Background. The 92 capsular serotypes of Streptococcus pneumoniae differ greatly in nasopharyngeal carriage prevalence, invasiveness, and disease inc

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. Changes in IPD incidence and mortality during baseline (2000–2007), 7-valent pneumococcal conjugate vaccine (PCV7) (2008–2010), and PCV13 (2011–2013) periods were estimated. Predicted incidences of serotypes were estimated controlling for cyclical trends from historical patterns observed during the past 20 years. Results. We observed a 21% reduction (95% confidence interval [CI], 17%–25%) in IPD incidence in the total population after PCV13's introduction, and a 71% reduction (95% CI, 62%–79%) in children aged <2 years, considered as the vaccine effectiveness. We estimated a 28% reduction (95% CI, 18%–37%) in IPD-related 30-day mortality, from 3.4 deaths (95% CI, 3.2–3.6) per 100 000 population in the pre-PCV period to 2.4 (95% CI, 2.2–2.7) in the PCV13 period. The decline in mortality was observed across all age groups but was mainly related to mortality reductions in the nonvaccinated population. For serotypes 1 and 3, there were no significant changes in incidence beyond what would be expected from natural cyclical patterns. Serotype 19A significantly increased following PCV7's introduction, but the incidence declined toward baseline in 2012. Conclusions. PCV13 has brought greater benefits than we had expected in our setting. We observed a further decline on IPD incidence shortly after the shift from PCV7 to PCV13 in the national immunization program. This decline was accompanied by a substantial population-level decline in pneumococcal-related mortality of nearly 30% among nonvaccinated persons.

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). 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. A total of 18,858 IPD patients were included. Overall 30-d mortality was 18%, and 3% in children younger than age 5 y. Age, male sex, meningitis, high comorbidity level, alcoholism, and early decade of diagnosis were significantly associated with mortality. Among individuals aged 5 y and older, serotypes 31, 11A, 35F, 17F, 3, 16F, 19F, 15B, and 10A were associated with highly increased mortality as compared with serotype 1 (all: adjusted odds ratio ≥3, p<0.001). In children younger than 5 y, associations between serotypes and mortality were different than in adults but statistical precision was limited because of low overall childhood-related mortality. Specific pneumococcal serotypes strongly and independently affect IPD associated mortality.

Due to urgency and demand, numerous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoassays are rapidly being developed and placed on the market with limited validation on clinical samples. Thorough validation of serological tests are required to facilitate their use in the accurate diagnosis of SARS-CoV-2 infection, confirmation of molecular results, contact tracing, and epidemiological studies. This study evaluated the sensitivity and specificity of nine commercially available serological tests. These included three enzyme-linked immunosorbent assays (ELISAs) and six point-of-care (POC) lateral flow tests. The assays were validated using serum samples from: i) SARS-CoV-2 PCR-positive patients with a documented first day of disease; ii) archived sera obtained from healthy individuals before the emergence of SARS-CoV-2 in China; iii) sera from patients with acute viral respiratory tract infections caused by other coronaviruses or non-coronaviruses; and iv) sera from patients positive for dengue virus, cytomegalovirus and Epstein Barr virus. The results showed 100% specificity for the Wantai SARS-CoV-2 Total Antibody ELISA, 93% for the Euroimmun IgA ELISA, and 96% for the Euroimmun IgG ELISA with sensitivities of 90%, 90%, and 65%, respectively. The overall performance of the POC tests according to manufacturer were in the rank order of AutoBio Diagnostics > Dynamiker Biotechnology = CTK Biotech > Artron Laboratories > Acro Biotech ≥ Hangzhou Alltest Biotech. Overall, these findings will facilitate selection of serological assays for the detection SARS-CoV-2-specific antibodies towards diagnosis as well as sero-epidemiological and vaccine development studies.

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). 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. 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%. The epidemiology of IPD and single serotypes has constantly changed over the past 7 decades. PCV serotypes appeared to dominate the pneumococcal population.

Streptococcus pneumoniaeis 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 inCCDC33associated 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 includingpspCandzmpD, and perform a human-bacteria interaction analysis. These genes are potential candidates for the development of more broadly-acting pneumococcal vaccines.