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1.
Rev Esc Enferm USP ; 55: e20200357, 2021.
Artigo em Inglês, Português | MEDLINE | ID: mdl-34495209

RESUMO

OBJECTIVE: To explore the scientific evidence regarding the leprosy patients quality of life. METHOD: Scoping review according to the Joanna Briggs Institute methodology, with articles indexed in PubMed, Cochrane, LILACS, Embase, CINAHL, Scopus, Web of Science, PsyINFO, INFOLEP, and Google Scholar databases, published in full in Portuguese, English, or Spanish. RESULTS: Seventy-four studies were identified, with 71 of quantitative approach and 3 with a mixed method. There was a predominance of studies published in Brazil (58.1%), with an adult population, (97.3%) and recruited in reference centers for the treatment of leprosy (52.7%). There was greater use of the WHOQOL-bref (50%) and SF-36 (18.9%) instruments to assess quality of life. The study showed that the greatest impairment in quality of life was related to the delay in the diagnosis of the disease, to leprosy reactions, physical disabilities, neuropathic pain, and stigma. CONCLUSION: Most studies were developed in endemic countries, with adults, and based on observational studies, and the worst scores obtained were associated with physical domain impairment.


Assuntos
Hanseníase , Qualidade de Vida , Adulto , Brasil , Humanos
2.
Artigo em Inglês | MEDLINE | ID: mdl-34586307

RESUMO

Acute pancreatitis (AP) is an inflammatory disease associated with abdominal pain and elevated serum pancreatic enzymes. The most common etiologies are gallstones and alcoholism. Drug-induced AP is quite rare, lacks a solid understanding and has been occasionally reported. The diagnosis requires a great suspicion and a careful exclusion of other causes. We present a case of a 37-year-old man, previously diagnosed with leprosy that developed acute pancreatitis after starting the multibacillary polychemotherapy (PCT/MB). After a month of treatment and the discontinuation of the PCT/MB, the therapy was restarted and a new episode of AP occurred. Three months after this last episode, the PCT/MB was reintroduced, changing one of the medications and the patient had no recurrence of AP or other reactions. Therefore, it is important to take into account that there is a risk of acute pancreatitis in patients on multidrug therapy (MDT) for leprosy.


Assuntos
Hanseníase Multibacilar , Hanseníase , Pancreatite , Doença Aguda , Adulto , Quimioterapia Combinada , Humanos , Hansenostáticos/efeitos adversos , Hanseníase/complicações , Hanseníase/tratamento farmacológico , Masculino , Pancreatite/induzido quimicamente
3.
Front Immunol ; 12: 662307, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34354699

RESUMO

The treatment of multibacillary cases of leprosy with multidrug therapy (MDT) comprises 12 doses of a combination of rifampicin, dapsone and clofazimine. Previous studies have described the immunological phenotypic pattern in skin lesions in multibacillary patients. Here, we evaluated the effect of MDT on skin cell phenotype and on the Mycobacterium leprae-specific immune response. An analysis of skin cell phenotype demonstrated a significant decrease in MRS1 (SR-A), CXCL10 (IP-10) and IFNG (IFN-γ) gene and protein expression after MDT release. Patients were randomized according to whether they experienced a reduction in bacillary load after MDT. A reduction in CXCL10 (IP-10) in sera was associated with the absence of a reduction in the bacillary load at release. Although IFN-γ production in response to M. leprae was not affected by MDT, CXCL10 (IP-10) levels in response to M. leprae increased in cells from patients who experienced a reduction in bacillary load after treatment. Together, our results suggest that CXCL10 (IP-10) may be a good marker for monitoring treatment efficacy in multibacillary patients.


Assuntos
Quimiocina CXCL10/sangue , Hansenostáticos/uso terapêutico , Hanseníase/tratamento farmacológico , Pele/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carga Bacteriana/efeitos dos fármacos , Biomarcadores/sangue , Quimiocina CXCL10/imunologia , Quimioterapia Combinada , Feminino , Humanos , Hansenostáticos/administração & dosagem , Hanseníase/imunologia , Masculino , Pessoa de Meia-Idade , Mycobacterium leprae/imunologia , Pele/microbiologia , Pele/patologia , Resultado do Tratamento , Adulto Jovem
4.
J Card Surg ; 36(10): 3749-3760, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34251716

