• Antigenic and molecular surveillance of influenza virus in the period 1993-1994

      Jong JC de; Verweij C; Bestebroer TM; Bijlsma K; Kleijne JAFW; Claas ECJ; Osterhaus ADME; Bartelds AIM; Loon AM van; VIR; EUR; NIVEL (1994-10-31)
      In order to formulate recommendations for the annual review of the influenza vaccine composition, the World Health Organization (WHO) coordinates a global network of virological laboratories. In this framework, the Erasmus University of Rotterdam (EUR) and RIVM together form the National Influenza Centre (NIC) of the Netherlands. EUR collects recent influenza virus strains isolated in the Dutch diagnostic laboratories, analyses them by serological and molecular methods, compares them with reference strains and with the vaccine strains proposed by WHO, and sends them to WHO. RIVM isolates influenza viruses in the NIVEL/RIVM surveillance of respiratory virus infections, sends them to WHO, and collects recent influenza virus strains from abroad. At RIVM, the foreign strains are examined with serological and molecular methods and compared with the Dutch virus strains. Of the seasons 1993 (southern hemisphere and tropical countries) and 1993/94 (temperate areas of the northern hemisphere), the influenza epidemics were almost exclusively caused by subtype A(H3N2). Of this period, 207 influenza virus strains originating from Singapore, Australia, New Zealand, Hong Kong, South Africa, Sweden, Norway, United Kingdom, France, Spain, and the Netherlands were analyzed. Of this collection, 195 strains belonged to subtype A(H3N2) and 12 to type B. All the H3N2 virus strains were related to the vaccine strain n/Beijing/32/92. This lineage of strains dates back to the sporadically circulating H3N2 virus strains of 1990. In this report a detailed picture is presented of the antigenic and molecular evolution of this lineage and of another, now (perhaps temporarily) extinct lineage. In 1993/94, we could distinguish three antigenic variants of A/Beijing/32/92-like H3N2 viruses. The main variant comprised 95% of the total number of tested strains. Haemagglutination inhibition (HI) tests indicated that this variant differed widely from the main variant of the previous large epidemic of H3N2 virus (1991/92), implying that the existing group immunity to this variant was very low in the human population. This may have contributed to the high excess mortality of 6200 cases registered during the influenza epidemic of 1993/94. The main variant was related to the 1993/94 vaccine strain A/Beijing/32/92. Still, the differences observed in HI assays suggest that the vaccine induced a less - than - optimal protection against influenza during the last season. With regard to influenza B virus, no significant antigenic changes could be detected when comparing the 1993/94 strains with the strains of 1990/91 and 1992/93.
    • Antigenic surveillance of influenza virus in the period 1995-1996

      Jong JC de; Verweij C; Bijlsma K; Bestebroer TM; Claas ECJ; Osterhaus ADME; Bartelds AIM; Kimman TG; LIO; LIS; NIVEL; EUR (1997-03-31)
      As a consequence of frequent antigenic changes of the virus, the composition of the influenza vaccine is annually adapted by WHO. In this framework, the National Influenza Centre (NIC, a collaboration of RIVM with the Erasmus University Rotterdam) generates and collects influenza virus strains isolated in the Netherlands from patients presenting to general physicians and in hospitals. NIC compares these strains with the vaccine strains recommended by WHO and with other foreign strains. In Europe, including the Netherlands, the influenza epidemic of 1995/96 was early and of an average extension. Subtype A(H3N2) dominated but A(H1N1) and B-viruses were also reported. The antigenic reactivities of the three major influenza virus variants of the seasons 1995 (southern hemisphere) and 1995/96 (northern hemisphere) did not differ significantly from those of the seasons 1994 and 1995/96, or from the vaccine strains used in the 1995/96 season. Therefore, both the infection-acquired and the vaccine-induced immunity will have rendered a relative good protection against influenza virus infections in 1995/96.
    • Comparison of adjuvants for immune potentiating properties and side effects in mice

