Early-onset group B streptococcal infections in five Nordic countries with different prevention policies, 1995 to 2019.

BackgroundNeonatal early-onset disease caused by group B Streptococcus (GBS) is a leading cause of infant morbidity. Intrapartum antibiotic prophylaxis (IAP) is effective in preventing early-onset GBS disease, but there is no agreement on the optimal strategy for identifying the pregnant women requiring this treatment, and both risk-based prophylaxis (RBP) and GBS screening-based prophylaxis (SBP) are used.AimThe aim of this study was to evaluate the effect of SBP as a public health intervention on the epidemiology of early-onset GBS infections.MethodsIn 2012, Finland started the universal SBP, while Denmark, Iceland, Norway and Sweden continued with RBP. We conducted an interrupted time series analysis taking 2012 as the intervention point to evaluate the impact of this intervention. The incidences of early- and late-onset GBS infections during Period I (1995-2011) and Period II (2012-2019) were collected from each national register, covering 6,605,564 live births.ResultsIn Finland, a reduction of 58% in the incidence of early-onset GBS disease, corresponding to an incidence rate ratio (IRR) of 0.42 (95% CI: 0.34-0.52), was observed after 2012. At the same time, the pooled IRR of other Nordic countries was 0.89 (95% CI: 0.80-1.0), specifically 0.89 (95% CI: 0.70-1.5) in Denmark, 0.34 (95% CI: 0.15-0.81) in Iceland, 0.72 (95% CI: 0.59-0.88) in Norway and 0.97 (95% CI: 0.85-1.1) in Sweden.ConclusionsIn this ecological study of five Nordic countries, early-onset GBS infections were approximately halved following introduction of the SBP approach as compared with RBP.

Gonorrhoea on the rise in Denmark since 2022: distinct clones drive increase in heterosexual individuals.

A surge in gonorrhoea in Denmark has occurred since 2022, a 46% increase from 2021. National surveillance, leveraging mandatory reporting and epidemiological data, highlights three distinct clades linked to heterosexual transmission. Despite the rise, these exhibit high susceptibility, contrasting MSM-associated strains. Geographical hotspots and age-specific patterns further illuminate transmission dynamics. The combination of genomic and epidemiological data provides novel insights into the evolving landscape of gonorrhoea, indicating potential shifts in infection dynamics and transmissibility.

Increase in invasive group A streptococcal infections and emergence of novel, rapidly expanding sub-lineage of the virulent Streptococcus pyogenes M1 clone, Denmark, 2023.

A highly virulent sub-lineage of the Streptococcus pyogenes M1 clone has been rapidly expanding throughout Denmark since late 2022 and now accounts for 30% of the new invasive group A streptococcal infections. We aimed to investigate whether a shift in variant composition can account for the high incidence rates observed over winter 2022/23, or if these are better explained by the impact of COVID-19-related restrictions on population immunity and carriage of group A Streptococcus.

Comorbidity Increases the Risk of Invasive Meningococcal Disease in Adults.

BACKGROUND: Risk of invasive meningococcal disease (IMD) is increased in patients with complement deficiency and human immunodeficiency virus (HIV) infection. Risk associated with comorbidity is not well described. METHODS: This was a nationwide adult case-control study. Cases for the period 1977-2018 were identified by the national meningococcus reference laboratory. Matched controls were identified by registry linkage. Comorbidities diagnosed prior to IMD were based on the International Classification of Diseases, Eighth or Tenth Revision. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated by logistic regression after adjustment for sex, age, and other comorbidities. RESULTS: We identified 1221 cases (45% male), with a median age of 45 years (interquartile range, 22-64 years). The dominant meningococcal serogroups were B (n = 738) and C (n = 337). Increased risk of IMD was associated with solid organ transplantation (SOT) (OR 40.47 [95% CI: 4.84-337.23]), hemolytic anemia (OR 7.56 [95% CI: 2.63-21.79]), renal disease (OR 2.95 [95% CI: 1.77-4.92]), liver disease (OR 2.54 [95% CI: 1.58-4.08]), cancer (OR 2.31 [95% CI: 1.85-2.89]), diabetes (OR 1.74 [95% CI: 1.27-2.39]), neurological disease (OR 1.72 [95% CI: 1.20-2.46]), and autoimmune disease (OR 1.70 [95% CI: 1.63-2.11]). Having 1, 2, and ≥3 comorbidities was associated with increased risk of IMD (ORs 1.6-3.5). Increased risk was not associated with specific serogroups. CONCLUSIONS: This study of adults with IMD over 4 decades showed increased risk of IMD associated with renal disease, immunological disorders, liver disease, cancer, and SOT ranging from a 2- to 40-fold increased risk. Vaccination may be warranted in these populations.

