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Advani A.,Swedish Institute for Communicable Disease Control | Hallander H.O.,Swedish Institute for Communicable Disease Control | Dalby T.,Statens Serum Institute | Krogfelt K.A.,Statens Serum Institute | And 10 more authors.
Journal of Clinical Microbiology | Year: 2013

Between 1998 and 2009, Bordetella pertussis clinical isolates were collected during three periods, i.e., 1998 to 2001 (n=102), 2004 to 2005 (n=154), and 2007 to 2009 (n=140), from nine countries with distinct vaccination programs, i.e., Denmark, Finland, France, Germany, The Netherlands, Norway, Poland, Sweden, and the United Kingdom. Pulsed-field gel electrophoresis (PFGE) analysis was performed according to standardized recommendations for epidemiological typing of B. pertussis. There were 81 different PFGE profiles, five of which (BpSR3, BpSR5, BpSR10, BpSR11, and BpSR12) were observed in 61% of the 396 isolates and shown to be predominant in almost all countries. The major profile, BpSR11, showed a decreasing trend from 25% to 30% in 1998 to 2005 to 13% in 2007 to 2009, and there were increases in BpSR3 and BpSR10 from 0% and 8% to 21% and 22%, respectively. One difference between these profiles is that BpSR11 contains isolates harboring the fim3-2 allele and BpSR3 and BpSR10 contain isolates harboring the fim3-1 allele. The total proportion of the five predominant profiles increased from 44% in 1998 to 2001 to 63% in 2004 to 2005 to 70% in 2007 to 2009. In conclusion, common PFGE profiles were identified in B. pertussis populations circulating in European countries with different vaccination programs and different vaccine coverages. These prevalent isolates contain the novel pertussis toxin promoter ptxP3 allele. However, there is evidence for diversifying selection between ptxP3 strains characterized by distinct PFGE profiles. This work shows that, even within a relatively short time span of 10 years, successful isolates which spread through Europe and cause large shifts in B. pertussis populations may emerge. Copyright © 2013, American Society for Microbiology.


Cockburn A.,Northumbria University | Bradford R.,Unilever | Constable A.,Nestlé | Edwards G.,63 Woodlands Road. | And 9 more authors.
Food and Chemical Toxicology | Year: 2012

A systematic, tiered approach to assess the safety of engineered nanomaterials (ENMs) in foods is presented. The ENM is first compared to its non-nano form counterpart to determine if ENM-specific assessment is required. Of highest concern from a toxicological perspective are ENMs which have potential for systemic translocation, are insoluble or only partially soluble over time or are particulate and bio-persistent. Where ENM-specific assessment is triggered, Tier 1 screening considers the potential for translocation across biological barriers, cytotoxicity, generation of reactive oxygen species, inflammatory response, genotoxicity and general toxicity. In silico and in vitro studies, together with a sub-acute repeat-dose rodent study, could be considered for this phase. Tier 2 hazard characterisation is based on a sentinel 90-day rodent study with an extended range of endpoints, additional parameters being investigated case-by-case. Physicochemical characterisation should be performed in a range of food and biological matrices. A default assumption of 100% bioavailability of the ENM provides a 'worst case' exposure scenario, which could be refined as additional data become available. The safety testing strategy is considered applicable to variations in ENM size within the nanoscale and to new generations of ENM. © 2012 Elsevier Ltd.


Tomasevic G.,Laboratory for Experimental Brain Research | Laurer H.L.,University of Pennsylvania | Mattiasson G.,Laboratory for Experimental Brain Research | Van Steeg H.,National Institute of Public Health and Environment | And 2 more authors.
Journal of Neurosurgery | Year: 2012

