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Scientific Reports May 2024Bacterial zoonoses are diseases caused by bacterial pathogens that can be naturally transmitted between humans and vertebrate animals. They are important causes of...
Bacterial zoonoses are diseases caused by bacterial pathogens that can be naturally transmitted between humans and vertebrate animals. They are important causes of non-malarial fevers in Kenya, yet their epidemiology remains unclear. We investigated brucellosis, Q-fever and leptospirosis in the venous blood of 216 malaria-negative febrile patients recruited in two health centres (98 from Ijara and 118 from Sangailu health centres) in Garissa County in north-eastern Kenya. We determined exposure to the three zoonoses using serological (Rose Bengal test for Brucella spp., ELISA for C. burnetti and microscopic agglutination test for Leptospira spp.) and real-time PCR testing and identified risk factors for exposure. We also used non-targeted metagenomic sequencing on nine selected patients to assess the presence of other possible bacterial causes of non-malarial fevers. Considerable PCR positivity was found for Brucella (19.4%, 95% confidence intervals [CI] 14.2-25.5) and Leptospira spp. (1.7%, 95% CI 0.4-4.9), and high endpoint titres were observed against leptospiral serovar Grippotyphosa from the serological testing. Patients aged 5-17 years old had 4.02 (95% CI 1.18-13.70, p-value = 0.03) and 2.42 (95% CI 1.09-5.34, p-value = 0.03) times higher odds of infection with Brucella spp. and Coxiella burnetii than those of ages 35-80. Additionally, patients who sourced water from dams/springs, and other sources (protected wells, boreholes, bottled water, and water pans) had 2.39 (95% CI 1.22-4.68, p-value = 0.01) and 2.24 (1.15-4.35, p-value = 0.02) times higher odds of exposure to C. burnetii than those who used unprotected wells. Streptococcus and Moraxella spp. were determined using metagenomic sequencing. Brucellosis, leptospirosis, Streptococcus and Moraxella infections are potentially important causes of non-malarial fevers in Garissa. This knowledge can guide routine diagnosis, thus helping lower the disease burden and ensure better health outcomes, especially in younger populations.
Topics: Humans; Kenya; Adolescent; Male; Child; Female; Adult; Child, Preschool; Middle Aged; Leptospirosis; Fever; Animals; Young Adult; Leptospira; Bacterial Zoonoses; Brucellosis; Brucella; Outpatients; Q Fever; Aged; Serologic Tests; Zoonoses
PubMed: 38806576
DOI: 10.1038/s41598-024-62714-8 -
Pharmaceuticals (Basel, Switzerland) May 2024Brucellosis is an infection widely distributed around the world, and in some countries it is considered a public health problem. Brucellosis causes insidious symptoms...
Brucellosis is an infection widely distributed around the world, and in some countries it is considered a public health problem. Brucellosis causes insidious symptoms that make it difficult to diagnose. Infection can also trigger chronic pain and neuropsychiatric complications. Antibiotics are not always effective to eradicate infection, contributing to chronicity. We aimed to investigate the effects of antibiotic treatment on proinflammatory cytokines, neurotransmitters, corticosterone, and behavior in a murine model of infecrion of strain 2308. Four study groups were created: (a) control; (b) antibiotic control; (c) infected with 2308; and (d) infected and treated with rifampicin and doxycycline. We determined 2308 colony-forming units (CFUs), the count of dendritic cells, and macrophages in the spleen; serum levels of cytokines and corticosterone; levels of serotonin, dopamine, epinephrine, and norepinephrine in the brain; and equilibrium, physical strength, anxiety, and hopelessness tests. The infected and treated mice group was compared with the control and infected mice to assess whether treatment is sufficient to recover neuroimmunoendocrine parameters. Our results showed that despite the treatment of brucellosis with rifampicin and doxycycline, antibiotic-treated mice showed a persistence of 2308 CFUs, an increased count in macrophage number, and higher circulating levels of corticosterone. Furthermore, the levels of IL-12, IL-6, and TNF-α remained higher. We found a decrease in muscular strength and equilibrium concomitant to changes in neurotransmitters in the hippocampus, cerebellum, and frontal cortex. Our data suggest that the remaining bacterial load after antibiotic administration favors inflammatory, neurochemical, and behavioral alterations, partly explaining the widespread and paradoxical symptomatology experienced by patients with chronic brucellosis.
