Pneumococcal Infection Research Articles

Immunoinformatics-aided design of a new multi-epitope vaccine adjuvanted with domain 4 of pneumolysin against Streptococcus pneumoniae strains

BackgroundStreptococcus pneumoniae (Pneumococcus) has remained a leading cause of fatal infections such as pneumonia, meningitis, and sepsis. Moreover, this pathogen plays a major role in bacterial co-infection in patients with life-threatening respiratory virus diseases such as influenza and COVID-19. High morbidity and mortality in over one million cases, especially in very young children and the elderly, are the main motivations for pneumococcal vaccine development. Due to the limitations of the currently marketed polysaccharide-based vaccines, non-serotype-specific protein-based vaccines have received wide research interest in recent years. One step further is to identify high antigenic regions within multiple highly-conserved proteins in order to develop peptide vaccines that can affect various stages of pneumococcal infection, providing broader serotype coverage and more effective protection. In this study, immunoinformatics tools were used to design an effective multi-epitope vaccine in order to elicit neutralizing antibodies against multiple strains of pneumococcus.ResultsThe B- and T-cell epitopes from highly protective antigens PspA (clades 1–5) and PhtD were predicted and immunodominant peptides were linked to each other with proper linkers. The domain 4 of Ply, as a potential TLR4 agonist adjuvant candidate, was attached to the end of the construct to enhance the immunogenicity of the epitope vaccine. The evaluation of the physicochemical and immunological properties showed that the final construct was stable, soluble, antigenic, and non-allergenic. Furthermore, the protein was found to be acidic and hydrophilic in nature. The protein 3D-structure was built and refined, and the Ramachandran plot, ProSA–web, ERRAT, and Verify3D validated the quality of the final model. Molecular docking analysis showed that the designed construct via Ply domain 4 had a strong interaction with TLR4. The structural stability of the docked complex was confirmed by molecular dynamics. Finally, codon optimization was performed for gene expression in E. coli, followed by in silico cloning in the pET28a(+) vector.ConclusionThe computational analysis of the construct showed acceptable results, however, the suggested vaccine needs to be experimentally verified in laboratory to ensure its safety and immunogenicity.

Severe community-acquired Streptococcus pneumoniae bacterial meningitis: clinical and prognostic picture from the intensive care unit

BackgroundSevere community-acquired pneumococcal meningitis is a medical emergency. The aim of the present investigation was to evaluate the epidemiology, management and outcomes of this condition.MethodsThis was a retrospective, observational and multicenter cohort study. Sixteen Spanish intensive care units (ICUs) were included. Demographic, clinical and microbiological variables from patients with Streptococcus pneumoniae meningitis admitted to ICU were evaluated. Clinical response was evaluated at 72 h after antibiotic treatment initiation, and meningitis complications, length of stay and 30-day mortality were also recorded.ResultsIn total, 255 patients were included. Cerebrospinal fluid (CSF) culture was positive in 89.7%; 25.7% were non-susceptible to penicillin, and 5.2% were non-susceptible to ceftriaxone or cefotaxime. The most frequent empiric antibiotic regimen was third-generation cephalosporin (47.5%) plus vancomycin (27.8%) or linezolid (12.9%). A steroid treatment regimen was administered to 88.6% of the patients. Clinical response was achieved in 65.8% of patients after 72 h of antibiotic treatment. Multivariate analysis identified two factors associated with early treatment failure: invasive mechanical ventilation (OR 10.74; 95% CI 3.04–37.95, p < 0.001) and septic shock (OR 1.18; 95% CI 1.03–1.36, p = 0.017). The 30-day mortality rate was 13.7%. Only three factors were independently associated with 30-day mortality: delay in start of antibiotic treatment (OR 18.69; 95% CI 2.13–163.97, p = 0.008), Sepsis-related Organ Failure Assessment (SOFA) score (OR 1.36; 95% CI 1.12–1.66, p = 0.002) and early treatment failure (OR 21.75 (3.40–139.18), p = 0.001). Neurological complications appeared in 124 patients (48.63%).ConclusionsMortality rate in critically ill patients with pneumococcal meningitis is lower than previously reported. Delay in antibiotic treatment following admission is the only amendable factor associated with mortality.

Nasopharyngeal colonization by Streptococcus pneumoniae in children and adults before the introduction of the 10-valent conjugate vaccine, Paraguay.

