Highlights • The effect of PCV on ten selected non-PCV serotypes in Denmark (1999–2014). • Children may not be the carrier for all pneumococcal serotypes causing IPD. • Carriage studies may be needed ...to identify among whom IPD serotypes are carried.
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.
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.
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.
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.
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.
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.
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).
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.
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.
Previous epidemiology reports on invasive
(GBS) infections in Denmark did not include all patient age groups. The aim of this study was therefore to analyze the GBS incidence in all age groups during ...the period 2005-2018 and to present the serotype distribution and the antibiotic susceptibility. Data were retrieved from the Danish laboratory surveillance system, and these included data on typing and susceptibility testing for erythromycin and clindamycin. Early-onset disease (EOD) (mean incidence 0.17 per 1,000 live births) and late-onset disease (LOD) (mean incidence 0.14 per 1,000 live births) showed a low level during the period. The incidence was stable in the age groups 91 days to 4 years, 5-19 years, and 20-64 years. From 2005 to 2018, the incidence in the elderly showed a significantly increasing trend (
< 0.05), that in the 65-74 years increased from 3.23 to 8.34 per 100,000, and that in the 75+ years increased from 6.85 to 16.01 per 100,000. Erythromycin and clindamycin resistance fluctuated over the period; however, the overall trend was increasing. Data showed that EOD and LOD incidence continued to be low, whereas an increasing trend in GBS infections in the elderly was observed. The prevalence of erythromycin and clindamycin resistance increased from 2005 to 2018.
The number of invasive
(GBS) non-typeable (NT) isolates in Denmark received since 1999 has in general accounted for 10% of all invasive GBS isolates. We present data on 55 clinical NT isolates based ...on clinical manifestations, clonal relationship, antimicrobial resistance (AMR) determinants, and virulence factors. The GBS isolates included in this study were phenotypic-based NT obtained from 2015 to 2017, as well as 10 reference isolates. Whole genome sequencing (WGS) was performed on all isolates and the data were analyzed for the presence of both species specific genes, capsular genes (genotype), and other relevant genes. We furthermore compared different procedures for detection of serotype specific capsular genes. Overall we were able to genotype 54 of the 55 isolates. After retesting the isolates a phenotype was detected for 20 (36%) isolates, of which the initial phenotyping problem for 13 isolates was found to be due to a problem with serotype Ia specific antiserum. Thirty-five isolates remained phenotypic non-typeable with a majority of genotype V isolates which do not express a capsular gene. From all the Danish invasive GBS isolates from 2015 to 2017, the 35 NT isolates were all detected in the age group above 21 years with bacteremia. The 35 NT isolates belonged to six different well-known human pathogenic clonal complexes. The CDC recommended sequences for capsule genotyping were the most optimal for serotype prediction, because of the sequence simplicity and clear cutoff values. However we recommend to also use other capsular sequences for the NT isolates, if they cannot be genotyped by the CDC method.
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.
Neisseria meningitidis serogroup W incidence has increased. Mortality associated with serogroup W has been higher than for other serogroups. Here we report epidemiological characteristics and risks ...of poor outcomes associated with invasive meningococcal disease in Denmark since 1980.
All cases of invasive meningococcal disease reported from 1980–2018 were analyzed. Incidence rates by age, sex, manifestation, and serogroup were calculated. Poisson regression was used to analyze the rise in serogroup W, and multivariate logistic analysis was used to analyze risk factors for mortality.
A total of 5825 cases were analyzed. Risk of serogroup W infection increased after 2015 compared with all previous periods. Younger (<20 years) and older age (≥60 years) was associated with an increased risk of serogroup W infection compared with being aged 20–39. Crude case fatality was 12.0%, 11.9%, 9.2%, and 7.9% for serogroups W, Y, C, and B, respectively. After adjustment for age, sex, and manifestation, 30-day mortality was comparable for serogroups. Older age and manifestation with sepsis independently predicted risk of death.
Invasive meningococcal disease caused by serogroup W has increased, but serogroup per se was not associated with an increased risk of 30-day mortality.
This study evaluates two procedures for typing of
(group B streptococci; GBS) isolates, using retrospective typing data from the period 2010 to 2014 with a commercial latex agglutination test (latex ...test) and the Lancefield precipitation test (LP test). Furthermore, the genotype distribution of phenotypically non-typable (NT) GBS isolates is presented. We also raise the awareness, that the difference in typing results obtained by phenotypical methods and genotype based methods may have implications on vaccine surveillance in case a GBS vaccine is introduced.
A total of 616 clinical GBS isolates from 2010 to 2014 were tested with both a latex test and the LP test. Among these, 66 isolates were genotyped by PCR, including 41 isolates that were phenotypically NT.
The latex test provided a serotype for 83.8% of the isolates (95% CI 80.7-86.6) compared to 87.5% (95% CI 84.6-90.0) obtained by the LP method. The two assays provided identical capsular identification for all sero-typeable isolates (excluding NT isolates). The PCR assay provided a genotype designation to the 41 isolates defined as phenotypically NT isolates.
We found that the latex test showed a slightly lower identification percentage than the LP test. Our recommendation is to use the latex agglutination as the routine primary assay for GBS surveillance, and then use the more labour intensive precipitation test on the NT isolates to increase the serotyping rate. A genotype could be assigned to all the phenotypically NT isolates, however, as a consequence genotyping will overestimate the coverage from possible future capsular polysaccharide based GBS vaccines.
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