Publications by authors named "Anneke Steens"

25 Publications

  • Page 1 of 1

Pre-screening and preventive quarantine likely explains the low SARS-CoV-2 prevalence among Norwegian conscripts.

Scand J Prim Health Care 2021 Mar 5;39(1):31-34. Epub 2021 Feb 5.

Department of Microbiology, Division of Laboratory Medicine, Oslo University Hospital-Ullevål, Oslo, Norway.

We aim to discuss whether preventive quarantine can mitigate the spread of Covid-19 during the pandemic. We did a cross-sectional, observational study design in a mass-screening program in the enrolment to the Norwegian military during April 19-28th 2020 (COVID-NOR-MIL). 1170 presumptively healthy young Norwegian conscripts. A structured interview encouraged the coming conscripts to a self-imposed preventive quarantine the last two weeks before enrolment. All conscripts underwent a PCR-based test with nasopharyngeal swabs at the day of enrolment. Only two tested positive. The study discusses the predictive value of the RT-PCR test and the risk of false positive and false negative results, particularly when using the test in a low-prevalent cohort, even if the test properties of sensitivity and specificity is almost 100%. Further, the study discusses the challenge of whether a positive SARS-CoV-2 PCR-test represent viable and contagious virus or only viral remnants. The adherence to self-imposed preventive quarantine is a challenge and is a subject to further research. Implications: We want to draw the attention to the potential value of a thorough pre-screening processes and self-imposed preventive quarantine to minimize the potential spread of SARS-Cov-2.
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http://dx.doi.org/10.1080/02813432.2021.1880101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7971252PMC
March 2021

Severe acute respiratory syndrome coronavirus 2 prevalence in 1170 asymptomatic Norwegian conscripts.

Health Sci Rep 2021 Mar 15;4(1):e233. Epub 2021 Jan 15.

Norwegian Armed Forces Joint Medical Services Sessvollmoen Norway.

Background: Accurate estimates of SARS-CoV-2 infection in different population groups are important for the health authorities. In Norway, public infection control measures have successfully curbed the pandemic. However, military training and service are incompatible with these measures; therefore extended infection control measures were implemented in the Norwegian Armed Forces. We aimed to describe these measures, discuss their value, and investigate the polymerase chain reaction (PCR) prevalence and seroprevalence of SARS-CoV-2, as well as changes in antibody titer levels over the 6-week military training period in a young, asymptomatic population of conscripts.

Methods: In April 2020, 1170 healthy conscripts (median age 20 years) enrolled in military training. Extended infection control measures included a pre-enrollment telephone interview, self-imposed quarantine, questionnaires, and serial SARS-CoV-2 testing. At enrollment, questionnaires were used to collect information on symptoms, and SARS-CoV-2 rapid antibody testing was conducted. Serial SARS-CoV-2 PCR and serology testing were used to estimate the prevalence of confirmed SARS-CoV-2 and monitor titer levels at enrollment, and 3 and 6 weeks thereafter.

Results: At enrollment, only 0.2% of conscripts were SARS-CoV-2 PCR-positive, and seroprevalence was 0.6%. Serological titer levels increased nearly 5-fold over the 6-week observation period. Eighteen conscripts reported mild respiratory symptoms during the 2 weeks prior to enrollment (all were PCR-negative; one was serology-positive), whereas 17 conscripts reported respiratory symptoms and nine had fever at enrollment (all were PCR- and serology-negative).

Conclusions: The prevalence of SARS-CoV-2 was less than 1% in our sample of healthy Norwegian conscripts. Testing of asymptomatic conscripts seems of no value in times of low COVID-19 prevalence. SARS-CoV-2 antibody titer levels increased substantially over time in conscripts with mild symptoms.
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http://dx.doi.org/10.1002/hsr2.233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810033PMC
March 2021

COVID-19 cases reported to the Norwegian Institute of Public Health in the first six weeks of the epidemic.

Tidsskr Nor Laegeforen 2020 12 11;140(18). Epub 2020 Dec 11.

Background: The first case of SARS-CoV-2 infection in Norway was confirmed on 26 February 2020. Following sharpened advice on general infection control measures at the beginning of the outbreak, extensive national control measures were implemented on 12 March, and testing was focused on those with severe illness. We describe the first six weeks of the outbreak in Norway, viewed in light of testing criteria and control measures.

Material And Method: We described all laboratory-confirmed cases of COVID-19 reported to three different surveillance systems under the Norwegian Institute of Public Health up to 5 April 2020, and compared cases reported up to 12 March with those reported from 13 March.

Results: By 12 March, 1 128 cases had been reported. Their median age was 47 years, 64 % were male, 66 % had travelled abroad, 6 % were hospitalised at the time of reporting, and < 1 % had died. The median age of the 4 742 cases reported from 13 March was 48 years, 47 % were male, 18 % had travelled abroad, 15 % were hospitalised, and 3 % died.

Interpetation: The distribution of COVID-19 cases before and after 12 March reflects different phases of the outbreak. However, findings must be interpreted in the light of criteria for testing, testing activity, control measures and characteristics of surveillance systems.
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http://dx.doi.org/10.4045/tidsskr.20.0525DOI Listing
December 2020

Poor self-reported adherence to COVID-19-related quarantine/isolation requests, Norway, April to July 2020.

