ABSTRACTBrucellosis is a zoonotic infection that passes to humans from infected animals via direct contact or the intake of raw milk and its products. The hematologic profile most frequently seen in acute brucellosis includes mild anemia and leukopenia. Severe form of thrombocytopenia and multiple wet purpura over the tongue and buccal mucosa are less frequently reported. This article describes a case of a 24‐year‐old man who presented with an absolute platelet count of 1000 × 103/L; multiple wet purpura over the tongue and buccal mucosa and petechial lesions on the distal shins. The patient was diagnosed with brucellosis according to a positive serologic test and was treated with an antibiotic regimen including ceftriaxone and doxycycline, dexamethasone and a transfusion of 6 units of platelets. Mucocutaneous lesions resolved after 3 days of hospitalization, and platelet counts showed a steady upward trend. Brucella infection may cause severe thrombocytopenia and wet purpura over the tongue and buccal mucosa, which can be reversed with appropriate antimicrobials and steroids.

Background: This study aimed to determine whether serum zonulin levels could serve as a potential diagnostic biomarker for distinguishing acute, subacute, and chronic stages of brucellosis and to evaluate their relationship with routine biochemical and hematological parameters. Methods: A total of 153 patients diagnosed with brucellosis and 51 healthy controls, were included in the study. Based on clinical findings, symptom duration, and serological test results, patients were classified as acute, subacute, or chronic. Serum zonulin concentrations were measured using a commercially available enzyme-linked immunosorbent assay ELISA kit (Human Zonulin ELISA Kit; BT LAB, Cat. No. E3704Hu, China). Results: Median zonulin levels were 24.57 (27.19) ng/mL in acute, 18.21 (14.00) ng/mL in subacute, 6.19 (2.87) ng/mL in chronic patients, and 5.81 (3.47) ng/mL in controls. Zonulin levels were significantly higher in the acute phase and decreased significantly with disease chronicity (p < 0.001). Conclusions: Serum zonulin levels were found to be higher in acute brucellosis compared to subacute and chronic cases. In brucellosis, more comprehensive research is needed to determine whether serum zonulin levels can be used as a diagnostic biomarker in the evaluation of different clinical forms.

Brucellosis has significant public health and human health consequences. It causes significant economic hardship, especially in areas where food safety measures, hygiene standards, and veterinary care are inadequate. This study aimed to analyze the demographic and clinical characteristics, laboratory results, complications, and treatment modalities of patients with brucellosis. This retrospective study included patients aged ≥18 years who were followed for brucellosis between December 2018 and December 2023 in the Infectious Diseases and Clinical Microbiology clinics of two hospitals located in endemic provinces of Türkiye. Demographic characteristics, risk factors, clinical manifestations, laboratory findings, focal complications, diagnostic methods, and treatment regimens were analyzed. Brucellosis was diagnosed based on compatible clinical findings together with culture positivity or serologic test results. The study included 748 patients diagnosed with brucellosis. Of these, 484 (64.7%) were female, and the mean age was 39.2 ± 15.0 years. A significant proportion of patients (91%) lived in rural areas. Regarding transmission routes, 79.4% of patients reported consuming unpasteurized fresh cheese. Patients were categorized as follows: 72.7% had acute brucellosis, 20.6% had subacute brucellosis, and 6.7% had chronic brucellosis. The most frequently reported symptoms were joint pain (89%) and malaise (65.3%). A comparative analysis showed that patients with acute brucellosis had significantly higher erythrocyte sedimentation rate (ESR), alanine aminotransferase (ALT) levels, and C-reactive protein (CRP) levels than those in other subgroups. The most prevalent laboratory findings were elevated CRP (50.3%), elevated ESR (37.6%), and anemia (33.3%). Hepatobiliary and osteoarticular complications developed in 22.6% and 6.5% of patients, respectively. Brucellosis in this endemic region predominantly affected women and individuals living in rural areas and was strongly associated with the consumption of unpasteurized dairy products. Our findings emphasize the need for improved public awareness and preventive measures, particularly regarding safe dairy consumption, in endemic settings. Graphic Abstract.

