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Emerging Microbes & Infections Dec 2024This study aimed to provide data for the clinical features of invasive pneumococcal disease (IPD) and the molecular characteristics of isolates from paediatric patients...
This study aimed to provide data for the clinical features of invasive pneumococcal disease (IPD) and the molecular characteristics of isolates from paediatric patients in China. We conducted a multi-centre prospective study for IPD in 19 hospitals across China from January 2019 to December 2021. Data of demographic characteristics, risk factors for IPD, death, and disability was collected and analysed. Serotypes, antibiotic susceptibility, and multi-locus sequence typing (MLST) of pneumococcal isolates were also detected. A total of 478 IPD cases and 355 pneumococcal isolates were enrolled. Among the patients, 260 were male, and the median age was 35 months (interquartile range, 12-46 months). Septicaemia (37.7%), meningitis (32.4%), and pneumonia (27.8%) were common disease types, and 46 (9.6%) patients died from IPD. Thirty-four serotypes were detected, 19F (24.2%), 14 (17.7%), 23F (14.9%), 6B (10.4%) and 19A (9.6%) were common serotypes. Pneumococcal isolates were highly resistant to macrolides (98.3%), tetracycline (94.1%), and trimethoprim/sulfamethoxazole (70.7%). Non-sensitive rates of penicillin were 6.2% and 83.3% in non-meningitis and meningitis isolates. 19F-ST271, 19A-ST320 and 14-ST876 showed high resistance to antibiotics. This multi-centre study reports the clinical features of IPD and demonstrates serotype distribution and antibiotic resistance of pneumococcal isolates in Chinese children. There exists the potential to reduce IPD by improved uptake of pneumococcal vaccination, and continued surveillance is warranted.
Topics: Child, Preschool; Female; Humans; Infant; Male; Anti-Bacterial Agents; China; East Asian People; Hospitals; Microbial Sensitivity Tests; Multilocus Sequence Typing; Pneumococcal Infections; Prospective Studies; Risk Factors; Serogroup; Streptococcus pneumoniae
PubMed: 38646911
DOI: 10.1080/22221751.2024.2332670 -
BMC Infectious Diseases Apr 2024Lobar pneumonia caused by Mycoplasma pneumoniae is a relatively difficult-to-treat pneumonia in children. The time of radiographic resolution after treatment is...
BACKGROUND
Lobar pneumonia caused by Mycoplasma pneumoniae is a relatively difficult-to-treat pneumonia in children. The time of radiographic resolution after treatment is variable, a long recovery time can result in several negative effects, and it has attracted our attention. Therefore, exploring factors associated with delayed radiographic resolution will help to identify these children at an early stage and prepare for early intervention.
METHODS
The data of 339 children with lobar pneumonia caused by Mycoplasma pneumoniae were collected from the Department of Pediatrics of Fu Yang People's Hospital, China from January 2021 to June 2022. After discharge, the children were regularly followed up in the outpatient department and on the WeChat platform for > 8 weeks. According to whether pulmonary imaging (chest radiography or plain chest computed tomography) returned to normal within 8 weeks, the children were divided into the delayed recovery group (DRG) (n = 69) and the normal recovery group (NRG) (n = 270). The children's general information, laboratory examination findings, bronchoscopy results, and imaging findings were retrospectively analyzed. Single-factor analysis was performed to identify the risk factors for delayed radiographic resolution of lobar pneumonia caused by Mycoplasma pneumoniae, and the factors with statistically significant differences underwent multiple-factor logistic regression analysis. Receiver operating characteristic (ROC) analysis was then performed to calculate the cutoff value of early predictive indicators of delayed radiographic resolution.
RESULTS
Single-factor analysis showed that the following were significantly greater in the DRG than NRG: total fever duration, the hospitalization time, C-reactive protein (CRP) level, lactate dehydrogenase (LDH) level, D-dimer level, pulmonary lesions involving two or more lobes, a large amount of pleural effusion, the time to interventional bronchoscopy, and mucus plugs formation. Multivariate logistic regression analysis showed that the hospitalization time, CRP level, LDH level, pulmonary lesions involving two or more lobes, and a large amount of pleural effusion were independent risk factors for delayed radiographic resolution of lobar pneumonia caused by Mycoplasma pneumoniae. The cutoff values on the receiver operating characteristic curve were a hospitalization time of ≥ 10.5 days, CRP level of ≥ 25.92 mg/L, and LDH level of ≥ 378 U/L.
