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1.
Clin Chest Med ; 43(4): 697-716, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36344075

RESUMO

Nontuberculous mycobacteria (NTM) are important pathogens, with a longitudinal prevalence of up to 20% within the cystic fibrosis (CF) population. Diagnosis of NTM pulmonary disease in people with CF (pwCF) is challenging, as a majority have NTM infection that is transient or indolent, without evidence of clinical consequence. In addition, the radiographic and clinical manifestations of chronic coinfections with typical CF pathogens can overlap those of NTM, making diagnosis difficult. Comprehensive care of pwCF must be optimized to assess the true clinical impact of NTM and to improve response to treatment. Treatment requires prolonged, multidrug therapy that varies depending on NTM species, resistance pattern, and extent of disease. With a widespread use of highly effective modulator therapy (HEMT), clinical signs and symptoms of NTM disease may be less apparent, and sensitivity of sputum cultures further reduced. The development of a disease-specific approach to the diagnosis and treatment of NTM infection in pwCF is a research priority, as a lifelong strategy is needed for this high-risk population.


Assuntos
Fibrose Cística , Infecções por Mycobacterium não Tuberculosas , Humanos , Fibrose Cística/complicações , Quimioterapia Combinada , Hansenostáticos/uso terapêutico , Micobactérias não Tuberculosas , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/epidemiologia
2.
Front Cell Infect Microbiol ; 12: 997283, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36325467

RESUMO

Tuberculosis (TB) is among the most difficult infections to treat, requiring several months of multidrug therapy to produce a durable cure. The reasons necessitating long treatment times are complex and multifactorial. However, one major difficulty of treating TB is the resistance of the infecting bacterium, Mycobacterium tuberculosis (Mtb), to many distinct classes of antimicrobials. This review will focus on the major gaps in our understanding of intrinsic drug resistance in Mtb and how functional and chemical-genetics can help close those gaps. A better understanding of intrinsic drug resistance will help lay the foundation for strategies to disarm and circumvent these mechanisms to develop more potent antitubercular therapies.


Assuntos
Mycobacterium tuberculosis , Tuberculose dos Linfonodos , Humanos , Mycobacterium tuberculosis/genética , Quimioterapia Combinada , Hansenostáticos/uso terapêutico , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Resistência a Medicamentos
3.
Virulence ; 13(1): 1985-2011, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36326715

RESUMO

Leprosy is caused by Mycobacterium leprae (M. leprae) and M. lepromatosis, an obligate intracellular organism, and over 200,000 new cases occur every year. M. leprae parasitizes histiocytes (skin macrophages) and Schwann cells in the peripheral nerves. Although leprosy can be treated by multidrug therapy, some patients relapse or have a prolonged clinical course and/or experience leprosy reaction. These varying outcomes depend on host factors such as immune responses against bacterial components that determine a range of symptoms. To understand these host responses, knowledge of the mechanisms by which M. leprae parasitizes host cells is important. This article describes the characteristics of leprosy through bacteriology, genetics, epidemiology, immunology, animal models, routes of infection, and clinical findings. It also discusses recent diagnostic methods, treatment, and measures according to the World Health Organization (WHO), including prevention. Recently, the antibacterial activities of anti-hyperlipidaemia agents against other pathogens, such as M. tuberculosis and Staphylococcus aureus have been investigated. Our laboratory has been focused on the metabolism of lipids which constitute the cell wall of M. leprae. Our findings may be useful for the development of future treatments.


Assuntos
Hanseníase , Mycobacterium leprae , Animais , Mycobacterium leprae/genética , Virulência , Quimioterapia Combinada , Hansenostáticos , Hanseníase/tratamento farmacológico , Hanseníase/epidemiologia
4.
Mem Inst Oswaldo Cruz ; 117: e220058, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36259791

