Invasive Pneumococcal Disease Epidemiology and Serotype Replacement After the Introduction of the 13-Valent Pneumococcal Conjugate Vaccine in Ontario, Canada, 2007-2022.

Background: New vaccine products were recently authorized for protection against invasive pneumococcal disease (IPD) in Canada. Our aim was to determine age- and serotype-specific trends in IPD incidence and severity in Canada's largest province, Ontario. Methods: We included all confirmed IPD cases reported in Ontario and defined the pre-pneumococcal 13-valent conjugate vaccine (PCV13) era (01/2007 to 12/2010), post-PCV13 era (01/2011 to 12/2019), and coronavirus disease 2019 (COVID-19) pandemic era (01/2020 to 12/2022). We estimated incidence, hospitalization, and case fatality rate (CFR) by age. We grouped IPD cases by vaccine-specific serotypes (PCV13; PCV15-non-PCV13; PCV20-non-PCV13; PCV20-non-PCV15; polysaccharide 23-valent vaccine-non-PCV20; and non-vaccine-preventable [NVP]). We then compared incidence rates by age and serotype group in the pre- and post-PCV13 eras by calculating rate ratios (RRs) and their 95% CIs. Results: Incidence and hospitalizations declined from the pre- to post-PCV13 era in children aged <5 years (RR, 0.7; 95% CI, 0.6-0.8; and RR, 0.8; 95% CI, 0.7-0.9, respectively), but the CFR increased (1.4% to 2.3%). Other age groups saw smaller declines or more stable incidence rates across the years; hospitalizations increased in adults aged 50-64 years (RR, 1.2; 95% CI, 1.1-1.4) and ≥65 years (RR, 1.1; 95% CI, 1.0-1.1). For all ages, IPD cases and hospitalizations attributable to PCV13 serotypes declined, and those attributable to PCV15-non-PCV13, PCV20-non-PCV13, and NVP serotypes increased. IPD incidence declined during the COVID-19 era. Conclusions: IPD incidence and hospitalizations due to PCV13 serotypes decreased after PCV13 introduction but increased for other serotypes. Continued surveillance is required to evaluate changes to pneumococcal vaccination programs and ongoing changes to the distribution of IPD-causing serotypes.

Invasive pneumococcal disease surveillance in Canada, 2021-2022.

Background: Invasive pneumococcal disease (IPD, Streptococcus pneumoniae) has been a nationally notifiable disease in Canada since 2000. The use of conjugate vaccines has caused a shift in the distribution of serotypes over time. This report is a summary of the demographics, serotypes and antimicrobial resistance of IPD isolates collected in Canada in 2021 and 2022. Methods: The National Microbiology Laboratory (NML) of the Public Health Agency of Canada in Winnipeg, Manitoba collaborates with provincial and territorial public health laboratories to conduct national surveillance of IPD. There were 1,999 isolates reported in 2021 and 3,775 isolates in 2022. Serotype was determined by the Quellung reaction or whole-genome sequencing (WGS). Antimicrobial susceptibilities were determined by WGS methods, broth microdilution, or data shared by collaborators in the Canadian Antimicrobial Resistance Alliance program at the University of Manitoba. Population-based IPD incidence rates were obtained through the Canadian Notifiable Disease Surveillance System. Results: The incidence of IPD in Canada was 5.62 cases per 100,000 population in 2021, decreasing from the peak of 10.86 cases per 100,000 population in 2018. Serotypes with increasing trends (p<0.05) between 2018 and 2022 included: 4 (6.1%-12.4%), 9V (1.0%-5.1%) and 12F (4.8%-5.4%). The overall prevalence of PCV13 serotypes increased over the same period (31.2%-41.5%, p<0.05) while the prevalence of non-vaccine types decreased significantly (27.3%-21.5%, p<0.0001). The highest rates of antimicrobial resistance in 2021 and 2022 were seen with clarithromycin (21%, 2021; 24%, 2022) and erythromycin (22%, 2021; 24%, 2022). Multidrug-resistant IPD continued to increase from 2018 to 2022 (6.7%-12.6%, p<0.05). Conclusion: The number of cases of IPD continued to decrease in 2021 in comparison to previous years, however, 2022 saw a return to pre-COVID-19 levels. Disease due to PCV13 serotypes 3, 4, 9V and 19F, as well as non-PCV13 serotypes 12F and 20, is increasing in prevalence. Surveillance of IPD to monitor changing serotype distribution and antimicrobial resistance is essential.

