Pneumococcal Infection Research Articles

Cerebral vasculitis as a complication of pneumococcal meningitis: A cohort study

ObjectiveCerebral vasculitis (CV) is a severe complication of pneumococcal meningitis (PM); whether dexamethasone use can reduce its occurrence remains to be determined. MethodsThis is a retrospective observational bicentric study analyzing all adults with proven PM hospitalized between January 2002 and December 2020 in two tertiary hospitals. Extrapolating from a standardized definition of primary angiitis of the central nervous system, we defined CV as worsened neurological symptoms associated with compatible imaging. All images were analyzed by a radiologist, and two neurologists reviewed all inconclusive cases of suspected CV for adjudication. Factors associated with CV were analyzed, including dexamethasone use. A subgroup analysis was limited to patients with a lumbar puncture at PM diagnosis. ResultsAmong 168 patients with PM, 49 (29.2%) had CV, occurring after a median of 8 days (IQR 5–13) of PM diagnosis. In multivariate analysis (N = 151), initial CRP was associated with CV (OR 1.28 per 50-unit increase, p = 0.003), which was marginally linked with delayed hospital admission more than 48 hours after first symptoms (OR 2.39, p = 0.06) and prior NSAID intake (OR 2.94, p = 0.05). Dexamethasone administration did not impact CV occurrence. In 133 patients having undergone lumbar puncture, CSF protein level > 4.4 g/L (OR 4.50, p = 0.006) was associated with CV. ConclusionsIn our cohort, CV was a frequent and severe complication of PM, often occurring in association with unduly delayed medical care, high CRP at admission, and high levels of protein in CSF.

Epidemiology of Streptococcus pneumoniae Serotypes in Jordan Amongst Children Younger than the Age of 5: A National Cross-Sectional Study.

Streptococcus pneumoniae infections are a major cause of mortality and morbidity worldwide. In Jordan, pneumococcal conjugate vaccines (PCVs) are not included in the national vaccination program. Due to the current availability of several PCVs, including PCV-10, PCV-13, and PCV-15, along with PCV-20, currently undergoing pediatric approvals globally, the decision to introduce PCVs and their selection should be based on valid local data on the common serotypes of Streptococcus pneumoniae. This cross-sectional study aimed to identify the frequency of serotypes of Streptococcus pneumoniae in children aged below 5 years hospitalized with invasive pneumococcal diseases (IPDs), including pneumonia, septicemia, and meningitis, during the study's duration in representative areas of Jordan. Serotyping for culture-positive cases was based on the capsular reaction test, known as the Quellung reaction. qPCR was conducted on the blood samples of patients with lobar pneumonia identified via X-ray or on cerebrospinal fluid for those with a positive latex agglutination test for Streptococcus pneumoniae. This study was based on the analysis of the serotypes of 1015 Streptococcus pneumoniae cases among children younger than the age of 5: 1006 cases with pneumonia, 6 cases with meningitis, and 3 cases with septicemia. Only 23 culture-positive cases were identified in comparison to 992 lobar pneumonia cases, which were PCR-positive but culture-negative, with a PCR positivity rate of 92%. Serotypes 6B, 6A, 14, and 19F were the most common serotypes identified in this study, with prevalence rates of 16.45%, 13.60%, 12.12%, and 8.18%, respectively. PCV-10, PCV-13, PCV-15, and PCV-20 coverage rates were 45.32%, 61.87%, 64.14%, and 68.47%, respectively. To the best of our knowledge, this is the largest prospective study from the Middle East and one of the largest studies worldwide showing the serotypes of Streptococcus pneumoniae. It reveals the urgency for the introduction of a PCV vaccination in Jordan, utilizing recently developed vaccines with a broader serotype coverage.

NLRP3 Activation Contributes to Memory Impairment in an Experimental Model of Pneumococcal Meningitis.

