Showing papers by "Swedish Institute published in 2008"

Comparative analysis of human gut microbiota by barcoded pyrosequencing.

Abstract: Humans host complex microbial communities believed to contribute to health maintenance and, when in imbalance, to the development of diseases. Determining the microbial composition in patients and healthy controls may thus provide novel therapeutic targets. For this purpose, high-throughput, cost-effective methods for microbiota characterization are needed. We have employed 454-pyrosequencing of a hyper-variable region of the 16S rRNA gene in combination with sample-specific barcode sequences which enables parallel in-depth analysis of hundreds of samples with limited sample processing. In silico modeling demonstrated that the method correctly describes microbial communities down to phylotypes below the genus level. Here we applied the technique to analyze microbial communities in throat, stomach and fecal samples. Our results demonstrate the applicability of barcoded pyrosequencing as a high-throughput method for comparative microbial ecology.

Prediction of outcome in individuals with diabetic foot ulcers: focus on the differences between individuals with and without peripheral arterial disease. The EURODIALE Study

Abstract: Aims/hypothesis Outcome data on individuals with diabetic foot ulcers are scarce, especially in those with peripheral arterial disease (PAD). We therefore examined the clinical characteristics that best predict poor outcome in a large population of diabetic foot ulcer patients and examined whether such predictors differ between patients with and without PAD.

Emergence and spread of vancomycin resistance among enterococci in Europe

Abstract: Nowadays, six types of acquired vancomycin resistance in enterococci are known; however, only VanA and to a lesser extent VanB are widely prevalent. Various genes encode acquired vancomycin resistance and these are typically associated with mobile genetic elements which allow resistance to spread clonally and laterally. The major reservoir of acquired vancomycin resistance is Enterococcus faecium; vancomycin-resistant Enterococcus faecalis are still rare. Population analysis of E. faecium has revealed a distinct subpopulation of hospital-acquired strain types, which can be differentiated by molecular typing methods (MLVA, MLST) from human commensal and animal strains. Hospital-acquired E. faecium have additional genomic content (accessory genome) including several factors known or supposed to be virulence-associated. Acquired ampicillin resistance is a major phenotypic marker of hospital-acquired E. faecium in Europe and experience has shown that it often precedes increasing rates of VRE with a delay of several years. Several factors are known to promote VRE colonisation and transmission; however, despite having populations with similar predispositions and preconditions, rates of VRE vary all over Europe.

Cognition counts: A working memory system for ease of language understanding (ELU)

Abstract: A general working memory system for ease of language understanding (ELU, Ronnberg, 2003a) is presented. The purpose of the system is to describe and predict the dynamic interplay between explicit and implicit cognitive functions, especially in conditions of poorly perceived or poorly specified linguistic signals. In relation to speech understanding, the system based on (1) the quality and precision of phonological representations in long-term memory, (2) phonologically mediated lexical access speed, and (3) explicit, storage, and processing resources. If there is a mismatch between phonological information extracted from the speech signal and the phonological information represented in long-term memory, the system is assumed to produce a mismatch signal that invokes explicit processing resources. In the present paper, we focus on four aspects of the model which have led to the current, updated version: the language generality assumption; the mismatch assumption; chronological age; and the episodic buffer function of rapid, automatic multimodal binding of phonology (RAMBPHO). We evaluate the language generality assumption in relation to sign language and speech, and the mismatch assumption in relation to signal processing in hearing aids. Further, we discuss the effects of chronological age and the implications of RAMBPHO.

The challenges of eliciting neutralizing antibodies to HIV-1 and to influenza virus

Abstract: Most viral vaccines protect against disease by generating neutralizing antibodies. This Review examines the problem of eliciting broad HIV-1 neutralization through vaccination by drawing parallels with the successful subunit influenza virus vaccine and with efforts to develop a pandemic influenza vaccine. The ability to elicit broadly neutralizing antibody responses against HIV-1 is a crucial goal for a prophylactic HIV-1 vaccine. Here, we discuss the difficulties of achieving broad HIV-1 neutralization in the context of both the effective annual human influenza virus vaccine and the need to develop a pandemic influenza vaccine. Immunogen-design strategies are underway to target functionally conserved regions of the HIV-1 envelope glycoproteins, and similar strategies might be applicable to pandemic influenza virus vaccine development. Efforts to develop broadly neutralizing vaccines against either HIV-1 or influenza virus might establish a paradigm for future vaccines against highly variable pathogens.

