Prognostic Performance of C-Reactive Protein for Tuberculosis Outcome: Protocol for a Systematic Review and Meta-Analysis.

Abstract

Tuberculosis (TB) remains a major global health challenge, with substantial mortality despite the availability of standardized treatment regimens. Accurate prognostication remains difficult, as no host-derived biomarker is routinely used to predict TB outcomes. C-reactive protein (CRP), a widely available acute-phase reactant, has been proposed as a potential prognostic biomarker, but its prognostic value for mortality in TB has not been systematically synthesized. This systematic review and meta-analysis aimed to evaluate the prognostic value of baseline CRP in predicting mortality among adult patients with TB and to examine whether the reported association varies across relevant clinical subgroups and study characteristics. This protocol was developed in accordance with PRISMA-P (Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols) guidelines. Eligible studies included full-text English-language cohort studies, observational studies, case-control studies, and control arms of randomized controlled trials involving adults (aged 18 years and older) with microbiologically confirmed pulmonary or extrapulmonary TB. Included studies were required to assess baseline CRP at or near the time of TB diagnosis and to report mortality using quantitative effect estimates such as hazard ratios, odds ratios, or risk ratios. Studies limited to pediatric or latent TB populations and nonoriginal publication types were excluded. The literature search was conducted in the Cochrane Library, PubMed, Scopus, MEDLINE via Ovid, ProQuest, and medRxiv. Risk of bias was assessed using the QUIPS (Quality in Prognosis Studies) tool, and certainty of evidence was assessed using GRADE (Grading of Recommendations Assessment, Development, and Evaluation). A structured qualitative synthesis was undertaken for all included studies, and a random-effects meta-analysis was performed where studies were sufficiently comparable. The protocol was prospectively registered in PROSPERO (CRD420251101984) in July 2025. The electronic search covered the period from database inception to June 30, 2025, and was conducted from July 10, 2025, to July 14, 2025. Screening, full-text assessment, data extraction, methodological appraisal, and evidence synthesis were completed. A full manuscript reporting the findings of the completed systematic review and meta-analysis was subsequently prepared. This protocol provides a transparent record of the rationale, objectives, and methodological approach used to evaluate CRP as a prognostic biomarker for TB mortality. The completed review is expected to inform the interpretation of CRP in TB care, identify evidence gaps, and guide future prognostic research.