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. The study included 437 children aged 12-72 months attending day care centres (DCC) and was conducted during 48 months. In total, 56% (n=247) of children were pneumococcal carriers with the highest prevalence in children aged 12–23 months (69%), the proportion significantly declining with increasing age. PCV7 serotypes accounted for 33%, PCV10 for 34%, and PCV13 for 57% of all carried isolates. The proportion of serotypes included in the three conjugate vaccines was higher among IPD isolates compared to carrier isolates (range 35– 90%). We found that the frequency of carriage was high among Danish pre-school children attending DCC and serotypes were not frequently covered by PCV7 in the pre-PCV7 period

Prediction of serotypes causing invasive pneumococcal disease in unvaccinated and vaccinated populations.

INTRODUCTION: Before the introduction of the heptavalent pneumococcal conjugate vaccine (Prevnar-7), the relative prevalence of serotypes of Streptococcus pneumoniae was fairly stable worldwide. We sought to develop a statistical tool to predict the relative frequency of different serotypes among disease isolates in the pre- and post-Prevnar-7 eras using the limited amount of data that is widely available. METHODS: We initially used pre-Prevnar-7 carriage prevalence and estimates of invasiveness derived from case-fatality data as predictors for the relative abundance of serotypes causing invasive pneumococcal disease during the pre- and post-Prevnar-7 eras, using negative binomial regression. We fit the model to pre-Prevnar-7 invasive pneumococcal disease data from England and Wales and used these data to (1) evaluate the performance of the model using several datasets and (2) evaluate the utility of the country-specific carriage data. We then fit an alternative model that used polysaccharide structure, a correlate of prevalence that does not require country-specific information and could be useful in determining the postvaccine population structure, as a predictor. RESULTS: Predictions from the initial model fit data from several pediatric populations in the pre-Prevnar-7 era. After the introduction of Prevnar-7, the model still had a good negative predictive value, though substantial unexplained variation remained. The alternative model had a good negative predictive value but poor positive predictive value. Both models demonstrate that the pneumococcal population follows a somewhat predictable pattern even after vaccination. CONCLUSIONS: This approach provides a preliminary framework to evaluate the potential patterns and impact of serotypes causing invasive pneumococcal disease

SARS-CoV-2 and risk of psychiatric hospital admission and use of psychopharmaceuticals: A nationwide registry study of 4,585,083 adult Danish citizens

Abstract Background Current evidence on the risk of admission- or medication-requiring psychiatric sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is limited to selected populations, short durations, and loss to follow-up. This study examined if SARS-CoV-2 infection was associated with increased long-term risk of psychiatric admissions and de novo prescription of psychoactive medication in the general population of Denmark. Methods Adults (≥18 years) were assigned to either the control or SARS-CoV-2 group based on polymerase chain reaction (PCR) tests between 1 January 2020 and 27 November 2021. Infected subjects were matched 1:5 to control subjects by propensity score. Incidence rate ratios (IRRs) were calculated. Adjusted Cox regression was applied to the unmatched population with SARS-CoV-2 infection as a time-dependent covariate. Follow-up time was 12 months or until the end of the study. Results A total of 4,585,083 adults were included in the study. Approximately 342,084 had a PCR-confirmed SARS-CoV-2 infection and were matched 1:5 with 1,697,680 controls. The IRR for psychiatric admission was 0.79 in the matched population (95% confidence interval [CI]: 0.73–0.85, p < 0.001). In the unmatched population, the adjusted hazard ratios (aHR) for psychiatric admission were either below 1.00 or with a 95% CI lower limit of 1.01. SARS-CoV-2 infection was associated with an increased risk of de novo prescription of psychoactive medication in both the matched (IRR 1.06, 95% CI: 1.02–1.11, p < 0.01) and unmatched population (HR 1.31, 95% CI: 1.28–1.34, p < 0.001). Conclusions We found a signal of increased use of psychoactive medication, specifically benzodiazepines, among SARS-CoV-2-positive persons, but the risk of psychiatric admissions did not increase

Robustness of genome-wide scanning using archived dried blood spot samples as a DNA source

<p>Abstract</p> <p>Background</p> <p>The search to identify disease-susceptible genes requires access to biological material from numerous well-characterized subjects. Archived residual dried blood spot (DBS) samples, also known as Guthrie cards, from national newborn screening programs may provide a DNA source for entire populations. Combined with clinical information from medical registries, DBS samples could provide a rich source for productive research. However, the amounts of DNA which can be extracted from these precious samples are minute and may be prohibitive for numerous genotypings. Previously, we demonstrated that DBS DNA can be whole-genome amplified and used for reliable genetic analysis on different platforms, including genome-wide scanning arrays. However, it remains unclear whether this approach is workable on a large sample scale. We examined the robustness of using DBS samples for whole-genome amplification following genome-wide scanning, using arrays from Illumina and Affymetrix.</p> <p>Results</p> <p>This study is based on 4,641 DBS samples from the Danish Newborn Screening Biobank, extracted for three separate genome-wide association studies. The amount of amplified DNA was significantly (P < 0.05) affected by the year of storage and storage conditions. Nine (0.2%) DBS samples failed whole-genome amplification. A total of 4,586 (98.8%) samples met our criterion of success of a genetic call-rate above 97%. The three studies used different arrays, with mean genotyping call-rates of 99.385% (Illumina Infinium Human610-Quad), 99.722% (Illumina Infinium HD HumanOmni1-Quad), and 99.206% (Affymetrix Axiom Genome-Wide CEU). We observed a concordance rate of 99.997% in the 38 methodological replications, and 99.999% in the 27 technical replications. Handling variables such as time of storage, storage conditions and type of filter paper were shown too significantly (P < 0.05) affect the genotype call-rates in some of the arrays, although the effect was minimal.</p> <p>Conclusion</p> <p>Our study indicates that archived DBS samples from the Danish Newborn Screening Biobank represent a reliable resource of DNA for whole-genome amplification and subsequent genome-wide association studies. With call-rates equivalent to high quality DNA samples, our results point to new opportunities for using the neonatal biobanks available worldwide in the hunt for genetic components of disease.</p

Pneumococcal Serotypes and Mortality following Invasive Pneumococcal Disease: A Population-Based Cohort Study

Analyzing population-based data collected over 30 years in more than 18,000 patients with invasive pneumococcal infection, Zitta Harboe and colleagues find specific pneumococcal serotypes to be associated with increased mortality

Seroprevalence of Pertussis among Danish Patients with Cough of Unknown Etiology▿ †

The common perception that pertussis is only a childhood disease is not correct. Vaccination or infection with Bordetella pertussis provides only short-lived protection against pertussis—and the majority of the population is consequently at risk of contracting pertussis. We evaluated the seroprevalence of pertussis antibodies (IgG against pertussis toxin) in serum samples from 265 Danish patients, aged 8 years and older, with coughs of unknown etiology. Depending on the cutoff chosen, we found that 2.6% to 10.9% of these patients were seropositive for pertussis. Of 178 patients with a reported duration of cough between 2 weeks and 3 months, 3.4% to 12.4% were seropositive for pertussis, indicating recent infection. Our study indicates that B. pertussis infection may be underdiagnosed among older children and adults with coughs in Denmark