RESUMO

BACKGROUND: Leprosy is curable by multidrug therapy (MDT) treatment regimen ranging from six to 12 months. The variable levels of tolerance and adherence among patients can, however, result in treatment failure and the emergence of drug-resistant strains. OBJECTIVES: Describe the impact of MDT over Mycobacterium leprae viability in patient's oral and nasal mucosa along treatment. METHODS: Mycobacterium leprae viability was monitored by quantitative polymerase chain reaction (qPCR) quantification of 16S rRNA in lateral and contralateral scrapings of oral and nasal mucosa of 10 multibacillary patients along the initial five months of treatment. FINDINGS: The results demonstrated high heterogenicity of M. leprae viability among patients and between nasal and oral samples. Of six patients who presented good adherence and tolerance to the treatment, only four displayed absence of M. leprae viability in both samples three months after the first MDT dose, while for the other two, the absence of M. leprae viability in the oral and nasal cavities was only detected five months after the first dose. MAIN CONCLUSIONS: We concluded that qPCR of 16S rRNA for the determination of M. leprae viability in nasal and oral scraping samples could represent an interesting approach to monitor treatment efficacy.


Assuntos
Hansenostáticos , Mycobacterium leprae , Humanos , Mycobacterium leprae/genética , RNA Ribossômico 16S/genética , Hansenostáticos/uso terapêutico , Quimioterapia Combinada , Mucosa Nasal/microbiologia , DNA Bacteriano/genética
5.
Dermatol Online J ; 28(3)2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-36259803

RESUMO

Lucio phenomenon is a rare vasculopathy that can occur in patients with Hansen disease, particularly diffuse lepromatous leprosy. It is characterized by retiform purpura and necrotic ulcerations, most commonly affecting the extremities. Diagnosing Lucio phenomenon can be challenging, especially when secondary bacterial infections occur. We report a patient with Lucio phenomenon who presented with acute necrotizing fasciitis of his left upper extremity and a 10-year history of chronic ulcerations. Shortly following admission, he also developed acute kidney injury. The necrotizing fasciitis was treated with prompt surgical debridement and intravenous antibiotics. Biopsy and PCR of a right upper extremity ulcer confirmed the presence of Mycobacterium lepromatosis. Multidrug therapy and prednisone were used to treat the Lucio phenomenon. After initiating treatment, no new lesions developed, kidney function improved, and the patient underwent successful skin graft of his left upper extremity. Although corticosteroid use is controversial, our patient's marked response to multidrug therapy with prednisone highlights the importance of this regimen in severe presentations of Lucio phenomenon. To the best of our knowledge, only two other cases of Lucio phenomenon confirmed to be caused by M. lepromatosis have been reported in living patients (rather than retrospectively identified post-mortem), underscoring the importance of the presented clinical course and treatment regimen.


Assuntos
Injúria Renal Aguda , Fasciite Necrosante , Paniculite , Doenças Vasculares , Masculino , Humanos , Hansenostáticos/uso terapêutico , Prednisona/uso terapêutico , Fasciite Necrosante/complicações , Fasciite Necrosante/diagnóstico , Fasciite Necrosante/terapia , Quimioterapia Combinada , Estudos Retrospectivos , Paniculite/tratamento farmacológico , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/tratamento farmacológico , Corticosteroides
8.
Front Cell Infect Microbiol ; 12: 917282, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35937686

RESUMO

Multidrug therapy (MDT) has been successfully used in the treatment of leprosy. However, although patients are cured after the completion of MDT, leprosy reactions, permanent disability, and occasional relapse/reinfection are frequently observed in patients. The immune system of multibacillary patients (MB) is not able to mount an effective cellular immune response against M. leprae. Consequently, clearance of bacilli from the body is a slow process and after 12 doses of MDT not all MB patients reduce bacillary index (BI). In this context, we recruited MB patients at the uptake and after 12-month of MDT. Patients were stratified according to the level of reduction of the BI after 12 doses MDT. A reduction of at least one log in BI was necessary to be considered a responder patient. We evaluated the pattern of host gene expression in skin samples with RNA sequencing before and after MDT and between samples from patients with or without one log reduction in BI. Our results demonstrated that after 12 doses of MDT there was a reduction in genes associated with lipid metabolism, inflammatory response, and cellular immune response among responders (APOBEC3A, LGALS17A, CXCL13, CXCL9, CALHM6, and IFNG). Also, by comparing MB patients with lower BI reduction versus responder patients, we identified high expression of CDH19, TMPRSS4, PAX3, FA2H, HLA-V, FABP7, and SERPINA11 before MDT. From the most differentially expressed genes, we observed that MDT modulates pathways related to immune response and lipid metabolism in skin cells from MB patients after MDT, with higher expression of genes like CYP11A1, that are associated with cholesterol metabolism in the group with the worst response to treatment. Altogether, the data presented contribute to elucidate gene signatures and identify differentially expressed genes associated with MDT outcomes in MB patients.


