Identification and characterization of <i>Mycobacterium tuberculosis</i> antigens in urine of patients with active pulmonary tuberculosis: an innovative and alternative approach of antigen discovery of useful microbial molecules

Kashino, Suely S.; Pollock, Nira R.; Napolitano, Danielle R.; Rodrigues, Virmondés; Campos-Neto, Antônio

doi:10.1111/j.1365-2249.2008.03672.x

Cited by 50 publications

(58 citation statements)

References 27 publications

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“…The gene (Rv1681) (Institute for Genomic Research [TIGR] no. MT_1721) coding for one of these antigens, the putative molybdopterin biosynthesis protein MoeX/MoeA, is unique to the M. tuberculosis complex, and no homologues of the Rv1681 protein have been found in the available databases for other representative Mycobacterium species (7). This uniqueness suggests that this molecule could be a particularly useful tool for the diagnosis of TB.…”

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confidence: 94%

“…Urine specimens from 9 subjects with active pulmonary TB were collected as described previously (7,8).…”

Section: Clinical Specimens (I) Specimens For Antigen Identificationmentioning

confidence: 99%

“…We previously demonstrated the identification by mass spectroscopy (MS) of four M. tuberculosis antigens in the urine of patients with active pulmonary TB (7,8). The gene (Rv1681) (Institute for Genomic Research [TIGR] no.…”

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confidence: 99%

“…(i) Specimens for antigen identification and biochemical validation. (a) Brazil (antigen discovery).Urine specimens from 9 subjects with active pulmonary TB were collected as described previously (7,8).(b) Peru (Foundation for Innovative New Diagnostics) (antigen discovery). Urine specimens were first-morning specimens from untreated smear-positive TB suspects who were ultimately confirmed to have sputum culture-positive pulmonary TB.…”

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confidence: 99%

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Validation of Mycobacterium tuberculosis Rv1681 Protein as a Diagnostic Marker of Active Pulmonary Tuberculosis

Pollock

Macovei²,

Kanunfre³

et al. 2013

J Clin Microbiol

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The development of an accurate antigen detection assay for the diagnosis of active tuberculosis (TB) would represent a major clinical advance. Here, we demonstrate that the Mycobacterium tuberculosis Rv1681 protein is a biomarker for active TB with potential diagnostic utility. We initially identified, by mass spectroscopy, peptides from the Rv1681 protein in urine specimens from 4 patients with untreated active TB. Rabbit IgG anti-recombinant Rv1681 detected Rv1681 protein in lysates and culture filtrates of M. tuberculosis and immunoprecipitated it from pooled urine specimens from two TB patients. An enzyme-linked immunosorbent assay formatted with these antibodies detected Rv1681 protein in unconcentrated urine specimens from 11/25 (44%) TB patients and 1/21 (4.8%) subjects in whom TB was initially clinically suspected but then ruled out by conventional methods. Rv1681 protein was not detected in urine specimens from 10 subjects with Escherichia coli-positive urine cultures, 26 subjects with confirmed non-TB tropical diseases (11 with schistosomiasis, 5 with Chagas' disease, and 10 with cutaneous leishmaniasis), and 14 healthy subjects. These results provide strong validation of Rv1681 protein as a promising biomarker for TB diagnosis.T uberculosis (TB) remains the second most common cause of death from an infectious disease in the world. According to a 2012 World Health Organization (WHO) report, there were an estimated 8.7 million new cases of TB globally in 2011 and approximately 1.4 million TB-related deaths (430,000 of which involved HIV-positive individuals) (1). Failure to control the spread of TB is due in large part to failure to adequately detect (and thus to efficiently treat) infectious cases (2); therefore, a major focus of the WHO's global plan to stop TB (3) is the development of new simple and cost-effective diagnostic methods to improve case detection. Historically, culture of Mycobacterium tuberculosis from a clinical specimen has been the gold standard for TB diagnosis; however, it is expensive, time-consuming, and not available worldwide. Thus, in resource-limited settings, diagnosis of active TB relies primarily on clinical evaluation and, where available, microscopic evaluation of sputum specimens. Sputum smears have widely varying sensitivities in different settings (20 to 80%) and are of limited utility in paucibacillary (e.g., pediatric and HIVassociated) TB (3-5). Due to the lack of accessible and effective diagnostic methods, many patients in resource-limited settings are treated empirically based on clinical information alone, exposing some patients to unneeded and potentially toxic drugs and missing others who have active TB.The ideal diagnostic method for tuberculosis would be a lowcost, point-of-care (POC), rapid, simple, and accurate test that could distinguish individuals with active TB from those with latent disease or no infection (including Mycobacterium bovis BCGvaccinated individuals) (2, 6). We previously demonstrated the identification by mass spectroscopy (MS) of four ...

