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Find video protocols related to scientific articles indexed in Pubmed.
The diagnostic accuracy of the GenoType(®) MTBDRsl assay for the detection of resistance to second-line anti-tuberculosis drugs.
Cochrane Database Syst Rev
PUBLISHED: 10-30-2014
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Accurate and rapid tests for tuberculosis (TB) drug resistance are critical for improving patient care and decreasing the transmission of drug-resistant TB. Genotype(®)MTBDRsl (MTBDRsl) is the only commercially-available molecular test for detecting resistance in TB to the fluoroquinolones (FQs; ofloxacin, moxifloxacin and levofloxacin) and the second-line injectable drugs (SLIDs; amikacin, kanamycin and capreomycin), which are used to treat patients with multidrug-resistant (MDR-)TB.
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Comparison of amplicor and GeneXpert MTB/RIF tests for diagnosis of tuberculous meningitis.
J. Clin. Microbiol.
PUBLISHED: 07-23-2014
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There are no data about the comparative accuracy of commercially available nucleic acid amplification tests (GeneXpert MTB/RIF and Roche Amplicor) for the diagnosis of tuberculous meningitis (TBM). A total of 148 patients with suspected TBM were evaluated, and cultures served as the reference standard. The sensitivities and specificities (95% confidence interval [CI]) for the Amplicor and Xpert MTB/RIF tests were similar: 46 (31-60) versus 50 (33-67) and 99 (93-100) and 94 (84-99), respectively.
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Determinants of PCR performance (Xpert MTB/RIF), including bacterial load and inhibition, for TB diagnosis using specimens from different body compartments.
Sci Rep
PUBLISHED: 05-09-2014
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The determinants of Xpert MTB/RIF sensitivity, a widely used PCR test for the diagnosis of tuberculosis (TB) are poorly understood. We compared culture time-to-positivity (TTP; a surrogate of bacterial load), MTB/RIF TB-specific and internal positive control (IPC)-specific C(T) values, and clinical characteristics in patients with suspected TB who provided expectorated (n = 438) or induced sputum (n = 128), tracheal aspirates (n = 71), bronchoalveolar lavage fluid (n = 152), pleural fluid (n = 76), cerebral spinal fluid (CSF; n = 152), pericardial fluid (n = 131), or urine (n = 173) specimens. Median bacterial load (TTP in days) was the strongest associate of MTB/RIF positivity in each fluid. TTP correlated with C(T) values in pulmonary specimens but not extrapulmonary specimens (Spearman's coefficient 0.5043 versus 0.1437; p = 0.030). Inhibition affected a greater proportion of pulmonary specimens than extrapulmonary specimens (IPC C(T) > 34: 6% (47/731) versus 1% (4/381; p < 0.0001). Pulmonary specimens had greater load than extrapulmonary specimens [TTPs (interquartile range) of 11 (7-16) versus 22 (18-33.5) days; p < 0.0001]. HIV-infection was associated with a decreased likelihood of MTB/RIF-positivity in pulmonary specimens but an increased likelihood in extrapulmonary specimens. Mycobacterial load, which displays significant variation across different body compartments, is the main determinant of MTB/RIF-positivity rather than PCR inhibition. MTB/RIF C(T) is a poor surrogate of load in extrapulmonary specimens.
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Xpert MTB/RIF as a measure of sputum bacillary burden. Variation by HIV status and immunosuppression.
Am. J. Respir. Crit. Care Med.
PUBLISHED: 05-03-2014
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Xpert MTB/RIF cycle threshold values are a measure of sputum mycobacterial burden. Data on the impact of HIV infection and immunosuppression on this measure are limited.
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The identification of tuberculosis biomarkers in human urine samples.
Eur. Respir. J.
PUBLISHED: 04-17-2014
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We aimed to determine whether shotgun proteomic approaches could be used to identify tuberculosis (TB)-specific biomarkers in the urine of well-characterised patients with active TB versus no TB. Patients with suspected TB (n=63) were classified as: definite TB (Mycobacterium tuberculosis positive culture, n=21); presumed latent-TB infection (LTBI) (M. tuberculosis negative culture, no radiological features of active TB, a positive QuantiFERON-TB Gold In-Tube (QFT-IT) test and a positive T-SPOT.TB test, n=24); and presumed non-TB/non-LTBI (M. tuberculosis negative culture, no radiological features of active TB, a negative QFT-IT test and a negative T-SPOT.TB test, n=18). Urine proteins, in the range of 3-50 kDa, were collected, separated by a one-dimensional SDS-PAGE gel and digested using trypsin, after which high-performance liquid chromatography-tandem mass spectrometry was used to identify the urinary proteome. 10 mycobacterial proteins were observed exclusively in the urine of definite TB patients, while six mycobacterial proteins were found exclusively in the urine of presumed LTBI patients. In addition, a gene ontology enrichment analysis identified a panel of 20 human proteins that were significant discriminators (p<0.05) for TB disease compared to no TB disease. Furthermore, seven common human proteins were differentially over- or under-expressed in the TB versus the non-TB group. These biomarkers hold promise for the development of new point-of-care diagnostics for TB.
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Comparison of same day diagnostic tools including Gene Xpert and unstimulated IFN-? for the evaluation of pleural tuberculosis: a prospective cohort study.
BMC Pulm Med
PUBLISHED: 04-03-2014
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The accuracy of currently available same-day diagnostic tools (smear microscopy and conventional nucleic acid amplification tests) for pleural tuberculosis (TB) is sub-optimal. Newer technologies may offer improved detection.
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Global control of tuberculosis: from extensively drug-resistant to untreatable tuberculosis.
Lancet Respir Med
PUBLISHED: 03-24-2014
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Extensively drug-resistant tuberculosis is a burgeoning global health crisis mainly affecting economically active young adults, and has high mortality irrespective of HIV status. In some countries such as South Africa, drug-resistant tuberculosis represents less than 3% of all cases but consumes more than a third of the total national budget for tuberculosis, which is unsustainable and threatens to destabilise national tuberculosis programmes. However, concern about drug-resistant tuberculosis has been eclipsed by that of totally and extremely drug-resistant tuberculosis--ie, resistance to all or nearly all conventional first-line and second-line antituberculosis drugs. In this Review, we discuss the epidemiology, pathogenesis, diagnosis, management, implications for health-care workers, and ethical and medicolegal aspects of extensively drug-resistant tuberculosis and other resistant strains. Finally, we discuss the emerging problem of functionally untreatable tuberculosis, and the issues and challenges that it poses to public health and clinical practice. The emergence and growth of highly resistant strains of tuberculosis make the development of new drugs and rapid diagnostics for tuberculosis--and increased funding to strengthen global control efforts, research, and advocacy--even more pressing.
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Aspergilloma and the surgeon.
J Thorac Dis
PUBLISHED: 03-14-2014
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Aspergillus fungus is a ubiquitous saprophyte that is the causative organism for the development of an aspergilloma. The most common species causing an aspergilloma is the Apergillus fumigatus. An aspergilloma is a conglomeration of mucus, inflammatory cells and altered blood elements. Aspergillomas typically form in pre-existing lung pathology, most notably and commonly in old healed tuberculosis cavities. They are classified into simple and complex types that have clinical relevance. Symptoms are very variable and it is not uncommon to incidentally find a lung aspergilloma. In most case series, the most common presenting symptom is haemoptysis which varies from mild to catastrophic bleeds. Given the limited information about the natural history of the disease, there is unfortunately no recognised factor or variable which can predict how an aspergilloma will manifest itself, hence the manner of treatment is a still a topic of debate among treating physicians. The mainstay of treatment is surgical intervention and medical options although disappointing at the current stage, require further investigation in light of the newer available anti-fungal agents. The need for surgical intervention is however not as clear-cut as one would like, since many patients have multiple co-morbidities and other diffuse or focal lung pathology, making the decision process indeterminate in certain instances. In this review, we focus on the different surgical options available for the management of aspergilloma across variable clinical settings, and we propose an approach to its management.
