Abstract Leprosy reactions are among the main causes of physical disability resulting from an infectious disease and can culminate in irreversible physical disabilities, therefore they should be considered a clinical emergency, as well as the elucidation of its cause. Co-infections are considered one of the main triggering causes of leprosy reactions, aggravating and maintaining these reactions for longer in these patients. After reporting a high rate of Bartonella henselae infection in patients with chronic type 2 leprosy reaction, 19/47 (40.4 %) compared to the control group, 9/50 (18.0 %), p = 0.0149, we conducted this study to observe the rate of infection by Bartonella sp. in a group of patients with chronic type 1 leprosy reactions. Blood samples from 14 patients with chronic type 1 leprosy reactions were analyzed by molecular and microbiological tests and compared. The results showed that, like patients with chronic type 2 leprosy reactions, this group of patients has a high proportion of B. henselae infection 6/14 (42.9 %), p = 0.88. We conclude that these bacteria can trigger chronic leprosy reactions and should be investigated in all chronic leprosy reactions patients. Summary Line: Our results showed that, like patients with chronic type 2 leprosy reactions, this group of patients has the same proportion of B. henselae DNA detection 6/14 (42.9 %), p = 0.88. disabilities emergency cause Coinfections Co infections reaction 1947 19 47 19/4 40.4 404 40 4 (40. % 950 9 50 9/5 18.0 180 18 0 (18. %, , 00149 0149 0.0149 sp B 614 6 6/1 42.9 429 42 (42. 088 88 0.88 Line 194 19/ 40. (40 95 5 9/ 18. (18 0014 014 0.014 61 6/ 42. (42 08 8 0.8 (4 (1 001 01 0.01 0. ( 00 0.0

Abstract Leprosy reactions are an acute inflammatory phenomenon that can arise before diagnosis, during treatment, or after cure of leprosy. These reactions are considered one of the main diseases that cause physical disabilities. Immunosuppressive treatment for these immune responses makes these patients susceptible to coinfections, which can trigger new leprosy reactions. The main objective of this study was to evaluate the occurrence of infection by Bartonella sp. in blood samples from 47 patients who had untreatable episodes of type 2 leprosy reactions for more than six months, comparing them with a control group. Cultures and molecular methods (PCR) were used. Amplicons from species-specific reactions and sequencing showed a higher prevalence of Bartonella henselae infection in patients, 19/47 (40.4 %), compared to control, 9/50 (18.0 %), p= 0.0149. Five patients accepted treatment for coinfection, and all showed improvement in leprosy reactions with treatment for B. henselae infection. We conclude that these bacteria can trigger chronic reactions of type 2 leprosy and should be investigated in these patients. Summary line Patients who have chronic type 2 leprosy reactions are more susceptible to Bartonella henselae infection than controls: 19/47 (40.4 %) compared 9/50 (18.0 %), p= 0.0149. diagnosis disabilities coinfections sp 4 months group PCR (PCR used speciesspecific species specific 1947 19 19/4 40.4 404 40 (40. %, % , 950 9 50 9/5 18.0 180 18 0 (18. p 00149 0149 0.0149 coinfection B controls 194 1 19/ 40. (40 95 5 9/ 18. (18 0014 014 0.014 (4 (1 001 01 0.01 ( 00 0.0 0.

RESUMO Antecedentes: A descompressão cirúrgica neural periférica (DCNP) é usada como uma terapia complementar ao tratamento clínico da neurite hansênica para preservar a função neural. Objetivo: Avaliar a longo prazo (≥ 1 ano) os resultados clínicos e funcionais da DCNP na neurite hansênica. Métodos: Este estudo transversal incluiu pacientes que estavam no pós-operatório tardio (POT) de cirurgia de descompressão dos nervos ulnares, medianos, tibiais e fibulares. Foram coletados dados socioeconômicos, epidemiológicos e clínicos. Os instrumentos utilizados foram: escala visual analógica de dor (EVA), questionário de dor neuropática 4 (DN4), escala SALSA e protocolo de avaliação neurológica simplificada. Os resultados obtidos foram comparados com os do pré-operatório (PrO) e pós-operatório de 180 dias (PO180). Resultados: Foram avaliados 246 nervos de 90 pacientes: 56,6% estavam em poliquimioterapia (PQT) e 43,3% em alta da PQT. Escores motores e intensidade da dor apresentaram melhora significante (p<0,01). Houve aumento nos escores sensitivos nos nervos ulnares bilaterais (p<0,05). Neurite ulnar foi indicação cirúrgica em 26,0% dos casos operados, seguida pela neurite tibial (23,6%). Dor neuropática foi relatada em 41% dos casos. Dose diária de prednisona reduziu de 39,6 mg (±3,0) na PrO, 16,3 mg (±5,2) na PO180, para 1,7 mg (±0,8) na POT. Escala SALSA mostrou limitação leve da atividade em 51% e moderada em 34% dos pacientes. 80% dos indivíduos relataram que os resultados atingiram suas expectativas. Conclusão: DCNP na hanseníase foi eficaz a longo prazo na redução da prevalência e intensidade da dor, na melhora da função motora e redução da dose de corticosteroides, refletindo na satisfação do paciente.