Bacterial meningitis is considered a life-threatening condition with high mortality rates. In response to the infection, signaling cascades, producing pro-inflammatory mediators trigger an exacerbated host immune response. Another inflammatory pathway occurs through the activation of inflammasomes. Studies highlight the role of the NLR family pyrin domain containing 3 (NLRP3) in central nervous system disorders commonly involved in neuroinflammation. We aimed to investigate the role of NLRP3 and its inhibitor MCC950 on neurochemical, immunological, and behavioral parameters in the early and late stages of experimental pneumococcal meningitis. For this, adult male Wistar rats received an intracisternal injection of Streptococcus pneumoniae or artificial cerebrospinal fluid as a placebo. The animals were divided into control/saline, control/MCC950, meningitis/saline, and meningitis/MCC950. Immediately after the meningitis induction, the animals received 140ng/kg MCC950 via intracisternal injection. For the acute protocol, 24h after induction, brain structures were collected to evaluate cytokines, NLRP3, and microglia. In the long-term group, the animals were submitted to open field and recognition of new objects tests at ten days after the meningitis induction. After the behavioral tests, the same markers were evaluated. The animals in the meningitis group at 24h showed increased levels of cytokines, NLRP3, and IBA-1 expression, and the use of the MCC950 significantly reduced those levels. Although free from infection, ten days after meningitis induction, the animals in the meningitis group had elevated cytokine levels and demonstrated behavioral deficits; however, the single dose of NLRP3 inhibitor rescued the behavior deficits and decreased the brain inflammatory profile.

Neuropeptide Calcitonin Gene-Related Peptide Promotes Immune Homeostasis of Bacterial Meningitis by Inducing Major Histocompatibility Complex Class II Ubiquitination.

Calcitonin gene-related peptide (CGRP), an immunomodulatory neuropeptide, is important for regulating pain transmission, vasodilation, and the inflammatory response. However, the molecular mechanisms of the CGRP-mediated immune response remain unknown. The effects of CGRP on bacterial meningitis (BM) and its underlying mechanisms were investigated in BM mice in vivo and macrophages in vitro. Peripheral injection of CGRP attenuated cytokine storms and protected mice from fatal pneumococcal meningitis, marked by increased bacterial clearance, improved neuroethology, and reduced mortality. When the underlying mechanisms were investigated, we found that CGRP induces proteasome-dependent degradation of major histocompatibility complex class II (MHC-II) in macrophages and then inhibits CD4+ T-cell activation. MARCH1 was identified as an E3 ligase that can be induced by CGRP engagement and promote K48-linked ubiquitination and degradation of MHC-II in macrophages. These results provide new insights into neuropeptide CGRP-mediated immune regulation mechanisms. We conclude that targeting the nervous system and manipulating neuroimmune communication is a promising strategy for treating intracranial infections like BM.

Comorbid infections in patients with spondyloarthritis: frequency, structure and risk factors

