| Autor: |
Zimmer AJ; Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada.; McGill International TB Centre, Montreal, Canada., Lainati F; Division of Clinical Tropical Medicine, Center of Infectious Diseases, Heidelberg University Hospital, Heidelberg, Germany., Aguilera Vasquez N; McGill International TB Centre, Montreal, Canada., Chedid C; Equipe Pathogenèse des Légionnelles, Centre International de Recherche en Infectiologie, INSERM U1111, Université Claude Bernard Lyon 1, CNRS UMR5308, École Normale Supérieure de Lyon, Lyon, France.; Medical and Scientific Department, Fondation Mérieux, Lyon, France.; Département de Biologie, Ecole Normale Supérieure de Lyon, Lyon, France., McGrath S; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, USA., Benedetti A; Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada.; McGill International TB Centre, Montreal, Canada., MacLean E; Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada.; McGill International TB Centre, Montreal, Canada., Ruhwald M; FIND, Geneva, Switzerland., Denkinger CM; Division of Clinical Tropical Medicine, Center of Infectious Diseases, Heidelberg University Hospital, Heidelberg, Germany., Kohli M; Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada.; McGill International TB Centre, Montreal, Canada.; FIND, Geneva, Switzerland. |
| Abstrakt: |
Current WHO recommendations for monitoring treatment response in adult pulmonary tuberculosis (TB) are sputum smear microscopy and/or culture conversion at the end of the intensive phase of treatment. These methods either have suboptimal accuracy or a long turnaround time. There is a need to identify alternative biomarkers to monitor TB treatment response. We conducted a systematic review of active pulmonary TB treatment monitoring biomarkers. We screened 9,739 articles published between 1 January 2008 and 31 December 2020, of which 77 met the inclusion criteria. When studies quantitatively reported biomarker levels, we meta-analyzed the average fold change in biomarkers from pretreatment to week 8 of treatment. We also performed a meta-analysis pooling the fold change since the previous time point collected. A total of 81 biomarkers were identified from 77 studies. Overall, these studies exhibited extensive heterogeneity with regard to TB treatment monitoring study design and data reporting. Among the biomarkers identified, C-reactive protein (CRP), interleukin-6 (IL-6), interferon gamma-induced protein 10 (IP-10), and tumor necrosis factor alpha (TNF-α) had sufficient data to analyze fold changes. All four biomarker levels decreased during the first 8 weeks of treatment relative to baseline and relative to previous time points collected. Based on limited data available, CRP, IL-6, IP-10, and TNF-α have been identified as biomarkers that should be further explored in the context of TB treatment monitoring. The extensive heterogeneity in TB treatment monitoring study design and reporting is a major barrier to evaluating the performance of novel biomarkers and tools for this use case. Guidance for designing and reporting treatment monitoring studies is urgently needed. |
