Seroepidemiology of human fascioliasis and its relationship with anti-Fasciola IgG and liver enzymes as biomarkers of pathogenicity

BackgroundFascioliasis has never been considered a public health concern in Pakistan, although the increasing numbers of human cases reported in south Asia need a re-consideration in the country. The current study aimed to find the seroprevalence of human fascioliasis, associated risk factors and its relationship with liver enzymes as biomarkers of pathogenicity.MethodsThe cross-sectional study was conducted in different districts of Punjab region from May 2014 to August 2016. A total of 546 respondents were screened by using enzyme-linked immunosorbent assay (ELISA) and serum biochemical tests.ResultsHigher seroprevalence was recorded in Muzaffargarh (6.2%) and Bhara kahu (5.9%), while low infection rate in Gujranwala (1.1%) and Islamabad (1.5%). The results of multiple logistic regression analysis showed rural inhabitants (OR=7.9, 95%CI: 2.5–24.8), females (OR=3.5, 95%CI: 1.7–7.1), family size 3–7 (OR=1.7, 95%CI: 1.0–2.9) and socioeconomic condition (OR=3.9, 95%CI: 1.5–10.4) were the significantly (p<0.005) associated risk factors with disease. The results of liver enzymes i.e. aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transferase and cholesterol levels were significantly (p=0.001) elevated and associated with fascioliasis pathogenicity.ConclusionThe higher prevalence recorded may explain with Fasciola IgG antibodies for both active and past infections and cross reactivity of the assay with other helminthes.     

What differs former,light and heavy smokers? Evidence from a post-conflict setting

BackgroundEvidence suggests that people who live in regions affected by the armed conflict are more likely to smoke.ObjectiveThe purpose of this study was to assess factors associated with smoking status in a sample of students in the northern Kosovo province.Materials and methodsA total of 514 students enrolled in University in Kosovska Mitrovica, Kosovo, were recruited between April to June 2015 at Student Public Health Center during mandatory health checks. Participants filled in socio-demographic and behavioral questionnaire and Beck Depression Inventory (BDI). Based on responses about smoking, students were categorized in non-smokers, former smokers, light smokers (1–13 cigarettes/day) and heavy smokers (> 13 cigarettes/day).ResultsOf 514 students, 116 (22.6%) classified themselves as smokers. Higher education level of fathers (Odds ratio [OR]=2.89, 95% confidence interval [CI] 1.30–6.44, p=0.009), not living with smokers (OR=0.42, 95%CI 0.15–0.97, p=0.017) and longer exposure to second hand smoke (OR=1.07, 95%CI 1.01–1.13, p=0.036) was associated with former smoking. Studying medical and natural sciences (OR=2.07, 95%CI 1.05–4.18, p=0.040), consuming alcohol (OR=2.98, 95%CI 1.19–10.03, p=0.020), living with smokers (OR=2.88, 95%CI 1.49–5.56, p=0.002), longer exposure to second hand smoke (OR=1.06, 95%CI 1.01–1.11, p=0.019) and having a more intense depressive symptoms (OR=1.08, 95%CI 1.03–1.13, p=0.002) was associated with light smoking. Being male (OR=0.22, 95%CI 0.07–0.41, p=0.001), older (OR=1.47, 95%CI 1.21–1.78, p=0.001), living with smokers (OR=3.78, 95%CI 1.69–8.07, p=0.001), longer daily exposure to second-hand smoke (OR=1.10, 95%CI 1.04–1.16, p=0.001), and having more severe depressive symptoms (OR=1.12, 95%CI 1.07–1.18, p=0.001) were associated with heavy smoking.ConclusionSmoking prevention and cessation programs should include the entire community, because exposure to environmental second hand smoke may facilitate initiation and more intense smoking. Screening of student smokers for depression should be prioritized in the process of rebuilding the framework for primary and secondary prevention in the post-conflict period.     

