-
PLoS Pathogens Mar 2024Mycobacterium tuberculosis (M.tb.) infection leads to over 1.5 million deaths annually, despite widespread vaccination with BCG at birth. Causes for the ongoing...
Mycobacterium tuberculosis (M.tb.) infection leads to over 1.5 million deaths annually, despite widespread vaccination with BCG at birth. Causes for the ongoing tuberculosis endemic are complex and include the failure of BCG to protect many against progressive pulmonary disease. Host genetics is one of the known factors implicated in susceptibility to primary tuberculosis, but less is known about the role that host genetics plays in controlling host responses to vaccination against M.tb. Here, we addressed this gap by utilizing Diversity Outbred (DO) mice as a small animal model to query genetic drivers of vaccine-induced protection against M.tb. DO mice are a highly genetically and phenotypically diverse outbred population that is well suited for fine genetic mapping. Similar to outcomes in people, our previous studies demonstrated that DO mice have a wide range of disease outcomes following BCG vaccination and M.tb. challenge. In the current study, we used a large population of BCG-vaccinated/M.tb.-challenged mice to perform quantitative trait loci mapping of complex infection traits; these included lung and spleen M.tb. burdens, as well as lung cytokines measured at necropsy. We found sixteen chromosomal loci associated with complex infection traits and cytokine production. QTL associated with bacterial burdens included a region encoding major histocompatibility antigens that are known to affect susceptibility to tuberculosis, supporting validity of the approach. Most of the other QTL represent novel associations with immune responses to M.tb. and novel pathways of cytokine regulation. Most importantly, we discovered that protection induced by BCG is a multigenic trait, in which genetic loci harboring functionally-distinct candidate genes influence different aspects of immune responses that are crucial collectively for successful protection. These data provide exciting new avenues to explore and exploit in developing new vaccines against M.tb.
Topics: Humans; Animals; Mice; Mycobacterium tuberculosis; BCG Vaccine; Tuberculosis; Tuberculosis Vaccines; Vaccination; Genetic Loci; Cytokines; Antigens, Bacterial; Mycobacterium bovis
PubMed: 38452145
DOI: 10.1371/journal.ppat.1012069 -
BMC Infectious Diseases Mar 2024Nontuberculous mycobacteria (NTM) are environmental bacteria which may cause chronic lung disease. The prevalence of NTM pulmonary infection and disease has been...
BACKGROUND
Nontuberculous mycobacteria (NTM) are environmental bacteria which may cause chronic lung disease. The prevalence of NTM pulmonary infection and disease has been increasing in the United States and globally. The predominant clinically relevant species of NTM in the United States are Mycobacterium avium complex (MAC) species and Mycobacterium abscessus. With the development of rapid species identification methods for NTM (e.g. PCR probes), more testing for NTM is being conducted through commercial labs, such as Laboratory Corporation of America (Labcorp), which provides deidentified real-time testing data to the Centers for Disease Control (CDC) pursuant to a data sharing agreement. Because NTM lung infections are not reportable in most states, other data sources are key to understanding NTM testing patterns, positivity rates, and species distributions to track infection trends and identify clinical care needs.
METHODS
We obtained national Labcorp data for the period January 2019 through mid-April 2022. We subset the data to only respiratory samples sent for Acid Fast Bacilli (AFB) cultures. NTM positive results were defined as those which identified an NTM species and are not Mycobacterium tuberculosis, Mycobacterium bovis, or Mycobacterium gordonae.
RESULTS
Overall, 112,528 respiratory samples were sent for AFB testing during the study period; 26.3% were from the Southeast U.S., identified as HSS Region IV in the Labcorp dataset, and 23.0% were from the Pacific and South Pacific region (Region IX). The culture positive prevalence ranged from 20.2% in the Southeast to 9.2% in the East North Central region (Region V). In the Southeast US, M. abscessus prevalence was 4.0%. For MAC, the highest prevalence was observed in the Mountain region (Region VII) (13.5%) and the lowest proportion was in the East South Central region (7.3%, Region III). Among positive tests, the proportion which was MAC varied from 61.8% to 88.9% and was highest in the Northeast U.S. The proportion of positive samples which were M. abscessus ranged from 3.8% to 19.7% and was highest in the Southeast.
