Pneumococcal Infection Research Articles

Progranulin Plays a Protective Role in Pneumococcal Meningitis by Inhibiting Pyroptosis.

Pneumococcal meningitis is a serious infectious disease with a high mortality rate and a global presence, and survivors have different degrees of neurological sequelae as a consequence of the host response to the infection. Progranulin (PGRN) is a multifunctional autocrine growth factor that is also a major immunoregulator. We want to investigate the role for PGRN in Pneumococcal meningitis in vivo and in vitro. Mouse and cell models were established to explore the protective effect and mechanism of PGRN against pneumococcal meningitis. Progranulin plays a protective role in pneumococcal meningitis by inhibiting pyroptosis. Pyroptosis resulted from exposure of BV-2 cells to the bacterium and this was confirmed in the in vivo model. Administration of the NLRP3 inflammasome inhibitor MCC950 to mice prior to infection inhibited pyroptosis and protected PGRN -/- mice and BV-2 cell model from meningitis. This study implicates a protective role for PGRN in pneumococcal meningitis by inhibiting pyroptosis, indicating that PGRN may have therapeutic potential.

Rev-erb-α antagonism in alveolar macrophages protects against pneumococcal infection in elderly mice

Rev-erb-α antagonism in alveolar macrophages protects against pneumococcal infection in elderly mice

P-48. Uptake of pneumococcal vaccination after invasive pneumococcal diseases in two centers in northern Italy

Abstract Background Aim of this study is to evaluate factors associated with uptake of pneumococcal vaccination after invasive pneumococcal disease (IPD). Since pneumococcal infection doesn’t protect from future ones, vaccination is recommended in patients who recover from IPD. Table 1 Population's characteristics. Methods Retrospective, bicenter cohort study of patients hospitalized with invasive pneumococcal disease at IRCCS San Raffaele Hospital (Milan, Italy) and ASST Manzoni Hospital (Lecco, Italy) between January 1st 2015 and December 31st 2019. Patients older than 18 years with positive blood or cerebrospinal fluid cultures for Streptococcus pneumoniae were included. Patients who died before discharge and whose vaccinal record and discharge documentations were not available were excluded. All vaccination data were retrieved through Italian national vaccination portal (SIAVR). Follow-up data were updated until March 31st, 2024. The characteristics of patients who were vaccinated (VAX) and were not vaccinated (UNVAX) after the event were compared using the chi-square test for categorical variables and the Mann-Whitney U-test for continuous variables. Table 2 Characteristics of vaccination cycles. Results The characteristics of the 211 included patients are described in table 1, completed vaccination cycles in table 2. Only 26 patients (12.3%) received an indication at discharge to get vaccinated for S. pneumoniae, and 47 (22.2%) patients were vaccinated during the observation period, after a median of 6.6 (2.3-29.9) months after the event. There was no difference in age between the two groups (70.7 [60.1-78.4] vs 69.5 [58.8-78.5], p-value=0.82), while a greater proportion of VAX patients was male (33 [70.2%] vs 86 [52.4%], p-value=0.03). Charlson comorbidity index was similar between the two groups (5 [3-6] vs 5 [3-6], p-value=0.845), but a significant higher percentage of VAX patients had lymphoma (8 [17%] vs 8 [4.9%], p-value=0.006). Patients who received an indication to vaccinate were significantly more likely to receive pneumococcal vaccination (16 [34%] vs 10 [6.1%], p-value< 0.001). Conclusion Our cohort revealed low pneumococcal vaccination uptake, with inadequate frequency of vaccination indication at discharge. Reinforcing prevention culture among patients and physicians is imperative. Disclosures Antonella Castagna, MD, Bristol-Myers Squibb: Advisor/Consultant|Gilead Sciences, Inc.: Advisor/Consultant|Gilead Sciences, Inc.: Grant/Research Support|Gilead Sciences, Inc.: Honoraria|Janssen: Advisor/Consultant|Janssen: Grant/Research Support|Janssen: Honoraria|Merck Sharp & Dohme: Advisor/Consultant|Merck Sharp & Dohme: Grant/Research Support|Merck Sharp & Dohme: Honoraria|ViiV Healthcare: Advisor/Consultant|ViiV Healthcare: Grant/Research Support|ViiV Healthcare: Honoraria

P-13. Awareness, Attitudes, Knowledge and Barriers Related to Adult Pneumococcal Vaccination among Internal Medicine Residents and Fellows in University Hospital, Thailand

