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H B Konradsen

Publications and source records attributed to H B Konradsen.

At least 19 recordsLinked to original sources

Invasive group A, B, C and G streptococcal infections in Denmark 1999-2002: epidemiological and clinical aspects.

Group A streptococci (GAS) have been described frequently as an emerging cause of severe invasive infections in population-based surveillance studies, whereas the descriptions of group B, C and G streptococci (GBS, GCS and GGS) have been less frequent. Enhanced surveillance for invasive GAS, GBS, GCS and GGS was performed in Denmark in 1999-2002. A detailed questionnaire was completed for 1237 (98%) of 1260 invasive infections. GAS infections dominated (40%), followed by GGS (32%), GBS (23%) and GCS (6%). Most (74%) patients had predisposing factors, and there were no significant differences between the four serogroups when comparing the prevalence of cancer, diabetes mellitus, chronic heart or lung diseases, immunodeficiency or alcohol abuse. The overall case fatality rate at day 30 was 21%, increasing significantly to 59% for patients with streptococcal toxic shock syndrome (STSS). STSS was significantly more frequent in GAS patients (10%) than in GCS (4%), GBS (2%) and GGS (2%) patients. Regression analyses showed that, despite a younger median age among GAS patients, the probability of developing septic shock and mortality was significantly higher among GAS patients than among GBS and GGS patients. These analyses showed no significant differences between GAS and GCS infections. Invasive infections caused by GAS, GBS, GCS and GGS are still a major challenge for clinicians. Continued epidemiological and microbiological surveillance is important to assess the development of these infections and to improve preventative strategies.

Adolescent↗

Invasive group B streptococcal disease in infants: a 19-year nationwide study. Serotype distribution, incidence and recurrent infection.

During the period 1984-2002, 472 cases of invasive group B streptococcal (GBS) disease in infants aged 0-90 days in Denmark were registered. The overall incidence was 0.4/1000 live births. Most infants (73%) had early-onset GBS infection with 53% registered within the first day. Serotype III predominated (59%) with other serotypes as follows: Ia (16%), Ib (8%), NT (7%), II (6%), other serotypes (5%). Recurrence of GBS infection was registered in six infants, and the interval with no antibiotic therapy varied from 2 to 39 days. The serotypes of the isolates obtained from first and second episodes were identical (serotype III in five, and serotype Ia in one infant). Paired isolates were indistinguishable by PFGE and antibiotic susceptibility testing. Invasive GBS infections in infants are still a problem in Denmark, and recurrent infections are registered in 1% of these infants.

Denmark↗

A prospective study on antibody response to repeated vaccinations with pneumococcal capsular polysaccharide in splenectomized individuals with special reference to Hodgkin's lymphoma.

BACKGROUND: Splenectomy is accompanied by a life-long risk of overwhelming postsplenectomy infection (OPSI), mainly caused by polysaccharide (PS) encapsulated bacteria such as Streptococcus pneumoniae. Despite extensive prophylactic efforts the mortality and morbidity rates remain high. The present study was based on a strategy with a predefined vaccination algorithm including repeated 23-valent pneumococcal vaccinations and monitoring of pneumococcal antibody levels. The antibody levels of splenectomized Hodgkin's lymphoma (HL) patients were compared with those patients splenectomized due to immune-mediated cytopenias [autoimmune haemolytic anaemia (AIHA) and immune thrombocytopenic purpura (ITP)] and also individuals who were splenectomized because of trauma (TRAUMA). METHODS: A total of 311 splenectomized individuals were included in this prospective study (208 HL; 15 AIHA; 60 ITP; 28 TRAUMA). Depending on their individual anti-PS antibody levels measured by enzyme-linked immunosorbent assay technique the patients were revaccinated with 23-valent pneumococcal PS vaccine up to four times in accordance with the predefined algorithm. For each vaccination occasion, serum was collected at vaccination, after 1 month +/- 2 weeks (peak), and after 1 year +/- 6 months (follow-up). Patient files, a national population-based database, and microbiological databases were checked for 124 HL patients to identify OPSI. RESULTS: A significant response was recorded on primary vaccination as well as on two revaccination occasions for HL, AIHA/ITP, as well as TRAUMA patients. None of the variables age, gender, or time elapsed between splenectomy and first pneumococcal vaccination was found to be associated with mean PS antibody levels at prevaccination, peak or follow-up. No severe adverse events were reported. Amongst 124 clinically monitored HL patients, 10 OPSI were recorded in seven patients during the study period. One of these patients, a middle-aged female, died as a result of fulminant pneumococcal bacteraemia, which was her third OPSI during a 7-year period. CONCLUSIONS: A significant response to pneumococcal PS vaccination was found in all three groups (HL, AIHA/ITP and TRAUMA) of splenectomized patients. Importantly, both primary and repeated vaccinations were safe. Until further knowledge is gained regarding the protective concentration of serotype-specific antibody concentrations we believe that the value of vaccination and frequent revaccination (every 1-5 years) in combination with education of patients and health care professionals and clinical monitoring is beneficial for these patients at risk for OPSI.

