Colistin-resistant Enterobacterales among veterinary healthcare workers and in the Dutch population.

Objectives: Plasmid-mediated colistin resistance can be transferred from animals to humans. We investigated the prevalence of carriage of mcr-mediated colistin-resistant Escherichia coli and Klebsiella pneumoniae (ColR-E/K) in veterinary healthcare workers and in the general population in the Netherlands. Methods: Two cross-sectional population studies were performed: one among veterinary healthcare workers and one in the general population. Participants sent in a faecal sample and filled in a questionnaire. Samples were analysed using selective enrichment and culture. Mobile colistin resistance genes (mcr) were detected by PCR and ColR-E/K were sequenced using Illumina and Nanopore technologies. Results: The prevalence of mcr-mediated ColR-E/K was 0.2% (1/482, 95% CI 0.04%-1.17%) among veterinary personnel and 0.8% (5/660, 95% CI 0.3%-1.8%) in the population sample. mcr-1 was found in E. coli from four persons, mcr-8 in K. pneumoniae from one person and another person carried both mcr-1 and mcr-8 in a K. pneumoniae isolate. mcr-1 was found on different plasmid types (IncX4, IncI1 and IncI2), while mcr-8 was found on IncF plasmids only. Conclusions: mcr-mediated ColR-E/K resistance was uncommon in both populations. Professional contact with animals does not increase the chance of carriage of these bacteria in the Netherlands at present. mcr-8 was found for the first time in the Netherlands. Surveillance of colistin resistance and its underlying mechanisms in humans, livestock and food is important in order to identify emerging trends in time.

Review of long-term immunogenicity following HPV vaccination: Gaps in current knowledge.

The licensed HPV vaccines are highly efficacious and induce high levels of neutralizing antibody levels, the assumed mediators of protection. However, a correlate of protection against HPV is lacking, and the evidence is still limited as to long-term persistence of antibodies, especially following reduced dosing schedules. The World Health Organization (WHO) urges immunization of young girls as part of the strategy to eliminate cervical cancer, thus long-lasting protection is required. The current review describes long-term follow-up regarding vaccine-induced seropositivity and antibody level development following the different vaccines and dosing schedules. Implications and opportunities of long-term vaccine-induced immune responses are discussed, such as the gaps in monitoring of long-term immunogenicity, the possibilities of reduced dosing schedules, and the importance of evidence for durable immunity.

The importance of supplementary immunisation activities to prevent measles outbreaks during the COVID-19 pandemic in Kenya.

BACKGROUND: The COVID-19 pandemic has disrupted routine measles immunisation and supplementary immunisation activities (SIAs) in most countries including Kenya. We assessed the risk of measles outbreaks during the pandemic in Kenya as a case study for the African Region. METHODS: Combining measles serological data, local contact patterns, and vaccination coverage into a cohort model, we predicted the age-adjusted population immunity in Kenya and estimated the probability of outbreaks when contact-reducing COVID-19 interventions are lifted. We considered various scenarios for reduced measles vaccination coverage from April 2020. RESULTS: In February 2020, when a scheduled SIA was postponed, population immunity was close to the herd immunity threshold and the probability of a large outbreak was 34% (8-54). As the COVID-19 contact restrictions are nearly fully eased, from December 2020, the probability of a large measles outbreak will increase to 38% (19-54), 46% (30-59), and 54% (43-64) assuming a 15%, 50%, and 100% reduction in measles vaccination coverage. By December 2021, this risk increases further to 43% (25-56), 54% (43-63), and 67% (59-72) for the same coverage scenarios respectively. However, the increased risk of a measles outbreak following the lifting of all restrictions can be overcome by conducting a SIA with ≥ 95% coverage in under-fives. CONCLUSION: While contact restrictions sufficient for SAR-CoV-2 control temporarily reduce measles transmissibility and the risk of an outbreak from a measles immunity gap, this risk rises rapidly once these restrictions are lifted. Implementing delayed SIAs will be critical for prevention of measles outbreaks given the roll-back of contact restrictions in Kenya.

Comparison of antibody response between boys and girls after infant and childhood vaccinations in the Netherlands.