Prevalence and associated factors of pneumonia among under-fives with acute respiratory symptoms: a cross sectional study at a Teaching Hospital in Bushenyi District,Western Uganda

ObjectivesThis study assessed the prevalence and associated factors of pneumonia among children under-five years presenting with acute respiratory symptoms.MethodologyThis was a cross sectional study at the Pediatric Department of Kampala International University – Teaching Hospital, from the month of April to August 2019. The study included 336 children aged 2 to 59 months presenting with acute respiratory symptoms to the pediatric clinic. Pneumonia diagnosis was made according to the World Health Organization definition, modified by a chest radiograph. Structured questionnaires were used to collect data on socio-demographic, environmental and nutrition factors and multivariate logistic regression analysis using STATA version 13.0 was done to assess for the factors independently associated with pneumonia.ResultsOf the 336 children with acute respiratory symptoms, eighty-six, 86 (25.6%) had pneumonia. Factors significantly associated with pneumonia included: age below 6 months (OR=3.2, 95%CI=1.17–8.51, p=0.023), rural residence (OR=5.7, 95%CI=2.97–11.05, p <0.001), not up-to-date for age immunization status (OR=2.9, 95%CI=1.05–7.98, p=0.039), severe acute malnutrition (OR=10.8, 95%CI=2.01–58.41, p=0.006), lack of exclusive breastfeeding during the first six months (OR=2.9, 95%CI=1.53–5.53, p=0.001) and exposure to cigarette smoke (OR=3.0, 95%CI=1.35–6.80, p=0.007).ConclusionThe prevalence of pneumonia in children under-five years was high. Most of the factors associated with pneumonia are modifiable; addressing these factors could reduce this prevalence.     

Evaluation of Lipopolysaccharides and Polysaccharides of Different Epitopic Structures in the Indirect Enzyme-Linked Immunosorbent Assay for Diagnosis of Brucellosis in Small Ruminants and Cattle

Brucella abortus and Brucella melitensis have surface lipopolysaccharides and polysaccharides carrying B. melitensis-type (M) and B. abortus-type (A) epitopes as well as common (C) epitopes present in all smooth Brucella biotypes. Crude lipopolysaccharides, hydrolytic O polysaccharides, and native hapten polysaccharides of MC or AC specificity were evaluated in indirect enzyme-linked immunosorbent assays with polyclonal, monoclonal, or protein G conjugates by using sera from cattle, sheep, and goats infected with AC, MC, or AMC Brucella biotypes. Regardless of the antigen, the levels of antibodies were lower in goats than in sheep and highest in cattle. The diagnostic performance of the assay was not affected by the absence of lipid A-core epitopes, the presence of contaminating outer membrane proteins, the AC or MC epitopic structure of the absorbed antigen, or the conjugate used. Moreover, with sera from cattle vaccinated with B. abortus S19 (AC) or from sheep and goats vaccinated with B. melitensis Rev 1 (MC), AC and MC antigens showed similar levels of reactivity. The results show that antibodies to the C epitopes largely dominate in infection, and this is consistent with the existence of multiple overlapping C epitopes (V. Weynants, D. Gilson, A. Cloeckaert, A. Tibor, P. A. Denoel, F. Godfroid, J. N. Limet, and J.-J. Letesson, Infect. Immun. 65:1939–1943, 1997) rather than with one or two C epitopes. It is concluded that, by adaptation to the corresponding antibody levels, brucellosis in cattle, sheep, and goats can be diagnosed by immunosorbent assay with a single combination of conjugate and antigen.     

Association between the Interleukin-10 -1082 G/A polymorphism and risk of hepatocellular carcinoma

BackgroundInconsistent results have been reported from studies investigating the relationship of the interleukin-10 (IL-10) -1082 G/A polymorphism and the susceptibility of hepatocellular carcinoma (HCC). Therefore, a thorough literature review of relatedstudies was performed in this meta-analysis to examine the association of the interleukin-10(IL-10) -1082 G/A polymorphism with HCC susceptibility.MethodsElectronic databases were searched for literature on the relationship between interleukin-10(IL-10) -1082 G/A polymorphism and the risk of HCC in accordance with the inclusion and exclusion criteria. The selected studies were analyzed using the Stata 12.0 software. Finally, the strength of the associations was evaluated using the odds ratio (OR) and 95% confidence intervals (95% CI).ResultsA total of six case-control studies were enrolled into the current meta-analysis, which included a total of 911 patients and 1889 control subjects. Our data revealed no association between the IL-10 -1082 G/A polymorphism and the risk of HCC (GG vs AA:OR=0.84, 95%CI=0.57–1.25; AG vs AA:OR=0.85, 95%CI=0.70–1.05; Dominant model: OR=0.85, 95%CI=0.70–1.03; and Recessive model: OR=0.92, 95%CI = 0.64–1.32). Similarly, no association was found in sub-group analysis based on ethnicity.ConclusionThe results of our study suggest no association between IL-10 -1082 G/A polymorphism and the risk of HCC.     

