Invasive Pneumococcal Infections Research Articles

Вакцинопрофилактика пневмококковой инфекции в особых группах риска: современные клинические рекомендации

Pneumococcal infection is a serious problem for practical healthcare. After the COVID-19 pandemic, there has been a significant increase in bacterial infections incidence, with pneumococcus remaining the main causative agent in all age groups. Among military personnel, pneumococcal pneumonia is the most common severe pathology requiring significant efforts in patient treatment. Vaccination remains an important factor in reducing the incidence of disease, and most importantly, in significant reduction of cases of invasive pneumococcal infection, which is characterized by high mortality. Currently, modern approaches to vaccination regimens in adults have been developed, which are reflected in this publication.

Retrospective study on the health and economic burden of hospitalized patients due to pneumonia and invasive pneumococcal infections in Belgium settings

Introductionpneumococcal infections are associated with high morbidity, hospitalisation and mortality. The objective of this study was to investigate the health and economic burden of all-cause pneumonia and invasive pneumococcal disease in Belgian hospital settings, by patient’s age and risk profile. Methods:This descriptive retrospective study was conducted in 17 Belgian hospitals. Univariate and multivariate logistic linear regression models were performed. The Health Insurance and patient’s cost perspectives were considered because a few studies report these costs. Results:The analysis has included 4,712 hospital admissions over the year 2018. Median hospitalization costs were higher for invasive pneumococcal infection diagnosis than for all-cause pneumonia (p < 0,001), respectively 4,051€ and 3,362€. Other factors associated with higher hospitalization cost were patient’s high-risk profile, admission to emergency unit, transfer from nursing home, admission to intensive care unit and length of stay. Conclusion:Streptococcus pneumoniae infections remain a public health problem with significant cost for the Health Insurance and poor prognosis. Invasive pneumococcal infections are associated with longer hospital stays and required more intensive care than all other causes of pneumonia, in addition to be more costly, which justifies more attention for vaccination. This study also suggests an increase of economic and health burden with age and presence of underlying conditions.

Performance Characteristics of a Real-Time PCR Assay for Direct Detection of Streptococcus pneumoniae in Clinical Specimens

Community-acquired pneumonia and complications, such as bacteremia and meningitis due to Streptococcus pneumoniae infection, still occur in at-risk populations, despite the availability of effective vaccines. Laboratory confirmation of S. pneumoniae remains challenging despite advances in blood culture techniques and the availability of nucleic acid amplification tests. The goal of this study was to determine the performance characteristics of a molecular assay designed as a diagnostic test using primary clinical specimens for invasive pneumococcal disease. The molecular assay adapted for the Luminex ARIES (Austin, Texas, USA) instrument targets an S. pneumoniae specific gene (autolysin, lytA) in clinical specimens. Using real-time PCR Multicode technology, four different clinical specimen types were evaluated. Specimen types included bronchoalveolar lavage, whole blood, cerebrospinal fluid, and urine to cover the various presentations and appropriate specimen types for invasive pneumococcal infections. The limit of detection for urine was 10 cfu/mL, while bronchoalveolar lavage, cerebrospinal fluid and whole blood were 100 cfu/mL. Accuracy and specificity were both 100%, and all specimen types were stable for 8 days at 4ºC. Finally, 38 clinical specimens were tested to further evaluate the assay. The performance characteristics met CLIA standards for a clinical diagnostic assay and offers a sensitive and specific real-time PCR test for direct detection of S. pneumoniae in relevant clinical specimens.

580. Changes in Serotype Distribution of Invasive Pneumococcal Infections in South Korea Before and After the COVID-19 Outbreak

