• Phylogeographic analysis reveals multiple international transmission events have driven the global emergence of Escherichia coli O157:H7.

      Franz, Eelco; Rotariu, Ovidiu; Lopes, Bruno S; MacRae, Marion; Bono, James L; Laing, Chad; Gannon, Victor; Söderlund, Robert; van Hoek, Angela H A M; Friesema, Ingrid; French, Nigel P; George, Tessy; Biggs, Patrick J; Jaros, Patricia; Rivas, Marta; Chinen, Isabel; Campos, Josefina; Jernberg, Cecilia; Gobius, Kari; Mellor, Glen E; Chandry, P Scott; Perez-Reche, Francisco; Forbes, Ken J; Strachan, Norval J C (2018-10-29)
      Shiga toxin-producing Escherchia coli O157:H7 is a zoonotic pathogen which causes numerous food and waterborne disease outbreaks. It is globally distributed but its origin and temporal sequence of geographical spread is unknown.
    • Harvesting the wisdom of the crowd: using online ratings to explore care experiences in regions.

      Hendrikx, Roy J P; Spreeuwenberg, Marieke D; Drewes, Hanneke W; Struijs, Jeroen N; Ruwaard, Dirk; Baan, Caroline A (2018-10-20)
      Regional population health management (PHM) initiatives need an understanding of regional patient experiences to improve their services. Websites that gather patient ratings have become common and could be a helpful tool in this effort. Therefore, this study explores whether unsolicited online ratings can provide insight into (differences in) patient's experiences at a (regional) population level.
    • The impact of influenza vaccination on infection, hospitalisation and mortality in the Netherlands between 2003 and 2015.

      Backer, J A; Wallinga, J; Meijer, A; Donker, G A; van der Hoek, W; van Boven, M (2018-10-11)
      Influenza epidemics annually cause substantial morbidity and mortality. For this reason, vaccination is offered yearly to persons with an elevated risk for complications. Assessments of the impact of vaccination are, however, hampered by year-to-year variation in epidemic size and vaccine effectiveness. We estimate the impact of the current vaccination programme comparing simulations with vaccination to counterfactual simulations without vaccination. The simulations rely on an age- and risk-structured transmission model that tracks the build-up and loss of immunity over successive seasons, and that allows the vaccine match to vary between seasons. The model parameters are estimated with a particle Monte Carlo method and approximate Bayesian computation, using epidemiological data on vaccine effectiveness and epidemic size in the Netherlands over a period of 11 years. The number of infections, hospitalisations and deaths vary greatly between years because waning of immunity and vaccine match may differ every season, which is in line with observed variation in influenza epidemic sizes. At an overall coverage of 21%, vaccination has averted on average 13% (7.2-19%, 95% range) of infections, 24% (16-36%) of hospitalisations, and 35% (16-50%) of deaths. This suggests that vaccination is mainly effective in protecting vaccinees from infection rather than reducing transmission. As the Dutch population continues to grow and age, the vaccination programme is projected (up to 2025) to gain in impact, despite a decreasing infection attack rate.
    • Global expansion of Mycobacterium tuberculosis lineage 4 shaped by colonial migration and local adaptation.

      Brynildsrud, Ola B; Pepperell, Caitlin S; Suffys, Philip; Grandjean, Louis; Monteserin, Johana; Debech, Nadia; Bohlin, Jon; Alfsnes, Kristian; Pettersson, John O-H; Kirkeleite, Ingerid; Fandinho, Fatima; da Silva, Marcia Aparecida; Perdigao, Joao; Portugal, Isabel; Viveiros, Miguel; Clark, Taane; Caws, Maxine; Dunstan, Sarah; Thai, Phan Vuong Khac; Lopez, Beatriz; Ritacco, Viviana; Kitchen, Andrew; Brown, Tyler S; van Soolingen, Dick; O'Neill, Mary B; Holt, Kathryn E; Feil, Edward J; Mathema, Barun; Balloux, Francois; Eldholm, Vegard (2018-10)
      On the basis of population genomic and phylogeographic analyses of 1669 Mycobacterium tuberculosis lineage 4 (L4) genomes, we find that dispersal of L4 has been completely dominated by historical migrations out of Europe. We demonstrate an intimate temporal relationship between European colonial expansion into Africa and the Americas and the spread of L4 tuberculosis (TB). Markedly, in the age of antibiotics, mutations conferring antimicrobial resistance overwhelmingly emerged locally (at the level of nations), with minimal cross-border transmission of resistance. The latter finding was found to reflect the relatively recent emergence of these mutations, as a similar degree of local restriction was observed for susceptible variants emerging on comparable time scales. The restricted international transmission of drug-resistant TB suggests that containment efforts at the level of individual countries could be successful.
    • Effectiveness of diabetes self-management education via a smartphone application in insulin treated type 2 diabetes patients - design of a randomised controlled trial ('TRIGGER study').

