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ABSTRACT: To obtain insight into the age-specific seroprevalence for seven high-risk human papillomavirus (hr-HPV) serotypes (HPV16, 18, 31, 33, 45, 52, and 58) among the general population in the pre-vaccination era in The Netherlands.
From a cross-sectional population-based study (ISRCTN 20164309) performed in 2006/2007 6384 sera of men, women and children were tested for seven hr-HPV specific antibodies using a fluorescent bead-based multiplex immunoassay with virus-like particles of the seven HPV serotypes.
An increase in seroprevalence was observed in adolescents, especially for the most prevalent HPV type 16 (up to 11.3%). The increase was most pronounced in women, but was less clear for the other six HPV serotypes. Relatively stable seroprevalences were found in the middle aged cohorts and a slight decrease in the elderly. For the age cohorts >14 years, the seroprevalence among women (25.2%) was higher compared with men (20.3%) (p=0.0002). We found that 10.1% of the population was seropositive for multiple HPV serotypes.
The HPV vaccination program is targeted at preadolescents as is justified by the results in this study in which a step-up in HPV seroprevalence is observed at ages of sexual debut. Although direct interpretation of seroprevalence data are hampered by cross-reactivity and seroconversion rate, these data are useful as baseline to evaluate long-term population effects of the HPV16/18 vaccination program.
Vaccine 09/2012; 30(47):6686-93. · 3.77 Impact Factor
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ABSTRACT: Parvovirus B19 (B19V) can cause infection in humans. To date, three genotypes of B19V, with subtypes, are known, of which genotype 1a is the most prevalent genotype in the Western world. We sequenced the genome of B19V strains of 65 asymptomatic, recently infected Dutch blood donors, to investigate the spatio-temporal distribution of B19V strains, in the years 2003-2009. The sequences were compared to B19V sequences from Dutch patients with fifth disease, and to global B19V sequences as available from GenBank. All Dutch B19V strains belonged to genotype 1a. Phylogenetic analysis of the strains from Dutch blood donors showed that two groups of genotype 1a co-exist. A clear-cut division into the two groups was also found among the B19V strains from Dutch patients, and among the B19V sequences in GenBank. The two groups of genotype 1a co-exist around the world and do not appear to differ in their ability to cause disease. Strikingly, the two groups of B19V predominantly differ in synonymous mutations, distributed throughout the entire genome of B19V. We propose to call the two groups of B19V genotype 1a respectively subtype 1a1 and 1a2.
PLoS ONE 01/2012; 7(8):e43206. · 4.09 Impact Factor
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ABSTRACT: OBJECTIVE: This study evaluates trends in antibody seroprevalences of seven high-risk human papillomavirus (hr-HPV) serotypes (HPV16, 18, 31, 33, 45, 52, and 58) between the 1995-96 and 2006-07 sero-surveys among the Dutch general population in the pre-vaccination era. METHODS: Serum samples of men and women (0-79 years of age) from two cross-sectional population-based serosurveillance studies performed in 1995-96 (n = 3303) and 2006-07 (n = 6384) were tested for HPV-specific antibodies in a VLP-based multiplex immunoassay. RESULTS: HPV16-specific antibody seroprevalence increased during adolescence and shifted to younger ages in the 2006-07 survey compared to the 1995-96 survey. This step-up in HPV16 seroprevalence was most pronounced in women, while a more gradual increase was observed in men. Also in cohorts older than 49 years, HPV16 seroprevalence was higher in 2006-07 as compared to 1995-96 survey. A higher overall seroprevalence in individuals older than 15 years of age was found for HPV16, 18, 31 and 45 in 2006-07 as compared to 1995-96. For HPV33, 52 and 58 seroprevalences were comparable over this 11-year time period. Seropositivity for one or more HPV types was significantly higher in 2006-07 (23.1%) than in 1995-96 (20.0%) (p = 0.013). Multi-seropositivity increased from 7.1% in 1995-96 up to 10.2% in 2006-07 (p<0.0001). Differences in HPV seropositivity for at least one of the seven HPV types between both surveys could be explained in addition to demographic characteristics (age, sex, urbanization degree and ethnicity), also by changes in sexual behaviour (marital status, age of sexual debut and ever reported an STI). CONCLUSION: The observed increase in particular HPV16 seroprevalence could be due to changes in sexual behaviour over the years, and especially in age of sexual debut. Seroprevalence studies provide insight into the distribution of HPV types and infection dynamics in the general population over time, which is important to assess the impact of HPV-vaccination.
