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Background: Streptococcus pneumoniae is the most frequent causative pathogen of bacterial pneumonia in children worldwide. Bangladesh introduced the 10-valent pneumococcal conjugate vaccine (PCV10) in their national immunization program for infants in 2015. We assessed its potential coverage in under-fives with community-acquired pneumonia (CAP) in the years before PCV10 was introduced. Methods: A total of 1502 childhood pneumonia cases (< 5 year olds living in the urban section Kamalapur, Dhaka) were enrolled between 2011 and 2013. Acute phase and late (convalescent) serum samples were collected from 1380 cases. Serotype-specific pneumococcal antibody concentrations were measured using a 25-plex immunoassay panel. Pneumococcal CAP was diagnosed based on a serotype-specific pneumococcal antibody response. Results: S. pneumoniae was serologically identified as causative pathogen in 406/1380 (29%) cases. The five most prevalent serotypes were (in descending order) 11A, 22F, 3, 2 and 19F. Based on the percentage of pneumonia cases associated with PCV10 vaccine types, the potential PCV10 coverage was 29% (116/406). Conclusions: In almost a third of the studied cases S. pneumoniae was identified as a causative pathogen. Because of the characteristics of the immunoassay, this might well be a gross underestimation. Nevertheless, the potential PCV10-coverage was low. Given the high serotype diversity, the region might benefit greatly from a higher-coverage PCV or recombinant protein vaccine. [ABSTRACT FROM AUTHOR]

Streptococcus pneumoniae (S. pneumoniae) is a major cause of community-acquired pneumonia. Current standard clinical therapies mainly focus on combating S. pneumoniae through antibiotics. However, the limited delivery of antibiotics and the undetoxified hydrogen peroxide (H 2 O 2) virulence factor secreted by S. pneumoniae impede the therapeutic outcomes. Here we report an inhalable catalase (CAT)-tannic acid (TA) nanoassembly for local antibiotic (levofloxacin) delivery and simultaneously neutralizing the secreted H 2 O 2 virulence factors to treat pneumococcal pneumonia. After aerosol inhalation, the inhalable formulation (denoted as CT@LVX) effectively accumulates in lung tissues through TA-mediated mucoadhesion. CAT can reduce alveolar epithelial cells apoptosis by catalyzing the decomposition of accumulated H 2 O 2 in the infected lung tissues. In synergy with antibiotic LVX-mediated S. pneumoniae elimination, CT@LVX significantly decreases lung injury companied with reduced inflammatory, resulting in 100 % survival of mice with pneumonia. In a clinically isolated S. pneumoniae strain-induced pneumonia mouse model, CT@LVX also shows superior outcomes compared to the traditional antibiotic treatment, highlighting its potential clinical application prospects. An inhalable LVX-loaded CAT-tannic acid (TA) nanoassembly (denoted as CT@LVX) was designed for the treatment of pneumococcal pneumonia, aiming neutralizing H 2 O 2 virulence factors and effectively delivering antibiotics. This nanoassembly has demonstrated strong tissue retention and protection capabilities, showing significant therapeutic potential in both standard and clinically isolated Streptococcus pneumoniae -induced pneumonia mouse models. [Display omitted] • An inhalable levofloxacin (LVX)-loaded catalase (CAT)-tannic acid (TA) nanoassembly (denoted as CT@LVX) was developed. • The inhalable CT@LVX formulation effectively accumulates in lung tissues via TA-mediated mucoadhesion. • CAT efficiently catalyzes H 2 O 2 secreted by Streptococcus pneumoniae , reducing alveolar epithelial cell apoptosis. • Combination of CAT neutralizing H 2 O 2 and LVX eliminating bacteria offers a promising treatment for pneumococcal pneumonia. [ABSTRACT FROM AUTHOR]

Streptococcus pneumoniae is an important cause of community-acquired pneumonia (CAP) in Japan. Here, we report the serotype distribution and antimicrobial susceptibility of cultured pneumococcal isolates from Japanese adults aged ≥18 years with CAP. This was a prospective, population-based, active surveillance study conducted in Goto City, Japan from December 2015 to November 2020. Pneumococcal isolates from sterile sites (blood and pleural fluid) and non-sterile sites (sputum and bronchoalveolar lavage) were cultured as part of the standard of care. S. pneumoniae were serotyped using the Quellung reaction. Antimicrobial susceptibility was tested using microdilution and interpreted according to the Clinical and Laboratory Standards Institute criteria. Isolates resistant to erythromycin were phenotyped using the triple-risk test and genotyped by polymerase chain reaction. A total of 156 pneumococcal isolates were collected (138 from sputum, 15 from blood, and 3 from bronchoalveolar lavage) from 1992 patients. Of these, 142 were non-duplicate isolates from unique patients and were included in the analyses. Serotypes contained within the 13-valent pneumococcal conjugate vaccine (PCV13) (including 6C), PCV15 (including 6C), and PCV20 (including 6C and 15C) were detected in 39 (27%), 45 (32%), and 80 (56%) of 142 isolates, respectively. The most common serotypes were 35B (12%), 11A (11%), and 3 (11%). Multidrug resistance (MDR) was detected in 96/142 (68%) isolates. Of the 96 MDR isolates, 31, 32, and 59% were PCV13, PCV15, and PCV20 serotypes, respectively; the most common MDR serotypes were 35B (16%), 6C, 10A, and 15A (9% each), and 3 and 11A (8% each). A total of 119 isolates were resistant to macrolides; 41 (35%) had an M phenotype, 53 (45%) had an iMcLS phenotype, and 25 (21%) had a cMLS phenotype. In conclusion, pneumococcal serotypes 35B, 11A and 3 were most frequently associated with pneumonia and antimicrobial resistance was common among pneumococcal isolates from adults with CAP in Goto City, Japan. Implementing higher-valency PCVs May help reduce vaccine-type CAP among Japanese adults. [ABSTRACT FROM AUTHOR]

Background: Community-acquired pneumonia (CAP) is associated with high morbidity and hospitalization rate. In infectious diseases, host genetics plays a critical role in susceptibility and immune response, and the immune pathways involved are highly dependent on the microorganism and its route of infection. Here we aimed to identify genetic risk loci for CAP using a case-control genome-wide association study (GWAS). Methods: We performed a GWAS on 3,765 Spanish individuals, including 257 adult patients hospitalized with CAP and 3,508 population controls. Pneumococcal CAP was documented in 30% of patients; the remaining 70% were selected among patients with unidentified microbiological etiology. We tested 7,6 million imputed genotypes using logistic regressions. UK Biobank GWAS of bacterial pneumonia were used for results validation. Subsequently, we prioritized genes and likely causal variants based on Bayesian fine mapping and functional evidence. Imputation and association of classical HLA alleles and amino acids were also conducted. Results: Six independent sentinel variants reached the genome-wide significance (p < 5 × 10-8), three on chromosome 6p21.32, and one for each of the chromosomes 4q28.2, 11p12, and 20q11.22. Only one variant at 6p21.32 was validated in independent GWAS of bacterial and pneumococcal pneumonia. Our analyses prioritized C4orf33 on 4q28.2, TAPBP on 6p21.32, and ZNF341 on 20q11.22. Interestingly, genetic defects of TAPBP and ZNF341 are previously known inborn errors of immunity predisposing to bacterial pneumonia, including pneumococcus and Haemophilus influenzae. Associations were all non-significant for the classical HLA alleles. Conclusions: We completed a GWAS of CAP and identified four novel risk loci involved in CAP susceptibility. [ABSTRACT FROM AUTHOR]

Background: The 13-valent pneumococcal conjugate vaccine (PCV-13) was introduced in Malawi in 2011 with an expected impact of reducing pneumococcal pneumonia in children. We aimed to describe clinical characteristics and nasopharyngeal (NP) carriage of pneumococcus by serotype in children hospitalized with primary end-point pneumonia (PEP) between 2013 and 19 after the introduction of PCV-13. Methods: We conducted a secondary analysis of children aged under-5-years hospitalized with acute respiratory illness (ARI) in Malawi. Chest radiographs conducted at admission were read by two independent clinicians according to WHO criteria for PEP, and a third reviewer resolved discordant diagnoses. NP swab specimens were processed and Streptococcus pneumoniae growth was serotyped. Multivariable regression analysis was conducted to assess the association between clinical characteristics, NP serotypes, and PEP. Results: We had complete radiographic and NP serotype data for 500 children, of which 54 isolates were vaccine-type (VT) (10.8%), 165 were non-VT (NVT; 33.0%), and 281 had no pneumococcal growth (56.2%). Among these, 176 (35.2%) had PEP on chest x-ray. Among those with PEP, pneumococcal carriage was documented in 43.8% of cases, and VT serotypes accounted for 10.8%. For children with PEP, we found no association between clinical characteristics and carrying either VT, NVT, or no pneumococcus. Conclusion: Carriage of S. pneumoniae remains high among children hospitalized with ARI in Malawi, but children with VT carriage were no more likely to have PEP than children carrying no pneumococcus or those with NVT carriage. There were no differences in clinical characteristics between those carrying VT, NVT, or no pneumococcus. [ABSTRACT FROM AUTHOR]