      Boels, Anne Meike; Rutten, Guy; Zuithoff, Nicolaas; de Wit, Ardine; Vos, Rimke (2018-10-22)
      Health care providers aim to stimulate self-management in type 2 diabetes (T2DM) patients. However, they have a limited number of patient contacts to do this. With the growing number of T2DM patients, innovative and cost-effective interventions to promote self-management are needed. We aim to evaluate the effectiveness of diabetes self-management education via a smartphone app in T2DM patients on insulin therapy.
    • The incidence of symptomatic infection with influenza virus in the Netherlands 2011/2012 through 2016/2017, estimated using Bayesian evidence synthesis.

      Teirlinck, A C; de Gier, B; Meijer, A; Donker, G; de Lange, M; Koppeschaar, C; van der Hoek, W; Kretzschmar, M E; McDonald, S A (2018-10-23)
      Due to differences in the circulation of influenza viruses, distribution and antigenic drift of A subtypes and B lineages, and susceptibility to infection in the population, the incidence of symptomatic influenza infection can vary widely between seasons and age-groups. Our goal was to estimate the symptomatic infection incidence in the Netherlands for the six seasons 2011/2012 through 2016/2017, using Bayesian evidence synthesis methodology to combine season-specific sentinel surveillance data on influenza-like illness (ILI), virus detections in sampled ILI cases and data on healthcare-seeking behaviour. Estimated age-aggregated incidence was 6.5 per 1000 persons (95% uncertainty interval (UI): 4.7-9.0) for season 2011/2012, 36.7 (95% UI: 31.2-42.8) for 2012/2013, 9.1 (95% UI: 6.3-12.9) for 2013/2014, 41.1 (95% UI: 35.0-47.7) for 2014/2015, 39.4 (95% UI: 33.4-46.1) for 2015/2016 and 27.8 (95% UI: 22.7-33.7) for season 2016/2017. Incidence varied substantially between age-groups (highest for the age-group <5 years: 23 to 47/1000, but relatively low for 65+ years: 2 to 34/1000 over the six seasons). Integration of all relevant data sources within an evidence synthesis framework has allowed the estimation - with appropriately quantified uncertainty - of the incidence of symptomatic influenza virus infection. These estimates provide valuable insight into the variation in influenza epidemics across seasons, by virus subtype and lineage, and between age-groups.
    • Inhibiting ex-vivo Th17 responses in Ankylosing Spondylitis by targeting Janus kinases.