Euro Surveill 2020 09;25(37)

Division for Health Services, Norwegian Institute of Public Health, Oslo, Norway.

To limit SARS-CoV-2 spread, quarantine and isolation are obligatory in several situations in Norway. We found low self-reported adherence to requested measures among 1,704 individuals (42%; 95% confidence interval: 37-48). Adherence was lower in May-June-July (33-38%) compared with April (66%), and higher among those experiencing COVID-19-compatible symptoms (71%) compared with those without (28%). These findings suggest that consideration is required of strategies to improve people's adherence to quarantine and isolation.
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http://dx.doi.org/10.2807/1560-7917.ES.2020.25.37.2001607DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7502884PMC
September 2020

COVID-19: we need randomised trials of school closures.

J Epidemiol Community Health 2020 12 9;74(12):1078-1079. Epub 2020 Sep 9.

Infection Control and Environmental Health, Norwegian Institute of Public Health, Oslo, Norway.

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http://dx.doi.org/10.1136/jech-2020-214262DOI Listing
December 2020

Antimicrobial susceptibility and clonality of Streptococcus pneumoniae isolates recovered from invasive disease cases during a period with changes in pneumococcal childhood vaccination, Norway, 2004-2016.

Vaccine 2020 07 30;38(34):5454-5463. Epub 2020 Jun 30.

Department of Infection Control and Vaccines, Division of Infection Control and Environmental Health, Norwegian Institute of Public Health, Oslo, Norway. Electronic address:

Changes in pneumococcal antimicrobial resistance (AMR) have been reported following use of pneumococcal conjugate vaccines (PCVs) in childhood vaccination programmes. We describe AMR trends and clonality in Norway during 2004-2016; we studied 10,239 invasive pneumococcal disease (IPD) isolates in terms of serotypes, antimicrobial susceptibility, and for a systematically collected subset of 2473 isolates, multilocus sequence types (ST). The IPD cases were notified to the Norwegian Surveillance System for Communicable Diseases and pneumococcal isolates were collected through the National Reference Laboratory for Pneumococci. The cases are sourced from the entire Norwegian population. We supplemented the IPD isolates with isolates from carriage studies in children attending day-care, performed in 2006 (before mass childhood vaccination with PCV7), 2008 (2 years after PCV7 introduction), 2013 (2 years after the transition to PCV13), and 2015. IPD cases were 0-102 years old; median 64 years. Carriage study participants were typically aged 1-5 years. Overall, AMR was low; a maximum of 7% of IPD isolates were resistant, depending on the antimicrobial. Erythromycin and trimethoprim/sulfamethoxazole resistant IPD (ERY-R and SXT-R, respectively) decreased in the PCV7 period (2006-2010). In the PCV13 period (2011-2016) however, we saw an indication of increased non-susceptibility among IPD isolates. This increase was mainly due to non-vaccine serotypes 15A-ST63 (multidrug resistant), 24F-ST162 (SXT-R), 23B-ST2372 (penicillin non-susceptible and SXT-R) and 33F (ERY-R and clindamycin resistant). Resistant or non-susceptible IPD isolates were often clones introduced into Norway during the study period. The exception was ERY-R isolates; initially, these largely consisted of an established serotype 14-ST9 clone, which disappeared after introducing PCV7. The carriage study results mostly resembled the changes seen in IPD with a maximum of 9% of the participants per study carrying resistant pneumococci. As actual PCVs are not fully limiting AMR, higher-valency vaccines and prudent use of antimicrobials are still needed to temper pneumococcal AMR.
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http://dx.doi.org/10.1016/j.vaccine.2020.06.040DOI Listing
July 2020

High overall confidence in childhood vaccination in Norway, slightly lower among the unemployed and those with a lower level of education.

Vaccine 2020 06 21;38(29):4536-4541. Epub 2020 May 21.

Division of Infection Control and Environmental Health, Norwegian Institute of Public Health, Oslo, Norway.

In Norway, childhood immunisation is offered on voluntary basis, free of charge and is delivered through trained nurses at > 650 child health centres and school health services. Maintaining high confidence in the vaccination programme is key to sustaining high vaccine uptake. We aimed to investigate confidence in childhood vaccination in the general population and to identify determinants for lower confidence. In 2017 and 2018, Statistics Norway asked questions on confidence in childhood vaccination (to all respondents) and children's vaccination history (to parents) in their routine cross-sectional survey. Respondents reported their level of agreement on a five-point Likert scale. Using a weighted analysis we calculated proportions agreeing [95% confidence interval] by respondent characteristics. Overall, 2169 individuals participated (54% response). 95.8% [94.8-96.7] answered that vaccination is important, 93.4% [92.2-94.4] thought that vaccines are safe, 96.0% [95.0-96.8] thought that vaccines are effective and for 93.4% [92.2-94.4] vaccination was compatible with their basic values. Those with lower level of education expressed lower confidence in vaccination due to conflict with their basic values (88.2% [84.7-91.0] answered positively). Those unemployed expressed lower confidence due to conflict with their basic values (81.9% [71.8-88.9]) and because of concerns about vaccines' safety (83.5% [73.7-90.1]). 96.3% [94.3-97.6] of parents (n = 580) had their children fully vaccinated, despite that one fifth answered that they at least once have had doubts on whether or not to vaccinate their children. There is high confidence in childhood vaccination in Norway. Those with a lower level of education and the unemployed reported comparatively lower confidence. To maintain high confidence in childhood vaccination, we recommend maintaining the well-informed system with easily accessible vaccinations. Furthermore, we recommend maintaining surveillance of vaccine confidence, supplemented with targeted studies on subgroups who are less confident, express doubts and/or oppose vaccination. Those studies should inform communication strategies tailored to subgroups.
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http://dx.doi.org/10.1016/j.vaccine.2020.05.011DOI Listing
June 2020

Management and control of an outbreak of vaccine-preventable severe pneumococcal disease at a shipyard in Norway.

