Brucellosis Patients Research Articles

Subclinical sacroiliitis in brucellosis. Clinical presentation and MRI findings.

The aim of this work was to detect subclinical sacroiliac joint involvement in patients with brucellosis and study their clinical and laboratory features. The study included 100brucellosis patients being followed-up in the Gastroenterology and Hepatology Unit, Theodor Bilharz Research Institute and Cairo University outpatient clinics. A thorough history, physical examination, routine laboratory tests, and abdominal ultrasound were obtained for all patients. Extended rheumatological examination was performed including clinical testing for sacroiliitis and enthesitis. None of the patients reported a history of back pain or any symptoms suggestive of sacroiliitis during the course of the infection. Plain x-ray and MRI scan of the sacroiliac joints were performed for all patients. Asymptomatic sacroiliitis was present in 24 % of the brucellosis patients; none of the patients had tenderness over their spine with preserved lumbar spine mobility. Sacroiliitis was mainly unilateral being bilateral in 20.83 %. There was an obvious relationship with animal contact and occupation of the patients. Osteoarticular involvement was common (67 %) including arthralgias, arthritis, myalgias, spondylitis, enthesitis and bursitis, being clearly higher in those with sacroiliitis. The MRI scan showed blurring of the margins in 66.67 %, widening in 25 %, narrowing in 54.17 %, erosions in 20.83 %, and sclerosis in 12.5 %. Osteoarticular manifestations of brucellosis are prevalent and subclinical sacroiliitis is evident, a finding that may classify these patients as having brucellar spondyloarthropathy (BSA). Referring brucellosis patients for rheumatological assessment has the advantage of early assessment of asymptomatic cases with sacroiliitis which is commonly overlooked.

Clinical and laboratory findings of 97 pediatric brucellosis patients in central Turkey.

Brucellosis is a disease transmitted to humans by consumption of unpasteurized animal milk, or through direct contact with infected animals. The aim of this study was to evaluate clinical, laboratory findings of pediatric patients with brucellosis. Data of 97 patients diagnosed with brucellosis between January 2000 and December 2010 were evaluated retrospectively.

Spatial and temporal characteristics of human brucellosis, from 2004 to 2012 in Shandong province

To explore the spatial and temporal characteristics of human brucellosis in Shandong province and to provide scientific basis for the development of related regional public health strategies. 1 802 diagnosed cases of human brucellosis patients were selected based on the data that was collected by Diseases Reporting Information System between year 2004 and 2012 in Shandong province. Methods on spatial thematic mapping, spatial autocorrelation analysis, spatial clustering analysis, and temporal clustering analysis were applied to describe the temporal and spatial distribution on human brucellosis cases. The incidence rate of human brucellosis increased from 0.038 2/100 000 (35 cases) to 0.620 5/100 000 (598 cases), with annual average incidence rate as 0.211 1/100 000 and the incidence was evidently increased. The value of M (0.375 3) showed that this disease was seasonal, with the epidemic months between March and June, accounting for 56.27% (1 014/1 802). The Global Moran's I index was 0.198 901 (P = 0.000 120), showing that there was a positive correlation between space and the incidence of brucellosis. The incidence rates in 2006, 2007, 2009 and 2012 and the space distribution appeared a positive correlation (P < 0.05) in Shandong province. The local Moran's I index showed that there were 8 "High-High" (HH) clustering areas, which were proved to have statistical significance (P < 0.05). Local indicators of spatial association (LISA) revealed that southwest and north districts of Shandong were highly clustered districts of brucellosis and the areas paralleled to the areas that having higher incidence rates. There were two spatial clustering areas in this study, one as the center of Juanchen with radiation radius at 33.83 km whose RR was 9.78 (P < 0.05) and the other was the center of Binchen with radiation radius at 62.78 km with RR as 4.99 (P < 0.05). All the 8 HH counties (districts) were included in the two cluster regions. Incidence of human brucellosis showed an obvious increase in Shandong during year 2004-2012. Months with epidemics were between March and June. The incidence of brucellosis in counties (districts) was non-randomly distributed. A positive spatial correlation and the feature of clusters was noticed.

Serum annexin A2 levels in acute brucellosis and brucellar spondylodiscitis.

