Vaccine Elicited Antibodies Restrict Glucose Availability to Control Brucella Infection.

The impact of vaccine-induced immune responses on host metabolite availability has not been well studied. Here we show prior vaccination alters the metabolic profile of mice challenged with Brucella melitensis. In particular, glucose levels were reduced in vaccinated mice in an antibody-dependent manner. We also found the glucose transporter gene, gluP, plays a lesser role in B. melitensis virulence in vaccinated wild-type mice relative to vaccinated mice unable to secrete antibodies. These data indicate vaccine-elicited antibodies protect the host in part by restricting glucose availability. Moreover, Brucella and other pathogens may need to employ different metabolic strategies in vaccinated hosts.

Efficacy of antibiotic prophylaxis to preventing brucellosis in accidental exposure: A systematic review.

BACKGROUND: Antibiotic prophylaxis to prevent brucellosis after accidental exposure to Brucella is an important topic in public health. This study aimed to systematically review the efficacy of antibiotic prophylaxis following accidental exposure to Brucella in preventing human brucellosis disease. METHODS: The study protocol was registered in PROSPERO (CRD42023456812). The outcomes included the incidence of brucellosis disease, adverse events rate, and antibiotic prophylaxis adherence. A comprehensive literature search, conducted until 20 November, 2023, involved Medline, Embase, Cochrane Library, and LILACS databases. Descriptive analysis and meta-analysis using R software were performed, risk of bias was assessed using JBI Critical appraisal tools, and certainty of evidence was assessed using the GRADE tool. RESULTS: Among 3102 initially identified records, eight studies involving 97 individuals accidentally exposed, all focused on high-risk accidental exposure to Brucella in laboratory settings, were included in the review. All studies reported the prophylactic treatment comprising doxycycline at a dosage of 100 mg twice daily, combined with rifampicin at 600 mg, both administered over 21 days. Prophylaxis adherence was reported in 86% of cases, and incidence of brucellosis post-treatment was 0.01. Adverse events, mainly gastrointestinal, occurred in 26% of cases. Critical appraisal revealed limitations in reporting demographics and clinical information. The certainty of evidence was rated as 'very low,' emphasising the need for caution in interpreting the observed outcomes due to study design constraints and the absence of comparative groups. CONCLUSIONS: PEP is an alternative practice reported in the literature, used in accidents with high-risk exposure to Brucella. The currently available evidence of the efficacy of antibiotic prophylaxis is insufficient to support a recommendation for or against the widespread use of antibiotic prophylaxis, so caution is needed in interpreting results due to the very low certainty of evidence, primarily stemming from case series and lack of comparative groups.

Two cases of MPO-ANCA-positive hypertrophic pachymeningitis mimicking as intracranial infection.

Hypertrophic pachymeningitis (HP) is a rare disorder marked by thickening of the dura mater due to diverse etiologies. MPO-ANCA-positive HP represents a variant of AAV confined to the central nervous system, distinguished by the presence of serum MPO antibodies. Distinguishing HP triggered by MPO-ANCA from other causes can be challenging.In this study, we present two cases of MPO-ANCA-positive HP initially misdiagnosed as intracranial infections. Case 1 underwent surgery for chronic suppurative otitis media, with histopathological findings revealing inflammatory changes without definitive suppuration. He was presumed to have a secondary intracranial infection resulting from the surgery. However, his condition deteriorated despite two weeks of antibiotic and antiviral treatment. Case 2 presented with headache and was initially suspected of having intracranial Brucellosis given his serum Brucella positivity. Despite treatment for brucellosis, his symptoms persisted, and he developed visual and hearing impairments. Both patients were ultimately diagnosed with MPO-ANCA-positive HP, exhibiting serum MPO antibody positivity. Their symptoms showed improvement with glucocorticoid and immunosuppressive therapy.Based on these observations, we propose that MPO-ANCA-positive HP may initially present as intracranial infection. For HP patients presenting with headache, mastoiditis, otitis media, and visual loss, it is imperative to conduct ANCA antibody-related tests to enhance diagnostic precision.

Construction of recombinant Omp25 or EipB protein loaded PLGA nanovaccines for Brucellosis protection.

