Center for Infectious Disease Control

Bilthoven, Netherlands

Center for Infectious Disease Control

Bilthoven, Netherlands
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De Vos A.S.,University Utrecht | Van der Helm J.J.,Public Health Service Amsterdam | Matser A.,University Utrecht | Matser A.,Public Health Service Amsterdam | And 3 more authors.
Addiction | Year: 2013

Aims: In Amsterdam, HIV prevalence has nearly halved among injecting drug users (IDU) since 1990. Hepatitis C virus (HCV) prevalence also declined; HIV and HCV incidence dropped to nearly zero. We examined possible explanations for these time trends, among which the implementation of harm reduction measures aimed at reducing the risk behaviour of IDU. Design: We used individual-based modelling of the spread of HIV and HCV. Information about demographic parameters was obtained from the Amsterdam Cohort Study (ACS) among drug users. The model included changes in inflow of new IDU and death rates over time, the latter dependent on age and time since HIV seroconversion. We considered different scenarios of risk behaviour. Setting: IDU in Amsterdam. Measurements: Simulated HIV and HCV incidence and prevalence were compared with ACS data. Findings: Assuming that harm reduction measures had led to a strong decrease in risk behaviour over time improved the model fit (squared residuals decreased by 30%). However, substantial incidence and HIV prevalence decline were already reproduced by incorporating demographic changes into the model. In particular, lowered disease spread might be a result of depletion of high-risk IDU among those at risk for disease, and a decrease in the number of high-risk individuals in the population due to HIV-related mortality. Conclusions: Marked decreases in HIV and HCV in Amsterdam since 1990 could be due partly to harm reduction measures; however, they may also be attributable largely to changes in the IDU population. Future research aimed at quantifying the benefits of interventions should not neglect the impact of natural epidemic progression and demographic changes. © 2013 Society for the Study of Addiction.


de Vos A.S.,University Utrecht | Prins M.,Public Health Service Amsterdam | Kretzschmar M.E.E.,University Utrecht | Kretzschmar M.E.E.,Center for Infectious Disease Control
Addiction | Year: 2015

Background and Aims: Treatment of injecting drug users (IDU) for hepatitis C virus (HCV) infection may prevent onward transmission. Treating individuals who often share injecting equipment is most likely to prevent new infections. However, these high-risk IDU are also more likely to become re-infected than low-risk IDU. We investigated to which group treatment is best targeted. Design: We modelled the expected benefits per treatment of one chronically HCV-infected IDU in a population of low- and high-risk IDU. The benefits of treating one low- or one high-risk IDU were compared. Measurements: Benefits included the probability for the treated IDU to become and remain uninfected, as well as the expected number of prevented infections to others (i.e. we quantified the total expected decrease in chronic infections). Findings: We found a threshold in HCV-RNA prevalence above which treating low-risk IDU, and below which treating high-risk IDU, resulted in the greatest benefits. This threshold was at 50% of exchanged syringes being HCV contaminated. When 42% of IDU engaged in high-risk behaviour (borrowing and lending out syringes 7.3 times more frequently than low-risk IDU), the corresponding threshold of HCV-RNA prevalence among IDU was at 32%. Larger-risk heterogeneity led to a lower corresponding threshold among IDU. A combination of HCV treatment and 50% risk reduction was best directed at high-risk IDU for prevalence among syringes up to 59%. The threshold was marginally sensitive to changes in disease and treatment variables. Conclusions: When more than half of all exchanged syringes in a population of injecting drug users (IDU) are contaminated by hepatitis C virus, it is most efficient to treat low-risk IDU first. Below this threshold, it is most efficient to treat high-risk IDU first. © 2015 Society for the Study of Addiction.


de Kraker M.E.A.,Center for Infectious Disease Control | de Kraker M.E.A.,University of Groningen | Jarlier V.,University Pierre and Marie Curie | Monen J.C.M.,Center for Infectious Disease Control | And 4 more authors.
Clinical Microbiology and Infection | Year: 2013