Abstract Background The introduction of extended-valency pneumococcal conjugate vaccine (PCV) since 2014 has changed the serotype distribution in South Korea. The COVID-19 pandemic in 2020 has changed the epidemiology of several infectious diseases significantly, involving the invasive pneumococcal disease (IPD). Methods This study obtained sterile body fluid samples of IPD in patients under 19 years old from January 2014 to April 2023 in South Korea, involved in multihospital-based surveillance system. Serotype distribution and multilocus sequence typing were performed for each sample. Vaccine serotypes (VTs) and nonvaccine serotypes (NVTs) were classified. The characteristics of IPD were compared between the pre-COVID-19 period (January 2014 to December 2019) and post-COVID-19 period (January 2021 to April 2023). Results A total of 230 isolates of Streptococcus pneumoniae from sterile body fluid samples were obtained. Among those, VTs accounted for 14.3% of cases (19A, 8.3%; 19F, 3.0%; and 6A, 1.3%), NVTs for 83.9% (10A, 23.0%; 15A, 9.1%; 15C, 7.8%; 15B, 6.1%; 23B, 6.1%), and four cases (1.7%) were nontypeable. Serotype 10A decreased to 14.6% in the post-COVID-19 period, which was the most common serotype in the pre-COVID-19 period (25.4%). Among the NVTs, isolates of serotype 6D, 7C, 11A, 12F, 13, 20, 22F, 33F, 37, and 38 were not found in the post-COVID-19 period, although they accounted for 18.5% in the pre-COVID-19 period. Meanwhile, serotypes 6C, 15B/C, and 23B increased from 0.6%, 12.7%, and 2.9% in the pre-COVID-19 period to 8.3%, 18.8%, and 16.7% in the post-COVID-19 period, respectively. All the serotype 6C isolates found in the post-COVID-19 period were sequence type 13556. 66.7% of serotype 15B/C and 87.5% of serotype 23B in the post-COVID-19 period showed clonal complex 166. Conclusion The COVID-19 pandemic has resulted in a shift in the predominant serotypes of invasive pneumococcal infections, with an increase in serotypes 6C, 15B/C, and 23B, which seems to be related with a certain clonal expansion. Notably, the cross-protection conferred by the PCV against serotype 6A appears to be insufficient for serotype 6C. Disclosures All Authors: No reported disclosures

Pneumococcus downregulates the molecular weight of the extracellular domain of the epidermal growth factor receptor of alveolar epithelial cells.

Pneumococcus is themajor cause of bacterial and invasive pneumococcal infections. Disrupting the alveolarepithelial barrier is an important step in the pathogenesis of invasivepneumococcal infections. The epidermal growth factor receptor (EGFR) maintainsthe integrity of the alveolar epithelial barrier. In this study, we showed that secretory pneumococcal molecules decrease the molecular weight of EGFR without peptide degradation and inhibit alveolar epithelial cell proliferation via EGFR.

Pneumococcal Polysaccharide Vaccination (PPSV23) in High-Risk Pediatric Patients With Diabetes.

The Advisory Committee on Immunization Practices recommends the pneumococcal polysaccharide vaccine (PPSV23) following the pneumococcal conjugate vaccine (PCV13) for pediatric patients aged 2 to 18 years with high-risk medical conditions. The PPSV23 is not a routine immunization for all pediatric patients and children who meet criteria for high-risk conditions may not consistently receive the PPSV23 vaccine, despite current recommendations. The goal of this study was to determine PPSV23 -vaccination rates in the high-risk pediatric patients with type 1 or type 2 diabetes. A single-center retrospective cohort study was conducted. Patients were included if they were 2 to 18 years of age on January 1, 2019, with a diagnosis of diabetes, and had ≥1 encounters within the health care system in 2019. The primary outcome was PPSV23 vaccination rates in the high-risk diabetic pediatric population. Secondary outcomes included identifying missed opportunities for vaccinations and the incidence of invasive pneumococcal infections. A total of 366 patients met criteria for study inclusion. Patients had a mean age of 13.3 years and were predominantly white (69.8%). A total of 32 (8.7%) patients had documentation of PPSV23 vaccination. Baseline characteristics were comparable between the two groups. There were 32 cases of pneumonia charted before patients received the PPSV23 and one case reported after patients received the PPSV23 vaccination. PPSV23 vaccination rates were low in this high-risk diabetic pediatric group, with many -documented missed opportunities for vaccination. This may be attributed to the vaccine not being a -routinely recommended for all pediatric patients.