COVID-19 preventive measures coincided with a marked decline in other infectious diseases in Denmark, spring 2020.

We aimed to descriptively analyse the possible impact of the national COVID-19 interventions on the incidence of common infectious diseases in Denmark during spring and summer 2020. This observational study focused on national register data on infections caused by 16 different bacterial and viral pathogens. We included new cases registered between 1 January 2016 and 31 July 2020. The weekly number of new cases were analysed with respect to the COVID-19-related interventions introduced during 2020. We found a marked decrease in infections associated with droplet transmission coinciding with the COVID-19 interventions in spring and summer 2020. These included decreases in both viral and bacterial airway infections and also decreases in invasive infections caused by Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis. There was also a reduction in cases associated with foodborne transmission during the COVID-19 lockdown period. We found no effect of the lockdown on infections by invasive beta-haemolytic streptococci group B, C and G, Staphylococcus aureus bacteraemia, Neisseria gonorrhoeae or Clostridioides difficile. In conclusion, we found that the widespread interventions such as physical distancing, less travel, hygiene measures and lockdown of schools, restaurants and workplaces together coincided with a marked decline in respiratory infections and, to a smaller extent, some foodborne-transmitted infections.

A Nationwide Observational Study of Chlamydia trachomatis Infections in Denmark during the COVID-19 Pandemic.

The aim of this study was to determine whether COVID-19 restrictions had an impact on Chlamydia trachomatis infections compared with 2018 and 2019. A retrospective nationwide observational study was performed using monthly incidences of laboratory-confirmed chlamydia cases and number of tests, obtained from Danish national surveillance data. Testing rates and positivity rates were compared using Poisson and logistic regression. The first Danish COVID-19 lockdown (12 March to 14 April 2020) resulted in a reduction in the number of chlamydia tests performed (rate ratio 0.72, 95% confidence interval  0.71-0.73) and a consequent reduction in the number of laboratory-identified cases (66.5 vs 88.3 per 100,000 population during the same period in 2018 to 2019). This period was followed by a return of testing and test positivity close to the level seen in 2018 to 2019. The second Danish COVID-19 lockdown (17 December to 31 March 2021) resulted in crude incidence rates of laboratory-confirmed chlamydia infection that were similar to the crude incidence rates seen during same period in 2018 to 2019. In conclusion, the Danish COVID-19 restrictions have had negligible effects on laboratory-confirmed C. trachomatis transmission.

Preterm birth, stillbirth and early neonatal mortality during the Danish COVID-19 lockdown.

Using provisional or opportunistic data, three nationwide studies (The Netherlands, the USA and Denmark) have identified a reduction in preterm or extremely preterm births during periods of COVID-19 restrictions. However, none of the studies accounted for perinatal deaths. To determine whether the reduction in extremely preterm births, observed in Denmark during the COVID-19 lockdown, could be the result of an increase in perinatal deaths and to assess the impact of extended COVID-19 restrictions, we performed a nationwide Danish register-based prevalence proportion study. We examined all singleton pregnancies delivered in Denmark during the COVID-19 strict lockdown calendar periods (March 12-April 14, 2015-2020, N = 31,164 births) and the extended calendar periods of COVID-19 restrictions (February 27-September 30, 2015-2020, N = 214,862 births). The extremely preterm birth rate was reduced (OR 0.27, 95% CI 0.07 to 0.86) during the strict lockdown period in 2020, while perinatal mortality was not significantly different. During the extended period of restrictions in 2020, the extremely preterm birth rate was marginally reduced, and a significant reduction in the stillbirth rate (OR 0.69, 0.50 to 0.95) was observed. No changes in early neonatal mortality rates were found.Conclusion: Stillbirth and extremely preterm birth rates were reduced in Denmark during the period of COVID-19 restrictions and lockdown, respectively, suggesting that aspects of these containment and control measures confer an element of protection. The present observational study does not allow for causal inference; however, the results support the design of studies to ascertain whether behavioural or social changes for pregnant women may improve pregnancy outcomes. What is Known: • The aetiologies of preterm birth and stillbirth are multifaceted and linked to a wide range of socio-demographic, medical, obstetric, foetal, psychosocial and environmental factors. • The COVID-19 lockdown saw a reduction in extremely preterm births in Denmark and other high-income countries. An urgent question is whether this reduction can be explained by increased perinatal mortality. What is New: • The reduction in extremely preterm births during the Danish COVID-19 lockdown was not a consequence of increased perinatal mortality, which remained unchanged during this period. • The stillbirth rate was reduced throughout the extended period of COVID-19 restrictions.