J Infect 2020 05 28;80(5):578-606. Epub 2019 Dec 28.

Department of Vaccine Preventable Diseases, Division of Infection Control and Environmental Health, Norwegian Institute of Public Health, Postboks 222 Skøyen, Oslo 0213, Norway. Electronic address:

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http://dx.doi.org/10.1016/j.jinf.2019.12.015DOI Listing
May 2020

Indirect Effects of Pneumococcal Childhood Vaccination in Individuals Treated With Immunosuppressive Drugs in Ambulatory Care: A Case-cohort Study.

Clin Infect Dis 2019 04;68(8):1367-1373

Department of Vaccine Preventable Diseases, Norwegian Institute of Public Health.

Background: The extent to which iatrogenically-immunosuppressed individuals benefit from indirect effects of childhood vaccination with pneumococcal conjugate vaccines (PCVs) is unknown. We determined how the sequential introduction of PCV7 (2006) and PCV13 (2011) in the Norwegian childhood vaccination program has affected the epidemiology of invasive pneumococcal disease (IPD) in individuals treated with immunosuppressants in ambulatory care.

Methods: We conducted a case-cohort study comprising 7926 IPD cases reported to the Norwegian Surveillance System for Communicable Diseases in 2005-2014 and 249998 individuals randomly selected from the National Registry in 2012. We defined immunosuppressive treatment groups based on dispensed prescriptions retrieved from the Norwegian Prescription Database. Incidences and age-adjusted relative risks (RR) were estimated.

Results: IPD incidences decreased in all groups. The PCV13 incidence decreased by 5-12% across groups. The non-PCV13 incidence increased by 4-10%, mostly in individuals on chemotherapy (overlapping 95% confidence intervals). In the PCV13 era, the RR for IPD was highest (significant) and the percentage of cases caused by the polysaccharide vaccine PPV23 serotypes lowest (numerical) in individuals on chemotherapy (RR = 20.4, PPV23 = 52%), followed by individuals on corticosteroids (RR = 6.2, PPV23 = 64%), other immunosuppressants (RR = 5.6, PPV23 = 68%), and no immunosuppressants (RR = 1 [reference], PPV23 = 74%).

Conclusions: IPD incidences declined after PCV introduction in both immunocompetent and iatrogenically-immunosuppressed individuals, underscoring the benefit of childhood vaccination for the entire population. Still, individuals treated with immunosuppressants in ambulatory care are at increased risk of IPD caused by a more diverse group of serotypes.
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http://dx.doi.org/10.1093/cid/ciy714DOI Listing
April 2019

The relative invasive disease potential of Streptococcus pneumoniae among children after PCV introduction: A systematic review and meta-analysis.

J Infect 2018 11 30;77(5):368-378. Epub 2018 Jun 30.

Sanofi Pasteur, Swiftwater, PA, USA.

Objectives: Burden of pneumococcal disease depends on the prevalence and invasive disease potential of serotypes. We aimed to estimate the invasive disease potential of serotypes in children under 5 years of age by combining data from different settings with routine immunisation with pneumococcal conjugate vaccines (PCV).

Methods: We conducted a systematic review, supplemented by unpublished data, to identify data on the frequency of pneumococcal serotypes in carriage and invasive pneumococcal disease (IPD). We estimated the invasive disease potential of serotypes as the ratio of IPD in relation to carriage (odds ratio and 95%CI) compared with 19A (reference serotype) by meta-analysis. We report results based on a random effects model for children aged 0-23, 24-29, and 0-59 months and by invasive clinical syndromes.

Results: In comparison with 19A, serotypes 1, 7F, and 12F had a significantly higher invasive disease potential in children aged 0-23 and 0-59 months for all IPD and clinical syndromes (OR > 5). Several non-vaccine types (NVTs) (6C, 15A, 15BC, 16F, 23B, in these two age groups) had a lower invasive disease potential than 19A (OR 0.1-0.3). NVTs 8, 12F, 24F, and 33F were at the upper end of the invasiveness spectrum.

Conclusions: There is substantial variation among pneumococcal serotypes in their potential to cause IPD and disease presentation, which is influenced by age and time after PCV introduction. Surveillance of IPD and carriage is critical to understand the expected effectiveness of current PCVs (in the longer term) and guide the development of future vaccines.
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http://dx.doi.org/10.1016/j.jinf.2018.06.004DOI Listing
November 2018

In vitro and in vivo comparison of transport media for detecting nasopharyngeal carriage of Streptococcus pneumoniae.

PeerJ 2016 22;4:e2449. Epub 2016 Sep 22.

Infection Control and Environmental Health, Norwegian Institute of Public Health , Oslo , Norway.