Brucellosis is a chronic granulomatous infection and may present with various clinical manifestations. Brucellar spondylodiscitis symptoms are initially subtle and nonspecific. Annexin A2 (ANXA2) is involved in various biological functions, including osteoclast formation, bone resorption, and cell growth regulation. In this study, we aimed to determine the clinical significance of serum ANXA2 levels in acute brucellosis and brucellar spondylodiscitis. This prospective study included 96 acute brucellosis patients and 51 healthy controls. Acute brucellosis was diagnosed by a 1/160 or higher titer in a standard tube agglutination (STA) test or a four-fold increase in titers between two STA tests performed two weeks apart in the presence of clinical symptoms within the last eight weeks and/or growth of Brucella spp. in appropriately prepared culture media. ANXA2 levels were determined with an enzyme-linked immunosorbent assay (ELISA). Forty (41.7%) of 96 acute brucellosis patients were male and 56 (58.3%) were female. Serum ANXA2 levels were elevated in patients compared to healthy controls (p = 0.001). Eighteen of 96 (18.7%) acute brucellosis patients had brucellar spondylodiscitis. The serum ANXA2 levels of patients with brucellar spondylodiscitis were higher than those of patients with acute disease without brucellar spondylodiscitis (p = 0.001). ANXA2, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) values were elevated in the brucellar spondylodiscitis group compared to patients without brucellar spondylodiscitis. Serum ANXA2 measurement together with ESR and CRP is thought to be indicative in the diagnosis of brucellar spondylodiscitis, a common complication of brucellosis.

Frequencies of CD4+ T Regulatory Cells and their CD25high and FoxP3high Subsets Augment in Peripheral Blood of Patients with Acute and Chronic Brucellosis

ObjectivesBrucellosis remains one of the most common zoonotic diseases worldwide. In humans, brucellosis can be a serious, debilitating, and sometimes chronic disease. Different mechanisms can be postulated as to the basis for the induction of the chronic status of infectious diseases that T regulatory cells are one of the most important related mechanisms. The current study was designed to determine whether percentage of CD4+Treg cells and their CD25high and FoxP3high subpopulations in peripheral blood are changed in human brucellosis samples in comparison to a control group. MethodsIn total, 68 brucellosis patients (acute form: n = 43, chronic form: n = 25) and 36 healthy volunteers entered our study. After isolating of peripheral blood mononuclear cells, heparinized venous blood samples were obtained from both patients and healthy donors, CD4, CD25, and FoxP3 molecules were evaluated by two- and three-color flow cytometric methods. ResultsThe results revealed a new finding in relation to Treg cells and human brucellosis. The numbers of CD4+Treg cells and their CD25high and FoxP3high subsets increase significantly in the peripheral blood of acute and chronic forms of brucellosis samples compared with healthy groups, with this increase being greater in the chronic group. ConclusionThere seems to be a correlation between increase of CD4+Treg cells and their subsets and the disease progress from healthy state to acute and chronic brucellosis.

Mean platelet volume may not be a biomarker monitoring of brucellosis

To the editor We read with great interest the research article by Kader et al. [1] entitled with evaluation of mean platelet volume (MPV) levels in brucellosis patients. They retrospectively investigated the complete blood count parameters in patients with brucellosis. They found that MPV values were statistically significantly low in pre-treatment group compared with post-treatment group and healthy controls. They suggested that MPV levels might be useful in the follow-up of brucellosis patients. We would like to comment on this study.