The human natural anti-αGal antibody targets common pathogens by broad-spectrum polyreactivity.

Naturally occurring antibodies are abundant in human plasma, but their importance in the defence against bacterial pathogens is unclear. We studied the role of the most abundant of such antibodies, the antibody against terminal galactose-α-1,3-galactose (anti-αGal), in the protection against pneumococcal infections (Streptococcus pneumonia). All known pneumococcal capsular polysaccharides lack terminal galactose-α-1,3-galactose, yet highly purified human anti-αGal antibody of the IgG class reacted with 48 of 91 pneumococcal serotypes. Anti-αGal was found to contain multiple antibody subsets that possess distinct specificities beyond their general reactivity with terminal galactose-α-1,3-galactose. These subsets in concert targeted a wide range of microbial polysaccharides. We found that anti-αGal constituted up to 40% of the total antibody reactivity to pneumococci in normal human plasma, that anti-αGal drives phagocytosis of pneumococci by human neutrophils and that the anti-αGal level was twofold lower in patients prone to pneumococcal infections compared with controls. Moreover, during a 48-year period in Denmark, the 48 anti-αGal-reactive serotypes caused fewer invasive pneumococcal infections (n = 10 927) than the 43 non-reactive serotypes (n = 18 107), supporting protection on the population level. Our findings explain the broad-spectrum pathogen reactivity of anti-αGal and support that these naturally occurring polyreactive antibodies contribute significantly to human protective immunity.

Genomic evolution of Neisseria gonorrhoeae since the preantibiotic era (1928-2013): antimicrobial use/misuse selects for resistance and drives evolution.

BACKGROUND: Multidrug-resistant Neisseria gonorrhoeae strains are prevalent, threatening gonorrhoea treatment globally, and understanding of emergence, evolution, and spread of antimicrobial resistance (AMR) in gonococci remains limited. We describe the genomic evolution of gonococci and their AMR, related to the introduction of antimicrobial therapies, examining isolates from 1928 (preantibiotic era) to 2013 in Denmark. This is, to our knowledge, the oldest gonococcal collection globally. METHODS: Lyophilised isolates were revived and examined using Etest (18 antimicrobials) and whole-genome sequencing (WGS). Quality-assured genome sequences were obtained for 191 viable and 40 non-viable isolates and analysed with multiple phylogenomic approaches. RESULTS: Gonococcal AMR, including an accumulation of multiple AMR determinants, started to emerge particularly in the 1950s-1970s. By the twenty-first century, resistance to most antimicrobials was common. Despite that some AMR determinants affect many physiological functions and fitness, AMR determinants were mainly selected by the use/misuse of gonorrhoea therapeutic antimicrobials. Most AMR developed in strains belonging to one multidrug-resistant (MDR) clade with close to three times higher genomic mutation rate. Modern N. gonorrhoeae was inferred to have emerged in the late-1500s and its genome became increasingly conserved over time. CONCLUSIONS: WGS of gonococci from 1928 to 2013 showed that no AMR determinants, except penB, were in detectable frequency before the introduction of gonorrhoea therapeutic antimicrobials. The modern gonococcus is substantially younger than previously hypothesized and has been evolving into a more clonal species, driven by the use/misuse of antimicrobials. The MDR gonococcal clade should be further investigated for early detection of strains with predispositions to develop and maintain MDR and for initiation of public health interventions.

