Risk transboundary transmission areas and driving factors of brucellosis along the borders between China and Mongolia.

OBJECTIVE: Brucellosis is a common and neglected zoonotic infectious disease worldwide caused by Brucella. However, transboundary transmissions among countries, particularly those with high incidences, are seldom investigated. In the present study, by taking China and Mongolia as examples, we aim to identify transboundary transmission risk and driving factors of brucellosis along borders. METHODS: 167 brucellosis outbreak locations along the border between China and Mongolia were collected. Wildlife distribution and cross-border activities were mapped. Maximum entropy approach modeling was conducted to predict the potential risk of prevalence of brucellosis with meteorological factors, geographical environment, economic development, living habits et al. The accuracy of the models was assessed by the area under the receiver operating characteristic (ROC) curve (AUC), Kappa test, and correctly classified instances (CCI). RESULTS: The spatial model performed excellent predictive performance with the predictor variables of soils, pastures, goat density, mean precipitation of the wettest month, temperature seasonality, and population density, which with the contribution and permutation important in 27.2 %, 31.9; 23.3 %, 6.8; 18.0 %, 17.2; 11.2 %, 18.1; 10. 3 %, 15.2; 10.0 %, 10.8. The calculated AUC, SD, Kappa, and CCI are 0.870, 0.001, 0.882, and 0.883, respectively. The distribution map of brucellosis showed high-risk areas along the borders. CONCLUSIONS: Our study identified high-risk areas and the driving effect of brucellosis along the borders between China and Mongolia. Moreover, there is the possibility of cross-border wildlife activities in high-risk areas, which increases the risk of cross-border brucellosis transmission. The funding provides clues for cooperative prevention and control of brucellosis by reducing transboundary transmission.

Atypical Presentation of Neurobrucellosis as Infection of Ventriculoperitoneal Shunt.

Brucellosis is a frequent zoonosis in some regions of the world and may cause various symptoms. Neurobrucellosis is a rare but serious complication of the infection. Our case report describes the course of neurobrucellosis in a patient who had received a ventriculoperitoneal shunt in his native country 13 years prior to diagnosis of brucellosis. He initially presented to us with symptoms of peritonitis, which misled us to perform abdominal surgery first. After the diagnosis of neurobrucellosis was confirmed and appropriate antibiotics were initiated, the symptoms soon disappeared. Although the ventriculoperitoneal shunt was subsequently removed, the patient did not develop a symptomatic hydrocephalus further on. This case displays the challenges in diagnosing an infection that occurred sporadically in Europe and may be missed by currently applied routine microbiological workup. Considering the political context, with increasing relocation from endemic areas to European countries, it is to be expected that the cases of brucellosis and neurobrucellosis will rise. Brucellosis should be considered and adequate investigations should be performed.

Brucella Laboratory Exposures in Brazil: Rare or Unnoticed?

Laboratory exposures to Brucella spp. are preventable. After an outbreak in Brazil, human brucellosis was made statutorily reportable as well as laboratory accidents. After the implementation of this law, three laboratorial accidents with Brucella abortus were reported in a Brazilian city, and 58 workers were exposed from January 2019 to April 2020. We describe the exposure level, prophylaxis, and serosurvey after 6 months, and we highlight the importance of disease report.

Epidemiological trends of notified human brucellosis in Germany, 2006-2018.

