• Pair formation models for sexually transmitted infections: A primer.

      Kretzschmar, Mirjam; Heijne, Janneke C M (2017-08)
      For modelling sexually transmitted infections, duration of partnerships can strongly influence the transmission dynamics of the infection. If partnerships are monogamous, pairs of susceptible individuals are protected from becoming infected, while pairs of infected individuals delay onward transmission of the infection as long as they persist. In addition, for curable infections re-infection from an infected partner may occur. Furthermore, interventions based on contact tracing rely on the possibility of identifying and treating partners of infected individuals. To reflect these features in a mathematical model, pair formation models were introduced to mathematical epidemiology in the 1980's. They have since been developed into a widely used tool in modelling sexually transmitted infections and the impact of interventions. Here we give a basic introduction to the concepts of pair formation models for a susceptible-infected-susceptible (SIS) epidemic. We review some results and applications of pair formation models mainly in the context of chlamydia infection.
    • A pan-European ring trial to validate an International Standard for detection of Vibrio cholerae, Vibrio parahaemolyticus and Vibrio vulnificus in seafoods.

      Hartnell, R E; Stockley, L; Keay, W; Rosec, J-P; Hervio-Heath, D; Van den Berg, H; Leoni, F; Ottaviani, D; Henigman, U; Denayer, S; Serbruyns, B; Georgsson, F; Krumova-Valcheva, G; Gyurova, E; Blanco, C; Copin, S; Strauch, E; Wieczorek, K; Lopatek, M; Britova, A; Hardouin, G; Lombard, B; In't Veld, P; Leclercq, A; Baker-Austin, C (2018-02-10)
      Globally, vibrios represent an important and well-established group of bacterial foodborne pathogens. The European Commission (EC) mandated the Comite de European Normalisation (CEN) to undertake work to provide validation data for 15 methods in microbiology to support EC legislation. As part of this mandated work programme, merging of ISO/TS 21872-1:2007, which specifies a horizontal method for the detection of V. parahaemolyticus and V. cholerae, and ISO/TS 21872-2:2007, a similar horizontal method for the detection of potentially pathogenic vibrios other than V. cholerae and V. parahaemolyticus was proposed. Both parts of ISO/TS 21872 utilized classical culture-based isolation techniques coupled with biochemical confirmation steps. The work also considered simplification of the biochemical confirmation steps. In addition, because of advances in molecular based methods for identification of human pathogenic Vibrio spp. classical and real-time PCR options were also included within the scope of the validation. These considerations formed the basis of a multi-laboratory validation study with the aim of improving the precision of this ISO technical specification and providing a single ISO standard method to enable detection of these important foodborne Vibrio spp.. To achieve this aim, an international validation study involving 13 laboratories from 9 countries in Europe was conducted in 2013. The results of this validation have enabled integration of the two existing technical specifications targeting the detection of the major foodborne Vibrio spp., simplification of the suite of recommended biochemical identification tests and the introduction of molecular procedures that provide both species level identification and discrimination of putatively pathogenic strains of V. parahaemolyticus by the determination of the presence of theromostable direct and direct related haemolysins. The method performance characteristics generated in this have been included in revised international standard, ISO 21872:2017, published in July 2017.
    • Parasitic nematodes of the genus Syphacia Seurat, 1916 infecting Muridae in the British Isles, and the peculiar case of Syphacia frederici.

      Stewart, Alex; Lowe, Ann; Smales, Lesley; Bajer, Anna; Bradley, Jan; Dwużnik, Dorota; Franssen, Frits; Griffith, Jack; Stuart, Peter; Turner, Cyan; Zaleśny, Grzegorz; Behnke, Jerzy M (2017-08-23)
      Syphacia stroma (von Linstow, 1884) Morgan, 1932 and Syphacia frederici Roman, 1945 are oxyurid nematodes that parasitize two murid rodents, Apodemus sylvaticus and Apodemus flavicollis, on the European mainland. Only S. stroma has been recorded previously in Apodemus spp. from the British Isles. Despite the paucity of earlier reports, we identified S. frederici in four disparate British sites, two in Nottinghamshire, one each in Berkshire and Anglesey, Wales. Identification was based on their site in the host (caecum and not small intestine), on key morphological criteria that differentiate this species from S. stroma (in particular the tail of female worms) and by sequencing two genetic loci (cytochrome C oxidase 1 gene and a section of ribosomal DNA). Sequences derived from both genetic loci of putative British S. frederici isolates formed a tight clade with sequences from continental worms known to be S. frederici, clearly distinguishing these isolates from S. stroma which formed a tight clade of its own, distinct from clades representative of Syphacia obvelata from Mus and S. muris from Rattus. The data in this paper therefore constitute the first record of S. frederici from British wood mice, and confirm the status of this species as distinct from both S. obvelata and S. stroma.
    • Particulate matter air pollution components and incidence of cancers of the stomach and the upper aerodigestive tract in the European Study of Cohorts of Air Pollution Effects (ESCAPE).