CONCLUSIONS
The Southeastern region of the U.S. has the highest rate of culture positivity in Labcorp tests for total NTM and, of all positive tests, the highest proportion of M. abscessus. These estimates may underrepresent the true number of M. abscessus infections because M. absesscus-specific probes are not commercially available and not all NTM testing in the United States is done by Labcorp. Analysis of real-time testing data from commercial laboratories may provide insights into risk factors for NTM culture positivity in 'hotspot' areas.
Topics: United States; Humans; Nontuberculous Mycobacteria; Mycobacterium avium Complex; Mycobacterium abscessus; Laboratories; Mycobacterium bovis; Opportunistic Infections
PubMed: 38448840
DOI: 10.1186/s12879-024-09059-9 -
Frontiers in Veterinary Science 2024Deer tuberculosis is a chronic zoonotic infectious disease, despite the existence of socio-economic and zoonotic risk factors, but at present, there has been no...
BACKGROUND
Deer tuberculosis is a chronic zoonotic infectious disease, despite the existence of socio-economic and zoonotic risk factors, but at present, there has been no systematic review of deer tuberculosis prevalence in mainland China. The aim of this meta-analysis was to estimate the overall prevalence of deer TB in mainland China and to assess possible associations between potential risk factors and the prevalence of deer tuberculosis.
METHODOLOGY
This study was searched in six databases in Chinese and English, respectively (1981 to December 2023). Four authors independently reviewed the titles and abstracts of all retrieved articles to establish the inclusion exclusion criteria. Using the meta-analysis package estimated the combined effects. Cochran's Q-statistic was used to analyze heterogeneity. Funnel plots (symmetry) and used the Egger's test identifying publication bias. Trim-and-fill analysis methods were used for validation and sensitivity analysis. we also performed subgroup and meta-regression analyses.
RESULTS
In this study, we obtained 4,400 studies, 20 cross-sectional studies were screened and conducted a systematic review and meta-analysis. Results show: The overall prevalence of tuberculosis in deer in mainland China was 16.1% (95% confidence interval (CI):10.5 24.6; (Deer tuberculosis infected 5,367 out of 22,215 deer in mainland China) 5,367/22215; 1981 to 2023). The prevalence in Central China was the highest 17.5% (95% CI:14.0-21.9; 63/362), and among provinces, the prevalence in Heilongjiang was the highest at 26.5% (95% CI:13.2-53.0; 1557/4291). was the most commonly infected species, with a prevalence of 35.3% (95% CI:18.5-67.2; 6/17). We also assessed the association between geographic risk factors and the incidence of deer tuberculosis.
CONCLUSION
Deer tuberculosis is still present in some areas of China. Assessing the association between risk factors and the prevalence of deer tuberculosis showed that reasonable and scientific-based breeding methods, a suitable breeding environment, and rapid and accurate detection methods could effectively reduce the prevalence of deer tuberculosis. In addition, in the management and operation of the breeding base, improving the scientific feed nutrition standards and establishing comprehensive standards for disease prevention, immunization, quarantine, treatment, and disinfection according to the breeding varieties and scale, are suggested as ways to reduce the prevalence of deer tuberculosis.
PubMed: 38440384
DOI: 10.3389/fvets.2024.1333975 -
Scientific Reports Mar 2024Although several brands of tuberculin purified protein derivatives (PPDs) are available for diagnosing bovine tuberculosis (bTB), comparative studies to determine their...
