Active Brucellosis Research Articles

Seroprevalence and Risk Factors of Brucellosis in Abattoir Workers in Fars Province, Iran

Background & Objectives: Brucellosis remains an important occupational zoonotic disease, especially in developing countries. The disease is endemic in Iran and the Fars province. One of the main routes of brucellosis infection is at slaughterhouses, where the workers directly contact infected animals. This study was designed to estimate the seroprevalence of brucellosis among slaughterhouse workers in the Fars province, Iran. Materials & Methods: Ninety blood samples were collected from workers of two livestock slaughterhouses (Marvdasht and Kazeroon), in Fars, Iran. The sera were assessed for the Rose Bengal test (RBT), as a screening test for brucellosis, and the positive samples were subjected to the Wright test. The positive Wright samples were finally tested for the 2 -mercaptoethanol (2 -ME) agglutination test. Results: Brucellosis prevalence was 13.33% using RBT and 4.44% of the workers showed active brucellosis. No significant relationship was found between the questionnaire variables and brucellosis tests; exceptionally, there was a relationship between the workers' statements regarding having had brucellosis and RBT (P=0.01). Conclusion : Our study highlights the practical application of serological tests, including RBT, Wright, and 2 - ME as a simple strategy to monitor brucellosis and to diagnose and treat its active form in endemic regions. Although a small frequency of the disease was found, it could cause significant health and economic damage to humans and animals in endemic areas. Furthermore, taking enough protective measures is highly recommended for slaughterhouse workers to prevent human brucellosis.

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

ObjectiveClinical 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. MethodsWe 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. ResultsA 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. ConclusionThese 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.

B. abortus Infection Promotes an Imbalance in the Adipocyte-Osteoblast Crosstalk Favoring Bone Resorption.

Osteoarticular injury is the most common presentation of active brucellosis in humans. Osteoblasts and adipocytes originate from mesenchymal stem cells (MSC). Since those osteoblasts are bone-forming cells, the predilection of MSC to differentiate into adipocytes or osteoblasts is a potential factor involved in bone loss. In addition, osteoblasts and adipocytes can be converted into each other according to the surrounding microenvironment. Here, we study the incumbency of B. abortus infection in the crosstalk between adipocytes and osteoblasts during differentiation from its precursors. Our results indicate that soluble mediators present in culture supernatants from B. abotus-infected adipocytes inhibit osteoblast mineral matrix deposition in a mechanism dependent on the presence of IL-6 with the concomitant reduction of Runt-related transcription factor 2 (RUNX-2) transcription, but without altering organic matrix deposition and inducing nuclear receptor activator ligand kβ (RANKL) expression. Secondly, B. abortus-infected osteoblasts stimulate adipocyte differentiation with the induction of peroxisome proliferator-activated receptor γ (PPAR-γ) and CCAAT enhancer binding protein β (C/EBP-β). We conclude that adipocyte-osteoblast crosstalk during B. abortus infection could modulate mutual differentiation from its precursor cells, contributing to bone resorption.

Interleukin-33 as a Potential Diagnostic and Prognostic Factor in Human Brucellosis.

The balance between T-helper 1 (Th1) and T-helper 2 (Th2) cells plays an important role in the pathogenesis of brucellosis. Interleukin (IL)-33 induces the activation of Th2 cells while soluble suppression of tumorigenicity 2 (sST2) is a decoy receptor to antagonize the effect of IL-33. Herein, we aimed to identify whether plasma IL-33/sST2 levels could reflect the state of brucellosis and help to monitor the treatment. A total of 78 patients were recruited and divided into acute, subacute, and chronic groups. The chronic group was further divided into chronic active brucellosis and chronic stable brucellosis according to the clinical manifestation. Twenty-six volunteers were assigned to the healthy control (HC) group. Plasma IL-33/sST2 levels were detected by enzyme linked immunosorbent assay (ELISA) and other routine laboratory parameters were obtained from the clinical central laboratory. The level of IL-33 in acute (49.48 ± 18.92), subacute (41.35 ± 17.12), chronic active (44.99 ± 16.80), and the chronic stable (28.92 ± 13.12) groups were higher than that in the HC group (11.66 ± 3.26) (p < 0.001). The IL-33 level in the acute group decreased significantly after treatment (49.48 ± 18.92 vs. 29.89 ± 12.92) (p < 0.001). Furthermore, the IL-33 level in the chronic active group (44.99 ± 16.80) was higher than that in the chronic stable group (28.92 ± 13.12) (p < 0.01). Interestingly, IL-33 correlated with white blood cells (WBC) (r = 0.268, p < 0.05) and C-reactive protein (CRP) (r = 0.272, p < 0.05). The level of sST2 increased in the acute (3,717.76 ± 2,036.25), subacute (3,130.41 ± 1,931.71), chronic active (3,381.43 ± 1,394.83), and the chronic stable group (2,707.03 ± 1,260.26) groups compared with the HC group (297.76 ± 290.93) (p < 0.001). However, the sST2 plasma level showed no differences among the groups and did not significantly change after treatment in the acute group. IL-33 can reflect the state of brucellosis and may be a potential biomarker for diagnosis and monitoring treatment for brucellosis.

