A model-based evaluation of the national immunization programme against rubella infection and congenital rubella syndrome in The Netherlands.

In order to improve the prevention of cases of congenital rubella syndrome in The Netherlands, in 1987 the selective vaccination strategy against rubella infection in girls was replaced by mass vaccination. This decision was supported by mathematical model analyses carried out by Van Druten and De Boo. In order to compare the predicted impact of the rubella vaccination programme with the current available data in more detail, a similar model was built. Although the model predicts elimination of the rubella virus, data show that virus circulation is still present at a higher level than expected by the model. Simulation studies indicate that import of infection and a lower vaccine effectiveness, related to possible asymptomatic reinfection of vaccinated people, could be sources contributing to the present virus circulation. Even though the number of infections is much higher than the number of reported cases of disease, limited serosurveillance data and case notification data show that females of childbearing age are well protected by immunization.

[Measles in The Netherlands; epidemiology and the effect of vaccination]. / Mazelen in Nederland; epidemiologie en de invloed van vaccinatie.

OBJECTIVE: To estimate the incidence of measles in the Netherlands and assess the effect of vaccination with regard to vaccination status. DESIGN: Retrospective study. METHOD: Data were collected from the Central Bureau for Statistics (CBS), reported cases at the National Health Department (NHD), data from hospitals concerning admissions, morbidity data from the General Practitioner Networks, serological data from virology laboratories and serological data from several other studies. RESULTS: After introduction of the measles vaccination in 1976, morbidity and reported cases decreased dramatically. Some data suggest that measles in children over 10 years old are reported more frequently. Death caused by measles did not occur after 1988. CONCLUSION: The massive vaccination since 1976 resulted in an initial decrease in incidence of measles. The increase in incidence thereafter was probably caused by an increase in, and crowding of vulnerable, older people. No effect on the severity of the complications were seen so far. Surveillance is necessary to follow groups at risk and to take proper preventive measures.

Blocking ELISA for detection of mumps virus antibodies in human sera.

A new blocking enzyme-linked immunosorbent assay (ELISA) for detection of mumps virus (MuV) specific antibodies in large numbers of human serum samples was developed. The blocking ELISA is based on the reaction of MuV-specific, conjugated monoclonal antibodies (mAbs) with immobilized virus antigen, that has previously been incubated with a two-fold dilution of human serum. Mouse hybridomas that produce antibodies against MuV proteins were generated. They could be divided into 4 groups according to their hemagglutination inhibiting- and virus neutralizing capacities and their reaction in the blocking ELISA with MuV strain Enders. Ascites material from 22 mAbs derived from the 4 groups was further characterized with the MuV strains Enders and Jeryl Lynn. When mAbs from different groups were mixed in the blocking ELISA, an additional increase in absorbance could be observed. A mixture of 2 MuV neutralizing mAbs that were directed against HN and F protein, was used to assay 3 consecutive pre-, early post- and late postvaccination serum samples of 138 children, vaccinated at the age of 1.5 yr. A correlation of 94% was found between the blocking ELISA and the normal indirect ELISA, and of 98% between the blocking ELISA and the neutralization enzyme immunoassay (N50-EIA). The specificity and rapidity of the blocking ELISA makes it suitable for routine use in the determination of MuV neutralizing antibodies in large quantities of serum samples.

Comparison of a neutralization enzyme immunoassay and an enzyme-linked immunosorbent assay for evaluation of immune status of children vaccinated for mumps.

A 50% neutralization enzyme immunoassay (N50-EIA) was compared with an indirect enzyme-linked immunosorbent assay (ELISA) for determining mumps virus antibodies in three consecutive serum samples from 138 children vaccinated with a live mumps vaccine at the age (in years) of 1.5. By the N50-EIA, most (132 of 138) preserum samples did not show neutralizing activity. Eight to 12 weeks after vaccination, 17 of the children were still negative, but only 7 remained so after 2.5 years, resulting in a seroconversion rate of 125 of 132 (95%). Over the same period, the neutralization geometric mean titer rose from 3.6 to 9.9. By an indirect ELISA, 128 of 138 preserum samples were found negative. The early and late postvaccination sera of 8 children were ELISA negative, resulting in a seroconversion rate of 120 of 128 (94%). Only two children remained seronegative by both methods. Seven of the late postvaccination serum samples yielded noncorresponding results, reflecting 95% correlation between both methods. Due to cross-reactivity with parainfluenza viruses, the ELISA proved to be less specific, but on the other hand, it showed a greater sensitivity than the N50-EIA.

