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Objectives The European Single Hub and Access point for paediatric Rheumatology in Europe initiative aimed to optimize care for children with rheumatic diseases. Kawasaki disease (KD) is the most common cause of acquired heart disease in children and an important cause of long-term cardiac disease into adulthood. Prompt diagnosis and treatment of KD is difficult due to the heterogeneity of the disease but is crucial for improving outcome. To date, there are no European internationally agreed, evidence-based guidelines concerning the diagnosis and treatment of KD in children. Accordingly, treatment regimens differ widely. The aim of this study is to provide consensus-based, European-wide evidence-informed recommendations for diagnosis and treatment of children with KD. Methods Recommendations were developed using the EULAR's standard operating procedures. An extensive systematic literature search was performed, and evidence-based recommendations were extrapolated from the included papers. These were evaluated by a panel of international experts via online surveys and subsequently discussed in three consensus meetings, using nominal group technique. Recommendations were accepted when ⩾80% agreed. Results In total, 17 recommendations for diagnosis and 14 for treatment of KD in children were accepted. Diagnostic recommendations included laboratory and imaging workup for complete as well as incomplete KD. Treatment recommendations included the importance of early treatment in both complete and incomplete KD, use of intravenous immunoglobulin, aspirin, corticosteroids for high-risk cases, and other treatment options for those with resistant disease. Conclusion The Single Hub and Access point for paediatric Rheumatology in Europe initiative provides international evidence-based recommendations for diagnosing and treating KD in children, facilitating improvement and uniformity of care. [ABSTRACT FROM AUTHOR]

Background: Knowledge of HIV status can be important in reducing the risk of HIV exposure. In a European sample of men-who-have-sex-with-men (MSM), we aimed to identify factors associated with HIV serostatus disclosure to the most recent anal intercourse (AI) partner. We also aimed to describe the impact of HIV serostatus disclosure on HIV exposure risks.Methods: During 2013 and 2014, 4901 participants were recruited for the bio-behavioural Sialon-II study in 13 European cities. Behavioural data were collected with a self-administered paper questionnaire. Biological specimens were tested for HIV antibodies. Factors associated with HIV serostatus disclosure with the most recent AI partner were examined using bivariate and multilevel multivariate logistic regression analysis. We also describe the role of serostatus disclosure for HIV exposure of the most recent AI partner.Results: Thirty-five percent (n = 1450) of the study participants reported mutual serostatus disclosure with their most recent AI partner or disclosed having HIV to their partner. Most of these disclosures occurred between steady partners (74%, n = 1077). In addition to the type of partner and HIV diagnosis status, other factors positively associated with HIV serostatus disclosure in the multilevel multivariate logistic regression model were recent testing, no condom use, and outness regarding sexual orientation. Disclosure rates were lowest in three south-eastern European cities. Following condom use (51%, n = 2099), HIV serostatus disclosure (20%, n = 807) was the second most common prevention approach with the most recent AI partner, usually resulting in serosorting. A potential HIV exposure risk for the partner was reported by 26% (111/432) of HIV antibody positive study participants. In 18% (20/111) of exposure episodes, an incorrect HIV serostatus was unknowingly communicated. Partner exposures were equally distributed between steady and non-steady partners.Conclusions: The probability of HIV exposure through condomless AI is substantially lower after serostatus disclosure compared to non-disclosure. Incorrect knowledge of one's HIV status contributes to a large proportion of HIV exposures amongst European MSM. Maintaining or improving condom use for anal intercourse with non-steady partners, frequent testing to update HIV serostatus awareness, and increased serostatus disclosure particularly between steady partners are confirmed as key aspects for reducing HIV exposures amongst European MSM. [ABSTRACT FROM AUTHOR]

Recent evidence brought by novel anti-human epidermal growth factor receptor 2 (HER2) antibody-drug conjugates is leading to significant changes in HER2-negative breast cancer (BC) best practices. A new targetable category termed 'HER2-low' has been identified in tumors previously classified as 'HER2-negative'. Daily practice in pathology and medical oncology is expected to align to current recommendations, but patient access to novel anticancer drugs across geographies might be impeded due to local challenges. An expert meeting involving ten regional pathology and oncology opinion leaders experienced in BC management in four Central and Eastern Europe (CEE) countries (Bulgaria, Croatia, Serbia, Slovenia) was held. Herein we summarized the current situation of HER2-low metastatic BC (mBC), local challenges, and action plans to prevent delays in patient access to testing and treatment based on expert opinion. Gaps and differences at multiple levels were identified across the four countries. These included variability in the local HER2-low epidemiology data, certification of pathology laboratories and quality control, and reimbursement conditions of testing and anticancer drugs for HER2-negative mBC. While clinical decisions were aligned to international guidelines in use, optimal access to testing and innovative treatment was restricted due to significant delays in reimbursement or limitative reimbursement conditions. Preventing delays in HER2-low mBC patient access to diagnosis and novel treatments is crucial to optimize outcomes. Multidisciplinary joint efforts and pro-active discussions between clinicians and decision makers are needed to improve care of HER2-low mBC patients in CEE countries. [ABSTRACT FROM AUTHOR]