Vaccination with recombinant L7/L12-truncated Omp31 protein induces protection against Brucella infection in BALB/c mice

Brucellosis is the most common bacterial zoonotic disease worldwide and no vaccine is available for the prevention of human brucellosis. In humans, brucellosis is mostly caused by Brucella melitensis and Brucella abortus. The Outer membrane protein 31 (Omp31) and L7/L12 are immunodominant and protective antigens conserved in human Brucella pathogens. In the present study, we evaluated the humoral and cellular immune responses induced by a fusion protein designed based on the Truncated form of Omp31 (TOmp31) and L7-L12 antigens. Vaccination of BALB/c mice with the recombinant fusion protein (rL7/L12-TOmp31) provided the significant protection level against B. melitensis and B. abortus challenge. Moreover, rL7/L12-TOmp31 elicited a strong specific IgG response (higher IgG2a titers) and significant IFN-γ/IL2 production and T-cell proliferation was also observed. The T helper1 (Th1) oriented response persisted for 12 weeks after the first immunization. The rL7/L12-TOmp31 could be a new potential antigen candidate for the development of a subunit vaccine against B. melitensis and B. abortus.     

Frequency of P16INK4a and P14ARF Genes Methylation and Its Impact on Bladder Cancer Cases in North Indian Population

Introduction: Amongst the genitourinary cancers, carcinoma of the urinary bladder is one of the leading causes of death in India. Hypermethylation of the CpG islands of gene promoter is one of the earliest and most frequent epigenetic alterations leading to cancer as well as in its development. Several studies have suggested that tumour suppressor genes play a key role in the development of cancer. Methylation in the CDKN2A has been associated with various malignant diseases, but information with respect to urinary bladder cancer is lacking in north Indian population. Materials and methods: We analyzed the methylation of P16INK4a and P14ARF in 80 tissues and matched blood samples of patients suffering from bladder cancer and 80 blood samples of cancer-free individuals by MS-PCR. Results: In tissue and matched blood samples of bladder cancer patients, the incidence of P14ARF hypermethylation significantly increased (OR = 0.31, 95%CI = 0.12–0.8, P = 0.01) and (OR = 0.0, 95%CI=0.0–0.62, P = 0.006) respectively with an increase in age. Clinicopathological analysis revealed that P14ARF hypermethylation in tissue and blood samples was significantly associated with invasive stage (≥ T2) (OR = 0.21, 95%CI = 0.08–0.51, P = 0.0002) and (OR = 0.09, 95%CI = 0.03–0.37, P = 0.00001) respectively. Muscle invasive tumour stage (≥T2) showed significant association with increased risk of P16INK4α promoter hypermethylation in tissue and blood samples of patients (OR = 0.38, 95%CI = 0.17–0.82, P = 0.01) and (OR = 0.13, 95%CI = 0.05–0.36, P = 0.00005) respectively. Conclusion: These results suggest that the CpG island hypermethylation status of the defined panel of genes may be a useful biomarker in patients suffering from bladder cancer.     

Bacteriospermia,extended spectrum beta lactamase producing Gram-negative bacteria and other factors associated with male infertility in Mwanza,Tanzania: a need of diagnostic bacteriology for management of male infertility

BackgroundInfections caused by Extended spectrum beta lactamase (ESBL) producing bacterial are global challenge. There is limited information on the magnitude of bacteriospermia, ESBL producing Gram-negative bacteria (GNB) causing bacteriospermia and factors associated with male infertility. This study determined magnitude of bacteriospermia, ESBL-GNB and other factors association with infertility among presumptive infertile men in Mwanza, Tanzania.MethodsA cross-sectional hospital-based study was conducted between May 2017 and July 2018 among 137 presumptive infertile men. Semen specimens were self-collected by masturbation into clean, sterile and none-spermicidal containers and processed following laboratory standard operating procedures (SOPs). Data analysis was done using STATA 13.0.ResultsGram-negative bacteria were predominantly isolated (86.4%), of which 31.6% were ESBL producers. In a total 44 bacteria were isolated from semen culture. The blaCTX-M gene was detected in 75% of phenotypically confirmed ESBL producers. Infertility was independently found to be associated with abnormal spermatozoa morphology (OR (95%CI): 14.48(3.17–66.05)) and abnormal spermatozoa motility (OR (95%CI): 0.05(0.01–0.24)). However, neither bacteriospermia (OR (95%CI): 0.86(0.29–2.59)) nor ESBL bacteriospermia (OR (95%CI): 0.13(0.01–1.22)) was found to be associated with infertility.ConclusionOne third of bacteriospermia is due to ESBL-producers with history of antibiotic use being protective factor for infertility. Abnormal spermatozoa morphology and poor spermatozoa forward motility independently predicted infertility.     

