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1.
Pan Afr Med J ; 39: 97, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34466199

RESUMO

Introduction: an estimated 25% of the world population is infected with Mycobacterium tuberculosis. In 2017, new tuberculosis cases were estimated at 10 million, while 1.6 million tuberculosis related deaths were recorded, 25% residing in Africa. Treatment outcomes of multi drug resistant Tuberculosis patients in Zimbabwe has been well documented but the role of bacteriological monitoring on treatment outcomes has not been systematically evaluated. The objective of the study was to determine the role of bacteriological monitoring using culture and drug susceptibility tests on treatment outcomes among patients with multi drug resistant tuberculosis. Methods: a retrospective, secondary data analysis was conducted using routinely collected data of patients with multi drug resistant TB in Zimbabwe. Frequencies were used to summarize categorical variables and a generalized linear model with a log-link function and a Poisson distribution was used to assess factors associated with unfavourable outcomes. The level of significance was set at P-Value<0.05. Results: about the study collected data from 473 records of patients with an average age of 36.35 years. Forty-nine percent (49%) were male and 51% were female. Results showed that when a patient has baseline culture result missing, has no culture conversion result, regardless of having a follow up culture and drug susceptibility test result, the risk of developing unfavourable outcomes increase by 3.9 times compared to a patient who has received all the three (3) bacteriological monitoring tests. Conclusion: results highlights the need for consistent bacteriological monitoring of patients to avert unfavourable treatment outcomes.


Assuntos
Antituberculosos/farmacologia , Mycobacterium tuberculosis/efeitos dos fármacos , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Adulto , Estudos de Coortes , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana/métodos , Pessoa de Meia-Idade , Mycobacterium tuberculosis/isolamento & purificação , Estudos Retrospectivos , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Adulto Jovem , Zimbábue/epidemiologia
2.
Nat Commun ; 12(1): 5236, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34475399

RESUMO

New drugs are urgently needed to combat the global TB epidemic. Targeting simultaneously multiple respiratory enzyme complexes of Mycobacterium tuberculosis is regarded as one of the most effective treatment options to shorten drug administration regimes, and reduce the opportunity for the emergence of drug resistance. During infection and proliferation, the cytochrome bd oxidase plays a crucial role for mycobacterial pathophysiology by maintaining aerobic respiration at limited oxygen concentrations. Here, we present the cryo-EM structure of the cytochrome bd oxidase from M. tuberculosis at 2.5 Å. In conjunction with atomistic molecular dynamics (MD) simulation studies we discovered a previously unknown MK-9-binding site, as well as a unique disulfide bond within the Q-loop domain that defines an inactive conformation of the canonical quinol oxidation site in Actinobacteria. Our detailed insights into the long-sought atomic framework of the cytochrome bd oxidase from M. tuberculosis will form the basis for the design of highly specific drugs to act on this enzyme.


Assuntos
Grupo dos Citocromos b/química , Grupo dos Citocromos d/química , Complexo de Proteínas da Cadeia de Transporte de Elétrons/química , Mycobacterium tuberculosis/enzimologia , Proteínas de Bactérias/química , Sítios de Ligação , Microscopia Crioeletrônica , Simulação de Dinâmica Molecular , Oxirredutases/química , Conformação Proteica , Subunidades Proteicas , Vitamina K 2/análogos & derivados , Vitamina K 2/química
3.
J Assoc Physicians India ; 69(8): 11-12, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34472816

RESUMO

With global resurgence of M. tuberculosis infection, cases of extra pulmonary TB have also shown an increase. Tuberculosis is a major cause of morbidity and mortality in India. Although disseminated tuberculosis can affect most of the organs, vasculitis presenting as peripheral gangrene as a manifestation of tuberculosis is very rare. We report the case of a 70 years old male who presented with gangrene of left leg complicating disseminated tuberculosis.