Abstract Background Pneumonia is the leading cause of global mortality with Streptococcus pneumoniae as a leading pathogen in high-risk adults. Although vaccination is crucial for preventing pneumococcal infections, its uptake remains suboptimal in Thailand. Internists, pivotal in managing such patients, are at the forefront of promoting vaccination. Therefore, this study aimed to explore factors related to physicians’ pneumococcal vaccine administration among high-risk adults in university hospital in Thailand. Methods This web-based survey cross-sectional study was conducted at King Chulalongkorn Memorial Hospital, Bangkok, Thailand (university hospital). Participants were residents and fellows in Department of Medicine. The questionnaire included demographic data and vaccine-related inquiries in various aspects including awareness, attitudes, and knowledge towards pneumococcal vaccination. Results The study involved 93 participants. Demographic data was presented in table 1. Awareness of pneumococcal vaccination was generally high and attitudes were positive. Overall, participants showed a good knowledge of pneumococcal infection, but participants with lower rate of vaccination administration had significant lower knowledge than participants with higher rate of vaccination administration (table 2). Key barriers to vaccination included limited access to advice and recording systems, cost issues, and a lack of specialized consultation. Potential quality improvement strategies were electronic vaccination record, easy-to-access guideline, and vaccine consultation clinic. Conclusion This study emphasizes the importance of addressing barriers like limited access to vaccination advice and recording systems, cost issues, and a lack of specialized consultation. Implementing targeted interventions and raising knowledge and awareness of vaccination are key steps toward reducing the burden of pneumococcal infections. These results would lead to improvement of residency and fellowship training program and vaccination practice in our hospital. Disclosures Pawat Phuensan, MD, MSc, GSK: Grant/Research Support|GSK: Honoraria|MSD: Honoraria|Pfizer: Grant/Research Support|Pfizer: Honoraria|Siam Pharmaceutical: Grant/Research Support|Takeda: Honoraria

P-659. Active Surveillance of Mucosal Pneumococcal Infections to Predict the Potential Added Benefits of Extended-Spectrum PCVs in Children < 24 Months in Southern Israel

Abstract Background Although mucosal infections, such as otitis media (OM) and acute conjunctivitis (AC) are the most common manifestations of pneumococcal disease in young children, surveillances have been based mainly on invasive pneumococcal disease (IPD) due to paucity of serotype-specific data on mucosal infection rates. We present rates and serotype dynamics of OM and AC as a means for assessing potential added benefits of the new PCVs, (PCV15/PCV20) against OM and AC in children < 24m. Annual incidence rates of P-OM and P-AC episodes, children <24 months of age*, southern Israel, July 2004 through June 2023 Methods A retrospective analysis of two prospective, population-based surveillance projects on OM (Ben-Shimol CID 63:611, 2016) and AC (Dagan CID 72:1200, 2021) in southern Israel. All episodes in children < 24m with OM and/or AC with cultures in southern Israel have been included. All middle-ear fluid (MEF) and conjunctival cultures in the region are processed in a single laboratory of the hospital where ∼95% of all children are born and treated, permitting incidence calculations. The current analysis covers all pneumococcal OM and AC (P-OM, P-AC) from July 2004 through June 2023. Distribution of individual serotypes in P-AC and P-OM episodes, children <24 months of age*, southern Israel, July 2015 through June 2023 (late PCV13 period) Results A total of 2,312 and 1,039 episodes of P-OM and P-AC, respectively, were observed. The P-OM and P-AC annual rates are presented in Figure 1. The respective incidence rate ratios (95% CI) for 2017-2023 (excluding Corona year 2020-2021) vs. 2004-2008 were 0.12 (0.09-0.16) and 0.37 (0.26-0.53). During the stable PCV13 period (2015-2023), 32% and 24% of all P-OM and P-AC, respectively, were PCV20 serotypes (Figure 2). In both diseases, the PCV13 serotypes 19A, 19F, 3, and 14, and the PCV20-non-PCV13 serotypes 10A, 11A, 33F, and 15 B/C, predominated. PCV13 serotypes 1, 4, 5, 6A, 6B, 7F, 9V, 18C, 23F (grouped) constituted only 0.6% and 1.7% of all P-OM and P-AC, respectively. Conclusion 1) PCV13 implementation resulted in a rapid and steep decline in both P-OM and P-AC rates, stabilizing within 3-4 years; 2) during the late PCV13 period, only 4 PCV13 serotypes persisted: PCV7 serotypes 19F and 14, and PCV13 non-PCV7 serotypes 3 and 19A; and 3) the non-PCV13 PCV20 serotypes constitute approximately one quarter and one third of P-AC and P-OM, respectively, in children < 24m in southern Israel. Implementation of PCV20 has the potential to add benefit against pneumococcal mucosal disease. Disclosures Ron Dagan, Professor MD, GSK: Advisor/Consultant|GSK: Honoraria|MedIMmune/AstraZeneca: Grant/Research Support|MedIMmune/AstraZeneca: Honoraria|MSD: Advisor/Consultant|MSD: Grant/Research Support|MSD: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Pfizer: Honoraria|Sanofi Pasteur: Honoraria