Total spinal involvement due to delayed diagnosis and treatment of noncontiguous brucellar spondylitis

Rational: Brucellosis is a globally prevalent zoonotic disease. Any part of the body can be affected by active brucellosis but osteoarticular involvement are the most common symptoms which was reported to vary from 10% to 85%. The spine is the most common site of brucellosis in the bones. However, noncontiguous brucellar spondylitis is rare, only few cases have been reported in the literature. Patient concerns: A 62-year-old woman with brucellar spondylitis presented with lower back pain and pain in the right lower extremity for six months. Diagnosis: Brucella agglutination test (1:320) and the result of polymerase chain reaction (PCR) confirmed the diagnosis of noncontiguous brucellar spondylitis. Intervention: During hospital stay, the women received intravenous treatment for brucellosis (A combination of doxycycline 200 mg/d, rifampicin 900 mg/d, levofloxacin 0.5 g/QD, and ceftriaxone 2 g/QD was administered for 1 week), The L4-S1 vertebral body was fixed by posterior lumbar debridement. Outcome: Six months after discharge, the follow-up radiographic images showed stable vertebral height and good lumbar stability. She complained no discomfort. Lessons: Multi-level involvement is an exceptional form of brucellar spondylitis. To the best of our knowledge, only few similar cases have been reported. PCR and bacterial culture is necessary for confirmed diagnosis.

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.

Clinical Interpretation of Detection of IgM Anti-Brucella Antibody in the Absence of IgG and Vice Versa; a Diagnostic Challenge for Clinicians.

Non-specific and often misleading clinical presentation of active brucellosis has made it a diagnostic puzzle for treating physicians. Clinicians rely greatly on the detection of IgG and IgM anti-Brucella antibodies by ELISA. Different patterns of positivity have been observed for IgG and IgM anti-Brucella antibodies in different cases, which further increases the risk of an erroneous diagnosis. Detailed herein is our two-years data with varied Brucella serology patterns and their clinical interpretation. Between January 2015 to December 2017, 1102 samples were processed in the Immunology Laboratory of KFHU for Brucella serology. 68 samples were positive for both IgG and IgM, 28 samples were positive for IgG and negative for IgM while 15 samples were positive for IgM and negative for IgG antibodies against Brucella. Electronic medical records, history of exposure, signs, symptoms, laboratory data, and the final diagnosis were recorded for all these patients. None of the patients with only positive IgM antibodies was finally diagnosed with brucellosis, while a diagnosis of brucellosis was established for only one patient with IgG antibodies positive in his serum. All the double-positive (IgG- and IgM-positive) serology patterns were diagnosed as having brucellosis. We concluded that determination of single IgM or IgG anti-Brucella-antibodies by ELISA could both be considered as definite and should ideally be interpreted in the context of appropriate clinical scenario and confirmation by other laboratory assays.

BRUCELLOSIS

Background: Human brucellosis is a zoonotic infectious disease transmitted from domesticated animals to humans. It remains a major public health problem in Saudi Arabia where 7% of the population still maintains a nomadic life style with domestication of animals. Objectives: This study aims to discover the prevalence of brucellosis and Brucella among patients attending a district government hospital in Majmaah, kingdom of Saudi Arabia. Period: 2 years (from 1st February 2016 to 31st January 2018). Design: Cross sectional descriptive. Settings: King Khalid Hospital, Al Majmaah, Saudi Arabia. Materials (Patients) &amp; Methods: Total 1098 serum samples from the patients with clinical suspicion of brucellosis were screened with rapid slide agglutination test (crescent diagnostics Jeddah) for Brucella antibodies and later confirmed by Serum Tube Agglutination Test. Main Outcome Measures: The result of our study showed that the prevalence of brucellosis among patients attending our study is 9.1%. Results: 100 individuals were found to be seropositive with titers ≥1:160. The result of our study showed that the prevalence of brucellosis among patients attending our study is 9.1%The Majority of the patients presented to the medical OPD and orthopedic unit of the hospital. The prevalence of disease in males was found to be higher as compared to females in the current studied group. The age group 21- 40 years, was found to be far more susceptible to this infection. Majority presented with fever and musculoskeletal complaints. The total seroprevalence rate calculated for the patients attending our hospital is 26.50%. Conclusion: Frequent serological surveillance should be carried out in areas that are endemic. Screening of risk groups, imported animals and household members of active brucellosis must be undertaken. This is a crucial epidemiological move allowing for timely diagnosis and control of disease. Limitations: Our prevalence rate represents a specific segment of the population (i.e., those attending the hospital) and not thegeneral population.