BACKGROUND: Infectious diseases can differ by sex in their incidence, prevalence, or severity of disease. These differences may be induced by sex-dependent immune responses and resulting protection, for example after vaccination. Therefore, this study aims to assess possible sex-differences in immunoglobulin levels (IgG) after infant and childhood vaccination. METHODS: Data from a national cross-sectional serosurvey conducted in 2006/2007 were used (Pienter 2). We compared IgG levels against measles, mumps, rubella, diphtheria, tetanus, poliomyelitis, pertussis, Haemophilus influenzae type b (Hib), and Neisseria meningitidis serogroup C (MenC) between girls and boys both short term (1 month to 1 year) and long term (1-3 year) after infant and childhood vaccinations, using linear regression analysis. Proportions of boys and girls reaching a protective IgG level were compared using Fishers exact test. RESULTS: Differences in IgG were found at specific time points after vaccination against measles, mumps, rubella, MenC, and polio. The geometric mean concentration or titer (GMC/T) girls:boys ratios ranged between 1.10 for polio type 1 <1 year after the first childhood booster to 1.90 for MenC <1 year after infant vaccination, indicating higher antibody levels in girls. No significant differences were found between boys and girls for diphtheria, tetanus, pertussis, and Hib at either time point. Proportions with protective levels differed only at 1-3 years after infant vaccination for mumps (82.5% boys vs. 91.9% girls, p = 0.046), and at the same time point for MenC (7.0% boys vs. 18.2% girls, p = 0.015), and polio type 1 (87.8% boys vs. 95.9% girls, p = 0.047). CONCLUSION: Differences in IgG between boys and girls were generally small and not consistent, neither between pathogens nor within pathogens. If differences were observed, girls were favored over boys. On the whole, the results suggest that there are no major sex differences in protection from the studied pathogens in the Netherlands.

The Netherlands Chlamydia cohort study (NECCST) protocol to assess the risk of late complications following Chlamydia trachomatis infection in women.

BACKGROUND: Chlamydia trachomatis (CT), the most common bacterial sexually transmitted infection (STI) among young women, can result in serious sequelae. Although the course of infection is often asymptomatic, CT may cause pelvic inflammatory disease (PID), leading to severe complications, such as prolonged time to pregnancy, ectopic pregnancy, and tubal factor subfertility. The risk of and risk factors for complications following CT-infection have not been assessed in a long-term prospective cohort study, the preferred design to define infections and complications adequately. METHODS: In the Netherlands Chlamydia Cohort Study (NECCST), a cohort of women of reproductive age with and without a history of CT-infection is followed over a minimum of ten years to investigate (CT-related) reproductive tract complications. This study is a follow-up of the Chlamydia Screening Implementation (CSI) study, executed between 2008 and 2011 in the Netherlands. For NECCST, female CSI participants who consented to be approached for follow-up studies (n = 14,685) are invited, and prospectively followed until 2022. Four data collection moments are foreseen every two consecutive years. Questionnaire data and blood samples for CT-Immunoglobulin G (IgG) measurement are obtained as well as host DNA to determine specific genetic biomarkers related to susceptibility and severity of infection. CT-history will be based on CSI test outcomes, self-reported infections and CT-IgG presence. Information on (time to) pregnancies and the potential long-term complications (i.e. PID, ectopic pregnancy and (tubal factor) subfertility), will be acquired by questionnaires. Reported subfertility will be verified in medical registers. Occurrence of these late complications and prolonged time to pregnancy, as a proxy for reduced fertility due to a previous CT-infection, or other risk factors, will be investigated using longitudinal statistical procedures. DISCUSSION: In the proposed study, the occurrence of late complications following CT-infection and its risk factors will be assessed. Ultimately, provided reliable risk factors and/or markers can be identified for such late complications. This will contribute to the development of a prognostic tool to estimate the risk of CT-related complications at an early time point, enabling targeted prevention and care towards women at risk for late complications. TRIAL REGISTRATION: Dutch Trial Register NTR-5597 . Retrospectively registered 14 February 2016.

Chlamydia trachomatis IgG seroprevalence in the general population of the Netherlands in 1996 and in 2007: differential changes by gender and age.