Brucellosis remains the most prevalent zoonotic disease globally and can cause chronic persistent infection, which in turn results in prolonged recovery challenges. Myeloid-derived suppressor cells (MDSCs) are pathologically activated neutrophils and monocytes with strong immunosuppressive activity. Toll-like receptor 4 (TLR4) can initiate the body's inflammatory response, leading to an inflammatory cytokine storm. Programmed death ligand 1 (PD-L1) modulates the strength and duration of the immune response, diminishing the immune system's ability to eliminate pathogens and subsequently affecting disease progression and prognosis. However, the clinical significance of TLR4+MDSC and PD-L1+MDSC in Brucella infection remains unclear. A total of 88 patients with acute brucellosis infection (ABI), 66 patients with chronic brucellosis infection (CBI), and 82 healthy controls (HC) subjects were enrolled. Flow cytometry was used to detect TLR4+MDSCs and PD-L1+MDSCs of patients. ELISA was used to detect ALT, AST, Arg1 and iNOS in the patient's serum. We characterized a mouse model of Brucella, and determined the effects of TLR4+MDSCs and PD-L1+MDSCs in this model. Our study found that the frequency of MDSC in CBI group was significantly elevated. The levels of Arg1 and iNOS were also positively correlated with the levels of TLR4+MDSCs and PD-L1+MDSCs. The levels of AST and ALT had elevated may reflect liver function. In addition, we also found that the number of TLR4+MDSCs and PD-L1+MDSCs increased in model mice with chronic brucellosis. These findings expand the current understanding of persistent Brucella infection, and highlight that TLR4+ and PD-L1+ MDSCs hold potential as candidate biomarkers for assessing the severity and progression of brucellosis.

This study aims to explore potential biological biomarkers for brucellosis by integrating transcriptomic profiling and bioinformatics-driven approaches. Differentially expressed genes (DEGs) associated with acute and chronic brucellosis were identified using transcriptomic data from the Gene Expression Omnibus (GEO). Functional annotation and pathway enrichment analysis of DEGs were performed using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Weighted Gene Co-expression Network Analysis (WGCNA) was applied to construct gene co-expression modules, followed by screening of modules significantly correlated with disease phenotypes. Notably, a multi-model machine learning framework was employed for systematic screening, cross-validation, and validation of diagnostically relevant biomarkers-ensuring robustness and generalizability of the findings. A total of 103 brucellosis patients and 46 healthy controls with whole blood transcriptomic profiles were included. Comparative analysis identified 264 DEGs, which were predominantly enriched in mitotic nuclear division, chromosome segregation, nucleocytoplasmic transport, cell cycle regulation, and cytokine-cytokine receptor interaction pathways-providing novel insights into the molecular pathogenesis of brucellosis. Immune infiltration profiling revealed that brucellosis progression was positively correlated with CD8+ T cells, follicular helper T cells, and resting NK cells-highlighting previously underappreciated immune regulatory mechanisms. Two co-expression modules were significantly associated with brucellosis clinical traits through WGCNA. Cross-validation using machine learning algorithms (LASSO, SVM, random forest) prioritized six overlapping hub genes: RTP5, KIF19, CDKN2A, RCAN2, GLB1L3, and IL12RB2. Receiver Operating Characteristic (ROC) curve analysis demonstrated robust diagnostic performance, supporting their potential as combinatorial biomarkers for brucellosis detection. These novel hub genes are closely implicated in inflammatory responses, neutrophil regulation, and B cell receptor signaling pathways-key processes underlying brucellosis pathogenesis that have not been previously targeted for diagnostic biomarker development. This work not only enhances our understanding of brucellosis biology but also lays a critical foundation for the development of non-invasive, accurate diagnostic tools and targeted therapeutic strategies-filling a significant gap in current brucellosis management.

The clinical manifestations and laboratory test results of Brucella melitensis and Brucella abortus in acute brucellosis patients.