Reduced In Vitro Susceptibility of Streptococcus pyogenes to ß-Lactam Antibiotics Associated with Mutations in the pbp2x Gene Is Geographically Widespread.

Recently, two related Streptococcus pyogenes strains with reduced susceptibility to ampicillin, amoxicillin, and cefotaxime, antibiotics commonly used to treat S. pyogenes infections, were reported. The two strains had the same nonsynonymous (amino acid-substituting) mutation in the pbp2x gene, encoding penicillin-binding protein 2X (PBP2X). This concerning report led us to investigate our library of 7,025 genome sequences of type emm1, emm28, and emm89S. pyogenes clinical strains recovered from intercontinental sources for mutations in pbp2x We identified 137 strains that, combined, had 37 nonsynonymous mutations in 36 codons in pbp2x Although to a lesser magnitude than the two previously published isolates, many of our strains had decreased susceptibility in vitro to multiple beta-lactam antibiotics. Many pbp2x mutations were found only in single strains, but 16 groups of two or more isolates of the same emm type had an identical amino acid replacement. Phylogenetic analysis showed that, with one exception, strains of the same emm type with the same amino acid replacement were clonally related by descent. This finding indicates that strains with some amino acid changes in PBP2X can successfully spread to new human hosts and cause invasive infections. Mapping of the amino acid changes onto a three-dimensional structure of the related Streptococcus pneumoniae PBP2X suggests that some substitutions are located in regions functionally important in related pathogenic bacterial species. Decreased beta-lactam susceptibility is geographically widespread in strains of numerically common emm gene subtypes. Enhanced surveillance and further epidemiological and molecular genetic study of this potential emergent antimicrobial problem are warranted.

Ten years of external quality assessment (EQA) of Neisseria gonorrhoeae antimicrobial susceptibility testing in Europe elucidate high reliability of data.

BACKGROUND: Confidence in any diagnostic and antimicrobial susceptibility testing data is provided by appropriate and regular quality assurance (QA) procedures. In Europe, the European Gonococcal Antimicrobial Susceptibility Programme (Euro-GASP) has been monitoring the antimicrobial susceptibility in Neisseria gonorrhoeae since 2004. Euro-GASP includes an external quality assessment (EQA) scheme as an essential component for a quality-assured laboratory-based surveillance programme. Participation in the EQA scheme enables any problems with the performed antimicrobial susceptibility testing to be identified and addressed, feeds into the curricula of laboratory training organised by the Euro-GASP network, and assesses the capacity of individual laboratories to detect emerging new, rare and increasing antimicrobial resistance phenotypes. Participant performance in the Euro-GASP EQA scheme over a 10 year period (2007 to 2016, no EQA in 2013) was evaluated. METHODS: Antimicrobial susceptibility category and MIC results from the first 5 years (2007-2011) of the Euro-GASP EQA were compared with the latter 5 years (2012-2016). These time periods were selected to assess the impact of the 2012 European Union case definitions for the reporting of antimicrobial susceptibility. RESULTS: Antimicrobial susceptibility category agreement in each year was ≥91%. Discrepancies in susceptibility categories were generally because the MICs for EQA panel isolates were on or very close to the susceptibility or resistance breakpoints. A high proportion of isolates tested over the 10 years were within one (≥90%) or two (≥97%) MIC log2 dilutions of the modal MIC, respectively. The most common method used was Etest on GC agar base. There was a shift to using breakpoints published by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) in the latter 5 years, however overall impact on the validity of results was limited, as the percentage categorical agreement and MIC concordance changed very little between the two five-year periods. CONCLUSIONS: The high level of comparability of results in this EQA scheme indicates that high quality data are produced by the Euro-GASP participants and gives confidence in susceptibility and resistance data generated by laboratories performing decentralised testing.

Establishment of the European meningococcal strain collection genome library (EMSC-GL) for the 2011 to 2012 epidemiological year.

