Brucellosis in a patient diagnosed with Coronavirus Disease 2019 (COVID-19).

Brucellosis is a common zoonotic infection. Brucellosis typically presents with fever, weakness, night sweats, and arthralgias. Symptoms associated with Coronavirus Disease 2019 (COVID-19) and infection with Brucella spp. are similar to one another, which may lead to delayed diagnosis of the latter condition. There are no previous reports of brucellosis in a patient previously diagnosed with COVID-19. We present here the case of a 20-year-old male who we diagnosed with brucellosis after joint pains and fever that persisted after resolution of COVID-19.

A 10-year retrospective comparative analysis of the clinical features of brucellosis in children and adults.

INTRODUCTION: Brucellosis is a zoonosis with a wide spectrum of clinical manifestations. However, it is still unclear whether the clinical manifestations in children are significantly different from those in adults. METHODOLOGY: Patients with brucellosis and treated at the General Hospital of Ningxia Medical University between 2009 and 2019 were divided into two groups; children (88) and adults (354). Thereafter, the records of the two groups were analyzed retrospectively. RESULTS: The findings showed that: 1. School-age children, young and middle-aged individuals were more likely to suffer from brucellosis and most were male; 2. Fever and arthralgia were the most common manifestations in the two groups. In addition, fatigue and low back pain were rare in children although fever and lymphadenopathy were more common in this group. However, hepatomegaly and splenomegaly were common in both groups; 3. The most common complication was osteoarthritis and peripheral arthritis occurred more frequently in children. On the other hand, spondylitis was the most common in adults (this particularly involved the lumbar and sacral vertebrae); 4. An increase in the erythrocyte sedimentation rate, levels of the C-reactive protein and liver enzymes was common in both two groups; 5. There was no significant difference in the positive rate of the standard agglutination test between children (96.59%) and adults (95.20%). However, the positive rate of blood culture was higher in children (65.85%) than in adults (51.00%). CONCLUSIONS: Brucellosis causes damage to multiple systems and differences in clinical characteristics were found between children and adults.

NLRP6-associated host microbiota composition impacts in the intestinal barrier to systemic dissemination of Brucella abortus.

Brucella abortus is a Gram-negative bacterium responsible for a worldwide zoonotic infection-Brucellosis, which has been associated with high morbidity rate in humans and severe economic losses in infected livestock. The natural route of infection is through oral and nasal mucosa but the invasion process through host gut mucosa is yet to be understood. Studies have examined the role of NLRP6 (NOD-like receptor family pyrin domain-containing-6 protein) in gut homeostasis and defense against pathogens. Here, we investigated the impact of gut microbiota and NLRP6 in a murine model of Ba oral infection. Nlrp6-/- and wild-type (WT) mice were infected by oral gavage with Ba and tissues samples were collected at different time points. Our results suggest that Ba oral infection leads to significant alterations in gut microbiota. Moreover, Nlrp6-/- mice were more resistant to infection, with decreased CFU in the liver and reduction in gut permeability when compared to the control group. Fecal microbiota transplantation from WT and Nlrp6-/- into germ-free mice reflected the gut permeability phenotype from the donors. Additionally, depletion of gut microbiota by broad-spectrum-antibiotic treatment prevented Ba replication in WT while favoring bacterial growth in Nlrp6-/-. Finally, we observed higher eosinophils in the gut and leukocytes in the blood of infected Nlrp6-/- compared to WT-infected mice, which might be associated to the Nlrp6-/- resistance phenotype. Altogether, these results indicated that gut microbiota composition is the major factor involved in the initial stages of pathogen host replication and partially also by the resistance phenotype observed in Nlrp6 -/- mice regulating host inflammation against Ba infection.

Brucella melitensis Rev.1 vaccination generates a higher shedding risk of the vaccine strain in Alpine ibex (Capra ibex) compared to the domestic goat (Capra hircus).

