• An Xpd mouse model for the combined xeroderma pigmentosum/Cockayne syndrome exhibiting both cancer predisposition and segmental progeria.

      Andressoo, Jaan-Olle; Mitchell, James R; Wit, Jan de; Hoogstraten, Deborah; Volker, Marcel; Toussaint, Wendy; Speksnijder, Ewoud; Beems, Rudolf B; Steeg, Harry van; Jans, Judith; Zeeuw, Chris I de; Jaspers, Nicolaas G J; Raams, Anja; Lehmann, Alan R; Vermeulen, Wim; Hoeijmakers, Jan H J; Horst, Gijsbertus T J van der (2006-08-01)
      Inborn defects in nucleotide excision DNA repair (NER) can paradoxically result in elevated cancer incidence (xeroderma pigmentosum [XP]) or segmental progeria without cancer predisposition (Cockayne syndrome [CS] and trichothiodystrophy [TTD]). We report generation of a knockin mouse model for the combined disorder XPCS with a G602D-encoding mutation in the Xpd helicase gene. XPCS mice are the most skin cancer-prone NER model to date, and we postulate an unusual NER dysfunction that is likely responsible for this susceptibility. XPCS mice also displayed symptoms of segmental progeria, including cachexia and progressive loss of germinal epithelium. Like CS fibroblasts, XPCS and TTD fibroblasts from human and mouse showed evidence of defective repair of oxidative DNA lesions that may underlie these segmental progeroid symptoms.
    • Year-to-year variation in the density of Ixodes ricinus ticks and the prevalence of the rodent-associated human pathogens Borrelia afzelii and B. miyamotoi in different forest types.

      Ruyts, Sanne C; Tack, Wesley; Ampoorter, Evy; Coipan, Elena C; Matthysen, Erik; Heylen, Dieter; Sprong, Hein; Verheyen, Kris (2017-08-26)
      The human pathogens Borrelia afzelii, which causes Lyme borreliosis and B. miyamotoi, which causes relapsing fever, both circulate between Ixodes ricinus ticks and rodents. The spatiotemporal dynamics in the prevalence of these pathogens have not yet been fully elucidated, but probably depend on the spatiotemporal population dynamics of small rodents. We aimed to evaluate the effect of different forest types on the density of infected nymphs in different years and to obtain more knowledge about the spatial and temporal patterns of ticks and tick-borne pathogens. We analysed unfed nymphal ticks from 22 stands of four different forest types in Belgium in 2009, 2010, 2013 and 2014 and found that the density of nymphs in general and the density of nymphs infected with B. afzelii and B. miyamotoi varied yearly, but without temporal variation in the infection prevalence. The yearly variation in density of infected nymphs in our study thus seems to be caused most by the variation in the density of nymphs, which makes it a good predictor of disease risk. The risk for rodent-associated tick-borne diseases also varied between forest types. We stress the need to elucidate the contribution of the host community composition to tick-borne disease risk.
    • Years of life lost due to influenza-attributable mortality in older adults in the Netherlands: a competing risks approach.

      McDonald, Scott A; van Wijhe, Maarten; van Asten, Liselotte; van der Hoek, Wim; Wallinga, Jacco (2018-02-06)
      We estimated the influenza mortality burden in adults 60 years of age and older in the Netherlands in terms of years of life lost, taking into account competing mortality risks. Weekly laboratory surveillance data for influenza and other respiratory pathogens and weekly extreme temperature served as covariates in Poisson regression models fitted to weekly age-group specific mortality data for the period 1999/2000 through 2012/13. Burden for age-groups 60-64 through 85-89 years was computed as years of life lost before age 90 (YLL90) using restricted mean lifetimes survival analysis and accounting for competing risks. Influenza-attributable mortality burden was greatest for persons aged 80-84 years, at 914 YLL90 per 100,000 persons (95% uncertainty interval:867, 963), followed by 85-89 years (787 YLL90/100,000; 95% uncertainty interval:741, 834). Ignoring competing mortality risks in the computation of influenza-attributable YLL90 would lead to substantial over-estimation of burden, from 3.5% for 60-64 years to 82% for persons aged 80-89 years at death. Failure to account for competing mortality risks has implications for accuracy of disease burden estimates, especially among persons aged 80 years and older. As the mortality burden borne by the elderly is notably high, prevention initiatives may benefit from being redesigned to more effectively prevent infection in the oldest age-groups.
    • Zieke hazen in het veld

      Montizaan M; Mulder A (2017-04-30)
    • Zika virus en seksuele transmissie.

      Duijster, J W; Brandwagt, D A H; Timen, A; van der Eijk, A A; Vennema, H; Te Wierik, M J M (2017)
      - More evidence has become available concerning the sexual transmission of Zika virus and viral shedding in semen, which has led to the expansion of international guidelines for prevention of sexual transmission; Dutch guidelines have not been altered.- Internationally, the use of condoms during sex or sexual abstinence is advised for the duration of the pregnancy. Furthermore, when actively trying to conceive one should use a condom for six months.- In the Dutch guidelines, men who have visited a Zika virus epidemic area are advised to use a condom for 2 months upon return, irrespective of their partner possibly being pregnant or their wish to conceive.- Based on reports to the World Health Organisation and patient reports, the serial interval between disease onsets of both sexual partners is 4-44 days (median: 15).- Zika virus RNA is often no longer detectable in semen 2-3 months after disease onset.- International guidelines are based on the maximum detection period of Zika virus RNA and on virus isolation. Dutch prevention guidelines, on the other hand, are based on the longest serial interval known for sexual transmission (44 days).- Detection of Zika virus RNA in semen does not give a definitive answer on contagiousness. Currently, following the Dutch prevention advice is the best option in order to prevent sexual transmission.
    • Zikavirusdiagnostiek; de (on)zin van uitgebreide serologische algoritmes bij zwangeren)

      Reusken C; Rockx B; Geurts van Kessel C; Pas S; Tienen C van; Kampen J van; Koopmans M; Eijk A van der (2016-06)
    • Zinc-induced Metallothionein in centenarian offspring from a large European population: the MARK-AGE Project.

