[No scientific lower threshold for compulsory vaccination]. / Geen wetenschappelijke ondergrens voor verplicht vaccineren.

The national vaccination rate in young children in the Netherlands has decreased in recent years. This has led to social and political discussions, for instance about compulsory vaccination for children in child-care. The national commission on child-care and vaccination has advised that vaccination should be made compulsory when the rate of vaccination has declined to a pre-determined lower threshold, to be determined by the government. A frequently quoted lower threshold is 95%. The idea behind this is the concept of a critical vaccination rate, a threshold needed for elimination of an infection in a large, well-mixed population. In this article we argue why the critical vaccination rate does not offer a scientific basis for a lower threshold to the national vaccination rate.

Chronic hepatitis B and C infections in the Netherlands: estimated prevalence in risk groups and the general population.

Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are usually asymptomatic for decades, thus targeted screening can prevent liver disease by timely diagnosis and linkage to care. More robust estimates of chronic HBV and HCV infections in the general population and risk groups are needed. Using a modified workbook method, the total number of ever chronically infected individuals in the Netherlands in 2016 was determined using population size and prevalence estimates from studies in the general and high-risk population. The estimated 2016 chronic HBV infection prevalence is 0.34% (low 0.22%, high 0.47%), corresponding to approximately 49 000 (low 31 000, high 66 000) HBV-infected individuals aged 15 years and older. The estimated ever-chronic HCV infection prevalence is 0.16% (low 0.06%, high 0.27%), corresponding to approximately 23 000 (low 8000, high 38 000) ever-chronic HCV-infected individuals. The prevalence of chronic HBV and HCV infections in the Netherlands is low. First-generation migrants account for most infections with 81% and 60% of chronic HBV and HCV infections, respectively. However, about one-fifth of HCV infections is found in the general population at low risk. This method can serve as an example for countries in need of more accurate prevalence estimates, to help the design and evaluation of prevention and control policies.

Estimating the scale of chronic hepatitis C virus infection in the EU/EEA: a focus on migrants from anti-HCV endemic countries.

BACKGROUND: Increasing the proportion diagnosed with and on treatment for chronic hepatitis C (CHC) is key to the elimination of hepatitis C in Europe. This study contributes to secondary prevention planning in the European Union/European Economic Area (EU/EEA) by estimating the number of CHC (anti-HCV positive and viraemic) cases among migrants living in the EU/EEA and born in endemic countries, defining the most affected migrant populations, and assessing whether country of birth prevalence is a reliable proxy for migrant prevalence. METHODS: Migrant country of birth and population size extracted from statistical databases and anti-HCV prevalence in countries of birth and in EU/EEA countries derived from a systematic literature search were used to estimate caseload among and most affected migrants. Reliability of country of birth prevalence as a proxy for migrant prevalence was assessed via a systematic literature search. RESULTS: Approximately 11% of the EU/EEA adult population is foreign-born, 79% of whom were born in endemic (anti-HCV prevalence ≥1%) countries. Anti-HCV/CHC prevalence in migrants from endemic countries residing in the EU/EEA is estimated at 2.3%/1.6%, corresponding to ~580,000 CHC infections or 14% of the CHC disease burden in the EU/EEA. The highest number of cases is found among migrants from Romania and Russia (50-60,000 cases each) and migrants from Italy, Morocco, Pakistan, Poland and Ukraine (25-35,000 cases each). Ten studies reporting prevalence in migrants in Europe were identified; in seven of these estimates, prevalence was comparable with the country of birth prevalence and in three estimates it was lower. DISCUSSION: Migrants are disproportionately affected by CHC, account for a considerable number of CHC infections in EU/EEA countries, and are an important population for targeted case finding and treatment. Limited data suggest that country of birth prevalence can be used as a proxy for the prevalence in migrants.

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.

[Mortality due to chronic viral hepatitis B and C infections in the Netherlands]. / Sterfte aan chronische hepatitis B en C in Nederland.

