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On 10. March 2006 , The Norwegian Food Safety Authority (Mattilsynet) decided that, on the basis of VKM’s previous risk assessment (2005), Nutramigen 1 with Lactobacillus rhamnosus GG (LGG) could not be marketed in Norway as medical foods for infants (0-4 months). In addition, The Norwegian Food Safety Authority (Mattilsynet) decided (08. November 2006) to withdraw permission for marketing of Nutramigen 2 with LGG, which is a milk supplement for infants aged between 4 and 6 months, with cow’s milk and soy protein allergy. On 13. December 2006, Mead Johnson Nutritionals appealed against this decision from The Norwegian Food Safety Authority (Mattilsynet). The Norwegian Food Safety Authority forwarded the appeal from the companies, asked the VKM Panel on biological hazards and the VKM Panel on nutrition, dietetic products, novel food and allergy, for a new risk assessment including the new data provided in the appeal. LGG is one of the most studied probiotic strains. Lactic acid produced by LGG in the human gut results in a decrease in faecal pH, which in turn inhibits colonisation by potentially pathogenic bacteria. Short-term beneficial effects from administration of LGG to infants and young children with infectious diarrhoea have been reported in a number of studies, but a prophylactic effect on diarrhoea has not been documented. Furthermore, whilst some studies have reported a prophylactic, or even a curative, effect of LGG on atopic eczema in young children, more recent studies do not report such effects. Some even suggest an increased incidence of allergic sensitization in children receiving LGG supplemented formula at an early age. There are no published data that demonstrate long-term clinical benefits of infant formula supplemented with LGG for children between 4 months and 3 years, although no immediate deleterious effects of LGG have been found. Possible long-term effects of LGG on intestinal colonisation, and its effects on long-term gastrointestinal and immune functions, are not known. LGG, as an ingredient in infant formula and baby foods, is intended for daily use in the target group, and not for short-term, specific treatment. Furthermore, the targeted consumer group includes children below the age of twelve months. These two aspects demand particular consideration with regard to the unknown effects of long-term treatment with large doses of live bacteria on the ecology of the microbiota of the gastrointestinal tract and on the immune system. Neither of these systems is fully matured in infants and small children, and therefore may be particularly susceptible. There is no documented prophylactic effect of LGG on any disease in children. The effect of treatment with LGG-supplemented formula in small children is questionable, except for a documented short-term effect on infectious diarrhoea. Panel on Biological Hazards and Panel on nutrition, dietetic products, novel food and allergy at the Norwegian Scientific Committee for Food Safety find that the data available are not sufficient to support the suggested beneficial effects, or the safety, of LGG in infant formula and baby foods for children aged between 4 months and 3 years, when the products are intended for daily use.

The Norwegian Scientific Committee for Food Safety (VKM) has appointed an ad hoc-group of experts to answer a request from the Norwegian Food Safety Authority regarding benefit and risk assessment of B. lactis Bb12 in baby foods focusing on the age groups 4-6 months, 612 months and 1-3 years. This assessment is based on the literature provided by the notifier as well as that found by a MEDLINE search. An notification for use of processed cereal-based baby foods (from now on called cereals) intended for infants and small children supplemented with the microorganism Bifidobacterium lactis (B. lactis) Bb12 in Norway initiated this work. Studies of potential hazards and positive health effects from cereals containing B. lactis Bb12 intended for infants and young children have not been reported in the available literature. However, reports on safety of and positive health effects from infant and follow on formula supplemented with B. lactis Bb12 are available and have been assessed by VKM. In most of these clinical studies B. lactis Bb12 was administered in combination with other probiotic strains. Clinical studies report no serious adverse events of infant formula supplemented with B. lactis Bb12. The effect of long term daily consumption of such supplemented formula by the actual age groups is not known. A few studies have demonstrated some effect of supplementing baby food with probiotics, including B. lactis Bb12, on diarrhoea and atopic eczema while other studies do not show such effects. Thus, the scientific evidence for a favourable effect of supplementing formula or solid food with B. lactis Bb12, is weak and in some cases lacking. There are no studies demonstrating a positive effect of cereals supplemented with B. lactis Bb12 intended for infants and small children. Several health claims related to probiotics have been assessed by EFSA, including claims on reduction of gastro-intestinal discomfort, normal functioning of the alimentary tract, building of the natural intestinal barrier, improvement of the general immunity, mental and cognitive developments of children and immune system of children during growth. In the opinions so far, EFSA has concluded that a cause and effect relationship has not been established between the consumption of the probiotic containing products and the claimed effect. None of the products assessed so far contained B. lactis Bb12 (1 November 2009). Commercially produced cereals are frequent given to infants and small children in Norway from an early age and this is particularly important for the establishment of the intestinal bacterial flora and the development of the intestinal mucosal immune system. According to the notifier, one portion (25gram) of the cereal powder contains 1 x 109 B. lactis Bb12 in monoculture. Taking into consideration that the daily intake is often greater than one portion of cereals, even in infants below 6 months of age, this would represent a daily intake of 1-2 x 109 cfu B. lactis Bb12 for an infant 4-6 months and even more in infants above 6 months. If a considerable amount of the B. lactis Bb12 survives the transport to the small intestine, it would represent a dominating and monocultural supply, often several times a day, to the small intestine. The immaturity and vulnerability of the intestinal microbiota and the immune system makes the two lowest age groups, 4 – 6 and 6 – 12 months, at the highest risk of unwanted health effects due to the daily intake of probiotics.

Source at https://doi.org/10.1371/journal.pone.0187618 We prospectively studied the consequences of extensive antibiotic treatment on faecal carriage of antibiotic-resistant enterobacteria in a cohort of children with cystic fibrosis (CF) and a cohort of children with cancer compared to healthy children with no or low antibiotic exposure. The study was conducted in Norway in a low resistance prevalence setting. Sixty longitudinally collected faecal samples from children with CF (n = 32), 88 samples from children with cancer (n = 45) and 127 samples from healthy children (n = 70) were examined. A direct MIC-gradient strip method was used to detect resistant Enterobacteriaceae by applying Etest strips directly onto agar-plates swabbed with faecal samples. Whole genome sequencing (WGS) data were analysed to identify resistance mechanisms in 28 multidrug-resistant Escherichia coli isolates. The prevalence of resistance to third-generation cephalosporins, gentamicin and ciprofloxacin was low in all the study groups. At inclusion the prevalence of ampicillin-resistant E. coli and trimethoprim-sulfamethoxazole-resistant E. coli in the CF group compared to healthy controls was 58.6% vs. 28.4% (p = 0.005) and 48.3% vs. 14.9% (p = 0.001), respectively, with a similar prevalence at the end of the study. The prevalence of resistant enterobacteria was not significantly different in the children with cancer compared to the healthy children, not even at the end of the study when the children with cancer had been treated with repeated courses of broad-spectrum antibiotics. Children with cancer were mainly treated with intravenous antibiotics, while the CF group mainly received peroral treatment. Our observations indicate that the mode of administration of antibiotics and the general level of antimicrobial resistance in the community may have an impact on emergence of resistance in intestinal enterobacteria during antibiotic treatment. The WGS analyses detected acquired resistance genes and/or chromosomal mutations that explained the observed phenotypic resistance in all 28 multidrug-resistant E. coli isolates examined.