RESUMO

BACKGROUND: Vasoplegic syndrome (VPS) is defined as systemic hypotension due to profound vasodilatation and loss of systemic vascular resistance (SVR), despite normal or increased cardiac index, and characterized by inadequate response to standard doses of vasopressors, and increased morbidity and mortality. It occurs in 9%-44% of cardiac surgery patients after cardiopulmonary bypass (CPB). The underlying pathophysiology following CPB consists of resistance to vasopressors (inactivation of Ca2+ voltage gated channels) on the one hand and excessive activation of vasodilators (SIRS, iNOS, and low AVP) on the other. Use of angiotensin-converting enzyme inhibitor (ACE-I), calcium channel blockers, amiodarone, heparin, low cardiac reserve (EF < 35%), symptomatic congestive heart failure, and diabetes mellitus are the perioperative risk factors for VPS after cardiac surgery in adults. Till date, there is no consensus about the outcome-oriented therapeutic management of VPS. Vasopressors such as norepinephrine (NE; 0.025-0.2 µg/kg/min) and vasopressin (0.06 U/min or 6 U/h median dose) are the first choice for the treatment. The adjuvant therapy (hydrocortisone, calcium, vitamin C, and thiamine) and rescue therapy (methylene blue [MB] and hydroxocobalamin) are also considered when perfusion goals (meanarterial pressure [MAP] > 60-70 mmHg) are not achieved with nor-epinephrine and/or vasopressin. AIMS: The aims of this systematic review are to collect all the clinically relevant data to describe the VPS, its potential risk factors, pathophysiology after CPB, and to assess the efficacy, safety, and outcome of the therapeutic management with catecholamine and non-catecholamine vasopressors employed for refractory vasoplegia after cardiac surgery. Also, to elucidate the current and practical approach for management of VPS after cardiac surgery. MATERIAL AND METHODS: "PubMed," "Google," and "Medline" weresearched, and over 150 recent relevant articles including RCTs, clinical studies, meta-analysis, reviews, case reports, case series and Cochrane data were analyzed for this systematic review. The filter was applied specificallyusing key words like VPS after cardiac surgery, perioperative VPS following CPB, morbidity, and mortality in VPS after cardiac surgery, vasopressors for VPS that improve outcomes, VPS after valve surgery, VPS after CABG surgery, VPS following complex congenital cardiac anomalies corrective surgery, rescue therapy for VPS, adjuvant therapy for VPS, definition of VPS, outcome in VPS after cardiac surgery, etiopathology of VPS following CPB. This review did not require any ethical approval or consent from the patients. RESULTS: Despite the recent advances in therapy, the mortality remains as high as 30%-50%. NE has been recommended the most frequent used vasopressor for VPS. It restores and maintain the MAP and provides the outcome benefits. Vasopressin rescue therapy is an alternative approach, if catecholamines and fluid infusions fail to improve hemodynamics. It effectively increases vascular tone and lowers CO, and significantly decreases the 30 days mortality. Hence, suggested a first-line vasopressor agent in postcardiac surgery VPS. Terlipressin (1.3µg/kg/h), a longer acting and more specific vasoconstrictor prevents the development of VPS after CPB in patients treated with ACE-I. MB significantly reduces morbidity and mortality of VPS. The Preoperative MB (1%, 2mg/kg/30min, 1h before surgery) administration in high risk (on ACE-I) patients for VPS undergoing CABG surgery, provides 100% protection against VPS, and early of MB significantly reduces operative mortality, and recommended as a rescue therapy for VPS. Hydroxocobalamin (5 g) has been recommended as a rescue agent in VPS refractory to multiple vasopressors. A combination of ascorbic acid (6 g), hydrocortisone (200 mg/day), and thiamine (400 mg/day) as an adjuvant therapy significantly reduces the vasopressors requirement, and provides mortality and morbidity benefits. CONCLUSION: Currently, the VPS is frequently encountered (9%-40%) in cardiac surgical patients with predisposing patient-specific risk factors and combined with inflammatory response to CPB. Multidrug therapy (NE, MB, AVP, ATII, terlipressin, hydroxocobalamin) targeting multiple receptor systems is recommended in refractory VPS. A combination of high dosage of ascorbic acid, hydrocortisone and thiamine has been used successfully as adjunctive therapyto restore the MAP. We also advocate for the early use of multiagent vasopressors therapy and catecholamine sparing adjunctive agents to restore the systemic perfusion pressure with a goal of preventing the progressive refractory VPS.


Assuntos
Vasoplegia , Adulto , Ponte Cardiopulmonar/efeitos adversos , Quimioterapia Combinada , Humanos , Hidroxocobalamina/uso terapêutico , Hansenostáticos/uso terapêutico , Vasoplegia/tratamento farmacológico , Vasoplegia/etiologia
5.
Trials ; 22(1): 453, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34266456

RESUMO

BACKGROUND: Leprosy is curable with multidrug therapy and treatment in the early stages can prevent disability. However, local nerve damage can lead to injury and consequently recurring and disfiguring ulcers. The aim of this study is to evaluate the treatment of leprosy ulcers using an autologous blood product; leukocyte and platelet-rich fibrin (L-PRF) to promote healing. METHODS: This is a single-centre study in the Anandaban Hospital, The Leprosy Mission Nepal, Kathmandu, Nepal. Consenting patients (n=130) will be individually randomised in a single-blinded, controlled trial. Participants will be 18 years of age or older, admitted to the hospital with a clean, dry and infection-free chronic foot ulcer between 2 and 20 cm2 in size. If the ulcer is infected, it will be treated before enrolment into the study. The intervention involves the application of leukocyte and platelet-rich fibrin (L-PRF) matrix on the ulcer beds during twice-weekly dressing changes. Controls receive usual care in the form of saline dressings only during their twice-weekly dressing changes. Primary outcomes are the rate of healing assessed using standardised photographs by observers blind to allocated treatment, and time to complete re-epithelialization. Follow-up is at 6 months from randomisation. DISCUSSION: This research will provide valuable information on the clinical and cost-effectiveness of L-PRF in the treatment of leprosy ulcers. An additional benefit is the evaluation of the effects of treatment on quality of life for people living with leprosy ulcers. The results will improve our understanding of the scalability of this treatment across low-income countries for ulcer healing in leprosy and potentially other conditions such as diabetic ulcers. TRIAL REGISTRATION: ClinicalTrials.gov ISRCTN14933421 . Registered on 16 June 2020.


