Acceptance and timeliness of post-exposure vaccination against mpox in high-risk contacts, Amsterdam, the Netherlands, May-July 2022.

BACKGROUND: May 2022, several countries reported mpox outbreaks among men-who-have-sex-with-men. In the Netherlands, high-risk contacts were offered the third-generation smallpox vaccine as post-exposure-prophylaxis (PEP) within 4 but maximum 14 days after exposure. We investigated their PEP acceptance, timeliness of uptake and development of mpox for the region of the Public Health Service (PHS) Amsterdam. METHODS: High-risk contacts identified during 20 May-22 July 2022 were included. Contacts were followed-up 21 days after exposure and classified as: no patient (no mpox symptoms or orthopoxvirus PCR-negative) or mpox patient (clinically suspected mpox or orthopoxvirus PCR-positive). We calculated time intervals between date of last exposure and first PHS consultation, PEP administration, and symptom onset. RESULTS: Two-hundred-ninety contacts were at high-risk of mpox predominantly due to sexual and/or direct skin-skin contact (212/290, 73 %). First PHS consultation was a median of 5 (IQR 3, 7) days after exposure, at which point 26/290 (9 %) contacts were ineligible for PEP. 84 % (223/264) of contacts eligible for PEP, received PEP within a median of 6 (IQR 3, 8) days after exposure. Of 282 contacts (missing outcome n = 8) 38 (14 %) developed mpox a median of 7 (IQR 5, 12) days after exposure, of whom 50 % (19/38) developed mpox before their first PHS consultation. Among contacts eligible for PEP, 2/38 (5 %) unvaccinated and 16/218 (7 %) vaccinated contact developed mpox. CONCLUSIONS: PEP acceptance among contacts of mpox patients was high. However, PEP timeliness was inadequate. Half of contacts received PEP 6 or more days after exposure, and half of contacts who developed mpox had an onset prior to their first PHS consultation. Estimating PEP vaccine effectiveness is problematic due to the timeliness of PEP and the time it takes to generate vaccine-induced immunity. It is important to assess how PEP timeliness may improve and to promote pre-exposure vaccination to control mpox outbreaks.

Vaccine effectiveness against COVID-19 related hospital admission in the Netherlands: A test-negative case-control study.

INTRODUCTION: Real-world vaccine effectiveness (VE) estimates are essential to identify potential groups at higher risk of break-through infections and to guide policy. We assessed the VE of COVID-19 vaccination against COVID-19 hospitalization, while adjusting and stratifying for patient characteristics. METHODS: We performed a test-negative case-control study in six Dutch hospitals. The study population consisted of adults eligible for COVID-19 vaccination hospitalized between May 1 and June 28, 2021 with respiratory symptoms. Cases were defined as patients who tested positive for SARS-CoV-2 by PCR during the first 48 h of admission or within 14 days prior to hospital admission. Controls were patients tested negative at admission and did not have a positive test during the 2 weeks prior to hospitalization. VE was calculated using multivariable logistic regression, adjusting for calendar week, sex, age, comorbidity and nursing home residency. Subgroup analysis was performed for age, sex and different comorbidities. Secondary endpoints were ICU-admission and mortality. RESULTS: 379 cases and 255 controls were included of whom 157 (18%) were vaccinated prior to admission. Five cases (1%) and 40 controls (16%) were fully vaccinated (VE: 93%; 95% CI: 81 - 98), and 40 cases (11%) and 70 controls (27%) were partially vaccinated (VE: 70%; 95% CI: 50-82). A strongly protective effect of vaccination was found in all comorbidity subgroups. No ICU-admission or mortality were reported among fully vaccinated cases. Of unvaccinated cases, mortality was 10% and 19% was admitted at the ICU. CONCLUSION: COVID-19 vaccination provides a strong protective effect against COVID-19 related hospital admission, in patients with and without comorbidity.

Impact analysis of rotavirus vaccination in various geographic regions in Western Europe.

