Meta-Analysis Systematic Review Journal Article Epublish 7 citations
PubMed: 37972202 DOI: 10.1371/journal.pone.0293535
Treatment for radiographically active, sputum culture-negative pulmonary tuberculosis: A systematic review and meta-analysis.
PLoS One 18(11):e0293535
Authors: Adam Thorburn Gray, Liana Macpherson, Ffion Carlin, Bianca Sossen, Alexandra S Richards, Sandra V Kik, Rein M G J Houben, Peter MacPherson, Matteo Quartagno, Ewelina Rogozińska, Hanif Esmail
Affiliations
- Institute for Global Health, University College London, London, United Kingdom.
- MRC Clinical Trials Unit at University College London, London, United Kingdom.
- Institute for Global Health, University College London, London, United Kingdom. Infectious Diseases Unit, Liverpool Royal Hospitals NHS Foundation Trust, Liverpool, United Kingdom.
- Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
- TB Modelling Group, TB Centre, London School of Hygiene and Tropical Medicine, London, United Kingdom.
- Department of Infectious Disease Epidemiology, Faculty of Epidemiology and Public Health, London School of Hygiene and Tropical Medicine, London, United Kingdom.
- FIND, The Global Alliance for Diagnostics, Geneva, Switzerland.
- School of Health & Wellbeing, University of Glasgow, Glasgow, United Kingdom.
- Clinical Research Department, London School of Hygiene and Tropical Medicine, London, United Kingdom.
- Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
Abstract
BACKGROUND
People with radiographic evidence for pulmonary tuberculosis (TB), but negative sputum cultures, have increased risk of developing culture-positive TB. Recent expansion of X-ray screening is leading to increased identification of this group. We set out to synthesise the evidence for treatment to prevent progression to culture-positive disease.
METHODS
We conducted a systematic review and meta-analysis. We searched for prospective trials evaluating the efficacy of TB regimens against placebo, observation, or alternative regimens, for the treatment of adults and children with radiographic evidence of TB but culture-negative respiratory samples. Databases were searched up to 18 Oct 2022. Study quality was assessed using ROB 2·0 and ROBINS-I. The primary outcome was progression to culture-positive TB. Meta-analysis with a random effects model was conducted to estimate pooled efficacy. This study was registered with PROSPERO (CRD42021248486).
FINDINGS
We included 13 trials (32,568 individuals) conducted between 1955 and 2018. Radiographic and bacteriological criteria for inclusion varied. 19·1% to 57·9% of participants with active x-ray changes and no treatment progressed to culture-positive disease. Progression was reduced with any treatment (6 studies, risk ratio [RR] 0·27, 95%CI 0·13-0·56), although multi-drug TB treatment (RR 0·11, 95%CI 0·05-0·23) was significantly more effective than isoniazid treatment (RR 0·63, 95%CI 0·35-1·13) (p = 0·0002).
INTERPRETATION
Multi-drug regimens were associated with significantly reduced risk of progression to TB disease for individuals with radiographically apparent, but culture-negative TB. However, most studies were old, conducted prior to the HIV epidemic and with outdated regimens. New clinical trials are required to identify the optimal treatment approach.
MeSH
Sputum, Risk, Tuberculosis, Pulmonary, Therapeutics