Pneumococcal Infection Research Articles

ОЦЕНКА БЕЗОПАСНОСТИ И ВЛИЯНИЯ ПНЕВМОКОККОВОЙ ВАКЦИНЫ «ПРЕВЕНАР-13» НА ПОКАЗАТЕЛИ ЗАБОЛЕВАЕМОСТИ ПНЕВМОНИЕЙ И ОТИТОВ У ДЕТЕЙ ПЕРВЫХ ПЯТИ ЛЕТ ЖИЗНИ

The scientific article presents an assessment of the clinical effectiveness and safety of the use of the pneumococcal conjugate 13-valent vaccine (PCV13, PCV 13) «Prevenar 13» in children from 0 to 5 years old, observed in the children's department of the State Budgetary Institution of Healthcare of the Secondary Educational Institution «SGKP N 15» in the city Samara. The study included 590 children, who were divided into 2 groups. The first (main, group PC-13) group included children born in 2018 - 2020 and vaccinated with the Prevenar 13 vaccine according to the «2 + 1» (n=490), the second (control) group included children born in 2013 and not vaccinated with a vaccine against pneumococcal infection, including Prevenar 13 (n=100). The study revealed that during the 2nd year of life in children of the first group, the incidence rate after vaccination decreased by 2 times. The incidence rate of pneumonia in the group of vaccinated children also decreased in all age periods, and the incidence rate of otitis media during the entire observation period in the second group of children (unvaccinated) was higher. Based on the data presented, we can conclude that vaccination with Prevenar-13 is a safe and effective measure in the prevention of ARI (acute respiratory infections) in children.

Uncovering the health system burden of pneumococcal infections in adult and elderly populations

Abstract Background Health system resources dedicated to vaccination and infectious disease prevention are often directed towards infants and children, through extensive childhood vaccination schedules. This focus has led to the near eradication of several preventable childhood diseases and had positive impacts on population health, but despite this track record of success, the ability of our health systems to make vaccinations accessible throughout the full life course has been less consistent. This project aims to address this issue by providing new data about the burden that pneumococcal infections, which are vaccine-preventable, have on adult and elderly populations. Methods This research aims to uncover the health system burden of invasive pneumococcal disease and pneumococcal pneumonia at all levels of the health system in 5 EU countries (Austria, Belgium, France, Italy & Portugal). This involves a survey of managers and care providers working in hospitals, long-term care facilities, and primary care centres who may be affected by the health system impacts of pneumococcal infections. The survey covers several dimensions of health service delivery to collect a broad range of data on existing disruptions. The survey was translated into the study country languages and its formulation was further validated through interviews with experts in each study country to ensure that it can capture context-specific health system insights. The data collected through this survey will be further enhanced through a series of in-depth interviews before being synthesised, analysed and eventually published in a detailed report. Results Data collection begins as of 15 May 2024, and full results are expected to be published and available for the EPH Conference in November 2024. The results of this research will offer valuable evidence to public health professionals, health managers and policy-makers across Europe who are working to improve life-course access to pneumococcal vaccination. Key messages • Effective vaccination programmes for adult and elderly populations require expanding focus beyond childhood. • Data about the health system burden of pneumococcal infections in adult and elderly populations improves evidence-based decision-making and public health services.

43 Etiology of community-acquired bacterial meningitis in children seen in the emergency department in Canada

Abstract Background Bacterial meningitis poses a significant threat to paediatric health, resulting in substantial morbidity and mortality in children. Though previous studies have delineated the causative agents behind community-acquired meningitis, recent vaccination initiatives may have reshaped its underlying etiology. Objectives This study aimed to identify the bacteria responsible for community-acquired bacterial meningitis in children in Canada. Design/Methods This was a retrospective cohort study including children aged 1 day-18 years with confirmed bacterial meningitis, evaluated at a tertiary-care, Canadian emergency department between July 1st 2014 and December 31st 2022. The primary outcome was the pathogen identified. Other variables of interest were mortality, complications, age, sex, and diagnostic method. Medical charts were identified via the hospital’s archives and reviewed by a single co-author. A random sample of 20 (23%) medical charts were independently reviewed by a second co-author to assess inter-rater reliability. We set a target of evaluating at least 50 cases to allow narrow confidence intervals (+/- 13%) for proportions. Results All variables showed excellent inter-rater reliability with Kappa scores and intraclass correlation coefficients higher than 0.60. All 79 eligible cases were included. The main causal agents were Group B Streptococcus (GBS) (n=20; 25%), Streptococcus pneumoniae (n=16; 20%), Neisseria meningitidis (n=16; 20%) and Haemophilus influenzae (n=9; 11%). Etiology exhibited age-dependent variations, with 85% of GBS and 100% of E. coli infections identified in children under two months, while all pneumococcal and Group A Streptococcus cases were in children older than six months. All children infected by S. pneumoniae were vaccinated against pneumococcal infection but the serotype was not covered by vaccination in 7/8 infections. All children with N. meningitidis were either too young to be vaccinated (n=10) or infected by a serotype not covered by the vaccine. Six (7%) patients died and 29 (34%) suffered complications, including hearing impairment (n=5), cerebral ischemia (n=4), seizures (n=4), and subdural abscess (n=3). Fifty-nine bacterias were identified by cerebrospinal fluid culture, 13 by PCR and 7 by both methods. Conclusion GBS is the leading etiology of paediatric community-acquired bacterial meningitis in Canada. Causal agents of bacterial meningitis vary greatly by age. Future studies should work on improving the serotype spectrum of vaccines, prophylaxis in mothers who are GBS carriers, and use of PCR as a diagnostic tool for timely clinical interventions.