BACKGROUND: Universal mass vaccination (UMV) against rotavirus has been implemented in many but not all European countries. This study investigated the impact of UMV on rotavirus incidence trends by comparing European countries with UMV: Belgium, England/Wales and Germany versus countries without UMV: Denmark and the Netherlands. METHODS: For this observational retrospective cohort study, time series data (2001-2016) on rotavirus detections, meteorological factors and population demographics were collected. For each country, several meteorological and population factors were investigated as possible predictors of rotavirus incidence. The final set of predictors were incorporated in negative binomial models accounting for seasonality and serial autocorrelation, and time-varying incidence rate ratios (IRR) were calculated for each age group and country separately. The overall vaccination impact two years after vaccine implementation was estimated by pooling the results using a random effects meta-analyses. Independent t-tests were used to compare annual epidemics in the pre-vaccination and post-vaccination era to explore any changes in the timing of rotavirus epidemics. RESULTS: The population size and several meteorological factors were predictors for the rotavirus epidemiology. Overall, we estimated a 42% (95%-CI 23;56%) reduction in rotavirus incidence attributable to UMV. Strongest reductions were observed for age-groups 0-, 1- and 2-years (IRR 0.47, 0.48 and 0.63, respectively). No herd effect induced by UMV in neighbouring countries was observed. In all UMV countries, the start and/or stop and corresponding peak of the rotavirus season was delayed by 4-7 weeks. CONCLUSIONS: The introduction of rotavirus UMV resulted in an overall reduction of 42% in rotavirus incidence in Western European countries two years after vaccine introduction and caused a change in seasonal pattern. No herd effect induced by UMV neighbouring countries was observed for Denmark and the Netherlands.

Effect of vaccination on severity and infectiousness of measles during an outbreak in the Netherlands, 2013-2014.

An outbreak of measles in the Netherlands in 2013-2014 provided an opportunity to assess the effect of MMR vaccination on severity and infectiousness of measles.Measles is notifiable in the Netherlands. We used information on vaccination, hospitalisation, complications, and most likely source(s) of infection from cases notified during the outbreak. When a case was indicated as a likely source for at least one other notified case, we defined it as infectious. We estimated the age-adjusted effect of vaccination on severity and infectiousness with logistic regression.Of 2676 notified cases, 2539 (94.9%) were unvaccinated, 121 (4.5%) were once-vaccinated and 16 (0.6%) were at least twice-vaccinated; 328 (12.3%) cases were reported to have complications and 172 (6.4%) cases were hospitalised. Measles in twice-vaccinated cases led less often to complications and/or hospitalisation than measles in unvaccinated cases (0% and 14.5%, respectively, aOR 0.1 (95% CI 0-0.89), P = 0.03). Of unvaccinated, once-vaccinated and twice-vaccinated cases, respectively, 194 (7.6%), seven (5.1%) and 0 (0%) were infectious. These differences were not statistically significant (P > 0.05).Our findings suggest a protective effect of vaccination on the occurrence of complications and/or hospitalisation as a result of measles and support the WHO recommendation of a two-dose MMR vaccination schedule.

The tip of the iceberg: incompleteness of measles reporting during a large outbreak in The Netherlands in 2013-2014.

Measles is a notifiable disease, but not everyone infected seeks care, nor is every consultation reported. We estimated the completeness of reporting during a measles outbreak in The Netherlands in 2013-2014. Children below 15 years of age in a low vaccination coverage community (n = 3422) received a questionnaire to identify measles cases. Cases found in the survey were matched with the register of notifiable diseases to estimate the completeness of reporting. Second, completeness of reporting was assessed by comparing the number of susceptible individuals prior to the outbreak with the number of reported cases in the surveyed community and on a national level.We found 307 (15%) self-identified measles cases among 2077 returned questionnaires (61%), of which 27 could be matched to a case reported to the national register; completeness of reporting was 8.8%. Based on the number of susceptible individuals and number of reported cases in the surveyed community and on national level, the completeness of reporting was estimated to be 9.1% and 8.6%, respectively. Estimating the completeness of reporting gave almost identical estimates, which lends support to the credibility and validity of both approaches. The size of the 2013-2014 outbreak approximated 31 400 measles infections.