Spondylodiscitis: a common complication of brucellosis.

Brucellar spondylodiscitis is a frequent and serious complication of brucellosis. The aim of this study is to describe the brucellosis patients with spondylodiscitis and the predictive factors related to spondylodiscitis in brucellosis. Laboratory-confirmed brucellosis patients from a low- to medium-endemic region were enrolled in the study and distributed into two groups. Group I consisted of patients with spondylodiscitis and Group II patients had no complications. Both groups were compared for predictive factors of spondylodiscitis. A total of 219 patients with active brucellosis were included in the study. We determined at least one complication in 91 (41.6%) patients. The most frequent complication was spondylodiscitis [n = 59 patients (26.9 %)]. In univariate analysis, age, time from symptom onset to diagnosis, presence of low back pain, increased levels of erythrocyte sedimentation rate, and alkaline phosphatases were the most significant predictive factors for spondylodiscitis among brucellosis cases. Presence of headache and thrombocytopenia were less frequent in patients with spondylodiscitis when compared to patients without complications (p = 0.024, p = 0.006 respectively). In multivariate analysis, old age (odds ratio [OR] 1,063; 95% confidence interval [CI] 1.026-1.101; p < 0.001), prolonged time between symptoms onset before diagnosis (OR 1.008; 95% CI 1.001-1.016; p = 0.031), and presence of low back pain (OR 12.886; 95% CI 3.978-41.739; p < 0.001) were indepedently associated with an increased risk of spondylodiscitis. Spondylodiscitis is the most frequent complication of systemic brucellosis. Patients with low back pain, older age, and longer duration of symptoms should be considered as candidates of potential spondylodiscitis in brucellosis.

Brucella abortus Promotes a Fibrotic Phenotype in Hepatic Stellate Cells, with Concomitant Activation of the Autophagy Pathway.

The liver is frequently affected in patients with active brucellosis. The present study demonstrates that Brucella abortus infection induces the activation of the autophagic pathway in hepatic stellate cells to create a microenvironment that promotes a profibrogenic phenotype through the induction of transforming growth factor-β1 (TGF-β1), collagen deposition, and inhibition of matrix metalloproteinase-9 (MMP-9) secretion. Autophagy was revealed by upregulation of the LC3II/LC3I ratio and Beclin-1 expression as well as inhibition of p62 expression in infected cells. The above-described findings were dependent on the type IV secretion system (VirB) and the secreted BPE005 protein, which were partially corroborated using the pharmacological inhibitors wortmannin, a phosphatidyl inositol 3-kinase inhibitor, and leupeptin plus E64 (inhibitors of lysosomal proteases). Activation of the autophagic pathway in hepatic stellate cells during Brucella infection could have an important contribution to attenuating inflammatory hepatic injury by inducing fibrosis. However, with time, B. abortus infection induced Beclin-1 cleavage with concomitant cleavage of caspase-3, indicating the onset of apoptosis of LX-2 cells, as was confirmed by the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay and Hoechst staining. These results demonstrate that the cross talk of LX-2 cells and B. abortus induces autophagy and fibrosis with concomitant apoptosis of LX-2 cells, which may explain some potential mechanisms of liver damage observed in human brucellosis.

Brucellosis in Endangered Hector's Dolphins (Cephalorhynchus hectori).