Assuntos
Hanseníase Multibacilar , Hanseníase , Citidina Desaminase , Quimioterapia Combinada , Expressão Gênica , Humanos , Hansenostáticos/farmacologia , Hansenostáticos/uso terapêutico , Hanseníase Multibacilar/tratamento farmacológico , Hanseníase Multibacilar/genética , Mycobacterium leprae/genética , Proteínas
9.
PLoS One ; 17(8): e0272151, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35947601

RESUMO

BACKGROUND: Leprosy neuropathy is the most common peripheral neuropathy of infectious etiology worldwide; it is characterized as asymmetric and focal multiple mononeuropathy. Semmes-Weinstein monofilament (SWM) test is a simple method to assess sensory nerve function. METHODS AND FINDINGS: In this prospective cohort study, a dermatologist carried out hands and feet tactile sensation test with SWM in 107 multibacillary leprosy patients at diagnosis and in 76 patients at the end of treatment from 2016 to 2019. At diagnosis, 81/107 (75.7%) patients had some degree of functional disability, and 46 (43%) of them had altered SWM-test in the hands and 94 (87.9%) of them in the feet. After one year of multibacillary multidrug therapy, the disability decreasing to 44/76 patients (57.9%) and decreasing of the percentual of patients with altered SWM-test to 18% for the hands, and to 28.7% for the feet. At the end of treatment, the number of SMW-test points presented improvement in the hands of 22 (28.9%) patients, and in the feet of 47 (61.8%). In the hands, by SWM-test, only the radial nerve point demonstrated a significant asymmetry, while in the feet, the difference between the sum of altered SWM-test points showed significant asymmetry between both sides, highlighting the tibial nerve for the establishment of asymmetric leprosy neuropathy. In Spearman's correlation analysis, a positive correlation with statistical significance was observed between the number of hands and feet SWM altered points at diagnosis and the degree of disability at diagnosis (0.69) and at the end of the treatment (0.80). CONCLUSION: The patterns of hands and feet tactile sensation at diagnosis and their consequent modifications with the anti-leprosy drugs define the bacterial etiology of neuropathy, an important tool for the clinical diagnosis and follow up of the disease, highlighting the tibial nerve findings, the most affected nerve among leprosy patients by SWM-test, with significant asymmetry and focality impairments.


Assuntos
Hanseníase , Doenças do Sistema Nervoso Periférico , Quimioterapia Combinada , Humanos , Hansenostáticos , Hanseníase/complicações , Hanseníase/diagnóstico , Hanseníase/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/diagnóstico , Doenças do Sistema Nervoso Periférico/etiologia , Estudos Prospectivos , Sensação , Tato
10.
Bioinformatics ; 38(18): 4387-4394, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-35904544