Resource utilisation and costs associated with the treatment of diabetic foot ulcers. Prospective data from the Eurodiale Study

Abstract: Aims/hypothesis The aim of the present study was to investigate resource utilisation and associated costs in patients with diabetic foot ulcers and to analyse differences in resource utilisation between individuals with or without peripheral arterial disease (PAD) and/or infection.

Analysis of Integrated Virological and Epidemiological Reports of Norovirus Outbreaks Collected within the Foodborne Viruses in Europe Network from 1 July 2001 to 30 June 2006

Abstract: The Foodborne Viruses in Europe network has developed integrated epidemiological and virological outbreak reporting with aggregation and sharing of data through a joint database. We analyzed data from reported outbreaks of norovirus (NoV)-caused gastroenteritis from 13 European countries (July 2001 to July 2006) for trends in time and indications of different epidemiology of genotypes and variants. Of the 13 countries participating in this surveillance network, 11 were capable of collecting integrated epidemiological and virological surveillance data and 10 countries reported outbreaks throughout the entire period. Large differences in the numbers and rates of reported outbreaks per country were observed, reflecting the differences in the focus and coverage of national surveillance systems. GII.4 strains predominated throughout the 5-year surveillance period, but the proportion of outbreaks associated with GII.4 rose remarkably during years in which NoV activity was particularly high. Spring and summer peaks indicated the emergence of genetically distinct variants within GII.4 across Europe and were followed by increased NoV activity during the 2002-2003 and 2004-2005 winter seasons. GII.4 viruses predominated in health care settings and in person-to-person transmission. The consecutive emergence of new GII.4 variants is highly indicative of immune-driven selection. Their predominance in health care settings suggests properties that facilitate transmission in settings with a high concentration of people such as higher virus loads in excreta or a higher incidence of vomiting. Understanding the mechanisms driving the changes in epidemiology and clinical impact of these rapidly evolving RNA viruses is essential to design effective intervention and prevention measures.

Delivery of care to diabetic patients with foot ulcers in daily practice: results of the Eurodiale Study, a prospective cohort study

Abstract: Aims To determine current management and to identify patient-related factors and barriers that influence management strategies in diabetic foot disease. Methods The Eurodiale Study is a prospective cohort study of 1232 consecutive individuals presenting with a new diabetic foot ulcer in 14 centres across Europe. We determined the use of management strategies: referral, use of offloading, vascular imaging and revascularization. Results Twenty-seven percent of the patients had been treated for > 3 months before referral to a foot clinic. This varied considerably between countries (6-55%). At study entry, 77% of the patients had no or inadequate offloading. During follow-up, casting was used in 35% (0-68%) of the plantar fore- or midfoot ulcers. Predictors of use of casting were male gender, large ulcer size and being employed. Vascular imaging was performed in 56% (14-86%) of patients with severe limb ischaemia; revascularization was performed in 43%. Predictors of use of vascular imaging were the presence of infection and ischaemic rest pain. Conclusion Treatment of many patients is not in line with current guidelines and there are large differences between countries and centres. Our data suggest that current guidelines are too general and that healthcare organizational barriers and personal beliefs result in underuse of recommended therapies. Action should be undertaken to overcome these barriers and to guarantee the delivery of optimal care for the many individuals with diabetic foot disease.