Optimization of manufacturing process for serotype 14 pneumococcal capsular polysaccharide

Streptococcus pneumoniae is a pathogenic bacterium that causes infections such as pneumonia, meningitis, otitis media, and bacteremia. The prevention of pneumococcal disease by vaccination has become more urgent due to increased antibiotic resistance. Pneumococcal capsular polysaccharides (CPS) are effective vaccine antigens that stimulate the host to produce protective antibodies. S. pneumoniae serotype 14 is one of most prevalent types in Latin America and across the world. However, the yield of S. pneumoniae serotype 14 CPS from existing fermentation processes remains low and requires improvement. In this study, various aspects of the fermentation process were optimized to improve pneumococcal growth and polysaccharide productivity, including feed medium, cultivation gas environment, fermentation pH, and temperature. A simplified purification method was also developed to obtain pure CPS, including ultrafiltration, acid and ethanol precipitation, diafiltration, and lyophilization. These fermentation optimizations significantly enhanced the optical density of pneumococcal bacterial cultures and increased fermentation yields to 2.4–2.6 g/L—significantly higher than previously achieved. Furthermore, the test results of pure CPS could meet the requirements in the European Pharmacopoeia (11th edition). These optimizations provide valuable insights into the nutritional requirements and impact of varying fermentation process parameters on pneumococcal growth and CPS productivity, thus contributing to the development of a more efficient and cost-effective method for the production of pneumococcal CPS—essential for manufacturing vaccines against pneumococcal infections.

Invasive Pneumococcal Diseases in People over 65 in Veneto Region Surveillance

Background: Elderly individuals over 65, along with children under 5, are the most affected by invasive pneumococcal diseases (IPDs). Monitoring vaccination coverage and conducting surveillance are essential for guiding evidence-based prevention campaigns and public health measures. Methods: Since 2007, the Veneto Region has relied on three sources for surveillance of invasive bacterial infections, contributing to an increase in reported IPD cases. This study analyzed notifications related to individuals aged ≥65 years from 2007 to 2023. Results: A total of 1527 cases of IPDs in elderly individuals were reported between 2007 and 2023. The notification rate significantly increased from 5.61 to 14.63 per 100,000 inhabitants, despite underreporting during the COVID-19 pandemic. Cases associated with sepsis increased from 3.89 to 9.58 per 100,000, while notifications of meningitis and case fatality rates remained stable at 1.5 per 100,000 and 11.8%, respectively. Serotyping was not performed in 52% of the notifications. The most common serotypes were 3 (21.6%), 8 (11.1%), and 19A (5.0%), with fluctuations over time. There was a significant decline in serotypes covered by PCV7 and PCV13 and an increase in non-vaccine serotypes. Conclusions: The regional surveillance system allows for an increasingly comprehensive profile of the epidemiological landscape of IPDs in Veneto. However, the surveillance of pneumococcal infections still presents challenges. The currently available data are likely to be underestimated, mainly referring to the most severe cases, and the serotyping necessary to identify the etiological agent is still not often performed.