Background: Vaccine‐preventable respiratory infections impact on healthcare systems globally. Despite availability of vaccines, fluctuations in vaccination rates, pathogen virulence and community transmission dynamics mean that these respiratory infections continue to pose substantial public health risks. To understand trends in vaccine‐preventable respiratory infections, we analysed linked data from emergency department (ED), hospitalisations and deaths in New South Wales, Australia, from 2012 to 2022. Methods: ED presentations with respiratory infection like illness were linked to hospitalisation and death records. Age‐standardised rates of ED presentations, proportions subsequently hospitalised for acute respiratory infection (ARI) and specific vaccine‐preventable disease diagnoses and 28‐day mortality rates were estimated by year and age. Results: From 2012 to 2022, there were 3,127,090 ARI‐like ED presentations. Age‐standardised rates increased until 2020, declined in 2021 and rebounded in 2022. Across all years, of these ARI‐like ED presentations, 16.6% were hospitalised for acute respiratory infections, including pneumonia (7.9%), influenza (1.1%), RSV disease (1.3%), COVID‐19 (0.8%) and pneumococcal disease (0.3%). Proportions hospitalised were highest in those aged 65+ years, except for RSV, which was highest in children aged 0–4 years. The highest 28‐day mortality post‐ARI‐like ED presentation was observed with COVID‐19 in adults aged 65+ years at 13.1%. Conclusions: This study highlights the continuing burden of vaccine‐preventable respiratory infections on an Australian healthcare system. These data can be used to monitor the effectiveness of vaccination programmes and other public health interventions. Future efforts should focus on enhancing surveillance and data linkage to improve precision and guide targeted public health strategies. [ABSTRACT FROM AUTHOR]

Background: In both the elderly and children, pneumonia remains one of the leading causes of hospitalization. This study aimed to assess the impact of pneumonia-related hospitalizations in the population over 65 years of age in the Veneto Region. Methods: This retrospective study analyzed hospital discharge records for patients aged 65 and older who resided in the Veneto Region and had a diagnosis of pneumonia from 2007 to 2023. The hospitalizations were identified using specific ICD-9-CM codes for pneumonia as a discharge diagnosis. Hospitalization rates, mortality rates, the prevalence of complications and comorbidities, the length of stay, and associated costs were calculated by age and year. Results: From 2007 to 2023, there were 139,201 hospitalizations for pneumonia. Emergency admissions accounted for 92.1% of these cases, and only 2.0% had a specific diagnosis of pneumococcal pneumonia. The median length of stay was 10 days, and the median diagnosis-related group (DRG) tariff per hospitalization was EUR 3307. Excluding the pandemic years, the hospitalization rates remained stable at approximately 850 cases per 100,000 inhabitants before 2019. After 2022, the rates started to increase again. Overall, in the investigated period, the results showed a negative trend (average Annual Percentage Change (AAPC) of −1.931, p < 0.0001). However, when only considering the pre-pandemic years, the trend was stable, while a decline was observed starting in 2020 (AAPC of −19.697, p = 0.001). The overall discharge mortality rates ranged from 13% to 19.3% but were significantly higher in those over 85 years of age (20.6% compared with 6.5% and 12.0% in the 65–74 and 75–84 age groups, respectively). Conclusions: This study highlights the substantial burden of pneumonia in individuals over 65 years of age, showing the impacts on public health. [ABSTRACT FROM AUTHOR]

Determining pneumococcal pneumonia (PP) burden in the elderly population is challenging due to limited data on invasive PP (IPP) and, in particular, noninvasive PP (NIPP) incidence. Using retrospective cohorts of adults aged ≥50 years in Denmark (2 782 303) and the Valencia region, Spain (2 283 344), we found higher IPP hospitalization rates in Denmark than Valencia (18.3 vs 9/100 000 person-years [PY], respectively). Conversely, NIPP hospitalization rates were higher in Valencia (48.2 vs 7.2/100 000 PY). IPP and NIPP rates increased with age and comorbidities in both regions, with variations by sex and case characteristics (eg, complications, mortality). The burden of PP in adults is substantial, yet its true magnitude remains elusive. Discrepancies in clinical practices impede international comparisons; for instance, Valencia employed a higher frequency of urinary antigen tests compared to Denmark. Additionally, coding practices and prehospital antibiotic utilization may further influence these variations. These findings could guide policymakers and enhance the understanding of international disparities in disease burden assessments. [ABSTRACT FROM AUTHOR]

Pneumococcal pneumonia is a significant cause of illness and death globally, particularly among young children and the elderly. The cpsB gene is involved in the biosynthesis of the capsule polysaccharide, and polymorphisms in the cpsB gene are the basis for sequetyping, a molecular biology-based approach to serotyping. In this study, we attempted the sequetyping of pneumococci directly from clinical sputum specimens collected from adult patients diagnosed with community-acquired pneumonia (CAP). We performed conventional PCR for the cpsB gene, followed by TA cloning and Sanger sequencing of the amplicon. The results showed the status of clonality of pneumococci in each specimen. We also performed real-time PCR targeting pneumococci for each specimen. It revealed a significant association between the Ct value of the real-time PCR and the clonality status of pneumococci among the specimens (p-value 0.0007 by Fisher's exact test analysis). Specifically, when the Ct value was below 22, there was a high probability that pneumococcus existed as a single clone. Thus, this study demonstrates the possible correlation between pneumococcal clonality and bacterial load in clinical specimens, which might indicate the infection status. [ABSTRACT FROM AUTHOR]

Background: This study aimed to establish a method for the rapid detection of highly virulent Klebsiella pneumoniae (hvKP) by using multienzyme isothermal rapid amplification (MIRA) technology. The laboratory can quickly, accurately, and conveniently diagnose highly virulent Klebsiella pneumoniae infection. Methods: For this study, 7 laboratory standard strains and 184 clinical isolates (including 70 strains of Klebsiella pneumoniae) were collected and screened for highly virulent Klebsiella pneumoniae based on its colony morphology, wire drawing test, and next-generation sequencing (NGS) results. Based on the nucleic acid sequence of the peg344 gene of highly virulent Klebsiella pneumoniae on GenBank (no. AP006726.1), specific conserved regions were selected to design MIRA and real-time fluorescence quantitative PCR (qPCR) specific primers and probes. The MIRA and qPCR methods were used to detect the tested strain, and the specificity, sensitivity, and clinical performance of the MIRA method for detecting hvKP were evaluated. Results: In total, 21 cases of hvKP were screened from clinical isolates. The MIRA detection method utilizes specific primers and probes to transmit significant fluorescence signals at 39°C, and the detection process takes 30 minutes. The specificity test results showed that only hvKP had a specific amplification curve, while the rest of nonhighly virulent Klebsiella pneumoniae (non-hvKP) had no specific amplification curve. The sensitivity test results showed that the sensitivity of MIRA for detecting hvKP is 7 × 10² CFU/mL, which is consistent with the sensitivity of the real-time fluorescence qPCR method. A simultaneous detection of 184 clinical isolates was accomplished by using MIRA and qPCR methods. Twenty-one strains of hvKP have specific amplification curves, while the remaining 163 strains of non-hvKP have no specific amplification curves. The accuracy of both methods for detecting hvKP is 100%. Conclusions: The established multienzyme isothermal rapid amplification (MIRA) has the following characteristics: a short detection time, high sensitivity, and a strong specificity, and it can be used as a powerful tool for an early diagnosis and epidemiological monitoring of hvKp. [ABSTRACT FROM AUTHOR]

Abstract Background S. pneumoniae (SPN) is the most common cause of pneumonia. The disease can be effectively prevented through immunisation. Since December 2020, the Malaysian Government has included the 10-valent pneumococcal conjugate vaccine (PCV10) for all infants born on or after 1 January 2020 as part of the National Immunisation Programme (NIP). However, the epidemiology of pneumonia remains poorly understood. To fill the knowledge gap, we established a multicentre surveillance study to understand the burden of pneumococcal pneumonia among young children in Peninsular Malaysia. Methods MY-Pneumo is a multicentre prospective case–control study conducted in three sentinel sites located in three different states of Peninsular Malaysia – Kuala Lumpur, Pahang, and Kelantan. A cohort of at least 500 incident cases and 500 controls is enrolled beginning in October 2021 and matched for age. Cases are hospitalised children