Short- and long-term effects of bacterial gastrointestinal infections

Abstract: During 1997–2004, microbiologically confirmed gastrointestinal infections were reported for 101,855 patients in Sweden. Among patients who had Salmonella infection (n = 34,664), we found an increased risk for aortic aneurysm (standardized incidence ratio [SIR] 6.4, 95% confidence interval [CI] 3.1–11.8) within 3 months after infection and an elevated risk for ulcerative colitis (SIR 3.2, 95% CI 2.2–4.6) within 1 year after infection. We also found this elevated risk for ulcerative colitis among Campylobacter infections (n = 57,425; SIR 2.8, 95% CI 2.0–3.8). Within 1 year, we found an increased risk for reactive arthritis among patients with Yersinia enteritis (n = 5,133; SIR 47.0, 95% CI 21.5–89.2), Salmonella infection (SIR 18.2, 95% CI 12.0–26.5), and Campylobacter infection (SIR 6.3, 95% CI 3.5–10.4). Acute gastroenteritis is sometimes associated with disease manifestations from several organ systems that may require hospitalization of patients.

The RNA binding protein CsrA controls cyclic di-GMP metabolism by directly regulating the expression of GGDEF proteins.

Abstract: The carbon storage regulator CsrA is an RNA binding protein that controls carbon metabolism, biofilm formation and motility in various eubacteria. Nevertheless, in Escherichia coli only five target mRNAs have been shown to be directly regulated by CsrA at the post-transcriptional level. Here we identified two new direct targets for CsrA, ycdT and ydeH, both of which encode proteins with GGDEF domains. A csrA mutation caused mRNA levels of ycdT and ydeH to increase more than 10-fold. RNA mobility shift assays confirmed the direct and specific binding of CsrA to the mRNA leaders of ydeH and ycdT. Overexpression of ycdT and ydeH resulted in a more than 20-fold increase in the cellular concentration of the second messenger cyclic di-GMP (c-di-GMP), implying that both proteins possess diguanylate cyclase activity. Phenotypic characterization revealed that both proteins are involved in the regulation of motility in a c-di-GMP-dependent manner. CsrA was also found to regulate the expression of five additional GGDEF/EAL proteins and a csrA mutation led to modestly increased cellular levels of c-di-GMP. All together, these data demonstrate a global role for CsrA in the regulation of c-di-GMP metabolism by regulating the expression of GGDEF proteins at the post-transcriptional level.

Broad Immunogenicity of a Multigene, Multiclade HIV-1 DNA Vaccine Boosted with Heterologous HIV-1 Recombinant Modified Vaccinia Virus Ankara

Abstract: Background A human immunodeficiency virus (HIV) vaccine that limits disease and transmission is urgently needed. This clinical trial evaluated the safety and immunogenicity of an HIV vaccine that combines a plasmid-DNA priming vaccine and a modified vaccinia virus Ankara (MVA) boosting vaccine.

Developmental switch of intestinal antimicrobial peptide expression.

Abstract: Paneth cell-derived enteric antimicrobial peptides provide protection from intestinal infection and maintenance of enteric homeostasis. Paneth cells, however, evolve only after the neonatal period, and the antimicrobial mechanisms that protect the newborn intestine are ill defined. Using quantitative reverse transcription-polymerase chain reaction, immunohistology, reverse-phase high-performance liquid chromatography, and mass spectrometry, we analyzed the antimicrobial repertoire in intestinal epithelial cells during postnatal development. Surprisingly, constitutive expression of the cathelin-related antimicrobial peptide (CRAMP) was observed, and the processed, antimicrobially active form was identified in neonatal epithelium. Peptide synthesis was limited to the first two weeks after birth and gradually disappeared with the onset of increased stem cell proliferation and epithelial cell migration along the crypt-villus axis. CRAMP conferred significant protection from intestinal bacterial growth of the newborn enteric pathogen Listeria monocytogenes. Thus, we describe the first example of a complete developmental switch in innate immune effector expression and anatomical distribution. Epithelial CRAMP expression might contribute to bacterial colonization and the establishment of gut homeostasis, and provide protection from enteric infection during the postnatal period.

Serum biomarkers provide an accurate method for diagnosis of atrophic gastritis in a general population: The Kalixanda study.