Background: As a standard method for pneumococcal carriage studies, the World Health Organization recommends nasopharyngeal swabs be transported and stored at cool temperatures in a medium containing skim-milk, tryptone, glucose and glycerol (STGG). An enrichment broth used for transport at room temperature in three carriage studies performed in Norway may have a higher sensitivity than STGG. We therefore compared the media in vitro and in vivo.

Methods: For the in vitro component, three strains (serotype 4, 19F and 3) were suspended in STGG and enrichment broth. Recovery was compared using latex agglutination, quantification of bacterial loads by real-time PCR of the lytA gene, and counting colonies from incubated plates. For the in vivo comparison, paired swabs were obtained from 100 children and transported in STGG at cool temperatures or in enrichment broth at room temperature. Carriage was identified by latex agglutination and confirmed by Quellung reaction.

Results: In vitro, the cycle threshold values obtained by PCR did not differ between the two media (p = 0.853) and no clear difference in colony counts was apparent after incubation (p = 0.593). In vivo, pneumococci were recovered in 46% of swabs transported in STGG and 51% of those transported in enrichment broth (Kappa statistic 0.90, p = 0.063).

Discussion: Overall, no statistical differences in sensitivity were found between STGG and enrichment broth. Nevertheless, some serotype differences were observed and STGG appeared slightly less sensitive than enrichment broth for detection of nasopharyngeal carriage of pneumococci by culturing. We recommend the continued use of STGG for transport and storage of nasopharyngeal swabs in pneumococcal carriage studies for the benefit of comparability between studies and settings, including more resource-limited settings.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5036082PMC
http://dx.doi.org/10.7717/peerj.2449DOI Listing
October 2016

Decreased Carriage and Genetic Shifts in the Streptococcus pneumoniae Population After Changing the Seven-valent to the Thirteen-valent Pneumococcal Vaccine in Norway.

Pediatr Infect Dis J 2015 Aug;34(8):875-83

From the *Division of Infectious Disease Control, Department of Bacteriology and Immunology, Norwegian Institute of Public Health, Oslo, Norway; †Faculty of Medicine, University of Oslo, Oslo, Norway; and ‡European Programme for Public Health Microbiology Training (EUPHEM), European Centre for Disease Prevention and Control (ECDC), Stockholm, Sweden.

Background: Shifts in the pneumococcal population colonizing healthy children are expected after switching from a 7-valent pneumococcal conjugate vaccine (PCV7) to a 13-valent (PCV13) in the childhood immunization program. We assessed effects of the switch by comparing pneumococcal carriage and serotype and genetic diversity of pneumococci carried by children in the PCV13-era with those carried in the prevaccination-era and PCV7-era.

Methods: Nasopharyngeal swabs were obtained in autumn 2013 from children attending day-care centers (874 swabs, 583 isolates). Serotyping, multilocus sequence typing and antimicrobial susceptibility testing were performed on all isolates. Results were compared with samples from 2006 (610 swabs, 538 isolates) and 2008 (600 swabs, 562 isolates).

Results: The carriage prevalence in 2013 was 62 of 100 children (95% confidence intervals: 58-66), a significant decrease from 2006 and 2008. PCV13 serotypes accounted for 7% of isolates in 2013. Non-PCV13 prevalence increased from 2006 to 2008 [prevalence ratio: 1.73 (1.40-2.15)] but remained stable in 2013 [0.99 (0.88-1.12)]. Still, non-PCV13 serotypes 21, 23B, 23A and 22F had increased. In 2013, the serotype and genetic diversity had decreased slightly, and distinct serotype and genetic profiles clustered more within day-care centers compared with the earlier samples. Serotype switch was uncommon. Overall, antimicrobial resistance was limited.

Conclusions: Carriage of PCV13 serotypes has decreased without a coinciding increase in non-PCV13 serotypes. The serotype and genetic shifts among non-PCV13 serotypes suggest that a new equilibrium has not yet been reached. As the few non-PCV13 serotypes that increased have generally a lower invasive capacity than vaccine serotypes, direct and indirect protection of PCV13 on invasive pneumococcal disease can be expected to continue.
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http://dx.doi.org/10.1097/INF.0000000000000751DOI Listing
August 2015

Pneumococcal vaccination in older adults in the era of childhood vaccination: Public health insights from a Norwegian statistical prediction study.

Epidemics 2015 Jun 19;11:24-31. Epub 2015 Jan 19.

Division of Infectious Disease Control, Norwegian Institute of Public Health, Norway; Oslo Center for Biostatistics and Epidemiology, Department of Biostatistics, Institute of Basic Medical Sciences, University of Oslo, Norway.