Brucella spp infections of marine mammals are often asymptomatic but have been associated with reproductive losses and deaths. Zoonotic infections originating from marine isolates have also been described. Hector's dolphins (Cephalorhynchus hectori) are an endangered species with a declining population, and the role of infectious disease in population dynamics is not fully understood. In this study, 27 Hector's dolphins found dead around the New Zealand coastline between November 2006 and October 2010 were evaluated for lesions previously associated with cetacean brucellosis. Tissues were examined using histological, immunohistochemical, and molecular (polymerase chain reaction [PCR]) techniques. Seven of 27 dolphins (26%) had at least 1 tissue that was positive on PCR for Brucella spp. Lesions consistent with brucellosis were present in 10 of 27 (37%) dolphins, but in 8 of these dolphins Brucella infection could not be demonstrated in lesional tissues. Two dolphins (7%) were diagnosed with active brucellosis: 1 female with placentitis and metritis, and 1 stillborn male fetus. Brucella identified in these 2 dolphins had genetic similarity (99%) to Brucella pinnipedialis. The omp2a gene amplicon from the uterus of the female had 100% homology with ST27 genotype isolates from a human in New Zealand and a bottlenose dolphin of Pacific origin. The remaining 5 PCR-positive dolphins were assessed as having asymptomatic or latent infection. While most Brucella infections identified in this study appeared to be subclinical, the finding of 2 dolphins with reproductive disease due to Brucella infection suggests that this disease has the potential to affect reproductive success in this species.

The prevalence and impact of brucellosis in patients with hepatitis delta virus infection: inside the Brucella outbreak with cirrhosis.

IntroductionHepatitis D virus (HDV) infection is a serious health problem leading to cirrhosis and hepatocellular carcinoma (HCC). Despite evidence that zoonotic infections are associated with end-stage liver disease, brucellosis in patients with delta hepatitis related to liver disease has not been well characterized. So, we examined this relationship using recent hospital-based data.Material and methodsWe analyzed data from 96 delta hepatitis patients (mean age: 52.5 ±12.8 years; 50 male; 52 cirrhotics) and 117 (mean age: 50.4 ±7 years; 60 male) control subjects who were selected from patients with splenomegaly. The Brucella Wright test in connection with blood culture was used to detect active Brucella infection. Demographic features, laboratory data, results of ultrasonographic examination of the abdomen and Wright agglutination titers were compared between groups.ResultsThere were 9 (9%) patients with active brucellosis in delta hepatitis patients. Compared to the control group, there was a statistically significant difference between groups in terms of having active brucellosis (9 vs. 2 patients; p < 0.001). Higher MELD scores were also associated with active Brucella infection (p < 0.005).ConclusionsPatients with chronic hepatitis D related cirrhosis (CHD-C) were at risk of developing brucellosis requiring hospitalization. Higher Wright titers among patients with more advanced liver disease may reflect a unique phenomenon that requires further investigation to determine underlying causative factors.

Brucellosis as a neglected disease in a neglected population: a seroepidemiological study of migratory nomads in the Fars province of Iran.

This study assessed the seroprevalence of brucellosis and its risk factors in migratory nomads in the Fars province of Iran. Active brucellosis was defined as the combination of clinical symptoms, including fever, chills, night sweats, headache, low back pain, arthralgia, or myalgia, and positive laboratory testing, including either a serum agglutination test (SAT) ⩾1:80 with a 2-mercaptoethanol (2-ME) test ⩾1:40, or a SAT <1:80 combined with a positive Coombs Wright test (CWT) at a titre of at least threefold higher than SAT titre results. For the 536 participants, the female (316, 59%) to male (220, 41%) ratio was 1·4 and the participants' mean age was 32·4 ± 18·9 (range 1-96) years. Of all participants, 325 (60·6%) showed clinical symptoms; in symptomatic participants, the Rose Bengal plate test was positive in 33 (6·1%) cases, the SAT was positive in 18 (3·3%) cases, and the 2-ME test was positive in 30 (5·5%) cases. Positive SAT and 2-ME results were seen in 18 (3·3%) cases, but a negative SAT and a positive CWT were found in 36 (6·7%) cases. As a result, active brucellosis was detected in 54 cases, indicating a prevalence of 10% (95% confidence interval 8-12). In conclusion, we determined that brucellosis is a prevalent yet neglected disease in this nomadic population. Brucellosis control is not possible as long as these high-risk populations remain neglected.

Relationship between CD14-159C/T gene polymorphism and acute brucellosis risk.