Assuntos
Mycobacterium tuberculosis , Tuberculose Miliar , Tuberculose Pulmonar , Vasculite , Idoso , Gangrena/etiologia , Humanos , Masculino , Tuberculose Miliar/complicações , Tuberculose Miliar/diagnóstico
4.
Rev Chilena Infectol ; 38(3): 410-416, 2021 Jun.
Artigo em Espanhol | MEDLINE | ID: mdl-34479299

RESUMO

BACKGROUND: Tuberculosis (TB) continues to be a global public health problem; its meningeal form leads to greater lethality and sequelae, particularly if it is associated with HIV / AIDS infection. AIM: To describe the demographic characteristics, clinical presentation, laboratory and images of patients with meningeal TB (isolation of Mycobacterium tuberculosis in CSF), analyzing differences between HIV and non-HIV patients. METHODS: We performed an observational and descriptive study, with retrospective analysis of patients attending at the Dr. Alejandro Posadas Hospital, Buenos Aires, since January 2005 to December 2017. RESULTS: Thirty-six patients were analyzed, with 22 women with a median age of 36.5 years. Twenty two patients had HIV coinfection, all in the AIDS stage. The symptom onset time was median 11 days. The predominant ones were fever, altered consciousness and headache. In the cerebrospinal fluid were lymphocitosis, hypoglycorrhachia, hyperproteinorrhachia and high lactic acid, according to previously described findings. Of 34 patients who underwent brain scan, 16 patients had no significant pathological findings. MRI was performed in 16 patients, 9 had vascular disorders. Brain MRI was more sensitive to identify meningeal reinforcement than computerized tomography, vascular disorders, and granulomatous lesions. The median onset of treatment was 1 day, with 72.2% of the total receiving coadjuvants with corticosteroids. Mortality of 27.7% and sequelae in 36.1% were observed. Only 5 patients required neurosurgical intervention. CONCLUSION: Since meningeal TB is a disease with high morbidity and mortality, it is imperative to ensure an early diagnosis in its evolution by incorporating molecular biology and imaging (MRI) into broad clinical use.


Assuntos
Síndrome de Imunodeficiência Adquirida , Infecções por HIV , Mycobacterium tuberculosis , Tuberculose Meníngea , Adulto , Feminino , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Humanos , Estudos Retrospectivos , Tuberculose Meníngea/diagnóstico , Tuberculose Meníngea/tratamento farmacológico , Tuberculose Meníngea/epidemiologia
5.
Ethiop J Health Sci ; 31(3): 653-662, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34483623

RESUMO

Background: Tuberculosis and human immunodeficiency virus (HIV) are among the major health problems in Ethiopia. This study assessed the proportion of tuberculosis lymphadenitis (TBLN), HIV infection and their co-infection among TBLN presumptive individuals at the selected hospitals in Northwest Ethiopia. Methods: Institution based cross sectional study was carried out. Data on demographic and clinical variables were collected with standardized questionnaire. Microbiological culture was done on specimen obtained by fine needle aspirates. The HIV status was determined by rapid anti-HIV antibody test. Data was entered and scrutinized using SPSS version 20 statistical packages. A stepwise logistic regression model was used. The result was considered as statistically significant at P<0. 05. Results: A total of 381 lymphadenitis patients were included in the study. The overall prevalence of TBLN and HIV were at 250(65.6%) and 9(2.4%), respectively and their co-infection was at 6(2.4%). Based on the cytological examination, 301(79.0%) of them were diagnosed as TBLN. The age group, (P=0.01) and residency, (P=0.01) were found significantly associated with TBLN. Similarly, unsafe sex was also statistically significant for HIV infection (P=0.007). Conclusion: Tuberculosis lymphadenitis is the leading cause of TB and lymphadenitis in the region. However, TBLN-HIV coinfection was promisingly low. High rate of discrepancy was noticed between cytological and culture results. Hence, the TBLN diagnostic criteria shall pursue revision.


