Subclinical tuberculosis disease - a review and analysis of prevalence surveys to inform definitions, burden, associations and screening methodology

While it is known that a substantial proportion of individuals with tuberculosis disease (TB) present subclinically, usually defined as bacteriologically-confirmed but negative on symptom screening, considerable knowledge gaps remain. Our aim was to review data from TB prevalence population surveys and generate a consistent definition and framework for subclinical TB, thus enabling an estimate of the proportion of TB that is subclinical, explore associations with overall burden and programme indicators, and performance of screening strategies. We extracted data from all publicly available prevalence surveys conducted since 1990. Between 36.1-79.7% (median 50.4%) of prevalent bacteriologically-confirmed TB was subclinical. No association was found between prevalence of subclinical and all bacteriologically confirmed TB, patient diagnostic rate or country-level HIV prevalence (p-values, 0.32, 0.4, 0.34, respectively). Chest X-ray detected 89% (range 73-98%) of bacteriologically-confirmed TB disease, highlighting the potential of optimizing current TB case-finding policies.