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1.
Indian J Med Res ; 154(1): 121-131, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34782538

RESUMO

Background & objectives: The elimination goal for leprosy as a public health problem at the national level was achieved in 2005 in India. However, the number of new cases reporting annually remained nearly the same during the last 10-15 years. Moreover, a substantial number of these new cases reported disabilities for the first time. Therefore, besides multidrug therapy (MDT), newer strategies with focus on effectively decreasing the number of new cases, optimizing the treatment of detected cases, averting disabilities and arresting the transmission of the disease are required. So the objective of this study was to assess the cost-effectiveness of Mycobacterium indicus pranii (MIP) vaccine implementation in National Leprosy Eradication Programme (NLEP) for newly diagnosed leprosy patients as well as their contacts to arrest/decrease the transmission and occurrence of new cases. Methods: This was a model-based estimation of incremental costs, total quality-adjusted life years (QALYs) gained, new cases averted, deaths averted, incremental cost-effectiveness ratio (ICER) and budget impact of the vaccination intervention. This model included the addition of MIP treatment intervention to the newly detected leprosy patients as well as vaccination with MIP to their contacts. Results: Using the societal perspective, discounted ICER was estimated to be ₹73,790 per QALY gained over a five-year time period. Probabilistic sensitivity analysis (PSA) was assessed by varying the values of input parameters. Majority (96%) of simulations fell in North East quadrant of cost-effectiveness plane, which were all below the willingness to pay threshold. Interpretation & conclusions: Introduction of MIP vaccination in the NLEP appears to be a cost-effective strategy for India. Significant health gains were reduction in the number of new leprosy cases, decreased incidence and severity of reactions during treatment, and after release from treatment, prevention of disabilities, thus reducing the cost as well as stigma of the disease.


Assuntos
Hanseníase , Vacinas , Análise Custo-Benefício , Quimioterapia Combinada , Humanos , Índia/epidemiologia , Hansenostáticos/uso terapêutico , Hanseníase/tratamento farmacológico , Hanseníase/epidemiologia , Hanseníase/prevenção & controle , Mycobacterium , Anos de Vida Ajustados por Qualidade de Vida , Resultado do Tratamento
2.
Int J Mycobacteriol ; 10(2): 155-161, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34558467

RESUMO

Background: Mycobacterium leprae was considered the only causal agent of leprosy until Mycobacterium lepromatosis was identified' which it has been suggested has greater pathogenicity and is linked to diffuse lepromatous leprosy (DLL) and Lucio's phenomenon (LPh). Our objective is to identify Mycobacterium spp. in an endemic area of leprosy in Colombia. Methods: The study included cases with a diagnosis of leprosy by clinical and histopathological analysis. DNA extraction and two specific rounds of semi-nested polymerase chain reaction (PCR) were performed in paraffin biopsies skin to identify M. leprae and M. lepromatosis. Demographic, clinical, and histopathological data were extracted and tabulated for analysis. Results: Forty-one cases of leprosy were analyzed. The most frequent clinical diagnosis was lepromatous leprosy (36.6%); there was one case with DLL and two with LPh. The most common histopathological finding was tuberculoid leprosy (36.59%); three cases had negative histopathology. M. lepromatosis was not detected; all cases corresponded to M. leprae including cases with negative histopathology' DLL, and LPh. Conclusion: In this study, M. leprae was the causative agent of leprosy, encompassing even its most severe phenotypic forms. It is appropriate to consider PCR as an indispensable tool for the diagnosis of leprosy and to continue to carry out the active search for M. lepromatosis.


Assuntos
Hanseníase Virchowiana , Hanseníase , Mycobacterium , Região do Caribe , Colômbia/epidemiologia , Humanos , Hanseníase/diagnóstico , Hanseníase/epidemiologia , Hanseníase Virchowiana/diagnóstico , Hanseníase Virchowiana/epidemiologia , Mycobacterium leprae/genética
3.
Molecules ; 26(15)2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34361751