Cost-effectiveness analysis of the 20-valent pneumococcal conjugate vaccine for the pediatric population in South Korea.

OBJECTIVES: To evaluate the cost-effectiveness of the 20-valent pneumococcal conjugate vaccine (PCV20) compared to 13-valent pneumococcal conjugate vaccine (PCV13) for the pediatric population in Korea, where the four-dose vaccine coverage rate is over 97%. METHODS: We constructed a Markov model to calculate the cost and quality-adjusted life-years (QALYs) over 10 years. The health states were susceptible states; disease states, which included invasive pneumococcal diseases such as meningitis, bacteremia, pneumonia, and acute otitis media; and death attributable to pneumococcal disease. The annual incidence and mortality due to pneumococcal diseases were estimated based on the serotypes covered by PCV13 and PCV20, vaccine coverage rate, vaccine effectiveness, and population size. Vaccine, administration, and disease costs were included in the model. RESULTS: In the total population (n = 51,431,305), PCV20 prevented more pneumococcal diseases and deaths, resulting in a gain of 74,855 QALY over PCV13. Meanwhile, the PCV20 group spent $275,136,631 less than the PCV13 group. As PCV20 gained more QALYs but spent less on total medical costs than PCV13, PCV20 was dominant over PCV13. CONCLUSIONS: In the Korean population, PCV20 is a cost-effective and dominant option over PCV13. Our findings provide evidence for decision-making regarding the introduction of PCV20 in countries with high vaccine coverage.

Follow-Up Study of Effectiveness of 23-Valent Pneumococcal Polysaccharide Vaccine Against All-Type and Serotype-Specific Invasive Pneumococcal Disease, Denmark.

As a follow-up to a previous study, we investigated vaccine effectiveness (VE) of 23-valent pneumococcal polysaccharide vaccine (PPSV23) against invasive pneumococcal disease (IPD) among 1,254,498 persons >65 years of age as part of a vaccination program in Denmark during April 2020-January 2023. We assessed VE by using a Cox regression model and adjusted for age, sex, and underlying conditions. Using nationwide data, we estimated a VE of PPSV23 against all-type IPD of 32% and against PPSV23-serotype IPD of 41%. Because this follow-up study had more statistical power than the original study, we also estimated VE against IPD caused by PPSV23-serotypes excluding serotype 3; serotype 3; serotype 8; serotype 22F; PPSV23 non-PCV15 serotypes; PPSV23 non-PCV20 serotypes; and IPD over time. Our findings suggest PPSV23 vaccination can protect persons >65 years of age against IPD caused by all serotypes or serotype groupings, except serotype 3.

Lifetime Health and Economic Burden of Invasive Pneumococcal Diseases Attributable to V116 Serotypes Among Adults in the United States.

INTRODUCTION: This study aimed to estimate and compare the lifetime clinical and economic burden of invasive pneumococcal diseases (IPD) attributable to the serotypes contained in a new 21-valent pneumococcal conjugate vaccine (V116) vs. the 20-valent pneumococcal conjugate vaccine (PCV20) among adults aged 18 years and above in the USA. METHODS: A state-transition Markov model was used to track IPD cases and deaths as well as the associated direct medical costs (in 2023 US dollars) from a US healthcare payer perspective at 3% annual discount rate. The results were summarized for V116, PCV20, and eight unique serotypes contained in V116. A sensitivity analysis was conducted to determine the most influential inputs on the overall total direct lifetime cost. RESULTS: For the total population of US adults aged 18 years and above in 2021 (approx. 258 million residents), the estimated lifetime numbers of cases of IPD, post-meningitis sequelae (PMS), and IPD-related deaths attributable to the serotypes contained in V116 were approximately 1.4 million, 17,608, and 186,200, respectively, with a total discounted lifetime direct cost of $32.6 billion. A substantial proportion (approx. 31%) of those were attributable to the unique eight serotypes. The corresponding estimates for PCV20 were approximately 35% lower-934,000, 11,500, and 120,000, respectively-with a total discounted direct lifetime cost of $21.9 billion. CONCLUSION: These results show that V116 serotypes (compared to PCV20) are associated with substantially higher clinical and economic burden of IPD. The addition of V116 to vaccination recommendations can help to reduce the residual burden of IPD in US adults.

Invasive pneumococcal serotype 3 infection following pneumococcal vaccination in a hematopoietic stem cell transplant patient: A case report.