OBJECTIVES: Chlamydia trachomatis (CT) reporting rates from sexually transmitted infection clinics and general practitioners have shown a rising trend in the Netherlands. It is unknown to what extent this reflects increased CT transmission or improved case finding. To achieve more insight into the CT epidemic, we explored the CT IgG seroprevalence (a marker of past CT infection) in the general population of the Netherlands in 1996 and in 2007. METHODS: From two population-based studies in 1996 and 2007, serum samples, demographic and sexual behaviour outcomes were examined, including 1246 men and 1930 women aged 15-39 years. Serum CT IgG antibodies were analysed using the Medac CT IgG ELISA test. Multivariate logistic regression analyses explored the seroprevalence and determinants over time. RESULTS: The CT IgG seroprevalence was higher in women than in men (10% vs 6%). Among women aged 25-39 years the seroprevalence was lower in 2007 (9%) than in 1996 (14%; adjusted OR (aOR) 0.6, 95% CI 0.4 to 0.8). There was no statistical evidence of a difference in seroprevalence within birth cohorts. Factors associated with seropositivity were male gender (aOR 0.4, 95% CI 0.3 to 0.7), a self-reported history of CT infection (aOR 5.1, 95% CI 2.6 to 10.0), age 25-39 years (aOR 1.7, 95% CI 1.1 to 2.7), non-Western ethnicity (aOR 2.2, 95% CI 1.4 to 3.3) and ≥ 2 recent sexual partners (aOR 2.2, 95% CI 1.3 to 3.5). CONCLUSIONS: Between 1996 and 2007 the proportion of individuals in the general population with CT IgG antibodies was lower among women aged 25-39 years, but remained similar among younger women and men.

Prevalence of genital HPV infections and HPV serology in adolescent girls, prior to vaccination.

INTRODUCTION: Monitoring the prevalence of type-specific HPV-DNA infections before and shortly after introduction of routine HPV vaccination offers the opportunity to evaluate early effects of the vaccination program. With this aim a cohort study was set up of 14- to 16-year-old girls eligible for HPV vaccination in the Netherlands. Annually, HPV-DNA and antibody status in vaginal self-samples and in serum respectively, will be studied among vaccinated (58%) and unvaccinated girls (42%). Here we present baseline data on vaginal HPV-DNA status in relation to serum antibodies. METHODS: The 1800 enrolled girls filled out an internet-based questionnaire and provided a vaginal self-sample for genotype specific HPV-DNA detection using SPF(10) PCR amplification and reverse line probe hybridization. Furthermore, 64% of the girls provided a blood sample for HPV antibody analysis. IgG antibodies against virus-like particles were determined for 7 HPV genotypes. RESULTS: At baseline, type-specific HPV-DNA was detected in 4.4% (n = 79) of the 1800 girls: 2.7% (n = 49) concerned a high risk HPV type (hrHPV-DNA). The three most common types were HPV type 16, 18 and 51 (40%). Out of the hrHPV-DNA positive girls, 32% was seropositive vs. 12% in HPV-DNA negative girls (p<0.001). Risk factors independently associated with hrHPV-DNA infection among the sexually active girls were age >15 years vs. 14-15 years (OR = 2.6 (1.2-5.9)), age of sexual debut <14 vs. above 14 years (OR = 3.0 (1.1-8.2)), total number of lifetime partners above two vs. less than two partners (OR = 3.2 (1.3-8.0)) and age of partner >17 vs. under 17 years (OR = 4.2 (1.5-13.0)). CONCLUSION: A low hrHPV-DNA prevalence was found in the adolescent girls. The observed vs. expected age-related increase in HPV-DNA prevalence in this cohort in the coming years (with increased sexual activity) will provide understanding of the effect of HPV vaccination. Furthermore, this cohort study will offer the opportunity to improve knowledge of antibody responses following natural infection and vaccination.

Prevalence of antibodies against seasonal influenza A and B viruses in children in Netherlands.

To gain insight into the age at which children become infected with influenza viruses for the first time, we analyzed the seroprevalence of antibodies against influenza viruses in children 0 to 7 years of age in the Netherlands. Serum samples were collected during a cross-sectional population-based study in 2006 and 2007 and were tested for the presence of antibodies against influenza A/H1N1, A/H3N2, and B viruses representative of viruses present in previous influenza seasons using the hemagglutination inhibition assay. The seroprevalence of antibodies to influenza virus was higher in children 1 to 6 months of age than in children 7 to 12 months of age, which likely reflects the presence of maternally derived antibodies. The proportion of study subjects >1 year of age with detectable antibodies against influenza viruses gradually increased with age until they reached the age of 6 years, when they all had antibodies to at least one influenza A virus. These findings may have implications for the development of vaccination strategies aiming at the protection of young children against seasonal and/or pandemic influenza virus infection.

Decreased prevalence and age-specific risk factors for Toxoplasma gondii IgG antibodies in The Netherlands between 1995/1996 and 2006/2007.