Streptococcus pneumoniae is a cause of invasive diseases such as pneumonia, meningitis, and other serious infections among children and adults in Paraguay. This study was conducted to establish S. pneumoniae baseline prevalence, serotype distribution, and antibiotic resistance patterns in healthy children aged 2 to 59 months and adults ≥60 years of age prior to the introduction of PCV10 in the national childhood immunization program in Paraguay. Between April and July 2012, a total of 1444 nasopharyngeal swabs were collected, 718 from children aged 2 to 59 months and 726 from adults ≥60 years of age. The pneumococcal isolation, serotyping, and antibiotic susceptibility testing were performed using standard tests. Pneumococcal colonization prevalence was 34.1% (245/718) in children and 3.3% (24/726) in adults. The most frequent pneumococcal vaccine-types (VT) detected in the children were 6B (42/245), 19F (32/245), 14 (17/245), and 23F (20/245). Carriage prevalence with PCV10 serotypes was 50.6% (124/245) and PCV13 was 59.5% (146/245). Among colonized adults, prevalence of PCV10 and PCV13 serotypes were 29.1% (7/24) and 41.6% (10/24), respectively. Colonized children were more likely to share a bedroom, have a history of respiratory infection or pneumococcal infection compared to non-colonized children. no associations were found in adults. However, no significant associations were found in children and neither in adults. Vaccine-type pneumococcal colonization was highly prevalent in children and rare in adults in Paraguay prior to vaccine introduction, supporting the introduction of PCV10 in the country in 2012. These data will be useful to evaluate the impact of PCV introduction in the country.

CSF-contacting neurons respond to Streptococcus pneumoniae and promote host survival during central nervous system infection

The pathogenic bacterium Streptococcus pneumoniae (S.pneumoniae) can invade the cerebrospinal fluid (CSF) and cause meningitis with devastating consequences. Whether and how sensory cells in the central nervous system (CNS) become activated during bacterial infection, as recently reported for the peripheral nervous system, is not known. We find that CSF infection by S.pneumoniae in larval zebrafish leads to changes in posture and behavior that are reminiscent of pneumococcal meningitis, including dorsal arching and epileptic-like seizures. We show that during infection, invasion of the CSF by S.pneumoniae massively activates invivo sensory neurons contacting the CSF, referred to as "CSF-cNs" and previously shown to detect spinal curvature and to control posture, locomotion, and spine morphogenesis. We find that CSF-cNs express orphan bitter taste receptors and respond invitro to bacterial supernatant and metabolites via massive calcium transients, similar to the ones observed invivo during infection. Upon infection, CSF-cNs also upregulate the expression of numerous cytokines and complement components involved in innate immunity. Accordingly, we demonstrate, using cell-specific ablation and blockade of neurotransmission, that CSF-cN neurosecretion enhances survival of the host during S.pneumoniae infection. Finally, we show that CSF-cNs respond to various pathogenic bacteria causing meningitis in humans, as well as to the supernatant of cells infected by a neurotropic virus. Altogether, our work uncovers that central sensory neurons in the spinal cord, previously involved in postural control and morphogenesis, contribute as well to host survival by responding to the invasion of the CSF by pathogenic bacteria during meningitis.

TNFR2+ regulatory Tcells protect against bacteremic pneumococcal pneumonia by suppressing IL-17A-producing γδ Tcells in the lung.

Streptococcus pneumoniae is a pathogen of global morbidity and mortality. Pneumococcal pneumonia can lead to systemic infections associated with high rates of mortality. We find that, upon pneumococcal infection, pulmonary Treg cells are activated and have upregulated TNFR2 expression. TNFR2-deficient mice have compromised Treg cell responses and highly activated IL-17A-producing γδ Tcell (γδT17) responses, resulting in significantly enhanced neutrophil infiltration, tissue damage, and rapid development of bacteremia, mirroring responses in Treg cell-depleted mice. Deletion of total Treg cells predominantly activate IFNγ-T cell responses, whereas adoptive transfer of TNFR2+ Treg cells specifically suppress the γδT17 response, suggesting a targeted control of γδT17 activation by TNFR2+ Treg cells. Blocking IL-17A at early stage of infection significantly reduces bacterial blood dissemination and improves survival in TNFR2-deficient mice. Our results demonstrate that TNFR2 is critical for Treg cell-mediated regulation of pulmonary γδT17-neutrophil axis, with impaired TNFR2+ Treg cell responses increasing susceptibility to disease.

Carriage prevalence, serotype distribution, antimicrobial resistance, pspA typing and pilus islets of Streptococcus pneumoniae isolated from adults living in a Brazilian urban slum.