Although several brands of tuberculin purified protein derivatives (PPDs) are available for diagnosing bovine tuberculosis (bTB), comparative studies to determine their diagnostic accuracy are infrequent. In Ecuador we compared two different PPD brands for bTB diagnosis using skin testing and measuring skin thickness increase. Additionally, we evaluated four PPD brands, including those used for skin testing, in the Bovine Tuberculosis Interferon Gamma Test (IFN-γ test) measuring IFN-γ induction in whole blood. The study included 17 naturally tuberculosis-infected PPD and IFN-γ test positive bovines. Both the field and laboratory results showed significant differences in classifying the 17 bovines as bTB positive or negative. We hypothesize that several factors, such as the genetic background of the cows, sensitization to environmental mycobacteria, M. bovis strains involved in the bTB infection, and the manufacturing procedures of the PPDs, could have influenced the immune reaction toward the different tuberculin PPD brands. Our study emphasizes the necessity for comparative studies aimed at determining the diagnostic accuracy of PPD brands for bTB diagnosis as well as the development of standardized methods for PPD production and potency determination.
Topics: Animals; Female; Cattle; Tuberculosis, Bovine; Tuberculin; Mycobacterium bovis; Tuberculin Test; Tuberculosis
PubMed: 38431678
DOI: 10.1038/s41598-024-52089-1 -
Journal of Dairy Science Jul 2024We investigated the prevalence and spatial distribution of selected pathogens associated with infectious diseases of dairy cattle in Ontario, Canada. The cross-sectional...
We investigated the prevalence and spatial distribution of selected pathogens associated with infectious diseases of dairy cattle in Ontario, Canada. The cross-sectional study surveyed bulk tank milk for antibodies against bovine leukemia virus (BLV), Mycobacterium avium ssp. paratuberculosis (MAP), and Salmonella Dublin, and for the presence of mastitis pathogens (Staphylococcus aureus, Streptococcus agalactiae, Mycoplasma bovis). Between October 2021 and June 2022, bulk tank milk samples were obtained from every commercial dairy farm in Ontario (n = 3,286). Samples underwent ELISA testing for the presence of BLV, MAP, and S. Dublin antibodies, and quantitative PCR testing for the detection of specific antigens of pathogens associated with mastitis. Bayesian models were used to estimate prevalence, and spatial analysis was carried out to identify regional clusters of high pathogen prevalence. Prevalence varied for different pathogens, and BLV was widespread across dairy farms in Ontario, with an estimated prevalence of 88.3%. The prevalence of MAP, Staph. aureus and S. Dublin in Ontario dairy herds was 39.8%, 31.5%, and 5.1%, respectively. The vast majority of dairy herds in Ontario were free of intramammary infections caused by Strep. agalactiae and M. bovis. Clusters of increased positive test rates were detected for S. Dublin, MAP, and Staph. aureus, indicating potential geographic risk factors for pathogen transmission. For S. Dublin, an area of increased test positivity rates was detected in southwestern Ontario, close to the Canada-United States border where most of the dairy herds in Ontario are located. Conversely, a localized cluster of positive test outcomes involving 14 subdivisions located in the southeastern region of Ontario was detected for Staph. aureus. Findings from our survey highlight the importance of the testing of aggregated samples and conducting spatial analysis as part of disease surveillance programs, and for implementing risk-based trading approaches among dairy producers.
Topics: Animals; Cattle; Ontario; Prevalence; Female; Cross-Sectional Studies; Cattle Diseases; Milk; Mastitis, Bovine; Staphylococcus aureus; Communicable Diseases; Mycobacterium avium subsp. paratuberculosis; Dairying; Streptococcus agalactiae
PubMed: 38428494
DOI: 10.3168/jds.2023-24197 -
Frontiers in Microbiology 2024Animal tuberculosis, caused by , presents a significant threat to both livestock industries and public health. tests rely on detecting antigen specific immune...
