RESUMO
BACKGROUND: Peripheral nerve injury and bone lesions, well known leprosy complications, lead to deformities and incapacities. The phosphate-regulating gene with homologies to endopeptidase on the X chromosome (PHEX) encodes a homonymous protein (PHEX) implicated in bone metabolism. PHEX/PHEX alterations may result in bone and cartilage lesions. PHEX expression is downregulated by intracellular Mycobacterium leprae (M. leprae) in cultures of human Schwann cells and osteoblasts. M. leprae in vivo effect on PHEX/PHEX is not known. METHODS: Cross-sectional observational study of 36 leprosy patients (22 lepromatous and 14 borderline-tuberculoid) and 20 healthy volunteers (HV). The following tests were performed: PHEX flow cytometric analysis on blood mononuclear cells, cytokine production in culture supernatant, 25-hydroxyvitamin D (OHvitD) serum levels and (99m)Tc-MDP three-phase bone scintigraphy, radiography of upper and lower extremities and blood and urine biochemistry. RESULTS: Significantly lower PHEX expression levels were observed in lepromatous patients than in the other groups (χ(2) = 16.554, p < 0.001 for lymphocytes and χ(2) = 13.933, p = 0.001 for monocytes). Low levels of 25-(OHvitD) were observed in HV (median = 23.0 ng/mL) and BT patients (median = 27.5 ng/mL) and normal serum levels were found in LL patients (median = 38.6 ng/mL). Inflammatory cytokines, such as TNF, a PHEX transcription repressor, were lower after stimulation with M. leprae in peripheral blood mononuclear cells from lepromatous in comparison to BT patients and HV (χ(2) = 10.820, p < 0.001). CONCLUSION: Downregulation of PHEX may constitute an important early component of bone loss and joint damage in leprosy. The present results suggest a direct effect produced by M. leprae on the osteoarticular system that may use this mechanism.
Assuntos
Regulação para Baixo , Hanseníase Dimorfa/metabolismo , Hanseníase Multibacilar/metabolismo , Endopeptidase Neutra Reguladora de Fosfato PHEX/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Osso e Ossos/microbiologia , Cartilagem/microbiologia , Estudos Transversais , Citocinas/metabolismo , Feminino , Citometria de Fluxo , Voluntários Saudáveis , Humanos , Inflamação/metabolismo , Inflamação/microbiologia , Leucócitos Mononucleares/metabolismo , Masculino , Pessoa de Meia-Idade , Osteoblastos/microbiologia , Células de Schwann/microbiologia , Medronato de Tecnécio Tc 99m , Adulto JovemRESUMO
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
Gelatinases A and B (matrix metalloproteinase 2 [MMP-2] and MMP-9, respectively) can induce basal membrane breakdown and leukocyte migration, but their role in leprosy skin inflammation remains unclear. In this study, we analyzed clinical specimens from leprosy patients taken from stable, untreated skin lesions and during reactional episodes (reversal reaction [RR] and erythema nodosum leprosum [ENL]). The participation of MMPs in disease was suggested by (i) increased MMP mRNA expression levels in skin biopsy specimens correlating with the expression of gamma interferon (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha), (ii) the detection of the MMP protein and enzymatic activity within the inflammatory infiltrate, (iii) increased MMP levels in patient sera, and (iv) the in vitro induction of MMP-9 by Mycobacterium leprae and/or TNF-alpha. It was observed that IFN-gamma, TNF-alpha, MMP-2, and MMP-9 mRNA levels were higher in tuberculoid than lepromatous lesions. In contrast, interleukin-10 and tissue inhibitor of MMP (TIMP-1) message were not differentially modulated. These data correlated with the detection of the MMP protein evidenced by immunohistochemistry and confocal microscopy. When RR and ENL lesions were analyzed, an increase in TNF-alpha, MMP-2, and MMP-9, but not TIMP-1, mRNA levels was observed together with stronger MMP activity (zymography/in situ zymography). Moreover, following in vitro stimulation of peripheral blood cells, M. leprae induced the expression of MMP-9 (mRNA and protein) in cultured cells. Overall, the present data demonstrate an enhanced MMP/TIMP-1 ratio in the inflammatory states of leprosy and point to potential mechanisms for tissue damage. These results pave the way toward the application of new therapeutic interventions for leprosy reactions.
Assuntos
Hanseníase/imunologia , Leucócitos/imunologia , Metaloproteinases da Matriz/imunologia , Mycobacterium leprae/imunologia , Pele/imunologia , Pele/microbiologia , Adulto , Movimento Celular , Feminino , Perfilação da Expressão Gênica , Humanos , Imuno-Histoquímica , Técnicas In Vitro , Inflamação , Mediadores da Inflamação/análise , Masculino , Microscopia Confocal , Pessoa de Meia-Idade , Pele/química , Pele/patologia , Adulto JovemRESUMO
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.