Vaccinations in pulmonary diseases - part 2: herpes zoste, RSV, pneumococcal infection and pertussis

RSV is a common cause of respiratory tract infections, posing a risk of severe disease, particularly for newborns and infants, as well as in older individuals with pre-existing conditions. Two safe and effective RSV vaccines were approved in 2023. These vaccines elicit protective antibodies and offer robust protection with no additional benefit from annual boosters. Both vaccines have been approved for individuals aged 60 years and older, while one of the vaccines has also been approved in pregnant women to elicit maternal immunity for passive protection of the unborn child. In Germany, RSV vaccination is currently recommended for all individuals aged 75 years and older, as well as people aged 60-74 years of age with severe underlying conditions. PNEUMOCOCCAL INFECTION: Streptococcus pneumoniae is a primary cause of community-acquired pneumonia (CAP). Since early 2022, a 20-valent conjugate vaccine (PCV20) is approved and recommended for people over 60 years of age and individuals over 18 years of age with risk factors. PCV20 replaces the 23-valent polysaccharide vaccine (PPV23) previously recommended for those over 60 years of age. Although viewed primarily as a childhood disease, the majority of infections affect adults. Patients with chronic respiratory diseases are at a higher risk for severe clinical course of pertussis infection. It has therefore been recommended that all adults should get a pertussis booster with their next scheduled tetanus vaccination, given as a combination vaccine (Tdap). For risk groups (healthcare personnel, community facilities) a booster vaccination every 10 years is recommended. Herpes Zoster (shingles) is caused by the varicella-zoster virus, and reactivations can lead to painful skin lesions and potential complications such as herpes zoster oticus, meningitis, or postherpetic neuralgia. People with chronic lung diseases such as COPD or asthma are at increased risk of herpes zoster-related complications. A recombinant adjuvanted inactivated vaccine was approved in 2018 and offers robust protection against herpes zoster and its complications. The vaccine is recommended for all people over 60 years of age and for certain risk groups over 50 years of age.

Effect of 10-valent pneumococcal conjugate vaccine on trends of pneumococcal meningitis in children under five years, Uganda, 2003-2022.

Pneumococcal meningitis, a vaccine-preventable disease caused by Streptococcus pneumoniae (Spn) is the leading bacterial meningitis in under five children. In April 2014, Uganda introduced routine immunization with 10-valent Pneumococcal Conjugate Vaccine (PCV10) for infants. The target coverage for herd immunity is ≥ 90% with three doses (PCV10-dose 3). We assessed the effect of PCV10 introduction and coverage on the trends of pneumococcal meningitis in under five children. We analyzed laboratory-confirmed pediatric bacterial meningitis (PBM) data at two high-volume WHO-accredited sentinel surveillance hospitals in Kampala City and Gulu District, from 2003 to 2022. We used confirmed cases to estimate the minimum incidence of pneumococcal meningitis in the host districts and calculated annual incidence of pneumococcal meningitis per one million populations, and the proportion of confirmed PBM attributable to Spn. We divided the study period into 2003-2013 (pre-PCV10) and 2014-2022 (post-PCV10), and conducted interrupted time series analysis using autoregressive integrated moving average models for the effect of PCV10 on trends of pneumococcal meningitis and PBM attributable to Spn. We analyzed reported PCV10 data in DHIS2 from 2014 to 2022 for annual PCV10-dose 3 coverage. Among the 534 confirmed PBM cases, 331(62%) were pneumococcal meningitis; 227(69%) from Gulu District and 104(31%) from Kampala City. The majority (95%) of the isolates were not serotyped. The majority (57%) were male and unimmunized (98%); median age = 14(IQR = 6-27) months with most (55%) aged ≥ 12 months. The case-fatality rate was 9%. During Pre-PCV10 period, the overall incidence of pneumococcal meningitis in the host districts increased; slope change = 1.0 (95%CI = 0.99999, 1.00001) but declined in post-PCV10 period (2014-2022) by 92% from 86 cases /1,000,000 in 2014 to 7/1,000,000 in 2022, slope change= -1.00006 (95%CI=-1.00033, -0.99979). Whereas there was an immediate decline in the proportion of confirmed PBM attributable to Spn in the host districts, level change=-1.84611(95%CI=-1.98365,-1.70856), an upward trend was recorded from 2016 to 2022, slope change = 1.0 (95%CI = 0.99997, 1.00003). During 2015-2022, PCV10-dose 3 coverage was largely > 90% for Gulu District and 52-72% for Kampala City. The PCV10 routine immunization program reduced the incidence of pneumococcal meningitis in Kampala City and Gulu District. There was no effect on the confirmed PBM proportionately attributable to Spn. Kampala City persistently recorded PCV10-dose3 coverage < 90%. We recommend enhancing serotyping and periodic nasopharyngeal carriage surveys to ascertain the maximum vaccine effectiveness and monitor Spn serotypes, and strengthening routine immunization in Kampala City.