P-8. Assessment of 13-valent pneumococcal conjugate vaccine effectiveness among people living with HIV in the United States

Abstract Background People living with HIV (PLWH) have increased risk of pneumococcal infections. Although pneumococcal conjugate vaccines (PCVs) have been recommended for immunocompromised (IC) people, data regarding PCV effectiveness among PLWH are limited.Table 1.Baseline characteristics prior to weighting of 350,399 PLWH by receipt of PCV13 by end of baseline, United States, 2014-2022 Methods People with an HIV diagnosis code (index) from 1/1/2014 through 12/31/2021 were identified in US administrative claims. PLWH age ≥ 18 years without prior PCV13 vaccination were followed from six months post-index (baseline period) through 9/30/2022 for first episodes of invasive pneumococcal disease (IPD), pneumococcal pneumonia (PP) due to any serotype, and all-cause pneumonia (ACP) using diagnosis codes. Marginal structural Cox models estimated hazard ratios (HR) for each outcome and inverse probability weights were used to control for confounding/dropout. Vaccine effectiveness (VE) was estimated as (1-HR) x 100%. Candidiasis, all-cause diarrhea, and accidental injury served as negative control outcomes to assess residual confounding.Table 2.PCV13 VE against IPD, PP, ACP, and negative control outcomes among 350,399 PLWH, United States, 2014 - 2022 Results 350,399 PLWH were included; 8% had received PCV13 during baseline, rising to 24% PCV13 by end of follow-up, and 25% received PPSV23. Mean follow-up was 2.9 years. Compared with PCV13-unvaccinated PLWH, greater proportions of PCV13-vaccinated PLWH were adherent to HIV medications and received CD4 tests, viral load tests, and influenza vaccination during baseline (Table 1). Overall weighted VEs (95% confidence intervals [CIs]) for IPD, PP, and ACP were 22% (5%, 36%), 17% (4%, 29%), and 8% (6%, 11%), respectively (Table 2). VE was highest for years 0 to < 3 of follow-up (0 to < 3 yr VE: 35% [13%, 51%]) for IPD, 26% [9%, 39%] for PP, and 11% [8%, 15%] for ACP) (Table 3). The negative control outcomes suggested residual confounding (Tables 2-3).Table 3.Weighted PCV13 VE against IPD, PP, ACP, and negative control outcomes among PLWH during 0 to < 3, 3 to < 5, and 5 to < 7 years of follow-up, United States, 2014 - 2022 Conclusion This study demonstrated real-world PCV13 VE against IPD and pneumonia among PLWH during the first three years of follow-up, but little evidence of VE thereafter. However, assessing VE after three years of follow-up was limited by decreased sample size and events. Overall, VE was relatively high considering pneumococcal outcomes were not specific to vaccine serotypes and ACP was not specific to pneumococcus. Residual confounding may also exist, but its direction remains unclear. Disclosures Amanda C. Miles, MPH, Pfizer: Pfizer employee|Pfizer: Pfizer employee|Pfizer: Stocks/Bonds (Public Company)|Pfizer: Stocks/Bonds (Public Company) Sarah J. Willis, PhD, MPH, Pfizer, Inc.: Employment|Pfizer, Inc.: Stocks/Bonds (Private Company) Erica Chilson, PharmD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds (Public Company) Lindsay Grant, PhD, MPH, Pfizer, Inc: Employee of company|Pfizer, Inc: Stocks/Bonds (Private Company) Christian Theilacker, MD, DTM&H, Pfizer Inc: I am a Pfizer Employee|Pfizer Inc: Stocks/Bonds (Public Company) Cassandra Hall-Murray, PharmD, Pfizer, Inc.: employee|Pfizer, Inc.: Stocks/Bonds (Public Company) Qi Yan, PhD, MS, Pfizer: Pfizer employee|Pfizer: Stocks/Bonds (Public Company) Jeffrey T. Vietri, PhD, Pfizer Inc.: Employment|Pfizer Inc.: Stocks/Bonds (Public Company) Tamuno Alfred, PhD, Astellas Pharma: Astellas Pharma employee|Pfizer: Previous Pfizer employee|Pfizer: Stocks/Bonds (Public Company) Alejandro D. Cane, MD, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds (Public Company)|Pfizer: Stocks/Bonds (Public Company) Bradford D. Gessner, M.D., M.P.H., Pfizer: Employee|Pfizer: Stocks/Bonds (Public Company)

Corynebacteria from the respiratory microbiota modulate inflammatory responses and associate with a reduced pneumococcal burden in the lungs

