ArticleEClinicalMedicine2022
How much do smear-negative patients really contribute to tuberculosis transmissions? Re-examining an old question with new tools.
Article in EClinicalMedicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed.
- Benefits of three consecutive sputum inductions using nebulized racemic salbutamol versus hypertonic saline in smear-negative or sputum-scarce pulmonary tuberculosis patients: a prospective randomized, double-blind study.Microbiology spectrum · 2026Trial
- Risk-stratified treatment for drug-susceptible pulmonary tuberculosis.Nature communications · 2024Trial
- Tuberculosis disease and infection among household contacts of bacteriologically confirmed vs unconfirmed tuberculosis in Cambodia: considerations for optimising contact investigation and preventive treatment.Annals of medicine · 2026Article
- Bronchoalveolar Lavage Fluid Lipoarabinomannan as a Rapid Rule-Out Tool for Smear-Negative Pulmonary Tuberculosis in a Nonhuman Immunodeficiency Virus-Predominant, High-Burden Setting: A Prospective Study.Open forum infectious diseases · 2026Article
- Diagnostic value of nanopore-based targeted sequencing technology for subclinical tuberculosis.BMC microbiology · 2026Article
- Characteristics of Plausible Source Cases Responsible for Recent Mycobacterium tuberculosis Transmission, United States, 2018-2022.Emerging infectious diseases · 2026Article
- Diagnostic accuracy of sputum smear microscopy compared with culture in patients with tuberculosis confirmed by XpertThe Journal of international medical research · 2025Article
- Tuberculosis Today: Microbial Insights, Epidemiological Trends, and the Role of Molecular Diagnostics.Pathogens (Basel, Switzerland) · 2025Review
- Quantification of tuberculosis exposure in a high-burdened setting.Scientific reports · 2025Article
- Pulmonary Tuberculosis Infectiousness of Persons Identified Through Active and Passive Case-finding in a High-burden Setting.Open forum infectious diseases · 2025Article
- Recent advances in nanomaterials for the detection of mycobacterium tuberculosis (Review).International journal of molecular medicine · 2025Review
- Assessing Infectiousness and the Impact of Effective Treatment to Guide Isolation Recommendations for People With Pulmonary Tuberculosis.The Journal of infectious diseases · 2025Review
- High prevalence and risk factors of positive sputum smear in newly diagnosed pulmonary tuberculosis patients in Vietnam.Le infezioni in medicina · 2025Article
- Prediction models for Mtb infection among adolescent and adult household contacts in high tuberculosis incidence settings.PLOS global public health · 2025Article
- Isolation of a nanobody specific to the PstS-1 protein and evaluation of its immunoreactivity with structural components ofFrontiers in immunology · 2025Article
- Advancing the fight against tuberculosis: integrating innovation and public health in diagnosis, treatment, vaccine development, and implementation science.Frontiers in medicine · 2025Review
- Concordance between initial GeneXpert MTB/RIF results and follow-up diagnostic testing in patients treated for multidrug-resistant tuberculosis in Lusaka, Zambia.The Pan African medical journal · 2025Article
- Community-Wide Active Case Finding for Tuberculosis: Time to Use the Evidence We Have.Tropical medicine and infectious disease · 2024Review
- Comparative Genomic Analysis ofTropical medicine and infectious disease · 2024Article
- Retrospective analysis of the clinical utility of multi-cytokine profiles in smear-negative pulmonary tuberculosis.Saudi medical journal · 2024Article
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSputum smear microscopy is a common surrogate for tuberculosis infectiousness. Previous estimates that smear-negative patients contribute 13-20% of transmissions and are, on average, 20 to 25% as infectious as smear-positive cases are understood to be high. Herein, we use an ideal real-world setting, a comprehensive dataset, and new high-resolution techniques to more accurately estimate the true transmission risk of smear-negative cases.
methodsWe treated all adult culture-positive pulmonary TB patients diagnosed in the province of Alberta, Canada from 2003 to 2016 as potential transmitters. The primary data sources were the Alberta TB Registry and the Provincial Laboratory for Public Health. We measured, as primary outcomes, the proportion of transmissions attributable to smear-negative sources and the relative transmission rate. First, we replicated previous studies by using molecular (DNA) fingerprint clustering. Then, using a prospectively collected registry of TB contacts, we defined transmission events as active TB amongst identified contacts who either had a 100% DNA fingerprint match to the source case or a clinical diagnosis. We supplemented our analysis with genome sequencing on temporally and geographically linked DNA fingerprint clusters of cases not identified as contacts.
findingsThere were 1176 cases, 563 smear-negative and 613 smear-positive, and 23,131 contacts. Replicating previous studies, the proportion of transmissions attributable to smear-negative source cases was 16% (95% CI, 12-19%) and the relative transmission rate was 0.19 (95% CI, 0.14-0.26). With our combined approach, the proportion of transmission was 8% (95% CI, 3-14%) and the relative transmission rate became 0.10 (95% CI, 0.05-0.19).
interpretationWhen we examined the same outcomes as in previous studies but refined transmission ascertainment with the addition of conventional epidemiology and genomics, we found that smear-negative cases were ∼50% less infectious than previously thought.
fundingAlberta Innovates Health Solutions.
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