ABSTRACT Background: Peripheral neural surgical decompression (PNSD) is used as a complementary therapy to the clinical treatment of neuritis to preserve neural function. Objective: To evaluate the long-term (≥ 1 year) clinical and functional results for PNSD in leprosy neuritis. Methods: This cross-sectional study included leprosy patients who were in late postoperative period (LPO) of surgical decompression of ulnar, median, tibial, and fibular nerves. Socioeconomic, epidemiological, and clinical data were collected. The following instruments were used in this evaluation: visual analogue pain scale (VAS), Douleur Neuropathique en 4 Questions (DN4), SALSA scale, and simplified neurological assessment protocol. The preoperative (PrO) and 180-day postoperative (PO180) results were compared. Results: We evaluated 246 nerves from 90 patients: 56.6% were on multidrug therapy (MDT) and 43.3% discharged from MDT. Motor scores and pain intensity showed statistically significant improvement (p<0.01). There was an increase in sensory scores only for bilateral ulnar nerves (p<0.05). Of the operated cases, 26.0% of patients were referred for surgery of ulnar neuritis and 23.6% of tibial neuritis. Neuropathic pain was reported in 41% of cases. Daily dose of prednisone reduced from 39.6 mg (±3.0) in PrO, 16.3 mg (±5.2) in PO180, to 1.7 mg (±0.8) in LPO. The SALSA scale results showed mild activity limitation in 51% and moderate in 34% of patients. Eighty percent of individuals reported that the results reached their expectations. Conclusions: PNSD in leprosy was effective in the long term to decrease the prevalence and intensity of pain, improve motor function, and reduce the dose of corticosteroids, which is reflected in the patients’ satisfaction.

Abstract INTRODUCTION: The occurrence of leprosy reactions, a common event during treatment, may be mostly related to the action of multidrug therapy on Mycobacterium leprae. The clinical and laboratory monitoring of patients with reactions is important, since collecting data that assists in predicting the risk of reactions may help to prevent disability. METHODS: This was a sectional study, in order to correlate clinical and laboratory diagnosis with the number of reactions during treatment. Spearman's correlation was used to verify the degree of association between the assessed variables. RESULTS: This study was conducted with 211 patients with leprosy reactions during treatment of M. leprae. The borderline tuberculoid group was the most prevalent clinical form (74/211; 35.1%) and the type one reaction showed the highest frequency (136/211; 64.5%). It was observed that 73.5% (155/211) of reactions occurred within 3 months of the initiation of multidrug therapy. The diagnostic values, including the bacterial indices (BIs) of dermal smears (r = 0.21, p < 0.05) and skin biopsies (r = 0.20; p < 0.05), showed a positive correlation with the number of reactions during treatment. CONCLUSIONS: This research showed a positive correlation between bacillary load markers and the number of leprosy reactions. This study provided scientific support to future research aiming to elucidate the influence of antigenic load on the number of leprosy reactions during treatment.