Dairy and beef farming is a central agricultural sector in the North Caucasus Federal District. Sick animals are the source of brucellosis infection for humans. In the Kabardino-Balkarian Republic, a region of the North Caucasus with a long-standing epidemiological risk for brucellosis, a cluster (6 individuals) epidemic outbreak of acute brucellosis was recorded in a household in 2024. An epidemiological investigation identified the epidemiological characteristics and presented an etiological explanation for the cluster “family” outbreak. The aim of the study was to analyze the results of the epidemiological investigation of the group “household” outbreak of acute brucellosis in Kabardino-Balkarian Republic in 2024 and to characterize the features of genome organization of isolated Brucella strains. Materials and methods . Epidemiological data from the Rospotrebnadzor Administration in the Kabardino-Balkarian Republic were used for the work. We also studied 467 whole-genome sequences, 504 MLVA genotypes of strains from the collection of the Stavropol Anti-Plague Institute of the Rospotrebnadzor. Results and discussion . Based on the analysis of epidemiological investigation data and molecular-genetic analysis of the isolated strains, the epidemiological and etiological features of a group “family” outbreak of brucellosis were determined. A regional genetic profile of the Brucella population circulating in the North Caucasus has been determined, allowing for differentiation of isolated strains based on the principle of “new” and “rooted” ones. The data obtained from the epidemiological investigation of the family outbreak of brucellosis provide for scientific substantiation of the phylogeny and relationships of brucellosis foci, confirmation of the introduction/importation of the infection to other (previously brucellosis-free) areas, and conducting genomic monitoring of the causative agent of brucellosis.

BackgroundBrucellosis is a major zoonotic disease affecting individuals of all ages, with varied clinical presentations depending on the site of infection. Pediatric cases, though less frequently reported, require particular attention due to the diagnostic and therapeutic challenges. We aimed to study the clinical and therapeutic features of brucellosis among children.MethodsA retrospective study was conducted including patients aged ≤ 18 years hospitalized for brucellosis in the infectious diseases department between 2002 and 2024.ResultsThirty-one cases were identified, among whom 19 were males (61.3%). The mean age was 13 ± 4 years. Previous personal history of brucellosis and family history brucellosis were noted in 32.3% and 38.7% of cases, respectively. The main symptoms included fever (87.1%), night sweats (67.7%), and arthro-myalgia (61.3%). Splenomegaly and peripheral lymphadenopathy were each found in 9.7% of cases. Acute brucellosis accounted for 77.5% of cases. Complications included neurobrucellosis (3 cases), hip arthritis (2 cases), and sacroiliitis (2 cases). Wright’s serology was positive in all cases. Blood cultures were positive in 25.8% of the cases. Cerebrospinal or synovial fluid cultures were positive in 6.4% and 3.2%, respectively. Treatment included rifampicin (100%) combined with doxycycline (64.5%) or trimethoprim-sulfamethoxazole (35.5%). The disease evolution was favorable in all cases (100%).ConclusionThe diagnosis of brucellosis should be ruled out among children from endemic areas presenting with fever, night sweats and musculoskeletal symptoms. Prompt diagnosis and appropriate antibiotic therapy are key to ensuring favorable outcomes.DisclosuresAll Authors: No reported disclosures

Brucellosis is a zoonotic infectious disease that is widely prevalent and remains a major public health concern worldwide. Although endemic in our country, there are limited pediatric case series concerning this disease. This study aims to analyze pediatric cases of brucellosis diagnosed in our clinic and to provide a contribution to the current body of medical literature. This study included 181 cases diagnosed with brucellosis who were followed up in the Pediatric Infectious Disease Department of Mersin University Faculty of Medicine between January 1, 2013, and July 1, 2023, in Turkey. The cases were retrospectively evaluated based on their demographic and epidemiologic characteristics, clinical symptoms, physical examination findings, laboratory and microbiologic results, complications and treatment responses from medical records. Brucellosis was diagnosed in patients through an integrated assessment of clinical manifestations, microbiologic culture results and serologic testing (Coombs anti-Brucella agglutination test). In this study, a total of 181 patients were included, of which 98 (54.1%) were male and 83 (45.9%) were female. The mean age of the patients was 10.52 ± 4.23 years, ranging from 1 to 17 years. Living in rural areas was identified in 48.1% of the cases, while 42.2% had contact with animals, 64.1% consumed unpasteurized milk/dairy products and 34.3% had a family history of brucellosis. Of the patients, 92.3% were diagnosed with acute brucellosis and 7.7% were diagnosed with subacute brucellosis. Standard tube agglutination at a titer of 1/160 or higher was observed in 71.8% of the cases. Brucella spp. growth was detected in 24.3% of blood cultures and 0.56% of bone marrow cultures, while no growth was observed in cerebrospinal fluid cultures. Patients with bacteremia exhibited significantly higher rates of fever, night sweats, abdominal pain, lymphadenopathy, positive standard tube agglutination test results and disease relapse. When evaluating brucellosis-related complications, bone and joint involvement was the most common, observed in 22.1% (n = 40) of the patients, followed by neurobrucellosis in 2 patients and pleuritis in 1 patient. All patients were treated with a combined regimen. Relapse was observed in 4 patients, while no mortality was reported. Brucellosis remains a major public health concern in Turkey. While brucellosis is frequently observed in adults engaged in livestock farming, children are also at risk due to the possibility of foodborne transmission.