Invasive meningococcal disease surveillance in Europe combines isolate characterisation and epidemiological data to support public health intervention. A representative European Meningococcal Strain Collection (EMSC) of IMD isolates was obtained, and whole genome sequenced to characterise 799 EMSC isolates from the epidemiological year July 2011-June 2012. To establish a genome library (GL), the isolate information was deposited in the pubMLST.org/neisseria database. Genomes were curated and annotated at 2,429 meningococcal loci, including those defining clonal complex, capsule, antigens, and antimicrobial resistance. Most genomes contained genes encoding B (n = 525; 65.7%) or C (n = 163; 20.4%) capsules; isolates were genetically highly diverse, with >20 genomic lineages, five of which comprising 60.7% (n = 485) of isolates. There were >350 antigenic fine-types: 307 were present once, the most frequent (P1.7-2,4:F5-1) comprised 8% (n = 64) of isolates. Each genome was characterised for Bexsero Antigen Sequence Typing (BAST): 25.5% (n = 204) of isolates contained alleles encoding the fHbp and/or the PorA VR1 vaccine component, but most genomes (n = 513; 64.2%) did not contain the NadA component. EMSC-GL will support an integrated surveillance of disease-associated genotypes in Europe, enabling the monitoring of hyperinvasive lineages, outbreak identification, and supporting vaccine programme implementation.

Evolutionary pathway to increased virulence and epidemic group A Streptococcus disease derived from 3,615 genome sequences.

We sequenced the genomes of 3,615 strains of serotype Emm protein 1 (M1) group A Streptococcus to unravel the nature and timing of molecular events contributing to the emergence, dissemination, and genetic diversification of an unusually virulent clone that now causes epidemic human infections worldwide. We discovered that the contemporary epidemic clone emerged in stepwise fashion from a precursor cell that first contained the phage encoding an extracellular DNase virulence factor (streptococcal DNase D2, SdaD2) and subsequently acquired the phage encoding the SpeA1 variant of the streptococcal pyrogenic exotoxin A superantigen. The SpeA2 toxin variant evolved from SpeA1 by a single-nucleotide change in the M1 progenitor strain before acquisition by horizontal gene transfer of a large chromosomal region encoding secreted toxins NAD(+)-glycohydrolase and streptolysin O. Acquisition of this 36-kb region in the early 1980s into just one cell containing the phage-encoded sdaD2 and speA2 genes was the final major molecular event preceding the emergence and rapid intercontinental spread of the contemporary epidemic clone. Thus, we resolve a decades-old controversy about the type and sequence of genomic alterations that produced this explosive epidemic. Analysis of comprehensive, population-based contemporary invasive strains from seven countries identified strong patterns of temporal population structure. Compared with a preepidemic reference strain, the contemporary clone is significantly more virulent in nonhuman primate models of pharyngitis and necrotizing fasciitis. A key finding is that the molecular evolutionary events transpiring in just one bacterial cell ultimately have produced millions of human infections worldwide.

Description and characterization of a penicillin-resistant Streptococcus dysgalactiae subsp. equisimilis clone isolated from blood in three epidemiologically linked patients.

BACKGROUND: During a 27 month period, we detected four incidents of penicillin-resistant (PR) Streptococcus dysgalactiae subsp. equisimilis (SDSE) isolated from blood cultures of three patients. METHODS: The 4 PR-SDSE were compared phenotypically and molecularly (using WGS) with 36 penicillin-susceptible SDSE from blood cultures obtained in the same catchment area and time period. RESULTS: Phylogenetic analysis showed that the four PR-SDSE belonged to a single clone and a possible epidemiological link between the three patients was identified to be a dermatology department. MICs of penicillin were determined to be 0.5-2 mg/L using Etest and 0.5 mg/L when tested by a broth microdilution method. The four PR-SDSE were unrelated to the 36 penicillin-susceptible isolates, which could suggest that they did not evolve locally from a susceptible clone, but have been introduced into the region. In silico genome-based resistome analysis revealed identical PBP mutations in all four isolates. We detected mutations in multiple PBPs, including two amino acid substitutions within the active sites of the transpeptidase domain of PBP2x (T341P and Q555E), which have also been detected in other PR streptococci. The remaining mutations were, however, all located outside the active-site motifs of the transpeptidase domain. CONCLUSIONS: To the best of our knowledge, this is the first description and characterization of invasive PR-SDSE. The resistant isolates had several amino acid changes in various PBPs compared with penicillin-susceptible SDSE. The observation that SDSE also can become PR emphasizes the importance of performing antimicrobial susceptibility testing.

