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International Journal of... Apr 2024Bacille Calmette-Guérin (BCG) is a live-attenuated vaccine routinely administered to newborns to prevent severe forms of tuberculosis (TB) in TB-endemic countries.... (Review)
Review
Infantile Disseminated Bacille Calmette-Guérin Disease with Hemophagocytosis and Mimicking Juvenile Myelomonocytic Leukemia: A Case Report with Concise Literature Review.
Bacille Calmette-Guérin (BCG) is a live-attenuated vaccine routinely administered to newborns to prevent severe forms of tuberculosis (TB) in TB-endemic countries. Disseminated BCG vaccine disease is a classic feature of children with human immunodeficiency virus (HIV) or primary immunodeficiency disorders (PIDs) and is associated with high mortality. We report a case of a 6-month-old infant with disseminated BCG disease and hemophagocytic lymphohistiocytosis mimicking juvenile myelomonocytic leukemia with no demonstrable features of HIV or PID even after extensive laboratory work-up and succumbed to progressive disease. Disseminated BCG disease is a rare and potentially fatal complication of BCG vaccine, and prompt immunological evaluation complemented by initiation of 4-drug antitubercular therapy and definitive treatment with antiretroviral therapy or hematopoietic stem cell transplant is warranted.
Topics: Humans; Leukemia, Myelomonocytic, Juvenile; Infant; Lymphohistiocytosis, Hemophagocytic; BCG Vaccine; Tuberculosis; Diagnosis, Differential; Fatal Outcome; Male; Mycobacterium bovis; Antitubercular Agents
PubMed: 38916394
DOI: 10.4103/ijmy.ijmy_48_24 -
Microbiology Spectrum Jun 2024A human challenge model has the potential to fundamentally advance our understanding of early human immune responses to infection, while rapidly evaluating vaccines and...
UNLABELLED
A human challenge model has the potential to fundamentally advance our understanding of early human immune responses to infection, while rapidly evaluating vaccines and other therapeutic interventions. Here, using a murine tail infection model, we tested a very well-characterized working cell bank of the proposed challenge isolate JKD8049 in naïve and bacille Calmette-Guérin (BCG)-vaccinated BALB/c mice. All 10 naïve mice were successfully infected with 20 colony-forming units (CFU) of [95% confidence interval (CI) 17-22 CFU] with a mean time to visible lesion of 86 days (95% CI 79-92 days). In the 10 vaccinated mice, there was a significant delay in the mean time to lesion compared to the naïve controls of 24 days ( = 0.0003), but all mice eventually developed ulcerative lesions. This study informs a future human infection model by demonstrating the successful application of the challenge agent in this model and highlights both the promise and the problems with trying to induce protective immunity against .
IMPORTANCE
In preparation for its proposed use in a controlled human infection model (CHIM), this study reports the successful infection of BALB/c mice using a carefully characterized, low-dose inoculum of JKD8049 (our proposed CHIM strain). We also demonstrate that bacille Calmette-Guérin delays the onset of disease but cannot alter the course of illness once a lesion becomes apparent. We also validate the findings of previous low-dose challenges that used less accurate methods to determine the inoculum, but our presented methodology is practical, accurate, and anticipated to be reproducible.
PubMed: 38916323
DOI: 10.1128/spectrum.00555-24 -
Frontiers in Veterinary Science 2024Wildlife represents an increasingly important source of pathogens of medical and veterinary importance. Surveillance in wildlife offers an insight on current...
INTRODUCTION
Wildlife represents an increasingly important source of pathogens of medical and veterinary importance. Surveillance in wildlife offers an insight on current epidemiological status of selected pathogens and help to prevent spillovers to humans and livestock.
MATERIAL AND METHODS
Our study included 312 wild ruminants belonging to five species: Roe deer ( = 134), red deer ( = 113), Alpine chamois ( = 53), European mouflon ( = 10) and Alpine ibex ( = 2). Seven pathogens that may have profound effect on human/livestock health and economic viability of the farms were tested using serological methods.