Epidemiological investigations implemented in wild and domestic ruminants evidenced a reservoir for Brucella in Capra ibex in the French Alps. Vaccination was considered as a possible way to control Brucella infection in this wildlife population. Twelve ibexes and twelve goats were allocated into four groups housed separately, each including six males or six non-pregnant females. Four to five animals were vaccinated and one or two animals were contact animals. Half of the animals were necropsied 45 days post-vaccination (pv), and the remaining ones at 90 days pv. Additional samples were collected 20 and 68 days pv to explore bacterial distribution in organs and humoral immunity. Neither clinical signs nor Brucella-specific lesions were observed and all vaccinated animals seroconverted. Brucella distribution and antibody profiles were highly contrasted between both species. Proportion of infected samples was significantly higher in ibex compared to goats and decreased between 45 and 90 days pv. Two male ibex presented urogenital excretion at 20 or 45 days pv. The bacterial load was higher 45 days in ibexes compared to goats, whereas it remained moderate to low 90 days pv in both species with large variability between animals. In this experiment, differences between species remained the main source of variation, with low impact of other individual factors. To conclude, multiplicative and shedding capacity of Rev.1 was much higher in ibex compared to goats within 90 days. These results provide initial information on the potential use in natura of a commercial vaccine.

Zoonotic Pathogen Seroprevalence in Cattle in a Wildlife-Livestock Interface, Kenya.

A cross-sectional study was conducted to determine the seroprevalence of Brucella spp. and Leptospira spp. and risk factors of exposure in cattle in three zones with varying land use types and wildlife-livestock interactions. Five villages were selected purposively; two in areas with intensive livestock-wildlife interactions (zone 1), another two in areas with moderate livestock-wildlife interactions (zone 2) and one in areas where wildlife-livestock interactions are rarer (zone 3). Sera samples were collected from 1170 cattle belonging to 390 herds in all the zones and tested for antibodies against Brucella abortus and Leptospira interrogans serovar hardjo using ELISA kits. Data on putative risk factors for seropositivity of these pathogens in cattle were collected using a questionnaire. The overall apparent animal-level seroprevalence of brucellosis and leptospirosis was, respectively, 36.9% (95% CI 34.1-39.8) and 23.5% (95% CI 21.1-26.0). Brucella spp. seroprevalence was higher in zone 1 than in zones 2 and 3 (χ2 = 25.1, df = 2, P < 0.001). Zones 1 and 2 had significantly higher Leptospira spp. seroprevalence than zone 3 (χ2 = 7.0, df = 2, P = 0.029). Results of multivariable analyses identified animal sex (female) and zones (high interface area) as significant predictors (P < 0.05) of animal-level seropositivity of Brucella spp. For Leptospira spp., important predictors of animal-level seropositivity were animal sex (female), zones (moderate interface area) and herds utilizing a communal grazing reserve. The seroprevalences of Brucella spp. and Leptospira spp. in cattle were higher in areas with moderate to high wildlife-livestock interactions than those with rare interactions.

Brucellosis, an uncommon cause of acute acalculous cholecystitis: two new cases and concise review.

Acalculous cholecystitis etiologies while numerous, some of them are less-known such as brucellosis. In this report, we elaborate the clinical findings, investigations and management of two female patients presenting acalculous cholecystitis in whom diagnosis of acute brucellosis was retained. Both patients had fever, asthenia and abdominal tenderness. Laboratory results showed evidence of inflammation as well as hepatic cytolysis while cholestasis was noted in one patient. In both cases, ultrasound study and CT confirmed the presence of acalculous cholecystitis. Serology (tube agglutination test) led to the diagnosis of brucellosis. Diagnosis of brucellosis-related acute cholecystitis was established in both cases based on imaging findings as well as serology without resorting to cholecystectomy. Favourable clinical response to specific antibiotic therapy further supported our diagnosis as well as our decision to avoid surgery. Although few cases have been reported, brucellosis must be considered as a cause of acalculous cholecystitis, especially in endemic countries.