Safe and effective vaccine candidates are needed to address the limitations of existing vaccines against Brucellosis, a disease responsible for substantial economic losses in livestock. The present study aimed to encapsulate recombinant Omp25 and EipB proteins, knowledged antigen properties, into PLGA nanoparticles, characterize synthesized nanoparticles with different methods, and assessed theirin vitro/in vivoimmunostimulatory activities to develop new vaccine candidates. The recombinant Omp25 and EipB proteins produced with recombinant DNA technology were encapsulated into PLGA nanoparticles by double emulsion solvent evaporation technique. The nanoparticles were characterized using FE-SEM, Zeta-sizer, and FT-IR instruments to determine size, morphology, zeta potentials, and polydispersity index values, as well as to analyze functional groups chemically. Additionally, the release profiles and encapsulation efficiencies were assessed using UV-Vis spectroscopy. After loading with recombinant proteins, O-NPs reached sizes of 221.2 ± 5.21 nm, while E-NPs reached sizes of 274.4 ± 9.51 nm. The cumulative release rates of the antigens, monitored until the end of day 14, were determined to be 90.39% for O-NPs and 56.1% for E-NPs. Following the assessment of thein vitrocytotoxicity and immunostimulatory effects of both proteins and nanoparticles on the J774 murine macrophage cells,in vivoimmunization experiments were conducted using concentrations of 16µg ml-1for each protein. Both free antigens and antigen-containing nanoparticles excessively induced humoral immunity by increasing producedBrucella-specific IgG antibody levels for 3 times in contrast to control. Furthermore, it was also demonstrated that vaccine candidates stimulated Th1-mediated cellular immunity as well since they significantly raised IFN-gamma and IL-12 cytokine levels in murine splenocytes rather than IL-4 following to immunization. Additionally, the vaccine candidates conferred higher than 90% protection from the infection according to challenge results. Our findings reveal that PLGA nanoparticles constructed with the encapsulation of recombinant Omp25 or EipB proteins possess great potential to triggerBrucella-specific humoral and cellular immune response.

National epidemiology of culture-confirmed brucellosis in Israel, 2004-2022.

Brucellosis, a global zoonosis, is endemic in Israel. We used a national database of culture-confirmed cases (2004-2022) to analyse the trends of brucellosis. Of 2,489 unique cases, 99.8% were bacteraemic, 64% involved males, and the mean age was 30.5 years. Brucella melitensis was the dominant species (99.6%). Most cases occurred among the Arab sector (84.9%) followed by the Jewish (8.5%) and Druze (5.5%) sectors. The average annual incidence rates overall and for the Arab, Druze, and Jewish sectors were 1.6/100,000, 6.6/100,000, 5.5/100,000, and 0.18/100,000, respectively. The annual incidence rates among the Arab (incidence rate ratio (IRR) = 36.4) and the Druze (IRR = 29.6) sectors were significantly higher than among the Jewish sector (p < 0.001). The highest incidence rates among the Arab sector occurred in the South District, peaking at 41.0/100,000 in 2012. The frequencies of B. melitensis isolated biotypes (biotype 1 - 69.1%, biotype 2 - 26.0%, and biotype 3 - 4.3%) differed from most Middle Eastern and European countries. A significant switch between the dominant biotypes was noted in the second half of the study period. Efforts for control and prevention should be sustained and guided by a One Health approach mindful of the differential trends and changing epidemiology.

Understanding brucellosis: knowledge, perceptions, and self-reported prevalence among agro-pastoralists in Nakasongola, Uganda.