For Brazilian adults, pneumococcal vaccines have been usually taken only by those who are at higher risk for development of pneumococcal diseases. Since populations from lower socioeconomic status are at high risk of acquiring pneumococcal infections, we investigated the carriage prevalence, colonization risk factors, capsular and surface protein types, and antimicrobial resistance among pneumococcal isolates recovered from adults living in a Brazilian urban slum. Between September-December 2016, we conducted a cross-sectional study among individuals aged≥18years who attended a public primary clinic in Niterói/RJ, Brazil. Pneumococci were isolated by culture on sheep blood agar plates with and without gentamicin. Antimicrobial susceptibility was determined for all isolates. We used PCR to determine capsular types, PspA families (Fam) and pilus islets (PI). Of 385 adults, 32 (8.3%) were pneumococcal carriers. Three carriers had two different pneumococci, totaling 35 isolates. After multivariate analysis, smoking, previous hospitalization, alcohol consumption and co-habitation with children aged<6years increased the odds of pneumococcal carriage, but antibiotic use in the previous 2weeks was found to be a protective factor. Fourteen different serogroups/serotypes were detected and the prevalent ones were 9N/L, 10A, 15B/C and 35F/47F (n=3; 8.6% each). Non-typeable (NT) isolates made up 31.4%. All isolates were susceptible to chloramphenicol, levofloxacin and vancomycin. We found eight (22.9%) penicillin non-susceptible pneumococci (PNSP) with minimum inhibitory concentrations (MICs) of 0.38-1.5μg/mL. The two (5.7%) erythromycin-resistant isolates had MIC>256μg/mL, cMLSB phenotype and the erm(B) gene. Twelve (34.3%) and 17 (48.6%) isolates had PspA Fam1 and Fam2, respectively. Three (8.6%) isolates had genes for pilitwo PI-1 and one PI-2. We detected a low frequency of pneumococcal carriage among the adult population, but a high diversity of serotypes. Frequencies of PNSP and NT isolates resistant to antimicrobial agents are concerning.

P725 Patients with Immune Mediated Inflammatory Diseases are insufficiently protected against vaccine-preventable influenza and pneumococcal infections due to low vaccination rates

Abstract Background Patients with Immune Mediated Inflammatory Diseases (IMIDs) treated with immunosuppressive drugs are at an increased risk of infections and a more complicated course of the infection, including vaccine-preventable infections. National and international guidelines have specified vaccination strategies in patients with IMIDs. However, the adherence to these guidelines in clinical practice is uncertain. Therefore, we evaluated the current vaccination status of patients with IMIDs at the outpatient clinic of the Erasmus MC Rotterdam. Methods Between August 2022 and October 2022, a survey was sent out to patients with various IMIDs at the rheumatology, dermatology and gastroenterology outpatient clinics. Only patients on immunosuppressive treatment were included. The survey contained questions on patient demographics, disease characteristics and current vaccination status. Results The survey was sent out to 3,345 patients with IMIDs, of whom 1,094 patients filled in the questionnaire (response rate 32.7%). Mean age was 51 ± 16 years and 40.8% were male (Table 1). Patients were treated by a dermatologist (n=306), gastroenterologist (n=414) and/or rheumatologist (n=527). Overall, 55.1% of patients received a yearly influenza vaccination and 9.2% occasionally (Table 2). Furthermore, 8.7% of patients received the pneumococcal vaccination five-yearly and 1.4% occasionally. Both the influenza and pneumococcal vaccination rates were highest in patients with rheumatoid arthritis (64.1%, and 14.7%, respectively). On the contrary, patients with hidradenitis suppurativa had the lowest rates for both the influenza vaccination (32.3%) and pneumococcal vaccination (n=0). Overall, 91.7% of patients (n=1,003) received one or more COVID-19 vaccinations. Conclusion Patients with Immune Mediated Inflammatory Diseases are insufficiently protected against vaccine-preventable infections due to low vaccination rates. Better implementation strategies of current guidelines on seasonal influenza vaccination and pneumococcal vaccination are required. A high rate of COVID-19 vaccination was observed, possibly indicating the willingness of patients to receive vaccinations. Further research into facilitators and barriers to vaccination in these specific patient populations is required.

Burden of Hospitalizations Related to Pneumococcal Infection in Spain (2016-2020).

