Serotype 19F Research Articles

Poststreptococcal acute glomerulonephritis with 22F pneumococcal bacteremia.

Pneumococcal vaccines have been available worldwide since the early 2000s; consequently, few reports exist of poststreptococcal acute glomerulonephritis (PSAGN) or complications of pneumococcal infection. We describe a patient with PSAGN and bacteremia with Streptococcus pneumoniae serotype 22F (not covered by the 13-valent pneumococcal vaccine (PCV 13)). A 5-year-old boy received the PCV13 vaccine and was admitted to our hospital with a fever and gross hematuria. A throat swab was positive for a streptococcal antigen, and his serum anti-streptolysin O and creatinine levels were increased. Low serum C3 levels suggested PSAGN, with an infiltrating shadow on chest X-ray. His blood culture isolated S. pneumoniae serotype 22F, and he was administered intravenous ceftriaxone for 10days. His kidney function, pneumonia, and bacteremia improved. Children with PSAGN should be evaluated for pneumococcal bacteremia due to strains not covered by the vaccine.

Invasive pneumococcal disease in a tertiary hospital in Madrid: are we using pneumococcal vaccine correctly?

IntroductionInvasive pneumococcal disease (IPD) is of concern. We describe the epidemiology and assess the vaccination schedule adequacy of IPD episodes (2019–2021) in northern Madrid. MethodsClinical, laboratory and vaccination data were collected from clinical/epidemiological records. Antimicrobial susceptibility testing was performed according to EUCAST and serotyping by Pneumotest-agglutination/Quellung. ResultsIPD was identified in 103 patients (71 [IQR 23.5] year-old; 50.4% males), 85.4% associated with bacteremia and a high mortality rate (19.4%). Serotypes 8 (29.9%), 3 and 22F (8% each) were dominant (45.9%), all antibiotic-susceptible. β-Lactams increased MICs and macrolide resistance were mainly linked to serotypes 19A, 23F, 24F, 6C, and 15A. Only 10.5% of adults eligible for vaccination had an adequate vaccine regimen before IPD being 40% due to nonvaccine-preventable serotypes (13, 23B, 24F, 31). ConclusionIPD episodes were dominated by antibiotic-susceptible ST8 and frequently occurred in adults at risk. Despite recommendations, vaccination adherence rates were very low.

Serotype distribution and antimicrobial resistance of Streptococcus pneumoniae isolated from children in Japan, 2023

BackgroundThe prevalence of serotypes and antimicrobial resistance of Streptococcus pneumoniae was characterized among children thirteen years after the licensure of the pneumococcal conjugate vaccine (PCV) in Japan. MethodsA total of 353 pneumococcal isolates were collected from Japanese children between March and July 2023. All the isolates were serotyped using genetic methods and tested for susceptibility to 14 antimicrobial agents. ResultsAmong the 353 isolates, the prevalence rates of non-PCV13 and non-PCV20 serotypes were 96.9 % and 77.9 %, respectively, including the dominant non-PCV13/PCV20 serotypes 23A (16.1 %), 35B (15.3 %), 15A (10.5 %), 15C (9.3 %), and 34 (9.1 %), which accounted for 60.3 % of all isolates. The high non-susceptibility rates were observed for macrolides (erythromycin, azithromycin, and clarithromycin; ≥81.9 %) and tetracycline (80.7 %). Penicillin non-susceptibility and multidrug resistance (MDR) were detected in 49.9 % (6.8 % resistant and 43.1 % intermediate) and 68.3 % of the isolates, respectively. The three most common non-PCV13/PCV20 serotypes 15A, 23A, and 35B exhibited high prevalence rates of penicillin non-susceptibility (≥89.5 %) and MDR (≥81.5 %). Extensive drug resistance was observed in 10.5 % of all isolates belonging to six different serotypes (12F, 23A, 11A, 15A, 35B, and 15B) and in the non-encapsulated strains of S. pneumoniae. ConclusionsOur study revealed a higher prevalence of non-susceptibility to penicillin with MDR in the three most common non-PCV13/PCV20 serotypes 15A, 23A, and 35B, in Japan, suggesting their persistence in the PCV13 era.