PLoS ONE 01/2012; 7(11):e48807. · 4.09 Impact Factor
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ABSTRACT: During a recent mumps epidemic in the Netherlands caused by a genotype D mumps virus strain, we investigated the potential of vaccinated people to spread mumps disease to close contacts. We compared mumps viral titers of oral fluid specimens obtained by quantitative PCR from vaccinated (n=60) and unvaccinated (n=111) mumps patients. We also investigated the occurrence of mumps infection among the household contacts of vaccinated mumps patients. We found that viral titers are higher for unvaccinated patients than for vaccinated patients during the 1st 3 days after onset of disease. While no symptomatic cases were reported among the household contacts (n=164) of vaccinated mumps patients (n=36), there were cases with serological evidence of asymptomatic infection among vaccinated household contacts (9 of 66 vaccinated siblings). For two of these siblings, the vaccinated index patient was the most probable source of infection. We conclude that, in this particular outbreak, the risk of a close contact becoming infected by vaccinated patients was small, but present.
Vaccine 11/2011; 29(51):9551-6. · 3.77 Impact Factor
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ABSTRACT: Herpes zoster (HZ) is a painful disease affecting a considerable part of the elderly. Programmatic HZ vaccination of elderly people may considerably reduce HZ morbidity and its related costs, but the extent of these effects is unknown. In this article, the potential effects and cost-effectiveness of programmatic HZ vaccination of elderly in the Netherlands have been assessed according to a framework that was developed to support evidence-based decision making regarding inclusion of new vaccines in the Dutch National Immunization Program.
An analytical framework was used combining a checklist, which structured relevant data on the vaccine, pathogen and disease, and a cost-effectiveness analysis. The cost-effectiveness analysis was performed from a societal perspective, using a Markov-cohort-model. Simultaneous vaccination with influenza was assumed.
Due to the combination of waning immunity after vaccination and a reduced efficacy of vaccination at high ages, the most optimal cost-effectiveness ratio (21716 euro per QALY) for HZ vaccination in the Netherlands was found for 70-year olds. This estimated ratio is just above the socially accepted threshold in the Netherlands of 20000 euro per QALY. If additional reduction of postherpetic neuralgia was included, the cost-effectiveness ratio improved (approximately 10000 euro per QALY) but uncertainty for this scenario is high.
Vaccination against HZ at the age of 70 years seems marginally cost-effective in the Netherlands. Due to limited vaccine efficacy a considerable part of the disease burden caused by HZ will remain, even with optimal acceptance of programmatic vaccination.
BMC Health Services Research 01/2010; 10:237. · 1.66 Impact Factor
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American journal of epidemiology 11/2009; · 5.59 Impact Factor
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ABSTRACT: The effect of vaccination programs on transmission of infectious disease is usually assessed by monitoring programs that rely on notifications of symptomatic illness. For monitoring of infectious diseases with a high proportion of asymptomatic cases or a low reporting rate, molecular sequence data combined with modern coalescent-based techniques offer a complementary tool to assess transmission. Here, the authors investigate the added value of using viral sequence data to monitor a vaccination program that was started in 1998 and was targeted against hepatitis B virus in men who have sex with men in Amsterdam, the Netherlands. The incidence in this target group, as estimated from the notifications of acute infections with hepatitis B virus, was low; therefore, there was insufficient power to show a significant change in incidence. In contrast, the genetic diversity, as estimated from the viral sequence collected from the target group, revealed a marked decrease after vaccination was introduced. Taken together, the findings suggest that introduction of vaccination coincided with a change in the target group toward behavior with a higher risk of infection. The authors argue that molecular sequence data provide a powerful additional monitoring instrument, next to conventional case registration, for assessing the impact of vaccination.
American journal of epidemiology 11/2009; 170(12):1455-63. · 5.59 Impact Factor
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Journal of Hepatology 08/2009; · 9.26 Impact Factor
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Nederlands tijdschrift voor geneeskunde 05/2009; 153(14):658-61.