Background: Around 20% of the population in Northern and Central Europe is affected by birch pollen allergy, with the major birch pollen allergen Bet v 1 as the main elicitor of allergic reactions. Together with its cross-reactive allergens from related trees and foods, Bet v 1 causes an impaired quality of life. Hence, new treatment strategies were elaborated, demonstrating the effectiveness of blocking IgG antibodies on Bet v 1-induced IgE-mediated reactions. A recent study provided evidence for the first time that Bet v 1-specific nanobodies reduce patients' IgE binding to Bet v 1. In order to increase the potential to outcompete IgE recognition of Bet v 1 and to foster cross-reactivity and cross-protection, we developed Bet v 1-specific nanobody trimers and evaluated their capacity to suppress polyclonal IgE binding to corresponding allergens and allergeninduced basophil degranulation. Methods: Nanobody trimers were engineered by adding isoleucine zippers, thus enabling trimeric formation. Trimers were analyzed for their cross-reactivity, binding kinetics to Bet v 1, and related allergens, and patients' IgE inhibition potential. Finally, their efficacy to prevent basophil degranulation was investigated. Results: Trimers showed enhanced recognition of cross-reactive allergens and increased efficiency to reduce IgE-allergen binding compared to nanobody monomers. Furthermore, trimers displayed slow dissociation rates from allergens and suppressed allergen-induced mediator release. Conclusion: We generated high-affine nanobody trimers that target Bet v 1 and related allergens. Trimers blocked IgE-allergen interaction by competing with IgE for allergen binding. They inhibited IgE-mediated release of biological mediators, demonstrating a promising potential to prevent allergic reactions caused by Bet v 1 and relatives. [ABSTRACT FROM AUTHOR]

Abstract: As women vaccinated against measles transfer low amounts of antibodies, an increasing number of infants lack early protection through maternal antibodies until being immunised themselves. This paper reviews the literature on disease burden of measles in the population too young to be immunized according to the respective national recommendations during recent outbreaks in EU and EEA/EFTA countries. In addition, specific control strategies adopted to protect this young population are reviewed. Pubmed, Unbound Medline, Web of Knowledge and the Eurosurveillance database were searched using MESH terms: measles and epidemiology, measles and infants, prevalence of measles, measles and outbreaks and measles and epidemic. Additionally, data from Euvac.net and ECDC were consulted. Databases were searched from January 2001 to September 2011. Fifty-three papers were included in the analysis. The percentage of all measles cases during outbreaks affecting young infants ranged from 0.25% to 83.0%. Specific control strategies were adopted: e.g. administration of the first or second vaccine dose earlier than recommended. Infants younger than 12 months are often involved in measles outbreaks, and advancing the first vaccine dose could reduce the burden of disease. However, immunization before 9 months of age is not systematically recommended because of dysmature humoral immune responses of infants. High coverage and timely administration of the recommended series of vaccines are the most important measures to decrease measles incidence and measles circulation and protect vulnerable infants from infection. [Copyright &y& Elsevier]

Please cite this paper as: De Vleeschauwer et al. (2011) Cross-protection between antigenically distinct H1N1 swine influenza viruses from Europe and North America. Influenza and Other Respiratory Viruses 5(2), 115-122. An avian-like H1N1 swine influenza virus (SIV) is enzootic in swine populations of Western Europe. The virus is antigenically distinct from H1N1 SIVs in North America that have a classical swine virus-lineage H1 hemagglutinin, as does the pandemic (H1N1) 2009 virus. However, the significance of this antigenic difference for cross-protection among pigs remains unknown. We examined protection against infection with a North American triple reassortant H1N1 SIV [A/swine/Iowa/H04YS2/04 (sw/IA/04)] in pigs infected with a European avian-like SIV [A/swine/Belgium/1/98 (sw/B/98)] 4 weeks earlier. We also examined the genetic relationships and serologic cross-reactivity between both SIVs and with a pandemic (H1N1) 2009 virus [A/California/04/09 (Calif/09)]. After intranasal inoculation with sw/IA/04, all previously uninfected control pigs showed nasal virus excretion, high virus titers in the entire respiratory tract at 4 days post-challenge (DPCh) and macroscopic lung lesions. Most pigs previously infected with sw/B/98 tested negative for sw/IA/04 in nasal swabs and respiratory tissues, and none had lung lesions. At challenge, these pigs had low levels of cross-reactive virus neutralizing and neuraminidase inhibiting (NI) antibodies to sw/IA/04, but no hemagglutination-inhibiting antibodies. They showed similar antibody profiles when tested against Calif/09, but NI antibody titers were higher against Calif/09 than sw/IA/04, reflecting the higher genetic homology of the sw/B/98 neuraminidase with Calif/09. Our data indicate that immunity induced by infection with European avian-like H1N1 SIV affords protection for pigs against North American H1N1 SIVs with a classical H1, and they suggest cross-protection against the pandemic (H1N1) 2009 virus. [ABSTRACT FROM AUTHOR]