Two different vaccines, a 23-valent polysaccharide vaccine (PPV23) and a 13-valent conjugate vaccine (PCV13), are available for prevention of invasive pneumococcal disease (IPD) in the population aged 65 years and older (65+). The IPD epidemiology in the 65+ is undergoing change due to indirect effects of childhood immunisation. Vaccine recommendations for the 65+ must take into account these trends in epidemiology. We therefore explored the preventive potential of vaccination strategies to prevent IPD in the 65+, including PPV23, PCV13 or PCV13 + PPV23 in 2014-2019. Quasi-Poisson regression models were fitted to 2004-2014 population-wide surveillance data and used to predict incidences for vaccine-type and non-vaccine type IPD. We determined the number of people needed to be vaccinated to prevent one case per season (NNV) for each strategy and estimated the public health impact on the IPD case counts from increasing the vaccine uptake to 28-45%. Our results indicate that PCV13-IPD will decrease by 71% from 58 (95% prediction interval 55-61) cases in 2014/15 to 17 (6-52) in 2018/19 and PPV23-IPD by 32% from 168 (162-175) to 115 (49-313) cases. The NNV will increase over time for all strategies because of a decreasing vaccine-type IPD incidence. In 2018/19, the PCV13-NNV will be 5.3 times higher than the PPV23-NNV. Increasing the vaccine uptake will lead to a larger public health impact for all scenarios. Combining PCV13 and PPV23 is most effective, but the additional effect of PCV13 will decrease and is only marginal in 2018/19. Our study demonstrates the importance of increasing PPV23 uptake and of developing vaccines that confer broader immunity.
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http://dx.doi.org/10.1016/j.epidem.2015.01.001DOI Listing
June 2015

What are the most important infectious diseases among those ≥65 years: a comprehensive analysis on notifiable diseases, Norway, 1993-2011.

BMC Infect Dis 2014 Feb 4;14:57. Epub 2014 Feb 4.

Norwegian Institute of Public Health, Oslo, Norway.

Background: As the population ages, the burden on the healthcare system might increase and require changed public health priorities. As infections are often more severe at older age, we rank notifiable infectious diseases (ID) and describe trends of ID among the general population aged ≥65 years in Norway in order to inform public health priorities for the aging population.

Methods: We included all eligible cases of the 58 IDs notified between 1993 and 2011 (n = 223,758; 12% ≥65 years) and determined annual notification rates as the number of notified cases divided by the number of inhabitants of the corresponding year. We ranked diseases using their average annual notification rate for 2007-2011. Trends in notification rates from 1993 onwards were determined with a non-parametric test for trend. Using notification rate ratios (NRR), we compared results in those aged ≥65 years to those aged 20-64 years.

Results: Invasive pneumococcal disease was the most common ID among the population ≥65 years (notification rate 58/100,000), followed by pertussis (54/100,000) and campylobacteriosis (30/100,000). Most ID notification rates did not change over time, though the notification rate of symptomatic MRSA infections increased from 1/100,000 in 1995 (first year of notification) to 14/100,000 in 2011.Overall, fewer cases were notified among the population ≥65 years compared to 20-64 year olds (NRR = 0.73). The NRR of each of the invasive bacterial diseases and antibiotic-resistant infections were above 1.5 (i.e. more common in ≥65), while the NRR of each food- and waterborne disease, blood-borne disease/STI and (non-invasive) vaccine preventable disease was below 1.

Conclusions: Based on our results, we emphasise the importance of focusing public health efforts for those ≥65 years on preventing invasive bacterial infections. This can be achieved by increasing pneumococcal and influenza vaccine uptake, and risk communication including encouraging those aged ≥65 years and their caretakers to seek healthcare at signs of systemic infection. Furthermore, good compliance to infection control measures, screening of the at-risk population, and careful use of antibiotics may prevent further increase in antibiotic-resistant infections.
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http://dx.doi.org/10.1186/1471-2334-14-57DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3923236PMC
February 2014

Prompt effect of replacing the 7-valent pneumococcal conjugate vaccine with the 13-valent vaccine on the epidemiology of invasive pneumococcal disease in Norway.

Vaccine 2013 Dec 29;31(52):6232-8. Epub 2013 Oct 29.

Division of Infectious Disease Control, Norwegian Institute of Public Health, Oslo, Norway; European Programme for Intervention Epidemiology Training (EPIET), European Centre for Disease Prevention and Control (ECDC), Stockholm, Sweden. Electronic address:

The introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in the childhood immunisation programme in Norway in 2006 substantially decreased the incidence of vaccine-type (VT) invasive pneumococcal disease (IPD) in all age groups. Additionally, a slight increase in the non-vaccine (NVT) serotype IPD incidence (serotype replacement) was observed. After replacing PCV7 with PCV13 in 2011, a further decrease in IPD incidence is expected. However, the protection by the six additional serotypes opens new nasopharyngeal niches for colonisation, which favours conditions for serotype replacement. Close monitoring of IPD therefore remains important in order to quickly detect changes. In this observational retrospective population-based cohort study we used data notified nationally between 1 January 2004 and 31 December 2012 to determine the VT- and NVT-IPD incidences. The diversity in serotype distribution per year was analysed using the Simpson's index of diversity. Immunisation history of young children was obtained from the Norwegian Vaccination Registry to determine vaccine failure. The incidence of VT-IPD decreased in the targeted (<5 years) and non-targeted (≥5) age groups since PCV7 introduction and further decreased after the replacement with PCV13. Only two cases of vaccine failure were identified. This indicates very high effectiveness of the 2+1 schedules with PCV7 or PCV13 and suggests that non-vaccinated individuals profit through indirect protection. The decrease in incidence of PCV7-IPD in non-targeted age groups became larger in later years, indicating a lag phase for the indirect effects, and suggests that the indirect protection of PCV13 will increase in coming years. The incidence of some NVT, specifically serotypes 23B and 15A, increased after PCV13 introduction. This coincided with an increased Simpson's index of diversity in the targeted age group. As this suggests that serotype replacement is again occurring, continues monitoring of IPD is important so that adaptations to vaccine recommendations can be promptly issued.
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http://dx.doi.org/10.1016/j.vaccine.2013.10.032DOI Listing
December 2013

Estimated global mortality associated with the first 12 months of 2009 pandemic influenza A H1N1 virus circulation: a modelling study.

