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

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.

Joint sequencing of human and pathogen genomes reveals the genetics of pneumococcal meningitis.

Streptococcus pneumoniae is a common nasopharyngeal colonizer, but can also cause life-threatening invasive diseases such as empyema, bacteremia and meningitis. Genetic variation of host and pathogen is known to play a role in invasive pneumococcal disease, though to what extent is unknown. In a genome-wide association study of human and pathogen we show that human variation explains almost half of variation in susceptibility to pneumococcal meningitis and one-third of variation in severity, identifying variants in CCDC33 associated with susceptibility. Pneumococcal genetic variation explains a large amount of invasive potential (70%), but has no effect on severity. Serotype alone is insufficient to explain invasiveness, suggesting other pneumococcal factors are involved in progression to invasive disease. We identify pneumococcal genes involved in invasiveness including pspC and zmpD, and perform a human-bacteria interaction analysis. These genes are potential candidates for the development of more broadly-acting pneumococcal vaccines.

Potential carrier priming effect in Australian infants after 7-valent pneumococcal conjugate vaccine introduction.

AIM: To investigate evidence of clinical protection in infants after one dose of 7-valent pneumococcal conjugate vaccine (7vPCV) owing to carrier priming. METHODS: Using Australian National Notifiable Diseases Surveillance System data, we conducted a descriptive analysis of cases of vaccine type invasive pneumococcal disease (VT-IPD) during "catch-up" years, when 7vPCV was carrier primed by prior administration of DTPa vaccine. We compared the number of VT-IPD cases occurring 2-9 wk after a single dose of 7vPCV (carrier primed), with those < 2 wk post vaccination, when no protection from 7vPCV was expected yet. Further comparison was conducted to compare the occurrence of VT-IPD cases vs non-VT-IPD cases after a single carrier-primed dose of 7vPCV. RESULTS: We found four VT-IPD cases occurring < 2 wk after one carrier primed dose of 7vPCV while only one case occurred 2-9 wk later. Upon further comparison with the non-VT-IPD cases that occurred after one carrier primed dose of 7vPCV, two cases were detected within 2 wk, whereas seven occurred within 2-9 wk later; suggesting a substantial level of protection from VT-IPD occurring from 2 wk after carrier-primed dose of 7vPCV. CONCLUSION: This data suggest that infants may benefit from just one dose of 7vPCV, likely through enhanced immunity from carrier priming effect. If this is proven, an adjusted 2-dose schedule (where the first dose of PCV is not given until after DTPa) may be sufficient and more cost-effective.

Recurrent invasive pneumococcal disease in children: epidemiological, microbiological, and clinical aspects from a Danish 33-year nationwide survey (1980-2013).

BACKGROUND: Pneumococcal diseases play a major role in human morbidity and mortality. We present the results of a Danish nationwide study of recurrent paediatric invasive pneumococcal disease (rIPD) focusing on the epidemiological, microbiological, and clinical aspects. METHODS: All laboratory-confirmed cases of IPD in children aged 0-15 y were identified from the Neisseria and Streptococcus Reference Laboratory, Statens Serum Institut, Denmark for the period 1980-2013. rIPD was defined as isolation of Streptococcus pneumoniae from any normally sterile site ≥ 30 days after an initial positive culture. Clinical data were obtained for all children with rIPD. RESULTS: Of all children with IPD, 2.4% (59/2418) experienced at least 1 episode of rIPD, and an underlying condition was documented in 39 (66%). Immune deficiency due to transplantation (n = 9) was the most common disease; however, anatomic abnormalities (n = 8), complement C2 deficiency (n = 4), and congenital asplenia (n = 3) were all registered more than once. No underlying disease was detected in 18 children (31%). Based on the serotype distribution of S. pneumoniae isolates in rIPD among children aged 0-5 y (n = 41), 51%, 66%, and 78% of the cases would have been covered by the 7-, 10-, and 13-valent pneumococcal conjugate vaccines, respectively. CONCLUSIONS: Of children with an IPD episode, 2.4% experienced rIPD, and an underlying disease was documented in 66% of these children. Investigation of underlying conditions is essential in episodes of rIPD.

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). We fitted Poisson regression models for invasive pneumococcal disease, with predictors of seasonality, trends and influenza activity, and allowed the influenza activity variable to vary by comorbidity level and clinical presentation. Influenza activity accounted for 8.4% (95% CI 4.8-11.9%) and 6.9% (95% CI 5.4-10.2%) of all invasive pneumococcal disease cases among those aged 15-39 and ≥40 years, respectively, but had no measurable impact among children aged <15 years. Influenza activity was associated with significant increases in the incidence of invasive pneumococcal pneumonia in both children and adults. The association was more pronounced among younger adults without comorbidities. Case fatality also varied seasonally among the elderly, and this variation might be associated with influenza activity. Pneumococcal incidence and the severity of disease varied seasonally and between age groups. The effect of influenza activity on pneumococcal disease varied between children and adults, and this difference was largely due to differences in disease presentation.