CONCLUSION
If patients with lobar pneumonia caused by Mycoplasma pneumoniae have a hospitalization time of ≥ 10.5 days, CRP level of ≥ 25.92 mg/L, and LDH level ≥ 378 U/L, the time of radiographic resolution is highly likely to exceed 8 weeks. Pediatricians must maintain a high level of vigilance for these factors, control the infection as early as possible, strengthen airway management, and follow up closely to avoid complications and sequelae of Mycoplasma pneumoniae pneumonia.
Topics: Child; Humans; Mycoplasma pneumoniae; Retrospective Studies; Pneumonia, Mycoplasma; Lung; Pneumonia, Pneumococcal; Pleural Effusion
PubMed: 38641804
DOI: 10.1186/s12879-024-09289-x -
Vaccine May 2024Vaccination against pneumococci is currently the most effective method of protection against pneumococcal infections. The aim of the study was to analyse changes in...
Effect of the PCV 10 vaccination on community-acquired pneumonia hospitalisations after four years of its introduction into the Polish National Immunisation Programme: Follow-up study.
BACKGROUND
Vaccination against pneumococci is currently the most effective method of protection against pneumococcal infections. The aim of the study was to analyse changes in hospitalisations and in-hospital deaths due to pneumonia before (2009-2016) and after (2017-2020) the introduction of PCV 10 vaccinations in the National Immunisation Programme in Poland.
METHODS
Data on hospitalisations related to community acquired pneumonia (CAP) in the years 2009-2020 were obtained from the Nationwide General Hospital Morbidity Study. Analyses were made in the age groups: <2, 2-3, 4-5, 6-19, 20-59, 60+ years in 2009-2016 and 2017-2020.
RESULTS
Overall, there were 1,503,105 CAP-related hospitalisations in 2009-2020, 0.7% of which were caused by Streptococcus pneumoniae infections. Children <2 years of age were the most frequently hospitalised for CAP per 100,000 population, followed by patients aged 2-3, 4-5 and 60+ years. In the years 2009-2016, the percentage of CAP hospital admissions increased significantly, and after the year 2017, it decreased significantly in each of the age groups (p<0.001). In the years 2009-2016, a significant increase in hospitalisations for Streptococcus pneumoniae infections was observed in the age groups <2, 2-3 and 4-5 years (p<0.05). A significant reduction in hospitalisations was observed in the age groups <2, 20-59 and 60+ in 2017-2020 (p<0.05). In the years 2009-2020, there were 84,367 in-hospital deaths due to CAP, 423 (0.5%) of which due to Streptococcus pneumoniae, with patients mainly aged 60+.
CONCLUSIONS
Implementation of the PCV vaccination programme has effectively decreased the incidence of CAP hospitalisations, including children <2 years of age. The group that is most at risk of death are persons aged 60+. The results of our study can be useful in evaluating the vaccine efficacy and benefits, and they can be an essential part of public health policy. Effective prevention strategies for CAP should be implemented in different age groups.
Topics: Humans; Pneumococcal Vaccines; Community-Acquired Infections; Hospitalization; Child, Preschool; Poland; Middle Aged; Adult; Male; Immunization Programs; Female; Infant; Young Adult; Child; Pneumonia, Pneumococcal; Adolescent; Aged; Vaccination; Follow-Up Studies; Streptococcus pneumoniae; Aged, 80 and over; Pneumococcal Infections
PubMed: 38641493
DOI: 10.1016/j.vaccine.2024.04.019 -
PloS One 2024While the 23-valent pneumococcal polysaccharide vaccine (PPV23) has demonstrated its role in preventing severe pneumococcal disease, its impact on more non-specific...
BACKGROUND
While the 23-valent pneumococcal polysaccharide vaccine (PPV23) has demonstrated its role in preventing severe pneumococcal disease, its impact on more non-specific conditions like acute respiratory tract infection (ARI) and lower respiratory tract infections (LRTI) remains unclear. We aimed to investigate the role of PPV23 in prevention of presentations for ARI and LRTI and related antibiotic prescriptions among older adults in primary care.
METHODS
Using a nationwide general practice dataset, we followed a cohort of regularly attending patients aged ≥65 years from 1 January 2014 until 31 December 2018 for presentations for ARI, LRTI, and related antibiotic prescriptions. Associations between PPV23 receipt and each outcome were assessed using a multiple failures survival model to estimate hazard ratios (HR) adjusted for age, sex, socioeconomic status, and various health measures.