Lancet Infect Dis 2012 Sep 26;12(9):687-95. Epub 2012 Jun 26.

Influenza Division, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.

Background: 18,500 laboratory-confirmed deaths caused by the 2009 pandemic influenza A H1N1 were reported worldwide for the period April, 2009, to August, 2010. This number is likely to be only a fraction of the true number of the deaths associated with 2009 pandemic influenza A H1N1. We aimed to estimate the global number of deaths during the first 12 months of virus circulation in each country.

Methods: We calculated crude respiratory mortality rates associated with the 2009 pandemic influenza A H1N1 strain by age (0-17 years, 18-64 years, and >64 years) using the cumulative (12 months) virus-associated symptomatic attack rates from 12 countries and symptomatic case fatality ratios (sCFR) from five high-income countries. To adjust crude mortality rates for differences between countries in risk of death from influenza, we developed a respiratory mortality multiplier equal to the ratio of the median lower respiratory tract infection mortality rate in each WHO region mortality stratum to the median in countries with very low mortality. We calculated cardiovascular disease mortality rates associated with 2009 pandemic influenza A H1N1 infection with the ratio of excess deaths from cardiovascular and respiratory diseases during the pandemic in five countries and multiplied these values by the crude respiratory disease mortality rate associated with the virus. Respiratory and cardiovascular mortality rates associated with 2009 pandemic influenza A H1N1 were multiplied by age to calculate the number of associated deaths.

Findings: We estimate that globally there were 201,200 respiratory deaths (range 105,700-395,600) with an additional 83,300 cardiovascular deaths (46,000-179,900) associated with 2009 pandemic influenza A H1N1. 80% of the respiratory and cardiovascular deaths were in people younger than 65 years and 51% occurred in southeast Asia and Africa.

Interpretation: Our estimate of respiratory and cardiovascular mortality associated with the 2009 pandemic influenza A H1N1 was 15 times higher than reported laboratory-confirmed deaths. Although no estimates of sCFRs were available from Africa and southeast Asia, a disproportionate number of estimated pandemic deaths might have occurred in these regions. Therefore, efforts to prevent influenza need to effectively target these regions in future pandemics.

Funding: None.
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http://dx.doi.org/10.1016/S1473-3099(12)70121-4DOI Listing
September 2012

Association between human papillomavirus vaccine uptake and cervical cancer screening in the Netherlands: implications for future impact on prevention.

Int J Cancer 2013 Feb 3;132(4):932-43. Epub 2012 Jul 3.

Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.

Several countries recently added human papillomavirus (HPV) vaccination to cervical cancer screening in the effort to prevent cervical cancer. They include the Netherlands, where both programs are free. To estimate their combined future impact on cancer prevention, information is needed on the association between participation in vaccination now and in screening in the future and on what groups are at risk for nonparticipation. We studied the association between participation in screening by mothers and in vaccination by their daughters. Girls' vaccination status was matched by house-address with their mothers' screening participation. We estimated the effect on cancer incidence by means of computer simulation. We investigated risk groups for nonparticipation using multivariable multilevel logistic regression and calculated population-attributable fractions. Our results, based on 89% of girls invited for vaccination in 2009 (n = 337,368), show that vaccination status was significantly associated with mothers' screening participation (odds ratio: 1.54 [95% confidence interval: 1.51-1.57]). If a mother's screening is taken as proxy of a girl's future screening, only 13% of the girls will not participate in either program compared to 23% if screening alone is available. The positive association between vaccination and screening resulted in slightly lower model estimates of the impact of vaccination on cancer incidence, compared to estimates assuming no association. Girls with nonwestern ethnicities, with young mothers, who live in urban areas with low socioeconomic status, are at risk for nonparticipation. A significant part of potential nonscreeners may be reached through HPV vaccination. Estimates made before vaccination was introduced only slightly overestimated its impact on cervical cancer incidence.
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http://dx.doi.org/10.1002/ijc.27671DOI Listing
February 2013

Acceptance of vaccination during pregnancy: experience with 2009 influenza A (H1N1) in the Netherlands.

Vaccine 2012 Apr 26;30(18):2892-9. Epub 2012 Feb 26.

Department of Epidemiology and Surveillance, Centre for Infectious Disease Control, National Institute for Public Health and the Environment, 3720 BA Bilthoven, the Netherlands.

Objectives: In 2009, the Dutch government advised pregnant women to get vaccinated against influenza A (H1N1). A study was set up to gain insight into vaccination coverage and reasons why pregnant women seek vaccination or not.

Methods: We invited 14,529 pregnant women to complete an internet survey on vaccination during pregnancy in general and against 2009 influenza A (H1N1). Differences in background characteristics between unvaccinated and vaccinated women were investigated. Prediction analyses were carried out to determine which survey statement had the greatest impact on vaccination status or intention to get vaccinated during pregnancy.