Objective: To investigate the frequency, structure, and risk factors of comorbid infections (CI) in patients with spondyloarthritis (SpA).Material and methods. The study included 332 patients with SpA. Patients were interviewed by the investigating physician, and additional information was obtained from medical records.Results and discussion. Respiratory tract (RT) and ear, nose, and throat (ENT) infections ranked first in the structure of CI. Exacerbation of SpA after CI was found in 42% of patients, and more severe CI against the background of SpA was found in 83 patients. 63 cases of severe CI (SCI) were documented, 63.5% of which were infections of the RT and ENT organs. Predictors for the development of lower RT (LRT) and ENT organ infections were the use of biologic disease-modifying antirheumatic drugs (bDMARDs) in general (odds ratio, OR 2.018; 95% confidence interval, CI 1.221-3.335; p=0.006 and OR 1.761; 95% CI 1.1-2.819, respectively; p=0.018) and tumor necrosis factor-α (TNF-α) inhibitors in particular (OR 2.376; 95% CI 1.417-3.983; p=0.001 and OR 1.833; 95% CI 1.123-2.994; p=0.015), and disease duration of more than 5 years (OR 1.774; 95% CI 1.034—3.042; p=0.037 and OR 2.22; 95% CI 1.378-3.576; p=0.001). The risk of developing LRT infection was higher in the presence of chronic lung disease (OR 3.673; 95% CI 1.602-8.425; p=0.002) and Charlesson Comorbidity Index ≥1 (OR 2.381; 95% CI 1.439-3.94; p=0.001), risk of developing ENT organ infections - with the use of >1 bDMARD (OR 2.4; 95% CI 1.199-4.804; p=0.013) and duration of methotrexate therapy over 5 years (OR 2.478; 95% CI 1.053-5.831; p=0.038). Risk factors for the development of SCI were the use of bDMARDs in general (OR 1.941; 95% CI 1.063-3.545; p=0.031) and TNFα in particular (OR 2.246; 95%, CI 1.218-4.139; p=0.01).Conclusion. The problem of CI in SpA is of great importance. The vast majority of patients with SpA should be vaccinated against pneumococcal infection and influenza.

The choline-binding proteins PspA, PspC, and LytA of Streptococcus pneumoniae and their interaction with human endothelial and red blood cells.

Streptococcus pneumoniae is a Gram-positive opportunistic pathogen that can colonize the upper respiratory tract. It is a leading cause of a wide range of infectious diseases, including community-acquired pneumonia and meningitis. Pneumococcal infections cause 1-2 million deaths per year, most of which occur in developing countries. Here, we focused on three choline-binding proteins (CBPs), i.e., PspC, PspA, and LytA. These pneumococcal proteins have different surface-exposed regions but share related choline-binding anchors. These surface-exposed pneumococcal proteins are in direct contact with host cells and have diverse functions. We explored the role of the three CBPs on adhesion and pathogenicity in a human host by performing relevant imaging and functional analyses, such as electron microscopy, confocal laser scanning microscopy, and functional quantitative assays, targeting biofilm formation and the hemolytic capacity of S. pneumoniae. In vitro biofilm formation assays and electron microscopy experiments were used to examine the ability of knockout mutant strains lacking the lytA, pspC, or pspA genes to adhere to surfaces. We found that LytA plays an important role in robust synthesis of the biofilm matrix. PspA and PspC appeared crucial for the hemolytic effects of S. pneumoniae on human red blood cells. Furthermore, all knockout mutants caused less damage to endothelial cells than wild-type bacteria, highlighting the significance of each CPB for the overall pathogenicity of S. pneumoniae. Hence, in addition to their structural function within the cell wall of S. pneumoniae, each of these three surface-exposed CBPs controls or mediates multiple steps during bacterial pathogenesis.

Chronic kidney disease in children: Vaccination – strategy, current recommendations and potentialities

The Immunization Schedule with additional vaccinations against certain infections is recognized as an effective strategy for preventing complications in children with Chronic Kidney Disease (CKD). The aim of this study is to highlight international experience regarding the immunization status of such patients in order to optimize the vaccinations process in Ukraine.
 The current Immunization Schedule for pediatric CKD, approved in international practice, is presented and has been compared to the national one. The approaches to the use of live and inactivated vaccines, to the immunization of persons on immunosuppressive therapy and the additional protective measures are clearly outlined. The international experience in the major vaccine-controlled disease prevention in children with CKD includes routine immunization (tuberculosis, hepatitis B, diphtheria, whooping cough, tetanus, poliomyelitis, measles, mumps, rubella, hemophilic infection), additional vaccination of immunocompromised hosts (influenza, pneumococcal infection, chicken pox) and in groups with risk factors (meningococcal, papillomavirus, rotavirus infections, hepatitis A, etc.) are summarized. It is emphasized that the optimal window of opportunity for vaccinations is the early stages of CKD or at least the pre-transplant time. The key principles of vaccine control prior and after kidney transplantation have been given.
 Increasing knowledge on protection from vaccine-controlled infections involved in children with CKD, including at the immunosuppressive therapy stage and kidney replacement therapy, makes implementation of current recommendations easier and advances the prevention strategy for this sensitive cohort. The process of harmonization of national recommendations on the vaccine status formation in this group of patients based on international experience and Ukrainian capabilities is proposed to initiate.

