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A Halstensen

Publications and source records attributed to A Halstensen.

At least 37 records · Page 2Linked to original sources

High levels of interleukin 10 in serum are associated with fatality in meningococcal disease.

Interleukin 10 (IL-10) suppresses the production of proinflammatory cytokines in vitro and in murine models of endotoxemia and has been suggested as a candidate for treatment of bacterial septicemia. To investigate the role of IL-10 in meningococcal disease, a sandwich IL-10 enzyme-amplified sensitivity immunoassay was used to quantitate IL-10 in serum and cerebrospinal fluid samples from 41 patients with meningococcal bacteremia or meningitis with or without septic shock. High levels of IL-10 were demonstrated in sera from patients with meningococcal septic shock (mean, 21,221 pg/ml; range, 25 to 64,500 pg/ml). All cases involving fatalities had IL-10 levels in serum of > or = 1,000 pg/ml (mean, 23,058 pg/ml; range, 1,000 to 64,500 pg/ml). Patients with meningococcal meningitis without septic shock had comparably low concentrations of IL-10 in serum (mean, 119 pg/ml; range, 0 to 1,050 pg/ml) but exhibited compartmentalized release of IL-10 in cerebrospinal fluid. Concentrations of IL-10 in serum were positively correlated with the previously reported concentrations of tumor necrosis factor alpha, IL-6, and IL-8 in serum in the same patients. We conclude that IL-10 is extensively activated along with the proinflammatory cytokines during the initial phase of meningococcal septic shock and that IL-10 is associated with fatality in meningococcal disease.

Adolescent↗

Strain differentiation of Neisseria meningitidis by small-fragment restriction endonuclease analysis (SF-REA).

Following an outbreak involving 3 cases of serogroup B meningococcal disease in a rural part of Western Norway, 2 clinical and 99 carrier isolates of Neisseria meningitidis were examined by small-fragment restriction endonuclease analysis (SF-REA) using EcoRI, to determine its potential for strain differentiation. SF-REA characterized all isolates and provided reproducible results with acceptable inter-clonal differentiation. The results of SF-REA correlated well with those of serological typing and were used to determine clonal diversity and prevalence of invasive strains among the carrier isolates. SF-REA was also useful in demonstrating acquisition of a new carrier strain after eradication of the initial strain by ofloxacin. Thirty-one different restriction patterns/pattern complexes were recognized among the 101 isolates. The two clinical isolates had identical restriction patterns and showed > or = 90% similarity to those of six carrier isolates. In three out of six apparent treatment failures, successful eradication of the original strain by ofloxacin was demonstrated by SF-REA. SF-REA proved valuable in strain differentiation of Neisseria meningitidis, complemented serology, and characterized all isolates which could not be typified by serology.

Carrier State↗

Necrotising fasciitis due to group A streptococci in western Norway: incidence and clinical features.

During November, 1992, to May, 1994, 13 patients were treated at Haukeland University Hospital, Norway, for necrotising fasciitis due to group A beta-haemolytic streptococci. 3 patients died, 1 before admission. Mucoid group A streptococci were isolated from affected tissue (12 patients) and/or blood (5). Strains from 11 patients were serotype M-1 (5 patients), M-3 (2), M-6 (2), M-28 (1), and M-untypable (T-1, opacity factor negative) (1). For the 12 patients admitted alive, the following preoperative events were recorded: 8 had clinical signs of shock with systolic blood pressure of 90 mm Hg or less, 8 had impaired renal function, and 7 had biochemical markers of disseminated intravascular coagulation. At least 6 patients fulfilled the criteria for streptococcal toxic shock syndrome. Preoperative C-reactive protein was substantially raised ( > 200 mg/L) in 10 patients. The 12 patients were given high doses of antibiotics and were operated on with aggressive debridement of necrotic skin and fascia, 7 of them within 24 h of admission. The increasing incidence of necrotising fasciitis in western Norway reflects the resurgence of invasive group A streptococcal infections documented in Scandinavia since 1987. The high case-fatality rate can be reduced by early diagnosis and aggressive surgery combined with adequate antibiotic therapy.