Liver involvement in patients with brucellosis: results of the Marmara study

Brucellosis is a zoonotic disease that primarily affects the reticuloendothelial system. But, the extent of liver damage in due course of the disease is unclear. This study included 325 brucellosis patients with significant hepatobiliary involvement identified with microbiological analyses from 30 centers between 2000 and 2013. The patients with ≥5 times of the upper limit of normal for aminotransferases, total bilirubin level ≥2 mg/dl or local liver lesions were enrolled. Clinical hepatitis was detected in 284 patients (87.3 %) and cholestasis was detected in 215 (66.1 %) patients. Fatigue (91 %), fever (86 %), sweating (83 %), arthralgia (79 %), and lack of appetite (79 %) were the major symptoms. Laboratory tests showed anemia in 169 (52 %), thrombocytopenia in 117 (36 %), leukopenia in 81 (25 %), pancytopenia in 42 (13 %), and leukocytosis in 20 (6 %) patients. The most commonly used antibiotic combinations were doxycycline plus an aminoglycoside (n = 73), doxycycline plus rifampicin (n = 71), doxycycline plus rifampicin and an aminoglycoside (n = 27). The duration of ALT normalization differed significantly in three treatment groups (p < 0.001). The use of doxycycline and an aminoglycoside in clinical hepatitis showed better results compared to doxycycline and rifampicin or rifampicin, aminoglycoside, doxycycline regimens (p < 0.05). However, the length of hospital stay did not differ significantly between these three combinations (p > 0.05). During the follow-up, treatment failure occurred in four patients (1 %) and relapse was seen in three patients (0.9 %). Mortality was not observed. Hepatobiliary involvement in brucellosis has a benign course with suitable antibiotics and the use of doxycycline and an aminoglycoside regimen seems a better strategy in select patients.

Investigation of CTLA‐4 and CD86 gene polymorphisms in Iranian patients with brucellosis infection

The protective immune response against Brucella involves T-cell-mediated immunity. T-lymphocyte receptors, CD28 and cytotoxic T-lymphocyte-associated protein-4 (CTLA-4), bind the same ligands, CD80 (B7-1) and CD86 (B7-2) on antigen-presenting cells and regulate T cell activation. CD28 delivers stimulatory signals whereas CTLA-4 provides inhibitory signals for T cell activation. Here, we investigated the association of four polymorphisms in CTLA4 (+49A/G [rs231775] and -318 C/T [rs5742909]) and its ligand CD86 (+1057 G/A [rs1129055] and +2379G/C [rs17281995]) with brucellosis infection. The study included 153 Iranian patients with active brucellosis and 128 healthy individuals as the control group. Genotyping of the CTLA4 and CD86 variants was performed using tetra amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) and PCR-restriction fragment length polymorphism analysis, respectively. It was found that the CTLA4 -318 CT genotype and T allele were present more frequently in cases than in controls and are therefore associated with an increased risk for brucellosis (-318 TT genotype; OR = 2.544, P = 0.002). Likewise, the CD86 +1057 GA and AA genotypes and A allele were associated with an increased risk of brucellosis (+1057 AA genotype; OR = 3.81, P = 0.001). However, no statistically significant difference between brucellosis patients and controls in the allele and genotype distributions of CTLA4, +49A/G (P = 0.859) and CD86, +2379G/C (P = 0.476) was found. In conclusion, CTLA4 -318 CT genotype and T allele and the CD86 +057 GA and AA genotypes and A allele play roles as risk factors for developing brucellosis infection in Iran.

Increased Serum Hepcidin Levels in Brucellosis

Both CD4+ and CD8+ T lymphocytes play crucial roles in immunity to Brucella, in part because they secrete interferon (IFN)-γ and activate the bactericidal functions in macrophages. Hepcidin is an antimicrobial and iron regulatory peptide produced by the liver in response to inflammation and elevated systemic iron. Recent studies suggest that circulating monocytes and resident liver macrophages may influence both basal and inflam- matory expression of hepcidin and these two cell types act in concert to regulate hepcidin production during in- flammation. Here, we aimed to investigate the association of hepcidin levels with Brucellosis. Serum hepcidin levels in 49 Brucellosis patients were compared with 52 healthy control subjects by com- mercial ELISA kit. The levels of serum hepcidin were significantly higher in Brucellosis patients compared with those of healthy controls (p < 0.001). There was no statistically significant difference in serum hepcidin levels among acute, subacute, and chronic cases with Brucellosis. Hepcidin levels were positively correlated with CRP in patients with brucellosis. Our first results may suggest that the levels of Hepcidin may be a useful adjunct to clinical and other laboratory findings suggestive of the disease for the diagnosis of Brucellosis, but cannot be used to differentiate the three different forms of this disease (acute, subacute, and chronic).