Epidemiology of pneumococcal meningitis in sentinel hospital surveillance of Viet Nam, 2015–2018

BackgroundStreptococcus pneumoniae (S. pneumoniae), Haemophilus influenzae (H. influenzae), and Neisseria meningitidis (N. meningitidis) are leading causes of childhood bacterial meningitis and preventable by vaccines. The aim of this hospital-based sentinel surveillance is to describe the epidemiological characteristics of pneumococcal meningitis, including disease burden, and to provide baseline data on pneumococcal serotype distribution to support decision making for pneumococcal conjugate vaccine (PCV) introduction in Vietnam.MethodsSurveillance for probable bacterial meningitis in children 1–59 months of age is conducted in three tertiary level pediatric hospitals: one in Hanoi and two in Ho Chi Minh City. Cerebrospinal fluid (CSF) specimens were collected via lumbar puncture from children with suspected meningitis. Specimens were transferred immediately to the laboratory department of the respective hospital for cytology, biochemistry, and microbiology testing, including culture. PCR testing was conducted on CSF specimens for bacterial detection (S. pneumoniae, H. influenzae, and N. meningitidis) and pneumococcal serotyping.ResultsDuring 2015–2018, a total of 1,803 children with probable bacterial meningitis were detected; 1,780 had CSF specimens available for testing. Of 245 laboratory-confirmed positive cases, the majority were caused by S. pneumoniae (229,93.5%). Of those with S. pneumoniae detected, over 70% were caused by serotypes included in currently available PCV products; serotypes 6 A/6B (27.1%), 14 (19.7%), and 23 F (16.2%) were the most common serotypes. Children with laboratory-confirmed pneumococcal meningitis were more likely to live in Hanoi (p < 0.0001) and children 12–23 months of age were at greater odds (OR = 1.65, 95% CI: 1.11, 2.43; p = 0.006) of having confirmed pneumococcal meningitis compared to children < 12 months of age when compared to those without laboratory-confirmed bacterial meningitis. Additionally, children with confirmed pneumococcal meningitis were more likely to exhibit signs and symptoms consistent with clinical meningitis compared to negative laboratory-confirmed meningitis cases (p < 0.0001) and had a greater odds of death (OR = 6.18, 95% CI: 2.98, 12.86; p < 0.0001).ConclusionsPneumococcal meningitis contributes to a large burden of bacterial meningitis in Vietnamese children. A large proportion are caused by serotypes covered by PCVs currently available. Introduction of PCV into the routine immunization program could reduce the burden of pneumococcal meningitis in Viet Nam.

Neonatal overfeeding attenuates microgliosis and hippocampal damage in an infant rat model of pneumococcal meningitis.

Pneumococcal meningitis (PM) triggers apoptotic neuronal and progenitor cell death in the hippocampal dentate gyrus (DG), resulting in subsequent cognitive impairment. Microglia play a crucial role in PM-induced hippocampal damage. While the lasting effects of neonatal nutrition on health are well documented, the influence of early-life overfeeding on the host response to neuroinfections remains uncertain. This study aimed to examine whether neonatal overfeeding affects the outcome of PM in the hippocampus (HC). Overfeeding was induced by adjusting litter size immediately after birth. On the eleventh day of life, rats were intracisternally injected with Streptococcus pneumoniae or saline, followed by euthanasia after 24 hours for brain dissection. Histological analysis evaluated apoptosis in the DG and the extent of inflammatory infiltrate in the hippocampal fissure, while microgliosis was assessed by immunohistochemistry. The hippocampal transcriptome was analyzed using RNAseq, and the mRNA levels of specific inflammatory biomarkers were evaluated via RT-qPCR. Overfed rats exhibited 40.5% greater body mass compared to their normal-fed counterparts. Intriguingly, PM-induced apoptosis in the DG was 50% lower in overfed rats. This effect was accompanied by significant alterations in the hippocampal transcriptional profile, particularly the lack of activation of the Programmed cell death pathway in overfed infected animals. RT-qPCR analysis of Aif1 and examination of Iba1-immunostained cells revealed mild microgliosis in the HC of infected-overfed animals. This reduced microglial reaction may be attributed to the diminished activation of interferon signaling pathways, as disclosed by the transcriptome analysis, potentially preventing microglial priming. Additionally, evidence of reduced neuroinflammation in overfed rats with PM was observed through the milder activation of pathways associated with Toll-like receptors, interleukins, and chemokine signaling. Furthermore, overfed animals exhibited increased transcription of proinflammatory Il6 and anti-inflammatory Il10 genes, with the latter showing higher expression even in the absence of PM, suggesting a priming effect of overfeeding on hippocampal immune cells. This study sheds light on the complex interplay between early-life overfeeding, immune response, and neuroprotection in infant rats with PM. The findings demonstrate the neuroprotective impact of early-life overfeeding in the context of PM, linked to the modulation of microglial function.