Current prevalence of chronic hepatitis B and C virus infection in the general population, blood donors and pregnant women in the EU/EEA: a systematic review.

This systematic review aimed at estimating chronic hepatitis B (HBV) and C virus (HCV) prevalence in the European Union (EU) and Economic Area (EEA) countries in the general population, blood donors and pregnant women. We searched PubMed©, Embase© and Cochrane Library databases for reports on HBV and HCV prevalence in the general population and pregnant women in EU/EEA countries published between 2005 and 2015. Council of Europe data were used for HBV and HCV blood donor prevalence. HBV general population estimates were available for 13 countries, ranging from 0·1% to 4·4%. HCV general population estimates were available for 13 countries, ranging from 0·1% to 5·9%. Based on general population and blood donor estimates, the overall HBV prevalence in the EU/EEA is estimated to be 0·9% (95% CI 0·7-1·2), corresponding to almost 4·7 million HBsAg-positive cases; and the overall HCV prevalence to be 1·1% (95% CI 0·9-1·4), equalling 5·6 million anti-HCV-positive cases. We found wide variation in HCV and HBV prevalence across EU/EEA countries for which estimates were available, as well as variability between groups often considered a proxy for the general population. Prevalence estimates are essential to inform policymaking and public health practice. Comparing to other regions globally, HBV and HCV prevalence in the EU/EEA is low.

Performance of a bedside test for tetanus immunity: results of a cross-sectional study among three EDs in the Netherlands in 2012-2013.

INTRODUCTION: Despite sustained high vaccination coverage and a national guideline by the Health Council (HC-guideline) on tetanus postexposure prophylaxis (T-PEP), tetanus sporadically occurs in the Netherlands. This study aims to assess the added value of a bedside test for tetanus immunity (Tetanos Quick Stick (TQS); Ingen BioSciences Group, France), in the context of routine T-PEP in two adult cohorts: those born before introduction of tetanus toxoid vaccination in the National Immunization Programme (NIP) in 1957 (pre-NIP-cohort; n=196) and those born after (NIP-cohort; n=405). METHODS: Adults included at the time of visiting one of three participating EDs received T-PEP as per routine recommendations. Subsequently, a nurse performed the TQS and filled in a questionnaire. We compared the indication for T-PEP based on TQS results with those based on the HC-guideline and with actually administration of T-PEP, stratified by cohort. RESULTS: Among the pre-NIP and NIP-cohort, 16% and 9%, respectively, received T-PEP, while this was not indicated based on the HC-guideline. Furthermore, 8% and 7%, respectively, did not get T-PEP, although it was indicated by the guideline. Comparing the indication derived from the HC-guideline with TQS result found that 22% (pre-NIP-cohort) and 8% (NIP-cohort) were not eligible for T-PEP according to the HC-guideline but had a negative TQS. Conversely, 36% (pre-NIP-cohort) and 73% (NIP-cohort) were eligible for T-PEP according to the HC-guideline but had positive TQS, indicating sufficient tetanus protection. CONCLUSION: Use of the TQS would allow better targeting of T-PEP. Furthermore, stricter adherence to the HC-guideline can prevent overimmunisation and decrease the risk of tetanus.

Tolerability of Early Measles-Mumps-Rubella Vaccination in Infants Aged 6-14 Months During a Measles Outbreak in The Netherlands in 2013-2014.