Given the high mortality rate of invasive pneumococcal disease (IPD) in hematopoietic stem cell transplant (HSCT) recipients, vaccination is recommended. These recipients respond to most vaccines; however, their immune response is typically weaker during the first months or years after transplantation, compared with that of healthy individuals. Here, we report a case of IPD with serotype 3 pneumonia and empyema in an HSCT recipient who had received three doses of the 13-valent pneumococcal conjugate vaccine (PCV) and one dose of the 23-valent pneumococcal polysaccharide vaccine; furthermore, the recipient had no relapse, graft-versus-host disease, or use of immunosuppressive agents after allogeneic HSCT for acute myeloid leukemia. Moreover, we discussed the characteristics of serotype 3 Streptococcus pneumoniae, a case series of breakthrough infections with S. pneumoniae in HSCT recipients who received pneumococcal vaccines, and the potential implications for the upcoming PCV15 and PCV20 vaccines for serotype 3.

Cost-effectiveness of PCV20 to Prevent Pneumococcal Disease in the Pediatric Population: A German Societal Perspective Analysis.

INTRODUCTION: Since 2009, a pneumococcal conjugate vaccine (PCV) covering 13 serotypes (PCV13) has been included by Germany's Standing Committee on Vaccinations for infants, resulting in major reductions in pneumococcal disease (PD). Higher-valent vaccines may further reduce PD burden. This cost-effectiveness analysis compared 20-valent PCV (PCV20) under a 3+1 schedule with 15-valent PCV (PCV15) and PCV13, both under 2+1 schedule, in Germany's pediatric population. METHODS: A Markov model with annual cycles over a 10-year time horizon was adapted to simulate the clinical and economic impact of pediatric vaccination with PCV20 versus lower-valent PCVs in Germany. The model used PCV13 clinical effectiveness and impact studies as well as PCV7 efficacy studies for vaccine direct and indirect effect estimates. Epidemiologic, utility, and medical cost inputs were obtained from published sources. Benefits and costs were discounted at 3% from a German societal perspective. Outcomes included PD cases, deaths, costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). RESULTS: In the base case, PCV20 provided greater health benefits than PCV13, averting more cases of invasive pneumococcal disease (IPD; 15,301), hospitalized and non-hospitalized pneumonia (460,197 and 472,365, respectively), otitis media (531,634), and 59,265 deaths over 10 years. This resulted in 904,854 additional QALYs and a total cost saving of €2,393,263,611, making PCV20 a dominant strategy compared with PCV13. Compared to PCV15, PCV20 was estimated to avert an additional 11,334 IPD, 704,948 pneumonia, and 441,643 otitis media cases, as well as 41,596 deaths. PCV20 was associated with a higher QALY gain and lower cost (i.e., dominance) compared with PCV15. The robustness of the results was confirmed through scenario analyses as well as deterministic and probabilistic sensitivity analyses. CONCLUSION: PCV20 3+1 dominated both PCV13 2+1 and PCV15 2+1 over 10 years. Replacing lower-valent PCVs with PCV20 would result in greater clinical and economic benefits, given PCV20's broader serotype coverage.

Pneumococcal diseases (e.g., ear infections, pneumonia, bloodstream infections) are among the leading causes of illness and death in children worldwide. The pneumococcal conjugate vaccine protects against pneumococcal diseases and has significantly reduced the number of newly diagnosed cases. Higher-valent vaccines (which provide coverage for a greater number of disease-causing serotypes) have recently received European Commission approval for use in adults and  children. This study examined costs and health benefits associated with the 20-valent pneumococcal conjugate vaccine (PCV20) under a 3+1 (i.e., three primary doses and one booster dose) schedule in Germany's childhood vaccination program compared with 13-valent pneumococcal conjugate vaccine (PCV13) and the 15-valent pneumococcal conjugate vaccine (PCV15), both under a 2+1 (two primary doses, one booster) schedule. PCV20 was estimated to result in greater health benefits from avoiding more cases in pneumococcal diseases and lower costs compared with both PCV13 and PCV15. PCV20, therefore, is considered the best option among the three vaccines for children in Germany.

Cost-effectiveness analysis of adult pneumococcal conjugate vaccines for pneumococcal disease in Japan.