Assuntos
Coinfecção , Infecções por HIV , Linfadenite , Mycobacterium tuberculosis , Tuberculose dos Linfonodos , Coinfecção/epidemiologia , Estudos Transversais , Etiópia/epidemiologia , HIV , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Humanos , Linfadenite/epidemiologia , Linfadenite/etiologia , Tuberculose dos Linfonodos/epidemiologia
6.
Medicine (Baltimore) ; 100(35): e27125, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34477155

RESUMO

ABSTRACT: We aimed to investigate the genetic and demographic differences and interactions between areas where observed genomic variations in Mycobacterium tuberculosis (M. tb) were distributed uniformly in cold and hot spots.The cold and hot spot areas were identified using the reported incidence of TB over the previous 5 years. Whole genome sequencing was performed on 291 M. tb isolates between January and June 2018. Analysis of molecular variance and a multifactor dimensionality reduction (MDR) model was applied to test gene-gene-environment interactions. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were computed to test the extent to which genetic mutation affects the TB epidemic using a multivariate logistic regression model.The percentage of the Beijing family strain in hot spots was significantly higher than that in cold spots (64.63% vs 50.69%, P = .022), among the elderly, people with a low BMI, and those having a history of contact with a TB patient (all P < .05). Individuals from cold spot areas had a higher frequency of out-of-town traveling (P < .05). The mutation of Rv1186c, Rv3900c, Rv1508c, Rv0210, and an Intergenic Region (SNP site: 3847237) showed a significant difference between cold and hot spots. (P < .001). The MDR model displayed a clear negative interaction effect of age groups with BMI (interaction entropy: -3.55%) and mutation of Rv0210 (interaction entropy: -2.39%). Through the mutations of Rv0210 and BMI had a low independent effect (interaction entropy: -1.46%).Our data suggests a statistically significant role of age, BMI and the polymorphisms of Rv0210 genes in the transmission and development of M. tb. The results provide clues for the study of susceptibility genes of M. tb in different populations. The characteristic strains showed a local epidemic. Strengthening genotype monitoring of strains in various regions can be used as an early warning signal of epidemic spillover.


Assuntos
Interações Hospedeiro-Patógeno/genética , Mycobacterium tuberculosis/genética , Tuberculose/microbiologia , Adulto , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tuberculose/epidemiologia
7.
East Mediterr Health J ; 27(8): 755-763, 2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34486711

RESUMO

Background: In pulmonary tuberculosis (PTB), the sputum conversion rate at 2 months is frequently used to evaluate treatment outcomes and effectiveness of a TB control programme. Aims: The study aimed to estimate the rate of delayed sputum conversion and explore its predicting factors at the end of the intensive phase among smear-positive PTB (PTB +ve) patients. Methods: A 3-year retrospective study was conducted in the government hospital in Pulau Pinang from 2016 to 2018. During the study, a standardized, data collection form was used to collect data from the patient record. Patients aged over 18 years were recruited. Multivariable logistic regression analysis was used to identify significant independent variables associated with delayed sputum conversion. Results: A total 1128 of PTB patients were recorded visiting the TB clinic, 736 (65.2%) were diagnosed as PTB +ve; of these, 606 (82.3%) PTB +ve had a record of sputum conversion at the end of the intensive phase. Age ≥ 50 years, blue-collar jobs, smoking, heavy bacillary load, relapsed and treatment interrupted were significantly (P < 0.05) associated with delayed sputum conversion. Delayed sputum conversion rate at the end of the intensive phase was 30.5%. Conclusion: The rate of sputum smear conversion in the intensive phase of treatment was independently associated with high sputum smear grading at diagnosis, relapsed and treatment interrupted categories, old age and blue-collar occupations.