Streptococcus pneumoniae in Medical Districts of Burkina Faso: Serotype Distribution and Antibiotic Susceptibility during 2010 to 2012

Introduction: Streptococcus pneumoniae is a highly virulent pathogen. Despite the recent introduction of vaccines in the program of prevention in Burkina Faso, treatment by antibiotics has remained in use. The aim of this study was to determine the serotypes implied in invasive pneumococcal infections and their resistance to antibiotics used for routine treatment in Burkina Faso. Methods: From March 2010 to December 2012, a total of 6,102 cerebrospinal fluid (CSF) and pleural fluid (PF) specimens were collected in Burkina Faso. The specimens were analyzed by latex agglutination assay, culture, and real time polymerase chain reaction (rt-PCR) for species identification. Serotyping was performed by rt-PCR and minimum inhibitory concentrations were determined by the E-test. Results: Among 562 S. pneumoniae strains identified from 6,102 specimens, 440 isolates were serotyped by rt-PCR. Serotypes 1 and 5 were the most common (50%); however, 70 (15.9%) strains were not detected by rt-PCR methodology. Among patients of less than 20 years of age, serotype 1 was the most frequent strain identified (9.3% to 13.2%). Ampicillin and ceftriaxone were the most active antibiotics in vitro against the strains identified. The rate of S. pneumoniae strains susceptible to chloramphenicol was 83%. Serotypes 1 (7/49) and 5 (5/7) were non-susceptible to chloramphenicol. Conclusion: Serotypes 1 and 5 were the common serotypes identified. Conjugate vaccines introduced in Burkina Faso should take in account these valences, to decrease the incidence of pneumococcal infections efficiently.

Immunization with recombinant Streptococcus pneumoniae PgdA protects mice against lung invasion.

Current pneumococcal vaccines, including the pneumococcal polysaccharide (PPV23) and conjugate (PCV13) vaccines, offer protection against specific serotypes but pose risks of serotype replacement that can alter the composition of the nasopharyngeal microbiota. To address this challenge, a novel strategy has been proposed to provide effective protection without disrupting the colonization of other bacterial populations. In our study, we found that subcutaneous immunization with recombinant peptidoglycan N-acetylglucosamine deacetylase A (rPgdA) elicited robust humoral and cellular immune responses, significantly reducing the invasion of Streptococcus pneumoniae in the lungs without affecting nasopharyngeal carriage. Furthermore, rPgdA antisera were shown to diminish bacterial invasion of lung epithelial cells in vitro. Notably, sera from patients with invasive pneumococcal infections exhibited higher levels of antibodies against the PgdA protein compared to sera from healthy adults, suggesting that a natural immune response to this protein occurs during infection. These results suggest a promising new target for the development of pneumococcal vaccines.

Endonuclease A in Streptococcus pneumoniae: escaping from neutrophil extracellular traps (NETs) and relationship in immunogenicity

Streptococcus pneumoniae (S. pneumoniae), which is a Gram-positive diplococcus, has emerged as a significant human pathogen. It is a primary cause of bacterial pneumonia, otitis media, meningitis, and septicemia, leading to a considerable impact on global morbidity and mortality. The investigation of S. pneumoniae and its virulence factors has resulted in the identification of surface endonuclease A (EndA). EndA functions in DNA uptake during natural transformation and plays a significant role in gene transfer. The ability of S. pneumoniae to degrade neutrophil extracellular traps (NETs) enhances its virulence and invasive potential in pneumococcal infections. NETosis occurs when neutrophils release chromatin into the extracellular space to form NETs, capturing and neutralizing pathogens. Currently, NETosis can be induced by several microbes, particulate matter, and sterile stimuli through distinct cellular mechanisms, and this includes the involvement of EndA in S. pneumoniae. Here, we reviewed the cellular functions of EndA, its role in S. pneumoniae as a virulence factor in relation to NETosis, its relationship to immunogenicity, and its involvement in several diseases. The discovery of this relationship would significantly impact therapeutic technology in reducing disease burden, especially pneumococcal infections.

