Mycobacterial lineages causing pulmonary and extrapulmonary tuberculosis, Ethiopia.
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ABSTRACT:
SUBMITTER: Firdessa R
PROVIDER: S-EPMC3647644 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:This study examined the genetic diversity and dynamicity of circulating Mycobacterium tuberculosis strains in Thailand using nearly neutral molecular markers. The single nucleotide polymorphism (SNP)-based genotypes of 1,414 culture-positive M. tuberculosis isolates from 1,282 pulmonary tuberculosis (PTB) and 132 extrapulmonary TB (EPTB) patients collected from 1995 to 2011 were characterized. Among the eight SNP cluster groups (SCG), SCG2 (44.1%), which included the Beijing (BJ) genotype, and SCG1 (39.4%), an East African Indian genotype, were dominant. Comparisons between the genotypes of M. tuberculosis isolates causing PTB and EPTB in HIV-negative cases revealed similar prevalence trends although genetic diversity was higher in the PTB patients. The identification of 10 reported sequence types (STs) and three novel STs was hypothesized to indicate preferential expansion of the SCG2 genotype, especially the modern BJ ST10 (15.6%) and ancestral BJ ST19 (13.1%). An association between SCG2 and SCG1 genotypes and particular patient age groups implies the existence of different genetic advantages among the bacterial populations. The results revealed that increasing numbers of young patients were infected with M. tuberculosis SCGs 2 and 5, which contrasts with the reduction of the SCG1 genotype. Our results indicate the selection and dissemination of potent M. tuberculosis genotypes in this population. The determination of heterogeneity and dynamic population changes of circulating M. tuberculosis strains in countries using the Mycobacterium bovis BCG (bacillus Calmette-Guérin) vaccine are beneficial for vaccine development and control strategies.
| S-EPMC4313297 | biostudies-literature
Project description:BACKGROUND. Novel rapid diagnostics for active tuberculosis (TB) are required to overcome the time delays and inadequate sensitivity of current microbiological tests that are critically dependent on sampling the site of disease. Multiparametric blood transcriptomic signatures of TB have been described as potential diagnostic tests. We sought to identify the best transcript candidates as host biomarkers for active TB, extend the evaluation of their specificity by comparison with other infectious diseases, and to test their performance in both pulmonary and extrapulmonary TB. METHODS. Support vector machine learning, combined with feature selection, was applied to new and previously published blood transcriptional profiles in order to identify the minimal TB‑specific transcriptional signature shared by multiple patient cohorts including pulmonary and extrapulmonary TB, and individuals with and without HIV-1 coinfection. RESULTS. We identified and validated elevated blood basic leucine zipper transcription factor 2 (BATF2) transcript levels as a single sensitive biomarker that discriminated active pulmonary and extrapulmonary TB from healthy individuals, with receiver operating characteristic (ROC) area under the curve (AUC) scores of 0.93 to 0.99 in multiple cohorts of HIV-1-negative individuals, and 0.85 in HIV-1-infected individuals. In addition, we identified and validated a potentially novel 4-gene signature comprising CD177, haptoglobin, immunoglobin J chain, and galectin 10 that discriminated active pulmonary and extrapulmonary TB from other febrile infections, giving ROC AUCs of 0.94 to 1. CONCLUSIONS. Elevated blood BATF2 transcript levels provide a sensitive biomarker that discriminates active TB from healthy individuals, and a potentially novel 4-gene transcriptional signature differentiates between active TB and other infectious diseases in individuals presenting with fever. FUNDING. MRC, Wellcome Trust, Rosetrees Trust, British Lung Foundation, NIHR.
| S-EPMC5053151 | biostudies-literature
Project description:Due to their initially seemingly high cost, timely diagnosis and effective treatment of tuberculosis (TB) are usually hampered by lack or shortage of resources in many high TB burden countries. However, the benefits of effective treatment can eventually outweigh those of empirical treatment. Here, a cross-sectional study was conducted on samples from smear-positive new and retreatment TB patients. Data on sociodemographic and HIV status were collected. Samples were cultured for identification, conventional drug sensitivity testing, and molecular typing by deletion typing and spoligotyping. The results showed the youth were disproportionately affected. New cases were being treated following general treatment guidelines only. Monoresistance or multiple drug resistance was found in 16.5% of new patients. Spoligotyping showed that there were 44 patterns with families H3 and T1 (lineage 4) and CAS-Delhi (lineage 3) being dominant. Some rare patterns from lineage 7 were also found. Spoligotype pattern, HIV positivity, and previous treatment were not associated with drug resistance. That the vast majority of the patients were new cases and young and the large number of these patients with mono- or multiple drug resistance indicate that most TB cases are due to recent transmissions and that urgent actions are needed to curb the transmissions.