RESUMO

Species of Mycobacteriaceae cause disease in animals and humans, including tuberculosis and leprosy. Individuals infected with organisms in the Mycobacterium tuberculosis complex (MTBC) or non-tuberculous mycobacteria (NTM) may present identical symptoms, however the treatment for each can be different. Although the NTM infection is considered less vital due to the chronicity of the disease and the infrequency of occurrence in healthy populations, diagnosis and differentiation among Mycobacterium species currently require culture isolation, which can take several weeks. The use of volatile organic compounds (VOCs) is a promising approach for species identification and in recent years has shown promise for use in the rapid analysis of both in vitro cultures as well as ex vivo diagnosis using breath or sputum. The aim of this contribution is to analyze VOCs in the culture headspace of seven different species of mycobacteria and to define the volatilome profiles that are discriminant for each species. For the pre-concentration of VOCs, solid-phase micro-extraction (SPME) was employed and samples were subsequently analyzed using gas chromatography-quadrupole mass spectrometry (GC-qMS). A machine learning approach was applied for the selection of the 13 discriminatory features, which might represent clinically translatable bacterial biomarkers.


Assuntos
Metaboloma , Mycobacterium abscessus/química , Complexo Mycobacterium avium/química , Mycobacterium avium/química , Mycobacterium bovis/química , Mycobacterium/química , Compostos Orgânicos Voláteis/isolamento & purificação , Biomarcadores/análise , Cromatografia Gasosa-Espectrometria de Massas/métodos , Aprendizado de Máquina/estatística & dados numéricos , Mycobacterium/metabolismo , Mycobacterium abscessus/metabolismo , Mycobacterium avium/metabolismo , Complexo Mycobacterium avium/metabolismo , Mycobacterium bovis/metabolismo , Análise de Componente Principal , Microextração em Fase Sólida , Compostos Orgânicos Voláteis/classificação , Compostos Orgânicos Voláteis/metabolismo
4.
Medicine (Baltimore) ; 100(31): e26744, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34397815

RESUMO

ABSTRACT: Cured leprosy patients have special physical conditions, which could pose challenges for safety and immunogenicity after immunization. We performed an observational clinical study aimed to identify the safety and immunogenicity of influenza vaccine in cured leprosy patients. A total of 65 participants from a leprosarium were recruited into leprosy cured group or control group, and received a 0.5 ml dose of the inactivated split-virion trivalent influenza vaccine and a follow-up 28 days proactive observation of any adverse events. Hemagglutination and hemagglutination inhibition test was performed to evaluate serum antibody titer, flow cytometry was conducted to screen of cytokines level. The total rate of reactogenicity was 0.0% [0/41] in leprosy cured group and 37.5% [9/24] in control group. The seroconversion rate for H1N1 was difference between leprosy cured group and control group (41.83% vs 79.17%, P = .0082), but not for H3N2 (34.25% vs 50.00%, P = .4468). At day 0, leprosy cured group have relatively high concentration of interleukin-6, interleukin-10, tumor necrosis factor, interferon-γ, and interleukin-17 compared to control group. The interleukin-2 concentration increased 2 weeks after vaccination compared to pre-vaccination in leprosy cured group, but declined in control group (0.92 pg/ml vs -0.02 pg/ml, P = .0147). Leprosy cured group showed a more rapid down-regulation of interleukin-6 when influenza virus was challenged compared to control group (-144.38 pg/ml vs -11.52 pg/ml, P < .0001). Subgroup analysis revealed that the immunization administration declined interleukin-17 concentration in Tuberculoid type subgroup, but not in Lepromatous type subgroup or control group. Clinically cured leprosy patients are relatively safe for influenza vaccine. Leprosy cured patient have immune deficit in producing antibody. Interleukin-6 and interleukin-17 were 2 sensitive indicators in immune response for leprosy affected patients. The identification of indicators might be help management of leprosy and used as predictive markers in leprosy early symptom monitoring.


