A case report of acute renal failure caused by anti-brucellosis treatment.

RATIONALE: Rifampicin, as a main chemotherapy drug treating brucellosis, is widely used in clinical practice. Rifampicin-associated ARF is not rare, especially in those rifampicin re-exposure patients. However, this was rare complication of severe renal involvement due to multiple factors including rifampicin, nephrotoxic gentamicin, and contrast medium, and few studies have reported it. PATIENT CONCERNS: A 59-year-old male presented to our hospital with acute renal failure (ARF) caused by anti-brucellosis treatment with rifampicin (675 mg/day), gentamicin (320 mg/day), and doxycycline (200 mg/day). He had a contrast-enhanced CT of the upper abdomen before the onset of. After stopping rifampicin and undergoing integrated therapy, the patient's renal function gradually recovered. DIAGNOSES: Considering that the patient had a history of using rifampicin for pulmonary tuberculosis in the past, based on the examination results, the patient was diagnosed with rifampicin-associated ARF. INTERVENTIONS: Symptomatic treatment such as hemodialysis, and anti-brucella treatment with doxycycline and moxifloxacin were given. OUTCOMES: The patient had significant anuric and polyuric periods and acute tubular necrosis is considered. After treatment, his renal function and urine volume returned to normal, and Brucella melitensis was not isolated from blood cultures. LESSONS: The case reveals that severe renal involvement due to multiple factors including rifampicin, nephrotoxic gentamicin, and contrast medium. Misdiagnosis and mistreatment can deteriorate the patient's condition. Renal function should be closely monitored in the susceptible patients. Early recognition can provide appropriate therapy to patients. If unexplained renal failure during the use of rifampicin, especially in those rifampicin re-exposure patients, rifampicin-associated ARF should be considered.

A multi-epitope subunit vaccine based on CU/ZN-SOD, OMP31 and BP26 against Brucella melitensis infection in BALB/C mice.

Brucellosis, a zoonosis caused by Brucella, is highly detrimental to both humans and animals. Most existing vaccines are live attenuated vaccines with safety flaws for people and animals. Therefore, it is advantageous to design a multi-epitope subunit vaccine (MEV) to prevent Brucella infection. To this end, we applied a reverse vaccinology approach. Six cytotoxic T cell (CTL) epitopes, seven T helper cell (HTL) epitopes, and four linear B cell epitopes from CU/ZN-SOD, Omp31, and BP26 were obtained. We linked the CTL, HTL, B-cell epitopes, the appropriate CTB molecular adjuvant, and the universal T helper lymphocyte epitope, PADRE, with linkers AAY, GPPGG, and KK, respectively. This yielded a 412-amino acid MEV construct, which we named MEVcob. The immunogenicity, stability, safety, and feasibility of the construct were evaluated by bioinformatics tools (including the AlphaFold2 prediction tool, the AlphaFold2 tool, NetMHC-I pan 4.0 server, IEDB MHC-I server, ABCpred service, and C-ImmSim server); the physicochemical properties, secondary and tertiary structures, and binding ability of MEVocb to toll-like receptor 4 (TLR4) was analyzed. Then, codon adaptation and computer cloning studies were performed. MEVocb is highly immunogenic in immunostimulation experiments, The proteins translated by these sequences were relatively stable, exhibiting a high antigenic index. Furthermore, mouse experiments confirmed that the MEVocb construct could raise IFN-γ, IgG, IgG2a, IgG1, IL-2, TNF-α levels in mice, indicating that induced a specific humoral and cellular immune response in BALB/c mice. This vaccine induced a statistically significant level of protection in BALB/c mice when challenged with Brucella melitensis 043 in Xinjiang. Briefly, we utilized immunoinformatic tools to design a novel multi-epitope subunit candidate vaccine against Brucella. This vaccine aims to induce host immune responses and confer specific protective effects. The study results offer a theoretical foundation for the development of a novel Brucella subunit vaccine.

DNA Sensor for the Detection of Brucella spp. Based on Magnetic Nanoparticle Markers.

