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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.
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Hanseníase/epidemiologia , Adolescente , Instituições de Assistência Ambulatorial , Brasil/epidemiologia , Feminino , Humanos , Masculino , Fatores SocioeconômicosRESUMO
Background: Leprosy is an infectious disease that mostly affects underserved populations. Although it has been largely eliminated, still about 200'000 new patients are diagnosed annually. In the absence of a diagnostic test, clinical diagnosis is often delayed, potentially leading to irreversible neurological damage and its resulting stigma, as well as continued transmission. Accelerating diagnosis could significantly contribute to advancing global leprosy elimination. Digital and Artificial Intelligence (AI) driven technology has shown potential to augment health workers abilities in making faster and more accurate diagnosis, especially when using images such as in the fields of dermatology or ophthalmology. That made us start the quest for an AI-driven diagnosis assistant for leprosy, based on skin images. Methods: Here we describe the accuracy of an AI-enabled image-based diagnosis assistant for leprosy, called AI4Leprosy, based on a combination of skin images and clinical data, collected following a standardized process. In a Brazilian leprosy national referral center, 222 patients with leprosy or other dermatological conditions were included, and the 1229 collected skin images and 585 sets of metadata are stored in an open-source dataset for other researchers to exploit. Findings: We used this dataset to test whether a CNN-based AI algorithm could contribute to leprosy diagnosis and employed three AI models, testing images and metadata both independently and in combination. AI modeling indicated that the most important clinical signs are thermal sensitivity loss, nodules and papules, feet paresthesia, number of lesions and gender, but also scaling surface and pruritus that were negatively associated with leprosy. Using elastic-net logistic regression provided a high classification accuracy (90%) and an area under curve (AUC) of 96.46% for leprosy diagnosis. Interpretation: Future validation of these models is underway, gathering larger datasets from populations of different skin types and collecting images with smartphone cameras to mimic real world settings. We hope that the results of our research will lead to clinical solutions that help accelerate global leprosy elimination. Funding: This study was partially funded by Novartis Foundation and Microsoft (in-kind contribution).
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The World Health Organization has raised concerns about the increasing number of Hansen disease (HD) relapses worldwide, especially in Brazil, India, and Indonesia that report the highest number of recurrent cases. Relapses are an indicator of MDT effectiveness and can reflect Mycobacterium leprae persistence or re-infection. Relapse is also a potential marker for the development or progression of disability. In this research, we studied a large cohort of persons affected by HD treated with full fixed-dose multibacillary (MB) multidrug therapy (MDT) followed for up to 20 years and observed that relapses are a rare event. We estimated the incidence density of relapse in a cohort of patients classified to receive MB regime (bacillary index (BI) > 0), diagnosed between September 1997 and June 2017, and treated with twelve-dose MB-MDT at a HD reference center in Rio de Janeiro, Brazil. We obtained the data from the data management system of the clinic routine service. We linked the selected cases to the dataset of relapses of the national HD data to confirm possible relapse cases diagnosed elsewhere. We diagnosed ten cases of relapse in a cohort of 713 patients followed-up for a mean of 12.1 years. This resulted in an incidence rate of 1.16 relapse cases per 1000 person-year (95% CI = 0.5915-2.076). The accumulated risk was 0.025 in 20 years. The very low risk observed in this cohort of twelve-dose-treated MB patients reinforces the success of the current MDT scheme.
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Hansenostáticos/uso terapêutico , Hanseníase Virchowiana/tratamento farmacológico , Hanseníase Virchowiana/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil/epidemiologia , Criança , Pré-Escolar , Clofazimina/uso terapêutico , Dapsona/uso terapêutico , Quimioterapia Combinada , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Mycobacterium leprae/efeitos dos fármacos , Recidiva , Estudos Retrospectivos , Rifampina/uso terapêutico , Pele/microbiologia , Pele/patologia , Adulto JovemRESUMO
BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has led to governments implementing a variety of public health measures to control transmission and has affected health services. Leprosy is a communicable neglected tropical disease caused by Mycobacterium leprae and is an important health problem in low- and middle-income countries. The natural history of leprosy means that affected individuals need long-term follow-up. The measures recommended to reduce transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can create barriers to health services. We evaluated the impact of the COVID-19 epidemic response on leprosy services and disease management. METHODS: We conducted a cross-sectional online survey with healthcare professionals in leprosy referral centres. RESULTS: Eighty percent of leprosy diagnostic services were reduced. All respondents reported that multidrug therapy (MDT) was available but two reported a reduced stock. Clinicians used alternative strategies such as telephone consultations to maintain contact with patients. However, patients were not able to travel to the referral centres. DISCUSSION: This study highlights the effects of the initial phase of the SARS-CoV-2 pandemic on leprosy services in a range of leprosy-endemic countries. Many services remained open, providing leprosy diagnosis, MDT and leprosy reaction medications. Centres developed innovative measures to counter the negative impacts of the COVID-19 pandemic.
