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1.
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
2.
BMJ Open ; 12(7): e058397, 2022 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-35851027

RESUMO

INTRODUCTION: Malaria is one of the major public health problems in sub-Saharan Africa. It contributes significantly to maternal and fetal morbidity and mortality in affected countries. This study aims to evaluate the impact of enhanced case detection using molecular testing called loop-mediated isothermal amplification (LAMP) on birth outcomes in a prospective study design. METHODS AND ANALYSIS: A pragmatic randomised diagnostic outcomes trial will be conducted in several health institutes in different Ethiopian regions. Women (n=2583) in their first and second trimesters of pregnancy will be included in the study and individually randomised to the standard of care or enhanced case detection arms, and followed until delivery. Enrolment will encompass the malaria peak transmission seasons. In the standard of care arm, a venous blood sample will be collected for malaria diagnosis only in symptomatic patients. In contrast, in the intervention arm, mothers will be tested by a commercially available Conformité Européene (CE)-approved LAMP malaria test, microscopy and rapid diagnostic test for malaria regardless of their symptoms at each antenatal care visit. The primary outcome of the study is to measure birth weight. ETHICS AND DISSEMINATION: The study was approved by the following ethical research boards: Armauer Hansen Research Institute/ALERT Ethics Review Committee (FORM AF-10-015.1, Protocol number PO/05/20), the Ethiopia Ministry of Science and Higher Education National Research Ethics Review Committee (approval SRA/11.7/7115/20), the Ethiopia Food and Drug Administration (approval 02/25/33/I), UCalgary Conjoint Health Research Ethics Board (REB21-0234). The study results will be shared with the institutions and stakeholders such as the Ethiopia Ministry of Health, the Foundation for Innovative Diagnostics, WHO's Multilateral initiative on Malaria - Tropical Diseases Research (TDR-MIM), Roll Back Malaria and the Malaria in Pregnancy Consortium. The study results will also be published in peer-reviewed journals and presented at international conferences. TRIAL REGISTRATION NUMBER: NCT03754322.


Assuntos
Malária , Programas de Rastreamento , Complicações Parasitárias na Gravidez , Feminino , Humanos , Malária/diagnóstico , Malária/terapia , Programas de Rastreamento/métodos , Técnicas de Diagnóstico Molecular , Técnicas de Amplificação de Ácido Nucleico , Ensaios Clínicos Pragmáticos como Assunto , Gravidez , Complicações Parasitárias na Gravidez/diagnóstico , Complicações Parasitárias na Gravidez/terapia , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Tecnologia
3.
BMJ Open ; 12(5): e054434, 2022 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-35613774

RESUMO

INTRODUCTION: Tanzania is adapting a shortened injectable-free multidrug resistant tuberculosis (MDR-TB) regimen, comprising new drugs such as bedaquiline and delamanid and repurposed drugs such as clofazimine and linezolid. The regimen is implemented using a pragmatic prospective cohort study within the National TB and Leprosy Programme and is accompanied by a process evaluation. The process evaluation aims to unpack the implementation processes, their outcomes and the moderating factors in order to understand the clinical effectiveness of the regimen. This protocol describes the methods employed in understanding the implementation processes of the new MDR-TB regimen in 15 regions of Tanzania. METHODS: This study adopts a concurrent mixed-methods design. Using multiple data collection tools, we capture information on: implementation outcomes, stakeholder response to the intervention and the influence of contextual factors. Data will be collected from the 22 health facilities categorised as dispensaries, health centres, district hospitals and referral hospitals. Health workers (n=132) and patients (n=220) will fill a structured questionnaire. For each category of health facility, we will conduct five focus group discussions and in-depth interviews (n=45) for health workers. Participant observations (n=9) and review documents (n=22) will be conducted using structured checklists. Data will be collected at two points over a period of 1 year. We will analyse quantitative data using descriptive and inferential statistical methods. Thematic analysis will be used for qualitative data. ETHICS AND DISSEMINATION: This study received ethical approval from National Institute of Medical research (NIMR), Ref. NIMR/HQ/R.8a/Vol.IX/3269 and from the Mbeya Medical Research and Ethics Review Committee, Ref. SZEC-2439/R.A/V.I/38. Our findings are expected to inform the wider implementation of the new MDR-TB regimen as it is rolled out countrywide. Dissemination of findings will be through publications, conferences, workshops and implementation manuals for scaling up MDR-TB treatments.


