Genetic Variation in NFKBIE Is Associated With Increased Risk of Pneumococcal Meningitis in Children.

Background: Streptococcus pneumoniae and Neisseria meningitidis are frequent pathogens in life-threatening infections. Genetic variation in the immune system may predispose to these infections. Nuclear factor-κB is a key component of the TLR-pathway, controlled by inhibitors, encoded by the genes NFKBIA, NFKBIE and NFKBIZ.

Mannose-Binding Lectin Gene, MBL2, Polymorphisms Do Not Increase Susceptibility to Invasive Meningococcal Disease in a Population of Danish Children.

Background.  Neisseria meningitidis is the cause of meningococcal bacteremia and meningitis, and nasopharyngeal colonization with this pathogen is common. The incidence of invasive disease is highest in infants, whereas adolescents more often are carriers.

Pneumococcal Capsules and Their Types: Past, Present, and Future.

Streptococcus pneumoniae (the pneumococcus) is an important human pathogen. Its virulence is largely due to its polysaccharide capsule, which shields it from the host immune system, and because of this, the capsule has been extensively studied. Studies of the capsule led to the identification of DNA as the genetic material, identification of many different capsular serotypes, and identification of the serotype-specific nature of protection by adaptive immunity.

Association between serotype-specific antibody response and serotype characteristics in patients with pneumococcal pneumonia, with special reference to degree of encapsulation and invasive potential.

We studied the immunoglobulin (Ig) response to causative serotype-specific capsular polysaccharides in adult pneumococcal pneumonia patients. The serotypes were grouped according to their degree of encapsulation and invasive potential. Seventy patients with pneumococcal pneumonia, 20 of whom were bacteremic, were prospectively studied.

Incidence and risk factors for invasive pneumococcal disease in HIV-infected and non-HIV-infected individuals before and after the introduction of combination antiretroviral therapy: persistent high risk among HIV-infected injecting drug users.

Background: Invasive pneumococcal disease (IPD) is an important cause of morbidity among individuals infected with human immunodeficiency virus (HIV). We described incidence and risk factors for IPD in HIV-infected and uninfected individuals.

Methods: Nationwide population-based cohort study of HIV-infected adults treated at all Danish HIV treatment centers during 1995-2012.

Impact of 13-valent pneumococcal conjugate vaccination in invasive pneumococcal disease incidence and mortality.

Background: The impact of the 13-valent pneumococcal conjugate vaccine (PCV13) at the population level is unclear. We explored PCV13's effect in reducing invasive pneumococcal disease (IPD)-related morbidity and mortality, and whether serotype-specific changes were attributable to vaccination or expected as a part of natural, cyclical variations.

Methods: This was a Danish nationwide population-based cohort study based on the linkage of laboratory surveillance data and the Danish Civil Registration System.

Mannose-binding lectin gene, MBL2, polymorphisms are not associated with susceptibility to invasive pneumococcal disease in children.

Background: Most children are transiently colonized with Streptococcus pneumoniae, but very few develop invasive pneumococcal disease (IPD). Host genetic variation of innate immunity may predispose to IPD. We investigated the effect of genetic variation in the mannose-binding lectin gene, MBL2, on susceptibility and disease severity of IPD in previously healthy children aged <5 years.

Pneumococcal disease seasonality: incidence, severity and the role of influenza activity.

We tested whether the effect of influenza activity on invasive pneumococcal disease incidence and severity varies between age and comorbidity groups. Weekly rates of invasive pneumococcal disease were obtained from the Danish National Laboratory Surveillance System (1977-2007). Influenza-like illness data were collected from a sentinel surveillance system at the Statens Serum Institut (Copenhagen, Denmark).

Serotype distribution in non-bacteremic pneumococcal pneumonia: association with disease severity and implications for pneumococcal conjugate vaccines.