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COVID-19 , Hanseníase , Estudos Transversais , Quimioterapia Combinada , Humanos , Hansenostáticos , Hanseníase/diagnóstico , Hanseníase/tratamento farmacológico , Hanseníase/epidemiologia , Pandemias/prevenção & controle , Encaminhamento e Consulta , SARS-CoV-2 , Inquéritos e QuestionáriosRESUMO
INTRODUCTION: Erythema nodosum leprosum (ENL) is an immunological complication of leprosy. ENL results in morbidity and disability and if it is not treated can lead to death. The current treatment consists of thalidomide or high doses of oral corticosteroids for prolonged periods. Thalidomide is not available in many leprosy endemic countries. The use of corticosteroids is associated with morbidity and mortality. Identifying treatment regimens that reduce the use of corticosteroids in ENL is essential. Methotrexate (MTX) is used to treat many inflammatory diseases and has been used successfully to treat patients with ENL not controlled by other drugs, including prednisolone and thalidomide. We present the protocol of the 'MTX and prednisolone study in ENL' (MaPs in ENL) a randomised controlled trial (RCT) designed to test the efficacy of MTX in the management of ENL. METHODS AND ANALYSIS: MaPs in ENL is an international multicentre RCT, which will be conducted in leprosy referral centres in Bangladesh, Brazil, Ethiopia, India, Indonesia and Nepal. Patients diagnosed with ENL who consent to participate will be randomly allocated to receive 48 weeks of weekly oral MTX plus 20 weeks of prednisolone or 48 weeks of placebo plus 20 weeks of prednisolone. Participants will be stratified by type of ENL into those with acute ENL and those with chronic and recurrent ENL. The primary objective is to determine whether MTX reduces the requirement for additional prednisolone. Patients' reported outcome measures will be used to assess the efficacy of MTX. Participants will be closely monitored for adverse events. ETHICS AND DISSEMINATION: Results will be submitted for publication in peer-reviewed journals. Ethical approval was obtained from the Observational/Interventions Research Ethics Committee of the London School of Hygiene & Tropical Medicine (15762); The Leprosy Mission International Bangladesh Institutional Research Board (in process); AHRI-ALERT Ethical Review Committee, Ethiopia; Ethics Committee of the Managing Committee of the Bombay Leprosy Project; and The Leprosy Mission Trust India Ethics Committee; the Nepal Health and Research Council and Health Research Ethics Committee Dr. Soetomo, Indonesia. This study is registered at www.clinicaltrials.gov. This is the first RCT of MTX for ENL and will contribute to the evidence for the management of ENL.Trial registration numberNCT 03775460.