Assuntos
Mycobacterium tuberculosis , Tuberculose Pulmonar , Adulto , Antituberculosos , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Escarro , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/epidemiologia
8.
Georgian Med News ; (316-317): 129-135, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34511459

RESUMO

Tuberculosis is one of the main problems of medicine in Kazakhstan. Kazakhstan is on the list of 30 countries with high rates of multidrug resistant tuberculosis in the world. Aim of this study is to conduct genotyping by MIRU-VNTR method to get preliminary data on M. tuberculosis genotypes distributed among the clinical isolates in Kazakhstan. 271 M. tuberculosis clinical isolates were gathered from new cases of tuberculosis from different regions of Kazakhstan in this study. Genotyping was done using 15 MIRU-VNTR (12 MIRU+3 ETR) loci. Obtained digital profiles of the clinical isolates were analyzed using the database on miru-vntrplus.org. Phylogenetic tree was built by UPGMA method. 97 genotypes were identified, 70 (25.8%) of them were unique and were determined in one isolate in the sample collection. The rest 201 (74.2%) isolates were grouped into 27 clusters, that contained from 2 to 102 isolates. According to genotyping results M. tuberculosis Beijing family strains were found in 65.3% cases. 121 out of 177 Beijing isolates (68.4%) were drug-resistant. Prevalence of MDR-TB was detected among drug-resistant Beijing (58.7% - 71/121) and LAM family (50% - 10/20) isolates.


Assuntos
Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos , Tuberculose , Genótipo , Humanos , Cazaquistão/epidemiologia , Repetições Minissatélites/genética , Mycobacterium tuberculosis/genética , Filogenia , Tuberculose/diagnóstico , Tuberculose/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia
9.
Adv Protein Chem Struct Biol ; 127: 343-364, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34340773

RESUMO

BACKGROUND AND AIM: The persistence of extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis (MTB) continue to pose a significant challenge to the treatment and control of tuberculosis infections worldwide. XDR-MTB strains exhibit resistance against first-line anti-TB drugs, fluoroquinolones, and second-line injectable drugs. The mechanisms of drug resistance of MTB remains poorly understood. Our study aims at identifying the differentially expressed genes (DEGs), associated gene networks, and signaling cascades involved in rendering this pathogen resistant to multiple drugs, namely, isoniazid, rifampicin, and capreomycin. METHODS: We used the microarray dataset GSE53843. The GEO2R tool was used to prioritize the most significant DEGs (top 250) of each drug exposure sample between XDR strains and non-resistant strains. The validation of the 250 DEGs was performed using volcano plots. Protein-protein interaction networks of the DEGs were created using STRING and Cytoscape tools, which helped decipher the relationship between these genes. The significant DEGs were functionally annotated using DAVID and ClueGO. The concomitant biological processes (BP) and molecular functions (MF) were represented as dot plots. RESULTS AND CONCLUSION: We identified relevant molecular pathways and biological processes, such as cell wall biogenesis, lipid metabolic process, ion transport, phosphopantetheine binding, and triglyceride lipase activity. These processes indicated the involvement of multiple interconnected mechanisms in drug resistance. Our study highlighted the impact of cell wall permeability, with the dysregulation of the mur family of proteins, as essential factors in the inference of resistance. Additionally, upregulation of genes responsible for ion transport such as ctpF, arsC, and nark3, emphasizes the importance of transport channels and efflux pumps in potentially driving out stress-inducing compounds. This study investigated the upregulation of the Lip family of proteins, which play a crucial role in triglyceride lipase activity. Thereby illuminating the potential role of drug-induced dormancy and subsequent resistance in the mycobacterial strains. Multiple mechanisms such as carboxylic acid metabolic process, NAD biosynthetic process, triglyceride lipase activity, phosphopantetheine binding, organic acid biosynthetic process, and growth of symbiont in host cell were observed to partake in resistance of XDR-MTB. This study ultimately provides a platform for important mapping targets for potential therapeutics against XDR-MTB.