We investigated bacteraemia trends for five major bacterial pathogens, Staphylococcus aureus, Escherichia coli, Streptococcus pneumoniae, Enterococcus faecalis and Enterococcus faecium, and determined how expanding antimicrobial resistance influenced the total burden of bacteraemias in Europe. Aetiological fractions of species and antibiotic phenotypes were extracted from the European Antimicrobial Resistance Surveillance System (EARSS) database for laboratories, which consistently reported between 2002 and 2008. Trend analyses used generalized linear models. Robustness of results was assessed by iterative analysis for different geographic regions. From 2002 to 2008, the overall number of reports increased annually by 6.4% (95% confidence interval (CI) 6.2-6.5%), from 46095 to 67876. In the subset of laboratories providing denominator information, the overall incidence increased from 0.58/1000 patient-days to 0.90/1000 patient-days (7.2% per year; 95% CI 6.9-7.5%). The frequency of reported bacteraemia isolates of S. aureus and Streptococcus pneumoniae increased moderately, while increase in E. coli and Enterococcus faecium was more pronounced. Bacteraemias caused by methicillin-resistant S. aureus increased until 2005 (7.6% per year; 95% CI 6.1-9.1%), and then decreased (-4.8% per year; 95% CI -6.1 to -3.5%), whereas the number attributable to methicillin-sensitive S. aureus increased continuously (3.4% per year; 95% CI 3.0-3.7). Increasing rates of E. coli were mainly caused by antibiotic-resistant phenotypes. Our data suggest that the burden of bacterial bloodstream infection has been increasing for all species during EARSS surveillance. Trends were mainly driven by resistant strains and clearly dissociated between resistant and susceptible isolates. It appears that infections with resistant clones add to rather than replace infections caused by susceptible bacteria. As a consequence, expansion of antibiotic resistance creates an additional strain on healthcare systems. © 2012 European Society of Clinical Microbiology and Infectious Diseases.


Kretzschmar M.,University Utrecht | Kretzschmar M.,Center for Infectious Disease Control | Satterwhite C.,Centers for Disease Control and Prevention | Leichliter J.,Centers for Disease Control and Prevention | Berman S.,Centers for Disease Control and Prevention
Sexually Transmitted Diseases | Year: 2012

Objectives: Model impact of increasing screening and partner notification (PN) on chlamydia positivity. Methods: We used a stochastic simulation model describing pair formation and dissolution in an age-structured heterosexual population. The model accounts for steady, casual, and concurrent partnerships and a highly sexually active core group. The model used existing sexual behavior data from the United States and was validated using chlamydia positivity data from Region X (Alaska, Idaho, Oregon, Washington). A screening program with a coverage rate of 20% was implemented among women aged 15 to 24 years. After 10 years, we increased screening coverage to 35%, 50%, and 65% and partner treatment rates from 20% to 40% and 55%. Finally, we included male screening (aged 15-24, screening coverage: 20% and 35%, partner treatment: 25% and 40%). We analyzed the effects on chlamydia positivity in women and the frequency of reinfection 6 months after treatment. Results: The model described the decline in positivity observed from 1988 to 1997 in Region X, given screening coverage of 20% and a 25% partner treatment rate. Increasing screening coverage from 35% to 65% resulted in incremental decreases in positivity as did increasing the PN rate; a 23% reduction in positivity was achieved by either increasing screening by 3-fold or PN by 2-fold. Adding male screening to the program had less impact than increasing screening coverage or PN among women. Increased PN and treatment reduced reinfection rates considerably. Conclusions: Increasing efforts in PN may contribute at least as much to control of chlamydia infection as increasing screening coverage rates. © 2012 American Sexually Transmitted Diseases Association All rights reserved.


Brooke R.J.,University Utrecht | Kretzschmar M.E.E.,University Utrecht | Kretzschmar M.E.E.,Center for Infectious Disease Control | Mutters N.T.,University of Heidelberg | And 2 more authors.
BMC Infectious Diseases | Year: 2013