Assuntos
Antituberculosos , Tuberculose Resistente a Múltiplos Medicamentos , Antituberculosos/uso terapêutico , Protocolos Clínicos , Humanos , Estudos Prospectivos , Tanzânia , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico
4.
Indian J Dermatol Venereol Leprol ; 88(5): 615-622, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35389029

RESUMO

Background Mycetoma is widespread in Yemen; however, there are only a few documented reports on the entity from this geographical area. Methods A prospective study of 184 cases of mycetoma (male 145 and female 39) from different regions of north-western Yemen was conducted between July 2000 and May 2014. Clinical profile was recorded in a standardized protocol. The diagnosis was based on clinical features, X-ray studies, examination of grains, and histopathology. Results Eumycetoma was diagnosed in 129, caused by Madurella mycetomatis in 124, Leptosphaeria senegalensis in one and pale grain fungus in four, whereas actinomycetoma occurred in 55, caused by Streptomyces somaliensis in 29, Actinomadura madurai in nine, Actinomadura pelletieri in one, and Nocardia in sixteen. Eumycetoma cases were treated with prolonged course of antifungal drugs, mostly ketoconazole, with itraconazole being used in four patients, along with excision or debulking. Results were better when antifungal drugs were given two to three months before surgery and in those who received itraconazole. Actinomycetoma cases were initially treated with co-trimoxazole monotherapy; later streptomycin was added in 30 cases. Six patients who did not show adequate improvement and two others from the start were treated with modified Welsh regimen and with good results. Limitations Identification of different causative agents was done by histopathology and could not be reconfirmed by culture. Conclusion Mycetoma is widespread in north-western Yemen with a higher incidence of eumycetoma and a majority of the cases were caused by Madurella mycetomatis. Modified Welsh regimen in actinomycetoma and itraconazole with excision in eumycetoma showed the best results.


Assuntos
Madurella , Micetoma , Antifúngicos/uso terapêutico , Feminino , Humanos , Índia , Itraconazol/uso terapêutico , Masculino , Micetoma/diagnóstico , Micetoma/tratamento farmacológico , Micetoma/epidemiologia , Estudos Prospectivos , Iêmen/epidemiologia
5.
Biomolecules ; 12(1)2022 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-35053231

RESUMO

The genus Mimosa belongs to the Fabaceae family and comprises almost 400 species of herbs, shrubs and ornamental trees. The genus Mimosa is found all over the tropics and subtropics of Asia, Africa, South America, North America and Australia. Traditionally, this genus has been popular for the treatment of jaundice, diarrhea, fever, toothache, wound healing, asthma, leprosy, vaginal and urinary complaints, skin diseases, piles, gastrointestinal disorders, small pox, hepatitis, tumor, HIV, ulcers and ringworm. The review covered literature available from 1959 to 2020 collected from books, scientific journals and electronic searches, such as Science Direct, Web of Science and Google scholar. Various keywords, such as Mimosa, secondary metabolites, medicines, phytochemicals and pharmacological values, were used for the data search. The Mimosa species are acknowledged to be an essential source of secondary metabolites with a wide-ranging biological functions, and up until now, 145 compounds have been isolated from this genus. Pharmacological studies showed that isolated compounds possess significant potential, such as antiprotozoal, antimicrobial, antiviral, antioxidant, and antiproliferative as well as cytotoxic activities. Alkaloids, chalcones, flavonoids, indoles, terpenes, terpenoids, saponins, steroids, amino acids, glycosides, flavanols, phenols, lignoids, polysaccharides, lignins, salts and fatty esters have been isolated from this genus. This review focused on the medicinal aspects of the Mimosa species and may provide a comprehensive understanding of the prospective of this genus as a foundation of medicine, supplement and nourishment. The plants of this genus could be a potential source of medicines in the near future.


Assuntos
Mimosa , Etnofarmacologia , Compostos Fitoquímicos/química , Extratos Vegetais/química , Estudos Prospectivos
6.
Indian J Dermatol Venereol Leprol ; 88(3): 367-371, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33666031

