Treatment for radiographically active, sputum culture-negative pulmonary tuberculosis: a systematic review and meta-analysis

Thorburn Gray, A. et al. (2023) Treatment for radiographically active, sputum culture-negative pulmonary tuberculosis: a systematic review and meta-analysis. PLoS ONE, 18(11), e0293535. (doi: 10.1371/journal.pone.0293535) (PMID:37972202) (PMCID:PMC10653609)

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 However, most studies were old, conducted prior to the HIV epidemic and with outdated regimens.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.

• Item Type: Articles
• Additional Information: This work was funded by an MRC grant (MR/V00476X/1) awarded to HE. HE, ER and MQ are partially supported through MRC unit grants (MC UU 00004/04, MC UU 00004/06, MC UU 00004/07, and MC UU 00004/09). RMGJH and ASR were funded by the European Research Council (Action number 757699). ASR was also supported by the UK FCDO (Leaving no-one behind: transforming gendered pathways to health for TB). This research has been partially funded by UK aid from the UK government (to ASR); however the views expressed do not necessarily reflect the UK government’s official policies. SVK is affiliated with FIND. FIND conducts multiple clinical research projects to evaluate new diagnostic tests against published target product profiles that have been defined through consensus processes. These include studies of diagnostic products developed by private sector companies who provide access to know-how, equipment/reagents, and may contribute through unrestricted donations according to FIND policies and in line with guidance from the organisation’s external scientific advisory council. PM is funded by Wellcome (206575/Z/17/Z). For the purpose of open access, the authors have applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: MacPherson, Professor Peter

Creator Roles

MacPherson, P.: Conceptualization, Writing – review and editing

• Authors: Thorburn Gray, A., Macpherson, L., Carlin, F., Sossen, B., Richards, A. S., Kik, S. V., Houben, R. M. G. J., MacPherson, P., Quartagno, M., Rogozińska, E., and Esmail, H.
• College/School: College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Public Health
• Journal Name: PLoS ONE
• Publisher: Public Library of Science
• ISSN: 1932-6203
• ISSN (Online): 1932-6203
• Published Online: 16 November 2023
• Copyright Holders: Copyright © 2023 Gray et al.
• First Published: First published in PLoS ONE 18(11):e0293535
• Publisher Policy: Reproduced under a Creative Commons license