Lung Organoids from Human Embryonic Stem Cells to Investigate Pneumococcal Serotype 23F that does not Infect Mouse

Lung Organoids from Human Embryonic Stem Cells to Investigate Pneumococcal Serotype 23F that does not Infect Mouse

Pneumococcal transposon profiling associated with macrolide, tetracycline, and chloramphenicol resistance from carriage isolates of serotype 19F in Indonesia

Genetic evolution of resistance due to mutations and transposon insertions is the primary cause of antimicrobial resistance in Streptococcus pneumoniae. Resistance to macrolide, tetracycline, and chloramphenicol is caused by the insertion of specific genes that carried by transposon (Tn). This study aims to analyze transposon profiling associated with macrolide, tetracycline, and chloramphenicol resistance from carriage isolates of S. pneumoniae serotype 19F in Indonesia. S. pneumoniae serotype 19F isolates were collected from nasopharyngeal swab specimens from different regions in Indonesia. Genomic DNA was extracted from sixteen isolates and whole genome sequencing was performed on Illumina platform. Raw sequence data were analyzed using de novo assembly by ASA3P and Microscope server. The presence of transposons was identified with detection of int and xis genes and visualized by pyGenomeViz. The genome size of S. pneumoniae ranges from 2,040,117 bp to 2,437,939 bp, with a GC content of around 39 %. ST1464 (4/16) and ST271 (3/16) were found as the predominant sequence type among isolates. Tn2010 was the most common transposon among S. pneumoniae serotype 19F isolates (7/16) followed by Tn2009 (4/16), and Tn5253 (3/16). We identified two deletion sites within the tetM gene (2 bp and 58 bp) that confer tetracycline susceptibility from one isolate. This study suggests that genomic analysis can be employed for the detection and surveillance of antimicrobial resistance genes among S. pneumoniae strains isolated from various regions in Indonesia.

Increased proportions of invasive pneumococcal disease cases amongs adults experiencing homelessness sets stage for new serotype 4 capsular-switch recombinant.

The Centers for Disease Control and Prevention's Active Bacterial Core surveillance (ABCs) identified increased serotype 4 invasive pneumococcal disease (IPD), particularly among adults experiencing homelessness (AEH). We quantified IPD cases during 2016-2022. Employing genomic-based characterization of IPD isolates, we identified serotype-switch variants. Recombinational analyses were used to identify the genetic donor and recipient strains that generated a serotype 4 progeny strain. We performed phylogenetic analyses of the serotype 4 progeny and serotype 12F genetic recipient to determine genetic distances. We identified 30 inter-related (0-21 nucleotide differences) IPD isolates recovered during 2022-2023, corresponding to a serotype 4 capsular-switch variant. This strain arose through a multi-fragment recombination event between serotype 4/ST10172 and serotype 12F/ST220 parental strains. Twenty-five of the 30 cases occurred within Oregon. Of 29 cases with known residence status, 16 occurred in AEH. Variant emergence coincided with a 2.6-fold increase (57 to 148) of cases caused by the serotype 4/ST10172 donor lineage in 2022 compared to 2019 and its first appearance in Oregon. Most serotypes showed sequential increases of AEH IPD/all IPD ratios during 2016-2022 (for all serotypes combined, 247/2198, 11.2% during 2022 compared to 405/5317, 7.6% for 2018-2019, p<0.001). Serotypes 4 and 12F each caused more IPD than any other serotypes in AEH during 2020-2022 (207 combined reported cases primarily in 4 western states accounting for 38% of IPD in AEH). Expansion and increased transmission of serotypes 4 and 12F among adults potentially led to recent genesis of an impactful hybrid "serotype-switch" variant.

Streptococcus pneumoniae carriage, serotypes, genotypes, and antimicrobial resistance trends among children in Portugal, after introduction of PCV13 in National Immunization Program: A cross-sectional study