      Giacconi, Robertina; Costarelli, Laura; Piacenza, Francesco; Basso, Andrea; Bürkle, Alexander; Moreno-Villanueva, Maria; Grune, Tilman; Weber, Daniela; Stuetz, Wolfgang; Gonos, Efstathios S; Schön, Christiane; Grubeck-Loebenstein, Beatrix; Sikora, Ewa; Toussaint, Olivier; Debacq-Chainiaux, Florence; Franceschi, Claudio; Hervonen, Antti; Slagboom, Eline; Ciccarone, Fabio; Zampieri, Michele; Caiafa, Paola; Jansen, Eugène; Dollé, Martijn E T; Breusing, Nicolle; Mocchegiani, Eugenio; Malavolta, Marco (2017-10-17)
      Metallothionein (MT) family are cysteine-rich proteins that regulate zinc (Zn) homeostasis and protect against oxidative damage. Studies in transgenic mice have shown that MT favourably influence longevity, although their role in human aging is not completely understood.Within the European multicenter study MARK-AGE, we analysed MT induction after Zn treatment in peripheral blood mononuclear cells (PBMCs) and its relation with redox biomarkers in 2936 age-stratified subjects (35-75 years) including the general population (RASIG), centenarian offspring (GO) and their spouses (SGO). We found that the lymphocyte capability to induce MT in response to Zn is not affected by aging. However, GO participants showed lower Zn-induced MT and increased basal expression of MT1A, MT1X and ZnT-1 genes than RASIG subjects. Moreover, Zn-induced MT levels were found to be inversely related with oxidative stress markers (plasma protein carbonyls, 3-nitrotyrosine and malondialdehyde) in the whole population, but not in GO subjects.In conclusion, our results support the hypothesis that the response to Zn is attenuated in PBMCs of centenarian offspring compared to the general population as a consequence of a tighter control of Zn homeostasis which is likely to provide them constant protection against stress stimuli over the whole lifespan.
    • Zoonotic bacteria and parasites found in raw meat-based diets for cats and dogs.

      van Bree, Freek P J; Bokken, Gertie C A M; Mineur, Robin; Franssen, Frits; Opsteegh, Marieke; van der Giessen, Joke W B; Lipman, Len J A; Overgaauw, Paul A M (2018-01-13)
      Feeding raw meat-based diets (RMBDs) to companion animals has become increasingly popular. Since these diets may be contaminated with bacteria and parasites, they may pose a risk to both animal and human health. The purpose of this study was to test for the presence of zoonotic bacterial and parasitic pathogens in Dutch commercial RMBDs. We analysed 35 commercial frozen RMBDs from eight different brands. Escherichia coli serotype O157:H7 was isolated from eight products (23 per cent) and extended-spectrum beta-lactamases-producing E coli was found in 28 products (80 per cent). Listeria monocytogenes was present in 19 products (54 per cent), other Listeria species in 15 products (43 per cent) and Salmonella species in seven products (20 per cent). Concerning parasites, four products (11 per cent) contained Sarcocystis cruzi and another four (11 per cent) S tenella In two products (6 per cent) Toxoplasma gondii was found. The results of this study demonstrate the presence of potential zoonotic pathogens in frozen RMBDs that may be a possible source of bacterial infections in pet animals and if transmitted pose a risk for human beings. If non-frozen meat is fed, parasitic infections are also possible. Pet owners should therefore be informed about the risks associated with feeding their animals RMBDs.
    • Zoonotic Infection with Pigeon Paramyxovirus Type 1 linked to Fatal Pneumonia.

      Kuiken, Thijs; Breitbart, Mya; Beer, Martin; Grund, Christian; Höper, Dirk; van den Hoogen, Bernadette; Kerkhoffs, Jean-Louis H; Kroes, Aloys C M; Rosario, Karyna; van Run, Peter; Schwarz, Matthias; Svraka, Sanela; Teifke, Jens; Koopmans, Marion (2018-01-24)
      The characteristics and risk factors of pigeon paramyxovirus type 1 (PPMV-1) infection in humans are poorly known. We performed virological, pathological and epidemiological analyses of a Dutch case, and compared the results with those of a US case. Both infections occurred in transplant patients under immunosuppressive therapy and caused fatal respiratory failure. Both virus isolates clustered with avian paramyxovirus type 1 (APMV-1) genotype VIb/1, which has pigeons and doves as reservoir. Experimentally inoculated pigeons became infected and transmitted the virus to naïve pigeons. Likely route of transmission to both patients was direct or indirect contact with infected pigeons or doves. Given the large populations of feral pigeons with endemic PPMV-1 infection in cities, increasing urbanisation and a higher proportion of immunocompromised individuals, the risk of severe human PPMV-1 infections may increase. We recommend to test for APMV-1, including PPMV-1, in respiratory disease cases where common respiratory pathogens cannot be identified.
    • Zwangerschap en de ziekte van Chagas.

      Hinfaran AD; Pattipeilohy J; Fanoy E; Kortbeek T; Gool T (2018-04)
    • Zwemmen in de gracht: hoe groot zijn de infectierisico's?

      Joosten R; Kliffen S; Hintaran P; Brandwagt D; Pijnacker R; Lodder W; Siedenburg E; Sonder G; Fanoy E (2019-01)