Assuntos
Proteínas de Bactérias , Farmacorresistência Bacteriana/genética , Tuberculose Extensivamente Resistente a Medicamentos , Regulação Bacteriana da Expressão Gênica , Mycobacterium tuberculosis , Biologia de Sistemas , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Tuberculose Extensivamente Resistente a Medicamentos/genética , Tuberculose Extensivamente Resistente a Medicamentos/metabolismo , Humanos
10.
BMJ Case Rep ; 14(8)2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34404638

RESUMO

A male refugee from the Middle East was diagnosed with pulmonary tuberculosis and Pott's disease with paravertebral abscess. After starting the standard regimen, the sputum culture converted to negative and the patient's general condition improved. Six weeks later, the patient presented with clinical worsening of known symptoms, new appearance of focal neurological deficits and progress of radiological features showing progression of the paravertebral abscess. Immune reconstitution inflammatory syndrome with Mycobacterium tuberculosis (TB-IRIS) was presumed, and treatment with high-dose steroids was started. Due to recurrent relapses while tapering, corticosteroids had to be given over a prolonged period. After treatment completion, the patient was in a good general condition, abscesses had decreased and neurological deficits were in complete remission. This case presents the rare manifestation of TB-IRIS in HIV-negative patients and its management in a high-income country.


Assuntos
Infecções por HIV , Síndrome Inflamatória da Reconstituição Imune , Mycobacterium tuberculosis , Tuberculose Pulmonar , Tuberculose da Coluna Vertebral , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Síndrome Inflamatória da Reconstituição Imune/complicações , Síndrome Inflamatória da Reconstituição Imune/diagnóstico , Síndrome Inflamatória da Reconstituição Imune/tratamento farmacológico , Masculino
11.
BMJ Open ; 11(8): e052212, 2021 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-34408058

RESUMO

INTRODUCTION: Tuberculosis (TB) continues to be a significant health burden, most commonly affecting the lungs and referred to as pulmonary TB (PTB). Diagnostic techniques of PTB primarily rely on expectorated sputum samples. However, the diagnostic yields are often hindered due to insufficient volume and quality of the sputum specimens. Moreover, some individuals are unable to provide sputum samples due to scanty sputum production or difficulty in coughing up and require an invasive procedure to obtain a respiratory sample, such as bronchoscopic or gastric aspiration. Thus, challenges in the acquisition of respiratory specimens warrant an alternate specimen. Therefore, this systematic review aims to evaluate the diagnostic accuracy of a stool specimen for the diagnosis of PTB in adults. METHODS AND ANALYSIS: We will search MEDLINE (Ovid), Embase (Ovid), Web of Science and Cochrane database from inception to April 2021 using a comprehensive search strategy. Two reviewers will independently perform screening, data extraction and quality assessment. The risk of bias assessment and applicability of results of eligible studies will be performed using the Quality of Diagnostic Accuracy Studies-2 tool. Bivariate random-effects models will be performed to calculate pooled sensitivity, specificity, positive likelihood ratio and negative likelihood ratio and diagnostic odds ratio along with 95% CI of stool specimen for each reported diagnostic method against any of the reference standard test (ie, mycobacterial culture or smear microscopy or Xpert assay using respiratory specimens). Heterogeneity between studies will be assessed by I2 statistics and Q statistic of the χ2 test. ETHICS AND DISSEMINATION: The results will be disseminated through publishing in a peer-reviewed medical journal and public presentations in relevant national and international conferences. As this is a systematic review of publicly available data, ethics approval is not required. PROSPERO REGISTRATION NUMBER: CRD42021245203.


Assuntos
Antibióticos Antituberculose , Mycobacterium tuberculosis , Tuberculose Pulmonar , Adulto , Antibióticos Antituberculose/uso terapêutico , Humanos , Metanálise como Assunto , Rifampina , Sensibilidade e Especificidade , Revisões Sistemáticas como Assunto , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/tratamento farmacológico
12.
Immunity ; 54(8): 1625-1627, 2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34380059

RESUMO

The impact of cellular apoptosis in controlling M. tuberculosis during tuberculosis (TB) infection remains unresolved. In this issue of Immunity, Stutz et al. provide compelling evidence that apoptosis controls M. tuberculosis infection in vivo and compounds that induce apoptosis limit M. tuberculosis growth in mice.