Background: S. pneumoniae (SPN) is the most common cause of pneumonia. The disease can be effectively prevented through immunisation. Since December 2020, the Malaysian Government has included the 10-valent pneumococcal conjugate vaccine (PCV10) for all infants born on or after 1 January 2020 as part of the National Immunisation Programme (NIP). However, the epidemiology of pneumonia remains poorly understood. To fill the knowledge gap, we established a multicentre surveillance study to understand the burden of pneumococcal pneumonia among young children in Peninsular Malaysia. Methods: MY-Pneumo is a multicentre prospective case–control study conducted in three sentinel sites located in three different states of Peninsular Malaysia – Kuala Lumpur, Pahang, and Kelantan. A cohort of at least 500 incident cases and 500 controls is enrolled beginning in October 2021 and matched for age. Cases are hospitalised children < 5 years with radiologically confirmed pneumonia, and the controls are children without any features suggestive of pneumonia. Clinical samples, including nasopharyngeal swabs (NPS) and urine, are collected according to the study protocol. Biological fluids such as blood, cerebrospinal fluid (CSF) and pleural fluid are obtained from invasive pneumonia disease (IPD) patients, if available. All children are tested for SPN using polymerase chain reaction (PCR) and pneumococcal urine antigen test (PUAT) using BinaxNow. Discussion: Surveillance data, including carriage rate, serotype variations and the phylogeny data structure of SPN among young children in Malaysia during PCV implementation, will be generated from this study. Trends and patterns of pneumococcal serotypes by different regions are important for targeted public health strategies. Our data will provide baseline information for estimating the impact of PCV10 implementation and will influence policymakers' decisions regarding the upgrade from PCV10 to a higher-valency conjugate vaccine in Malaysia. Trial registration: This project was registered at ClinicalTrials.gov (NCT04923035) on 2021, June 11. The study protocol was approved by the International Medical University Joint-Committee on Research & Ethics (4.15/JCM-216/2021) and the Institutional Review Board at sentinel sites (USM/JEPeM/21020190, IREC 2021–114, MREC ID No: 2021128–9769) and University of Southampton's Ethics and Research Governance (ERGo II 64844). [ABSTRACT FROM AUTHOR]

Aims: To collect all available evidence on the effect of diabetes mellitus (DM) as a risk factor for pneumococcal disease incidence and related complications, and on the efficacy/effectiveness of vaccines in patients with DM. Methods: Two distinct systematic searches on MEDLINE, Cochrane, ClinicalTrials.gov and EMBASE databases were performed, one for each meta-analysis, collecting all observational (cohort and case–control) studies and randomized clinical trials performed on humans up to June 1st, 2023. Results: We retrieved 36 observational studies comparing risk for pneumococcal disease and related complications in people with or without DM, and 11 studies (1 randomized clinical trial and 10 observational studies) assessing conjugated and polysaccaridic vaccines efficacy/effectiveness on preventing such outcomes. People with DM were at higher risk for Invasive Pneumococcal Disease (unadjusted OR 2.42 [2.00; 2.92]); Case-Fatality Rate (unadjusted OR 1.61 [1.25; 2.07], Pneumococcal pneumonia (unadjusted OR 2.98 [2.76; 3.22), and Intensive care unit admission for pneumococcal disease (unadjusted OR 2.09 [1.20; 3.66]). In diabetic individuals vaccinated with conjugated vaccine, incidence of pneumonia specific for vaccine type in a clinical trial (OR 0.237 [0.008; 0.704]), and hospitalization for overall pneumonia during the year following the polysaccharide vaccination in observational studies (unadjusted OR 0.63 [0.45–0.89]) were significantly lower in comparison with unvaccinated DM subjects, with no significant differences for other outcomes. Conclusions: People with diabetes mellitus are at higher risk for less favourable course of pneumococcal disease and should be therefore targeted in vaccination campaigns; more evidence needs to be collected on vaccination outcomes in people with diabetes. [ABSTRACT FROM AUTHOR]

Background: Parenteral penicillin G (PENG) and oral amoxicillin (AMOX) are recommended as treatment for pediatric community‐acquired pneumonia (CAP). With recent epidemiologic penicillin susceptibility data for Streptococcus pneumoniae, the most common etiology of CAP, the objective of this study was to evaluate optimal dosing regimens of PENG and AMOX based on population pharmacokinetics linked to current susceptibility data. Methods: Using NONMEM v7.3, Monte Carlo simulations (N = 10,000) were conducted for AMOX 15 mg/kg/dose PO every 8 h (standard‐dose), AMOX 45 mg/kg/dose PO every 12 h (high‐dose), and PENG 62,500 units/kg/day IV every 6 h using six virtual subjects with ages spanning 3 months to 15 years old. The probability of target attainment (PTA) was determined for both serum and epithelial lining fluid (ELF) to achieve free drug concentrations above the minimum inhibitory concentration (%fT>MIC) across the population of pneumococci for 30%–50% of the dosing interval. Results: In 2018, all 21 (100%) pneumococcal isolates were susceptible to both PENG and AMOX based on Clinical and Laboratory Standards Institute (CLSI; MIC at 2 mg/L) breakpoints, and 15 of 21 (71%) were susceptible based on EUCAST (MIC at 0.5 mg/L) breakpoints. As compared to CLSI, EUCAST breakpoints consistently achieved higher PTA for all antibiotic regimens. At 50% fT>MIC in the serum at the susceptible MICs, standard‐dose AMOX achieved >4% PTA (CLSI) and >86% PTA (EUCAST); high‐dose AMOX achieved >73% PTA (CLSI) and >99% PTA (EUCAST); and PENG achieved 0% PTA (using CLSI) and 100% PTA (using EUCAST). Standard‐dose AMOX, high‐dose AMOX, and PENG achieved >71%, >93%, and 100% PTA, respectively, in the serum at 30%–50% fT>MIC when each patient was stochastically linked to an MIC based on the frequency distribution of national susceptibility data. The PTA was consistently lower in ELF as compared with serum for all regimens. Conclusion: Based on the recent rates of resistance, antibiotic doses evaluated provide appropriate exposure for pediatric CAP based on the serum and ELF data associated with predicted clinical and microbiologic success for pneumococcus. High‐dose AMOX may still be required to treat pediatric CAP, especially if using CLSI breakpoints. Ongoing surveillance for resistance is essential. [ABSTRACT FROM AUTHOR]

Neutrophils are the first leukocytes to be recruited to sites of inflammation in response to chemotactic factors released by activated macrophages and pulmonary epithelial and endothelial cells in bacterial pneumonia, a common cause of acute respiratory distress syndrome (ARDS). Although neutrophilic inflammation facilitates the elimination of pathogens, neutrophils also may cause bystander tissue injury. Even though the presence of neutrophils in alveolar spaces is a key feature of acute lung injury and ARDS especially from pneumonia, their contribution to the pathogenesis of lung injury is uncertain. The goal of this study was to elucidate the role of neutrophils in a clinically relevant model of bacterial pneumonia. We investigated the effect of reducing neutrophils in a mouse model of pneumococcal pneumonia treated with antibiotics. Neutrophils were reduced with anti-lymphocyte antigen 6 complex locus G6D (Ly6G) monoclonal antibody 24 h before and immediately preceding infection. Mice were inoculated intranasally with Streptococcus pneumoniae and received ceftriaxone 12 h after bacterial inoculation. Neutrophil reduction in mice treated with ceftriaxone attenuated hypoxemia, alveolar permeability, epithelial injury, pulmonary edema, and inflammatory biomarker release induced by bacterial pneumonia, even though bacterial loads in the distal air spaces of the lung were modestly increased as compared with antibiotic treatment alone. Thus, when appropriate antibiotics are administered, lung injury in the early phase of bacterial pneumonia is mediated in part by neutrophils. In the early phase of bacterial pneumonia, neutrophils contribute to the severity of lung injury, although they also participate in host defense. NEW & NOTEWORTHY: Neutrophil accumulation is a key feature of ARDS, but their contribution to the pathogenesis is still uncertain. We investigated the effect of reducing neutrophils in a clinically relevant mouse model of pneumococcal pneumonia treated with antibiotics. When appropriate antibiotics were administered, neutrophil reduction with Ly6G antibody markedly attenuated lung injury and improved oxygenation. In the early phase of bacterial pneumonia, neutrophils contribute to the severity of lung injury, although they also participate in host defense. [ABSTRACT FROM AUTHOR]

Streptococcus pneumoniae is a major pathogen responsible for severe complications in patients with prior influenza A virus (IAV) infection. We have previously demonstrated that S. pneumoniae exhibits increased intracellular survival within IAV-infected cells. Fluoroquinolones (FQs) are widely used to treat pneumococcal infections. However, our prior work has shown that S. pneumoniae can develop intracellular FQ persistence, a phenomenon triggered by oxidative stress within host cells. This persistence allows the bacteria to withstand high FQ concentrations. In this study, we show that IAV infection enhances pneumococcal FQ persistence during intracellular survival within pneumocytes, macrophages, and neutrophils. This enhancement is partly due to increased oxidative stress induced by the viral infection. We find that this phenotype is particularly pronounced in autophagy-proficient host cells, potentially resulting from IAV-induced blockage of autophagosome-lysosome fusion. Moreover, we identified several S. pneumoniae genes involved in oxidative stress response that contribute to FQ persistence, including sodA (superoxide dismutase), clpL (chaperone), nrdH (glutaredoxin), and psaB (Mn+2 transporter component). Our findings reveal a novel mechanism of antibiotic persistence promoted by viral infection within host cells. This underscores the importance of considering this phenomenon when using FQs to treat pneumococcal infections, especially in patients with concurrent influenza A infection. [ABSTRACT FROM AUTHOR]

