Acute phase proteins and IP-10 as triage tests for the diagnosis of tuberculosis: systematic review and meta-analysis

V. S. Santos, D. Goletti, K. Kontogianni, E. R. Adams, B. Molina-Moya, J. Dominguez, V. Crudu, P. R.S. Martins-Filho, M. Ruhwald, L. Lawson, J. S. Bimba, A. L. Garcia-Basteiro, L. Petrone, B. S. Kabeer, K. Reither, L. E. Cuevas

Research output: Contribution to journalArticle


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.

Original languageEnglish
JournalClinical Microbiology and Infection
Publication statusE-pub ahead of print - Aug 1 2018


  • Acute phase proteins
  • IP-10
  • screening
  • systematic review
  • tuberculosis

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

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