Sputum scarcity among adolescents and adults with presumptive tuberculosis: a systematic review and meta-analysis

BackgroundThe diagnosis of tuberculosis (TB) typically relies on being able to produce a sputum sample for microbiological testing. However, sputum scarcity, the inability to self-expectorate an adequate sputum sample for TB testing, is a well-known concern. Our systematic review and meta-analysis investigated the proportion of sputum scarcity among adolescents and adults being evaluated for presumptive TB in healthcare facilities. MethodsWe searched PubMed, Embase, Cochrane Library, Web of Science, and clinical trials databases with no language restrictions from January 2010 to October 2023 using terms for TB, sputum, and diagnostic studies. We excluded studies with participants aged <15 years, that enrolled patients already providing sputum, or not adequately reporting information on sputum collection. Published summary data was extracted, and the risk of bias was assessed. Summary estimates for the proportion of sputum scarcity were calculated overall and by pre-specified sub-groups. The pooled proportion of sputum scarcity was calculated by random effects meta-analysis. The review protocol was registered on PROSPERO (CRD42023473882). FindingsOur search identified 9895 records, of which 114 studies were included and 81 were rated as a low risk of bias. The median proportion of sputum scarcity across all 114 studies was 6.0% (95% CI: 2.9-9.1%, IQR: 0-19.9%). In subgroup meta-analyses limited to studies collecting one or two self-expectorated spot sputum samples, the pooled estimate of sputum scarcity was 23% (95%CI: 14-33%, n=27). Sputum scarcity was higher in PLHIV sub-groups. The pooled estimate of sputum scarcity in studies enrolling only PLHIV was 24% (95% CI: 15-33%, n=9) for collection of one or two self-expectorated spot sputum samples. Sputum scarcity was the highest in PLHIV inpatients or with advanced disease, with 32% (95% CI: 22-41%, n=5) unable to provide one or two self-expectorated samples. Patients without HIV had the lowest pooled estimate of scarcity, with 12% (95% CI: 3-21%, n=5) unable to provide a self-expectorated sample of any number or collection time. And studies using sputum induction to collect one or two spot samples had a pooled scarcity of 10% (95% CI: 0-21%, n=12). InterpretationSputum scarcity is seen in nearly a quarter of patients being evaluated for TB and this compromises TB detection. These findings support the ongoing work to develop non-sputum TB tests. FundingGates Foundation (INV-069540) Research in Context Evidence before this studyCurrent diagnostics for tuberculosis (TB) rely on testing sputum samples, and patients unable to produce sputum at the time of evaluation may have a delayed or missed diagnosis. However, there are no reliable estimates about how many patients being evaluted for presumptive TB are unable to produce a sputum sample (sputum scarce) and how this varies in different settings and populations. Added value of this studyThis systematic review included data from 114 studies, and found approximately 24% of patients with presumed TB could not produce one or two sputum samples at the time of evaluation. We found higher proportions of sputum scarcity in people living with HIV, and in people living with HIV who were hospital inpatients. We found sputum scarcity was lowest in people without HIV. Implications of all the available evidenceSputum scarcity can impact nearly a quarter of patients being evaluated for TB and is more common in people living with HIV. These data support the need for non-sputum diagnostics.