Adult↗

Sequelae one year after meningococcal disease.

Of 99 consecutive patients with meningococcal disease, 6 died during the acute stage. The 93 survivors were examined one year after hospitalization. 21 (40%) of the adults and 6 (15%) of the children had definite sequelae, and an additional 27% and 11% possible sequelae. 6 adults (12%) and 1 child (2%) had definite neurological sequelae. Electroencephalography (EEG) abnormalities were observed in 7 adults (14%) and 2 children (5%). Epileptogenic activity was present in 3 of these, but none had experienced seizures. 8 adults (19%) and 5 children (14%) had sensorineural hearing loss or impaired vestibular function. Cerebral computerized tomography (CT) scan showed definite and possible abnormalities in 1 (3%) and 6 (18%), respectively, of the 34 patients tested. Neuropsychological tests were performed in 9 patients, 2 of these showed definite impairment. The frequency of neurological abnormalities was higher than in many previous studies, probably reflecting the more comprehensive examinations performed in the present study. However, only 3 patients had serious sequelae. The results suggest that the occurrence of sequelae after meningococcal disease is related to the severity of the acute disease. This may explain the higher rate of sequelae in adults, who have a higher proportion of seriously ill patients. The presence of meningitis is not required for the occurrence of neurological sequelae.

Adolescent↗

Mixed bacteremia with Vibrio metschnikovii in an 83-year-old female patient.

An 83-year-old woman suddenly fell ill and was admitted to the hospital on suspicion of a heart attack. After admission she developed high fever, chills and malaise. Vibrio metshnikovii and Staphylococcus hominis were isolated from 2 separately obtained blood cultures. One of the cultures also yielded Escherichia coli. The patient's condition improved rapidly after treatment with ampicillin intravenously. To our knowledge, this is the fourth reported case of V. metschnikovii bacteremia in humans.

Aged↗

Interleukin-8 in serum and cerebrospinal fluid from patients with meningococcal disease.

To evaluate the role of interleukin (IL)-8 in meningococcal disease, a solid-phase double-ligand ELISA was used to quantitate IL-8 in sera and cerebrospinal fluid (CSF) from patients with meningococcal meningitis, bacteremia, or both with or without septic shock. IL-8 was demonstrated in sera from 28 of 62 patients; levels were significantly higher in patients with septic shock without meningitis (median, 36.1 ng/mL) than in patients with other manifestations (median, < 0.02 ng/mL), and 4 of 5 patients who died had high levels. IL-8 was detected in all 27 CSF samples. Serum IL-8 levels correlated highly significantly with those of IL-6 (r = .83) and tumor necrosis factor (TNF; r = .64), while the correlations between corresponding CSF levels were less pronounced (r = .43 and r = .38, respectively) but still significant. Serum IL-8 levels were highest in patients with a symptom history < 12 h. The elimination rate of IL-8 from serum varied and was similar to that of IL-6 and TNF. IL-8 appears to participate in the complex cytokine network during the initial phase of systemic meningococcal infections.

Adolescent↗

Cross-reacting serum opsonins to meningococci after vaccination.

The opsonic activity of sera from healthy volunteers immunized with an outer membrane vesicle vaccine prepared from a Neisseria meningitidis (class 3, 44/76, B:15:P1.7,16), characteristic of the present Norwegian epidemic, has been examined. A marked increase in the phagocytosis of class 3 and nontypeable strains of different serogroups, serotypes, and serosubtypes was demonstrated in the presence of postvaccination sera. Sera from vaccinees also caused a significant increase in leukocyte oxidative metabolism as measured by luminol-enhanced chemoluminescence during phagocytosis of class 3 and nontypeable meningococci. An increase in serum opsonins cross-reacting with class 2 (type 2a) meningococci of different serogroups was not observed, suggesting that future meningococcal outer membrane vesicle vaccine preparations should contain both class 2 and class 3 porins in geographic areas where both class 2 and class 3 strains cause disease.

Antibodies, Bacterial↗

Use of single-dose ofloxacin to eradicate tonsillopharyngeal carriage of Neisseria meningitidis.

