Accuracy of upper respiratory tract samples to diagnose Mycobacterium tuberculosis: a systematic review and meta-analysis

Savage, H., Rickman, H. M., Burke, R. M., Odland, M. L., Savio, M., Ringwald, B., Cuevas, L. E. and MacPherson, P. (2023) Accuracy of upper respiratory tract samples to diagnose Mycobacterium tuberculosis: a systematic review and meta-analysis. Lancet Microbe, 4(10), e811-e821. (doi: 10.1016/S2666-5247(23)00190-8) (PMID:37714173) (PMCID:PMC10547599)

Abstract

Background: Pulmonary tuberculosis due to Mycobacterium tuberculosis can be challenging to diagnose when sputum samples cannot be obtained, which is especially problematic in children and older people. We systematically appraised the performance characteristics and diagnostic accuracy of upper respiratory tract sampling for diagnosing active pulmonary tuberculosis. Methods: In this systematic review and meta-analysis, we searched MEDLINE, Cinahl, Web of Science, Global Health, and Global Health Archive databases for studies published between database inception and Dec 6, 2022 that reported on the accuracy of upper respiratory tract sampling for tuberculosis diagnosis compared with microbiological testing of sputum or gastric aspirate reference standard. We included studies that evaluated the accuracy of upper respiratory tract sampling (laryngeal swabs, nasopharyngeal aspirate, oral swabs, saliva, mouth wash, nasal swabs, plaque samples, and nasopharyngeal swabs) to be tested for microbiological diagnosis of tuberculous (by culture and nucleic acid amplification tests) compared with a reference standard using either sputum or gastric lavage for a microbiological test. We included cohort, case-control, cross-sectional, and randomised controlled studies that recruited participants from any community or clinical setting. We excluded post-mortem studies. We used a random-effects meta-analysis with a bivariate hierarchical model to estimate pooled sensitivity, specificity, and diagnostics odds ratio (DOR; odds of a positive test with disease relative to without), stratified by sampling method. We assessed bias using QUADAS-2 criteria. This study is registered with PROSPERO (CRD42021262392). Findings: We screened 10 159 titles for inclusion, reviewed 274 full texts, and included 71, comprising 119 test comparisons published between May 13, 1933, and Dec 19, 2022, in the systematic review (53 in the meta-analysis). For laryngeal swabs, pooled sensitivity was 57·8% (95% CI 50·5–65·0), specificity was 93·8% (88·4–96·8), and DOR was 20·7 (11·1–38·8). Nasopharyngeal aspirate sensitivity was 65·2% (52·0–76·4), specificity was 97·9% (96·0–99·0), and DOR was 91·0 (37·8–218·8). Oral swabs sensitivity was 56·7% (44·3–68·2), specificity was 91·3% (CI 81·0–96·3), and DOR was 13·8 (5·6–34·0). Substantial heterogeneity in diagnostic accuracy was found, probably due to differences in reference and index standards. Interpretation: Upper respiratory tract sampling holds promise to expand access to tuberculosis diagnosis. Exploring historical methods using modern microbiological techniques might further increase options for alternative sample types. Prospective studies are needed to optimise accuracy and utility of sampling methods in clinical practice. Funding: UK Medical Research Council, Wellcome, and UK Foreign, Commonwealth and Development Office.

• Item Type: Articles
• Additional Information: This research was funded in whole, or in part, by Wellcome (200901/Z/16/Z); was supported by UK Foreign, Commonwealth and Development Office (“Leaving no-one behind: transforming gendered pathways to health for TB”); and partially funded by the UK National Institute for Health Research (16/136/35) using UK aid from the UK Government to MS, BR, LEC, and PMP. HRS is funded by the UK Medical Research Council through the Medical Research Council Doctoral Training Partnership programme at Liverpool School of Tropical Medicine (MR/N013514/1). RMB and HMR are supported by Wellcome PhD fellowships (203905/Z/16/Z and 225482/Z/22/Z). The views expressed do not necessarily reflect the UK Government's official policies.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: MacPherson, Professor Peter
• Authors: Savage, H., Rickman, H. M., Burke, R. M., Odland, M. L., Savio, M., Ringwald, B., Cuevas, L. E., and MacPherson, P.
• College/School: College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Public Health
• Journal Name: Lancet Microbe
• Publisher: Elsevier
• ISSN: 2666-5247
• ISSN (Online): 2666-5247
• Published Online: 12 September 2023
• Copyright Holders: Copyright © 2023 The Author(s).
• First Published: First published in Lancet Microbe 4(10):e811-e821
• Publisher Policy: Reproduced under a Creative Commons license