Due to the limitations of conventional Brucella detection methods, including safety concerns, long incubation times, and limited specificity, the development of a rapid, selective, and accurate technique for the early detection of Brucella in livestock animals is crucial to prevent the spread of the associated disease. In the present study, we introduce a magnetic nanoparticle marker-based biosensor using frequency mixing magnetic detection for point-of-care testing and quantification of Brucella DNA. Superparamagnetic nanoparticles were used as magnetically measured markers to selectively detect the target DNA hybridized with its complementary capture probes immobilized on a porous polyethylene filter. Experimental conditions like density and length of the probes, hybridization time and temperature, and magnetic binding specificity, sensitivity, and detection limit were investigated and optimized. Our sensor demonstrated a relatively fast detection time of approximately 10 min, with a detection limit of 55 copies (0.09 fM) when tested using DNA amplified from Brucella genetic material. In addition, the detection specificity was examined using gDNA from Brucella and other zoonotic bacteria that may coexist in the same niche, confirming the method's selectivity for Brucella DNA. Our proposed biosensor has the potential to be used for the early detection of Brucella bacteria in the field and can contribute to disease control measures.

Treatment Outcomes in COVID-19 Patients with Brucellosis: Case Series in Heilongjiang and Systematic Review of Literature.

Objective: Clinical characteristics and outcome in COVID-19 with brucellosis patients has not been well demonstrated, we tried to analyze clinical outcome in local and literature COVID-19 cases with brucellosis before and after recovery. Methods: We retrospectively collected hospitalization data of comorbid patients and prospectively followed up after discharge in Heilongjiang Infectious Disease Hospital from January 15, 2020 to April 29, 2022. Demographics, epidemiological, clinical symptoms, radiological and laboratory data, treatment medicines and outcomes, and follow up were analyzed, and findings of a systematic review were demonstrated. Results: A total of four COVID-19 with brucellosis patients were included. One patient had active brucellosis before covid and 3 patients had nonactive brucellosis before brucellosis. The median age was 54.5 years, and all were males (100.0%). Two cases (50.0%) were moderate, and one was mild and asymptomatic, respectively. Three cases (75.0%) had at least one comorbidity (brucellosis excluded). All 4 patients were found in COVID-19 nucleic acid screening. Case C and D had only headache and fever on admission, respectively. Four cases were treated with Traditional Chinese medicine, western medicines for three cases, no adverse reaction occurred during hospitalization. All patients were cured and discharged. Moreover, one case (25.0%) had still active brucellosis without re-positive COVID-19, and other three cases (75.0%) have no symptoms of discomfort except one case fell fatigue and anxious during the follow-up period after recovery. Conducting the literature review, two similar cases have been reported in two case reports, and were both recovered, whereas, no data of follow up after recovery. Conclusion: These cases indicate that COVID-19 patients with brucellosis had favorable outcome before and after recovery. More clinical studies should be conducted to confirm our findings.

Use of camel urine is of no benefit to cancer patients: observational study and literature review.

Background: Complementary and alternative medicine is widely used in Saudi Arabia. One of the common practices is the use of camel urine alone or mixed with camel milk for the treatment of cancer, which is often supported by religious beliefs. Aims: To observe and follow-up cancer patients who insisted on using camel urine, and to offer some clinically relevant recommendations. Methods: We observed 20 cancer patients (15 male, 5 female) from September 2020 to January 2022 who insisted on using camel urine for treatment. We documented the demographics of each patient, the method of administering the urine, reasons for refusing conventional treatment, period of follow-up, and the outcome and side effects. Results: All the patients had radiological investigations before and after their treatment with camel urine. All of them used a combination of camel urine and camel milk, and treatment ranged from a few days to 6 months. They consumed an average of 60 ml urine/milk per day. No clinical benefit was observed after the treatment; 2 patients developed brucellosis. Eleven patients changed their mind and accepted conventional antineoplastic treatment and 7 were too weak to receive further treatment; they died from the disease. Conclusion: Camel urine had no clinical benefits for any of the cancer patients, it may even have caused zoonotic infection. The promotion of camel urine as a traditional medicine should be stopped because there is no scientific evidence to support it.

Intracellular growth of Brucella is mediated by Dps-dependent activation of ferritinophagy.

