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Brucella are facultative intracellular bacteria that chronically infect humans and animals causing brucellosis. Brucella are able to invade and replicate in a broad range of cell lines in vitro, however the cells supporting bacterial growth in vivo are largely unknown. In order to identify these, we used a Brucella melitensis strain stably expressing mCherry fluorescent protein to determine the phenotype of infected cells in spleen and liver, two major sites of B. melitensis growth in mice. In both tissues, the majority of primary infected cells expressed the F4/80 myeloid marker. The peak of infection correlated with granuloma development. These structures were mainly composed of CD11b⁺ F4/80⁺ MHC-II⁺ cells expressing iNOS/NOS2 enzyme. A fraction of these cells also expressed CD11c marker and appeared similar to inflammatory dendritic cells (DCs). Analysis of genetically deficient mice revealed that differentiation of iNOS⁺ inflammatory DC, granuloma formation and control of bacterial growth were deeply affected by the absence of MyD88, IL-12p35 and IFN-γ molecules. During chronic phase of infection in susceptible mice, we identified a particular subset of DC expressing both CD11c and CD205, serving as a reservoir for the bacteria. Taken together, our results describe the cellular nature of immune effectors involved during Brucella infection and reveal a previously unappreciated role for DC subsets, both as effectors and reservoir cells, in the pathogenesis of brucellosis.

Background. Brucellosis has a wide spectrum of clinical manifestations and it may last several days or even several years; however, it is often misdiagnosed and therefore may cause inadequate therapy and prolonged illness. Previous studies about meta-analysis of manifestations of brucellosis reported in English lacked the data published in Chinese, which did not provide details about the contact history, laboratory tests, and misdiagnosis. We undertake a meta-analysis of clinical manifestations of human brucellosis in China to identify those gaps in the literature. We have searched published articles in electronic databases up to December 2016 identified as relating to clinical features of human brucellosis in China. 68 studies were included in the analysis. The main clinical manifestations were fever, fatigue, arthralgia, and muscle pain (87%, 63%, 62%, and 56%, resp.). There are significant differences between adults and children. Rash, respiratory and cardiac complications, and orchitis/epididymitis were more prevalent in children patients. The common complications of brucellosis were hepatitis, followed by osteoarthritis, respiratory diseases, cardiovascular diseases, central nervous system dysfunction, hemophagocytic syndrome, and orchitis/epididymitis in male. In the nonpastoral areas, brucellosis has a high ratio of misdiagnosis. Our analysis provides further evidence for the accurate diagnosis, particularly in assessing severe, debilitating sequelae of this infection.

Human brucellosis still presents scientists and clinicians with several challenges, such as the understanding of pathogenic mechanisms of Brucella spp, the identification of markers for disease severity, progression, and treatment response, and the development of improved treatment regimens. Molecular studies have shed new light on the pathogenesis of Brucella spp, and new technologies have permitted the development of diagnostic tools that will be useful in developing countries, where brucellosis is still a very common but often neglected disease. However, further studies are needed to establish optimum treatment regimens and local and international control programmes. This Review summarises current knowledge of the pathogenic mechanisms, new diagnostic advances, therapeutic options, and the situation of developing countries in regard to human brucellosis.

A northern Gulf of Mexico (GoM) cetacean unusual mortality event (UME) involving primarily bottlenose dolphins (Tursiops truncatus) in Louisiana, Mississippi, and Alabama began in February 2010 and continued into 2014. Overlapping in time and space with this UME was the Deepwater Horizon (DWH) oil spill, which was proposed as a contributing cause of adrenal disease, lung disease, and poor health in live dolphins examined during 2011 in Barataria Bay, Louisiana. To assess potential contributing factors and causes of deaths for stranded UME dolphins from June 2010 through December 2012, lung and adrenal gland tissues were histologically evaluated from 46 fresh dead non-perinatal carcasses that stranded in Louisiana (including 22 from Barataria Bay), Mississippi, and Alabama. UME dolphins were tested for evidence of biotoxicosis, morbillivirus infection, and brucellosis. Results were compared to up to 106 fresh dead stranded dolphins from outside the UME area or prior to the DWH spill. UME dolphins were more likely to have primary bacterial pneumonia (22% compared to 2% in non-UME dolphins, P = .003) and thin adrenal cortices (33% compared to 7% in non-UME dolphins, P = .003). In 70% of UME dolphins with primary bacterial pneumonia, the condition either caused or contributed significantly to death. Brucellosis and morbillivirus infections were detected in 7% and 11% of UME dolphins, respectively, and biotoxin levels were low or below the detection limit, indicating that these were not primary causes of the current UME. The rare, life-threatening, and chronic adrenal gland and lung diseases identified in stranded UME dolphins are consistent with exposure to petroleum compounds as seen in other mammals. Exposure of dolphins to elevated petroleum compounds present in coastal GoM waters during and after the DWH oil spill is proposed as a cause of adrenal and lung disease and as a contributor to increased dolphin deaths.