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The medical and surgical treatment of drug-resistant tuberculosis.
J Thorac Dis
PUBLISHED: 03-14-2014
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Multi drug-resistant tuberculosis (MDR-TB) and extensively drug-resistant TB (XDR-TB) are burgeoning global problems with high mortality which threaten to destabilise TB control programs in several parts of the world. Of alarming concern is the emergence, in large numbers, of patients with resistance beyond XDR-TB (totally drug-resistant TB; TDR-TB or extremely drug resistant TB; XXDR-TB). Given the burgeoning global phenomenon of MDR-TB, XDR-TB and TDR-TB, and increasing international migration and travel, healthcare workers, researchers, and policy makers in TB endemic and non-endemic countries should familiarise themselves with issues relevant to the management of these patients. Given the lack of novel TB drugs and limited access to existing drugs such as linezolid and bedaquiline in TB endemic countries, significant numbers of therapeutic failures are emerging from the ranks of those with XDR-TB. Given the lack of appropriate facilities in resource-limited settings, such patients are being discharged back into the community where there is likely ongoing disease spread. In the absence of effective drug regimens, in appropriate patients, surgery is a critical part of management. Here we review the diagnosis, medical and surgical management of MDR-TB and XDR-TB.
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TRIM5? and TRIM22 are differentially regulated according to HIV-1 infection phase and compartment.
J. Virol.
PUBLISHED: 01-29-2014
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The antiviral role of TRIM E3 ligases in vivo is not fully understood. To test the hypothesis that TRIM5? and TRIM22 have differential transcriptional regulation and distinct anti-HIV roles according to infection phase and compartment, we measured TRIM5?, TRIM22, and type I interferon (IFN-I)-inducible myxovirus resistance protein A (MxA) levels in peripheral blood mononuclear cells (PBMCs) during primary and chronic HIV-1 infection, with chronic infection samples being matched PBMCs and central nervous system (CNS)-derived cells. Associations with biomarkers of disease progression were explored. The impact of IFN-I, select proinflammatory cytokines, and HIV on TRIM E3 ligase-specific expression was investigated. PBMCs from individuals with primary and chronic HIV-1 infection had significantly higher levels of MxA and TRIM22 than did PBMCs from HIV-1-negative individuals (P < 0.05 for all comparisons). PBMCs from chronic infection had lower levels of TRIM5? than did PBMCs from primary infection or HIV-1-uninfected PBMCs (P = 0.0001 for both). In matched CNS-derived samples and PBMCs, higher levels of MxA (P = 0.001) and TRIM5? (P = 0.0001) in the CNS were noted. There was a negative correlation between TRIM22 levels in PBMCs and plasma viral load (r = -0.40; P = 0.04). In vitro, IFN-I and, rarely, proinflammatory cytokines induced TRIM5? and TRIM22 in a cell type-dependent manner, and the knockdown of either protein in CD4(+) lymphocytes resulted in increased HIV-1 infection. These data suggest that there are infection-phase-specific and anatomically compartmentalized differences in TRIM5? and TRIM22 regulation involving primarily IFN-I and specific cell types and indicate subtle differences in the antiviral roles and transcriptional regulation of TRIM E3 ligases in vivo.
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Long-term outcomes of patients with extensively drug-resistant tuberculosis in South Africa: a cohort study.
Lancet
PUBLISHED: 01-17-2014
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Long-term treatment-related outcomes in patients with extensively drug-resistant (XDR) tuberculosis are unknown. We followed up a cohort of patients to address knowledge gaps.
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Do high rates of empirical treatment undermine the potential effect of new diagnostic tests for tuberculosis in high-burden settings?
Lancet Infect Dis
PUBLISHED: 01-15-2014
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In tuberculosis-endemic settings, patients are often treated empirically, meaning that they are placed on treatment based on clinical symptoms or tests that do not provide a microbiological diagnosis (eg, chest radiography). New tests for tuberculosis, such as the Xpert MTB/RIF assay (Cepheid, Sunnyvale, CA, USA), are being implemented at substantial cost. To inform policy and rationally drive implementation, data are needed for how these tests affect morbidity, mortality, transmission, and population-level tuberculosis burden. If people diagnosed by use of new diagnostics would have received empirical treatment a few days later anyway, then the incremental benefit might be small. Will new diagnostics substantially improve outcomes and disease burden, or simply displace empirical treatment? Will the extent and accuracy of empirical treatment change with the introduction of a new test? In this Personal View, we review emerging data for how empirical treatment is frequently same-day, and might still be the predominant form of treatment in high-burden settings, even after Xpert implementation; and how Xpert might displace so-called true-positive, rather than false-positive, empirical treatment. We suggest types of studies needed to accurately assess the effect of new tuberculosis tests and the role of empirical treatment in real-world settings. Until such questions can be addressed, and empirical treatment is appropriately characterised, we postulate that the estimated population-level effect of new tests such as Xpert might be substantially overestimated.
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Gamma interferon release assays for detection of Mycobacterium tuberculosis infection.
Clin. Microbiol. Rev.
PUBLISHED: 01-08-2014
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Identification and treatment of latent tuberculosis infection (LTBI) can substantially reduce the risk of developing active disease. However, there is no diagnostic gold standard for LTBI. Two tests are available for identification of LTBI: the tuberculin skin test (TST) and the gamma interferon (IFN-?) release assay (IGRA). Evidence suggests that both TST and IGRA are acceptable but imperfect tests. They represent indirect markers of Mycobacterium tuberculosis exposure and indicate a cellular immune response to M. tuberculosis. Neither test can accurately differentiate between LTBI and active TB, distinguish reactivation from reinfection, or resolve the various stages within the spectrum of M. tuberculosis infection. Both TST and IGRA have reduced sensitivity in immunocompromised patients and have low predictive value for progression to active TB. To maximize the positive predictive value of existing tests, LTBI screening should be reserved for those who are at sufficiently high risk of progressing to disease. Such high-risk individuals may be identifiable by using multivariable risk prediction models that incorporate test results with risk factors and using serial testing to resolve underlying phenotypes. In the longer term, basic research is necessary to identify highly predictive biomarkers.
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Diagnostic accuracy of quantitative PCR (Xpert MTB/RIF) for tuberculous pericarditis compared to adenosine deaminase and unstimulated interferon-? in a high burden setting: a prospective study.
BMC Med
PUBLISHED: 01-07-2014
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Tuberculous pericarditis (TBP) is associated with high morbidity and mortality, and is an important treatable cause of heart failure in developing countries. Tuberculous aetiology of pericarditis is difficult to diagnose promptly. The utility of the new quantitative PCR test (Xpert MTB/RIF) for the diagnosis of TBP is unknown. This study sought to evaluate the diagnostic accuracy of the Xpert MTB/RIF test compared to pericardial adenosine deaminase (ADA) and unstimulated interferon-gamma (uIFN?) in suspected TBP.
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Cigarette smoke impairs cytokine responses and BCG containment in alveolar macrophages.
Thorax
PUBLISHED: 11-28-2013
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There is a strong epidemiological link between smoking and tuberculosis (TB), but the association is confounded by socioeconomic and other factors. A direct relationship between cigarette smoke and poor treatment-related outcomes in patients with TB is therefore questionable. We investigated whether constituents of tobacco smoke impair mycobacterial host immune responses in vitro.
