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

Frascella, Beatrice; Richards, Alexandra S; Sossen, Bianca; Emery, Jon C; Odone, Anna; Law, Irwin; Onozaki, Ikushi; Esmail, Hanif; Houben, Rein M. G. J.

doi:10.1093/cid/ciaa1402

Cited by 160 publications

(188 citation statements)

References 22 publications

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“…Further, more than 70% of participants with prevalent tuberculosis were asymptomatic, contributing to the low sensitivity of tuberculosis symptom screening. This finding is consistent with the 36-80% prevalence of subclinical tuberculosis found in a review of prevalence surveys, 22 but higher than the 41% prevalence of asymptomatic tuberculosis reported in a prevalence survey in people living with HIV in South Africa. 23 LAM assay testing was not useful for intensive case-finding in this community setting, with a sensitivity of 10•0%, consistent with previous evidence.…”

Section: Discussionsupporting

confidence: 90%

Validation of a host blood transcriptomic biomarker for pulmonary tuberculosis in people living with HIV: a prospective diagnostic and prognostic accuracy study

Mendelsohn

Fioré-Gartland

Penn-Nicholson

et al. 2021

The Lancet Global Health

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Background A rapid, blood-based triage test that allows targeted investigation for tuberculosis at the point of care could shorten the time to tuberculosis treatment and reduce mortality. We aimed to test the performance of a host blood transcriptomic signature (RISK11) in diagnosing tuberculosis and predicting progression to active pulmonary disease (prognosis) in people with HIV in a community setting.Methods In this prospective diagnostic and prognostic accuracy study, adults (aged 18-59 years) with HIV were recruited from five communities in South Africa. Individuals with a history of tuberculosis or household exposure to multidrug-resistant tuberculosis within the past 3 years, comorbid risk factors for tuberculosis, or any condition that would interfere with the study were excluded. RISK11 status was assessed at baseline by real-time PCR; participants and study staff were masked to the result. Participants underwent active surveillance for microbiologically confirmed tuberculosis by providing spontaneously expectorated sputum samples at baseline, if symptomatic during 15 months of follow-up, and at 15 months (the end of the study). The coprimary outcomes were the prevalence and cumulative incidence of tuberculosis disease confirmed by a positive Xpert MTB/RIF, Xpert Ultra, or Mycobacteria Growth Indicator Tube culture, or a combination of such, on at least two separate sputum samples collected within any 30-day period.

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Section: Discussionsupporting

confidence: 90%

Validation of a host blood transcriptomic biomarker for pulmonary tuberculosis in people living with HIV: a prospective diagnostic and prognostic accuracy study

Mendelsohn

Fioré-Gartland

Penn-Nicholson

et al. 2021

The Lancet Global Health

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“…This finding is consistent with 46–79% prevalence (median 50%) of subclinical tuberculosis reported in prevalence surveys. 12 , 13 , 14 It is not known whether subclinical tuberculosis would have progressed to symptomatic disease, spontaneously halted, or even reversed if left untreated, 15 , 16 nor whether subclinical disease directly contributes to M tuberculosis transmission. 17 Further research is needed to determine the importance of detection, treatment, and prevention of subclinical disease for global tuberculosis control.…”

Section: Discussionmentioning

confidence: 99%

Biomarker-guided tuberculosis preventive therapy (CORTIS): a randomised controlled trial