      Leenaars PPAM; Hendriksen CFM; Koedam MA; Claassen I; Claassen E; CDL; EUR; TNO/PG (1994-09-30)
      Four types of adjuvants were evaluated as alternative to the use of Freund's complete adjuvant in mice. The evaluation was based on clinical observations, behavioural and physiological state, gross and histo-pathological lesions and capacity to support immunological responses to weak immunogens. The adjuvants included water-in-oil emulsion containing Mycobacteria (Freund's complete adjuvant; substituted for Freund's incomplete adjuvant in booster immunization), a water-in-oil emulsion (Specol), a micro-organism (Lactobacillus), preformed immune-stimulating complexes containing rabies virus glycoprotein and a saponin, Quil A. The adjuvants were combined with three types of weak immunogens including: a synthetic peptide, an 'auto'antigen (myelin basic protein) and a particulate antigen (inactivated Mycoplasma pneumoniae). Each adjuvant/antigen preparation was injected (primary and booster) either intraperitoneally (i.p.), subcutaneously in the neck or groin (s.c.) or subcutaneously at the dorsal side of the hind feet. The injection of adjuvant/antigen preparations resulted in most severe pathological lesions, including granulomatous peritonitis and tissue necrosis, after administration of Freund's adjuvant/antigen or Quil A/antigen mixtures. Injection of Specol/antigen had mild to moderate inflammatory effects, while injection of Lactobacillus/antigen or antigen-iscom conjugates caused minimal side effects. Lesions were most frequently seen after injection of Mycoplasma pneumoniae preparations where i.p. injection resulted in relatively severe pathological changes as compared to s.c. injection. Despite these pathological changes, no signs of prolonged pain or distress could be demonstrated based on clinical observations and physiological and behavioural parameters. Minimal antibody responses and T-cell activation were found after injection of antigen in combination with saline or Lactobacillus. T-cell activation and high antibody responses were found after injection of antigen-iscom conjugates or antigen in Freund's adjuvant emulsions. T-cell activation was demonstrated after Specol/antigen immunizations and high antibody titers were found except for Specol/'auto'antigen immunizations. In studying adjuvant activity the influence of type of antigen, on side effects and immune response, should be taken into account. Despite severe inflammatory lesions found at necropsy after injection of Freund's adjuvant/antigen no prolonged signs of pain and distress could be detected. Presented data suggest that Specol is a possible alternative to Freund's complete adjuvant for the induction of an immune response against weak immunogens except possibly autoantigens, for which preformed iscoms seem very well suitable.
    • Socioeconomic status of the Dutch population

      Stronks K; Mheen H van de; Mackenbach JP; (VTV); EUR (1995-01-31)
      It is clear now that in Western European countries, a lower socioeconomic status is associated with a higher frequency of a wide range of health problems, and with higher mortality. In the Netherlands, this association has been observed for several health indicators measured by means of questionnaires, such as chronic conditions, health complaints and perceived health. Data on mortality, only available for men, also show a negative socioeconomic gradient. A 20-50% reduction of health problems is to be expected if the level of illness of the highest socioeconomic level applies to the whole population. Information on trends in the size of the socioeconomic inequalities in health is limited in the Netherlands. There is some evidence of an increase of the differences in mortality since the fifties, but data on differences in the height of children point at the opposite conclusion. Although part of the socioeconomic inequalities in health are probably the result of the effect of health on socioeconomic status (selection mechanism), most of the inequalities are expected to be caused by the effect of socioeconomic status on health, via an uneven distribution of more specific determinants of health. A lot of these determinants have been shown to be differentially distributed among socioeconomic groups in the Netherlands, e.g. smoking, high blood pressure, working and housing conditions, life-events and social support. There are hardly any studies, however, which try to assess the contribution of these more specific determinants to the observed socioeconomic inequalities in health. More and more powerful explanatory data should be generated to learn more about the background of these inequalities, in order to design policy measures.
    • Virological NIVEL/RIVM surveillance of respiratory virus infections in the 1996/97 season