Abstract: Objective. Serological biomarkers can be used for non-invasive diagnosis of gastritis and atrophic gastritis. The aim of this study was to compare the validity of serum levels of pepsinogen I (PGI) and II (PGII), gastrin-17 (G-17) and Helicobacter pylori antibodies (Hpab) with that of the gold standard histology for diagnosis of atrophic gastritis in a population sample from Northern Sweden. Material and methods. In all, 1000 subjects underwent endoscopies with biopsies. Serum biomarkers were available in 976 subjects for independent diagnosis of gastric mucosal status using a predetermined diagnostic algorithm. Results. Overall agreement between histology and serological biomarkers in diagnosing corpus atrophy was 96% (CI 95%: 95–97%). Sensitivity and specificity of markers for atrophic gastritis were 71% (CI 68–74%) and 98% (CI 97–99%) respectively, corresponding to 69% (CI 95%: 66–72%) and 98% (95% CI 97–99%) positive and negative predictive values. The positive likelihood ratio was 35.5 (95% CI: 35.0–...

Autism spectrum conditons in myotonic dystrophy type 1: A study on 57 individuals with congenital and childhood forms

Abstract: Myotonic dystrophy type 1 (DM1) is an autosomal dominant disorder, caused by an expansion of a CTG triplet repeat in the DMPK gene. The aims of the present study were to classify a cohort of children with DM1, to describe their neuropsychiatric problems and cognitive level, to estimate the size of the CTG expansion, and to correlate the molecular findings with the neuropsychiatric problems. Fifty-seven children and adolescents (26 females; 31 males) with DM1 (CTG repeats > 40) were included in the study. The following instruments were used: Autism Diagnostic Interview-Revised (ADI-R), 5-15, Griffiths Mental Development Scales, and the Wechsler Scales. Based on age at onset and presenting symptoms, the children were divided into four DM1 groups; severe congenital (n = 19), mild congenital (n = 18), childhood (n = 18), and classical DM1 (n = 2). Forty-nine percent had an autism spectrum disorder (ASD) and autistic disorder was the most common diagnosis present in 35% of the subjects. Eighty-six percent of the individuals with DM1 had mental retardation (MR), most of them moderate or severe MR. ASD was significantly correlated with the DM1 form; the more severe the form of DM1, the higher the frequency of ASD. The frequency of ASD increased with increasing CTG repeat expansions. ASD and/or other neuropsychiatric disorders such as attention deficit hyperactivity disorder, and Tourette's disorder were found in 54% of the total DM1. group. In conclusion, awareness of ASD comorbidity in DM1. is essential. Further studies are warranted to elucidate the molecular etiology causing neurodevelopmental symptoms such as ASD and MR in DM1. (c) 2008 Wiley-Liss, Inc.

The nitrate reductase assay for the rapid detection of isoniazid and rifampicin resistance in Mycobacterium tuberculosis: a systematic review and meta-analysis

Abstract: Objectives: The reference standard methods for drug susceptibility testing (DST) of M. tuberculosis are very slow to give results, and due to the emergence of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis, there is an urgent demand for new, rapid and accurate DST methods, particularly in low-income countries. The nitrate reductase assay (NRA) has been proposed as a rapid method for the detection of resistance to rifampicin and isoniazid, but its accuracy has not been systematically evaluated. Methods: We performed a systematic review and meta-analysis to evaluate the accuracy of the NRA for the detection of rifampicin- and isoniazid-resistant tuberculosis. We searched Medline PubMed (NCBI), Global Health-CAB, EJS-E (EbscoHost), ISI Web, Web of Science and IFCC and contacted authors if additional information was required. Fifteen studies met our inclusion criteria for rifampicin resistance detection and 13 for isoniazid. Of these, the majority of the studies used culture isolates on solid medium, four used culture isolates on liquid medium and three used sputum samples. We applied the summary receiver operating characteristic (SROC) curve to perform meta-analysis and to summarize diagnostic accuracy. Results: For rifampicin, the majority of the studies that applied NRA to isolates had a sensitivity and specificity >94% and for isoniazid, >92%. The three studies that applied NRA directly on sputum samples had a sensitivity and specificity that ranged between 88% and 100%. The SROC curve had an area of >0.99 for both drugs. Conclusions: There is evidence that NRA is highly sensitive and specific for the rapid detection of rifampicin and isoniazid resistance in culture isolates. More evidence is required for the NRA applied directly on sputum samples, but preliminary results appear promising and show a good sensitivity and specificity. Additional studies are required in countries with a high prevalence of MDR-TB and also cost-effectiveness analysis in order to obtain a complete picture on the utility of this method for rapid drug resistance detection in tuberculosis.