Animal tuberculosis, caused by , presents a significant threat to both livestock industries and public health. tests rely on detecting antigen specific immune responses, which can be influenced by exposure to non-tuberculous mycobacteria, test technique, and duration and severity of infection. Despite advancements in direct detection, mycobacterial culture remains the primary diagnostic standard. Recent efforts have explored culture-independent PCR-based methods for identifying mycobacterial DNA in respiratory samples. This study aimed to detect in nasal swabs from goats () cohabiting with -infected cattle in KwaZulu-Natal, South Africa. Nasal swabs were collected from 137 communal goats exposed to -positive cattle and 20 goats from a commercial dairy herd without history. Swabs were divided into three aliquots for analysis. The first underwent GeneXpert® MTB/RIF Ultra assay (Ultra) screening. DNA from the second underwent mycobacterial genus-specific PCR and Sanger sequencing, while the third underwent mycobacterial culture followed by PCR and sequencing. Deep sequencing identified DNA in selected Ultra-positive swabs, confirmed by region-of-difference (RD) PCR. Despite no other evidence of infection, viable was cultured from three communal goat swabs, confirmed by PCR and sequencing. Deep sequencing of DNA directly from swabs identified in the same culture-positive swabs and eight additional communal goats. No was found in commercial dairy goats, but various NTM species were detected. This highlights the risk of exposure or infection in goats sharing pastures with infected cattle. Rapid Ultra screening shows promise for selecting goats for further testing. These techniques may enhance detection in paucibacillary samples and serve as valuable research tools.
PubMed: 38419629
DOI: 10.3389/fmicb.2024.1349163 -
Scientific Reports Feb 2024Persistent tuberculosis (TB) in cattle populations in England has been associated with an exchange of infection with badgers (Meles meles). A badger control policy (BCP)...
Persistent tuberculosis (TB) in cattle populations in England has been associated with an exchange of infection with badgers (Meles meles). A badger control policy (BCP) commenced in 2013. Its aim was to decrease TB incidence in cattle by reducing the badger population available to provide a wildlife reservoir for bovine TB. Monitoring data from 52 BCP intervention areas 200-1600 km in size, starting over several years, were used to estimate the change in TB incidence rate in cattle herds, which was associated with time since the start of the BCP in each area. A difference in differences analysis addressed the non-random selection and starting sequence of the areas. The herd incidence rate of TB reduced by 56% (95% Confidence Interval 41-69%) up to the fourth year of BCP interventions, with the largest drops in the second and third years. There was insufficient evidence to judge whether the incidence rate reduced further beyond 4 years. These estimates are the most precise for the timing of declines in cattle TB associated with interventions primarily targeting badgers. They are within the range of previous estimates from England and Ireland. This analysis indicates the importance of reducing transmission from badgers to reduce the incidence of TB in cattle, noting that vaccination of badgers, fertility control and on farm biosecurity may also achieve this effect.
Topics: Animals; Cattle; Tuberculosis, Bovine; Mycobacterium bovis; Mustelidae; England; Policy; Disease Reservoirs
PubMed: 38418486
DOI: 10.1038/s41598-024-54062-4 -
Scientific Reports Feb 2024Gram-negative spiral-shaped Helicobacter pylori (Hp) bacteria induce the development of different gastric disorders. The growing resistance of Hp to antibiotics prompts...
Gram-negative spiral-shaped Helicobacter pylori (Hp) bacteria induce the development of different gastric disorders. The growing resistance of Hp to antibiotics prompts to search for new therapeutic formulations. A promising candidate is Mycobacterium bovis BCG (BCG) with immunomodulatory properties. Biodegradable mucoadhesive chitosan is a good carrier for delivering BCG mycobacteria to the gastric mucosal environment. This study aimed to show whether BCG bacilli are able to increase the phagocytic activity of Cavia porcellus-guinea pig macrophages derived from the bone marrow towards fluorescently labeled Escherichia coli. Furthermore, to encapsulate live BCG bacilli, in spray-dried chitosan microparticles (CHI-MPs), and assess the pH-dependent release of mycobacteria in pH conditions mimicking gastric (acidic) or gut (alkaline) milieu. Microparticles (MPs) were made of chitosan and coated with Pluronic F-127-(Plur) or N-Acetyl-D-Glucosamine-(GlcNAc) to increase the MPs resistance to low pH or to increase anti-Hp effect, respectively. Spray-drying method was used for microencapsulation of live BCG. The biosafety of tested CHI-MPs has been confirmed using cell models in vitro and the model of guinea pig in vivo. The CHI-MPs loaded with BCG released live mycobacteria at pH 3.0 (CHI-GlcNAc-MPs) or pH 8.0. (CHI-Plur-MPs). The CHI-MPs loaded with live BCG can be used for per os inoculation of Cavia porcellus to check the effectiveness of delivered mycobacteria in increasing anti-H. pylori host response.