RESUMO

MOTIVATION: Approaches for the diagnosis and treatment of diseases often adopt the multidrug therapy method because it can increase the efficacy or reduce the toxic side effects of drugs. Using different drugs simultaneously may trigger unexpected pharmacological effects. Therefore, efficient identification of drug interactions is essential for the treatment of complex diseases. Currently proposed calculation methods are often limited by the collection of redundant drug features, a small amount of labeled data and low model generalization capabilities. Meanwhile, there is also a lack of unique methods for multidrug representation learning, which makes it more difficult to take full advantage of the originally scarce data. RESULTS: Inspired by graph models and pretraining models, we integrated a large amount of unlabeled drug molecular graph information and target information, then designed a pretraining framework, MGP-DR (Molecular Graph Pretraining for Drug Representation), specifically for drug pair representation learning. The model uses self-supervised learning strategies to mine the contextual information within and between drug molecules to predict drug-drug interactions and drug combinations. The results achieved promising performance across multiple metrics compared with other state-of-the-art methods. Our MGP-DR model can be used to provide a reliable candidate set for the combined use of multiple drugs. AVAILABILITY AND IMPLEMENTATION: Code of the model, datasets and results can be downloaded from GitHub (https://github.com/LiangYu-Xidian/MGP-DR). SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Hansenostáticos , Redes Neurais de Computação , Quimioterapia Combinada , Interações Medicamentosas , Combinação de Medicamentos
11.
PLoS Negl Trop Dis ; 16(7): e0010641, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35867720

RESUMO

BACKGROUND: The numbers of circulating regulatory T cells (Tregs) are increased in lepromatous leprosy (LL) but reduced in erythema nodosum leprosum (ENL), the inflammatory complication of LL. It is unclear whether the suppressive function of Tregs is intact in both these conditions. METHODS: A longitudinal study recruited participants at ALERT Hospital, Ethiopia. Peripheral blood samples were obtained before and after 24 weeks of prednisolone treatment for ENL and multidrug therapy (MDT) for participants with LL. We evaluated the suppressive function of Tregs in the peripheral blood mononuclear cells (PBMCs) of participants with LL and ENL by analysis of TNFα, IFNγ and IL-10 responses to Mycobacterium leprae (M. leprae) stimulation before and after depletion of CD25+ cells. RESULTS: 30 LL participants with ENL and 30 LL participants without ENL were recruited. The depletion of CD25+ cells from PBMCs was associated with enhanced TNFα and IFNγ responses to M. leprae stimulation before and after 24 weeks treatment of LL with MDT and of ENL with prednisolone. The addition of autologous CD25+ cells to CD25+ depleted PBMCs abolished these responses. In both non-reactional LL and ENL groups mitogen (PHA)-induced TNFα and IFNγ responses were not affected by depletion of CD25+ cells either before or after treatment. Depleting CD25+ cells did not affect the IL-10 response to M. leprae before and after 24 weeks of MDT in participants with LL. However, depletion of CD25+ cells was associated with an enhanced IL-10 response on stimulation with M. leprae in untreated participants with ENL and reduced IL-10 responses in treated individuals with ENL. The enhanced IL-10 in untreated ENL and the reduced IL-10 response in prednisolone treated individuals with ENL was abolished by addition of autologous CD25+ cells. CONCLUSION: The findings support the hypothesis that the impaired cell-mediated immune response in individuals with LL is M. leprae antigen specific and the unresponsiveness can be reversed by depleting CD25+ cells. Our results suggest that the suppressive function of Tregs in ENL is intact despite ENL being associated with reduced numbers of Tregs. The lack of difference in IL-10 response in control PBMCs and CD25+ depleted PBMCs in individuals with LL and the increased IL-10 response following the depletion of CD25+ cells in individuals with untreated ENL suggest that the mechanism of immune regulation by Tregs in leprosy appears independent of IL-10 or that other cells may be responsible for IL-10 production in leprosy. The present findings highlight mechanisms of T cell regulation in LL and ENL and provide insights into the control of peripheral immune tolerance, identifying Tregs as a potential therapeutic target.


Assuntos
Eritema Nodoso , Hanseníase Virchowiana , Hanseníase , Anti-Inflamatórios/uso terapêutico , Quimioterapia Combinada , Humanos , Interleucina-10 , Hansenostáticos/uso terapêutico , Hanseníase/tratamento farmacológico , Hanseníase Virchowiana/complicações , Leucócitos Mononucleares , Estudos Longitudinais , Mycobacterium leprae , Prednisolona/farmacologia , Prednisolona/uso terapêutico , Linfócitos T Reguladores , Fator de Necrose Tumoral alfa
12.
BMJ Case Rep ; 15(7)2022 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-35790324