      Weinmayr, Gudrun; Pedersen, Marie; Stafoggia, Massimo; Andersen, Zorana J; Galassi, Claudia; Munkenast, Jule; Jaensch, Andrea; Oftedal, Bente; Krog, Norun H; Aamodt, Geir; Pyko, Andrei; Pershagen, Göran; Korek, Michal; De Faire, Ulf; Pedersen, Nancy L; Östenson, Claes-Göran; Rizzuto, Debora; Sørensen, Mette; Tjønneland, Anne; Bueno-de-Mesquita, Bas; Vermeulen, Roel; Eeftens, Marloes; Concin, Hans; Lang, Alois; Wang, Meng; Tsai, Ming-Yi; Ricceri, Fulvio; Sacerdote, Carlotta; Ranzi, Andrea; Cesaroni, Giulia; Forastiere, Francesco; de Hoogh, Kees; Beelen, Rob; Vineis, Paolo; Kooter, Ingeborg; Sokhi, Ranjeet; Brunekreef, Bert; Hoek, Gerard; Raaschou-Nielsen, Ole; Nagel, Gabriele (2018-08-07)
      Previous analysis from the large European multicentre ESCAPE study showed an association of ambient particulate matter <2.5 μm (PM2.5) air pollution exposure at residence with the incidence of gastric cancer. It is unclear which components of PM are most relevant for gastric and also upper aerodigestive tract (UADT) cancer and some of them may not be strongly correlated with PM mass. We evaluated the association between long-term exposure to elemental components of PM2.5 and PM10 and gastric and UADT cancer incidence in European adults.
    • Partner notification and partner treatment for chlamydia: attitude and practice of general practitioners in the Netherlands; a landscape analysis.

      van den Broek, Ingrid V F; Donker, Gé A; Hek, Karin; van Bergen, Jan E A M; van Benthem, Birgit H B; Götz, Hannelore M (2017-12-20)
      Chlamydia prevalence remains high despite scaling-up control efforts. Transmission is not effectively interrupted without partner notification (PN) and (timely) partner treatment (PT). In the Netherlands, the follow-up of partners is not standardized and may depend on GPs' time and priorities. We investigated current practice and attitude of GPs towards PN and PT to determine the potential for Patient-Initiated Partner Treatment, which is legally not supported yet.
    • Paternal cholestasis exacerbates obesity-associated hypertension in male offspring but is prevented by paternal ursodeoxycholic acid treatment.

      Pataia, Vanessa; Papacleovoulou, Georgia; Nikolova, Vanya; Samuelsson, Anne-Maj; Chambers, Stephanie; Jansen, Eugene; Taylor, Paul D; Poston, Lucilla; Williamson, Catherine (2018-05-24)
      Obesity is a heterogeneous phenotype and risk associations to non-communicable diseases such as cardiovascular disease and type 2 diabetes are influenced by several factors. The paternal metabolic status at the time of conception influences offspring susceptibility to developing obesity and adiposity-associated cardiometabolic disease. Cholestatic liver diseases are characterized by raised circulating serum bile acid levels and dyslipidemia, and are commonly treated with ursodeoxycholic acid (UDCA). We hypothesized that paternal cholestasis alters offspring susceptibility to developing obesity and adiposity-associated cardiometabolic disease and that this may be modified by paternal UDCA treatment.
    • Paternal Exposure to Environmental Chemical Stress Affects Male Offspring's Hepatic Mitochondria.