Asymptotic analysis of endemic equilibrium to a brucellosis model.

Brucellosis is one of the worlds major infectious and contagious bacterial disease. In order to study different types of brucellosis transmission models among sheep, we propose a deterministic model to investigate the transmission dynamics of brucellosis with the flock of sheep divided into basic ewes and other sheep. The global dynamical behavior of this model is given: including the basic repro-duction number, the existence and uniqueness of positive equilibrium, the global asymptotic stability of the equilibrium. We prove the uniqueness of positive endemic equilibrium through using proof by contradiction, and the global stability of endemic equilibrium by using Lyapunov function. Especially, we give the specific coefficients of global Lyapunov function, and show the calculation method of these specific coefficients. By running numerical simulations for the cases with the basic reproduction number to demonstrate the global stability of the equilibria and the unique endemic equilibrium, re-spectively. By some sensitivity analysis of the basic reproduction number on parameters, we find that vaccination rate of sheep and seropositive detection rate of recessive infected sheep are very important factor for brucellosis.

Flow-Diverter Stenting of Intracavernous Internal Carotid Artery Mycotic Aneurysm.

This is the first reported case in which a mycotic aneurysm refractory to the first medical treatment was treated with a Pipeline embolization device (PED), and the first case of a mycotic aneurysm from Brucella treated by endovascular therapy. A 35-year-old man presented with left eye pain and ptosis, and fever for 2 weeks. Before symptom onset, he visited Vietnam where he developed a flu-like illness; however, antibiotics were ineffective. We suspected Brucella as the most likely infectious etiology for the patient's intracavernous aneurysm. Since the aneurysm did not reduce in size following 2 weeks of antibiotic therapy, we placed a PED in the left internal carotid artery. Follow-up angiogram 4 months later showed no residual aneurysm, and cranial nerve palsies had completely resolved. From the results of this case, it appears that flow diverter stenting may be a safe and effective treatment of mycotic aneurysms of the cavernous segment of ICA.

When brucellosis met the Assessment of SpondyloArthritis international Society classification criteria for spondyloarthritis: a comparative study.

OBJECTIVES: To distinguish brucellosis patients fulfilling the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for spondyloarthritis (SpA) from SpA patients. METHODS: Brucellosis patients diagnosed from September 2012 to December 2017 who met the ASAS classification criteria for SpA were analyzed with clinical characteristics and laboratory and imaging examinations. Axial or peripheral SpA patients were respectively included into the comparative analysis with a 4:1 ratio. RESULTS: Twenty-two brucellosis (10 axial and 12 peripheral) patients (male, 16 cases; 72.72%; mean (S.D.) age, 40.23 (16.49) years) and 88 SpA patients were included. All brucellosis patients had been misdiagnosed or considered as SpA before admission to our center. The brucellosis patients had shorter disease duration (axial, P = 0.001; peripheral, P = 0.108). More than half (59.09%) of the patients had contact history with livestock. The low back pain (LBP) of brucellosis patients was generally less improved with exercise (axial, P = 0.001; peripheral, P = 0.008). More brucellosis patients had myalgia (axial, P < 0.001; peripheral, P = 0.071) or fever (axial, P < 0.001; peripheral, P = 0.107). None of them had positive HLA-B27. Blood culture tests were performed in all brucellosis patients and only 4 (18.18%) were positive. Twenty (90.91%) brucellosis patients were gold-immunochromatographic assay (GICA) positive. Bone marrow edema and bone erosion in sacroiliac joints were respectively detected in 100% (10/10) and 90% (9/10) axial brucellosis patients by MRI. Adjacent muscle involvement was found in 80% (8/10) of the patients. CONCLUSIONS: Indicators including disease duration, contact history of livestock, features of LBP, myalgia, fever, and HLA-B27 can help the differential diagnosis of brucellosis and SpA. GICA test and sacroiliac joints MRI can furtherly confirm the diagnosis of brucellosis.