Assuntos
Hanseníase , Fibrina Rica em Plaquetas , Adolescente , Adulto , Quimioterapia Combinada , Humanos , Hansenostáticos , Hanseníase/diagnóstico , Hanseníase/terapia , Leucócitos , Nepal , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Úlcera
6.
Am J Trop Med Hyg ; 105(1): 31-36, 2021 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-34232909

RESUMO

Leprosy is an infectious disease caused by Mycobacterium leprae. China was once one of the countries with severe leprosy epidemics, but its incidence has remained low in recent years. Despite this, there has been no decrease in its incidence more recently, and it is still a public health problem which needs to be controlled. In this study, we analyzed the epidemiological characteristics and trends in the detection rate of new cases of leprosy in China between 2004 and 2016. There were 4,519 cases of leprosy in 28 provinces, municipalities, and autonomous regions between 2004 and 2016, and the total incidence was 0.02815 (per 100,000 individuals) and 21 deaths. The overall incidence of leprosy showed an inverted "V" distribution (i.e., an increase followed by a decrease). Yunnan, Sichuan, Guangdong, Guizhou, and Guangxi were the top five regions with the highest incidence rates, and they accounted for 68.7% of the total cases. There were more male patients than female patients, and peasants accounted for 71.7% of the leprosy cases. The patients with leprosy in China were mainly concentrated in the age-group 15-44 years, as this group accounted for 57.2% of the total cases. The purpose of this study is to explore the epidemiology of leprosy in China. This analysis will be useful for future monitoring of leprosy and establishment of public health measures in China, in keeping with the "Programme for the Elimination of Leprosy in China 2011-2020."


Assuntos
Hanseníase/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , China/epidemiologia , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Mycobacterium leprae/isolamento & purificação , Estudos Retrospectivos , Adulto Jovem
7.
Cien Saude Colet ; 26(5): 1805-1816, 2021 May.
Artigo em Português, Inglês | MEDLINE | ID: mdl-34076121

RESUMO

This study aimed to describe the prevalence of leprosy and verify the factors associated with multibacillary clinical types in a Family Health Strategy priority setting to control and monitor the disease in northeastern Brazil. This cross-sectional study used data from the Notifiable Diseases Information System related to leprosy cases notified in Imperatriz, Maranhão, between 2008 and 2017. The prevalence was determined yearly and for the period. Poisson regression models with a significance level of 5% were employed to associate the variables and the multibacillary clinical types. Most of the 2,476 leprosy cases analyzed referred to multibacillary clinical types. The prevalence ranged from 7.8 and 15.6/10,000 inhabitants, with high and very high endemicity levels. The variables male, age groups between 30 and 59 years and ≥60 years, schooling <8 years, level 2 physical disability, types 1 and 2 reactive episodes, and urban residence area showed significant associations (p≤0.05) with multibacillary clinical types. Such findings can serve as a basis for elaborating and implementing leprosy control and surveillance measures, gearing actions to the most vulnerable groups, and becoming more effective.


Assuntos
Saúde da Família , Hanseníase , Adulto , Brasil/epidemiologia , Estudos Transversais , Humanos , Hanseníase/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência
8.
PLoS Negl Trop Dis ; 15(6): e0009495, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34125854

RESUMO

BACKGROUND: This study evaluates implementation strategies for leprosy diagnosis based on responses to a Leprosy Suspicion Questionnaire (LSQ), and analyzes immunoepidemiological aspects and follow-up of individuals living in a presumptively nonendemic area in Brazil. METHODOLOGY/PRINCIPAL FINDINGS: Quasi-experimental study based on LSQ throughout Jardinópolis town by community health agents, theoretical-practical trainings for primary care teams, dermatoneurological examination, anti-PGL-I serology, RLEP-PCR, and spatial epidemiology. A Leprosy Group (LG, n = 64) and Non-Leprosy Group (NLG, n = 415) were established. Overall, 3,241 LSQs were distributed; 1,054 (32.5%) LSQ were positive for signs/symptoms (LSQ+). Among LSQ+ respondents, Q2-Tingling (pricking)? (11.8%); Q4-Spots on the skin? (11.7%); Q7-Pain in the nerves? (11.6%); Q1-Numbness in your hands and/or feet? (10.7%) and Q8-Swelling of hands and feet? (8.5%) were most frequently reported symptoms. We evaluated 479 (14.8%) individuals and diagnosed 64 new cases, a general new case detection rate (NCDR) of 13.4%; 60 were among 300 LSQ+ (NCDR-20%), while 4 were among 179 LSQ negative (NCDR-2.23%). In LG, Q7(65%), Q2(60%), Q1(45%), Q4(40%) and Q8(25%) were most frequent. All 2x2 crossings of these 5 questions showed a relative risk for leprosy ranging from 3 to 5.8 compared with NLG. All patients were multibacillary and presented hypochromatic macules with loss of sensation. LG anti-PGL-I titers were higher than NLG, while 8.9% were positive for RLEP-PCR. The leprosy cases and anti-PGL-I spatial mappings demonstrated the disease spread across the town. CONCLUSIONS/SIGNIFICANCE: Implementation actions, primarily LSQ administration focused on neurological symptoms, indicate hidden endemic leprosy in a nonendemic Brazilian state.


Assuntos
Agentes Comunitários de Saúde/educação , Hanseníase/diagnóstico , Hanseníase/epidemiologia , Mycobacterium leprae/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mycobacterium leprae/genética , Mycobacterium leprae/isolamento & purificação , Prevalência , Inquéritos e Questionários
9.
Am J Phys Anthropol ; 176(1): 36-53, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34096038