OBJECTIVE: We describe epidemiological trends of human brucellosis in Germany over a 13 year period based on national surveillance data. METHODS: We analyzed demographic, clinical, laboratory and exposure information of symptomatic laboratory-confirmed brucellosis cases notified 2006-18. Using official population data, we calculated incidences and risk ratios (RR). RESULTS: From 2006 to 2018, 408 brucellosis cases were notified in Germany (mean annual incidence: 0.38/1,000,000 population), of which 75% were travel-associated. Yearly notifications peaked in 2014 (n = 47) and remained elevated compared to 2006-2013 (mean: n = 25). Asylum seekers (AS) arriving in Germany accounted for 9/44 (2015) and 15/36 (2016) cases, respectively. RR AS/non-AS 2015-2016: 28, 95% CI: 17-45. Unpasteurized milk products were most frequently notified as source of infection. Imported food and occupational exposure played a role in autochthonous cases. CONCLUSIONS: The incidence of human brucellosis has markedly increased in recent years. Most of the observed rise in notifications can be explained by infections in AS. Exposure still predominantly occurs abroad. Risk factors for autochthonous infections need to be investigated further, though imported dairy products seem to play a role. Physicians should consider brucellosis as differential diagnosis in AS and people with travel to endemic regions with compatible symptoms.

Comparison of the serum level of interleukin-4 in patients with brucellosis and healthy controls.

INTRODUCTION: Evaluation of cytokines such as interleukin-4 (IL-4) can be an important tool in examining immune responses to brucellosis. Also, determining the response rate to treatment is necessary for controlling and eradicating of disease. The review of previous studies reveals contradictory results that require further research in this regard. The aim of this study was to compare the serum level of IL-4 in patients with brucellosis and healthy controls. MATERIAL AND METHODS: In this descriptive-analytical study for comparison of two groups, a total of 165 participants, including 83 patients with brucellosis and 82 non-infected people, were evaluated after matching of sex and age in Hamadan (northwest of Iran) in 2017 and the serum level of IL-4 was compared by ELISA method. The collected data were analyzed by SPSS software version 21 at 95% significant level. RESULTS: Mean of age in the case and control groups were 50.25 ± 16.01 and 43.26 ± 15.6 years, respectively. The serum levels of IL-4 in the case and control groups were 1.42 ± 0.51 pg/mL and 1.31 ± 1.02 pg/mL, respectively. Based on the non-parametric Mann-Whitney test, the IL-4 level was significantly higher in the case group, compared with the control (P < .001), but no statistically significant relationship was found between serum levels of IL-4 with age, sex, and serologic titers of Wright and 2ME. CONCLUSION: In patients with brucellosis, the level of IL-4 increases independently of the duration and severity of the disease, which indicates the role of this cytokine of immune system in this infectious disease.

Brucella Exposure Risk Events in 10 Clinical Laboratories, New York City, USA, 2015 to 2017.

From 2015 to 2017, 11 confirmed brucellosis cases were reported in New York City, leading to 10 Brucella exposure risk events (Brucella events) in 7 clinical laboratories (CLs). Most patients had traveled to countries where brucellosis is endemic and presented with histories and findings consistent with brucellosis. CLs were not notified that specimens might yield a hazardous organism, as the clinicians did not consider brucellosis until they were notified that bacteremia with Brucella was suspected. In 3 Brucella events, the CLs did not suspect that slow-growing, small Gram-negative bacteria might be harmful. Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), which has a limited capacity to identify biological threat agents (BTAs), was used during 4 Brucella events, which accounted for 84% of exposures. In 3 of these incidents, initial staining of liquid media showed Gram-positive rods or cocci, including some cocci in chains, suggesting streptococci. Over 200 occupational exposures occurred when the unknown isolates were manipulated and/or tested on open benches, including by procedures that could generate infectious aerosols. During 3 Brucella events, the CLs examined and/or manipulated isolates in a biological safety cabinet (BSC); in each CL, the CL had previously isolated Brucella Centers for Disease Control and Prevention recommendations to prevent laboratory-acquired brucellosis (LAB) were followed; no seroconversions or LAB cases occurred. Laboratory assessments were conducted after the Brucella events to identify facility-specific risks and mitigations. With increasing MALDI-TOF MS use, CLs are well-advised to adhere strictly to safe work practices, such as handling and manipulating all slow-growing organisms in BSCs and not using MALDI-TOF MS for identification until BTAs have been ruled out.

Associated factors in distinguishing patients with brucellosis from suspected cases.

