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At least 19 recordsLinked to original sources
PubMed2025

Integrating genomic and spatial analyses to describe tuberculosis transmission: a scoping review.

Tuberculosis remains a leading cause of infection-related mortality, and efforts to reduce its incidence have been hindered by an incomplete understanding of local Mycobacterium tuberculosis transmission dynamics. Advances in pathogen sequencing and spatial analysis have created new opportunities to map M tuberculosis transmission patterns more precisely. In this scoping review, we searched for studies combining pathogen genetics and location data to analyse the spatial patterns of M tuberculosis transmission and identified 142 studies published between 1994 and 2024. Secular changes in genetic methods were observed, with genome sequencing approaches largely replacing lower-resolution genotyping methods since 2020. The included studies addressed four primary research questions: how are tuberculosis cases and M tuberculosis transmission clusters geographically distributed; do spatially concentrated M tuberculosis clusters exist, and where are these areas located; when spatial concentration occurs, what host, pathogen, or environmental factors contribute to these patterns; and do identifiable relationships exist between the spatial proximity of tuberculosis cases and the genetic similarity of the M tuberculosis isolates infecting these individuals? Collectively, in this Review, we examined the available study data, evaluated the analytical requirements for addressing these questions, and discussed opportunities and challenges for future research. We found that the integration of spatial and genomic data can inform a detailed understanding of local M tuberculosis transmission patterns, but improved study designs and new analytical methods to address gaps in sampling completeness and to integrate additional movement data are needed to fully realise the potential of these tools.

Humans↗
PubMed2026

Phylogenetic inconsistency of pairwise SNP clustering for inferring tuberculosis transmission in a high-burden, endemic setting: a case study from Thailand.

Whole-genome sequence analysis is now widely used to delineate tuberculosis transmission clusters. A standard practice is to cluster bacterial isolates based on a fixed maximum genome-wide pairwise single nucleotide polymorphism (pwSNP) distance threshold. In this study, we evaluated the phylogenetic consistency of pwSNP-distance clustering with thresholds ranging between 1 and 25 single nucleotide polymorphisms (SNPs) using two contrasting data sets: (i) a data set from the UK (N = 390) published by T. M. Walker, C. L. C. Ip, R. H. Harrell, J. T. Evans, et al. (Lancet Infect Dis 13:137-146, 2013, https://doi.org/10.1016/S1473-3099(12)70277-3), which was foundational to the establishment of this method, and (ii) a data set from Thailand (N = 3,341), characterized by persistent transmission and sparse, non-systematic sampling. For the UK data set, the standard pwSNP-distance clustering using thresholds of &#x2265;12 SNPs yielded entirely monophyletic clusters and showed high concordance with a comparative monophyly constrained, tree-based method. In contrast, for the Thai data set, pwSNP-distance clustering often generated non-monophyletic clusters, even by the 25-SNP threshold. The pwSNP-distance and comparative tree-based clustering methods only showed large consistency at thresholds of &#x2265;22 SNPs. This suggests that SNP clusters defined by low distance thresholds (i.e., <12 SNPs for the UK data set, and <22 SNPs for the Thai data set) may lack robustness, and the problem is particularly severe for data sets characterized by persistent transmission, likely due to poorer cluster separation. Moreover, our findings indicate that large cluster sizes, high maximum intra-cluster genetic distances, and broad sample collection time spans may serve as useful indicators of potentially non-monophyletic clusters. We also demonstrate that mixed infections can produce spurious, phylogenetically long-range SNP linkages, underscoring the necessity of strict sequence quality control.IMPORTANCEFixed-threshold pairwise single nucleotide polymorphism (pwSNP)-distance clustering is commonly used to delineate tuberculosis transmission clusters. From an epidemiological perspective, a genuine transmission cluster must be monophyletic, originating from a single source. However, pwSNP-distance clustering is inherently simplistic and can therefore violate this principle, making the assessment of its phylogenetic consistency critical. Our results demonstrate that while this method effectively delineated complete transmission clusters for the data set from the UK, a low-burden and non-persistent transmission setting, it frequently generated non-monophyletic clusters when applied to the Thai data set, characterized by persistent transmission alongside sparse and non-systematic sampling. Furthermore, we found that clusters derived using low distance thresholds could notably vary between the pwSNP-distance and comparative tree-based clustering methods, suggesting limited reliability and robustness. To accurately delineate tuberculosis transmission clusters, especially for complex data from high-burden, endemic settings, we recommend transitioning from pwSNP-distance clustering toward more robust, phylogenetic clustering that respects evolutionary descent.