| S-EPMC4477223 | biostudies-literature
Project description:BackgroundTuberculosis (TB) incidence remains low in health departments of Castellon and La Plana-Vila-real, but TB elimination is challenging. The objective of this study was to estimate associated factors of pulmonary tuberculosis (PTB) compared with extrapulmonary tuberculosis (ETB) and investigate epidemiological characteristics of these pathologies to orient control and prevention actions.Materials and methodsA prospective case-case study was implemented by comparing PTB and ETB incidences during 2013-2016 from notification reports, epidemiological surveillance, and microbiological results of hospitals' laboratories Hospital General Castellon and La Plana-Vila-Real in the province of Castellon of Valencia region in Spain. In this design, cases were patients with PTB and controls were patients with ETB. Directed acyclic graph approach was used for selection of potential risk and confounding factors. Adjusted odds ratios (AORs) were estimated by logistic regression models.ResultsThe study included 136 patients with PTB and 57 patients with ETB, with microbiological confirmation of 93.4% and 52.6%, and the annual median of incidence rates were 7.5 and 3.1 per 100 000 inhabitants, respectively. In general, patients with PTB were younger with higher male proportion than patients with ETB. Risk factors of PTB were smoking tobacco (AOR = 3.98; 95% confidence interval [CI] = 1.66-9.56), social problems (social marginalization, homeless, residence in shelters for the poor, or stay in prison) (AOR = 3.39; 95% CI = 1.05-10.94), and contact with patients with TB (AOR = 2.51; 95% CI = 1.06-5.95). No-smoking tobacco and no-drug abuse interaction decrease PTB risk (AOR = 0.27; 95% CI = 0.12-0.64). From these results, specific measures of health promotion and prevention can be addressed.ConclusionsThe estimated associated factors of PTB may be prevented, and it was demonstrated that the case-case design is useful in the study of TB.
| S-EPMC6449815 | biostudies-literature
Project description:BackgroundMolecular characterization of Mycobacterium tuberculosis (MTB) is important to understand the pathogenesis, diagnosis, treatment, and prevention of tuberculosis (TB). However, there is limited information on molecular characteristics and drug-resistant patterns of MTB in patients with extra-pulmonary tuberculosis (EPTB) in Ethiopia. Thus, this study aimed to determine the molecular characteristics and drug resistance patterns of MTB in patients with EPTB in Addis Ababa, Ethiopia.MethodsThis study was conducted on frozen stored isolates of EPTB survey conducted in Addis Ababa, Ethiopia. A drug susceptibility test was performed using BACTEC-MGIT 960. Species and strain identification were performed using the Geno-Type MTBC and spoligotyping technique, respectively. Data were entered into the MIRU-VNTRplus database to assess the spoligotype patterns of MTB. Analysis was performed using SPSS version 23, and participants' characteristics were presented by numbers and proportions.ResultsOf 151 MTB isolates, 29 (19.2%) were resistant to at least one drug. The highest proportion of isolates was resistant to Isoniazid (14.6%) and Pyrazinamide (14.6%). Nine percent of isolates had multidrug-resistant TB (MDR-TB), and 21.4% of them had pre-extensively drug-resistant TB (pre-XDR-TB). Among the 151 MTB isolates characterized by spoligotyping, 142 (94.6%) had known patterns, while 9 (6.0%) isolates were not matched with the MIRU-VNTRplus spoligotype database. Of the isolates which had known patterns, 2% was M.bovis while 98% M. tuberculosis. Forty-one different spoligotype patterns were identified. The most frequently identified SpolDB4 (SIT) wereSIT149 (21.2%), SIT53 (14.6%) and SIT26 (9.6%). The predominant genotypes identified were T (53.6%), Central Asia Strain (19.2%) and Haarlem (9.9%).ConclusionThe present study showed a high proportion of MDR-TB and pre-XDR-TB among EPTB patients. The strains were mostly grouped into SIT149, SIT53, and SIT26. The T family lineage was the most prevalent genotype. MDR-TB and pre-XDR-TB prevention is required to combat these strains in EPTB. A large scale study is required to describe the molecular characteristics and drug resistance patterns of MTB isolates in EPTB patients.