Assuntos
Imunidade/efeitos dos fármacos , Imunogenicidade da Vacina , Vacinas contra Influenza/normas , Hanseníase/tratamento farmacológico , Formação de Anticorpos/efeitos dos fármacos , Humanos , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza A Subtipo H3N2/efeitos dos fármacos , Vírus da Influenza A Subtipo H3N2/imunologia , Vacinas contra Influenza/efeitos adversos , Vacinas contra Influenza/uso terapêutico , Hanseníase/imunologia , Mycobacterium/efeitos dos fármacos , Mycobacterium/patogenicidade , Mycobacterium leprae/efeitos dos fármacos , Mycobacterium leprae/patogenicidade
5.
Int J Mol Sci ; 22(14)2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34299217

RESUMO

The mycobacterial cell wall is composed of large amounts of lipids with varying moieties. Some mycobacteria species hijack host cells and promote lipid droplet accumulation to build the cellular environment essential for their intracellular survival. Thus, lipids are thought to be important for mycobacteria survival as well as for the invasion, parasitization, and proliferation within host cells. However, their physiological roles have not been fully elucidated. Recent studies have revealed that mycobacteria modulate the peroxisome proliferator-activated receptor (PPAR) signaling and utilize host-derived triacylglycerol (TAG) and cholesterol as both nutrient sources and evasion from the host immune system. In this review, we discuss recent findings that describe the activation of PPARs by mycobacterial infections and their role in determining the fate of bacilli by inducing lipid metabolism, anti-inflammatory function, and autophagy.


Assuntos
Infecções por Mycobacterium/microbiologia , Mycobacterium/metabolismo , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , Animais , Autofagia/fisiologia , Colesterol/metabolismo , Humanos , Metabolismo dos Lipídeos , Mycobacterium/crescimento & desenvolvimento , Mycobacterium/imunologia , Infecções por Mycobacterium/imunologia , Infecções por Mycobacterium/metabolismo , Receptores Ativados por Proliferador de Peroxissomo/genética , Transdução de Sinais
6.
Methods Mol Biol ; 2314: 1-58, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34235647

RESUMO

Building upon the foundational research of Robert Koch, who demonstrated the ability to grow Mycobacterium tuberculosis for the first time in 1882 using media made of coagulated bovine serum, microbiologists have continued to develop new and more efficient ways to grow mycobacteria. Presently, all known mycobacterial species can be grown in the laboratory using either axenic culture techniques or in vivo passage in laboratory animals. This chapter provides conventional protocols to grow mycobacteria for diagnostic purposes directly from clinical specimens, as well as in research laboratories for scientific purposes. Detailed protocols used for production of M. tuberculosis in large scale (under normoxic and hypoxic conditions) in bioreactors and for production of obligate intracellular pathogens such as Mycobacterium leprae and "Mycobacterium lepromatosis" using athymic nude mice and armadillos are provided.


Assuntos
Técnicas Bacteriológicas , Infecções por Mycobacterium/microbiologia , Mycobacterium/crescimento & desenvolvimento , Animais , Tatus , Técnicas Bacteriológicas/instrumentação , Reatores Biológicos , Modelos Animais de Doenças , Humanos , Camundongos Nus , Viabilidade Microbiana , Mycobacterium/isolamento & purificação , Mycobacterium leprae/crescimento & desenvolvimento , Mycobacterium leprae/isolamento & purificação , Fatores de Tempo
7.
Front Immunol ; 12: 674241, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34113346

RESUMO

Pathogenic mycobacteria species may subvert the innate immune mechanisms and can modulate the activation of cells that cause disease in the skin. Cutaneous mycobacterial infection may present different clinical presentations and it is associated with stigma, deformity, and disability. The understanding of the immunopathogenic mechanisms related to mycobacterial infection in human skin is of pivotal importance to identify targets for new therapeutic strategies. The occurrence of reactional episodes and relapse in leprosy patients, the emergence of resistant mycobacteria strains, and the absence of effective drugs to treat mycobacterial cutaneous infection increased the interest in the development of therapies based on repurposed drugs against mycobacteria. The mechanism of action of many of these therapies evaluated is linked to the activation of autophagy. Autophagy is an evolutionary conserved lysosomal degradation pathway that has been associated with the control of the mycobacterial bacillary load. Here, we review the role of autophagy in the pathogenesis of cutaneous mycobacterial infection and discuss the perspectives of autophagy as a target for drug development and repurposing against cutaneous mycobacterial infection.