The antibodies cyclic citrullinated peptides (anti-CCP) positivity could be a promising marker in brucellosis patients presented with peripheric arthritis

Introduction The anti-cyclic citrullinated peptide (anti-CCP) enzyme-linked immunosorbent assay has a high sensitivity and specificity for rheumatoid arthritis (RA). It has been used in especially early diagnosis of RA, and used to discriminate from other forms of arthritis. Anti-CCP positivity is unknown in brucellosis presented with peripheric arthritis (BPA), like other rheumatic diseases. The objective of this study was to investigate the positivity of anti-CCP in patients with BPA in contrast to the patients with RA and healthy controls. Additionally, we have aimed to monitor changes of anti-CCP levels following the brucellosis treatment.Methods The study group consisted of 137 subjects. 62 brucellosis patients presented with peripheric arthritis. Additionally, 33 RA patients and 42 healthy subjects selected as control groups. The anti-CCP, rheumatoid factor and anti-nuclear antibody levels of the subjects were measured.Results Concerning the 62 BPA, 20 % (13 patients) of them had elevated anti-CCP levels. On the other side, of the 33 RA patients, 78.78 % (26 patients) of them had increased anti-CCP levels. Only one healthy subject’s anti-CCP level was positive. There was statistically significant difference among the groups. After brucellosis treatment, monitorisation of the 13 patients with BPA who have the positive anti-CCP levels, were challengingly interesting because none of the patients had positive anti-CCP levels.Conclusions Anti-CCP may be positive marker in the diagnosis of BPA but clinicians need to be careful during the follow up period because it may turn into normal ranges. Additionally, patients presented with peripheric arthritis and anti-CCP positivity need to be evaluated also for the differential diagnosis of BPA.

Relationship between γ‐interferon gene polymorphisms and susceptibility to brucellosis infection

Interferon-gamma (IFN-γ) is a pro-inflammatory cytokine that plays a pivotal role in the defense mechanism against Brucella infection. It was hypothesized that the IFN-γ in (+874 A/T in intron 1) TT and +5644 T/A, TT genotypes, which are reportedly associated with high IFN production, are associated with susceptibility to brucellosis in Iranian subjects. Genotyping of these IFN-γ variants by an allele-specific polymerase chain reaction method was performed in 281 subjects, comprising 153 patients with active brucellosis and 128 healthy controls. It was found that the +874 minor allele (A) and homozygote genotype (AA) were significantly more frequently present in brucellosis patients than in controls (OR = 2.588; 95% CI, 1.313-5.104; P = 0.006 for the AA genotype; OR = 1.575; 95% CI, 1.124-2.216; P = 0.010 for the A allele). However, the allelic and genotypic distribution of the IFN-γ polymorphism at position UTR5644 A>T did not differ significantly between patients and controls (P > 0.05). The distribution of haplotypes in this study suggests that the T/A haplotype (+874/UTR5644), which was present more frequently in controls than in patients, may protect subjects against Brucella infection. It is suggested that IFN-γ +874 AA genotype and A allele are risk factors for developing brucellosis infection in Iranian subjects.

Simultaneous emergence of several biotypes of &amp;lt;italic&amp;gt;Brucella&amp;lt;/italic&amp;gt; among Baotou's brucellosis patients by combined diagnostic strategy

Yaoxia Kang1,2, Enhou Jia2, Liang Lin2, Xiangyang Duan2, Pei Xiao3, Jingxian Peng2, Wei Gao2, Chaobao Zhang4, Xiaokui Guo1*, Buyun Cui3*, and Xiangqi Li4* Department of Medical Microbiology and Parasitology, Institutes of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China Baotou Municipal Center for Disease Control and Prevention, Baotou 014030, China State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Beijing 102206, China Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China *Correspondence address. Tel: þ86-21-63846590-776712; Fax: þ86-21-64453285; E-mail: microbiology@sjtu.edu.cn (X.G.); Tel: þ86-10-58900768; Fax: þ86-10-58900767; E-mail: cuibuyun@icdc.cn (B.C.); Tel: þ86-21-54921267; Fax: þ86-21-54921011; E-mail: lixq@sibs.ac.cn (X.L.)