Loss to follow-up in an international, multicentre observational study

Abstract: Objective The aim of this work was to assess loss to follow-up (LTFU) in EuroSIDA, an international multicentre observational cohort study. Methods LTFU was defined as no follow-up visit, CD4 cell count measurement or viral load measurement after 1 January 2006. Poisson regression was used to describe factors related to LTFU. Results The incidence of LTFU in 12 304 patients was 3.72 per 100 person-years of follow-up [95% confidence interval (CI) 3.58–3.86; 2712 LTFU] and varied among countries from 0.67 to 13.35. After adjustment, older patients, those with higher CD4 cell counts, and those who had started combination antiretroviral therapy all had lower incidences of LTFU, while injecting drug users had a higher incidence of LTFU. Compared with patients from Southern Europe and Argentina, patients from Eastern Europe had over a twofold increased incidence of LTFU after adjustment (incidence rate ratio 2.16; 95% CI 1.84–2.53; P 1 year with no CD4 cell count or viral load measured during the year; 743 (27.1%) subsequently returned to follow-up. Conclusions Some patients thought to be LTFU may have died, and efforts should be made to ascertain vital status wherever possible. A significant proportion of patients who have a year with no follow-up visit, CD4 cell count measurement or viral load measurement subsequently return to follow-up.

An outbreak of Escherichia coli O157:H7 infection in southern Sweden associated with consumption of fermented sausage; aspects of sausage production that increase the risk of contamination.

Abstract: A large outbreak of enterohaemorrhagic Escherichia coli (EHEC) infections occurred in southern Sweden during autumn 2002. A matched case-control study was performed and indicated an association between consumption of fermented sausage and EHEC infection (odds ratio 5.4, P<0.002). Pulsed-field gel electrophoresis analysis identified a strain of E. coli O157:H7 in clinical faecal isolates, which was identical to a strain isolated from sausage samples obtained from households of infected individuals. A combination of microbiological and epidemiological results established a link between sausage consumption and the outbreak in 30 out of a total of 39 investigated cases. Contaminated beef was suspected to be the source of infection. Delayed start of fermentation, lack of heat-treatment and a short curing period in cold temperature were identified as the main factors enabling EHEC survival. EHEC can survive throughout the entire production process of fermented sausage if curing conditions are inadequate.

The role of the episodic buffer in working memory for language processing.

Abstract: A body of work has accumulated to show that the cognitive process of binding information from different mnemonic and sensory sources as well as in different linguistic modalities can be fractionated from general executive functions in working memory both functionally and neurally. This process has been defined in terms of the episodic buffer (Baddeley in Trends Cogn Sci 4(11):417-423, 2000). This paper considers behavioural, neuropsychological and neuroimaging data that elucidate the role of the episodic buffer in language processing. We argue that the episodic buffer seems to be truly multimodal in function and that while formation of unitary multidimensional representations in the episodic buffer seems to engage posterior neural networks, maintenance of such representations is supported by frontal networks. Although, the episodic buffer is not necessarily supported by executive processes and seems to be supported by different neural networks, it may operate in tandem with the central executive during effortful language processing. There is also evidence to suggest engagement of the phonological loop during buffer processing. The hippocampus seems to play a role in formation but not maintenance of representations in the episodic buffer of working memory.

rBCG induces strong antigen-specific T cell responses in rhesus macaques in a prime-boost setting with an adenovirus 35 tuberculosis vaccine vector.