Object. This study investigates the outcome after traumatic brain injury (TBI) in mice lacking the essential DNA repair gene xeroderma pigmentosum group A (XPA). As damage to DNA has been implicated in neuronal cell death in various models, the authors sought to elucidate whether the absence of an essential DNA repair factor would affect the outcome of TBI in an experimental setting. Methods. Thirty-seven adult mice of either wild-type (n = 18) or XPA-deficient ("knock-out" [n = 19]) genotype were subjected to controlled cortical impact experimental brain trauma, which produced a focal brain injury. Shaminjured mice of both genotypes were used as controls (9 in each group). The mice were subjected to neurobehavoral tests evaluating learning/acquisition (Morris water maze) and motor dysfunction (Rotarod and composite neuroscore test), pre- and postinjury up to 4 weeks. The mice were killed after 1 or 4 weeks, and cortical lesion volume, as well as hippocampal and thalamic cell loss, was evaluated. Hippocampal staining with doublecortin antibody was used to evaluate neurogenesis after the insult. Results. Brain-injured XPA -/- mice exhibited delayed recovery from impairment in neurological motor function, as well as pronounced cognitive dysfunction in a spatial learning task (Morris water maze), compared with injured XPA +/+ mice (p < 0.05). No differences in cortical lesion volume, hippocampal damage, or thalamic cell loss were detected between XPA +/+ and XPA -/- mice after brain injury. Also, no difference in the number of cells stained with doublecortin in the hippocampus was detected. Conclusions. The authors' results suggest that lack of the DNA repair factor XPA may delay neurobehavioral recovery after TBI, although they do not support the notion that this DNA repair deficiency results in increased cell or tissue death in the posttraumatic brain.


Gotz H.M.,Rotterdam Rijnmond Public Health Service | Van Den Broek I.V.F.,National Institute of Public Health and Environment | Hoebe C.J.P.A.,South Limburg Public Health Service | Brouwers E.E.H.G.,South Limburg Public Health Service | And 6 more authors.
Sexually Transmitted Infections | Year: 2013

Introduction In a systematic internet-based Chlamydia Screening Implementation Programme in The Netherlands, all chlamydia-positive participants automatically received a testkit after 6 months to facilitate early detection of repeat infections. The authors describe participation in repeat testing and prevalence and determinants of repeat infection during three consecutive annual screening rounds. Methods Data collection included information on testkits sent, samples received and results of laboratory tests at time of baseline test and retest; (sexual) behavioural variables and socio-demographic variables were assessed. Chlamydia positives were requested to answer additional questions about treatment and partner notification 10 days after checking their results. Results Retest rate was 66.3% (2777/4191). Retest chlamydia positivity was 8.8% (242/2756) compared with a chlamydia positivity at first screening test of 4.1%. Chlamydia positivity was significantly higher in younger age groups (14.6% in 16e19 years, 8.5% and 5.5% in 20e24 and 25e29 years; p<0.01); in participants with lower education (15.2% low, 11.1% medium and 5.1% high; p<0.001) and in Surinamese/ Antillean (13.1%), Turkish/Moroccan (12.9%) and Sub-Saharan African participants (18.6%; p<0.01). At baseline, 88.7% infected participants had reportedly been treated and treatment of current partner was 80.1%. Discussion Automated retesting by sending a testkit after 6 months to all chlamydia positives achieved high retest uptake and yielded a positivity rate twice as at baseline and can therefore be recommended as an additional strategy for chlamydia control. The high rate of repeat infections among known risk groups suggests room for improvement in patient case management and in effective risk reduction counselling.


Bar-Oz B.,Hebrew University of Jerusalem | Weber-Schoendorfer C.,esCharit Universittsmedizin Berlin | Berlin M.,Tel Aviv University | Clementi M.,University of Padua | And 10 more authors.
Drug Safety | Year: 2012

