NIPH annals最新文献

We have successfully developed a restriction endonuclease fingerprinting (REF) technique for the study of meningococcal chromosomal DNA. A review of our application of this method in studies of meningococcal epidemiology and pathogenicity is given. By REF we could show that fingerprints of apparently identical B15 carrier strains were remarkably heterogeneous, whereas invasive B15 isolates possessed very similar fingerprints. We could also demonstrate REF heterogeneity among B15 isolates collected from cases with meningococcal disease and their close contacts during an outbreak of meningococcal disease in a military camp in North Norway. The REF technique has also proved valuable for our studies on meningococcal piliation and adherence. At present, we are studying 67 different meningococcal isolates collected from all parts of Norway during the MenOPP project.

The development in the epidemiological patterns of meningococcal disease in Norway after 1979 is briefly described for the general and military population. With the high incidence levels which have lasted for about nine years, the situation may be described as Norway having experienced a shift in 1974 to a new endemic level. The predicted incidence for 1983 is higher than for any year since 1941.

In a prospective case control study in Norway during the winter 1981-1982, 115 patients with systemic meningococcal disease were compared with 61 patient controls. Initially, skin bleedings, reduced general condition and consciousness, and body pain were seen more often, but irritability less often in meningococcal patients than in the patient controls. The meningococcal patients presented symptoms typical of infectious diseases in general. Symptoms that correlated with a poor prognosis of the meningococcal disease were reduced consciousness, cyanosis, and early diarrhea. The mean time interval from start of the meningococcal disease until admission to hospital was 34 hours. No deaths occurred when less than six hours elapsed before it was decided to admit the patient. All fatal cases were admitted by the first doctor who saw the meningococcal patient. Contact with the family doctor does not seem to have reduced the risk of death. To avoid unnecessary delays, access to hospitals should be facilitated, and efforts should be made to shorten the time interval before patients with relevant symptoms are seen by a doctor.

The antibody response of a group of adult volunteers given a combined meningococcal group B polysaccharide and serotype 2 outer membrane protein vaccine, has been studied by the ELISA technique. The antigen was an outer membrane preparation from a non-capsular strain of Neisseria meningitidis (the vaccine strain). The vaccination was performed as a double-blind experiment where one group of 27 persons was given the vaccine and a similar group of 28 persons was given a placebo. In addition, five volunteers from the laboratory staff were given the vaccine. Two weeks after the primary vaccination, 31 of the 32 vaccinated persons demonstrated a significant increase of specific IgG antibodies. The number with significant IgA and IgM increase was 21 and 12, respectively. A booster effect after revaccination four weeks later was found in 18 persons for IgG, in 10 for IgA and in one for IgM. Twenty-five weeks after the primary vaccination the ELISA values were significantly reduced, mostly for IgM antibodies. The mean values for IgG, IgM and IgA were then 150%, 130% and 110%, respectively, of the values before vaccination. A new way of analysing the data has also been tried for IgG determination. Instead of comparing OD values, we calculate the expression: B = D/2 . In(1 + OD/A)/(1-OD/A), where A is an experimental constant and D is the serum dilution. B then becomes linearly proportional to the antibody concentration. This way of expressing the results shows the geometric mean IgG titer 25 weeks after vaccination to be three times higher for the vaccinated than for the placebo group.

Three hundred and eighty-two human streptococcal strains of serogroup B, collected from different sources and from different parts of Norway have been serotyped and phagetyped . The results of serotyping show a predominance of serotype Ia; 150 strains belonged to this type. Only 32 strains belonged to serotype III, a serotype well-known as the dominating cause of neonatal septicemia and meningitis (11, 23). The other serotypes were evenly represented. The phagetyping was performed by the procedure and with phages described by Stringer (19). The strains were lysed by phages at a frequency of 70%. A total of 145 strains (38%) was lysed by one or two phages, while 124 strains (32%) were typable by different phage patterns. When combined with serotyping, phagetyping of group B streptococci is an important tool in characterizing these microbes for epidemiological and other purposes.