Purpose: Visceral leishmaniasis (VL) has become a rising concern to transplantation teams, being associated with graft dysfunction and reduced survival of renal transplant recipients. Here, we describe a case of VL occurring in a kidney transplant (KT) recipient in Italy, a country in which Leishmania infantum is endemic and we reviewed the literature on the clinical course and diagnosis of VL in KT recipients residing or travelling to southern Europe. Results: The VL case was diagnosed 18 months after transplant and 28 days after the onset of symptoms by quantitative PCR (qPCR) on peripheral blood. A graft biopsy showed renal involvement, and PCR performed on graft tissue displayed the presence of Leishmania DNA. The retrospective confirmation of Leishmania-positive serology in a serum sample collected before transplantation, as well as the absence of anti-Leishmania IgG in the graft donor strongly suggest that reactivation of a latent parasitic infection caused VL in the current case. Conclusion: VL is often underdiagnosed in transplant recipients, despite the presence of latent Leishmania infection being reported in endemic countries. This case report, as well as the literature review on leishmaniasis in KT recipients, underline the importance of rapid VL diagnosis to promptly undergo treatment. Serology is scarcely sensitive in immunocompromised patients, thus molecular tests in peripheral blood should be implemented and standardized for both VL identification and follow-up. [ABSTRACT FROM AUTHOR]

Background: Lyme borreliosis (LB) is the most common tick-borne infectious disease in the northern hemisphere. The diagnosis of LB is usually made by clinical symptoms and subsequently supported by serology. In Europe, a two-step testing consisting of an enzyme-linked immunosorbent assay (ELISA) and an immunoblot is recommended. However, due to the low sensitivity of the currently available tests, antibody detection is sometimes inaccurate, especially in the early phase of infection, leading to underdiagnoses.Methods: To improve upon Borrelia diagnostics, we developed a multiplex Borrelia immunoassay (Borrelia multiplex), which utilizes the new INTELLIFLEX platform, enabling the simultaneous dual detection of IgG and IgM antibodies, saving further time and reducing the biosample material requirement. In order to enable correct classification, the Borrelia multiplex contains eight antigens from the five human pathogenic Borrelia species known in Europe. Six antigens are known to mainly induce an IgG response and two antigens are predominant for an IgM response.Results: To validate the assay, we compared the Borrelia multiplex to a commercial bead-based immunoassay resulting in an overall assay sensitivity of 93.7% (95% CI 84.8-97.5%) and a specificity of 96.5% (95%CI 93.5-98.1%). To confirm the calculated sensitivity and specificity, a comparison with a conventional 2-step diagnostics was performed. With this comparison, we obtained a sensitivity of 95.2% (95% CI 84.2-99.2%) and a specificity of 93.0% (95% CI 90.6-94.7%).Conclusion: Borrelia multiplex is a highly reproducible cost- and time-effective assay that enables the profiling of antibodies against several individual antigens simultaneously. [ABSTRACT FROM AUTHOR]

Aims and Objectives: This systematic review and meta‐analysis reports the seroprevalence of SARS‐CoV‐2 antibodies among nurses. Background: With a growing body of literature reporting the positive serology for SARS‐CoV‐2 antibodies among healthcare workers, it remains unclear whether staff at the point of direct patient care are more prone to developing and transmitting the virus. Given nurses make up the majority of the global health workforce, outbreaks among these workers could severely undermine a health system's capability to manage the pandemic. We aimed to summarise and report the seroprevalence of SARS‐CoV‐2 antibodies among nurses globally. Design: Systematic review and meta‐analyses. Methods: This systematic review was developed, undertaken and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guideline. We searched the electronic medical literature databases: MEDLINE; CINAHL; and EMBASE for studies reporting the seroprevalence of SARS‐CoV‐2 antibodies among nursing staff. Studies that reported nursing specific data were included in this review. Study quality was evaluated using the Joanna Briggs Institute checklist for studies reporting prevalence data. Studies were stratified according to the World Health Organisation region classifications, and results were presented using forest plots and summary prevalence and variance was estimated using a random effects model. Results: Our electronic search identified 1687 potential studies, of which 1148 were screened for eligibility after duplicates were removed, and 51 of the studies were included in our meta‐analysis. The overall seroprevalence of SARS‐CoV‐2 antibodies among nurses was estimated to be 8.1% (95% CI 6.9%–9.4%) among the 60,571 participants included in the studies. Seropositivity was highest in the African region (48.2%, 95% CI 39.2%–57.3%), followed by the European region (10.3%, 95% CI 8.0%–12.5%), the Region of the Americas (8.4%, 95% CI 6.0%–10.7%), the South‐East Asia region (3.0%, 95% CI 0.00%–6.5%) and the Western Pacific region (0.5%, 95% CI 0.0%–1.0%). Pooled estimates were unable to be calculated in the Eastern Mediterranean region due to insufficient studies. Conclusion: The seroprevalence of SARS‐CoV‐2 antibodies among nurses is comparable to other healthcare workers, and possibly similar to the general population. Early adoption and adherence to personal protective equipment and social distancing measures could explain these similarities, meaning the majority of staff contracted the virus through community transmission and not in a healthcare setting. Relevance to clinical practice: Fear and uncertainty have been features of this pandemic, including among nurses. This meta‐analysis should provide some comfort to nurses that risks are similar to community exposure when adequate PPE is available and there is an adherence to infection control measures. [ABSTRACT FROM AUTHOR]