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Feasibility, accuracy, and clinical effect of point-of-care Xpert MTB/RIF testing for tuberculosis in primary-care settings in Africa: a multicentre, randomised, controlled trial.
Lancet
PUBLISHED: 10-28-2013
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The Xpert MTB/RIF test for tuberculosis is being rolled out in many countries, but evidence is lacking regarding its implementation outside laboratories, ability to inform same-day treatment decisions at the point of care, and clinical effect on tuberculosis-related morbidity. We aimed to assess the feasibility, accuracy, and clinical effect of point-of-care Xpert MTB/RIF testing at primary-care health-care facilities in southern Africa.
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Diagnostic accuracy of quantitative PCR (Xpert MTB/RIF) for tuberculous meningitis in a high burden setting: a prospective study.
PLoS Med.
PUBLISHED: 10-01-2013
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Tuberculous meningitis (TBM) is difficult to diagnose promptly. The utility of the Xpert MTB/RIF test for the diagnosis of TBM remains unclear, and the effect of host- and sample-related factors on test performance is unknown. This study sought to evaluate the sensitivity and specificity of Xpert MTB/RIF for the diagnosis of TBM.
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South African tobacco smoking cessation clinical practice guideline.
S. Afr. Med. J.
PUBLISHED: 09-09-2013
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Tobacco smoking (i.e. cigarettes, rolled tobacco, pipes, etc.) is associated with significant health risks, reduced life expectancy and negative personal and societal economic impact. Smokers have an increased risk of cancer (i.e. lung, throat, bladder), chronic obstructive pulmonary disease (COPD), tuberculosis and cardiovascular disease (i.e. stroke, heart attack). Smoking affects unborn babies, children and others exposed to second hand smoke. Stopping or quitting is not easy. Nicotine is highly addictive and smoking is frequently associated with social activities (e.g. drinking, eating) or psychological factors (e.g. work pressure, concerns about body weight, anxiety or depressed mood). The benefits of quitting, however, are almost immediate, with a rapid lowering of blood pressure and heart rate, improved taste and smell, and a longer-term reduction in risk of cancer, heart attack and COPD. Successful quitting requires attention to both the factors surrounding why an individual smokes (e.g. stress, depression, habit, etc.) and the symptoms associated with nicotine withdrawal. Many smokers are not ready or willing to quit and require frequent motivational input outlining the benefits that would accrue. In addition to an evaluation of nicotine dependence, co-existent medical or psychiatric conditions and barriers to quitting should be identified. A tailored approach encompassing psychological and social support, in addition to appropriate medication to reduce nicotine withdrawal, is likely to provide the best chance of success. Relapse is not uncommon and reasons for failure should be addressed in a positive manner and further attempts initiated when the individual is ready.Key steps in smoking cessation include: (i) identifying all smokers, alerting them to the harms of smoking and benefits of quitting; (ii) assessing readiness to initiate an attempt to quit; (iii) assessing the physical and psychological dependence to nicotine and smoking; (iv) determining the best combination of counselling/support and pharmacological therapy; (v) setting a quit date and provide suitable resources and support; (vi) frequent follow-up as often as possible via text/telephone or in person; (vii) monitoring for side-effects, relapse and on-going cessation; and (viii) if relapse occurs, providing the necessary support and encourage a further attempt when appropriate. 
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Point-of-care diagnosis of tuberculosis: past, present and future.
Respirology
PUBLISHED: 08-31-2013
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Diagnosis represents only one aspect of tuberculosis (TB) control but is perhaps one of the most challenging. The drawbacks of current tools highlight several unmet needs in TB diagnosis, that is, necessity for accuracy, rapidity of diagnosis, affordability, simplicity and the ability to generate same-day results at point-of-care (POC). When a return visit is required to access test results, time to treatment is prolonged, and default rates are significant. However, a good diagnostic tool is also critically dependent on obtaining an adequate biological sample. Here, we review the accuracy and potential impact of established and newer potential POC diagnostic tests for TB, including smear microscopy, the Xpert MTB/RIF assay (Cepheid) and the Determine TB lipoarabinomannan antigen test (Alere). Novel experimental approaches and detection technologies for POC diagnosis of active TB, including nucleic acid amplification tests, detection of volatile organic compounds or metabolites, mass spectroscopy, microfluidics, surface-enhanced Raman spectroscopy, electrochemical approaches, and aptamers among others, are discussed. We also discuss future applications, including the potential POC diagnosis of drug-resistant TB and presumed latent TB infection. Challenges to the development and roll-out of POC tests for TB are also reviewed.
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Determine TB-LAM lateral flow urine antigen assay for HIV-associated tuberculosis: recommendations on the design and reporting of clinical studies.
BMC Infect. Dis.
PUBLISHED: 07-11-2013
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Detection of the Mycobacterium tuberculosis cell wall antigen lipoarabinomannan (LAM) in urine permits diagnoses of tuberculosis (TB) to be made in HIV-infected patients with advanced immunodeficiency. This can be achieved at the point-of-care within just 30 minutes using the Determine TB-LAM, which is a commercially available, lateral-flow urine strip test assay. The assay has been shown to have useful diagnostic accuracy in patients enrolling in antiretroviral treatment services or in HIV-infected patients requiring admission to hospital medical wards in sub-Saharan Africa. Such patients have high mortality risk and have most to gain from rapid diagnosis of TB and immediate initiation of treatment. However, few studies using this assay have yet been reported and many questions remain concerning the correct use of the assay, interpretation of results, the role of the assay as an add-on test within existing diagnostic algorithms and the types of further studies needed. In this paper we address a series of questions with the aim of informing the design, conduct and interpretation of future studies. Specifically, we clarify which clinical populations are most likely to derive benefit from use of this assay and how patients enrolled in such studies might best be characterised. We describe the importance of employing a rigorous microbiological diagnostic reference standard in studies of diagnostic accuracy and discuss issues surrounding the specificity of the assay in different geographical areas and potential cross-reactivity with non-tuberculous mycobacteria and other organisms. We highlight the importance of careful procedures for urine collection and storage and the critical issue of how to read and interpret the test strips. Finally, we consider how the assay could be used in combination with other assays and outline the types of studies that are required to build the evidence base concerning its use.
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Accuracy and impact of Xpert MTB/RIF for the diagnosis of smear-negative or sputum-scarce tuberculosis using bronchoalveolar lavage fluid.
Thorax
PUBLISHED: 06-29-2013
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The accuracy and impact of new tuberculosis (TB) tests, such as Xpert MTB/RIF, when performed on bronchoalveolar lavage fluid (BALF) obtained from patients with sputum-scarce or smear-negative TB is unclear.
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Regulatory T cells attenuate mycobacterial stasis in alveolar and blood-derived macrophages from patients with tuberculosis.
Am. J. Respir. Crit. Care Med.
PUBLISHED: 04-18-2013
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There are hardly any data about the frequency of CD4(+)CD25(+)Foxp3(+) regulatory T cells (T-Regs) in the lungs of patients with active tuberculosis (TB).
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Sputum induction to aid diagnosis of smear-negative or sputum-scarce tuberculosis in adults in HIV-endemic settings.
Eur. Respir. J.