Ex Vivo Innate Immune Cytokine Signature of Enhanced Risk of Relapsing Brucellosis

BackgroundBrucellosis, a zoonotic infection caused by one of the Gram-negative intracellular bacteria of the Brucella genus, is an ongoing public health problem in Perú. While most patients who receive standard antibiotic treatment recover, 5–40% suffer a brucellosis relapse. In this study, we examined the ex vivo immune cytokine profiles of recovered patients with a history of acute and relapsing brucellosis.Methodology/Principal FindingsBlood was taken from healthy control donors, patients with a history of acute brucellosis, or patients with a history of relapsing brucellosis. Peripheral blood mononuclear cells were isolated and remained in culture without stimulation or were stimulated with a panel of toll-like receptor agonists or heat-killed Brucella melitensis (HKBM) isolates. Innate immune cytokine gene expression and protein secretion were measured by quantitative real-time polymerase chain reaction and a multiplex bead-based immunoassay, respectively.Acute and relapse patients demonstrated consistently elevated cytokine gene expression and secretion levels compared to controls. Notably, these include: basal and stimulus-induced expression of GM-CSF, TNF-α, and IFN-γ in response to LPS and HKBM; basal secretion of IL-6, IL-8, and TNF-α; and HKBM or Rev1-induced secretion of IL-1β, IL-2, GM-CSF, IFN-Υ, and TNF-α. Although acute and relapse patients were largely indistinguishable by their cytokine gene expression profiles, we identified a robust cytokine secretion signature that accurately discriminates acute from relapse patients. This signature consists of basal IL-6 secretion, IL-1β, IL-2, and TNF-α secretion in response to LPS and HKBM, and IFN-γ secretion in response to HKBM.Conclusions/SignificanceThis work demonstrates that informative cytokine variations in brucellosis patients can be detected using an ex vivo assay system and used to identify patients with differing infection histories. Targeted diagnosis of this signature may allow for better follow-up care of brucellosis patients through improved identification of patients at risk for relapse.

The antibodies cyclic citrullinated peptides (anti-CCP) positivity could be a promising marker in brucellosis patients presented with peripheric arthritis

IntroductionThe anti-cyclic citrullinated peptide (anti-CCP) enzyme-linked immunosorbent assay has a high sensitivity and specificity for rheumatoid arthritis (RA). It has been used in especially early diagnosis of RA, and used to discriminate from other forms of arthritis. Anti-CCP positivity is unknown in brucellosis presented with peripheric arthritis (BPA), like other rheumatic diseases. The objective of this study was to investigate the positivity of anti-CCP in patients with BPA in contrast to the patients with RA and healthy controls. Additionally, we have aimed to monitor changes of anti-CCP levels following the brucellosis treatment.MethodsThe study group consisted of 137 subjects. 62 brucellosis patients presented with peripheric arthritis. Additionally, 33 RA patients and 42 healthy subjects selected as control groups. The anti-CCP, rheumatoid factor and anti-nuclear antibody levels of the subjects were measured.ResultsConcerning the 62 BPA, 20 % (13 patients) of them had elevated anti-CCP levels. On the other side, of the 33 RA patients, 78.78 % (26 patients) of them had increased anti-CCP levels. Only one healthy subject’s anti-CCP level was positive. There was statistically significant difference among the groups. After brucellosis treatment, monitorisation of the 13 patients with BPA who have the positive anti-CCP levels, were challengingly interesting because none of the patients had positive anti-CCP levels.ConclusionsAnti-CCP may be positive marker in the diagnosis of BPA but clinicians need to be careful during the follow up period because it may turn into normal ranges. Additionally, patients presented with peripheric arthritis and anti-CCP positivity need to be evaluated also for the differential diagnosis of BPA.

Diagnostic value of serum concentrations of high‐mobility group‐box protein 1 and soluble hemoglobin scavenger receptor in brucellosis