RESUMO

BACKGROUND: Neisseria gonorrhoeae and Chlamydia trachomatis are the two most prevalent bacterial sexually transmitted infections. For over two decades, treatment guidelines have recommended empirical co-treatment for N.gonorrhoeae and C.trachomatis as symptoms overlap and co-infection is common. Studies from India estimating the same are limited and mostly based on conventional techniques. AIM AND OBJECTIVE: The aim of this study was to determine the frequency of N.gonorrhoeae and C.trachomatis coinfection using nucleic acid amplification tests. Further, we assessed the utility of pus cell estimation in Gram stained smears as a screening tool for inclusion of samples for molecular diagnosis. METHODS: This was a prospective study conducted at two tertiary care hospitals; 100 patients (55 females and 45 males) with genitourinary discharge attending STI clinics were recruited, and endocervical or urethral swabs were collected. PCRs for N.gonorrhoeae and C.trachomatis were put up. In addition, microscopy and culture for gonococcus was performed followed by antimicrobial susceptibility testing. Statistical analysis was performed using the SPSS 16 software. RESULTS: N.gonorrhoeae infection was more common than C.trachomatis. A total of 14 patients were positive by PCR (9 males and 5 females) for gonococcus. However, culture was positive only in 8 male patients. PCR for C.trachomatis was positive in 9 (4 males and 5 females) and the co-infection rate was 5%. The sensitivity and negative predictive value of pus cell estimation was 100% for males and 64% and 94.6% respectively for females. All isolates were susceptible to extended spectrum cephalosporins and azithromycin. LIMITATION: The sample size of the study was small. CONCLUSION: Frequency of N.gonorrhoeae/C.trachomatis coinfection in symptomatic STI patients is low. Coinfection is considerably overestimated and necessary confirmation of etiological diagnosis could reduce widespread empirical administration of broad-spectrum antibiotics.


Assuntos
Infecções por Chlamydia , Coinfecção , Gonorreia , Infecções por Chlamydia/diagnóstico , Infecções por Chlamydia/tratamento farmacológico , Infecções por Chlamydia/epidemiologia , Chlamydia trachomatis , Coinfecção/diagnóstico , Coinfecção/epidemiologia , Feminino , Gonorreia/complicações , Gonorreia/diagnóstico , Gonorreia/tratamento farmacológico , Humanos , Índia/epidemiologia , Masculino , Neisseria gonorrhoeae , Projetos Piloto , Estudos Prospectivos , Sensibilidade e Especificidade , Supuração
7.
J Ultrasound ; 25(2): 265-272, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33959898

RESUMO

PURPOSE: Grayscale ultrasonography when complemented with shear wave elastography helps in better evaluation of treatment response of leprosy neuropathy and in guiding appropriate management of the patient. There is limited literature regarding the use of shear wave elastography in ulnar nerve neuropathy. Our purpose was to evaluate the role of shear wave elastography in assessing stiffness changes within the ulnar nerve during treatment of leprosy. METHODS: This was a prospective study which included 30 patients diagnosed with leprosy neuropathy. Recruited patients were followed up, during the course of treatment, i.e. for 1 year. Serial ultrasonography of these patients was done at 0, 3, 6 and 12 months interval. RESULTS: Significant (P < 0.05) decrease in elastography parameters was seen in transverse imaging plane between first and third, as well as first and fourth visits (mean stiffness and velocity pretreatment ~ 25.78 ± 18 kPa and 2.74 ± 0.98 m/s, mean stiffness and velocity post-treatment 15.67 ± 5.89 kPa and 2.24 ± 0.428 m/s). Although elastography parameters decreased during these visits in the long-axis imaging plane, they were not found to be statistically significant. However, gross morphology and cross-sectional area of the nerve did not change significantly across visits. Interestingly, elastography values were higher in patients with neuritis, though not statistically significant. CONCLUSION: Shear wave elastography is a novel, upcoming modality in musculoskeletal imaging especially in the evaluation of peripheral neuropathy. It can act as an adjunct to grey-scale imaging, which can help in early diagnosis and in guiding treatment of leprosy neuropathy.


Assuntos
Técnicas de Imagem por Elasticidade , Hanseníase , Doenças do Sistema Nervoso Periférico , Infecções dos Tecidos Moles , Neuropatias Ulnares , Técnicas de Imagem por Elasticidade/métodos , Seguimentos , Humanos , Hanseníase/complicações , Hanseníase/diagnóstico por imagem , Hanseníase/terapia , Doenças do Sistema Nervoso Periférico/diagnóstico por imagem , Doenças do Sistema Nervoso Periférico/terapia , Estudos Prospectivos
8.
Indian J Dermatol Venereol Leprol ; 88(3): 313-321, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34623059

RESUMO

BACKGROUND: Chronic urticaria, in many cases, has an unsatisfactory response to antihistamines. The current recommendations in urticaria do not mention the dose and duration for methotrexate. AIMS: This study aims to systematically review the use/efficacy of methotrexate in chronic urticaria. METHODS: A systematic search in four databases, that is, PubMed/Medline, Cochrane central, Google Scholar and Clinicaltrials.gov was done to identify studies on the use of methotrexate in chronic urticaria using key words "methotrexate [MeSH terms]" and "urticaria" or "urticaria, chronic" or "urticaria, chronic spontaneous." RESULTS: Nine articles (study participants 127), including three randomized control trials, one prospective interventional trial without control, three retrospective reviews and two case reports, were identified and finally included in the systematic review. There was a paucity of literature and the three randomized control trials did not show any benefit of methotrexate over antihistamines alone. However, in studies where steroid-dependent cases were given methotrexate, marked benefit was reported with steroid-sparing effect, particularly on methotrexate dose escalation. LIMITATIONS: Due to a paucity of published literature on methotrexate in urticaria, a meta-analysis could not be done. CONCLUSION: In chronic recalcitrant or steroid-dependent cases, methotrexate may be a therapeutic agent of interest; however, current evidence does not point to any added advantage in efficacy over antihistamines. More evidence based on larger, well-executed randomized control trials is needed in the future to get more definitive answers.