BackgroundCertain species from the normal respiratory tract microbiota have recently been proposed to positively influence human health. Corynebacterium propinquum and C. pseudodiphtheriticum (Corynebacteria) are two Gram-positive species that frequently colonize the upper respiratory tract and strongly associate with a reduced incidence of respiratory tract infections. The specific role of Corynebacteria during respiratory health and disease is, however, largely uncharacterized.MethodRespiratory tract epithelial cells NCI-H292 and BALB/cByJ mice were inoculated with Corynebacteria (C. propinquum 2018M3 and 2019M4, and C. pseudodiphtheriticum 2019M8 and 2020M12) alone or with subsequent challenge with Streptococcus pneumoniae (pneumococci). The inflammatory response and the bacterial burden of both species over time were determined by Western blot, luciferase assay, cytokine bead array, flow cytometry and viable plate counts on blood agar plates.ResultsClinical isolates of Corynebacteria were well tolerated by human cells and mice. Corynebacteria induced a transient inflammatory response during healthy conditions in the absence of known pathogens. Pre-exposure or nasal priming with Corynebacteria did not affect subsequent acquisition of pneumococci but were associated with a modulated inflammatory response in vitro and in vivo as well as with a reduced pneumococcal burden in the respiratory tract of mice. This indicates that the presence of C. propinquum or C. pseudodiphtheriticum may protect against severe pneumococcal infections.ConclusionsIn this study, we delineate the role of Corynebacteria from the normal microbiota that epidemiologically associate with respiratory health. We show that the presence of Corynebacteria modulates the inflammatory response to pneumococci and associate with faster decrease in pneumococcal burden, primarily in the lower respiratory tract. Our data indicate that Corynebacteria has potential to protect against severe pneumococcal infections.

Delayed completion of pneumococcal conjugate vaccination among children 4–48 months in rural Uganda: a socio-demographic inquiry

In spite of the commendable global Pneumococcal Conjugate Vaccine (PCV) coverage in the last two decades, completion and timeliness of receipt of all the required doses are still below target. In Uganda, the 3 + 0 PCV regimen has been reported to have a steady decline in the completion rate and the reasons for the delayed completion are unidentified. This study aimed at assessing the influence of socio-demographic factors on delayed PCV completion among young children. A cross-sectional study design among 362 child/caretakers pairs in Bugongi Town Council was employed. Using stratified sampling – Allocation Proportional to Size, data was collected using pretested questionnaires; entered and analysed using STATA v14 and significant statistical association was considered at P ≤ 0.05. Of the 362 children, majority (53.87%) were boys. Child mean age was 25.1 ± 14.3 months. 87.6% caretakers were females and majorities of them were aged 20–29yrs (47.8%), peasant farmers (79.8%), married (90.6%), attained primary education (63.5%) and earned average monthly income of UGX 10,000 – UGX 50,000 (41.4%). Of the 362 children, 92 (25.4%) had delayed to receive their PCV-3 doses. Only boy child [cOR = 1.65, (95%CI: 1.03–2.66); P = 0.039) and caretaker’s age 30–39 [cOR = 2.12 (95%CI: 1.06–4.24); P = 0.033) showed statistical significance at bivariate analysis. The multivariate model found parent’s age 20–29 years [aOR = 2.39 (1.14–5.01); P = 0.021] and 30–39 years [aOR = 2.51 (1.16–5.45); P = 0.020] as positively associated factors whereas being married [aOR = 0.20 (0.04–0.96); P = 0.044] was the only negatively associated factors to delayed completion of PCV vaccination among young children. Among children who complete the last dose of PCV vaccination, a considerable proportion are actually receiving it late which may result into eventual failure to curb the targeted pneumococcal infections. Thus, concerted efforts in terms of sensitization are un-doubtfully desired especially among caretakers aged 20–39 years as well as those who are not married.

Effectively preventing pneumococcal diseases in the elderly and the young

Pneumococcal disease (PD) caused by Streptococcus pneumoniae (Sp) is a global public health concern. Children younger than 5 years and elderly over 60 years, due to immature development of the immune system early in life or the gradual decline of immune function with age, are high-risk groups for pneumococcal infections, which makes the disease burden particularly serious and the situation of prevention and control grim. Vaccination is the most effective measure to prevent PD and reduce pneumococcal antimicrobial resistance. Improving health consciousness and vaccination rates are particularly necessary and urgent for the prevention and control of PD. Based on the disease burden, this article discusses the problems and challenges of PD in China regarding surveillance, laboratory testing, antimicrobial resistance, and vaccination. Recommended strategies concerning the surveillance system, clinical diagnosis and treatment, vaccination, and health promotion were made to increase the vaccination rate of pneumococcal vaccine among the elderly and young and to improve the level of PD prevention and control.