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Eritema Nodoso , Hanseníase Virchowiana , Metotrexato/uso terapêutico , Prednisolona/uso terapêutico , Bangladesh , Brasil , Eritema Nodoso/tratamento farmacológico , Etiópia , Humanos , Índia , Indonésia , Hansenostáticos/uso terapêutico , Hanseníase Virchowiana/tratamento farmacológico , Londres , NepalRESUMO
OBJECTIVE: The diagnosis of paucibacillary (PB) leprosy cases remains a challenge because of the absence of a confirmatory laboratory method. While quantitative polymerase chain reaction (qPCR) has been shown to provide reliable sensitivity and specificity in PB diagnoses, a thorough investigation of its efficacy in clinical practice has not yet been published. The present study evaluated patients with suspected leprosy skin lesions by using qPCR to identify PB individuals in the Leprosy Outpatient clinic at the Oswaldo Cruz Foundation in Rio de Janeiro, Brazil. METHODS: One hundred seventy-two suspected PB cases were included in the study. The patients were evaluated by a dermatologist at three different times. The clinical dermato-neurological examination and collected samples were performed on the first visit. On the second visit, the results of the histopathological analysis and PCR assay (DNA-based Mycobacterium leprae qPCR-targeting 16S gene) results were analyzed, and a decision regarding multi-drug therapy was made. A year later, the patients were re-examined, and the consensus diagnosis was established. RESULTS: In 58% (100/172) of cases, a conclusive diagnosis via histopathological analysis was not possible; however, 30% (30/100) of these cases had a positive PCR. One hundred ten patients (110/172) attended the third visit. The analysis showed that while the sensitivity of the histopathological test was very low (35%), a qPCR alone was more effective for identifying leprosy, with 57% sensitivity. CONCLUSION: The use of qPCR in suspected PB cases with an inconclusive histology improved the sensitivity of leprosy diagnoses.
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Hanseníase Paucibacilar/diagnóstico , Técnicas de Diagnóstico Molecular/métodos , Mycobacterium leprae/isolamento & purificação , Reação em Cadeia da Polimerase em Tempo Real/métodos , Adolescente , Adulto , Idoso , Brasil , DNA Bacteriano/genética , DNA Ribossômico/genética , Feminino , Histocitoquímica , Humanos , Masculino , Pessoa de Meia-Idade , Mycobacterium leprae/genética , Pacientes Ambulatoriais , RNA Ribossômico 16S/genética , Sensibilidade e Especificidade , Adulto JovemRESUMO
Household contacts (HHC) of leprosy patients exhibit high-risk of developing leprosy and contact tracing is helpful for early diagnosis. From 2011 to 2018,2,437 HHC were examined in a clinic in Rio de Janeiro, Brazil and 16S qPCR was used for diagnosis and monitoring of contacts. Fifty-four HHCs were clinically diagnosed with leprosy at intake. Another 25 exhibited leprosy-like skin lesions at intake, 8 of which were confirmed as having leprosy (50% of which were qPCR positive) and 17 of which were diagnosed with other skin diseases (6% qPCR positive). In skin biopsies, qPCR presented a sensitivity of 0.50 and specificity of 0.94. Furthermore, 955 healthy HHCs were followed-up for at least 3 years and skin scrapings were collected from earlobes for qPCR detection. Positive qPCR indicated a non-significant relative risk of 2.52 of developing the disease. During follow-up, those who progressed towards leprosy exhibited 20% qPCR positivity, compared to 9% of those who remained healthy. Disease-free survival rates indicated that age had a significant impact on disease progression, where patients over 60 had a greater chance of developing leprosy [HR = 32.4 (3.6-290.3)]. Contact tracing combined with qPCR may assist in early diagnosis and age is a risk factor for leprosy progression.
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Busca de Comunicante/métodos , DNA Bacteriano/análise , DNA Ribossômico/análise , Características da Família , Hanseníase/diagnóstico , Mycobacterium leprae/isolamento & purificação , Reação em Cadeia da Polimerase em Tempo Real/métodos , Adolescente , Adulto , Brasil/epidemiologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Seguimentos , Humanos , Lactente , Hanseníase/epidemiologia , Hanseníase/genética , Masculino , Pessoa de Meia-Idade , Técnicas de Diagnóstico Molecular , Mycobacterium leprae/genética , Fatores de Tempo , Adulto JovemRESUMO
It has been speculated that, as seen in tuberculosis, human immunodeficiency virus (HIV) and Mycobacterium leprae (M. leprae) co-infection may exacerbate the pathogenesis of leprosy lesions and/or lead to increased susceptibility to leprosy. However, to date, HIV infection has not appeared to increase susceptibility to leprosy. In contrast, initiation of antiretroviral treatment (ART) has been reported to be associated with anecdotal activation of M. leprae infection and exacerbation of existing leprosy lesions. To determine whether ART is associated with worsening of the manifestations of leprosy, a cohort of leprosy patients recruited between 1996 and 2006 at the Oswaldo Cruz Foundation (FIOCRUZ) Leprosy Outpatient Clinic in Rio de Janeiro, Brazil, was studied longitudinally. ART treatment of HIV/leprosy co-infection was associated with the tuberculoid type, paucibacillary disease, and lower bacillary loads. CD4 lymphocyte counts were higher among HIV/leprosy patients at the time of leprosy diagnosis, while viral loads were lower compared with the time of HIV diagnosis. The conclusion was that ART and immune reconstitution were critical factors driving the development and/or clinical appearance of leprosy lesions.