RESUMO

Leprosy is a chronic granulomatous infection predominantly involving the skin and peripheral nervous system. The condition is caused by infection with the obligate intracellular bacillus Mycobacterium leprae and the clinical phenotype is largely dependent on the host immune response to the organism. Transmission is suspected to occur via respiratory secretions with infection usually requiring prolonged periods of contact. The incubation period is highly variable with disease manifestations appearing up to several decades after the initial exposure. The disease can be broadly divided into 'paucibacillary' and 'multibacillary', and treatment with multidrug therapy including dapsone, clofazimine and rifampicin offers high rates of cure. Here, we report of a case of leprosy with a suspected incubation period in excess of 50 years following occupational exposure in rural Australia. To our knowledge, this incubation period is the longest reported to date.


Assuntos
Hanseníase Multibacilar , Hanseníase , Quimioterapia Combinada , Humanos , Período de Incubação de Doenças Infecciosas , Hansenostáticos/uso terapêutico , Hanseníase/tratamento farmacológico , Hanseníase Multibacilar/diagnóstico , Hanseníase Multibacilar/tratamento farmacológico , Mycobacterium leprae
13.
Jpn J Ophthalmol ; 66(5): 434-439, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35906503

RESUMO

PURPOSE: To evaluate omidenepag isopropyl (OMDI) for its efficacy in intraocular pressure control (IOP) and adverse reactions following administrations in Japanese patients with open-angle glaucoma (OAG) over a 3-month period. STUDY DESIGN: Retrospective observational study. SUBJECTS AND METHODS: Group 1 included untreated OAG patients, Group 2 included OAG patients treated with prostaglandin F (FP) receptor agonists (monotherapy) and Group 3 included OAG patients treated with multidrug therapy, including FP receptor agonists. OMDI was newly administered in Group 1, and FP receptor agonists were switched to OMDI in Group 2. In Group 3, all other ocular hypotensive medications were continued except FP receptor agonists. IOP changes were examined, and adverse reactions were retrieved from the medical records. RESULTS: Group 1 included 32 eyes, Group 2, 20 eyes and Group 3, 17 eyes. In Group 1, the baseline IOP was 15.7 mmHg (95% confidence interval [CI] 14.7-16.8 mmHg). After eyedrop treatment, the IOP was 14.1 mmHg (P < 0.001) at 1 month and 13.7 mmHg (P < 0.001) at 3 months. By contrast, in Group 2 and Group 3, switching FP receptor agonists to OMDI did not result in significant IOP changes (P ≥ 0.71). Six patients developed adverse reactions (hyperemia, headache, ocular pain, and swollen eyelids). CONCLUSIONS: New administration of OMDI significantly reduced the IOP. Furthermore, the IOP did not change after switching from FP receptor agonists to OMDI, including multidrug therapy. OMDI can be used as a first-line drug and is comparable to FP receptor agonists in Japanese patients with OAG.


Assuntos
Glaucoma de Ângulo Aberto , Hipertensão Ocular , Anti-Hipertensivos/uso terapêutico , Quimioterapia Combinada , Glaucoma de Ângulo Aberto/tratamento farmacológico , Humanos , Pressão Intraocular , Japão/epidemiologia , Hansenostáticos/uso terapêutico , Hipertensão Ocular/tratamento farmacológico
14.
Indian J Med Microbiol ; 40(4): 590-592, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35820982

RESUMO

Leprosy is caused by Mycobacterium leprae (M. leprae) and is unique in terms of the chronicity of the disease and its prolonged treatment protocol. Even after the introduction of multidrug therapy (MDT) by World health organization (WHO), large numbers of new cases (nearly 200,000) of leprosy are reported yearly, indicating active transmission, especially in developing countries. Recurrent clinical manifestations after MDT can occur due to leprosy reactions, relapse or reinfection. It is very difficult to differentiate reaction, relapse and reinfection. Here we categorized a recent case of reoccurrence of leprosy as reinfection by differentiating it from reaction and relapse based on evidence and by analysing the clinical data of the patient.