Background: Macrolides are a group of commonly prescribed antibiotics. There is some doubt surrounding the use of the newer macrolides in pregnancy. Objective: The present study aimed to compare outcomes of pregnancies exposed to the new macrolides clarithromycin, azithromycin and roxithromycin with non-teratogenic preparations. Methods: In this prospective, multinational, multicentre, controlled, observational study, information was obtained either from pregnant women or their healthcare professionals who contacted their local teratogen information services in Italy, Israel, the Czech Republic, the Netherlands and Germany seeking information after exposure to macrolides. The comparison group included women or their healthcare professional who contacted these centres with questions regarding known non-teratogenic preparations. Information on obstetric and other background parameters was collected at enrollment; after delivery, subjects or their healthcare professionals were contacted to ascertain pregnancy outcome parameters and other exposures through the remainder of the pregnancy. Results: A total of 608 women exposed to macrolides during pregnancy were enrolled; 511 of the exposures occurred during the first trimester. The comparison group comprised 773 women exposed to non-teratogenic preparations during the first trimester of pregnancy. No significant difference in the rate of major congenital malformations was found between the study group and the comparison group (3.4% vs 2.4%; p = 0.36; odds ratio (OR) 1.42; 95% CI 0.70, 2.88) or in the rate of cardiovascular malformations (1.6% vs 0.9%; p = 0.265; OR 1.91; 95% CI 0.63, 5.62). No significant differences were found between subgroups of macrolides in the rates of major congenital malformations or cardiac malformations, although for azithromycin this was of borderline significance. Conclusions: This study, in agreement with earlier smaller studies, suggests that the new macrolides do not pose a significantly increased risk of major congenital malformations or cardiac malformations. © 2012 Springer International Publishing AG. All rights reserved.


Xiridou M.,National Institute of Public Health and Environment | Soetens L.C.,National Institute of Public Health and Environment | Koedijk F.D.H.,National Institute of Public Health and Environment | Koedijk F.D.H.,Municipal Health Service Twente | And 3 more authors.
Epidemiology and Infection | Year: 2015

Gonorrhoea is one of the most common sexually transmitted infections. The control of gonorrhoea is extremely challenging because of the repeated development of resistance to the antibiotics used for its treatment. We explored different strategies to control the spread of antimicrobial resistance and prevent increases in gonorrhoea prevalence. We used a mathematical model that describes gonorrhoea transmission among men who have sex with men and distinguishes gonorrhoea strains sensitive or resistant to three antibiotics. We investigated the impact of combination therapy, switching first-line antibiotics according to resistance thresholds, and other control efforts (reduced sexual risk behaviour, increased treatment rate). Combination therapy can delay the spread of resistance better than using the 5% resistance threshold. Increased treatment rates, expected to enhance gonorrhoea control, may reduce gonorrhoea prevalence only in the short term, but could lead to more resistance and higher prevalence in the long term. Re-treatment of resistant cases with alternative antibiotics can substantially delay the spread of resistance. In conclusion, combination therapy and re-treatment of resistant cases with alternative antibiotics could be the most effective strategies to prevent increases in gonorrhoea prevalence due to antimicrobial resistance. Copyright © Cambridge University Press 2014.


Hayashi T.,U.S. National Institutes of Health | Hayashi E.,U.S. National Institutes of Health | Fujimoto M.,U.S. National Institutes of Health | Sprong H.,National Institute of Public Health and Environment | Su T.-P.,U.S. National Institutes of Health
Journal of Biological Chemistry | Year: 2012

The glycosphingolipid biosynthesis is initiated by monoglycosylation of ceramides, the action of which is catalyzed either by UDP-glucose:ceramide glucosyltransferase or by UDP-galactose:ceramide galactosyltransferase (CGalT). CGalT is expressed predominantly at the endoplasmic reticulum (ER) of oligodendrocytes and is responsible for synthesizing galactosylceramides (GalCer) that play an important role in regulation of axon conductance. However, despite the importance of ceramide monoglycosylation enzymes in a spectrum of cellular functions, the mechanism that fine tunes activities of those enzymes is largely unknown. In the present study, we demonstrated that the sigma-1 receptor (Sig-1R) chaperone, the mammalian homologue of a yeast C8-C7 sterol isomerase, controls the protein level and activity of the CGalT enzyme via a distinct ER-associated degradation system involving Insig. The Sig-1R forms a complex with Insig via its transmembrane domain partly in a sterol-dependent manner and associates with CGalT at the ER. The knockdown of Sig-1Rs dramatically prolonged the lifetime of CGalT without affecting the trimming of N -linked oligosaccharides at CGalT. The increased lifetime leads to the up-regulation of CGalT protein as well as elevated enzymatic activity in CHO cells stably expressing CGalT. Knockdown of Sig-1Rs also decreased CGalT degradation endogenously expressed in D6P2T-schwannoma cells. Our data suggest that Sig-1Rs negatively regulate the activity of GalCer synthesis under physiological conditions by enhancing the degradation of CGalT through regulation of the dynamics of Insig in the lipid-activated ER-associated degradation system. The GalCer synthesis may thus be influenced by sterols at the ER.