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. We fit Poisson regression models for each age and comorbidity group, with predictors for seasonality and secular changes, ILI activity, and serotype. RESULTS: Among individuals with low levels of comorbidities, influenza had the largest impact on IPP incidence among low-invasiveness serotypes (influenza attributable percent: 17.9%, 95% confidence interval [CI], 13.6-21.9) as compared with high-invasiveness serotypes (6.7%, 95% CI, 3.8%-11.7%). Among those with higher levels of comorbidities, the effect of influenza was smaller, but high-invasiveness serotypes increased more than low-invasiveness serotypes (8.9% [95% CI, 6.6-11.8] vs. 1.3% [95% CI, -1.6-5.4]. CONCLUSIONS: Influenza was associated with the greatest increases in the incidence of disease caused by serotypes with lower invasive potential and among individuals with low levels of comorbid conditions. The importance of influenza for adult IPP varies by serotype and host comorbidity.

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. The period between April 19 and December 31, 2010 was considered a PCV7/PCV13 transitional period, where both vaccines were offered. We identified 45 episodes of IPD caused by a PCV7 serotype (23% of the total number) and 105 (55%) caused by one of the 6 additional serotypes in PCV13. Ten children had received at least one PCV7 dose before the onset of IPD caused by a PCV7 serotype. Seven children were considered to be incompletely vaccinated before IPD, but only three cases fulfilled the criteria of vaccine failure (caused by serotypes 14, 19F and 23F). One case of vaccine failure was observed in a severely immunosuppressed child following three PCV7 doses, and two cases were observed in immunocompetent children following two infant doses before they were eligible for their booster. None of the IPD cases caused by the additional PCV13 serotypes had been vaccinated by PCV13 and there were therefore no PCV13-vaccine failures in the first 8-months after PCV13 introduction in Denmark.

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.

Impact of pneumococcal vaccination in Denmark during the first 3 years after PCV introduction in the childhood immunization programme.

BACKGROUND AND AIMS: The 7-valent pneumococcal conjugate vaccine (PCV7) was introduced in Denmark in October 2007 in a 2+1 schedule with a catch-up programme for children up to 17 months of age. To assess the impact of PCV we evaluated on the whole population: (1) direct and indirect effects on incidence of invasive pneumococcal disease (IPD), (2) changes in pneumococcal serotype distribution and (3) IPD related mortality. METHODS: We compared disease incidence in pre-PCV (years 2000-2007) and PCV periods (years 2008-2010) based on national surveillance data. RESULTS: In children aged 0-5 years the overall incidence of IPD decreased from 26.7 to 16.3 cases per 100,000 (IRR 0.58; 95% Confidence Interval (CI) [0.48-0.69]) and case fatality declined from 1.8% (12 deaths) in the eight-year pre-PCV period to 0% (no deaths) in the three-year PCV period. In the whole population the overall incidence of IPD and of IPD caused by vaccine serotypes declined significantly from 19.5 to 17.7 and from 7.7 to 3.8 cases per 100,000 persons comparing the two periods. The incidence of IPD due to non-vaccine serotypes (NVT-IPD) increased significantly from 11.8 to 13.9 cases per 100,000 in the whole population (incidence rate ratio 1.18; 95% CI [1.12-1.24]) with predominance of the serotypes 1.7F and 19A. CONCLUSIONS: We report a marked decline in incidence in IPD in both vaccinated and non-vaccinated age groups and a minor but statistically significant increase in incidence of IPD due to NVTs in both vaccinated and non-vaccinated groups with predominance of serotypes covered by higher valence pneumococcal conjugate vaccines.

Risk factors for pneumococcal nasopharyngeal colonization before and after pneumococcal conjugate vaccination in persons with HIV: brief report.

HIV-infected individuals have excess rates of invasive pneumococcal disease. We investigated risk factors for nasopharyngeal pneumococcal colonization at baseline and after 9 months in 96 HIV patients immunized twice with 7- valent pneumococcal conjugate vaccine ±1mg CPG 7909. In total, 22 patients (23%) were colonized, 11 at baseline only, four at both baseline and 9 months, and seven at 9 months only. Compared to non-colonized patients, more colonized patients were smokers, had lower CD4+ nadir and had an AIDS-diagnosis. Immunization, antiretroviral treatment and the CPG adjuvant had no impact on colonization. These results suggest preventive strategies in addition to pneumococcal immunization.

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

BACKGROUND: 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. RESULTS: 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. CONCLUSION: 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.

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.

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.