Assuntos
Autofagia/efeitos dos fármacos , Infecções por Mycobacterium/tratamento farmacológico , Infecções por Mycobacterium/patologia , Dermatopatias Bacterianas/tratamento farmacológico , Dermatopatias Bacterianas/patologia , Descoberta de Drogas , Humanos , Mycobacterium
8.
mSphere ; 6(3)2021 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-33952660

RESUMO

Mycobacterium tuberculosis infections claim more than a million lives each year, and better treatments or vaccines are required. A crucial pathogenicity factor is translocation from phagolysosomes to the cytosol upon phagocytosis by macrophages. Translocation from the phagolysosome to the cytosol is an ESX-1-dependent process, as previously shown in vitro Here, we show that in vivo, mycobacteria also translocate to the cytosol but mainly when host immunity is compromised. We observed only low numbers of cytosolic bacilli in mice, armadillos, zebrafish, and patient material infected with M. tuberculosis, M. marinum, or M. leprae In contrast, when innate or adaptive immunity was compromised, as in severe combined immunodeficiency (SCID) or interleukin-1 receptor 1 (IL-1R1)-deficient mice, significant numbers of cytosolic M. tuberculosis bacilli were detected in the lungs of infected mice. Taken together, in vivo, translocation to the cytosol of M. tuberculosis is controlled by adaptive immune responses as well as IL-1R1-mediated signals.IMPORTANCE For decades, Mycobacterium tuberculosis has been one of the deadliest pathogens known. Despite infecting approximately one-third of the human population, no effective treatment or vaccine is available. A crucial pathogenicity factor is subcellular localization, as M. tuberculosis can translocate from phagolysosome to the cytosol in macrophages. The situation in vivo is more complicated. In this study, we establish that high-level cytosolic escape of mycobacteria can indeed occur in vivo but mainly when host resistance is compromised. The IL-1 pathway is crucial for the control of the number of cytosolic mycobacteria. The establishment that immune signals result in the clearance of cells containing cytosolic mycobacteria connects two important fields, cell biology and immunology, which is vital for the understanding of the pathology of M. tuberculosis.


Assuntos
Citosol/microbiologia , Mycobacterium/imunologia , Mycobacterium/patogenicidade , Fagossomos/microbiologia , Receptores de Interleucina-1/genética , Receptores de Interleucina-1/imunologia , Transdução de Sinais/imunologia , Animais , Tatus/microbiologia , Translocação Bacteriana , Citosol/imunologia , Feminino , Humanos , Hanseníase/microbiologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos SCID , Mycobacterium/classificação , Fagossomos/imunologia , Pele/microbiologia , Pele/patologia , Células THP-1 , Peixe-Zebra
9.
mBio ; 12(2)2021 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-33653882

RESUMO

Functional characterization of bacterial proteins lags far behind the identification of new protein families. This is especially true for bacterial species that are more difficult to grow and genetically manipulate than model systems such as Escherichia coli and Bacillus subtilis To facilitate functional characterization of mycobacterial proteins, we have established a Mycobacterial Systems Resource (MSR) using the model organism Mycobacterium smegmatis This resource focuses specifically on 1,153 highly conserved core genes that are common to many mycobacterial species, including Mycobacterium tuberculosis, in order to provide the most relevant information and resources for the mycobacterial research community. The MSR includes both biological and bioinformatic resources. The biological resource includes (i) an expression plasmid library of 1,116 genes fused to a fluorescent protein for determining protein localization; (ii) a library of 569 precise deletions of nonessential genes; and (iii) a set of 843 CRISPR-interference (CRISPRi) plasmids specifically targeted to silence expression of essential core genes and genes for which a precise deletion was not obtained. The bioinformatic resource includes information about individual genes and a detailed assessment of protein localization. We anticipate that integration of these initial functional analyses and the availability of the biological resource will facilitate studies of these core proteins in many Mycobacterium species, including the less experimentally tractable pathogens M. abscessus, M. avium, M. kansasii, M. leprae, M. marinum, M. tuberculosis, and M. ulcerans IMPORTANCE Diseases caused by mycobacterial species result in millions of deaths per year globally, and present a substantial health and economic burden, especially in immunocompromised patients. Difficulties inherent in working with mycobacterial pathogens have hampered the development and application of high-throughput genetics that can inform genome annotations and subsequent functional assays. To facilitate mycobacterial research, we have created a biological and bioinformatic resource (https://msrdb.org/) using Mycobacterium smegmatis as a model organism. The resource focuses specifically on 1,153 proteins that are highly conserved across the mycobacterial genus and, therefore, likely perform conserved mycobacterial core functions. Thus, functional insights from the MSR will apply to all mycobacterial species. We believe that the availability of this mycobacterial systems resource will accelerate research throughout the mycobacterial research community.