Background: There is limited knowledge of serotypes that cause non-bacteremic pneumococcal pneumonia (NBP). Here we report serotypes, their associated disease potential and coverage of pneumococcal conjugate vaccines (PCV) in adults with NBP and compare these to bacteremic pneumonia (BP).

Methods: Adults with pneumonia and Streptococcus pneumoniae isolated from the lower respiratory tract or blood were included 1 year in a population-based design in Denmark.

Serotype-specific effect of influenza on adult invasive pneumococcal pneumonia.

Background:  Influenza affects host susceptibility to pneumococcus. We sought to evaluate whether this relationship varies by pneumococcal serotype using a large epidemiological database covering 3 decades.

Methods:  Weekly rates of invasive pneumococcal pneumonia (IPP) were obtained from the Danish National Laboratory Surveillance System, and influenza-like illness (ILI) data were collected from Danish sentinel surveillance, Statens Serum Institut, 1977-2007.

Impact of positive chest X-ray findings and blood cultures on adverse outcomes following hospitalized pneumococcal lower respiratory tract infection: a population-based cohort study.

Background: Little is known about the clinical presentation and outcome of pneumococcal lower respiratory tract infection (LRTI) without positive chest X-ray findings and blood cultures. We investigated the prognostic impact of a pulmonary infiltrate and bacteraemia on the clinical course of hospitalized patients with confirmed pneumococcal LRTI.

Methods: We studied a population-based multi-centre cohort of 705 adults hospitalized with LRTI and Streptococcus pneumoniae in LRT specimens or blood: 193 without pulmonary infiltrate or bacteraemia, 250 with X-ray confirmed pneumonia, and 262 with bacteraemia.

Pediatric invasive pneumococcal disease caused by vaccine serotypes following the introduction of conjugate vaccination in Denmark.

A seven-valent pneumococcal conjugate vaccine (PCV7) was introduced in the Danish childhood immunization program (2+1 schedule) in October 2007, followed by PCV13 starting from April 2010. The nationwide incidence of IPD among children younger than 5 years nearly halved after the introduction of PCV7 in the program, mainly due to a decline in IPD caused by PCV7-serotypes. We report the results from a nationwide population-based cohort study of laboratory confirmed IPD cases in children younger than 5 years during October 1, 2007 to December 31, 2010 and describe the characteristics of children suspected to present with a vaccine failure.

A Pneumococcal Carriage Study in Danish Pre-school Children before the Introduction of Pneumococcal Conjugate Vaccination.

We present data on pneumococcal carriage before the introduction of the heptavalent-pneumococcal conjugated vaccine (PCV7) in Denmark. In the pre-PCV7 period, the incidence of invasive pneumococcal disease (IPD) among children younger than 5 years was approximately 25 per 100.000 population, with the highest incidence rates observed in children younger than 2 years of age.

Early effectiveness of heptavalent conjugate pneumococcal vaccination on invasive pneumococcal disease after the introduction in the Danish Childhood Immunization Programme.

We evaluated the effectiveness of the heptavalent pneumococcal conjugate vaccine (PCV7) on invasive pneumococcal disease (IPD) 1 year after PCV7's introduction in the childhood immunization programme through a nationwide cohort study based on laboratory surveillance data. There was a decline in the overall incidence of IPD from 19.4 to 17.

Temporal trends in invasive pneumococcal disease and pneumococcal serotypes over 7 decades.

Background: Pneumococcal infections have historically played a major role in terms of morbidity and mortality. We explored historical trends of invasive pneumococcal disease (IPD) and pneumococcal serotypes in a population exposed to limited antibiotic selective pressure and conjugate pneumococcal vaccination (PCV).

Methods: Retrospective cohort study based on nationwide laboratory surveillance data on IPD collected uninterruptedly in Denmark during 1938-2007.

Non-invasive erythromycin-resistant pneumococcal isolates are more often non-susceptible to more antimicrobial agents than invasive isolates.

Multiresistant Streptococcus pneumoniae infections are of great concern as treatment failures may occur with commonly used treatment regimens using beta-lactams and macrolides. The proportion of non-susceptible S. pneumoniae differs from country to country.