PUBLISHED: 03-21-2013
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Sputum induction can aid tuberculosis (TB) diagnosis, but adult data from HIV-endemic environments are limited, and it is unclear how performance varies depending on the clinical context (in-patient versus outpatient), HIV status and whether patients are smear-negative or sputum-scarce. 696 adults with suspected smear-negative or sputum-scarce TB from Cape Town (South Africa) were referred for routine sputum induction. Liquid culture for Mycobacterium tuberculosis served as the reference standard. 82% (573 out of 696) of patients provided a specimen ?1 mL, 83% (231 out of 278) of which were of adequate quality. 15% (96 out of 652) of sputum induction specimens were culture-positive, and this yield was higher among inpatients versus outpatients (17% (71 out of 408) versus 10% (25 out of 244), p=0.01) and HIV-infected versus uninfected patients (17% (51 out of 294) versus 9% (16 out of 173), p=0.02), but similar for CD4 (>200 versus ?200 cells·?L(-1)) and patient (smear-negative versus sputum-scarce) subcategories. Overall sensitivity (95% CI) of smear-microscopy was 49% (39-59%), higher among in-patients versus outpatients (55% (43-67%) versus 32% (14-50%), p=0.05), but unaffected by HIV co-infection, CD4 count or patient type. 29% (203 out of 696) of patients commenced anti-TB treatment and sputum induction offered microbiological confirmation and susceptibility testing in only 47% (96 out of 203). Under programmatic conditions in an HIV-endemic environment although the yield of culture was approximately two-fold higher amongst HIV-infected patients and inpatients, a fifth of all patients were unable to provide a specimen following sputum induction. Same-day microbiological diagnosis was only possible in ?50% of patients.
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EDCTP regional networks of excellence: initial merits for planned clinical trials in Africa.
BMC Public Health
PUBLISHED: 03-14-2013
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Achieving the Millennium Development Goals (MDGs) and combating hotspots with escalating but preventable communicable diseases remain major challenges in Africa. The European and Developing Countries Clinical Trials Partnership (EDCTP) intervened to combat poverty-related diseases including malaria, tuberculosis and HIV/AIDS, and to conduct multi-centre clinical trials and multi-disciplinary health research through an innovative model of regional Networks of Excellence (NoEs).
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Supervised and unsupervised self-testing for HIV in high- and low-risk populations: a systematic review.
PLoS Med.
PUBLISHED: 02-22-2013
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Stigma, discrimination, lack of privacy, and long waiting times partly explain why six out of ten individuals living with HIV do not access facility-based testing. By circumventing these barriers, self-testing offers potential for more people to know their sero-status. Recent approval of an in-home HIV self test in the US has sparked self-testing initiatives, yet data on acceptability, feasibility, and linkages to care are limited. We systematically reviewed evidence on supervised (self-testing and counselling aided by a health care professional) and unsupervised (performed by self-tester with access to phone/internet counselling) self-testing strategies.
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Increased production of IL-4 and IL-12p40 from bronchoalveolar lavage cells are biomarkers of Mycobacterium tuberculosis in the sputum.
PLoS ONE
PUBLISHED: 02-18-2013
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Tuberculosis (TB) causes 1.45 million deaths annually world wide, the majority of which occur in the developing world. Active TB disease represents immune failure to control latent infection from airborne spread. Acid-fast bacillus (AFB) seen on sputum smear is a biomarker for contagiousness.
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Can point-of-care urine LAM strip testing for tuberculosis add value to clinical decision making in hospitalised HIV-infected persons?
PLoS ONE
PUBLISHED: 02-04-2013
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The urine lipoarabinomannan (LAM) strip-test (Determine®-TB) can rapidly rule-in TB in HIV-infected persons with advanced immunosuppression. However, given high rates of empiric treatment amongst hospitalised patients in high-burden settings (? 50%) it is unclear whether LAM can add any value to clinical decision making, or identify a subset of patients with unfavourable outcomes that would otherwise have been missed by empiric treatment.
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What is the cost of diagnosis and management of drug resistant tuberculosis in South Africa?
PLoS ONE
PUBLISHED: 01-18-2013
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Drug-resistant tuberculosis (DR-TB) is undermining TB control in South Africa. However, there are hardly any data about the cost of treating DR-TB in high burden settings despite such information being quintessential for the rational planning and allocation of resources by policy-makers, and to inform future cost-effectiveness analyses.
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Development of a simple reliable radiographic scoring system to aid the diagnosis of pulmonary tuberculosis.
PLoS ONE
PUBLISHED: 01-18-2013
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Chest radiography is sometimes the only method available for investigating patients with possible pulmonary tuberculosis (PTB) with negative sputum smears. However, interpretation of chest radiographs in this context lacks specificity for PTB, is subjective and is neither standardized nor reproducible. Efforts to improve the interpretation of chest radiography are warranted.
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Will an Unsupervised Self-Testing Strategy for HIV Work in Health Care Workers of South Africa? A Cross Sectional Pilot Feasibility Study.
PLoS ONE
PUBLISHED: 01-01-2013
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In South Africa, stigma, discrimination, social visibility and fear of loss of confidentiality impede health facility-based HIV testing. With 50% of adults having ever tested for HIV in their lifetime, private, alternative testing options are urgently needed. Non-invasive, oral self-tests offer a potential for a confidential, unsupervised HIV self-testing option, but global data are limited.
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Drug-associated adverse events and their relationship with outcomes in patients receiving treatment for extensively drug-resistant tuberculosis in South Africa.
PLoS ONE
PUBLISHED: 01-01-2013
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Treatment-related outcomes in patients with extensively drug-resistant tuberculosis (XDR-TB) are poor. However, data about the type, frequency and severity of presumed drug-associated adverse events (AEs) and their association with treatment-related outcomes in patients with XDR-TB are scarce.
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The use of an automated quantitative polymerase chain reaction (Xpert MTB/RIF) to predict the sputum smear status of tuberculosis patients.
Clin. Infect. Dis.
PUBLISHED: 12-01-2011
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Xpert MTB/RIF-generated cycle-threshold (C(T)) values have poor clinical utility as a rule-in test for smear positivity (cut-point ?20.2; sensitivity 32.3%, specificity 97.1%) but moderately good rule-out value (cut-point >31.8; negative predictive value 80.0%). Thus, 20% of individuals with C(T) values >31.8 were erroneously ruled out as smear-negative. This group had a significantly lower sputum bacillary load relative to correctly classified smear-positive patients (C(T) ? 31.8; P < .001). These data inform on public health and contact tracing strategies.
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Do adjunct tuberculosis tests, when combined with Xpert MTB/RIF, improve accuracy and the cost of diagnosis in a resource-poor setting?
Eur. Respir. J.
PUBLISHED: 11-10-2011
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Information regarding the utility of adjunct diagnostic tests in combination with Xpert MTB/RIF (Cepheid, Sunnyvale, CA, USA) is limited. We hypothesised adjunct tests could enhance accuracy and/or reduce the cost of tuberculosis (TB) diagnosis prior to MTB/RIF testing, and rule-in or rule-out TB in MTB/RIF-negative individuals. We assessed the accuracy and/or laboratory-associated cost of diagnosis of smear microscopy, chest radiography (CXR) and interferon-? release assays (IGRAs; T-SPOT-TB (Oxford Immunotec, Oxford, UK) and QuantiFERON-TB Gold In-Tube (Cellestis, Chadstone, Australia)) combined with MTB/RIF for TB in 480 patients in South Africa. When conducted prior to MTB/RIF: 1) smear microscopy followed by MTB/RIF (if smear negative) had the lowest cost of diagnosis of any strategy investigated; 2) a combination of smear microscopy, CXR (if smear negative) and MTB/RIF (if imaging compatible with active TB) did not further reduce the cost per TB case diagnosed; and 3) a normal CXR ruled out TB in 18% of patients (57 out of 324; negative predictive value (NPV) 100%). When downstream adjunct tests were applied to MTB/RIF-negative individuals, radiology ruled out TB in 24% (56 out of 234; NPV 100%), smear microscopy ruled in TB in 21% (seven out of 24) of culture-positive individuals and IGRAs were not useful in either context. In resource-poor settings, smear microscopy combined with MTB/RIF had the highest accuracy and lowest cost of diagnosis compared to either technique alone. In MTB/RIF-negative individuals, CXR has poor rule-in value but can reliably rule out TB in approximately one in four cases. These data inform upon the programmatic utility of MTB/RIF in high-burden settings.