      Godschalk, Roger; Remels, Alex; Hoogendoorn, Camiel; van Benthem, Jan; Luijten, Mirjam; Duale, Nur; Brunborg, Gunnar; Olsen, Ann-Karin; Bouwman, Freek G; Munnia, Armelle; Peluso, Marco; Mariman, Edwin; van Schooten, Frederik Jan (2018-03-01)
      Preconceptional paternal exposures may affect offspring's health, which cannot be explained by mutations in germ cells, but by persistent changes in the regulation of gene expression. Therefore, we investigated whether pre-conceptional paternal exposure to benzo[a]pyrene (B[a]P) could alter the offspring's phenotype. Male C57BL/6 mice were exposed to B[a]P by gavage for 6 weeks, 3× per week, and were crossed with unexposed BALB-c females 6 weeks after the final exposure. The offspring was kept under normal feeding conditions and was sacrificed at 3 weeks of age. Analysis of the liver proteome by 2D-gel electrophoresis and mass spectrometry indicated that proteins involved in mitochondrial function were significantly downregulated in the offspring of exposed fathers. This down-regulation of mitochondrial proteins was paralleled by a reduction in mitochondrial DNA copy number and reduced activity of citrate synthase and β-hydroxyacyl-CoA dehydrogenase, but in male offspring only. Surprisingly, analysis of hepatic mRNA expression revealed a male-specific up-regulation of the genes, whose proteins were downregulated, including Aldh2 and Ogg1. This discrepancy could be related to several selected microRNA (miRNA)'s that regulate the translation of these proteins; miRNA-122, miRNA-129-2-5p, and miRNA-1941 were upregulated in a gender-specific manner. Since mitochondria are thought to be a source of intracellular reactive oxygen species, we additionally assessed oxidatively-induced DNA damage. Both 8-hydroxy-deoxyguanosine and malondialdehyde-dG adduct levels were significantly reduced in male offspring of exposed fathers. In conclusion, we show that paternal exposure to B[a]P can regulate mitochondrial metabolism in offspring, which may have profound implications for our understanding of health and disease risk inherited from fathers.
    • Pathogen communities of songbird-derived ticks in Europe's low countries.

      Heylen, Dieter; Fonville, Manoj; Docters van Leeuwen, Arieke; Stroo, Arjan; Duisterwinkel, Martin; van Wieren, Sip; Diuk-Wasser, Maria; de Bruin, Arnout; Sprong, Hein (2017-10-18)
      Birds play a major role in the maintenance of enzootic cycles of pathogens transmitted by ticks. Due to their mobility, they affect the spatial distribution and abundance of both ticks and pathogens. In the present study, we aim to identify members of a pathogen community [Borrelia burgdorferi (s.l.), B. miyamotoi, 'Ca. Neoehrlichia mikurensis', Anaplasma phagocytophilum and Rickettsia helvetica] in songbird-derived ticks from 11 locations in the Netherlands and Belgium (2012-2014).
    • Pathogenic helminths in the past: Much ado about nothing.

      Mulder, Christian (2017)
      Despite a long tradition on the extent to which Romanisation has improved human health, some recent studies suggest that Romanisation in general, and Roman sanitation in particular, may not have made people any healthier, given that in Roman times gastrointestinal parasites were apparently widespread, whilst in the present day such parasites rarely cause diseases. Unfortunately, this novel claim neglects the empirical evidence that worldwide infections in over 1.5 billion people are caused by ubiquitous foodborne nematodes. Therefore, many may wonder if fossil remains of soil-transmitted helminths have been reported in ancient sanitation infrastructures. Beneficial access to improved sanitation should always be prioritized, hence how can historical sanitation efforts have ever been harmful? In this short article, a strong plea for caution is given, asking for an augmented nematological record and showing that there is not any evidence against Roman sanitation, neither in the past nor in the present.
    • Patient support for tuberculosis patients in low-incidence countries: A systematic review.

      van de Berg, Sarah; Jansen-Aaldring, Niesje; de Vries, Gerard; van den Hof, Susan (2018)
      Patient support during tuberculosis treatment is expected to be more often available and more customized in low tuberculosis incidence, high-resource settings than in lower-resource settings. The aim of this systematic review is to provide an overview of tuberculosis patient support interventions implemented in low-incidence countries and an evaluation of their effects on treatment-related outcomes as well as their acceptability by patients and providers.
    • Patiënten en dokters makens samen een onderzoeksagenda ; De methode van de Britse James Lind Alliance.