Mycobacterium tuberculosis↗
PubMedDate not supplied

Responses of dairy cows to badger urine and faeces on pasture with reference to bovine tuberculosis transmission.

Grazing cattle were observed when they encountered badger urine or faeces which, in all but the first study, came only from badgers which were not infected with bovine tuberculosis. The faeces were very strongly avoided and there was generally a strong avoidance of ingestion of badger urine. There was no evidence that cattle were attracted to badger latrines in an area where some infected badgers were present and cows actively avoided faeces up to 28 days old which was placed on grass turves or on pasture. 99.3% of cows took no bites from small grass plots contaminated with faeces and 88.7% of cows took no bites from urine-treated plots. There was generally avoidance of pasture treated with badger urine up to 14 days old. However, two cows out of 240 were willing to graze close to faeces and seven out of 240 were willing to graze near urine. Contaminated herbage was eaten most when attractive herbage became scarce. Wet weather did not reduce the strength of avoidance of urine. Some cows responded to badger urine, and to a lesser extent to faeces, by more sniffing, particularly when herbage was scarce. The odour of faeces, and sometimes that of urine, often resulted in the ejection of mouth contents. As a consequence of their avoidance of badger faeces and urine, the vast majority of cows are unlikely to contract tuberculosis from infected badgers by ingestion. Most cows totally avoid badger products so they are unlikely to be infected via inhalation. However, the small minority of unselective cows must be more at risk and this finding warrants further investigation.

Animals↗
PubMed1992

Tuberculosis transmission in a state correctional institution--California, 1990-1991.

During September and October 1991, active tuberculosis (TB) was diagnosed in two inmates and one employee of a California state correctional institution (1991 average annual inmate population, 5421; employees, 1500). This report presents findings from an investigation by the California Department of Health Services (CDHS), the California Department of Corrections (CDOC), and CDC to determine whether ongoing transmission of Mycobacterium tuberculosis was occurring in the institution.

Antitubercular Agents↗
PubMedDate not supplied

Mycobacterium tuberculosis transmission in a health clinic.

Between January 1 and June 30, 1988, 30 (39.5%) of 76 staff members tested at a health clinic in Florida had positive tuberculin skin test reactions. This case-control study showed that people whose skin test converted were more likely than those whose skin test did not convert to have been present while patients were being treated with aerosolized pentamidine (odds ratio = 15.0; 95% confidence interval = 1.4 - 730.0) and to have worked on the first floor of the clinic (odds ratio = 9.3; 95% confidence interval = 1.1 - 420). The clinic building was poorly ventilated, and aerosolized pentamidine treatments were given in a room from which the air tended to flow into the hallway. Aerosolized pentamidine should be administered in a well-ventilated area from which the air is exhausted directly outside. All persons who are given such treatments should first be screened for tuberculosis. Use of trade names is for identification only and does not constitute endorsement by the Public Health Services or the U.S. Department of Health and Human Services.

Administration, Inhalation↗
PubMed1979

[Experimental study on the possibility of tuberculosis transmission by coitus].

The following conslusion can be drawn from the results obtained: 1. A male guinea pig, in which tuberculosis of genitals was caused by BK-typus humanus, might infect a healthy female guinea pig in cohabitation. The experiments proved that the possibility of such infection was expressed as the ratio of 1:6. 2. On the basis of the results obtained, we feel entitled to draw our patients' attention to the possibility of infection resulting from sexual intercourse and the necessity of application of suitable contraceptives. It should also be noted that appropriate examination of the patients' present partners is indispensable.

Animals↗
PubMed1977

Tuberculosis transmission in a large urban jail.

Following diagnosis of moderately advanced tuberculosis in an inmate of Cook County Jail, tuberculin testing was performed to assess the degree of transmission of tuberculosis within the jail. Twenty-three percent of inmates exposed to the index patient were initially found to be tuberculin positive. Subsequent tuberculin testing three months later demonstrated a 71% rate of skin-test conversion in previously tuberculin-negative inmates exposed to the index patient. The rate of infectivity of tuberculosis within a jail is analogous to a household situation. Despite major obstacles, modern programs of tuberculosis screening and treatment are essential in correctional institutions.

Adult↗
PubMed2026

Lineage-specific transmission and spatial clustering of Mycobacterium tuberculosis in Kaohsiung, Taiwan, in 2019-23: a population-based genomic study.