OBJECTIVE: To estimate mortality due to chronic hepatitis B-virus (HBV) and hepatitis C-virus (HCV) infections in the Netherlands from 2002 to 2015. DESIGN: A cross-sectional analysis based on cause-of-death statistics. METHOD: From Statistics Netherlands we obtained detailed data regarding the number of deaths per year in the following ICD-10 categories: chronic viral hepatitis; malignant neoplasm of the liver and intrahepatic bile ducts; fibrosis and cirrhosis of the liver; and alcoholic liver disease. We determined the population-attributable fractions (PAF) of HBV and HCV infections in mortality due to hepatocellular carcinoma (HCC) and cirrhosis of the liver, and added these to the recorded mortality from viral hepatitis in order to calculate total mortality. We used Dutch research as a basis for allocation to HCC, and a range of PAFs from 3 studies for cirrhosis. Poisson regression was used to assess mortality trends over time and any differences in demographic characteristics. RESULTS: Around 500 Dutch people died annually of chronic viral hepatitis from 2002 to 2015, according to our 'middle' estimate; the 'lowest' estimate yields 340 and the 'highest' 600 people per year. The total mortality due to a chronic HBV and HCV infection did not change over time. The mortality for HCC due to viral hepatitis increased slightly over time and the mortality for cirrhosis decreased slightly. HCC mortality due to viral hepatitis was higher in Dutch people of non-western origin. CONCLUSION: Mortality from chronic viral hepatitis is mostly the result of cirrhosis of the liver and HCC. About 500 persons died annually from 2002 to 2015 from causes linked to viral hepatitis.

The estimated future disease burden of hepatitis C virus in the Netherlands with different treatment paradigms.

BACKGROUND & AIMS: Prevalence of hepatitis C virus (HCV) infection in the Netherlands is low (anti-HCV prevalence 0.22%). All-oral treatment with direct-acting antivirals (DAAs) is tolerable and effective but expensive. Our analysis projected the future HCV-related disease burden in the Netherlands by applying different treatment scenarios. METHODS: Using a modelling approach, the size of the HCV-viraemic population in the Netherlands in 2014 was estimated using available data and expert consensus. The base scenario (based on the current Dutch situation) and different treatment scenarios (with increased efficacy, treatment uptake, and diagnoses) were modelled and the future HCV disease burden was predicted for each scenario. RESULTS: The estimated number of individuals with viraemic HCV infection in the Netherlands in 2014 was 19,200 (prevalence 0.12%). By 2030, this number is projected to decrease by 4 5% in the base scenario and by 85% if the number of treated patients increases. Furthermore, the number of individuals with hepatocellular carcinoma and liver-related deaths is estimated to decrease by 19% and 27%, respectively, in the base scenario, but may both be further decreased by 68% when focusing on treatment of HCV patients with a fibrosis stage of ≥ F2. CONCLUSIONS: A substantial reduction in HCV-related disease burden is possible with increases in treatment uptake as the efficacy of current therapies is high. Further reduction of HCV-related disease burden may be achieved through increases in diagnosis and preventative measures. These results might inform the further development of effective disease management strategies in the Netherlands.

The state of hepatitis B and C in Europe: report from the hepatitis B and C summit conference*.

Worldwide, the hepatitis B virus (HBV) and the hepatitis C virus (HCV) cause, respectively, 600,000 and 350,000 deaths each year. Viral hepatitis is the leading cause of cirrhosis and liver cancer, which in turn ranks as the third cause of cancer death worldwide. Within the WHO European region, approximately 14 million people are chronically infected with HBV, and nine million people are chronically infected with HCV. Lack of reliable epidemiological data on HBV and HCV is one of the biggest hurdles to advancing policy. Risk groups such as migrants and injecting drug users (IDU) tend to be under-represented in existing prevalence studies; thus, targeted surveillance is urgently needed to correctly estimate the burden of HBV and HCV. The most effective means of prevention against HBV is vaccination, and most European Union (EU) countries have universal vaccination programmes. For both HBV and HCV, screening of individuals who present a high risk of contracting the virus is critical given the asymptomatic, and thereby silent, nature of disease. Screening of migrants and IDUs has been shown to be effective and potentially cost-effective. There have been significant advances in the treatment of HCV and HBV in recent years, but health care professionals remain poorly aware of treatment options. Greater professional training is needed on the management of hepatitis including the treatment of liver cancer to encourage adherence to guidelines and offer patients the best possible outcomes. Viral hepatitis knows no borders. EU Member States, guided by the EU, need to work in a concerted manner to implement lasting, effective policies and programmes and make tackling viral hepatitis a public health priority.

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.