Abstract: Background: BCG vaccination, combined with adenoviral-delivered boosts, represents a reasonable strategy to augment, broaden and prolong immune protection against tuberculosis (TB). We tested BCG (SSI1331) (in 6 animals, delivered intradermally) and a recombinant (rBCG) AFRO-1 expressing perfringolysin (in 6 animals) followed by two boosts (delivered intramuscullary) with non-replicating adenovirus 35 (rAd35) expressing a fusion protein composed of Ag85A, Ag85B and TB10.4, for the capacity to induce antigen-specific cellular immune responses in rhesus macaques (Macaca mulatta). Control animals received diluent (3 animals). Methods and Findings: Cellular immune responses were analyzed longitudinally (12 blood draws for each animal) using intracellular cytokine staining (TNF-alpha, IL-2 and IFN-gamma), T cell proliferation was measured in CD4 + , CD8alpha/beta + , and CD8alpha/alpha + T cell subsets and IFN-gamma production was tested in 7 day PBMC cultures (whole blood cell assay, WBA) using Ag85A, Ag85B, TB10.4 recombinant proteins, PPD or BCG as stimuli. Animals primed with AFRO-1 showed i) increased Ag85B-specific IFN-gamma production in the WBA assay (median .400 pg/ml for 6 animals) one week after the first boost with adenoviral-delivered TB-antigens as compared to animals primed with BCG (,200 pg/ml), ii) stronger T cell proliferation in the CD8alpha/alpha + T cell subset (proliferative index 17%) as compared to BCG-primed animals (proliferative index 5% in CD8alpha/alpha + T cells). Polyfunctional T cells, defined by IFN-gamma, TNF-alpha and IL-2 production were detected in 2/6 animals primed with AFRO-1 directed against Ag85A/b and TB10.4; 4/6 animals primed with BCG showed a Ag85A/b responses, yet only a single animal exhibited Ag85A/b and TB10.4 reactivity. Conclusion: AFRO-1 induces qualitatively and quantitatively different cellular immune responses as compared with BCG in rhesus macaques. Increased IFN-gamma-responses and antigen-specific T cell proliferation in the CD8alpha/alpha+ T cell subset represents a valuable marker for vaccine-take in BCG-based TB vaccine trials

Cognitive and linguistic skills in Swedish children with cochlear implants - measures of accuracy and latency as indicators of development

Abstract: The purpose of the present study was to examine working memory (WM) capacity, lexical access and phonological skills in 19 children with cochlear implants (CI) (5;7-13;4 years of age) attending grades 0-2, 4, 5 and 6 and to compare their performance with 56 children with normal hearing. Their performance was also studied in relation to demographic factors. The findings indicate that children with CI had visuospatial WM capacities equivalent to the comparison group. They had lower performance levels on most of the other cognitive tests. Significant differences between the groups were not found in all grades and a number of children with CI performed within 1 SD of the mean of their respective grade-matched comparison group on most of the cognitive measures. The differences between the groups were particularly prominent in tasks of phonological WM. The results are discussed with respect to the effects of cochlear implants on cognitive development.

Lipopolysaccharide diversity evolving in Helicobacter pylori communities through genetic modifications in fucosyltransferases.