Results: Of the 2993 included respondents, 63% reported to be vaccinated against 2009 influenza A (H1N1). Vaccination coverage was higher among older birth cohorts, women who had been pregnant before, women with underlying medical conditions, and women who reported no defined 'life philosophy'. Protection of the child (after birth), the government's advice and possible harmful effects of the vaccine for the unborn child had the greatest predictive value for vaccination status. With regards vaccination during future pregnancies, 39% had a positive intention to obtain vaccination and 45% were neutral. The government's advice was the strongest predictor for intention. Furthermore, women expressed concern over lack of sufficient knowledge about vaccine safety.

Conclusions: A considerable number of pregnant women in the Netherlands reported to be vaccinated against 2009 influenza A (H1N1). The challenge for the government in the future will be to provide pregnant women and health care professionals with sufficient and clear information about disease severity and the benefits and safety of vaccination.
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http://dx.doi.org/10.1016/j.vaccine.2012.02.030DOI Listing
April 2012

Age-dependent patterns of infection and severity explaining the low impact of 2009 influenza A (H1N1): evidence from serial serologic surveys in the Netherlands.

Am J Epidemiol 2011 Dec 24;174(11):1307-15. Epub 2011 Oct 24.

Centre for Infectious Disease Control, National Institute for Public Health and theEnvironment (RIVM), the Netherlands.

Despite considerable research efforts in specific subpopulations, reliable estimates of the infection attack rates and severity of 2009 influenza A (H1N1) in the general population remain scarce. Such estimates are essential to the tailoring of future control strategies. Therefore, 2 serial population-based serologic surveys were conducted, before and after the 2009 influenza A (H1N1) epidemic, in the Netherlands. Random age-stratified samples were obtained using a 2-stage cluster design. Participants donated blood and completed a questionnaire. Data on sentinel general practitioner-attended influenza-like illness and nationwide hospitalization and mortality were used to assess the severity of infection. The estimated infection attack rates were low in the general population (7.6%, 95% confidence interval: 3.6, 11) but high in children aged 5-19 years (35%, 95% confidence interval: 25, 45). The estimated hospitalization and mortality rates per infection increased significantly with age (5-19 years: 0.042% and 0.00094%, respectively; 20-39 years: 0.12% and 0.0025%; 40-59 years: 0.68% and 0.032%; 60-75 years: >0.81% and >0.068%). The high infection attack rate in children and the very low attack rate in older adults, together with the low severity of illness per infection in children but substantial severity in older adults, produced an epidemic with a low overall impact.
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http://dx.doi.org/10.1093/aje/kwr245DOI Listing
December 2011

Fatigue perceived by multiple sclerosis patients is associated with muscle fatigue.

Neurorehabil Neural Repair 2012 Jan 19;26(1):48-57. Epub 2011 Aug 19.

Deptartment of Neuroscience, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.

Background: Fatigue is a debilitating symptom in multiple sclerosis (MS). Previous studies showed no association between fatigue as perceived by the patient and physiological measures of fatigability.

Objective: The authors investigated associations between perceived fatigue and measures of fatigability after correction for differences in maximal voluntary contraction (MVC).

Methods: A total of 20 people with relapsing-remitting MS with an Extended Disability Severity Score less than 5.5 and 20 healthy controls filled out the Fatigue Severity Score questionnaire of perceived fatigue. The authors obtained the MVC from the first dorsal interosseus muscle, voluntary muscle activation, and force decline during a sustained MVC (124 s, muscle fatigue).

Results: Patients perceived increased levels of fatigue compared with controls (P < .001). Although patients and controls developed similar amounts of muscle fatigue during the sustained contraction, a linear regression model that included both muscle fatigue and MVC was positively associated with perceived fatigue in patients only (R (2) = 0.45; P = .01). Voluntary activation during the sustained contraction was negatively associated with perceived fatigue (R (2) = 0.25; P = .02).

Conclusion: The data indicate that fatigue perceived by MS patients is associated with measures of fatigability. This observation helps in the understanding of mechanisms underlying the increased levels of fatigue perceived by MS patients. These data also emphasize that for comparison of fatigue-related parameters between groups, correction for individual maximal force is essential.
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http://dx.doi.org/10.1177/1545968311416991DOI Listing
January 2012

Effectiveness of a MF-59™-adjuvanted pandemic influenza vaccine to prevent 2009 A/H1N1 influenza-related hospitalisation; a matched case-control study.

BMC Infect Dis 2011 Jul 18;11:196. Epub 2011 Jul 18.

Epidemiology and Surveillance Unit, Centre for Infectious Disease Control, National institute for Public Health and the Environment, Bilthoven, The Netherlands.

Background: During the 2009 influenza A/H1N1 pandemic, adjuvanted influenza vaccines were used for the first time on a large scale. Results on the effectiveness of the vaccines in preventing 2009 influenza A/H1N1-related hospitalisation are scanty and varying.

Methods: We conducted a matched case-control study in individuals with an indication for vaccination due to underlying medical conditions and/or age ≥ 60 years in The Netherlands. Cases were patients hospitalised with laboratory-confirmed 2009 A/H1N1 influenza infection between November 16, 2009 and January 15, 2010. Controls were matched to cases on age, sex and type of underlying medical condition(s) and drawn from an extensive general practitioner network. Conditional logistic regression was used to estimate the vaccine effectiveness (VE = 1 - OR). Different sensitivity analyses were used to assess confounding by severity of underlying medical condition(s) and the effect of different assumptions for missing dates of vaccination.