Introduction: In this study, we examined the effects of Brucella infection on endothelial dysfunction. Flow-mediated dilatation (FMD) measurement is indicator of the endothelial function, and abnormal values indicating endothelial dysfunction are accepted as the first stage of atherosclerosis. Methodology: Twenty-four patients who had been treated for acute brucellosis two years before, and who had had no relapses in the follow-up, were prospectively included in the study, along with 30 healthy individuals in the control group. Results: While the highly sensitive C-reactive protein (hs-CRP) value was 2.42 ± 1.45 in the patient group, it was 1.72 ± 0.61 in the control group (p = 0.025). While the FMD value was 3.50 ± 1.58 in the patient group, it was 5.88 ± 1.88 in the control group (p < 0.001). While the percentage increase in FMD was 9.88 ± 4.92 in the patient group, it was 17.49 ± 6.3 in the control group (p < 0.001). It was observed that FMD value, the percentage increase in FMD, and basal radius were correlated with hs-CRP (r = -0.644, p < 0.001; r = - 0.558, p = 0.002; r = 0.444, p = 0.018, respectively). The carotid artery intima media thickness (IMT) value was found to be 0.61 ± 0.17 in the patient group and 0.49 ± 0.12 in the control group (p = 0.004). Conclusions: The abnormal FMD and IMT values observed in brucellosis patients might be an indicator of more frequent arterial dysfunction, increased cardiovascular risk, and atherosclerosis.

The objectives of this systematic review, commissioned by WHO, were to assess the frequency and severity of clinical manifestations of human brucellosis, in view of specifying a disability weight for a DALY calculation. Thirty three databases were searched, with 2,385 articles published between January 1990-June 2010 identified as relating to human brucellosis. Fifty-seven studies were of sufficient quality for data extraction. Pooled proportions of cases with specific clinical manifestations were stratified by age category and sex and analysed using generalized linear mixed models. Data relating to duration of illness and risk factors were also extracted. Severe complications of brucellosis infection were not rare, with 1 case of endocarditis and 4 neurological cases per 100 patients. One in 10 men suffered from epididymo-orchitis. Debilitating conditions such as arthralgia, myalgia and back pain affected around half of the patients (65%, 47% and 45%, respectively). Given that 78% patients had fever, brucellosis poses a diagnostic challenge in malaria-endemic areas. Significant delays in appropriate diagnosis and treatment were the result of health service inadequacies and socioeconomic factors. Based on disability weights from the 2004 Global Burden of Disease Study, a disability weight of 0.150 is proposed as the first informed estimate for chronic, localised brucellosis and 0.190 for acute brucellosis. This systematic review adds to the understanding of the global burden of brucellosis, one of the most common zoonoses worldwide. The severe, debilitating, and chronic impact of brucellosis is highlighted. Well designed epidemiological studies from regions lacking in data would allow a more complete understanding of the clinical manifestations of disease and exposure risks, and provide further evidence for policy-makers. As this is the first informed estimate of a disability weight for brucellosis, there is a need for further debate amongst brucellosis experts and a consensus to be reached.

Neurobrucellosis is a severe and rare complication of human brucellosis, particularly in the pediatric population. It manifests with diverse clinical presentations, with meningoencephalitis being the most common. Limited cases have been reported in Saudi Arabia. Here, we present the case of an 11-year-old boy diagnosed with neurobrucellosis who developed diplopia, inward deviation of the left eye, and ophthalmoplegia. Cerebrospinal fluid analysis revealed pleocytosis, elevated protein levels, and high opening pressure. Brain magnetic resonance imaging demonstrated microabscesses with nodular enhancement, dural thickening in the quadrigeminal cistern, and swelling with edema of the left optic nerve. To the best of our knowledge, this is the first reported case of a patient with brain microabscesses secondary to Brucella infection in Saudi Arabia. This case highlights the need for heightened awareness of neurobrucellosis as a differential diagnosis in children presenting with unusual neurological symptoms in endemic regions.