Two COVID-19 mRNA (of BNT162b2, mRNA-1273) and two adenovirus vector vaccines (ChAdOx1 and Janssen) are licensed in Europe, but optimization of regime and dosing is still ongoing. Here we show in health care workers (n = 328) that two doses of BNT162b2, mRNA-1273, or a combination of ChAdOx1 adenovirus vector and mRNA vaccines administrated with a long 12-week dose interval induce equally high levels of anti-SARS-CoV-2 spike antibodies and neutralizing antibodies against D614 and Delta variant. By contrast, two doses of BNT162b2 with a short 3-week interval induce 2-3-fold lower titers of neutralizing antibodies than those from the 12-week interval, yet a third BNT162b2 or mRNA-1273 booster dose increases the antibody levels 4-fold compared to the levels after the second dose, as well as induces neutralizing antibody against Omicron BA.1 variant. Our data thus indicates that a third COVID-19 mRNA vaccine may induce cross-protective neutralizing antibodies against multiple variants. Vaccination shows efficacy in protecting from COVID-19, but regime and dosing optimization is still ongoing. Here the authors show that BNT162b2, mRNA-1273, or their combination with ChAdOx1 induces similar antibody responses, and those receiving three doses of BNT162b2 induce neutralizing antibodies against the Omicron variant. [ABSTRACT FROM AUTHOR]

Adequate follow-up in celiac disease is important to improve dietary compliance and treat disease-related symptoms and possible complications. However, data on the follow-up of celiac children is scarce. We aimed to assess current pediatric celiac follow-up practices across Europe. Pediatricians and pediatric gastroenterologists from 35 countries in Europe, Israel, Turkey, and Russia completed an anonymous survey which comprised a 52-item questionnaire developed by the ESPGHAN Special Interest Group on Celiac Disease. A total of 911 physicians, the majority of whom exclusively worked in pediatric care (83%) and academic institutions (60%), completed the questionnaire. Mean age and mean experience with celiac care were 48.7 years (± 10.6) and 15.7 years (± 9.9), respectively. The vast majority (≥ 92%) always assessed anthropometry, dietary adherence, and tissue-transglutaminase IgA-antibodies at every visit, with the first visit being between 3 and 6 months after diagnosis. Other parameters (% always tested) were as follows: complete blood count (60%), iron status (48%), liver enzymes (42%), thyroid function (38%), and vitamin D (26%). Quality of life was never assessed by 35% of the responding physicians. Transition to adult care was mostly completed via a written transition report (37%) or no formal transition at all (27%). Conclusions: Follow-up of celiac children and adolescents in Europe may be improved, especially regarding a more rational use of (laboratory) tests, dietary and QoL assessment, and transition to adult care. Evidence-based advice from international scientific societies is needed. What is Known: • Follow-up in celiac disease is important to treat disease-related symptoms, improve dietary compliance, and prevent possible complications. • There is a lack of consensus about the appropriate follow-up. What is New: • Almost all European physicians assess anthropometry, tissue-transglutaminase IgA-antibodies, and dietary adherence at every visit, but there are large variations in other follow-up aspects. • Follow-up could be improved by a more rational use of (laboratory) tests, increased intention to dietary compliance, and quality of life together with transition programs to adult care. [ABSTRACT FROM AUTHOR]

Abstract: Meningococcal disease is particularly severe. The case-fatality rate is 7.78% in Europe and 10–14% in the USA. This paper reports the results of a sero-epidemiological study in Italy on meningitis due to Meningococcus C before the introduction of the monovalent conjugate vaccine. In 2003–2004, a total of 577 sera were collected in 17 of the 20 Italian Regions. Serum Bactericidal Assay (SBA) was performed by using rabbit complement serum according to standardized SBA. The results showed that the percentages of protected subjects decreased from 6 to 12 months of age, increased from 1 to 4 years, decreased again until the age of 8 years and from 13 to 16 years, and were particularly high in 9- and 17-year-old subjects. The geometric mean titre of bactericidal antibodies (SBAbs GMT) was low in subjects under 1 year of age, significantly increased in 1–9-year-old children and decreased in adolescents and young adults. Finally, in each one-year age-group, low levels of antibodies were observed in subjects under 1 year of age, in 10-year-old subjects and in 14–16-year-old adolescents. High titres were observed in 3-, 8-, 9- and 17-year-old subjects. Our results therefore indicate that meningococcus C has the highest probability of spreading among 1–4, 8–10 and 14–17-year-old subjects in Italy. [Copyright &y& Elsevier]

An International Reference Preparation for Human Serum Immunoglobulins G, A, and M has been established by the World Health Organization and international units have been assigned to it. This paper describes international collaborative assays carried out by 10 specialized laboratories, which attempted to define the immunoglobulin contents of the International Reference Preparation by weight. For all immunoglobulins the estimates of contents by weight were imprecise, largely owing to heterogeneity of estimates between laboratories. Mean estimates of immunoglobulin contents by weight are given, but it is considered that the results of assays of immunoglobulin against the International Reference Preparation or related preparations are more precisely expressed in terms of international units.