Trends in Pneumococcal and Bacterial Meningitis in Brazil from 2007 to 2019.

The pneumococcal conjugate vaccination (PCV) was introduced into the Brazilian Childhood National Immunization Program in 2010; however, universal pneumococcal vaccination for older adults has not been implemented yet. Our aim is to evaluate the trends in pneumococcal meningitis incidence and case fatality rate (CFR) across all age groups from 2007 to 2019 using data from the National Surveillance System. The pre-PCV (2007-2009) and post-PCV (2011-2019) periods were compared; changes in incidence and CFR were assessed by joinpoint regression. Additional analyses of bacterial meningitis were performed to compare the patterns and trends. Over the 13-year period, 81,203 and 13,837 cases were classified as bacterial and pneumococcal meningitis, respectively. S. pneumoniae was the main etiological agent of bacterial meningitis in adults aged ≥50 years and the most lethal in all age groups. In the post-PCV period, a 56.5% reduction in the average incidence was seen in pneumococcal meningitis in the pediatric population. In contrast, there was an increasing trend among adults. The CFR for pneumococcal and bacterial meningitis remained stable in most age groups during the study period. These findings highlight the value of expanding pneumococcal vaccination policies, including vaccines that provide better indirect protection from children to adults and broadening vaccination to older adults.

Impact of a clinical pharmacist’s intervention on pneumococcal vaccination in a population of at- risk hospitalized patients: The IP-VAC study

ObjectivesThe aim of this study was to evaluate the impact of clinical pharmacist intervention on compliance with pneumococcal vaccination (PV) recommendations in hospitalized patients. MethodsThis was a prospective, single-center, before-and-after study conducted in 2019–2020. Patients had to be over 18 years of age, at risk of pneumococcal infection, and with no PV. No changes were made in the observational phase. During the interventional phase, the clinical pharmacist discussed a prescription for preventive PV and a mention in the discharge letter. A pharmaceutical consultation sensitized the patient to the interest of PV. The clinical pharmacist ensured that a complete vaccination protocol would be carried out by the retail pharmacist within 3 months of hospitalization. ResultsOne hundred and sixty-seven (167) patients were included. In the observational phase, 2.3% of patients received a complete vaccination protocol after discharge from primary care. The rate increased to 63.8% after the clinical pharmacist’s intervention (p < 0.001). Vaccines were prescribed by hospital physicians in 97.5% of cases, while 40% of discharge letters included the indication for PV. ConclusionThe clinical pharmacist’s intervention led to delivery of a complete PV protocol after discharge for over half the patients. This study demonstrated the feasibility of a pharmaceutical intervention to promote PV in hospital activities.

Pneumococcal carriage, serotype distribution, and antimicrobial susceptibility in Papua New Guinean children vaccinated with PCV10 or PCV13 in a head-to-head trial