RESUMO

OBJECTIVES: By focusing on two Danish leprosaria (Naestved and Odense; 13th-16th c. CE) and using diet and origin as proxies, we follow a multi-isotopic approach to reconstruct life histories of patients and investigate how leprosy affected both institutionalized individuals and the medieval Danish community as a whole. MATERIALS AND METHODS: We combine archaeology, historical sources, biological anthropology, isotopic analyses (δ13 C, δ15 N, δ34 S, 87 Sr/86 Sr) and radiocarbon dating, and further analyze bones with different turnover rates (ribs and long bones). RESULTS: The δ13 C, δ15 N and δ34 S results indicate a C3 terrestrial diet with small contributions of marine protein for leprosy patients and individuals from other medieval Danish sites. A similar diet is seen through time, between males and females, and patients with and without changes on facial bones. The isotopic comparison between ribs and long bones reveals no significant dietary change. The δ34 S and 87 Sr/86 Sr results suggest that patients were local to the regions of the leprosaria. Moreover, the radiocarbon dates show a mere 50% agreement with the arm position dating method used in Denmark. CONCLUSIONS: A local origin for the leprosy patients is in line with historical evidence, unlike the small dietary contribution of marine protein. Although only 10% of the analyzed individuals have rib/long bone offsets that undoubtedly show a dietary shift, the data appear to reveal a pattern for 25 individuals (out of 50), with elevated δ13 C and/or δ15 N values in the ribs compared to the long bones, which points toward a communal type of diet and reveals organizational aspects of the institution.


Assuntos
Osso e Ossos/química , Isótopos/análise , Hanseníase/etnologia , Hanseníase/história , Adulto , Antropologia Física , Osso e Ossos/metabolismo , Dinamarca/etnologia , Feminino , História Medieval , Humanos , Isótopos/metabolismo , Masculino , Datação Radiométrica
10.
Hum Reprod ; 36(9): 2576-2586, 2021 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-34166497

RESUMO

STUDY QUESTION: Is the rate of fatherhood among men diagnosed with cancer in childhood and early adulthood different from men without cancer, and, if so, have the differences changed over time? SUMMARY ANSWER: Men diagnosed with cancer have had significantly reduced rates of fatherhood compared with undiagnosed men; however, the rates of fatherhood among the cancer survivors have increased markedly over time. WHAT IS KNOWN ALREADY: The number of children and young adolescents who survive cancer has steadily increased over recent decades, with a current 5-year survival rate of approximately 80%. Consequently, life circumstances after cancer have gained increasing importance, including the desire among survivors to have children and a family. ARTs to aid reproduction among cancer survivors have been developed, and fertility preservation is increasingly a topic being discussed before undergoing cancer treatment. But the potential for fertility preservation differs dependent on age at diagnosis and type of cancer. Earlier studies have shown a decreased fertility rate among survivors of child and adolescent cancer compared to those diagnosed in early adulthood. STUDY DESIGN, SIZE, DURATION: This study is a national, register-based cohort study. Men diagnosed with cancer in childhood and early adulthood (<30 years of age) were registered in the Danish Cancer Register in 1978-2016 (n = 9353). According to the time of diagnosis, each cancer-diagnosed man was randomly matched with 150 undiagnosed men from the background population within the same birth year. The men were followed until having their first child, death, migration or the end of the study (31 December 2017) in medical registers and socio-demographic population registers. PARTICIPANTS/MATERIALS, SETTING, METHODS: Fatherhood among the boys and young men diagnosed with cancer were compared with the age-matched comparison group in all statistical analyses. Cancer diagnoses were categorised as central nervous system (CNS) cancers, haematological cancers or solid cancers. Analyses were stratified by age at diagnosis (0-9, 10-19, 20-29 years) and time of diagnosis (1978-1989, 1990-1999, 2000-2009, 2010-2016). Death was incorporated as a competing risk in all analyses. MAIN RESULTS AND THE ROLE OF CHANCE: The study population consisted of 9353 boys and young men diagnosed with cancer between 1978 and 2016 and 1 386 493 men in the age-matched comparison group. Those surviving CNS cancer as young men had the lowest hazard ratio (HR) of fatherhood compared with the age-matched comparison group (HR 0.67, 95% CI 0.57-0.79), followed by survivors of haematological cancers (HR 0.90, 95% CI 0.81-1.01), while the highest chance of fatherhood was among survivors of solid cancers (HR 1.16, 95% CI 1.12-1.20) with a slightly increased HR compared with undiagnosed males. The HR of becoming a father increased over time. From the first decade to the last decade 30 years later, the HR of becoming a father increased for solid tumours (HR 0.78, 95% CI 0.73-0.83 to HR 1.08, 95% CI 0.95-1.22), haematological cancers (HR 0.64, 95% CI 0.53-0.79 to HR 0.97, 95% CI 0.73-1.30) and CNS cancers (HR 0.44, 95% CI 0.34-0.57 to HR 0.98, 95% CI 0.49-1.95) compared to the age-matched comparison group. Also, when compared with the age-matched comparison group, men diagnosed with cancer when aged 20-29 years were more likely became fathers over the time of the study (HR 0.80, 95% CI 0.74-0.86 to HR 1.08, 95% CI 0.96-1.22). LIMITATIONS, REASONS FOR CAUTION: The study was based on register data, and information was not available about the men's fertility potential, whether they had a desire to have children and whether it was possible for them to find a partner. Information about fertility preservation, e.g. sperm freezing, could also have provided additional insights. Furthermore, information about diagnosis and ART treatment would have been beneficial. WIDER IMPLICATIONS OF THE FINDINGS: Information and education of male patients diagnosed with cancer about fertility preservation options and their chances to create their own family is crucial. Reassuringly, time trends showed more men with a previous cancer diagnosis becoming fathers in recent years than in earlier years, reflecting that survival and fertility preservation have improved over time. STUDY FUNDING/COMPETING INTEREST(S): R.S. received a PhD grant from the Rosa Ebba Hansen Foundation and from the Health Foundation (J.nr. 15-B-0095). The funding for the establishment of the DANAC II Cohort was obtained from the Rosa Ebba Hansen Foundation. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.