WGS analysis and molecular resistance mechanisms of azithromycin-resistant (MIC >2 mg/L) Neisseria gonorrhoeae isolates in Europe from 2009 to 2014.

OBJECTIVES: To elucidate the genome-based epidemiology and phylogenomics of azithromycin-resistant (MIC >2 mg/L) Neisseria gonorrhoeae strains collected in 2009-14 in Europe and clarify the azithromycin resistance mechanisms. METHODS: Seventy-five azithromycin-resistant (MIC 4 to >256 mg/L) N. gonorrhoeae isolates collected in 17 European countries during 2009-14 were examined using antimicrobial susceptibility testing and WGS. RESULTS: Thirty-six N. gonorrhoeae multi-antigen sequence typing STs and five phylogenomic clades, including 4-22 isolates from several countries per clade, were identified. The azithromycin target mutation A2059G (Escherichia coli numbering) was found in all four alleles of the 23S rRNA gene in all isolates with high-level azithromycin resistance (n = 4; MIC ≥256 mg/L). The C2611T mutation was identified in two to four alleles of the 23S rRNA gene in the remaining 71 isolates. Mutations in mtrR and its promoter were identified in 43 isolates, comprising isolates within the whole azithromycin MIC range. No mutations associated with azithromycin resistance were found in the rplD gene or the rplV gene and none of the macrolide resistance-associated genes [mef(A/E), ere(A), ere(B), erm(A), erm(B), erm(C) and erm(F)] were identified in any isolate. CONCLUSIONS: Clonal spread of relatively few N. gonorrhoeae strains accounts for the majority of the azithromycin resistance (MIC >2 mg/L) in Europe. The four isolates with high-level resistance to azithromycin (MIC ≥256 mg/L) were widely separated in the phylogenomic tree and did not belong to any of the main clades. The main azithromycin resistance mechanisms were the A2059G mutation (high-level resistance) and the C2611T mutation (low- and moderate-level resistance) in the 23S rRNA gene.

Serological Response to Treatment of Syphilis with Doxycycline Compared with Penicillin in HIV-infected Individuals.

Serological response to treatment of syphilis with orally administered doxycycline or intramuscularly administered penicillin was assessed in patients with concurrent HIV. All HIV-infected individuals diagnosed with syphilis attending 3 hospitals in Copenhagen, Denmark were included. Odds ratios (ORs) with 95% confidence intervals (CI) associated with serological outcome were modelled using propensity-score-adjusted logistic regression analysis. In total, 202 cases were treated with doxycycline or intramuscular penicillin. At 12 months, serological failure was observed in 12 cases (15%) treated with doxycycline and in 8 cases (17%) treated with penicillin (OR 0.78 (95% CI 0.16-3.88), p = 0.76). The serological cure rate at 12 months was highest in patients with primary syphilis (100%), followed by patients with secondary (89%), early latent (71%) and late latent (67%) syphilis (p = 0.006). In conclusion, this study provides evidence for the use of doxycycline as a treatment option when treating a HIV-infected population for syphilis.

Molecular Typing of Treponema pallidum in Denmark: A Nationwide Study of Syphilis.

The aim of this nationwide study is to determine the strain type diversity among patients diagnosed with syphilis by PCR during a 4-year period in Denmark. Epidemiological data, including HIV status, for all patients were obtained from the Danish national syphilis registration system. Molecular strain typing was based on characterization of 3 variable treponemal genes, arp, tpr and tp0548. A total of 278 specimens from 269 patients were included. Among the fully typeable specimens (n = 197), 22 strain types were identified, with 1 type, 14d/g, accounting for 54%. The majority (93%) of the patients reported acquiring syphilis in Denmark. Among patients with concurrent HIV, 9 full strain types were identified and no difference in strain type was found by HIV status (p = 0.197). In conclusion, the majority of patients were infected in Denmark and the HIV-infected syphilis patients were diagnosed with a wide spectrum of different strain types of Treponema pallidum.

Epidemiology of pertussis in Denmark, 1995 to 2013.