Pneumococcal serotypes and mortality following invasive pneumococcal disease: a population-based cohort study.

Background: Pneumococcal disease is a leading cause of morbidity and mortality worldwide. The aim of this study was to investigate the association between specific pneumococcal serotypes and mortality from invasive pneumococcal disease (IPD).

Methods And Findings: In a nationwide population-based cohort study of IPD in Denmark during 1977-2007, 30-d mortality associated with pneumococcal serotypes was examined by multivariate logistic regression analysis after controlling for potential confounders.

Invasive pneumococcal disease in Danish children, 1996-2007, prior to the introduction of heptavalent pneumococcal conjugate vaccine.

Aim: The aim of this study was to document the epidemiology, microbiology and outcome of invasive pneumococcal disease (IPD) among children <16 years with quality surveillance data, just prior to the introduction of the heptavalent pneumococcal conjugate vaccine (PCV7) into the Danish routine immunization programme October 2007.

Methods: Clinical and microbiological records on cases of IPD in children <16 years admitted to Hvidovre Hospital, Denmark 1996-2007, were retrospectively reviewed.

Results: We identified 106 cases of IPD.

An easy method for detection of nasopharyngeal carriage of multiple Streptococcus pneumoniae serotypes.

In this paper, a simplified method for detection of pneumococcal carriage and for revealing the presence of several serotypes in a nasopharyngeal sample is evaluated. Enrichment broth was used for transportation and for the initial culturing of samples. All specimens were examined directly by the capsular reaction test for the presence of any of the 91 known pneumococcal serotypes.

Estimated effect of pneumococcal conjugate vaccination on invasive pneumococcal disease and associated mortality, Denmark 2000-2005.

In order to provide an estimation of the direct and indirect benefits of pneumococcal vaccination with three protein-conjugate pneumococcal vaccines (PCV) we described the epidemiology and mortality from invasive pneumococcal disease (IPD) in Denmark between 2000 and 2005. Approximately 1080 cases were registered annually during the period. The overall incidence of IPD increased significantly, from 15.

Purification and structure characterization of the active component in the pneumococcal 22F polysaccharide capsule used for adsorption in pneumococcal enzyme-linked immunosorbent assays.

Protection against pneumococcal disease is thought to be mediated primarily by antibodies that are opsonic [Musher DM, Chapman AJ, Goree A, Jonsson S, Briles D, Baughn RE. Natural and vaccine-related immunity to Streptococcus pneumoniae. J Infect Dis 1986;154(2):245-56].

Serotypes of Streptococcus pneumoniae isolated from blood and cerebrospinal fluid related to vaccine serotypes and to clinical characteristics.

Pneumococci isolated from blood and cerebrospinal fluid from 1998 to 2001 in 2 counties in south-west Sweden were serotyped with the capsular reaction test. Of the 836 strains, 353 (42%), 598 (72%) and 789 (94%) belonged to serotypes included in the 7- and 11-valent pneumococcal conjugate vaccines and in the 23-valent polysaccharide vaccine, respectively. The most common serotype was type 1 (119 isolates) followed in descending frequency by serotypes 7F, 9V, 14, 4 and 12F (90-49 isolates per serotype).

Prehospital diagnostic and therapeutic management of otogenic Streptococcus pneumoniae meningitis.

Prehospital diagnostics and therapeutic management, as well as clinical and laboratory data from 57 consecutive cases with otogenic pneumococcal meningitis (OPM) in Denmark during a 2-y period (1999-2000) were studied by review of discharge and medical records including a questionnaire sent to the general practitioners responsible for the individual patient. 12 cases were <2 y of age, whereas the remaining 45 cases were >21 y of age. Fever (in 98%) and altered consciousness (in 98%), respectively, were significantly more frequent prehospital symptoms (median duration of symptoms: 2 d (1-4)) than earache (in 71%, p < 0.