Assuntos
Sobreviventes de Câncer , Neoplasias , Adolescente , Adulto , Criança , Estudos de Coortes , Dinamarca/epidemiologia , Humanos , Masculino , Homens , Neoplasias/epidemiologia , Adulto Jovem
11.
Nat Immunol ; 22(7): 839-850, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34168371

RESUMO

Granulomas are complex cellular structures composed predominantly of macrophages and lymphocytes that function to contain and kill invading pathogens. Here, we investigated the single-cell phenotypes associated with antimicrobial responses in human leprosy granulomas by applying single-cell and spatial sequencing to leprosy biopsy specimens. We focused on reversal reactions (RRs), a dynamic process whereby some patients with disseminated lepromatous leprosy (L-lep) transition toward self-limiting tuberculoid leprosy (T-lep), mounting effective antimicrobial responses. We identified a set of genes encoding proteins involved in antimicrobial responses that are differentially expressed in RR versus L-lep lesions and regulated by interferon-γ and interleukin-1ß. By integrating the spatial coordinates of the key cell types and antimicrobial gene expression in RR and T-lep lesions, we constructed a map revealing the organized architecture of granulomas depicting compositional and functional layers by which macrophages, T cells, keratinocytes and fibroblasts can each contribute to the antimicrobial response.


Assuntos
Hanseníase Virchowiana/imunologia , Hanseníase Tuberculoide/imunologia , Mycobacterium leprae/imunologia , Pele/imunologia , Adolescente , Adulto , Idoso , Feminino , Fibroblastos/imunologia , Fibroblastos/microbiologia , Fibroblastos/patologia , Perfilação da Expressão Gênica , Interações Hospedeiro-Patógeno , Humanos , Queratinócitos/imunologia , Queratinócitos/microbiologia , Queratinócitos/patologia , Hanseníase Virchowiana/genética , Hanseníase Virchowiana/microbiologia , Hanseníase Virchowiana/patologia , Hanseníase Tuberculoide/genética , Hanseníase Tuberculoide/microbiologia , Hanseníase Tuberculoide/patologia , Macrófagos/imunologia , Macrófagos/microbiologia , Macrófagos/patologia , Masculino , Pessoa de Meia-Idade , Mycobacterium leprae/patogenicidade , RNA-Seq , Análise de Célula Única , Pele/microbiologia , Pele/patologia , Linfócitos T/imunologia , Linfócitos T/microbiologia , Linfócitos T/patologia , Transcriptoma
12.
PLoS Negl Trop Dis ; 15(5): e0009382, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33939710

RESUMO

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.


Assuntos
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 Jovem
13.
J Pak Med Assoc ; 71(3): 838-842, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34057932

RESUMO

OBJECTIVE: To determine the occurrence and characteristics of the two types of lepra reactions in new leprosy cases at initial diagnosis. Methods: The retrospective descriptive study was conducted at the Marie Adelaide Leprosy Centre, Karachi, and comprised all new leprosy cases registered from January 1, 2016, to June 30, 2018. Data was collected from the medical record database using a predesigned proforma. RESULTS: Of the 50 cases, 2(4%) were children and 48 (96%) were adults, with overall age ranging from 12 to 85 years. There were 41(82%) males and 9(18%) females.. Of the total, 30(60%) cases presented with type 1 reaction and 20(40%) with type 2. Further, 30(60%) cases were classified as borderline lepromatous. Among them, 17(57%) had type 2 reaction. Inflamed plaques were the main feature in 27(90%) cases of type 1. Crops of painful, erythematous nodules were seen in 19(95%) cases of type 2. Conclusion: Lepra reactions were found to be a presenting feature in a significant number of new leprosy cases at initial diagnosis.


Assuntos
Hanseníase , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Grupos Étnicos , Feminino , Humanos , Hanseníase/diagnóstico , Hanseníase/epidemiologia , Masculino , Pessoa de Meia-Idade , Paquistão/epidemiologia , Estudos Retrospectivos , Adulto Jovem
14.
Am J Case Rep ; 22: e931655, 2021 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-34038399

RESUMO

BACKGROUND Leprosy is an infection caused by Mycobacterium leprae. An extensive literature search did not reveal many reports of melioidosis in association with leprosy. CASE REPORT A 22-year-old woman, who was diagnosed with multibacillary leprosy, developed dapsone-induced methemoglobinemia and hemolytic anemia, complicated by melioidosis. Methemoglobinemia was treated with methylene blue and vitamin C. Two weeks of ceftazidime was initiated to treat melioidosis, and the patient was discharged on amoxicillin/clavulanic acid and doxycycline as melioidosis eradication therapy. However, she developed drug-induced hypersensitivity. Trimethoprim/sulfamethoxazole, as an alternative treatment for melioidosis eradication, was commenced and was successfully completed for 12 weeks. During the fifth month of multidrug therapy, the patient developed type II lepra reaction with erythema nodosum leprosum reaction, which was treated with prednisolone. Leprosy treatment continued with clofazimine and ofloxacin, and complete resolution of skin lesions occurred after 12 months of therapy. CONCLUSIONS Our case highlighted the challenges posed in managing a patient with multibacillary leprosy with multiple complications. Clinicians should be aware that dapsone-induced methemoglobinemia and hemolysis might complicate the treatment of leprosy. Our case also highlighted the safety and efficacy of combining ofloxacin and clofazimine as a leprosy treatment regimen in addition to gradual steroid dose titration in the presence of type II lepra reaction.