Association of serotype with risk of death due to pneumococcal pneumonia: a meta-analysis.

BACKGROUND: The 92 capsular serotypes of Streptococcus pneumoniae differ greatly in nasopharyngeal carriage prevalence, invasiveness, and disease incidence. There has been some debate, though, regarding whether serotype independently affects the outcome of invasive pneumococcal disease (IPD). Published studies have shown variable results with regard to case-fatality ratios for specific serotypes and the role of host factors in affecting these relationships. We evaluated whether risk of death due to IPD is a stable serotype-associated property across studies and then compared the pooled effect estimates with epidemiologic and biological correlates. METHODS: We performed a systematic review and meta-analysis of serotype-specific disease outcomes for patients with pneumonia and meningitis. Study-specific estimates of risk of death (risk ratio [RR]) were pooled from 9 studies that provided serotype-specific data on pneumonia and meningitis using a random-effects method with serotype 14 as the reference. Pooled RRs were compared with RRs from adults with low comorbidity scores to evaluate potential confounding by host factors. RESULTS: Significant differences were found in the RR estimates among serotypes in patients with bacteremic pneumonia. Overall, serotypes 1, 7F, and 8 were associated with decreased RRs, and serotypes 3, 6A, 6B, 9N, and 19F were associated with increased RRs. Outcomes among meningitis patients did not differ significantly among serotypes. Serotypes with increased RRs had a high carriage prevalence, had low invasiveness, and were more heavily encapsulated in vitro. CONCLUSIONS: These results suggest that IPD outcome, like other epidemiologic measures, is a stable serotype-associated property.

Pneumococcal conjugate vaccination in persons with HIV: the effect of highly active antiretroviral therapy.

OBJECTIVE: Vaccination responses may be affected by concomitant use of highly active antiretroviral therapy (HAART). We aimed to determine HAART's impact on seven-valent pneumococcal conjugate (7vPnC) vaccine immunization with or without a Toll-like receptor 9 (TLR9) agonist adjuvant. DESIGN: Observational cohort study. METHODS: Adults with HIV were immunized with double doses of 7vPnC +/-1 mg CPG 7909, a TLR9 agonist and vaccine adjuvant, at 0 and 3 months, and 23-valent pneumococcal polysaccharide vaccine at 9 months. We measured IgG levels (ELISA) and opsonophagocytic activity (OPA) at months 0, 3, 4, 9, and 10. Persistent 7vPnC vaccine responders were defined as individuals with two-fold IgG increases to 1 microg/ml or more for at least five of the 7vPnC serotypes at 9 months. RESULTS: We included 75 participants on HAART and 20 HAART-naive. Forty-one received CPG 7909 and 48 received placebo adjuvant. More persistent 7vPnC vaccine responders were found among HAART-treated than among HAART-naive (42.3 vs. 15.0%, P = 0.03). Mean loss of vaccine-specific IgG from month 4 to 9 was greater among HAART-naive than among HAART-treated (54.8 vs. 38.1%, P = 0.001). Functional activity (OPA) was higher among HAART-treated than among HAART-naive at 4, 9, and 10 months. In a logistic regression analysis (adjusted for baseline CD4 cell count, CPG 7909, smoking status, BMI, AIDS diagnosis, and age), HAART use was significantly associated with being persistent 7vPnC vaccine responder at month 9 [odds ratio = 4.65, 95% confidence interval (CI) 1.07-20.2]. CONCLUSIONS: HIV-infected adults on HAART achieved a more durable antibody response of higher functional activity following pneumococcal conjugate vaccination than HAART-naive individuals, independently of baseline CD4 cell count.

Improving the immunogenicity of pneumococcal conjugate vaccine in HIV-infected adults with a toll-like receptor 9 agonist adjuvant: a randomized, controlled trial.

BACKGROUND: Persons infected with human immunodeficiency virus (HIV) are often hyporesponsive to immunization, including pneumococcal vaccines. We hypothesized that adding CPG 7909, a toll-like receptor 9 (TLR9) agonist and vaccine adjuvant, to 7-valent pneumococcal conjugate vaccine (7vPnC) would increase its immunogenicity in HIV-infected adults. METHODS: We performed a double-blind, placebo-controlled, phase 1b/2a trial randomizing HIV-positive patients to receive double doses of 7vPnC (Prevnar) at 0 and 3 months and 1 dose of 23-valent pneumococcal polysaccharide vaccine (PPV-23; Pneumo Novum) at 9 months, with experimental patients receiving 1 mg of CPG 7909 added to each of their 3 vaccine doses; control patients had phosphate-buffered saline added instead. Immunogenicity and safety were evaluated for up to 10 months. The primary end point was the proportion of vaccine high responders at 9 months, defined as a 2-fold increase in IgG levels to > or = 1 microg/mL for at least 5 of 7 of the 7vPnC serotypes. RESULTS: Ninety-seven participants were included in the study. The proportion of vaccine high responders was higher in the experimental group (n = 48) than among controls (n = 49; 48.8% vs 25.0%; P = .02) at 9 months. Greater proportions of high responders were also observed at 3 (51.1% vs 39.6%; P = .26), 4 (77.3% vs 56.3%; P = .03), and 10 months (87.8% vs 51.1%; P < .001). Mild systemic and injection site reactions to 7vPnC were more common in the experimental group than the control group (100% vs 81.3%; P = .002). CPG 7909 did not increase non-7vPnC IgG levels after PPV-23 immunization. No adverse effects on CD4(+) cell count or organ functions occurred in either group. CONCLUSIONS: The addition of a TLR9 agonist to 7vPnC significantly enhanced the proportion of vaccine high responders. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00562939 .