We describe incidence and age distribution of laboratory-confirmed pertussis in Denmark from 1995 to 2013. Notification has been mandatory since 2007. Since 1997, an acellular monocomponent vaccine has been used. The latest epidemic occurred in 2002 with an incidence of 36 per 100,000; since 1995, only six infant deaths have been recorded. The inter-epidemic incidence lies below 10 per 100,000. In 1995, the mean age of confirmed cases was 9.2 years (95% confidence interval (CI): 7.9-10.5; median: 5.1), this gradually increased to 23.9 years in 2013 (95% CI: 22.0-25.8; median: 15.7). In 1995, 14% of laboratory-confirmed cases were 20 years and older, 43% in 2013. In the study period, the highest incidence among children was among those younger than one year with incidences between 84 and 331 per 100,000 in inter-epidemic periods (mean: 161/100,000) and 435 for the epidemic in 2002. After introduction of a preschool booster in 2003, the highest incidence among children one year and older changed gradually from three to five-year-olds in 2003 to 12 to 14-year-olds in 2013. In 2013, PCR was the primary method used for laboratory-diagnosis of pertussis in Denmark, while serology was the method with the highest percentage of positive results.

Inflammatory Bowel Disease Patients Are at Increased Risk of Invasive Pneumococcal Disease: A Nationwide Danish Cohort Study 1977-2013.

OBJECTIVES: Inflammatory bowel disease (IBD), Crohn's disease (CD), and ulcerative colitis (UC) are chronic diseases characterized by an inappropriate immune response, which may also increase the risk of infections. We investigated the risk of invasive pneumococcal disease (IPD) before and after diagnosis of IBD in a population-based cohort study. METHODS: In a cohort of 74,156 IBD patients and 1,482,363 non-IBD controls included and followed during 1977-2013, hazard rate ratios (HRs) for IPD in IBD patients vs. controls were calculated by Cox regression. Within the IBD group, we also calculated the risk according to ever use of specific IBD medications. Next, using conditional logistic regression, we evaluated the odds of IPD prior to IBD diagnosis. RESULTS: The HRs for IPD within the first 6 months after IBD diagnosis were significantly and more than threefold increased and then decreased to a constant level, which for CD was significantly increased (approximately twofold, HR, 1.99; 95% confidence interval (CI), 1.59-2.49) and for UC non-significantly just above 1. IBD medication use including tumor necrosis factor alpha antagonists had limited impact on the risk of IPD, although having ever used azathioprine increased the risk of IPD in patients with UC (HR, 2.38; 95% CI, 1.00-5.67). Up to 4 years prior to IBD diagnosis, the odds ratio for IPD was significantly increased (UC HR, 1.51, 95% CI, 1.05-2.17; CD HR, 1.79, 95% CI, 1.05-3.03). CONCLUSIONS: The risk of IPD is significantly increased both before and after diagnosis of IBD, with limited impact of IBD medications. This suggests that the risk of IPD in patients with IBD is related to the underlying altered immune response in these patients.

Recurrent severe invasive pneumococcal disease in an adult with previously unknown hyposplenia.

BACKGROUND: The risk of life-threatening and invasive infections with encapsulated bacteria is increased in patients with hyposplenia or asplenia. We report a case of recurrent invasive pneumococcal meningitis in a woman with previous unknown hyposplenia. She was vaccinated after the first episode of meningitis and developed sufficient levels of pneumococcal antibodies. The pneumococcal strains isolated were serotype 7 F and 17 F. To our knowledge, there has been no previously reported case of recurrent invasive pneumococcal disease in a pneumococcal vaccinated adult with hyposplenia and apparently sufficient antibody response. CASE PRESENTATION: We report the course of a 38-year-old Caucasian woman presenting with recurrent episodes of invasive pneumococcal disease (IPD) and previously unknown hyposplenia. Hyposplenia was discovered during the second episode of IPD and no underlying medical condition was found. Despite immunization against S. pneumoniae and measurement of what was interpreted as protective levels of serotype-specific IgG antibodies after vaccination, the patient suffered from a third episode of IPD. CONCLUSIONS: Individuals with predisposing medical conditions or a history of severe infections with encapsulated bacteria should be screened for spleen dysfunction. If splenic function is impaired, prevention against severe invasive infection with encapsulated bacteria are a major priority.