Background: The recent outbreak of Q fever in the Netherlands between 2007 and 2009 is the largest recorded Q fever outbreak. Exposure to Coxiella burnetii may cause Q fever but the size of the population exposed during the outbreak remained uncertain as little is known of the infectivity of this pathogen. The quantification of the infectiousness and the corresponding response is necessary for assessing the risk to the population.Methods: A human challenge study was published in the 1950s but this study quantified the dose of C. burnetii in relative units. Data from a concurrent guinea pig challenge study were combined with a recent study in which guinea pigs were challenged with a similar aerosol route to quantify human exposure. Concentration estimates for C. burnetii are made jointly with estimates of the dose response parameters in a hierarchical Bayesian framework.Results: The dose for 50% infection (InfD50%) in human subjects is 1.18 bacteria (95% credible interval (CI) 0.76-40.2). The dose for 50% illness (IllD50) in challenged humans is 5.58 (95%CI 0.89-89.0) bacteria. The probability of a single viable C. burnetii causing infection in humans is 0.44 (95%CI 0.044-0.59) and for illness 0.12 (95%CI 0.0006-0.55).Conclusions: To our knowledge this is the first human dose-response model for C. burnetii. The estimated dose response relation demonstrates high infectivity in humans. In many published papers the proportion of infected individuals developing illness is reported to be 40%. Our model shows that the proportion of symptomatic infections may vary with the exposure dose. This implies that presence of these bacteria in the environment, even in small numbers, poses a serious health risk to the population. © 2013 Brooke et al.; licensee BioMed Central Ltd.


Peirano G.,University of Calgary | Van Der Bij A.K.,Center for Infectious Disease Control | Van Der Bij A.K.,Reinier Of Graaf Hospital | Freeman J.L.,Auckland District Health Board | And 6 more authors.
Antimicrobial Agents and Chemotherapy | Year: 2014

We designed a study to describe the characteristics of sequence type 131 (ST131) lineages, including the H30-Rx sublineage, among a global collection of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli isolates from 9 countries collected from 2000 to 2011. A total of 240 nonrepeat isolates from Canada, the United States, Brazil, the Netherlands, France, the United Arab Emirates (UAE), India, South Africa, and New Zealand were included. Established PCR, sequencing, and typing methods were used to define ST131 lineages, H30 and H30-Rx phylogenetic groups, gyrA and parC mutations, virotypes, and plasmid-mediated quinolone resistance determinants. The majority of the isolates produced CTX-M-15 with aac(6′)-lb-cr, belonged to phylogenetic group B2, and were positive for the H30 lineage with the gyrA1AB and parC1aAB mutations. ST131 showed 15 distinct pulsotypes; 43% of the isolates belonged to four pulsotypes, with a global distribution. Seventy-five percent of the ST131 isolates belonged to H30-Rx; this sublineage was present in all the countries and was associated with multidrug resistance, blaCTX-M-15, aac(6′)-lb-cr, and virotypes A and C. The H41 lineage was negative for the ST131 pabB allele-specific PCR. The multidrug-resistant H30-Rx sublineage poses an important public health threat due to its global distribution, association with virotype C, and high prevalence among ST131 isolates that produce CTX-M-15. Copyright © 2014, American Society for Microbiology. All Rights Reserved.


Wiers R.W.,University of Amsterdam | Houben K.,Maastricht University | Fadardi J.S.,Ferdowsi University of Mashhad | Fadardi J.S.,Bangor University | And 4 more authors.
Addictive Behaviors | Year: 2015

Following successful outcomes of cognitive bias modification (CBM) programs for alcoholism in clinical and community samples, the present study investigated whether different varieties of CBM (attention control training and approach-bias re-training) could be delivered successfully in a fully automated web-based way and whether these interventions would help self-selected problem drinkers to reduce their drinking. Participants were recruited through online advertising, which resulted in 697 interested participants, of whom 615 were screened in. Of the 314 who initiated training, 136 completed a pretest, four sessions of computerized training and a posttest. Participants were randomly assigned to one of four experimental conditions (attention control or one of three varieties of approach-bias re-training) or a sham-training control condition. The general pattern of findings was that participants in all conditions (including participants in the control-training condition) reduced their drinking. It is suggested that integrating CBM with online cognitive and motivational interventions could improve results. © 2014 Elsevier Ltd.