Assuntos
Anemia Hemolítica , Hanseníase Virchowiana , Melioidose , Metemoglobinemia , Adulto , Anemia Hemolítica/induzido quimicamente , Anemia Hemolítica/tratamento farmacológico , Dapsona/efeitos adversos , Quimioterapia Combinada , Feminino , Humanos , Hansenostáticos/efeitos adversos , Hanseníase Virchowiana/complicações , Hanseníase Virchowiana/tratamento farmacológico , Metemoglobinemia/induzido quimicamente , Metemoglobinemia/tratamento farmacológico , Adulto Jovem
15.
Front Immunol ; 12: 661135, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34017337

RESUMO

HLA-B*13:01 allele has been identified as the genetic determinant of dapsone hypersensitivity syndrome (DHS) among leprosy and non-leprosy patients in several studies. Dapsone hydroxylamine (DDS-NHOH), an active metabolite of dapsone, has been believed to be responsible for DHS. However, studies have not highlighted the importance of other genetic polymorphisms in dapsone-induced severe cutaneous adverse reactions (SCAR). We investigated the association of HLA alleles and cytochrome P450 (CYP) alleles with dapsone-induced SCAR in Thai non-leprosy patients. A prospective cohort study, 16 Thai patients of dapsone-induced SCARs (5 SJS-TEN and 11 DRESS) and 9 Taiwanese patients of dapsone-induced SCARs (2 SJS-TEN and 7 DRESS), 40 dapsone-tolerant controls, and 470 general Thai population were enrolled. HLA class I and II alleles were genotyped using polymerase chain reaction-sequence specific oligonucleotides (PCR-SSOs). CYP2C9, CYP2C19, and CYP3A4 genotypes were determined by the TaqMan real-time PCR assay. We performed computational analyses of dapsone and DDS-NHOH interacting with HLA-B*13:01 and HLA-B*13:02 alleles by the molecular docking approach. Among all the HLA alleles, only HLA-B*13:01 allele was found to be significantly associated with dapsone-induced SCARs (OR = 39.00, 95% CI = 7.67-198.21, p = 5.3447 × 10-7), SJS-TEN (OR = 36.00, 95% CI = 3.19-405.89, p = 2.1657 × 10-3), and DRESS (OR = 40.50, 95% CI = 6.38-257.03, p = 1.0784 × 10-5) as compared to dapsone-tolerant controls. Also, HLA-B*13:01 allele was strongly associated with dapsone-induced SCARs in Asians (OR = 36.00, 95% CI = 8.67-149.52, p = 2.8068 × 10-7) and Taiwanese (OR = 31.50, 95% CI = 4.80-206.56, p = 2.5519 × 10-3). Furthermore, dapsone and DDS-NHOH fit within the extra-deep sub pocket of the antigen-binding site of the HLA-B*13:01 allele and change the antigen-recognition site. However, there was no significant association between genetic polymorphism of cytochrome P450 (CYP2C9, CYP2C19, and CYP3A4) and dapsone-induced SCARs (SJS-TEN and DRESS). The results of this study support the specific genotyping of the HLA-B*13:01 allele to avoid dapsone-induced SCARs including SJS-TEN and DRESS before initiating dapsone therapy in the Asian population.


Assuntos
Alelos , Dapsona/efeitos adversos , Antígenos HLA-B/genética , Polimorfismo Genético , Pele/efeitos dos fármacos , Pele/patologia , Adolescente , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático/estatística & dados numéricos , Criança , Pré-Escolar , Sistema Enzimático do Citocromo P-450/genética , Feminino , Estudos de Associação Genética , Marcadores Genéticos , Genótipo , Antígenos HLA-B/classificação , Humanos , Masculino , Pessoa de Meia-Idade , Simulação de Acoplamento Molecular , Estudos Prospectivos , Adulto Jovem
16.
Front Immunol ; 12: 647832, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33936067

RESUMO

Leprosy is a disease with a clinical spectrum of presentations that is also manifested in diverse histological features. At one pole, lepromatous lesions (L-pole) have phagocytic foamy macrophages heavily parasitized with freely multiplying intracellular Mycobacterium leprae. At the other pole, the presence of epithelioid giant cells and granulomatous formation in tuberculoid lesions (T-pole) lead to the control of M. leprae replication and the containment of its spread. The mechanism that triggers this polarization is unknown, but macrophages are central in this process. Over the past few years, leprosy has been studied using large scale techniques to shed light on the basic pathways that, upon infection, rewire the host cellular metabolism and gene expression. M. leprae is particularly peculiar as it invades Schwann cells in the nerves, reprogramming their gene expression leading to a stem-like cell phenotype. This modulatory behavior exerted by M. leprae is also observed in skin macrophages. Here, we used live M. leprae to infect (10:1 multiplicity of infection) monocyte-derived macrophages (MDMs) for 48 h and analyzed the whole gene expression profile using microarrays. In this model, we observe an intense upregulation of genes consistent with a cellular immune response, with enriched pathways including peptide and protein secretion, leukocyte activation, inflammation, and cellular divalent inorganic cation homeostasis. Among the most differentially expressed genes (DEGs) are CCL5/RANTES and CYP27B1, and several members of the metallothionein and metalloproteinase families. This is consistent with a proinflammatory state that would resemble macrophage rewiring toward granulomatous formation observed at the T-pole. Furthermore, a comparison with a dataset retrieved from the Gene Expression Omnibus of M. leprae-infected Schwann cells (MOI 100:1) showed that the patterns among the DEGs are highly distinct, as the Schwann cells under these conditions had a scavenging and phagocytic gene profile similar to M2-like macrophages, with enriched pathways rearrangements in the cytoskeleton, lipid and cholesterol metabolism and upregulated genes including MVK, MSMO1, and LACC1/FAMIN. In summary, macrophages may have a central role in defining the paradigmatic cellular (T-pole) vs. humoral (L-pole) responses and it is likely that the multiplicity of infection and genetic polymorphisms in key genes are gearing this polarization.