Streptococcus pneumoniae carriage studies are crucial to monitor changes induced by use of pneumococcal conjugate vaccines and inform vaccination policies. In this cross-sectional study, we examined changes within the pneumococcal population following introduction of PCV13 in 2015 in the National Immunization Program (NIP), in Portugal. In 2018–2020 (NIP-PCV13), we obtained 1450 nasopharyngeal samples from children ≤6 years attending day-care. We assessed serotypes, antimicrobial resistance, and genotypes (MLST and GPSC) and compared findings with earlier periods: 2009–2010 (pre-PCV13), 2011–2012 (early-PCV13), and 2015–2016 (late-PCV13). Pneumococcal carriage prevalence remained stable at 60.2 %. Carriage of PCV13 serotypes was 10.7 %, markedly reduced compared to pre-PCV13 period (47.6 %). The most prevalent PCV13 serotypes were 19F, 3, and 19A all showing a significant decreasing trend compared to the pre-PCV13 period (from 7.1 % to 4.7 %, 10.1 % to 1.8 %, and 14.1 % to 1.8 %, respectively), a notable observation given the described limited effectiveness of PCV13 against serotype 3. Non-vaccinated children and children aged 4–6 years were more likely to carry PCV13 serotypes (2.5-fold, 95 %CI [1.1–5.6], and 2.9-fold, 95 %CI [1.3–6.8], respectively). The most prevalent non-PCV13 serotypes were 15B/C, 11A, 23B, 23A, and NT, collectively accounting for 51.9 % of all isolates. In total, 30.5 % of all pneumococci were potentially covered by PCV20. Resistance to penicillin (low-level) and macrolides increased significantly, from 9.3 % and 13.4 %, respectively, in the late-PCV13 period, to approximately 20 % each, mostly due to lineages expressing non-PCV13 serotypes, nearing pre-PCV13 levels. An expansion of lineages traditionally associated with PCV13 serotypes, like CC156-GPSC6 (serotype 14) and CC193-GPSC11 (serotype 19F), but now predominantly expressing non-PCV13 serotypes (11A, 15B/C, and 24F for GPSC6; and 15A and 21 for GPSC11) was noted. These findings indicate that the pneumococcal population is adapting to the pressures conferred by PCV13 and antimicrobial use and indicate the need to maintain close surveillance.

Molecular and phenotypic characterization of Streptococcus pneumoniae isolates in a Japanese tertiary care hospital.

This study aimed to investigate the bacterial characteristics of pneumococcal isolates obtained from a tertiary care hospital in Japan. We analyzed the antimicrobial susceptibility, possession of macrolide resistance genes, pneumococcal serogroup/serotype, and sequence type (ST) of pneumococcal isolates from patients aged 15 years or older between 2011 and 2020 at Nagasaki University Hospital. Of the 73 isolates analyzed, 86.3% showed resistance to macrolides, and 28.8%, 46.6%, and 11.0% harbored mefA, ermB, and both, respectively. Of the isolates possessing ermB, 97.6% showed high levels of macrolide resistance [minimal inhibitory concentration (MIC) range, > 16 µg/mL]. Solithromycin (MIC range, 0.03-0.25 µg/mL), regardless of the presence of macrolide resistance genes, and lascufloxacin (MIC range, 0.06-0.5 µg/mL) showed potent in vitro activity against pneumococci. Serotype 19A was the most prevalent (six isolates), followed by serotypes 10A, 15A, and 15B/C (five isolates each). Four serotypes (11A, 19A, 22F, and 23B) and five STs (36, 99, 433, 558, and 3111) were significantly correlated with the presence of macrolide resistance genes. All four isolates with serotype 11A/ST99 and three isolates with serotype 19A/ST3111 harbored both mefA and ermB. No macrolide resistance genes were detected in either of the two isolates with serotype 22F/ST433, while all ten isolates with serogroup 15 (serotypes 15A and 15B/C, five isolates each) possessed ermB alone. Our study revealed the bacterial characteristics of the pneumococcal isolates obtained from our hospital. In vitro activity of solithromycin and lascufloxacin against these isolates was confirmed.

Characterization of Streptococcus pneumoniae isolates obtained from the middle ear fluid of US children, 2011-2021.