Molecular Identification and Detection of Streptococcus pneumoniae Serotypes Isolated from the Cerebrospinal Fluid of Children with Suspected Meningitis: First Report From Alborz, Iran

Background: Pneumococcus causes various infections, some of which are life-threatening, including pneumonia, meningitis, otitis media, bacteremia, and sinusitis. Currently, more than 95 serotypes have been identified. Objectives: The purpose of this study was to isolate and determine Streptococcus pneumoniae serotypes from the cerebrospinal fluid (CSF) of children with suspected meningitis using the multiplex polymerase chain reaction (PCR) method. Materials and Methods: A total of 864 CSF samples were taken from children with suspected meningitis who were admitted to Imam Ali Hospital of Karaj for one year (January 2019 to January 2020). To collect positive S. pneumonia samples, the lytA gene was traced using specific primers and PCR techniques. Results: The results of this study indicated that only 16 patients have a pneumococcal infection (1.85%), of whom 50% have encapsulated pneumococci. Furthermore, serotypes 38 (12.5%), 7F (12.5%), 23F (25%), and 6A/B (50%) were the most common serotypes causing invasive pneumococcal infections in the included samples. Conclusion: Among the techniques for serotyping S. pneumoniae, the multiplex PCR technique is known as a fast, easy, and low-cost method that can serotype a large number of samples. The results also showed that the 13-valent pneumococcal conjugate vaccine can cover at least 50% of the strains that cause invasive pneumococcal diseases (IPDs), which are life-threatening, especially in children. Therefore, it is suggested that the healthcare administrators of Iran design and implement a public vaccination program.

Selective Change in the Bacteria Cultured and Isolated in Respiratory Sputum from Elderly Patients during the SARS-CoV-2 Pandemic

The SARS-CoV-2 pandemic has affected social patterns and consequently the prevalence of infections, such as seasonal influenza. It has been reported that invasive pneumococcal infection has markedly decreased worldwide. Method: We retrospectively investigated the bacteria cultured and isolated from 23,052 respiratory sputum samples obtained at our hospital from April 2015 to March 2022. The average patient age was 71.8 years old, with a standard deviation of 16.0 years old. There was no significant difference in the age of the patients or the female-to-male ratio between each year. The detection ratio of bacteria was analyzed in accordance with sputum quality based on the Geckler classification. Results: The detection ratio of community-acquired pneumonia pathogens such as Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae increased in parallel with the quality of the sputum, while that of hospital-acquired pneumonia pathogens such as Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus was not significantly affected by the quality of the sputum. The detection ratio of former pathogens in the good-quality respiratory sputum had decreased significantly since April 2020 by 60–80%, while that of P. aeruginosa and S. aureus had increased by 40–50%. Conclusions: The SARS-CoV-2 pandemic reduced the detection ratio of H. influenzae, M. catarrhalis, and S. pneumoniae but increased that of P. aeruginosa and S. aureus in the good-quality respiratory sputum from elderly patients. The influence of this selective change in isolated bacteria on the health and comorbidity of elderly patients remains to be investigated.

Development of a bivalent protein-based vaccine candidate against invasive pneumococcal diseases based on novel pneumococcal surface protein A in combination with pneumococcal histidine triad protein D.

Extensive efforts have been made toward improving effective strategies for pneumococcal vaccination, focusing on evaluating the potential of multivalent protein-based vaccines and overcoming the limitations of pneumococcal polysaccharide-based vaccines. In this study, we investigated the protective potential of mice co-immunization with the pneumococcal PhtD and novel rPspA proteins against pneumococcal sepsis infection. The formulations of each antigen alone or in combination were administered intraperitoneally with alum adjuvant into BALB/c mice three times at 14-day intervals. The production of antigen-specific IgG, IgG1 and IgG2a subclasses, and IL-4 and IFN-γ cytokines, were analyzed. Two in vitro complement- and opsonophagocytic-mediated killing activities of raised antibodies on day 42 were also assessed. Finally, the protection against an intraperitoneal challenge with 106 CFU/mouse of multi-drug resistance of Streptococcus pneumoniae ATCC49619 was investigated. Our findings showed a significant increase in the anti-PhtD and anti-rPspA sera IgG levels in the immunized group with the PhtD+rPspA formulation compared to each alone. Moreover, the results demonstrated a synergistic effect with a 6.7- and 1.3- fold increase in anti-PhtD and anti-rPspA IgG1, as well as a 5.59- and 1.08- fold increase in anti-PhtD and anti-rPspA IgG2a, respectively. Co-administration of rPspA+PhtD elicited a mixture of Th-2 and Th-1 immune responses, more towards Th-2. In addition, the highest complement-mediated killing activity was observed in the sera of the immunized group with PhtD+rPspA at 1/16 dilution, and the opsonophagocytic activity was increased from 74% to 86.3%. Finally, the survival rates showed that mice receiving the rPspA+PhtD formulation survived significantly longer (100%) than those receiving protein alone or PBS and exhibited the strongest clearance with a 2 log10 decrease in bacterial load in the blood 24h after challenge compared to the control group. In conclusion, the rPspA+PhtD formulation can be considered a promising bivalent serotype-independent vaccine candidate for protection against invasive pneumococcal infection in the future.