Assuntos
Imunidade Celular/genética , Hanseníase Virchowiana/genética , Hanseníase Virchowiana/imunologia , Macrófagos/imunologia , Macrófagos/virologia , Mycobacterium leprae/imunologia , Transcriptoma , Adulto , Doadores de Sangue , Polaridade Celular/genética , Células Cultivadas , Feminino , Voluntários Saudáveis , Humanos , Hanseníase Virchowiana/microbiologia , Masculino , Polimorfismo de Nucleotídeo Único , Células de Schwann/imunologia , Células de Schwann/virologia , Adulto Jovem
17.
Acta Neurol Scand ; 144(2): 155-160, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33899225

RESUMO

OBJECTIVES: Median nerve enlargement in leprosy seems to be more proximal than in carpal tunnel syndrome (CTS), but this feature has not been studied systematically. The aim of the study was to compare the sites of median nerve enlargement in patients with leprosy with that of patients with CTS. MATERIALS AND METHODS: Transverse sections of the median nerve were recorded from wrist to the mid-forearm (at distal wrist crease and at 2-cm: M1, 4-cm: M2, 6-cm: M3, 8-cm: M4 and 10-cm: M5, proximal to the distal wrist crease in the forearm) in patients with leprosy, CTS and healthy subjects using high-resolution ultrasound. RESULTS: Twenty-six patients each with leprosy and CTS were compared with healthy controls. Patients with leprosy included 6 (23.1%), 7 (26.9%), 7 (26.9%) and 6 (23.1%) patients with borderline tuberculoid, borderline-borderline, borderline lepromatous and lepromatous leprosy, respectively. Cross-sectional area (CSA) of median nerve was increased in all patients with leprosy as compared to healthy controls at all points of measurement. CSA was higher among patients with leprosy as compared to CTS at all points except at the wrist. In patients with leprosy, the maximal enlargement was noted 2-cm (M1) proximal to the wrist crease with gradual tapering of the CSA proximally (p < .05). In contrast, in patients with CTS the median nerve was maximally enlarged at the distal wrist crease (p<.05). CONCLUSIONS: Median nerve enlargement 2-cm proximal to the distal wrist crease distinguishes leprosy from CTS. This important discriminating sign can be used at point-of-care to identify patients with leprosy.


Assuntos
Síndrome do Túnel Carpal/diagnóstico por imagem , Síndrome do Túnel Carpal/patologia , Hanseníase/patologia , Nervo Mediano/diagnóstico por imagem , Nervo Mediano/patologia , Adulto , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ultrassonografia
18.
PLoS Negl Trop Dis ; 15(4): e0009329, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33798199

RESUMO

BACKGROUND: Leprosy and leprosy-related stigma can have a major impact on psychosocial wellbeing of persons affected and their family members. Resilience is a process that incorporates many of the core skills and abilities which may enable people to address stigma and discrimination. The current study aimed to develop and pilot an intervention to strengthen individual and family resilience against leprosy-related discrimination. METHODOLOGY: We used a quasi-experimental, before-after study design with a mixed methods approach. The 10-week family-based intervention was designed to strengthen the resilience of individuals and families by enhancing their protective abilities and capacity to overcome adversity. The study was conducted in two sites, urban areas in Telangana state, and in rural areas in Odisha state, India. Persons affected and their family members were included using purposive sampling. Two questionnaires were used pre-and post-intervention: the Connor-Davidson Resilience Scale (CD-RISC, maximum score 100, with high scores reflecting greater resilience) and the WHOQOL-BREF (maximum score of 130, with higher scores reflecting higher quality of life). In addition, semi-structured interviews were conducted post-intervention. Data were collected at baseline, a few weeks after completion of the intervention, and in the Odisha cohort again at six months after completion. Paired t-tests measured differences pre- and post- intervention. Qualitative data were thematically analysed. FINDINGS: Eighty participants across 20 families were included in the study (23 persons affected and 57 family members). We found a significant increase in CD-RISC scores for persons affected and family members from Odisha state (baseline 46.5, first follow-up 77.0, second follow-up 70.0), this improvement was maintained at six-month follow-up. There was no increase in CD-RISC scores post-intervention among participants from Telangana state. WHOQOL-BREF scores were significantly higher at follow-up for persons affected in both states, and for family members in Odisha state. No families dropped out of the study. In the qualitative feedback, all participants described drawing benefit from the programme. Participants especially appreciated the social dimensions of the intervention. CONCLUSION: This pilot study showed that the 10-week family-based intervention to strengthen resilience among persons affected by leprosy and their family members was feasible, and has the potential to improve resilience and quality of life. A large-scale efficacy trial is necessary to determine the effectiveness and long-term sustainability of the intervention.


Assuntos
Saúde da Família , Família/psicologia , Hanseníase/psicologia , Qualidade de Vida/psicologia , Resiliência Psicológica , Adulto , Feminino , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Pesquisa Qualitativa , Estigma Social , Inquéritos e Questionários , Adulto Jovem
19.
Rev Bras Enferm ; 74(1): e20200649, 2021.
Artigo em Inglês, Português | MEDLINE | ID: mdl-33886930

RESUMO

OBJECTIVES: to analyze activity limitations in patients with leprosy and their association to cognition and neuropsychiatric symptoms. METHODS: this cross-sectional design study included sixty patients with multibacillary leprosy assisted at a reference center. Participants were divided according to their physical disability and submitted to instruments assessing daily activities (basic and instrumental), cognitive functions, and neuropsychiatric symptoms. The order of the instruments was random to avoid any interference of test sequence on the results. RESULTS: fifty-five percent of the participants presented physical disabilities. All patients were independent in performing basic activities but sixty-six percent presented difficulties in performing instrumental activities. Cognitive decline and neuropsychiatric symptoms were seen in advanced stages of the disease, but they were more associated to patient age than to leprosy. CONCLUSIONS: leprosy patients presented physical disabilities and difficulties in performing instrumental daily activities. Cognitive decline and neuropsychiatric symptoms were more associated to aging than to leprosy itself.