Introduction: Cytomegalovirus (CMV) is the most common congenital viral infection and is regarded as the leading nongenetic cause of sensorineural hearing loss. Currently, international consensuses discourage prenatal screening of pregnant women. However, in few countries mainly in Southern Europe, screening of pregnant women for CMV infection is common practice. Management of women found with IgG+/IgM + and IgG avidity titers in the grey zone during first trimester causes significant stress to both families and health care workers.Patients and Methods: Pregnant women referred to our outpatient clinic with the diagnosis of acute CMV infection (IgM+/IgG+) during early pregnancy (gestational age ≤ 14 weeks) and IgG avidity in the grey zone were prospectively followed. The administration of CMV-HIG was offered and follow-up included fetal U/S, amniocentesis for CMV-DNA detection and MRI when appropriate. All neonates were examined by urine PCR and prospectively followed according to existing recommendations.Results: Ninety women (mean age 30.8 years) were retrospectively analyzed. Most (79.6%) received CMV-HIG. Four women terminated pregnancy (2 unrelated to CMV reasons and 2 because of CMV-positive amniotic fluid). Eighty-seven babies were born asymptomatic. Two newborns were diagnosed with congenital CMV infection. The overall transmission rate was 4.4%; 4.3 versus 5.6% for those receiving or not CMV-HIG. No adverse outcomes were detected during follow-up (median 24 months). Maternal age, parity, detection of maternal CMV-viremia upon diagnosis, delay between diagnosis and consultation, gestational week of first consultation, administration of CMV-HIG and number of doses were not associated with the risk of vertical CMV transmission.Discussions: Vertical transmission of CMV infection in pregnancies with acute CMV-infection and IgG avidity titers in the grey zone during first trimester was 4.4%, higher than that in infants born post nonprimary infection (NPI) during pregnancy. More powered studies are needed to prove a significant reduction in transmission using CMV-HIG. [ABSTRACT FROM AUTHOR]

For wildlife diseases, one often relies on host density to predict host infection prevalence and the subsequent force of infection to humans in the case of zoonoses. Indeed, if transmission is mainly indirect, i.e., by way of the environment, the force of infection is expected to increase with host density, yet the laborious field data supporting this theoretical claim are often absent. Hantaviruses are among those zoonoses that have been studied extensively over the past decades, as they pose a significant threat to humans. In Europe, the most widespread hantavirus is the Puumala virus (PUUV), which is carried by the bank vole and causes nephropathia epidemica (NE) in humans. Extensive field campaigns have been carried out in Central Finland to shed light on this supposed relationship between bank vole density and PUUV prevalence and to identify other drivers for the infection dynamics. This resulted in the surprising observation that the relationship between bank vole density and PUUV prevalence is not purely monotonic on an annual basis, contrary to what previous models predicted: a higher vole density does not necessary result in a higher infection prevalence, nor in an increased number of humans reported having NE. Here, we advance a novel individual-based spatially-explicit model which takes into account the immunity provided by maternal antibodies and which simulates the spatial behavior of the host, both possible causes for this discrepancy that were not accounted for in previous models. We show that the reduced prevalence in peak years can be attributed to transient immunity, and that the density-dependent spatial vole behavior, i.e., the fact that home ranges are smaller in high density years, plays only a minor role. The applicability of the model is not limited to the study and prediction of PUUV (and NE) occurrence in Europe, as it could be easily adapted to model other rodent-borne diseases, either with indirect or direct transmission. [ABSTRACT FROM AUTHOR]

Background: Malaria is a major travel medicine issue. Retrospective confirmation of a malaria episode diagnosed in an endemic area can have relevant implications in transfusional medicine in Europe, where blood donors are excluded from donation on the basis of positive malaria serology. However, there is scarce evidence on the dynamics of anti-malarial antibodies after a first malaria episode in non-immune individuals. The first aim of this study was to describe the dynamics of anti-malarial antibodies in a first malaria episode in non-immune travellers. Secondary objectives were to assess the sensitivity of serology for a retrospective diagnosis in non-immune travellers diagnosed while abroad and to discuss the implications in transfusional medicine. Methods: Retrospective analysis of the results of an indirect fluorescence antibody test (IFAT) for malaria available for patients with a first malaria episode by Plasmodium falciparum and admitted at the IRCCS Sacro Cuore Don Calabria hospital in a 14-year period. The antibody titres were collected at baseline and during further follow up visits. Epidemiological, demographic and laboratory test results (including full blood count and malaria parasite density) were anonymously recorded in a study specific electronic Case Report Form created with OpenClinica software. Statistical analysis was performed with SAS software version 9.4. Results: Thirty-six patients were included. Among them, all but two were Europeans (one African and one American). Median length of fever before diagnosis was 2 days (IQR 1–3). Thirty-five patients had seroconversion between day 1 and day 4 from admission, and the titre showed a sharply rising titre, often to a very high level in a few days. Only a single patient remained negative in the first 5 days from admission, after which he was no more tested. Six patients were followed up for at least 2 months, and they all showed a decline in IFAT titre, tending to seroreversion (confirmed in one patient with the longest follow up, almost 4 years). Conclusions: Serology demonstrated reliable for retrospective diagnosis in non-immune travellers. The decline in the anti-malarial titre might be included in the screening algorithms of blood donors, but further studies are needed. [ABSTRACT FROM AUTHOR]

Background. Chronic lymphocytic leukemia (CLL), the most common form of adult leukemia in Caucasian populations, is characterized by a decrease in anti-infective immunity. Clinical evidence of antiviral immunity decrease is the reactivation of herpes virus in the form of skin lesions. In Europe, rubella infection is common and creates lifelong persistence of IgG antibodies. Objectives. The aim of our study was to determine whether hemagglutination inhibition (HAI) rubella test can be used to determine antiviral immunity in CLL patients. Material and methods. The titers of the HAI test against rubella were examined in a group of 26 healthy subjects, 7 subjects with herpes labialis infection and 56 patients with CLL, among which 9 patients were co-infected with herpes virus. Results. Statistical tests have shown differences between groups and a significant decrease of the titers of the test in patients with CLL, compared with healthy persons and the herpes group compared with other persons. Conclusions. Our results indicate a significant decrease of antiviral immunity in patients with CLL and persons with herpes-type skin lesions. Simultaneously, relying on our previous studies, we also suggest that the result of this test may be an important indicator of antiviral immunity in patients with CLL. [ABSTRACT FROM AUTHOR]