Cerebrovascular accidents differ between patients with atrial flutter and patients with atrial fibrillation

IntroductionFew studies have explored the potential impact of atrial flutter (AFl) on ischaemic stroke (IS) outcome. The aim of the present study was to compare the clinical course of IS in patients with AFl and patients with atrial fibrillation (AF).Material and methodsA retrospective analysis of patients consecutively admitted to a tertiary care centre between 2013 and 2015 due to IS or transient ischaemic attack with permanent AFl or permanent or persistent AF was performed.ResultsThe study groups consisted of 528 patients, including 490 (92.8%) patients with AF and 38 (7.2%) patients with AFl. The mean age and prestroke CHA2DS2-VASc scores were similar between the patients with AFl and those with AF. Most IS cases in the AF group were classified as cardioembolic strokes (74.9% vs. 39.5% in AFl, p < 0.01), and lacunar strokes were the most common in the AFl group (47.4% vs. 14.3% in AF, p < 0.01). The multivariable analysis revealed that the presence of AF (OR = 8.6, 95% CI: 1.2–57, p = 0.02), lacunar stroke (OR = 0.1, 95% CI: 0.03–0.31, p < 0.001), baseline Rankin scale score (OR = 16.6, 95% CI: 9.8–28), lack of prestroke therapeutic anticoagulation (OR = 6.1, 95% CI: 1.1–33), diabetes (OR = 2.9, 95% CI: 1.3–6.5, p < 0.01), chronic heart failure (OR = 14.2, 95% CI: 5.8–34, p < 0.001), and current smoking (OR = 0.92, 95% CI: 0.39–0.99, p < 0.01) were significantly associated with the stroke outcome.ConclusionsDisabling or fatal IS was observed less often in patients with AFl than in patients with AF. This finding can possibly be explained by the more frequent occurrence of lacunar strokes in the AFl group compared with that in the AF group.     

Bacteriological and molecular investigation of B. melitensis in dairy cows in Iran

It is extremely important to investigate the presence of Brucella melitensis as a nonspecific and heterogeneous agent in dairy cows in Iran due to mixed populations of sheep, goats, and cattle. B. melitensis from infected sheep or goat herds may be introduced into the cattle population in this area. Hence, it is essential to obtain epidemiological data on the probable existence of B. melitensis as a different source of the infection or new exotic Brucella phenotypes development in dairy cow herds in Iran. The purpose of this study was to investigate the presence of B. melitensis infection in cows, using both traditional bacteriological tests and polymerase chain reaction (PCR)-based assay. Traditional biotyping and PCR results of 42 Brucella spp. isolates from Tehran and Fars (northern and southern) provinces of Iran identified five (11.9%) and 37 (88.1%) as B. melitensis (four biovar 1 and one biovar 2) and 37 (88.1%) Brucella abortus biovar 3. This study demonstrated that B. melitensis infection in dairy cows of Iran is still present at a low level. However, the Iranian Veterinary Organization should be careful to have dairy cow herds free of B. melitensis infection as a nonspecific agent of brucellosis, since this type of brucellosis may be extended and act as a potential source of severe infection in humans.     

Brucellosis – Regionally Emerging Zoonotic Disease?

Aim

To gain deeper insight into the seroprevalence of brucellosis, which remains a zoonotic disease of worldwide public health concern, by reviewing studies from countries including North Africa, the Middle East, and India.

Methods

Studies on brucellosis performed in countries that are neighbors or important trading partners of the European Union and on trade animals and their products were analyzed. We reviewed 37 seroprevalence studies on brucellosis published from 1948 to 2009 retrieved from PubMed, Google, and ScienceDirect.

Results

The set of studies was heterogeneous in the number of samples and laboratory tests used. We included studies from Algeria (n = 1), Egypt (n = 7), India (n = 3), Iran (n = 3), Iraq (n = 1), Jordan (n = 5), Libya (n = 3), Saudi Arabia (n = 3), Syria (n = 1), Turkey (n = 5), and Yemen (n = 2). The total number of animals in these studies was 116 317 (cattle 75 375; buffalo 9644; sheep 10 550; goats 14 447; camels 6301). The prevalence of brucellosis in different animal species varied widely. Representative surveillance data have not recently been published in any of the countries.