Both cluster of differentiation (CD)4(+) and CD8(+) T lymphocytes play key roles in immunity to Brucella, in part because they secrete interferon (IFN)-γ and activate bactericidal functions in macrophages. Therefore, use of markers of macrophage activation may have diagnostic and prognostic significance. High-mobility group-box 1 protein (HMGB1), a late-onset pro-inflammatory cytokine, is secreted by activated macrophages. Soluble hemoglobin scavenger receptor (sCD163) is a specific marker of anti-inflammatory macrophages. The aim of this study was to investigate the diagnostic value of HMGB1 and sCD163 concentrations in brucellosis and its various clinical forms. Serum HMGB1 and sCD163 concentrations in 49 brucellosis patients were compared with those in 52 healthy control subjects. Both serum HMGB1 and sCD163 concentrations were significantly higher in brucellosis patients than in healthy controls (P < 0.001). There were no statistically significant differences in serum concentrations of HMGB1 and sCD163 between cases of acute, subacute and chronic brucellosis. Additionally, serum HMGB1 concentrations were positively correlated with sCD163 concentrations, whereas neither HMGB1 nor sCD163 concentrations were correlated with C-reactive protein concentrations, white cell counts or erythrocyte sedimentation rates. Therefore, serum concentrations of HMGB1 and sCD163 may be diagnostic markers for brucellosis, but neither can be used to differentiate the three different forms of this disease (acute, subacute and chronic).

Identification and determination of antibiotic susceptibilities of Brucella strains isolated from patients in van, Turkey by conventional and molecular methods.

Purpose: Brucellosis is a worldwide zoonotic disease and still constitutes a major public health problem. In this study, we aimed to identify biovars of Brucella strains isolated from clinical specimens taken from brucellosis patients from the Eastern Anatolia region as well determine the susceptibility of these isolates to tigecycline and azithromycin, drugs that may serve as alternatives to the conventional drugs used in the therapy.Materials and methods: Seventy-five Brucella spp. isolates were included in the study. All strains were identified by both conventional and molecular methods. Brucella Multiplex PCR kit (FC-Biotech, Code: 0301, Turkey) and B. melitensis biovar typing PCR kit (FC-Biotech, Code: 0302, Turkey) were used for molecular typing. Antimicrobial susceptibilities of all strains were determined by E-tests.Results: By conventional biotyping, 73 strains were identified as B. melitensis biovar 3 and two strains as B. abortus biovar 3. Molecular typing results were compatible with conventional methods. The MIC50 and MIC90 values of doxycycline were 0.047 and 0.094; tigecycline 0.094 and 0.125; trimethoprim/sulfamethoxazole 0.064 and 0.19; ciprofloxacin 0.19 for both; streptomycin 0.75 and 1; rifampin 1 and 2 and azithromycin 4 and 8. According to the MIC values, doxycycline was found to be the most effective antibiotic, followed by tigecycline, trimethoprim-sulfamethoxazole and ciprofloxacin.Conclusion: Currently recommended antibiotics for the treatment of brucellosis such as doxycycline, rifampin, streptomycin, trimethoprim-sulfamethoxazole and ciprofloxacin were found to be still effective. While our results showed that tigecycline can be used an alternative agent in the treatment of brucellosis, azithromycin has not been confirmed as an appropriate agent for the treatment.

Evaluation of Four Hundred and Forty Seven Brucellosis Cases

Brucellosis remains as a widespread zoonosis, both worldwide and in our country that causes serious public health problems with the potential to create disease in humans and animals. The aim of the present study was to examine the characteristics of brucellosis patients followed in our clinic and to compare these cases with those reported in the literature. Four hundred and forty-seven patients who were treated in our clinic between March 2004 and March 2011 for a diagnosis of brucellosis and who were followed for one year after the completion of treatment were retrospectively examined. Data for the patients were obtained using brucellosis follow-up forms. Of the 447 patients, 261 (58.4%) were women, and the mean age was 48±17 years. Focal organ involvement was detected in 178 (40%) cases, with the musculoskeletal system being the leading site (30.6%), followed by the central nervous system (5.4%). Spondylodiscitis exhibited a significant correlation with an advanced age, a high erythrocyte sedimentation rate (ESR) and the C-reactive protein (CRP) level on admission (p=0.001, p=0.0001 and p=0.001, respectively). A significant correlation was found between sacroiliitis and a younger age (p=0.003). Relapse was observed in 35 (7.8%) cases. The present study allowed us to scrutinize the characteristics and complications of patients with brucellosis. Focal organ involvement of the musculoskeletal system was observed in the present cases, particularly spondylodiscitis and sacroiliitis. Spondylodiscitis was detected in elderly patients with high CRP and ESR values, whereas sacroiliitis was seen in younger patients. We believe that age, symptom duration and laboratory parameters should be evaluated in patients with brucellosis and that older patients in particular should be precisely examined for bone and joint complications.

