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E Holten

Publications and source records attributed to E Holten.

At least 19 recordsLinked to original sources
PubMed1995

Emergence of a new virulent clone within the electrophoretic type 5 complex of serogroup B meningococci in Norway.

An increase in B:15:P1.12 meningococci among isolates from patients with Neisseria meningitidis infection in Norway in recent years led to further characterization of such strains. Between 1987 and 1992, B:15:P1.12 strains constituted 9.8% (24 strains) of B:15 isolates. The B:15:P1.12 strains belonged to the electrophoretic type 5 (ET-5) complex, but 17 (71%) strains were a new clone (ET-5c) not found elsewhere in the world. All but one strain of ET-5c were responsible for a localized outbreak of systemic meningococcal disease in western Norway. A novel monoclonal antibody (202,G-12), developed against the unknown variable region 2 on the class 1 protein of one of these strains, bound to 19 of the 15:P1.12 strains, 4 strains bound the subtype P1.13 reference monoclonal antibody MN24H10.75, and the remaining strain showed no reaction. Sequencing of porA genes demonstrated a series of nine threonine residues in the deduced variable region 2 of the latter strain, while four and five threonine residues were found in the corresponding regions of strains reacting with the monoclonal antibodies 202,G-12 and MN24H10.75, respectively. Epitope mapping with synthetic peptides showed that 202,G-12 bound to a sequence of 11 amino acids which included the four threonine residues specific for subtype P1.13a. Immunoglobulin G antibodies against the P1.7,16 subtype protein, induced in volunteers after vaccination with the Norwegian meningococcal vaccine, did not cross-react on immunoblots with the subtype protein of clone ET-5c. Thus, postvaccination class 1 protein antibodies, assumed to be protective, may not be effective against infection with the new clone.

Adolescent↗
PubMed1991

Effect of outer membrane vesicle vaccine against group B meningococcal disease in Norway.

For more than 15 years, Norway has had the highest incidence of meningococcal disease in northern Europe, with 80% of cases being due to serogroup B meningococci. The case-fatality has remained high, at about 10%. In this study, an outer membrane vaccine, which had previously been shown to induce an increase in bactericidal antibodies to the parent strain, was assessed in a large-scale, randomised, double-blind trial. From October, 1988, 171,800 students in secondary schools volunteered to take part in a double-blind, placebo-controlled, efficacy trial with school as the randomisation unit. Hospitals and clinics that routinely receive patients with infectious disease were asked to report urgently all cases of suspected meningitis and/or septicaemia in 13-21-year-old students in Norway. These cases were registered and further investigated according to a detailed protocol. 89 out of the 221 cases investigated by June 3, 1991, were shown to be severe systemic disease due to group B meningococci. 36 cases in 35 schools took part in the trial (11 schools with vaccinated students and 24 with students given placebo). The calculated rate of protection was thus 57.2% (p = 0.012, one-sided test). The findings suggest that, although the vaccine conferred protection against group B meningococcal disease, the effect was insufficient to justify a public vaccination programme.

Adolescent↗
PubMed1987

Intercontinental spread of Neisseria meningitidis clones of the ET-5 complex.

The genetic structure of populations of Neisseria meningitidis was examined by an analysis of electrophoretically demonstrable allelic variation at 15 structural genes encoding enzymes in 688 isolates. Variation among strains in serogroup and serotype has little relationship to the complex structure of populations revealed by enzyme electrophoresis, which involves 14 major lineages of clones diverging from one another at more than half their genetic loci. Clones of one of these lineages, the ET-5 complex, have been identified as the causative agent of recent outbreaks and epidemics of meningococcal disease in Europe, South Africa, Latin America, and the United States. There is evidence that organisms of the ET-5 complex reached Florida via human immigrants from Cuba.

Cuba↗
PubMed1987

Endotoxin release from invasive meningococci related to sulfonamide resistance, serogroup and serotype.