Conclusions

Wars in the Middle East, insufficient preventive measures, the lack of adequate control programs in some countries, as well as uncontrolled animal transportation through “open” borders increased the risk that brucellosis will spread in some regions. New seroprevalence data are needed urgently to evaluate the current situation and for continuous monitoring of necessary control programs.Brucellosis is one of the most important worldwide zoonoses affecting livestock and humans (1). Brucellae are facultative intracellular, Gram-negative coccobacilli that lack capsules, flagelle, and endospores. The genus Brucella comprises a group of closely related bacteria. The species B. melitensis (which infects sheep and goats), B. suis (swine), and B. abortus (cattle) cause significant economic losses for animal owners and severe human disease. Brucella spp are also a focus of interest as they are categorized as biological agents due to their high contagiousness and their impact on human and animal health. The zoonotic pathogens B. abortus, B. melitensis, and B. suis were designated as select agents of Category B by the Centres for Disease Control in Atlanta, USA. This review analyzes studies from North Africa, the Middle East, and India to gain a clear picture of our current understanding of brucellosis and assess threats to transmission into the European Union (EU). The review also identifies areas where research is sorely needed to ensure that brucellosis epidemics are avoided in the future.     

Systematic review with meta-analysis: Non-alcoholic fatty liver disease and the association with pregnancy outcomes

Background/AimsMaternal and fetal outcomes in pregnant patients with Non-alcoholic fatty liver disease (NAFLD) have been largely unexplored. To determine the level of evidence associated with maternal and fetal outcomes in pregnant women with NAFLD.MethodsWe conducted a comprehensive literature search. The studies included pregnant patients with a previous, current or subsequent diagnosis of NAFLD. We used a random-effects model using odds ratios (OR) with 95% confidence intervals (CI).ResultsTwenty-two studies, with 13,641 female NAFLD patients were reviewed. The results highlight that NAFLD patients had a statistically significant increased likelihood of baseline diabetes mellitus (OR, 6.00; 95% CI, 2.21–16.31; P<0.001; n=7), baseline Hypertension (OR, 3.75; 95% CI, 2.13–6.59; P<0.001; n=4), gestational hypertension (OR, 1.83; 95% CI, 1.03–3.26; P=0.041; n=2), and pre-eclampsia (OR, 2.43; 95% CI, 1.46–4.04; P=0.001; n=3). The odds for a past and current history of gestational diabetes mellitus were OR, 3.78; 95% CI, 2.21–6.44; P<0.001; n=5 and OR, 3.23; 95% CI, 1.97– 5.31; P<0.001; n=6, respectively. As for fetal outcomes, pregnant NAFLD patients were significantly more likely to have a premature birth (OR, 2.02; 95% CI, 1.44–2.85; P<0.001; n=4), large for gestational age birth (OR, 2.01; 95% CI, 1.72–2.37; P<0.001; n=2) or a history of prior miscarriage or abortion (OR, 1.15; 95% CI, 1.02–1.30; P=0.02; n=2). Egger’s regression revealed no evidence of publication bias (P>0.05).ConclusionsThis meta-analysis provides pooled evidence that NAFLD is associated with a substantial increase in maternal diabetic and hypertensive complications and multiple adverse fetal outcomes. This data is important for clinicians managing these patients before, during and after pregnancy.     

Aerosol infection of BALB/c mice with Brucella melitensis and Brucella abortus and protective efficacy against aerosol challenge

Brucellosis is a zoonotic disease with a worldwide distribution that can be transmitted via intentional or accidental aerosol exposure. In order to engineer superior vaccine strains against Brucella species for use in animals as well as in humans, the possibility of challenge infection via aerosol needs to be considered to properly evaluate vaccine efficacy. In this study, we assessed the use of an aerosol chamber to infect deep lung tissue of mice to elicit systemic infections with either Brucella abortus or B. melitensis at various doses. The results reveal that B. abortus causes a chronic infection of lung tissue in BALB/c mice and peripheral organs at low doses. In contrast, B. melitensis infection diminishes more rapidly, and higher infectious doses are required to obtain infection rates in animals similar to those of B. abortus. Whether this difference translates to severity of human infection remains to be elucidated. Despite these differences, unmarked deletion mutants BAΔasp24 and BMΔasp24 consistently confer superior protection to mice against homologous and heterologous aerosol challenge infection and should be considered viable candidates as vaccine strains against brucellosis.     