Background Community-acquired pneumonia (CAP) is associated with significant morbidity and mortality. The study objective was to describe the hospital burden of pneumonia in the adult population in France. Methods This retrospective study was conducted from the National Health Insurance Database. All hospitalizations for pneumonia (all-cause) between 2013 and 2019 were included. Different risk categories for patients were established based on pneumococcal vaccine recommendations by French health authorities. Results A total of 2 199 240 episodes of CAP were registered over the study period (annual mean, 314 177 [standard deviation, 17 818.6]); 75% occurred in patients aged ≥65 years, among whom 47% were not classified in the moderate- or high-risk categories recommended for French pneumococcal vaccination. The incidence of CAP increased with age (117.9, 395.3, and 1916.7 per 100 000 for the age groups 18–49, 50–64, and ≥65 years, respectively, in 2019). Furthermore, being at risk of pneumococcal disease resulted in more severe outcomes, including longer episode duration (mean, 14 days in low-risk vs 17 days in high-risk patients) and higher risk of referral to critical care units (from 20% to 27%), of rehospitalization up to 180 days (from 39% to 67%), of in-hospital death (from 12% to 19%), and of 1-year mortality (from 26% to 49%). Conclusions This study establishes the incidence of CAP in adults in France, describes the significant burden of disease, and highlights the need for better prevention policies. [ABSTRACT FROM AUTHOR]

Pneumonia is an acute infectious or inflammatory disease affecting the lung parenchyma that can be caused by microorganisms such as bacteria, viruses, and fungi. This study aims to determine the image of thorax photos and the distribution of pathogenic bacteria in pneumonia patients, as well as to see the image of thorax photos in certain pathogens. The method in this study was to search for articles through Google Scholar and Pubmed. The results showed that the distribution of pathogenic bacteria in pneumonia cases varied, but the most common bacteria causing pneumonia were Streptococcus pneumoniae, Klebsiella pneumoniae, and Mycoplasma pneumonia. The thorax photographs were also quite diverse, and the most common results were consolidation, infiltrates, and pleural effusion. In patients with pneumonia caused by Mycoplasma pneumoniae, the most common thorax images are lobar pneumonia or lobar consolidation. [ABSTRACT FROM AUTHOR]

Patients with axial spondyloarthritis (axSpA) who receive immunosuppressive therapy are at risk of infection due to impaired immune function and immunosuppressive medication. Vaccination plays a crucial role in preventing infections in this population. However, vaccination rates and factors influencing vaccination uptake in axSpA patients still need to be adequately studied. This study was designed to determine the vaccination rates of vaccines covered by health insurance in this particular group in Turkey and attitudes towards vaccines and infections. This survey included 199 patients with axSpA who visited our outpatient clinic in June, July, and August 2023 and received biologic and targeted synthetic disease-modifying antirheumatic drugs. The mean age of the participants was 43.7 ± 0.7 years, and the majority were male (66.3%). The majority of the patients were vaccinated against COVID-19 (85.4%), followed by hepatitis B (41.2%), influenza (20.1%), and pneumococcal pneumonia (10.5%). While awareness of COVID-19 vaccination was widespread (100%), knowledge of other vaccines was lower (hepatitis B 80.9%, influenza 70.3%, pneumococcal 60.3%, respectively). Educational interventions targeting patients and healthcare professionals are needed to improve vaccination rates in this population. Our findings emphasize the need for strategies to increase vaccination rates in axSpA patients receiving immunosuppressive therapy. Removing barriers to vaccination and raising awareness of the importance of vaccination are critical to optimizing vaccination practices in this vulnerable population. [ABSTRACT FROM AUTHOR]

Influenza is an important respiratory viral pathogen in adults, with secondary bacterial pneumonia being a common complication. While pneumococcal vaccines can prevent pneumococcal pneumonia and invasive pneumococcal disease, whether they can also prevent the severe in-hospital outcomes among patients hospitalized for influenza has not been examined. A territory-wide retrospective study was conducted in Hong Kong, which included all adult patients having chronic airway diseases (asthma, bronchiectasis, and chronic obstructive pulmonary disease) hospitalized for influenza and who had received seasonal influenza vaccine. The occurrence of secondary bacterial pneumonia, mortality, and other severe in-hospital outcomes were compared among subjects with or without pneumococcal vaccination. There was a total of 3066 eligible patients who were hospitalized for influenza in public hospitals in Hong Kong from 1 January 2016 to 30 June 2023. Completed pneumococcal vaccination with PSV23/PCV13 conferred protection against secondary bacterial pneumonia, all-cause mortality, and respiratory cause of mortality with adjusted odds ratios of 0.74 (95% CI = 0.57–0.95, p = 0.019), 0.12 (95% CI = 0.03–0.53, p = 0.005), and 0.04 (95% CI = 0.00–0.527, p = 0.0038), respectively. [ABSTRACT FROM AUTHOR]

Background: There are various reports regarding the suicide commission by HIV positive persons, but as such postmortem serological studies are yet not done to document the status in autopsy. Also it's vital to test a body before autopsy to avoid infection to the forensic experts and concerned persons in autopsy and allied work. Objectives: The objective of the study was to estimate the prevalence of HIV infection, in unreported post-mortem cases in the autopsy room. Material and Methods: The prospective study was done at the Department of Forensic Medicine in collaboration with the Department of Microbiology located in the Tertiary Care Government Hospital, Mumbai. Total of 216 cases were examined during a span of one year. Cases selected as per inclusion and exclusion criteria, tested for HIV after taking consent from guardians. Results: Most common age group was found to be 31-40 years. Males were 72.22% while females were 27.78% of study. Out of total 6 were tested positive for HIV. Out of total 6 HIV cases 4 (80%) were males and 2 (20%) were females. Out of 6 cases 5 (83.3%) were below 50 yrs. 82.3% tested positive in first 24 hours of death. 3 (50%) died due to pulmonary tuberculosis, 2 (33.3%) due to meningitis and 1 (16.7%) due to lobar pneumonia. Conclusions: HIV among dead bodies presenting to autopsy is not uncommon. [ABSTRACT FROM AUTHOR]

Background: Pneumococcal pneumonia (PP) is a serious infection caused by Streptococcus pneumoniae (pneumococcus), with a wide spectrum of clinical manifestations. The aim of this study was to analyze the comorbidity factors that influenced the mortality in patients with asplenia according to PP. Methods: Discharge reports from the Spanish Minimum Basic Data Set (MBDS) was used to retrospectively analyze patients with asplenia and PP, from 1997 to 2021. Elixhauser Comorbidity Index (ECI) was calculated to predict in-hospital mortality (IHM). Results: 97,922 patients with asplenia were included and 381 cases of PP were identified. The average age for men was 63.87 years and for women 65.99 years. In all years, ECI was larger for splenectomized than for non-splenectomized patients, with men having a higher mean ECI than women. An association was found between risk factors ECI, splenectomy, age group, sex, pneumococcal pneumonia, and increased mortality (OR = 0.98; 95% CI: 0.97–0.99; p < 0.001). The IHM increased steadily with the number of comorbidities and index scores in 1997–2021. Conclusions: Asplenia remain a relevant cause of hospitalization in Spain. Comorbidities reflected a great impact in patients with asplenia and PP, which would mean higher risk of mortality. [ABSTRACT FROM AUTHOR]

Burns are a significant problem with high associated morbidity and mortality worldwide. Bacteremia is a serious complication that is important in increasing the overall fatality rate in burn injury patients. In this study, we report a case of Streptococcus mitis and Klebsiella pneumoniae mixed infection in severe burns in a 40-year-old female. The patient was transferred from an outside hospital to the emergency unit after burn injuries in a gas explosion accident at home. The patient underwent surgical debridement and antibiotics treatment but died due to sepsis and multiorgan failure. Our case study will help to underscore the important role of Streptococcus mitis and Klebsiella pneumoniae as human opportunistic pathogens in severe burn injury patients. [ABSTRACT FROM AUTHOR]