In Norway, initial treatment of febrile neutropenia (FN) has traditionally been benzylpenicillin plus an aminoglycoside. Internationally, FN is often treated with a broad-spectrum β-lactam antibiotic. We aimed to compare these two regimens in a prospective, randomized, trial in patients with lymphoma or leukaemia with an expected period of neutropenia ≥7 days, and a suspected bacterial infection.Adult neutropenic patients with lymphoma or leukaemia, and a suspected bacterial infection, were randomized for treatment with benzylpenicillin plus an aminoglycoside or meropenem. The primary endpoint was clinical success, defined as no modification of antibiotics and clinical stability 72 h after randomization.Among 322 randomized patients, 297 proved evaluable for analyses. Fifty-nine per cent (95% CI 51%-66%), (87/148) of the patients given benzylpenicillin plus an aminoglycoside were clinically stable, and had no antibiotic modifications 72 h after randomization, compared with 82% (95% CI 75%-87%), (122/149) of the patients given meropenem (p0.001). When the antibiotic therapy was stopped, 24% (95% CI 18%-32%), (36/148) of the patients given benzylpenicillin plus an aminoglycoside, compared with 52% (95% CI 44%-60%), (78/149) of the patients given meropenem, had no modifications of their regimens (p0.001). In the benzylpenicillin plus an aminoglycoside arm, the all-cause fatality within 30 days of randomization was 3.4% (95% CI 1.2%-7.9%), (5/148) of the patients, compared with 0% (95% CI 0.0%-3.0%), (0/149) of the patients in the meropenem arm (p 0.03).Clinical success was more common in FN patients randomized to meropenem compared with the patients randomized to benzylpenicillin plus an aminoglycoside. The all-cause fatality was higher among the patients given benzylpenicillin plus an aminoglycoside.

The occurrence of antibiotic resistance and the use of broad-spectrum antibiotics are relatively low in Norway. The national recommendation in febrile neutropenia (FN) is prompt initial therapy with penicillin G plus an aminoglycoside. We sought to evaluate the evidence behind this recommendation.We did a literature search in Medline and EMBASE with search terms penicillin, aminoglycoside and febrile neutropenia.Seven Norwegian studies (six adult and one pediatric) conducted over the last 25 years were identified. They all conclude that penicillin G plus an aminoglycoside are effective and safe initial empiric antibiotic therapy in FN provided the regimen is modified if the clinical response is unsatisfactory. Overall 40-50% of the patients required only penicillin G and an aminoglycoside during their FN episode. The overall fatality rate was similar in the Norwegian and in international studies.Many countries use a broad-spectrum β-lactam as initial therapy in FN. International experts are sceptic towards the Norwegian recommendations. We discuss the arguments for and against penicillin G plus an aminoglycoside in FN. The main arguments to continue the Norwegian treatment tradition are the satisfactory clinical results and the reason to believe that it contributes to the low levels of antibiotic resistance in Norway.

A longitudinal, prospective study was conducted intermittently in Norway, from 1999 to 2008, to investigate the Candida colonization rates and species distributions in the tonsillopharyngeal and faecal flora in: (i) children with cancer; (ii) children with cystic fibrosis (CF); and (iii) healthy children. The effect of antibiotic treatment on Candida colonization was also studied, and we looked for changes in antifungal susceptibility over time within each child and between the different groups of children. In total, 566 tonsillopharyngeal swabs and 545 faecal samples were collected from 45 children with cancer, 37 children with CF, and 71 healthy, age-matched controls. The overall colonization rate with Candida was not significantly higher in the two groups of children undergoing extensive treatment with broad-spectrum antibiotics than in healthy controls. Approximately one-third of the cancer patients had a total lack of Candida colonization or had only one Candida-positive sample, despite multiple samples being taken, treatment with broad-spectrum antibiotics, long hospital stays, and periods with neutropenia. Children with CF had the highest prevalence of Candida albicans. Amoxycillin, azithromycin, thirdgeneration cephalosporins and oral vancomycin resulted in a significantly increased Candida colonization rate. Phenoxymethylpenicillin, second-generation cephalosporins, metronidazole, trimethoprim–sulphamethoxazole, ciprofloxacin, penicillinase-resistant penicillins and inhaled tobramycin or colistin showed minimal effects on the Candida colonization rate. We found no evidence of development of antifungal resistance over time.

We evaluated inflammatory markers in febrile neutropenic lymphoma patients undergoing high-dose chemotherapy with autologous stem cell support. Based on MASCC scores, our patients had a low risk of serious complications and a perspective of a benign initial clinical course of the febrile neutropenia. We also studied the impact of tobramycin given once versus three times daily on these immune markers. Sixty-one patients participating in a Norwegian multicentre prospective randomized clinical trial, comparing tobramycin once daily versus three times daily, given with penicillin G to febrile neutropenic patients, constituted a clinically homogenous group. Four patients had bacteraemia, all isolates being Gram-positive. Thirty-two patients received tobramycin once daily, and 29 patients received tobramycin three times daily. Blood samples were taken at the onset of febrile neutropenia and 1-2 days later. All samples were frozen at -70 °C and analysed at the end of the clinical trial for C-reactive protein (CRP), procalcitonin (PCT), complement activation products, mannose-binding lectin (MBL) and 17 cytokines. We found a mild proinflammatory response in this series of patients. CRP was non-specifically elevated. Ten patients with decreased MBL levels showed the same mild clinical and proinflammatory response. Patients receiving tobramycin once daily showed a more pronounced proinflammatory response compared with patients receiving tobramycin three times daily. Overall, febrile neutropenic cancer patients with a benign clinical course show a mild proinflammatory immune response.