Pneumococcal infection strongly contributes to morbidity and mortality in Spain. A total of 253,899 hospitalizations related to pneumococcal infection occurred from 2016 to 2020. Fifty-eight percent were men, the mean age was 67 years old, and the average length of hospitalization was 12.72 days. The annual hospitalization rate was 10.84 hospitalizations per 10,000 population, increasing significantly with age, reaching 65.75 per 10,000 population in those aged &gt;85 years. The hospitalization rates for pneumococcal pneumonia, sepsis, and meningitis were 2.91, 0.12, and 0.08 hospitalizations per 10,000, respectively, and reached the highest value in those aged &gt;85 for pneumococcal pneumonia and sepsis, with 22.29 and 0.71 hospitalizations per 10,000, respectively, and in children up to 1 year old for pneumococcal meningitis, with 0.33 hospitalizations per 10,000. The total number of deaths during the study period was 35,716, with a case-fatality rate of 14.07%. For pneumococcal pneumonia, sepsis, and meningitis, the case-fatality rates were 8.47%, 23.71%, and 9.99%, respectively. The case-fatality rate increased with age and did not vary by sex. The annual cost of these hospitalizations was more than EUR 359 million. There is therefore a high burden of disease and mortality caused by pneumococcal infection in our country, especially in elderly individuals.

Dual Action of Eeyarestatin 24 on Sec-Dependent Protein Secretion and Bacterial DNA.

Eeyarestatin 24 (ES24) is a promising new antibiotic with broad-spectrum activity. It shares structural similarity with nitrofurantoin (NFT), yet appears to have a distinct and novel mechanism: ES24 was found to inhibit SecYEG-mediated protein transport and membrane insertion in Gram-negative bacteria. However, possible additional targets have not yet been explored. Moreover, its activity was notably better against Gram-positive bacteria, for which its mechanism of action had not yet been investigated. We have used transcriptomic stress response profiling, phenotypic assays, and protein secretion analyses to investigate the mode of action of ES24 in comparison with NFT using the Gram-positive model bacterium Bacillus subtilis and have compared our findings to Gram-negative Escherichia coli. Here, we show the inhibition of Sec-dependent protein secretion in B. subtilis and additionally provide evidence for DNA damage, probably caused by the generation of reactive derivatives of ES24. Interestingly, ES24 caused a gradual dissipation of the membrane potential, which led to delocalization of cytokinetic proteins and subsequent cell elongation in E. coli. However, none of those effects were observed in B. subtilis, thereby suggesting that ES24 displays distinct mechanistic differences with respect to Gram-positive and Gram-negative bacteria. Despite its structural similarity to NFT, ES24 profoundly differed in our phenotypic analysis, which implies that it does not share the NFT mechanism of generalized macromolecule and structural damage. Importantly, ES24 outperformed NFT in vivo in a zebrafish embryo pneumococcal infection model. Our results suggest that ES24 not only inhibits the Sec translocon, but also targets bacterial DNA and, in Gram-negative bacteria, the cell membrane.

Age-related changes in antigen-specific natural antibodies are influenced by sex.

Natural antibody (NAb) derived from CD5+ B-1 cells maintains tissue homeostasis, controls inflammation, aids in establishing long-term protective responses against pathogens, and provides immediate protection from infection. CD5+ B-1 cell NAbs recognize evolutionarily fixed epitopes, such as phosphatidylcholine (PtC), found on bacteria and senescent red blood cells. Anti-PtC antibodies are essential in protection against bacterial sepsis. CD5+ B-1 cell-derived NAbs have a unique germline-like structure that lacks N-additions, a feature critical for providing protection against infection. Previously, we demonstrated the repertoire and germline status of PtC+CD5+ B-1 cell IgM obtained from male mice changes with age depending on the anatomical location of the B-1 cells. More recently, we demonstrated serum antibody from aged female mice maintains protection against pneumococcal infection, whereas serum antibody from male mice does not provide protection. Here, we show that aged female mice have significantly more splenic PtC+CD5+ B-1 cells and more PtC specific serum IgM than aged male mice. Furthermore, we find both age and biological sex related repertoire differences when comparing B cell receptor (BCR) sequencing results of PtC+CD5+ B-1 cells. While BCR germline status of PtC+CD5+ B-1 cells from aged male and female mice is similar in the peritoneal cavity, it differs significantly in the spleen, where aged females retain germline configuration and aged males do not. Nucleic acid sensing toll-like receptors are critical in the maintenance of PtC+ B-1 cells; therefore, to begin to understand the mechanism of differences observed between the male and female PtC+CD5+ B-1 cell repertoire, we analyzed levels of cell-free nucleic acids and found increases in aged females. Our results suggest the antigenic milieu differs between aged males and females, leading to differential selection of antigen-specific B-1 cells over time. Further elucidation of how biological sex differences influence the maintenance of B-1 cells within the aging environment will be essential to understand sex and age-related disparities in the susceptibility to bacterial infection and will aid in the development of more effective vaccination and/or therapeutic strategies specific for males and females.

Dendritic spine loss deep in the neocortex and dendrite distortion with diffusion disturbances occur early in experimental pneumococcal meningitis.