Assuntos
Hansenostáticos , Hanseníase , Diagnóstico Diferencial , Quimioterapia Combinada , Humanos , Hansenostáticos/uso terapêutico , Hanseníase/diagnóstico , Hanseníase/tratamento farmacológico , Hanseníase/microbiologia , Mycobacterium leprae/genética , Recidiva , Reinfecção
15.
Lancet Microbe ; 3(9): e693-e700, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35850123

RESUMO

BACKGROUND: Despite strong leprosy control measures, including effective treatment, leprosy persists in the Comoros. As of May, 2022, no resistance to anti-leprosy drugs had been reported, but there are no nationally representative data. Post-exposure prophylaxis (PEP) with rifampicin is offered to contacts of patients with leprosy. We aimed to conduct a countrywide drug resistance survey and investigate whether PEP led to the emergence of drug resistance in patients with leprosy. METHODS: In this observational, deep-sequencing analysis we assessed Mycobacterium leprae genomes from skin biopsies of patients in Anjouan and Mohéli, Comoros, collected as part of the ComLep (NCT03526718) and PEOPLE (NCT03662022) studies. Skin biopsies that had sufficient M leprae DNA (>2000 bacilli in 2 µl of DNA extract) were assessed for the presence of seven drug resistance-associated genes (ie, rpoB, ctpC, ctpI, folP1, gyrA, gyrB, and nth) using Deeplex Myc-Lep (targeted next generation deep sequencing), with a limit of detection of 10% for minority M leprae bacterial populations bearing a polymorphism in these genes. All newly registered patients with leprosy for whom written informed consent was obtained were eligible for inclusion in the survey. Patients younger than 2 years or with a single lesion on the face did not have biopsies taken. The primary outcome of our study was the proportion of patients with leprosy (ie, new cases, patients with relapses or reinfections, patients who received single (double) dose rifampicin-PEP, or patients who lived in villages where PEP was distributed) who were infected with M leprae with a drug-resistant mutation for rifampicin, fluoroquinolone, or dapsone in the Comoros. FINDINGS: Between July 1, 2017, and Dec 31, 2020, 1199 patients with leprosy were identified on the basis of clinical criteria, of whom 1030 provided a skin biopsy. Of these 1030 patients, 755 (73·3%) tested positive for the M leprae-specific repetitive element-quantitative PCR (qPCR) assay. Of these 755 patients, 260 (34·4%) were eligible to be analysed using Deeplex Myc-Lep. 251 (96·5%) were newly diagnosed with leprosy, whereas nine (3·4%) patients had previously received multidrug therapy. 45 (17·3%) patients resided in villages where PEP had been administered in 2015 or 2019, two (4·4%) of whom received PEP. All seven drug resistance-associated targets were successfully sequenced in 216 samples, 39 samples had incomplete results, and five had no results. No mutations were detected in any of the seven drug resistance-related genes for any patient with successfully sequenced results. INTERPRETATION: This drug resistance survey provides evidence to show that M leprae is fully susceptible to rifampicin, fluoroquinolones, and dapsone in the Comoros. Our results also show, for the first time, the applicability of targeted sequencing directly on skin biopsies from patients with either paucibacillary or multibacillary leprosy. These data suggest that PEP had not selected rifampicin-resistant strains, although further support for this finding should be confirmed with a larger sample size. FUNDING: Effect:Hope, The Mission To End Leprosy, the Fonds Wetenschappelijk Onderzoek, the EU.


Assuntos
Hanseníase , Mycobacterium leprae , Comores , Dapsona/farmacologia , Farmacorresistência Bacteriana/genética , Quimioterapia Combinada , Humanos , Hansenostáticos/farmacologia , Hanseníase/tratamento farmacológico , Mycobacterium leprae/genética , Rifampina/farmacologia
16.
Trans R Soc Trop Med Hyg ; 116(8): 694-703, 2022 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-35713983