Highly Resistant Serotype19A Streptococcus pneumoniae of the GPSC1/CC320 Clone from Invasive Infections in Poland Prior to Antipneumococcal Vaccination of Children.

The introduction of pneumococcal conjugate vaccines (PCV) into the national immunization programs (NIPs) has significantly reduced the number of pneumococcal infections. However, infections caused by isolates of non-vaccine serotypes (NVT) started spreading shortly thereafter and strains of NVT 19A have become the main cause of invasive pneumococcal disease burden worldwide. The aim of the study was to characterize serotype19A invasive pneumococci of GPSC1/CC320 circulating in Poland before the introduction of PCV into the Polish NIP in 2017 and to compare them to isolates from other countries where PCVs were implemented much earlier than in Poland. All the GPSC1/CC320 isolates were analyzed by serotyping, susceptibility testing, and whole genome sequencing followed by analyses of resistome, virulome, and core genome multilocus sequence typing (cgMLST), including comparative analysis with isolates with publicly accessible genomic sequences (PubMLST). During continuous surveillance the NRCBM collected 4237 invasive Streptococcus pneumoniae isolates between 1997 and 2016, including 200 isolates (4.7%) of serotype19A. The most prevalent among 19A pneumococci were highly resistant representatives of Global Pneumococcal Sequence Cluster1/Clonal Complex320, GPSC1/CC320 (n = 97, 48.5%). Isolates of GPSC1/CC320 belonged to three sequence types (STs): ST320 (75.2%) ST4768 (23.7%), and ST15047 (1.0%), which all represented the 19A-III cps subtype and had complete loci for both PI-1 and PI-2 pili types. On the basis of the cgMLST analysis the majority of Polish GPSC1/CC320 isolates formed a group clearly distinct from pneumococci of this clone observed in other countries. Before introduction of PCV in the Polish NIP we noticed an unexpected increase of serotype19A in invasive pneumococcal infections, with the most common being representatives of highly drug-resistant GPSC1/CC320 clone, rarely identified in Europe both before and even after PCV introduction.

Regulation of inflammation and protection against invasive pneumococcal infection by the long pentraxin PTX3.

Streptococcus pneumoniae is a major pathogen in children, elderly subjects, and immunodeficient patients. Pentraxin 3 (PTX3) is a fluid-phase pattern recognition molecule (PRM) involved in resistance to selected microbial agents and in regulation of inflammation. The present study was designed to assess the role of PTX3 in invasive pneumococcal infection. In a murine model of invasive pneumococcal infection, PTX3 was strongly induced in non-hematopoietic (particularly, endothelial) cells. The IL-1β/MyD88 axis played a major role in regulation of the Ptx3 gene expression. Ptx3-/- mice presented more severe invasive pneumococcal infection. Although high concentrations of PTX3 had opsonic activity in vitro, no evidence of PTX3-enhanced phagocytosis was obtained in vivo. In contrast, Ptx3-deficient mice showed enhanced recruitment of neutrophils and inflammation. Using P-selectin-deficient mice, we found that protection against pneumococcus was dependent upon PTX3-mediated regulation of neutrophil inflammation. In humans, PTX3 gene polymorphisms were associated with invasive pneumococcal infections. Thus, this fluid-phase PRM plays an important role in tuning inflammation and resistance against invasive pneumococcal infection.

Streptococcus pneumoniae serotyping and antimicrobial susceptibility: assessment for vaccine efficacy in Canada after the introduction of PCV13.