BackgroundChildren in Papua New Guinea (PNG) are at high risk of pneumococcal infections. We investigated pneumococcal carriage rates, serotype distribution, and antimicrobial susceptibility in PNG children after vaccination with 10-valent or 13-valent pneumococcal conjugate vaccines (PCV10; PCV13). MethodsInfants (N = 262) were randomized to receive 3 doses of PCV10 or PCV13 at 1-2-3 months of age, followed by pneumococcal polysaccharide vaccination (PPV) or no PPV at 9 months of age. Nasopharyngeal swabs (NPS) collected at ages 1, 4, 9, 10, 23 and 24 months were cultured using standard bacteriological procedures. Morphologically distinct Streptococcus pneumoniae colonies were serotyped by the Quellung reaction. Antimicrobial susceptibility was determined by Kirby-Bauer disc diffusion and minimum inhibitory concentration (MIC). ResultsS. pneumoniae was isolated from 883/1063 NPS collected at 1–23 months of age, including 820 serotypeable (64 different serotypes) and 144 non-serotypeable isolates. At age 23 months, 93.6% (95%CI 86.6–97.6%) of PCV10 recipients and 88.6% (95%CI 80.1–94.4%) of PCV13 recipients were pneumococcal carriers, with higher carriage of PCV10 serotypes by PCV10 recipients (19.8%, 95%CI 12.2–29.5) than PCV13 recipients (9.3%, 95%CI 4.1–17.3) (p = 0.049). There were no other statistically significant differences between PCV10 and PCV13 recipients and children receiving PPV or no PPV. Nearly half (45.6%) of carried pneumococci were non-susceptible to penicillin based on the meningitis breakpoint (MIC ≥ 0.12 µg/mL), but resistance was rare (1.1%) using the non-meningitis cut-off (MIC ≥ 8 µg/mL). Non-susceptibility to trimethoprim-sulfamethoxazole (SXT) was common: 23.2% of isolates showed intermediate resistance (MIC 1/19–2/38 µg/mL) and 16.9% full resistance (MIC ≥ 4/76 µg/mL). PCV serotypes 14 and 19A were commonly non-susceptible to both penicillin (14, 97%; 19A, 70%) and SXT (14, 97%; 19A, 87%). ConclusionEven after PCV10 or PCV13 vaccination, children living in a high-risk setting such as PNG continue to experience high levels of pneumococcal colonization, including carriage of highly antimicrobial-resistant PCV serotypes.The study is registered with ClinicalTrials.gov (CTN NCT01619462).

Systematic Literature Review of the Epidemiological Characteristics of Pneumococcal Disease Caused by the Additional Serotypes Covered by the 20-Valent Pneumococcal Conjugate Vaccine.

Higher valency pneumococcal conjugate vaccines (PCV15 and PCV20) have been developed to address the disease burden of current non-vaccine serotypes. This review describes the epidemiological characteristics of serotypes beyond PCV13 (serotypes 8, 10A, 11A, 12F, 15B/C, 22F, and 33F; PCV20nonPCV13 serotypes). Peer-reviewed studies published between 1 January 2010 (the year PCV13 became available) and 18 August 2020 were systematically reviewed (PROSPERO number: CRD42021212875). Data describing serotype-specific outcomes on disease proportions, incidence, severity, and antimicrobial non-susceptibility were summarized for individual and aggregate PCV20nonPCV13 serotypes by age group and by type and duration of pediatric PCV immunization program. Of 1168 studies, 127 (11%) were included in the analysis. PCV20nonPCV13 serotypes accounted for 28% of invasive pneumococcal disease (IPD), although the most frequent serotypes differed between children (10A, 15B/C) and adults (8, 12F, 22F). In children, serotype 15B/C tended to be more frequently associated with pneumococcal meningitis and acute otitis media; in adults, serotype 8 was more frequently associated with pneumonia and serotype 12F with meningitis. Serotypes 10A and 15B/C in children and 11A and 15B/C in adults were often associated with severe IPD. Serotype 15B/C was also among the most frequently identified penicillin/macrolide non-susceptible PCV20nonPCV13 serotypes. These results could inform decision making about higher valency PCV choice and use.