BACKGROUND: Brucellosis is an infectious zoonotic disease that poses serious health threats around the world including Uganda. Brucellosis is caused by Brucella spp., the bacteria being transmitted via contact through skin breaks, via inhalation, or orally through the consumption of raw milk and other dairy products. The aim of this study was to investigate self-reported prevalence, knowledge, and perceptions towards brucellosis transmission, within agro-pastoralist communities in the Nakasongola district, central Uganda. METHODS: This study employed a cross-sectional survey design. A semi-structured questionnaire was developed and administered to 398 participants selected through convenience sampling method. The survey gathered information on socio-demographic characteristics, knowledge of brucellosis transmission, symptoms, preventive measures, and self-reported prevalence of brucellosis. Qualitative data involved the use of six focus group discussions, identifying factors for transmission based on their perceived level of risk or impact using ranking by proportional piling. RESULTS: A majority (99.2%, n = 398) had heard about brucellosis and 71.2% were aware of the zoonotic nature of the disease. There were varied responses regarding transmission routes, symptoms, and preventive measures. Self-reported prevalence was relatively high (55.5%). Following adjusted analysis, factors such as subcounty, source of income, knowledge about symptoms of brucellosis, whether brucellosis is treatable, perception, and living close to animals were statistically significant. Participants from Wabinyonyi had 2.7 higher odds of reporting brucellosis than those from Nabiswera, aOR = 2.7, 95%CI 1.4-5.5. Crop farming and livestock had much higher odds of reporting brucellosis than those earning from casual sources, aOR = 8.5, 95%C 1.8-40.1 and aOR = 14.4, 95%CI 3.1-67.6, respectively. Those who had knowledge about symptoms had 6.9 higher odds of reporting brucellosis than who mentioned fever, aOR = 4.5, 95%CI 2.3-18.3. Likewise, living close with animals and handling aborted fetuses (aOR = 0.4, 95%CI: 0.17-0.86), (aOR = 0.2,95% CI: 0.07-0.0.42,) had significantly lower odds for self-reported prevalence compared to those who believed did not cause brucellosis. Risk factors identified included, handling of aborted fetuses and living in close proximity with animals. Overall, there was a moderate statistical agreement in the ranking across the focus groups discussion (Wc = 0.48, p < 0.01; n = 6). CONCLUSION: While awareness of brucellosis is high in the community, understanding of the transmission routes, clinical symptoms, and preventive measures varied. Investigating the understanding and assessing knowledge, perceptions and self-reported prevalence in this region indicated a necessity for risk communication strategies and community-based interventions to better control brucellosis transmission.

Spatiotemporal dynamics and influencing factors of human brucellosis in Mainland China from 2005-2021.

BACKGROUND: Brucellosis poses a significant public health concern. This study explores the spatial and temporal dynamic evolution of human brucellosis in China and analyses the spatial heterogeneity of the influencing factors related to the incidence of human brucellosis at the provincial level. METHODS: The Join-point model, centre of gravity migration model and spatial autocorrelation analysis were employed to evaluate potential changes in the spatial and temporal distribution of human brucellosis in mainland China from 2005 to 2021. Ordinary Least Squares (OLS), Geographically Weighted Regression (GWR), and Multi-scale Geographically Weighted Regression (MGWR) models were constructed to analyze the spatial and temporal correlation between the incidence rate of human brucellosis and meteorological and social factors. RESULTS: From 2005 to 2021, human brucellosis in China showed a consistent upward trend. The incidence rate rose more rapidly in South, Central, and Southwest China, leading to a shift in the center of gravity from the North to the Southwest, as illustrated in the migration trajectory diagram. Strong spatial aggregation was observed. The MGWR model outperformed others. Spatio-temporal plots indicated that lower mean annual temperatures and increased beef, mutton, and milk production significantly correlated with higher brucellosis incidence. Cities like Guangxi and Guangdong were more affected by low temperatures, while Xinjiang and Tibet were influenced more by beef and milk production. Inner Mongolia and Heilongjiang were more affected by mutton production. Importantly, an increase in regional GDP and health expenditure exerted a notable protective effect against human brucellosis incidence. CONCLUSIONS: Human brucellosis remains a pervasive challenge. Meteorological and social factors significantly influence its incidence in a spatiotemporally specific manner. Tailored prevention strategies should be region-specific, providing valuable insights for effective brucellosis control measures.

Chronic meningitis in adults: a comparison between neurotuberculosis and neurobrucellosis.