BACKGROUND: The 23-valent pneumococcal polysaccharide vaccine (PPSV23) is used in the Japanese National Immunization Program for older adults and adults with increased risk for pneumococcal disease, however, disease incidence and associated burden remain high. We evaluated the cost-effectiveness of pneumococcal conjugate vaccines (PCVs) for adults aged 65 years and high-risk adults aged 60-64 years in Japan. RESEARCH DESIGN AND METHODS: Using a Markov model, we evaluated lifetime costs using societal and healthcare payer perspectives and estimated quality-adjusted life-years (QALYs), and number of prevented cases and deaths caused by invasive pneumococcal disease (IPD) and non-IPD. The base case analysis used a societal perspective. RESULTS: In comparison with PPSV23, the 20-valent PCV (PCV20) prevented 127 IPD cases 10,813 non-IPD cases (inpatients: 2,461, outpatients: 8,352) and 226 deaths, and gained more QALYs (+0.0015 per person) with less cost (-JPY22,513 per person). All sensitivity and scenario analyses including a payer perspective analysis indicated that the incremental cost-effectiveness ratios (ICERs) were below the cost-effectiveness threshold value in Japan (JPY5 million/QALY). CONCLUSIONS: PCV20 is both cost saving and more effective than PPSV23 for adults aged 65 years and high-risk adults aged 60-64 years in Japan.

Effectiveness of 13-valent pneumococcal conjugate vaccine for prevention of invasive pneumococcal disease among children in the United States between 2010 and 2019: An indirect cohort study.

BACKGROUND: A U.S. case-control study (2010-2014) demonstrated vaccine effectiveness (VE) for ≥ 1 dose of the thirteen-valent pneumococcal conjugate vaccine (PCV13) against vaccine-type (VT) invasive pneumococcal disease (IPD) at 86 %; however, it lacked statistical power to examine VE by number of doses and against individual serotypes. METHODS: We used the indirect cohort method to estimate PCV13 VE against VT-IPD among children aged < 5 years in the United States from May 1, 2010 through December 31, 2019 using cases from CDC's Active Bacterial Core surveillance, including cases enrolled in a matched case-control study (2010-2014). Cases and controls were defined as individuals with VT-IPD and non-PCV13-type-IPD (NVT-IPD), respectively. We estimated absolute VE using the adjusted odds ratio of prior PCV13 receipt (1-aOR x 100 %). RESULTS: Among 1,161 IPD cases, 223 (19.2 %) were VT cases and 938 (80.8 %) were NVT controls. Of those, 108 cases (48.4 %; 108/223) and 600 controls (64.0 %; 600/938) had received > 3 PCV13 doses; 23 cases (17.6 %) and 15 controls (2.4 %) had received no PCV doses. VE ≥ 3 PCV13 doses against VT-IPD was 90.2 % (95 % Confidence Interval75.4-96.1 %), respectively. Among the most commonly circulating VT-IPD serotypes, VE of ≥ 3 PCV13 doses was 86.8 % (73.7-93.3 %), 50.2 % (28.4-80.5 %), and 93.8 % (69.8-98.8 %) against serotypes 19A, 3, and 19F, respectively. CONCLUSIONS: At least three doses of PCV13 continue to be effective in preventing VT-IPD among children aged < 5 years in the US. PCV13 was protective against serotypes 19A and 19F IPD; protection against serotype 3 IPD did not reach statistical significance.

Austrian syndrome: Report of one case and a systematic review of case reports - new insights.

OBJECTIVE: The objective of this review was to gain new insight into the rare condition, Austrian syndrome: the triad of endocarditis, meningitis and pneumonia caused by Streptococcus pneumoniae. METHODS: A systematic review of case reports was conducted using the PRISMA guideline. Cases were rigorously screened to meet a set of well-defined inclusion criteria. Relevant data was aggregated and reported using descriptive statistics. RESULTS: Seventy-one cases from 69 case reports were included in the final review. The mean age was 56.5 years with a male-to-female ratio of 2.4:1. Alcoholism was reported in 41% of patients. Altered mental state (69%) and fever (65%) (mean temperature on admission = 38.9°C) were the commonest presenting symptoms. The mean duration of symptoms before presentation to the hospital was 8 days. The aortic valve was most commonly affected (56%). The mean duration of antibiotic therapy was 5.6 weeks. Seventy percent of patients were admitted to the intensive care unit (ICU). Fifty-six percent of patients had valvular surgery. The average length of stay in the hospital was 36.9 days. Mortality was recorded in 28% of patients. CONCLUSION: Austrian syndrome is rare but deadly. The true incidence is unknown but is commoner in middle-aged men and in alcoholics. Affected patients are usually critically unwell, often requiring ICU admission and prolonged hospital stays. Treatment is aggressive including prolonged courses of antibiotics and often, surgery. Despite these, the case fatality rate is high, with death occurring in over a quarter of patients. Surgery appears to be associated with better prognosis.