Assuntos
Genes Bacterianos , Mycobacterium smegmatis/genética , Mycobacterium/genética , Pesquisa , Biologia Computacional , Biblioteca Gênica , Mycobacterium/classificação , Mycobacterium/patogenicidade , Mycobacterium smegmatis/crescimento & desenvolvimento
13.
mBio ; 11(4)2020 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-32665276

RESUMO

Inteins, as posttranslational regulatory elements, can tune protein function to environmental changes by conditional protein splicing (CPS). Translated as subdomains interrupting host proteins, inteins splice to scarlessly join flanking sequences (exteins). We used DnaB-intein1 (DnaBi1) from a replicative helicase of Mycobacterium smegmatis to build a kanamycin intein splicing reporter (KISR) that links splicing of DnaBi1 to kanamycin resistance. Using expression in heterologous Escherichia coli, we observed phenotypic classes of various levels of splicing-dependent resistance (SDR) and related these to the insertion position of DnaBi1 within the kanamycin resistance protein (KanR). The KanR-DnaBi1 construct demonstrating the most stringent SDR was used to probe for CPS of DnaB in the native host environment, M. smegmatis We show here that zinc, important during mycobacterial pathogenesis, inhibits DnaB splicing in M. smegmatis Using an in vitro reporter system, we demonstrated that zinc potently and reversibly inhibited DnaBi1 splicing, as well as splicing of a comparable intein from Mycobacterium leprae Finally, in a 1.95 Å crystal structure, we show that zinc inhibits splicing through binding to the very cysteine that initiates the splicing reaction. Together, our results provide compelling support for a model whereby mycobacterial DnaB protein splicing, and thus DNA replication, is responsive to environmental zinc.IMPORTANCE Inteins are present in a large fraction of prokaryotes and localize within conserved proteins, including the mycobacterial replicative helicase DnaB. In addition to their extensive protein engineering applications, inteins have emerged as environmentally responsive posttranslational regulators of the genes that encode them. While several studies have shown compelling evidence of conditional protein splicing (CPS), examination of splicing in the native host of the intein has proven to be challenging. Here, we demonstrated through a number of measures, including the use of a splicing-dependent sensor capable of monitoring intein activity in the native host, that zinc is a potent and reversible inhibitor of mycobacterial DnaB splicing. This work also expands our knowledge of site selection for intein insertion within nonnative proteins, demonstrating that splicing-dependent host protein activation correlates with proximity to the active site. Additionally, we surmise that splicing regulation by zinc has mycobacteriocidal and CPS application potential.


Assuntos
DnaB Helicases/antagonistas & inibidores , Mycobacterium/efeitos dos fármacos , Processamento de Proteína/efeitos dos fármacos , Zinco/farmacologia , Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Bactérias/genética , DnaB Helicases/química , DnaB Helicases/genética , Escherichia coli/genética , Inteínas/genética , Mycobacterium/enzimologia , Mycobacterium/genética , Processamento de Proteína Pós-Traducional
14.
Actas Dermosifiliogr (Engl Ed) ; 111(8): 671-677, 2020 Oct.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-32574720

RESUMO

BACKGROUND AND OBJECTIVE: Hansen disease, or leprosy, is caused by Mycobacterium leprae or Mycobacterium lepromatosis. Because these bacteria enter the body via the upper airways, they generate clinical manifestations in the nasal mucous membranes and the mouth. We aimed to describe the characteristics of oral lesions in patients with Hansen disease. MATERIAL AND METHODS: Cross-sectional observational study of 100 patients diagnosed with Hansen disease. We examined the oral cavity and recorded clinical findings on a disease reporting form for each patient. We also included the histopathologic findings for lesions that required a biopsy. Samples suggestive of Hansen disease were processed with hematoxylin-eosin, Ziehl-Neelsen, and Fite-Faraco staining. Variables were analyzed, as appropriate, with the χ2 test, the Mann-Whitney U test, or the Spearman correlation coefficient. RESULTS: Sixty-seven men and 33 women were included. The mean (SD) age was 48.1±16.4 years. Thirty-four patients had oral lesions. Lesions related to Hansen disease were found in 9 patients. The locations were the hard palate and upper lip. Oral lesions were significantly more frequent in patients with lepromatous leprosy, borderline lepromatous leprosy (P = .029), and erythema nodosum leprosum (P = .031). CONCLUSIONS: The frequency of oral lesions is low in Hansen disease. Such lesions present as lepromas and leprous plaques on the hard palate and upper lip.