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Comparative utility of cytokine levels and quantitative RD-1-specific T cell responses for rapid immunodiagnosis of tuberculous meningitis.
J. Clin. Microbiol.
PUBLISHED: 08-31-2011
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The rapid diagnosis of tuberculous meningitis (TBM) is problematic. We found in 150 patients with suspected TBM that, similar to RD-1-specific quantitative cerebrospinal fluid (CSF) T-cell responses, unstimulated CSF gamma interferon (IFN-?) levels when used together with other rapid confirmatory tests (Gram stain and cryptococcal latex agglutination test) may allow the accurate and rapid diagnosis of TBM in a setting in which tuberculosis (TB) and HIV are endemic. In resource-poor settings, a clinical prediction rule (CPR) may be useful to clinicians, and thus the IFN-? assay may potentially need to be used only when the clinical score is below a prespecified threshold. These preliminary findings will need to be confirmed in further studies.
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Comparison of quantitative techniques including Xpert MTB/RIF to evaluate mycobacterial burden.
PLoS ONE
PUBLISHED: 08-12-2011
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Accurate quantification of mycobacterial load is important for the evaluation of patient infectiousness, disease severity and monitoring treatment response in human and in-vitro laboratory models of disease. We hypothesized that newer techniques would perform as well as solid media culture to quantify mycobacterial burden in laboratory specimens.
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A historical review of XDR tuberculosis in the Western Cape province of South Africa.
S. Afr. Med. J.
PUBLISHED: 07-26-2011
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There are limited data on the temporal relationship between the regional introduction of multidrug-resistant tuberculosis (MDR-TB) treatment and the subsequent development of extensively drug-resistant TB (XDR-TB). The first XDR-TB case in the Western Cape province of South Africa was recorded in 1992, approximately 5 - 7 years after the regional introduction of MDR-TB-like treatment. Between 1990 and 2002 we identified 48 patients with XDR-TB in the Cape Metropole region of the Western Cape province. Patients were predominantly HIV-uninfected and median survival was 10.8 months. XDR-TB has therefore been present in the Western Cape at least since 1992. These data inform public health policy relevant to the introduction of new anti-TB drug regimens.
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Functional capacity of Mycobacterium tuberculosis-specific T cell responses in humans is associated with mycobacterial load.
J. Immunol.
PUBLISHED: 07-20-2011
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High Ag load in chronic viral infections has been associated with impairment of Ag-specific T cell responses; however, the relationship between Ag load in chronic Mycobacterium tuberculosis infection and functional capacity of M. tuberculosis-specific T cells in humans is not clear. We compared M. tuberculosis-specific T cell-associated cytokine production and proliferative capacity in peripheral blood from adults with progressively higher mycobacterial loads-that is, persons with latent M. tuberculosis infection (LTBI), with smear-negative pulmonary tuberculosis (TB), and smear-positive TB. Patients with smear-positive TB had decreased polyfunctional IFN-?(+)IL-2(+)TNF-?(+) and IL-2-producing specific CD4 T cells and increased TNF-? single-positive cells, when compared with smear-negative TB and LTBI. TB patients also had increased frequencies of M. tuberculosis-specific CD8 T cells, compared with LTBI. M. tuberculosis-specific CD4 and CD8 T cell proliferative capacity was profoundly impaired in individuals with smear-positive TB, and correlated positively with ex vivo IFN-?(+)IL-2(+)TNF-?(+) CD4 T cells, and inversely with TNF-? single-positive CD4 T cells. During 6 mo of anti-TB treatment, specific IFN-?(+)IL-2(+)TNF-?(+) CD4 and CD8 T cells increased, whereas TNF-? and IFN-? single-positive T cells decreased. These results suggest progressive impairment of M. tuberculosis-specific T cell responses with increasing mycobacterial load and recovery of responses during therapy. Furthermore, these data provide a link between specific cytokine-producing subsets and functional capacity of M. tuberculosis-specific T cells, and between the presence of specific CD8 T cells ex vivo and active TB disease. These data have potentially significant applications for the diagnosis of TB and for the identification of T cell correlates of TB disease progression.
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Transcriptional profiling of innate and adaptive human immune responses to mycobacteria in the tuberculin skin test.
Eur. J. Immunol.
PUBLISHED: 06-08-2011
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The tuberculin skin test (TST) is a model of integrated innate and adaptive human immune responses to Mycobacterium tuberculosis, but the component processes that are involved in this model have not previously been defined in vivo. We used transcriptional profiling to study these responses within the TST at molecular and system levels. Skin biopsies from TST injection sites were examined in subjects classified as TST(+) or TST(-) by clinical and histological criteria. Genome-wide expression arrays showed evolution of immune responses reflecting T-cell activation and recruitment with uniquely Th1-polarized responses and cytotoxic T cells (CTLs). In addition, distinct innate immune and IFN-?-stimulated gene expression signatures were identified, under the regulation of NF-?B and STAT1 transcriptional control. These were highly enriched for chemokines and MHC class II molecules providing a potential mechanism for paracrine amplification of inflammatory responses in the TST, by supporting cellular recruitment and enhancing antigen presentation. The same repertoire of innate and adaptive immune responses was evident in TST(+) and TST(-) subjects alike, clinically positive TSTs being distinguished only by quantitatively greater differences. These data provide new insights into complex multifaceted responses within the TST, with much greater sensitivity than previous clinical or histological assessments.
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Interferon-? release assays for diagnosis of latent tuberculosis infection: evidence in immune-mediated inflammatory disorders.
Curr Opin Rheumatol
PUBLISHED: 04-27-2011
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To provide a narrative synthesis of evidence on interferon-gamma release assays (IGRAs) for the diagnosis of latent tuberculosis infection (LTBI) in individuals with immune-mediated inflammatory disorders (IMIDs).
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Evaluation of the Xpert MTB/RIF assay for the diagnosis of pulmonary tuberculosis in a high HIV prevalence setting.
Am. J. Respir. Crit. Care Med.
PUBLISHED: 04-14-2011
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Xpert MTB/RIF is a novel automated molecular diagnostic recently endorsed by the World Health Organization. However, performance-related data from high HIV prevalence settings are limited.
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Predominance of interleukin-22 over interleukin-17 at the site of disease in human tuberculosis.
Tuberculosis (Edinb)
PUBLISHED: 03-08-2011
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The inflammatory response to Mycobacterium tuberculosis (M.tb) at the site of disease is Th1 driven. Whether the Th17 cytokines, IL-17 and IL-22, contribute to this response in humans is unknown. We hypothesized that IL-17 and IL-22 contribute to the inflammatory response in pleural and pericardial disease sites of human tuberculosis (TB). We studied pleural and pericardial effusions, established TB disease sites, from HIV-uninfected TB patients. Levels of soluble cytokines were measured by ELISA and MMP-9 by luminex. Bronchoalveolar lavage or pericardial mycobacteria-specific T cell cytokine expression was analyzed by intracellular cytokine staining. IL-17 was not abundant in pleural or pericardial fluid. IL-17 expression by mycobacteria-specific disease site T cells was not detected in healthy, M.tb-infected persons, or patients with TB pericarditis. These data do not support a major role for IL-17 at established TB disease sites in humans. IL-22 was readily detected in fluid from both disease sites. These IL-22 levels exceeded matching peripheral blood levels. Further, IL-22 levels in pericardial fluid correlated positively with MMP-9, an enzyme known to degrade the pulmonary extracellular matrix. We propose that our findings support a role for IL-22 in TB-induced pathology or the resulting repair process.