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ABSTRACT: Individuals who reach the antibody threshold level of 10IU/l against the surface protein of the hepatitis B virus (HBV) after completion of a series of hepatitis B vaccination are considered to be long-term protected against a clinically manifest HBV infection.
Here we describe an acute hepatitis B infection in a patient who received five hepatitis B vaccinations. Although his initial response to vaccination was moderate, he finally reached an excellent hepatitis B surface antibody level (anti-HBs) titres of more than 1000 IU/l in response to a booster vaccination with a recombinant DNA vaccine. Nevertheless, he developed full-blown acute hepatitis due to an HBV infection 14years after this booster vaccination. A DNA analysis of the surface protein encoding region followed by phylogenetic analysis showed that our patient was infected with a normal HBV strain that is circulating among men who have sex with men. To our knowledge, this is the first report of a genuine hepatitis B vaccination failure in someone who acquired a high anti-HBs level in response to a recombinant DNA hepatitis B vaccine.
Healthcare workers whose response to the initial hepatitis B vaccination is moderate might be vulnerable to hepatitis B virus infection.
Journal of Hepatology 01/2009; 50(2):426-31. · 9.26 Impact Factor
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Robert S van Binnendijk,
Susan Hahné,
Aura Timen,
Gijs van Kempen,
Robert H G Kohl, Hein J Boot,
Katja C Wolthers,
José C F M Wetsteijn,
Anne de Vries,
Krista Westert,
Kevin E Brown,
Rik L de Swart
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ABSTRACT: Epidemiological and molecular investigation of two small measles clusters in The Netherlands in July/August 2007 revealed an association with travel by air of the index cases and nosocomial spread in the first cluster. Although these importations did not result in an outbreak among unvaccinated subjects, the observations illustrate the challenges for measles control in a country with high measles vaccination coverage (> 95%) but with pockets of low coverage.
Vaccine 10/2008; 26(46):5775-7. · 3.77 Impact Factor
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ABSTRACT: An effective vaccine is available for the hepatitis B virus (HBV), which is a very contagious human pathogen. The prevalence of chronic HBV infection is very low in the Netherlands (<0.5%), and no universal vaccination is in place. Instead, a program of vaccination for targeted groups at high risk of HBV exposure has been implemented. Because transmission of HBV can occur by various routes, the effectiveness of this targeted vaccination strategy is difficult to assess. Molecular typing data for the surface protein encoding gene of HBV isolates, in combination with epidemiological data, provide some insight into the main transmission routes. Due to the low mutation rate of the HBV genome, many isolates have identical S region sequences, which hampers phylogenetic analysis and identification of transmission chains. The molecular epidemiological analysis of acute HBV isolates based on the surface and core protein encoding regions were compared. The nucleotide diversity found in the C region was statistically significant greater (1.5 times) than in the S region, and phylogenetic analysis based on the C region showed a higher resolution. C region analysis resulted in an almost 50% reduction of genotype A isolates with identical sequences. C region analysis also indicated that no long-chain transmission of genotype D strains is occurring in the Netherlands, as all genotype D isolates have unique C region sequences. Defining the goals of molecular typing of HBV isolates should precede the choice for phylogenetic analysis on the basis of either C or S region sequences.
Journal of Medical Virology 02/2008; 80(2):233-41. · 2.82 Impact Factor
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ABSTRACT: A persistent infection with human papillomavirus (HPV) is a prerequisite for the development of cervical cancer. Clinical trials with HPV-vaccines have been very successful in preventing persistent HPV16/18 infections, the two most oncogenic HPV-genotypes. We assessed the introduction of universal HPV-vaccination for preadolescent girls in the Dutch National Immunization Programme. Long-term vaccine efficacy, the need and extent of a catch-up programme for young women, and the impact of vaccination on the cervical cancer screening programme are major unresolved issues. Preliminary conservative estimates (80% vaccine efficacy and no effects on the screening programme, transmission rate, non-cervical cancer incidence, and cross protection) predict an acceptable cost-effectiveness ratio for universal vaccination of preadolescent girls.