Topics: Animals; Guinea Pigs; Chitosan; Mycobacterium bovis; Helicobacter pylori; BCG Vaccine; Helicobacter Infections; Hydrogen-Ion Concentration
PubMed: 38413775
DOI: 10.1038/s41598-024-55353-6 -
Veterinary Journal (London, England :... Apr 2024Cases of canine tuberculosis, a zoonotic infection of significant public health significance, are typically only sporadically reported in the literature. For this... (Review)
Review
Cases of canine tuberculosis, a zoonotic infection of significant public health significance, are typically only sporadically reported in the literature. For this observational study, case details were collated both retrospectively and prospectively for dogs infected with Mycobacterium tuberculosis-complex (MTBC) organisms. A total of 18 previously unreported cases as well as 565 historically reported confirmed cases were reviewed. A variety of diagnostic techniques were used to make a confirmed diagnosis of tuberculosis (culture, interferon-gamma release assay [IGRA], and PCR). The reference standard for diagnosis is culture; however, this was negative or not attempted in some dogs. Where fully speciated, all cases were caused by infection with one of three MTBC organisms: M. tuberculosis, Mycobacterium bovis, or Mycobacterium microti. This study includes the first documented canine infections with M. microti in the UK. All cases were assigned to one of four clinical groups based on the presenting signs: 44.1% were primarily pulmonary, 14.5% were primarily abdominal, and the remainder were disseminated or miscellaneous. The development of adjunctive tests remains necessary to support early treatment decisions pending reporting of culture for MTBC organisms, which can take weeks to months. Definitive treatment, where attempted, was successful in most cases. Of the 13 dogs treated by the authors with triple combination antimicrobial therapy, a good clinical outcome was seen in 12 (92%) of them.
Topics: Animals; Dogs; Retrospective Studies; Tuberculosis; Mycobacterium bovis; Mycobacterium tuberculosis; Zoonoses; Dog Diseases; Observational Studies as Topic; Observational Studies, Veterinary as Topic
PubMed: 38412886
DOI: 10.1016/j.tvjl.2024.106089 -
Frontiers in Cellular and Infection... 2024(BCG) is a live strain of m () for use as an attenuated vaccine to prevent (TB) infection, while it could also lead to an infection in immunodeficient patients.... (Review)
Review
(BCG) is a live strain of m () for use as an attenuated vaccine to prevent (TB) infection, while it could also lead to an infection in immunodeficient patients. could infect patients with immunodeficiency via BCG vaccination. Disseminated BCG disease (BCGosis) is extremely rare and has a high mortality rate. This article presents a case of a 3-month-old patient with disseminated BCG infection who was initially diagnosed with hemophagocytic syndrome (HPS) and eventually found to have X-linked severe combined immunodeficiency (X-SCID). and its drug resistance genes were identified by metagenomics next-generation sequencing (mNGS) combined with targeted next-generation sequencing (tNGS) in blood and cerebrospinal fluid. Whole exome sequencing (WES) revealed a pathogenic variant in the common γ-chain gene (), confirming X-SCID. Finally, antituberculosis therapy and umbilical cord blood transplantation were given to the patient. He was successfully cured of BCGosis, and his immune function was restored. The mNGS combined with the tNGS provided effective methods for diagnosing rare BCG infections in children. Their combined application significantly improved the sensitivity and specificity of the detection of .
Topics: Male; Infant; Child; Humans; Mycobacterium bovis; BCG Vaccine; X-Linked Combined Immunodeficiency Diseases; Tuberculosis; Immunologic Deficiency Syndromes; Latent Tuberculosis; High-Throughput Nucleotide Sequencing
PubMed: 38410723
DOI: 10.3389/fcimb.2024.1341236