After an outbreak of three cases of serogroup B meningococcal disease at a Norwegian college, 84 of 392 (21%) subjects were tonsillopharyngeal carriers of Neisseria meningitidis. To eradicate meningococcal carriage, 80 volunteers received a single dose of 400 mg of ofloxacin. Three days after treatment, all 75 evaluable volunteers were culture negative for N. meningitidis, and after 7 days none carried the strain that they carried initially, as judged by DNA fingerprinting. A single dose of ofloxacin was found to be 97.2% effective in eradicating carriage of N. meningitidis for a period of 33 days. The carriage acquisition rate among treated students was four times higher than that among nontreated noncarriers (P = 0.02). After ofloxacin treatment, no case of meningococcal disease occurred for 6 months. Ofloxacin may thus prevent the outbreak and spread of meningococcal disease.

Carrier State↗

Spectrum of disease in bacteraemic patients during a Streptococcus pyogenes serotype M-1 epidemic in Norway in 1988.

All 87 known cases of bacteraemia due to Streptococcus pyogenes (beta-haemolytic group A streptococci) occurring during the peak of a nationwide outbreak in Norway (population 4.2 million) between January and June 1988 were reviewed. Clinical features varied widely and appeared largely to be dependent on the patients' age. The case fatality rate ranged from 11% in the age group under 30 years to 44% in patients over 60 years. Clinical complications such as shock, severe renal or respiratory failure or serious local infection occurred particularly in 30-to 59-year old individuals. Shock was manifest in 32% of the patients and carried a 68% case fatality rate. Chronic heart disease in the elderly and pneumonia seemed to be associated with a fatal outcome. In the 25 patients (29%) who died the disease showed a fulminant course, 80% dying within 48 hours after admission. However, 56% of the patients had experienced symptoms for more than two days before admission, suggesting that early diagnosis and treatment might possibly have prevented the development of a serious disease. This study revealed a wide spectrum of clinical manifestations in bacteraemia cases in a unique epidemiological situation caused largely by a single serotype of Streptococcus pyogenes; 89% of the 27 preserved bacteraemia strains carried the M-1 antigen. The observations call attention to the ability of these organisms to cause fulminant clinical illness, indicating a probable increase in both invasiveness and toxicity of group A streptococci responsible for the epidemic.

Adolescent↗

Cross-reacting serum opsonins in patients with meningococcal disease.

We have examined the opsonic activity of sera from patients with Neisseria meningitidis (B:15:P1.16) infections against different meningococcal strains, using flow cytometry and luminol-enhanced chemiluminescence. A marked increase in the phagocytosis of ethanol-fixed meningococcal strains of different serogroups, serotypes, and serosubtypes was demonstrated in the presence of convalescence sera compared with acute sera. Convalescence sera also caused a significant increase of leukocyte oxidative metabolism during phagocytosis, as measured by luminol-enhanced chemiluminescence. The sera contained a broad range of opsonins cross-reacting with serogroup A, B, C, W-135, and Y meningococci of different serotypes and serosubtypes, indicating that the cross-reacting opsonins recognized surface epitopes other than those determined by current serotyping schemes.

Adolescent↗

ELISA test for antimeningococcal IgG and IgM antibodies: application to epidemiology and diagnosis.

We have developed an enzyme-linked immunosorbent assay (ELISA) in order to quantitate antimeningococcal IgM and IgG serum antibodies. The B:15 meningococcal strain was used as coating antigen, and class specific antibodies were detected by using alkaline phosphatase labelled rabbit anti-human IgM or IgG as conjugate. The specific IgG activity was higher in sera from healthy meningococcal carriers than non-carriers, but the difference was not statistically significant. Antimeningococcal IgM serum antibodies were more frequent in carriers that in non-carriers. Acute sera from 34 patients with fulminant meningococcal disease contained less specific IgG and had a higher prevalence of IgM than healthy carriers and non-carriers. By combining measurement of antimeningococcal IgG and IgM antibodies in both acute and convalescent sera 15/18 meningococcal patients demonstrated an increase in either IgG and IgM antibodies during the hospital stay, giving a sensitivity of 83%. 8/118 individuals without meningococcal disease had detectable specific IgM antibodies in their serum, giving a clinical specificity of the test of 93%. We conclude that quantitation of specific IgG antimeningococcal antibodies by a whole bacteria ELISA test may be a useful test for the study of immunity against meningococcal disease in single individuals as well as in epidemiological studies. The combined use of the IgG and IgM tests is helpful in the diagnosis of meningococcal disease when blood or cerebrospinal fluid cultures are negative.