Bacteria of the genus Brucella cause brucellosis, one of the world's most common zoonotic diseases. A major contributor to Brucella's virulence is the ability to circumvent host immune defense mechanisms. Here, we find that the DNA-binding protein Dps from Brucella is secreted within the macrophage cytosol, modulating host iron homeostasis and mediating intracellular growth of Brucella. In addition to dampening iron-dependent production of reactive oxygen species (ROS), a key immune effector required for immediate bacterial clearance, cytosolic Dps mediates ferritinophagy activation to elevate intracellular free-iron levels, thereby promoting Brucella growth and inducing host cell necrosis. Inactivation of the ferritinophagy pathway by Ncoa4 gene knockout significantly inhibits intracellular growth of Brucella and host cell death. Our study uncovers an unconventional role of bacterial Dps, identifying a crucial virulence mechanism used by Brucella to adapt to the harsh environment inside macrophages.

Comparing efficacy and safety of high-dose and standard-dose rifampicin in the treatment of brucellosis: a randomized clinical trial.

BACKGROUND: In a few studies, higher doses of rifampicin improved the outcome of patients with TB. There is no information regarding efficacy and safety of higher doses of rifampicin in patients with brucellosis. OBJECTIVES: To compare efficacy and safety of higher and standard doses of rifampicin, each with doxycycline, in the treatment of patients with brucellosis. METHODS: Within a randomized clinical trial, clinical response and adverse events of high-dose rifampicin (900-1200 mg/day) plus doxycycline 100 mg twice daily were compared with standard-dose rifampicin (600 mg/day) plus doxycycline 100 mg twice daily in 120 patients with brucellosis. RESULTS: Clinical response occurred in 57 (95%) of patients in the high-dose group and 49 (81.66%) of patients in the standard-dose group (P = 0.04). The most common adverse events of the treatment were nausea (37.5%), skin rash (13.33%), vomiting (10%) and transaminitis (7.22%). Incidence of these events was comparable between the groups. CONCLUSIONS: The rate of clinical response in patients with brucellosis who were treated with high-dose rifampicin plus standard-dose doxycycline was significantly higher than in the patients who received the standard doses of rifampicin and doxycycline, without further adverse events. The high-dose rifampicin therefore improved clinical response in patients with brucellosis with a similar safety profile to the standard dose. If these findings are confirmed in future studies, higher doses of rifampicin may be recommended for treatment of patients with brucellosis.

Network Pharmacology-based Strategy to Investigate Pharmacological Mechanisms of Qingbutongluo Pill for Treatment of Brucellosis.

BACKGROUND AND OBJECTIVES: Qingbutongluo pill (QBTLP), a Chinese herbal preparation, has been developed to treat brucellosis for many years with a good therapeutic effect. This study preliminarily explored its potential molecular mechanisms against brucellosis through network pharmacology. METHODS: The active ingredients of QBTLP were screened out mainly from the Traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP), and their potential targets were predicted through the PubChem database and Swiss Target Prediction platform. GeneCards, DisGeNET Digsee and the Comparative Toxicogenomics Database (CTD) searched the targets corresponding to brucellosis. Then, the Venn diagram obtained intersection targets of QBTLP and diseases. Protein-protein interaction (PPI) network analysis was performed using the Search Tool for the Retrieval of Interacting Genes database (STRING) and visualized in Cytoscape software. Module analysis of the PPI network and core target identification was performed using the Molecular Complex Detection (MCODE) and the Cytohubba plugins. The Metascape data platform was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis on the intersection targets, and then the "active ingredientstargets- pathways" network was constructed using Cytoscape to screen key active ingredients. RESULTS: 19 key active ingredients were identified by network pharmacological, including Baicalein, Cryptopin, etc. The core targets of QBTLP for treating brucellosis contained TNF, TLR4, MAPK3, MAPK1, MAPK8, MAPK14, MMP9, etc. And the main pathways included the Toll-like receptor signaling pathway, NOD-like receptor signaling pathway, TNF signaling pathway, MAPK signaling pathway, Th17 cell differentiation, and IL-17 signaling pathway. CONCLUSIONS: This study explored the mechanisms of QBTLP for treating brucellosis, which may provide a scientific basis for the clinical application of QBTLP.