Invasive pneumococcal diseases in Chinese children: a multicentre hospital-based active surveillance from 2019 to 2021.

This study aimed to provide data for the clinical features of invasive pneumococcal disease (IPD) and the molecular characteristics of Streptococcus pneumoniae isolates from paediatric patients in China. We conducted a multi-centre prospective study for IPD in 19 hospitals across China from January 2019 to December 2021. Data of demographic characteristics, risk factors for IPD, death, and disability was collected and analysed. Serotypes, antibiotic susceptibility, and multi-locus sequence typing (MLST) of pneumococcal isolates were also detected. A total of 478 IPD cases and 355 pneumococcal isolates were enrolled. Among the patients, 260 were male, and the median age was 35 months (interquartile range, 12-46 months). Septicaemia (37.7%), meningitis (32.4%), and pneumonia (27.8%) were common disease types, and 46 (9.6%) patients died from IPD. Thirty-four serotypes were detected, 19F (24.2%), 14 (17.7%), 23F (14.9%), 6B (10.4%) and 19A (9.6%) were common serotypes. Pneumococcal isolates were highly resistant to macrolides (98.3%), tetracycline (94.1%), and trimethoprim/sulfamethoxazole (70.7%). Non-sensitive rates of penicillin were 6.2% and 83.3% in non-meningitis and meningitis isolates. 19F-ST271, 19A-ST320 and 14-ST876 showed high resistance to antibiotics. This multi-centre study reports the clinical features of IPD and demonstrates serotype distribution and antibiotic resistance of pneumococcal isolates in Chinese children. There exists the potential to reduce IPD by improved uptake of pneumococcal vaccination, and continued surveillance is warranted.

Unveiling the role of preceding seasonal influenza in the development of bacteremic pneumococcal pneumonia in older adults before the COVID-19 pandemic in Japan.

OBJECTIVE: We aimed to investigate the impact of preceding seasonal influenza on the clinical characteristics of adult patients with invasive pneumococcal disease (IPD) in Japan. METHODS: Data for 1722 adult patients with IPD were analyzed before (2017-2019) and during the COVID-19 pandemic (2020-2022). RESULTS: The seasonal influenza epidemic disappeared soon after the emergence of the pandemic. Compared with that before the pandemic (66.7%), we observed a lower bacteremic pneumonia proportion in patients with IPD during the pandemic (55.6%). The clinical presentations of IPD cases significantly differed between those with and without preceding influenza. The proportion of bacteremic pneumonia was higher in IPD patients with preceding influenza than in those without in both younger (44.9% vs 84.2%) and older adults (65.5% vs 87.0%) before the pandemic. The case fatality rate was significantly higher in IPD patients with preceding influenza (28.3%) than in those without (15.3%) in older adults before the pandemic (P = 0.020). Male and aging are high risk factors for death in older patients with IPD who had preceding influenza. CONCLUSION: Our study reveals that preceding seasonal influenza plays a role in the development of bacteremic pneumococcal pneumonia, increasing the risk of death in older adults.

Exploring factors shaping antibiotic resistance patterns in Streptococcus pneumoniae during the 2020 COVID-19 pandemic.

Non-pharmaceutical interventions implemented to block SARS-CoV-2 transmission in early 2020 led to global reductions in the incidence of invasive pneumococcal disease (IPD). By contrast, most European countries reported an increase in antibiotic resistance among invasive Streptococcus pneumoniae isolates from 2019 to 2020, while an increasing number of studies reported stable pneumococcal carriage prevalence over the same period. To disentangle the impacts of the COVID-19 pandemic on pneumococcal epidemiology in the community setting, we propose a mathematical model formalizing simultaneous transmission of SARS-CoV-2 and antibiotic-sensitive and -resistant strains of S. pneumoniae. To test hypotheses underlying these trends five mechanisms were built into the model and examined: (1) a population-wide reduction of antibiotic prescriptions in the community, (2) lockdown effect on pneumococcal transmission, (3) a reduced risk of developing an IPD due to the absence of common respiratory viruses, (4) community azithromycin use in COVID-19 infected individuals, (5) and a longer carriage duration of antibiotic-resistant pneumococcal strains. Among 31 possible pandemic scenarios involving mechanisms individually or in combination, model simulations surprisingly identified only two scenarios that reproduced the reported trends in the general population. They included factors (1), (3), and (4). These scenarios replicated a nearly 50% reduction in annual IPD, and an increase in antibiotic resistance from 20% to 22%, all while maintaining a relatively stable pneumococcal carriage. Exploring further, higher SARS-CoV-2 R0 values and synergistic within-host virus-bacteria interaction mechanisms could have additionally contributed to the observed antibiotic resistance increase. Our work demonstrates the utility of the mathematical modeling approach in unraveling the complex effects of the COVID-19 pandemic responses on AMR dynamics.