Abstract: INTRODUCTION: Despite multidrug therapy, leprosy remains a public health issue. The intradermal Bacillus Calmette-Guérin (BCG) vaccine, Mitsuda test (lepromin skin test), and anti-phenolic glycolipid I (PGL-I) serology are widely used in leprosy studies and have shown great epidemiological value. METHODS: This longitudinal study evaluated the relative risks and benefits of these three tools by comparing results observed in household contacts (HHCs) of leprosy patients who developed leprosy with those of HHCs who did not in a population of 2,992 individuals monitored during a 10-year period. RESULTS : Seventy-five (2.5%) new leprosy cases were diagnosed, including 28 (0.9%) co-prevalent cases. Therefore, for the risk-benefit assessment, 47 (1.6%) HHCs were considered as truly diagnosed during follow-up. The comparison between healthy and affected contacts demonstrated that not only did BCG vaccination increase protection, but boosters also increased to 95% relative risk (RR) reduction when results for having two or more scars were compared with having no scars [RR, 0.0459; 95% confidence interval (CI), 0.006-0.338]. Similarly, Mitsuda reactions >7mm in induration presented 7-fold greater protection against disease development compared to reactions of 0-3mm (RR, 0.1446; 95% CI, 0.0566-0.3696). In contrast, anti-PGL-I ELISA seropositivity indicated a 5-fold RR increase for disease outcome (RR, 5.688; 95% CI, 3.2412-9.9824). The combined effect of no BCG scars, Mitsuda reaction of <7mm, and seropositivity to anti-PGL-I increased the risk for leprosy onset 8-fold (RR, 8.109; 95% CI, 5.1167-12.8511). CONCLUSIONS: The adoption of these combined assays may impose measures for leprosy control strategies.

INTRODUÇÃO: A hanseníase é uma doença infectocontagiosa cujo agente etiológico é o Mycobacterium leprae, que se manifesta por sinais e sintomas dermatoneurológicos. OBJETIVO: investigar as complicações neurais e o grau de incapacidades físicas nos olhos, mãos e pés antes e após o tratamento, bem como o perfil sociodemográfico e clínico dos pacientes acometidos pela hanseníase. MÉTODO: Estudo epidemiológico do tipo longitudinal constituído por 155 pacientes com hanseníase, a partir da demanda espontânea, diagnosticados no período de março de 2010 a fevereiro de 2011 e tratados com poliquimioterapia (PQT) entre março de 2010 a julho de 2012, em um programa de eliminação da hanseníase, no município de São Luís (MA). RESULTADOS: Antes do tratamento, 46,5% dos pacientes apresentaram forma dimorfa, 51,6% possuíam alguma alteração nos olhos e 52,3% nos pés, sendo o nervo radial (18,7%) o mais acometido. Houve diferença estatisticamente significante entre as complicações do nervo radial no inicio e após o tratamento. CONCLUSÕES: Evidenciou-se a presença do diagnóstico tardio, posto que alguns pacientes já apresentavam complicações neurais e incapacidades físicas antes do tratamento.

INTRODUCTION: Leprosy is an infectious disease whose etiologic agent is Mycobacterium leprae, manifested by dermatological and neurological signs and symptoms. OBJECTIVE: To investigate neural changes and the degree of physical disability in the eyes, hands and feet before and after treatment, as well as sociodemographic and clinical profile of patients affected by leprosy. METHOD: A longitudinal epidemiological study comprising 155 patients with leprosy, from a spontaneous demand, diagnosed between March 2010 and February 2011, and treated with multidrug therapy (MDT) between March 2010 and July 2012 in a program for leprosy eradication in São Luis (MA), Brazil. RESULTS: Before treatment, 46.5% of patients were considered as borderline, 51.6% had some alteration in the eyes and 52.3% in the feet, and the radial nerve (18.7%) was the most affected. There was a statistically significant difference between the changes in the radial nerve at the beginning of and after treatment. CONCLUSIONS: The analysis points to late diagnosis, as some patients have had abnormal neural and physical disabilities before treatment.

INTRODUÇÃO: A hanseníase é uma doença infectocontagiosa cujo agente etiológico é o Mycobacterium leprae, que se manifesta por sinais e sintomas dermatoneurológicos. OBJETIVO: investigar as complicações neurais e o grau de incapacidades físicas nos olhos, mãos e pés antes e após o tratamento, bem como o perfil sociodemográfico e clínico dos pacientes acometidos pela hanseníase. MÉTODO: Estudo epidemiológico do tipo longitudinal constituído por 155 pacientes com hanseníase, a partir da demanda espontânea, diagnosticados no período de março de 2010 a fevereiro de 2011 e tratados com poliquimioterapia (PQT) entre março de 2010 a julho de 2012, em um programa de eliminação da hanseníase, no município de São Luís (MA). RESULTADOS: Antes do tratamento, 46,5% dos pacientes apresentaram forma dimorfa, 51,6% possuíam alguma alteração nos olhos e 52,3% nos pés, sendo o nervo radial (18,7%) o mais acometido. Houve diferença estatisticamente significante entre as complicações do nervo radial no inicio e após o tratamento. CONCLUSÕES: Evidenciou-se a presença do diagnóstico tardio, posto que alguns pacientes já apresentavam complicações neurais e incapacidades físicas antes do tratamento.