Results: 149 cases and 28,238 matched controls were included. It was estimated that 22% of the cases and 28% of the controls received vaccination more than 7 days before the date of onset of symptoms in cases. A significant number of breakthrough infections were observed. The VE was estimated at 19% (95%CI -28-49). After restricting the analysis to cases with controls suffering from severe underlying medical conditions, the VE was 49% (95% CI 16-69).

Conclusions: The number of breakthrough infections, resulting in modest VE estimates, suggests that the MF-59™ adjuvanted vaccine may have had only a limited impact on preventing 2009 influenza A/H1N1-related hospitalisation in this setting. As the main aim of influenza vaccination programmes is to reduce severe influenza-related morbidity and mortality from influenza in persons at high risk of complications, a more effective vaccine, or additional preventive measures, are needed.
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http://dx.doi.org/10.1186/1471-2334-11-196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3154871PMC
July 2011

High tetanus antitoxin antibody concentrations in the Netherlands: a seroepidemiological study.

Vaccine 2010 Nov 25;28(49):7803-9. Epub 2010 Sep 25.

Epidemiology and Surveillance Unit, Centre for Infectious Disease Control, National Institute of Public Health and Environment, Bilthoven, The Netherlands.

We assessed the level and determinants of tetanus-antitoxin (TT)-antibodies in the Dutch population. Additionally, we evaluated the national guidelines for post-exposure prophylaxis. Serum samples and questionnaire data from a cross-sectional, population-based study were obtained from 7903 individuals. Serum antitoxin antibodies were assessed with a multiplex immunoassay. Multivariable linear regression was used to explore factors associated with antibody concentration. The overall seroprevalence was 94% with a geometric mean concentration (GMC) of 0.91 IU/ml. The TT-GMC increased with age in the age-cohorts of 13-23 years, which coincides with the meningococcal C conjugate mass-vaccination in 2002. Lower seroprevalences were found in individuals born before introduction of routine vaccination, first-generation migrants from non-Western countries born before 1984, and conservative Protestants living in the Dutch 'Bible belt'. Only 10% of those eligible for post-exposure prophylaxis were not sufficiently protected against tetanus.
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http://dx.doi.org/10.1016/j.vaccine.2010.09.036DOI Listing
November 2010

Voluntary activation and cortical activity during a sustained maximal contraction: an fMRI study.

Hum Brain Mapp 2009 Mar;30(3):1014-27

Department of Medical Physiology, University Medical Center Groningen, University of Groningen, The Netherlands.

Motor fatigue is an exercise-induced reduction in the force-generating capacity. The underlying mechanisms can be separated into factors residing in the periphery or in the central nervous system. We designed an experiment in which we investigated central processes underlying motor fatigue by means of magnetic resonance imaging in combination with the twitch interpolation technique. Subjects performed a sustained maximal abduction (2 min) with the right index finger. Brain activation was recorded with an MR scanner, together with index finger abduction force, EMG of several hand muscles and interpolated twitches. Mean activity per volume was calculated for the primary motor cortex and the secondary motor areas (supplementary motor, premotor, and cingulate areas) as well as mean force and mean rectified EMG amplitude. Results showed a progressive decline in maximal index finger abduction force and EMG of the target muscles combined with an increase in brain activity in the contralateral primary motor cortex and secondary motor areas. Analysis of the twitches superimposed on the sustained contraction revealed that during the contraction the voluntary drive decreased significantly. In conclusion, our data showed that despite an increase in brain activity the voluntary activation decreased. This suggests that, although the CNS increased its input to the relevant motor areas, this increase was insufficient to overcome fatigue-related changes in the voluntary drive.
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http://dx.doi.org/10.1002/hbm.20562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6871255PMC
March 2009

Reduced cortical activity during maximal bilateral contractions of the index finger.

Neuroimage 2007 Mar 12;35(1):16-27. Epub 2007 Jan 12.

Department of Medical Physiology, University Medical Center Groningen, University of Groningen, The Netherlands.

The bilateral deficit refers to the phenomenon in which homologous muscles produce per muscle less force when contracting simultaneously than when contracting individually. The mechanism underlying the bilateral deficit is still unknown, but the most likely cause is a decline in the activation of motor units during bilateral contractions. In the present study, we used functional magnetic resonance imaging (fMRI) to measure the degree of brain activity during unilateral and bilateral maximal contractions in combination with force and EMG measurements. Subjects performed, in a semi-randomized order, maximal isometric contractions (MVC) with the right index finger, the left index finger and with both fingers simultaneously. During the task, brain activation was measured with a 3 T MR scanner, in combination with force and EMG recordings. The most important activated areas in the brain during the contractions were the sensorimotor cortex (precentral and postcentral gyrus), cerebellum, premotor cortex and supplementary motor area. During bilateral contractions, a significant decline in force and EMG values was found and detailed analysis of the brain activation data showed that this decline was accompanied with a significant decline in the activation of the precentral gyrus. This result suggests that the bilateral decline is the resultant of a decline in input to the primary motor area and shows that the main source of the bilateral deficit lies upstream of the primary motor cortex.
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http://dx.doi.org/10.1016/j.neuroimage.2006.11.050DOI Listing
March 2007