BACKGROUND: In regions endemic for tuberculosis and brucellosis, distinguishing between tuberculous meningitis (TBM) and brucella meningitis (BM) poses a substantial challenge. This study investigates the clinical and paraclinical characteristics of patients with TBM and BM. METHODS: Adult patients diagnosed with either TBM or BM who were admitted to two referral hospitals between March 2015 and October 2022, were included, and the characteristics of the patients were analyzed. RESULTS: Seventy patients formed the study group, 28 with TBM and 42 with BM, were included. TBM patients had a 2.06-fold (95% CI: 1.26 to 3.37, P-value: 0.003) higher risk of altered consciousness and a 4.80-fold (95% CI: 1.98 to 11.61, P-value: < 0.001) higher risk of extra-neural involvement as compared to BM patients. Cerebrospinal fluid (CSF) analysis revealed a significantly higher percentage of polymorphonuclear leukocytes (PMN) in TBM compared to BM (Standardized mean difference: 0.69, 95% CI: 0.18 to 1.20, P-value: 0.008). Neuroimaging findings indicated higher risks of hydrocephalus (P-value: 0.002), infarction (P-value: 0.029), and meningeal enhancement (P-value: 0.012) in TBM compared to BM. Moreover, TBM patients had a 67% (95% CI: 21% to 131%, P-value:0.002) longer median length of hospital stay and a significantly higher risk of unfavorable outcomes (Risk ratio: 6.96, 95% CI: 2.65 to 18.26, p < 0.001). CONCLUSIONS: Our study emphasizes that TBM patients displayed increased frequencies of altered consciousness, PMN dominance in CSF, extra-neural involvement, hydrocephalus, meningeal enhancement, and brain infarction. The findings emphasize the diagnostic difficulties and underscore the importance of cautious differentiation between these two conditions to guide appropriate treatment strategies.

Delay in the diagnosis of Brucella abortus bacteremia in a nonendemic country: a case report.

BACKGROUND: It is challenging to diagnose brucellosis in nonendemic regions because it is a nonspecific febrile disease. The accurate identification of Brucella spp. in clinical microbiology laboratories (CMLs) continues to pose difficulties. Most reports of misidentification are for B. melitensis, and we report a rare case of misidentified B. abortus. CASE PRESENTATION: A 67-year-old man visited an outpatient clinic complaining of fatigue, fever, and weight loss. The patient had a history of slaughtering cows with brucellosis one year prior, and his Brucella antibody tests were negative twice. After blood culture, the administration of doxycycline and rifampin was initiated. The patient was hospitalized due to a positive blood culture. Gram-negative coccobacilli were detected in aerobic blood culture bottles, but the CML's lack of experience with Brucella prevented appropriate further testing. Inaccurate identification results were obtained for a GN ID card of VITEK 2 (bioMérieux, USA) and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) using a MALDI Biotyper (Bruker, Germany). The strain showed 100.0% identity with Brucella spp. according to 16S rRNA sequencing. MALDI-TOF MS peaks were reanalyzed using the CDC MicrobeNet database to determine Brucella spp. (score value: 2.023). The patient was discharged after nine days of hospitalization and improved after maintaining only doxycycline for six weeks. The isolate was also identified as Brucella abortus by genomic evidence. CONCLUSION: Automated identification instruments and MALDI-TOF MS are widely used to identify bacteria in CMLs, but there are limitations in accurately identifying Brucella spp. It is important for CMLs to be aware of the possibility of brucellosis through communication with clinicians. Performing an analysis with an additional well-curated MALDI-TOF MS database such as Bruker security-relevant (SR) database or CDC MicrobeNet database is helpful for quickly identifying the genus Brucella.

MicroRNA -21 expression as an auxiliary diagnostic biomarker of acute brucellosis.

BACKGROUND: This study aimed to measure the expression levels of peripheral blood miRNAs in brucellosis and their involvement in the different phases of the brucellosis. METHODS: The expression levels of miRNAs including miR-210, miR-155, miR-150, miR-146a, miR-139-3p, miR-125a-5p, miR-29 and miR-21 were quantified in 57 brucellosis patients subgrouped into acute, under treatment & relapse phase and 30 healthy controls (HCs) using real-time polymerase chain reaction (RT-PCR). The receiver operating characteristic (ROC) analysis curve analysis was performed to find a biomarker for discrimination of different phases of brucellosis. RESULTS: The expression of miR-155, miR-146a, miR-125a-5p, miR-29, and miR-21 was found to be elevated in the acute brucellosis patients compared to HCs. miR-29 changed in under-treatment patients, while miR-139-3p and miR-125a-5p showed alterations in relapse cases. The ROC curve analysis depicted the potential involvement of miR-21 in the pathogenesis of acute brucellosis. CONCLUSION: The expression level of miR-21 is significantly augmented in acute brucellosis and has the potential to be a contributing diagnostic factor for acute infection.

