V S Santos1, D Goletti2, K Kontogianni3, E R Adams3, B Molina-Moya4, J Dominguez4, V Crudu5, P R S Martins-Filho6, M Ruhwald7, L Lawson8, J S Bimba8, A L Garcia-Basteiro9, L Petrone2, B S Kabeer2, K Reither10, L E Cuevas11. 1. Centre for Epidemiology and Public Health, Federal University of Alagoas, Arapiraca, Brazil. 2. Department of Clinical and Clinical Research, 'L. Spallanzani' National Institute for Infectious Diseases (INMI), IRCCS, Rome, Italy. 3. Liverpool School of Tropical Medicine, Liverpool, United Kingdom. 4. Servei de Microbiologia, Hospital Universitari Germans Trias i Pujol, Institut d'Investigació Germans Trias i Pujol, Universitat Autònoma de Barcelona, Carretera del Canyet s/n, 08916, Badalona, Spain. 5. National TB Reference Laboratory, Phthisiopneumology Institute 'Chiril Draganiuc,' Chişinău, Republic of Moldova. 6. Investigative Pathology Laboratory, Federal University of Sergipe, Aracaju, Brazil. 7. Center for Vaccine Research, Statens Serum Institut, Copenhagen, Denmark. 8. Zankli Research Laboratory, Bingham University, Nassarawa State, Nigeria. 9. Centro de Investigação em Saude de Manhiça (CISM), Rua 12, Cambeve CP 1929, Maputo, Mozambique; Amsterdam Institute for Global Health (AIGHD), Amsterdam, The Netherlands; Barcelona Institute for Global Health (ISGLobal), Barcelona, Spain. 10. Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland. 11. Liverpool School of Tropical Medicine, Liverpool, United Kingdom. Electronic address: luis.cuevas@lstmed.ac.uk.
Abstract
OBJECTIVES: We examined the data reported in studies for diagnostic purposes and to discuss whether their intended use could be extended to triage, as rule-in or rule-out tests to select individuals who should undergo further confirmatory tests. METHODS: We searched Scopus, PubMed and Web of Science with the terms 'acute phase proteins,' 'IP-10,' 'tuberculosis,' 'screening' and 'diagnosis,' extracted the sensitivity and specificity of the biomarkers and explored methodologic differences to explain performance variations. Summary estimates were calculated using random-effects models for overall pooled accuracy. The hierarchical summary receiver operating characteristic model was used for meta-analysis. RESULTS: We identified 14, four and one studies for C-reactive protein (CRP), interferon γ-induced protein 10 (IP-10) and alpha-1-acid glycoprotein (AGP). The pooled CRP sensitivity/specificity (95% confidence interval) was 89% (80-96) and 57% (36-65). Sensitivity/specificity were higher in high-tuberculosis-burden countries (90%/64%), HIV-infected individuals (91%/61%) and community-based studies (90%/62%). IP-10 sensitivity/specificity in TB vs. non-TB studies was 85%/63% and in TB and HIV coinfected vs. other lung conditions 94%/21%. However, IP-10 studies included diverse populations and a high risk of bias, resulting in very low-quality evidence. AGP had 86%/93% sensitivity/specificity. CONCLUSIONS: Few studies have evaluated CRP, IP-10 and AGP for the triage of symptomatic patients. Their high sensitivity and moderate specificity warrant further prospective studies exploring whether their combined use could optimize performance.
OBJECTIVES: We examined the data reported in studies for diagnostic purposes and to discuss whether their intended use could be extended to triage, as rule-in or rule-out tests to select individuals who should undergo further confirmatory tests. METHODS: We searched Scopus, PubMed and Web of Science with the terms 'acute phase proteins,' 'IP-10,' 'tuberculosis,' 'screening' and 'diagnosis,' extracted the sensitivity and specificity of the biomarkers and explored methodologic differences to explain performance variations. Summary estimates were calculated using random-effects models for overall pooled accuracy. The hierarchical summary receiver operating characteristic model was used for meta-analysis. RESULTS: We identified 14, four and one studies for C-reactive protein (CRP), interferon γ-induced protein 10 (IP-10) and alpha-1-acid glycoprotein (AGP). The pooled CRP sensitivity/specificity (95% confidence interval) was 89% (80-96) and 57% (36-65). Sensitivity/specificity were higher in high-tuberculosis-burden countries (90%/64%), HIV-infected individuals (91%/61%) and community-based studies (90%/62%). IP-10 sensitivity/specificity in TB vs. non-TB studies was 85%/63% and in TB and HIV coinfected vs. other lung conditions 94%/21%. However, IP-10 studies included diverse populations and a high risk of bias, resulting in very low-quality evidence. AGP had 86%/93% sensitivity/specificity. CONCLUSIONS: Few studies have evaluated CRP, IP-10 and AGP for the triage of symptomatic patients. Their high sensitivity and moderate specificity warrant further prospective studies exploring whether their combined use could optimize performance.
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