Assuntos
Mycobacterium tuberculosis , Tuberculose , Animais , Apoptose , Camundongos
13.
J Immunol ; 207(5): 1239-1249, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34389623

RESUMO

HIV-1 infection substantially increases the risk of developing tuberculosis (TB). Mechanisms such as defects in the Th1 response to Mycobacterium tuberculosis in HIV-infected persons have been widely reported. However, Th1-independent mechanisms also contribute to protection against TB. To identify a broader spectrum of defects in TB immunity during HIV infection, we examined IL-17A and IL-22 production in response to mycobacterial Ags in peripheral blood of persons with latent TB infection and HIV coinfection. Upon stimulating with mycobacterial Ags, we observed a distinct CD4+ Th lineage producing IL-22 in the absence of IL-17A and IFN-γ. Mycobacteria-specific Th22 cells were present at high frequencies in blood and contributed up to 50% to the CD4+ T cell response to mycobacteria, comparable in magnitude to the IFN-γ Th1 response (median 0.91% and 0.55%, respectively). Phenotypic characterization of Th22 cells revealed that their memory differentiation was similar to M. tuberculosis-specific Th1 cells (i.e., predominantly early differentiated CD45RO+CD27+ phenotype). Moreover, CCR6 and CXCR3 expression profiles of Th22 cells were similar to Th17 cells, whereas their CCR4 and CCR10 expression patterns displayed an intermediate phenotype between Th1 and Th17 cells. Strikingly, mycobacterial IL-22 responses were 3-fold lower in HIV-infected persons compared with uninfected persons, and the magnitude of responses correlated inversely with HIV viral load. These data provide important insights into mycobacteria-specific Th subsets in humans and suggest a potential role for IL-22 in protection against TB during HIV infection. Further studies are needed to fully elucidate the role of IL-22 in protective TB immunity.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Infecções por HIV/imunologia , HIV-1/fisiologia , Interleucinas/metabolismo , Tuberculose Latente/imunologia , Mycobacterium tuberculosis/fisiologia , Subpopulações de Linfócitos T/imunologia , Adulto , Células Cultivadas , Coinfecção , Feminino , Soropositividade para HIV , Humanos , Interleucina-17/metabolismo , Masculino , África do Sul , Carga Viral , Adulto Jovem
14.
Molecules ; 26(16)2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34443334

RESUMO

Background. The past decades have seen numerous efforts to develop new antitubercular agents. Currently, the available regimens are lengthy, only partially effective, and associated with high rates of adverse events. The challenge is therefore to develop new agents with faster and more efficient action. The versatile quinoxaline ring possesses a broad spectrum of pharmacological activities, ensuring considerable attention to it in the field of medicinal chemistry. Objectives. In continuation of our program on the pharmacological activity of quinoxaline derivatives, this review focuses on potential antimycobacterial activity of recent quinoxaline derivatives and discusses their structure-activity relationship for designing new analogs with improved activity. Methods. The review compiles recent studies published between January 2011 and April 2021. Results. The final total of 23 studies were examined. Conclusions. Data from studies of quinoxaline and quinoxaline 1,4-di-N-oxide derivatives highlight that specific derivatives show encouraging perspectives in the treatment of Mycobacterium tuberculosis and the recent growing interest for these scaffolds. These interesting results warrant further investigation, which may allow identification of novel antitubercular candidates based on this scaffold.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Mycobacterium tuberculosis/efeitos dos fármacos , Quinoxalinas/química , Quinoxalinas/farmacologia , Relação Estrutura-Atividade
15.
Theriogenology ; 173: 202-210, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34399384