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Terapia Antirretroviral de Alta Atividade/efeitos adversos , Infecções por HIV/tratamento farmacológico , Síndrome Inflamatória da Reconstituição Imune/etiologia , Hanseníase/imunologia , Adulto , Brasil/epidemiologia , Estudos de Casos e Controles , Comorbidade , Suscetibilidade a Doenças , Feminino , Infecções por HIV/epidemiologia , Humanos , Síndrome Inflamatória da Reconstituição Imune/epidemiologia , Hanseníase/epidemiologia , Masculino , Análise Multivariada , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Análise de SobrevidaRESUMO
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.
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Glucocorticoides/administração & dosagem , Hansenostáticos/administração & dosagem , Hanseníase Tuberculoide/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/prevenção & controle , Prednisona/administração & dosagem , Adulto , Idoso , Clofazimina/administração & dosagem , Dapsona/administração & dosagem , Quimioterapia Combinada , Eletrofisiologia , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Rifampina/administração & dosagem , Resultado do TratamentoRESUMO
OBJECTIVES: We wished to validate our recently devised 16-item ENLIST ENL Severity Scale, a clinical tool for measuring the severity of the serious leprosy associated complication of erythema nodosum leprosum (ENL). We also wished to assess the responsiveness of the ENLIST ENL Severity Scale in detecting clinical change in patients with ENL. METHODS: Participants, recruited from seven centres in six leprosy endemic countries, were assessed using the ENLIST ENL Severity Scale by two researchers, one of whom categorised the severity of ENL. At a subsequent visit a further assessment using the scale was made and both participant and physician rated the change in ENL using the subjective categories of "Much better", "somewhat better", "somewhat worse" and "much worse" compared with "No change" or "about the same". RESULTS: 447 participants were assessed with the ENLIST ENL Severity Scale. The Cronbach alpha of the scale and each item was calculated to determine the internal consistency of the scale. The ENLIST ENL Severity Scale had good internal consistency and this improved following removal of six items to give a Cronbach's alpha of 0.77. The cut off between mild ENL and more severe disease was 9 determined using ROC curves. The minimal important difference of the scale was determined to be 5 using both participant and physician ratings of change. CONCLUSIONS: The 10-item ENLIST ENL Severity Scale is the first valid, reliable and responsive measure of ENL severity and improves our ability to assess and compare patients and their treatments in this severe and difficult to manage complication of leprosy. The ENLIST ENL Severity Scale will assist physicians in the monitoring and treatment of patients with ENL. The ENLIST ENL Severity Scale is easy to apply and will be useful as an outcome measure in treatment studies and enable the standardisation of other clinical and laboratory ENL research.
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Eritema Nodoso/patologia , Hanseníase Virchowiana/patologia , Índice de Gravidade de Doença , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Nerve damage in leprosy can be directly induced by Mycobacterium leprae in the early stages of infection, however, immunomediated mechanisms add gravity to the impairment of neural function in symptomatic periods of the disease. This study investigated the immunohistochemical expression of immunomarkers involved in the pathogenic mechanisms of leprosy nerve damage. These markers selected were CXCL10, CCL2 chemokines and immunomarkers as CD3, CD4, CD8, CD45RA, CD45RO, CD68, HLA-DR, and metalloproteinases 2 and 9 (MMP2 and MMP9) occurring in nerve biopsy specimens collected from leprosy (23) and nonleprosy patients (5) suffering peripheral neuropathy. CXCL10, CCL2, MMP2, and MMP9 immunoreactivities were found in the leprosy nerves but not in nonleprosy samples. Immunolabeling was predominantly found in recruited macrophages and Schwann cells composing the inflammatory cellular population in the leprosy-affected nerves. The immunohistochemical expression of all the markers, but CXCL10, was associated with fibrosis, however, only CCL2 was, independently from the others, associated with this excessive deposit of extracellular matrix. No difference in the frequency of the immunolabeling was detected between the AFB⺠and AFB⻠leprosy subgroups of nerve, exception made to some statistical trend to difference in regard to CD68⻠and HLA-DR⺠cells in the AFB⻠nerves exhibiting epithelioid granuloma. MMP9 expression associated with fibrosis is consistent with previous results of research group. The findings conveys the idea that CCL2 and CXCL10 chemokines at least in advanced stages of leprosy nerve lesions are not determinant for the establishment of AFB⺠or AFB⻠leprosy lesions, however, CCL2 is associated with macrophage recruitment and fibrosis.
