Biomedical subjects

Tjeerd G Kimman

Publications and source records attributed to Tjeerd G Kimman.

14 recordsLinked to original sources

PubMed2006

Identification, phenotypic analysis, and full-length nucleotide sequence of a Dutch Coxsackievirus A20 isolate.

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).

Blotting, Western↗

PubMed2006

Assessing the introduction of universal varicella vaccination in the Netherlands.

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.

Chickenpox↗

PubMed2006

Developing a vaccination evaluation model to support evidence-based decision making on national immunization programs.

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.

Cost-Benefit Analysis↗

PubMed2006

Preclinical and clinical safety studies on DNA vaccines.

DNA vaccines are based on the transfer of genetic material, encoding an antigen, to the cells of the vaccine recipient. Despite high expectations of DNA vaccines as a result of promising preclinical data their clinical utility remains unproven. However, much data is gathered in preclinical and clinical studies about the safety of DNA vaccines. Here we review current knowledge about the safety of DNA vaccines. Safety concerns of DNA vaccines relate to genetic, immunologic, toxic, and environmental effects. In this review we provide an overview of findings related to the safety of DNA vaccines, obtained so far. We conclude that the potential risks of DNA vaccines are minimal. However, their safety issues may differ case-by-case, and they should be treated accordingly.

Animals↗

PubMed2006

The polio eradication effort has been a great success--let's finish it and replace it with something even better.

The polio eradication campaign has greatly reduced the effects of this disease, but many new challenges have emerged. These challenges include the occurrence of polio outbreaks caused by wild-type polioviruses or circulating vaccine-derived polioviruses (cVDPVs) in areas where vaccination coverage is low, the existence of people who excrete poliovirus persistently, and the inability to know definitely that poliovirus has gone. As a result, there is uncertainty about if, when, and how we can end polio immunisation. In this article, we discuss several scenarios for the future of polio control. Because the emergence of cVDPVs necessitates discontinuing the use of live oral polio vaccine, we propose to strive towards a global coverage of near 100% vaccination against all major childhood infections using combination vaccines that contain inactivated poliovirus vaccine. Such a policy will present multiple challenges.

Child↗

PubMed2005

Poliovirus-specific memory immunity in seronegative elderly people does not protect against virus excretion.

BACKGROUND: Dutch people born between 1925 and 1945 were ineligible for vaccination with the inactivated poliovirus vaccine (IPV) introduced in 1957 and may have escaped natural infection because of reduced poliovirus circulation. We examined whether people with low or undetectable antibody levels are susceptible to infection and whether memory immunity provides protection against virus excretion. METHODS: A total of 429 elderly participants were challenged with monovalent oral poliovirus vaccine (type 1 or 3) and followed for 8 weeks. Immune responses and virus excretion were compared for 4 groups, defined on the basis of seronegativity for poliovirus type 1 or 3, natural immunity, and IPV-induced immunity. RESULTS: On the basis of the rapidity of the antibody response and the absence of immunoglobulin M, we saw clear evidence of memory immune responses in 33% of the participants without detectable antibodies against poliovirus type 1 and in 5% of the participants without detectable antibodies against poliovirus type 3. Fecal virus-excretion patterns were not significantly different for seronegative participants, regardless of whether they showed evidence of memory immunity. CONCLUSIONS: Rapid antibody responses after challenge with oral polio vaccine provide evidence for poliovirus-specific memory immunity in seronegative elderly people. However, in contrast to preexisting immunity, memory immunity does not protect against virus excretion. These results have important implications for the poliomyelitis-eradication initiative, in particular for future immunization policies after eradication has been achieved.

Aged↗

PubMed2004

Rapid RT-PCR amplification of full-length poliovirus genomes allows rapid discrimination between wild-type and recombinant vaccine-derived polioviruses.

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.

Genes, Viral↗

PubMed2004

Influence of promoter variants of interleukin-10, interleukin-9, and tumor necrosis factor-alpha genes on respiratory syncytial virus bronchiolitis.