Pneumococcal Vaccination Coverage Among Adults at Risk in the Russian Federation

Relevance. Pneumococcal infection remains one of the most significant health problems worldwide. Vaccination of adults against it has been carried out in the Russian Federation for over 10 years. During this time, more than 9 million people have been vaccinated. However, data on the level of coverage among adults of certain risk categories are not routinely collected. Our study in 2019 showed that it was low in most groups. Given the significant increase in the volume of vaccination over the past five years, it seems appropriate to conduct a study to assess changes in the level of coverage.Aim. To study the level of vaccination coverage against pneumococcal infection in adult risk groups in the Russian Federation.Materials and methods. An observational descriptive retrospective epidemiological study was conducted. Information on the number and contingents of people vaccinated against pneumococcal infection was collected by sending a request to the executive authorities of the constituent entities of the Russian Federation in the field of healthcare. The depth of data collection was 8 years (from 2015 to 2023 inclusive), information was received from 74 out of 89 regions. In addition, federal statistical observation forms were used: No. 5 «Information on preventive vaccinations» and No. 6 «Information on the contingents of children and adults vaccinated against infectious diseases», data from the Unified Interdepartmental Information and Statistical System. The results obtained were compared with the indicators obtained in the 2019 study, which was conducted according to a similar design. The analysis was carried out using descriptive statistics methods.Results. The coverage rate of vaccination against pneumococcal infection among the adult population in the Russian Federation increased from 1.5% in 2018 to 7.7% in 2023. The most significant coverage rates were achieved among persons subject to conscription for military service (78.5%) and persons over 60 years old, living in residential care facilities (87.7%). By 2023, vaccination coverage has increased among the following risk categories: individuals with chronic bronchopulmonary diseases (from 15.1% in 2018 to 47.9% in 2023), chronic heart diseases (from 3.8% to 17.0%), patients with endocrine diseases (from 1.1% to 17.6%), liver diseases (from 4.0% to 12.0%), healthcare workers (from 4.9% to 19.7%), school and preschool employees (from 3.1% to 12.9%), employees of residential care facilities (homes for elderly, nursing homes, ect.) (from 0.1% to 26.9%), the elderly population as a whole (from 1.4% to 12.7%), and working-age men (from 1.4% to 7.0%). There was virtually no increase in coverage among all groups of immunocompromised patients (1.0% in 2018, 6.2% in 2023), the working population with risk factors harmful to the respiratory system (0.9% in 2018, 5.0% in 2023), workers in the oil and gas and chemical industries (1.3% in 2018, 1.8% in 2023).Conclusion. The obtained results indicate the need to develop a strategy of measures to promote increased vaccination coverage in risk groups that are insufficiently covered by vaccination against pneumococcal infection.

Interactions of the Pneumococcus with the Central Nervous System: Postnatal Meningitis Versus Fetal Neurodevelopment.

In young children, pneumococcal meningitis epitomizes the paradigm of a destructive innate inflammatory response in the central nervous system: a five-alarm fire. In contrast, cell-free bacterial components reaching the fetal brain from an infected mother signal a quiet, noninflammatory immune response that drives abnormal neurodevelopment, changing brain architecture through neuroproliferation. This review addresses the difference between prenatal and postnatal bacterial-host signaling within the brain.

Global impact of 10- and 13-valent pneumococcal conjugate vaccines on pneumococcal meningitis in all ages: the PSERENADE project.

Pneumococcal conjugate vaccines (PCVs) introduced in childhood national immunization programs lowered vaccine-type invasive pneumococcal disease (IPD), but replacement with non-vaccine-types persisted throughout the PCV10/13 follow-up period. We assessed PCV10/13 impact on pneumococcal meningitis incidence globally. The number of cases with serotyped pneumococci detected in cerebrospinal fluid and population denominators were obtained from surveillance sites globally. Site-specific meningitis incidence rate ratios (IRRs) comparing pre-PCV incidence to each year post-PCV10/13 were estimated by age (<5, 5-17 and ≥18 years) using Bayesian multi-level mixed effects Poisson regression, accounting for pre-PCV trends. All-site weighted average IRRs were estimated using linear mixed-effects regression stratified by age, product (PCV10 or PCV13) and prior PCV7 impact (none, moderate, or substantial). Changes in pneumococcal meningitis incidence were estimated overall and for product-specific vaccine-types and non-PCV13-types. Analyses included 10,168 cases <5y from PCV13 sites and 2,849 from PCV10 sites, 3,711 and 1,549 for 5-17y and 29,187 and 5,653 for ≥18y from 42 surveillance sites (30 PCV13, 12 PCV10, 2 PCV10/13) in 30 countries, primarily high-income (84%). Six years after PCV10/PCV13 introduction, pneumococcal meningitis declined 4874% across products and PCV7 impact strata for children <5y, 3562% for 5-17y and 036% for ≥18y. Impact against PCV10-types at PCV10 sites, and PCV13-types at PCV13 sites was high for all age groups (<5y: 96100%; 5-17y: 7785%; ≥18y: 7385%). After switching from PCV7 to PCV10/13, increases in non-PCV13-types were generally low to none for all age groups. Pneumococcal meningitis declined in all age groups following PCV10/PCV13 introduction. Plateaus in non-PCV13-type meningitis suggest less replacement than for all IPD. Data from meningitis belt and high-burden settings were limited.