Assuntos
Hanseníase Virchowiana , Hanseníase , Mycobacterium , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
15.
Infect Genet Evol ; 84: 104399, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32512206

RESUMO

Mycobacterium lepromatosis was identified as a causative agent for leprosy in the year 2008 in the United States and later more cases were identified in Canada, Singapore, Brazil, and Myanmar. It is known to cause diffuse lepromatosis leprosy among humans. Since it is invasive, the mortality rates are higher in comparison to the M. leprae. At genomic level, there exists 90.9% similarity between M. lepromatosis and M. leprae. Codon usage analysis based on analyses of 228 coding sequences (CDSs) of M. lepromatosis, revealed that the genome is GC rich. Among the total 16 dinucleotides, CpG dinucleotide possesses the highest dinucleotide frequency in M. lepromatosis, that is strikingly an unobvious observation since higher CpG is associated with higher proinflammatory cytokine production and NF-κB activation that eventually leads to high pathogenicity. To evade immune response, CpG content is generally less in pathogens. The unusually high CpG content can be explained by the fact that the nucleotide composition of M. lepromatosis is CG rich. Various forces interplay to shape codon usage pattern of any organism including selection; mutation, nucleotide composition as well as GC biased gene conversion. To understand the interplay between various forces; neutrality, parity, Nc-GC3 (Effective number of codons-GC content at 3rd position of the codon), aromaticity (AROMO) and the general average hydropathicity score (GRAVY) analyses have been carried out. The analyses revealed that selection force is the major contributory force. Along with the selection; mutation, nucleotide composition as well as GC biased gene conversion also play role in shaping codon usage bias in M. lepromatosis. This is the first report on the codon usage in M. lepromatosis.


Assuntos
Códon/metabolismo , Ilhas de CpG/genética , Regulação Bacteriana da Expressão Gênica/fisiologia , Genoma Bacteriano , Mycobacterium/genética , Códon/genética
16.
Int J Mycobacteriol ; 9(2): 223-225, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32474550

RESUMO

Patients with leprosy rarely present ulcerated lesions that can appear during reactional states like Lucio's phenomenon (LP), as in our case. LP is a rare complication of multibacillary leprosy due to massive bacilli invasion of endothelial cells causing a thrombotic syndrome. The initial macular lesion is purpuric followed by multiple infiltrated papules and nodules, some of them ulcerated, associated to loss of sensation on lower limbs. The importance of recognizing ulcers as a specific cutaneous manifestation of leprosy allows early diagnosis and treatment, and therefore avoiding the development of disabilities and persistence of illness. Infection by Mycobacterium lepromatosis is associated with LP and it should be especially sought in patients from endemic areas.


Assuntos
Infecções por Mycobacterium/diagnóstico , Mycobacterium/patogenicidade , Úlcera/microbiologia , Úlcera/patologia , Adulto , Diagnóstico Diferencial , Células Endoteliais/patologia , Feminino , Humanos , Hansenostáticos/uso terapêutico , Hanseníase Multibacilar/diagnóstico , Infecções por Mycobacterium/complicações , Infecções por Mycobacterium/tratamento farmacológico , Pele/microbiologia , Pele/patologia , Fatores de Tempo , Úlcera/diagnóstico
17.
Prev Vet Med ; 181: 105060, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32540717

