Biomarkers That Correlate with Active Pulmonary Tuberculosis Treatment Response: a Systematic Review and...

Area of Science:

• Biomarker discovery and development
• Infectious disease diagnostics
• Tuberculosis research

Background:

• Current World Health Organization (WHO) recommendations for monitoring pulmonary tuberculosis (TB) treatment response rely on sputum smear microscopy and/or culture conversion.
• These diagnostic methods present limitations, including suboptimal accuracy and lengthy turnaround times, necessitating the identification of alternative biomarkers.
• The need for improved tools to accurately and efficiently monitor TB treatment response is critical for patient outcomes.

Purpose of the Study:

• To conduct a systematic review to identify and evaluate potential biomarkers for monitoring active pulmonary TB treatment response.
• To analyze available data on identified biomarkers, focusing on changes in levels during the initial phase of TB treatment.
• To highlight promising biomarkers for further investigation and address challenges in current TB treatment monitoring research.

Main Methods:

• Systematic review of 9,739 articles published between January 1, 2008, and December 31, 2020, focusing on active pulmonary TB treatment monitoring biomarkers.
• Inclusion of 77 studies meeting specific criteria, with meta-analysis of biomarker fold changes from pre-treatment to week 8, and between time points.
• Identification and quantitative analysis of 81 biomarkers, with a focus on C-reactive protein (CRP), interleukin-6 (IL-6), interferon gamma-induced protein 10 (IP-10), and tumor necrosis factor alpha (TNF-α).

Main Results:

• A total of 81 biomarkers were identified across 77 studies, revealing significant heterogeneity in study design and data reporting.
• C-reactive protein (CRP), interleukin-6 (IL-6), interferon gamma-induced protein 10 (IP-10), and tumor necrosis factor alpha (TNF-α) showed sufficient data for meta-analysis.
• All four analyzed biomarkers (CRP, IL-6, IP-10, TNF-α) demonstrated decreased levels during the first 8 weeks of TB treatment, indicating potential as monitoring indicators.

Conclusions:

• C-reactive protein (CRP), interleukin-6 (IL-6), interferon gamma-induced protein 10 (IP-10), and tumor necrosis factor alpha (TNF-α) are promising biomarkers that warrant further exploration for TB treatment monitoring.
• Significant heterogeneity in study design and reporting poses a major challenge for evaluating novel TB biomarkers.
• Standardized guidance for designing and reporting TB treatment monitoring studies is urgently needed to advance biomarker validation and clinical application.