Prospects of vaccination against pneumococcal infection based on the asthma phenotype

According to recent studies, bronchial asthma is characterized by a wide variability of the mechanisms of occurrence and progression. This heterogeneity is caused by patterns of predominant cells and inflammatory mediators, which determine differences in immunological parameters observed in patients with certain endotypes depending on the dominant type of mediators (high and low T2 inflammation). In long-term observations, a substantial research base has been accumulated justifying the effectiveness of vaccination against pneumococcal infection in patients with asthma. The vaccination decreases the frequency of exacerbations of the disease and hospitalizations in the short and medium term. However, these studies evaluated the asthma patients as a wholesome population, and it remains unexplored whether the effect of pneumococcal vaccines on asthma differs depending on the endotype of the disease and what are the mechanisms of such a differentiated effect.The aim of this work is to present the results of recent quality studies on changes in the profile of inflammatory asthma mediators under the action of immunobiological substances based on Streptococcus pneumoniae antigens, primarily from the vaccines.Conclusion. The asthma heterogeneity can lead to different clinical outcomes in pneumococcal infection and, respectively, the clinical effects of immunization in patients differentiate according to the nature of inflammation. In other words, the uniformity of the clinical effect of vaccination against pneumococcal infection in all patients in ongoing studies may represent the combined effect of molecular mechanisms regulating the specific activity of Th1-, Th2-, Th17-, NKT-, and Treg-cells. The results of studies proving the ability of pneumococcal vaccines to modulate the Th1-, Th2-, Th17-, Treg immune response in patients with asthma contributed to increased interest in developing new immunoregulatory therapeutic agents based on S. pneumoniae antigens.

Haemophilus influenzae and pneumococci: Co-colonization, interactions, cooperation and competition.

Nontypeable Haemophilus influenzae (NTHi) and Streptococcus pneumoniae (pneumococcus) are pathobionts that share common environmental niches within the upper respiratory tract. They can form part of the resident upper airway microbiota, but under certain environmental circumstances become pathogenic and induce disease. In children, both organisms have a considerable impact on the healthcare system, commonly causing acute otitis media and pneumonia. They are also associated with chronic biofilm-mediated respiratory infections, such as persistent middle ear effusions and chronic suppurative otitis media, and in the lower airways with protracted bacterial bronchitis and bronchiectasis. Consequently, both organisms are responsible for large numbers of antibiotic prescriptions and substantial healthcare costs. The complex relationship between NTHi and pneumococcal co-interaction during colonization, infection and biofilm formation is poorly understood and a greater understanding is needed to facilitate development of future therapies, and novel interventions and prevention strategies. Co-infections with both bacteria can result in more severe disease, with disease severity likely mediated by their ability to cooperate in some in vivo niches. However, this relationship is not always straightforward, as under certain conditions, these two bacteria compete rather than cooperate. Current opinion supports developing a vaccine targeting NTHi strains, as well as a combined vaccine targeting both NTHi and pneumococci to decrease the respiratory disease burden in young children. This review summarizes our current knowledge of the interactions between NTHi and pneumococci and speculates on the future directions of research to understand how these bacteria co-exist and how to better prevent and treat NTHi and pneumococcal infection.

How effective is 13-valent pneumococcal conjugate vaccine (PCV13) combined with 23-valent pneumococcal polysaccharide vaccine (PPSV23)?

The bacterium Streptococcus pneumoniae remains a major causeof morbidity and mortality worldwide. Currently, the 2 leading vaccines targeted against it are: 23-valent pneumococcal polysaccharide vaccine (PPSV23) and 13-valent pneumococcal conjugate vaccine (PCV13). It was only very recently, starting 22 November 2019, that the Advisory Committee on Immunisation Practices (ACIP) no longer recommends routine administration of PCV13 for all adults aged 65 and above. As such, this systematic review aims to investigate how the use of PCV13 combined with PPSV23 compares to using PPSV23 alone in older adults. Relevant research papers were chosen through an electronic searchin PubMed. A set of selection criteria was then applied to ensure that the papers aligned with the objectives of this paper. The majority of the studies included in this paper demonstrated that in adults aged 50 years and above, PCV13 had the ability to generate a strong immune response in adults, even more so than PPSV23 for all of the twelve serotypes common to both vaccines. The safety of PCV13 was also demonstrated in the studies as no PCV13-related serious adverse events (SAEs) had surfaced. Only one study included in this systematic review opposed the trend.While the evidence for both PCV13’s and PPSV23’s ability to generate an immune response have been persuasive, more research that focuses on the clinical endpoint in older adults, as well as the incidence of pneumococcal infections in the population, could be done to fully address the main question of this paper.

Bacteriological characteristics and changes of Streptococcus pneumoniae serotype 35B after vaccine implementation in Japan.