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Quimiocina CCL2/metabolismo , Quimiocina CXCL10/metabolismo , Hanseníase Tuberculoide/mortalidade , Nervos Periféricos/metabolismo , Nervos Periféricos/patologia , Adolescente , Adulto , Idoso , Biomarcadores/metabolismo , Feminino , Humanos , Hanseníase Tuberculoide/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
Erythema nodosum leprosum (ENL) is a severe multisystem immune mediated complication of borderline lepromatous leprosy and lepromatous leprosy. ENL is associated with skin lesions, neuritis, arthritis, dactylitis, eye inflammation, osteitis, orchitis, lymphadenitis and nephritis. The treatment of ENL requires immunosuppression, which is often required for prolonged periods of time and may lead to serious adverse effects. ENL and its treatment is associated with increased mortality and economic hardship. Improved, evidence-based treatments for ENL are needed; however, defining the severity of ENL and outcome measures for treatment studies is difficult because of the multiple organ systems involved. A cross-sectional study was performed, by the members of the Erythema Nodosum Leprosum International STudy (ENLIST) Group, of patients with ENL attending seven leprosy referral centres in Brazil, Ethiopia, India, Nepal, the Philippines and the United Kingdom. We systematically documented the clinical features and type of ENL, its severity and the drugs used to treat it. Patients with chronic ENL were more likely to be assessed as having severe ENL. Pain, the most frequent symptom, assessed using a semi-quantitative scale was significantly worse in individuals with "severe" ENL. Our findings will determine the items to be included in a severity scale of ENL which we are developing and validating. The study also provides data on the clinical features of ENL, which can be incorporated into a definition of ENL and used for outcome measures in treatment studies.
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Eritema Nodoso/patologia , Hanseníase Virchowiana/complicações , Índice de Gravidade de Doença , Adolescente , Adulto , Idoso , Criança , Estudos Transversais , Eritema Nodoso/complicações , Eritema Nodoso/tratamento farmacológico , Feminino , Humanos , Cooperação Internacional , Hansenostáticos/uso terapêutico , Masculino , Pessoa de Meia-Idade , Dor/fisiopatologia , Adulto JovemRESUMO
The clinical diagnosis of pure neural leprosy (PNL) remains a public health care problem mainly because skin lesions-the cardinal features of leprosy-are always absent.Moreover, the identification of the leprosy bacillus is not easily achieved even when a nerve biopsy can be performed. In an attempt to reach a reliable PNL diagnosis in patients referred to our Leprosy Outpatient Clinic, this study employed a variety of criteria. The nerve biopsies performed on the 67 individuals whose clinical, neurological, and electrophysiological examination findings strongly suggested peripheral neuropathy were submitted to M. leprae identification via a polymerase chain reaction (PCR). Mononeuropathy multiplex was the most frequent clinical and electrophysiological pattern of nerve dysfunction, while sensory impairment occurred in 89% of all cases and motor dysfunction in 81%. Axonal neuropathy was the predominant electrophysiological finding, while the histopathological nerve study showed epithelioid granuloma in 14% of the patients, acid fast bacilli in 16%, and nonspecific inflammatory infiltrate and/or fibrosis in 39%. PCR for M. leprae was positive in 47% of the nerve biopsy samples (n=23). PCR, in conjunction with clinical and neurological examination results, can be a powerful tool in attempting to identify and confirm a PNL diagnosis.