Utility of quantitative loop mediated isothermal amplification (qLAMP) assay for the diagnosis of invasive pneumococcal disease (IPD).

PURPOSE: Quantitative LAMP (qLAMP) assay is one of the recent and emerging diagnostic tests for infectious diseases. Only a few studies exist comparing this assay with quantitative real-time PCR (qPCR) for the diagnosis of invasive pneumococcal disease (IPD). AIM: To compare the diagnostic performance of qLAMP assay with qPCR targeting autolysin gene for the diagnosis of invasive pneumococcal disease. METHODS: Ninety six blood samples and 73 CSF samples from patients clinically suspected with community acquired pneumonia and acute meningitis were tested by qPCR and qLAMP assays using previously published primers and protocols. The qPCR was considered as the gold standard test and the diagnostic performance was assessed by calculating sensitivity, specificity, positive and negative predictive values, and kappa coefficient for the level of agreement between the tests. Chi-squared/Fisher exact test was used to compare categorical variables (positive/negative). RESULTS: Thirty two blood samples and 22 CSF samples were positive by qPCR while 24 and 20 samples were positive by qLAMP assay respectively. The sensitivity of qLAMP assay was only 86.4% and 75% when tested on CSF and blood samples respectively. However, the qLAMP assay was in substantial to almost perfect agreement when compared with qPCR. The results were statistically significant in both sample types (P < 0.001). CONCLUSIONS: The performance of qLAMP assay can vary based on the specimen type. It has very high specificity and had substantial to almost perfect agreement, and thus may be an alternative to qPCR for the diagnosis of IPD.

Beneath the surface: a case report on nonencapsulated Streptococcus pneumoniae-associated invasive disease in an immunocompromised patient.

Background: Streptococcus pneumoniae, a prominent human pathogen linked to various systemic diseases, includes non-typeable pneumococci marked by the absence of a detectable capsule. However, the majority of invasive infections are attributed to encapsulated strains. This case report details the first documented instance of invasive disease caused by non-typeable S. pneumoniae in Argentina since 2017. Case Presentation: A 19-year-old woman presented with haemorrhagic injuries attributed to chronic oral mucosa irritation. Subsequent hospitalization revealed bone marrow aplasia, leading to antibiotic, antifungal, antiviral, and immunosuppressive treatments, culminating in her discharge. Two weeks later, she was readmitted with sepsis related to a respiratory focus, exhibiting a negative COVID-PCR test. After ten days, ICU admission revealed additional infections: positive COVID-PCR test, fungal sinusitis, and S. pneumoniae bacteremia. Targeted treatments led to improvement, and the patient was subsequently discharged. S pneumoniae characterization: Verification of the capsule's absence utilized traditional methods such as the Quellung reaction, transmission electron microscopy, molecular assays, and Whole Genome Sequencing (WGS). The isolate, identified as ST18335, displayed genetic features and antibiotic resistance patterns, concordant between WGS and the agar dilution method. It demonstrated non-susceptibility to penicillin and cefotaxime, based on meningitis breakpoints, as well as meropenem and cotrimoxazole. Conclusion: This case underscores the clinical significance of non-typeable S. pneumoniae, emphasizing the necessity for a comprehensive approach to identification and characterization. The findings contribute to ongoing discussions regarding the challenges posed by non-typeable strains in vaccine development, understanding clinical impacts, and addressing antibiotic resistance. As the pneumococcal epidemiological landscape evolves, this case serves as a valuable addition to the evolving knowledge surrounding non-typeable S. pneumoniae, highlighting the continued need for surveillance and research in infectious diseases.