Molecular epidemiological characteristics of osteoarthritis-associated Brucella melitensis in China: evidence from whole-genome sequencing-based analysis.

BACKGROUND: Brucellosis, developing complications including arthritis, spondylitis, sacroiliitis, and osteomyelitis, is one of the most common zoonotic diseases in the current world which causes economic losses to the livestock industry and is a great public health concern. Brucella melitensis are the main pathogen of brucellosis epidemics in China, most of which are located in northern China. However, there is limited knowledge about the epidemiology of osteoarthritis-associated brucellosis. This study was aimed to reveal the prevalence of osteoarthritis-associated brucellosis in Inner Mongolia and also to investigate the molecular characteristics of B. melitensis isolates. METHODS AND RESULTS: In 2018, the osteoarthritis symptoms of brucellosis in the Brucellosis department of a hospital in Inner Mongolia were investigated. Twenty osteoarthritis-associated B. melitensis strains, isolated from the inpatients in Inner Mongolia during 2013-2017, were subjected to whole genome sequencing. The multilocus sequence type (MLST) and core genome SNP (cgSNP) analysis were conducted to detect molecular epidemiological characteristics. The incidence of brucellosis osteoarthritis symptoms in males (85/120, 70.8%) was significantly higher than that in females (35/120, 29.2%), and the age of patients was concentrated between 41 and 60 years old. In silico analyses indicated ST8 was the prevalent sequence type and the transmission of osteoarthritis-associated B. melitensis among different geographical areas. All strains carry virulence genes, including cgs, lpsA, manCoAg, pgm, pmm, virB4, wbdA and wboA. CONCLUSION: Our study showed the close epidemiologically connection of osteoarthritis-associated B. melitensis strains in northern China. And ST8 was the prevalent sequence type which need our attention.

A study on the epidemiology of brucellosis in bovine population of peri-urban and rural areas of district Multan, southern Punjab, Pakistan.

BACKGROUND: Brucellosis is a zoonotic disease caused by a bacterial pathogen belonging to the genus Brucella. It is one of the most frequent bacterial zoonoses globally but unfortunately, it is still considered as a neglected disease in the developing world. Keeping in view, this study was conducted to determine the prevalence and risk determinants of brucellosis in large ruminants of peri-urban and rural areas of district Multan-Pakistan. For this purpose, blood samples (n = 490) were collected from the cattle (n = 245) and buffalo (n = 245) population of the study area and subjected to preliminary screening of brucellosis using local and imported RBPT reagents. All the samples were further analyzed using commercially available multi-specie indirect ELISA kit followed by their confirmation by PCR using genus and species-specific primers. Data obtained from lab analysis and questionnaires were subjected to statistical analysis for Pearson Chi-square, Odds Ratio and Confidence intervals (95%). RESULTS: The results showed that the maximum seropositivity was recorded with local RBPT reagent (VRI, Pakistan; 12.45%; 95%CI = 9.72-15.65%) followed by RBPT-IDEXX (12.24%; 95%CI = 9.52-15.45%) and RBPT-ID.vet (11.84%; 95%CI = 9.18-14.95%) however statistical difference was non-significant (P = 0.956). The ELISA results showed an overall seroprevalence rate of 11.22% (95%CI = 8.59-14.33%) with comparatively higher rate in cattle (12.65%; 95%CI = 8.82-17.44%) as compared to buffaloes (9.80%; 95%CI = 6.49-14.15%). The PCR analysis confirmed the presence of genus Brucella in all seropositive samples whereas frequency of B. abortus and B. melitensis in seropositive samples was 80% and 20%, respectively. The co-existence of both species was also observed in 5.45% samples. The statistical analysis showed a significant association of bovine brucellosis with herd size, breed, reproductive disorders, mode of insemination, educational status and farmers' awareness about brucellosis (P < 0.05). Conversely, locality, age, weight, gender, pregnancy status, parity and puberty status had no associations with brucellosis (P > 0.05). CONCLUSION: In conclusion, brucellosis is prevalent in large ruminants of district Multan, Pakistan. It is suggested to devise and implement stringent policies for the effective control and prevention of brucellosis in the region. Further, the current situation also warrants the need to strengthen interdisciplinary coordination among veterinarians and physicians in one health perspective to ensure and strengthen the human and animal health care systems in the region.