The relationship between endotoxin liberation, sulfonamide resistance, serogroups and serotypes was studied in 28 Neisseria meningitidis strains isolated from patients with meningococcal disease. Sulfonamide resistance was present in 15/28 strains. 22 strains belonged to serogroup B, and 5 to group C; 1 strain was non-groupable. Free endotoxin activity in growing cultures of meningococci with endotoxin titre of greater than or equal to 10(2) was found in 27/28 strains. A high endotoxin activity was present in both sulfonamide-sensitive and -resistant invasive meningococci. A high endotoxin release with titre greater than or equal to 10(3) seemed to be more associated with serogroup C than B, and more to the serotypes 2 and 15/16 than to the non-typable strains.

Drug Resistance, Microbial↗
PubMed1986

Intercontinental spread of a genetically distinctive complex of clones of Neisseria meningitidis causing epidemic disease.

Strains of Neisseria meningitidis responsible for an epidemic of meningococcal disease occurring in Norway since the mid-1970s and for recent increases in the incidence of disease in several other parts of Europe have been identified by multilocus enzyme electrophoresis as members of a distinctive group of 22 closely related clones (the ET-5 complex). Clones of this complex have also colonized South Africa, Chile, Cuba, and Florida, where they have been identified as the causative agents of recent outbreaks of meningococcal disease. There is strong circumstantial evidence that outbreaks of disease occurring in Miami in 1981 and 1982 were caused in large part by bacteria that reached Florida via human immigrants from Cuba.

Disease Outbreaks↗
PubMed1986

Multilocus genotypes determined by enzyme electrophoresis of Neisseria meningitidis isolated from patients with systemic disease and from healthy carriers.

Variation in nine enzymes in 152 isolates of Neisseria meningitidis from Norway (118 from blood or cerebrospinal fluid of patients with systemic disease and 34 from the pharynx of healthy carriers) was analysed by starch-gel electrophoresis. All nine enzymes were polymorphic and the number of allozymes (electromorphs) identified per locus ranged from 3 to 12, with a mean of 6.1. Among the 152 isolates, 55 unique combinations of electromorphs (electrophoretic types, ETs) were distinguished. Twenty ETs were represented among the carrier isolates and 37 among the systemic isolates; hence, only two ETs were found in both groups of isolates. ET-5 was identified 67 times among the 118 systemic isolates (58%), indicating an association of this ET with invasiveness; ET-5 was also the most common type among the carrier isolates (18%). Genetic similarity between ETs was analysed by pairwise comparison of all 55 ETs with respect to the number of electromorphs by which they differed. No evidence of a general genetic difference between carrier and case isolates was found. Two well-defined clusters of ETs were observed, each including one of the two most common ETs identified among the systemic isolates (ET-5 and ET-37), together with isolates differing from them only at one or two loci. All isolates of ET-5 and ET-37, as well as their closely related variants defined by the similarity matrix, were resistant to sulphonamide, independent of their antigenic characteristics and isolation site. The extensive allozyme variation among isolates of the same serogroup demonstrated the limited value of serogrouping as an epidemiological tool. All but one isolate of serotype 15:P1.16 were electrophoretically similar, as were all the 2a:P1.2 isolates. The 15:P1.15 isolates, however, were genetically heterogeneous. The distribution of alleles in genotypes identified among the systemic isolates indicated that genetic recombination may occur in natural populations of N. meningitidis.

Aconitate Hydratase↗
PubMed1984

Differentiation of B15 strains of Neisseria meningitidis by DNA restriction endonuclease fingerprinting.

The restriction endonuclease fingerprinting technique was applied to meningococcal DNA in an attempt to identify individual strains of Neisseria meningitidis B15 (serogroup B, serotype 15), which causes approximately 90% of cases of meningococcal disease in northern Norway. Thirty representative strains (10 each from asymptomatic pharyngeal carriers, patients with septicemia, and patients with meningitis) were investigated with the restriction endonucleases Hind III and Eco RI. The 10 carrier strains showed a remarkable heterogeneity of fingerprints that rendered each strain easily distinguishable from the others. The 10 strains from the blood and the 10 from the cerebrospinal fluid showed similar but not identical restriction patterns. The results obtained with the two endonucleases were in perfect agreement. Our data suggest that a large number of different B15 clones are present in the population of northern Norway, but that only one single clone causes invasive meningococcal disease.

Carrier State↗
PubMed1984

Virulence markers in patient and carrier strains of Neisseria meningitidis.