ObjectiveTo investigate the association between the cluster of differentiation 14 (CD14)-159C/T (rs2569190) gene polymorphism and susceptibility to acute brucellosis in an Iranian population.MethodsThe study included 153 Iranian patients with active brucellosis and 128 healthy individuals as the control group. Genotyping of the CD14 variant was performed using an amplification refractory mutation system-polymerase chain reaction method.ResultsThe prevalence of CD14-159 TT and CT genotypes were associated with increased risk of brucellosis [odds ratio (OR) = 1.993, 95% confidence interval (95% CI) = 1.07–3.71, P = 0.03 for CT; OR = 3.869, 95% CI = 1.91–7.84, P = 0.01 for TT genotype. Additionally, the minor allele (T) was significantly more frequently present in brucellosis patients than in controls (61% vs. 45%, respectively), and was a risk factor for brucellosis (OR = 3.058, 95% CI = 1.507–6.315, P = 0.01).ConclusionsThe findings provided suggestive evidence of association of the CD14-159C/T gene polymorphism with susceptibility to acute brucellosis in the Iranian population.

The Effector Protein BPE005 from Brucella abortus Induces Collagen Deposition and Matrix Metalloproteinase 9 Downmodulation via Transforming Growth Factor β1 in Hepatic Stellate Cells.

The liver is frequently affected in patients with active brucellosis. In the present study, we identified a virulence factor involved in the modulation of hepatic stellate cell function and consequent fibrosis during Brucella abortus infection. This study assessed the role of BPE005 protein from B. abortus in the fibrotic phenotype induced on hepatic stellate cells during B. abortus infection in vitro and in vivo. We demonstrated that the fibrotic phenotype induced by B. abortus on hepatic stellate (LX-2) cells was dependent on BPE005, a protein associated with the type IV secretion system (T4SS) VirB from B. abortus. Our results indicated that B. abortus inhibits matrix metalloproteinase 9 (MMP-9) secretion through the activity of the BPE005-secreted protein and induces concomitant collagen deposition by LX-2 cells. BPE005 is a small protein containing a cyclic nucleotide monophosphate binding domain (cNMP) that modulates the LX-2 cell phenotype through a mechanism that is dependent on the cyclic AMP (cAMP)/protein kinase A (PKA) signaling pathway. Altogether, these results indicate that B. abortus tilts LX-2 cells to a profibrogenic phenotype employing a functional T4SS and the secreted BPE005 protein through a mechanism that involves the cAMP and PKA signaling pathway.

TNF-α -238, -308, -863 polymorphisms, and brucellosis infection

BackgroundBrucella abortus is an intracellular bacterium that affects humans and domestic animals. Tumor necrosis factor-alpha (TNF-α) has been shown as a key player in the induction of cell-mediated resistance against Brucella infection. We aimed to evaluate the possible influence of the TNF-α promoter polymorphisms (-308 G/A, -238 G/A, and -863 C/A) on the susceptibility of human brucellosis. MethodologyA total of 153 patients with active brucellosis and 128 healthy individuals were recruited. All subjects were genotyped for the polymorphisms in the TNF-α gene by Allele-Specific polymerase chain reaction analysis. ResultsOur results showed that the TNF-α -308 GG genotype was significantly more frequently present in controls than in brucellosis patients (91% vs. 75%), thus was a protective factor against developing brucellosis (OR=0.313, p=0.001). In contrast, the -308 GA genotype (OR=3.026, p=0.002) and minor allele (A) (OR=3.058, p=0.001) as well as AAG haplotype (OR=4.014, p=0.001) conferred an increased risk of brucellosis. However, the -238 G/A and -863 C/A polymorphisms were not associated with the risk of brucellosis at both allelic and genotypic levels (p>0.05). ConclusionOur study revealed that the TNF-α -308 A allele or GA heterozygosity or AAG haplotype were associated with an increased risk of brucellosis in our population.

Brucellosis in pregnancy: clinical aspects and obstetric outcomes

Brucellosis is a zoonosis with high morbidity in humans. This disease has gained interest recently due to its re-emergence and potential for weaponization. Pregnant women with this disease can develop severe complications. Its association with adverse obstetric outcomes is not clearly understood. The objective of this study was to describe the obstetric outcomes of brucellosis in pregnancy. Cases of pregnant women with active brucellosis seen at the Hospital Nacional Cayetano Heredia from 1970 to 2012 were reviewed. Diagnostic criteria were a positive agglutination test and/or positive blood/bone marrow culture. Presentation and outcomes data were collected. The Chi-square test was used for nominal variables. A p-value of <0.05 indicated significance. One hundred and one cases were included; 27.7% had a threatened abortion/preterm labor, 12.8% experienced spontaneous abortion, 13.9% preterm delivery, 8.1% fetal death, and 1.1% congenital malformations. There was one maternal death secondary to severe sepsis. After delivery, neonatal death occurred in 8.1%, low birth weight in 14.5%, and congenital brucellosis in 6.4%. The most common treatment was aminoglycosides plus rifampicin (42.2% of cases). Complication rates decreased if treatment was started within 2 weeks of presentation (p < 0.001). This is the largest series of brucellosis in pregnancy reported in the literature. Brucella presents adverse obstetric outcomes including fetal and maternal/neonatal death. Cases with unexplained spontaneous abortion should be investigated for brucellosis. Prompt treatment is paramount to decrease the devastating outcomes.

