Subclinical Tuberculosis Disease-A Review and Analysis of Prevalence Surveys to Inform Definitions, Burden, Associations, and Screening Methodology

Abstract

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, enabling us to estimate the proportion of TB that is subclinical, explore associations with overall burden and program indicators, and evaluate the performance of screening strategies. We extracted data from all publicly available prevalence surveys conducted since 1990. Between 36.1% and 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, .32, .4, and .34, respectively). Chest Xray detected 89% (range, 73%-98%) of bacteriologically confirmed TB, highlighting the potential of optimizing current TB case-finding policies.

Keywords: TB prevalence surveys; TB screening; chest X-ray screening; subclinical TB; symptom screening.

Figure 1.

Selection flow chart for tuberculosis prevalence surveys.

Figure 2.

Proportion of subclinical tuberculosis disease (TB) in prevalence surveys. The proportion of all prevalent TB cases that were subclinical (bars: left side y-axis) by the adult crude prevalence of bacteriologically confirmed TB found in that survey (crosses: right side y-axis). The first 3 bars show the median (bar) and interquartile range (error bars) for values found in surveys in Africa, Asia, and overall. Abbreviations: DPR, Democratic People’s Republic; PDR, People’s Democratic Republic; sub, subnational surveys.

Figure 3.

Screening modality for bacteriologically confirmed tuberculosis disease (TB) cases. The proportion of bacteriologically confirmed cases in prevalence surveys that screened positive on X ray (y-axis) or on symptom screen only (x-axis). Raw data are available in Table 3. Note: The Vietnam 2007 and Sudan 2014 surveys did not report symptom screening and X-ray results for TB cases who were under treatment or had a history of treatment within 2 years but did receive bacteriological examination. In the Philippines 2016 survey, 5% of bacteriologically confirmed cases were exempted from X ray (see Table 1). Abbreviations: DPR, Democratic People’s Republic; PDR, People’s Democratic Republic.

Figure 4.

Population screening results. The proportion of population included in prevalence surveys that screened positive on X ray, symptom screen, both, or neither. Abbreviations: DPR, Democratic People’s Republic; PDR, People’s Democratic Republic.

Figure 5.

Model representation of the natural history of Mycobacterium tuberculosis (Mtb) infection and tuberculosis disease. Different states of Mtb infection (green) and tuberculosis disease are shown (purple). Infected individuals can progress and regress across the spectrum. Clinical disease: bacteriologically confirmed and symptomatic; incipient disease, transition from minimal to subclinical disease; infected, viable Mtb infection with potential to progress to disease; minimal disease, pathological changes caused by Mtb, but bacteriologically negative; naive-infected-minimal-incipient-subclnical-clinical-self-cleared, individual has cleared the Mtb infection and cannot progress to disease without reinfection (dashed arrows); subclinical disease, bacteriologically confirmed, negative at symptom screening.