Assuntos
Urticária Crônica , Urticária , Doença Crônica , Antagonistas dos Receptores Histamínicos/uso terapêutico , Humanos , Metotrexato/uso terapêutico , Estudos Prospectivos , Estudos Retrospectivos , Urticária/diagnóstico , Urticária/tratamento farmacológico
9.
Indian J Dermatol Venereol Leprol ; 88(5): 641-644, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34951937

RESUMO

Introduction Neuropathic pain is a common and disabling late complication of leprosy. We investigated the clinical and electrophysiological characteristics of neuropathic pain in leprosy patients by evaluating nerve conduction, sympathetic skin response (SSR) and A-waves. Methods Twenty one leprosy patients with neuropathic pain validated by the Douleur Neuropathique en 4 (DN4)Questionnaire were selected for study. Pain intensity was measured by the visual analog scale. Demographic and clinical data were collected for all patients. Clinical data included appraisal of the median, ulnar, radial, tibial and common peroneal nerves, assessment of the sympathetic skin response and conventional electrophysiological recordings. Results Among all electroneuromyographic presentations, multifocal mononeuropathy was still the most prevalent. Sensory loss was observed more frequently than motor deficits. As most patients presented advanced clinical forms of leprosy and were under treatment, this high mean was found and the ulnar nerve was most frequently affected. The sympathetic skin response was absent in 16 patients. Higher DN4 Questionnaire scores were observed in women and in those receiving corticosteroid therapy. These inferences are possible to be made, but our study's limitations don't allow us to be certain about it. The statistical significance found only permits us to evidence what we related on the textual part of the study. Limitations The small number of patients studied, the lack of sophisticated diagnostic methods for leprosy, as well as the difficulties in assessing nerve conduction were the main limitations of this study. Conclusion The neurophysiological and clinical findings in leprous neuropathy were modest despite the conspicuous neuropathic pain. Although electrophysiological studies are a vital tool to verify nerve damage, variations in the clinical presentation of leprosy neuropathic pain render the diagnosis challenging. Further studies are needed to describe the neurophysiological evolution of this disease.


Assuntos
Hanseníase , Neuralgia , Estudos Transversais , Feminino , Humanos , Hanseníase/complicações , Hanseníase/diagnóstico , Condução Nervosa/fisiologia , Neuralgia/diagnóstico , Neuralgia/epidemiologia , Neuralgia/etiologia , Estudos Prospectivos
10.
Int J Mycobacteriol ; 10(4): 393-397, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34916457

RESUMO

Background: The diagnosis of leprosy is based on the characteristic signs and symptoms of the disease, subsidized by laboratory tests. When positive, the bacilloscopy closes the diagnosis for leprosy. Phenolic glycolipid-I, or PGL-I, is a molecule in the bacillus cell wall that confers a greater immune response. The ML Flow test is an immunochromatographic test for the detection of anti-PGL-I IgM in human blood or serum. Methods: A prospective study with data collection and biological materials in patients with suspected leprosy from August 2020 to May 2021. For microscopy, intradermal smears were stained with Auramine O, and after reading under a fluorescence microscope, reviewed by Ziehl-Neelsen. The ML flow test was performed according to the Bührer-Sékula protocol. To assess the agreement between the methods, the Kappa index was estimated. Results: Of the 94 suspected leprosy patients, 31 (32.9%) were diagnosed with leprosy. There was moderate agreement between the results of the ML Flow and Auramine O tests (Kappa = 0.58) and substantial agreement between the ML Flow and Ziehl-Neelsen microscopy (Kappa = 0.72). In paucibacillary cases, serology was positive in 100% of patients. Conclusions: This study concluded that the Ziehl-Neelsen technique remains the best option for standard leprosy staining, and the ML flow test is more positive among the three techniques evaluated and can be an effective tool in the early diagnosis of leprosy cases.