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Rapid and accurate detection of Mycobacterium tuberculosis in sputum samples by Cepheid Xpert MTB/RIF assay--a clinical validation study.
PLoS ONE
PUBLISHED: 03-05-2011
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A crucial impediment to global tuberculosis control is the lack of an accurate, rapid diagnostic test for detection of patients with active TB. A new, rapid diagnostic method, (Cepheid) Xpert MTB/RIF Assay, is an automated sample preparation and real-time PCR instrument, which was shown to have good potential as an alternative to current reference standard sputum microscopy and culture.
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Viewpoint: Scientific dogmas, paradoxes and mysteries of latent Mycobacterium tuberculosis infection.
Trop. Med. Int. Health
PUBLISHED: 02-24-2011
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Worldwide, there are nearly 10 million new cases of active TB and 1.8 million associated deaths every year. WHO estimates that one-third of the worlds population is infected with Mycobacterium tuberculosis (Mtb), forming a huge latent Mtb global reservoir. This renders the prospect of ever eliminating Mtb from the human race almost impossible. Several controversial issues regarding host-pathogen interactions and existing prevention and eradication strategies for latent Mtb infections need to be critically re-examined. In this viewpoint, widely held assumptions on Mtb latency and isoniazid monotherapy and chemoprophylaxis are challenged. We highlight the need for future research to resolve these issues and to develop evidence-based strategies for better understanding of equilibrium and escape of Mtb in the human body, eventually leading to global recommendations for elimination of the latent Mtb state through informed policy and practice. Until such strategies and policies are realized, WHO and TB experts will have to settle for global TB control rather than eradication.
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Novel developments in the epidemic of human immunodeficiency virus and tuberculosis coinfection.
Am. J. Respir. Crit. Care Med.
PUBLISHED: 12-22-2010
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Tuberculosis (TB) disease remains one of the highest causes of mortality in HIV-infected individuals, and HIV-TB coinfection continues to grow at alarming rates, especially in sub-Saharan Africa. Surprisingly, a number of important areas regarding coinfection remain unclear. For example, increased risk of TB disease begins early in the course of HIV infection; however, the mechanism by which HIV increases this risk is not well understood. In addition, there is lack of consensus on the optimal way to diagnose latent TB infection and to manage active disease in those who are HIV infected. Furthermore, effective point-of-care testing for TB disease remains elusive. This review discusses key areas in the epidemiology, pathogenesis, diagnosis, and management of active and latent TB in those infected with HIV, focusing attention on issues related to high- and low-burden areas. Particular emphasis is placed on controversial areas where there are gaps in knowledge and on future directions of study.
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Human lung immunity against Mycobacterium tuberculosis: insights into pathogenesis and protection.
Am. J. Respir. Crit. Care Med.
PUBLISHED: 11-12-2010
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The study of human pulmonary immunity against Mycobacterium tuberculosis (M.tb) provides a unique window into the biological interactions between the human host and M.tb within the broncho-alveolar microenvironment, the site of natural infection. Studies of bronchoalveolar cells (BACs) and lung tissue evaluate innate, adaptive, and regulatory immune mechanisms that collectively contribute to immunological protection or its failure. In aerogenically M.tb-exposed healthy persons lung immune responses reflect early host pathogen interactions that may contribute to sterilization, the development of latent M.tb infection, or progression to active disease. Studies in these persons may allow the identification of biomarkers of protective immunity before the initiation of inflammatory and disease-associated immunopathological changes. In healthy close contacts of patients with tuberculosis (TB) and during active pulmonary TB, immune responses are compartmentalized to the lungs and characterized by an exuberant helper T-cell type 1 response, which as suggested by recent evidence is counteracted by local suppressive immune mechanisms. Here we discuss how exploring human lung immunity may provide insights into disease progression and mechanisms of failure of immunological protection at the site of the initial host-pathogen interaction. These findings may also aid in the identification of new biomarkers of protective immunity that are urgently needed for the development of new and the improvement of current TB vaccines, adjuvant immunotherapies, and diagnostic technologies. To facilitate further work in this area, methodological and procedural approaches for bronchoalveolar lavage studies and their limitations are also discussed.
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High incidence of hospital admissions with multidrug-resistant and extensively drug-resistant tuberculosis among South African health care workers.
Ann. Intern. Med.
PUBLISHED: 10-20-2010
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Nosocomial transmission has been described in extensively drug-resistant tuberculosis (XDR-TB) and HIV co-infected patients in South Africa. However, little is known about the rates of drug-resistant tuberculosis among health care workers in countries with high tuberculosis and HIV burden.
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Comparison of a clinical prediction rule and a LAM antigen-detection assay for the rapid diagnosis of TBM in a high HIV prevalence setting.
PLoS ONE
PUBLISHED: 09-30-2010
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The diagnosis of tuberculous meningitis (TBM) in resource poor TB endemic environments is challenging. The accuracy of current tools for the rapid diagnosis of TBM is suboptimal. We sought to develop a clinical-prediction rule for the diagnosis of TBM in a high HIV prevalence setting, and to compare performance outcomes to conventional diagnostic modalities and a novel lipoarabinomannan (LAM) antigen detection test (Clearview-TB®) using cerebrospinal fluid (CSF).
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Extensively drug-resistant tuberculosis (XDR-TB) among health care workers in South Africa.
Trop. Med. Int. Health
PUBLISHED: 09-14-2010
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To determine the clinical profile and outcomes of health care workers (HCWs) with extensively drug resistant tuberculosis (XDR-TB) in the Eastern and Western Cape Provinces of South Africa.
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Extensively drug-resistant tuberculosis: epidemiology and management challenges.
Infect. Dis. Clin. North Am.
PUBLISHED: 08-03-2010
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Widespread global use of rifampin for 2 decades preceded the emergence of clinically significant multidrug-resistant tuberculosis (MDR-TB) in the early 1990s. The prevalence of MDR-TB has gradually increased such that it accounts for approximately 5% of the global case burden of disease (approximately half a million cases in 2007). Eclipsing this worrying trend is the widespread emergence of extensively drug-resistant TB (XDR-TB). This article reviews the insights provided by clinical and molecular epidemiology regarding global trends and transmission dynamics of XDR-TB, and the challenges clinicians have to face in diagnosing and managing cases of XDR-TB. The ethical and management dilemmas posed by recurrent defaulters, XDR-TB treatment failures, and isolation of incurable patients are also discussed. Given the past global trends in MDR-TB, if aggressive preventive and management strategies are not implemented, XDR-TB has the potential to severely cripple global control efforts of TB.
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Review of multidrug-resistant and extensively drug-resistant TB: global perspectives with a focus on sub-Saharan Africa.