Treatment Outcomes in COVID-19 Patients with Brucellosis: Case Series in Heilongjiang and Systematic Review of Literature / 生物医学与环境科学（英文）

OBJECTIVE@#Clinical characteristics and outcome in COVID-19 with brucellosis patients has not been well demonstrated, we tried to analyze clinical outcome in local and literature COVID-19 cases with brucellosis before and after recovery.@*METHODS@#We retrospectively collected hospitalization data of comorbid patients and prospectively followed up after discharge in Heilongjiang Infectious Disease Hospital from January 15, 2020 to April 29, 2022. Demographics, epidemiological, clinical symptoms, radiological and laboratory data, treatment medicines and outcomes, and follow up were analyzed, and findings of a systematic review were demonstrated.@*RESULTS@#A total of four COVID-19 with brucellosis patients were included. One patient had active brucellosis before covid and 3 patients had nonactive brucellosis before brucellosis. The median age was 54.5 years, and all were males (100.0%). Two cases (50.0%) were moderate, and one was mild and asymptomatic, respectively. Three cases (75.0%) had at least one comorbidity (brucellosis excluded). All 4 patients were found in COVID-19 nucleic acid screening. Case C and D had only headache and fever on admission, respectively. Four cases were treated with Traditional Chinese medicine, western medicines for three cases, no adverse reaction occurred during hospitalization. All patients were cured and discharged. Moreover, one case (25.0%) had still active brucellosis without re-positive COVID-19, and other three cases (75.0%) have no symptoms of discomfort except one case fell fatigue and anxious during the follow-up period after recovery. Conducting the literature review, two similar cases have been reported in two case reports, and were both recovered, whereas, no data of follow up after recovery.@*CONCLUSION@#These cases indicate that COVID-19 patients with brucellosis had favorable outcome before and after recovery. More clinical studies should be conducted to confirm our findings.

[The effectiveness of the use of non-drug treatment complexes and their impact on quality of life indicators, the psychosomatic status of patients with residual brucellosis with lesions of the musculoskeletal system]. / Effektivnost' primeneniya kompleksov nemedikamentoznogo lecheniya i ikh vliyanie na pokazateli kachestva zhizni, psikhosomaticheskii status patsientov s rezidual'nym brutsellezom s porazheniem oporno-dvigatel'nogo apparata.

Secondary focal lesions of the musculoskeletal system that occur with residual brucellosis are characterized by a variety of localizations and simultaneous damage to several groups of joints, a deterioration in the quality of life and a high percentage of disability in people of working age. At present, there are many different schemes for the treatment and rehabilitation of developed residual brucellosis, in which, in addition to the "basic" course, including systemic anti-inflammatory therapy, much attention is paid to physiotherapeutic procedures, but the choice of the most effective treatment tactics remains an unresolved problem. PURPOSE OF THE STUDY: To determine the effectiveness of the use of options for non-drug methods of treatment in the complex rehabilitation of patients with residual brucellosis with lesions of musculoskeletal system. MATERIAL AND METHODS: Study included 140 patients treated for osteoarthritis of brucellosis etiology, who were divided into three groups matched by age, gender, average duration and stage of the disease, place of residence. Patients of all groups received standard medical treatment and different sets of physiotherapeutic procedures: in the 1st group (45 patients) - electrophoresis of novocaine on the knee joints, therapeutic massage of the cervical-collar zone; in the 2nd group (45 patients) - magnetotherapy on the area of the knee joints, sinusoidal modulated currents (SMC) on the shoulder joints, decimeter wave therapy of the lumbosacral zone (DMW-therapy); in the 3rd group (50 patients) - magnetic laser therapy on the shoulder, elbow, knee joints, therapeutic massage of the lumbosacral zone. Complaints, clinical symptoms, goniometry results, and blood parameters were assessed: ESR, C-reactive protein, fibrinogen, before the start of treatment, immediately after the course of rehabilitation, and after 6 and 12 months. At the same time, testing was carried out according to the SF-36 Health Status Survey questionnaire to monitor the quality of life. RESULTS: The applied scheme of drug treatment in combination with magnetic laser therapy and therapeutic massage in the 3rd group made it possible to achieve a significant reduction in arthralgic syndrome, a statistically significant increase in the range of motion in the joints, positive dynamics of laboratory data and an improvement in the psychological state and quality of life of patients compared to other observation groups. CONCLUSION: The results of the study indicate the high efficiency of magnetic laser therapy in the complex treatment of patients with residual brucellosis with lesions of the musculoskeletal system.