Streptococcus pneumoniae (pneumococcus) meningitis is a serious disease with substantial lethality and long-term disability in survivors. Loss of synaptic staining in the superficial layers of the neocortex in rodent models and in humans, and pneumolysin (a major pneumococcal toxin)-dependent dendritic spine collapse in brain slices have been described. It remains unclear how deep in the neocortex more discrete changes are present, how soon after disease onset these changes occur, and whether other properties of dendrites are also affected. Using a mouse model of pneumococcal meningitis, we studied changes in the neocortex shortly (3-6 h) after the onset of clinical symptoms via modified Golgi-Cox silver staining. Dendritic changes were present in areas with otherwise unchanged cell numbers and no signs of necrosis or other apparent neuronal pathology. Mature dendritic spines were reduced in the pyramidal neurons running through layers 1-5. Additionally, spine morphology changes (swelling, spine neck distortion), were also observed in the deeper layers 4 and 5 of the neocortex. Immature spines (filopodia) remained unchanged between groups, as well as the dendritic arborization of the analyzed neurons. In a third of the animals with meningitis, massive mechanical distortion of the primary dendrites of most of the pyramidal neurons through layers 1-5 was observed. This distortion was reproduced in acute brain slices after exposure to pneumolysin-containing bacterial lysates (S. pneumoniae D39 strain), but not to lysates of pneumolysin-deficient bacteria, which we explain by the tissue remodeling effect of the toxin. Experimental mechanical dendrite distortion in primary neural cultures demonstrated diminished FRAP diffusion of neuronally-expressed enhanced green fluorescent protein (eGFP), indicative of disturbed dendritic diffusion. Our work extends earlier knowledge of synaptic loss in the superficial cortical layers during meningitis to deeper layers. These changes occurred surprisingly early in the course of the disease, substantially limiting the effective therapeutic window. Methodologically, we demonstrate that the dendritic spine collapse readout is a highly reliable and early marker of neural damage in pneumococcal meningitis models, allowing for reduction of the total number of animals used per a group due to much lower variation among animals.

A study to evaluate the knowledge, vaccination status and acceptance of adult vaccinations against respiratory infections in patients with type 2 diabetes in South India.

Respiratory infections like influenza and pneumococcus increase mortality, morbidity, hospitalisation risks and healthcare costs in people with type 2 diabetes which can be prevented by vaccinations. However, there is not much data regarding how many people with type 2 diabetes in India receive pneumococcal and influenza vaccinations. This is a cross-sectional study conducted between March 2022 to May 2022 at a tertiary care centre in South India. Patients were interviewed through face to face questionnaire regarding awareness, knowledge of influenza and pneumococcal infections, availability and need of vaccines, vaccination status and the possible reasons for not receiving vaccines. A total of 388 patients were recruited in the study. Knowledge about influenza and pneumococcal infections were present only in 4.8% and 4.1% respectively. And 98.7% of patients had no awareness about the availability and need for vaccines. Only 0.5% and 0.7% of patients received influenza and pneumococcal vaccinations respectively. After counselling and spreading awareness, 76.2% of patients said that they would receive vaccination in the next visit. Also, 23.19% of the patients refused to take any vaccinations even after counselling. And 23.7% of patients feared complications after vaccinations. Pneumococcal and Influenza vaccination uptake rates are extremely low in people with type 2 diabetes in India. Urgent measures are required to increase the awareness in patients and healthcare workers about the availability, need for vaccinations and effectiveness of vaccines which would lead to improvement in vaccination rates.

Characterization of the innate immune response to Streptococcus pneumoniae infection in zebrafish

Streptococcus pneumoniae (pneumococcus) is one of the most frequent causes of pneumonia, sepsis and meningitis in humans, and an important cause of mortality among children and the elderly. We have previously reported the suitability of the zebrafish (Danio rerio) larval model for the study of the host-pathogen interactions in pneumococcal infection. In the present study, we characterized the zebrafish innate immune response to pneumococcus in detail through a whole-genome level transcriptome analysis and revealed a well-conserved response to this human pathogen in challenged larvae. In addition, to gain understanding of the genetic factors associated with the increased risk for severe pneumococcal infection in humans, we carried out a medium-scale forward genetic screen in zebrafish. In the screen, we identified a mutant fish line which showed compromised resistance to pneumococcus in the septic larval infection model. The transcriptome analysis of the mutant zebrafish larvae revealed deficient expression of a gene homologous for human C-reactive protein (CRP). Furthermore, knockout of one of the six zebrafish crp genes by CRISPR-Cas9 mutagenesis predisposed zebrafish larvae to a more severe pneumococcal infection, and the phenotype was further augmented by concomitant knockdown of a gene for another Crp isoform. This suggests a conserved function of C-reactive protein in anti-pneumococcal immunity in zebrafish. Altogether, this study highlights the similarity of the host response to pneumococcus in zebrafish and humans, gives evidence of the conserved role of C-reactive protein in the defense against pneumococcus, and suggests novel host genes associated with pneumococcal infection.