Streptococcus pneumoniae continues to be an important bacterial pathogen associated with invasive (e.g. bacteraemia, meningitis) and non-invasive (e.g. community-acquired respiratory tract) infections worldwide. Surveillance studies conducted nationally and globally assist in determining trends over geographical areas and allow comparisons between countries. To characterize invasive isolates of S. pneumoniae in terms of their serotype, antimicrobial resistance, genotype and virulence and to use the serotype data to determine the level of coverage by different generations of pneumococcal vaccines. SAVE (Streptococcus pneumoniae Serotyping and Antimicrobial Susceptibility: Assessment for Vaccine Efficacy in Canada) is an ongoing, annual, national collaborative study between the Canadian Antimicrobial Resistance Alliance (CARE) and the National Microbiology Laboratory, focused on characterizing invasive isolates of S. pneumoniae obtained across Canada. Clinical isolates from normally sterile sites were forwarded by participating hospital public health laboratories to the Public Health Agency of Canada-National Microbiology Laboratory and CARE for centralized phenotypic and genotypic investigation. The four articles in this Supplement provide a comprehensive examination of the changing patterns of antimicrobial resistance and MDR, serotype distribution, genotypic relatedness and virulence of invasive S. pneumoniae obtained across Canada over a 10 year period (2011-2020). The data highlight the evolution of S. pneumoniae under pressure by vaccination and antimicrobial usage, as well as vaccine coverage, allowing both clinicians and researchers nationally and globally to view the current status of invasive pneumococcal infections in Canada.

Sensitivity of &lt;&gt;iStreptococcus pneumoniae&lt;/i&gt; to antibiotics and the sex of the patient: A systematic review and meta-analysis

BACKGROUND: The spread of microbial resistance to antibiotics is a recent global problem, which has become more acute in recent years because of a significant increase in the consumption of antibiotics, against the background of the COVID-19 pandemic. A direct consequence of the spread of antibiotic-insensitive strains of pneumococci limits the treatment options for such patients and deterioration of the prognosis.&#x0D; AIM: To determine whether sex is a factor associated with the development of diseases caused by antibiotic-resistant strains of Streptococcus pneumoniae.&#x0D; MATERIALS AND METHODS: Using the electronic databases PubMed, ScienceDirect, and Google Scholar, a search was conducted for articles published from January 1980 to December 2020, and studies in English and Russian were selected. The selection of articles and meta-analysis was based on the recommendations of the PRISMA Group and MOOSE. After combining the data, the odds ratio (OR) was calculated with a 95% confidence interval (95% CI). Heterogeneity was assessed.&#x0D; RESULTS: After applying the exclusion criteria, 41 publications covering 16635 patients with invasive and non-invasive forms of pneumococcal infection were selected for analysis. Of these, 36 case-control studies and 5 cross-sectional studies were identified. Accordingly, the sex of the patient does not affect the frequency of isolation of pneumococcal strains insensitive to penicillin (odds ratio [OR]=0.92, 95% confidence interval [CI] 0.821.03, I2=7%), resistant to penicillin (OR=0.85, 95% CI 0.671.07, I2=1%), and insensitive to erythromycin (OR=0.80, 95% CI 0.511.24, I2=0%). Male sex is associated with pneumococcal resistance to levofloxacin (OR=1.85, 95% CI 1.033.33, I2=0%).&#x0D; CONCLUSIONS: The sex of the patient is not a factor associated with the isolation of S. pneumonia strains insensitive and resistant to penicillin and erythromycin. Moreover, the male sex probably increases the chance of isolation of levofloxacin-resistant pneumococci in adults with invasive pneumococcal infections.

The current status of antimicrobial resistance of &lt;i&gt;Streptococcus pneumoniae&lt;/i&gt; and specific vaccine prevention of pneumococcal infection

The constant increase in the level of resistance of Streptococcus pneumoniae to antimicrobial drugs significantly affects the algorithms for the pharmacotherapy of pneumococcal infection, reduces the effectiveness of the therapy and increases the healthcare costs. In this regard, specific vaccine prevention of pneumococcal diseases is a socially significant and economically promising and profitable area. The aim of the study is to analyze the current status of antimicrobial resistance of S. pneumoniae in healthy carriers and patients with non-invasive and invasive pneumococcal infections, as well as specific vaccine prevention of pneumococcal infection. Conclusion. An increase in the number of pneumococcal strains resistant to macrolides and tetracycline has been noted, as well as a trend toward an increase in resistance to beta-lactam antibiotics. Given the spread of resistant strains of S. pneumoniae, a continuous epidemiological surveillance of pneumococcal infection with an assessment of the dynamics of pneumococcal serotype resistance and the effectiveness of vaccination is needed on a global scale.