Strategies for pneumococcal vaccination in older adults in the coming era.

Pneumonia, predominantly caused by Streptococcus pneumoniae, remains a leading cause of global mortality. The 23-valent Pneumococcal polysaccharide vaccine (PPSV23) and conjugate vaccines (PCVs) are vital measures to fight against it. This paper discussed the changes in pneumococcal vaccination strategies, particularly for older adults, as vaccine effectiveness and epidemiological patterns shift. While PPSV23 maintains effectiveness against invasive pneumococcal disease (IPD), its effectiveness against pneumococcal pneumonia is declining. Conversely, PCV13 consistently demonstrates effectiveness against both IPD and pneumonia. Consequently, the US Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices recommends using PCVs, notably PCV20 and PCV15, over PPSV23. Japanese studies indicate a change in the efficacy/effectiveness of PPSV23 following PCV introduction in children, likely owing to serotype replacement and herd immunity. Additionally, recent data reveals a plateau in the reduction of PCV13 and PPSV23-covered serotypes, posing a challenge to current strategies. This paper indicates a paradigm shift in pneumonia management, acknowledging its chronic nature and potential to exacerbate other diseases. The future of pneumococcal vaccination lies in broader serotype coverage through PCVs, adapting to serotype changes driven by childhood vaccination programs. Furthermore, continuous research and vaccine development are crucial in this evolving field.

Reduction in the incidence of invasive infections caused by encapsulated bacteria after the onset of the COVID-19 pandemic / Reducción de la incidencia de infecciones invasivas por bacterias capsuladas luego del inicio de la Pandemia por COVID-19

Abstract Interaction between severe acute respiratory coronavirus 2 (SARS-CoV-2) and IIEB remains under investigation. Objective: to compare IIEB incidence before and during COVID-19 pandemic, and assess incidence of coinfection with COVID-19 and case fatality. A cross-sectional study was performed on data from a centralized microbiology laboratory serving a network of healthcare centers comprising 713 pediatric and adult inpatient beds, expanded by 20% during the pandemic. Three periods were evaluated: (1) pre-pandemic: March 1, 2019-February 29, 2020; (2) pandemic year 1: March 1, 2020-February 28, 2021; (3) pandemic year 2: March 1, 2021-July 31, 2021. Descriptive statistical analysis was performed. 56502 samples (96% blood cultures) from 27224 patients were analyzed. Of these, 54 samples (from 54 patients) were positive for encapsulated bacteria. IIEB incidence was: 167.4, 32.6, and 50.4 per 100000 samples for periods 1, 2, and 3, respectively. Twelve IIEB episodes occurred during the pandemic period: 10 Streptococcus pneumoniae, and 2 Haemophilus influenzae, of which 7 were SARS-CoV-2/S. pneumoniae coinfections, with an incidence of 5.68 per 10000 COVID-19-related hospitalizations (0.056%). IIEB case fatality was 31%, 29%, and 60% for each period, respectively, 3/7 patients with coinfection died (43%). Case fatality for invasive pneumococcal disease (IPD) in patients without COVID-19, was 32.5%. Significant reduction in IIEB incidence was observed during the pandemic, coinciding with implementation of containment measures. The incidence of SARS-CoV-2/S. pneumoniae coinfection was low, with higher case fatality than IPD patients without COVID-19.

Resumen La interacción entre SARS-CoV-2 e infecciones invasivas por bacterias capsuladas (IIBC) continúa bajo estudio. Objetivos: comparar la incidencia de IIBC antes y durante la pandemia por COVID-19, evaluar la incidencia de coinfección con COVID-19 y la letalidad. Estudio transversal de registros de un laboratorio centralizado de Microbiología, que asiste a una red de centros asistenciales con 713 camas de internación para adultos y pediátricos, expandida 20% durante la pandemia. Tres periodos evaluados: 1) Pre-pandemia: 1-Marzo-2019 al 29-Febrero-2020; 2) Primer año de Pandemia: 1-Marzo-2020 al 28-Febrero-2021; 3) Pandemia 2021: 1-Marzo-2021 al 31-Julio-2021. Análisis estadístico descriptivo: Se analizaron 56.502 muestras (96% hemocultivos) correspondientes a 27.224 pacientes. De estas, 54 muestras (de 54 pacientes) fueron positivas para bacterias capsuladas. La incidencia de IIBC fue 167,4, 32,6 y 50,4 por cada 100.000 muestras para los periodos 1, 2 y 3, respectivamente. Doce IIBC ocurrieron durante la pandemia: 10 Streptococcus pneumoniae y dos Haemophilus influenzae, siete de ellos corresponden a coinfección SARS-CoV-2/S. pneumoniae, con una incidencia de 5,68 por cada 10.000 internaciones por COVID 19 (0,056%). La letalidad de las IIBC fue de 31, 29 y 60% para los tres periodos, respectivamente, 3/7 coinfectados fallecieron (43%). La letalidad por enfermedad neumocócica invasiva (ENI), sin COVID fue de 32,5%. Se evidenció una reducción significativa de la incidencia de IIBC luego del comienzo de la pandemia, coincidente con la implementación de las medidas sanitarias de contención de la pandemia. La incidencia de coinfección de SARS-CoV-2/S. pneumoniae fue baja y presentó mayor letalidad que las ENI sin COVID-19.