      Hammitzsch, Ariane; Chen, Liye; de Wit, Jelle; Al-Mossawi, M Hussein; Ridley, Anna; Sekine, Takuya; Simone, Davide; Doig, Karen; Skapenko, Alla; Bowness, Paul (2018-10-23)
      Treatment options for Ankylosing Spondylitis (AS) are still limited. The T helper cell 17 (Th17) pathway has emerged as a major driver of disease pathogenesis and a good treatment target. Janus kinases (JAK) are key transducers of cytokine signals in Th17 cells and therefore promising targets for the treatment of AS. Here we investigate the therapeutic potential of four different JAK inhibitors on cells derived from AS patients and healthy controls, cultured in-vitro under Th17-promoting conditions. Levels of IL-17A, IL-17F, IL-22, GM-CSF and IFNγ were assessed by ELISA and inhibitory effects were investigated with Phosphoflow. JAK1/2/3 and TYK2 were silenced in CD4+ T cells with siRNA and effects analyzed by ELISA (IL-17A, IL-17F and IL-22), Western Blot, qPCR and Phosphoflow. In-vitro inhibition of CD4+ T lymphocyte production of multiple Th17 cytokines (IL-17A, IL-17F and IL-22) was achieved with JAK inhibitors of differing specificity, as well as by silencing of JAK1-3 and Tyk2, without impacting on cell viability or proliferation. Our preclinical data suggest JAK inhibitors as promising candidates for therapeutic trials in AS, since they can inhibit multiple Th17 cytokines simultaneously. Improved targeting of TYK2 or other JAK isoforms may confer tailored effects on Th17 responses in AS.
    • Tick-borne pathogens in Finland: comparison of Ixodes ricinus and I. persulcatus in sympatric and parapatric areas.

      Laaksonen, Maija; Klemola, Tero; Feuth, Eeva; Sormunen, Jani J; Puisto, Anna; Mäkelä, Satu; Penttinen, Ritva; Ruohomäki, Kai; Hänninen, Jari; Sääksjärvi, Ilari E; Vuorinen, Ilppo; Sprong, Hein; Hytönen, Jukka; Vesterinen, Eero J (2018-10-24)
      Almost 3500 tick samples, originally collected via a nationwide citizen science campaign in 2015, were screened to reveal the prevalence and distribution of a wide spectrum of established and putative tick-borne pathogens vectored by Ixodes ricinus and I. persulcatus in Finland. The unique geographical distribution of these two tick species in Finland allowed us to compare pathogen occurrence between an I. ricinus-dominated area (southern Finland), an I. persulcatus-dominated area (northern Finland), and a sympatric area (central Finland).
    • Effect of childhood pneumococcal conjugate vaccination on invasive disease in older adults of 10 European countries: implications for adult vaccination.

      Hanquet, Germaine; Krizova, Pavla; Valentiner-Branth, Palle; Ladhani, Shamez N; Nuorti, J Pekka; Lepoutre, Agnes; Mereckiene, Jolita; Knol, Mirjam; Winje, Brita A; Ciruela, Pilar; Ordobas, Maria; Guevara, Marcela; McDonald, Eisin; Morfeldt, Eva; Kozakova, Jana; Slotved, Hans-Christian; Fry, Norman K; Rinta-Kokko, Hanna; Varon, Emmanuelle; Corcoran, Mary; van der Ende, Arie; Vestrheim, Didrik F; Munoz-Almagro, Carmen; Latasa, Pello; Castilla, Jesus; Smith, Andrew; Henriques-Normark, Birgitta; Whittaker, Robert; Pastore Celentano, Lucia; Savulescu, Camelia (2018-10-24)
      Pneumococcal conjugate vaccines (PCVs) have the potential to prevent pneumococcal disease through direct and indirect protection. This multicentre European study estimated the indirect effects of 5-year childhood PCV10 and/or PCV13 programmes on invasive pneumococcal disease (IPD) in older adults across 13 sites in 10 European countries, to support decision-making on pneumococcal vaccination policies.
    • Towards a sustainable EU health information system infrastructure: A consensus driven approach.

      Bogaert, Petronille; van Oers, Hans; Van Oyen, Herman (2018-10-16)
      Health information in the EU is characterised by diversity and fragmentation of health information infrastructures. A well-defined and sustainable EU health information system infrastructure is lacking. The potential of a European Research Infrastructure Consortium on Health Information for Research and Evidence-based Policy (HIREP-ERIC) to take up this role is investigated.
    • Can we predict tuberculosis cure? What tools are available?