RESULTS
A cohort of 75,264 patients aged ≥65 years (mean 75.4, 56% female) in 2014 was followed. The incidence of presentations for ARI, ARI-related antibiotic prescription, LRTI, and LRTI-related antibiotic prescription was 157.6, 76.0, 49.6, and 24.3 per 1000 person-years, respectively. Recent PPV23 vaccine receipt was associated with a small reduction in ARI presentations (adjusted HR vaccinated vs. unvaccinated 0.96; 95%CI 0.94-0.98; p = 0.002); however, there was no reduction in ARI-related antibiotic prescription, LRTI presentation, nor LRTI-related antibiotic prescription (adjusted HR were 0.99[95%CI 0.96-1.03], 1.04[95%CI 0.99-1.09], 1.07[95%CI 1.00-1.14]).
CONCLUSION
PPV23 vaccination in older adults may result in a small reduction in the incidence of total ARI presentations in primary care. However, the effect is small and residual confounding cannot be excluded.
Topics: Humans; Female; Aged; Male; Anti-Bacterial Agents; Respiratory Tract Infections; Streptococcus pneumoniae; Vaccination; Pneumococcal Vaccines; Primary Health Care; Pneumococcal Infections
PubMed: 38635814
DOI: 10.1371/journal.pone.0299924 -
IScience Apr 2024Bacterial meningitis, frequently caused by (pneumococcus), represents a substantial global health threat leading to long-term neurological disorders. This study focused...
Bacterial meningitis, frequently caused by (pneumococcus), represents a substantial global health threat leading to long-term neurological disorders. This study focused on the cholesterol-binding toxin pneumolysin (PLY) released by pneumococci, specifically examining clinical isolates from patients with meningitis and comparing them to the PLY-reference strain D39. Clinical isolates exhibit enhanced PLY release, likely due to a significantly higher expression of the autolysin LytA. Notably, the same single amino acid (aa) D380 substitution in the PLY D4 domain present in all clinical isolates significantly enhances cholesterol binding, pore-forming activity, and cytotoxicity toward SH-SY5Y-derived neuronal cells. Scanning electron microscopy of human neuronal cells and patch clamp electrophysiological recordings on mouse brain slices confirm the enhanced neurotoxicity of the PLY variant carrying the single aa substitution. This study highlights how a single aa modification enormously alters PLY cytotoxic potential, emphasizing the importance of PLY as a major cause of the neurological sequelae associated with pneumococcal meningitis.
PubMed: 38632998
DOI: 10.1016/j.isci.2024.109583 -
Infection and Immunity May 2024, a common colonizer of the upper respiratory tract, invades nasopharyngeal epithelial cells without causing disease in healthy participants of controlled human...
, a common colonizer of the upper respiratory tract, invades nasopharyngeal epithelial cells without causing disease in healthy participants of controlled human infection studies. We hypothesized that surface expression of pneumococcal lipoproteins, recognized by the innate immune receptor TLR2, mediates epithelial microinvasion. Mutation of in serotype 4 (TIGR4) and serotype 6B (BHN418) pneumococcal strains abolishes the ability of the mutants to activate TLR2 signaling. Loss of also led to the concomitant decrease in interferon signaling triggered by the bacterium. However, only BHN418 but not TIGR4 was significantly attenuated in epithelial adherence and microinvasion compared to their respective wild-type strains. To test the hypothesis that differential lipoprotein repertoires in TIGR4 and BHN418 lead to the intraspecies variation in epithelial microinvasion, we employed a motif-based genome analysis and identified an additional 525 a.a. lipoprotein (neumococcal ccessory ipoprotein ; ) encoded by BHN418 that is absent in TIGR4. The gene encoding sits within a putative genetic island present in ~10% of global pneumococcal isolates. While was enriched in the carriage and otitis media pneumococcal strains, neither mutation nor overexpression of the gene encoding this lipoprotein significantly changed microinvasion patterns. In conclusion, mutation of attenuates epithelial inflammatory responses during pneumococcal-epithelial interactions, with intraspecies variation in the effect on microinvasion. Differential lipoprotein repertoires encoded by the different strains do not explain these differences in microinvasion. Rather, we postulate that post-translational modifications of lipoproteins may account for the differences in microinvasion.IMPORTANCE (pneumococcus) is an important mucosal pathogen, estimated to cause over 500,000 deaths annually. Nasopharyngeal colonization is considered a necessary prerequisite for disease, yet many people are transiently and asymptomatically colonized by pneumococci without becoming unwell. It is therefore important to better understand how the colonization process is controlled at the epithelial surface. Controlled human infection studies revealed the presence of pneumococci within the epithelium of healthy volunteers (microinvasion). In this study, we focused on the regulation of epithelial microinvasion by pneumococcal lipoproteins. We found that pneumococcal lipoproteins induce epithelial inflammation but that differing lipoprotein repertoires do not significantly impact the magnitude of microinvasion. Targeting mucosal innate immunity and epithelial microinvasion alongside the induction of an adaptive immune response may be effective in preventing pneumococcal colonization and disease.