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Hanseníase Tuberculoide/diagnóstico , Hanseníase Tuberculoide/microbiologia , Mycobacterium leprae , Adolescente , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Nervos Periféricos/microbiologia , Nervos Periféricos/patologiaRESUMO
BACKGROUND: Many articles have shown that HIV infection can modify the clinical course of leprosy, but very scant epidemiological and clinical data about this co-infection are available in the peer-reviewed literature. METHODS: We herein describe the geographical distribution and demographic characteristics of 92 HIV/Mycobacterium leprae co-infected patients assisted in a Brazilian Leprosy referral center. A multivariate analysis was performed in order to establish clinical factors associated with type 1 reaction. RESULTS: Co-infected patient admissions have steadily increased over the last years at this referral center. Most patients were men, with a mean age of 32.3 years and presenting with the paucibacillary form of leprosy. The use of antiretroviral therapy (ART) was the only factor associated with type 1 reaction. Most patients were living in the metropolitan area and the north sub area of Rio de Janeiro City. CONCLUSION: Co-infected patients receiving ART have a greater chance to develop type 1 reaction. Patients living with both HIV and leprosy are likely to live in regions characterized by a high density impoverished population.
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Infecções por HIV/epidemiologia , Hanseníase/epidemiologia , Adolescente , Adulto , Fatores Etários , Idoso , Brasil/epidemiologia , Coinfecção/epidemiologia , Coinfecção/microbiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Mycobacterium leprae , Distribuição por Sexo , Adulto JovemRESUMO
BACKGROUND: Contacts of leprosy patients are at increased risk of developing leprosy and need to be targeted for early diagnosis. Seropositivity to the phenolic glycolipid I (PGL-I) antigen of Mycobacterium leprae has been used to identify contacts who have an increased risk of developing leprosy. In the present study, we studied the effect of seropositivity in patient contacts, on the risk of developing leprosy, stratified by Bacille Calmette Guerin (BCG) vaccination after index case diagnosis. METHODOLOGY/PRINCIPAL FINDINGS: Leprosy contacts were examined as part of the surveillance programme of the Oswaldo Cruz Institute Leprosy Outpatient Clinic in Rio de Janeiro. Demographic, social, epidemiological and clinical data were collected. The presence of IgM antibodies to PGL-I in sera and BCG vaccination status at the time of index case diagnosis were evaluated in 2,135 contacts. During follow-up, 60 (2.8%; 60/2,135) leprosy cases were diagnosed: 41 among the 1,793 PGL-I-negative contacts and 19 among the 342 PGL-I-positive contacts. Among PGL-I-positive contacts, BCG vaccination after index case diagnosis increased the adjusted rate of developing clinical manifestations of leprosy (Adjusted Rate Ratio (aRR)â=â4.1; 95% CI: 1.8-8.2) compared with the PGL-I-positive unvaccinated contacts (aRRâ=â3.2; 95% CI: 1.2-8.1). The incidence density was highest during the first year of follow-up for the PGL-I-positive vaccinated contacts. However, all of those contacts developed PB leprosy, whereas most MB cases (4/6) occurred in PGL-I-positive unvaccinated contacts. CONCLUSION: Contact examination combined with PGL-I testing and BCG vaccination remain important strategies for leprosy control. The finding that rates of leprosy cases were highest among seropositive contacts justifies targeting this specific group for close monitoring. Furthermore, it is recommended that PGL-I-positive contacts and contacts with a high familial bacteriological index, regardless of serological response, should be monitored. This group could be considered as a target for chemoprophylaxis.