Assuntos
Antígenos de Bactérias , Hanseníase , Anticorpos Antibacterianos , Humanos , Hanseníase/diagnóstico , Microscopia de Fluorescência , Mycobacterium leprae , Estudos Prospectivos , Coloração e Rotulagem
11.
Dermatol Ther ; 34(6): e15125, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34490707

RESUMO

Management of chronic/recurrent erythema nodosum leprosum (ENL) is challenging. The majority of these patients become steroid-dependent and suffer from the adverse effects of long-term corticosteroid use. Minocycline has shown promising results in a small series of chronic/recurrent ENL patients. The aim of this study was to compare the efficacy and safety of minocycline and clofazimine in patients with chronic/recurrent ENL. In this prospective randomized clinical trial, 60 participants with chronic/recurrent ENL were randomized (1:1) to receive either minocycline 100 mg once daily or clofazimine 100 mg thrice daily for 12 weeks along with prednisolone according to WHO protocol and followed up for 6 months. The outcome measures were mean time for initial control of ENL, proportion of patients having a recurrence of ENL, mean time for recurrence after initial control, additional prednisolone requirement, and frequency of adverse events. Initial control of ENL was achieved earlier in the minocycline group as compared to the clofazimine group (2.97 ± 1.9 weeks vs. 4 ± 1.96 weeks, respectively; p-0.048). The number of participants having ENL flares/recurrences during the study period was comparable in both groups (71.4% in clofazimine vs. 55.2% in minocycline group; p-0.2). The participants in the minocycline group remained in remission for a longer duration after initial control of ENL as compared to the clofazimine group (p-0.001). Mean additional prednisolone dose required for control of ENL flares/recurrences was also comparable in both groups (p-0.09). The minocycline group had fewer side effects than the clofazimine group (p-0.047). Minocycline led to a rapid and sustained improvement of ENL episodes with fewer adverse events showing a superior efficacy to clofazimine.


Assuntos
Eritema Nodoso , Hanseníase Virchowiana , Clofazimina/efeitos adversos , Eritema Nodoso/diagnóstico , Eritema Nodoso/tratamento farmacológico , Humanos , Hansenostáticos/efeitos adversos , Hanseníase Virchowiana/diagnóstico , Hanseníase Virchowiana/tratamento farmacológico , Minociclina/efeitos adversos , Estudos Prospectivos
12.
Indian J Dermatol Venereol Leprol ; 87(6): 778-786, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34491679

RESUMO

BACKGROUND: Serration pattern analysis helps in the classification of subepidermal autoimmune blistering disorders; more precisely, it helps to differentiate epidermolysis bullosa acquisita from other subepidermal autoimmune blistering disorders. Most of the published reports of this tool have come from a single center. OBJECTIVES: The objectives of the study were to study the utility of serration pattern analysis in classifying subepidermal autoimmune blistering disorders. METHODS: Seventy five cases of subepidermal autoimmune blistering disorders were enrolled in this prospective study. A three millimeter punch biopsy was taken from the perilesional skin or mucosa for direct immunofluorescence; indirect immunofluorescence was carried out using salt-split skin. Subclassification of subepidermal autoimmune blistering disorders was done based on direct immunofluorescence, indirect immunofluorescence on salt-split skin, indirect immunofluorescence using knockout skin and serration pattern analysis findings. RESULTS: Indirect immunofluorescence was positive in 68 cases; 14 cases showed a dermal staining pattern while the rest showed either an epidermal or a combined pattern. All patients with epidermal or combined staining patterns showed "n" serrated pattern on direct immunofluorescence. Nine patients with dermal staining on indirect immunofluorescence also revealed an "n" serration pattern on direct immunofluorescence indicating the diagnosis of anti-p200 pemphigoid, and the rest showed a "u" serrated pattern. Three patients with negative indirect immunofluorescence showed "u" serration on direct immunofluorescence while the rest showed "n" serration. LIMITATIONS: ELISA and immunoblotting could not be performed due to resource constraints. CONCLUSION: Based on indirect immunofluorescence and serration pattern analysis, classification of the majority of patients with subepidermal autoimmune blistering disorders was possible in our study. Pattern recognition is a cost-effective tool and can be easily learnt. It is recommended to be practiced in all laboratories where facilities for advanced immunological diagnosis are unavailable.