In July 2006, the seven-valent pneumococcal conjugate vaccine (PCV7) was introduced in Norway with a reduced (2 doses + 1 boost) dose schedule. Post-PCV7 shifts in pneumococcal reservoirs were assessed by two point prevalence studies of nasopharyngeal colonization among children in day care centers, before (2006) and after (2008) widespread use of PCV7. Nasopharyngeal swabs were obtained from 1,213 children, 611 in 2006 and 602 in 2008. A total of 1,102 pneumococcal isolates were recovered. Serotyping, multilocus sequence typing, and antimicrobial drug susceptibility testing were performed on all isolates. Although carriage of PCV7 serotypes decreased among both vaccinated and unvaccinated children, the overall prevalence of pneumococcal carriage remained high (80.4%) after vaccine introduction. The pneumococcal populations were diverse, and in the shift toward non-PCV7 serotypes, expansion of a limited number of established clonal complexes was observed. While non-antimicrobial-susceptible clones persisted among PCV7 serotypes, antimicrobial resistance did not increase among non-PCV7 serotypes. Direct and indirect protection of PCV7 against nasopharyngeal colonization was inferred from an overall decrease in carriage of PCV7 serotypes. No preference was found for nonsusceptible clones among the replacing non-PCV7 serotypes.

A major virulence factor of group A streptococci (GAS) is the M protein. Strains with the M3 type are more often associated with necrotizing fasciitis (NF) and streptococcal toxic shock syndrome, and have a higher case fatality rate than strains of other M types. To better understand the epidemiology of M3 GAS strains in Norway, we analyzed 59 invasive and 69 pharyngeal isolates with respect to prophage content, allelic variation in emm3, mtsR encoding the metal transporter of Streptococcus repressor (mtsR), and sclB coding for streptococcal collagen-like protein B. The Norwegian emm3 strains were very homogeneous, mainly harboring the emm allele 3.1 and prophage profile PhiG3.01. Other prophage profiles were transient. The mutation in mtsR known to truncate the protein and result in decreased capacity to cause NF was not found in our isolates. The sclB gene usually harbored five or eight contiguous repeats of a CAAAA pentanucleotide sequence and a highly modular and variable collagen structural motif (CSM) region with 9 and 12 amino acid M3-specific conserved motif repeats distributed across the entire CSM region. Strains with 5 CAAAA repeats emerged in 1993 and these strains were associated with the increase in invasive M3 cases in the period 1993-2003.

Aim: To investigate the epidemiology and clinical characteristics of community acquired pneumonia (CAP) in children before the introduction of the 7-valent pneumococcal vaccine in the national vaccination programme. Methods: For the period 21 May 2003 to 20 May 2005 hospitalization rates for pneumonia in children were obtained from retrospective studies of medical journals. Pneumonia was also studied prospectively in children less than sixteen years old referred to Ulleval University Hospital (Oslo) in the same time period. Results: The overall observed hospitalization rate of pneumonia was 14.7/10 000 (95% CI: 12.2–17.1), for children under five it was 32.8/10 000 (95% CI: 26.8–38.8), and for children under two 42.1/10 000 (95% CI: 32.0–52.3). In the clinical study 123 children, of whom 59% (73) were boys, met the inclusion criteria and were enrolled. Only 2.4% (3) had pneumonia complicated with pleural effusion and in general few complications were observed. No patients required assisted ventilation, and none were transferred to the intensive care unit. Penicillin was effective as treatment for pneumonia. Conclusion: Pneumonia, seen in a paediatric department in Oslo, is a common but benign disease. Penicillin is effective as treatment for pneumonia in Norwegian children.

An observational study to examine Streptococcus pneumoniae carriage in Norwegian children was initiated after two cases of pneumococcal meningitis, caused by the England(14)-9 clone, occurred in one day-care centre in Oslo. All children recruited from the day-care centre where the cases occurred were vaccinated with a seven-valent pneumococcal conjugate vaccine; the other participants who attended three other day-care centres nearby were not. The children were followed for 9 months, and three samplings took place. At the first visit, 45.7% of the children were colonised by pneumococci in the nasopharynx. The children harboured a variety of serotypes, with serotypes 6A, 23F, 6B and 19F being the most frequent. The numbers of children carrying vaccine serotypes decreased in both the vaccinated and the non-vaccinated groups. Thus, no significant effect of vaccine on carriage was detected in this relatively small study.

Norway has a low prevalence of antimicrobial resistance, including macrolide-resistant Streptococcus pneumoniae (MRSP). In a nationwide surveillance program, a total of 2,200 S. pneumoniae isolates were collected from blood cultures and respiratory tract specimens. Macrolide resistance was detected in 2.7%. M-type macrolide resistance was found in 60% of resistant isolates, and these were mainly mef (A)-positive, serotype-14 invasive isolates. The erm (B)-encoded macrolide-lincosamide-streptogramin B (MLS B ) type dominated among the noninvasive isolates. One strain had an A2058G mutation in the 23S rRNA gene. Coresistance to other antibiotics was seen in 96% of the MLS B -type isolates, whereas 92% of the M-type isolates were susceptible to other commonly used antimicrobial agents. Serotypes 14, 6B, and 19F accounted for 84% of the macrolide-resistant isolates, with serotype 14 alone accounting for 67% of the invasive isolates. A total of 29 different sequence types (STs) were detected by multilocus sequence typing. Twelve STs were previously reported international resistant clones, and 75% of the macrolide-resistant isolates had STs identical or closely related to these clones. Eleven isolates displayed 10 novel STs, and 7/11 of these “Norwegian strains” coexpressed MLS B and tetracycline resistance, indicating the presence of Tn 1545 . The invasive serotype-14 isolates were all classified as ST9 or single-locus variants of this clone. ST9 is a mef -positive M-type clone, commonly known as England 14 -9, reported from several European countries. These observations suggest that the import of major international MRSP clones and the local spread of Tn 1545 are the major mechanisms involved in the evolution and dissemination of MRSP in Norway.

Scand J Prim Health Care 2004;22:239/243. ISSN 0281-3432 Objective / The objectives of this study were to explore how frequently group A streptococci (GAS) were giving additional cases of clinical GAS tonsillitis within the households and to analyse predictors for such spread of GAS infection. Setting / Two Norwegian general practice populations in Stokke and Kongsberg communities. Patients / 110 households with at least one member with sore throat lasting less than 7 days, and GAS demonstrated in throat culture. Among the 110 index patients 51 (46%) were parents, 35 mothers and 16 fathers; 23 were children 6 years and younger, while 36 were children aged 7/15 years. Main outcome measures / Frequency of spread of clinical GAS infection to another household member within 4 weeks. Distribution of age and size of household in families with and without spread of GAS infection. Results / In 30 (27%) households one or more new cases of GAS tonsillitis was found, adding 40 new infections. No spread of GAS disease was found in households with only adult members. A significantly higher proportion of spread was found in households with 4 or more members compared with households with fewer members, and low age of the index person. Short duration of symptoms before seeing a doctor was also associated with spread of GAS. In a logistic regression analysis carried out in the households with children, short duration of symptoms before diagnosis and treatment and low age of index person were significantly associated with spread of the infection. Conclusions / Even with standard penicillin treatment, GAS infection is frequently spread within households, and most frequently in households with children and many members.