      Goletti, Delia; Lindestam Arlehamn, Cecilia S; Scriba, Thomas J; Anthony, Richard; Cirillo, Daniela Maria; Alonzi, Tonino; Denkinger, Claudia M; Cobelens, Frank (2018-11)
      Antibiotic treatment of tuberculosis takes ≥6 months, putting a major burden on patients and health systems in large parts of the world. Treatment beyond 2 months is needed to prevent tuberculosis relapse by clearing remaining, drug-tolerant Mycobacterium tuberculosis bacilli. However, the majority of patients treated for only 2-3 months will cure without relapse and do not need prolonged treatment. Assays that can identify these patients at an early stage of treatment may significantly help reduce the treatment burden, while a test to identify those patients who will fail treatment may help target host-directed therapies.In this review we summarise the state of the art with regard to discovery of biomarkers that predict relapse-free cure for pulmonary tuberculosis. Positron emission tomography/computed tomography scanning to measure pulmonary inflammation enhances our understanding of "cure". Several microbiological and immunological markers seem promising; however, they still need a formal validation. In parallel, new research strategies are needed to generate reliable tests.
    • Threats to timely sharing of pathogen sequence data.

      Dos S Ribeiro, Carolina; Koopmans, Marion P; Haringhuizen, George B (2018)
    • Data on child complementary feeding practices, nutrient intake and stunting in Musanze District, Rwanda.

      Uwiringiyimana, Vestine; Ocké, Marga C; Amer, Sherif; Veldkamp, Antonie (2018-12)
      Stunting prevalence in Rwanda is still a major public health issue, and data on stunting is needed to plan relevant interventions. This data, collected in 2015, presents complementary feeding practices, nutrient intake and its association with stunting in infants and young children in Musanze District in Rwanda. A household questionnaire and a 24-h recall questionnaire were used to collect the data. In total 145 children aged 5-30 months participated in the study together with their caregivers. The anthropometric status of children was calculated using WHO Anthro software [1] according to the WHO growth standards [2]. The complementary feeding practices together with households' characteristics are reported per child stunting status. The nutrient intake and food group consumption are presented per age group of children. Also, the percentage contribution of each food groups to energy and nutrient intake in children is reported. The data also shows the association between zinc intake and age groups of children. Using multiple linear regression, a sensitivity analysis was done with height-for-age z-score as the dependent variable and exclusive breastfeeding, deworming table use, BMI of caregiver, dietary zinc intake as independent variables. The original linear regression model and a detailed methodology and analyses conducted are presented in Uwiringiyimana et al. [3].
    • Active commuting through natural environments is associated with better mental health: Results from the PHENOTYPE project.

      Zijlema, Wilma L; Avila-Palencia, Ione; Triguero-Mas, Margarita; Gidlow, Christopher; Maas, Jolanda; Kruize, Hanneke; Andrusaityte, Sandra; Grazuleviciene, Regina; Nieuwenhuijsen, Mark J (2018-12)
      Commuting routes with natural features could promote walking or cycling for commuting. Commuting through natural environments (NE) could have mental health benefits as exposure to NE can reduce stress and improve mental health, but there is little evidence. This study evaluates the association between NE and commuting, whether active or not, and the association between commuting (through NE), whether active or not, and mental health. We also evaluate the moderating effect of NE quality on the association between NE commuting and mental health.
    • Genetic determinants of telomere length and risk of pancreatic cancer: A PANDoRA study.

