Discriminating Active from Latent Tuberculosis in Patients Presenting to Community Clinics
Open Access
- 30 May 2012
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 7 (5) , e38080
Abstract
Because of the high global prevalence of latent TB infection (LTBI), a key challenge in endemic settings is distinguishing patients with active TB from patients with overlapping clinical symptoms without active TB but with co-existing LTBI. Current methods are insufficiently accurate. Plasma proteomic fingerprinting can resolve this difficulty by providing a molecular snapshot defining disease state that can be used to develop point-of-care diagnostics. Plasma and clinical data were obtained prospectively from patients attending community TB clinics in Peru and from household contacts. Plasma was subjected to high-throughput proteomic profiling by mass spectrometry. Statistical pattern recognition methods were used to define mass spectral patterns that distinguished patients with active TB from symptomatic controls with or without LTBI. 156 patients with active TB and 110 symptomatic controls (patients with respiratory symptoms without active TB) were investigated. Active TB patients were distinguishable from undifferentiated symptomatic controls with accuracy of 87% (sensitivity 84%, specificity 90%), from symptomatic controls with LTBI (accuracy of 87%, sensitivity 89%, specificity 82%) and from symptomatic controls without LTBI (accuracy 90%, sensitivity 90%, specificity 92%). We show that active TB can be distinguished accurately from LTBI in symptomatic clinic attenders using a plasma proteomic fingerprint. Translation of biomarkers derived from this study into a robust and affordable point-of-care format will have significant implications for recognition and control of active TB in high prevalence settings.Keywords
This publication has 28 references indexed in Scilit:
- Role of QuantiFERON-TB Gold, Interferon Gamma Inducible Protein-10 and Tuberculin Skin Test in Active Tuberculosis DiagnosisPLOS ONE, 2010
- A Recipe for Proteomics Diagnostic Test Development: The OVA1 Test, from Biomarker Discovery to FDA ClearanceClinical Chemistry, 2010
- The spectrum of latent tuberculosis: rethinking the biology and intervention strategiesNature Reviews Microbiology, 2009
- Biomarkers for tuberculosis disease activity, cure, and relapseThe Lancet Infectious Diseases, 2009
- Potential Biomarkers of Acute Cerebral Infarction Detected by SELDI-TOF-MSAmerican Journal of Clinical Pathology, 2008
- Predicting left ventricular remodeling after a first myocardial infarction by plasma proteome analysisProteomics, 2008
- Eliminating human tuberculosis in the twenty-first centuryJournal of The Royal Society Interface, 2007
- Commercial Serological Antibody Detection Tests for the Diagnosis of Pulmonary Tuberculosis: A Systematic ReviewPLOS Medicine, 2007
- Microscopic-Observation Drug-Susceptibility Assay for the Diagnosis of TBNew England Journal of Medicine, 2006
- Interferon-γ assays in the immunodiagnosis of tuberculosis: a systematic reviewThe Lancet Infectious Diseases, 2004