To compare an antigen detection test (GAS antigen test) with the results from combinations of two various bacteriological test media in general practice patients with sore throat. Furthermore to assess the diagnostic properties of the chosen GAS antigen test and to compare semi-quantitative results of this test with the bacterial load found in the throat culture.Two Norwegian general practices in Stokke and Kongsberg communities.306 patients with sore throat lasting less than 7 days; 244 were adults, 62 were children under 10 years old, mean age 23.9 years (SD 15.0), 40% were men.Results from GAS antigen test, and distribution of bacteriological findings in throat cultures, compared with the results of our GAS antigen test; semi-quantitative results of the GAS antigen test compared with the bacterial load by culture.In the primary culture 110 patients harboured group A streptococci (GAS) infection, while the second culture identified another 17, giving a total of 127 patients. Some 33 patients harboured large-colony groups C and G. The GAS antigen test used had a sensitivity of 97% and specificity of 95% regarding GAS when compared with the two cultures. We found a significant correlation between the bacterial loads by culture and the semi-quantitative results of the GAS antigen test.By using a second, different set of bacteriological media, we identified an additional 17 patients with GAS infections. This raises the question of validity of frequently used reference standards in studies related to streptococcal infections. Compared with the combined results of the two throat cultures, the GAS antigen test used showed high sensitivity and specificity. Semi-quantitative evaluations of the rapid immunological test may also be of clinical value.

Objective To analyze plasma interferon-gamma and interleukin-10 concentrations in patients with systemic meningococcal disease and patients with severe Gram-positive septic shock caused by Streptococcus pneumoniae or Staphylococcus aureus. To study the in vitro cytokine (interferon-gamma and interleukin-10) responses in a whole blood model boosted with heat-killed Neisseria meningitidis, S. pneumoniae, and S. aureus before and after treatment with recombinant interleukin-10 or recombinant interferon-gamma. Design Experimental study. Setting Laboratory. Subjects Plasma samples were collected from patients with systemic meningococcal disease (n = 66) and patients with severe Gram-positive septic shock caused by S. pneumoniae (n = 4) or S. aureus (n = 3). Interventions Whole blood was boosted with heat-killed N. meningitidis, S. pneumoniae, and S. aureus (1 x 106 colony forming units/mL), and plasmas were analyzed for interleukin-10 or interferon-gamma at 0, 5, 12, and 24 hrs. Furthermore, recombinant interleukin-10 or recombinant interferon-gamma was added before bacteria, and the effect on the secretion of interferon-gamma and interleukin-10, respectively, was analyzed after 24 hrs. Measurements and main results The median concentration of interferon-gamma was 15 pg/mL and of interleukin-10 was 10,269 pg/mL in patients with meningococcal septic shock (n = 24) compared with median interferon-gamma concentration of 3400 pg/mL and interleukin-10 concentration of 465 pg/mL in patients with severe Gram-positive shock (p =.001). Increased interferon-gamma concentrations were associated with case fatality (p =.011). In a whole blood model we demonstrated that 1 x 106 colony forming units/mL of N. meningitidis induced more interleukin-10 but less interferon-gamma than S. pneumoniae. S. aureus induced minimal secretion of both cytokines. Recombinant interleukin-10 efficiently down-regulated the secretion of interferon-gamma, and vice versa, as shown in a whole blood model. Conclusion We speculate whether high concentrations of interleukin-10 contribute to the low concentrations of interferon-gamma in fulminant meningococcal septicemia. In addition, it appears as if interferon-gamma plays a minor role in the pathophysiology of meningococcal septic shock.

Flow cytometry was used to study the expression of leukocyte adhesion molecules CD 11a, CD 11b, CD11c, CD14, and CD62L (L-selectin) and production of reactive oxygen species (ROS) in an ex vivo human whole-blood system stimulated with lipopolysaccharide-containing outer membrane vesicles (LPS-OMV) from N. meningitidis. Results demonstrated a dose-dependent increase in surface expression of CD1 la, CD11b, CD11c and CD14 in granulocytes and monocytes (maximal at 30-120 min) upon OMV-LPS challenge, whereas CD62L expression was heavily downregulated (maximal at 30-120 min). The OMV-associated LPS was almost as potent (on a weight basis) as purified LPS from E. coli in inducing adhesion molecule modulation but the response was delayed. Upon stimulation with OMV-LPS or E. coli-LPS, the production of intracellular ROS increased in both granulocytes and monocytes when dihydroethidium (DHE, mainly reflecting superoxide anion) was used as a probe, whereas peroxynitrite production monitored with dihydrorhodamine 123 (DHR) was not significantly changed. The OMV-mediated modulation of leukocyte adhesion molecule expression and increased ROS production may certainly lead to increased entrapment of leukocytes in the micro-circulation and contribute to untoward inflammatory reactions as seen in systemic meningococcal disease.

The Norwegian group B meningococcal outer membrane vesicle (OMV) vaccine consists of outer membrane proteins (OMPs) as main antigens with significant amounts of lipopolysaccharide (LPS; 5-9% relative to protein). We have studied the ability of this OMV vaccine preparation to induce secretion of pro-inflammatory cytokines, tumour necrosis factor alpha (TNF-alpha), interleukin 1beta (IL-1beta), interleukin 6 (IL-6), interleukin 8 (IL-8) and anti-inflammatory cytokines, interleukin 4 (IL-4), interleukin 10 (IL-10) and interleukin 13 (IL-13) in a human whole blood model. Plasma levels of TNF-alpha, IL-1beta, IL-6 and IL-8 were massively increased; mean peak levels of TNF-alpha 44 696+/-7764, IL-1beta 38 043+/-5411, IL-6 10 057+/-1619 and IL-8 30 449+/-5397 pg/ml were obtained with an OMV-LPS concentration of 1 microg/ml; corresponding levels in control plasmas were below the detection limit of the assay. Mean maximal level of IL-10 (2540+/-144 pg/ml) was obtained at OMV-LPS concentration of 10 microg/ml, after 24 h; while the level in control plasma was below detection limit. OMV-LPS did not induce release of IL-4 and IL-13 in doses from 0.001-10 microg/ml. The present results show that OMVs from meningococci have potent pro-inflammatory properties and are likely to contribute to the observed local and systemic inflammatory effects.