Neurobrucellosis Presenting with Motor Damage or Hearing Loss, and Use of Steroids are Associated with a Higher Risk of Sequelae or Relapse: A Systematic Review of Individual Participant Data.

BACKGROUND: Neurobrucellosis presents diverse clinical challenges and risks of long-term complications. OBJECTIVE: We aimed to assess the relationship between the duration of antibiotic therapy, clinical factors, and the outcome of neurobrucellosis with a case report combined with a systematic review of the literature. METHODS: We present a case of a 31 years-old man successfully treated at our Institution. We then searched Ovid MEDLINE, Embase and Scopus for articles that encompassed neurobrucellosis cases, duration of treatment, and outcome. The primary outcome was to assess an association between the duration of treatment and the risk of sequelae or relapses. Univariate, multivariate and sensitivity analysis were carried out to define which variables affect​ed​ the clinical outcome. Quality assessment was performed using a dedicated tool. RESULTS: A total of 123 studies were included, totaling 221 patients. Median duration of treatment was 4 months (IQR 3 - 6), 69% patients recovered without sequelae, 27% had sequelae. Additionally, five patients had a relapse, and 4 patients died. Multivariate analysis found that the duration of treatment, age, and the use of ceftriaxone were not associated with a higher risk of sequelae or relapses. A significant association was found for corticosteroids use (OR 0.39, 95% IC 0.16 - 0.96, p = 0.038), motor impairment (OR 0.29, 95% IC 0.14 - 0.62, p = 0.002), and hearing loss (OR 0.037, 95% IC 0.01 - 0.11, p < 0.001). CONCLUSIONS: This study highlights the variability in clinical presentations and treatment approaches for neurobrucellosis. Patients with factors indicating higher sequelae risk require meticulous follow-up.

Effect of selection genotype on immune response to Brucella abortus RB51 in Holstein cattle.

Genetic selection for milk production traits in US Holsteins has affected numerous genes associated with reproduction and immunity. This study compares the transcriptomic response of peripheral blood mononuclear cells to an in vitro Brucella abortus strain RB51 (RB51) bacterial challenge between contemporary Holsteins and Holsteins that have not been selected for milk production traits since the mid-1960s. Total RNA was extracted from peripheral blood mononuclear cells from four contemporary and four unselected lactating, primiparous cows following 24-h incubation with or without stimulation with RB51 bacteria. RNA was sequenced and reads analyzed using tools from galaxy.scinet.usda.gov. A total of 412 differentially expressed genes (false discovery rate p < 0.05, log fold change > |1|) were identified. The upregulated genes (genes with higher expression in contemporary than unselected cattle) were enriched for 19 terms/pathways, including alanine, aspartate, and glutamate metabolism, indicating a cellular stress response. Downregulated genes (genes with higher expression in unselected than contemporary cows) were enriched for 37 terms/pathways, representing diverse immune responses, including natural killer cell-mediated immunity, interferon-γ production, negative regulation of interleukin-10 production, and cytokine receptor activity indicating a broad immune response with an emphasis on immune defense. These results provide evidence that differences exist between the two genotypes in response to in vitro bacterial challenge. This suggests that contemporary cows, genetically selected for milk production, may have reduced immune function, including limitations in response to intracellular bacteria.

Detection of Brucella S19 Vaccine Strain DNA in Domestic and Wild Ungulates from Brazilian Pantanal.