RESULTS
Antibodies against spp., subsp. (MAP) and were detected in 34.62% (108/312), 0.96% (3/312), 2.24% (7/312), 0, 0.96% (3/312), 0, 0.64% (2/312) of animals tested, respectively. Because of low prevalences, risk factors were assessed only for . Sex (female>male) and species (roe deer>red deer, roe deer>Alpine chamois) were significantly associated with the positive outcome, while age was not.
DISCUSSION
Adult males had the lowest prevalence which offers future research opportunities. The lower seroprevalence of most investigated pathogens suggests game meat, if properly cooked, as being relatively safe for human consumption. This is the first study investigating the seroprevalence and associated risk factors of selected pathogens in wild ruminants in Slovenia.
PubMed: 38915887
DOI: 10.3389/fvets.2024.1415304 -
Scientific Reports Jun 2024Bovine tuberculosis (bTB) is endemic and has a substantial impact on the livestock sector in Ethiopia and other low and middle-income countries (LMICs). With a national...
Bovine tuberculosis (bTB) is endemic and has a substantial impact on the livestock sector in Ethiopia and other low and middle-income countries (LMICs). With a national emphasis on dairy farm intensification to boost milk production and spur economic growth, the incidence of bTB is anticipated to rise. However, Ethiopia, like other LMICs, lacks a comprehensive national bTB control strategy due to the economic and social infeasibility of traditional test-and-cull (TC) approaches. To inform the development of such a strategy, we evaluated the effectiveness and feasibility of TC and test-and-segregation (TSg) strategies for bTB control on Ethiopian dairy farms. A TC approach was used at Farm A [N = 62; comparative cervical test (CCT) > 4 mm, starting prevalence 11.3%] while TSg was implemented at Farm B (N = 45; CCT > 4 mm, prevalence 22.2%), with testing intervals of 2-4 months. Both strategies achieved a reduction in bTB prevalence to 0%, requiring seven rounds of TC over 18 months at Farm A, and five rounds of TSg over 12 months at Farm B's negative herd. The results show that adopting more sensitive thresholds [CCT > 0 mm or single cervical test (SCT) > 2 mm] during later rounds was pivotal in identifying and managing previously undetected infections, emphasizing the critical need for optimized diagnostic thresholds. Cost analysis revealed that TC was approximately twice as expensive as TSg, primarily due to testing, labor, and cow losses in TC, versus construction of new facilities and additional labor for TSg. This underscores the economic and logistical challenges of bTB management in resource-limited settings. Taken together, our study highlights an urgent need for the exploration of alternative approaches including TSg and or vaccination to mitigate within herd transmission and enable implementation of bTB control in regions where TC is not feasible.
Topics: Cattle; Animals; Tuberculosis, Bovine; Ethiopia; Dairying; Prevalence; Feasibility Studies; Farms; Female; Mycobacterium bovis
PubMed: 38906922
DOI: 10.1038/s41598-024-64884-x -
Acta Biochimica Et Biophysica Sinica Jun 2024Tuberculosis (TB), caused by ( . ), remains one of the leading causes of fatal infectious diseases worldwide. The only licensed vaccine, Bacillus Calmette-Guérin...
Tuberculosis (TB), caused by ( . ), remains one of the leading causes of fatal infectious diseases worldwide. The only licensed vaccine, Bacillus Calmette-Guérin (BCG), has variable efficacy against TB in adults. Insufficiency of immune cell function diminishes the protective effects of the BCG vaccine. It is critical to clarify the mechanism underlying the antimycobacterial immune response during BCG vaccination. Macrophage mannose receptor (MR) is important for enhancing the uptake and processing of glycoconjugated antigens from pathogens for presentation to T cells, but the roles of macrophage MR in the BCG-induced immune response against . are not yet clear. Here, we discover that macrophage MR deficiency impairs the antimycobacterial immune response in BCG-vaccinated mice. Mechanistically, macrophage MR triggers JAK-STAT1 signaling, which promotes antigen presentation via upregulated MHC-II and induces IL-12 production by macrophages, contributing to CD4 T cell activation and IFN-γ production. MR deficiency in macrophages reduces the vaccine efficacy of BCG and increases susceptibility to . H37Ra challenge in mice. Our results suggest that MR is critical for macrophage antigen presentation and the antimycobacterial immune response to BCG vaccination and offer valuable guidance for the preventive strategy of BCG immunization.