Adolescent↗

Evaluation of gastrointestinal symptoms as primary sign of severe invasive group A streptococcal infections.

BACKGROUND & OBJECTIVES: Severe invasive infections caused by group A Streptococcus (GAS) are often associated with shock and organ failure. We describe epidemiological and disease related data from the national surveillance of invasive GAS infection in Denmark in addition to three fatal cases that occurred in Denmark in 2002 with gastrointestinal (GI) symptoms as the dominating preliminary signs. METHODS: As the National Streptococcal Reference Centre The Streptococcus Unit, Statens Serum Institut (SSI) receives the vast majority of the invasive GAS isolates from patients admitted to all the hospitals in Denmark. The isolates were T-typed by slide agglutination test emm-squencing and pulsed field gel electrophoresis (PFGE) were also performed. RESULTS: During January 2002 three patients died at home and GAS were found at autopsy. Cases 1 (12 yr) and 3 (25 yr) had been ill for less than two days with nausea, diarrhoea and vomiting. Case 2 (25 yr) had the same symptoms for two weeks. None of the three had any underlying diseases. The GAS isolates from cases 1 and 2 were T-type 3-13-B3264, emm89 and SpeA-, SpeC-. The third isolate was Ttype 1, emm1 and SpeA+, SpeC-. PFGE could not discriminate between the two isolates with T-type 3-13-B3264. The PFGE patterns of the three isolates were similar to those identified from GAS isolated elsewhere in Denmark at different times and from non-fatal cases. In 1999-2002, SSI received 409 isolates from patients with invasive GAS infection, and the mortality rate was 18 per cent. In 40 patients the primary symptoms were gastrointestinal, and in 30 per cent of these the outcome was fatal. INTERPRETATION & CONCLUSION: The various early clinical manifestations of severe GAS infections are still a major challenge for clinicians because of the importance of a fast and appropriate diagnosis and immediate start of treatment.

Adolescent↗

Latex assay for serotyping of group B Streptococcus isolates.

We developed a group B streptococcus (GBS) latex serotyping kit that reduces the numbers of GBS nontypeable isolates by nearly 50%. A total of 232 isolates were tested, and 203 isolates were serotyped by the GBS latex test, while the capillary precipitation test serotyped 184 isolates.

Cross Reactions↗

Negligible adjuvant effect for antibody responses and frequent adverse events associated with IL-12 treatment in humans vaccinated with pneumococcal polysaccharide.

To assess whether co-administration of recombinant human IL-12 (rhIL-12) and 23-valent pneumococcal polysaccharide vaccine (PPV) enhances the antibody response to this T cell-independent antigen, healthy immunocompetent volunteers (n=34, 55-65 years old) were vaccinated intramusculary with PPV and concurrently-treated subcutaneously with either rhIL-12 (1 or 4 microg) or placebo. The increases of total anti-pneumococcal IgG antibodies were numerically higher among the rhIL-12 recipients compared with placebo recipients, but the difference was not significant. The rhIL-12 recipients had a high incidence of local and systemic side effects. Given the lack of convincing evidence that rhIL-12 enhances the antibody response to PPV, the frequency and severity of the side effects was unacceptable.