To estimate the change in the seroprevalence and risk factors for toxoplasmosis in The Netherlands, a study was conducted in the general population in 2006/2007, similarly designed as a previous study in 1995/1996. Testing 5541 sera for IgG antibodies against Toxoplasma gondii showed a marked decrease of the overall seroprevalence to 26·0% [95% confidence interval (CI) 24·0-28·0], compared to 40·5% (95% CI 37·5-43·4) in 1995/1996. In women of reproductive age the seroprevalence decreased from 35·2% (95% CI 32·9-38·6) in 1995/1996 to 18·5% (95% CI 16·2-20·7) in 2006/2007, leaving the majority of pregnant women susceptible to primary infection with T. gondii and their babies to congenital toxoplasmosis. In participants aged ≥20 years, Toxoplasma seropositivity was associated with living in the Northwest, living in urban areas, low educational level, consumption of raw pork, keeping a cat, and not having occupational contact with clients or patients. For younger participants, risk factors were keeping sheep or cattle, consumption of raw unwashed vegetables and putting sand in the mouth.

Transplacental transport of IgG antibodies to preterm infants: a review of the literature.

Newborn infants, especially preterm infants, have an immature immune system, which is not capable to actively protect against vaccine-preventable infections. Therefore, the newborn is dependent on transplacental transport of Immunoglobulin G (IgG), an active, FcRn receptor mediated process. Fetal IgG rises from approximately 10% of the maternal concentration at 17-22weeks of gestation to 50% at 28-32weeks of gestation. If transplacental acquired IgG is lower in preterm than in term infants, preterm infants are especially at risk for these vaccine-preventable diseases. The aim of this study was to review the transplacental transfer of IgG against vaccine-preventable diseases (measles, rubella, varicella-zoster, mumps, Haemophilus influenza type B, diphtheria, tetanus, pertussis and polio) to (pre)term infants and to identify factors that influence the transplacental transfer of these antigens. After selection, 18 studies on transplacental transport to preterm infants were included. In general, these studies showed for all antibodies that preterm infants have lower antibody concentrations compared with term infants. Maternal and infants antibody concentrations showed a strong correlation in 7 of the included studies. Infant antibody concentration was not associated with parity, maternal age, height or weight. Infants of vaccinated mothers had lower anti-measles antibody titers than infants of natural immunized mothers. IgG titers of preterm infants decrease earlier in life below protective antibody titers than term infants. Combined with their immature immune system, this puts preterm infants at increased risk for vaccine-preventable diseases.

Seroprevalence of IgG antibodies against 13 vaccine Streptococcus pneumoniae serotypes in the Netherlands.

In this study the seroprevalence of IgG antibodies against 13 vaccine serotypes of the pneumococcus was assessed in the Netherlands. Sera from 7904 persons obtained in a cross-sectional population-based study were analysed. The 13 serotype specific IgG concentrations were assessed simultaneously using a fluorescent bead-based multiplex immuno assay (MIA). Overall, the geometric mean IgG concentrations (GMCs) against the 13 serotypes in unvaccinated individuals increased with age up to 5 years and remained at a plateau thereafter. The data also show that individuals develop antibodies against an increasing number of different serotypes with increasing age. The highest GMCs were found for antibodies directed against serotype 14 and 19F, whereas antibodies against serotypes 4 and 5 had the lowest GMCs. There was no uniform relationship between the occurrence of serotypes causing invasive pneumococcal disease (IPD) and the GMCs against these serotypes. Increased IPD incidence in the elderly did not seem to be the result of a decline in the concentration of IgG antibodies.

Second national serum bank for population-based seroprevalence studies in the Netherlands.

In 2006/2007 a large serum bank was established by means of a cross-sectional population-based study. This serum bank will be used to evaluate the Dutch national immunisation programme (NIP) by serosurveillance and additional immunological and epidemiological research. In this paper we describe the design of this population-based cross-sectional serosurvey and report the participation rates as well as general characteristics of the study population. A similar serum bank was collected in 1995/1996. Dutch inhabitants (aged 0-79 years, men and women) were invited from 40 municipalities throughout the country and also from eight additional municipalities known with low vaccination coverage (LVC). An oversampling of the migrant population was performed. Blood samples were obtained from all participants accompanied with extensive information on demographic and epidemiological data, such as vaccination history, risk factors and travelling. In addition, sociodemographic data are available from individuals who declined to participate (non-response survey). Overall 33% of all invitees were included in this study. The serum bank comprises 6386 sera in the nationwide sample including the extra sample of immigrants (n=646) and 1518 sera from the LVC municipalities. The sera will be analysed for antibodies against all NI P antigens but will also be used for other infectious diseases research. Results of this second serosurveillance study will contribute to the discussion whether it is needed to reconsider the schedule and/or the vaccine components of the current National Immunisation Programme.