INTRODUCTION: Leprosy is an infectious disease whose etiologic agent is Mycobacterium leprae, manifested by dermatological and neurological signs and symptoms. OBJECTIVE: To investigate neural changes and the degree of physical disability in the eyes, hands and feet before and after treatment, as well as sociodemographic and clinical profile of patients affected by leprosy. METHOD: A longitudinal epidemiological study comprising 155 patients with leprosy, from a spontaneous demand, diagnosed between March 2010 and February 2011, and treated with multidrug therapy (MDT) between March 2010 and July 2012 in a program for leprosy eradication in São Luis (MA), Brazil. RESULTS: Before treatment, 46.5% of patients were considered as borderline, 51.6% had some alteration in the eyes and 52.3% in the feet, and the radial nerve (18.7%) was the most affected. There was a statistically significant difference between the changes in the radial nerve at the beginning of and after treatment. CONCLUSIONS: The analysis points to late diagnosis, as some patients have had abnormal neural and physical disabilities before treatment.

Introduction Leprosy is a chronic infectious disease that is caused by Mycobacterium leprae. The objective of this study was to evaluate the risk factors that are associated with neural alterations and physical disabilities in leprosy patients at the time of diagnosis. Methods A prospective cross-sectional study was conducted on 155 leprosy patients who participated in a program that aimed to eliminate leprosy from São Luis, State of Maranhão. Results Patients who were 31-45 years of age, were older than 60 years of age or had a partner were more likely to have a disability. Patients with partners were 1.14 times more likely (p = 0.025) to have disabilities of the hands. The frequency of disabilities in the feet among the patients with different clinical forms of leprosy was statistically significant. Conclusions The identification of risk factors that are associated with neural alterations and physical disabilities in leprosy patients is important for diagnosing the disease because this approach enables physicians to plan and prioritize actions for the treatment and monitoring of patients.

This cross-sectional retrospective study evaluated 440 leprosy patients; 57% (251/440) had leprosy reactions during and/or after multidrug therapy, 80.5% (202/251) of whom presented with multibacillary leprosy. At diagnosis, positive bacterial index (BI) [odds ratio (OR) = 6.39; 95% confidence interval (CI): 4.1-10.1)] or polymerase chain reaction (PCR) (OR = 9.15; 95% CI: 5.4-15.5) in skin smears, anti-phenolic glycolipid-1 (anti-PGL-1) ELISA (OR = 4.77; 95% CI: 2.9-7.9), leucocytosis (OR = 9.97; 95% CI: 3.9-25.7), thrombocytopenia (OR = 5.72; 95% CI: 2.3-14.0) and elevated lactate dehydrogenase (OR = 2.38; 95% CI: 1.4-4.0) were potential markers for the development of reactions during treatment. After treatment, positive BI (OR = 8.47; 95% CI: 4.7-15.3) and PCR (OR = 6.46; 95% CI: 3.4-12.3) in skin smears, anti-PGL-1 ELISA (OR = 2.25; 95% CI: 1.3-3.9), anaemia (OR = 2.36; 95% CI: 1.2-4.5), leucocytosis (OR = 4.14; 95% CI: 1.5-11.6) and thrombocytopenia (OR = 3.70; 95% CI: 1.3-2.2) were risk factors for the occurrence of reactions during the study period. The identification of groups with an increased risk for developing reactions will allow for the timely development of a treatment plan to prevent nerve damage and, therefore, the appearance of the disabling sequelae associated with the stigma of leprosy.

Leprosy transmission still occurs despite the availability of highly effective treatment. The next step towards successfully eliminating leprosy is interrupting the chain of transmission of the aetiological agent, Mycobacterium leprae. In this investigation, we provide evidence that household contacts (HHCs) of leprosy patients might not only have subclinical infections, but may also be actively involved in bacilli transmission. We studied 444 patients and 1,352 contacts using anti-phenolic glycolipid-I (PGL-I) serology and quantitative polymerase chain reaction (qPCR) to test for M. leprae DNA in nasal swabs. We classified the patients according to the clinical form of their disease and the contacts according to the characteristics of their index case. Overall, 63.3% and 34.2% of patients tested positive by ELISA and PCR, respectively. For HHCs, 13.3% had a positive ELISA test result and 4.7% had a positive PCR test result. The presence of circulating anti-PGL-I among healthy contacts (with or without a positive PCR test result from nasal swabs) was considered to indicate a subclinical infection. DNA detected in nasal swabs also indicates the presence of bacilli at the site of transmission and bacterial entrance. We suggest that the concomitant use of both assays may allow us to detect subclinical infection in HHCs and to identify possible bacilli carriers who may transmit and disseminate disease in endemic regions. Chemoprophylaxis of these contacts is suggested.