BACKGROUND: To investigate the risk factors for brucellosis in suspected cases of the disease. METHODS: A self-designed questionnaire was developed to collect data from 3557 people whose initial visit site was the Songyuan Center for Disease Control and Prevention (CDC) from January 1st, 2009 to December 31st, 2012. After collecting blood samples, a plate agglutination test (PAT) and serum agglutination test (SAT) were used to distinguish the patients with brucellosis from the suspected cases. RESULTS: Sex, occupation (farmers and herdsmen), contact with abortion products, and contact with feces were the main risk factors for brucellosis in the suspected cases (all P < 0.05). No difference existed between the confirmed cases and suspected cases in the demographic characteristics, contact with animals (except swine), contact with substances, or clinical symptoms (except fever). However, the confirmed cases showed significant differences from people without brucellosis in demographic characteristics, contact with animals (except cattle and swine), contact with substances, and clinical symptoms. Suspected cases exhibited significant differences from people without brucellosis in the demographic characteristics (except education), contact with animals (except swine), contact with substances (except dust), and clinical symptoms (except chills and acratia). Brucella was cultured from the blood samples of three of 30 suspected cases with fever. Using AMOS-PCR and agarose electrophoresis, the detailed species of Brucella strain was identified as Brucella melitensis. CONCLUSIONS: Abortion products and feces are the main risk factors for brucellosis in suspected cases of the disease. Pyrexia in suspected cases with a history of contact with abortion products or feces should raise suspicion for the disease.

Serum prolidase level in patients with brucellosis and its possible relationship with pathogenesis of the disease: a prospective observational study

Background/aim: Changes in collagen metabolism and fibroblastic activity may play a role in the pathogenesis of brucellosis. The prolidase enzyme plays an important role in collagen synthesis. We aimed to investigate the association of prolidase levels with brucellosis. Materials and methods: Serum prolidase levels in 20 patients newly diagnosed with brucellosis were compared with levels in 30 healthy control subjects. Patients with brucellosis were reassessed 3 months later for prolidase, other laboratory measurements, and response to treatment. Results: The levels of serum prolidase were significantly higher in brucellosis patients compared with those of healthy controls. Prolidase, sedimentation, and C-reactive protein levels were significantly lower after antibrucellosistreatment than before treatment. Conclusion: The current study is the first to demonstrate significantly increased serum prolidase levels in patients with brucellosis compared with healthy controls. Prolidase levels also significantly decreased with antibrucellosis treatment. This finding provides a new experimental basis to understand the pathogenesis of brucellosis in relation to collagen metabolism. The increase in serum prolidase levels might be related to several factors such as tissue destruction, increased fibroblastic activity, and granuloma formation, all of which are involved in the natural history of brucellosis.

A case report on mother-to-child transmission of Brucella in human, China.

BACKGROUND: Human brucellosis is endemic in China and commonly occurs through contact with infected animals from working with livestock or consumption of unpasteurized dairy products. Although rare, human-to-human, and possible sexual transmission, of Brucella has been reported. In this report, we describe a case of likely mother-to-child transmission of Brucella in Hunan Province, China. CASE PRESENTATION: Between June and October 2016, a 28-year old man sought care for testicular swelling and pain at several health facilities. His 26-year old wife developed intermittent fever along with right thigh and hip pain between November 2016 and February 2017 respectively. On April 5, 2017, the female patient delivered a male neonate at 34 weeks of gestation through natural labor. The child's venal blood sample was cultured on April 5, 2017. Brucella was isolated and identified on April 12, 2017. On the same date, serum antibodies of the father and mother were above 1:100 (based on the serum agglutination test [SAT]). The strains isolated from the mother and neonate were identified as Brucella melitensis biotype 1. CONCLUSIONS: This report highlights a family cluster of brucellosis. Culture results strongly support mother-to-child transmission, and a high probability of sexual transmission from husband to wife.

An exploratory study of factors associated with human brucellosis in mainland China based on time-series-cross-section data from 2005 to 2016.