[Chronic hepatitis B virus (HBV) infection: usefulness of the combination of HBeAg and ALT determination to predict a high HBV-DNA level and therefore the necessity of referral to a specialist for possible antiviral treatment]. / Chronische hepatitis B-virus(HBV)-infectie: bruikbaarheid van de combinatie van HBeAg- en ALAT-bepaling als voorspeller van een hoog HBV-DNA-niveau en voor verwijzing naar de 2e lijn voor eventuele antivirale behandeling.

OBJECTIVE: To assess the usefulness of a simple practical guideline based on hepatitis B e-antigen (HBeAg) status and a single alanine aminotransferase (ALT) determination to predict hepatitis B virus (HBV) load in chronic HBV patients as a criterion for referral to a specialist for possible antiviral therapy. DESIGN: Prospective observational study. METHOD: 420 patients with chronic HBV infection were seen at the Municipal Health Service (MHS) in Rotterdam between 2002 and 2005. The usefulness ofa guideline based on HBeAg positivity and/or elevated ALT levels to predict high HBV DNA levels (defined as more than 10(5) copies/ml) was determined. Patients with HBeAg or an elevated ALT level were referred to a specialist according to the practical guideline. Positive and negative predictive value, sensitivity, and specificity of the referral guideline for a high HBV-DNA level were calculated. RESULTS: Less than half, 43% (181/420) of the patients, were eligible for referral to specialist care. The positive predictive value of the referral guideline was 45% (82/181, 95% CI: 38-53). The negative predictive value, i.e. the proportion of patients with low viral loads who were (rightly) not selected for referral, was 95% (227/239; 95% CI: 71-97). The sensitivity was 87% (95% CI: 80-93): the patients selected included 82 of 94 patients with a high HBV DNA level. Of the 12 patients with high viral loads not referred according to the guideline, 11 had a viral load of between 10(5)-10(6) copies/ml. CONCLUSION: A referral guideline based on HBeAg status and a single ALT determination can successfully predict viral load in chronic HBV patients and can be used in primary care to select patients for referral to specialist care. This guideline may limit the number of unnecessarily referred patients, enhancing the efficiency of the care for patients with chronic HBV infection.

Transmission routes of hepatitis B virus infection in chronic hepatitis B patients in The Netherlands.

The Netherlands is a low endemic country for hepatitis B virus (HBV). Rotterdam, a city in The Netherlands harbors a large group of chronic hepatitis B (CHB) patients of which most are born abroad. The study included 464 consecutive CHB patients who were reported to the Municipal Public Health Service in Rotterdam from January 1, 2002 to September 15, 2005. The HBV genotypes, possible transmission routes of infection and travel history of CHB patients born in The Netherlands, were compared with those CHB patients living in The Netherlands but who were foreign-born, taking into account the ethnicity of the mother. Of the 464 patients with CHB infection, 14% were Dutch-born and 86% were foreign-born. The CHB patients in the Dutch-born group had genotypes A (35%), B (15%), C (11%), D (37%), and G (2%). In the foreign-born group, the distribution of genotypes was A (20%), B (15%), C (11%), D (40%), and E (15%). In the Dutch-born group, sexual transmission accounted for a larger proportion of infections (P < 0.0001) compared to the foreign-born group, whereas perinatal transmission is reported to be higher in the foreign-born group and in the Dutch-born group with a foreign mother. The genotypes of the chronic HBV strains determined corresponded well with the HBV genotypes expected from the countries of origin of the patients or their mothers. Genotypes A and D are predominant in CHB patients in The Netherlands.

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.

Chlamydia trachomatis infections in multi-ethnic urban youth: a pilot combining STI health education and outreach testing in Rotterdam, Netherlands.

BACKGROUND/OBJECTIVES: Testing for Chlamydia trachomatis (Ct) is less accepted in people of non-Dutch ethnicity than Dutch people. We offered additional Ct and gonorrhoea testing through our outreach sexually transmitted infections (STI) prevention programme to determine whether this intervention strategy is feasible and efficient. METHODS: Outreach workers offered test kits to women and men aged 15-29 years, in group and street settings and in a vocational training school. Demographic and behavioural data and characteristics of non-responders were assessed. DNA was isolated (using the MagNA Pure LC system) from urine and tested using the Cobas Amplicor test. RESULTS: Among sexually active people, the test rate differed by venue (groups 80% (74/93), school 73% (49/67), street 17% (49/287); p<0.001). There was no difference in test rate between group and school settings by gender or ethnicity. Ct positivity was 14.5% (25/172); women 20.2% (20/99) versus men 6.8% (5/73); p = 0.01. Ct positivity was highest at school (24.5% (12/49)) and among Surinamese/Antillean people (17.5% (14/80)). Treatment rate of index cases and current partners was 100% and 78%, respectively. CONCLUSIONS: We found a high acceptance of chlamydia testing in group and school settings in both men and women of non-Dutch ethnicity. The prevalence indicates that we have accessed high risk people. Outreach testing and is feasible and most efficient in school and group settings. School screening may have an impact on community prevalence of Ct infections.