Previously, we reported genetic associations between severe respiratory syncytial virus (RSV) bronchiolitis in infants and polymorphisms in the interleukin (IL)-4 and IL-4 receptor alpha (IL-4Ralpha) genes, providing evidence for involvement of T helper type 2 cytokines in the pathogenesis of RSV bronchiolitis. We expanded our studies to polymorphisms in genes encoding IL-9, IL-10, and tumor necrosis factor (TNF)-alpha, using both a transmission/disequilibrium test and a case-control approach. Children homozygous for the IL-10 -592C or -592A allele had a higher risk of hospitalization for RSV bronchiolitis than did heterozygous carriers (odds ratio [OR], 1.73 vs. 2.55; 95% confidence interval [CI], 1.13-2.66 vs. 1.21-5.39). In children hospitalized at < or =6 months of age, a significant association between RSV bronchiolitis and the IL-10 -592C allele was found (OR, 1.61; 95% CI, 1.10-2.35). No significant associations of TNF-alpha and IL-9 polymorphisms with RSV bronchiolitis were observed. We also explored the interactions between different polymorphisms and found an interaction between the IL-4Ralpha Q551R and IL-10 C-592A polymorphisms.

Adult↗

PubMed2004

Combining the transmission disequilibrium test and case-control methodology using generalized logistic regression.

To study the role of genetic factors in the etiology, susceptibility, or severity of disease, several methods are available. In a transmission disequilibrium test, genotypes of cases are compared to those of their parents to explore whether a specific allele, or marker, at a locus of interest appears to be transmitted in excess of what is expected on the basis of Mendelian inheritance. Such apparent excess transmission indicates that cases are being selected for that allele, thereby providing evidence that this allele is a risk factor for disease. In case-control studies, genotypes of cases are compared to those of controls from the same population to identify whether a specific allele is associated with disease. If so, either the allele at this locus or one in linkage disequilibrium with it may be causally related to the etiology of the disease. Here, we discuss the problem of combining a transmission disequilibrium test and a case-control comparison, in order to integrate all available information, and thereby increase statistical power. As the same cases are used in both approaches, the two results are not independent. However, parents of cases can be independently compared to controls. Both the issue of testing for a genetic effect and the estimation of relative risks under the multiplicative model using generalized logistic regression are discussed.

Case-Control Studies↗

PubMed2003

Evaluation of serological and virological tests in the diagnosis of clinical and subclinical measles virus infections during an outbreak of measles in The Netherlands.

We evaluated different approaches for diagnosing measles virus (MV) infection in unvaccinated children and in healthy contact persons (n=194) during a measles epidemic in The Netherlands. MV RNA was detected by reverse-transcriptase polymerase chain reaction in throat-swab specimens from 93% of the patients with clinical symptoms. MV RNA was detected from 5 days before until 12 days after the onset of symptoms. Most patients (88%) also secreted MV RNA in their urine until 5 weeks after the onset of symptoms. Oral fluid proved to be the most practical specimen for the simultaneous detection of MV-specific IgM antibody and viral RNA, which, together, confirmed 93% of measles cases. Viral RNA was also detected in oropharyngeal specimens from 3 healthy contact persons with serological proof of MV infection. The results of this study emphasize the feasibility of combined detection of viral RNA and MV-specific IgM antibodies in oropharyngeal specimens for the diagnosis of clinical and subclinical MV infection.

Adolescent↗

PubMed2003

Respiratory syncytial virus enhances respiratory allergy in mice despite the inhibitory effect of virus-induced interferon-gamma.

In mice, respiratory syncytial virus (RSV) infection during allergic provocation aggravates the allergic Th2 immune response, characterised by production of interleukin (IL)-4, IL-5, and IL-13, and eosinophilic inflammation. This enhancement of the Th2 response occurs simultaneously with a strong RSV-induced Th1 cytokine response (IL-12 and IFN-gamma). The present study investigated whether IFN-gamma and IL-12 are critically involved in this RSV-enhanced OVA allergy. Therefore, IFN-gammaR- and IL-12-deficient mice (both on a 129/Sv/Ev background) were sensitised and challenged with ovalbumin (OVA) and infected with RSV during the OVA challenge period. Neither gene deletion affected the development of ovalbumin-induced allergic inflammation in mice. However, when OVA-allergic IFN-gammaR deficient mice were infected with RSV, an increased pulmonary eosinophilic infiltrate and increased IL-4 and IL-13 mRNA expression in lung tissue were observed compared with identically treated wild-type mice. In contrast, deficiency of IL-12 did not aggravate the Th2 immune and inflammatory response in OVA/RSV-treated mice, compared with wild-type. In conclusion, the virus-induced IFN-gamma response diminishes the Th2 inflammatory response during OVA allergy but fails to prevent totally the enhancement of the OVA allergy by RSV. In contrast, IL-12 is not involved in inhibiting nor increasing the RSV-enhanced allergy in 129/Sv/Ev mice.