BACKGROUND: The epidemiology of tuberculosis in Taiwan has been influenced by the introduction of multiple Mycobacterium tuberculosis lineages and by the ageing of the population. We conducted a population-based study to investigate M tuberculosis transmission in Kaohsiung, a city in southern Taiwan. METHODS: In this study, we performed whole-genome sequencing (WGS) of M tuberculosis isolates from all culture-positive cases of tuberculosis notified in Kaohsiung between Jan 1, 2019 and Dec 31, 2023. We obtained routine epidemiological data for each case collected through the national tuberculosis control programme. We characterised the lineage composition of the isolate collection and evaluated genomic clustering of isolates, defined as a difference of 12 or fewer single-nucleotide polymorphisms. Univariable and multivariable logistic regression analyses were performed to estimate the odds of a case belonging to a genomic cluster based on host factors (age, sex, sputum smear status, and residential region) and pathogen factors (drug resistance status and strain lineage). Spatial aggregation of large genomic clusters (including greater than or equal to ten isolates) was assessed using a non-parametric statistical clustering method. We used a Bayesian transmission tree inference method to explore the patterns of age-dependent transmission. FINDINGS: During the study period, 5667 tuberculosis cases were notified in Kaohsiung, 4916 (86&#xb7;7%) of which were culture-positive. Of these 4916 cases, whole-genome sequencing was successfully performed for 4168 (84&#xb7;8%) isolates. 1219 (29&#xb7;2%) of 4168 individuals were female and 2947 (70&#xb7;7%) were male; the median age was 69&#xb7;7 years (IQR 57&#xb7;4-80&#xb7;7). The dominant lineages were lineage 1 (1749 [42&#xb7;0%] of 4168 isolates), lineage 2 (1510 [36&#xb7;2%]), and lineage 4 (905 [21&#xb7;7%]). 1069 (25&#xb7;6%) of 4168 were genomically linked and formed 287 clusters. Lineage 2 isolates had higher odds (aOR 2&#xb7;15 [95% CI 1&#xb7;80-2&#xb7;52]) than lineage 1 isolates of genomic clustering across all regions, whereas lineage 4 isolates had a significantly higher risk (2&#xb7;75 [1&#xb7;16-6&#xb7;89]) of genomic clustering than lineage 1 only in the rural northeast region, inhabited primarily by indigenous populations. Spatial clustering analysis corroborated these lineage-region interactions. Although younger adults (<35 years) had the highest individual-level odds (5&#xb7;64 [4&#xb7;16-7&#xb7;68]) of clustering in the logistic regression analysis compared with those aged 80 years or older, the transmission inference indicated that individuals aged 55-74 years were responsible for a greater proportion of inferred transmission events, contributing 50&#xb7;8% of all transmission events. INTERPRETATION: This sequencing study revealed that older adults (aged &#x2265;65 years) might have played a substantial and under-recognised role in the transmission of tuberculosis in Taiwan. The lineage-specific clustering and spatial patterns suggested that both pathogen characteristics and host demographics shaped tuberculosis transmission dynamics. These findings support the use of integrated genomic surveillance to guide precision tuberculosis control and motivate further research on age-specific transmission pathways and targeted interventions to advance tuberculosis elimination efforts. FUNDING: Taiwan National Health Research Institutes and Taiwan National Science and Technology Council.

Mycobacterium tuberculosis↗
PubMed2026

Comparison of phylogenetic metrics of transmission between symptomatic and asymptomatic tuberculosis in individuals who were incarcerated in Brazil in 2008-24: a retrospective genomic epidemiology study.