PubMed: 38794208
DOI: 10.3390/ph17050638 -
Microorganisms May 2024Human brucellosis caused by is a widespread zoonosis that is prevalent in many countries globally. The high homology between members of the genus and spp. often...
Human brucellosis caused by is a widespread zoonosis that is prevalent in many countries globally. The high homology between members of the genus and spp. often complicates the determination of disease etiology in patients. The efficient and reliable identification and distinction of are of primary interest for both medical surveillance and outbreak purposes. A large amount of genomic data for the genus was analyzed to uncover novel probes containing single-nucleotide polymorphisms (SNPs). GAMOSCE v1.0 software was developed based on the above novel eProbes. In conjunction with clinical requirements, an RPA-Cas12a detection method was developed for the on-site determination of and by fluorescence and lateral flow dipsticks (LFDs). We demonstrated the potential of these probes for rapid and accurate detection of the genus and five significant species in silico using GAMOSCE. GAMOSCE was validated on different datasets and correctly identified all strains, demonstrating a strong discrimination ability. The RPA-Cas12a detection method showed good performance in detection in clinical blood samples and veterinary isolates. We provide both in silico and on-site methods that are convenient and reliable for use in local hospitals and public health programs for the detection of brucellosis.
PubMed: 38792847
DOI: 10.3390/microorganisms12051018 -
Microorganisms Apr 2024Brucellosis is one of the most common and widespread bacterial zoonoses and is caused by Gram-negative bacteria belonging to the genus . These organisms are able to... (Review)
Review
Brucellosis is one of the most common and widespread bacterial zoonoses and is caused by Gram-negative bacteria belonging to the genus . These organisms are able to infect and replicate within the placenta, resulting in abortion, one of the main clinical signs of brucellosis. Although the mouse model is widely used to study virulence and, more recently, to evaluate the protection of new vaccines, there is no clear consensus on the experimental conditions (e.g., mouse strains, doses, routes of inoculation, infection/pregnancy time) and the natural host reproducibility of the pregnant mouse model for reproductive brucellosis. This lack of consensus calls for a review that integrates the major findings regarding the effect of wild-type and vaccine strains infections on mouse pregnancy. We found sufficient evidence on the utility of the pregnant mouse model to study -induced placentitis and abortion and propose suitable experimental conditions (dose, time of infection) and pregnancy outcome readouts for and studies. Finally, we discuss the utility and limitations of the pregnant mouse as a predictive model for the abortifacient effect of live vaccines.
PubMed: 38792696
DOI: 10.3390/microorganisms12050866 -
Antioxidants (Basel, Switzerland) May 2024virulence relies on its successful intracellular life cycle. Modulating host cell death is a strategy for to survive and replicate intracellularly. Ferroptosis is a...
virulence relies on its successful intracellular life cycle. Modulating host cell death is a strategy for to survive and replicate intracellularly. Ferroptosis is a novel regulated cell death characterized by iron-triggered excessive lipid peroxidation, which has been proven to be associated with pathogenic bacteria infection. Thus, we attempted to explore if smooth-type infection triggers host cell ferroptosis and what role it plays in infection. We assessed the effects of infection on the lactate dehydrogenase release and lipid peroxidation levels of RAW264.7 macrophages; subsequently, we determined the effect of infection on the expressions of ferroptosis defense pathways. Furthermore, we determined the role of host cell ferroptosis in the intracellular replication and egress of . The results demonstrated that M5 could induce ferroptosis of macrophages by inhibiting the GPX4-GSH axis at the late stage of infection but mitigated ferroptosis by up-regulating the GCH1-BH4 axis at the early infection stage. Moreover, elevating host cell ferroptosis decreased intracellular survival and suppressing host cell ferroptosis increased intracellular replication and egress. Collectively, may manipulate host cell ferroptosis to facilitate its intracellular replication and egress, extending our knowledge about the underlying mechanism of how completes its intracellular life cycle.
PubMed: 38790682
DOI: 10.3390/antiox13050577 -
Scientific Reports May 2024Brucellosis is a zoonotic disease with significant economic and healthcare costs. Despite the eradication efforts, the disease persists. Vaccines prevent disease in...