Invasive pneumococcal infections in France: Changes from 2009 to 2021 in antibiotic resistance and serotype distribution of Streptococcus pneumoniae based on data from the French Regional Pneumococcal Observatories network

ObjectiveThe 23 French Regional Pneumococcal Observatories (ORPs) analyzed antibiotic resistance and serotypes of Streptococcus pneumoniae strains isolated from invasive infections in France over a 12-year period. MethodsBetween 2009 and 2021, the ORPs analyzed 19,319 strains, including 1,965 in children and 17,354 in adults. Strains were assessed for their resistance to penicillin G, amoxicillin and cefotaxime. Serotypes were identified in collaboration with the National Reference Centre. ResultsDuring this period, the number of strains collected yearly decreased significantly. The decrease was particularly pronounced up until 2013, especially in children (-61.0%). However, penicillin non-susceptible strains (PNSPs) increased in children (24.7% in 2009 vs 45.0% in 2021, p < 0.0001) and in adults (27.1% in 2009 vs 31.3% in 2021, p < 0.05), as well as resistance (I + R) to amoxicillin (children: 12.5% in 2009 vs 19.4% in 2021, p < 0.05; adults: 13.4% in 2009 vs 14.5% in 2021, NS) and resistance (I + R) to cefotaxime (children: 8.0% in 2009 vs 13.1% in 2021, p < 0.05; adults: 7.1% in 2009 vs 11.9% in 2021, p < 0.0001). All in all, the proportion of strains belonging to serotypes present in the PCV13 vaccine has fallen sharply, from 64.8% in 2009 to 23.6 % in 2021. At the same time, serotypes such as 8, 10A, 11A, 15B/C and 9N, not included in PCV13, were increasing. ConclusionDuring the study period, data collected by the network highlighted an increase of invasive PNSPs in children and non-vaccine serotypes. Surveillance of resistance and serotypes remains instrumental, particularly to monitor the evolution of vaccine efficacy.

Pneumococcal Conjugate Vaccine Does Not Induce Humoral Response When Administrated Within the Six Months After CD19 CAR T-Cell Therapy

CD19 targeted chimeric antigen receptor-modified T cell therapy (CAR-T) leads to B cell aplasia and low serum immunoglobulin levels. Long-lived CD19–negative plasma cells may persist through the therapy and generate antibodies. There is a paucity of data describing how CAR-T impacts the persistence of antibodies against vaccine-related antigens and the degree to which CAR-T recipients may respond to vaccines. We characterized the effect of CAR-T on pneumococcal immunoglobulin G (IgG) titers and determine whether pneumococcal conjugate vaccine (PCV13) administered after CAR-T develops long-term humoral protection against pneumococcus. A retrospective chart review was performed to identify CAR-T recipients who had serum pneumococcal IgG titers drawn before (baseline) or at days +90, +180, +270, +360, or +540 after CAR-T. We then determined whether they received PCV13 vaccination at these timepoints. IgG concentration ≥1.3 μg/mL was considered protective for that serotype, and patients with ≥6/11 tested vaccine-specific serotypes meeting this threshold were deemed to have humoral protection against pneumococcus. Absolute pneumococcal IgG titers and the proportion of patients with humoral protection, stratified by serotype, and vaccination status were compared by paired nonparametric t-tests. Absolute counts for lymphocyte, CD4 T-cell, and CD19 cell and total IgG level, along with the rate of invasive pneumococcal infections, were measured at these timepoints. A total of 148 CAR-T recipients with pneumococcal IgG titers measured for at least one of the defined time points were identified. At baseline, 25% (19/76) patients with evaluable pneumococcal IgG titers met the definition of humoral protection. Among 44 patients with paired pneumococcal IgG titers at baseline and day+90, absolute IgG titers of all serotypes decreased (geometric mean = 0.41 and 0.32 µg/mL, respectively; P < .001). Thirteen patients were vaccinated following the titer blood draw at day+90 and had paired pneumococcal IgG titers at day+90 and day180. Absolute IgG titers of all vaccine specific serotypes in these vaccinated patients decreased from day+90 to day+180 (geometric mean = 0.36 and 0.29 µg/mL, respectively; P = .03). The proportion of patients meeting the criteria of humoral protection remained the same at day+180 despite vaccination at day+90. The results were similar among 8 patients vaccinated at day+180, as well as 7 patients consecutively vaccinated at day+90 and day+180 with corresponding pneumococcal IgG titers. When all vaccine-specific pneumococcal IgG titers were pooled together by timepoint regardless of vaccination status, the proportion of patients with humoral protection decreased until day+540. Some patients developed humoral protection after vaccination at day+360, maintained seroprotective IgG titers from baseline, or developed protection after receiving intravenous immunoglobulin treatment secondary to recurrent infections. Our study demonstrated that few large B cell lymphoma patients had humoral protection against pneumococcus at baseline, and existing IgG titers decreased after CAR-T. PCV13 vaccination at day+90 or day+180 after CAR-T did not increase humoral protection against pneumococcus. Only at day+540 was there evidence of humoral protection against pneumococcus in a modest proportion of patients. Clinical trials are needed to determine the optimal timing of vaccination, before or after CAR-T, to develop protective immunity against Streptococcus pneumoniae infections.