IFN-γ +874 A>T (rs2430561) gene polymorphism and risk of pulmonary tuberculosis: a meta-analysis

IntroductionThe role of interferon gamma (IFN-γ) +874 A>T (rs2430561) gene polymorphism has been evaluated in different ethnicities with pulmonary tuberculosis (PTB) infection, and inconsistent results have been reported. In this study, a meta-analysis was performed to determine the precise association between IFN-γ +874 A>T gene polymorphism and PTB susceptibility.Material and methodsA total of 21 studies comprising 4281 confirmed PTB cases and 5186 healthy controls were included in this meta-analysis by searching the PubMed (Medline), EMBASE, and Google Scholar web-databases.ResultsWe observed reduced risk of PTB in allelic contrast (T vs. A: p = 0.001; OR = 0.818, 95% CI: 0.723–0.926), homozygous (TT vs. AA: p = 0.017; OR = 0.715, 95% CI: 0.543–0.941), heterozygous (AT vs. AA: p = 0.002; OR = 0.782, 95% CI: 0.667–0.917), dominant (TT+AT vs. AA: p = 0.002; OR = 0.768, 95% CI: 0.652–0.906), and recessive (TT vs. AA+AT: p = 0.042; OR = 0.802, 95% CI: 0.649–0.992) genetic models. In ethnicity-wise subgroup analysis, reduced risk of PTB was found in the Caucasian population. However, we did not find an association with any of the genetic models in the Asian population.ConclusionsIn conclusion, the IFN-γ +874 A>T gene polymorphism is significantly associated with reduced risk of PTB, showing a protective effect in the overall and in the Caucasian population. However, this polymorphism is not associated with PTB risk in the Asian population.     

Relationships of depression and anxiety to readmission rates among patients with diabetes from Harare and Parirenyatwa referral hospitals in Zimbabwe

BackgroundThe knowledge of determinants of readmission among individuals with diabetes minimises relapse and decreases diabetes associated morbidity and mortality.ObjectivesTo explore the prevalence of depression and anxiety as well as determinants of readmission in individuals with diabetes from Harare, Zimbabwe.MethodsA cross sectional study was carried out at Parirenyatwa and Harare group of hospitals. Participants were recruited through purposive sampling and interviewed at the diabetic clinics. Depression and anxiety were measured using the Hospital Anxiety and Depression Scale. Binary logistic regression was used to determine predictors of readmission.ResultsIn total 65 participants took part, 36.9% were males. The mean age ±SD was 44.89±14.2 years. Anxiety affected 40% and 20% were at risk of anxiety, while depression was reported in 27.7% and 30.8% were at risk of depression. Depression [OR=0.64, 95%CI: 0.42–0.97 (p=0.037)] and checking of blood glucose [OR=0.06, 95%CI: 0.01–0.71 (p=0.025)] were significant negative predictors of readmission among diabetic patients while anxiety was a significant positive predictor OR=1.55, 95%CI: 1.09–2.21 (p=0.015).ConclusionsMental health conditions in people living with diabetes are factors contributing to increased re admissions and are more prevalent with aging. Psychotherapy and education interventions are recommended for the elderly diabetic population.     

VirB12 is a serological marker of Brucella infection in experimental and natural hosts

The Brucella species type IV secretion system, encoded by the virB1-12 locus, is required for intracellular replication and persistent infection in vivo. The requirement of VirB proteins for infection suggests that they are expressed in vivo and may therefore represent serological markers of infection. To test this idea, we purified recombinant VirB1, VirB5, VirB11, and VirB12 and tested for their recognition by antibodies in sera from experimentally infected mice and goats by using an indirect enzyme-linked immunosorbent assay. Antibody responses to VirB12 but not to VirB1, VirB5, or VirB11 were detected in 20/20 mice experimentally inoculated with Brucella abortus and 12/12 goats experimentally infected with Brucella melitensis. The potential use of VirB12 as a serological tool for the diagnosis of brucellosis was evaluated in the natural bovine host. Serum samples from 145 cattle of known serology (29% negative and 71% positive) were analyzed for the production of antibody responses to VirB12. One hundred two cattle samples (70.3%) were positive for antibodies to VirB12, while 43 samples were negative (29.7%). A positive serological response to VirB12 correlated with positive serology to whole B. abortus antigen in 99% of samples tested. These results show that VirB12 is expressed during infection of both experimental and natural hosts of Brucella species, and they suggest that VirB12 may be a useful serodiagnostic marker for brucellosis.     