Acceptability and consequences of screening for chlamydia trachomatis by home-based urine testing.

OBJECTIVE: The objective of this study was to study the acceptability and consequences of home-based chlamydia (CT) screening by Municipal Health Services (MHS) among 15- to 29-year-old participants. STUDY: This study consisted of a cross-section of 156 CT-positives and 600 random sampled CT-negatives after receiving the result of their CT test. RESULTS: Thirty-eight percent of the men and 59% of the women responded. The screening method was well-accepted. Seventy percent (52) of the CT-positives were surprised about their result. Infected women more often than men reported a feeling of being dirty and of anxiety about infertility. Curiosity for the CT result was decisive for participation in 68% and perception of personal risk was poor. The willingness to be tested regularly was determined by present chlamydial infection, young age, multiple lifetime partners, short relationship, and earlier test for chlamydia. CONCLUSIONS: Chlamydia screening organised by MHS is acceptable for future screening. Participants with an elevated risk are interested in screening as long as test kits are easily available. Counseling with focus on effects of CT, especially on women, is essential. Alternative approaches are needed to motivate men and non-Dutch high-risk groups.

A prediction rule for selective screening of Chlamydia trachomatis infection.

BACKGROUND: Screening for Chlamydia trachomatis infections is aimed at the reduction of these infections and subsequent complications. Selective screening may increase the cost effectiveness of a screening programme. Few population based systematic screening programmes have been carried out and attempts to validate selective screening criteria have shown poor performance. This study describes the development of a prediction rule for estimating the risk of chlamydial infection as a basis for selective screening. METHODS: A population based chlamydia screening study was performed in the Netherlands by inviting 21,000 15-29 year old women and men in urban and rural areas for home based urine testing. Multivariable logistic regression was used to identify risk factors for chlamydial infection among 6303 sexually active participants, and the discriminative ability was measured by the area under the receiver operating characteristic curve (AUC). Internal validity was assessed with bootstrap resampling techniques. RESULTS: The prevalence of C trachomatis (CT) infection was 2.6% (95% CI 2.2 to 3.2) in women and 2.0% (95% CI 1.4 to 2.7) in men. Chlamydial infection was associated with high level of urbanisation, young age, Surinam/Antillian ethnicity, low/intermediate education, multiple lifetime partners, a new contact in the previous two months, no condom use at last sexual contact, and complaints of (post)coital bleeding in women and frequent urination in men. A prediction model with these risk factors showed adequate discriminative ability at internal validation (AUC 0.78). CONCLUSION: The prediction rule has the potential to guide individuals in their choice of participation when offered chlamydia screening and is a promising tool for selective CT screening at population level.

The importance of imported infections in maintaining hepatitis B in The Netherlands.

In The Netherlands, in May 1999 an enhanced surveillance of hepatitis B was begun to collect detailed information of patients with acute hepatitis B virus (HBV) infection. The objective was to gain insight in transmission routes and source of infection of new HBV cases. Through public health services, patients were interviewed on risk factors. It appeared that the majority (59%) acquired the infection through sexual contact; 52% of these by homosexual and 48% by heterosexual contact. In 60% of the heterosexual cases, the source of infection was a partner originating from a hepatitis B-endemic region. Sexual transmission is the most common route of transmission of acute hepatitis B in The Netherlands and introduction of infections from abroad plays a key role in the current epidemiology of HBV. As well as prevention programmes targeted at sexual high-risk groups, prevention efforts should focus more on the heterosexual transmission from HBV carriers.

Population-based Toxoplasma seroprevalence study in The Netherlands.