Deep vein thrombosis (DVT) is a potentially serious vascular condition with multiple well-established risk factors, including immobility, surgery, trauma, malignancy, and inherited or acquired thrombophilias. Infectious causes of DVT are rare but have been increasingly recognized, with brucellosis being one such unusual infectious etiology. Brucellosis is a zoonotic infection caused by Brucella species, endemic in many regions, including the Middle East, Mediterranean countries, and parts of Latin America. While musculoskeletal manifestations such as arthritis, spondylitis, and sacroiliitis are commonly reported, vascular complications like DVT are seldom described. Highlighting these rare presentations is important for early recognition and appropriate management. We report the case of a 22-year-old woman with no prior chronic illnesses who presented with a 10-day history of bilateral leg pain, swelling, and redness. She was initially referred to the rheumatology clinic with a provisional diagnosis of arthritis. On physical examination, both ankles were erythematous, warm, and edematous; Homan’s sign was positive in the left leg. Doppler ultrasonography confirmed DVT in the affected limbs. Laboratory tests revealed elevated acute-phase reactants, including erythrocyte sedimentation rate and C-reactive protein. Blood cultures grew Gram-negative coccobacilli, and serological tests, including rose bengal and serum tube agglutination, were positive for Brucella. Following infectious diseases consultation, a diagnosis of acute brucellosis was made, and combination therapy with rifampicin and doxycycline was initiated. Concurrently, anticoagulation therapy with warfarin was initiated under the guidance of the cardiovascular surgery team. The patient’s clinical symptoms gradually improved with combined antimicrobial and anticoagulant therapy. Brucellosis, though rare, should be considered in the differential diagnosis of DVT, especially in endemic regions. Early recognition allows timely antimicrobial and anticoagulant therapy. Clinicians should suspect infectious causes of DVT in patients with limb swelling, pain, or systemic symptoms, even without classical risk factors.

Introduction: This study was designed to determine the differences between brucellosis patients whose standard tube agglutination test (SAT) titers decreased or not after successful treatment. Methods: This retrospective study included patients with a course of antibiotic therapy at least 6 weeks for acute brucellosis or 12 weeks for osteoarticular involvement, and whose post-treatment clinical findings improved. Results: The mean age of the 276 patients was 45.2 years, and 50.7% were female. The SAT titer decreased in 166 patients (60%). No significant differences were found in terms of demographical and epidemiological characteristics between the groups. Patients with decreased SAT titers exhibited an elevated pre-treatment erythrocyte sedimentation rate (ESR) and the lymphocytosis was more prevalent. In the non-decreased SAT group, liver enzymes such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT) values after treatment were higher. The initial SAT titer of 1/160 and the pre-treatment rates of anaemia and thrombocytopenia were significantly higher in patients whose SAT titers became negative. Among patients whose SAT titers remained positive, the initial SAT titer was more frequently ≥1/320, and the post-treatment AST value was higher. Conclusions: This study showed that a serological response can be obtained with a high ESR and lymphocytosis prior to treatment. It should be noted that SAT negativity cannot be observed immediately in patients with pre-treatment SAT titers ≥ 1/320. The healthcare providers are advised to consider the complete clinical picture without relying solely on serological results.

Laboratory parameters and serum tube agglutination test as markers for brucellosis treatment response.