      Schoemaker, C G; Prakken, A B J; Furth, E F (2017-11-27)
      The British James Lind Alliance (JLA) has developed a method to allow practitioners, patients and family members together to develop a research agenda for a disease or a form of treatment. In a 'priority setting partnership', they gradually establish a top-10 list of the most important unanswered research questions. Input from patients and their relatives is given the same weight when determining priorities as that from practitioners. More than 50 of these top-10 lists have been created so far, one of which was created in the Netherlands. The JLA method combines elements of the two very different methods currently prevailing in the Netherlands: the dialog model, developed by the VU and the 'health care evaluation agenda', developed by the Dutch Association of Medical Specialists. The JLA method is quite practicable and leads to new research questions. The biggest advantage is that it leads to a dialogue between creators and users of knowledge about what the relevant research questions are.
    • Pattern of risks of rheumatoid arthritis among patients using statins: A cohort study with the clinical practice research datalink.

      de Jong, Hilda J I; Cohen Tervaert, Jan Willem; Lalmohamed, Arief; de Vries, Frank; Vandebriel, Rob J; van Loveren, Henk; Klungel, Olaf H; van Staa, Tjeerd P (2018)
      We examined the association between statin use and the risk of rheumatoid arthritis (RA), with special focus on describing the patterns of risks of RA during statin exposure in a large population-based cohort in the United Kingdom. In the Clinical Practice Research Datalink, patients aged ≥40 years with at least one prescription of statins (1995-2009) were selected, and matched by age (+/-5 years), sex, practice and date of first prescription of statins to non-users. The follow-up period of statin use was divided into periods of current, recent and past exposure, with patients moving between these three exposure categories over time. Time-dependent Cox models were used to derive hazard ratios (HRs) of RA, adjusted for disease history and previous drug use. The study population included 1,023,240 patients, of whom 511,620 were statin users. No associations were found between RA and current (HRadj,1.06;99%CI:0.88-1.27) or past statin users (HRadj,1.18;99%CI:0.88-1.57). However, in patients who currently used statins, hazard rates were increased shortly after the first prescription of statins and then gradually decreased to baseline level. The risk of developing RA was increased in recent statin users, as compared to non-users (HRadj,1.39;99%CI:1.01-1.90). The risk of RA is substantially increased in the first year after the start of statins and then diminishes to baseline level. These findings may suggest that statins might accelerate disease onset in patients susceptible to develop RA, but in other patients, statins are probably safe and well tolerated, even after prolonged use. Alternatively, we cannot rule out that confounding by cardiovascular risk factors and ascertainment bias may have influenced the findings.
    • Pattern of risks of systemic lupus erythematosus among statin users: a population-based cohort study.

      De Jong, Hilda J I; van Staa, Tjeerd P; Lalmohamed, Arief; de Vries, Frank; Vandebriel, Rob J; Van Loveren, Henk; Klungel, Olaf H; Cohen Tervaert, Jan Willem (2017-10)
      To examine the association between the use of statins and the risk of systemic lupus erythematosus (SLE) with focus on describing the patterns of risks over time.
    • Perceived usefulness of the International Classification of Functioning, Disability and Health (ICF) increases after a short training: A randomized controlled trial in master of advanced nursing practice students.

      Stallinga, Hillegonda A; Dijkstra, Pieter U; Napel, Huib Ten; Roodbol, Gabriël; Peters, Jeroen W B; Heerkens, Yvonne F; Roodbol, Petrie F (2018-11)
      The Master program of Advanced Nursing Practice (MANP) educates nurses to become a nurse practitioner. Nurse practitioners are health care professionals focusing on the intersection of cure and care. However, a clear model covering that area is lacking. The use of the International Classification of Functioning, Disability and Health (ICF) may be considered for incorporation in curricula due to its focus on the integration of cure and care. The purpose of this study is to test the effects of a short (= 4-h instructor-led) ICF training on perceived usefulness of the ICF. In a randomized controlled trial, 76 MANP students were randomly allocated to intervention or control group. Data were collected using an 'ICF survey and learning assessment tool'. Data of 56 students were included for analysis. Perceived usefulness of the ICF increased significantly in the intervention group immediately after training (p = 0.001) but no longer at 3-months follow-up (p = 0.388). Attitude and knowledge related to the ICF were significantly increased in the intervention group at both post-training assessments (p < 0.001 and 0.02). The positive influence of the ICF training on perceived usefulness of the ICF is relevant for including ICF in MANP curriculum.
    • Perceptions and Reasons Regarding E-Cigarette Use among Users and Non-Users: A Narrative Literature Review.