Animals↗

PubMed2003

Excretion of wild-type and vaccine-derived poliovirus in the feces of poliovirus receptor-transgenic mice.

The emergence of circulating vaccine-derived poliovirus (cVDPV) strains in suboptimally vaccinated populations is a serious threat to the global poliovirus eradication. The genetic determinants for the transmissibility phenotype of polioviruses, and in particularly of cVDPV strains, are currently unknown. Here we describe the fecal excretion of wild-type poliovirus, oral polio vaccine, and cVDPV (Hispaniola) strains after intraperitoneal injection in poliovirus receptor-transgenic mice. Both the pattern and the level of fecal excretion of the cVDPV strains resemble those of wild-type poliovirus type 1. In contrast, very little poliovirus was present in the feces after oral polio vaccine administration. This mouse model will be helpful in elucidating the genetic determinants for the high fecal-oral transmission phenotype of cVDPV strains.

Animals↗

PubMed2002

Association of severe respiratory syncytial virus bronchiolitis with interleukin-4 and interleukin-4 receptor alpha polymorphisms.

The association of variants of genes encoding interleukin (IL)-4 and the IL-4 receptor alpha chain (IL-4Ralpha) with respiratory syncytial virus (RSV) bronchiolitis was examined in hospitalized infants. Polymorphisms in IL-4 (C-590T) and IL-4Ralpha (I50V and Q551R) were genotyped by restriction fragment-length polymorphism analysis. Control subjects included parents of the hospitalized children (for the transmission/disequilibrium test), and a random population sample (for the case-control study). Results were also analyzed in a combination of these 2 tests, using Fisher's method. The IL-4 590T allele was found more frequently among children hospitalized with RSV than expected in the case-control (odds ratio [OR], 1.43; P=.04) and combination (OR, 1.41; P=.02) tests. Among children who were >6 months old when they were hospitalized, compared with the control group or with the <6 months old who were hospitalized for RSV infection, higher frequencies of both the IL-4 590T allele and the IL-4Ralpha R551 allele were found. These results indicate that gain-of-function variants of T helper type 2 cytokine genes may play a role in increasing the severity of RSV disease, which appears more pronounced after the first half-year of life.

Bronchiolitis↗

PubMed2002

Immunoglobulin a as a serological marker for the (silent) circulation of poliovirus in an inactivated poliovirus-vaccinated population.

Poliovirus-specific immunoglobulin A (IgA) is detected after infection with wild-type virus or vaccination with live attenuated oral poliovirus (OPV) but not after vaccination with inactivated poliovirus (IPV). We examined whether the presence of IgA in serum can be used as a marker for poliovirus circulation in IPV-vaccinated populations in The Netherlands. In seronegative persons challenged with OPV, the sensitivity of this marker was 76%-86%. Results from a serosurvey showed a high seroprevalence (63%-73%) of IgA in the population born before vaccination was introduced in The Netherlands, which reflects natural exposure. The start of the vaccination program in 1957 corresponded to a reduction in the IgA seroprevalence in both vaccinated (2.1%-4.5%) and nonvaccinated groups (8.3%-11.7%). The presence of IgA-positive persons in the population could largely be explained by the occurrence of episodes of proven poliovirus circulation. We propose to use the detection of poliovirus-specific IgA as a tool to monitor virus circulation in IPV-vaccinated and nonvaccinated populations, to aid the poliovirus eradication process.

Biomarkers↗