Pneumococcal Vaccination in Adults: What Can We Learn From Observational Studies That Evaluated PCV13 and PPV23 Effectiveness in the Same Population?

IntroductionFifteen and 20-valent pneumococcal conjugate vaccines (PCV15; PCV20) were recently licensed to prevent pneumococcal disease in adults. In the absence of efficacy or effectiveness data for these new vaccines, studies comparing 23-valent pneumococcal polysaccharide vaccine (PPV23) and PCV13 might help inform decision-making on how to best implement expanded-valency PCVs. Comparing PPV23 and PCV13 is problematic, as no head-to-head clinical trials evaluated efficacy. Comparing effectiveness results across observational studies that vary by population, design, and outcomes is difficult. To address these limitations, we undertook a narrative review of studies that assessed PPV23 and PCV13 vaccine effectiveness (VE) in the same adult populations. MethodsWe conducted a literature search in PubMed and Google Scholar and screened 525 studies using a standardized evaluation framework. ResultsNine studies met inclusion criteria, all from high-income countries. None evaluated invasive pneumococcal disease (IPD) alone. VE against vaccine-type pneumococcal pneumonia ranged from 2 to 6% for PPV23 and 41 to 71% for PCV13. VE against pneumococcal pneumonia or severe pneumococcal disease (IPD or pneumococcal pneumonia) ranged from −10 to 11% for PPV23, 40 to 79% for PCV13, and 39 to 83% for sequential PCV13/PPV23. VE against all-cause pneumonia or lower respiratory tract infection ranged from −8 to 3% for PPV23 and 9 to 12% for PCV13. ConclusionsOverall, PCV13 demonstrated better protection than PPV23 against pneumococcal disease and all-cause respiratory outcomes in the included studies. Where evaluated, sequential PCV13/PPV23 vaccination showed little benefit over PCV13 alone. Results support the use of PCVs to protect against pneumococcal disease and respiratory infections in adults.

Чaстота носительства S. pneumoniae у организованных детей г. Ханты-Мансийска

Aim: to assess the landscape of pneumococcus serotypes among children organized in kindergarten groups in Khanty-Mansiysk city. Patients and Methods: the study included 510 children (2-6 years old) attending kindergartens in Khanty-Mansiysk city. The children were divided into 2 groups: vaccinated (n=50) and non-vaccinated against pneumococcal infection (n=460). The data on vaccination status were received from the prophylactic immunization records (Form 063/u) and child's medical records (Form 112/u). In addition, the following data were analysed: age, gender, gestation age at birth, attitudes of child's legal representatives towards vaccinations, and the presence of chronic health problems. Pneumococcal polysaccharide conjugate adsorbed 13-valent vaccine (PCV-13) was used for the prevention of pneumococcal disease. Nasopharyngeal swabs were collected from children as a source of biological material. The pneumococcus was detected using a culture-based method and PCR assay. Results: the average age of organized children examined in Khanty-Mansiysk for Streptococcus pneumoniae (S. pneumoniae, pneumococcus) was 54.31 [53.46–55.16] months. In 56% of the examined children, pneumococcal DNA was found in nasopharyngeal swabs by polymerase chain reaction assay. The identified serotypes in 71.1% of cases were the same as in the PCV13 vaccine formulation. The most common serotypes detected were 4 (27%), 19 F (13.3%), 23 F (3.6%) and serogroup 6 (11.6%). In children immunized against S. рneumoniae, the pneumococcal strain DNAs, same as the vaccine strain DNAs, were found in 53.7% of cases, while in non-immunized children — in 73% of cases (OR 0.54, 95% CI 0.29–0.97). Conclusion: the increasing prevalence of S. рneumoniae carriage in children as they get older and attend organized children's groups for a longer time, along with the predominance within the population of the same pneumococcus strains as those in the vaccine formulation, dictate the need for timely immunization against pneumococcal infection in compliance with the National Vaccination Schedule (vaccination at 2 and 4.5 months of age, revaccination at 15 months of age). KEYWORDS: children, pneumococcal infection, S. pneumoniae, vaccination, pneumococcal conjugate vaccine, children in organized groups, carriage. FOR CITATION: Girina A.A., Petrovsky F.I., Petrovskaya Yu.A., Zaplatnikov A.L. Prevalence of S. pneumoniae carriage among children organized in kindergarten groups in Khanty-Mansiysk city. Russian Journal of Woman and Child Health. 2023;6(2):164–168 (in Russ.). DOI: 10.32364/2618-8430-2023-6-2-164-168.