Antibody responses to pertussis toxin display different kinetics after clinical Bordetella pertussis infection than after vaccination with an acellular pertussis vaccine.

The measurement of IgG anti-pertussis toxin (IgG anti-PT) antibodies by ELISA is a frequently used method for studying the antibody responses after pertussis vaccination and after Bordetella pertussis infection. Such responses vary according to the different vaccines used as well as to the immunization and infection history of the participants. In the present study, the decay kinetics of the IgG anti-PT antibody response was determined for 71 Danish children and adults with bacteriologically confirmed B. pertussis infection and for 20 Danish adults booster-vaccinated with an acellular pertussis vaccine. For both groups, biphasic decay was seen, but the individual antibody responses varied greatly. No differences related to age were seen. Within each group, individual decay profiles showed parallel log-linear decay for the late part of the response. Antibody half-life was calculated for the late, slower part of the biphasic response curves for both groups (>5 months after diagnosis for individuals with confirmed infection; >3 months for vaccinated individuals). The median half-life for post-infection antibodies was 221 days [interquartile range (IQR) 159-314 days, 36 individuals], and the median half-life for post-vaccination antibodies was 508 days (IQR 428-616 days, 14 individuals). This difference was statistically significant (P<0.0001). Thus, in this setting, we found that the IgG anti-PT antibody decay after an infection with B. pertussis is more than twice as fast as the decay after booster vaccination with an acellular pertussis vaccine. Such knowledge of the IgG anti-PT decay kinetics is crucial for interpretation of serological data that will be used either for diagnosis or for epidemiological studies and surveillance of B. pertussis infections.

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. Changes in the reported incidence and trends of pneumococcal serotypes were explored using nonlinear regression analysis. RESULTS: There were 25,502 IPD cases included in our study. The median incidence of IPD increased from 2.8 cases per 100,000 population (interquartile range [IQR], 1.5-2.6) during the first 4 decades to 15.7 cases per 100,000 population (IQR, 7-20.4) during the 1980s and 1990s, mainly attributed to an increase in the number of bacteremia cases. The incidence of meningitis remained relatively stable, with a median of 1.3 cases per 100,000 population (IQR, 0.9-1.6). The proportions of serotypes/groups 4 and 9 increased; the proportion of serotype 18C decreased; the proportions of serotypes 6, 7F, 14, and 23F remained stable; and serotype 2 nearly disappeared. Before the 1960s, serotypes 1, 2, 3, and 5 presented peaks every 2-3 years, becoming less frequent during the 1970s with peaks every 7-10 years. Between 20% and 90% of IPD in children <5 years were caused by PCV serotypes during the last 4 decades. Cases of IPD caused by serotype 19A increased before introduction of PCV. Between 1993 and 2007, the level of resistance to macrolides and beta-lactams was 6%. CONCLUSIONS: The epidemiology of IPD and single serotypes has constantly changed over the past 7 decades. PCV serotypes appeared to dominate the pneumococcal population.

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 17.1 cases per 100,000 population (incidence rate ratios (IRR) 0.87; 95% confidence interval (CI) [0.81-0.96]), and of meningitis from 1.56 to 1.16 (IRR 0.74; 95% CI [0.57-0.97]) comparing pre-PCV7 (years 2000-2007) and PCV7 (year 2008) periods. In children <2 years, the incidence decreased from 54 to 23 cases per 100,000 (IRR 0.43; 95% CI [0.29-0.62]) and for vaccine-serotypes from 36.7 to 7.7 (IRR 0.20; 95% CI [0.09-0.38]). The incidence of IPD declined approximately 10% (IRR 0.90; 95% CI [0.84-0.97]) in patients aged >or=2 years. The case fatality was 17% in both periods. The administration of PCV7 was followed by a marked decline in the incidence of IPD in both vaccinated and non-vaccinated individuals.