,9%), y en la proporción de pacientes menores de 15 años de edad (de 12,8% a 8,7%). En los pacientes multibacilares, los índices baciloscópicos promedio inicial y final fueron significativamente mayores en el período 2003-2007. En comparación con los casos del SINAN, en el ASA hubo más casos con discapacidad y en menores de 15 años de edad. CONCLUSIONES: Los pacientes con lepra de la zona metropolitana del Estado de Río de Janeiro pertenecen al estrato social más bajo y no se han beneficiado con el mejoramiento general de la situación socioeconómica en el Brasil.

A poliquimioterapia (PQT), com rifampicina, dapsona, e clofazimina, trata a infecção na hanseníase, mas é insuficiente para interromper ou prevenir o comprometimento neurológico que causa as incapacidades e desabilidades, nesta enfermidade. Este estudo de série de casos avalia o benefício do uso combinado de prednisona e PQT na prevenção do dano neurológico em pacientes com a forma neural pura da hanseníase (FNP). Além do PQT, 24 pacientes (88% homens, com idade variando entre 20-79, mediana=41) receberam uma dose diária de 60 mg prednisona que foi reduzida gradualmente na dose de 10 mg durante cada um dos 5 meses subseqüentes. FNP foi diagnosticada clinicamente e confirmada através do estudo histopatológico ou PCR. Baixa prevalência de reação (8,3%) foi observada apenas após o final do tratamento. A maioria dos parâmetros clínicos mostrou melhora significativa e redução do bloqueio de condução foi observada em 42% dos pacientes. A administração de doses altas de prednisona melhora a evolução clínica e eletrofisiológica de pacientes com a FNP de hanseníase, contribuindo na prevenção de novos comprometimentos neurológicos.

Multidrug therapy (MDT), with rifampicin, dapsone, and clofazimine, treats leprosy infection but is insufficient in arresting or preventing the nerve damage that causes impairments and disabilities. This case-series study evaluates the benefits of the combined use of steroids and MDT in preventing nerve damage in patients with pure neural leprosy (PNL). In addition to MDT, 24 patients (88% male aged 20-79 years, median=41) received a daily morning dose of 60 mg prednisone (PDN) that was gradually reduced by 10 mg during each of the following 5 months. PNL was clinically diagnosed and confirmed by nerve histopathology or PCR. A low prevalence (8.3%) of reaction was observed after release from treatment. However, most of the clinical parameters showed significant improvement; and a reduction of nerve conduction block was observed in 42% of the patients. The administration of full-dose PDN improved the clinical and electrophysiological condition of the PNL patients, contributing to the prevention of further neurological damage.

O reconhecimento clínico precoce dos episódios reacionais traz grandes benefícios para os pacientes com hanseníase, devido à possibilidade de intervenção terapêutica imediata e adequada, evitando o desenvolvimento de incapacidades que tanto estigmatizam e complicam a doença. Existem três formas de episódios reacionais: os tipos 1 e 2, e a neurite. Esta última pode aparecer isoladamente ou acompanhar as formas anteriores. Em alguns casos só são observadas as manifestações cutâneas e/ou neurológicas das reações, enquanto em outros, alterações sistêmicas podem acrescentar-se ao quadro. O tratamento utilizando a associação de medicamentos antiinflamatórios e imunossupressores parece ser o mais adequado para evitar as recorrências e os efeitos colaterais.

The early clinical recognition of reactional states brings great benefits to leprosy patients due to the possibility of appropriate and immediate therapeutic intervention, thus avoiding the development of disabilities that so much stigmatize and complicate the disease. There are three types of reactional episodes: types 1, 2 and neuritis. The latter may occur alone or together with the former forms. In some cases only neurological and/or skin manifestations are observed in the reactions; in others, patients present systemic alterations. The treatment with an association of immunosuppressors and anti-inflammatory drugs seems to be the most effective to avoid recurrences and side effects

Com o objetivo de estudar o comportamento biológico de cepas do T. cruzi e determinar a possível relação entre o biodema da cepa e as formas clínicas da doença de Chagas, 14 cepas do protozoário isoladas de humanos, procedentes de Pains, Iguatama e Berilo, foram avaliadas. Para estudar o comportamento biológico das cepas, grupos de camundongos albinos suíços, machos, pesando entre 10-15 gramas foram infectados com 1x10(4) tripomastigotas sangüíneos para avaliação da infectividade, parasitemia, morfologia dos tripomastigotas sangüíneos, virulência e distribuição do protozoário nos tecidos. Nove cepas apresentaram comportamento similar ao da cepa São Felipe do biodema II e cinco se caracterizaram como pertencentes ao biodema III. Não foi possível estabelecer uma relação entre o biodema da cepa e gravidade da doença nos pacientes.

In order to study the biological behavior of T. cruzi strains and to determine a putative association between their biodeme and the clinical forms of Chagas disease, 14 strains isolated from humans were evaluated. The individuals were from the municipalities of Pains, Iguatama and Berilo (Minas Gerais State). The biological behavior was evaluated in albino swiss mice, weighing 10 to 15 grams, which were infected with 1x10(4) blood tripomastigotes. The infectivity, parasitemia, tripomastigote morphology, virulence and the tissue distribution of the protozoan were analyzed. A behavior similar to biodeme II (São Felipe strain) was observed in 9 strains, while 5 stocks were characterized as belonging to biodeme III. It was not possible to establish a relationship between the biodeme strain and the severity of the disease in the patients.