Gum and Nose Bleeding as a Presentation of Pediatric Brucellosis

Introduction: Brucellosis symptoms are nonspecific; the most common complaints include fever, sweats, anorexia, headache, malaise, and arthralgia. Hematological manifestations of active brucellosis vary from mild anemia and leukopenia to thrombocytopenia and rarely pancytopenia. Case Presentation: We report on an eight-year-old boy who presented epistaxis and gum bleeding. The physical examination revealed petechiae, purpura, ecchymosis, and cervical while inguinal lymphadenopathy and splenomegaly were noted. Brucella agglutinin titer was positive. After five days of specific therapy for brucellosis, fever was controlled, clinical signs and symptoms were improved and platelet count was dramatically increased. Conclusions: Sever thrombocytopenia and bleeding may be the presentation of brucellosis.

TGFβ1 genetic variants are associated with an increased risk of acute brucellosis

Objective: Cytokines play a critical role in the regulation of the immune response against brucellosis infection, and mediate production of many pro- and anti-inflammatory signals. Transforming growth factor-beta 1 (TGFβ1), a powerful suppressive cytokine, inhibits macrophage activation and modulates T-cell function, and plays crucial roles in regulation of microbial replication and host responses to brucella. Methods: The association of three polymorphisms in the TGFβ1 gene (–509 C/T [rs1800469], + 868 C/T [rs1800470], and + 913 G/C [rs1800471]) in promoter, codons 10 and 25, respectively, with brucellosis infection was evaluated. This case-control study was performed on a total of 281 Iranian subjects including 153 patients with active brucellosis and 128 age- and sex-matched healthy individuals as controls. Genotyping for the TGFβ1 –509 C/T and + 868 C/T variants was performed using tetra amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR). Also, the + 913 G/C polymorphism was genotyped using an allele-specific PCR. Results: The results demonstrated that the TGFβ1 + 868 C/T mutant homozygote genotype (TT vs CC), was a risk factor for developing brucellosis in the co-dominant and recessive models (odds ratio (OR) = 2.60, p = 0.023; OR = 2.602, p = 0.014, respectively). Additionally, the diplotype analyses revealed that TGFβ1 codon 10 and 25 diplotype, TT/GG, was associated with an increased risk of brucellosis (OR = 2.49, p = 0.038). Other TGFβ1 variants did not increase the risk of brucellosis infection. Conclusions: Our findings propose that TGFβ1 + 868 TT genotype and TT/GG diplotype may confer increased risk of brucellosis in the examined population.

Molecular typing of Brucella species isolates from Human and livestock bloods in Isfahan province.

Background:Human brucellosis is caused by infection with certain species of the genus Brucella and is characterized by bacterial persistence and inflammation of many host tissues. Handling all live Brucella involves risk of laboratory infection and very strict biosafety rules must be observed. In order to avoid these disadvantages, method based on the PCR-RFLP shows excellent typeability, reproducibility, stability, and epidemiological concordance. The omp2 locus contains two gene copies (named omp2a and omp2b) coding for porin proteins and has been found particularly useful for molecular typing and identification of Brucella at the species, biovar, or strain level. This study is designed to evaluate the molecular epidemiology of Brucella spp from human and livestock in Isfahan province, central region of Iran in order to use the findings in efficient disease prevention programs.Materials and Methods:One hundred ninety blood samples were collected from human and cattle with active brucellosis and 40 aborted ewes fetuses were collected and genotyped using PCR-RFLP technique, DNA polymorphisms such as the restriction patterns of the PCR-amplified omp2a and omp2b genes.Results:The molecular characterization performed to assess the species and the biovar of the Brucella strains. Analysis of the 230 isolates examined in this study generated three unique RFLP profiles. One of the profiles was the most common being present in 134/180.Conclusion:Our findings confirm abundance of B. melitensis, particularly biovar 1 in human and sheep are identical but B. abortus biovar 3 as the etiological agent of cattle brucellosis most frequently isolated in the Isfahan area.