Clinical profiles of subclinical disease among pulmonary tuberculosis patients: a prospective cohort study in South Korea

Abstract

Background Subclinical tuberculosis (TB) is a potential target for public health intervention because its early identification may reduce TB transmission. We aimed to describe the clinical and laboratory findings of subclinical disease among pulmonary TB patients and compared treatment outcomes for subclinical and active diseases. Methods In this prospective cohort study, we enrolled adult patients aged ≥ 19 years with pulmonary TB between 2016 and 2018. Subclinical TB was defined as radiographic or microbiologic test results consistent with TB without clinical symptoms. We implemented a two-stage symptom assessment using a predefined TB symptom checklist. Demographic, clinical, and laboratory data were compared between subclinical and active diseases using multivariable binary logistic regression analysis. We evaluated treatment outcomes in the drug-susceptible cohort. Results Among 420 enrolled patients, 81 (19.3%) had subclinical TB. Multivariable analysis showed that age < 65 years was the only variable significantly associated with subclinical disease. Subclinical disease had a significantly lower proportion of acid-fast bacilli smear and culture positivity and multiple lobe involvement compared to active disease. The white blood cell counts, platelet counts, and C-reactive protein levels were significantly higher among patients with active disease than among those with subclinical disease. Among 319 patients with treatment success in the drug-susceptible cohort, six (1.9%) recurrent cases were identified, and all were active disease. Patients with subclinical disease had a higher proportion of favourable outcomes; however, its odds ratio was insignificant. Conclusions Nearly one-fifth of tuberculosis cases were subclinical in South Korea. Despite its milder clinical presentation and lower level of inflammatory markers, the treatment outcomes of subclinical TB were not significantly different from that of active disease.

How much do smear-negative patients really contribute to tuberculosis transmissions? Re-examining an old question with new tools

“… 38 This could mean that we may be systematically underestimating the contribution of subclinical cases, 37 the vast majority of which are smear-negative. 39 Mechanistically, if you consider the significant aerosol production arising from routine activities like speaking or singing, cough would not be required for transmission. 40 While we believe our findings are an accurate reflection of transmission ascertainment reliant on routine contact tracing practice and while we attempt to account for unidentified secondary cases, the evolving literature around the role of transmission from subclinical cases shows the challenge in attributing precise transmission rates based on smear-status.…”

Screening performance of C-reactive protein for active pulmonary tuberculosis in HIV-positive patients: A systematic review with a meta-analysis

“…In case of HIV infection—the most important risk factor in developing active TB ( 22 )—as soon as antiretroviral therapy is administered, the mortality rate decreases and the prognosis is improved ( 3 , 21 , 23 ). This particular need of early bacterial identification is increased by low-adherence antituberculotic regimens: first-line agents represented by isoniazid, rifampicin, pyrazinamide, ethambutol, and streptomycin (mostly used in primary active TB), and second-line agents (mostly used in resistant bacilli strains) ( 5 , 24 – 26 ). First-line regimens are recommended as a directly observed therapy (DOT) in drug-susceptible TB in individuals residing in settings with a low proportion of resistant strains for 6 months as follows: intensive phase (rapid mycobacterial reduction) when agents are administered daily for 2 months and continuation phase (sterilization phase with isoniazid and rifampicin given thrice every week) for the next 4 months ( 21 , 24 , 27 ).…”

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

“…Among studies that compared the screening and diagnostic test outcomes between people with subclinical TB and clinical TB disease ( table 2 ), those with clinical disease were more likely to test positive on NAAT or culture. Five studies reported a higher proportion of positive radiologic tests among those with clinical TB disease, of which two were statistically significantly different [ 18 , 23 , 37 , 41 , 76 ]. However, this review also identified two studies that described a higher proportion of chest radiographs suggestive of TB disease among people with subclinical TB relative to those with clinical disease [ 19 , 75 ].…”

“…Specific chest radiography findings included a higher proportion of multilobar infiltrates among those with clinical TB disease [ 23 , 76 ]. Two studies that examined the radiographic findings of chest computed tomography (CT) found higher proportions of multi-lobar involvement [ 37 , 41 ], consolidation [ 37 ], and fibrotic scar [ 37 ] among those with the clinical disease compared to subclinical TB. The presence of cavitary lesions was significantly associated with clinical TB disease [ 76 ].…”