      Campa, Daniele; Matarazzi, Martina; Greenhalf, William; Bijlsma, Maarten; Saum, Kai-Uwe; Pasquali, Claudio; van Laarhoven, Hanneke; Szentesi, Andrea; Federici, Francesca; Vodicka, Pavel; Funel, Niccola; Pezzilli, Raffaele; Bueno-de-Mesquita, H Bas; Vodickova, Ludmila; Basso, Daniela; Obazee, Ofure; Hackert, Thilo; Soucek, Pavel; Cuk, Katarina; Kaiser, Jörg; Sperti, Cosimo; Lovecek, Martin; Capurso, Gabriele; Mohelnikova-Duchonova, Beatrice; Khaw, Kay-Tee; König, Anna-Katharina; Kupcinskas, Juozas; Kaaks, Rudolf; Bambi, Franco; Archibugi, Livia; Mambrini, Andrea; Cavestro, Giulia Martina; Landi, Stefano; Hegyi, Péter; Izbicki, Jakob R; Gioffreda, Domenica; Zambon, Carlo Federico; Tavano, Francesca; Talar-Wojnarowska, Renata; Jamroziak, Krzysztof; Key, Timothy J; Fave, Gianfranco Delle; Strobel, Oliver; Jonaitis, Laimas; Andriulli, Angelo; Lawlor, Rita T; Pirozzi, Felice; Katzke, Verena; Valsuani, Chiara; Vashist, Yogesh K; Brenner, Hermann; Canzian, Federico (2018-10-16)
      Telomere deregulation is a hallmark of cancer. Telomere length measured in lymphocytes (LTL) has been shown to be a risk marker for several cancers. For pancreatic ductal adenocarcinoma (PDAC) consensus is lacking whether risk is associated with long or short telomeres. Mendelian randomization approaches have shown that a score built from SNPs associated with LTL could be used as a robust risk marker. We explored this approach in a large scale study within the PANcreatic Disease ReseArch (PANDoRA) consortium. We analyzed 10 SNPs (ZNF676-rs409627, TERT-rs2736100, CTC1-rs3027234, DHX35-rs6028466, PXK-rs6772228, NAF1-rs7675998, ZNF208-rs8105767, OBFC1-rs9420907, ACYP2-rs11125529 and TERC-rs10936599) alone and combined in a LTL genetic score ("teloscore", which explains 2.2% of the telomere variability) in relation to PDAC risk in 2,374 cases and 4,326 controls. We identified several associations with PDAC risk, among which the strongest were with the TERT-rs2736100 SNP (OR = 1.54; 95%CI 1.35-1.76; p = 1.54 × 10-10 ) and a novel one with the NAF1-rs7675998 SNP (OR = 0.80; 95%CI 0.73-0.88; p = 1.87 × 10-6 , ptrend = 3.27 × 10-7 ). The association of short LTL, measured by the teloscore, with PDAC risk reached genome-wide significance (p = 2.98 × 10-9 for highest vs. lowest quintile; p = 1.82 × 10-10 as a continuous variable). In conclusion, we present a novel genome-wide candidate SNP for PDAC risk (TERT-rs2736100), a completely new signal (NAF1-rs7675998) approaching genome-wide significance and we report a strong association between the teloscore and risk of pancreatic cancer, suggesting that telomeres are a potential risk factor for pancreatic cancer.
    • Effect of incident hepatitis C infection on CD4 count and HIV RNA trajectories based on a multinational HIV seroconversion cohort.

      van Santen, Daniela K; van der Helm, Jannie J; Touloumi, Giota; Pantazis, Nikos; Muga, Roberto; Gunsenheimer-Bartmeyer, Barbara; Gill, M John; Sanders, Eduard; Kelleher, Anthony; Zangerle, Robert; Porter, Kholoud; Prins, Maria; Geskus, Ronald B (2018-10-15)
      Most studies on hepatitis C virus (HCV)/HIV co-infection do not account for the order and duration of these two infections. We aimed to assess the effect of incident HCV infection, and its timing relative to HIV seroconversion (HIVsc) in HIV-positive men who have sex with men (MSM) on their subsequent CD4 T-cell count (CD4) and HIV-RNA viral load (VL) trajectories.
    • Do people living with HIV experience greater age advancement than their HIV-negative counterparts?

      De Francesco, Davide; Wit, Ferdinand W; Bürkle, Alexander; Oehlke, Sebastian; Kootstra, Neeltje A; Winston, Alan; Franceschi, Claudio; Garagnani, Paolo; Pirazzini, Chiara; Libert, Claude; Grune, Tilman; Weber, Daniela; Jansen, Eugène H J M; Sabin, Caroline A; Reiss, Peter (2018-10-16)
      Despite successful antiretroviral (ARV) therapy, people living with HIV (PLWH) may show signs of premature/accentuated aging. We compared established biomarkers of aging in PLWH, appropriately-chosen HIV-negative individuals, and blood donors, and explored factors associated with biological age advancement.
    • Timing of eating across ten European countries - results from the European Prospective Investigation into Cancer and Nutrition (EPIC) calibration study.