Topics: Streptococcus pneumoniae; Humans; Lipoproteins; Epithelial Cells; Pneumococcal Infections; Bacterial Proteins; Toll-Like Receptor 2; Nasopharynx; Mutation; Bacterial Adhesion
PubMed: 38629841
DOI: 10.1128/iai.00447-23 -
EClinicalMedicine May 2024The Sanofi/GSK AS03-adjuvanted (VidPrevtyn Beta) vaccine and the Pfizer-BioNTech mRNA (Comirnaty Original/Omicron BA.4-5) bivalent vaccine were offered to adults aged 75...
BACKGROUND
The Sanofi/GSK AS03-adjuvanted (VidPrevtyn Beta) vaccine and the Pfizer-BioNTech mRNA (Comirnaty Original/Omicron BA.4-5) bivalent vaccine were offered to adults aged 75 years and over in England from 3rd April 2023. This is the first time an adjuvanted COVID-19 vaccine has been administered as part of a UK COVID-19 vaccination programme. In clinical trials, antibody levels generated were comparable with mRNA vaccines but there are no real-world data on the effectiveness or duration of protection.
METHODS
We used a test-negative case-control study design to estimate the incremental vaccine effectiveness of the Sanofi/GSK and Pfizer bivalent BA.4-5 boosters against hospitalisation amongst those aged 75 years and older in England. Cases (those testing positive) and controls (those testing negative) were identified from the national COVID-19 PCR testing data undertaken in hospital settings. The study period included tests from 3rd April 2023 to 27th August 2023. Tests were linked to the COVID-19 vaccination register and to the national hospital admission database, restricting to those with an acute respiratory infection coded in the primary diagnosis field. Vaccine effectiveness was estimated using multivariable logistic regression amongst those who had last received an autumn 2022 booster given at least 3 months prior. The test result was the outcome and vaccination status the exposure. Analyses were adjusted for week of test, gender, age, clinical risk group status, care home resident status, region, index of multiple deprivation, ethnicity, influenza vaccination status and recent COVID-19 positivity.
FINDINGS
There were 14,169 eligible tests from hospitalised individuals aged 75 years and older; 3005 cases (positive tests) and 11,164 controls (negative tests). Effectiveness was highest in the period 9-13 days post vaccination for both manufacturers at about 50%; 43.7% (95% CI, 20.1-60.3%) and 56.1% (95% CI, 25.2-74.2%) for Sanofi/GSK and Pfizer BA.4-5, respectively. There was evidence of waning with a reduction to about 30% for both manufacturers after 5-9 weeks. The longest time interval post vaccination for which we were able to estimate effectiveness was 10+ weeks post vaccination, at which point vaccine effectiveness was 17.6% (95% CI, -3.6 to 34.5%) and 37.9% (95% CI, 13.2-55.5%) for the Sanofi/GSK and Pfizer BA.4-5 boosters, respectively.
INTERPRETATION
Both boosters provided good protection against hospitalisation amongst older adults. The finding that the adjuvanted vaccine targeting the distant Beta strain had similar effectiveness to the bivalent mRNA vaccine targeting more closely matched Omicron sub-lineages is notable and highlights the need for further real-world studies into the effectiveness of vaccines from different vaccine platforms and formulations in the presence of matched and unmatched strains.
FUNDING
No external funding.
PubMed: 38618208
DOI: 10.1016/j.eclinm.2024.102587 -
Vaccine May 2024To assess the health and economic outcomes of a PCV13 or PCV15 age-based (65 years-and-above) vaccination program in Switzerland.
OBJECTIVE
To assess the health and economic outcomes of a PCV13 or PCV15 age-based (65 years-and-above) vaccination program in Switzerland.
INTERVENTIONS
The three vaccination strategies examined were:Target population: All adults aged 65 years-and-above. Perspective(s): Switzerland health care payer.
TIME HORIZON
35 years. Discount rate: 3.0%. Costing year: 2023 Swiss Francs (CHF).
STUDY DESIGN
A static Markov state-transition model.
DATA SOURCES
Published literature and publicly available databases or reports.