Vaccine 09/2007; 25(33):6245-56. · 3.77 Impact Factor
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ABSTRACT: Live oral poliovirus vaccine (OPV) strains can mutate and recombine during replication in the host. Trivalent OPV has long been used to restrain wild-type poliovirus in developing countries. However, recently WHO advocates using monovalent OPV (mOPV) to finally eradicate poliovirus world-wide. We analysed polioviruses recovered from the faeces of 101 elderly patients (divided into three groups by immune status) challenged with mOPV-1 or mOPV-3. A high number of nucleotide mutations was found in the viral capsid-protein-encoding regions. Some of these mutations caused amino acid changes in or near regions with neutralizing epitopes, especially in mOPV-1-derived strains. The quantities of mutations in recovered poliovirus strains correlated with prevaccination immune status (seronegatives have more mutations) and excretion duration. Duration of excretion appears to be the dominant factor for the accumulation of mutations in mOPV-derived strains in vaccinated elderly people.
Vaccine 07/2007; 25(24):4706-14. · 3.77 Impact Factor
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ABSTRACT: Recombination between (human) enteroviruses is a common event in nature. Recently, it has been recognised that this feature has a major impact on the use of the live-attenuated polio vaccine during the end stage of polio eradication. The constraints for successful recombination between (vaccine-derived) polioviruses and human enteroviruses are, however, largely unknown. Here, we describe the identification and characterisation of a HEV-C field strain, isolated from the stool of a 2-year-old Dutch boy. Serotyping indicated that strain 89490 is a variant of strain CAV20a, which is already a variant of the prototype CAV20 strain. Amino acid sequence identity of 94.1% for the entire P1-region, and 92.4% for the major structural protein (VP1) indicates that this strain is indeed related to CAV20. However, virus neutralisation and Western blot analysis failed to show antigenic homology between the prototype CAV20 strain and our field strain. Furthermore, the 89490 field strain, just like the sub-prototype CAV20a, is able to replicate on RD-cells, while the prototype CAV20 and another sub-prototype CAV20b are not. On the basis of the phylogenetic analysis of the P2 and P3 region we expect that strain 89490 can act as recombination partner for the attenuated poliovirus strains of the Oral Polio Vaccine (OPV).
Virus Genes 02/2007; 34(1):75-85. · 1.85 Impact Factor
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ABSTRACT: Although varicella is seen as a benign disease in the Netherlands, about 40,000 visits to a general practitioner (GP) are made, over 200 hospital admission occur, and 2.3 persons die on average each year. Most of this burden of disease can be prevented by universal varicella childhood vaccination. Ten years after the introduction of the single-shot, single-component varicella childhood vaccination in the USA, a major reduction in hospitalization, mortality, and burden of disease has been reported. Using our recently vaccine evaluation model for the introduction of a new vaccine in our national immunization program, we have analyzed the feasibility of universal varicella vaccination by replacing the measles-mumps-rubella (MMR) vaccine with a measles-mumps-rubella-varicella (MMRV) vaccine. After structuring and reviewing the available data, two major points of uncertainty remain: (1) the influence of universal childhood vaccination on the incidence of zoster later in life; (2) the cost-effectiveness ratio for the Dutch situation. Despite these uncertainties it is clear that universal childhood vaccination will prevent most of the varicella related GP-visits, hospitalizations, and deaths.
Vaccine 10/2006; 24(37-39):6288-99. · 3.77 Impact Factor
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ABSTRACT: Among all public health provisions national immunization programs (NIPs) are beyond doubt one of the most effective in reducing mortality, morbidity, and costs associated with major infectious diseases. To maintain their success, NIPs have to modernize in response to many new and old demands regarding efficacy, safety, availability of new vaccines, emerging and evolving pathogens, waning immunity, altered epidemiological situations, and the public's trust in the program. In this paper we present an evaluation model in the form of a checklist that may help in collecting relevant scientific information that is necessary for evaluation and decision making when considering changes in a NIP. Such a checklist points to relevant information on the vaccine-preventable disease, the pathogen causing it, the vaccine, and the cost-effectiveness ratio of the vaccine. However, the final judgment on a potential change in the NIP cannot be based on a simple algorithm, as the relevant information reflects factors of a very different kind and magnitude, to which different value judgements may be added, and which may have certain degrees of uncertainty. Because any change in the NIP may be accompanied by more or less unforeseen changes in the vaccine's efficacy, evolutionary consequences, including the antigenic composition of the pathogen, and the vaccine's safety profile, an intensive surveillance program should accompany any NIP. Elements thereof include clinical-epidemiological surveillance, surveillance of vaccination coverage, immune surveillance, surveillance of microbial population dynamics, and surveillance of adverse events and safety issues. We emphasize that the decision to introduce a vaccine in the NIP should be taken as seriously, both scientifically and ethically, as the decision to withhold a vaccine from the NIP. In the latter case one might be responsible for vaccine-preventable disease and mortality.