Trop. Med. Int. Health
PUBLISHED: 06-10-2010
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Tuberculosis (TB) remains a global emergency and is responsible for 1.7 million deaths annually. Widespread global misuse of isoniazid and rifampicin over three decades has resulted in emergence of the ominous spread of multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) globally. These difficult to treat resistant forms of TB are increasingly seen in Asia, Eastern Europe, South America and sub-Saharan Africa, disrupting TB and HIV control programmes. We review the latest available global epidemiological and clinical evidence on drug-resistant TB in HIV-infected and uninfected populations, with focus on Africa where data are scanty because of poor diagnostic and reporting facilities. The difficult management and infection control problems posed by drug-resistant TB in HIV-infected patients are discussed. Given the increasing current global trends in MDR-TB, aggressive preventive and management strategies are urgently required to avoid disruption of global TB control efforts. The data suggest that existing interventions, public health systems and TB and HIV programmes must be strengthened significantly. Political and funder commitment is essential to curb the spread of drug-resistant TB.
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Early treatment outcomes and HIV status of patients with extensively drug-resistant tuberculosis in South Africa: a retrospective cohort study.
Lancet
PUBLISHED: 05-22-2010
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Data from Kwazulu Natal, South Africa, suggest that almost all patients with extensively drug-resistant (XDR) tuberculosis are HIV-positive, with a fatal outcome. Since, there are few data for the treatment-related outcomes of XDR tuberculosis in settings with a high HIV prevalence, we investigated the associations of these diseases in such settings to formulate recommendations for control programmes.
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Multidrug-resistant and extensively drug-resistant tuberculosis: a threat to global control of tuberculosis.
Lancet
PUBLISHED: 05-22-2010
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Although progress has been made to reduce global incidence of drug-susceptible tuberculosis, the emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis during the past decade threatens to undermine these advances. However, countries are responding far too slowly. Of the estimated 440,000 cases of MDR tuberculosis that occurred in 2008, only 7% were identified and reported to WHO. Of these cases, only a fifth were treated according to WHO standards. Although treatment of MDR and XDR tuberculosis is possible with currently available diagnostic techniques and drugs, the treatment course is substantially more costly and laborious than for drug-susceptible tuberculosis, with higher rates of treatment failure and mortality. Nonetheless, a few countries provide examples of how existing technologies can be used to reverse the epidemic of MDR tuberculosis within a decade. Major improvements in laboratory capacity, infection control, performance of tuberculosis control programmes, and treatment regimens for both drug-susceptible and drug-resistant disease will be needed, together with a massive scale-up in diagnosis and treatment of MDR and XDR tuberculosis to prevent drug-resistant strains from becoming the dominant form of tuberculosis. New diagnostic tests and drugs are likely to become available during the next few years and should accelerate control of MDR and XDR tuberculosis. Equally important, especially in the highest-burden countries of India, China, and Russia, will be a commitment to tuberculosis control including improvements in national policies and health systems that remove financial barriers to treatment, encourage rational drug use, and create the infrastructure necessary to manage MDR tuberculosis on a national scale.
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Cerebrospinal T-cell responses aid in the diagnosis of tuberculous meningitis in a human immunodeficiency virus- and tuberculosis-endemic population.
Am. J. Respir. Crit. Care Med.
PUBLISHED: 05-04-2010
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Current tools for the rapid diagnosis of tuberculous meningitis (TBM) are suboptimal. We evaluated the clinical utility of a quantitative RD-1 IFN-gamma T-cell enzyme-linked immunospot (ELISPOT) assay (T-SPOT.TB), using cerebrospinal fluid cells for the rapid immunodiagnosis of TBM.
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The immunology of tuberculosis: from bench to bedside.
Respirology
PUBLISHED: 04-27-2010
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Tuberculosis (TB) is an international public health priority and kills almost two million people annually. TB is out of control in Africa due to increasing poverty and HIV coinfection, and drug-resistant TB threatens to destabilize TB control efforts in several regions of the world. Existing diagnostic tools and therapeutic interventions for TB are suboptimal. Thus, new vaccines, immunotherapeutic interventions and diagnostic tools are urgently required to facilitate TB control efforts. An improved understanding of the immunopathogenesis of TB can facilitate the identification of correlates of immune protection, the design of effective vaccines, the rational selection of immunotherapeutic agents, the evaluation of new drug candidates, and drive the development of new immunodiagnostic tools. Here we review the immunology of TB with a focus on aspects that are clinically and therapeutically relevant. An immunologically orientated approach to tackling TB can only succeed with concurrent efforts to alleviate poverty and reduce the global burden of HIV.
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Urine for the diagnosis of tuberculosis: current approaches, clinical applicability, and new developments.
Curr Opin Pulm Med
PUBLISHED: 04-09-2010
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Urine is increasingly being investigated as a convenient clinical sample for the identification of mycobacterial products for the diagnosis of tuberculosis. The available literature on mycobacterial lipoarabinomannan (LAM) and urine mycobacterial DNA is reviewed.
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Feasibility and diagnostic utility of antigen-specific interferon-gamma responses for rapid immunodiagnosis of tuberculosis using induced sputum.
PLoS ONE
PUBLISHED: 03-23-2010
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The diagnosis of smear-negative or sputum-scarce tuberculosis (TB) is problematic as culture takes several weeks and representative biological samples are difficult to obtain. RD-1 antigen-specific interferon-gamma release assays (IGRAs) are sensitive and specific blood-based tests for the diagnosis of M. tuberculosis infection. The feasibility and diagnostic utility of this rapid immunodiagnostic assay, using cells from induced sputum, is unknown.
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Different screening strategies (single or dual) for the diagnosis of suspected latent tuberculosis: a cost effectiveness analysis.
BMC Pulm Med
PUBLISHED: 02-22-2010
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Previous health economic studies recommend either a dual screening strategy [tuberculin skin test (TST) followed by interferon-gamma-release assay (IGRA)] or a single one [IGRA only] for latent tuberculosis infection (LTBI), the former largely based on claims that it is more cost-effective. We sought to examine that conclusion through the use of a model that accounts for the additional costs of adverse drug reactions and directly compares two commercially available versions of the IGRA: the Quantiferon-TB-Gold-In-Tube (QFT-GIT) and T-SPOT.TB.
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Tuberculosis in association with HIV/AIDS emerges as a major nonobstetric cause of maternal mortality in Sub-Saharan Africa.
Int J Gynaecol Obstet
PUBLISHED: 01-13-2010
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Every year, approximately 250,000 African women die during pregnancy, delivery, or the puerperium. Maternal mortality rates due to infectious diseases in Sub-Saharan Africa now supersede mortality from obstetric causes. Evidence is accumulating that tuberculosis associated with HIV/AIDS, malaria, sepsis, and other opportunistic infections are the main infectious causes of maternal deaths. Screening for these killer infections within prenatal healthcare programs is essential at this stage to prevent and treat causes of maternal mortality. The combination of proven effective interventions that avert the greatest number of maternal deaths should be prioritized and expanded to cover the greatest number of women at risk, and incorporated into a "prophylaxis and treatment community package of care." The effectiveness of these "packages of care" will need to be determined subsequently. Maternal deaths from tuberculosis are now on the increase in the UK, and due diligence and watchful surveillance are required in European prenatal services.
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Clinical utility of a commercial LAM-ELISA assay for TB diagnosis in HIV-infected patients using urine and sputum samples.
PLoS ONE
PUBLISHED: 01-11-2010
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The accurate diagnosis of TB in HIV-infected patients, particularly with advanced immunosuppression, is difficult. Recent studies indicate that a lipoarabinomannan (LAM) assay (Clearview-TB(R)-ELISA) may have some utility for the diagnosis of TB in HIV-infected patients; however, the precise subgroup that may benefit from this technology requires clarification. The utility of LAM in sputum samples has, hitherto, not been evaluated.