Adjuvants, Immunologic↗

Recurrence of pneumonia in relation to the antibody response after pneumococcal vaccination in middle-aged and elderly adults.

We have recently studied the efficacy of pneumococcal vaccine in preventing pneumonia recurrences after hospital treatment for community-acquired pneumonia in non-immunocompromised patients aged 50-85 y. Among these patients, we have now compared the antibody response to the pneumococcal vaccine between patients who developed pneumonia (n = 50) and patients without pneumonia recurrences (n = 100), during a mean follow-up period of 32 months after vaccination. The antibody levels of 5 pneumococcal serotypes were measured before, and 4 weeks, 1 y and 3 y after vaccination. A lower risk of pneumonia recurrences was seen in patients with antibody fold increases (FIs) > 4 from pre-vaccination to post-vaccination compared with patients with lower FIs (p = 0.02). The results suggest that in this patient category, the antibody response to pneumococcal vaccination is of importance for the risk of pneumonia recurrence.

Aged↗

Characteristics of the major etiologic agents of bacterial meningitis isolated in Poland in 1997-1998.

Bacterial meningitis remains a major cause of morbidity and mortality worldwide, especially in children. In this paper, we present the results of the first two years (1997-98) of activity of the National Reference Centre for Bacterial Meningitis (NRCBM) on the etiologic agents of bacterial meningitis in Poland. Of the 220 isolates sent to the NRCBM, the most frequently identified was Neisseria meningitidis (n = 90, 40.9%), followed by Haemophilus influenzae (n = 58, 26.4%), and Streptoccus pneumoniae (n = 46, 20.9%). Of the meningococcal isolates, 88.9% belonged to serogroup B and 10.0% to serogroup C, and the most prevalent serotype was 22 (43.3%). Most meningococci were highly sensitive to penicillin; however, 10% of them had decreased susceptibility to penicillin. More than 90% of H. influenzae belonged to serotype b, and all were susceptible to third generation cephalosporins and chloramphenicol. A broad distribution of serotypes was found among pneumococcal isolates, of which the most common were serotypes 3 and 8. Penicillin nonsusceptible isolates constituted 13% of all pneumococcal isolates. Three of the resistant pnemococci belonged to serotype 23F. Data presented in this paper demonstrate the current epidemiological situation of bacterial meningitis in Poland.

Adolescent↗

Epidemiology of invasive pneumococcal infections in children aged 0-6 years in Denmark: a 19-year nationwide surveillance study.

UNLABELLED: The impact of the new pneumococcal conjugate vaccines on invasive disease burden in Danish children was evaluated by analysing the results from the last 19 years of a nationwide surveillance of invasive pneumococcal infections. During 1981-1999, the Streptococcus Unit at Statens Serum Institut, Copenhagen, received 1123 invasive pneumococcal isolates from children aged 0-6 years. Nearly 72% (71.8%) of the pneumococcal isolates were from children aged <2 y. The median ages of children with pneumococcal meningitis and bacteraemia were 10.2 mo and 15.9 mo, respectively. The incidence of pneumococcal meningitis remained stable during the study period. The mean annual incidence rates of pneumococcal meningitis among children aged <1, <2, and <7 years were 17.4, 12.4, and 4.3 per 100,000, respectively, during 1981-1999 (overlapping age groups are used throughout this article to facilitate the comparison of incidence data from different countries or among different studies). The annual incidence of pneumococcal bacteraemia increased from 1981 to 1996, after which a slight fall was noted. During the last six years of the study period, the mean annual incidence rates of bacteraemia were 30.1, 32.5, and 14.0 per 100,000 children aged < 1, < 2, and < 7 years. In the 1990s, pneumococcal isolates with reduced sensitivity to penicillin (0-5% each year) and erythromycin (7.4% in 1999) emerged as a cause of invasive infections in children aged 0-6 years in Denmark. During 1981-1999, 10 serotypes (1, 4, 6A, 6B, 7F, 9V, 14, 18C, 19F, 23F) caused 82% of invasive infections in Danish children. Importantly, no significant temporal changes in overall serotype distribution or differences in serotype distributions between girls and boys could be documented during the study period. CONCLUSION: According to the Kaiser Permanente trial, the 7-, 9-, and 11-valent pneumococcal conjugate vaccines will probably cover around 60%, 70%, and 80%, respectively, of all invasive pneumococcal infections in Danish children aged 0-6y, corresponding to 12-14 episodes of meningitis and 40-60 episodes of bacteraemia per year.