The antimicrobial resistance of 809 Salmonella Typhimurium isolates collected from humans in Norway between 1975 and 1998 was studied. The material was subdivided into domestic and foreign isolates according to whether the patient had recently travelled abroad or not. In imported isolates the largest increase in resistance was in 1996 when 35% of the isolates were multi-resistant. The first multi-resistant isolate acquired in Norway appeared in 1994, but already in 1998 23% of the isolates domestically acquired were multi-resistant, and a majority were S. Typhimurium DT104. We found no ciprofloxacin resistance in domestically acquired isolates. Amplified fragment length polymorphism analysis was performed on selected multi-resistant isolates. The method discriminated well between different multi-resistant isolates, but not between DT104 isolates. Resistant and multi-resistant S. Typhimurium were until 1998 essentially recovered from patients who had travelled abroad, but multi-resistant isolates, mainly DT104, are now also being transmitted within the country.

A new sulphonamide resistant (SR) C[ratio ]15[ratio ]P1.7,16 meningococcal strain, a variant of the ET-5 clone, dominated in an outbreak of 22 cases in western Norway commencing in 1995. The first eight patients were 15–21 years old from the Nordhordland area, initiating a carrier study in the local high schools. Carriage of SR serogroup C meningococci was detected by routine methods and treated with a single dose of ofloxacin 400 mg. Of 20 treated carriers, 14 harboured the outbreak strain C[ratio ]15[ratio ]P1.7,16. Vaccination of 4000 children, adolescents and close contacts of patients was also performed. After the intervention, 14 additional cases of meningococcal disease occurred, 8 due to the outbreak strain. However, incidence rates dropped from 180 to 30 per 100000 per year in the student population, but increased from 0 to 13 in the rest of the population in Nordhordland. Carriage eradication is not generally recommended in Norway. However, tracing and treating meningococcal carriage may have reduced transmission and disease in this outbreak situation.

The infant rat infection model previously developed to evaluate protective ability of passively administered murine antibodies to group B meningococcal (MenB) surface antigens was adapted for human sera. Several challenge doses were tested, aiming at sensitive detection of protection with little interassay variability. Doses of 105 and 106 colony forming units of strain IH5341 (MenB:15:P1.7,16) injected intraperitoneally gave consistently high levels of bacteremia and meningitis developed in 6 h in 50–100% of the pups. A monoclonal antibody mAb735 to the MenB capsule, injected 1–2 h before bacterial challenge, gave full protection at a dose of 2 μg/pup. Sera from adult volunteers immunized with a MenB outer membrane vesicle vaccine reproducibly reduced bacterial counts in the blood and cerebrospinal fluid, whereas a normal human serum, lacking bactericidal and opsonophagocidal activity, was unprotective.

The aim of this study was to investigate the antibiotic resistance rates of major bacterial pathogens causing bloodstream infections in two very different types of hospital in Norway. We examined all Escherichia coli and staphylococci (330 isolates) causing bloodstream infections from one general county hospital and one specialist national cancer hospital during the periods 1991–92 and 1995–96. Minimal inhibitory concentrations (MICs) were determined using the E-test. E. coli and staphylococci constituted 46.7% of all isolates from bloodstream infections in the two hospitals. Overall, E. coli isolates were resistant to amoxicillin (21%), trimethoprim (21%), doxycycline (20%) and trimethoprim-sulphamethoxazole (17%), while Staphylococcus aureus strains were resistant to benzylpenicillin (66%). No methicillin-resistant S. aureus was detected. Coagulase-negative staphylococci were often multires-istant, but remained fully sensitive to vancomycin. For a few antibiotics, significantly more resistance was found in the specialist hospital. In our material we found no significant increase in resistance between 1991–92 and 1995–96. In conclusion, antimicrobial resistance still remains low in important bacterial pathogens causing bloodstream infections in Norway.

Outer membrane vesicle (OMV) vaccines were made from Neisseria meningitidis strain 44/76 and its two short-chain lipopolysaccharide (LPS) mutants, Mu-1 and Mu-4. Only the 44/76 vaccine contained LPS with the host antigen lacto-N-neotetraose. The protein composition of the vaccines was similar. The LPS carbohydrate chain length proved to influence drastic changes in the LPS immunogenicity as well as the outer membrane proteins (OMPs) ability to elicit functional antibodies in mice. Only LPS in the Mu-1 and Mu-4 vaccines were immunogenic, and the 44/76 vaccine differed also by not inducing antibodies to the class 4 OMP. The Mu-1 vaccine, with a LPS carbohydrate chain comprising only two residues of 2-keto-3-deoxy-octonic acid, induced lower bactericidal activity and less antibodies to the class 1 OMP, compared to the two other vaccines. This indicates that LPS of a certain carbohydrate chain length is required for adequate exposure of the class 1 OMP epitopes essential for inducing bactericidal antibodies.

Three outbreaks of meningitis caused by Neisseria meningitidis serogroup A (subgroup III) are described: Niger (1991), Burundi (1992), and Guinea (1993). These outbreaks showed unusual characteristics: a shorter inter-epidemic interval (Niger), unusual geographical location outside the meningitis belt (Burundi and Guinea), and high age-specific attack rates in all age groups (Burundi and Guinea). Mass immunization campaigns mobilized considerable human and financial means (US$ 322000 and 3000 person-days of work for health personnel to immunize 629000 people in Guinea). The vaccination coverage was over 80% in densely populated areas (Burundi and urban Guinea), but below 50% in less populated areas ( 24 27 and 26 30 sub-districts in Niger and Guinea, respectively). The preventive fraction (proportion of cases prevented by vaccination) was substantial in Guinea (35% for a vaccine efficacy of 85%) and was higher where the campaign was initiated earlier. An ‘alert’ threshold indicating the onset of an epidemic of 15 100000 cases in one week showed good sensitivity (94%), specificity (98%) and positive predictive value (89%) in Burundi, permitting quick decision making outside the meningitis belt. These 3 meningococcal meningitis outbreaks show the need for epidemic emergency preparedness and for vigilance on the whole African continent.

In the period from May through June 1994, an increase in the number of domestic cases of Shigella sonnei infection was detected in several European countries, including Norway, Sweden, and the United Kingdom. In all three countries epidemiological evidence incriminated imported iceberg lettuce of Spanish origin as the vehicle of transmission. The outbreaks shared a number of common features: a predominance of adults among the case patients, the presence of double infections with other enteropathogens, and the finding of two dominant phage types among the bacterial isolates. In Norway 110 culture-confirmed cases of infection were recorded; more than two-thirds (73%) were adults aged 30 to 60 years. A nationwide case-control study comprising 47 case patients and 155 matched control individuals showed that the consumption of imported iceberg lettuce was independently associated with an increased risk of shigellosis. Epidemiological investigation of a local outbreak incriminated iceberg lettuce from Spain, consumed from a salad bar, as the source. The presence of shigellae in the suspected food source could not be documented retrospectively. However, high numbers of fecal coliforms were detected in iceberg lettuce from patients' homes. Three lettuce specimens yielded salmonellae. The imported iceberg lettuce harbored Escherichia coli strains showing resistance to several antimicrobial agents, including ampicillin, ciprofloxacin, gentamicin, and trimethoprim-sulfamethoxazole. During the outbreak it is likely that thousands of Norwegians and an unknown number of consumers in other countries were exposed to coliforms containing antibiotic resistance genes.