Tick-borne encephalitis virus (TBEV) is the most important tick-transmitted pathogen. It belongs to the Flaviviridae family and causes severe human neuroinfections. In this study, protective efficacy of the chimeric antibody chFVN145 was examined in mice infected with strains belonging to the Far-Eastern, European, and Siberian subtypes of TBEV, and the antibody showed clear therapeutic efficacy when it was administered once one, two, or three days after infection. The efficacy was independent of the TBEV strain used to infect the mice; however, the survival rate of the mice was dependent on the dose of TBEV and of the antibody. No enhancement of TBEV infection was observed when the mice were treated with non-protective doses of chFVN145. Using a panel of recombinant fragments of the TBEV glycoprotein E, the neutralizing epitope for chFVN145 was localized in domain III of the TBEV glycoprotein E, in a region between amino acid residues 301 and 359. In addition, three potential sites responsible for binding with chFVN145 were determined using peptide phage display libraries, and 3D modeling demonstrated that the sites do not contact the fusion loop and, hence, their binding with chFVN145 does not result in increased attachment of TBEV to target cells. [ABSTRACT FROM AUTHOR]

Adeno-associated virus (AAV) vectors represent promising candidates for gene therapy; however, pre-existing neutralizing antibodies (NAb) may reduce AAV vector delivery efficiency. In this study, the presence of AAV NAb was investigated in cats, which serve as a larger and outbred animal model for the prediction of gene therapy outcomes in humans but also in cats.Serum/plasma samples from 230 client-owned Swiss cats and 20 specified pathogen-free cats were investigated for NAb to AAV1, AAV2, AAV5, AAV6, AAV7, AAV8 and AAV9 using in vitro transduction inhibition and a beta-galactosidase assay. NAb to all tested AAV serotypes were found. Of the client-owned cats, 53% had NAb to one or more of the AAV serotypes. NAb (≥1:10) were found at frequencies of 5% (AAV6) to 28% (AAV7). The highest titers were found against AAV7 (≥1:160). The NAb prevalence to AAV2, AAV7 and AAV9 differed geographically. Regarding titers ≥1:10 against single AAV serotypes, age, breed and sex of the cats were not associated with the NAb prevalence. Cats with titers ≥1:20 against AAV2 and titers ≥1:40 against AAV7 were significantly younger than cats with low/no titers, and purebred cats were significantly more likely than non-purebred cats to have NAb to AAV2 (≥1:40). Additionally, regarding NAb to all AAV combined, female cats were significantly more likely than male cats to have NAb titers ≥1:40. Preliminary data using AAV-DJ indicated that less pre-existing NAb to the hybrid AAV-DJ can be expected compared to the wild-type AAV serotypes. AAV NAb will need to be taken into account for future in vivo gene therapy studies in cats. [ABSTRACT FROM AUTHOR]

Objectives The Scleroderma Patient-centered Intervention Network (SPIN) Cohort is a web-based cohort designed to collect patient-reported outcomes at regular intervals as a framework for conducting trials of psychosocial, educational, self-management and rehabilitation interventions for patients with SSc. The aim of this study was to present baseline demographic, medical and patient-reported outcome data of the SPIN Cohort and to compare it with other large SSc cohorts. Methods Descriptive statistics were used to summarize SPIN Cohort characteristics; these were compared with published data of the European Scleroderma Trials and Research (EUSTAR) and Canadian Scleroderma Research Group (CSRG) cohorts. Results Demographic, organ involvement and antibody profile data for SPIN (N = 1125) were generally comparable with that of the EUSTAR (N = 7319) and CSRG (N = 1390) cohorts. There was a high proportion of women and White patients in all cohorts, though relative proportions differed. Scl70 antibody frequency was highest in EUSTAR, somewhat lower in SPIN, and lowest in CSRG, consistent with the higher proportion of interstitial lung disease among dcSSc patients in SPIN compared with in CSRG (48.5 vs 40.3%). RNA polymerase III antibody frequency was highest in SPIN and remarkably lower in EUSTAR (21.1 vs 2.4%), in line with the higher prevalence of SSc renal crisis (4.5 vs 2.1%) in SPIN. Conclusion Although there are some differences, the SPIN Cohort is broadly comparable with other large prevalent SSc cohorts, increasing confidence that insights gained from the SPIN Cohort should be generalizable, although it should be noted that all three cohorts include primarily White participants. [ABSTRACT FROM AUTHOR]

Background: Current political crises in the Middle East and economic discrepancies led millions of people to leave their home countries and to flee to Western Europe. This development raises unexpected challenges for receiving health care systems. Although pan-European initiatives strive for updated and optimized vaccination strategies, little data on immunity against vaccine-preventable diseases in the current refugee population exist. Methods: We quantified serum IgG against tetanus and diphtheria (TD) in n = 678 refugees currently seeking shelter in six German refugee centers. Findings: Reflecting current migration statistics in Europe, the median age within the cohort was 26 years, with only 23.9 % of female subjects. Insufficient IgG levels without long-term protection against tetanus were found in 56.3 % of all refugees. 76.1 % of refugees had no long-term protection against diphtheria. 47.7 % of subjects needed immediate vaccination against tetanus, and 47.7 % against diphtheria. For both diseases, an age-dependent decline in protective immunity occurred. Interpretation: We observed a considerably low rate of tetanus-protected refugees, and the frequency of diphtheria-immune refugees was far from sufficient to provide herd immunity. These findings strongly support recent intentions to implement and enforce stringent guidelines for refugee vaccination in the current crisis. [ABSTRACT FROM AUTHOR]