BACKGROUND: In 2013-2014, a measles outbreak spread through the Netherlands. To protect young infants, measles-mumps-rubella (MMR) vaccination was offered to those aged 6-14 months in municipalities with routine first-dose MMR vaccine coverage of <90%. We assessed the tolerability of this early administration of MMR vaccine. METHODS: After study entry (n = 1866), parents of eligible infants (n = 10 097) completed a questionnaire (n = 1304). For infants who received an early MMR vaccine dose (n = 962), we asked for information about adverse events (AEs) associated with the dose. AE frequencies were compared between infants aged 6-8, 9-11, and 12-14 months. Using multivariable logistic regression, we assessed the association between the risk of AEs and age at early MMR vaccination. RESULTS: The response rate was 13%. Parents of 59 infants (6.1%) and 350 infants (36.4%) who received early MMR vaccination reported local and systemic AEs, respectively. Parents of infants vaccinated at 6-8 months of age reported systemic AEs less frequently (32%) than parents of children vaccinated at 9-11 months (45%) and 12-14 months (43%) of age (P= <.001). For local AEs, there were no differences (5%, 7%, and 10%, respectively;P= .08). Compared with vaccination at 6 months, all older infants except those aged 14 months showed an increased risk for any AE and for systemic AEs starting 5-12 days after vaccination. CONCLUSIONS: Early MMR vaccination is well tolerated, with the lowest AE frequencies found in infants aged 6-8 months. It is a safe intervention for protecting young infants against measles.

High risk of a large measles outbreak despite 30 years of measles vaccination in The Netherlands.

Our aim was to assess progress towards measles elimination from The Netherlands by studying humoral measles immunity in the Dutch population. A population-based seroepidemiological study was conducted in 2006-2007 (N = 7900). Serum samples were analysed by a bead-based multiplex immunoassay. IgG levels ⩾0·2 IU/ml were considered protective. The overall seroprevalence in the Dutch population was 96%. However, 51% of socio-geographically clustered orthodox Protestant individuals aged <10 years were susceptible. Infants might be susceptible to measles between ages 4 months and 14 months, the age at which maternal antibodies have disappeared and the first measles, mumps, rubella (MMR) vaccination is administered, respectively. Waning of antibody concentrations was slower after the second MMR vaccination than after the first. The Netherlands is at an imminent risk of a measles outbreak in the orthodox Protestant minority. To prevent subsequent transmission to the general population, efforts to protect susceptible age groups are needed.

Prevalence of hepatitis B virus infection in The Netherlands in 1996 and 2007.

We aimed to assess differences in the prevalence of hepatitis B virus (HBV) infection in The Netherlands between 1996 and 2007, and to identify risk factors for HBV infection in 2007. Representative samples of the Dutch population in 1996 and 2007 were tested for antibodies to hepatitis B core antigen (anti-HBc), hepatitis B surface antigen (HBsAg) and HBV-DNA. In 2007, the weighted anti-HBc prevalence was 3·5% (95% CI 2·2-5·5) and the HBsAg prevalence was 0·2% (95% CI 0·1-0·4). In indigenous Dutch participants, the anti-HBc prevalence was lower in 2007 than in 1996 (P=0·06). First-generation migrants (FGMs) had a 13-fold greater risk of being HBsAg- and/or HBV-DNA-positive than indigenous Dutch participants. In indigenous Dutch participants, risk factors for anti-HBc positivity were older age and having received a blood product before 1990. In FGMs, being of Asian origin was a risk factor. In second-generation migrants, having a foreign-born partner and injecting drug use were risk factors. FGMs are the main target group for secondary HBV prevention in The Netherlands.

Mumps epidemic in orthodox religious low-vaccination communities in the Netherlands and Canada, 2007 to 2009.

We assessed the epidemiological characteristics of a mumps virus epidemic (genotype D) that occurred in the Netherlands between August 2007 and May 2009 and its association with a subsequent mumps outbreak in Canada. In the Netherlands, five data sources were used: notifications (only mandatory since the end of 2008) (56 cases), laboratory confirmation data (177 cases), a sentinel general practitioner (GP) database (275 cases), hospitalisation data (29 cases) and weekly virological reports (96 cases). The median age of cases in the notification, laboratory and GP databases ranged from 13 to 15 years. The proportion of cases that were unvaccinated ranged from 65% to 85% in the notification, laboratory and GP databases. Having orthodox Protestant beliefs was the main reason for not being vaccinated. In Canada, a mumps virus strain indistinguishable from the Dutch epidemic strain was detected between February and October 2008 in an orthodox Protestant community with historical and family links to the affected community in the Netherlands, suggesting that spread to Canada had occurred. Prevention and control of vaccine-preventable diseases among population subgroups with low vaccination coverage remains a priority.