The Pantanal region, the largest floodplain in the world, has a huge biodiversity and is an important livestock center. Bovine brucellosis has been reported in the region over the last three decades, posing implications for cattle industry as well as for the maintenance of biodiversity. We aimed to investigate the presence of B. abortus S19 vaccine strain DNA in unvaccinated domestic and wild ungulates from the Brazilian Pantanal. Fifty-two heifers, 63 ovine, 24 domestic pigs, 28 feral pigs, and three Pampas deer were sampled. Brucella spp. was detected through bcsp31 PCR of blood samples in 45.3% (77/170) of the sampled animals, of which 36.4% (28/77) showed positivity in ery PCR corresponding to B. abortus S19 strain. Feral pigs presented the highest occurrence of positive samples in bcsp31 PCR (75%), followed by ovine (47.6%), domestic pigs (41.7%), and unvaccinated heifers (30.8%). We did not observe positivity in Pampas deer. Our results strongly suggest that vaccination against bovine brucellosis may promote spill-over of B. abortus S19 strain in the Pantanal region. Moreover, our data indicate that wild strains of Brucella circulates in the Pantanal Biome.

Quantification of Brucella abortus population structure in a natural host.

Cattle are natural hosts of the intracellular pathogen Brucella abortus, which inflicts a significant burden on the health and reproduction of these important livestock. The primary routes of infection in field settings have been described, but it is not known how the bovine host shapes the structure of B. abortus populations during infection. We utilized a library of uniquely barcoded B. abortus strains to temporally and spatially quantify population structure during colonization of cattle through a natural route of infection. Introducing 108 bacteria from this barcoded library to the conjunctival mucosa resulted in expected levels of local lymph node colonization at a 1-wk time point. We leveraged variance in strain abundance in the library to demonstrate that only 1 in 10,000 brucellae introduced at the site of infection reached a parotid lymph node. Thus, cattle restrict the overwhelming majority of B. abortus introduced via the ocular conjunctiva at this dose. Individual strains were spatially restricted within the host tissue, and the total B. abortus census was dominated by a small number of distinct strains in each lymph node. These results define a bottleneck that B. abortus must traverse to colonize local lymph nodes from the conjunctival mucosa. The data further support a model in which a small number of spatially isolated granulomas founded by unique strains are present at 1 wk postinfection. These experiments demonstrate the power of barcoded transposon tools to quantify infection bottlenecks and to define pathogen population structure in host tissues.

Is it safe to use ovarian follicular fluid from cows seropositive for brucellosis in the production of in vitro embryos?

Animal reproduction biotechniques are important tools for the technological advancement of livestock, as they allow the selection of the reproductive potential of superior quality females and males; however, infectious diseases that have a predilection for the reproductive system can be a hindrance for the use of these technologies. Therefore, the present study aimed to detect Brucella spp. in the ovarian follicular fluid of brucellosis-positive bovine cows. A total of 47 bovine ovarian follicular fluid aspirates from cows, positive in tests for brucellosis and from Brucella-positive herd, were submitted to PCR. The primers used in the PCR were specific to the genus Brucella (bcsp31 gene). All 47 bovine aspirates were negative for Brucella spp. 0.00% (95% CI: 0.00-4.00%). Our results demonstrated that Brucella spp. was absent in the ovarian follicular fluid from seropositive cows, which indicates that Brucella spp.-infected cows could be used for reproductive biotechnologies carried out with follicular aspirates. Future studies are needed to more precisely evaluate the feasibility and safety of using these oocytes from brucellosis-seropositive cows to transfer embryos to heifers/cows not infected by Brucella, aiming to produce calves free of the infection.

Clinical Characteristics, Treatment, and Prognosis of Osteoarticular Brucellosis: A Retrospective Real-World Study in Shenyang, China, 2014-2019.

This study aimed to assess the clinical characteristics, treatment, and prognosis of osteoarticular brucellosis. We conducted a retrospective study enrolling brucellosis patients from the Sixth People's Hospital of Shenyang between September 2014 and June 2019. A total of 1917 participants were admitted during this period. After applying propensity score matching, we retrospectively analyzed 429 patients with osteoarthritis and 429 patients without osteoarthritis. The primary outcome was treatment completion. The secondary outcome was symptom disappearance and seroconversion. Brucellosis patients with osteoarthritis had longer treatment course (160 [134.3-185.7] vs. 120 [102.3-137.7] d, p = 0.008) than those without osteoarthritis. The most common involved site was lumbar vertebrae (290 [67.6%]) in brucellosis patients with osteoarthritis. Longer symptom duration (90 [83.0-97.0] vs. 42 [40.2-43.8], p < 0.001) along with no significant difference in seroconversion (180 [178.8-181.2] vs. 180 [135.1-224.9], p = 0.212) was observed in osteoarthritis patients with treatment course >90 d. Peripheral joint involvement (adjusted hazard ratio [95% confidence interval] 1.485 [1.103-1.999]; p = 0.009) had a shorter symptom duration compared with shaft joint involvement. No significant differences were observed in treatment therapy between doxycycline plus rifampin (DR) or plus cephalosporins (DRC) in treatment course (p = 0.190), symptom persistence (p = 0.294), and seroconversion (p = 0.086). Lumbar vertebra was the most commonly involved site. Even if all symptoms disappeared, Serum agglutination test potentially remained positive in some patients. Compared with peripheral arthritis, shaft arthritis was the high-risk factor for longer symptom duration. The therapeutic effects were similar between DR and DRC. In summary, our study provided important insights into the clinical characteristics, treatment, and outcomes of osteoarticular brucellosis. Clinical Trial Registration number: NCT04020536.