Vaccine 06/2006; 24(22):4769-78. · 3.77 Impact Factor
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ABSTRACT: Poliomyelitis outbreaks in areas that were free for a long time of wild-type polioviruses have been reported. Characterization at nucleotide level of the causative agents showed that the isolated viruses were recombinant oral polio vaccine (OPV)-derived polioviruses. To allow rapid identification and detailed analysis of such recombinant polioviruses, a robust full-length reverse transcriptase-PCR (RT-PCR) was developed using SuperScript II (RT) and expand (PCR). Without extensive purification, it was possible to amplify and characterize the full-length genomes of all selected vaccine, wild-type, and recombinant vaccine-derived polioviruses within a week. Endonuclease nuclease analysis (SpeI) of the full-length amplicons allowed easy discrimination between recombinant and non-recombinant polioviruses. Furthermore, sequence analysis of cloned full-length amplicons of a recombinant vaccine-derived poliovirus strain showed that the quasi-species nature of a viral stock is preserved during the RT-PCR procedure. This robust and rapid RT-PCR method will allow rapid characterization of (recombinant) poliovirus strains in case of a local poliomyelitis outbreak, and will help to assess the risk of the appearance of such strains after wild-type poliovirus has been eradicated globally.
Journal of Virological Methods 04/2004; 116(1):35-43. · 2.01 Impact Factor
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ABSTRACT: Many questions regarding the initiation of replication and translation of the segmented, double-stranded RNA genome of infectious bursal disease virus (IBDV) remain to be solved. Computer analysis shows that the non-polyadenylated extreme 3'-untranslated regions (UTRs) of the coding strand of both genomic segments are able to fold into a single stem-loop structure. To assess the determinants for a functional 3'-UTR, we mutagenized the 3'-UTR stem-loop structure of the B-segment. Rescue of infectious virus from mutagenized cDNA plasmids was impaired in all cases. However, after one passage, the replication kinetics of these viruses were restored. Sequence analysis revealed that additional mutations had been acquired in most of the stem-loop structures, which compensated the introduced ones. A rescued virus with a modified stem-loop structure containing four nucleotide substitutions, but preserving its overall secondary structure, was phenotypically indistinguishable from wild-type virus, both in vitro (cell culture) and in vivo (chickens, natural host). Sequence analysis showed that the modified stem-loop structure of this virus was fully preserved after four serial passages. Apparently, it is the stem-loop structure and not the primary sequence that is the functional determinant in the 3'-UTRs of IBDV.
Nucleic Acids Research 02/2004; 32(1):211-22. · 8.03 Impact Factor
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ABSTRACT: The food grade bacterium Lactococcus lactis is a potential vehicle for protein delivery in the gastrointestinal tract. As a model, we constructed lactococcal strains producing antigens of infectious bursal disease virus (IBDV). IBDV infects chickens and causes depletion of B-lymphoid cells in the bursa of Fabricius and subsequent immunosuppression, morbidity, or acute mortality. The two major IBDV antigens, i.e., VP2 and VP3, that form the viral capsid were expressed and targeted to the cytoplasm, the cell wall, or the extracellular compartment of L. lactis. Whereas VP3 was successfully targeted to the three compartments by the use of relevant expression and export vectors, VP2 was recalcitrant to export, thus confirming the difficulty of translocating naturally nonsecreted proteins across the bacterial membrane. This defect could be partly overcome by fusing VP2 to a naturally secreted protein (the staphylococcal nuclease Nuc) that carried VP2 through the membrane. Lactococcal strains producing Nuc-VP2 and VP3 in various bacterial compartments were administered orally to chickens. The chickens did not develop any detectable immune response against VP2 and VP3 but did exhibit an immune response against Nuc when Nuc-VP2 was anchored to the cell wall of lactococci.
Applied and Environmental Microbiology 01/2004; 69(12):7281-8. · 3.83 Impact Factor