Serotype replacement and an increase in non-encapsulated isolates among community-acquired infections of Streptococcus pneumoniae during post-vaccine era in Japan

ObjectivesIt is feared that the serotype replacement of Streptococcus pneumoniae occurred by the introduction of pneumococcal vaccines as periodical inoculation leads to reduced efficacy of the approved vaccines and altered antimicrobial susceptibility. MethodsWe determined serotypes of 351 S. pneumoniae isolates collected at a commercial clinical laboratory in Hokkaido prefecture, Japan, from December 2018 to February 2019 by using the polymerase chain reaction procedure of the US Centers for Disease Control and Prevention. Antimicrobial susceptibility and resistance gene profiles were also examined. ResultsVaccine coverage rates were 7.9% for 13-valent conjugate vaccine, and 32.5% for 23-valent polysaccharide vaccine, respectively. Non-typable strains were 19.7%. cpsA-positive isolates (group I), and null capsule clade (NCC)1, NCC2 and NCC3 (group II) comprised 31.3%, 28.4%, 32.8%, and 7.5% of the 69 non-typable strains, respectively. No penicillin-resistant/intermediate isolates were found; however, serotypes 35B and 15A/F showed low susceptibility to β-lactams. Only five strains (1.4%) were levofloxacin-resistant, and all were from the older persons, and three strains were serotype 35B. ConclusionThe progression of serotype replacement in non-invasive pneumococcal infections has occurred during the post-vaccine era in Japan, and non-encapsulated isolates, such as NCC, have increased. Antimicrobial susceptibility is not worsened.

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

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

Antibody response to pneumococcal conjugate vaccine 10 among Nigerian children under 5 years.

Invasive pneumococcal diseases have been a major contributor to childhood mortality, particularly in the developing world and pneumococcal vaccines were introduced to reduce the burden. The Pneumococcal Conjugate Vaccine 10 (PCV 10) was incorporated into the Nigerian National Programme on Immunization (NPI) in 2014 to reduce the incidence of childhood pneumococcal infections. This study was done to determine the immunogenicity of the vaccine in our clime. This cross-sectional study was carried out between September 2019 and January 2020 at the Children Outpatient Clinic of the Federal Medical Center, Owerri, Nigeria. Two hundred and forty five children between the ages of 20 weeks and 59 months, who had received three doses of Pneumococcal Conjugate Vaccine 10 (PCV 10) at 6, 10 and 14 weeks according to the NPI schedule, were recruited into the study. The anti-pneumococcal PCV 10 IgG concentration was determined using Human Anti-Pneumococcal CPS 10 IgG vaccine ELISA Kit ®. Simple proportions, means and median (as appropriate) were used to analyse the data. Kruskal Wallis test and Spearman's correlation were done to test association. Significance was set as p< 0.05. The mean anti-pneumococcal IgG concentration was 11.01±1.23 IU/ml and all the study participants formed protective levels of anti-pneumococcal IgG. There was a slight positive correlation between antibody response and age (r=0.13, p=0.04), and the antibody response was slightly more in males than females. All the children under the age of five years who had received PCV 10 at 6, 10 and 14 weeks of age, who participated in this study formed protective levels of antibodies to the vaccine. Antibody levels increased slightly with age. The PCV 10 currently used in the Nigerian programme is sufficiently antigenic and a downward trend in pneumococcal diseases should soon be noticeable.

20‑Valent Pneumococcal Conjugate Vaccine: Pediatric First Approval.

20‑valent pneumococcal conjugate vaccine (PCV20; Prevnar 20®; Apexxnar®) is a pneumococcal conjugate vaccine (PCV) developed by Pfizer for active immunization for the prevention of pneumococcal infections. PCV20 has a similar structure and formulation to Pfizer's 13-valent PCV (PCV13; Prevnar 13®; Prevenar 13®), with the addition of polysaccharides to target seven further Streptococcus pneumoniae serotypes (8, 10A, 11A, 12F, 15B, 22F and 33F). PCV20 has been approved for active immunization for the prevention of pneumonia and invasive disease caused by S.pneumoniae in adults since June 2021 in the USA and since February 2022 in the EU. Following further evaluation of its safety, immunogenicity, and effectiveness in pediatric populations, in April 2023 PCV20 received its first pediatric approval, in the USA, for active immunization for the prevention of invasive pneumococcal disease (IPD) caused by S.pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, 23F, and 33F in individuals 6weeks to 17years of age and for the prevention of otitis media caused by S.pneumoniae serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F in individuals 6weeks to 5years of age. This article summarizes the milestones in the development of PCV20 leading to this first pediatric approval for active immunization for the prevention of IPD and otitis media caused by S.pneumoniae.