A health promotion perspective for the control and prevention of Brucellosis (Brucella melitensis); Israel as a case study.

BACKGROUND: Brucellosis (Brucella melitensis) is endemic in many countries around the world, therefore, identifying what is required to control and prevent the disease is essential. The health promotion concept and five areas of action, presented in the Ottawa Charter (1986) may help understand how to go forward in the prevention of the disease. Israel serves as a case study. AIM: To identify barriers to the control and prevention of brucellosis (Brucella melitensis) in Israel by analyzing trends in incidence in conjunction with interventions implemented over the last seven decades, applying the health promotion areas of action. METHODS: 1. A document review approach was adopted to develop a list of interventions implemented in Israel to prevent and control brucellosis and identify barriers to implementation. These were analysed using the health promotion areas of action. 2. Data from the mandatory reporting of infectious diseases in Israel regarding brucellosis in humans between 1951 and 2021 are presented and analyzed in conjunction with the interventions implemented. RESULTS: A large range of interventions were implemented following outbreaks of the disease. These interventions followed the health promotion areas of action, including mainly: policy, education and environment and brought about a decrease in the disease among both animals and humans. However, major interventions were discontinued after a few years. In addition, we identified some areas of action that could be much improved on. The interventions, in many cases were not simultaneously implemented or coordinated, decreasing the chances of them having the expected long term impact. CONCLUSIONS: Control and prevention of the disease in Israel is partial. Areas of action that could be improved include enforcement of regulations, strengthening community action and improving personal skills. Simultaneous and continuous implementation of the interventions may achieve the goals of sustained prevention and control. There seems to be a lack of a long-term strategy and an integrated holistic intervention approach that may contribute to the control and prevention of the disease.

The perspective of antibiotic therapeutic challenges of brucellosis in the Middle East and North African countries: Current situation and therapeutic management.

Brucellosis is among the most prevalent zoonotic infections in Middle Eastern and North African (MENA) countries, critically impacting human and animal health. A comprehensive review of studies on antibiotic susceptibility and therapeutic regimes for brucellosis in ruminants and humans in the MENA region was conducted to evaluate the current therapeutic management in this region. Different scientific databases were searched for peer-reviewed original English articles published from January 1989 to February 2021. Reports from research organizations and health authorities have been taken into consideration. Brucella melitensis and Brucella abortus have been reported from the majority of MENA countries, suggesting a massive prevalence particularly of B. melitensis across these countries. Several sporadic cases of brucellosis relapse, therapeutic failure, and antibiotic resistance of animal and human isolates have been reported from the MENA region. However, several studies proved that brucellae are still in-vitro susceptible to the majority of antibiotic compounds and combinations in current recommended World Health Organization (WHO) treatment regimens, for example, levofloxacin, tetracyclines, doxycycline, streptomycin, ciprofloxacin, chloramphenicol, gentamicin, tigecycline, and trimethoprim/sulfamethoxazole. The current review presents an overview on resistance development of brucellae and highlights the current knowledge on effective antibiotics regimens for treating human brucellosis.

Proteomics-based screening and antibiotic resistance assessment of clinical and sub-clinical Brucella species: An evolution of brucellosis infection control.

