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

OBJECTIVES

We examined the data reported in studies for diagnostic purposes and 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 methodological differences to explain performance variations. Summary estimates were calculated using random-effects models for overall pooled accuracy. Hierarchical Summary Receiver Operating Characteristic (HSROC) model was used for meta-analysis.

RESULTS

We identified 14, four and one studies for C-reactive protein (C-RP), Interferon-γ-induced-protein-10 (IP-10) and α-1-acid glycoprotein (A1AG). The pooled C-RP sensitivity/specificity (95%CI) was 89% (80%-96%) and 57% (36%-65%). Sensitivity/specificity were higher in high TB-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 co-infected 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. A1AG had 86%/93% sensitivity/specificity.

CONCLUSION

Few studies have evaluated C-RP, IP-10 and A1AG for the triage of symptomatic patients. Their high sensitivity and moderate specificity warrant further prospective studies exploring whether their combined use could optimise performance.