PubMed | National Institute of Public Health and Environment, Academy of Sciences of the Czech Republic and University of Agricultural Sciences and Veterinary Medicine, Cluj-Napoca
Type: Journal Article | Journal: PloS one | Year: 2015

Borrelia turcica comprises the third major group of arthropod-transmitted borreliae and is phylogenetically divergent from other Borrelia groups. The novel group of Borrelia was initially isolated from Hyalomma aegyptium ticks in Turkey and it was recently found in blood and multiple organs of tortoises exported from Jordan to Japan. However, the ecology of these spirochetes and their development in ticks or the vertebrate hosts were not investigated in detail; our aims were to isolate the pathogen and to evaluate the possibility of transstadial transmission of Borrelia turcica by H. aegyptium ticks. Ticks were collected from Testudo graeca tortoises during the summer of 2013 from southeastern Romania. Engorged nymphs were successfully molted to the adult stage. Alive B. turcica was isolated from molted ticks by using Barbour-Stoenner-Kelly (BSK) II medium. Four pure cultures of spirochetes were obtained and analyzed by PCR and sequencing. Sequence analysis of glpQ, gyrB and flaB revealed 98%-100% similarities with B. turcica. H. aegyptium ticks collected from T. graeca tortoises were able to pass the infection with B. turcica via transstadial route, suggesting its vectorial capacity.


PubMed | National Institute of Public Health and Environment
Type: Journal Article | Journal: Epidemiology and infection | Year: 2015

Gonorrhoea is one of the most common sexually transmitted infections. The control of gonorrhoea is extremely challenging because of the repeated development of resistance to the antibiotics used for its treatment. We explored different strategies to control the spread of antimicrobial resistance and prevent increases in gonorrhoea prevalence. We used a mathematical model that describes gonorrhoea transmission among men who have sex with men and distinguishes gonorrhoea strains sensitive or resistant to three antibiotics. We investigated the impact of combination therapy, switching first-line antibiotics according to resistance thresholds, and other control efforts (reduced sexual risk behaviour, increased treatment rate). Combination therapy can delay the spread of resistance better than using the 5% resistance threshold. Increased treatment rates, expected to enhance gonorrhoea control, may reduce gonorrhoea prevalence only in the short term, but could lead to more resistance and higher prevalence in the long term. Re-treatment of resistant cases with alternative antibiotics can substantially delay the spread of resistance. In conclusion, combination therapy and re-treatment of resistant cases with alternative antibiotics could be the most effective strategies to prevent increases in gonorrhoea prevalence due to antimicrobial resistance.


PubMed | National Institute of Public Health and Environment and Szent Istvan University
Type: Journal Article | Journal: Experimental & applied acarology | Year: 2015

Tick-borne rickettsioses belong to the important emerging infectious diseases worldwide. We investigated the potential human exposure to rickettsiae by determining their presence in questing ticks collected in an urban park of Budapest and a popular hunting and recreational forest area in southern Hungary. Differences were found in the infectious risk between the two habitats. Rickettsia monacensis and Rickettsia helvetica were identified with sequencing in questing Ixodes ricinus, the only ticks species collected in the city park. Female I. ricinus had a particularly high prevalence of R. helvetica (45%). Tick community was more diverse in the rural habitat with Dermacentor reticulatus ticks having especially high percentage (58%) of Rickettsia raoultii infection. We conclude that despite the distinct eco-epidemiological traits, the risk (hazard and exposure) of acquiring human pathogenic rickettsial infections in both the urban and the rural study sites exists.

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