Monoclonal human IgG SS269 reacts with Neisseria meningitidis expressing the P1.7 PorA protein and with linear peptides containing NGGAS, which accounts for the P1.7 specificity. Murine monoclonal antibody to P1.7 reacts with peptides containing the overlapping epitope, ASGQ. The human and murine antibodies have similar affinities. The low avidity human antibody is very inefficient at stimulating complement-mediated bactericidal killing while the high avidity murine antibody efficiently kills bacteria. However, efficient opsonophagocytosis was mediated even at low concentrations of the human antibody and in the absence of complement, suggesting that low avidity antibodies might be protective against disease.

(1994). Increased incidence of severe group a streptococcal infections in Norway 1993-94: some obstetric aspects. Journal of Obstetrics and Gynaecology: Vol. 14, No. sup2, pp. s92-s96.

To investigate the epidemiology and clinical characteristics of community acquired pneumonia (CAP) in children before the introduction of the 7-valent pneumococcal vaccine in the national vaccination programme.For the period 21 May 2003 to 20 May 2005 hospitalization rates for pneumonia in children were obtained from retrospective studies of medical journals. Pneumonia was also studied prospectively in children less than sixteen years old referred to Ullevål University Hospital (Oslo) in the same time period.The overall observed hospitalization rate of pneumonia was 14.7/10 000 (95% CI: 12.2-17.1), for children under five it was 32.8/10 000 (95% CI: 26.8-38.8), and for children under two 42.1/10 000 (95% CI: 32.0-52.3). In the clinical study 123 children, of whom 59% (73) were boys, met the inclusion criteria and were enrolled. Only 2.4% (3) had pneumonia complicated with pleural effusion and in general few complications were observed. No patients required assisted ventilation, and none were transferred to the intensive care unit. Penicillin was effective as treatment for pneumonia.Pneumonia, seen in a paediatric department in Oslo, is a common but benign disease. Penicillin is effective as treatment for pneumonia in Norwegian children.

During June and July 2008, five cases of Legionnaires' disease (LD) were reported to the local health authorities and the Norwegian Institute of Public Health (NIPH). The patients all lived in the industrial twin cities Sarpsborg and Fredrikstad in southeast Norway. In the same area, a large outbreak of LD with 56 cases and 10 deaths had occurred in 2005. The source at the time had been traced to an industrial air scrubber at the factory of one of the world's leading suppliers of wood-based chemicals (company A). During this outbreak patients were infected up to 10km away from the source [1]. .

Invasive pneumococcal disease (IPD) is an important cause of morbidity and mortality in Norwegian children.This retrospective study included all children (under 16 years) with isolates of Streptococcus pneumoniae from a normally sterile site admitted to the Department of Paediatrics at Ullevaal University Hospital in the period 1998 to 2004. We studied the epidemiology, predisposing factors, clinical picture, antimicrobial resistance, outcome of IPD and the theoretical coverage of the 7-valent conjugate pneumococcal vaccine (PCV7) in these children. The isolates were tested for antimicrobial susceptibility, serogrouped and serotyped.68 children were identified; 31 of them had one or more predisposing factors. Six children died, all of them had a predisposing factor. Six of the seven children who survived with sequelae were previously healthy. 67 of 68 isolates were fully susceptible to benzyl penicillin and 13 isolates showed intermediate susceptibility or resistance to erythromycin. Serogroups or serotypes were obtained in 66 children. 24 (36.8%) children fulfilled the criteria for PCV7. 35 (51.1%) children had serotypes covered by the vaccine. Only 12 (17.6%) fulfilled the criteria for PCV7 and had serotypes covered by it. Four of the six children who died had serotypes covered by PCV7.Invasive pneumococcal disease is a serious condition in children and vaccination can prevent disease in many children.

In September 1988, an epidemic of meningococcal disease started in Ethiopia. 21 Neisseria meningitidis isolates recovered from patients in Addis Ababa and towns 200 km south of the capital were characterized by serogrouping, serotyping, testing of susceptibility to antibiotics, restriction endonuclease fingerprinting, and multilocus enzyme electrophoresis. The 21 isolates were essentially homogeneous for all properties tested and belonged to clone III-1 of serogroup A N. meningitidis, which was also responsible for the epidemics in Saudi Arabia in 1987 and in Sudan and Chad in 1988.

Two new methods for serogrouping of meningococci, whole-cell ELISA and dot-blotting, with monoclonal antibodies against serogroups A, B, C, Y and W135 were compared with slide-agglutination applying polyclonal sera. In addition to a panel of strains with previously determined serogroups by slide-agglutination, two strain collections of meningococci were studied: 1) 50 strains isolated from patients with systemic meningococcal disease in Norway during the winter 1987-1988; 2) 133 throat strains isolated from asymptomatic carriers over the same period. For the disease strains all three methods gave identical results, whereas some carrier strains which were non-agglutinable or polyagglutinable by slide-agglutination were serogroupable by the two other methods. All the systemic strains and about half of the carrier strains were serogroupable. We find that whole-cell ELISA and dot-blotting are specific, easy to read and more sensitive compared to slide-agglutination, but the former methods are at present limited by the availability of monoclonal antibodies against only serogroups A, B, C, Y and W135.

A marked increase in case fatality has been observed among reported cases of invasive group B streptococcal

A 2.7% prevalence of macrolide resistance in 1,657 Norwegian clinical Streptococcus pyogenes isolates was primarily due to erm (TR) (59%) and mef (A) (20%). Four clonal complexes comprised 75% of the strains. Macrolide resistance in S. pyogenes in Norway is imported as resistant strains or locally selected in internationally disseminated susceptible clones.