      Bestebroer TM; Bartelds AIM; Peeters MF; Andeweg AC; Kerssens JJ; Bijlsma K; Rimmelzwaan GF; Kimman TG; Verweij C; Jong JC de; LIO; LIS; NIVEL; EUR; St Elisabeth Ziekenhuis Tilbutg (1999-02-18)
      The purpose of the Netherlands Institute of Primary Health Care (NIVEL)/National Institute of Public Health and the Environment (RIVM) surveillance is to establish the incidence of acute respiratory virus infections (ARI) in patients who consult their family doctor with ARI complaints. Since the 1992/93 season, the general practitioners (GPs) of the NIVEL network have been sending nose-throat swabs for this purpose from a selection of ARI patients to the RIVM. At the RIVM, these swabs were examined using virus culture, and in the 1994/95 and 1996/97 seasons, also polymerase chain reactions (PCR) for the detection of selected viruses, Mycoplasma pneumoniae (Mp) and Chlamydia pneumoniae (Cp). In the 1996/97 season, some of the patients were also examined for conventional bacteria. A potentially respiratory pathogenic agent was detected using culture and/or PCR in 64% of the 540 examined specimens. Viruses were found in 55% and conventional bacteria in 16% of the samples. Influenza virus, cultured from 24% of the samples, was the predominant virus, followed by rhinovirus (22%), respiratory syncytial (RS) virus (5%), and enterovirus (4%). As in previous years, a temporary increase in the rate of positive samples - especially those containing rhinoviruses - was noted in September, coinciding with the opening of schools at the end of August. In the Netherlands, the influenza epidemic of the 1996/97 season started in the second half of December and had the usual size and length. The epidemic began with a major wave of subtype A(H3N2) virus infections, followed by a small overlapping wave of type B virus infections in weeks 4 - 9. Sixty-one percent of the influenza viruses isolated from GP patients were H3N2, while 88% of those isolated in diagnostic laboratories were this subtype. In fact, this is a yearly recurring phenomenon and probably reflects the higher pathogenicity of subtype A(H3N2), compared with type B. Over the five seasons studied, influenza virus infections accounted for at least 26% of the ILI registered by NIVEL. Calculated over the same five seasons, an estimated 2.7% of the Dutch population developed per season an ILI caused by an influenza virus infection. According to the ILI registration, the highest incidence of ILI occurred among 0 to 4-year-old children. After correction for the influenza virus isolation rate and the fraction of ILI patients who consulted their GP, however, the highest incidence of influenza, 5.3%, occurred among the 5 to 14-year olds. Influenza occurred most frequently in the (according to popular belief 'healthy') countryside and least frequently in the northern region of the Netherlands.
    • Virologische NIVEL/RIVM-surveillance van respiratoire virusinfecties in het seizoen 1995/96

      Bestebroer TM; Bartelds AIM; Andeweg AC; Bijlsma K; Claas ECJ; Kimman TG; Verweij C; Jong JC de; LIO; LIS; NIVEL; EUR (1996-12-31)
      The purpose of the NIVEL/RIVM surveillance of respiratory virus infections is to clarify the etiology of acute respiratory illnesses (ARI) at the level of patients who consult their family doctor. Since the season of 1992/93, the general practitioners (GPs) participating in the nation-wide sentinel network of the Netherlands institute of primary health care (NIVEL) sent nose/throat swabs from their patients with ARI to the RIVM. At RIVM, these swabs were examined for the presence of viruses by virus culture. This surveillance provides more accurate information on the etiology of ARI in the general population than the results of the diagnostic laboratories, which are mainly dealing with specimens from hospitalised patients. A temporary increase of the rate of positive samples - especially yielding rhinoviruses - was noted in September, coinciding with the opening of schools at the end of August. The influenza epidemic of the season of 1995/96 started early and was of a moderate size. In the Netherlands and in a number of other countries, subtype A(H3N2) virus predominated.