RESUMO

BACKGROUND: The burden of leprosy-related disability, stigma and social participation after completing treatment is not well documented in Nigeria. We assessed the extent of disability, level of stigma and predictors of activity limitation and social participation restriction after completing multidrug therapy (MDT) for leprosy in Kano, Nigeria. METHODS: A consecutively recruited cross-section of 354 persons discharged from MDT and 360 community members were interviewed. The Eyes, Hands and Feet sum score, Screening of Activity Limitation and Safety Awareness scale, Participation scale and Jacoby Stigma scale were used for affected persons. The Exploratory Model Interview Catalogue scale was used to assess community-perceived stigma. Levels of disability, activity limitation, participation restriction and stigma were scored. Adjusted ORs for predictors were generated from logistic regression models. RESULTS: Most (91.5%, n=324) respondents had a disability; (8.2%, n=29) and (83.3%, n=295) were WHO grades 1 and 2, respectively. Similarly, 321 participants (90.7%) had activity limitation and 316 respondents (89.3%) experienced participation restriction. Further, 88.7% of participants (n=314) anticipated stigma. Activity limitation was higher among unemployed participants, men, persons with disability and those who anticipated stigma. Participation restriction was higher among low income earners (≤1000 Nigerian Naira per month (equivalent to US$2.50 per month)) and persons with disability, limited activity and anticipated stigma. CONCLUSION: Leprosy-related disability, stigma, activity limitation and social participation restriction are high after treatment. We recommend community-based rehabilitation to sustain self-care, reduce stigma and ensure social inclusion.


Assuntos
Pessoas com Deficiência , Hanseníase , Estudos Transversais , Quimioterapia Combinada , Humanos , Hansenostáticos/uso terapêutico , Hanseníase/tratamento farmacológico , Masculino , Nigéria/epidemiologia , Alta do Paciente , Participação Social
17.
BMJ Open ; 12(5): e057173, 2022 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-35545382

RESUMO

INTRODUCTION: The mainstay of leprosy treatment is multidrug treatment (MDT), which contains rifampicin, dapsone and clofazimine. The occurrence of dapsone hypersensitivity syndrome (DHS), a sudden, potentially fatal and traumatic adverse reaction due to dapsone, may affect treatment adherence and may result in fatality if untreated. Before MDT administration, screening for HLA-B*13:01 in patients with leprosy can potentially reduce DHS risk. The study aims to assess the effectiveness of using a screening test for HLA-B*13:01 in reducing the incidence of DHS and to evaluate the feasibility of using the quantitative PCR-based screening tool as DHS predictors before dapsone administration using individual patient testing in a referral centralised-lab model. METHODS AND ANALYSIS: A total of 310 newly diagnosed patients with leprosy will be recruited from health centres in two highly endemic districts in Indonesia. Dried blood will be taken on filter paper as the specimen receptacle to collect DNA from the patients and transported at room temperature to the leprosy referral laboratory before MDT administration. Checking for HLA-B*13:01 from human DNA is performed using the Nala PGx 1301 V.1 kit. The results will be shared with the leprosy health workers on the site via phone call and courier. Patients with a positive test result will be treated with MDT without dapsone, and patients with a negative result will be treated with complete MDT. Physical examination (weight, height, skin, muscle and nerve function examination), complete blood tests (including renal function test) will be carried out at baseline. Follow-up will be performed at the fourth and eighth weeks to observe any development of adverse drug reactions. ETHICS AND DISSEMINATION: The ethical approval for the study was issued by the Ethical Committee of the National Institute of Health Research and Development, Ministry of Health, Indonesia. Written informed consent will be sought from all participants.


Assuntos
Hipersensibilidade a Drogas , Hanseníase , Dapsona/efeitos adversos , Hipersensibilidade a Drogas/tratamento farmacológico , Hipersensibilidade a Drogas/epidemiologia , Hipersensibilidade a Drogas/genética , Quimioterapia Combinada , Testes Genéticos , Humanos , Incidência , Indonésia , Hansenostáticos/efeitos adversos , Hanseníase/tratamento farmacológico , Síndrome
18.
Ther Deliv ; 13(4): 249-273, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35615860