A cost-utility analysis of antenatal screening to prevent congenital rubella syndrome.

In low vaccination coverage regions (LVR) in The Netherlands people often reject participation in the National Immunization Programme for religious reasons. During a rubella epidemic in 2004-2005, 32 pregnant women were notified with rubella, and 11 babies were born with defects related to maternal infection. This study presents a cost-utility analysis of a screening and vaccination programme for rubella focusing on three scenarios: (1) screening non-vaccinated pregnant women in LVR; (2) screening all pregnant women in LVR; (3) screening all non-vaccinated pregnant women in The Netherlands (including pregnant first-generation non-Western immigrant women). Cost-utility was estimated over a 16-year period which included two rubella outbreaks. Observed complications from the 2004-2005 epidemic were used to estimate average cost savings and quality-adjusted life-years (QALY) gained. The programme would be cost-effective (euro1100/QALY gained) when assuming an acceptability of vaccination of 20% in women belonging to orthodox protestant risk groups.

Hepatitis B vaccination targeted at behavioural risk groups in the Netherlands: does it work?

In November 2002, the Netherlands adopted a vaccination program targeted at behavioural risk groups. Between January 2003 and December 2007, 1386 patients acutely infected with HBV were reported. Reported cases declined from 326 in 2003 to 220 in 2007. Sexual intercourse was the most frequently reported mode of transmission (65%), especially among men having sex with men. Genotypes A and D remained predominant. In total, 40,600 participants were fully vaccinated, the overall compliance was 62%, and the estimated overall program coverage was 12% of the at-risk population. With more effort, more susceptibles may be reached, but the program will not be sufficient to substantially reduce HBV in the Netherlands. Therefore, universal vaccination should be considered.

Feasibility of a rubella screening and vaccination programme for unvaccinated young women.

The feasibility of a rubella screening and vaccination programme for unvaccinated young women was assessed after the 2004/2005 epidemic in The Netherlands. All 640 young women in two villages with low vaccination coverage were invited for a rubella seroprevalence test. Information on vaccination status was gathered by written questionnaire. Women testing seronegative were offered free rubella vaccination. The feasibility of the programme was evaluated in terms of participation, rubella susceptibility, and acceptance of the vaccination offer by seronegative women. The participation rate was 48% [95% confidence interval (CI) 44-52] with 108 unvaccinated participants. Eleven per cent (95% CI 6-19) of the women were identified as susceptible to rubella, of whom 17% (95% CI 2-48) accepted the vaccination offer. In the end only 0.9% (95% CI 0.1-2.5) of the target population was given protection by the programme. Under the present conditions this programme proved to be an inefficient strategy for rubella protection.

Hepatitis B virus transmission in The Netherlands: a population-based, hierarchical case-control study in a very low-incidence country.

We report the first population-based case-control study on acute hepatitis B in a very low-incidence country. A case was a Netherlands resident, notified between May 1999 and July 2000 with symptoms and serology compatible with acute hepatitis B. Population controls were randomly selected, with oversampling from men and persons aged 20-39 years. Risk factors were studied using logistical regression, distinguishing confounders and mediators through hierarchical analysis. Participants were 120 cases and 3948 controls. The risk of acute hepatitis B was increased in men who have sex with men, with reporting to have had more than two partners in the past 6 months the only significant risk. In children, adult females and heterosexual males, having parents born in a hepatitis B endemic country was a significant risk. For adult females and heterosexual males, this was largely explained by having a foreign partner. For children this was partly explained by parenteral exposures abroad.