Introduction: In Argentina, vaccination with 13-valent pneumococcal conjugate vaccine (PCV13) followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23; PCV13 → PPSV23) has been recommended for all adults aged ≥ 65 years and younger adults with chronic medical ("moderate-risk") or immunocompromising ("high-risk") conditions since 2017. With the approval of a 20-valent PCV (PCV20), we evaluated the cost-effectiveness of PCV20 versus current recommendations for moderate-/high-risk adults aged 18–64 years and all adults 65–99 years. Methods: A probabilistic cohort model was used to project lifetime outcomes and costs associated with invasive pneumococcal disease (IPD) and all-cause non-bacteremic pneumonia (NBP), and the expected impact of vaccination. Clinical outcomes were projected annually based on Argentinean data. Economic costs were estimated based on cases and corresponding medical costs (adjusted to 2023 USD) and costs of vaccine and administration. Cost-effectiveness of PCV20 was evaluated versus the current strategy, PCV13 → PPSV23, and alternatively, versus sequentially administered 15-valent PCV and PPSV23 (PCV15 → PPSV23), and presented as cost per quality-adjusted life year gained; a healthcare system perspective was used. Costs and benefits were discounted at 3%/year. Results: PCV20 in lieu of PCV13 → PPSV23 among moderate-/high-risk adults aged 18–64 years and all adults 65–99 years (N = 13.4M) prevented 3838 IPD, 4377 inpatient NBP, and 6003 outpatient NBP cases, and 1865 disease-related deaths; relative to PCV15 → PPSV23 the corresponding reductions were 2775, 3285, 4518, and 1348. PCV20 was projected to be the dominant strategy versus PCV13 → PPSV23 and PCV15 → PPSV23 as overall costs were lower by $87.6M and $80.8M, respectively. In probabilistic sensitivity analyses, PCV20 was dominant (i.e., more effective, less costly) in 100% of 1000 simulations. Conclusions: Analyses suggest implementing a PCV20 vaccination program in moderate-/high-risk adults aged 18–64 years and all adults ≥ 65 years—in lieu of PCV13 → PPSV23—would yield substantial reductions in pneumococcal disease and would be cost saving to the Argentinean healthcare system. Plain Language Summary: Pneumococcal pneumonia has a high disease burden in both children and adults. Older adults and those with certain underlying conditions are more susceptible to severe pneumococcal disease resulting in considerable economic burden on the healthcare system. In Argentina, vaccination with 13-valent pneumococcal conjugate vaccine (PCV13) followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23) a year later is recommended for all adults aged ≥ 65 years and adults aged 18–64 years with underlying risk conditions. Despite vaccination efforts, prevalence of pneumococcal disease remains high. Two higher-valent PCVs—15-valent PCV (PCV15) and 20-valent PCV (PCV20)—are available for use in adults with PCV20 offering additional serotype coverage. This study assessed the cost-effectiveness of replacing current (PCV13 → PPSV23) and alternative (PCV15 → PPSV23) vaccination strategies with PCV20 alone. The use of PCV20 was evaluated among Argentinean adults aged 18–64 years with underlying risk conditions and all adults aged 65–99 years (N = 13 million). Over a lifetime time horizon, compared to PCV13 → PPSV23, PCV20 use would avert 14,218 cases and 1865 deaths, and increase quality-adjusted life years by 8655. Compared to PCV15 → PPSV23, PCV20 reduced cases and deaths by 10,578 and 1348, respectively, and increased quality-adjusted life years by 6341. In both comparisons, PCV20 use was cost saving with $87.6 million and $80.8 million lower costs compared to PCV13 → PPSV23 and PCV15 → PPSV23, respectively. Results of the cost-effectiveness analyses suggest that the use of PCV20 is a cost-saving strategy, reducing overall costs to the healthcare system and improving public health. [ABSTRACT FROM AUTHOR]

Introduction: Pneumonia is a common infection in the intensive care unit (ICU), and gram-negative bacilli are the most common bacterial cause. The purpose of the study was to investigate the risk factors for 30-day mortality in patients with gram-negative bacillary pneumonia in the ICU, construct a predictive model, and stratify patients based on risk to assess their short-term survival. Methods: Patients admitted to the ICU with gram-negative bacillary pneumonia at Fujian Medical University Affiliated First Hospital between January 2018 and September 2020 were selected. Patients were divided into deceased and survivor groups based on whether death occurred within 30 days. Multifactorial logistic regression analysis was used to identify independent risk factors for 30-day mortality in these patients, and a predictive nomogram model was constructed based on these factors. Patients were categorized into low-, medium-, and high-risk groups according to the model's predicted probability, and Kaplan-Meier survival curves were plotted to assess short-term survival. Results: The study included 305 patients. Lactic acid (odds ratio [OR], 1.524, 95% CI: 1.057-2.197), tracheal intubation (OR: 4.202, 95% CI: 1.092-16.169), and acute kidney injury (OR:4.776, 95% CI: 1.632-13.978) were identified as independent risk factors for 30-day mortality. A nomogram prediction model was established based on these three factors. Internal validation of the model showed a Hosmer-Lemeshow test result of X2=5.770, P=0.834, and an area under the ROC curve of 0.791 (95% CI: 0.688-0.893). Bootstrap resampling of the original data 1000 times yielded a C-index of 0.791, and a decision curve analysis indicated a high net benefit when the threshold probability was between 15%-90%. The survival time for low-, medium-, and high-risk patients was 30 (30, 30), 30 (16.5, 30), and 17 (11, 27) days, respectively, which were significantly different. Conclusion: Lactic acid, tracheal intubation, and acute kidney injury were independent risk factors for 30-day mortality in patients in the ICU with gram-negative bacillary pneumonia. The predictive model constructed based on these factors showed good predictive performance and helped assess short-term survival, facilitating early intervention and treatment. [ABSTRACT FROM AUTHOR]

In patients with cancer, tumor- and treatment-induced immunosuppression are responsible for a four-fold increase in morbidity and mortality caused by influenza and invasive Streptococcus pneumoniae infections compared to the general population. The main oncology societies strongly recommend vaccination in patients with cancer to prevent these infections. However, vaccine hesitancy is a main concern in this population. The aim of this study was to assess the feasibility of in-hospital vaccination for patients under anticancer treatment and their family members (FMs) against influenza and pneumococcal infections during the COVID-19 pandemic in order to increase vaccine coverage. This was a single-center, prospective, observational study conducted at the Department of Oncology of Luigi Sacco University Hospital (Milan, Italy) between October 2020 and April 2021. The main primary outcome was the incidence of influenza-like illness (ILI) and pneumococcal infections. The main secondary outcome was safety. A total of 341 subjects were enrolled, including 194 patients with cancer and 147 FMs. The incidence of ILI was higher among patients than among FMs (9% vs. 2.7%, OR 3.92, p = 0.02). Moreover, two subjects were diagnosed with pneumococcal pneumonia. The most frequent vaccine-related AEs were pain in the injection site (31%) and fatigue (8.7%). In conclusion, this hospital-based vaccination strategy was feasible during the COVID-19 pandemic, representing a potential model to maximize vaccine coverage during a public health emergency. [ABSTRACT FROM AUTHOR]

Invasive pneumococcal disease typically occurs in immunocompromised patients, although some vaccine strains of Streptococcus pneumoniae have been reported to cause invasive pneumococcal disease in immunocompetent vaccine recipients. In this study, we presented a case of a 16-month-old immunocompetent patient with lung abscess and empyema caused by nonvaccine S. pneumoniae serotype 24B. A consolidation occupying the right upper lobe in the chest computed tomography results, as observed at presentation, changed to thick-walled cavitary lesions at the end of a month of intravenous antibiotics, and antibiotics were continued for a total of two months. To the best of our knowledge this is the first report that focuses on the risk of invasive pneumococcal disease caused by S. pneumoniae serotype 24B in an immunocompetent child.

Background. Community-acquired pneumonia remains one of the most common and life-threatening forms of pathology among respiratory diseases.The aim of the study. To identify the features of the epidemiology of communityacquired pneumonia in the conditions of mass immunization against pneumococcal infection in the Irkutsk region.Materials and methods. We conducted a descriptive epidemiological retrospective study. We studied the incidence of community-acquired pneumonia (including community-acquired pneumonia of bacterial and viral etiology) and mortality from this disease in the Irkutsk region for 2011–2022 according to statistical reporting forms No. 2, No. 5, No. 6, C51.Results. The incidence of community-acquired pneumonia during the observation period remained at a high level: the long-term annual average rate among the total population was 627.3 [467.8÷786.8]. At the same time, there was a persistent decrease in the incidence of community-acquired pneumonia of bacterial etiology (Tdecrease = 6.8 %). Incidence rates of community-acquired pneumonia of bacterial etiology were distributed unevenly over the years and the compared population groups. The highest levels were recorded in children in 2018–2019 – 12.3 [10.8÷13.8] and 19.3 [17.8÷20.8], respectively. A decrease in the mortality rate from community-acquired pneumonia among children, adults and in the general population in 2020 was shown, with a subsequent increase in the rate among adults and the general population by 2.5 times. Against the background of ongoing immunization of the population against pneumococcal infection, there is a statistically significant decrease in the incidence of community-acquired pneumonia, including communityacquired bacterial pneumonia, and mortality from community-acquired pneumonia among different population groups.Conclusion. Despite the high incidence of community-acquired pneumonia, a statistically significant decrease in the incidence of community-acquired pneumonia of bacterial etiology has been shown among children and adults. The decrease in mortality from community-acquired pneumonia has continued since the introduction of immunization against pneumococcal infection. The results of the study can be used to optimize epidemiological surveillance and epidemiological control of community-acquired pneumonia at the regional level.

ABSTRACTPneumonia, predominantly caused by Streptococcus pneumoniae, remains a leading cause of global mortality. The 23-valent Pneumococcal polysaccharide vaccine (PPSV23) and conjugate vaccines (PCVs) are vital measures to fight against it. This paper discussed the changes in pneumococcal vaccination strategies, particularly for older adults, as vaccine effectiveness and epidemiological patterns shift. While PPSV23 maintains effectiveness against invasive pneumococcal disease (IPD), its effectiveness against pneumococcal pneumonia is declining. Conversely, PCV13 consistently demonstrates effectiveness against both IPD and pneumonia. Consequently, the US Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices recommends using PCVs, notably PCV20 and PCV15, over PPSV23. Japanese studies indicate a change in the efficacy/effectiveness of PPSV23 following PCV introduction in children, likely owing to serotype replacement and herd immunity. Additionally, recent data reveals a plateau in the reduction of PCV13 and PPSV23-covered serotypes, posing a challenge to current strategies. This paper indicates a paradigm shift in pneumonia management, acknowledging its chronic nature and potential to exacerbate other diseases. The future of pneumococcal vaccination lies in broader serotype coverage through PCVs, adapting to serotype changes driven by childhood vaccination programs. Furthermore, continuous research and vaccine development are crucial in this evolving field.