Pneumococcal conjugate vaccines (PCVs), including higher valency vaccines such as PCV20, have the potential to reduce pediatric otitis media. We assessed serotype distribution, potential PCV coverage, and antimicrobial susceptibility of Streptococcus pneumoniae isolates cultured from middle ear fluid (MEF) of US children age ≤5 years. S. pneumoniae isolates identified from US hospitals participating in the SENTRY Antimicrobial Surveillance program from 2011 to 2021 were included. Serotypes were determined by in silico analysis based on Pneumococcal Capsular Typing methodology. The percentage of isolates belonging to serotypes included in PCV13 (serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F), PCV15 (PCV13 plus 22F, 33F), and PCV20 (PCV13 plus, 8, 10A, 11A, 12F, 15B, 22F and 33F) was calculated. Antimicrobial susceptibility testing was performed by broth microdilution and interpreted using CLSI criteria. Nonsusceptibility was defined as isolates that were intermediate or resistant to a selected antimicrobial. Among the 199 S. pneumoniae isolates that were identified, 56.8% were from children age <2 years. Six serotypes accounted for around 60% of isolates: 35B (16.6%), 15B (14.6%), 15A (7.5%), 19A (7.5%), 19F (7.5%), and 3 (7.0%). Serotypes included in PCV13, PCV15, and PCV20 accounted for 23.1%, 30.2%, and 54.8% of isolates, respectively. Overall, 45.2% of isolates were penicillin non-susceptible, and 13.6% were MDR, of which 48% were serotype 19A. Seven serotypes (19A, 15A, 15B, 15C, 23A, 33F, and 35B) accounted for the majority of non-susceptible isolates. PCVs, particularly PCV20, may prevent a substantial fraction of S. pneumoniae otitis media (OM), including OM due to non-susceptible serotypes. The addition of serotypes 15A, 23A, and 35B would improve coverage against susceptible and non-susceptible pneumococcal OM.

Evaluation of GC-MS for identification and characterization of pneumococcal serotype 24A, 24B, and 24F capsular polysaccharide

Analysis of pneumococcal polysaccharides (PnPs) has been an arduous task, especially in similar serotypes. Pneumococci invades the host immune response by modulating capsule structure with small genetic changes making them indistinguishable from similar serotypes by conventional modes of analysis. The new serotype 24F causing invasive pneumococcal-resistant infection is an analytical challenge for its analysis as related serotypes 24A and 24B Ps share a common backbone. The difference in the branched chain which contains arabinitol and ribitol in 24F and 24B respectively are stereoisomers making their identification even more challenging. The composition analysis by GC-MS revealed distinct peaks for arabinitol in 24F and 24A Ps and ribitol in Pn 24B serotype polysaccharide. The mass spectral analysis confirmed their identification along with a heterologous cross-reactivity which confirmed anti-Pn-24F mAb reactive to Pn 24B than Pn 24A. The quantitative analysis of pneumococcal 24A, 24B and 24F using GC-MS showed sensitive analysis over the concentration range 3.125–200 μg/mL with regression coefficient >0.99 making ideal modality for the characterization, identification, and quantitation of pneumococcal 24A, 24B and 24F similar serotypes.

Expansion of pneumococcal serotype 23F and 14 lineages with genotypic changes in capsule polysaccharide locus and virulence gene profiles post introduction of pneumococcal conjugate vaccine in Blantyre, Malawi.

Since the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) in Malawi in 2011, there has been persistent carriage of vaccine serotype (VT) Streptococcus pneumoniae, despite high vaccine coverage. To determine if there has been a genetic change within the VT capsule polysaccharide (cps) loci since the vaccine's introduction, we compared 1022 whole-genome-sequenced VT isolates from 1998 to 2019. We identified the clonal expansion of a multidrug-resistant, penicillin non-susceptible serotype 23F GPSC14-ST2059 lineage, a serotype 14 GPSC9-ST782 lineage and a novel serotype 14 sequence type GPSC9-ST18728 lineage. Serotype 23F GPSC14-ST2059 had an I253T mutation within the capsule oligosaccharide repeat unit polymerase Wzy protein, which is predicted in silico to alter the protein pocket cavity. Moreover, serotype 23F GPSC14-ST2059 had SNPs in the DNA binding sites for the cps transcriptional repressors CspR and SpxR. Serotype 14 GPSC9-ST782 harbours a non-truncated version of the large repetitive protein (Lrp), containing a Cna protein B-type domain which is also present in proteins associated with infection and colonisation. These emergent lineages also harboured genes associated with antibiotic resistance, and the promotion of colonisation and infection which were absent in other lineages of the same serotype. Together these data suggest that in addition to serotype replacement, modifications of the capsule locus associated with changes in virulence factor expression and antibiotic resistance may promote vaccine escape. In summary, the study highlights that the persistence of vaccine serotype carriage despite high vaccine coverage in Malawi may be partly caused by expansion of VT lineages post-PCV13 rollout.