Duration of Protection From Pneumonia After Pneumococcal Vaccination in Hemodialysis Patients (DOPPIO): Protocol for a Prospective Multicenter Study.

Pneumonia is a leading cause of death in patients with end-stage chronic kidney disease treated with dialysis. Current vaccination schedules recommend pneumococcal vaccination. However, this schedule disregards findings of rapid titer decline in adult hemodialysis patients after 12 months. The primary objective is to compare pneumonia rates between recently vaccinated patients and patients vaccinated more than 2 years ago. As an exploratory objective, antipneumococcal antibody titers in hemodialysis patients will be determined as a function. Factors influencing antibody kinetics will be identified. Within this prospective multicenter study, we aim to compare 2 strata of vaccinated patients: those recently vaccinated and those vaccinated more than 2 years ago. A total of 792 patients will be enrolled. Twelve partner sites (within the German Centre for Infection Research [DZIF]) with allocated dialysis practices participate in this study. All dialysis patients who are vaccinated against pneumococcal infection in accordance with Robert Koch Institute guidelines prior to enrollment will be eligible. Data on baseline demographics, vaccination history, and underlying disease will be assessed. Pneumococcal antibody titers will be determined at baseline and every 3 months for 2 years. DZIF clinical trial units coordinate titer assessment schedules and actively follow-up on study patients for 2-5 years after enrollment, including validation of end points of hospitalization, pneumonia, and death. The study has enrolled 792 patients and the last follow-up has been completed. Currently, the statistical and laboratory analyses are ongoing. Results will increase physician adherence to current recommendations. Establishing a framework for the efficient evaluation of guideline recommendations through a combination of routine and study data will inform the evidence base for future guidelines. ClinicalTrials.gov NCT03350425; https://clinicaltrials.gov/ct2/show/NCT03350425. DERR1-10.2196/45712.

Impacts of the COVID-19 pandemic on immunization with pneumococcal vaccines in children and older adults in Brazil

The COVID-19 pandemic has profoundly impacted individuals, resulting in long-lasting consequences. One of the effects has been a decline in vaccine adherence attributed to physical distancing measures, potentially contributing to the resurgence of preventable diseases, and posing diagnostic challenges. Consequently, monitoring immunization rates becomes crucial as an indicator for health promotion campaigns and to mitigate the strain on healthcare systems. This study aims to assess the effects of the COVID-19 pandemic on immunization with pneumococcal vaccines in children and older adults in Brazil from 2018 to 2021. Data was collected from the Department of Informatics of the Unified Health System, focusing on the number of doses administered and vaccination coverage with pneumococcal vaccines across the country. A total of 21,780,450 doses were administered, with a decline of 19.97% in vaccine coverage throughout the evaluation period. An overall negative trend was observed in the time series analysis for all states in Brazil. However, not all showed a statistically significant change associated with the pandemic. Therefore, it is essential for states that experienced a decline in vaccination rates during the COVID-19 pandemic to closely monitor changes in pneumococcal vaccination. Failure in the process may lead to an increase in pneumococcal infections and place an additional burden on the healthcare system.

Levels of Fibrinogen Variants Are Altered in Severe COVID-19.