Changes and determinants of pneumococcal vaccine uptake in Ethiopia.

Pneumococcal pneumonia is one of the most common causes of severe pneumonia and pneumonia-related mortality globally. It ranked among the leading causes of morbidity and mortality in children under five years in Ethiopia. Vaccination reduces the burden of pneumonia and pneumococcal infections in both children and adults. This study assesses changes in pneumococcal vaccine coverage over time and identifies factors associated with the vaccine uptake. The study was based on secondary data from the Ethiopian Demographic and Health Surveys (EDHS) in 2016 and 2019, involving 1,929 children in 2016 and 1,008 in 2019, aged 12-23 months. A cross-sectional study design was conducted. The percentage change in pneumococcal conjugate vaccine (PCV) coverage was used to quantify the degree of change over time, while multilevel ordinal logistic regression identifies significant factors. All statistical tests were performed using a 5% significance threshold. The study found a significant 21.8% (95% CI: 9.8-35.2) change in the proportion of children receiving complete doses of PCV, from 49.1% in 2016 to 59.8% in 2019. Children in rural areas were 69% less likely to receive more doses of PCV vaccinations than those living in urban areas (AOR = 0.307, 95% CI: 0.127 - 0.742). Second or higher-order births were associated with greater uptake doses of PCV (AOR = 2.519, 95% CI: 1.143-5.548). Child born in health facilities were 2.35 times more likely to receive full vaccination than those born at home (AOR = 2.350, 95% CI: 1.132-4.882). Additionally, children whose mothers had more antenatal care (ANC) visits were more likely to complete their pneumococcal vaccination. Despite the increase in uptake, Ethiopia remains far from reaching its immunization goals. The study showed that place of residence, birth order, place of delivery, antenatal care and regional variation were significantly associated with pneumococcal vaccine uptake.

Mathematical Analysis of the Role of Treatment and Vaccination in the Management of the HIV/AIDS and Pneumococcal Pneumonia Co‐Infection

Concomitant infections by two or more pathogens are on upsurge and among these is the interplay between HIV/AIDS and pneumococcal pneumonia infections. A mathematical co‐infection model that fronts vaccination and treatment against pneumococcal pneumonia and antiretroviral therapy for HIV/AIDS in the management of the co‐infection burden is presented. The model is also extended to include optimal control plans, in line with protection, early detection, and treatment of both HIV/AIDS and pneumococcal pneumonia. Co‐infection model analysis manifests that the solutions are positive and bounded, and the disease equilibria stabilities are established in reference to the computed effective reproduction numbers. Sensitivity analysis indicated that infection rate parameters are by far the most influential in the co‐infection escalation, whereas treatment and vaccination associated parameters have inhibiting effect towards the co‐infection. Numerical simulations reveal that treatment and vaccination interventions are important in co‐infection reduction but not sufficient for co‐infection elimination. Further analysis indicates that, in addition to treatment and vaccination, adopting all optimal control plans can be a concrete start to co‐infection elimination.

Pneumococcal Septic Arthritis among Adults, France, 2010-2018.

Streptococcus pneumoniae infection is considered an uncommon cause of arthritis in adults. To determine the clinical and microbiological characteristics of pneumococcal septic arthritis, we retrospectively studied a large series of cases among adult patients during the 2010-2018 conjugate vaccine era in France. We identified 110 patients (56 women, 54 men; mean age 65 years), and cases included 82 native joint infections and 28 prosthetic joint infections. Most commonly affected were the knee (50/110) and hip (25/110). Concomitant pneumococcal infections were found in 37.2% (38/102) and bacteremia in 57.3% (55/96) of patients, and underlying conditions were noted for 81.4% (83/102). Mortality rate was 9.4% (8/85). The proportion of strains not susceptible to penicillin was 29.1% (32/110). Of the 55 serotyped strains, 31 (56.4%) were covered by standard pneumococcal vaccines; however, several nonvaccine serotypes (mainly 23B, 24F, and 15A) had emerged, for which susceptibility to β-lactams was low.