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mentioning

confidence: 94%

“…Urine specimens from 9 subjects with active pulmonary TB were collected as described previously (7,8).…”

Section: Clinical Specimens (I) Specimens For Antigen Identificationmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Validation of Mycobacterium tuberculosis Rv1681 Protein as a Diagnostic Marker of Active Pulmonary Tuberculosis

Pollock

Macovei²,

Kanunfre³

et al. 2013

J Clin Microbiol

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“…AGRANOFF et al [12] used proteomic fingerprinting of serum to look for diagnostic biomarkers that could differentiate between active TB, latent tuberculosis infection (LTBI) and no TB in HIV positive and negative patients. In another study, KASHINO et al [13] used one-dimensional LC combined with MS/MS to identify four M. tuberculosis-derived proteins in the urine of patients with pulmonary TB. A more recent follow-up urinary proteomics study found that a putative molybdopterin biosynthesis protein (Rv1681) was detected in 11 out of 21 TB patients [14].…”

Section: Introductionmentioning

confidence: 99%

The identification of tuberculosis biomarkers in human urine samples

Young

Mlamla

Gqamana

et al. 2014

European Respiratory Journal

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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 (n563) were classified as: definite TB (Mycobacterium tuberculosis positive culture, n521); 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, n524); 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, n518). 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. @ERSpublicationsThe application of proteomics for the identification of novel urinary tuberculosis biomarkers

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Lateral flow urine lipoarabinomannan assay for detecting active tuberculosis in HIV-positive adults

Shah

Hanrahan

Wang

et al. 2016

Cochrane Database of Systematic Reviews

122

118

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BackgroundRapid detection of tuberculosis (TB) among people living with human immunodeficiency virus (HIV) is a global health priority. HIV-associated TB may have different clinical presentations and is challenging to diagnose. Conventional sputum tests have reduced sensitivity in HIV-positive individuals, who have higher rates of extrapulmonary TB compared with HIV-negative individuals. The lateral flow urine lipoarabinomannan assay (LF-LAM) is a new, commercially available point-of-care test that detects lipoarabinomannan (LAM), a lipopolysaccharide present in mycobacterial cell walls, in people with active TB disease.ObjectivesTo assess the accuracy of LF-LAM for the diagnosis of active TB disease in HIV-positive adults who have signs and symptoms suggestive of TB (TB diagnosis).To assess the accuracy of LF-LAM as a screening test for active TB disease in HIV-positive adults irrespective of signs and symptoms suggestive of TB (TB screening).Search methodsWe searched the following databases without language restriction on 5 February 2015: the Cochrane Infectious Diseases Group Specialized Register; MEDLINE (PubMed,1966); EMBASE (OVID, from 1980); Science Citation Index Expanded (SCI-EXPANDED, from 1900), Conference Proceedings Citation Index-Science (CPCI-S, from 1900), and BIOSIS Previews (from 1926) (all three using the Web of Science platform; MEDION; LILACS (BIREME, from 1982); SCOPUS (from 1995); the metaRegister of Controlled Trials (mRCT); the search portal of the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP); and ProQuest Dissertations & Theses A&l (from 1861).Selection criteriaEligible study types included randomized controlled trials, cross-sectional studies, and cohort studies that determined LF-LAM accuracy for TB against a microbiological reference standard (culture or nucleic acid amplification test from any body site). A higher quality reference standard was one in which two or more specimen types were evaluated for TB, and a lower quality reference standard was one in which only one specimen type was evaluated for TB. Participants were HIV-positive people aged 15 years and older.Data collection and analysisTwo review authors independently extracted data from each included study using a standardized form. We appraised the quality of studies using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. We evaluated the test at two different cut-offs: (grade 1 or 2, based on the reference card scale of five intensity bands). Most analyses used grade 2, the manufacturer's currently recommended cut-off for positivity. We carried out meta-analyses to estimate pooled sensitivity and specificity using a bivariate random-effects model and estimated the models using a Bayesian approach. We determined accuracy of LF-LAM combined with sputum microscopy or Xpert® MTB/RIF. In addition, we explored the influence of CD4 count on the accuracy estimates. We assessed the quality of the evidence using the Grading of Recommendations Assessment, Development and...

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Identification and characterization of Mycobacterium tuberculosis antigens in urine of patients with active pulmonary tuberculosis: an innovative and alternative approach of antigen discovery of useful microbial molecules

Cited by 50 publications

References 27 publications

Validation of Mycobacterium tuberculosis Rv1681 Protein as a Diagnostic Marker of Active Pulmonary Tuberculosis

Validation of Mycobacterium tuberculosis Rv1681 Protein as a Diagnostic Marker of Active Pulmonary Tuberculosis

The identification of tuberculosis biomarkers in human urine samples

Lateral flow urine lipoarabinomannan assay for detecting active tuberculosis in HIV-positive adults

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