The Pattern of Tpeak-Tend Interval and QTdis, and Pdis in Children with Brucellosis.

OBJECTIVE: To investigate the effect of inflammation on the conducting system of the heart in patients diagnosed with brucellosis. METHODS: A total of 42 patients diagnosed with brucellosis and 39 age and sex-matched healthy children were enrolled into the study. Pre- and post-treatment electrocardiographic parameters in brucellosis and control group were recorded from an electrocardiogram for each patient. RESULTS: The results indicated that the parameters including Pmax, Pdis, QTmax, QTdis, QTcdis, Tp-edis interval and Tp-emax/QTmax and Tp-emax/QTcmax ratios, which are known to be key indicators for the prediction of severe atrial or ventricular arrhythmia and sudden cardiac death and also important parameters used as the indicators for the non-invasive evaluation of the transmural heterogeneity were significantly longer in the study group compared with the control group (p < 0.05). CONCLUSION: In this study, it was determined that the brucella disease had more cardiac involvement than thought, and this was more in the subclinical form of cardiac involvement.

Clinical features of 2041 human brucellosis cases in China.

BACKGROUND: Human brucellosis has become a major public health problem in China. However, the available clinical data on brucellosis cases are limited. METHODS: We retrospectively reviewed medical charts of 2041 patients with confirmed human brucellosis and prospectively recorded their outcomes by telephone interview. These patients were admitted to the Sixth People's Hospital of the Xinjiang Uygur Autonomous region between 1st January and 31st December 2014. Data on these patients were collected from hospital medical records. RESULTS: Many patients presented with fatigue (67%), fever (64%), arthralgia (63%) and sweating (54%). High erythrocyte sedimentation rate (ESR) (69%), high C-reactive protein (CRP) (39%), high alanine aminotransferase (ALT) (33%) and high aspartate aminotransferase (AST) (20%) were the most common laboratory findings, especially in acute patients. There was evidence of focal involvement in 90% of patients. A total of 61.5% of brucellosis patients recovered. Multivariate logistic regression analyses suggested that the risk factors key to unfavorable prognosis were: age≥45 years (OR = 1.75, 95% CI 1.36-2.24), back pain (OR = 1.50, 95% CI 1.16-1.94) and joint tenderness (OR = 1.73, 95% CI 1.13-2.65). The increasing duration of the illness increased the risk of poor prognosis. CONCLUSION: Patients with brucellosis showed different characteristics in different clinical stages. In China, the chronicity rate of human brucellosis is high. The risk of poor prognosis is increased in patients aged 45 years or older, patients who have had brucellosis for a substantial period of time, and patients with back pain or joint tenderness. The clinical management of brucellosis should be improved to include sensitive diagnostic methods for subacute and chronic brucellosis.

Erectile dysfunction among patients with chronic brucellosis.

OBJECTIVE: Only a single study investigated erectile dysfunction (ED) among patients with chronic brucellosis without including a control group. Our study objective was to determine the prevalence of ED among patients with chronic brucellosis compared to normal subjects, and to explore the predictors of ED. MATERIALS AND METHODS: We included 93 chronic brucellosis patients and 92 subjects as a control, from June 2013 to August 2017. Chronic brucellosis was diagnosed based on persistent symptoms for ≥1 year with positive immunoglobulin G antibody titer (≥1:160) by standard tube agglutination test; the mean duration was 21 ± 6.2 months. Clinical evaluation (including an Arabic validated version of the five-item International Index of Erectile Function to diagnose ED; score of 5-21 was diagnostic), imaging studies (including scrotal ultrasonography) and laboratory investigations (including estimation of fasting serum level of glucose (after fasting for 8 h), lipids profile (after fasting for 14 h), and serum level of testosterone) were conducted. A fasting serum glucose level of ≥ 7 mmol/L defined diabetes mellitus (DM). Predictors of ED were identified using multivariate analysis (binary logistic regression). RESULTS: The mean age of patients was 35.4 ± 13.7 years; 24.7% of them had DM, while low serum level of testosterone was detected among 54.8%. Among the patients, ED was significantly more frequent compared to the control subjects (69.9% vs. 19.6%, p < 0.001). Low serum level of testosterone (OR 4.8, 95% CI 1.7-29.3, p 0.008), and DM (OR 3.5, 95% CI 1.2-34.6, p 0.011) were the predictors of ED among the patients. CONCLUSIONS: The prevalence of ED among patients with chronic brucellosis is high. Low serum level of testosterone and DM are associated with ED among such patients.