Reduced risk of serious pneumococcal infections up to 10years after a dose of pneumococcal conjugate vaccine in established arthritis.

To examine rates of serious pneumococcal infections up to 10years after vaccination with 7-valent conjugated pneumococcal vaccine (PCV7) in patients with arthritis compared to non-vaccinated arthritis patients. In total, 595 adult arthritis patients (rheumatoid arthritis; RA=342, 80% women and spondylarthropathy; SpA=253, 45% women) received one dose of PCV7. Mean age/disease duration were 62/16 and 51/14years, respectively. For each patient, 4 matched reference subjects were identified. At vaccination, 420 patients received bDMARDs (anti-TNF=330, tocilizumab=15, abatacept=18, anakinra=1, rituximab=56). Methotrexate was given as monotherapy (n=86) or in combination with bDMARD (n=220). 89 SpA patients received NSAIDs without DMARD. The Skåne Healthcare Register was searched for ICD-10 diagnostic codes for pneumococcal infections (pneumonia, lower respiratory tract infection, septicemia, meningitis, septic arthritis) between January 2000 and December 2018. Frequency of infections after vs before vaccination were calculated (relative risks). Relative risk ratio (RRR) and relative risk reduction (1-RRR) were calculated comparing patients vs non-vaccinated references. Kaplan-Meier and Cox regression were used to investigate time to first event and predictors of infections. Among vaccinated RA and SpA patients, there was a significant relative risk reduction of pneumonia and all serious infections; 53% and 46%, respectively. There was no significant difference in time to first pneumonia or all serious infections after vaccination between patients and references. Higher age, RA diagnosis and concomitant prednisolone were associated with infections. One dose of pneumococcal conjugate vaccine may decrease risk of serious pneumococcal infection up to 10years in patients with arthritis receiving immunomodulating treatment.

Preclinical study of mutagenicity and safety of a vaccine against pneumococcal infection based on a recombinant hybrid protein

Pneumococcal infection is the cause of pneumo-nia. Vaccination can prevent the severe course of this disease. The pneumococcal vaccine considered in the work was created by a genetically modified method based on a hybrid recombinant protein. The aim of the work was preclinical investigation of the mutagenic, genetic safety of the new pneumococcal vaccine, Irivax, against pneumococcal infection in rats. Materials and methods. Studies of the Irivax vaccine were carried out in male Wistar rats’ cell populations of the bone marrow and peripheral blood mononuclear cells. The karyoty-pic stability of cells and myelogram of the bone mar-row were studied. Results. After the introduction of the vaccine, the content of the lymphoid germ cells in the blood of rats was increased to 74.2% (p &lt;0.05), which proves the body’s immune response. The frequency of cells with an unstable genome, as an indicator of the genetic safety of the AL-vaccine, was rare both in expe-rimental and control animals, and did not exceed 1.5%. Conclusion. Thus, the new pneumococcal vaccine Irivax and its components have mutagenic and toxic safety.

Synergistic Protection against Secondary Pneumococcal Infection by Human Monoclonal Antibodies Targeting Distinct Epitopes.

Streptococcus pneumoniae persists as a leading cause of bacterial pneumonia despite the widespread use of polysaccharide-based vaccines. The limited serotype coverage of current vaccines has led to increased incidence of nonvaccine serotypes, as well as an increase in antibiotic resistance among these serotypes. Pneumococcal infection often follows a primary viral infection such as influenza virus, which hinders host defense and results in bacterial spread to the lungs. We previously isolated human monoclonal Abs (mAbs) against the conserved surface Ag pneumococcal histidine triad protein D (PhtD), and we demonstrated that mAbs to this Ag are protective against lethal pneumococcal challenge prophylactically and therapeutically. In this study, we elucidated the mechanism of protection of a protective anti-pneumococcal human mAb, PhtD3, which is mediated by the presence of complement and macrophages in a mouse model of pneumococcal infection. Treatment with mAb PhtD3 reduced blood and lung bacterial burden in mice, and mAb PhtD3 is able to bind to bacteria in the presence of the capsular polysaccharide, indicating exposure of surface PhtD on encapsulated bacteria. In a mouse model of secondary pneumococcal infection, protection mediated by mAb PhtD3 and another mAb targeting a different epitope, PhtD7, was reduced; however, robust protection was restored by combining mAb PhtD3 with mAb PhtD7, indicating a synergistic effect. Overall, these studies provide new insights into anti-pneumococcal mAb protection and demonstrate, to our knowledge, for the first time, that mAbs to pneumococcal surface proteins can protect against secondary pneumococcal infection in the mouse model.