Factors associated with gastro-duodenal ulcer in compensated type 2 diabetic patients: a Romanian single-center study

IntroductionHelicobacter pylori infection is accepted as the leading cause of chronic gastritis, ulcer disease and gastric cancer, with an important impact on health care burden, especially in countries with a high prevalence of infection. The aim of the study was to investigate the influence of H. pylori infection, medication, associated medical conditions or social habits on endoscopic ulcer occurrence in the compensated type 2 diabetic population.Material and methodsTwo hundred and sixty type 2 diabetic patients investigated on endoscopy (57 patients with peptic ulcer and 203 controls) with a complete set of biopsies, demographic and medical data were enrolled.ResultsOn univariate regression analysis, H. pylori infection (42.1% vs. 35.5%, p = 0.359) or a history of peptic ulcer (61.4% vs. 61.6%, p = 0.981) was not a predictor for ulcer on endoscopy in the diabetic population, and heartburn was more frequent in diabetics without ulcer (21.2% vs. 8.8%, p = 0.033). Anemia was the best predictor for ulcer on endoscopy in both diabetics with (p < 0.001, OR = 4.77, 95% CI: 2.02–11.28) and without (p = 0.027, OR = 2.76, 95% CI: 1.10–6.91) chronic proton pump inhibitor (PPI) therapy. In diabetic patients on PPI more than 1 month anticoagulants – acenocoumarol or low-weight molecular heparin (p = 0.038, OR = 2.37, 95% CI: 1.04–5.40), low-dose aspirin 75–125 mg/day (p = 0.029, OR = 2.61, 95% CI: 1.08–6.28) and alcohol consumption (p = 0.015, OR = 2.70, 95% CI: 1.19–6.13) were predictors for ulcer on endoscopy.ConclusionsIn diabetic patients, anemia is the most important predictor for ulcer on endoscopy, but not H. pylori or digestive symptoms, while low-dose aspirin or anticoagulant therapy and alcohol consumption are the most important predictors for ulcer in diabetics on chronic proton pump inhibitor therapy.     

Improved immunogenicity and protective efficacy of a divalent DNA vaccine encoding Brucella L7/L12-truncated Omp31 fusion protein by a DNA priming and protein boosting regimen

Brucellosis is one of the most common zoonotic diseases caused by species of Brucella. At present, there is no commercially available vaccine for the human brucellosis. Brucella melitensis and Brucella abortus are the main causes of human brucellosis, worldwide. The outer membrane protein 31 (Omp31) and L7/L12 are immunodominant and protective antigens conserved among human Brucella pathogens. The purpose of the current study was to evaluate and compare the immunogenicity and protective efficacy of the L7/L12-TOmp31 construct administered as DNA/DNA and DNA/Pro vaccine regimens. Vaccination of BALB/c mice with the DNA/Pro regimen provided more protection levels against B. melitenisis and B. abortus challenge than did the DNA/DNA regimen. IgG1 and IgG2a titers were higher in the sera from DNA/Pro-immunized mice than in those from mice immunized with DNA alone. Moreover, splenocytes from DNA/Pro-immunized mice produced significantly higher levels of IFN-γ than did those from mice given DNA alone. The pcDNA-L7/L12-TOmp31 priming followed by rL7/L12-TOmp31 boosting led to improved protection against B. abortus or B. melitensis infection.     

Inhaled Corticosteroid and Secondary Glaucoma: A Meta-analysis of 18 Studies

PurposeGuidelines and systematic reviews frequently warn of inhaled corticosteroid (ICS)-induced glaucoma. However, most of the published studies deny it.MethodsWe performed a systematic review of randomized, cohort, nested-case control, cross-sectional studies by using Meta-analyses of Observational Studies in Epidemiology statement. Four major databases, PubMed, EMBASE, Cochrane Search Manager, and the Web of Science Core Collection as well as meta-analysis were used. Studies comparing incidence, prevalence and intraocular pressure (IOP) between patients who were treated with and without ICSs were included. A random-model meta-analysis was performed using the inverse variance method.ResultsOut of 623 studies screened, 18 with 31,665 subjects were finally included. No significant difference between the 2 groups was observed for crude glaucoma incidence (odds ratio [OR], 0.95; 95% confidence interval [CI], 0.86–1.04; P = 0.26; I ² = 0%; P for heterogeneity = 0.57) as a primary endpoint, adjusted glaucoma incidence (OR, 0.90; 95% CI, 0.65–1.24; P = 0.64), crude prevalence (OR, 1.82; 95% CI, 0.23–14.19; P = 0.57), adjusted prevalence (OR, 1.22; 95% CI, 0.50–2.96; P = 0.66), IOP change during ICS treatment (mean difference [MD] +0.01 mmHg; 95% CI, −0.19–0.20; P = 0.95), and single measurement IOP (MD +0.37 mmHg; 95% CI, −0.24–0.97; P = 0.23). Time-to-event analysis for glaucoma development as one of the secondary endpoints (adjusted hazard ratio, 0.52; 95% CI, 0.28–0.96) suggested a reverse association between ICS and glaucoma.ConclusionsThe ophthalmological side effects of ICSs, such as glaucoma and intraocular hypertension, should not be exaggerated.Trial RegistrationUniversity Hospital Medical Information Network Center Clinical Trial Registry Identifier: UMIN000040351     