| S-EPMC7721190 | biostudies-literature
Project description:Extrapulmonary Tuberculosis (EPTB) and Human Immunodeficiency Virus (HIV) infection are interrelated as a result of immune depression. The aim of this study was to determine the prevalence of Mycobacterium tuberculosis complex isolates and the burden of HIV co-infection among EPTB suspected patients.An institution based cross-sectional study was conducted among EPTB suspected patients at the University of Gondar Hospital. Socio-demographic characteristics and other clinical data were collected using a pretested questionnaire. GeneXpert MTB/RIF assay was performed to diagnosis Mycobacterium tuberculosis complex and Rifampicin resistance. All samples were also investigated by cytology and culture. The HIV statuses of all patients were screened initially by KHB, and all positive cases were further re-tested by STAT-pack. Data was analyzed using SPSS version 20 computer software and a P-value of < 0.05 was taken as statistically significant.A total of 141 extrapulmonary suspected patients were enrolled in this study. The overall prevalence of culture confirmed extrapulmonary tuberculosis infection was 29.8%, but the GeneXpert result showed a 26.2% prevalence of Mycobacterium tuberculosis complex infection. The 78.4% prevalence of extrapulmonary tuberculosis infection was found to be higher among the adult population. The prevalence of HIV infection among EPTB suspected patients was 14.1%, while it was 32.4% among GeneXpert-confirmed extrapulmonary TB cases (12/37). Tuberculosis lymphadenitis was the predominant (78.4%) type of EPTB infection followed by tuberculosis cold abscess (10.7%). Adult hood, previous history of contact with known pulmonary tuberculosis patients, and HIV co-infection showed a statistically significant association with extrapulmonary tuberculosis infection (P<0.013).The prevalence of culture confirmed-EPTB infection was high, and a higher EPTB-HIV co-infection was also observed.
| S-EPMC4780813 | biostudies-other
Project description:Personalised medicine, in which clinical management is individualised to the genotypic and phenotypic data of patients, offers a promising means by which to enhance outcomes in the management of mycobacterial pulmonary infections. In this review, we provide an overview of how personalised medicine approaches may be utilised to identify patients at risk of developing tuberculosis (TB) or non-tuberculous mycobacterial pulmonary disease (NTM-PD), diagnose these conditions and guide effective treatment strategies. Despite recent technological and therapeutic advances, TB and NTM-PD remain challenging conditions to diagnose and treat. Studies have identified a range of genetic and immune factors that predispose patients to pulmonary mycobacterial infections. Molecular tests such as nucleic acid amplification assays and next generation sequencing provide a rapid means by which to identify mycobacterial isolates and their antibiotic resistance profiles, thus guiding selection of appropriate antimicrobials. Host-directed therapies and therapeutic drug monitoring offer ways of tailoring management to the clinical needs of patients at an individualised level. Biomarkers may hold promise in differentiating between latent and active TB, as well as in predicting mycobacterial disease progression and response to treatment.
| S-EPMC8624359 | biostudies-literature
Project description:Introduction Delayed diagnosis contributes to the high burden and transmission of tuberculosis and extrapulmonary tuberculosis (EPTB) and continued to be a major public health problem in Ethiopia. Currently, there is insufficient knowledge on the contributing factors to diagnostic delay of EPTB patients in healthcare settings in Ethiopia, because of unique cultural and societal issues in this country. This study assessed patients’ knowledge of symptoms and contributing factors of delay in diagnosis of EPTB patients at selected public health facilities in North Shewa zone, Ethiopia. Methods An institutional-based study was conducted from March to April 2021. All recently registered EPTB patients were included. Logistic regression was performed to analyze the data. A significant association was declared at a p-value of < 0.05, and the results were presented with an adjusted odds ratio (AOR) and the corresponding 95% confidence interval (CI). Results In this study, only 15.5% of respondents knew EPTB symptoms. The median patient and healthcare system delay was 55 days. A patient delay of greater than 3 weeks and a health system delay of greater than 2 weeks were observed among 85.2% and 81% of patients, respectively. After the end of 5 weeks, 87.3% of EPTB patients had been diagnosed with the disease and the total median delay was 108.5 days. Living more than ten kilometers far from a health facility (AOR = 1.54; 95% CI = 1.11, 4.63), having never heard of EPTB disease (AOR = 5.52; 95% CI = 1.73, 17.56), and having ever taken antibiotics at the first health facility visit (AOR = 7.62; 95% CI = 2.26, 25.65) were associated with a total diagnostic delay of beyond 5 weeks. Conclusions The diagnostic delays of EPTB remain high. Both patient and health system delays equally contributed to the total diagnosis delay. Improving community awareness of EPTB and advancing diagnostic efficiencies of healthcare facilities could help reduce both delays.