Abstract: Helicobacter pylori persistently colonizes the gastric mucosa of half the human population. It is one of the most genetically diverse bacterial organisms and subvariants are continuously emerging within an H. pylori population. In this study we characterized a number of single-colony isolates from H. pylori communities in various environmental settings, namely persistent human gastric infection, in vitro bacterial subcultures on agar medium, and experimental in vivo infection in mice. The lipopolysaccharide (LPS) O-antigen chain revealed considerable phenotypic diversity between individual cells in the studied bacterial communities, as demonstrated by size variable O-antigen chains and different levels of Lewis glycosylation. Absence of high-molecular-weight O-antigen chains was notable in a number of experimentally passaged isolates in vitro and in vivo. This phenotype was not evident in bacteria obtained from a human gastric biopsy, where all cells expressed high-molecular-weight O-antigen chains, which thus may be the preferred phenotype for H. pylori colonizing human gastric mucosa. Genotypic variability was monitored in the two genes encoding α1,3-fucosyltransferases, futA and futB, that are involved in Lewis antigen expression. Genetic modifications that could be attributable to recombination events within and between the two genes were commonly detected and created a diversity, which together with phase variation, contributed to divergent LPS expression. Our data suggest that the surrounding environment imposes a selective pressure on H. pylori to express certain LPS phenotypes. Thus, the milieu in a host will select for bacterial variants with particular characteristics that facilitate adaptation and survival in the gastric mucosa of that individual, and will shape the bacterial community structure.

Towards elimination: measles susceptibility in Australia and 17 European countries

Abstract: OBJECTIVE: To evaluate age-specific measles susceptibility in Australia and 17 European countries. METHODS: As part of the European Sero-Epidemiology Network 2 (ESEN2), 18 countries collected large national serum banks between 1996 and 2004. These banks were tested for measles IgG and the results converted to a common unitage to enable valid intercountry comparisons. Historical vaccination and disease incidence data were also collected. Age-stratified population susceptibility levels were compared to WHO European Region targets for measles elimination of < 15% in those aged 2-4 years, < 10% in 5-9-year-olds and < 5% in older age groups. FINDINGS: Seven countries (Czech Republic, Hungary, Luxembourg, Spain, Slovakia, Slovenia and Sweden) met or came very close to the elimination targets. Four countries (Australia, Israel, Lithuania and Malta) had susceptibility levels above WHO targets in some older age groups indicating possible gaps in protection. Seven countries (Belgium, Bulgaria, Cyprus, England and Wales, Ireland, Latvia and Romania) were deemed to be at risk of epidemics as a result of high susceptibility in children and also, in some cases, adults. CONCLUSION: Although all countries now implement a two-dose measles vaccination schedule, if the WHO European Region target of measles elimination by 2010 is to be achieved higher routine coverage as well as vaccination campaigns in some older age cohorts are needed in some countries. Without these improvements, continued measles transmission and outbreaks are expected in Europe.

BK-viruria and haemorrhagic cystitis are more frequent in allogeneic haematopoietic stem cell transplant patients receiving full conditioning and unrelated-HLA-mismatched grafts

Abstract: The influence of conditioning regimen, donor background and HLA matching on development of BK virus (BKV)-associated haemorrhagic cystitis (HC) was examined in 175 allogeneic haematopoietic stem cell transplant (HSCT) patients, undergoing 179 HSCT events. Twenty-seven patients presented late-onset HC, and BK viruria was verified in 23/27 HC events. Seventy-one (40%) HSCTs were performed with myeloablative conditioning (MC), 108 (60%) were performed with reduced intensity conditioning (RIC), 66 (37%) were performed with a related donor (RD) grafts and 113 (63%) with an unrelated donor (URD) graft. BK viruria was more common during HC, than non-HC events, after MC as compared to RIC (both P<0.001), and with an HLA-mismatched donor (P<0.01). By multivariate logistical regression analysis, independent risk factors for HC were BKV (OR 6.7; 95% CI 2.0-21.7; P=0.001), MC (OR 6.0; 95% CI 2.1-17.3; P<0.001) and URD (OR 3.4; 95% CI 1.1-10.6; P=0.03). However, when analysing HSCT performed with URD or RD grafts separately, BKV (OR 8.5; 95% CI 1.8-19.3; P=0.004) and MC (OR 5.9; 95% CI 1.3-11.3; P=0.009) increased the risk for HC only with a URD, but not with an RD graft.