      Huseinovic, Ena; Winkvist, Anna; Freisling, Heinz; Slimani, Nadia; Boeing, Heiner; Buckland, Genevieve; Schwingshackl, Lukas; Olsen, Anja; Tjønneland, Anne; Stepien, Magdalena; Boutron-Ruault, Marie-Christine; Mancini, Francesca; Artaud, Fanny; Kühn, Tilman; Katzke, Verena; Trichopoulou, Antonia; Naska, Androniki; Orfanos, Philippos; Tumino, Rosario; Masala, Giovanna; Krogh, Vittorio; Santucci de Magistris, Maria; Ocké, Marga C; Brustad, Magritt; Jensen, Torill Enget; Skeie, Guri; Rodríguez-Barranco, Miguel; Huerta, José María; Ardanaz, Eva; Quirós, José Ramón; Jakszyn, Paula; Sonestedt, Emily; Ericson, Ulrika; Wennberg, Maria; Key, Timothy J; Aune, Dagfinn; Riboli, Elio; Weiderpass, Elisabete; Bertéus Forslund, Heléne (2018-10-17)
      To examine timing of eating across ten European countries.
    • Maternal measles antibodies and their influence on all-cause mortality following measles vaccination: an alternative to measure very low maternal antibody levels.

      Smits, Gaby; Stabell Benn, Christine; Whittle, Hilton; van Binnendijk, Rob; Aaby, Peter; van der Klis, Fiona (2018-10-16)
      It was previously shown by hemagglutination inhibition that measles-vaccination in the presence of maternal measles antibodies was associated with reduced all-cause mortality. We confirmed this serological association using a multiplexed immunoassay as a sensitive alternative and estimated a threshold concentration (28.7 mIU/ml), that correlates with lower all-cause mortality (p=0.02).
    • Newborn screening for sickle cell disease in Europe: recommendations from a Pan-European Consensus Conference.

      Lobitz, Stephan; Telfer, Paul; Cela, Elena; Allaf, Bichr; Angastiniotis, Michael; Backman Johansson, Carolina; Badens, Catherine; Bento, Celeste; Bouva, Marelle J; Canatan, Duran; Charlton, Matthew; Coppinger, Cathy; Daniel, Yvonne; de Montalembert, Marianne; Ducoroy, Patrick; Dulin, Elena; Fingerhut, Ralph; Frömmel, Claudia; García-Morin, Marina; Gulbis, Béatrice; Holtkamp, Ute; Inusa, Baba; James, John; Kleanthous, Marina; Klein, Jeannette; Kunz, Joachim B; Langabeer, Lisa; Lapouméroulie, Claudine; Marcao, Ana; Marín Soria, José L; McMahon, Corrina; Ohene-Frempong, Kwaku; Périni, Jean-Marc; Piel, Frédéric B; Russo, Giovanna; Sainati, Laura; Schmugge, Markus; Streetly, Allison; Tshilolo, Leon; Turner, Charles; Venturelli, Donatella; Vilarinho, Laura; Yahyaoui, Rachel; Elion, Jacques; Colombatti, Raffaella (2018-10-18)
      Sickle Cell Disease (SCD) is an increasing global health problem and presents significant challenges to European health care systems. Newborn screening (NBS) for SCD enables early initiation of preventive measures and has contributed to a reduction in childhood mortality from SCD. Policies and methodologies for NBS vary in different countries, and this might have consequences for the quality of care and clinical outcomes for SCD across Europe. A two-day Pan-European consensus conference was held in Berlin in April 2017 in order to appraise the current status of NBS for SCD and to develop consensus-based statements on indications and methodology for NBS for SCD in Europe. More than 50 SCD experts from 13 European countries participated in the conference. This paper aims to summarise the discussions and present consensus recommendations which can be used to support the development of NBS programmes in European countries where they do not yet exist, and to review existing programmes.