The Prevalence of Brucella Spp. in Dairy Products in Iran: A Systematic Review and Meta-Analysis.

Brucellosis, a significant zoonotic disease, threatens food safety substantially, particularly in developing nations such as the Middle East. This study aimed to comprehensively assess the prevalence of Brucella spp. in Iranian milk and dairy products through a systematic review and meta-analysis. A thorough search of international and domestic databases from January 2008 to October 2023 identified 38 relevant studies encompassing 11,130 samples for meta-analysis. The overall prevalence of Brucella spp. in Iranian dairy products was 22% (95% CI: 16-28%). The highest and lowest overall prevalence of Brucella spp. in milk were found in raw goat milk 27% (95% CI: 11-42%) and raw camel milk 15% (95% CI: -0.42 to 72%), respectively. The overall prevalence of traditional cheese, ice cream, and cream is estimated to be 9% (95% CI: -16 to 35%), 2% (95% CI: -2.78 to 2.82%), and 9% (95% CI: -0.94 to 1.12%). Geographical disparities were evident, with Zanjan province reporting the highest contamination rate, 53%, while Razavi Khorasan province had the lowest, 1%. However, the prevalence of Brucella spp. in Iranian dairy products has fluctuated over time, with a significant association between the study year and sample size. Comprehensive planning, robust policy implementation, and rigorous monitoring are imperative to mitigate and ultimately eliminate Brucella contamination in dairy products effectively. Further research is essential to refine prevalence estimates and develop targeted prevention strategies to safeguard public health.

Can Hematological Inflammatory Indices Be Used to Differentiate Modic Type 1 Changes from Brucella Spondylodiscitis?

Background and Objectives: Differentiation between brucella spondylodiscitis and Modic type I changes (MC1) includes difficulties. Hematological inflammatory indices (HII) such as neutrophil to lymphocyte ratio (NLR) and aggregate index of systemic inflammation (AISI) are suggested as indicators of inflammation and infection and have diagnostic, prognostic, and predictive roles in various diseases. This study aimed to evaluate differences between brucella spondylodiscitis and MC1 in terms of HII. Materials and Methods: Thirty-five patients with brucella spondylodiscitis and thirty-seven with MC1 were enrolled in the study. Brucella spondylodiscitis and MC1 were diagnosed by microbiological, serological, and radiological diagnostic tools. HII (NLR, MLR, PLR, NLPR, SII, SIRI, AISI) were derived from baseline complete blood count. Results: The two groups were similar for age (p = 0.579) and gender (p = 0.092), leukocyte (p = 0.127), neutrophil (p = 0.366), lymphocyte (p = 0.090), and monocyte (p = 0.756) scores. The Brucella spondylodiscitis group had significantly lower pain duration (p < 0.001), higher CRP and ESR levels (p < 0.001), and lower platelet count (p = 0.047) than the MC1 group. The two groups had similarity in terms of HII: NLR (p = 0.553), MLR (p = 0.294), PLR (p = 0.772), NLPR (p = 0.115), SII (p = 0.798), SIRI (p = 0.447), and AISI (p = 0.248). Conclusions: Increased HII can be used to differentiate infectious and non-infectious conditions, but this may be invalid in brucellosis. However, pain duration, CRP and ESR levels, and platelet count may be useful to distinguish brucella spondylodiscitis from MC1.