RESUMO

Bovine Nodular Thelitis (BNT) is a granulomatous dermatitis of teat skin associated with acid-fast bacilli. A similar condition has been recorded in a dairy goat flock in France recently. The causative agent was shown to be related to the leprosy-causing bacilli Mycobacterium leprae and M. lepromatosis, then sequenced and named M. uberis. Following the initial report in goats, the aim of this study was to investigate new cases of Caprine Nodular Thelitis (CNT) in the same area to confirm the presence of M. uberis by molecular techniques and to get a better description of the clinical signs and of the affected flocks. Twenty-six animals (25 females and 1 male) from 11 flocks were included in the study. Lesions were located on the udder/teat skin (24/25), on the body skin (6/25) or on the scrotum skin (1/1). Udder skin lesions were circular, nodular and/or ulcerate covered with a crust and associated with supramammary lymph node enlargement. Body skin lesions were located at different parts of the body, showed large necrotizing ulcers with undetermined edges and were associated with regional lymph node enlargement. Histopathological results indicated granulomatous dermatitis and lymphadenitis of varying intensity with no acid-fast bacilli seen after Fite-Faraco staining. M. uberis DNA was amplified from 26 samples out of 47 (udder: 11/22; lymph node: 11/20; body: 4/5). The female goats were mostly older than 4 year of age and originated from breeding units characterized by large flock size and high proportion of goat in continuous lactation.


Assuntos
Doenças das Cabras/patologia , Mastite/veterinária , Infecções por Mycobacterium/veterinária , Mycobacterium/isolamento & purificação , Animais , Feminino , Doenças dos Genitais Masculinos/microbiologia , Doenças dos Genitais Masculinos/patologia , Doenças dos Genitais Masculinos/veterinária , Doenças das Cabras/microbiologia , Cabras , Masculino , Mastite/microbiologia , Mastite/patologia , Infecções por Mycobacterium/microbiologia , Infecções por Mycobacterium/patologia , Escroto/patologia
18.
Salud(i)ciencia (Impresa) ; 24(1/2): 12-18, jun. 2020. graf.
Artigo em Espanhol | LILACS, BINACIS | ID: biblio-1129948

RESUMO

El aumento de las infecciones por micobacterias ambientales u oportunistas (MAO) coincide mundialmente con el declive de la infección tuberculosa e incremento de la infección por el virus de inmunodeficiencia humana (VIH). El presente trabajo es un estudio retrospectivo realizado en el Laboratorio Nacional de Referencia-Investigaciones de Tuberculosis/Micobacterias/Lepra (LNRI-TB/Lepra/Micobacterias), del Instituto de Medicina Tropical Pedro Kourí (IPK), La Habana, Cuba, durante el período enero 2014-diciembre 2018. El objetivo de nuestro estudio fue conocer la variabilidad de especies aisladas para establecer un referente actualizado sobre las infecciones causadas por estas. En este trabajo se clasificaron-identificaron 413 cepas procedentes de pacientes sintomáticos; 162 (39.22%) eran aislamientos de pacientes con VIH/sida atendidos en nuestro Hospital Nacional de Referencia a Atención al paciente VIH/sida (IPK), y el resto (n = 251 [60.77%]), procedentes de pacientes inmunocompetentes, incluyendo aislamientos recibidos de los Centros Provinciales de Higiene, Epidemiología, y Microbiología (CPHEM). Las muestras fueron analizadas con las técnicas convencionales establecidas: las pulmonares fueron descontaminadas por el método de Petroff modificado; las extrapulmonares, por el método del ácido sulfúrico al 4%; el cultivo se realizó en medio de Löwenstein-Jensen modificado. Posteriormente se realizó la clasificación-identificación de especies según el esquema fenotípico-bioquímico establecido. Las especies con mayor porcentaje de aislamiento pertenecieron a los Grupos III y IV, complejo Mycobacterium avium-intracellulare (34.14%) y complejo M. fortuitum (20.82%), respectivamente. Estos resultados permitirán conocer la prevalencia de estas especies en nuestro país, reafirmando la importancia diagnóstica de estos microorganismos para aplicar tratamiento específico, sobre todo en pacientes con factores de riesgo, en quienes es más probable la diseminación de la infección.