Background & objectives Brucellosis, an occupational zoonosis, poses notable difficulties in diagnosis because of the need for secure facilities and the risk of exposure when using culture-based methods. Conventional serological tests often suffer from cross-reactivity, highlighting the need for more specific diagnostic markers. The purpose of this study was to understand the differences in whole-cell protein expression of Brucella melitensis isolates from patients with acute and chronic brucellosis and to identify immunodominant proteins that could serve as potential diagnostic markers. Methods The study included 16 blood culture-confirmed patients with acute or chronic brucellosis from a cohort of 185 individuals. Clinical isolates of B. melitensis were subjected to two-dimensional gel electrophoresis (2-DE) and PDQuest software analysis to compare proteomic profiles. Differentially expressed proteins were identified using western blotting with infected human serum samples. Further identification of the protein spots was conducted using Matrix-Assisted Laser Desorption/Ionization - Time-of-flight Mass Spectrometry (MALDI-TOF MS). Results The proteomic analysis of B. melitensis identified an average of 249 protein spots. PDQuest software revealed 65 differentially expressed spots, with 17 of these spots successfully identified via MALDI-TOF MS. Western blot assays demonstrated that human sera containing anti-Brucella antibodies reacted with seven immunodominant protein spots. Among these, the outer membrane porin protein (omp25), aldehyde dehydrogenase, and universal stress protein showed potential for differentiating acute from chronic brucellosis. Interpretation & conclusions The findings indicate that omp25, aldehyde dehydrogenase, and universal stress protein are highly specific to B. melitensis infections and could serve as valuable targets for serodiagnosis.

BackgroundBrucellosis is a zoonotic disease that is widely prevalent in the Xinjiang region of China. Once it progresses to a chronic stage, it can lead to significant complications. Immune checkpoints markers on Myeloid-derived suppressor cells (MDSCs) may lead to the chronic stage of the disease. This study analyzed the changes in MDSCs, immune checkpoints markers and cytokines in the patients with acute and chronic Brucella infections and after antibiotic treatment, to explore their roles and provide new ideas for future clinical treatment.MethodsA total of 37 patients with acute brucellosis infection (ABI) and 46 patients with chronic brucellosis infection (CBI) and 43 healthy controls (HC) subjects were enrolled. Flow cytometry was used to detect the expression of MDSCs, Siglec-9+MDSCs, PD-1+MDSCs and Tim-3+MDSCs before and after antibiotic treatment. In addition, ELISA was used to measure the levels of cytokines and the changes in IL-6 and Arg-1 of them were assessed again after antibiotic treatment.ResultsOur study found that the levels of MDSCs in the patients significantly increased, with CBI patients exhibiting higher levels than ABI patients. The cytokines showed varying degrees of elevation. Furthermore, after antibiotic treatment, the levels of MDSCs, Siglec-9+ MDSCs, PD-1+ MDSCs and Tim-3+ MDSCs in effective treatment patients significantly decreased. In contrast, the levels of MDSCs in ineffective treatment patients increased, while there were no significant differences in PD-1+ MDSCs and Tim-3+ MDSCs levels compared to before treatment. Notably, the levels of Siglec-9+MDSCs in ineffective treatment showed a significant increase. In the ineffective treatment patients, the serum levels of Arg-1 and IL-6 both increased compared to before treatment. Correlation analysis revealed a positive correlation in ineffective treatment patients between serum Arg-1 levels and MDSCs, as well as Siglec-9+ MDSCs levels, while no correlation was observed between IL-6 levels and immune cell parameters.ConclusionMDSCs are increased in both ABI and CBI. Siglec-9 acts as an immune checkpoint on MDSCs in patients with ineffective treatment responses. Therefore, Siglec-9 represents a potential prognostic marker for Brucella infection. Ongoing research on prognostic markers of brucellosis is promising, and further clinical studies are warranted to validate these findings.