During 1995--1996 a population-based seroprevalence study was conducted in The Netherlands. Risk factors were established for postnatally acquired toxoplasmosis. The results were compared with a study conducted during 1987-1988 in pregnant women in the Southwest of The Netherlands in order to estimate the change in seroprevalence. In total, 7521 sera were tested and the national seroprevalence was 40.5 % (95 % CI 37.5-43.4). Living in the Northwest, having professional contact with animals, living in a moderately urbanized area, being divorced or widowed, being born outside The Netherlands, frequent gardening and owning a cat were independently associated with Toxoplasma seropositivity. Risk factors like eating undercooked meat could not be studied. The seroprevalence among women aged 15-49 years was 10 % lower (35.2 %, 95 % CI 32.9-38.6) in the study of 1995-1996, compared to the Toxoplasma study of 1987--1988 (45.8 %, 95 % CI 45.2-46.3). The steepest rise in seroprevalence still occurred among the subjects aged 25-44 years.

Seroprevalence of hepatitis A virus antibodies in Turkish and Moroccan children in Rotterdam.

Seasonal fluctuations in hepatitis A have been observed in the Netherlands related to Turkish and Moroccan children after visiting their home countries. This study determined the prevalence and associated factors of hepatitis A virus (HAV) antibodies in Turkish and Moroccan children in Rotterdam. A random sample was taken of children in Rotterdam, aged 5-16 years, of Turkish and Moroccan origin, together with a random sample of native Dutch children aged 5-7 and 14-16 years. Blood was collected by finger prick on filter paper. IgG and IgM anti-HAV was detected by an enzyme-linked immunoassay (EIA). The 319 Turkish, 329 Moroccan, and 248 native Dutch children participated in the study. In Turkish children, IgG anti-HAV increased from 2.2% to 22.2% over the age groups. In Moroccan children, IgG anti-HAV increased from 10.2% to 57.7%. In native Dutch children, 0.8% had IgG anti-HAV in the youngest and 3.1% in the oldest age group. The percentage IgG-positive also having IgM anti-HAV was 21% in Turkish, and 41% in Moroccan children. No IgG-positive native Dutch children had IgM anti-HAV. The prevalence of IgG anti-HAV was associated with increased age, being Moroccan, longer stay in the country of origin before migrating to the Netherlands, and known contact to HAV. The majority of Turkish and Moroccan children aged 4-16 years in Rotterdam are not protected against HAV, but do have a high risk of becoming infected while visiting their native country. Active vaccination against HAV of these children is indicated, with as primary aim their own protection. Prevention of HAV-transmission in the general community should be seen as a secondary benefit. In addition, possible Dutch contacts of nonvaccinated Turkish and Moroccan children, such as day care workers and teachers, should also be vaccinated against HAV.

[Significant decline of the number of invasive Haemophilus influenzae infections in the first 4 years after introduction of vaccination against H. influenzae type B in children]. / Sterke daling van het aantal invasieve infecties door Haemophilus influenzae in de eerste 4 jaar na de introductie van de vaccinatie van kinderen tegen H. influenzae type b.

OBJECTIVE: To evaluate the effect of four years of immunisation against Haemophilus influenzae type b (Hib) on the occurrence of invasive H. influenzae infection and of vaccine failure in children. DESIGN: Descriptive. METHOD: Through the Nederlands Signalerings-Centrum Kindergeneeskunde (NSCK; Dutch Paediatric Surveillance Unit), invasive H. influenzae infections in children under 15 years of age reported by paediatricians were registered from October 1993 until December 1997. On the basis of the NSCK data the incidence of invasive H. influenzae infections was determined for 1994-1997 in relation to the children's age. RESULTS: The numbers of cases of invasive H. influenzae infection were 129 in 1994, 41 in 1995, 24 in 1996 and 8 in 1997. The decrease mainly concerned type b infections. The mean age at infection increased in the first two years after the introduction of vaccination. No apparent change in the clinical presentation of infection was observed. In four years of surveillance a total of nine cases of vaccine failure was reported. CONCLUSION: The progressive effect of vaccination against Hib was reflected in the strong decline of the number of invasive Hib infections, mainly in the youngest children. In accordance with the high level of voluntary vaccination in the Netherlands (95.5% as of January 1st 1997) and the expected high vaccine efficacy the number of vaccine failures was low. A further beneficial effect for the youngest children may be expected from starting the vaccination scheme at a still earlier age.