Age Distribution↗

An analytical model applied to a multicenter pneumococcal enzyme-linked immunosorbent assay study.

Pneumococcal conjugate vaccines will eventually be licensed after favorable results from phase III efficacy trials. After licensure of a conjugate vaccine for invasive pneumococcal disease in infants, new conjugate vaccines will likely be licensed primarily on the basis of immunogenicity data rather than clinical efficacy. Analytical methods must therefore be developed, evaluated, and validated to compare immunogenicity results accurately within and between laboratories for different vaccines. At present no analytical technique is uniformly accepted and used in vaccine evaluation studies to determine the acceptable level of agreement between a laboratory result and the assigned value for a given serum sample. This multicenter study describes the magnitude of agreement among 12 laboratories quantifying an identical series of 48 pneumococcal serum specimens from 24 individuals (quality-control sera) by a consensus immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) developed for this study. After provisional or trial antibody concentrations were assigned to the quality-control serum samples for this study, four methods for comparison of a series of laboratory-determined values with the assigned concentrations were evaluated. The percent error between assigned values and laboratory-determined concentrations proved to be the most informative of the four methods. We present guidelines that a laboratory may follow to analyze a series of quality-control sera to determine if it can reproduce the assigned antibody concentrations within an acceptable level of tolerance. While this study focused on a pneumococcal IgG ELISA, the methods that we describe are easily generalizable to other immunological assays.

Antibodies, Bacterial↗

Rapid loss of specific antibodies after pneumococcal vaccination in patients with human immunodeficiency virus-1 infection.

Pneumococcal infections are frequently observed in patients with human immunodeficiency virus (HIV) infection and active immunization has been recommended as prophylaxis in this patient group. We studied 103 out-patients with asymptomatic or mildly symptomatic HIV infection with respect to specific IgG and IgG2 pneumococcal antibodies before and after vaccination with a 23-valent pneumococcal polysaccharide vaccine. A significant increase ( > 2-fold) in IgG and IgG2 antibody levels was observed after 1 month in 69/103 patients (67%) with no correlation with the CD4 cell count at the time of vaccination. The response rate was not influenced by concurrent treatment with anti-retroviral monotherapy, or by age or gender. After immunization a strong correlation between IgG and IgG2 anti-pneumococcal antibodies was demonstrated. Nevertheless, 12 months after vaccination the specific antibody titres were not significantly different from pre-vaccination values. In conclusion, antibodies induced by pneumococcal vaccination in patients with HIV infection have a short duration. This raises the question as to whether vaccination will have any impact on clinical end-point in this group of patients.

Acquired Immunodeficiency Syndrome↗

[Group B streptococcal infection in adults].

Three cases of infection with Streptococcus agalactiae, or Lancefield group B beta-haemolytic streptococcus (GBS), in adults are described and the literature is reviewed. During a period of 14 years the incidence of GBS-disease in adults aged above 15 years has increased in Denmark. The most common clinical presentations of GBS-disease in adults are puerpural fever, bacteraemia without evident focus, skin or soft-tissue infection, pneumonia, urosepsis and meningitis, preceded by a few days of influenza-like symptoms. The features of this fulminant disease include rapid development of multiple organ dysfunction syndrome (MODS) with renal impairment, adult respiratory distress syndrome (ARDS) and, in many patients, also cardiovascular instability. The therapy includes parenteral antibiotics, usually with high doses of benzylpenicillin, and symptomatic treatment. GBS-disease in both infants and adults may be prevented by the development of effective GBS-vaccines.

Adult↗