Scriba¹,

Fioré-Gartland²,

Penn-Nicholson³

et al. 2021

The Lancet Infectious Diseases

109

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Summary Background Targeted preventive therapy for individuals at highest risk of incident tuberculosis might impact the epidemic by interrupting transmission. We tested performance of a transcriptomic signature of tuberculosis (RISK11) and efficacy of signature-guided preventive therapy in parallel, using a hybrid three-group study design. Methods Adult volunteers aged 18–59 years were recruited at five geographically distinct communities in South Africa. Whole blood was sampled for RISK11 by quantitative RT-PCR assay from eligible volunteers without HIV, recent previous tuberculosis (ie, <3 years before screening), or comorbidities at screening. RISK11-positive participants were block randomised (1:2; block size 15) to once-weekly, directly-observed, open-label isoniazid and rifapentine for 12 weeks (ie, RISK11 positive and 3HP positive), or no treatment (ie, RISK11 positive and 3HP negative). A subset of eligible RISK11-negative volunteers were randomly assigned to no treatment (ie, RISK11 negative and 3HP negative). Diagnostic discrimination of prevalent tuberculosis was tested in all participants at baseline. Thereafter, prognostic discrimination of incident tuberculosis was tested in the untreated RISK11-positive versus RISK11-negative groups, and treatment efficacy in the 3HP-treated versus untreated RISK11-positive groups, during active surveillance through 15 months. The primary endpoint was microbiologically confirmed pulmonary tuberculosis. The primary outcome measures were risk ratio [RR] for tuberculosis of RISK11-positive to RISK11-negative participants, and treatment efficacy. This trial is registered with ClinicalTrials.gov , NCT02735590 . Findings 20 207 volunteers were screened, and 2923 participants were enrolled, including RISK11-positive participants randomly assigned to 3HP (n=375) or no 3HP (n=764), and 1784 RISK11-negative participants. Cumulative probability of prevalent or incident tuberculosis disease was 0·066 (95% CI 0·049 to 0·084) in RISK11-positive (3HP negative) participants and 0·018 (0·011 to 0·025) in RISK11-negative participants (RR 3·69, 95% CI 2·25–6·05) over 15 months. Tuberculosis prevalence was 47 (4·1%) of 1139 versus 14 (0·78%) of 1984 in RISK11-positive compared with RISK11-negative participants, respectively (diagnostic RR 5·13, 95% CI 2·93 to 9·43). Tuberculosis incidence over 15 months was 2·09 (95% CI 0·97 to 3·19) vs 0·80 (0·30 to 1·30) per 100 person years in RISK11-positive (3HP-negative) participants compared with RISK11-negative participants (cumulative incidence ratio 2·6, 95% CI 1·2 to 5·9). Serious adverse events related to 3HP included one hospitalisation for seizures (unintentional isoniazid overdose) and one death of unknown cause (possibly temporally related). Tuberculosis incidence over 15 months was 1·94 (95% CI 0·35 to 3·50) versus 2·09 (95% CI 0·97 to 3·19) per 100 person-years in 3H...

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“…These individuals often do not feel compelled to seek out screening and care services and, thus, are frequently missed by health programs. Across Asia, modern TB prevalence surveys have shown that 40–79% of adults with culture-confirmed, pulmonary TB do not report a prolonged cough (≥2 weeks) [ 6 ], and a recent meta-analysis indicates that the proportion of people with sub-clinical and low-grade TB may be significantly higher in Asia compared to Africa [ 7 ]. Vietnam’s second TB prevalence survey results seem to affirm these findings; 42% of the people with TB detected by the survey did not report a prolonged cough [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

An Evaluation of Programmatic Community-Based Chest X-ray Screening for Tuberculosis in Ho Chi Minh City, Vietnam

Nguyen

Codlin²,

Vo³

et al. 2020

TropicalMed

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Across Asia, a large proportion of people with tuberculosis (TB) do not report symptoms, have mild symptoms or only experience symptoms for a short duration. These individuals may not seek care at health facilities or may be missed by symptom screening, resulting in sustained TB transmission in the community. We evaluated the yields of TB from 114 days of community-based, mobile chest X-ray (CXR) screening. The yields at each step of the TB screening cascade were tabulated and we compared cohorts of participants who reported having a prolonged cough and those reporting no cough or one of short duration. We estimated the marginal yields of TB using different diagnostic algorithms and calculated the relative diagnostic costs and cost per case for each algorithm. A total of 34,529 participants were screened by CXR, detecting 256 people with Xpert-positive TB. Only 50% of those diagnosed with TB were detected among participants reporting a prolonged cough. The study’s screening algorithm detected almost 4 times as much TB as the National TB Program’s standard diagnostic algorithm. Community-based, mobile chest X-ray screening can be a high yielding strategy which is able to identify people with TB who would likely otherwise have been missed by existing health services.

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

Cited by 160 publications

References 22 publications

Validation of a host blood transcriptomic biomarker for pulmonary tuberculosis in people living with HIV: a prospective diagnostic and prognostic accuracy study

Validation of a host blood transcriptomic biomarker for pulmonary tuberculosis in people living with HIV: a prospective diagnostic and prognostic accuracy study

Biomarker-guided tuberculosis preventive therapy (CORTIS): a randomised controlled trial

An Evaluation of Programmatic Community-Based Chest X-ray Screening for Tuberculosis in Ho Chi Minh City, Vietnam

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