BACKGROUND: Tuberculosis control efforts have traditionally targeted symptomatic individuals; however, the role of asymptomatic cases in sustaining transmission is increasingly recognised. We aimed to quantify the contribution of asymptomatic tuberculosis to recent transmission using genomic and epidemiological data from a high-transmission setting. METHODS: We conducted a retrospective genomic epidemiology study of Mycobacterium tuberculosis isolates collected in Mato Grosso do Sul, Brazil, between Aug 25, 2008, and March 19, 2024. Available isolates underwent whole-genome sequencing. Demographic, clinical, incarceration history, and laboratory metadata were obtained from surveillance records. From Jan 1, 2017, to March 19, 2024, active case finding was conducted in the state's three largest prisons (all male-only facilities), during which sputum samples were collected from individuals irrespective of symptoms and tested using GeneXpert and culture. Comparisons of transmission between individuals with and without symptoms were restricted to individuals who were incarcerated and were identified through active case finding and for whom high-quality, M tuberculosis lineage 4 genomes were available. Metrics of recent transmission included phylogenetic clustering, time-scaled haplotype density (THD), local branching index (LBI), and transmission probabilities inferred using Bayesian Reconstruction and Evolutionary Analysis of Transmission Histories. FINDINGS: 4448 tuberculosis cases were notified in Mato Grosso do Sul in 2008-24. After excluding cases for which M tuberculosis isolates were not available or had low sequencing quality, who had contaminated cultures or mixed infection, or who were infected with non-lineage 4 M tuberculosis, we included 2362 lineage 4 M tuberculosis isolates with high-quality genome sequences. 1849 (78&#xb7;3%) of 2362 isolates were part of a genomic cluster. Among 2362 individuals with tuberculosis, 1137 (48&#xb7;1%) were incarcerated at diagnosis. Of these individuals, 505 were identified through active case finding in three male-only prisons. The median age was 30 years (IQR 25-37); 304 (60&#xb7;2%) had mixed ethnicity, 90 (17&#xb7;8%) were White, 56 (11&#xb7;1%) were Black, 13 (2&#xb7;6%) were Indigenous, and six (1&#xb7;2%) were Asian. 277 (54&#xb7;9%) had symptomatic disease and 228 (45&#xb7;1%) had asymptomatic tuberculosis. There were no significant differences between symptomatic and asymptomatic individuals in phylogenetic clustering (213 [76&#xb7;9%] of 277 vs 195 [85&#xb7;5%] of 228; p=0&#xb7;37), THD (median 0&#xb7;39 [IQR 0&#xb7;06-0&#xb7;62] vs 0&#xb7;50 [0&#xb7;09-0&#xb7;65]; p=0&#xb7;12), or LBI (0&#xb7;00863 [0&#xb7;00810-0&#xb7;00988] vs 0&#xb7;00871 [0&#xb7;00829-0&#xb7;01020]; p=0&#xb7;088). Bayesian transmission trees showed no significant difference in the number of secondary infections inferred from symptomatic compared with asymptomatic individuals (p=0&#xb7;56). These findings were consistent across genomic clusters and robust to model assumptions. INTERPRETATION: We identified no differences in transmission between individuals who were symptomatic and those who were asymptomatic using multiple genomic measures. In this high-transmission setting, where systematic screening is implemented, our findings indicate that asymptomatic tuberculosis substantially contributes to tuberculosis transmission at the population level. These results suggest that symptom-based case detection alone is likely to be insufficient to interrupt transmission and highlight the importance of expanded screening strategies in high-risk populations. FUNDING: US National Institutes of Health and the Brazilian National Research Council (CNPq).

Humans↗
PubMed2026

Assessment of differentially culturable tubercle bacteria assays for the detection of tuberculosis infection in asymptomatic household contacts and the implications for intra-household transmission: a longitudinal cohort study.