Background: Most cases of adult pertussis probably remain undiagnosed.Aim: To explore the prevalence, diagnosis, and disease course of acute pertussis infection in adult patients presenting with acute cough.Design and Setting: Prospective observational study between 2007 and 2010 in primary care in 12 European countries.Method: Adults presenting with acute cough (duration of ≤28 days) were included. Bordetella pertussis infection was determined by polymerase chain reaction (from nasopharyngeal flocked swabs and sputa) and by measurement of immunoglobulin G antibodies to pertussis toxin (PT) in venous blood at day 28. An antibody titre to PT of ≥125 IU/ml or PCR positive result in a respiratory sample defined recent infection. Patients completed a symptom diary for 28 days.Results: Serum and/or respiratory samples were obtained in 3074 patients. Three per cent (93/3074) had recent B. pertussis infection. Prior cough duration >2 weeks discriminated to some extent between those with and without pertussis (adjusted odds ratio 1.89, 95% confidence interval = 1.17 to 3.07; P = 0.010). Median cough duration after presentation was 17 and 12 days in patients with and without pertussis, respectively (P = 0.008). Patients with pertussis had longer duration of phlegm production (P = 0.010), shortness of breath (P = 0.037), disturbed sleep (P = 0.013) and interference with normal activities or work (P = 0.033) after presentation.Conclusion: Pertussis infection plays a limited role among adults presenting with acute cough in primary care, but GPs should acknowledge the possibility of pertussis in uncomplicated lower respiratory tract infection. As in children, pertussis also causes prolonged symptoms in adults. However, pertussis is difficult to discern from other acute cough syndromes in adults at first presentation. [ABSTRACT FROM AUTHOR]

Background: The mosquito-borne Chikungunya virus (CHIKV) causes high fever and severe joint pain in humans. It is expected to spread in the future to Europe and has recently reached the USA due to globalization, climate change and vector switch. Despite this, little is known about the virus life cycle and, so far, there is no specific treatment or vaccination against Chikungunya infections. We aimed here to identify small antigenic determinants of the CHIKV E2 protein able to induce neutralizing immune responses. Methodology/Principal Findings: E2 enables attachment of the virus to target cells and a humoral immune response against E2 should protect from CHIKV infections. Seven recombinant proteins derived from E2 and consisting of linear and/or structural antigens were created, and were expressed in and purified from E. coli. BALB/c mice were vaccinated with these recombinant proteins and the mouse sera were screened for neutralizing antibodies. Whereas a linear N-terminally exposed peptide (L) and surface-exposed parts of the E2 domain A (sA) alone did not induce neutralizing antibodies, a construct containing domain B and a part of the β-ribbon (called B+) was sufficient to induce neutralizing antibodies. Furthermore, domain sA fused to B+ (sAB+) induced the highest amount of neutralizing antibodies. Therefore, the construct sAB+ was used to generate a recombinant modified vaccinia virus Ankara (MVA), MVA-CHIKV-sAB+. Mice were vaccinated with MVA-CHIKV-sAB+ and/or the recombinant protein sAB+ and were subsequently challenged with wild-type CHIKV. Whereas four vaccinations with MVA-CHIKV-sAB+ were not sufficient to protect mice from a CHIKV infection, protein vaccination with sAB+ markedly reduced the viral titers of vaccinated mice. Conclusions/Significance: The recombinant protein sAB+ contains important structural antigens for a neutralizing antibody response in mice and its formulation with appropriate adjuvants might lead to a future CHIKV vaccine. Author Summary: Chikungunya virus (CHIKV) is transmitted by mosquitos and causes high fever and severe joint pain in humans. It is expected to spread in the future to Europe and has recently reached the USA due to vector switch and climate change. There is no specific treatment or vaccination against CHIKV infections. However, vaccination should be an efficient way to control its spread. The CHIKV envelope glycoprotein E2 enables attachment of the virus to target cells and a humoral immune response against E2 should protect from CHIKV infections. We aimed to identify small antigens of the CHIKV E2 protein that are able to induce neutralizing antibodies. These antigens should enable the production of cost effective, safe and efficient vaccines. The surface-exposed parts of the E2 domain A (sA) fused to domain B and a part of the β-ribbon that joins domain A with B (sAB+) induced most effectively neutralizing antibodies and mice vaccinated with this protein were partially protected from a CHIKV challenge infection. The protein sAB+ was identified as a useful antigen for developing a vaccine when formulated with an appropriate adjuvant. [ABSTRACT FROM AUTHOR]