The Formyl Peptid Receptor Ligand Ac2-26 Improves the Integrity of the Blood-Brain Barrier in the Course of Pneumococcal Meningitis.

The brain is protected from invading pathogens by the blood-brain barrier (BBB) and the innate immune system. Pattern recognition receptors play a crucial role in detecting bacteria and initiating the innate immune response. Among these are G-protein-coupled formyl peptide receptors (FPR), which are expressed by immune cells in the central nervous system. In this study, we investigated the influence of the FPR ligand Ac2-26 on the integrity of the BBB during pneumococcal meningitis. Wild-type (WT) and Fpr1- and Fpr2-deficient mice were intrathecally infected with Streptococcus pneumoniae. Subsequently, different groups of mice were treated with intraperitoneal injections of Ac2-26. The integrity of the BBB was analyzed using various markers through immunohistochemistry and immunofluorescence. The results showed reduced BBB integrity during the course of bacterial meningitis. Treatment with Ac2-26 in WT mice significantly prolonged the maintenance of BBB integrity. However, this effect was not observed in Fpr2-deficient mice. This study extends previous findings on the anti-inflammatory properties of Ac2-26 by demonstrating that Ac2-26 positively affects BBB integrity via FPR2 during pneumococcal meningitis. These findings suggest that further investigation of Ac2-26 and other FPR modulators as potential therapies for Streptococcus pneumoniae-induced meningitis is warranted.

Intracranial complications in adult patients with severe pneumococcal meningitis: a retrospective multicenter cohort study

BackgroundWe aimed to investigate the association of intracranial complications diagnosed on neuroimaging with neurological outcomes of adults with severe pneumococcal meningitis.MethodsWe performed a retrospective multicenter study on consecutive adults diagnosed with pneumococcal meningitis requiring at least 48 h of stay in the intensive care unit (ICU) and undergoing neuroimaging, between 2005 and 2021. All neuroimaging were reanalyzed to look for intracranial complications which were categorized as (1) ischemic lesion, (2) intracranial hemorrhage (3) abscess/empyema, (4) ventriculitis, (5) cerebral venous thrombosis, (6) hydrocephalus, (7) diffuse cerebral oedema. The primary outcome was unfavorable outcome at 90 days after ICU admission, defined by a modified Rankin Scale (mRS) score > 2.ResultsAmong the 237 patients included, intracranial complications were diagnosed in 68/220 patients (31%, 95%CI 0.25–0.37) who underwent neuroimaging at ICU admission and in 75/110 patients (68%, 95%CI 0.59–0.77) who underwent neuroimaging during ICU stay. At 90 days, 103 patients (44%, 95%CI 37–50) had unfavorable outcome, including 71 (30%) deaths. The most frequent intracranial complications were ischemic lesion (69/237 patients, 29%), diffuse cerebral oedema (43/237, 18%) and ventriculitis (36/237, 15%). Through multivariable analysis, we found that intracranial complications (adjusted odds ratio (aOR) 2.88, 95%CI 1.37–6.21) were associated with unfavorable outcome, along with chronic alcohol consumption (aOR 3.10, 95%CI 1.27–7.90), chronic vascular disease (aOR 4.41, 95%CI 1.58–13.63), focal neurological sign(s) (aOR 2.38, 95%CI 1.11–5.23), and cerebrospinal fluid leukocyte count < 1000 cell/microL (aOR 4.24, 95%CI 2.11–8.83). Competing risk analysis, with persistent disability (mRS score 3–5) as the primary risk and ICU-death as the competing risk, revealed that chronic alcohol consumption was the sole significant variable associated with persistent disability at 90 days (cause-specific hazard ratio 4.26, 95%CI 1.83–9.91), whereas the remaining variables were associated with mortality.ConclusionsIn adults with severe pneumococcal meninigitis, intracranial complications were independently associated with a higher risk of poor functional outcome, in the form of persistent disability or death. This study highlights the value of neuroimaging studies in this population, and provides relevant information for prognostication.