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Multidrug- and extensively drug-resistant tuberculosis in Africa and South America: epidemiology, diagnosis and management in adults and children.
Clin. Chest Med.
PUBLISHED: 11-21-2009
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Available data show that Africa, together with the Americas and western and central Europe, reported the lowest prevalence of multidrug-resistant tuberculosis (MDR-TB). However, sub-Saharan Africa has a high TB incidence and the highest human immunodeficiency virus (HIV) prevalence in the world, and because of the high number of TB cases, Africa still presents 14% of the global burden of new MDR-TB cases. Until recently, Africa and South America were deprived of second-line antituberculosis drugs, preventing the development of extensively drug-resistant TB (XDR-TB). Current efforts, introducing improved laboratory infrastructure and second-line TB treatment in resource-limited countries, need to be carried out with care to minimize the development of MDR/XDR-TB in these countries. Recent diagnostic developments now need evaluation and implementation in resource-limited areas, and delays in diagnosis also need to be addressed. Outcomes for MDR/XDR-TB have improved, but prevention of MDR/XDR-TB by early diagnosis and treatment, improvement of adherence, and proper infection control remains the mainstay for the future.
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Within-subject variability of interferon-g assay results for tuberculosis and boosting effect of tuberculin skin testing: a systematic review.
PLoS ONE
PUBLISHED: 10-07-2009
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Variability in interferon-gamma release assays (IGRAs) results for tuberculosis has implications for interpretation of results close to the cut-point, and for defining thresholds for test conversion and reversion. However, little is known about the within-subject variability (reproducibility) of IGRAs. Several national guidelines recommend a two-step testing procedure (tuberculin skin test [TST] followed by IGRA) for the diagnosis of LTBI. However, the effect of a preceding TST on subsequent IGRA results has been reported in studies with apparently conflicting results.
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HIV-1 infection impairs the bronchoalveolar T-cell response to mycobacteria.
Am. J. Respir. Crit. Care Med.
PUBLISHED: 09-24-2009
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The risk of developing active tuberculosis in persons with latent Mycobacterium tuberculosis infection is substantially increased shortly after HIV-1 seroconversion. Immune responses in the lung are important to restrict the growth of M. tuberculosis to prevent the development of disease.
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TB diagnostic tests: how do we figure out their costs?
Expert Rev Anti Infect Ther
PUBLISHED: 08-18-2009
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Tuberculosis continues to be a major global health problem. Lack of accurate, rapid and cost-effective diagnostic tests poses a huge obstacle to global TB control. While several new diagnostic tools are being developed and evaluated for TB, it is important that new tools are introduced for widespread use only after careful validation of accuracy, impact as well as cost-effectiveness in real-world settings. While there are large numbers of studies on the accuracy of TB diagnostic tests, there are few studies that are focused on cost and cost-effectiveness. There are currently no widely accepted standards on how to evaluate costs of a TB test. In this review, we describe the basic approach for computing the costs of TB diagnostic tests, and provide templates for various data elements and parameters that go into the costing analysis. We hope this will pave the way for a standardized methodology for costing of TB diagnostic tests. Such a tool would enable improved and more generalizable costing analyses that can provide a strong foundation for more sophisticated economic analyses that evaluate the full economic and epidemiological impact resulting from the implementation and routine use of performance-verified new and innovative diagnostic tools. This, in turn, will facilitate evidence-based adoption and use of new diagnostics, especially in resource-limited settings.
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Utility of a novel lipoarabinomannan assay for the diagnosis of tuberculous meningitis in a resource-poor high-HIV prevalence setting.
Cerebrospinal Fluid Res
PUBLISHED: 07-03-2009
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In Africa, tuberculous meningitis (TBM) is an important opportunistic infection in HIV-positive patients. Current diagnostic tools for TBM perform sub-optimally. In particular, the rapid diagnosis of TBM is challenging because smear microscopy has a low yield and PCR is not widely available in resource-poor settings.
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T-cell interferon-gamma release assays for the rapid immunodiagnosis of tuberculosis: clinical utility in high-burden vs. low-burden settings.
Curr Opin Pulm Med
PUBLISHED: 04-24-2009
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The utility of T-cell interferon-gamma (IFN-gamma) responses to Mycobacterium tuberculosis specific antigens [interferon-gamma release assays (IGRAs)] in high-burden settings remains unclear and there is growing evidence that IGRA performance varies across high tuberculosis (TB) burden vs. low TB burden settings. Here we review the evidence supporting the utility of IGRAs in specific subgroups and compare their performance in high-burden vs. low-burden settings.
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Within-subject variability and boosting of T-cell interferon-gamma responses after tuberculin skin testing.
Am. J. Respir. Crit. Care Med.
PUBLISHED: 04-02-2009
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The optimal strategy for the diagnosis of latent tuberculosis infection is controversial. Adoption of a two-step strategy (tuberculin skin test [TST] followed by an IFN-gamma release assay [IGRA], compared with an IGRA alone), may be limited by TST-mediated boosting of subsequent IGRA responses. Assessment of within-subject IGRA variability will aid in establishing thresholds for conversions and reversions, and interpretation of serial testing results.
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Clinical diagnostic utility of IP-10 and LAM antigen levels for the diagnosis of tuberculous pleural effusions in a high burden setting.
PLoS ONE
PUBLISHED: 01-23-2009
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Current tools for the diagnosis of tuberculosis pleural effusions are sub-optimal. Data about the value of new diagnostic technologies are limited, particularly, in high burden settings. Preliminary case control studies have identified IFN-gamma-inducible-10 kDa protein (IP-10) as a promising diagnostic marker; however, its diagnostic utility in a day-to-day clinical setting is unclear. Detection of LAM antigen has not previously been evaluated in pleural fluid.
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ICU-associated Acinetobacter baumannii colonisation/infection in a high HIV-prevalence resource-poor setting.
PLoS ONE
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There are hardly any data about the incidence, risk factors and outcomes of ICU-associated A.baumannii colonisation/infection in HIV-infected and uninfected persons from resource-poor settings like Africa.
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Scoring systems using chest radiographic features for the diagnosis of pulmonary tuberculosis in adults: a systematic review.
Eur. Respir. J.
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Chest radiography for the diagnosis of active pulmonary tuberculosis (PTB) is limited by poor specificity and reader inconsistency. Scoring systems have been employed successfully for improving the performance of chest radiography for various pulmonary diseases. We conducted a systematic review to assess the diagnostic accuracy and reproducibility of scoring systems for PTB. We searched multiple databases for studies that evaluated the accuracy and reproducibility of chest radiograph scoring systems for PTB. We summarised results for specific radiographic features and scoring systems associated with PTB. Where appropriate, we estimated pooled performance of similar studies using a random effects model. 13 studies were included in the review, nine of which were in low tuberculosis (TB) burden settings. No scoring system was based solely on radiographic findings. All studies used systems with various combinations of clinical and radiological features. 11 studies involved scoring systems that were used for making decisions concerning hospital respiratory isolation. None of the included studies reported data on intra- or inter-reporter reproducibility. Upper lobe infiltrates (pooled diagnostic OR 3.57, 95% CI 2.38-5.37, five studies) and cavities (diagnostic OR range 1.97-25.66, three studies) were significantly associated with PTB. Sensitivities of the scoring systems were high (median 96%, IQR 93-98%), but specificities were low (median 46%, IQR 35-50%). Chest radiograph scoring systems appear useful in ruling out PTB in hospitals, but their low specificity precludes ruling in PTB. There is a need to develop accurate scoring systems for people living with HIV and for outpatient settings, especially in high TB burden settings.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.