Comparison of rubella seroepidemiology in 17 countries: progress towards international disease control targets

Abstract: Objective To standardize serological surveillance to compare rubella susceptibility in Australia and 16 European countries, and measure progress towards international disease-control targets. Methods Between 1996 and 2004, representative serum banks were established in 17 countries by collecting residual sera or community sampling. Serum banks were tested in each country and assay results were standardized. With a questionnaire, we collected information on current and past rubella vaccination programmes in each country. The percentage of seronegative ( 10%). The proportion of women of childbearing age without rubella protection ( 10 IU/ml) was calculated and compared with WHO targets of < 5%. Findings Only Romania had no rubella immunization programme at the time of the survey; the remaining countries had a two-dose childhood schedule using the measles, mumps and rubella (MMR) vaccine. The percentage of susceptible children defined five countries as group I, seven as group II and four as group III. Women of childbearing age without rubella protection were < 5% in only five countries. Conclusion Despite the low reported incidence in many countries, strengthening the coverage of the routine two-dose of MMR vaccine among children is needed, especially in group III countries. Catch-up campaigns in older age groups and selective targeting of older females are needed in many countries to ensure necessary levels of protective immunity among women of childbearing age. Bulletin of the World Health Organization 2008;86:118–125.

Pattern recognition in pulmonary tuberculosis defined by high content peptide microarray chip analysis representing 61 proteins from M. tuberculosis.

Abstract: Background Serum antibody-based target identification has been used to identify tumor-associated antigens (TAAs) for development of anti-cancer vaccines A similar approach can be helpful to identify biologically relevant and clinically meaningful targets in Mtuberculosis (MTB) infection for diagnosis or TB vaccine development in clinically well defined populations Method We constructed a high-content peptide microarray with 61 Mtuberculosis proteins as linear 15 aa peptide stretches with 12 aa overlaps resulting in 7446 individual peptide epitopes Antibody profiling was carried with serum from 34 individuals with active pulmonary TB and 35 healthy individuals in order to obtain an unbiased view of the MTB epitope pattern recognition pattern Quality data extraction was performed, data sets were analyzed for significant differences and patterns predictive of TB+/− Findings Three distinct patterns of IgG reactivity were identified: 89/7446 peptides were differentially recognized (in 34/34 TB+ patients and in 35/35 healthy individuals) and are highly predictive of the division into TB+ and TB−, other targets were exclusively recognized in all patients with TB (eg sigmaF) but not in any of the healthy individuals, and a third peptide set was recognized exclusively in healthy individuals (35/35) but no in TB+ patients The segregation between TB+ and TB− does not cluster into specific recognition of distinct MTB proteins, but into specific peptide epitope ‘hotspots’ at different locations within the same protein Antigen recognition pattern profiles in serum from TB+ patients from Armenia vs patients recruited in Sweden showed that IgG-defined MTB epitopes are very similar in individuals with different genetic background Conclusions A uniform target MTB IgG-epitope recognition pattern exists in pulmonary tuberculosis Unbiased, high-content peptide microarray chip-based testing of clinically well-defined populations allows to visualize biologically relevant targets useful for development of novel TB diagnostics and vaccines

Crimean-Congo hemorrhagic fever virus delays activation of the innate immune response.

Abstract: As a first line of defence against virus infection, mammalian cells elicit an innate immune response, characterized by secretion of type I interferons and the up-regulation of interferon stimulated genes. Many viruses down-regulate the innate immune responses in order to enhance their virulence. Crimean-Congo hemorrhagic fever virus (CCHFV), a Nairovirus of the family Bunyaviridae is the causative agent of severe hemorrhagic fever in humans with high mortality. Knowledge regarding the innate immune response against CCHFV is most limited. Interestingly, in this study it is shown that replicating CCHFV delays substantially the IFN response, possibly by interfering with the activation pathway of IRF-3. In addition, it is demonstrated that CCHFV replication is almost insensitive to subsequent treatment with interferon-alpha. Once the virus is replicating, virus replication is more or less insensitive to the antiviral effects induced by the interferon. By using an interferon bioassay, it is shown that infected cells secrete interferon relatively late after infection, that is, 48 hr post-infection. In summary, the results suggest the presence of a virulence factor encoded by CCHFV that delays the host defence in order to allow rapid viral spread in the host.