Background Fibrinogen variants as a result of alternative messenger RNA splicing or protein degradation can affect fibrin(ogen) functions. The levels of these variants might be altered during coronavirus disease 2019 (COVID-19), potentially affecting disease severity or the thrombosis risk. Aim To investigate the levels of fibrinogen variants in plasma of patients with COVID-19. Methods In this case-control study, we measured levels of functional fibrinogen using the Clauss assay. Enzyme-linked immunosorbent assays were used to measure antigen levels of total, intact (nondegraded Aα chain), extended Aα chain (α E ), and γ' fibrinogen in healthy controls, patients with pneumococcal infection in the intensive care unit (ICU), ward patients with COVID-19, and ICU patients with COVID-19 (with and without thrombosis, two time points). Results Healthy controls and ward patients with COVID-19 ( n = 10) showed similar fibrinogen (variant) levels. ICU patients with COVID-19 who later did ( n = 19) or did not develop thrombosis ( n = 18) and ICU patients with pneumococcal infection ( n = 6) had higher absolute levels of functional, total, intact, and α E fibrinogen than healthy controls ( n = 7). The relative α E fibrinogen levels were higher in ICU patients with COVID-19 than in healthy controls, while relative γ' fibrinogen levels were lower. After diagnosis of thrombosis, only the functional fibrinogen levels were higher in ICU patients with COVID-19 and thrombosis than in those without, while no differences were observed in the other fibrinogen variants. Conclusion Our results show that severe COVID-19 is associated with increased levels of α E fibrinogen and decreased relative levels of γ' fibrinogen, which may be a cause or consequence of severe disease, but this is not associated with the development of thrombosis.

Addition of daptomycin for the treatment of pneumococcal meningitis: protocol for the AddaMAP study

BackgroundThe leading cause of acute bacterial meningitis in adults is Streptococcus pneumoniae. This infection is associated with high rates of mortality and morbidity related, among other factors, to the excessive...

Regional Features of the Serotype Composition of Streptococcus pneumoniae isolated from Bacterial Carriers of Preschool Age in the Republic of Tatarstan

Relevance. Vaccination of the child population against pneumococcal infection (PI) has been carried out in the Republic of Tatarstan according to the national calendar of preventive vaccinations since 2014. The vaccination scheme includes vaccination with PCV-13 conjugated pneumococcal vaccine.Aim. Study of the the frequency of bacterial transmission and the serotype landscape of S. pneumoniae isolated from healthy children- bacterial carriers of preschool age in the Republic of Tatarstan (RT).Materials and methods. During the period from 2016 to 2022, 1,426 children from Kazan and the districts of the Republic of Tatarstan were examined. Examination of nasopharyngeal smears was carried out by the classical bacteriological method. Serotyping was performed using molecular genetic methods (PCR).Results. The detection rate of S. pneumoniae among healthy preschool children varied in different years from 29.5 to 63%, averaging 38.5%. In urban children, the incidence of pneumococcal transmission was significantly higher than in rural children (p&lt;0.01). Also, when analyzing the serotype landscape, mixed colonization by several serotypes was observed. As of January 1, 2021, the immune layer to the pathogen PI among preschool children was 81.7%. Monitoring of the serotype landscape of S.pneumoniae strains circulating in the RT showed the dominance of vaccine serotypes (67.2%), of which 44.4% are PCV13 serotypes. The proportion of non–vaccinated serotypes is 26%, untyped - 6.8%. Unvaccinated serotypes 35B (21.3%) and 23A (13.6%) dominated in vaccinated children, as well as serotypes not included in the PKV-13 vaccine cocktail, but included in the PPSV-23 polysaccharide vaccine not used for vaccination of children, namely 11AD (15.3%) 9LN (9.6%). In unvaccinated children, on the contrary, vaccine serotypes included in PCV-13 prevailed: 6ABCD (17.3%), 19F (20.9%), and unvaccinated serotypes 11AD, 9LN, 35B, 23A were detected with lower frequency 11,8%, 10,0%, 4,2%, 7,3% accordingly.Conclusion. Data on the regional features of the pneumococcal serotype landscape can be the basis for expanding the vaccine cocktail due to the dominant serotypes: 9LN,11 AD, 35B, 23A.