PubMed: 38894685
DOI: 10.3724/abbs.2024100 -
International Journal of Molecular... Jun 2024() is the causative agent of bovine tuberculosis (bTb). Genetic selection aiming to identify less susceptible animals has been proposed as a complementary measure in...
Genome-Wide Association Study Reveals Quantitative Trait Loci and Candidate Genes Associated with High Interferon-gamma Production in Holstein Cattle Naturally Infected with .
() is the causative agent of bovine tuberculosis (bTb). Genetic selection aiming to identify less susceptible animals has been proposed as a complementary measure in ongoing programs toward controlling infection. However, individual animal phenotypes for bTb based on interferon-gamma (IFNɣ) and its use in bovine selective breeding programs have not been explored. In the current study, IFNɣ production was measured using a specific IFNɣ ELISA kit in bovine purified protein derivative (bPPD)-stimulated blood samples collected from Holstein cattle. DNA isolated from the peripheral blood samples collected from the animals included in the study was genotyped with the EuroG Medium Density bead Chip, and the genotypes were imputed to whole-genome sequences. A genome-wide association analysis (GWAS) revealed that the IFNɣ in response to bPPD was associated with a specific genetic profile (heritability = 0.23) and allowed the identification of 163 SNPs, 72 quantitative trait loci (QTLs), 197 candidate genes, and 8 microRNAs (miRNAs) associated with this phenotype. No negative correlations between this phenotype and other phenotypes and traits included in the Spanish breeding program were observed. Taken together, our results define a heritable and distinct immunogenetic profile associated with strong production of IFNɣ in response to .
Topics: Animals; Cattle; Quantitative Trait Loci; Mycobacterium bovis; Genome-Wide Association Study; Interferon-gamma; Tuberculosis, Bovine; Polymorphism, Single Nucleotide; Phenotype; Genotype
PubMed: 38892353
DOI: 10.3390/ijms25116165 -
Foods (Basel, Switzerland) May 2024Brazilian artisanal cheeses have recently gained significant commercial prominence and consumer favor, primarily due to their distinctive sensory attributes and cultural... (Review)
Review
Brazilian artisanal cheeses have recently gained significant commercial prominence and consumer favor, primarily due to their distinctive sensory attributes and cultural and historical appeal. Many of these cheeses are made with raw milk and undergo a relatively short ripening period, sometimes ranging from 4 to 8 days, though it is usually shorter than the period stated by law. Moreover, there is insufficient evidence regarding the efficacy of a short ripening period in reducing certain zoonotic foodborne pathogens, such as spp., , and (as part of the complex). Additionally, a literature analysis revealed that the usual ripening conditions of Brazilian artisanal cheeses made with raw milk may be inefficient in reducing the levels of some hazardous bacterial, including spp., , coagulase-positive , , and , to the acceptable limits established by law, thus failing to ensure product safety for all cheese types. Moreover, the assessment of the microbiological safety for this type of cheese should be broader and should also consider zoonotic pathogens commonly found in bovine herds. Finally, a standardized protocol for evaluating the effectiveness of cheese ripening must be established by considering its peculiarities.
PubMed: 38890872
DOI: 10.3390/foods13111644 -
Foods (Basel, Switzerland) May 2024(), the microorganism responsible for bovine tuberculosis (bTB), is transferred to people by the ingestion of unpasteurized milk and unprocessed fermented milk products...