      Romijnders, Kim A G J; van Osch, Liesbeth; de Vries, Hein; Talhout, Reinskje (2018-06-06)
      This paper aims to provide an in-depth understanding of the attractiveness of e-cigarettes for several different groups. For this purpose, perceptions of and reasons for e-cigarette use were systematically reviewed as reported by e-cigarette users, cigarette smokers, dual users, and non-users, among both adults and youth. MEDLINE® and Scopus were used to search for relevant articles, and references of included studies were also investigated. Two reviewers screened all titles and abstracts independently, blinded to authors and journal titles (Cohen’s Kappa = 0.83), resulting in 72 eligible articles. Risk perceptions, perceived benefits, and reasons for e-cigarette use were categorized in themes and sub-themes. Risk perceptions included harmfulness in general, and specific health risks. Perceived benefits included improved taste and smell, and safety for bystanders. Reasons for use included (health) benefits, curiosity, smoking cessation, and friends using e-cigarettes. The findings highlight that there is a variety of perceptions and reasons mentioned by adult and youth e-cigarette users, cigarette smokers, dual users, and non-users. As such, this overview provides valuable information for scientists, public health professionals, behavior change experts, and regulators to improve future research, risk communication, and possibilities to effectively regulate e-cigarettes.
    • Performance of the Brighton collaboration case definition for hypotonic-hyporesponsive episode (HHE) on reported collapse reactions following infant vaccinations in the Netherlands.

      Vermeer-de Bondt, Patricia E; Dzaferagić, Aida; David, Silke; Maas, Nicoline A T van der (2006-11-30)
      We reviewed collapse (sudden onset of pallor, limpness and hyporesponsiveness) following the first infant (DPTP+Hib) vaccination reported to the enhanced passive surveillance system of the Netherlands in 1994-2003. All 1303 reports identified by the current RIVM (National Institute for Public Health and Environment) case definition were captured by the Brighton Collaboration (BC) case definition, with in 17 (1.3%) reports insufficient information. Over the years the proportion of the highest level of diagnostic certainty (level 1) increased due to more complete data from 70% to over 90%. We checked the BC case definition also on a sample of cases (with pallor or hyporesponsiveness) not meeting RIVM's case definition for collapse at the time. Sixty out of 200 cases were captured by BC but again rejected by RIVM. The sensitivity BC levels 2 and 3 appeared too high. We recommend a more restrict case definition by the Brighton Collaboration with certain exclusion criteria to make it more specific. Furthermore a change in the specifications for levels 2 and 3 will increase specificity and accommodate for the loss of sensitivity.
    • Performance of Xpert MTB/RIF Ultra: a matter of dead or alive.

      Arend, Sandra M; van Soolingen, Dick (2018-01)
    • Persistence of immune response following bivalent HPV vaccination: A follow-up study among girls routinely vaccinated with a two-dose schedule.