Kretzschmar M.,University Utrecht | Kretzschmar M.,Center for Infectious Disease Control | Carael M.,University Utrecht | Carael M.,Free University of Brussels
AIDS and Behavior | Year: 2012

Recently, there has been debate about the role of concurrent partnerships in driving the transmission of HIV, particularly in Southern Africa, where HIV prevalence is up to 25 % in many heterosexual populations and where evidence from sexual behavior surveys also suggests high levels of male concurrency. While mathematical modeling studies have shown that concurrency has the potential to enhance the speed at which HIV spreads in a population, empirical studies up to now have failed to provide conclusive evidence supportive of these effects. Here we discuss some reasons for the apparent discrepancy between theoretical and empirical studies. We propose that studying the impact of concurrency on HIV transmission should be differentiated by taking more insight from social and behavioral studies on sexual partnerships into account. We also suggest that a more rigorous definition is needed for when a factor is considered a driving force for HIV epidemic spread. We illustrate this with a modeling example. © Springer Science+Business Media, LLC 2012.


Kretzschmar M.,University Utrecht | Kretzschmar M.,Center for Infectious Disease Control | Teunis P.F.M.,University Utrecht | Teunis P.F.M.,Emory University | Pebody R.G.,Public Health England
PLoS Medicine | Year: 2010

Background: Despite large-scale vaccination programmes, pertussis has remained endemic in all European countries and has been on the rise in many countries in the last decade. One of the reasons that have been discussed for the failure of vaccination to eliminate the disease is continued circulation of the pathogen Bordetella pertussis by mostly asymptomatic and mild infections in adolescents and adults. To understand the impact of asymptomatic and undiagnosed infection on the transmission dynamics of pertussis we analysed serological data from five European countries in combination with information about social contact patterns from five of those countries to estimate incidence and reproduction numbers. Methods and Findings: We compared two different methods for estimating incidence from individual data on IgG pertussis toxin (PT) titres. One method combines the cross-sectional surveys of titres with longitudinal information about the distribution of amplitude and decay rate of titres in a back-calculation approach. The second method uses age-dependent contact matrices and cross-sectional surveys of IgG PT titres to estimate a next generation matrix for pertussis transmission among age groups. The next generation approach allows for computation of basic reproduction numbers for five European countries. Our main findings are that the seroincidence of infections as estimated with the first method in all countries lies between 1% and 6% per annum with a peak in the adolescent age groups and a second lower peak in young adults. The incidence of infections as estimated by the second method lies slightly lower with ranges between 1% and 4% per annum. There is a remarkably good agreement of the results obtained with the two methods. The basic reproduction numbers are similar across countries at around 5.5. Conclusions: Vaccination with currently used vaccines cannot prevent continued circulation and reinfection with pertussis, but has shifted the bulk of infections to adolescents and adults. If a vaccine conferring lifelong protection against clinical and subclinical infection were available pertussis could be eliminated. Currently, continuing circulation of the pathogen at a subclinical level provides a refuge for the pathogen in which it can evolve and adjust to infect vaccinated populations. © 2010 Kretzschmar et al.


Groenwold R.H.H.,University Utrecht | Knol M.J.,Center for Infectious Disease Control
BMC Medical Education | Year: 2013

Background: Distance learning through the internet is increasingly popular in higher education. However, it is unknown how participants in epidemiology courses value live vs. distance education. Methods. All participants of a 5-day specialisation course in epidemiology were asked to keep a diary on the number of hours they spent on course activities (both live and distance education). Attendance was not compulsory during the course and participants were therefore also asked for the reasons to attend live education (lectures and practicals). In addition, the relation between participants' learning styles (Index of Learning Styles) and their participation in live and distance education was studied. Results: All 54 (100%) participants in the course completed the questionnaire on attendance and 46 (85%) completed the questionnaire on learning styles. The number of hours attending live education was negatively correlated with the number of hours going studying distance learning materials (Pearson correlation -0.5; p < 0.001). The most important reasons to attend live education was to stay focused during lectures (50%), and to ask questions during practicals (50%). A lack of time was the most important reason not to attend lectures (52%) or practicals (61%). Learning styles were not association with the number of hours spent on live or distance education. Conclusion: Distance learning may play an important role in epidemiology courses, since it allows participants to study whenever and wherever they prefer, which provides the opportunity to combine courses with clinical duties. An important requirement for distance learning education appears to be the possibility to ask questions and to interact with instructors. © 2013Groenwold and Knol; licensee BioMed Central Ltd. © 2013 Groenwold and Knol; licensee BioMed Central Ltd.

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