Brucellosis is a zoonotic disease with significant economic and healthcare costs. Despite the eradication efforts, the disease persists. Vaccines prevent disease in animals while antibiotics cure humans with limitations. This study aims to design vaccines and drugs for brucellosis in animals and humans, using protein modeling, epitope prediction, and molecular docking of the target proteins (BvrR, OMP25, and OMP31). Tertiary structure models of three target proteins were constructed and assessed using RMSD, TM-score, C-score, Z-score, and ERRAT. The best models selected from AlphaFold and I-TASSER due to their superior performance according to CASP 12 - CASP 15 were chosen for further analysis. The motif analysis of best models using MotifFinder revealed two, five, and five protein binding motifs, however, the Motif Scan identified seven, six, and eight Post-Translational Modification sites (PTMs) in the BvrR, OMP25, and OMP31 proteins, respectively. Dominant B cell epitopes were predicted at (44-63, 85-93, 126-137, 193-205, and 208-237), (26-46, 52-71, 98-114, 142-155, and 183-200), and (29-45, 58-82, 119-142, 177-198, and 222-251) for the three target proteins. Additionally, cytotoxic T lymphocyte epitopes were detected at (173-181, 189-197, and 202-210), (61-69, 91-99, 159-167, and 181-189), and (3-11, 24-32, 167-175, and 216-224), while T helper lymphocyte epitopes were displayed at (39-53, 57-65, 150-158, 163-171), (79-87, 95-108, 115-123, 128-142, and 189-197), and (39-47, 109-123, 216-224, and 245-253), for the respective target protein. Furthermore, structure-based virtual screening of the ZINC and DrugBank databases using the docking MOE program was followed by ADMET analysis. The best five compounds of the ZINC database revealed docking scores ranged from (- 16.8744 to - 15.1922), (- 16.0424 to - 14.1645), and (- 14.7566 to - 13.3222) for the BvrR, OMP25, and OMP31, respectively. These compounds had good ADMET parameters and no cytotoxicity, while DrugBank compounds didn't meet Lipinski's rule criteria. Therefore, the five selected compounds from the ZINC20 databases may fulfill the pharmacokinetics and could be considered lead molecules for potentially inhibiting Brucella's proteins.
Topics: Molecular Docking Simulation; Computational Biology; Brucella; Bacterial Outer Membrane Proteins; Humans; Bacterial Proteins; Epitopes, B-Lymphocyte; Brucellosis; Animals
PubMed: 38789443
DOI: 10.1038/s41598-024-61991-7 -
Cureus Apr 2024There are reports that the neglected zoonotic tropical disease brucellosis is reemerging today. Serological tests are being widely used in the diagnosis of brucellosis....
There are reports that the neglected zoonotic tropical disease brucellosis is reemerging today. Serological tests are being widely used in the diagnosis of brucellosis. In the present study, we performed a standard agglutination test (SAT) on 1348 suspected cases of brucellosis during the period of four years from April 2018 to March 2022. We noticed an increase in seropositivity from 2.6% in the year 2018-19 to 7.4% in the year 2021-22. We also noticed a spike in seropositivity in the years 2019-20 (12.5%). Our study shows the recent trend in seropositivity of the disease in Chandigarh and, hence, can be a meaningful addition to the existing serological diagnostic data related to brucellosis.
PubMed: 38779281
DOI: 10.7759/cureus.58711 -
Veterinary Research Forum : An... 2024Bovine brucellosis, an infectious disease transmitted by and , presents a significant zoonotic risk for agricultural economics and animal health. The primary objective...
Bovine brucellosis, an infectious disease transmitted by and , presents a significant zoonotic risk for agricultural economics and animal health. The primary objective of this study was to present a comprehensive understanding of the prevalence and features of strains within the industrial dairy farming sector in Iran. Rose Bengal plate test, standard agglutination test, and indirect enzyme linked immunosorbent assay tests were used to confirm all seropositive animals. A total number of 1,311 bovine samples from seropositive animals including were collected from 224 farms in 21 provinces of different regions of Iran and examined. The discovered isolates were phenotyped and molecularly characterized. The isolates were all or . Bacteria analysis revealed that 70.53% of seropositive farms were tested positive for strains, predominantly biovar 1 (43.42%) and biovar 3 (27.11%). Geographical distribution revealed that biovar 1 was the most common in dairy cow farms (16 provinces), followed by biovar 3 (six provinces). Also, the prevalence of biovar 2, biovar 3, biovar 1, biovar 2 and RB51 vaccine were restricted to certain provinces. AMOS ()-polymerase chain reaction and Bruce-ladder PCR confirmed species identification. These results highlighted the complexity of bovine brucellosis in Iran and illustrated that was spread from small ruminants to cattle. This study provided important epidemiological insights for targeting future brucellosis control programs in the Iranian dairy farms.