RESUMO

Most old, intact male dogs usually have prostate disorders, especially benign prostatic hypertrophy and prostatitis with or without abscesses, and concurrent cystitis. The successful treatment of dogs with prostatitis concurrent with cystitis has relied on choosing an appropriate antimicrobial drug based on a bacterial culture and drug sensitivity testing. The objective of the study was to compare the prevalence of bacterial species and results of drug susceptibility testing of bacteria that were isolated from the prostatic fluids and urine samples that were collected from dogs with both prostatitis and cystitis. One hundred and sixty intact male dogs, who presented with both diseases, were recruited for the study. The disease diagnoses were based on clinical history notes, physical examinations, abdominal ultrasonography, prostatic fluid cytology, urinalysis and bacterial cultures from both prostatic fluid and urine samples. The bacterial culture results demonstrated that the major species that were detected in either the prostatic fluid or urine samples were Staphylococcus spp., Escherichia coli, Pseudomonas spp., Streptococcus spp., Proteus mirabilis and Klebsiella pneumoniae. Staphylococcus spp. (26.5 %, 43/162) and Escherichia coli (26.1 %, 12/46) were the most prevalent species from the prostatic fluid and urine samples, respectively. Statistical tests revealed that there were no significantly different prevalence levels among the isolated bacteria between the prostatic fluid and urine samples. Imipenem and gentamicin were the most potent antimicrobial drugs tested against the bacterial isolates in the present study. However, the administration of imipenem to treat prostatitis and cystitis in dogs was of concern. Interestingly, there were no significant differences in the antimicrobial drug susceptibility trends between the prostatic fluid and urine samples. Based on these results, a urine sample might be considered as an optional sample for bacterial cultures and antimicrobial drug susceptibility testing when it is not possible to collect a prostatic fluid sample.


Assuntos
Anti-Infecciosos , Cistite , Doenças do Cão , Mycobacterium tuberculosis , Prostatite , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Cistite/tratamento farmacológico , Cistite/veterinária , Doenças do Cão/tratamento farmacológico , Cães , Masculino , Testes de Sensibilidade Microbiana/veterinária , Prostatite/tratamento farmacológico , Prostatite/veterinária
17.
Med Sci Monit ; 27: e934292, 2021 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-34366429

RESUMO

The World Health Organization (WHO) estimated that in 2019, 10.0 million people worldwide developed tuberculosis (TB), with 1.4 million deaths from TB in that year. Infection with Mycobacterium tuberculosis that is resistant to at least isoniazid and rifampin and an additional chemotherapeutic agent is known as multidrug-resistant TB (MDR TB). Until recently, the prevalence of drug resistance in patients with TB has been poorly understood due to a lack of infection surveillance and molecular testing. Countries with the highest prevalence of TB, including MDR TB, are also those most affected by the COVID-19 pandemic. The identification of MDR TB requires careful monitoring and resources for molecular testing. Previous treatment regimens have required intravenous treatments of long duration and high cost. The 2020 and 2021 recommendations from the WHO for the management of drug-susceptible TB and MDR TB have included oral treatment regimens and reduced treatment duration. This Editorial aims to present the rationale for the 2020 and 2021 recommendations from the WHO for the management of drug-susceptible TB and MDR TB.


Assuntos
Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose/tratamento farmacológico , Antituberculosos/uso terapêutico , Protocolos Clínicos/normas , Saúde Global , Humanos , Mycobacterium tuberculosis/isolamento & purificação , Tuberculose/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Pulmonar/epidemiologia , Organização Mundial da Saúde
18.
Braz J Biol ; 83: e244311, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34431905

RESUMO

Tuberculosis is a communicable disease with high morbidity and mortality rates in developing countries. The study's primary objective is to compare conventional methods such as acid-fast bacillus (AFB) culture and microscopy with rapid diagnostic methods. The secondary objective is to compare histopathological and microbiological findings in suspected patients with tubercular lymphadenitis. A total of 111 samples (August 2018 to September 2019) of lymph nodes were processed for AFB microscopy, AFB cultures, drug-susceptibility testing (DST), histopathology, and Xpert Mycobacterium Tuberculosis (MTB)/resistance to Rifampin (RIF) assays. Out of 111 lymph node samples, 6 (5.4%) were positive for AFB smear microscopy, 84 (75.6%) were positive for AFB culture, 80 (70.7%) were positive on Gene Xpert, and 102 (91.8%) were indicative of tuberculosis for histopathology studies. Mycobacteria growth indicator tube (MGIT) culture positivity was 84 (75.6%) higher than solid Lowenstein-Jensen (LJ) culture 74 (66.6%). Positive cultures underwent phenotypic DST. Two cases were Multidrug-resistant (MDR) on DST, while three cases were Rifampicin resistant on Gene Xpert. The sensitivity of Genexpert was (62%) against the conventional AFB culture method. The poor performance of conventional lymphadenitis diagnostic methods requires early and accurate diagnostic methodology. Xpert MTB/RIF test can help in the treatment of multidrug-resistant TB cases. Nonetheless, rapid and conventional methods should be used for complete isolation of Mycobacterium tuberculosis.