Assuntos
Atividades Cotidianas , Sintomas Comportamentais/epidemiologia , Transtornos Cognitivos/epidemiologia , Cognição/fisiologia , Hanseníase/complicações , Transtornos Mentais/epidemiologia , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos
20.
J Manag Care Spec Pharm ; 27(4): 455-468, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33769850

RESUMO

BACKGROUND: Oral semaglutide is the first oral formulation of a glucagon-like peptide 1 (GLP-1) receptor agonist to be approved in the United States for glycemic control in people with type 2 diabetes mellitus (T2DM). While oral semaglutide is not indicated for reduction of cardiovascular event risk, its label does include evidence of no increase in cardiovascular risk in people who received oral semaglutide. OBJECTIVE: To estimate the incremental value of oral semaglutide added to existing antihyperglycemic treatment for people with T2DM with additional risk for cardiovascular disease. METHODS: We estimated the lifetime cost-effectiveness of oral semaglutide added to current antihyperglycemic treatment for T2DM using a microsimulation model based primarily on the UK Prospective Diabetes Study (UKPDS) Outcomes Model 2 (OM2) equations. Oral semaglutide added to current antihyperglycemic treatment was separately compared with (a) ongoing background antihyperglycemic treatment, (b) sitagliptin, (c) empagliflozin, and (d) liraglutide. Comparators sitagliptin, empagliflozin, and liraglutide were added to ongoing antihyperglycemic treatment. We applied hazard ratios derived from a network meta-analysis for cardiovascular and renal outcomes to the UKPDS OM2 estimated baseline rates. Health state utilities and costs were derived from the published literature. We estimated total costs, life-years (LYs), quality-adjusted life-years (QALYs), clinical events, and cost per major adverse cardiovascular event (MACE) avoided, over a lifetime time horizon using discount rates of 3% for costs and outcomes. RESULTS: The lifetime total cost for people treated with oral semaglutide was $311,300, with costs for the other comparators ranging from $262,800 (background treatment alone) to $287,800 (liraglutide). Oral semaglutide resulted in the fewest MACE, including the fewest cardiovascular deaths. Among the 5 modeled treatment strategies, oral semaglutide had the highest LYs gained (8.43 vs. 7.76 [background treatment alone] to 8.29 [empagliflozin and liraglutide]) and the highest QALYs gained (4.11 vs. 3.70 [background treatment alone] to 4.03 [empagliflozin]). Oral semaglutide would likely be considered cost-effective compared with liraglutide (incremental cost-effectiveness ratio [ICER] = $40,100), and moderately cost-effective versus background treatment alone ([ICER] = $117,500/QALY) and sitagliptin (ICER = $145,200/QALY). The ICER for oral semaglutide compared with empagliflozin was approximately $458,400 per QALY. CONCLUSIONS: As modeled, oral semaglutide as an add-on therapy to background antihyperglycemic treatment produced incremental benefits in MACE avoided, along with greater QALYs compared with background antihyperglycemic treatment alone. Oral semaglutide use resulted in better outcomes than background treatment alone or sitagliptin, and similar outcomes to liraglutide or empagliflozin with overlapping 95% confidence ranges for QALYs. Oral semaglutide was estimated to be cost-effective compared with liraglutide and to have incremental cost-effectiveness ratios between $100,000 and $150,000 per QALY versus sitagliptin and background therapy alone, but it did not meet these thresholds compared with empagliflozin. DISCLOSURES: Funding for this study was provided by the Institute for Clinical and Economic Review, an independent organization that evaluates the evidence on the value of health care interventions. ICER reports grants from Laura and John Arnold Foundation, California Health Care Foundation, Harvard Pilgrim Health Care, and Kaiser Foundation Health Plan. ICER's annual policy summit is supported by dues from AbbVie, Aetna, America's Health Insurance Plans, Anthem, Alnylam, AstraZeneca, Biogen, Blue Shield of CA, Cambia Health Services, CVS, Editas, Evolve Pharmacy, Express Scripts, Genentech/Roche, GlaxoSmithKline, Harvard Pilgrim, Health Care Service Corporation, Health Partners, Humana, Johnson & Johnson (Janssen), Kaiser Permanente, LEO Pharma, Mallinckrodt, Merck, Novartis, National Pharmaceutical Council, Premera, Prime Therapeutics, Regeneron, Sanofi, Spark Therapeutics, uniQure, and United Healthcare. Rind, Fazioli, Chapman, and Pearson are employed by ICER. Guzauskas and Hansen have nothing to disclose. Study results were presented at the New England Comparative Effectiveness Public Advisory Council (New England CEPAC), November 14, 2019, at Brown University, Providence, RI.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Peptídeos Semelhantes ao Glucagon/uso terapêutico , Hipoglicemiantes/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise Custo-Benefício , Quimioterapia Combinada , Feminino , Peptídeos Semelhantes ao Glucagon/administração & dosagem , Peptídeos Semelhantes ao Glucagon/economia , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/economia , Masculino , Pessoa de Meia-Idade , Modelos Econômicos , Anos de Vida Ajustados por Qualidade de Vida , Estados Unidos , Adulto Jovem
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