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Cited by 315Tuberculosis Research and EpidemiologyInfectious Diseases and TuberculosisHIV, TB, and STIs Epidemiology

The DOI matches its Crossref record; 25 of the 27 references it cites were found in a registry or an index.

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

Open access
Frascella, Beatrice, Richards, Alexandra S, Sossen, Bianca, Emery, Jon C, Odone, Anna, Law, Irwin, Onozaki, Ikushi, Esmail, Hanif, Houben, Rein M G J·2021·Clinical Infectious Diseases
DOI 10.1093/cid/ciaa1402PMC PMC8326537
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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.

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Crossref · 10.1093/cid/ciaa1402

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Figures

Figure 1. Selection flow chart for tuberculosis prevalence surveys.
Figure 1. Selection flow chart for tuberculosis prevalence surveys.CC BY-NC-ND · PubMed Central
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 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.CC BY-NC-ND · PubMed Central
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 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.CC BY-NC-ND · PubMed Central
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 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.CC BY-NC-ND · PubMed Central
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.
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.CC BY-NC-ND · PubMed Central

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Research works printed but not linked: 2

  1. World Health Organization, 2013, Systematic screening for active tuberculosis: principles and recommendations
  2. 2017, Consensus meeting report: development of a target product profile (TPP) and a framework for evaluation for a test for predicting progression from tuberculosis infection to active disease

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Metadata

Authors
Frascella, B., Richards, A. S., Sossen, B., Emery, J. C., Odone, A., Law, I., Onozaki, I., Esmail, H., & Houben, R. M. G. J.
Affiliations
  • Vita-Salute San Raffaele University (IT)
  • London School of Hygiene & Tropical Medicine (GB)
  • University of Cape Town (ZA)
  • World Health Organization (CH)
Corresponding author
Houben, Rein M G J
ORCID
Venue
Clinical Infectious Diseases
Publisher
Oxford University Press (OUP)
Published
2020-09-16
Volume
73
Issue
3
Pages
e830-e841
ISSN
  • 1058-4838 (ISSN-L)
  • 1537-6591
DOI
10.1093/cid/ciaa1402
PMC
PMC8326537
OpenAlex
W3087646693
Cited by
315
References
27
Citations by year
2026: 49 · 2025: 65 · 2024: 63 · 2023: 57 · 2022: 46 · 2021: 30 · 2020: 5
FWCI
4.53
Type
journal article
Language
en
Open access
Licence
Locations
  • Clinical Infectious Diseases (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion, cc-by-nc-sa)
  • LSHTM Research Online (London School of Hygiene and Tropical Medicine) (submittedVersion, cc-by-nc-sa)
  • UCL Discovery (University College London) (submittedVersion)
Funders
European Research Council starting (757699)
Topics
  • Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
  • Health Sciences › Medicine › Infectious Diseases › Infectious Diseases and Tuberculosis
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › HIV, TB, and STIs Epidemiology
Keywords
subclinical tuberculosis, bacteriologically confirmed tuberculosis, prevalence survey, tuberculosis screening, chest radiography, case finding, HIV coinfection, diagnostic rate, tuberculosis burden
MeSH terms
Humans, Mass Screening, Surveys and Questionnaires, Thorax, Tuberculosis, Prevalence

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