The present study, using robotized DNA isolation and quantitative PCR based on the Neisseria meningitidis-specific capsular transport A gene, demonstrates the ease, rapidity, specificity, and sensitivity of quantifying neisserial DNA in plasma (n = 65) and cerebrospinal fluid (CSF) (n = 12) from patients with systemic meningococcal disease. We found a close correlation between the levels of neisserial DNA and lipopolysaccharides in plasma (r = 0.905) and in CSF (r = 0.964). The median concentration of neisserial DNA in plasma in 23 patients with persistent shock was 2 x 10(7) copies/ml, versus10(3) copies/ml in 42 nonshock patients. Furthermore, quantitative PCR made possible estimates of the total number of meningococci in plasma, as opposed to conventional blood cultures, suggesting about 1,000 dead meningococci for every viable bacterium. Finally, with logistic regression analyses, neisserial DNA may predict a patient's disease severity and outcome at hospital admission. The number of meningococci in plasma and CSF appears to be the main determinant of the lipopolysaccharide levels, clinical presentation, and outcome.

Mouse monoclonal antibodies (MoAbs) of the four IgG isotypes, all specific for the P1.16 epitope on the meningcoccal PorA protein, were tested for functional activities. The avidities of the antibodies, measured by NH4SCN elution in enzyme-linked immunosorbent assay, showed similar values for all the MoAbs. The serum bactericidal activity (SBA) defined as the lowest concentration of antibodies giving 50% reduction in the number of meningococcal colony-forming units using human serum as complement, showed a hierarchy of IgG3 >> IgG2b > IgG2a >> IgG1. For the opsonophagocytosis (OP), the hierarchy was IgG3 > IgG2b = IgG2a >> IgG1. OP was measured in flow cytometry using log-phase live meningococci as target cells, normal human peripheral blood polymorphonuclear cells (PMNs) as effector cells and human serum as a complement source. The mouse MoAbs were negative in OP when using human PMNs in the absence of complement. The results demonstrate the importance of choosing the right isotype of mouse MoAbs when using them to judge the potential vaccine importance of their corresponding antigen. If such MoAbs should be used for passive vaccination against infectious diseases, the isotype would presumably play an important role for their anticipated clinical effects.

A serogroup B meningococcal outer membrane vesicle (OMV) vaccine was delivered either intranasally or intramuscularly to 12 and 10 volunteers, respectively. The mucosal vaccine was given as four weekly doses followed by a fifth dose after 5 months; each dose consisted of OMVs equivalent to 250 microg of protein. The intramuscular (i.m.) vaccine, consisting of the same OMVs but adsorbed to Al(OH)(3), was administered as three doses each of 25 microg of protein, with 6 weeks interval between first and second doses and the third dose after 10 months. Both groups of vaccinees demonstrated significant immune responses when measured as specific IgG antibodies against live meningococci, as serum bactericidal activity (SBA) and as opsonophagocytic activity. Two weeks after the last dose, the anti-meningococcal IgG concentrations were significantly higher in the i.m. group (median IgG concentration: 43.1 microg/ml) than in the intranasal group (10.6 microg/ml) (P=0.001). The corresponding opsonophagocytic activity was 7.0 and 3.0 (median log(2) titre) (P=0.001), and the SBA was 5.0 and 2.0 (median log(2) titre) (P=0.005), for the i.m. and intranasal groups, respectively. The last immunisation induced an enhanced immune response in the i.m. group, whereas the intranasal group showed no significant booster response. Accordingly, affinity maturation of anti-OMV-specific IgG antibodies was seen only after i.m. vaccination. The IgG1 subclass dominated the responses in both groups, whereas the significant IgG3 responses observed in the i.m. group were absent in the intranasal group. Although the intranasal OMV vaccination schedule used here induced functional immune responses relevant to protection, an improved vaccine formulation and/or a modified mucosal immunisation regimen may be needed to achieve a systemic effect comparable to that seen after three doses of intramuscular vaccination.

Lipopolysaccharide-containing outer membrane vesicles (OMV-LPS) which are spontaneously released from Neisseria meningitidis during logarithmic growth were studied for their ability to induce procoagulant (tissue factor), profibrinolytic (urokinase-type plasminogen activator) and antifibrinolytic (plasminogen activator inhibitor-2) factors in purified human monocytes. Cell-associated tissue factor was 5.0-fold (n=5) increased, peaking after 8 h, in the presence of OMV-LPS (1 microg/ml, final concentration). Plasminogen activator inhibitor-2 release from monocytes was maximal after 24 h OMV-LPS (1 microg/ml) stimulation and 13.7-fold (n=5) increased compared to controls; whereas urokinase-type plasminogen activator antigen in culture medium remained uninfluenced by OMV-LPS. In conclusion, these OMV-induced imbalances favor fibrin deposition in the monocyte microenvironment and is probably of great importance in the development of disseminated intravascular coagulation, microthrombosis and organ dysfunction related to fulminant meningococcal septicemia.

A total of 22 strains of Neisseria meningitidis isolated from cerebrospinal fluid samples of patients in Dakar, Senegal, in the course of an epidemic of meningococcal meningitis in 1999 were studied. All the strains were serogroup A, serotype 21:P1.9 and belonged to clonal subgroup III-1. The strains were resistant to sulphonamide, but were susceptible to ampicillin, ceftriaxone and chloramphenicol, which are used in the treatment of cerebrospinal meningitis in Senegal.

To study how the different immunoglobulin (Ig)G subclass antibodies may confer protection against systemic meningococcal disease, we isolated IgG1, IgG2 and IgG3 antibodies from plasma from vaccinees immunized with the Norwegian meningococcal outer membrane vesicle vaccine. Four IgG1, one IgG2 and four IgG3 preparations were purified. The IgG2 and IgG3 subclass preparations were free from contaminating subclasses, whereas the IgG1 preparations contained from 0 to 14% of IgG2 and/or IgG3. Immunoblotting against whole-cell meningococcal antigens showed broad specificities of the various preparations, both within and between subclasses. These subclass preparations were tested for opsonophagocytic and bactericidal activity. As targets we used two different variants of the meningococcal vaccine strain, with low (44/76-SL) and high (44/76-1) expression of the outer membrane protein Opc. Using polymorphonuclear leucocytes as effector cells in the presence of human complement, all three IgG subclass preparations revealed high, and similar, opsonophagocytic activities against 44/76-SL, whereas against 44/76-1 the IgG2 preparation showed a reduced activity and most IgG3 preparations were slightly more active than the IgG1 preparations. Regarding bactericidal activity, all the three subclasses were highly active against 44/76-SL. Against 44/76-1 the bactericidal activities were somewhat more varied: all IgG1 and three IgG3 preparations exhibited higher activities than against 44/76-SL. Due to the low concentration in the IgG2 preparations, only a weak activity was seen against 44/76-1. One IgG3 preparation that was highly opsonophagocytic revealed no bactericidal activity against either of the two bacterial variants examined. In conclusion, we have shown that the IgG subclass effector functions differ from person to person, but that antibodies of IgG1, IgG2 and IgG3 subclasses, judged by their behaviour in the functional tests, may all contribute to protection against meningococcal disease.