Este estudo avaliou a concordância entre o diagnóstico clínico e o diagnóstico laboratorial da hanseníase, utilizando os resultados de biópsias dos laboratórios A e B e o teste ML-Flow. A concordância diagnóstica clínico-histopatológica foi de 67,6%. Os laboratórios apresentaram um índice de concordância de 73,7% em relação ao índice baciloscópico, e o laboratório B detectou 25,4% a mais de casos positivos. A maior concordância foi obtida para a forma V, e a menor para a forma I. A maior discrepância diagnóstica ocorreu para a forma DD. A concordância clínico-laboratorial foi de 41,3% para o laboratório A e 54% para o B. O teste ML-Flow reclassificou 10,7% dos pacientes. A classificação espectral é importante para o melhor entendimento da doença e para seu tratamento adequado, mas não é utilizada em centros de saúde, que adotam os critérios simplificados da OMS, que poderiam ser complementados pelo teste ML-Flow. Tal simplificação é inaceitável para os Centros de Referência em assistência, ensino e pesquisa em hanseníase, de modo que é recomendada a padronização pela classificação de Ridley-Jopling.

This study examined the correlation between the clinical and laboratory diagnosis of leprosy, using biopsy results from laboratories "A" and "B" and the ML Flow test. Clinical and histopathological diagnoses presented 67.6% agreement. The laboratories showed 73.7% agreement in the bacterial index and laboratory 'B' detected 25.4% more positives. The highest agreement was in the LL form and lowest, in the I form. The highest diagnostic discrepancy was for the BB form. Clinical diagnosis agreement was 41.3% for laboratory 'A' and 54% for 'B'. The ML Flow test reclassified 10.7% of the patients. The spectrum of leprosy classification is important for a clearer understanding of the disease and its proper treatment, but is not used in health services, which use the simplified WHO criteria. This could be complemented by ML Flow testing. Such simplification is unacceptable for Leprosy Reference Centers regarding patient attendance, teaching and research, for which the standardization of the Ridley-Jopling classification is recommended.

A hanseníase, cujo agente etiológico Mycobacterium Ieprae, é doença de amplo espectro clínico e imunopatológico. Suas apresentações clínicas estão correlacionadas com padrões imunológicos distintos, variando de uma vigorosa resposta imune mediada por células ao M. Ieprae, com padrão Th1 no pólo tuberculóide, a uma ausência de resposta celular específica aos antígenos do M. Ieprae no pólo lepromatoso, com predomínio da resposta Th2 e exacerbação da resposta humoral. É provável que a suscetibilidade ao M. Ieprae é determinada por diferentes genes polimórficos. Estudos adicionais são necessários para esclarecer os mecanismos das interações complexas entre as citocinas e a participação da diversidade fenotípica da rede de células que contribuem para a defesa do hospedeiro. O entendimento de tais mecanismos poderá oferecer novas abordagens para identificar agonistas e/ou antagonistas para os efeitos pró- ou anti-inflamatórios e em quais circunstâncias sua utilização seria apropriada para intervenções imunológicas e/ou imunoterapeuticas.

Leprosy, whose etiologic agent Mycobacterium Ieprae, is an illness of ample clinical and immunopathological spectrum. Its clinical manifestations are correlated with distinct immunologic forms, varying from a vigorous immune response mediated by cells to M. Ieprae, with Th1 standard in the tuberculoid polar region, to an absence of specific cellular response to antigens of M. Ieprae in the lepromatous polar region, with predominance of Th2 response and exacerbation of humoral response. It is probable that different polymorphic genes determine susceptibility to M. Ieprae. Additional studies are necessary to clarify the complex interactions between cytokines and the role of the phenotypic diversity of cells network that contribute to the host defense. The comprehension of such mechanisms will provide new insights for the identification of agonists and/or antagonists for pro- or anti-inflammatory effects, and also will indicate possible situations for its appropriate use in immunologic and/or immunotherapeutic interventions.