OBJECTIVE: Many studies focused on reasons behind the increasing incidence and the spread of human brucellosis in mainland China, yet most of them lacked comprehensive consideration with quantitative evidence. Hence, this study aimed to further investigate the epidemic mechanism and associated factors of human brucellosis so as to provide thoughts for future countermeasures in China and the rest of the world. METHODS: Data of human brucellosis incidence and some associated factors in economy, animal husbandry, transportation as well as health and hygiene were collected at provincial level from 2005-2016. Time series plots were first used to visualize the annual incidence and annual rate of change of human brucellosis for each province, then cluster analysis categorized all the 31 provinces of mainland China based on their incidence time series during the study period. In addition, according to the characteristics of data, the dynamic panel data model in combination with supervised principal component analysis was proposed to explore effects of associated factors on human brucellosis. RESULTS: 1. The incidence rate of human brucellosis in mainland China increased three-fold from 1.41 per 100,000 people in 2005 to 4.22 per 100,000 people in 2014, though it went down a little in 2015 and 2016. Incidence rates in the north have always been higher than those in the south, but the latter also experienced an upward trend especially between 2012 and 2016. 2. The 31 provinces of mainland China were categorized into three clusters, and each cluster had its own characteristics of incidence time series. 3. The impact of health and hygiene situations on the prevention and control work of human brucellosis was still very limited and trivial (regression coefficient = -0.02). Therefore, it was plausible to presume that improving the personal average number of medical institutes and the proportion of rural medical expenditure might be helpful in preventing and controlling human brucellosis. CONCLUSIONS: The epidemic status of human brucellosis has changed in both spatial and temporal dimensions in recent years in mainland China. Apart from traditional control measures, more attention should be paid to the improvement of medical healthcare especially in rural areas in the hope of enhancing the control effect.

Inmunopatología de la brucelosis osteoarticular / Immunopathology of osteoarticular brucelosis

La brucelosis es una de las enfermedades zoonóticas más importantes a nivel mundial capaz de producir enfermedad crónica en los seres humanos. La localización osteoarticular es la presentación más común de la enfermedad activa en el hombre. Sin embargo, algunos de los mecanismos moleculares implicados en la enfermedad osteoarticular han comenzado a dilucidarse recientemente. Brucella abortus induce daño óseo a través de diversos mecanismos en los cuales están implicados TNF-α y RANKL. En estos procesos participan células inflamatorias que incluyen monocitos/macrófagos, neutrófilos, linfocitos T del tipo Th17 y linfocitos B. Además, B. abortus puede afectar directamente las células osteoarticulares. La bacteria inhibe la deposición de la matriz ósea por los osteoblastos y modifica el fenotipo de estas células para producir metaloproteinasas de matriz (MMPs) y la secreción de citoquinas que contribuyen a la degradación del hueso. Por otro lado, la infección por B. abortus induce un aumento en la osteoclastogénesis, lo que aumenta la resorción de la matriz ósea orgánica y mineral y contribuye al daño óseo. Dado que la patología inducida por Brucella afecta el tejido articular, se estudió el efecto de la infección sobre los sinoviocitos. Estos estudios revelaron que, además de inducir la activación de estas células para secretar quemoquinas, citoquinas proinflamatorias y MMPs, la infección inhibe la muerte por apoptosis de los sinoviocitos. Brucella es una bacteria intracelular que se replica en el retículo endoplásmico de los macrófagos. El análisis de los sinoviocitos infectados con B. abortus indicó que las bacterias también se multiplican en el retículo endoplasmático, lo que sugiere que la bacteria podría usar este tipo celular para la multiplicación intracelular durante la localización osteoarticular de la enfermedad. Los hallazgos presentados en esta revisión intentan responder a preguntas sobre los mediadores inflamatorios implicados en el daño osteoarticular causado por Brucella. (AU)