Diversity of amino acid substitutions of penicillin-binding proteins in penicillin-non-susceptible and non-vaccine type Streptococcus pneumoniae

PurposeIn Japan, the introduction of pneumococcal conjugate vaccine (PCV) in children has decreased vaccine-type (VT) pneumococcal infections caused by penicillin (PEN)-non-susceptible Streptococcus pneumoniae. PEN-non-susceptible strains have gradually emerged among non-vaccine types (NVT). In this study, we aim to investigate the pbp gene mutations and the characteristics of PEN-binding proteins (PBPs) that mediate PEN resistance in NVT strains. Materials and methodsPneumococcal 41 strains of NVT isolated from patients with invasive pneumococcal infection were randomly selected. Nucleotide sequences for pbp genes encoding PBP1A, PBP2X, and PBP2B were analyzed, and amino acid (AA) substitutions that contribute to β-lactam resistance were identified. In addition, the three-dimensional (3D) structure of abnormal PBPs in the resistant strain was compared with that of a reference R6 strain via homology modeling. ResultsIn PEN-non-susceptible NVT strains, Thr to Ala or Ser substitutions in the conserved AA motif (STMK) were important in PBP1A and PBP2X. In PBP2B, substitutions from Thr to Ala, adjacent to the SSN motif, and from Glu to Gly were essential. The 3D structure modeling indicated that AA substitutions are characterized by accumulation around the enzymatic active pocket in PBPs. Many AA substitutions detected throughout the PBP domains were not associated with resistance, except for AA substitutions in or adjacent to AA motifs. Clonal complexes and sequence types showed that almost all NVT cases originated in other countries and spread to Japan via repeat mutations. ConclusionsNVT with diverse AA substitutions increased gradually with pressure from both antimicrobial agents and vaccines.

New Pneumococcal Vaccines for Prevention of Invasive Pneumococcal Disease in Adult Patients With Inflammatory Bowel Disease.

Patients with inflammatory bowel disease (IBD) are at a high risk of developing invasive pneumococcal infection both before and after they are diagnosed. The Advisory Committee on Immunization Practices now endorses use of 2 new pneumococcal conjugate vaccines, PCV15 (Vaxneuvance) and PCV20 (Prevnar 20), for patients who have never received a pneumococcal conjugate vaccine or those with unknown vaccination history. Previous studies have shown that pneumococcal vaccination can decrease the risk of developing severe pneumococcal disease; therefore, it is important that patients with IBD receive pneumococcal vaccination. This report aims to inform clinicians who care for patients with IBD about the changes in immunization practices, as it pertains to pneumococcal vaccination and provides appropriate direction on administering vaccination series.

Association of Nonpharmaceutical Interventions During the COVID-19 Pandemic With Invasive Pneumococcal Disease, Pneumococcal Carriage, and Respiratory Viral Infections Among Children in France

