Subclinical tuberculosis: a meta-analysis of prevalence and scoping review of definitions, prevalence and clinical characteristics.

ABSTRACT

BACKGROUND: This scoping review aimed to characterise definitions used to describe subclinical tuberculosis (TB), estimate the prevalence in different populations and describe the clinical characteristics and treatment outcomes in the scientific literature. METHODS: A systematic literature search was conducted using PubMed. We included studies published in English between January 1990 and August 2022 that defined "subclinical" or "asymptomatic" pulmonary TB disease, regardless of age, HIV status and comorbidities. We estimated the weighted pooled proportions of subclinical TB using a random-effects model by World Health Organization reported TB incidence, populations and settings. We also pooled the proportion of subclinical TB according to definitions described in published prevalence surveys. RESULTS: We identified 29 prevalence surveys and 71 other studies. Prevalence survey data (2002-2022) using "absence of cough of any duration" criteria reported higher subclinical TB prevalence than those using the stricter "completely asymptomatic" threshold. Prevalence estimates overlap in studies using other symptoms and cough duration. Subclinical TB in studies was commonly defined as asymptomatic TB disease. Higher prevalence was reported in high TB burden areas, community settings and immunocompetent populations. People with subclinical TB showed less extensive radiographic abnormalities, higher treatment success rates and lower mortality, although studies were few. CONCLUSION: A substantial proportion of TB is subclinical. However, prevalence estimates were highly heterogeneous between settings. Most published studies incompletely characterised the phenotype of people with subclinical TB. Standardised definitions and diagnostic criteria are needed to characterise this phenotype. Further research is required to enhance case finding, screening, diagnostics and treatment options for subclinical TB.