Противопневмококковая иммунизация у детей раннего возраста с хронической сердечной недостаточностью

Aim: To determine the coverage, efficacy and tolerability of pneumococcal vaccination in young children with cardiovascular disease associated with chronic heart failure. Design: Retro- and prospective randomized comparative study. Materials and methods. The study included 250 patients at the age of 2 months to 5 years with confirmed chronic cardiac failure caused by cardiomyopathy or congenital heart disorder. Within the scope of a specialised laboratory and instrumental examination, all children underwent an assessment of specific immunoglobulin (Ig) levels to the most common pneumococcal serotypes (1-5, 6B, 7F, 8, 9N, 9V, 10A, 11A,12F, 14, 15B, 17F, 18C, 19F, 19A, 20, 22F, 23F, 33F) using VaccZyme Anti-PCP IgG test system. During consultations and vaccination schedule development, pneumococcal vaccination coverage and the reasons for long-term medical exemptions or refusals were analysed. Provided the primary disease was stable, there were no contraindications and a parent gave their consent, patients were vaccinated with 13-valent pneumococcal conjugate vaccine (PCV13). Results. When questioning the parents of patients, it was revealed that before admission to the department, only 97 (38.8%) patients received at least 1 dose of pneumococcal vaccine, while the remaining 153 (61.2%) were not vaccinated. During hospitalization, 65 (42.5%) of 153 unvaccinated patients under 5 years of age who had not received a single pneumococcal vaccine received the first dose (V1) of PCV13; of 97 children vaccinated, 20 (20.6%) received a second dose, 18 (18.6%) — pneumococcal booster. There was a significant difference in the levels of antibodies to Streptococcus pneumoniae between the group of patients who received a full course of immunization according to age and the group of unvaccinated children: 108.1 ± 58.4 vs. 12.14 ± 7.8 mg/l (p &lt; 0.05). In children with an incomplete course of vaccination, the levels of specific IgG to pneumococcal serotypes were lower. In groups of children who received only one dose of the vaccine in the first or second year of life, they amounted to 42.2 ± 11.7 and 40.2 ± 16.2 mg/l, respectively. Children who received at least two doses of vaccine without revaccination (starting before 12 months) had a relatively higher level of 68.2 ± 6.3 mg/L. But, despite a clear trend, there was no significant difference between these groups in our study. In the post-vaccination period, no serious complications were recorded in the examined children. Conclusion. Vaccination against pneumococcal infection in children with chronic heart failure is effective, safe and should be carried out as close as possible to the schedule of the national vaccination calendar, with a limited set of contraindications. Keywords: vaccination, 13-valent pneumococcal conjugate vaccine, immunoglobulin G, chronic heart failure.

Pneumococcal vaccine uptake and its associated factors among adult patients with congestive cardiac failure seen in a tertiary facility in Lagos, Nigeria

Background: Patients with congestive cardiac failure (CCF) are at increased risk of morbidities and mortality associated with pneumococcal infections and thus should be vaccinated against Streptococcus pneumoniae. However, there is dearth of scientific data on pneumococcal vaccine uptake in this environment. This study set out to assess the vaccination status and its associated factors among CCF patients in Lagos State University Teaching Hospital (LASUTH), Lagos, Nigeria.&#x0D; Methodology: A questionnaire based cross-sectional study of one hundred patients with CCF conducted at the adult cardiology out-patient clinic of LASUTH between December 2021 and March 2022. Socio-demographic and clinical characteristics were recorded as well as Pneumococcal vaccination status, source of vaccination, challenges and reasons for non-vaccination. The likelihood of recommending vaccination for others was also obtained.&#x0D; Results: The mean age of the study population was 51.55±16.36 years (range 21-78 years). The male to female ratio was 56:44. Pneumococcal vaccination rate was 9% with only 4% fully vaccinated. Lack of information about vaccine was the commonest reason for non-vaccination. Healthcare providers were the source of vaccine information in only 58% of the vaccinated subjects. Majority of the vaccinated respondents (67%) had their vaccines outside the country and most of them will likely recommend vaccination to others.&#x0D; Conclusion: Pneumococcal vaccination rate among CCF patients was poor. Better patients’ education and prompt vaccine recommendation by the managing physicians will improve vaccination uptake. A National guideline for adult pneumococcal vaccine in Nigeria is desirable.