IL-22 plays a critical role in defending against mucosal infections, but how IL-22 production is regulated is incompletely understood. Here, we show that mice lacking IL-33 or its receptor ST2 (IL-1RL1) were more resistant to Streptococcus pneumoniae lung infection than wild-type animals and that single-nucleotide polymorphisms in IL33 and IL1RL1 were associated with pneumococcal pneumonia in humans. The effect of IL-33 on S. pneumoniae infection was mediated by negative regulation of IL-22 production in innate lymphoid cells (ILCs) but independent of ILC2s as well as IL-4 and IL-13 signaling. Moreover, IL-33's influence on IL-22-dependent antibacterial defense was dependent on housing conditions of the mice and mediated by IL-33's modulatory effect on the gut microbiota. Collectively, we provide insight into the bidirectional crosstalk between the innate immune system and the microbiota. We conclude that both genetic and environmental factors influence the gut microbiota, thereby impacting the efficacy of antibacterial immune defense and susceptibility to pneumonia. [ABSTRACT FROM AUTHOR]

Background: Streptococcus pneumoniae is a leading cause of morbidity and mortality globally, causing bacteremic pneumonia, meningitis, sepsis, and other invasive pneumococcal diseases. Evidence supports nasopharyngeal pneumococcal carriage as a reservoir for transmission and precursor of pneumococcal disease. Objectives: To estimate the pneumococcal nasopharyngeal burden in all age groups in Latin America and the Caribbean (LAC) before, during, and after the introduction of pneumococcal vaccine conjugate (PVC). Methods: Systematic literature review of international, regional, and country-published and unpublished data, together with reports including data from serotype distribution in nasopharyngeal carriage in children and adults from LAC countries following Cochrane methods. The protocol was registered in PROSPERO database (ID: CRD42023392097). Results: We included 54 studies with data on nasopharyngeal pneumococcal carriage and serotypes from 31,803 patients. In children under five years old, carriage was found in 41% and in adults over 65, it was 26%. During the study period, children under five showed a colonization proportion of 34% with PCV10 serotypes and 45% with PCV13 serotypes. When we analyze the carriage prevalence of PCV serotypes in all age groups between 1995 and 2019, serotypes included in PCV10 and those included in PCV13, both showed a decreasing trend along analysis by lustrum. Conclusion: The data presented in this study highlights the need to establish national surveillance programs to monitor pneumococcal nasopharyngeal carriage to monitor serotype prevalence and replacement before and after including new pneumococcal vaccines in the region. In addition, to analyze differences in the prevalence of serotypes between countries, emphasize the importance of approaches to local realities to reduce IPD effectively. [ABSTRACT FROM AUTHOR]

Resolving inflammation is thought to return the affected tissue back to homoeostasis but recent evidence supports a non-linear model of resolution involving a phase of prolonged immune activity. Here we show that within days following resolution of Streptococcus pneumoniae-triggered lung inflammation, there is an influx of antigen specific lymphocytes with a memory and tissue-resident phenotype as well as macrophages bearing alveolar or interstitial phenotype. The transcriptome of these macrophages shows enrichment of genes associated with prostaglandin biosynthesis and genes that drive T cell chemotaxis and differentiation. Therapeutic depletion of post-resolution macrophages, inhibition of prostaglandin E2 (PGE2) synthesis or treatment with an EP4 antagonist, MF498, reduce numbers of lung CD4+/CD44+/CD62L+ and CD4+/CD44+/CD62L-/CD27+ T cells as well as their expression of the α-integrin, CD103. The T cells fail to reappear and reactivate upon secondary challenge for up to six weeks following primary infection. Concomitantly, EP4 antagonism through MF498 causes accumulation of lung macrophages and marked tissue fibrosis. Our study thus shows that PGE2 signalling, predominantly via EP4, plays an important role during the second wave of immune activity following resolution of inflammation. This secondary immune activation drives local tissue-resident T cell development while limiting tissue injury The post-resolution phase of inflammation is not simply a linear path towards cessation of immune response but rather a regulated process involving fluctuating immune activity. Here authors show a pivotal role for post-resolution macrophages in driving a wave of T cell recruitment and activation via prostaglandin E2 and α-integrin signalling during the resolution phase of murine pneumococcal pneumonia. [ABSTRACT FROM AUTHOR]

• A published model was used to estimate and compare the health and economic outcomes of three pneumococcal vaccination strategies (PCV15, PCV13 and no vaccination) for 65 years-and-above in Switzerland. • The PCV15 strategy prevented the largest number of pneumococcal disease cases and deaths when compared to the no vaccination strategy. • The PCV15 strategy dominated (more effective and less costly) the PCV13 strategy. • Under various ranges of uncertainty around the input parameters, the PCV15 strategy maintained a favorable incremental cost-effectiveness ratio when compared to the no vaccination strategy. 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: 1) Vaccination with PCV13. 2) Vaccination with PCV15. 3) No vaccination (do-nothing alternative). 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. 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). 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. 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. [ABSTRACT FROM AUTHOR]

Background: Limited data exists regarding risk factors for adverse outcomes in older adults hospitalized with Community-Acquired Pneumonia (CAP) in low- and middle-income countries such as India. This multisite study aimed to assess outcomes and associated risk factors among adults aged ≥60 years hospitalized with pneumonia. Methods: Between December 2018 and March 2020, we enrolled ≥60-year-old adults admitted within 48 hours for CAP treatment across 16 public and private facilities in four sites. Clinical data and nasal/oropharyngeal specimens were collected by trained nurses and tested for influenza, respiratory syncytial virus (RSV), and other respiratory viruses (ORV) using the qPCR. Participants were evaluated regularly until discharge, as well as on the 7th and 30th days post-discharge. Outcomes included ICU admission and in-hospital or 30-day post-discharge mortality. A hierarchical framework for multivariable logistic regression and Cox proportional hazard models identified risk factors (e.g., demographics, clinical features, etiologic agents) associated with critical care or death. Findings: Of 1,090 CAP patients, the median age was 69 years; 38.4% were female. Influenza viruses were detected in 12.3%, RSV in 2.2%, and ORV in 6.3% of participants. Critical care was required for 39.4%, with 9.9% in-hospital mortality and 5% 30-day post-discharge mortality. Only 41% of influenza CAP patients received antiviral treatment. Admission factors independently associated with ICU admission included respiratory rate >30/min, blood urea nitrogen>19mg/dl, altered sensorium, anemia, oxygen saturation <90%, prior cardiovascular diseases, chronic respiratory diseases, and private hospital admission. Diabetes, anemia, low oxygen saturation at admission, ICU admission, and mechanical ventilation were associated with 30-day mortality. Conclusion: High ICU admission and 30-day mortality rates were observed among older adults with pneumonia, with a significant proportion linked to influenza and RSV infections. Comprehensive guidelines for CAP prevention and management in older adults are needed, especially with the co-circulation of SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Background: Data available for RSV and influenza infections among children < 2 years in Mongolia are limited. We present data from four districts of Ulaanbaatar from April 2015 to June 2021. Methods: This study was nested in an enhanced surveillance project evaluating pneumococcal conjugate vaccine (PCV13) impact on the incidence of hospitalized lower respiratory tract infections (LRTIs). Our study was restricted to children aged < 2 years with arterial O2 saturation < 93% and children with radiological pneumonia. Nasopharyngeal (NP) swabs collected at admission were tested for RSV and influenza using qRT‐PCR. NP swabs of all patients with radiological pneumonia and of a subset of randomly selected NP swabs were tested for S. pneumoniae (S.p.) by qPCR and for serotypes by culture and DNA microarray. Results: Among 5705 patients, 2113 (37.0%) and 386 (6.8%) had RSV and influenza infections, respectively. Children aged 2–6 months had a higher percentage of very severe RSV infection compared to those older than 6 months (42.2% versus 31.4%, p‐value Fisher's exact = 0.001). S.p. carriage was detected in 1073/2281 (47.0%) patients. Among S.p. carriage cases, 363/1073 (33.8%) had S.p. and RSV codetection, and 82/1073 (7.6%) had S.p. and influenza codetection. S.p. codetection with RSV/influenza was not associated with more severe LRTIs, compared to only RSV/influenza cases. Conclusion: In Mongolia, RSV is an important pathogen causing more severe LRTI in children under 6 months of age. Codetection of RSV or influenza virus and S.p. was not associated with increased severity. [ABSTRACT FROM AUTHOR]

