The Epidemiological Importance of Subclinical Tuberculosis. A Critical Reappraisal

Kendall, Emily A.; Shrestha, Sourya; Dowdy, David W.

doi:10.1164/rccm.202006-2394pp

Cited by 119 publications

(109 citation statements)

References 43 publications

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“…Our priority now is the deployment of the RASC to identify viable Mtb in aerosol collected from potentially infectious subclinical cases [19]. The capacity for non-invasive capture and isolation of viable Mtb from bioaerosol within 24 hours of collection also supports the potential utility of the RASC to measure the impact of TB treatment on the viability of Mtb bioaerosol release.…”

Section: Plos Pathogensmentioning

confidence: 99%

“…Molecular methods have enabled detection of Mtb DNA in bioaerosols [16], however they do not distinguish live from dead organisms, and even protocols which target RNA [17] require extraction of intracellular nucleic acid, obviating the potential to investigate the physiological and metabolic state(s) of aerosolized bacilli. The method of bacillary capture is also important: approaches based on cough assume symptomatic spread, ignoring the possibility of Mtb transmission during normal respiratory activity and, therefore, potentially not capturing other natural transmission events [18], especially those from sub-clinical infections [19]. Facemask and equivalent sampling methodologies either render live-cell analyses impossible or in vitro propagation (via microbiological culture) unavoidable [20].…”

Section: Introductionmentioning

confidence: 99%

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Capture and visualization of live Mycobacterium tuberculosis bacilli from tuberculosis patient bioaerosols

et al. 2021

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Interrupting transmission is an attractive anti-tuberculosis (TB) strategy but it remains underexplored owing to our poor understanding of the events surrounding transfer of Mycobacterium tuberculosis (Mtb) between hosts. Determining when live, infectious Mtb bacilli are released and by whom has proven especially challenging. Consequently, transmission chains are inferred only retrospectively, when new cases are diagnosed. This process, which relies on molecular analyses of Mtb isolates for epidemiological fingerprinting, is confounded by the prolonged infectious period of TB and the potential for transmission from transient exposures. We developed a Respiratory Aerosol Sampling Chamber (RASC) equipped with high-efficiency filtration and sampling technologies for liquid-capture of all particulate matter (including Mtb) released during respiration and non-induced cough. Combining the mycobacterial cell wall probe, DMN-trehalose, with fluorescence microscopy of RASC-captured bioaerosols, we detected and quantified putative live Mtb bacilli in bioaerosol samples arrayed in nanowell devices. The RASC enabled non-invasive capture and isolation of viable Mtb from bioaerosol within 24 hours of collection. A median 14 live Mtb bacilli (range 0–36) were isolated in single-cell format from 90% of confirmed TB patients following 60 minutes bioaerosol sampling. This represented a significant increase over previous estimates of transmission potential, implying that many more organisms might be released daily than commonly assumed. Moreover, variations in DMN-trehalose incorporation profiles suggested metabolic heterogeneity in aerosolized Mtb. Finally, preliminary analyses indicated the capacity for serial image capture and analysis of nanowell-arrayed bacilli for periods extending into weeks. These observations support the application of this technology to longstanding questions in TB transmission including the propensity for asymptomatic transmission, the impact of TB treatment on Mtb bioaerosol release, and the physiological state of aerosolized bacilli.

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Section: Plos Pathogensmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Capture and visualization of live Mycobacterium tuberculosis bacilli from tuberculosis patient bioaerosols

et al. 2021

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“…In Japan, TB incidence rates in 2014 among people aged 65 years or older were 55 per 100,000 persons for males and 27 per 100,000 persons for females [4]. Upon infection with Mycobacterium tuberculosis, TB patients can display a dynamic spectrum of the disease, ranging from asymptomatic and non-transmissible TB infection (TBI) to transmissible active disease [5][6][7]. Progression from TBI to active TB as a result of immune senescence is thought to account for most of the active TB cases among the elderly in Japan [4].…”

Section: Introductionmentioning

confidence: 99%

Clinical evaluation of QuantiFERON®-TB Gold Plus directly compared with QuantiFERON®-TB Gold In-Tube and T-Spot®.TB for active pulmonary tuberculosis in the elderly

Fukushima

Kubo

Akagi

et al. 2021

Journal of Infection and Chemotherapy

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Background: Reduced sensitivity of tuberculosis (TB) interferon-γ release assays (IGRAs) among the elderly has been reported, which is presumably due to diminished immune function. We evaluated the clinical performance of QuantiFERON®-TB Gold plus (QFT-Plus) compared with QuantiFERON®-TB Gold In-Tube (QFT-GIT) and T-Spot®.TB (T-SPOT) in the elderly. Methods: Blood samples for all three IGRAs were drawn at the same time from all the participants. Both CD4 and CD8 T-cell counts in patients' peripheral blood were also measured. Results: A total of 142 active pulmonary TB patients (median age: 84, interquartile range; 76-89 years) were recruited. The sensitivities of the tested IGRAs (excluding invalid/indeterminate cases) were as follows: QFT-Plus, 93.6%; QFT-GIT, 91.4%; and T-SPOT 68.1%. QFT-Plus displayed significantly higher sensitivity than T-SPOT (p < 0.00001). All three IGRAs exhibited the same specificity (100%), as assessed using blood samples from healthy, low TB-risk individuals (n = 118; median age: 39, IQR; 32-47 years). Positivity in 43 active TB patients with CD4 T-cell counts <200/μL, 39 of whom were ≥80 years of age, was as follows: QFT-Plus, 83.7%; QFT-GIT, 74.4%; and T-SPOT, 58.1%. The difference between TB2-TB1 of the QFT-Plus assay was statistically correlated with CD8 but not CD4 T-cell counts in blood (r = 0.193, p = 0.0298). Conclusions: QFT-Plus showed high performance in the detection of TB infection in patients irrespective of their advanced age (≥80 years) or lower CD4 counts. QFT-Plus can be useful for the diagnosis of TB infection in all patients, including those who are elderly and/or immunocompromised.

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“…To the Editor: Clinical, epidemiological, and biological evidence convincingly supports the existence of subclinical tuberculosis (TB), as argued by Kendall and colleagues (1). However, a certain imprecision of definition, compounded by varying usages in research literature, hampers conceptual clarity.…”

mentioning

confidence: 98%

Subclinical Tuberculosis: Some Flies in the Ointment

Pierce

2021

Am J Respir Crit Care Med

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The Epidemiological Importance of Subclinical Tuberculosis. A Critical Reappraisal

Cited by 119 publications

References 43 publications

Capture and visualization of live Mycobacterium tuberculosis bacilli from tuberculosis patient bioaerosols

Capture and visualization of live Mycobacterium tuberculosis bacilli from tuberculosis patient bioaerosols

Clinical evaluation of QuantiFERON®-TB Gold Plus directly compared with QuantiFERON®-TB Gold In-Tube and T-Spot®.TB for active pulmonary tuberculosis in the elderly

Subclinical Tuberculosis: Some Flies in the Ointment

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