BACKGROUND: Conventional culture methods for tuberculosis diagnosis miss differentially culturable tubercle bacteria (DCTB), which grow only in liquid assays supplemented with growth-enhancing factors. This limitation, combined with inadequate contact tracing and screening, often fails to identify asymptomatic individuals, with live bacilli detectable by enhanced culture methods. This shortfall results in undiagnosed reservoirs of bacteria, potentially fuelling ongoing transmission. In this study, we aimed to investigate whether DCTB assays provide greater sensitivity by detecting more Mycobacterium tuberculosis infections than conventional culture and whether this enhanced detection improves the resolution of intrahousehold transmission mapping. In addition, we sought to evaluate whether DCTB populations can progress to conventional culture positivity, thereby highlighting their clinical and epidemiological relevance. METHODS: In this prospective observational longitudinal cohort study, drug-susceptible or rifampicin-resistant tuberculosis index participants aged 12 years or older, were recruited from primary healthcare clinics from two South African districts. Inclusion criteria were informed consent, Xpert MTB/RIF Ultra-positive results, tuberculosis symptoms (>2 weeks), provision of baseline samples, at least one consenting household contact, and documented HIV status. Household contacts of the index patients and control households were also recruited. Sputum specimens were collected at baseline and 2, 4, 8, 12, and 16 months from the index participants and household contacts. Samples were analysed by conventional mycobacterial growth indicator tube (MGIT) culture, and colony-forming unit assays to identify viable bacteria. Enhanced culture to detect DCTB involved serial dilution of sputum in liquid culture, supplemented with M tuberculosis culture filtrate as a source of growth stimulatory factors. Whole-genome sequencing (WGS) of cultured isolates was performed to trace household transmission. FINDINGS: Between June 1, 2020, and Feb 6, 2024, 293 index participants (183 [62%] male), 701 household contacts (453 [65%] female), and 122 control participants (67 [55%] female) were enrolled. At baseline, 249 (85%) of 293 index participants and 110 (16%) of 701 household contact sputum samples were positive for M tuberculosis by MGIT conventional culture. For baseline MGIT-negative specimens, DCTB assays detected M tuberculosis in an additional 21 (7%) of 293 index participants and 26 (4%) of 701 household contacts. Over 16 months of follow-up, DCTB assays identified 61 (8&#xb7;7%) of 701 additional tuberculosis-positive household contacts not detected by conventional culture. WGS-guided transmission mapping using conventional culture identified transmission in 16 (15%) of 104 households, whereas DCTB assays detected an additional 19 (18%) of 104 transmission events. No evidence of intrahousehold transmission was found in the remaining 69 (66%) of 104 tuberculosis-positive households. Over the 16-month follow-up period, conventional culture identified 233 positive household contacts, of which 195 (84%) were asymptomatic. DCTB assays detected an additional 94 cases of M tuberculosis positivity in household contacts, of which 79 (84%) were asymptomatic. In control households, tuberculosis prevalence at baseline was two (2%) of 122, with an additional three (3%) of 122 identified during follow-up. INTERPRETATION: DCTB assays provide substantial value by detecting asymptomatic individuals missed by conventional culture, revealing a potentially important reservoir of subclinical infection, which could sustain transmission. In addition, DCTB detection uncovers transmission linkages missed by conventional culture, providing a more comprehensive understanding of M tuberculosis transmission dynamics and highlighting the need to incorporate enhanced culture methods into diagnostic and surveillance strategies, to strengthen early case identification and tuberculosis control efforts. FUNDING: National Institutes of Health.

Humans↗
PubMed1990

Nosocomial transmission of tuberculosis associated with a draining abscess.

Nine secondary cases of tuberculosis and 59 tuberculin skin test conversions occurred after exposure to a hospitalized patient with a large tuberculous abscess of the hip and thigh. Among 442 tuberculin-negative hospital employees, the relative risk of skin test conversion associated with recalled exposure to the patient was 14.0 (95% confidence limits, 6.8, 28.7). Four of 5 surgical suite employees who assisted with incision and debridement of the abscess had skin test conversions, as did 85% of 33 employees on a general medical floor who recalled exposure to the patient and 30% of 20 intensive care unit employees who recalled exposure. The prevalence of tuberculin reactivity in visitors and other patients on two floors also showed a strong association with exposure to the patient. A high concentration of Mycobacterium tuberculosis in the abscessed tissue, disturbance of the surface of liquid drainage from the abscess by irrigations and by the agitated behavior of the patient, and positive air pressure in the patient's room are factors that appear to have contributed to the high risk of tuberculosis transmission.

Abscess↗
PubMedDate not supplied

Contemporary approaches to the serology of tuberculosis.

The current approaches in serological methods for the diagnosis of tuberculosis have been towards the use of M. tuberculosis-specific antigens or epitopes of protein antigens. Although sensitivity by using such antigens might be similar to that obtained by using crude or semipurified antigens, specificity was somewhat improved to over 95%. Among serological tools, ELISA has been the method of choice for detecting serum antibodies and mycobacterial antigens from clinical specimens because of its high sensitivity, simplicity, reproducibility and versatility in screening a large number of specimens. Further simple and rapid tests such as the agglutination test by coating various particles with purified or synthetic M. tuberculosis-specific antigens or antibodies will soon become available for field evaluation in endemic areas of tuberculosis. However, all these efforts can be justified only if serological tests give any meaningful information for the diagnosis and management of tuberculosis or for determining the degree of M. tuberculosis transmission in a community as a complement to the current tuberculin test, chest X-ray, or sputum examination. Although the detection of mycobacterial antigens from CSF or sputum specimens using polyclonal or monoclonal antibodies gave more direct evidence for M. tuberculosis infection, the information by the assays was not sufficient to determine whether these immunological tools could be used in clinical laboratories for the diagnosis of tuberculosis. Meanwhile, recent introduction of the very sensitive polymerase chain reaction (PCR) technology for the detection of M. tuberculosis DNA from clinical specimens (37-40) may eventually replace the immunological assays for the detection of mycobacterial antigens.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Bacterial↗