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.

A Misdiagnosis of MIS-C: Acute Pneumococcal Meningitis Due to Serotype 19F in A Child with Acute SARS-CoV-2 Infection with a Severe Disease Course.

According to the 2020 CDC criteria, multisystem inflammatory syndrome in children (MIS-C) due to Coronavirus disease-19 (COVID-19) is diagnosed when all of the following criteria are met: fever for+≥+24 hours, laboratory evidence of inflammation, multisystem (+≥+2) organ involvement, evidence of SARS-CoV-2 infection or exposure, and no alternative plausible diagnoses (CDC, 2020). Alternative diagnosis need to be excluded before coming upon an MIS-C diagnosis since there are plenty of infectious diseases that may mimic MIS-C (Dworsky et al., Pediatr Infect Dis J 2021; 40; e159-e161; Yalçinkaya et al., Pediatr Infect Dis J 2021; 40; e524-e525; Kaneta et al., Pediatr Infect Dis J 2023; 42; 590-593; Stanzelova et al., Pediatr Infect Dis J 2023; 42; e201-e203; Kolsi et al., Arch Pediatr 2023; 30; 521-523). Herein, we present a 6-year-old girl who was preliminarily diagnosed with MIS-C and received intravenous immunoglobulin (IVIG) treatment before referral to our center. She was diagnosed with acute pneumococcal meningitis due to serotype 19 F and ultimately suffered from sensorineural hearing loss (SNHL) as a sequela. We present this case to remind physicians that MIS-C should not be diagnosed unless other infectious causes are excluded.

Invasive pneumococcal disease surveillance in Canada, 2021-2022.

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. 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. 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). 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.

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

BackgroundA 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. MethodsWe 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 %). ResultsAmong 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. ConclusionsAt 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.

Neuropeptide Y affects B-cell activation functions

Introduction: Sympathetic nerves secrete neurotransmitters in response to pathogenic organisms in various immunological contexts. Most studies have focused on norepinephrine (NE) which has shown numerous immunomodulatory effects involving pro- and anti-inflammatory responses. However, sympathetic neurons contain also varicosities where neuropeptides, mainly neuropeptide Y (NPY), are stored. NPY play roles in various physiological processes, including regulating metabolism, vascular function, and immune function but little is known on its action during bacterial respiratory infection. The regulation of its secretion and its impact on the immune system during infection remains unclear. We investigated the role of NPY in B-cell responses during bacterial infection. Methods: Naïve B-cells isolated from mice splenocytes (2M/2F) were stimulated with IL-4 and LPS, along with NE or NPY. After 96 hours, cells were stained and analyzed by flow cytometry and transcripts were isolated for quantitative real-time PCR. Media was collected until immunoglobulin analysis. To investigate NPY role during infection, we used a mice model of bacterial lung infection. Mice were intranasally exposed twice with streptococcus pneumoniae (serotype 19F on day 0: 104 CFU and on day 9: 108 CFU); experiments took place 16 hours later. Control animals were infused with vehicle only. Results: Apart from beta2-adrenergic receptor, isolated B-cells were found to express alpha2- and beta1-adrenergic receptor transcripts. In vitro stimulation of B-cell with IL-4 and LPS (T-cell independent activation) downregulated beta-adrenergic and upregulated alpha2-adrenergic, as well as NPY receptors (Npy1r, Npy2r, Npy4r, Npy5r). Unlike NE, NPY has shown to affect B-cell proliferation and drastically increases IgG positive-cells during stimulation. However, neither NE nor NPY seem to regulate IgG release in this condition. In vivo experiments indicate that NPY level increased in the lung in response to streptococcal challenge, contrasting with the unchanged levels of NE. Conclusion: Our findings contribute to our understanding of how sympathetic neurotransmitters regulates B-cell expansion, memory, and antibody production during infection. Furthermore, our research gives new insights into the function(s) and antimicrobial capacity of neuropeptide Y. These findings allow for the development of new and more effective therapeutic strategies for invasive bacterial infections. 1R21AI159221, UCOP TRDRP T32KT4708. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