OUTCOME MEASURES
Pneumococcal diseases (PD) i.e., invasive pneumococcal diseases (IPD) and non-bacteremic pneumococcal pneumonia (NBPP); total quality-adjusted life-years (QALYs), total costs and incremental cost-effectiveness ratios (CHF/QALY gained).
RESULTS
Using an assumed coverage of 60%, the PCV15 strategy prevented a substantially higher number of cases/deaths than the PCV13 strategy when compared to the No vaccination strategy (1,078 IPD; 21,155 NBPP; 493 deaths). The overall total QALYs were 10,364,620 (PCV15), 10,364,070 (PCV13), and 10,362,490 (no vaccination). The associated overall total costs were CHF 741,949,814 (PCV15), CHF 756,051,954 (PCV13) and CHF 698,329,579 (no vaccination). Thus, the PCV13 strategy was strongly dominated by the PCV15 strategy. The ICER of the PCV15 strategy (vs. no vaccination) was CHF 20,479/QALY gained. In two scenario analyses where the vaccine effectiveness for serotype 3 were reduced (75% to 39.3% for IPD; 45% to 23.6% for NBPP) and NBPP incidence was increased (from 1,346 to 1,636/100,000), the resulting ICERs were CHF 29,432 and CHF 13,700/QALY gained, respectively. The deterministic and probabilistic sensitivity analyses demonstrated the robustness of the qualitative results-the estimated ICERs for the PCV15 strategy (vs. No vaccination) were all below CHF 30,000/QALYs gained.
CONCLUSIONS
These results demonstrate that using PCV15 among adults aged 65 years-and-above can prevent a substantial number of PD cases and deaths while remaining cost-effective over a range of inputs and scenarios.
Topics: Humans; Switzerland; Pneumococcal Vaccines; Aged; Cost-Benefit Analysis; Quality-Adjusted Life Years; Pneumococcal Infections; Aged, 80 and over; Immunization Programs; Male; Female; Vaccination; Markov Chains; Streptococcus pneumoniae; Vaccines, Conjugate; Pneumonia, Pneumococcal
PubMed: 38609806
DOI: 10.1016/j.vaccine.2024.04.016 -
The Journal of Biological Chemistry May 2024The major human pathogen Streptococcus pneumoniae encounters the immune-derived oxidant hypothiocyanous acid (HOSCN) at sites of colonization and infection. We recently...
The major human pathogen Streptococcus pneumoniae encounters the immune-derived oxidant hypothiocyanous acid (HOSCN) at sites of colonization and infection. We recently identified the pneumococcal hypothiocyanous acid reductase (Har), a member of the flavoprotein disulfide reductase enzyme family, and showed that it contributes to the HOSCN tolerance of S. pneumoniae in vitro. Here, we demonstrate in mouse models of pneumococcal infection that Har is critical for colonization and invasion. In a colonization model, bacterial load was attenuated dramatically in the nasopharynx when har was deleted in S. pneumoniae. The Δhar strain was also less virulent compared to wild type in an invasion model as reflected by a significant reduction in bacteria in the lungs and no dissemination to the blood and brain. Kinetic measurements with recombinant Har demonstrated that this enzyme reduced HOSCN with near diffusion-limited catalytic efficiency, using either NADH (k/K = 1.2 × 10 Ms) or NADPH (k/K = 2.5 × 10 Ms) as electron donors. We determined the X-ray crystal structure of Har in complex with the FAD cofactor to 1.50 Å resolution, highlighting the active site architecture characteristic for this class of enzymes. Collectively, our results demonstrate that pneumococcal Har is a highly efficient HOSCN reductase, enabling survival against oxidative host immune defenses. In addition, we provide structural insights that may aid the design of Har inhibitors.
Topics: Streptococcus pneumoniae; Animals; Mice; Pneumococcal Infections; Bacterial Proteins; Crystallography, X-Ray; Humans; Female; Oxidoreductases Acting on CH-CH Group Donors; Thiocyanates
PubMed: 38604564
DOI: 10.1016/j.jbc.2024.107282 -
Asian Journal of Surgery Jul 2024
Successful treatment of penicillin-resistant pneumococcal meningitis following ventriculo-peritoneal shunt for congenital hydrocephalus: A case report on the efficacy of linezolid.
Topics: Humans; Linezolid; Ventriculoperitoneal Shunt; Hydrocephalus; Meningitis, Pneumococcal; Penicillin Resistance; Male; Postoperative Complications; Anti-Bacterial Agents; Female; Treatment Outcome
PubMed: 38599973
DOI: 10.1016/j.asjsur.2024.04.007