Assuntos
Dermatopatias Vesiculobolhosas/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Criança , Pré-Escolar , Feminino , Imunofluorescência , Humanos , Masculino , Microscopia de Fluorescência , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
13.
Artigo em Inglês | MEDLINE | ID: mdl-34379946

RESUMO

BACKGROUND: Melasma is the commonest cause of facial hypermelanosis in skin type IV-VI. First-line treatment includes a triple combination containing topical corticosteroid and hydroquinone which have side effects on prolonged use. Chemical peels are a second-line management option with the laser being used in refractory cases, but the worsening of hyperpigmentation in darker skin types can occur following laser therapy. Sunscreen is a must to prevent relapses. AIMS AND OBJECTIVES: (i) To compare the effects of treatment with a proprietary combination (phenyl ethyl resorcinol, nonapeptide-1, aminoethyl phosphinic acid, antioxidants and sunscreen) versus sunscreen alone in limiting or reducing, melasma and preventing recurrence as a maintenance regimen after the initial use of triple combination,(ii) to evaluate the safety of the formulation studied, and (iii) to study the improvement of the quality of life of the patients after using the study formulation versus placebo. METHODS: It was a prospective double-blinded parallel-group randomized controlled pilot study. A total of 46 subjects were recruited by consecutive sampling methods and randomized to 23 each in case and control groups. The study period was eight months with three phases. Phase 1 constituted the application of triple combination for eight weeks by both groups followed by phase 2 with the case group applying proprietary medicine and the control group applying sunscreen. Phase 3 was a follow-up period to see the sustenance of results in both groups as well as any evidence of relapses. Sunscreen was applied in all three phases. RESULTS: Case group in the study showed improvement in the melasma severity score and mean melanin index as measured by mexameter but it did not attain statistical significance as compared to the control group. The melasma area and severity index score showed a consistent reduction in the case group, whereas it increased in the control group from baseline. LIMITATIONS: Small sample size and a short follow-up period of our study were major limitations. CONCLUSION: The proprietary combination, which has sunscreen as one of its constituents, is more effective in maintaining remission after triple combination without any added inconvenience of application of two separate preparations as compared to sunscreen alone.


Assuntos
Fármacos Dermatológicos/administração & dosagem , Melanose/tratamento farmacológico , Protetores Solares/administração & dosagem , Adulto , Antioxidantes/administração & dosagem , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Humanos , Masculino , Éteres Fenílicos/administração & dosagem , Ácidos Fosfínicos/administração & dosagem , Projetos Piloto , Estudos Prospectivos , Resorcinóis/administração & dosagem , Índice de Gravidade de Doença
14.
Artigo em Inglês | MEDLINE | ID: mdl-34379957

RESUMO

BACKGROUND: Contacts of leprosy patients have an increased risk of infection with Mycobacterium leprae. Contact tracing and chemo- or immunoprophylaxis are important means of preventing leprosy transmission. AIMS: We aimed to evaluate the efficacy of immunoprophylaxis with Mycobacterium indicus pranii vaccine in reducing anti-phenolic glycolipid-1 titers in household contacts of leprosy patients. METHODS: This prospective single-center study was conducted in a tertiary care center in North India from January 2015 to December 2016. Contacts of leprosy patients (both paucibacillary and multibacillary) were screened for anti-phenolic glycolipid-1 antibodies with enzyme-linked immunosorbent assay. Those found positive were given immunoprophylaxis with a single dose of Mycobacterium indicus pranii vaccine, and anti-phenolic glycolipid-1 titers were evaluated at six and 12 months. All contacts were clinically followed for three years. RESULTS: Of the 135 contacts of 98 leprosy patients that were screened, 128 were recruited. Seventeen of these contacts were positive for anti-phenolic glycolipid-1 antibodies and were given Mycobacterium indicus pranii vaccine. Two contacts were lost to follow-up. After immunoprophylaxis, anti-phenolic glycolipid-1 titers were negative in all patients at all intervals, and no contact developed any clinical signs or symptoms of leprosy during the three-year follow-up. LIMITATIONS: The small number of contacts studied, the short follow-up period and the absence of a control group were limitations of this study. Dicussion: We could not find any papers on natural decline of PGL 1 titres in contacts, although in leprosy patients, these titres may even increase after completion of treatment. However the titres do correlate with bacterial load (reference: Int J Lepr Other Mycobact Dis. 1998 Sep;66(3):356-64) so if the tires decrease or become negative it may be considered as an indirect evidence of bacillary clearance. Hence we may suggest the protective efficacy. Furthermore, as the editor mentioned, considering the small number of positive patients, a control group was not possible in the present pilot study, but such studies may be carried out in the future. CONCLUSION: Immunoprophylaxis with Mycobacterium indicus pranii vaccine is effective and safe in preventing disease in contacts of leprosy patients. However, these findings need to be replicated in larger studies.