Streptococcus pneumoniae serotype 35B, a non-vaccine type, is a major contributor to the increase in pneumococcal infection post-vaccination. We aimed to understand the mechanism of its spread by characterizing 35B. The serotype, type 1 pilus (T1P) positivity, and antimicrobial susceptibility of 319 isolates in 2018-2022 were analysed and compared with those of isolates in 2014-2017 to find the changes. 35B accounted for 40 (12.5%) isolates. T1P positivity was notably higher in 35B (87.5%) than in the other serotypes. To confirm the role of T1P, an adhesion factor, we compared adherence to A549 cells between T1P-positive 35B isolates and their T1P-deficient mutants, showing contribution of T1P to adherence. Penicillin-non-susceptible rate of 35B was 87.5%, and meropenem-resistant 35B rate was 35.0%, which increased from 14.5% of 2014-2017 (p=0.009). Multilocus sequence typing was performed in 35B strains. Prevalence of clonal complex 558, harbouring T1P and exhibiting multidrug non-susceptibility, suggested the advantages of 35B in attachment and survival in the host. The emergence of ST156 isolates, T1P-positive and non-susceptible to β-lactams, has raised concern about expansion in Japan. The increase of serotype 35B in pneumococcal diseases might have occurred due to its predominant colonizing ability after the elimination of the vaccine-serotypes.

Seizure prophylaxis in pneumococcal meningitis, cohort study.

Our aim was to assess seizure development as a complication of pneumococcal meningitis and its possible prevention with antiseizure medication prophylaxis. Antiseizure medication (ASM) prophylaxis has been practiced for a long time at our center. We assessed all cases of community-acquired pneumococcal meningitis admitted from January 2010 to April 2021 recorded in our prospective database and conducted further retrospective studies. Of the 86 cases recorded, 21 (24.4%) developed acute symptomatic seizures, more than half of which (11/21; 52.4%) before admission. Seizure development increased the need for orotracheal intubation and intensive care unit admission, while also lengthening hospital stays and suggesting more risk of death and disability at discharge [adjusted odds ratio (aOR), 3.13; 95% confidence interval (CI): 1-9.8]. Of the 74 patients eligible for ASM prophylaxis, 64 received it and 10 did not. ASM prophylaxis seemed effective in preventing seizure development, as only six seizure events were recorded in 64 patients with ASM prophylaxis (9.4%) compared with four in the 10 patients without prophylaxis (40%). Its preventive capacity was especially notable when administered within 4 h of admission. Differences in mortality did not reach statistical significance. Adverse effects were rare. Seizure development is a common complication in pneumococcal meningitis and is associated with increased risks of Intensive Care Unit admission, orotracheal intubation, and longer hospital stays. ASM prophylaxis may be effective in blocking seizure development in patients with preventable seizures and may be associated with better prognosis. Further studies are now warranted. Infection of the meninges (the covering of the brain) due to the common bacteria S pneumoniae, used to be a fatal disease before the introduction of antibiotics and corticoids. Thanks to these drugs, more people survive this disease but, due to the frequent complications, they may have several sequelae. Seizures are a common complication. Our study suggests that they might be prevented by using antiseizure drugs which may reduce both severity and hospital stay.

Pneumolysin contributes to dysfunction of nasal epithelial barrier for promotion of pneumococcal dissemination into brain tissue.

Streptococcus pneumoniae is one of the major pathogens responsible for bacterial meningitis and neurological sequelae. The present study was conducted to identify a non-hematogenous route used by S. pneumoniae to gain access to brain tissue without causing bacteremia or pneumonia, as well as bacterial and host factors involved in this process. To investigate the molecular mechanisms and dissemination pathways of pneumococcal infection in brain tissue, mice were intranasally inoculated with S. pneumoniae strain EF3030, a clinical isolate from a patient with otitis media. Pneumococci were isolated from the frontal olfactory bulb, caudal cerebrum, and cerebellum, with neither bacteremia nor pneumonia observed in the present model. Immunostaining imaging revealed the presence of S. pneumoniae organisms in olfactory nerve fibers. Knockout of the ply gene encoding pneumolysin (PLY) markedly compromised the ability of the bacterial organisms to disseminate into brain tissue, whereas the dissemination efficiency of the complemented strain was restored to nearly the same level as the wild type. Notably, distinct upregulation of Gli1 and Snail1, which are involved in the transcriptional repression of junctional proteins, along with downregulation of E-cadherin, was detected in nasal lavage samples from mice infected with the wild-type or complemented strain, but not in those from mice infected with the ply mutant. Taken together, the present findings indicate that PLY induces Gli1-Snail1-dependent dysfunction of the nasal epithelial barrier, thus allowing pneumococcal dissemination to brain tissue that occurs in a non-hematogenous manner.IMPORTANCEBacterial meningitis, considered to be caused by bacteremia, can lead to blood-brain barrier disruption and bacterial dissemination into the central nervous system. Despite the availability of intravenously administered antibiotics with cerebrospinal fluid transferability, bacterial meningitis remains associated with high rates of morbidity and mortality. Here, we utilized Streptococcus pneumoniae strain EF3030, clinically isolated from otitis media, for the construction of a murine infection model to investigate the molecular mechanisms by which nasally colonized pneumococci disseminate into brain tissue. The obtained findings indicate that pneumolysin (PLY) induces Gli1-Snail1-dependent dysfunction of the nasal epithelial barrier, which facilitates pneumococcal dissemination to brain tissue in a non-hematogenous manner. Our results support the existence of an alternative route by which S. pneumoniae can reach the central nervous system and indicate the need for the development of novel therapeutic strategies, which would be an important contribution to the clinical management of bacterial meningitis.