Medical Countermeasures, Protection and Treatment, against the Brucella species

The Brucella species are easily grown, highly infectious to humans by the aerosol route and resistant to harsh environments. These traits have contributed to these being part of the biological weapons programs in the United States (1943-1969), former Soviet Union (1920s-1990s), and Iraq (1973-1991). Brucella species also continue to be an agricultural and public health concern, afflicting about 10% of the livestock and about 500,000 people in developing countries. Although it is generally assumed that infections can be readily cleared with aggressive antibiotic therapy, relapses occur and recent PCR results on the sera of former brucellosis patients suggest that the infections are never totally eliminated. However, within this decade there is likely to be several successes for improved medical countermeasures (protection and treatment) against this bacterium, spurred by recent advances for subunit vaccines, immunomodulators, anti-Brucella antibodies, serum surrogate markers, and liposomal delivery of therapeutics. These discoveries are exciting but perhaps the greatest contribution will be indirect. The new concepts and approaches to improve medical countermeasures against the Brucella species may in turn also apply to several other pathogens equally difficult to protect against or treat.

Epidemiologic, clinical and laboratory findings of patients with brucellosis in Hamadan, west of Iran.

Brucellosis is one of the most common infectious diseases in some areas of Iran. Brucellosis has various clinical manifestations and should be considered in the differential diagnosis of many infectious and non-infectious diseases. The aims of this study were to determine the epidemiological, clinical and laboratory findings of the disease in patients with brucellosis in Hamadan, west of Iran. In this cross- sectional study, 230 brucellosis patients admitted in Farshchian Hospital in Hamadan from March 2005 to March 2010 were studied for epidemiological, clinical and laboratory characteristics of brucellosis. The patients who had manifestations compatible with brucellosis and standard tube agglutination test or Coombs test ≥1/80 plus 2ME ≥1/40 were enrolled. Data were analyzed using SPSS statistical package, version 15. About 43.5% of patients were female with mean age of 40.84 yr old. 27.8% of cases were living in urban and 72.2% in rural areas. The most contagious seasons were spring and summer. The most common transmission way was consuming of contaminated dairy products (60.3%); however, 39.7% of patients had a history of animal contacts. The most common symptoms were fever (77.4%), arthralgia (70%), sweating (47%), malaise and fatigue (46.5%). The most common clinical signs were fever and peripheral arthritis. Leukocytosis and elevated ESR (>20 mm/h) were reported in 20.8% and 59.5% of cases, respectively. Elevated CRP was detected in 52.9% of patients. Brucellosis should be considered in the differential diagnosis of patients with prolonged fever, spondylitis or peripheral arthritis in endemic areas.

Sustained and differential antibody responses to virulence proteins of Brucella melitensis during acute and chronic infections in human brucellosis

Brucellosis is an important zoonotic disease caused primarily by the bacterial pathogens Brucella melitensis and B. abortus. The pathogens cause debilitating febrile illness that can progress into a long-lasting disease with severe complications in humans. Understanding the mechanisms by which the host immune system responds to the infection will provide important information on the pathogenesis and development of differential diagnostic assays. In this study, a protein microarray was used to evaluate the antibody responses of brucellosis patients at different infection stages. A total of 107 outer membrane proteins, surface-exposed or secreted proteins, and known or putative virulence-associated proteins of B. melitensis were successfully expressed in Escherichia coli and used to fabricate the protein microarray. Then, 99 serum samples from acute, chronic, primary infection, or relapse brucellosis patients were probed with the protein microarray. Antibodies to 66 of the proteins were detected at least in one serum sample. Among the antigens, the combination of BMEII0318, BMEII0513, BMEI0748, and BMEII1116 could be used as serodiagnostic antigens for brucellosis. Patients at different infection stages show distinct antibody profiles. The numbers of antibodies in the relapse patients were superior to those in the primary infection patients, and the response magnitude of antibodies in the chronic infection patients was higher than those in the acute brucellosis patients. The sustained and differential antibody profiles of patients at different infection stages have implications for the development of new serological methods for the accurate diagnosis of human brucellosis, and contribute to a more detailed understanding of the pathogenesis of chronic brucellosis.