Brucellosis, a prevalent zoonotic disease in endemic regions like Saudi Arabia, poses diagnostic challenges due to its nonspecific clinical manifestations. This disease is endemic in various regions, including the Mediterranean basin, the Middle East, Asia, Africa, and Latin America. This retrospective study is designed to evaluate the diagnostic utility of the slide agglutination method for brucellosis. By examining its sensitivity, specificity, and overall performance, this research will provide insights into the reliability of the slide agglutination method as a diagnostic tool in a high-prevalence setting. This retrospective study, conducted at the International Medical Center, Jeddah, compared the real-world diagnostic performance of the Slide Agglutination Method (SAM) with gold-standard blood cultures and Brucella serology. Over 734 cases (37 Brucella-positive and 697 Brucella-negative) were reviewed between 2019 and 2022. SAM achieved 86.5% sensitivity and 99.3% specificity, with an average turnaround time of 2.32 hours. In contrast, blood culture showed 40.9% sensitivity and 94.5% accuracy, and conventional serology demonstrated comparable sensitivity but longer processing times. SAM combines speed, simplicity, and robust accuracy, making it an ideal first-line screen for acute brucellosis in endemic, resource-limited settings. However, its performance in chronic or low-titer infections remains less well characterized. Our detailed operational metrics fill a local evidence gap and support the Saudi Ministry of Health in updating national screening guidelines.

BackgroundBrucellosis, a prevalent zoonotic disease in endemic regions like Saudi Arabia, poses diagnostic challenges due to its nonspecific clinical manifestations. This disease is endemic in various regions, including the Mediterranean basin, the Middle East, Asia, Africa, and Latin America. This retrospective study is designed to evaluate the diagnostic utility of the slide agglutination method for brucellosis. By examining its sensitivity, specificity, and overall performance, this research will provide insights into the reliability of the slide agglutination method as a diagnostic tool in a high-prevalence setting.MethodsThis retrospective study, conducted at the International Medical Center, Jeddah, compared the real-world diagnostic performance of the Slide Agglutination Method (SAM) with gold-standard blood cultures and Brucella serology. Over 734 cases (37 Brucella-positive and 697 Brucella-negative) were reviewed between 2019 and 2022.ResultsSAM achieved 86.5% sensitivity and 99.3% specificity, with an average turnaround time of 2.32 hours. In contrast, blood culture showed 40.9% sensitivity and 94.5% accuracy, and conventional serology demonstrated comparable sensitivity but longer processing times.ConclusionSAM combines speed, simplicity, and robust accuracy, making it an ideal first‐line screen for acute brucellosis in endemic, resource‐limited settings. However, its performance in chronic or low-titer infections remains less well characterized. Our detailed operational metrics fill a local evidence gap and support the Saudi Ministry of Health in updating national screening guidelines.

Ama: Krm-Kongo kanamal atei (KKKA) ve akut brusellozun endemik olduu blgelerde, yksek ate nedeniyle acil servise bavuran ve lkopeni ile trombositopeni saptanan hastalarda tansal bir ikilem ortaya

ZGiri: NETozis, ntrofiller iin bir hcre lm ekli olup, ntrofillerin hcre d kromatin, proteinler ve granllerle tuzaklanmasn ieren bir savunma sistemidir.Peptidil arjinin deiminaz 4 (PAD4), ntrofil elastaz (NE) ve ntrofil jelatinaz ilikili lipokalin (NGAL), NETozis ile ilikili biyobelirtelerdir.Bu almada, bruselloz hastal srecinde NETozis belirtelerinin zamansal deiimlerinin tanmlanmas

Molecular epidemiology, immunobiology, genomics and proteomics insights into bovine brucellosis.

Brucellosis is a significant zoonotic disease that may lead to metabolic profile changes, which remain insufficiently studied. This study utilized an ultra-high performance liquid chromatography coupled with Q Exactive-Orbitrap mass spectrometry (UHPLC-QExactive-Orbitrap MS/MS) to investigate serum samples of acute brucellosis in 32 male patients against 32 well-matched healthy controls. The results revealed nine differential metabolites that correlated with human acute brucellosis, all showing increased levels, except cis-4-hydroxy-D-proline, inosine, hypoxanthine and azelaic acid. These differential metabolites were predominantly involved in metabolic pathways, such as primary bile acid biosynthesis, purine metabolism, taurine and hypotaurine metabolism, and d-amino acid metabolism. This study identified potential metabolite biomarkers of acute brucellosis and laid the foundation for its early diagnosis and prognostic assessment, thus helping to prevent the chronicity of acute brucellosis.