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Anticorpos Antibacterianos/sangue , Antígenos de Bactérias/imunologia , Vacina BCG/imunologia , Glicolipídeos/imunologia , Hanseníase/epidemiologia , Hanseníase/imunologia , Mycobacterium leprae/patogenicidade , Adolescente , Adulto , Idoso , Vacina BCG/administração & dosagem , Criança , Pré-Escolar , Estudos de Coortes , Humanos , Imunoglobulina M/sangue , Incidência , Lactente , Masculino , Pessoa de Meia-Idade , Mycobacterium leprae/imunologia , Medição de Risco , Adulto JovemRESUMO
BACKGROUND: This study aimed to evaluate the risk factors associated with developing leprosy among the contacts of newly-diagnosed leprosy patients. METHODOLOGY/PRINCIPAL FINDINGS: A total of 6,158 contacts and 1,201 leprosy patients of the cohort who were diagnosed and treated at the Leprosy Laboratory of Fiocruz from 1987 to 2007 were included. The contact variables analyzed were sex; age; educational and income levels; blood relationship, if any, to the index case; household or non-household relationship; length of time of close association with the index case; receipt of bacillus Calmette-Guérin (BGG) vaccine and presence of BCG scar. Index cases variables included sex, age, educational level, family size, bacillary load, and disability grade. Multilevel logistic regression with random intercept was applied. Among the co-prevalent cases, the leprosy-related variables that remained associated with leprosy included type of household contact, [odds ratio (OR) = 1.33, 95% confidence interval (CI): 1.02, 1.73] and consanguinity with the index case, (OR = 1.89, 95% CI: 1.42-2.51). With respect to the index case variables, the factors associated with leprosy among contacts included up to 4 years of schooling and 4 to 10 years of schooling (OR = 2.72, 95% CI: 1.54-4.79 and 2.40, 95% CI: 1.30-4.42, respectively) and bacillary load, which increased the chance of leprosy among multibacillary contacts for those with a bacillary index of one to three and greater than three (OR = 1.79, 95% CI: 1.19-2.17 and OR: 4.07-95% CI: 2.73, 6.09), respectively. Among incident cases, household exposure was associated with leprosy (OR = 1.96, 95% CI: 1.29-2.98), compared with non-household exposure. Among the index case risk factors, an elevated bacillary load was the only variable associated with leprosy in the contacts. CONCLUSIONS/SIGNIFICANCE: Biological and social factors appear to be associated with leprosy among co-prevalent cases, whereas the factors related to the infectious load and proximity with the index case were associated with leprosy that appeared in the incident cases during follow-up.
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Transmissão de Doença Infecciosa , Hanseníase/epidemiologia , Hanseníase/transmissão , Adolescente , Adulto , Criança , Pré-Escolar , Busca de Comunicante/métodos , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Mycobacterium leprae/isolamento & purificação , Medição de Risco , Adulto JovemRESUMO
OBJECTIVES: To develop a valid and reliable quantitative measure of leprosy Type 1 reactions. METHODS: A scale was developed from previous scales which had not been validated. The face and content validity were assessed following consultation with recognised experts in the field. The construct validity was determined by applying the scale to patients in Bangladesh and Brazil who had been diagnosed with leprosy Type 1 reaction. An expert categorized each patient's reaction as mild or moderate or severe. Another worker applied the scale. This was done independently. In a subsequent stage of the study the agreement between two observers was assessed. RESULTS: The scale had good internal consistency demonstrated by a Cronbach's alpha >0.8. Removal of three items from the original scale resulted in better discrimination between disease severity categories. Cut off points for Type 1 reaction severities were determined using Receiver Operating Characteristic curves. A mild Type 1 reaction is characterized using the final scale by a score of 4 or less. A moderate reaction is a score of between 4.5 and 8.5. A severe reaction is a score of 9 or more. CONCLUSIONS: We have developed a valid and reliable tool for quantifying leprosy Type 1 reaction severity and believe this will be a useful tool in research of this condition, in observational and intervention studies, and in the comparison of clinical and laboratory parameters.
Assuntos
Hanseníase/classificação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bangladesh , Brasil , Criança , Feminino , Humanos , Hanseníase/fisiopatologia , Masculino , Nervo Mediano/fisiopatologia , Pessoa de Meia-Idade , Sistema Nervoso/fisiopatologia , Índice de Gravidade de Doença , Inquéritos e Questionários , Nervo Ulnar/fisiopatologiaRESUMO
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.
Assuntos
Humanos , Feminino , Adolescente , Hanseníase/epidemiologia , Instituições de Assistência Ambulatorial , Brasil/epidemiologia , Fatores SocioeconômicosRESUMO
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 percent 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 percent) 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 percent 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.
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 por cento 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 por cento) 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 por cento 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.