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

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.

How international research consortia can strengthen organisations' research systems and promote a conducive environment and culture.

Research systems and cultures have been criticised for their detrimental effect on members' mental health and well-being. Many international research programmes operate through research consortia that have the resources to make a substantial contribution to improving the research environment in their member organisations. This paper collates real-life examples from several large international consortia-based research programmes about how they strengthened organisations' research capacity. The consortia primarily involved academic partners from the UK and/or sub-Saharan Africa and covered research topics including health, natural sciences, conservation agriculture and vector control. They were partly or wholly funded by UK agencies including the Wellcome, Foreign and Commonwealth Development Office, UK Research and Innovation Fund, and the Medical Research Council and they operated for 2-10 years between 2012 and 2022.Consortia's size and ability to access and share resources among their member organisations according to need meant they were uniquely placed to target actions to address weaknesses in member organisations' research capacity, to widen networks and collaborations, and to build in sustainability of capacity gains. Consortia's actions covered: (a) individuals' knowledge and skills; (b) capacity strengthening ethos; (c) organisations' visibility and prestige; and (d) inclusive and responsive management practices. Evidence about these actions formed the basis of recommendations for funders and leaders of consortium-based programmes about how they could make more effective use of consortia's resources to enhance organisations' research systems, environments and cultures.Key lessons were that training should cover management and research leadership and should be offered beyond consortium members, including to research support staff such as technicians and managers. Consortia often tackle complex problems requiring multidisciplinary inputs, but overcoming disciplinary boundaries-and making everyone feel valued and respected-takes time and skill on the part of consortium leaders. Consortia need clear guidance from funders about their commitment to strengthening research capacity. Without this, consortia leaders may continue to prioritise research outputs over creating and embedding sustainable improvements in their organisations' research systems.