An association between pneumococcal nasopharyngeal carriage and invasive pneumococcal disease (IPD) has been previously established. However, it is unclear whether the decrease in IPD incidence observed after implementation of nonpharmaceutical interventions (NPIs) during the COVID-19 pandemic was associated with concomitant changes in pneumococcal carriage and respiratory viral infections. To assess changes in IPD incidence after the implementation of NPIs during the COVID-19 pandemic and examine their temporal association with changes in pneumococcal carriage rate and respiratory viral infections (specifically respiratory syncytial virus [RSV] and influenza cases) among children in France. This cohort study used interrupted time series analysis of data from ambulatory and hospital-based national continuous surveillance systems of pneumococcal carriage, RSV and influenza-related diseases, and IPD between January 1, 2007, and March 31, 2021. Participants included 11 944 children younger than 15 years in France. Implementation of NPIs during the COVID-19 pandemic. The estimated fraction of IPD change after implementation of NPIs and the association of this change with concomitant changes in pneumococcal carriage rate and RSV and influenza cases among children younger than 15 years. The estimated fraction of change was analyzed using a quasi-Poisson regression model. During the study period, 5113 children (median [IQR] age, 1.0 [0.6-4.0] years; 2959 boys [57.9%]) had IPD, and 6831 healthy children (median [IQR] age, 1.5 [0.9-3.9] years; 3534 boys [51.7%]) received a swab test. Data on race and ethnicity were not collected. After NPI implementation, IPD incidence decreased by 63% (95% CI, -82% to -43%; P < .001) and was similar for non-13-valent pneumococcal conjugate vaccine serotypes with both high disease potential (-63%; 95% CI, -77% to -48%; P < .001) and low disease potential (-53%; 95% CI, -70% to -35%; P < .001). The overall pneumococcal carriage rate did not significantly change after NPI implementation (-12%; 95% CI, -37% to 12%; P = .32), nor did the carriage rate for non-PCV13 serotypes with high disease potential (-26%; 95% CI, -100% to 52%; P = .50) or low disease potential (-7%; 95% CI, -34% to 20%; P = .61). After NPI implementation, the estimated number of influenza cases decreased by 91% (95% CI, -74% to -97%; P < .001), and the estimated number of RSV cases decreased by 74% (95% CI, -55% to -85%; P < .001). Overall, the decrease in influenza and RSV cases accounted for 53% (95% CI, -28% to -78%; P < .001) and 40% (95% CI, -15% to -65%; P = .002) of the decrease in IPD incidence during the NPI period, respectively. The decrease in IPD incidence was not associated with pneumococcal carriage, with carriage accounting for only 4% (95% CI, -7% to 15%; P = .49) of the decrease. In this cohort study of data from multiple national continuous surveillance systems, a decrease in pediatric IPD incidence occurred after the implementation of NPIs in France; this decrease was associated with a decrease in viral infection cases rather than pneumococcal carriage rate. The association between pneumococcal carriage and IPD was potentially modified by changes in the number of RSV and influenza cases, suggesting that interventions targeting respiratory viruses, such as immunoprophylaxis or vaccines for RSV and influenza, may be able to prevent a large proportion of pediatric IPD cases.

Population genomics of pneumococcal carriage in South Africa following the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) immunization.

Streptococcus pneumoniae is a major human pathogen responsible for over 317000 deaths in children <5 years of age with the burden of the disease being highest in low- and middle-income countries including South Africa. Following the introduction of the 7-valent and 13-valent pneumococcal conjugate vaccine (PCV) in South Africa in 2009 and 2011, respectively, a decrease in both invasive pneumococcal infections and asymptomatic carriage of vaccine-type pneumococci were reported. In this study, we described the changing epidemiology of the pneumococcal carriage population in South Africa, by sequencing the genomes of 1825 isolates collected between 2009 and 2013. Using these genomic data, we reported the changes in serotypes, Global Pneumococcal Sequence Clusters (GPSCs), and antibiotic resistance before and after the introduction of PCV13. The pneumococcal carriage population in South Africa has a high level of diversity, comprising of 126 GPSCs and 49 serotypes. Of the ten most prevalent GPSCs detected, six were predominantly found in Africa (GPSC22, GPSC21, GPSC17, GPSC33, GPSC34 and GPSC52). We found a significant decrease in PCV7 serotypes (19F, 6B, 23F and 14) and an increase in non-vaccine serotypes (NVT) (16F, 34, 35B and 11A) among children <2 years of age. The increase in NVTs was driven by pneumococcal lineages GPSC33, GPSC34, GPSC5 and GPSC22. Overall, a decrease in antibiotic resistance for 11 antimicrobials was detected in the PCV13 era. Further, we reported a higher resistance prevalence among vaccine types (VTs), as compared to NVTs; however, an increase in penicillin resistance among NVT was observed between the PCV7 and PCV13 eras. The carriage isolates from South Africa predominantly belonged to pneumococcal lineages, which are endemic to Africa. While the introduction of PCV resulted in an overall reduction of resistance in pneumococcal carriage isolates, an increase in penicillin resistance among NVTs was detected in children aged between 3 and 5 years, driven by the expansion of penicillin-resistant clones associated with NVTs in the PCV13 era.