Serological,Bacteriological, and Molecular Diagnosis of Brucellosis in Domestic Animals in Croatia

Aim

To present the surveillance data on Brucella melitensis, B. suis, and B. ovis infection in cattle, sheep, goats, and swine in Croatia obtained in 2008 by serological, bacteriological, and molecular methods for diagnostics of brucellosis in domestic animals.

Methods

We serologically tested 42 785 cattle serums, 22 686 sheep and goat serums, and 28 520 swine serums using the Rose Bengal test, complement fixation test, and various immunosorbent assays. We also tested 10 173 ram blood samples for B. ovis infection using the complement fixation test. Bacteriological examination was conducted on 214 samples collected from 34 serologically positive animals. Different molecular methods were employed in the identification and typing of 20 isolates from the samples.

Results

B. melitensis biovar (bv.) 3 was confirmed with different identification methods in 2 flocks in 2 Croatian counties and B. suis bv. 2 in 3 herds in 3 counties. B. melitensis in cows was confirmed for the first time in Croatia. Infection with B. ovis was serologically confirmed in 202 rams in 12 counties.

Conclusions

In 2008, the size of the brucellosis-affected area in Croatia and the efficiency of detection and prevention of brucellosis in sheep, goats, and swine were satisfactory. Infection with B. melitensis in cattle was confirmed for the first time and possible links for infection in humans were detected. More efficient measures for suppression and control of ovine epididymitis are required and a new strategy may be necessary for complete eradication of this disease.Brucellosis is a chronic infectious disease caused by bacteria of the genus Brucella that affects animals and humans. Each species of Brucella has their preferred host: B. abortus infects cattle, B. metitensis sheep and goats, B. suis swine, B. canis dogs, and B. ovis sheep, although they can also infect other animals (1). Brucellosis in sheep and goats is endemic in the Mediterranean region but is spread throughout Asia, Africa, and Central and South America (2,3). Along with tuberculosis and rabies, brucellosis is the most important bacterial zoonosis and remains an important public health and economic concern.With the exception of B. ovis and B. neotomae, all Brucella species can cause infections in humans. New Brucella species pathogenic for humans – B. ceti and B. pinnipedialis – have recently been discovered in marine mammals (4). Infection is transmitted to humans though direct contact with the infected animals or by consuming infected milk or fresh cheese (1).In Croatia, brucellosis in domestic animals is controlled in accordance with the annual order issued by the Ministry of Agriculture. Serological blood examination of all male breeding animals is mandatory twice per year, and all cases of abortion must be reported and tested for brucellosis. On large cattle and pig farms, 20% of breeding animals must be tested annually. Castration of seropositive rams without the obligation of bacteriological testing is required as an eradication measure for B. ovis infection.Bovine brucellosis (B. abortus) was eradicated in Croatia in 1964, while brucellosis in sheep and goats has occurred sporadically in the recent years, limited to 1-2 sheep flocks per year. All of the occurrences have resulted from epizooty originating in the neighboring country of Bosnia and Herzegovina (BH) (5,6). Swine brucellosis has been detected in swine and wild boars during regular controls (7,8) and B. suis isolates were determined as biovars (bv.) 1, 2, or 3 (7-11).B. ovis in rams and sheep causes either clinical or subclinical disease and is not pathogenic for humans (12). According to simulation models, B. ovis infection causes significant economic losses in flocks with no control measures, but there is no exact confirmation of the extent of such losses (13,14). Eradication is possible, but requires considerable resources.The aim of this study was to determine the effectiveness of the existing programs for diagnosis and control of brucellosis in domestic animals in order to prevent transmission of disease to humans and to reduce economic losses in animal production. This article describes the spread of brucellosis caused by B. melitensis, B. suis, and B. ovis in cattle, sheep, goats, and swine in the Republic of Croatia in 2008, as determined using different diagnostic methods.