High-resolution genomics identifies pneumococcal diversity and persistence of vaccine types in children with community-acquired pneumonia in the UK and Ireland

BackgroundStreptococcus pneumoniae is a global cause of community-acquired pneumonia (CAP) and invasive disease in children. The CAP-IT trial (grant No. 13/88/11; https://www.capitstudy.org.uk/) collected nasopharyngeal swabs from children discharged from hospitals with clinically diagnosed CAP, and found no differences in pneumococci susceptibility between higher and lower antibiotic doses and shorter and longer durations of oral amoxicillin treatment. Here, we studied in-depth the genomic epidemiology of pneumococcal (vaccine) serotypes and their antibiotic resistance profiles.MethodsThree-hundred and ninety pneumococci cultured from 1132 nasopharyngeal swabs from 718 children were whole-genome sequenced (Illumina) and tested for susceptibility to penicillin and amoxicillin. Genome heterogeneity analysis was performed using long-read sequenced isolates (PacBio, n = 10) and publicly available sequences.ResultsAmong 390 unique pneumococcal isolates, serotypes 15B/C, 11 A, 15 A and 23B1 were most prevalent (n = 145, 37.2%). PCV13 serotypes 3, 19A, and 19F were also identified (n = 25, 6.4%). STs associated with 19A and 19F demonstrated high genome variability, in contrast to serotype 3 (n = 13, 3.3%) that remained highly stable over a 20-year period. Non-susceptibility to penicillin (n = 61, 15.6%) and amoxicillin (n = 10, 2.6%) was low among the pneumococci analysed here and was independent of treatment dosage and duration. However, all 23B1 isolates (n = 27, 6.9%) were penicillin non-susceptible. This serotype was also identified in ST177, which is historically associated with the PCV13 serotype 19F and penicillin susceptibility, indicating a potential capsule-switch event.ConclusionsOur data suggest that amoxicillin use does not drive pneumococcal serotype prevalence among children in the UK, and prompts consideration of PCVs with additional serotype coverage that are likely to further decrease CAP in this target population. Genotype 23B1 represents the convergence of a non-vaccine genotype with penicillin non-susceptibility and might provide a persistence strategy for ST types historically associated with vaccine serotypes. This highlights the need for continued genomic surveillance.

Immunogenicity and safety of a 14-valent pneumococcal polysaccharide conjugate vaccine (PNEUBEVAX 14™) administered to 6–8 weeks old healthy Indian Infants: A single blind, randomized, active-controlled, Phase-III study

BackgroundIntroduction of pneumococcal conjugate vaccines (PCVs) reduced the number of cases of pneumococcal disease (PD). However, there is an increase in clinical and economic burden of PD from serotypes that are not part of the existing pneumococcal vaccines, particularly impacting pediatric and elder population. In addition, the regions where the PCV is not available, the disease burden remains high. In this study, immunogenicity and safety of the BE’s 14-valent PCV (PNEUBEVAX 14™; BE-PCV-14) containing two additional epidemiologically important serotypes (22F and 33F) was evaluated in infants in comparison to licensed vaccine, Prevenar-13 (PCV-13). MethodsThis is a pivotal phase-3 single blind randomized active-controlled study conducted at 12 sites across India in 6–8 weeks old healthy infants at 6–10–14 weeks dosing schedule to assess immunogenic non-inferiority and safety of a candidate BE-PCV-14. In total, 1290 infants were equally randomized to receive either BE-PCV-14 or PCV-13. Solicited local reactions and systemic events, adverse events (AEs), serious AEs (SAEs), and medically attended AEs (MAAEs) were recorded. Immunogenicity was assessed by measuring anti-PnCPS (anti-pneumococcal capsular polysaccharide) IgG concentration and functional antibody titers through opsonophagocytic activity (OPA), one month after completing three dose schedule. Cross protection to serotype 6A offered by serotype 6B was also assessed in this study. FindingsThe safety profile of BE-PCV-14 was comparable to PCV-13 vaccine. Majority of reported AEs were mild in nature. No severe or serious AEs were reported in both the treatment groups. For the twelve common serotypes and for the additional serotypes (22F and 33F) in BE-PCV-14, NI criteria was demonstrated as defined by WHO TRS-977. Primary immunogenicity endpoint was met in terms of IgG immune responses for all 14 serotypesof BE-PCV-14. Moreover, a significant proportion of subjects (69%) seroconverted against serotype 6A, even though this antigen was not present in BE-PCV-14. This indicates that serotype 6B of BE-PCV-14 cross protects serotype 6A. BE-PCV-14 also elicited comparable serotype specific functional OPA immune responses to all the serotypes common to PCV-13. InterpretationsBE-PCV-14 was found to be safe and induced robust and functional serotype specific immune responses to all 14 serotypes. It also elicited cross protective immune response against serotype 6B.These findings suggest that BE-PCV-14 can be safely administered to infants and achieve protection against pneumococcal disease caused by serotypes covered in the vaccine.The study was prospectively registered with clinical trial registry of India – CTRI/2020/02/023129.