Neighborhood-level disadvantages increase risk for invasive pneumococcal disease.

BACKGROUND: Streptococcus pneumoniae (Spn) infection remains common worldwide despite recent vaccine efforts. Invasive pneumococcal disease (IPD) is the most severe form of Spn infection. Known individual risk factors for IPD include male gender and African American race. However, area-level socioeconomic factors have not been assessed. We examined the association of neighborhood-level disadvantages and risk of IPD in a tertiary medical center located in a socioeconomic diverse urban area in the Southeastern United States. METHODS: Patients hospitalized with culture-confirmed Streptococcus pneumoniae (Spn) infection from 01/01/2010 - 12/31/2019 were identified from electronic health record (EHR). The cohort's demographic and clinical information were obtained from EHR. Patients' residential address was geocoded and matched to 2015 area deprivation index (ADI). The association of ADI and IPD was evaluated using logistic regression after controlling for the demographic information (age, sex, race) and clinical factors (BMI, smoking status, alcoholism, immunosuppressive status, vaccination status, comorbidities). RESULTS: A total of 268 patients were hospitalized with culture-positive Streptococcus pneumoniae infection and 92 (34.3%) of them had IPD. The analysis showed that higher neighborhood deprivation (ADI in 79-100) was associated with increased risk of developing IPD in younger patients with age less than 65 (p = 0.007) after controlling for the individual demographic information and clinical factors. CONCLUSIONS: ADI is a risk factor for IPD in younger adults. Community-level socioeconomic risk factors should be considered when developing prevention strategies such as increasing vaccine uptake in high risk population to reduce the disease burden of IPD.

A clade of Streptococcus pneumoniae clonal complex 320 with increased tolerance to ß-lactam antibiotics in a Chinese metropolitan city.

OBJECTIVES: We characterized the population structure and features of clinical Streptococcus pneumoniae isolates associated with invasive pneumococcal disease (IPD) from 2009 to 2017 in a Chinese metropolitan city using a whole-genome sequencing approach. METHODS: Seventy-nine pneumococcal strains, including 60 serogroup-19 strains from children enduring IPD from a paediatric hospital in Shenzhen, were subjected to whole-genome sequencing. Population structure was characterized through phylogenetic analysis, sequence typing, serotyping, virulence factor, and antimicrobial drug resistance (AMR) gene profiling, combining the publicly available related WGS data. Clinical demography and antibiotic susceptibility profiles were compared among different populations to emphasize the higher-risk populations. Genetic regions associated with AMR gene mobilization were identified through comparative genomics. RESULTS: These IPD strains mainly belonged to clonal complex 320 (CC320) and were composed of serotypes 19A and 19F. In addition to sporadic possible importation-related isolates (ST320), we identified an independent clade, CC320_SZpop (ST271), that predominantly circulated in Shenzhen and possibly expanded its range. Clinical features and antibiotic susceptibility analysis revealed that CC320_SZpop might manifest much higher pathogenicity and tolerance to ß-lactams. Specific virulence factors in Shenzhen isolates of CC320_SZpop were identified. Furthermore, an ca. 40 kb hotspot genomic region enduring frequent recombination was identified, possibly associated with the divergence of S. pneumoniae strains. CONCLUSION: A novel pneumococcal clade, CC320_SZpop, circulating in Shenzhen and other regions in China, possibly under expansion, was found and deserves more study and surveillance. Our study also emphasizes the importance of continuous genomic surveillance of clinical S. pneumoniae isolates, especially IPD isolates.