(), the microorganism responsible for bovine tuberculosis (bTB), is transferred to people by the ingestion of unpasteurized milk and unprocessed fermented milk products obtained from animals with the infection. The identification of in milk samples is of the utmost importance to successfully prevent zoonotic diseases and maintain food safety. This study presents a comprehensive description of a highly efficient molecular test utilizing recombinase-aided amplification (RPA)-clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein (Cas) 13a-lateral flow detection (LFD) for detection. In contrast to ELISA, RPA-CRISPR-Cas13a-LFD exhibited greater accuracy and sensitivity in the detection of in milk, presenting a detection limit of 2 × 10 copies/μL within a 2 h time frame. The two tests exhibited a moderate level of agreement, as shown by a kappa value of 0.452 (95%CI: 0.287-0.617, < 0.001). RPA-CRISPR-Cas13a-LFD holds significant potential as a robust platform for pathogen detection in complex samples, thereby enabling the more dependable regulation of food safety examination, epidemiology research, and medical diagnosis.
PubMed: 38890830
DOI: 10.3390/foods13111601 -
BioRxiv : the Preprint Server For... May 2024Previous studies have demonstrated the efficacy and feasibility of an anti-viral vaccine strategy that takes advantage of pre-existing CD4 helper T (Th) cells induced...
Previous studies have demonstrated the efficacy and feasibility of an anti-viral vaccine strategy that takes advantage of pre-existing CD4 helper T (Th) cells induced by bacille Calmette-Guérin (BCG) vaccination. This strategy uses immunization with recombinant fusion proteins comprised of a cell surface expressed viral antigen, such as a viral envelope glycoprotein, engineered to contain well-defined BCG Th cell epitopes, thus rapidly recruiting Th cells induced by prior BCG vaccination to provide intrastructural help to virus-specific B cells. In the current study, we show that Th cells induced by BCG were localized predominantly outside of germinal centers and promoted antibody class switching to isotypes characterized by strong Fc receptor interactions and effector functions. Furthermore, BCG vaccination also upregulated FcγR expression to potentially maximize antibody-dependent effector activities. Using a mouse model of Ebola virus (EBOV) infection, this vaccine strategy provided sustained antibody levels with strong IgG2c bias and protection against lethal challenge. This general approach can be easily adapted to other viruses, and may be a rapid and effective method of immunization against emerging pandemics in populations that routinely receive BCG vaccination.
PubMed: 38853867
DOI: 10.1101/2024.05.28.595735 -
Scientific Reports Jun 2024The short-lived nature and heterogeneity of Natural Killer (NK) cells limit the development of NK cell-based therapies, despite their proven safety and efficacy against...
The short-lived nature and heterogeneity of Natural Killer (NK) cells limit the development of NK cell-based therapies, despite their proven safety and efficacy against cancer. Here, we describe the biological basis, detailed phenotype and function of long-lived anti-tumour human NK cells (CD56CD16), obtained without cell sorting or feeder cells, after priming of peripheral blood cells with Bacillus Calmette-Guérin (BCG). Further, we demonstrate that survival doses of a cytokine combination, excluding IL18, administered just weekly to BCG-primed NK cells avoids innate lymphocyte exhaustion and leads to specific long-term proliferation of innate cells that exert potent cytotoxic function against a broad range of solid tumours, mainly through NKG2D. Strikingly, a NKG2CCD57FcεRIγ NK cell population expands after BCG and cytokine stimulation, independently of HCMV serology. This strategy was exploited to rescue anti-tumour NK cells even from the suppressor environment of cancer patients' bone marrow, demonstrating that BCG confers durable anti-tumour features to NK cells.
Topics: Killer Cells, Natural; Humans; Cell Proliferation; Neoplasms; BCG Vaccine; Mycobacterium bovis; Lymphocyte Activation; NK Cell Lectin-Like Receptor Subfamily K; Interleukins; CD56 Antigen; NK Cell Lectin-Like Receptor Subfamily C
PubMed: 38849432
DOI: 10.1038/s41598-024-62968-2