Nasopharyngeal Carriage of Streptococcus pneumoniae in Tunisian Healthy under-Five Children during a Three-Year Survey Period (2020 to 2022).

We aimed to assess the prevalence of nasopharyngeal pneumococcal carriage and to determine serotype distribution, antibiotic susceptibility patterns, and evolutionary dynamics of Streptococcus pneumoniae isolates in healthy under-five children. Nasopharyngeal swabs were collected from healthy children over three survey periods between 2020 and 2022. All pneumococcal isolates were serotyped and tested for antimicrobial susceptibility. A total of 309 S. pneumoniae isolates were collected, with an overall prevalence of nasopharyngeal pneumococcal carriage of 24.4% (CI95%: [22-26.8%]). These isolates were classified into 25 different serotypes. The most common serotypes were 14 (14.9%), 19F (12%), 6B (10.4%), and 23F (7.4%), which are covered by the PCV10 vaccine, as well as 19A (8.4%) and 6A (7.8%), which are covered by the PCV13 vaccine. A significant decrease in the proportion of serotype 19F (p = 0.001) and an increase in serotypes 19A (p = 0.034) and 6A (p = 0.029) were observed between the three survey periods. Multidrug resistance (MDR) was noted for 56.6% of the isolates. A significant association with antimicrobial resistance was observed for the most frequent serotypes, mainly serotype 19A. In conclusion, one-quarter of healthy under-five children in Tunisia carried S. pneumoniae in their nasopharynx. A dominance of vaccine serotypes significantly associated with antimicrobial resistance was recorded.

Impact of steroids on the immune profiles of children with asthma living in the inner-city.

Background: Inner-city asthma is associated with high morbidity and systemic steroid use. Chronic steroid use impacts immune function; however, there is a lack of data with regard to the extent of immunosuppression in patients with asthma and who are receiving frequent systemic steroids. Objective: To identify the impact of frequent systemic steroid bursts on the immune function of children with asthma who live in the inner city. Methods: Children ages 3-18 years with asthma were divided into study (≥2 systemic steroid bursts/year) and control groups (0-1 systemic steroid bursts/year). Lymphocyte subsets; mitogen proliferation assay; total immunoglobulin G (IgG) value, and pneumococcal and diphtheria/tetanus IgG values were evaluated. Results: Ninety-one participants were enrolled (study group [n = 42] and control group [n = 49]). There was no difference in adequate pneumococcal IgG value, diphtheria/tetanus IgG value, mitogen proliferation assays, lymphocyte subsets, and IgG values between the two groups. Children who received ≥2 steroid bursts/year had a significantly lower median pneumococcal IgG serotype 7F value. Most of the immune laboratory results were normal except for the pneumococcal IgG value. Most of the participants (n/N = 72/91 [79%]) had an inadequate pneumococcal IgG level (<7/14 serotypes ≥1.3 µg/mL). The participants with inadequate pneumococcal IgG level and who received a pneumococcal polysaccharide vaccine 23 (PPSV23) boost had a robust response. There was no significant difference in infection, steroid exposure, asthma severity, or morbidities between those with adequate versus inadequate pneumococcal IgG values. Conclusion: Children with asthma who live in the inner city and receive ≥2 steroid bursts/year do not have a significantly different immune profile from those who receive ≤1 steroid bursts/year do not have a significantly different immune profile from those who do not. Although appropriately vaccinated, most participants had an inadequate pneumococcal IgG level, regardless of steroid exposure and asthma severity. These children may benefit from PPSV23.