Brucellosis is a recognized zoonotic disease caused by various Brucella species with significant economic and animal welfare ramifications worldwide. The spread of brucellosis from domestic livestock and wild animals, as well as its emergence in new regions, present novel epidemiological challenges. The consumption of unpasteurized milk and dairy products from unsanitary farms in endemic areas poses a serious risk to public health from brucellosis. Determining the accurate prevalence of brucellosis, particularly in regions with persistently high prevalence, basically requires careful and frequent surveillance. Furthermore, transmission and detection of the illness in non-endemic areas have become more complex due to global human and animal migration as well as the trade in animal products. This review presents an updated understanding of brucellosis, covering its classification and taxonomy, pathogenesis, diagnosis and treatment approaches, epidemiology, available control and prevention measures, antimicrobial resistance and the role of metal uptake in bacterial virulence. It highlights the consequences of brucellosis for global health and underscores the need for continuous research, knowledge sharing, and interdisciplinary cooperation for effective disease control and prevention.

Although Yunnan Province is not an endemic region for brucellosis, the disease remains a diagnostic and therapeutic challenge in children due to its atypical clinical manifestations and potential for severe complications. This study aims to explore the clinical features of pediatric brucellosis in the region and establish a prediction model for severe complications. This study included 62 children diagnosed with brucellosis at the Kunming Children's Hospital between 2015 and 2024. The patients were divided into two groups based on the presence of severe complications: the severe complications group (n = 15) and the general group (n = 47). Clinical features were extracted from electronic medical records, and the Boruta algorithm was used to select core predictive factors. Six machine learning models, including Random Forest and XGBoost, were constructed. The performance of the models was assessed using receiver operating characteristic curve (ROC) curves and decision curve analysis (DCA), and a web-based prediction tool was developed. The study revealed that the most common clinical symptoms were fever (95.2%), joint pain (51.6%). Meningoencephalitis was observed in 13 cases (21%), and sacroiliitis was present in 2 cases (3%). Laboratory findings indicated that the erythrocyte sedimentation rate (ESR) and IgM levels were significantly higher in the severe complications group compared to the general group. Culture results showed that the positive rate of bone marrow cultures was 95% (19/20), blood cultures had a positive rate of 84% (52/62), synovial fluid cultures had a positive rate of 67% (2/3), and cerebrospinal fluid cultures had a low positive rate of 2% (1/43). Machine learning models demonstrated that the Random Forest model performed best in predicting severe complications (AUC = 0.970), and DCA indicated that it had the best clinical utility. Key predictive factors were disease duration, fever duration, IgM, and ESR. A Shiny-based web tool was developed for real-time clinical risk assessment. This study indicated that pediatric brucellosis should not be neglected in non-endemic areas like Yunnan Province, China. Combining inflammatory markers with Random Forest models can effectively predict the risk of severe complications in pediatric brucellosis.

Neurobrucellosis is a rare manifestation of brucella infection, which would be life-threatening and result in multiple disabilities. Brucellosis commonly manifests with fever, arthralgia, and myalgia. Moreover, most patients with Neurobrucellosis present with significant lesions in the brain, spinal cord, or vertebral column; some cases show no lesions in their magnetic resonance imaging (MRI). The present case is a 32-year-old rural man with suspicious contact with animals at his work who was presented with ataxia, paraplegia, and urine-fecal incontinence without typical symptoms of brucellosis. Broad-spectrum diagnostic methods for neurobrucellosis were employed, including the Wright and 2-mercaptoethanol (2-ME) tests on plasma and brain, as well as spinal MRI. However, no significant pathologies were found in the brain or spinal imaging that could explain the patient’s clinical condition, and the Wright and 2-ME tests were negative. Also, despite a comprehensive approach to different viral, bacterial, autoimmune, systemic, metabolic, and organic etiologies, the symptoms of the patient got worse, and he experienced depression, sensorineural hearing loss (SNHL), and visual impairment in the following months. Eventually, the patient’s cerebrospinal fluid specimen Wright & 2-ME tests became positive, and a standard antibiotic regimen, including doxycycline, rifampin, and ceftriaxone, was administered for several months. In his last follow-up two years later, all neurological and psychological issues had disappeared except mild ataxia and hearing impairment. Hence, the prozone phenomenon should be considered in the false-negative Wright tests in endemic regions for brucellosis.