Assuntos
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
A magnetic resonance imaging (MRI) protocol was performed in leprosy patients with a neuropathic foot and superficial ulcers and/or localized cellulitis but no clinical suspicion of osteomyelitis. The aim of the study was to determine if unsuspected osteomyelitis was present in this defined group of leprosy patients. A total of 15 neuropathic feet from 9 patients were included. Clinically and on MRI, the forefoot was predominantly affected. MRI findings of osteomyelitis were found in 4 feet. In feet with osteomyelitis, 3 had a superficial ulcer and 3 had clinical signs of localized cellulitis. A clinical diagnosis of cellulitis was confirmed on MRI in 2 feet.A striking discrepancy between clinical and MRI findings was found.This study shows that, compared with clinical evaluation, MRI is a sensitive method for the detection of unsuspected osteomyelitis in neuropathic feet with superficial ulcers and/or cellulitis. MRI findings in this group of patients may influence clinical decision making and may prevent further complications, because osteomyelitis requires more aggressive medical treatment. This preliminary communication should pave the wave for designed controlled studies so that patients with Hansen's neuropathy may get the best medical care.
Assuntos
Celulite (Flegmão)/diagnóstico , Doenças do Pé/diagnóstico , Hanseníase/diagnóstico , Imageamento por Ressonância Magnética/métodos , Adulto , Celulite (Flegmão)/etiologia , Diagnóstico Diferencial , Feminino , Seguimentos , Humanos , Hanseníase/complicações , Masculino , Pessoa de Meia-Idade , Osteomielite/diagnóstico , Reprodutibilidade dos Testes , Estudos Retrospectivos , Adulto JovemRESUMO
Type 2 reaction (T2R) or erythema nodosum leprosum (ENL), a sudden episode of acute inflammation predominantly affecting lepromatous leprosy patients (LL), characterized by a reduced cellular immune response. This possibly indicates a close relationship between the onset of T2R and the altered frequency, and functional activity of T lymphocytes, particularly of memory subsets. This study performed ex vivo and in vitro characterizations of T cell blood subpopulations from LL patients with or without T2R. In addition, the evaluation of activity of these subpopulations was performed by analyzing the frequency of these cells producing IFN-γ, TNF, and IL-10 by flow cytometry. Furthermore, the expression of transcription factors, for the differentiation of T cells, were analyzed by quantitative real-time polymerase chain reaction. Our results showed an increased frequency of CD8+/TNF+ effector memory T cells (TEM) among T2Rs. Moreover, there was evidence of a reduced frequency of CD4 and CD8+ IFN-γ-producing cells in T2R, and a reduced expression of STAT4 and TBX21. Finally, a significant and positive correlation between bacteriological index (BI) of T2R patients and CD4+/TNF+ and CD4+/IFN-γ+ T cells was observed. Thus, negative correlation between BI and the frequency of CD4+/IL-10+ T cells was noted. These results suggest that CD8+/TNF+ TEM are primarily responsible for the transient alteration in the immune response to Mycobacterium leprae in ENL patients. Thus, our study improves our understanding of pathogenic mechanisms and might suggest new therapeutic approaches for leprosy.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Eritema Nodoso/imunologia , Hanseníase Virchowiana/imunologia , Mycobacterium leprae/patogenicidade , Fator de Necrose Tumoral alfa/imunologia , Adolescente , Adulto , Idoso , Linfócitos T CD4-Positivos/microbiologia , Linfócitos T CD8-Positivos/microbiologia , Estudos de Casos e Controles , Eritema Nodoso/genética , Eritema Nodoso/patologia , Feminino , Regulação da Expressão Gênica , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Memória Imunológica , Imunofenotipagem , Interferon gama/genética , Interferon gama/imunologia , Interleucina-10/genética , Interleucina-10/imunologia , Hanseníase Virchowiana/genética , Hanseníase Virchowiana/patologia , Masculino , Pessoa de Meia-Idade , Mycobacterium leprae/crescimento & desenvolvimento , Mycobacterium leprae/imunologia , Cultura Primária de Células , Fator de Transcrição STAT4/genética , Fator de Transcrição STAT4/imunologia , Transdução de Sinais , Proteínas com Domínio T/genética , Proteínas com Domínio T/imunologia , Fator de Necrose Tumoral alfa/genéticaRESUMO
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.
Assuntos
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
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.