Brucellae are intracellular sneaky bacteria and they can elude the host's defensive mechanisms, resulting in therapeutic failure. Therefore, the goal of this investigation was to rapid identification of Brucella species collected from animals and humans in Saudi Arabia, as well as to evaluate their resistance to antibiotics. On selective media, 364 animal samples as well as 70 human blood samples were cultured. Serological and biochemical approaches were initially used to identify a total of 25 probable cultured isolates. The proteomics of Brucella species were identified using the MALDI Biotyper (MBT) system, which was subsequently verified using real-time polymerase chain reaction (real-time PCR) and microfluidic electrophoresis assays. Both Brucella melitensis (B. melitensis) and Brucella abortus (B. abortus) were tested for antimicrobial susceptibility using Kirby Bauer method and the E-test. In total, 25 samples were positive for Brucella and included 11 B. melitensis and 14 B. abortus isolates. Twenty-two out of 25 (88%) and 24/25 (96%) of Brucella strains were recognized through the Vitek 2 Compact system. While MBT was magnificently identified 100% of the strains at the species level with a score value more than or equal to 2.00. Trimethoprim-sulfamethoxazole, rifampin, ampicillin-sulbactam, and ampicillin resistance in B. melitensis was 36.36%, 31.82%, 27.27%, and 22.70%, respectively. Rifampin, trimethoprim-sulfamethoxazole, ampicillin, and ampicillin-sulbactam resistance was found in 35.71%, 32.14%, 32.14%, and 28.57% of B. abortus isolates, correspondingly. MBT confirmed by microfluidic electrophoresis is a successful approach for identifying Brucella species at the species level. The resistance of B. melitensis and B. abortus to various antibiotics should be investigated in future studies.

Spatial variation in direct and indirect contact rates at the wildlife-livestock interface for informing disease management.

Little is known about disease transmission relevant contact rates at the wildlife-livestock interface and the factors shaping them. Indirect contact via shared resources is thought to be important but remains unquantified in most systems, making it challenging to evaluate the impact of livestock management practices on contact networks. Free-ranging wild pigs (Sus scrofa) in North America are an invasive, socially-structured species with an expanding distribution that pose a threat to livestock health given their potential to transmit numerous livestock diseases, such as pseudorabies, brucellosis, trichinellosis, and echinococcosis, among many others. Our objective in this study was to quantify the spatial variations in direct and indirect contact rates among wild pigs and cattle on a commercial cow-calf operation in Florida, USA. Using GPS data from 20 wild pigs and 11 cattle and a continuous-time movement model, we extracted three types of spatial contacts between wild pigs and cattle, including direct contact, indirect contact in the pastoral environment (unknown naturally occurring resources), and indirect contact via anthropogenic cattle resources (feed supplements and water supply troughs). We examined the effects of sex, spatial proximity, and cattle supplement availability on contact rates at the species level and characterized wild pig usage of cattle supplements. Our results suggested daily pig-cattle direct contacts occurred only occasionally, while a significant number of pig-cattle indirect contacts occurred via natural resources distributed heterogeneously across the landscape. At cattle supplements, more indirect contacts occurred at liquid molasses than water troughs or molasses-mineral block tubs due to higher visitation rates by wild pigs. Our results can be directly used for parameterizing epidemiological models to inform risk assessment and optimal control strategies for controlling transmission of shared diseases.

[Study on the effect of integrated traditional Chinese and western medicine in the treatment of brucellosis].

Objective: To observe the clinical effect of integrated traditional Chinese and western medicine on brucellosis and its influence on humoral immune indexes. Methods: In October 2019, 169 cases of brucellosis hospitalized in Tianjin Second People's Hospital were selected as the research objects, and divided into two groups according to the random number method, 84 cases in the integrated treatment group and 85 cases in the western medicine treatment group. The western medicine treatment group was given antibiotics and other routine western medicine support treatment. The integrated treatment group was given traditional Chinese medicine for treatment based on syndrome differentiation, on the basis of western medicine treatment group, and 6 weeks was a course of treatment. The clinical efficacy and Traditional Chinese Medicine (TCM) syndrome scores were compared between the two groups of patients after treatment, and the changes in humoral immune indexes, biochemical, and liver and kidney functions of the patients before and after treatment were analyzed. Results: The total effective rate was 100.00% (84/84) in the integrated treatment group and 97.65% (83/85) in the western medicine treatment group. The difference was not statistically significant (P>0.05) . The difference was not statistically significant (P>0.05) . There was no statistically significant difference in TCM syndrome scores between the two groups before treatment (P>0.05) , and the TCM syndrome scores after treatment were lower than before treatment (P<0.05) . Among them, the TCM syndrome scores of the integrated treatment group were lower than those of the western medicine treatment group (P<0.05) . There was no significant difference in IgG, IgA, IgM, C3, C4, miRNA-155, C-reactive protein (CRP) , erythrocyte sedimention rate (ESR) , alanine aminotransferase (ALT) and aspartate aminotransferase (AST) between the two groups before treatment (P>0.05) . After treatment, IgG, IgA, IgM, miRNA-155, CRP, ESR, ALT and AST were all lower than before treatment, and C3 and C4 complement levels were higher than before treatment (P<0.05) . Among them, IgG, IgA, IgM, miRNA-155, CRP, ESR, ALT and AST in the integrative treatment group were all lower than the western medicine treatment group, while the C3 and C4 complement levels were higher than the western medicine treatment group (P<0.05) . Conclusion: The treatment of brucellosis with integrated traditional Chinese and western medicine can significantly improve the TCM syndrome score and reduce the levels of CRP and ESR. The mechanism of action may be related to the regulation of the patient's humoral immunological indicators.