Predicting the dynamic effects of rubella vaccination programmes.

In the Netherlands, prepubertal girls have been vaccinated against rubella since 1974 (the UK strategy). Recently the Dutch Health Council advocated the introduction of an elimination strategy: vaccination of 1- and 9-year-old children. Dynamic effects of both strategies are studied using deterministic and stochastic models. Estimates of several epidemiological parameters are given. All computations and simulations were performed using as much field data as possible. Under the old strategy a new equilibrium is expected around the years 1995 to 2000; the new strategy is estimated to eliminate rubella (CRS) in large parts of the population 3 to 5 years after its initiation. Possible consequences of the new strategy on a cluster of people who refuse vaccination are investigated.

Measles, mumps and rubella: control by vaccination.

In 1984, the Health Council of the Netherlands advised that a new vaccination strategy against measles, mumps and rubella (MMR) should be initiated. The use of a combined MMR vaccine, to be given at 14 months and 9 years of age was recommended. An analysis of this strategy based on mathematical models, predicted that rubella and mumps and very probably measles will be eliminated in The Netherlands before 1990. The use of a combined MMR vaccine has a number of logistical and financial advantages over immunization with separate vaccines. Another factor to be considered is of course the mutual interference regarding immune response or immunization reactions. Less obviously, and often not recognised as an important factor, is the possibility of an adverse effect on the incidence of the congenital rubella syndrome (CRS), when vaccine coverage is low or the natural force of infection of rubella is high. Vaccine induced herd immunity can act to the disadvantage of the unvaccinated individuals. Following earlier work we show that certain vaccination programmes could actually increase the incidence of serious cases. At first sight, this may seem inconceivable. Mathematical analysis, however, reveals that this is indeed a real possibility. Implementing a vaccination programme that is not sufficiently intensive to eradicate the infection in the population will ultimately lead to a new steady state in which the force of infection is lower than in the period before the start of the programme. As a consequence those who are not (effectively) vaccinated have a higher chance of contracting the infection at an older age. For many viral infections, the chance of serious complications is greater if the infection is acquired at an older age. Congenital rubella and measles encephalitis are striking examples (with respect to mumps the situation is less clear). When boys and girls are vaccinated around one year of age and MMR vaccine coverage is lower than approximately 50%, the total number of cases with the congenital rubella syndrome can increase in the long term. When the force of infection of rubella before implementing the vaccination programme is high - which may be the case in developing countries - the effect is more pronounced and even a relatively high vaccine uptake of 80-90% may not be sufficient to keep CRS incidence below the level prior to control.(ABSTRACT TRUNCATED AT 400 WORDS)

HLA and the rubella-specific immune response following vaccination.

A group of 88 seronegative 11-year-old Dutch girls was selected to be tested for human leukocyte antigens (HLA) and for both the in vivo and in vitro immune response to rubella virus, 6 and 12 weeks after rubella vaccination. Although a slight influence of HLA-associated factors on the antibody levels, as measured by the enzyme-linked immunosorbent assay could not be excluded, no evidence for HLA-associated control of the rubella-specific immune response following vaccination was obtained. From these data it is concluded that HLA-associated factors cannot be expected to hamper the effectiveness of large-scale rubella vaccination procedures.

Inactivation of Semliki Forest Virus in aerosols.

Purified Semliki forest virus in aerosols is inactivated rapidly at 40% and above 70% relative humidity. At all humidities tested the decay of virus infectivity runs parallel with the decrease in hemagglutination activity, whereas the biological integrity of the virus ribonucleic acid is preserved. Also, free infectious ribonucleic acid is stable after spraying at all relative humidities. Evidence is presented for the hypothesis that above 20% relative humidity, virus inactivation in aersols is mainly due to surface-dependent factors, damaging the virus coat.