Subclinical disease among people with culture-confirmed pulmonary tuberculosis in Singapore - a retrospective study

Introduction: Subclinical tuberculosis (TB) is challenging to diagnose due to the lack of a clear definition and symptoms. This study aimed to describe the subclinical disease spectrum among people with culture confirmed pulmonary tuberculosis routinely diagnosed in Singapore, a country with moderate incidence, utilising different definitions. It also aimed to identify risk factors for subclinical TB and the current diagnostic approaches in detecting subclinical TB.

Methods: A retrospective analysis of sputum culture-positive pulmonary TB cases reported to the Singapore National TB Registry from January 1, 2004, to December 31, 2023, was conducted. Two definitions for subclinical TB were used: sputum culture-positive TB with no cough or cough for less than two weeks for definition one and no cough for definition two.

Results: Of 18,693 pulmonary TB cases notified, 41.6% and 31.6% met the first and second definition of subclinical TB respectively. However, neither definition performed better in detecting subclinical TB (ROC curve). Majority of cases (96.7% and 96.0% respectively) had abnormal chest X-ray (CXR) findings, and a high proportion had smear-positive results (40.0% and 35.6% respectively). Sputum TB Polymerase Chain Reaction (PCR) was significant in picking up subclinical TB AOR 1.20 (95%CI 1.10-31), although 42.2% with no persistent cough and 41.2% with no cough did not have sputum TB PCR tested, highlighting gaps in diagnostic practices. Together, older adults (≥70 years) and immunocompromised individuals, including those with end-stage renal failure, steroid therapy, malignancy, and human immunodeficiency virus (HIV) were more likely to have subclinical TB.

Conclusions: Our study suggests that subclinical TB are more likely to occur in those above age of 70 years, and those with immunocompromising conditions. Use of diagnostics such as CXR and sputum TB PCR are helpful in diagnosing subclinical TB. Further research is necessary to evaluate other screening tools in detecting these early disease states.