Protection of palmitic acid treatment in RAW264.7 cells and BALB/c mice during Brucella abortus 544 infection.

BACKGROUND: We previously elucidated the protective mechanism of Korean red ginseng oil (RGO) against Brucella abortus infection, and our phytochemical analysis revealed that palmitic acid (PA) was an abundant component of RGO. Consequently, we investigated the contribution of PA against B. abortus. OBJECTIVES: We aimed to investigate the efficacy of PA against B. abortus infection using a murine cell line and a murine model. METHODS: Cell viability, bactericidal, internalization, and intracellular replication, western blot, nitric oxide (NO), and superoxide (O2⁻) analyses and flow cytometry were performed to determine the effects of PA on the progression of B. abortus infection in macrophages. Flow cytometry for cytokine analysis of serum samples and bacterial counts from the spleens were performed to determine the effect of PA in a mouse model. RESULTS: PA did not affect the growth of B. abortus. PA treatment in macrophages did not change B. abortus uptake but it did attenuate the intracellular survivability of B. abortus. Incubation of cells with PA resulted in a modest increase in sirtuin 1 (SIRT1) expression. Compared to control cells, reduced nitrite accumulation, augmented O2⁻, and enhanced pro-inflammatory cytokine production were observed in PA-treated B. abortus-infected cells. Mice orally treated with PA displayed a decreased serum interleukin-10 level and enhanced bacterial resistance. CONCLUSIONS: Our results suggest that PA participates in the control of B. abortus within murine macrophages, and the in vivo study results confirm its efficacy against the infection. However, further investigations are encouraged to completely characterize the mechanisms involved in the inhibition of B. abortus infection by fatty acids.

Hospital-based evidence on cost-effectiveness of brucellosis diagnostic tests and treatment in Kenyan hospitals.

Hospitals in Kenya continue to use the Febrile Antigen Brucella Agglutination Test (FBAT) to diagnose brucellosis, despite reports showing its inadequacy. This study generated hospital-based evidence on the performance and cost-effectiveness of the FBAT, compared to the Rose Bengal Test (RBT).Twelve hospitals in western Kenya stored patient serum samples that were tested for brucellosis using the FBAT, and these were later re-tested using the RBT. Data on the running time and cost of the FBAT, and the treatment prescribed for brucellosis, were collected. The cost-effectiveness of the two tests, defined as the cost in US Dollars ($) per Disability Adjusted Life Year (DALY) averted, was determined, and a basic sensitivity analysis was run to identify the most influential parameters. Over a 6-month period, 180 patient serum samples that were tested with FBAT at the hospitals were later re-tested with RBT at the field laboratory. Of these 24 (13.3%) and 3 (1.7%) tested positive with FBAT and RBT, respectively. The agreement between the FBAT and RBT was slight (Kappa = 0.12). Treatment prescribed following FBAT positivity varied between hospitals, and only one hospital prescribed a standardized therapy regimen. The mean $/DALY averted when using the FBAT and RBT were $2,065 (95% CI $481-$6,736) and $304 (95% CI $126-$604), respectively. Brucellosis prevalence was the most influential parameter in the cost-effectiveness of both tests. Extrapolation to the national level suggested that an estimated $338,891 (95% CI $47,000-$1,149,000) per year is currently spent unnecessarily treating those falsely testing positive by FBAT. These findings highlight the potential for misdiagnosis using the FBAT. Furthermore, the RBT is cost-effective, and could be considered as the mainstay screening test for human brucellosis in this setting. Lastly, the treatment regimens must be harmonized to ensure the appropriate use of antibiotics for treatment.