Assuntos
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
Leprosy is a chronic human disease caused by the yet-uncultured pathogen Mycobacterium leprae. Although readily curable with multidrug therapy (MDT), over 200,000 new cases are still reported annually. Here, we obtain M. leprae genome sequences from DNA extracted directly from patients' skin biopsies using a customized protocol. Comparative and phylogenetic analysis of 154 genomes from 25 countries provides insight into evolution and antimicrobial resistance, uncovering lineages and phylogeographic trends, with the most ancestral strains linked to the Far East. In addition to known MDT-resistance mutations, we detect other mutations associated with antibiotic resistance, and retrace a potential stepwise emergence of extensive drug resistance in the pre-MDT era. Some of the previously undescribed mutations occur in genes that are apparently subject to positive selection, and two of these (ribD, fadD9) are restricted to drug-resistant strains. Finally, nonsense mutations in the nth excision repair gene are associated with greater sequence diversity and drug resistance.
Assuntos
Anti-Infecciosos/farmacologia , Farmacorresistência Bacteriana/genética , Mycobacterium leprae/efeitos dos fármacos , Filogenia , Códon sem Sentido , DNA Bacteriano/química , Genoma Bacteriano , Humanos , Testes de Sensibilidade Microbiana , Mycobacterium leprae/genética , Mycobacterium leprae/isolamento & purificaçãoRESUMO
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.
Assuntos
Eritema Nodoso/patologia , Hanseníase Virchowiana/patologia , Índice de Gravidade de Doença , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
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.
Assuntos
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
Matrix metalloproteinases (MMPs) and tumor necrosis factor alpha (TNF-alpha) play important and related roles in the pathogenesis of nerve injury. MMP-dependent and TNF-alpha-dependent processes of neurodegeneration, such as blood-nerve breakdown and immune cell recruitment, are characteristic of leprosy nerve damage. Our work has contributed to the understanding of the role of cytokines in the process, but the role of MMPs in the pathogenesis of neuritic leprosy has not been investigated. This study analyzed the changes in mRNA expression and immunodistribution of MMP-2, MMP-9, TNF-alpha-converting enzyme (TACE), TNF-alpha in nerves of 27 pure neuritic leprosy (PNL) patients, both acid-fast bacilli positive (AFB(+)) and acid-fast bacilli negative (AFB(-)), and 8 non-leprosy patients with control peripheral neuropathic conditions. MMP-2, MMP-9, and TNF-alpha mRNA expression was significantly induced in the AFB(-) relative to the AFB(+) neuritic leprosy group and nonlepritic controls; TACE levels were also elevated in the AFB(-) group, but this change was not statistically significant. Immunoreactive profiles for TNF-alpha and MMPs demonstrated strong reactivity of myelinated axons, infiltrating macrophages, Schwann cells, endothelial cells, and perineurial cells in neuritic leprosy biopsies. This study provides the evidence of the involvement of MMPs in the pathogenesis of PNL neuropathy.
Assuntos
Proteínas ADAM/biossíntese , Hanseníase/metabolismo , Metaloproteinase 2 da Matriz/biossíntese , Metaloproteinase 9 da Matriz/biossíntese , Nervos Periféricos/metabolismo , Fator de Necrose Tumoral alfa/biossíntese , Proteína ADAM17 , Adulto , DNA Complementar/genética , DNA Complementar/isolamento & purificação , Feminino , Imunofluorescência , Humanos , Imuno-Histoquímica , Hanseníase/enzimologia , Masculino , Pessoa de Meia-Idade , Nervos Periféricos/enzimologia , RNA/genética , RNA/isolamento & purificação , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
A sífilis é uma doença infectocontagiosa de alta prevalência, especialmente nos países em desenvolvimento, e costuma ser denominada a "grande imitadora",devido seu polimorfismo lesional. A divisão da doença em fases é apenas didática e tem importância no manejo terapêutico, entretanto a sífilis deve ser tratada como doença dinâmica, pela possibilidade de sobreposição de seus estágios. Os autores relatam dois casos em que há concomitância do primarismo com o secundarismo sifilítico e enfatizam a importância da avaliação global do paciente em DST.
Syphilis is an infectious disease of high prevalence, especially in underdeveloped countries, and is often called the "great imitator" due to its versatile andvaried disease presentations. The disease's division into stages is only didactic and has importance in the therapeutic management, however syphilis should be managed as a dynamic disease, due to its possibility of overlapping stages. The authors report two cases in which there is concomitance of primary and secondary syphilis and emphasize the importance of patient global assessment in STD.