Assuntos
Anticorpos Antibacterianos/sangue , Vacinas Bacterianas , Glicolipídeos/imunologia , Hanseníase/imunologia , Mycobacterium/imunologia , Adulto , Busca de Comunicante , Feminino , Humanos , Hanseníase/transmissão , Masculino , Projetos Piloto , Estudos Prospectivos , Centros de Atenção Terciária
15.
PLoS Negl Trop Dis ; 15(8): e0009716, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34415916

RESUMO

BACKGROUND: Regarding the leprosy transmission through the upper airways, overcrowded locations such as prisons can become a risk to get sick. Like the leprosy hidden endemic demonstrated in male prison population, being interesting to assess the leprosy scene also among confined women. METHODS: A prospective descriptive study conducted at Female Penitentiary, Brazil. Leprosy Suspicion Questionnaire (LSQ) were applied to the participants, and submitted to specialized dermatoneurological exam, peripheral nerve ultrasonography, and anti-PGL-I serology. FINDINGS: 404 female inmates were evaluated, 14 new cases were diagnosed (LG-leprosy group), a new case detection rate (NCDR) of 3.4%, 13 multibacillary, while another 390 constituted the Non-Leprosy group (NLG). Leprosy cases were followed up during multidrug therapy with clinical improvement. The confinement time median was 31 months in LG, similar to NLG, less than the time of leprosy incubation. Regarding LSQ, the neurological symptoms reached the highest x2 values as Q1-numbness (5.6), Q3-anesthetizes areas in the skin (7.5), Q5-Stinging sensation (5.8), and Q7-pain in the nerves (34.7), while Q4-spots on the skin was 4.94. When more than one question were marked in the LSQ means a 12.8-fold higher to have the disease than a subject who marked only one or none. The high 34% rate of anti-PGL-I seropositivity in the penitentiary, higher levels in LG than NLG. Three additional leprosy cases each were diagnosed on the second (n = 66) and third (n = 14) reevaluations 18 and 36 months after the initial one. Semmes-Weinstein monofilaments demonstrated lower limbs (32.2%) more affected than the upper limbs (25%) with improvement during the follow-up. INTERPRETATION: The NCDR in this population showed an hidden endemic of leprosy as well as the efficacy of a search action on the part of a specialized team with the aid of the LSQ and anti-PGL-I serology as an auxiliary tracking tools.


Assuntos
Hanseníase/diagnóstico , Prisões/estatística & dados numéricos , Adulto , Brasil/epidemiologia , Feminino , Seguimentos , Humanos , Hansenostáticos/efeitos adversos , Hansenostáticos/uso terapêutico , Hanseníase/tratamento farmacológico , Hanseníase/epidemiologia , Hanseníase/microbiologia , Pessoa de Meia-Idade , Mycobacterium leprae/efeitos dos fármacos , Mycobacterium leprae/fisiologia , Estudos Prospectivos , Adulto Jovem
17.
PLoS Negl Trop Dis ; 15(7): e0009635, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34319982

RESUMO

BACKGROUND: Protective effects of Bacillus Calmette-Guérin (BCG) vaccination and clofazimine and dapsone treatment against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been reported. Patients at risk for leprosy represent an interesting model for assessing the effects of these therapies on the occurrence and severity of coronavirus disease 2019 (COVID-19). We assessed the influence of leprosy-related variables in the occurrence and severity of COVID-19. METHODOLOGY/PRINCIPAL FINDINGS: We performed a 14-month prospective real-world cohort study in which the main risk factor was 2 previous vaccinations with BCG and the main outcome was COVID-19 detection by reverse transcription polymerase chain reaction (RT-PCR). A Cox proportional hazards model was used. Among the 406 included patients, 113 were diagnosed with leprosy. During follow-up, 69 (16.99%) patients contracted COVID-19. Survival analysis showed that leprosy was associated with COVID-19 (p<0.001), but multivariate analysis showed that only COVID-19-positive household contacts (hazard ratio (HR) = 8.04; 95% CI = 4.93-13.11) and diabetes mellitus (HR = 2.06; 95% CI = 1.04-4.06) were significant risk factors for COVID-19. CONCLUSIONS/SIGNIFICANCE: Leprosy patients are vulnerable to COVID-19 because they have more frequent contact with SARS-CoV-2-infected patients, possibly due to social and economic limitations. Our model showed that the use of corticosteroids, thalidomide, pentoxifylline, clofazimine, or dapsone or BCG vaccination did not affect the occurrence or severity of COVID-19.