Increased serum levels of hepcidin and C-reactive protein in patients with brucellosis.

Background: Increased serum level of C-reactive protein (CRP) as a classic acute phase protein has commonly been reported in acute brucellosis. Hepcidin is also an acute phase protein and has a critical role in host defense. The aim of this study was to compare the level of hepcidin and CRP in patients with brucellosis. Methods: All patients with brucellosis referred to Sina Hospital during a 10-month period were included. Serum samples were checked for hepcidin levels in patients and also in the control group. Information on demographic and clinical characteristics was determined through completion of a questionnaire. Results: A total of 42 patients with brucellosis and 42 healthy controls were enrolled. The most common symptoms of brucellosis were fever (76%) and arthralgia (69%). The mean serum level of hepcidin in patients (42.6±11.7 pg/mL) was significantly higher than in the controls (17.3±4.2 pg/mL) (p<0.001). The mean serum levels of CRP in patients and controls were 12.6±12.2 and 3.1±2.4 mg/L, respectively (p=0.001). Conclusions: Increased serum levels of hepcidin in brucellosis can be considered a diagnostic biomarker of inflammation and active disease. Further studies are needed to identify the role of hepcidin as a host defense mechanism in brucellosis.

Successful Management of Infected Facial Filler with Brucella.

BACKGROUND: The widespread desire to maintain youth and beauty with minimally invasive procedures made the use of soft tissue fillers an attractive option to correct numerous aesthetic problems. However, many complications have emerged recently especially with the use of non-FDA-approved permanent materials. In this case report, we are demonstrating the effective management of a patient with Brucella isolated from a facial abscess at the site of prior permanent filler injection done 17 years ago. METHODS: A 56-year-old woman presented complaining of painful swelling of the right cheek after a failed trial of filler evacuation and intralesional corticosteroid injection. The patient was interviewed carefully, and physical examination was performed, followed by culture and imaging. RESULTS: The patient had a facial abscess that was complicated by parotid infiltration by Brucella. Eventually she was managed successfully by anti-Brucella antibiotics for 6 months with no further complaints. A review of causative organisms in the literature along with recommendations for management is discussed. CONCLUSION: Permanent fillers have shown many complications that can occur even years after injection. Therefore, physicians should be careful when using permanent fillers and should restrict their use to certain situations. Moreover, rare infections must be kept in mind and careful history, including travel history and animal contact, needs to be considered particularly in the unusual scenarios. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Acute liver failure complication of brucellosis infection: a case report and review of the literature.

BACKGROUND: Brucellosis is one of the most widespread zoonoses worldwide. It can affect any organ system, particularly the gastrointestinal system, but there is no report of acute liver failure as a brucellosis complication. CASE PRESENTATION: We present a case of acute liver failure secondary to brucellosis infection. A 75-year-old Hispanic man presented to a University Hospital in Chía, Colombia, with a complaint of 15 days of fatigue, weakness, decreased appetite, epigastric abdominal pain, jaundice, and 10 kg weight loss. On examination in an emergency room, abdomen palpation was normal with hepatosplenomegaly and the results of a liver function test were elevated. The diagnosis of brucellosis was confirmed by epidemiological contact and positive Rose Bengal agglutination with negative enzyme-linked immunosorbent assay immunoglobulin M for Brucella. He was then treated with doxycycline plus trimethoprim/sulfamethoxazole, with a favorable clinical outcome. CONCLUSIONS: The clinical presentation of brucellosis can be very imprecise because it can affect any organ system; however, there is no report of acute liver failure as a brucellosis complication. This is the first reported case in the Colombian literature of acute liver failure due to brucellosis. We found this case to be of interest because it could be taken into account for diagnosis in future appearances and we described adequate treatment and actions to be taken at presentation.