The consumption of hospital resources for treatment of gastrointestinal diseases in six counties in Norway (population 1.07 million) has been estimated based on hospital admission data. The number of discharges for men (1345/100 000 inhabitants) is about 30% higher than for female patients (1021/100 000 inhabitants) whereas the number of bed-days is only 8% higher, reflecting a difference in length of stay of about 2 days. The proportion of digestive diseases compared with the total somatic care varies between 8.8--10.3% depending upon the method of estimation. The consumption of resources is both age and sex dependent with an almost exponential age-dependence for patients older than 14, and with a male dominance for all age groups except for patients between 15 and 24 years of age. The proportion of digestive diseases compared with the total somatic care shows also sex- and age-group variations with high proportion (i e high consumption) for men in productive ages, whereas women in the same age groups have a considerably lower consumption. A marked increase in hospitalization time is found for older patients. Relatively low mortality rates are found for gastrointestinal diseases. Regional differences in consumption are revealed with differences in discharge rates of up to 50%, in bed-days up to 70% and with differences up to 20% for length of stay.

Treatment of agar-grown meningococci with dilute hydrochloric acid and suspension in saline after washing gave a preparation suitable for meningococcal serotyping by staphylococcal coagglutination with monoclonal antibodies. The monoclonal antibodies available for use and attached to protein A on the staphylococci were directed against the serotype protein antigens 2a, 2b (class 2), 15 (class 3) and the subtype protein antigens P1. 2 and P1. 16 (class 1). Ninety per cent of systemic strains and thirty-four per cent of a collection of carrier isolates, both from Norway late 1981/early 1982, were typable. The serotype antigen 15 alone or in combination with P1. 16 or P1. 16 alone were detected in about 85 per cent of the systemic strains. The quality of the whole-cell meningococcal antigen was important for the test to be easily read.

Meningococcal disease has been a serious problem in Norway for nearly a decade. A nation-wide study of this disease revealed that almost 40% of all cases in clinical practice remained without a microbiological diagnosis. In the hope that this situation can be improved, a brief review is given of information available in the literature concerning collection and handling of microbiological specimens from patients with possible systemic meningococcal disease.

To investigate the relative importance of the many possible influencing factors and developmental traits of systemic meningococcal disease (MCd) in the practical Norwegian context, a comprehensive multipurpose case control study was carried out during the winter of 1981-1982 on incident cases in the whole country. The design of the study, the MenOPP project, is outlined. The main inclusion criteria for patients were suspected bacterial meningitis and/or septicemia on referral to hospital. This resulted in 115 verified or probable cases of MCd and 61 patient controls. Randomly drawn from three age strata, 320 population controls were actually approached and 293 (92%) of these responded to the "environmental questionnaire". So did most of the patients (98%). The clinical data mainly comprised information from the commencement of the disease to a sequelae check about six weeks after hospital admission. Laboratory data on strain and serum characteristics were, and still are, collected. The results are to be published in several papers. Here, some epidemiological characteristics of the material are given. Regional, seasonal, and age/sex differences in case fatality are reported and discussed.

In September 1982 two siblings were admitted to hospital within a few days of each other, with almost identical symptoms of meningococcemia. One of them had been discharged from hospital four days previously, fully treated to meningococcal meningitis. Two systemic meningococcal isolates and nasopharyngeal meningococci from patient No 1 were B:15:P1. 16 strains as well as one nasopharyngeal isolate from patient No 2. One nasopharyngeal isolate from the father was a non-encapsulated 15:P1. 16 strain. The two systemic isolates were clearly different with respect to the class 5 outer membrane protein(s); the second closely resembled the various nasopharyngeal isolates, all of which were identical. Only the two patients mounted detectable bactericidal antibody activity as measured by using human complement. Convalescent serum from patient No 1 after the second episode was bactericidal against the first but not the second isolate. No differences among patients and parents were found by measuring opsonizing activity. The clinical picture and the laboratory results seem to indicate that both children, one after a treated meningitis episode, had benign meningococcemia which subsequently ran its course untreated and without complications.