Brucellosis is one of the most important zoonotic diseases that can produce chronic disease in humans worldwide. Osteoarticular involvement is the most common presentation of human active disease. The molecular mechanisms implicated in bone damage have started to be elucidated. B. abortus induces bone damage through diverse mechanisms in which TNF-α and RANKL are implicated. These processes are driven by inflammatory cells, including monocytes/macrophages, neutrophils, Th17 lymphocytes and B cells. Also, Brucella abortus (B. abortus) can directly affect osteoarticular cells. The bacterium inhibits bone matrix deposition by osteoblast and modifies the phenotype of these cells to produce matrix methalloproteinases (MMPs) and cytokine secretion that contribute to bone matrix degradation. B. abortus also affects osteoclast increasing mineral and organic bone matrix resorption and contributing to bone damage. Since the pathology induced by Brucella species involves joint tissue, experiments conducted in sinoviocytes revealed that besides inducing the activation of these cells to secrete chemokines, proinflammatory cytokines and MMPS, the infection also inhibits sinoviocyte apoptosis. Brucella is an intracellular bacterium that replicate in the endoplasmic reticulum of macrophages. The analysis of B. abortus infected sinoviocytes indicated that bacteria also replicate in their reticulum suggesting that the bacterium could use this cell type for intracellular replication during the osteoarticular localization of the disease. The findings presented in this review try to answer key questions about the inflammatory mediators involved in osteoarticular damage caused by Brucella. (AU)

Brucellosis After Cardiac Transplantation.

Brucellosis is being increasingly recognized after solid organ transplantation but has not been reported after orthotopic heart transplantation. We present the case of a 51-year-old farmer who underwent orthotopic heart transplantation and was readmitted after 3 months in a severely immunosuppressed state with significant nonspecific complaints. He posed a diagnostic and management dilemma to all disciplines, but finally turned out to be harboring Brucella infection. He responded well to medical management and was discharged in a stable clinical status. Although rare, brucellosis should be included in the investigative workup for nonspecific symptoms after cardiac transplantation.

Immunopathogenesis of Hepatic Brucellosis.

The hepatic immune system can induce rapid and controlled responses to pathogenic microorganisms and tumor cells. Accordingly, most of the microorganisms that reach the liver through the blood are eliminated. However, some of them, including Brucella spp., take advantage of the immunotolerant capacity of the liver to persist in the host. Brucella has a predilection for surviving in the reticuloendothelial system, with the liver being the largest organ of this system in the human body. Therefore, its involvement in brucellosis is practically invariable. In patients with active brucellosis, the liver is commonly affected, and the most frequent clinical manifestation is hepatosplenomegaly. The molecular mechanisms implicated in liver damage have been recently elucidated. It has been demonstrated how Brucella interacts with hepatocytes inducing its death by apoptosis. The inflammatory microenvironment and the direct effect of Brucella on hepatic stellate cells (HSC) induce their activation and turn these cells from its quiescent form to their fibrogenic phenotype. This HSC activation induced by Brucella infection relies on the presence of a functional type IV secretion system and the effector protein BPE005 through a mechanism involved in the activation of the autophagic pathway. Finally, the molecular mechanisms of liver brucellosis observed so far are shedding light on how the interaction of Brucella with liver cells may play an important role in the discovery of new targets to control the infection. In this review, we report the current understanding of the interaction between liver structural cells and immune system cells during Brucella infection.

Risk factors of brucellosis seropositivity in Bactrian camels of Mongolia.