Antibodies, Bacterial↗

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↗

Current understanding of the pathogenesis of gram-negative shock.

There is increasing evidence that gram-negative bacteria via endotoxin induce the excessive production of inflammatory cytokines, which are active in the pathogenesis of septic shock, multiorgan failure, and ARDS. In animals the injection of TNF induces pathophysiologic and histopathologic changes that are characteristic of the septic shock syndrome, and in patients there is a close association between levels of TNF and the severity of the shock. IL-1 and IFN-gamma markedly potentiate the toxic TNF effects in animal experiments. IL-6 is frequently released into serum during septic shock, and its levels are associated with the severity of the shock. The cytokine is probably not directly involved in the pathogenesis of the shock but may contribute to fever, neutrophilia, and production of acute-phase proteins. Endothelial cells and neutrophils are important target cells for the cytokines in mediation of septic shock and late complications. Underlying conditions like cancer, trauma, burns, and other kinds of stress may alter the induction mechanism of the cytokines and the susceptibility of the organism. The pathogenetic significance of TNF and other cytokines in different categories of septic shock remains to be clarified.

Animals↗

The Norwegian meningococcal serogroup B outer membrane vesicle vaccine protection trials: case tracing, meningococcal antigen detection and serological diagnosis.

A survey is given of the efforts made to inform the general public, the potential vaccinees and their parents, and the health care personnel about meningococcal disease in general and the vaccination trial in particular, as a preparation for the meningococcal outer membrane vesicle serogroup B vaccine (MenB-vaccine "Folkehelsa") trials in secondary school students and military conscripts in Norway. Our case reporting system, supplementing the official notification, concerning even vaguely suspected cases in the age cohorts involved, is described. The efforts made to collect clinical material as well as laboratory and clinical data from 221 registered suspected cases are delineated. We also briefly summarize our cerebrospinal fluid antigen detection methods and diagnostic meningococcal serology work on these suspected cases. The compiled information on findings done at the admitting hospital of the possible cases and the additional diagnostic data provided at the National Institute of Public Health were put at the disposal of the independent Diagnosis Review Committee (DRC) as a basis for their diagnostic decisions before code opening for the meningococcal serogroup B outer membrane vesicle vaccine protection trial 3 June 1991.

Bacterial Capsules↗

Serum opsonins to serogroup B meningococci after disease and vaccination.

In this review the results of three previous studies are compared and discussed. Sera from 101 patients with meningococcal disease and from 113 volunteers immunized twice with vaccine preparations against serogroup B meningococci were examined for antimeningococcal opsonic activity using a chemiluminescence (CL) method. Twelve groups of vaccinees were immunized twice with one of four different doses of an outer membrane vesicle (OMV) preparation either alone or complexed to serogroup C polysaccharide and/or the adjuvant Al(OH)3. The OMV vaccine strain (44/76) was a patient isolate characterized as B:15:P1.16. The 89 surviving patients and 97/113 volunteers responded with significantly increased opsonic activity to the vaccine strain. Sera from all vaccinees with low preimmunization levels demonstrated a significant postimmunization increase in opsonic activity. The vaccine response was dose related, and the second injection induced a booster response in those who received preparations containing Al(OH)3. At 26 weeks a reduction in opsonic activity to preimmunization levels was noted in 19/97 previous responders. The reduction was less pronounced in those who were immunized with the higher doses. Using CL and flow cytometry we found vaccinee sera to show cross reacting opsonin responses to other serogroups and serotypes of meningococci except meningococci of serotype 2a and 2b. The increase in antimeningococcal opsonins after vaccination suggests that the serogroup B OMV vaccine may induce protection against clinical disease.

Adolescent↗