The increase in infections by environmental or opportunistic mycobacteria (MAO) coincides worldwide with the decline in tuberculosis infection and an increase in infection by the human immunodeficiency virus (HIV). The present work is a retrospective study carried out at the National Reference Laboratory-Tuberculosis/Mycobacterial/Leprosy Research (LNRI-TB / Leprosy / Mycobacteria), of the Pedro Kourí Institute of Tropical Medicine (IPK), La Habana, Cuba, during the period January 2014-December 2018. The objective of our study was to know the variability of isolated species to establish an updated reference on the infections caused by MAO. In this study, 413 strains from symptomatic patients were classified and identified; 162 (39.22%) were isolates from patients with HIV/AIDS treated at our National Hospital of Reference for Attention to HIV/AIDS patients (IPK), and the remaining (n=251 [60.77%]), from immunocompetent patients, including isolates received from the Provincial Centers of Hygiene, Epidemiology, and Microbiology (CPHEM). The samples were analyzed with the established conventional techniques: the lung samples were decontaminated by the modified Petroff method; the extrapulmonary, by the 4% sulfuric acid method; the culture was carried out in modified Löwenstein-Jensen medium. Subsequently, the classification-identification of species was carried out according to the established phenotypic-biochemical scheme. The species with the highest percentage of isolation belonged to Groups III and IV, Mycobacterium avium-intracellulare complex (34.14%), and M. fortuitum complex (20.82%), respectively. These results will allow us to know the prevalence of these species in our country, emphasizing the diagnostic importance of these microorganisms and thus apply a specific treatment, especially in patients with risk factors, in whom the spread of the infection is more likely


Assuntos
Tuberculose , Complexo Mycobacterium avium , Fatores de Risco , Síndrome de Imunodeficiência Adquirida , HIV , Mycobacterium , Mycobacterium avium
20.
BMC Infect Dis ; 20(1): 258, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32234012

RESUMO

BACKGROUND: Mycobacterial species other than Mycobacterium tuberculosis and Mycobacterium leprae are generally free-living organisms and Mycobacterium simiae is one of the slowest growing Non-tuberculous mycobacteria. This is the first case report of Mycobacterium simiae infection in Sri Lanka and only very few cases with extrapulmonary manifestation reported in the literature. CASE PRESENTATION: A 24-year-old, previously healthy Sri Lankan male presented with generalized lymphadenopathy with discharging sinuses, evening pyrexia, weight loss, poor appetite and splenomegaly. Lymph node biopsies showed sheets of macrophages packed with organisms in the absence of granulomata. Ziehl Neelsen, Wade Fite and Giemsa stains revealed numerous red coloured acid-fast bacilli within foamy histiocytes. Slit skin smear for leprosy was negative and tuberculosis, fungal and bacterial cultures of the lymph node and bone marrow did not reveal any growth. Later he developed watery diarrhea and colonoscopy revealed multiple small polyps and ulcers throughout the colon extending up to the ileum, Which was confirmed to be due to cytomegalovirus confirmed by PCR and successfully treated with ganciclovir. Positron emission tomography scan guided biopsies of the gut and lymph nodes confirmed presence of mycobacterial spindle cell pseudo-tumours and PCR assays revealed positive HSP65. The culture grew Mycobacterium Simiae. Flow cytometry analysis on patient's blood showed extremely low T and B cell counts and immunofixation revealed low immunoglobulin levels. His condition was later diagnosed as adult onset immunodeficiency due to anti- interferon - gamma autoantibodies. He was initially commenced on empirical anti-TB treatment with atypical mycobacterial coverage. He is currently on a combination of daily clarithromycin, ciprofloxacin, linezolid with monthly 2 g/kg/intravenous immunoglobulin to which, he had a remarkable clinical response with complete resolution of lymphadenopathy and healing of sinuses. CONCLUSIONS: This infection is considered to be restricted to certain geographic areas such as mainly Iran, Cuba, Israel and Arizona and this is the first case report from Sri lanka. Even though the infection is mostly seen in the elderly patients, our patient was only 24 years old. In the literature pulmonary involvement was common presentation, but in this case the patient had generalized lymphadenopathy and colonic involvement without pulmonary involvement.


Assuntos
Síndromes de Imunodeficiência/imunologia , Infecções por Mycobacterium não Tuberculosas/microbiologia , Mycobacterium/patogenicidade , Autoanticorpos/sangue , Ciprofloxacina/uso terapêutico , Claritromicina/uso terapêutico , Humanos , Biópsia Guiada por Imagem , Interferon gama/sangue , Linfonodos/microbiologia , Linfadenopatia/etiologia , Masculino , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/patologia , Tomografia por Emissão de Pósitrons , Sri Lanka , Adulto Jovem
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