BACKGROUND: More information on brucellosis epidemiology in Bactrian camels is needed due to their growing economic and livelihood importance for herders and renewed efforts in Mongolia to eliminate brucellosis through mass vaccination of ruminants excluding camels. Brucellosis prevalence in camels increased over the past two decades. Random multi-stage cluster surveys were done in the Eastern provinces of Dornod and Sukhbaatar in 2013 and 2014 and in the Southern & Western provinces of Dornogobi, Umnogobi and Khovd in 2014 and 2015. A total of 1822 camels, 1155 cattle, and 3023 small ruminant sera were collected and tested with the Rose Bengal Test. In addition, 195 vaginal swabs and 250 milk samples for bacteriological culture were taken from livestock with history of abortion. RESULTS: The overall apparent seroprevalence in camels was 2.3% (95% confidence interval 1.6-3.3). The main risk factor for camel seropositivity was being in an Eastern province when compared to Southern & Western provinces (odds ratio 13.2, 95% CI 5.3-32.4). Camel seroprevalences were stable over the two consecutive survey years, despite introduction of ruminant vaccination: 5.7% (95% CI 3.1-10.2%) and 5.8% (3.3-10.1%) in Eastern provinces and 0.4% (0.2-1.2%) and 0.5% (0.1-2.0%) in Southern & Western provinces. We isolated Brucella abortus from camels and cattle. Camel seropositivity was associated to keeping cattle together with camels. Monitoring of vaccination campaigns showed that coverage in cattle was insufficient because animals could not be adequately restrained. CONCLUSIONS: The present study reveals that brucellosis is present with important seroprevalence in Mongolian camels and was endemic in Eastern provinces. Camel herd seropositivity was most closely associated to infection in cattle. Longer term monitoring is needed to assess whether camel seroprevalance decreases with ongoing vaccination in Mongolia. This should be coupled with further confirmation on Brucella spp. isolates. To date, only Brucella abortus was isolated, but camels are also susceptible to Brucella melitensis. Clear verbal and written information on disease prevention in livestock and household members is important, particularly for remote camel herders who had only moderate knowledge on brucellosis epidemiology and preventive measures.

Seroreactivity and Risk Factors Associated with Human Brucellosis among Cattle Slaughterhouse Workers in South Korea.

The prevalence rate of human brucellosis in high-risk populations, as well as their risk factors, have not been well understood in South Korea. In this cross-sectional study, we investigated the seroreactivity and risk factors associated with human brucellosis among South Korean cattle slaughterhouse workers. We enrolled 922 subjects working in 71 slaughterhouses across the country in 2012. A structured questionnaire was used to obtain data from the subjects, following which blood samples were collected and tested using the microagglutination test; serum titers ≥ 1:20 were considered reactive. Independent risk factors were identified using multivariate logistic regression analysis with backward elimination. Overall, 62 of 922 participants (6.7%) exhibited seroreactivity for brucellosis, and 0.4% had a seroprevalence at a dilution of 1:160. Multivariate analysis revealed that the risk factors for human brucellosis seroreactivity included large-scale slaughtering (≥100 cattle per day; odds ratio (OR), 5.41; 95% confidence interval (CI), 2.95⁻9.91) and medium-scale slaughtering (50⁻99 cattle per day; OR, 2.53; 95% CI, 1.16⁻5.51). Moreover, the risk of brucellosis infection was significantly lower among slaughterhouse workers who always wear protective glasses (OR, 0.27; 95% CI, 0.11⁻0.69) than in those who sometimes or rarely wore such glasses. Regular and consistent use of personal protective equipment, especially protective glasses, should be encouraged among cattle slaughterhouse workers to reduce brucellosis infection.

Brucella Peritonitis in a Patient on Peritoneal Dialysis: Case Report and Literature Review.

Peritonitis is the most common complication in patients undergoing peritoneal dialysis (PD). Peritoneal dialysis-related peritonitis caused by Brucella species has been reported in only 7 patients before. Here, we report a further case of Brucella peritonitis. This patient was successfully treated with both intraperitoneal and prolonged oral antibiotics, without removal of the PD catheter. We review relevant literature and make recommendations for the diagnosis and treatment of Brucella PD-related peritonitis from the cumulative published clinical experience.

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 .

Mucosal bacterial dissemination in a rhesus macaque model of experimental brucellosis.

Animals were experimentally infected with Brucella melitensis via aerosol. B. melitensis was cultured from the saliva and vaginal vault of infected animals, corresponding to bacterial dissemination in other target tissues. This is the first report of bacterial dissemination to these mucosal surfaces in a non-human primate model of brucellosis.