Due to the increasing number of infections related to injecting drug use, both the pattern of hepatitis C virus (HCV) transmission, and the circulating genotypes in Europe have changed. As there are little available data in this respect for Romania, the aim of our study was a preliminary analysis of the distribution of HCV genotypes circulating among injecting drug users (IDUs). Of the 45 IDUs evaluated (86.7% men, mean age − 27.6 ± 3.7 years, mean age at first drug use − 17.5 ± 3.9 years), 88.9% presented anti-HCV antibodies, with higher rates in those with an injecting history of more than 10 years; 57.8% of the subjects had detectable HCV viral load. Only 6.7% had markers of chronic hepatitis B infection, and none had anti-HIV antibodies. While HCV subtype 1b is still prevalent (in 50% of the viraemic subjects), other subtypes begin to emerge, especially in younger patients (1a - in 23.1%, 4 - in 11.5%, 3a - in 7.7% of the cases). These data indicate the possibility of major shifts in the distribution of the dominant subtype, underlining the need for close surveillance of HCV infections in IDUs, who can act as a bridging group toward the general population. [ABSTRACT FROM AUTHOR]

Background: Birch pollen belongs to the major allergen triggers in the spring season in Europe. Our rapidly expanding knowledge of the allergenic molecules enables us to better recognize the individual differences between the reactivity of specific IgE antibodies of individual patients and allergic populations living in various regions of the world. Method: In a group of birch pollen-allergic patients living in the Czech Republic (107 children, 71 adults) we detected the presence of Bet v1, Bet v2 and Bet v4 specific IgE antibodies. Results: Bet v1 specific IgE antibodies were identified in most patients without any significant differences between children and adults. Bet v2 positivity was found more frequently in the group of children than in adults (p = 0.02). In most adult patients Bet v1 monospecificity was more expressed as compared to the pediatric group. More allergic subjects reacted against minor birch allergens in the pediatric group (p = 0.02). Specific IgE antibodies against Bet v1 were not detected in 10% of the tested patients. In this group, 5% of birch pollen-allergic patients were found to not have specific IgE antibodies against any of the tested recombinant allergens. Conclusion: The investigation of specific IgE antibodies against Bet v1, Bet v2 and Bet v4 demonstrated that the specificity of allergen-induced IgE antibodies in birch pollen-allergic individuals is dependent not only on the region in which a patient lives but also on age. Especially in children, there is an increase in the number of allergic subjects who do not react exclusively against the major allergen. The question is whether some allergen-specific IgE antibodies will disappear depending on age or on the contrary whether their synthesis will be increased. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The article focuses on study of antibodies to virus haemagglutinin for mediation of heterosubtype neutralizing responses to influenza A (H5N1) viruses. In many Asian and African countries, avian influenza is considered to be endemic in poultry flocks. Antibodies that may provide protection against zoonotic infections are induced by influenza A infection. In this study, H5-neutralization antibody titers pre- and post-vaccination were measured through micro-neutralization test in volunteers of Europe. Evidences of serological response were found.

Background: Low sensitization rates to common allergens have been observed in farm children, which might be due to high exposure to microbial agents. It is not known how microbial agents modify the association between specific allergen exposure and sensitization. Objective: To examine the relations between house dust mite allergen exposure and mite sensitization in farm and nonfarm children and to assess the effects of microbial agents levels on this association. Methods: Major mite allergens of Dermatophagoides pteronyssinus (Der p 1) and Dermatophagoides farinae (Der f 1), endotoxin, β(1,3)-glucans and fungal extracellular polysaccharides were measured in mattress dust of 402 children participating in a cross-sectional study in five European countries. Mite allergen (Der p 1 + Der f 1) levels were divided into tertiles with cut-offs 1.4 and 10.4 μg/g. Sensitization was assessed by measurement of allergen-specific immunoglobulin E against house dust mite. Results: Prevalence ratios of mite sensitization for medium and high when compared with low mite allergen levels were 3.1 [1.7–5.7] and 1.4 [0.7–2.8] respectively. Highest mite sensitization rates at intermediate exposure levels were consistently observed across country (except for Sweden) and in both farm and nonfarm children. The shape of the dose–response curve was similar for above and below median mattress microbial agent levels, but the ‘sensitization peak’ appeared to be lower for above median levels. Conclusions: Our data suggest a bell-shaped dose–response relationship between mite allergen exposure and sensitization to mite allergens. In populations with high microbial agent levels and low sensitization rates, the curve is shifted down. [ABSTRACT FROM AUTHOR]

Our objective was to determine the HLA-DPB1 allele associations of anticardiolipin (aCL) anti-β[sub 2]GPI (aβ[sub 2]GPI) antibodies, and of clinical manifestations of the antiphospholipid syndrome (APS), in systemic lupus erythematosus (SLE). We studied 577 European patients with SLE. aCL and aβ[sub 2]GPI antibodies were measured by ELISA. Molecular typing of HLA-DPB1 locus was performed by polymerase chain reaction-sequence specific oligonucleotide probe (PCR-SSOP) method. aCL showed positive association with -DPB1*1501 (P = 0.005, OR = 7.4), and -DPB1*2301 (P = 0.009, OR 3.3). aβ[sub 2]GPI showed positive association with -DPB1*0301 (P = 0.01, OR = 1.9), and -DPB1*1901 (P = 0.004, OR 8.1). In addition, livedo reticularis was associated with -DPB1*1401, and Raynaud's phenomenon with -DPB1*2001. In conclusion, HLA-DPB1 locus may contribute to the genetic predisposition to develop antiphospholipid antibodies and clinical manifestations of the APS in patients with SLE. [ABSTRACT FROM AUTHOR]