Assuntos
Mycobacterium tuberculosis , Tuberculose dos Linfonodos , Tuberculose Resistente a Múltiplos Medicamentos , Humanos , Rifampina/farmacologia , Rifampina/uso terapêutico , Tuberculose dos Linfonodos/diagnóstico
19.
Front Public Health ; 9: 706651, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34368069

RESUMO

Tuberculosis (TB), an airborne infectious disease caused by Mycobacterium tuberculosis complex (MTBC), remains a global health problem. West Africa has a unique epidemiology of TB that is characterized by medium- to high-prevalence. Moreover, the geographical restriction of M. africanum to the sub-region makes West Africa have an extra burden to deal with a two-in-one pathogen. The region is also burdened with low case detection, late reporting, poor treatment adherence leading to development of drug resistance and relapse. Sporadic studies conducted within the subregion report higher burden of drug resistant TB (DRTB) than previously thought. The need for more sensitive and robust tools for routine surveillance as well as to understand the mechanisms of DRTB and transmission dynamics for the design of effective control tools, cannot be overemphasized. The advancement in molecular biology tools including traditional fingerprinting and next generation sequencing (NGS) technologies offer reliable tools for genomic epidemiology. Genomic epidemiology provides in-depth insight of the nature of pathogens, circulating strains and their spread as well as prompt detection of the emergence of new strains. It also offers the opportunity to monitor treatment and evaluate interventions. Furthermore, genomic epidemiology can be used to understand potential emergence and spread of drug resistant strains and resistance mechanisms allowing the design of simple but rapid tools. In this review, we will describe the local epidemiology of MTBC, highlight past and current investigations toward understanding their biology and spread as well as discuss the relevance of genomic epidemiology studies to TB control in West Africa.


Assuntos
Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos , Tuberculose , África Ocidental/epidemiologia , Genômica , Humanos , Mycobacterium tuberculosis/genética , Tuberculose/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico
20.
Microb Pathog ; 159: 105147, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34400280

RESUMO

Tuberculosis caused by Mycobacterium tuberculosis remains a serious global public health threat. M. tuberculosis PE and PPE proteins are closely involved in pathogen-host interaction. To explore the predicted function of the M. tuberculosis PE17 (Rv1646), we heterologously expressed PE17 in a non-pathogenic Mycobacterium smegmatis strain (Ms_PE17). PE17 can reduce the survival of M. smegmatis within macrophages associated with altering the transcription levels of inflammatory cytokines IL1ß, IL6, TNFα, and IL10 in Ms_PE17 infected macrophages through JNK signaling. Furthermore, macrophages apoptosis was increased upon Ms_PE17 infection in a caspases-dependent manner, accompanied by the activation of the Endoplasmic Reticulum stress IRE1α/ASK1/JNK signaling pathway. This can be largely interpreted by the epigenetic changes through reduced H3K9me3 chromatin occupancy post Ms_PE17 infection. To our knowledge, this is the first report that PE17 altered the macrophages apoptosis via H3K9me3 mediated chromatin remodeling.


Assuntos
Mycobacterium tuberculosis , Apoptose , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Montagem e Desmontagem da Cromatina , Endorribonucleases , Mycobacterium smegmatis/genética , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/metabolismo , Proteínas Serina-Treonina Quinases
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