| S-EPMC9202887 | biostudies-literature
Project description:BACKGROUNDControl of the tuberculosis (TB) pandemic remains hindered in part by a lack of simple and accurate measures of treatment efficacy, as current gold standard markers rely on sputum-based assays that are slow and challenging to implement. However, previous work identified urinary N1, N12-diacetylspermine (DiAcSpm), neopterin, hydroxykynurenine, N-acetylhexosamine, ureidopropionic acid, sialic acid, and mass-to-charge ratio (m/z) 241.0903 as potential biomarkers of active pulmonary TB (ATB). Here, we evaluated their ability to serve as biomarkers of TB treatment response and mycobacterial load.METHODSWe analyzed urine samples prospectively collected from 2 cohorts with ATB. A total of 34 study participants from African countries treated with first-line TB therapy rifampin, isoniazid, pyrazinamide, and ethambutol (HRZE) were followed for 1 year, and 35 participants from Haiti treated with either HRZE or an experimental drug were followed for 14 days. Blinded samples were analyzed by untargeted HPLC-coupled high-resolution TOF-mass spectrometry.RESULTSUrinary levels of all 7 molecules significantly decreased by week 26 of successful treatment (P = 0.01 to P < 0.0001) and positively correlated with sputum mycobacterial load (P < 0.0001). Urinary DiAcSpm levels decreased significantly in participants treated with HRZE as early as 14 days (P < 0.0001) but remained unchanged in cases of ineffective therapy (P = 0.14).CONCLUSIONUrinary DiAcSpm, neopterin, hydroxykynurenine, N-acetylhexosamine, ureidopropionic acid, sialic acid, and m/z 241.0903 reductions correlated with successful anti-TB treatment and sputum mycobacterial load. Urinary DiAcSpm levels exhibited reductions capable of differentiating treatment success from failure as early as 2 weeks after the initiation of chemotherapy, advocating its further development as a potentially simple, noninvasive biomarker for assessing treatment response and bacterial load.FUNDINGThis work was supported by the Clinical and Translational Science Center at Weill Cornell College of Medicine (NIH/NCATS 1 UL1 TR002384-02 and KL2TR000458), the Department of Defense (PR170782), the National Institute of Allergy and Infectious Disease grants (NIAID T32AI007613-16, K24 AI098627, and K23 AI131913), the NIH Fogarty International Center grants (R24 TW007988 and TW010062), NIH grant (R01 GM135926), the Abby and Howard P. Milstein Program in Chemical Biology and Translational Medicine, and the Tuberculosis Research Units Networks (TBRU-N, AI111143).
| S-EPMC7526545 | biostudies-literature
Project description:BackgroundDrug-resistant tuberculosis and extrapulmonary tuberculosis are the world major public health issues. Although some primary studies have been reported on the burden of drug-resistant tuberculosis in extrapulmonary tuberculosis patients in Ethiopia, there is no systematic review and meta-analysis that attempt to summarize the available literature. Thus, we aimed to estimates the prevalence of drug-resistance in extrapulmonary tuberculosis patients and summarize the risk factors associated with the occurrence of extrapulmonary tuberculosis in Ethiopia.MethodsWe conducted a systematic review of the published primary studies on extrapulmonary drug-resistant tuberculosis in Ethiopia.ResultsEight observational studies were included in this review from different regions of Ethiopia. The overall pooled prevalence of rifampicin resistance was 6% (95% CI 0.03-0.10), while isoniazid resistance was 7% (95% CI 0.03-0.12). The pooled prevalence of multidrug-resistant tuberculosis was 4% (95% CI 0.01-0.07). Previous tuberculosis treatment history and male gender are frequently reported risk factors for developing drug-resistant tuberculosis in extrapulmonary tuberculosis patients.ConclusionThe current review has identified a high proportion of resistance to rifampicin, isoniazid, and multidrug-resistant tuberculosis in patients with extrapulmonary tuberculosis in Ethiopia. Clinicians should request drug susceptibility testing for all patients with presumptive extrapulmonary tuberculosis to detect drug-resistance.
| S-EPMC8500428 | biostudies-literature