Assuntos
COVID-19/epidemiologia , COVID-19/terapia , Hanseníase/tratamento farmacológico , Hanseníase/epidemiologia , Corticosteroides/uso terapêutico , Vacina BCG/administração & dosagem , Brasil/epidemiologia , COVID-19/diagnóstico , COVID-19/tratamento farmacológico , Teste para COVID-19 , Clofazimina/uso terapêutico , Estudos de Coortes , Dapsona/uso terapêutico , Humanos , Pentoxifilina/uso terapêutico , Estudos Prospectivos , Fatores de Risco , SARS-CoV-2/isolamento & purificação , Análise de Sobrevida , Talidomida/uso terapêutico
18.
Artigo em Inglês | MEDLINE | ID: mdl-34161550

RESUMO

Leprosy may present kidney and endothelial abnormalities, being a risk factor for complications. However, the involvement of renal and vascular endothelia has been poorly investigated. We aimed to investigate if the levels of systemic endothelial biomarkers are associated with kidney abnormalities and the clinical forms of leprosy. This is a cross-sectional study with leprosy patients enrolled in January 2017 to December 2018, before the initiation of the multidrug therapy. Leprosy-associated clinical and epidemiological data were collected. Two groups were investigated: Paucibacillary (PB) and Multibacillary (MB) infections, for the comparisons. Serum and urine samples were obtained for laboratory analysis. In serum samples, were evaluated the endothelial biomarkers VCAM-1 and ICAM-1. In total, 101 leprosy patients were included, the mean age was 48±Ù¡Ù¥ years and 71 (70%) were male. The multibacillary form occurred in 81 cases (80%), among which 22 had the Virchowian form. Serum creatinine was more elevated in the MB group than in PB patients. In addition, VCAM-1 was elevated in the MB group and was correlated with the bacteriological index (rho = 0.372, p <0.01), the duration of disease symptoms (rho = 0.234, p = 0.04), and the number of skin lesions (rho = 0.468, p <0.001). Moreover, in MB patients who presented albuminuria >15 mg/g of creatinine, VCAM-1 showed a significant correlation with increased albuminuria and improved the correlation with the number of skin lesions (rho= 0.563, p=0.010). In conclusion, higher systemic VCAM-1 levels were associated with the multibacillary clinical form of leprosy and with increased albuminuria. Prospective studies are necessary to establish a cause-effect and evaluate the preventive role of these biomarkers to improve the clinical care.


Assuntos
Albuminúria , Hanseníase Multibacilar , Albuminúria/tratamento farmacológico , Estudos Transversais , Quimioterapia Combinada , Humanos , Hansenostáticos/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
19.
EBioMedicine ; 68: 103379, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34090257

RESUMO

BACKGROUND: Leprosy, a chronic infectious disease caused by Mycobacterium leprae, is often late- or misdiagnosed leading to irreversible disabilities. Blood transcriptomic biomarkers that prospectively predict those who progress to leprosy (progressors) would allow early diagnosis, better treatment outcomes and facilitate interventions aimed at stopping bacterial transmission. To identify potential risk signatures of leprosy, we collected whole blood of household contacts (HC, n=5,352) of leprosy patients, including individuals who were diagnosed with leprosy 4-61 months after sample collection. METHODS: We investigated differential gene expression (DGE) by RNA-Seq between progressors before presence of symptoms (n=40) and HC (n=40), as well as longitudinal DGE within each progressor. A prospective leprosy signature was identified using a machine learning approach (Random Forest) and validated using reverse transcription quantitative PCR (RT-qPCR). FINDINGS: Although no significant intra-individual longitudinal variation within leprosy progressors was identified, 1,613 genes were differentially expressed in progressors before diagnosis compared to HC. We identified a 13-gene prospective risk signature with an Area Under the Curve (AUC) of 95.2%. Validation of this RNA-Seq signature in an additional set of progressors (n=43) and HC (n=43) by RT-qPCR, resulted in a final 4-gene signature, designated RISK4LEP (MT-ND2, REX1BD, TPGS1, UBC) (AUC=86.4%). INTERPRETATION: This study identifies for the first time a prospective transcriptional risk signature in blood predicting development of leprosy 4 to 61 months before clinical diagnosis. Assessment of this signature in contacts of leprosy patients can function as an adjunct diagnostic tool to target implementation of interventions to restrain leprosy development. FUNDING: This study was supported by R2STOP Research grant, the Order of Malta-Grants-for-Leprosy-Research, the Q.M. Gastmann-Wichers Foundation and the Leprosy Research Initiative (LRI) together with the Turing Foundation (ILEP# 702.02.73 and # 703.15.07).


Assuntos
Biomarcadores/sangue , Perfilação da Expressão Gênica/métodos , Redes Reguladoras de Genes , Hanseníase/diagnóstico , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Criança , Progressão da Doença , Feminino , Regulação da Expressão Gênica , Humanos , Hanseníase/sangue , Hanseníase/genética , Aprendizado de Máquina , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Análise de Sequência de RNA , Adulto Jovem
20.
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 , 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
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