      Schurink-van 't Klooster, Tessa M; Donken, Robine; Schepp, Rutger M; van der Klis, Fiona R M; de Melker, Hester E (2018-11-26)
      In this cohort study, we examined antibody levels and avidity after a two-dose schedule (0, 6 months) of the bivalent HPV-vaccine in girls routinely vaccinated in the Dutch HPV-vaccination program, up to 2 years following vaccination. A blood sample at 7, 12 and 24 months after the first dose and questionnaire data were collected (n = 56). HPV type-specific antibody concentrations (lU/ml) against seven types (HPV16/18/31/33/45/52/58) were assessed using a validated virus-like particles (VLP) multiplex immunoassay. Avidity was tested using a modification of this assay. Seropositivity for vaccine types HPV 16 and 18 was 100% up to month 24, but declined for HPV-types 31/33/45/52/58, although not statistically significant for HPV45. All Geometric Mean Concentrations (GMCs) declined by months 12 and 24, but remained high for HPV16/18. Between month 7 and 12, GMCs declined more for other types. High avidity antibodies were induced up to 24 months for vaccine types (75%, 76-78% and 81-82% at months 7, 12 and 24, respectively), but for other types antibody avidity was 16-29% at month 7, 20-32% at month 12 and 19-32% at month 24. GMCs declined over time for HPV-types 16/18/31/33/45/52/58, but remained high for vaccine-types HPV16/18 up to 24 months of follow-up. Antibody avidity was >75% for vaccine types but <35% for other HPV-types. Further follow-up of this cohort will provide insight into antibody and avidity kinetics over time.
    • Pharmacokinetics of favipiravir during continuous venovenous haemofiltration in a critically ill patient with influenza.

      Favié, Laurent Ma; Murk, Jean-Luc; Meijer, Adam; Nijstad, A Laura; van Maarseveen, Erik M; Sikma, Maaike A (2017-11-29)
      Favipiravir is a novel antiviral drug approved for influenza treatment in Japan. Little is known about favipiravir pharmacokinetics in critically ill patients. Here, we report a patient with influenza treated with favipiravir and undergoing continuous venovenous hemofiltration (CVVH) on the Intensive Care Unit of a tertiary hospital in the Netherlands. Pharmacokinetic analyses showed increased clearance and decreased plasma levels compared to healthy volunteers. CVVH has no clinically relevant contribution to total clearance. Despite susceptibility to favipiravir, the influenza virus was not cleared. A multi-disciplinary approach is needed to ensure optimal favipiravir treatment in critically ill patients.
    • Pharmacokinetics of Levofloxacin in Multidrug- and Extensively Drug-Resistant Tuberculosis Patients.

      Van't Boveneind-Vrubleuskaya, Natasha; Seuruk, Tatiana; van Hateren, Kai; van der Laan, Tridia; Kosterink, Jos G W; van der Werf, Tjip S; van Soolingen, Dick; van den Hof, Susan; Skrahina, Alena; Alffenaar, Jan-Willem C (2017-08)
      Pharmacodynamics are especially important in the treatment of multidrug- and extensively drug-resistant tuberculosis (M/XDR-TB). The free area under the concentration time curve in relation to MIC (fAUC/MIC) is the most relevant pharmacokinetic (PK)-pharmacodynamic (PD) parameter for predicting the efficacy of levofloxacin (LFX). The objective of our study was to assess LFX PK variability in M/XDR-TB patients and its potential consequence for fAUC/MIC ratios. Patients with pulmonary M/XDR-TB received LFX as part of the treatment regimen at a dose of 15 mg/kg administered once daily. Blood samples obtained at steady state before and 1, 2, 3, 4, 7, and 12 h after drug administration were measured by validated liquid chromatography-tandem mass spectrometry. The MIC values of LFX were determined by the agar dilution method on Middlebrook 7H10 and the MGIT960 system. Twenty patients with a mean age of 31 years (interquartile range [IQR] = 27 to 35 years) were enrolled in this study. The median AUC0-24 was 98.8 mg/h/liter (IQR = 84.8 to 159.6 mg/h/liter). The MIC median value for LFX was 0.5 mg/liter with a range of 0.25 to 2.0 mg/liter, and the median fAUC0-24/MIC ratio was 109.5 (IQR = 48.5 to 399.4). In 4 of the 20 patients, the value was below the target value of ≥100. When MICs of 0.25, 0.5, 1.0, and 2.0 mg/liter were applicable, 19, 18, 3, and no patients, respectively, had an fAUC/MIC ratio that exceeded 100. We observed a large variability in AUC. An fAUC0-24/MIC of ≥100 was only observed when the MIC values for LFX were 0.25 to 0.5 mg/liter. Dosages exceeding 15 mg/kg should be considered for target attainment if exposures are assumed to be safe. (This study has been registered at ClinicalTrials.gov under registration no. NCT02169141.).