PubMed: 38770201
DOI: 10.30466/vrf.2024.2012972.4028 -
ACS Omega May 2024Brucellosis is a bacterial zoonotic disease that requires major attention for both health and financial facilities in many parts of the world including the Mediterranean...
Brucellosis is a bacterial zoonotic disease that requires major attention for both health and financial facilities in many parts of the world including the Mediterranean and the Middle East. The existing gold standard diagnosis relies on the culturing technique, which is costly and time-consuming with a duration of up to 45 days. The protease biosensor represents a new detection approach that will lead to low-cost point-of-care devices for sensitive detection. In addition, the described diagnostic device is portable and simple to operate by a nurse or non-skilled clinician making it appropriate for the low-resource setting. In this study, we rely on the total extracellular protease proteolytic activity on specific peptide sequences identified using the FRET assay by high-throughput screening from the library of peptide (96 short peptides such as dipeptides and tripeptides) substrates for (). The -specific protease substrate was utilized in the development of the paper-based colorimetric assay. Two specific and highly active dipeptide substrates were identified (FITC-Ahx-K-r-K-Ahx-DABCYL and FITC-Ahx-R-r-K-Ahx-DABCYL). The peptide-magnetic bead nanoprobe sensors developed based on these substrates were able to detect the with LOD as low as 1.5 × 10 and 1.5 × 10 CFU/mL using K-r dipeptide and R-r dipeptide substrates, respectively, as the recognition element. The samples were tested using this sensor in few minutes. Cross-reactivity studies confirmed that the other proteases extracted from closely related pathogens have no significant effect on the sensor. To the best of our knowledge, this assay is the first assay that can be used with low-cost, rapid, direct, and visual detection of .
PubMed: 38764637
DOI: 10.1021/acsomega.4c00192 -
Vaccine May 2024One of the main causes of human brucellosis is Brucella melitensis infecting small ruminants. To date, Rev1 is the only vaccine successfully used to control ovine and...
One of the main causes of human brucellosis is Brucella melitensis infecting small ruminants. To date, Rev1 is the only vaccine successfully used to control ovine and caprine brucellosis. However, it is pathogenic for pregnant animals, resulting in abortions and vaginal and milk shedding, as well as being infectious for humans. Therefore, there is an urgent need to develop an effective vaccine that is safer than Rev1. In efforts to further attenuate Rev1, we recently used wzm inactivation to generate a rough mutant (Rev1Δwzm) that retains a complete antigenic O-polysaccharide in the bacterial cytoplasm. The aim of the present study was to evaluate the placental pathogenicity of Rev1Δwzm in trophoblastic cells, throughout pregnancy in mice, and in ewes inoculated in different trimesters of pregnancy. This mutant was evaluated in comparison with the homologous 16MΔwzm derived from a virulent strain of B. melitensis and the naturally rough sheep pathogen B. ovis. Our results show that both wzm mutants triggered reduced cytotoxic, pro-apoptotic, and pro-inflammatory signaling in Bewo trophoblasts, as well as reduced relative expression of apoptosis genes. In mice, both wzm mutants produced infection but were rapidly cleared from the placenta, in which only Rev1Δwzm induced a low relative expression of pro-apoptotic and pro-inflammatory genes. In the 66 inoculated ewes, Rev1Δwzm was safe and immunogenic, displaying a transient serological interference in standard RBT but not CFT S-LPS tests; this serological response was minimized by conjunctival administration. In conclusion, these results support that B. melitensis Rev1Δwzm is a promising vaccine candidate for use in pregnant ewes and its efficacy against B. melitensis and B. ovis infections in sheep warrants further study.
PubMed: 38755066
DOI: 10.1016/j.vaccine.2024.04.085