Lack of an association between spleen volume and risk of pneumococcal infection in cancer patients: a nested case-control study

BackgroundThe spleen is a key organ in preventing pneumococcal infection, especially in patients with immunocompromised condition such as those with cancer. Previous studies have shown that a small spleen volume in pneumococcal pneumonia patients is associated with severe disease course. However, it is unknown whether a small spleen increases risk of pneumococcal infection. We investigated the association between spleen volume and risk of pneumococcal infection.MethodsThis study was a retrospective cohort study using a nested case-control design and involved adult patients with malignancy who underwent chest and/or abdominal CT scans from January 1, 2008, to September 30, 2020, at a tertiary care center in Japan. Exclusion criteria comprised patients diagnosed with hepatic cirrhosis, leukemia, lymphoma, and/or post-splenectomy. From the cohort group that met all selection criteria (n = 22475), we identified all incident cases of pneumococcal infection (pneumococcal pneumonia and/or invasive pneumococcal diseases) and matched them with four controls by age, sex, and follow-up duration. Odds ratios (ORs) for the association between spleen volume and pneumococcal infection were estimated using conditional logistic regression models adjusted for body surface area, performance status, Charlson comorbidity index, and metastatic cancer.ResultsThe median spleen volume was 85.8 (interquartile range, 65.8–120.8) cm3. Over a median follow-up of 4.95 (interquartile range, 1.54–9.25) years, 60 patients were diagnosed with pneumococcal infection (20 with invasive pneumococcal disease and 40 with pneumonia without invasive pneumococcal disease) and matched with 240 controls. Spleen volume reduction (per 10 cm3) did not increase risk of pneumococcal infection in a crude analysis [OR 1.04 (95% CI 0.98–1.11)]. The outcome remained unchanged in the multivariable analysis (OR 1.01 [95% CI 0.95–1.08]).ConclusionsSmall spleen volume did not increase risk of pneumococcal infection in cancer patients.

The effectiveness of vaccination against pneumococcal infection in patients with severe bronchial asthma

The article discusses topical issues of the use of conjugated 13-valent pneumococcal vaccine Prevenar®13 (PCV13) in patients with severe bronchial asthma (SBA), including those receiving targeted therapy with genetically engineered biological drugs (GEBD). To study the effectiveness of vaccination against pneumococcal infection (PI) in patients with SBA. The study included 381 patients with SBA. The average age in the study groups was 45.5 (42.0; 52.5) years. All patients underwent clinical and instrumental studies, including spirography with bronchodilation test. After confirming the diagnosis of BA, the patients were divided into 2 observation groups. Group 1 (n=191) consisted of patients undergoing treatment with GEBD. Group 2 included patients with asthma receiving standard therapy, according to the 4th-5th stage according to the criteria of the Global Initiative for Asthma 2022 (Global Initiative for Asthma - GINA). The observation group consisted of 190 patients. In each group, there are subgroups of patients who have been vaccinated against PI and have not been vaccinated for various reasons. The following criteria were used as the main endpoints of observation for 12 months to assess the effectiveness: the number of pneumonia during the observation period, the number of exacerbations of asthma (severe, non-severe), the number of hospitalizations, the duration of exacerbations, the level of control according to the Asthma Control Questionnaire (ACQ5), functional indicators. The coverage of PI vaccination in patients with BA remains quite low, further organizational and methodological work is required to increase their involvement in vaccination. Immunization of PCV13 in patients with SBA at the 4th-5th stage of therapy reduces the risk of community-acquired pneumonia by at least 28.5%. PCV13 vaccination may be an additional effective tool for controlling the symptoms of SBA, including in patients undergoing treatment with GEBD. Vaccination allows to normalize the functional parameters of respiratory function in patients with SBA. PCV13 is well tolerated and does not cause any significant allergic reactions in patients with asthma. PCV13 vaccination is an effective tool for reducing the risk of community-acquired pneumonia in patients with severe bronchial asthma, including those on targeted therapy with genetically engineered biological drugs.

Orally Administered Lactobacilli Strains Modulate Alveolar Macrophages and Improve Protection Against Respiratory Superinfection.

Orally administered immunomodulatory lactobacilli can stimulate respiratory immunity and enhance the resistance to primary infections with bacterial and viral pathogens. However, the potential beneficial effects of immunomodulatory lactobacilli against respiratory superinfection have not been evaluated. In this work, we showed that the feeding of infant mice with Lacticaseibacillus rhamnosus CRL1505 or Lactiplantibacillus plantarum MPL16 strains can reduce susceptibility to the secondary pneumococcal infection produced after the activation of TLR3 in the respiratory tract or after infection with RVS. The treatment of mice with CRL1505 or MPL16 strains by the oral route improved the production of interferons in the respiratory tract, differentially modulated the balance of pro- and anti-inflammatory cytokines, reduced bacterial replication, and diminished lung damage. Additionally, we demonstrated that orally administered lactobacilli confer longstanding protection against secondary Streptococcus pneumoniae infection and that this effect would be mediated by the stimulation of trained alveolar macrophages. This work contributes to revealing the mechanisms involved in the modulation of the gut-lung axis by beneficial microbes by demonstrating that specific lactobacilli strains, through the stimulation of the common mucosal immune system, would be able to support the development of trained alveolar macrophages that would confer longstanding protection against secondary bacterial challenges produced after a primary inflammatory event in the respiratory mucosa.