Molecular Docking and In vitro Analysis of Fagonia Cretica and Berberis Lyceum Extracts Against Brucella Melitensis.

BACKGROUND: Brucellosis is an economically important zoonotic disease caused by the Gram-negative bacteria belonging to the genus Brucella. Medicinal plants are well known for a wide variety of potential antimicrobial agents that can be used as antimicrobial drugs. METHODS: In the present study, crude ethanolic and methanolic extracts of local plants (Berberis lyceum and Fagonia cretica) were tested in vitro against Brucella melitensis via a well diffusion method for their antibacterial activity. In the in silico study, phytochemicals previously identified in the selected plants were docked with a homology model of the cytotoxic factor malate synthase G (MSG) highly conserved among Brucella spp., in Molecular Operating Environment (MOE) to predict a potential drug against B. melitensis. A molecular dynamic simulation was performed to predict the stability of MSG through MOE. RESULTS: Ethanolic crude extracts of B. lyceum showed maximum zone of inhibition (32.5 mm) followed by methanolic extracts (30 mm), while ethanolic extracts of F. cretica showed zone of inhibition (29 mm) followed by methanolic extracts (27.5 mm). In silico screening predicted phytic acid as the most potent inhibitor followed by jehlumine, barbamine, oxyberberine and sindamine. CONCLUSION: The synergistic utilization of phytochemicals derived from B. lyceum may potentially provide protection against B. melitensis.

Hepatic brucelloma: a rare complication of a common zoonotic disease.

Hepatic brucelloma (HB), a rare manifestation of brucellosis, refers to liver involvement in the form of abscess. A 35-year-old woman stockbreeder was admitted due to 1-month history of evening fever, sweating and weight loss, while she was on 3-week course of rifampicin/doxycycline for suspected brucellosis. On admission, she had hepatosplenomegaly and a systolic murmur, while cholestasis, increased inflammation markers and a strong-positive Wright-Coombs test were the main laboratory findings. As blood and bone marrow cultures were unrevealing, further investigation with CT imaging showed a central liver calcification surrounded by heterogeneous hypodense area being compatible with HB. Material from CT-guided drainage tested negative for Brucella spp. After failure to improve on a 10-week triple regiment, surgical excision was decided and Brucella spp were identified by PCR. Our case highlights challenges in establishing HB diagnosis, which should be considered on the right epidemiological context and when serological and radiological evidence favour its diagnosis.

Treatment of Brucellosis in Guinea Pigs via a Combination of Engineered Novel pH-Responsive Curcumin Niosome Hydrogel and Doxycycline-Loaded Chitosan-Sodium Alginate Nanoparticles: an In Vitro and In Vivo Study.

Brucellosis is a common zoonotic infection, particularly in the developing world. The recommended treatment regimens for brucellosis involve the use of two medications such as doxycycline and curcumin in order to avoid relapses and prolonged use of these drugs. Doxycycline has excellent activity in the acidic phagolysosomal environment, while curcumin modulates the immune system function and macrophage activity. Due to the intracellular existence of Brucellae and the different anti-immune mechanisms of Brucella, the treatment of Brucella infection faces many limitations. The design of nanosystems is a promising treatment approach for brucellosis. The objective of this study was to design and evaluate the efficacy of in situ pH-responsive curcumin-loaded niosome hydrogel and doxycycline-loaded chitosan-sodium alginate nanoparticles as chemotherapeutic agents against brucellosis. The prepared formulae showed a spherical nano shape with a slow drug release pattern and small particle size. The prepared formulae were evaluated in vivo using Guinea pigs experimentally infected with Brucella melitensis biovar3. The prepared formula combination gave a significant high reduction rate of Brucella spleen viable count compared with that of untreated controls at p < 0.05. The results showed that the treatment schemes were not fully successful in eliminating Brucella infection in Guinea pigs; however, they significantly (p < 0.05) reduced the viable Brucella count in a shorter time and sub-therapeutic doses. Collectively the novel prepared formulae could be a successful therapy for the effective treatment of brucellosis infection at the recommended therapeutic doses. Graphical abstract.