Glycyrrhetinic acid reduces lung inflammation caused by pneumococcal infection by reducing the toxicity of pneumolysin

ObjectiveIn this study, to provide new methods for the treatment of Streptococcus pneumoniae infection, we aimed to describe the anti-inflammatory and antibacterial value of glycyrrhetinic acid on the basis of its inhibitory effect on bacterial growth (without killing the bacteria) and its reduction of the toxicity of S. pneumoniae. MethodsA mouse model was established via intranasal administration of Streptococcus pneumoniae D39, and glycyrrhetinic acid was subcutaneously injected for treatment. The wet‒dry ratio, bacterial flora content and inflammatory factor levels in the mouse lungs were determined. Cell experiments were used to evaluate glycyrrhetinic acid-mediated inhibition of PLY hemolysis and A549 cell death, and WB was used to measure glycyrrhetinic acid-mediated inhibition of PLY oligomerization. ResultsGlycyrrhetinic acid reduced the levels of inflammatory factors, the dry‒wet ratio, the abundance of S. pneumoniae in the lungs of infected mice, pneumolysin-mediated A549 cell death, erythrocyte hemolysis and PLY oligoplasia. ConclusionGlycyrrhetinic acid can reduce the virulence of S. pneumoniae by preventing the oligomerization of PLY.

Pneumococcal infection in children with recurrent respiratory diseases

In frequently ill children with recurrent respiratory diseases (RRD), violations of local immunity and microbiocenosis of the mucous membranes can contribute to the development of acute and chronic bronchopulmonary diseases. Vaccination against major pathogens, including S. pneumoniae, can help prevent respiratory infections in children.Objective: to study the microbiocenosis and local immunological factors of the nasopharyngeal mucosa in children with RRD, the serotype composition of S. pneumoniae in children with community-acquired pneumococcal pneumonia (CAP) and pneumococcal carriers, as well as the correspondence of the serotype landscape to the composition of modern pneumococcal vaccines.Materials and methods: The study included 150 patients (104 children with RRD and 46 patients with CAP). To assess the condition of the nasopharyngeal mucosa cultural methods, morphofunctional, immunological and capsule PCR typing of S. pneumoniae isolates were performed. Statistical analysis was performed using the Statistica 10.0 package.Results: The age structure was dominated by children aged 3 to 6 years (36%). The majority of patients with RRD had pronounced nasopharyngeal mucosal dysbiosis (n=60), as well as destruction of epithelial cells (n=97). These factors may predispose to the development of bronchopulmonary diseases, including community-acquired pneumonia (CAP). Capsule PCR typing of S. pneumoniae isolates from the nasopharynx was performed in 46 patients. It has been established that in the structure of nasopharyngeal carrier S. pneumoniae in children with CAP, serotypes “3” and 19F prevailed, which were also the main pathogens in pneumococcal CAP. In nasopharyngeal pneumococcal carrier, the thirteen–valent pneumococcal conjugate vaccine (PCV13) overlapped 39.6% (95%CI 27.6–53.1%) of serotypes, in pneumococcal VP – 57.2% (95% CI 36.5-75.5%), while PCV20 overlapped 22.6% more S. pneumoniae serotypes in children with CAP.Conclusion: The strategy for the prevention of acute respiratory infections in children is immunization against pneumococcal infection, which should be carried out taking into account the regional prevalence of S. pneumoniae serotypes.