Assuntos
Humanos , Masculino , Feminino , Adulto , Sífilis/diagnóstico , Sífilis/terapia , Infecções Sexualmente Transmissíveis , PreservativosRESUMO
In spite of the decrease in the number of registered leprosy patients, the number of new cases diagnosed each year (400,000) has remained essentially unchanged. Leprosy diagnosis is difficult due to the low sensitivity of current methodologies to identify new cases. In this study, conventional and TaqMan real-time PCR assays for detection of Mycobacterium leprae DNA were compared to current classification based on clinical, bacteriological, and histological evaluation. M. leprae DNA was extracted from frozen skin biopsy specimens from 69 leprosy patients enrolled in the study and was amplified using specific primers for either the antigen 85B-coding gene or the 85A-C intergenic region by using conventional and real-time PCR. The detection rate was 100% among multibacillary (MB) patients and ranged from 62.5% to 79.2% among paucibacillary (PB) patients according to the assay used. The TaqMan system for 85B gene amplification showed the highest sensitivity, although conventional PCR using the 85A-C gene as a target was also efficient. The cycle threshold (C(T)) values obtained using the TaqMan system were able to statistically (P < 0.0001) differentiate MB (mean C(T), 28.06; standard deviation [SD], 4.51) from PB (mean C(T), 33.06; SD, 2.24) patients. Also, there was a correlation between C(T) values and the bacteriological index for MB patients (Pearson's r, -0.444; P = 0.008). Within the PB patients' group, we tested normal skin from six patients exhibiting the pure neuritic form of leprosy (PNL). Five out of six PNL patients were positive for the presence of M. leprae DNA, even in the absence of skin lesions. In conclusion, the TaqMan real-time PCR developed here seems to be a useful tool for rapidly detecting and quantifying M. leprae DNA in clinical specimens in which bacilli were undetectable by conventional histological staining.
Assuntos
Antígenos de Bactérias/genética , Hanseníase/microbiologia , Mycobacterium leprae/isolamento & purificação , Reação em Cadeia da Polimerase/métodos , Pele/microbiologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Biópsia , DNA Bacteriano/análise , DNA Bacteriano/isolamento & purificação , Humanos , Hanseníase/diagnóstico , Mycobacterium leprae/genética , Sensibilidade e Especificidade , Taq Polimerase/metabolismoRESUMO
Single skin lesion, paucibacillary (SSL-PB) leprosy is considered an early diseasemanifestation. This study evaluated the clinical outcome of a cohort of 259 newlydiagnosed SSL-PB treated with one dose of rifampicin, ofloxacin, minocycline (ROM)and followed-up for three-years. Patients were recruited from the North, Central Westand Southeast regions in Brazil (1997-2001). The result expected with ROM therapywas disappearance or the reduction of lesion size. Manifestations that required additional intervention were considered as poor clinical outcome: type-1 reaction (T1R) with orwithout neuritis, neuritis alone, increase in lesion size and shift from paucibacillary tomultibacillary. The incidence of poor clinical outcome was calculated by personmonthand with the Kaplan-Meier methods. 61.8% of the participants were females,mean age 32.2, and 67.2% had borderline tuberculoid (BT) or tuberculoid forms. T1Rwas the predominant event; shift from paucibacillary to multibacillary was rare. 92.0%of the volunteers shown no events during the first year, the same occurring to 80.6%of them after 3 years of clinical monitoring. The probability of remaining event-freewas highest among those 40 years old or younger. Poor outcome predominated amongBT patients. Extended monitoring of SSL-PB leprosy cases under minimal therapyprovided valuable case management information for reference centers.
Lesão única paucibacilar (SSL-PB) é considerada manifestação clínica inicial dahanseníase. Este estudo avaliou resultado clínico de coorte de 259 pacientes SSL-PBrecém-diagnosticados, tratados com esquema de dose única Rifampicina, Ofloxacina,Minociclina (ROM) e acompanhados por 3 anos (1997-2001) nas regiões Norte,Centro-Oeste e Sudeste. O resultado esperado do tratamento ROM compreendedesaparecimento ou diminuição da lesão. O desfecho foi definido como qualquerevento clínico com indicação de terapia adicional: reação tipo 1 (T1R) com ou semneurite, neurite, aumento de tamanho de lesão e mudança de paucibacilar paramultibacilar. Estas manifestações foram consideradas eventos clínicos desfavoráveis,calculados por densidade de incidência (pessoa-tempo) e por Kaplan-Meier. 61,8%dos participantes eram mulheres (32,2 média idade), 67,2% borderline-tuberculoide(BT) e tuberculoide. T1R foi o desfecho predominante; mudança de paucibacilar paramultibacilar foi rara. 92,0% não apresentaram eventos desfavoráveis no primeiro anoe 80,6% ao final de três anos de monitoramento clínico. Participantes com idade d?40 anos tiveram maior probabilidade de permanecerem sem evento e evolução clínicadesfavorável predominou entre pacientes BT. Monitoramento prolongado de hanseníaselesão-única PB tratados com esquema mínimo forneceu dados importantes sobremanejo clínico para os centros de referência.