Soft tissue infections caused by spore-forming bacteria in injecting drug users in the United Kingdom.

From 2000 to May 2004 there has been a marked increase in illness resulting from spore-forming bacteria in injecting heroin users in the United Kingdom. Clostridium novyi caused 63 cases of severe illness in 2000 and seven further cases from 2001. Wound botulism first occurred in 2000 (six cases) with 51 further cases to March 2004. Tetanus occurred in 20 cases between late 2003 and March 2004. Infections with C. histolyticum (nine cases), C. sordellii (one case) and Bacillus cereus (one case) were also reported. The reasons for the increase in illness are unclear. The major risk factor was skin- or muscle-popping. The problem appears to be here to stay. This review describes the causative organisms, pathogenesis, clinical presentation, epidemiology and treatment of cases. Clinical vigilance and a high standard of anaerobic microbiology are essential. Clinicians and laboratories must report such cases (or likely cases) rapidly so that clusters can be rapidly identified, in order to control disease. Prevention relies on tetanus immunization.

[Rubella epidemic in the Netherlands, 2004/'05: awareness of congenital rubella syndrome required]. / Rubella-epidemie in Nederland in 2004/'05: alertheid op congenitaal rubellasyndroom vereist.

Rubella is a public health problem due to the teratogenic effects associated with primary rubella infection during pregnancy (congenital rubella syndrome). Following universal rubella vaccination of infants in the Netherlands, the incidence of rubella has declined dramatically. However, since September 2004, an outbreak has occurred among unvaccinated individuals, most of whom declined vaccination based on religious beliefs. In the period 1 September 2004-22 March 2005, 166 cases of rubella were reported, including 12 pregnant women. Monitoring for signs that the epidemic has spread to other populations in the Netherlands is important because this might indicate the need for additional interventions. Awareness among health-care workers of the possible occurrence of congenital rubella syndrome should be raised. The clinical manifestations of congenital rubella syndrome are diverse, can be transient or permanent, and may not present until adolescence or adulthood. All cases of laboratory-confirmed rubella infection and congenital rubella syndrome should be reported to municipal health authorities. There is a possibility that this outbreak will spread abroad. The WHO aims to reduce the incidence of congenital rubella syndrome to < 1/100,000 live births. Health-care workers in the Netherlands should be extra alert to detect and notify rubella in a timely manner.

Sex difference in Aroclor 1254 induction of rat hepatocytes: Consequences for in vitro embryotoxicity and mutagenicity of cyclophosphamide.

The sequential culture of rat hepatocytes and post-implantation rat embryos has been proposed as a model for the in vitro testing of pro-teratogens. Comparing this model with a model in which embryos and hepatocytes are cultured simultaneously a striking difference in sensitivity was noted. To address the question of whether this difference could be explained by different sex and/or Aroclor 1254 pretreatment of the rats providing the hepatocytes, an experiment was designed with four groups: male Aroclor 1254 pretreated (M(1)), male untreated, pregnant female Aroclor 1254 pretreated (F(1)) and pregnant female untreated rats. Hepatocytes were incubated in the presence of cyclophosphamide (CP) and rat embryos were cultured in the media derived from the hepatocyte culture (i.e. the sequential culture model). Additionally, the CP concentrations of the media were analysed and subsequently the media were tested in a bacterial mutagenicity test (Salmonella typhimurium TA1535). With a CP concentration of 300 mum, M(1) produced maximum embryotoxicity and mutagenicity after 4 hr of hepatocytes incubation. All other groups showed no or only a slight increase in embryotoxicity and mutagenicity for all hepatocyte incubations. M(1) was also quickest to eliminate CP from the medium. These results indicate that despite a strong increase in total cytochrome P-450 in both sexes as a result of Aroclor 1254 pretreatment, and in the absence of a significant difference in total cytochrome P-450 between M(1) and F(1), Aroclor 1254 pretreatment has a much more pronounced effect in male rats than in pregnant female rats with regard to the production of embryotoxic and mutagenic metabolites of CP.