RESUMO

Glioblastoma (GBM) is a deadly malignancy with a poor prognosis. An important factor contributing to GBM recurrence is high resistance of GBM cancer stem cells (GSCs). While temozolomide (TMZ), has been shown to consistently extend survival, GSCs grow resistant to TMZ through upregulation of DNA damage repair mechanisms and avoidance of apoptosis. Since a single-drug approach has failed to significantly alter prognosis in the past 15 years, unique approaches such as multidrug combination therapy together with distinctive targeted drug-delivery approaches against cancer stem cells are needed. In this review, a rationale for multidrug therapy using a targeted nanotechnology approach that preferentially target GSCs is proposed with discussion and examples of drugs, nanomedicine delivery systems, and targeting moieties.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Quimioterapia Combinada , Glioblastoma/tratamento farmacológico , Humanos , Hansenostáticos/farmacologia , Hansenostáticos/uso terapêutico , Células-Tronco Neoplásicas/patologia , Temozolomida/farmacologia , Temozolomida/uso terapêutico
19.
An Bras Dermatol ; 97(3): 366-368, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35428530

RESUMO

The number of skin infections caused by atypical mycobacteria has increased in recent decades. They usually appear after contact with wounds and interruptions in the integrity of the skin. The present report describes a case of cutaneous infection by Mycobacterium marinum, in a young, immunocompetent patient, with a prolonged evolution, diagnosed through a skin lesion culture (from a spindle biopsy of the skin). The patient was treated with multidrug therapy, including clarithromycin, doxycycline, and rifampicin, due to the lesion extent, with satisfactory results. A brief review of the literature is also provided.


Assuntos
Infecções por Mycobacterium não Tuberculosas , Mycobacterium marinum , Dermatopatias Bacterianas , Dermatopatias Infecciosas , Antibacterianos/uso terapêutico , Celulite (Flegmão) , Quimioterapia Combinada , Humanos , Hansenostáticos/uso terapêutico , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/microbiologia , Micobactérias não Tuberculosas , Dermatopatias Bacterianas/diagnóstico , Dermatopatias Bacterianas/tratamento farmacológico , Dermatopatias Bacterianas/microbiologia
20.
Microbes Infect ; 24(6-7): 104981, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35462022

RESUMO

Leprosy is an infectious disease influenced by genetic, immunological, and environmental factors. Reduced gene expressions may be associated with the immunological response pattern and leprosy susceptibility. We investigated the direct and indirect effects of Vitamin D Receptor (VDR) and Cathelicidin Antimicrobial Peptide (CAMP) gene expressions on the serum levels of vitamin D, Cathelicidin, and cytokines in newly-diagnosed leprosy patients and post-six-months of multidrug therapy (MDT). Thirty-four leprosy patients were assessed, paucibacillary (PB; n = 14) and multibacillary (MB; n = 20) cases, untreated or having received six months of MDT, 18 healthy controls, and 25 household contacts. VDR and CAMP gene expression levels were strongly correlated to some important cytokines in both, untreated leprosy patients (PB, r = 0.9319; MB, r = 0.9569) and patients who had undergone MDT (PB, r = 0.9667; MB, r = 0.9569). We observed that both gene expressions directly influenced IL-2, IFN-γ, and IL-17F serum levels in leprosy patients compared to the household contacts and healthy individuals. VDR and CAMP gene expressions induced a persistent inflammatory response in PB and MB leprosy patients, even after six months of MDT, to fight the Mycobacterium leprae infection. Due to the persistent inflammatory profile, multidrug therapy is suggested to be maintained for more than six months, especially for MB patients. Vitamin D supplementation is recommended from the onset as a transcription factor to improve VDR and CAMP gene expression in leprosy patients.


Assuntos
Hanseníase , Receptores de Calcitriol , Peptídeos Catiônicos Antimicrobianos , Peptídeos Antimicrobianos , Citocinas/genética , Quimioterapia Combinada , Expressão Gênica , Humanos , Imunidade , Interleucina-17/genética , Interleucina-2/uso terapêutico , Hansenostáticos/uso terapêutico , Hanseníase/tratamento farmacológico , Mycobacterium leprae , Receptores de Calcitriol/genética , Fatores de Transcrição/genética , Vitamina D , Catelicidinas
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