• Pneumococcal infections are associated with high morbidity, hospitalisation and mortality. • Invasive pneumococcal infections remain a public health problem with significant cost. • The Health Insurance and patient's cost perspectives were considered. • Estimation of the hospitalization cost per age- and risk- groups were considered. • Pneumococcal infections justify more attention for vaccination. pneumococcal infections are associated with high morbidity, hospitalisation and mortality. The objective of this study was to investigate the health and economic burden of all-cause pneumonia and invasive pneumococcal disease in Belgian hospital settings, by patient's age and risk profile. This descriptive retrospective study was conducted in 17 Belgian hospitals. Univariate and multivariate logistic linear regression models were performed. The Health Insurance and patient's cost perspectives were considered because a few studies report these costs. The analysis has included 4,712 hospital admissions over the year 2018. Median hospitalization costs were higher for invasive pneumococcal infection diagnosis than for all-cause pneumonia (p < 0,001), respectively 4,051€ and 3,362€. Other factors associated with higher hospitalization cost were patient's high-risk profile, admission to emergency unit, transfer from nursing home, admission to intensive care unit and length of stay. Streptococcus pneumoniae infections remain a public health problem with significant cost for the Health Insurance and poor prognosis. Invasive pneumococcal infections are associated with longer hospital stays and required more intensive care than all other causes of pneumonia, in addition to be more costly, which justifies more attention for vaccination. This study also suggests an increase of economic and health burden with age and presence of underlying conditions. [ABSTRACT FROM AUTHOR]

Multiplex panel tests identify many individual pathogens at once, using a set of component tests. In some panels the number of components can be large. If the panel is detecting causative pathogens for a single syndrome or disease then we might estimate the burden of that disease by combining the results of the panel, for example determining the prevalence of pneumococcal pneumonia as caused by many individual pneumococcal serotypes. When we are dealing with multiplex test panels with many components, test error in the individual components of a panel, even when present at very low levels, can cause significant overall error. Uncertainty in the sensitivity and specificity of the individual tests, and statistical fluctuations in the numbers of false positives and false negatives, will cause large uncertainty in the combined estimates of disease prevalence. In many cases this can be a source of significant bias. In this paper we develop a mathematical framework to characterise this issue, we determine expressions for the sensitivity and specificity of panel tests. In this we identify a counter-intuitive relationship between panel test sensitivity and disease prevalence that means panel tests become more sensitive as prevalence increases. We present novel statistical methods that adjust for bias and quantify uncertainty in prevalence estimates from panel tests, and use simulations to test these methods. As multiplex testing becomes more commonly used for screening in routine clinical practice, accumulation of test error due to the combination of large numbers of test results needs to be identified and corrected for. Author summary: During analysis of pneumococcal incidence data obtained from serotype specific multiplex urine antigen testing, we identified that despite excellent test sensitivity and specificity, the small error rate in each individual serotype test has the potential to compound and cause large uncertainty in the resulting estimates of pneumococcal prevalence, obtained by combining individual results. This limits the accuracy of estimates of the burden of disease caused by vaccine preventable pneumococcal serotypes, and in certain situations can produce marked bias. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Currently, there are more than 500 million people suffering from diabetes around the world. People aged 65 years or older are the most affected by this disease, and it is estimated that approximately 96% of diabetes cases worldwide are type 2 diabetes. People with diabetes mellitus are at an increased risk of infections such as pneumonia, due to a series of factors that may contribute to immune dysfunction, including hyperglycemia, inhibition of neutrophil chemotaxis, impaired cytokine production, phagocytic cell dysfunction, altered T cell-mediated immune responses and the co-existence of chronic comorbidities. Rates of infection, hospitalization and mortality in diabetic patients are reported to be higher than in the general population. Research into the risk of infectious diseases such as pneumonia in these patients is very important because it will help improve their management and treatment. [ABSTRACT FROM AUTHOR]

Coccidioidomycosis occurs after inhalation of airborne spores of the endemic, dimorphic fungus, Coccidioides. While the majority of individuals resolve the infection without coming to medical attention, the fungus is a major cause of community-acquired pneumonia in the endemic region, and chronic pulmonary and extrapulmonary disease poses significant personal and economic burdens. This review explores the literature surrounding human susceptibility to coccidioidomycosis, including chronic pulmonary and extrapulmonary dissemination. Over the past century of study, themes have emerged surrounding factors impacting human susceptibility to severe disease or dissemination, including immune suppression, genetic susceptibility, sex, pregnancy, and genetic ancestry. Early studies were observational, frequently with small numbers of cases; several of these early studies are highly cited in review papers, becoming part of the coccidioidomycosis "canon". Specific genetic variants, sex, and immune suppression by TNF inhibitors have been validated in later cohort studies, confirming the original hypotheses. By contrast, some risk factors, such as ABO blood group, Filipino ancestry, or lack of erythema nodosum among black individuals, are repeated in the literature despite the lack of supporting studies or biologic plausibility. Using examination of historical reports coupled with recent cohort and epidemiology studies, evidence for commonly reported risk factors is discussed. [ABSTRACT FROM AUTHOR]

Non-vaccine serotype (NVT) pneumococcal pneumonia in Japan has increased with the spread of pneumococcal vaccinations. However, there is no data regarding the clinical background and antimicrobial susceptibility of NVT isolates compared with those of vaccine serotype (VT) isolates in adult pneumococcal pneumonia. The serotypes and antimicrobial susceptibilities of pneumococcal isolates obtained from patients with pneumonia at the University of Occupational and Environmental Health, Japan, from January 2011 to December 2020 were retrospectively evaluated along with the patients' clinical information. In total, 252 patients with pneumococcal pneumonia (98 NVT and 154 VT isolates) were included. Among NVTs, the most common serotype was 35B, followed by 15A, 34, 6C, 23A, and 15C. The MIC 50 and MIC 90 of each antibiotic in 35B and 15A tend to be higher than those in 34, 6C, and 23A. Regarding background characteristics, the percentages of patients with dementia and liver disease were significantly higher in patients in the VT group than in those in the NVT group (p = 0.048 and p = 0.012, respectively). There were no significant differences in the severity of pneumonia and mortality rate between patients with the VT and NVT isolates. This study first demonstrated that NVT isolates included those with reduced susceptibility to antibiotics in adult pneumonia in Japan. The data of the present study can be useful in optimizing treatment strategies for pneumococcal pneumonia because of the increasing number of NVT cases in Japan. [ABSTRACT FROM AUTHOR]

Introduction: Despite the success of vaccination in reducing overall rate of pneumococcal pneumonia, Streptococcus pneumoniae is still held responsible for high mortality and modality rates worldwide. Our study aimed to investigate the potential role played by NK cells in immune response generated by pneumococcal vaccination, which could contribute to the development of more effective vaccines. Methods: The study included mice with and without NK cell depletion which were immunized with pneumococcus polysaccharide-conjugated vaccine followed by pneumococcus polysaccharide vaccine (PPV). Serum samples and splenocytes were collected from mice sacrificed 4 weeks after the last PPV dose. Serum samples were used for antibody level quantification by ELISA assay, while splenocytes were treated with PPV in vitro before monitoring CD4+ T-cell subsets (TH1, TH2, and TH17) and cytokine (IFN-γ, IL-4, and IL-17) secretion levels by flow cytometry and ELISA analysis, respectively. Results: Results demonstrated reduced pneumococcal IgG and TH1 cell levels due to NK cell depletion. Nevertheless, in contrast to these observations, IFN-γ secretion levels after in vitro PPV-23 treatment of splenocytes did not exhibit any statistically significant difference between the two mice groups. Conclusions: The data indicate a positive contribution of NK cells to both T-cell and B-cell responses triggered against pneumococcal vaccination. Further studies are required to confirm our data and investigate the potential benefit of NK cell targeting in promoting vaccine efficacy, especially in the elderly population who continues to be affected significantly by pneumococcal pneumonia. [ABSTRACT FROM AUTHOR]

Background: Inflammation serves as a key pathologic mediator in the progression of infections and various diseases, involving significant alterations in the gut microbiome and metabolism. This study aims to probe into the potential causal relationships between gut microbial taxa and human blood metabolites with various serum inflammatory markers (CRP, SAA1, IL-6, TNF-α, WBC, and GlycA) and the risks of seven common infections (gastrointestinal infections, dysentery, pneumonia, bacterial pneumonia, bronchopneumonia and lung abscess, pneumococcal pneumonia, and urinary tract infections). Methods: Two-sample Mendelian randomization (MR) analysis was performed using inverse variance weighted (IVW), maximumlikelihood, MR-Egger, weighted median, and MR-PRESSO. Results: After adding other MRmodels and sensitivity analyses, genus Roseburia was simultaneously associated adversely with CRP (Beta IVW = -0.040) and SAA1 (Beta IVW = -0.280), and family Bifidobacteriaceae was negatively associated with both CRP (Beta IVW = -0.034) and pneumonia risk (Beta IVW = -0.391). After correction by FDR, only glutaroyl carnitine remained significantly associated with elevated CRP levels (Beta IVW = 0.112). Additionally, threonine (Beta IVW = 0.200) and 1-heptadecanoylglycerophosphocholine (Beta IVW = -0.246) were found to be significantly associated with WBC levels. Three metabolites showed similar causal effects on different inflammatory markers or infectious phenotypes, stearidonate (18:4n3) was negatively related to SAA1 and urinary tract infections, and 5-oxoproline contributed to elevated IL-6 and SAA1 levels. In addition, 7-methylguanine showed a positive correlation with dysentery and bacterial pneumonia. Conclusion: This study provides novel evidence confirming the causal effects of the gut microbiome and the plasma metabolite profile on inflammation and the risk of infection. These potential molecular alterations may aid in the development of new targets for the intervention and management of disorders associated with inflammation and infections. [ABSTRACT FROM AUTHOR]