Comparative experimental study of Brucella melitensis and its lipopolysaccharide in mouse model infected via subcutaneous route of exposure.

Brucella melitensis is a major zoonotic pathogen in which lipopolysaccharide (LPS) is believed to play a major role in the diseases pathogenesis. To study the immunopathophysiological aspects, we established a mouse model experimentally infected with whole cell of B. melitensis and its lipopolysaccharide via subcutaneous route of exposure. Eighty four mice, BALB/c, both sexes with equal gender distribution and 6-8 weeks-old were randomly assigned into 3 groups. Group 1 (n = 36) were subcutaneoulsy inoculated with 0.4 mL 109 of B. melitensis while group 2 (n = 36) were subcutaneously challenged with 0.4 mL 109 of LPS. Group 3 (n = 12) was challenged subcuatneously with phosphate buffered saline and served as a control group. Animals were observed for clinical signs, haematological and histopathological analysis for a period of 24 days post-inoculation. Our results revealed that B. melitensis infected group demonstrated significant clinical signs and histopathological evidence than LPS infected group. However, both infected groups showed elevated levels of interleukins (IL-1ß & IL6), antibody levels (IgM & IgG) as early as 3 days post-infection with predominance in LPS infected group. For hormone analysis, low levels of progesterone, estradiol and testosterone were observed in both B. melitensis and LPS challenged groups throughout the study period. Moreover, in B. melitensis infected groups, the organism was re-isolated from the organs and tissues of gastrointestinal, respiratory and reproductive systems; thereby confirming the possible transmission of the disease dynamics. Moreover, LPS stimulated significantly the innate and acquired immune system without significant systemic dysfunction suggesting the potentiality of the protective properties of this component as an alternative vaccine for brucellosis infection. This report is the first detailed investigation comparing the infection progression and host responses in relation to the immunopathophysiological aspects in mouse model after subcutaneous inoculation with B. melitensis and its lipopolysaccharide.

Brucellosis Causes Alteration in Trace Elements and Oxidative Stress Factors.

Brucellosis is regarded as one of the most common diseases among humans and livestock. In the present study, we aimed to assess the effect of this disease on the level of various cations including copper (Cu), manganese (Mn), zinc (Zn), and magnesium (Mg) as well as oxidative stress status in the serum of people suffering from brucellosis. The present case-study was carried out on 40 patients with brucellosis (case) and 20 healthy people (control). Blood specimens were taken from all the people and the level of essential trace elements and oxidative stress status were measured. The serum level of copper in the case group (165.39 ± 43.19 µg/dl) was significantly higher compared with that in the control group (122.12 ± 28.88 µg/dl). Whereas the serum level of zinc was significantly lower in the case group compared with that in the control group (76.47 ± 28.88 vs. 92.85 ± 23.16 µg/dl). The manganese and magnesium serum levels did not differ significantly between the two groups. Furthermore, total antioxidant capacity level was significantly lower in the case group (122.12 ± 28.22 µmol/ml) than that in the control group (3.08 ± 0.12 µmol/ml) and the level of serum malondialdehyde was significantly higher in the case group (7.20 ± 0.23 mmol/ml) than that in the control group (4.0 ± 0.19 mmol/ml). Brucellosis can cause alteration in the serum level of essential trace elements. Moreover, the present study indicated that brucellosis produces oxidative stress in patients.