We surveyed, during 1994, all 325 patients who underwent staging laparotomy with splenectomy for Hodgkin's disease in Norway 1969-80, before pneumococcal vaccine was available in this country. The patients were thus not immunized preoperatively. Of 162 patients (49.8%) who died before 1994, 8 (2.4% of the total study) died from pneumococcal septicaemia and 16 (6.2%) from infections totally. Of 163 patients (50.2%) who were alive in 1994, 158 cooperated and filled in a questionnaire: 22 had been hospitalized for serious infections; 2 with pneumococcal septicaemia, and 6 with pneumonia, although lacking a specified microbiological diagnosis. We observed 325 patients representing 4420 patient-years, 3066 patient-years among survivors and 1354 patient-years among the dead. This resulted in an incidence rate of systemic pneumococcal disease of 226 per 100,000 patient-years, which is a relative risk of 20.5 compared to the general Norwegian population during 1994. Septicaemia for these patients most often had an abrupt clinical start even for relapse-free individuals and occurred from 2 to 17 yr after splenectomy (mean 10 yr). The risk of developing an overwhelming pneumococcal septicaemia with high case-fatality in asplenic patients seems to persist for these patients at about the same level even 15-20 yr after splenectomy. Only 12.7% of the survivors had been given pneumococcal vaccine in the autumn of 1993. Despite the fact that medical journals and media in Norway focused upon the problem of pneumococcal disease in asplenic individuals in the autumn of 1993 and spring of 1994, a substantial proportion of these patients (55.3%) still remained unimmunized when interviewed in the autumn of 1994. None of our systemic pneumococcal disease patients was vaccinated. Our data underline the need for prophylactic immunization with effective vaccines against pneumococcal infection in splenectomized Hodgkin's disease patients.

SUMMARYA total of 125 strains ofNeisseria meningitidisrecovered in the course of outbreaks from patients with systemic disease in 11 African countries between 1989 and 1994 were analysed by serogrouping, serotyping and multilocus enzyme electrophoresis. Of the 125 patient strains 115 (92%) belonged to the clone-complex of serogroup A meningococci, designated subgroup III. Among the remaining strains, 4 were also serogroup A, but belonged to the clonal groups I and IV-1 (2 strains each), whilst 6 strains (4 serogroup C and 2 serogroup W135) represented clones of the ET-37 complex. Our results indicated that the second pandemic caused by clones of subgroup III is still spreading in Africa. Towards the West it has reached Niger, Mali, Guinea and The Gambia, and towards the South, the Central African Republic, Uganda, Rwanda, Burundi, Tanzania and Zambia.

To improve the diagnosis of systemic meningococcal disease we used a nested polymerase chain reaction (nPCR) test to detect meningococcal DNA in cerebrospinal fluid (CSF) samples from patients. The nPCR test was based on the gene coding for the PorA outer membrane protein, a major antigen of Neisseria meningitidis, which is the basis for determining the subtype of the strains. The method was tested on CSF samples from 87 patients with various disease aetiology, including 37 patients with systemic meningococcal disease. It was also applied to all 67 CSF samples from culture-negative patients with suspected meningococcal disease which were collected in the course of the Norwegian serogroup B vaccination trials, between 1987 and 1993. Of the 67 culture-negative CSF samples, 10 were nPCR positive. Two of the 67 CSF were positive with the antigen test, and both of these were nPCR positive. Serum pairs from 46 of the 67 culture-negative patients were analysed for serological serogroup response in an enzyme-linked immunosorbent assay (ELISA) against meningococcal capsular polysaccharides. Nine of the 10 nPCR-positive CSF samples belonged to patients with serological response judged as either typical of, or compatible with systemic meningococcal disease. Sequence analysis of the nPCR products was performed to determine the subtype of the infecting meningococcal strains. Four of the 10 positive CSF samples were infected with a strain of subtype P1.7,16, which is similar to the epidemic strain used to produce the vaccine. Inclusion of nPCR for diagnosis of meningococcal meningitis did not significantly alter the results of the vaccination trial, but added important information about the strain causing disease in 5 of 13 serogroup B cases without preserved isolates.

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.

To estimate the extent of meningococcal carriage in the Norwegian population and to investigate the relationship of several characteristics of the population to the carrier state, 1,500 individuals living in rural and small-town areas near Oslo were selected at random from the Norwegian National Population Registry. These persons were asked to complete a questionnaire and to volunteer for a bacteriological tonsillopharyngeal swab sampling. Sixty-three percent of the selected persons participated in the survey. Ninety-one (9.6%) of the volunteers harbored Neisseria meningitidis. The isolates were serogrouped, serotyped, tested for antibiotic resistance, and analyzed by multilocus enzyme electrophoresis. Eight (8.8%) of the 91 isolates represented clones of the two clone complexes that have been responsible for most of the systemic meningococal disease in Norway in the 1980s. Age between 15 and 24, male sex, and active and passive smoking were found to be independently associated with meningococcal carriage in logistic regression analyses. Working outside the home and having an occupation in transportation or industry also increased the risk for meningococcal carriage in individuals older than 17, when corrections for gender and smoking were made. Assuming that our sample is representative of the Norwegian population, we estimated that about 40,000 individuals in Norway are asymptomatic carriers of isolates with epidemic potential. Thus, carriage eradication among close contacts of persons with systemic disease is unlikely to have a significant impact on the overall epidemiological situation.

A case of septicaemia that repeatedly showed growth of Lactobacillus rhamnosus in blood cultures is reported. The patient improved after removal of a Goretex patch in the inferior vena cava that was the focus of the infection. Lactobacilli can, in certain settings, be the cause of clinically important infections.

SUMMARYFollowing the occurrence of a case of systemic meningococcal disease in a military camp in Norway, throat cultures and blood samples were collected from 33 healthy individuals belonging to the same troop as the patient (troop A) and from 29 individuals from a different troop (troop B) in the same camp. Serological studies showed that 91% of the recruits had bactericidal antibodies against the disease-causing strain. The isolates ofNeisseria meningitidisrecovered from the throat cultures were serogrouped, serotyped, and assigned to a clone on the basis of an analysis of the electrophoretic mobilities of 14 metabolic enzymes. None of the 23 carriers in troop A harboured the clone responsible for the case of disease, but 6 carried isolates of the same electrophoretic type, ET-7, which was not identified in any of the 19 carriers of troop B. Individuals in troop A were resampled 2 and 17 weeks after the meningococcal disease episode. Five of the carriers had acquired different clones and one of them changed clone twice in that period. Four of the six newly acquired clones had previously been identified in other carriers of troop A, demonstrating transmission of clones among individuals living and working in close proximity.