Patient and carrier strains of Neisseria meningitidis from 2 different periods were compared with respect to serogroups, serotypes and sensitivity to sulphadiazine. The majority of 249 patient strains were resistant to sulphadiazine, and belonged to the groups A, B or C. The group B and C strains were mainly type 15/16 and 2, respectively. In contrast, most of the 400 carrier strains belonged to serotypes other than 2 or 15/16, or were non-typable, and most strains were sensitive to sulphadiazine. Among the resistant group B and C carrier strains there were more type 2 and 15/16 strains than would have been expected from the average. The virulence markers: serogroup A, B and C, serotype 2 and 15/16, and resistance to sulphadiazine, coexist in more carrier strains than would be expected if the distribution of these markers was random.

Carrier State↗
PubMed1983

Some agent characteristics and their coexistence related to occurrence and severity of systemic meningococcal disease in Norway, Winter 1981-1982.

Characteristics of 67 strains of Neisseria meningitidis causing systemic disease in Norway during the winter 1981-82 are reported and related to clinical manifestations. Included in the study were also pharyngeal isolates of meningococci collected in the same period from 35 healthy military recruits. The strains were examined for serogroup, serotype as determined with monoclonal antisera (against antigens 2a, 2b, 12, 15 and 16), and sulfonamide susceptibility. Predominating in the systemic disease material were serogroup B, serotype 15, 16 (or 15), and sulfonamide-resistant strains. This complex of characteristics also appeared to be associated with the severity of manifestations (septicemia and death). The material of meningococci from healthy carriers unassociated with cases of disease was clearly different; these strains were typically non-groupable, non-typable and sulfonamide-sensitive. The full combination of traits usually seen in strains causing systemic disease was rare in carrier isolates. The results are discussed in relation to the epidemiological development of meningococcal disease in Norway.

Humans↗
PubMed1983

Gas-chromatographic screening of capsular polysaccharides of Neisseria meningitidis.

Thirteen systemic strains, i e strains isolated from systemic infections, and 77 carrier isolates of Neisseria meningitidis were serogrouped by agglutination and analyzed by gas chromatography (GC) of phenol extracts. For systemic strains the sugar patterns were in accordance with their group-specific capsular polysaccharides (CPS). Some carrier isolates revealed unexpected GC profiles. Upon immunological retesting with new sera, GC results were generally confirmed. Occasional isolates initially serogrouped as B or Y completely lacked neuraminic acid. Some non-groupable isolates were shown by ultracentrifugation and GC to have significant amounts of this sugar likely to originate from CPS of known composition or from unknown polysaccharides. One such originally non-groupable isolate showed a weak agglutination reaction specifically with group B antiserum when reexamined. Generally, carrier isolates had lower amounts of CPS than systemic strains of the same group. Five successive isolates from one carrier were first serogrouped as X, Z or non-groupable, but they had high amounts of galactosamine and 2-keto-3-deoxy octonate, sugars characterizing CPS of serogroup 29E. These isolates were confirmed by agglutination with recently available group 29E antiserum to be of this serogroup, which has not been reported before in Norway. Ultracentrifugation revealed the presence of unknown polysaccharides containing glucose, galactose or glucosamine, but further purification of these polymers is required to determine their composition and immunological importance.

Chromatography, Gas↗
PubMed1983

Serotyping of meningococci by coagglutination with monoclonal antibodies.

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.

Agglutination Tests↗
PubMed1983

Meningococcal group B vaccine trial in Norway 1981--1982. Preliminary report of results available November 1982.

A combined serogroup B capsular polysaccharide and serotype 2a outer membrane complex meningococcal vaccine and a placebo preparation were tested double-blindly in 55 adult, male volunteers. The vaccine gave twofold increased binding antibodies, measured by ELISA, against non-capsular outer membrane antigen in 85 per cent of those vaccinated. Bactericidal antibodies towards a meningococcal serogroup C serotype 2a strain also increased fourfold or more among 85% vaccinated. New acquisition of meningococcal carriage was associated with antibody increase in one person from the placebo group.

Antibodies, Bacterial↗
PubMed1983

Untreated meningococcemia in two siblings.

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.

Adult↗