Previously, it was shown that intranasally (i.n.) administered Corynebacterium pseudodiphtheriticum 090104 (Cp) or CP-derived bacterium-like particles (BLPs) improve the immunogenicity of the pneumococcal conjugate vaccine (PCV). This work aimed to deepen the characterization of the adjuvant properties of Cp and CP-derived BLPs for their use in the development of pneumococcal vaccines. The ability of Cp and CP-derived BLPs to improve both the humoral and cellular specific immune responses induced by i.n. administered polysaccharide-based commercial pneumococcal vaccine (Pneumovax 23®) and the chimeric recombinant PSPF (PsaA-Spr1875-PspA-FliC) protein was evaluated, as well as the protection against Streptococcus pneumoniae infection in infant mice. Additionally, whether the immunization protocols, including Cp and CP-derived BLPs, together with the pneumococcal vaccines can enhance the resistance to secondary pneumococcal pneumonia induced after inflammatory lung damage mediated by the activation of Toll-like receptor 3 (TLR3) was assessed. The results showed that both Cp and CP-derived BLPs increased the immunogenicity and protection induced by two pneumococcal vaccines administered through the nasal route. Of note, the nasal priming with the PSPF T-dependent antigen co-administered with Cp or CP-derived BLPs efficiently stimulated humoral and cellular immunity and increased the resistance to primary and secondary pneumococcal infections. The CP-derived BLPs presented a stronger effect than live bacteria. Given safety concerns associated with live bacterium administration, especially in high-risk populations, such as infants, the elderly, and immunocompromised patients, BLPs emerge as an attractive mucosal adjuvant to improve the host response to pneumococcal infections and to enhance the vaccines already in the market or in development. [ABSTRACT FROM AUTHOR]

Globally, sepsis and pneumonia account for significant mortality and morbidity. A complex interplay of immune-molecular pathways underlies both sepsis and pneumonia, resulting in similar and overlapping disease characteristics. Sepsis could result from unmanaged pneumonia. Similarly, sepsis patients have pneumonia as a common complication in the intensive care unit. A significant percentage of pneumonia is misdiagnosed as septic shock. Therefore, our knowledge of the clinical relationship between pneumonia and sepsis is imperative to the proper management of these syndromes. Regarding pathogenesis and etiology, pneumococcus is one of the leading pathogens implicated in both pneumonia and sepsis syndromes. Growing evidence suggests that pneumococcal pneumonia can potentially disseminate and consequently induce systemic inflammation and severe sepsis. Streptococcus pneumoniae could potentially exploit the function of dendritic cells (DCs) to facilitate bacterial dissemination. This highlights the importance of pathogen-immune cell crosstalk in the pathophysiology of sepsis and pneumonia. The role of DCs in pneumococcal infections and sepsis is not well understood. Therefore, studying the immunologic crosstalk between pneumococcus and host immune mediators is crucial to elucidating the pathophysiology of pneumonia-induced lung injury and sepsis. This knowledge would help mitigate clinical diagnosis and management challenges. [ABSTRACT FROM AUTHOR]

Objective: To analyze the clinical epidemiological characteristics including clinical features, disease prognosis of pneumococcal meningitis (PM), and drug sensitivity of S. pneumoniae isolates in Chinese children. Methods: A retrospective analysis was performed on the clinical, laboratory microbiological data of 160 hospitalized children less than 15 years of age with PM from January 2019 to December 2020 in 33 tertiary hospitals in China. Results: A total of 160 PM patients were diagnosed, including 103 males and 57 females The onset age was 15 days to 15 years old, and the median age was 1 year and 3 months. There were 137 cases (85.6%) in the 3 months to <5 years age group, especially in the 3 months to <3 years age group (109 cases, 68.2%); S. pneumoniae was isolated from cerebrospinal fluid (CSF) culture in 95(35.6%), and 57(35.6%) in blood culture. The positive rates of S. pneumoniae detection by CSF metagenomic next-generation sequencing (mNGS)and antigen detection method were 40.2% (35/87) and 26.9% (21/78). Fifty-five cases (34.4%) had one or more predisposing factors of bacterial meningitis; and 113 cases (70.6%) had one or more extracranial infection diseases Fever (147, 91.9%) was the most common clinical symptom, followed by vomiting (61, 38.1%) and altered mental status (47,29.4%). Among 160 children with PM, the main intracranial imaging complications were subdural effusion and (or) empyema in 43 cases (26.9%), hydrocephalus in 24 cases (15.0%), cerebral abscess in 23 cases (14.4%), intracranial hemorrhage in 8 cases (5.0%), and other cerebrovascular diseases in 13 cases (8.1%) including encephalomalacia, cerebral infarction, and encephalatrophy. Subdural effusion and (or) empyema and hydrocephalus mainly occurred in children < 1 years old (90.7% (39/43) and 83.3% (20/24), respectively). 17 cases with PM (39.5%) had more than one intracranial imaging abnormality. S. pneumoniae isolates were completely sensitive to vancomycin (100.0%, 75/75), linezolid (100.0%,56/56), ertapenem (6/6); highly sensitive to levofloxacin (81.5%, 22/27), moxifloxacin (14/17), rifampicin (96.2%, 25/26), and chloramphenicol (91.3%, 21/23); moderately sensitive to cefotaxime (56.1%, 23/41), meropenem (51.1%, 23/45) and ceftriaxone (63.5, 33/52); less sensitive to penicillin (19.6%, 27/138) and clindamycin (1/19); completely resistant to erythromycin (100.0%, 31/31). The cure and improvement rate were 22.5% (36/160)and 66.3% (106/160), respectively. 18 cases (11.3%) had an adverse outcome, including 6 cases withdrawing treatment therapy, 5 cases unhealed, 5 cases died, and 2 recurrences. S. pneumoniae was completely susceptible to vancomycin (100.0%, 75/75), linezolid (100.0%, 56/56), and ertapenem (6/6); susceptible to cefotaxime, meropenem, and ceftriaxone in the order of 56.1% (23/41), 51.1% (23/45), and 63.5 (33/52); completely resistant to erythromycin (100.0%, 31/31). Conclusion: Pediatric PM is more common in children aged 3 months to < 3 years old. Intracranial complications mostly occur in children < 1 year of age with fever being the most common clinical manifestations and subdural effusion and (or) empyema and hydrocephalus being the most common complications, respectively. CSF non-culture methods can facilitate improving the detection rate of pathogenic bacteria. More than 10% of PM children had adverse outcomes. S. pneumoniae strains are susceptible to vancomycin, linezolid, ertapenem, levofloxacin, moxifloxacin, rifampicin, and chloramphenicol. [ABSTRACT FROM AUTHOR]

Background: Klebsiella pneumoniae has become one of the major threats to public health as it causes nosocomial and community-acquired infections like lobar pneumonia. This infection causes acute inflammation in the lung, characterized by the recruitment of polymorphonuclear cells, generating free radicals, and decreasing the endogenous antioxidant balance system. Many experimental studies have focused on the induction, progression and resolution of infection up to its peak, but these documented processes remain highly random and their sex dependence un-elicited. These fluctuations of physiopathological parameters would impact disease progression depending on the animal's model and bacterial strain used. The present study investigated the sex-dependent vulnerability of Wistar rats to K. pneumoniae ATCC 43816 lobar pneumonia induced by the intranasal instillation method. Methods: Experimental pneumonia was induced by K. pneumoniae ATCC 43816 in male and female Wistar rats following intranasal instillation. The physiopathogenesis of the disease was studied by bacteriological and histopathological exams, histomorphometric analysis of the blood and/or lung tissue, and body weight loss in infected animals. In addition, the overall severity of lesions was determined by the total score obtained by averaging the individual scores from the same group of animals. Results: The K. pneumoniae ATCC 43816 strain showed inoculation dose-, incubation time of the disease- and sex-dependent- differences in its ability to induce lobar pneumonia. Evaluation of different parameters showed that the disease peaked on day 15 post-inoculation, with more pathogenic effects on female rats. This observed sex-dependence difference in Wistar rats was mainly highlighted by the determined lethal dose 50 (LD50), bacterial load count in whole blood and lung tissues, body weight loss, inflammatory granulomas forming and diffuse alveolar damages. The pathogenicity was confirmed by scoring the severity of pathologic lesions of lung tissues. Conclusions: The results obtained highlighted the gender-dependency in the physiopathogenesis processes of K. pneumoniae ATCC 43816 induced-lobar pneumonia, in Wistar rats. Female Wistar rats' susceptibility is useful in studying pathology and in preclinical trial investigations of new treatments for infectious pneumonia. [ABSTRACT FROM AUTHOR]

Background: Neisseria meningitides, Streptococcus pneumonia, and hemophilic influenza type B are frequently linked to bacterial meningitis (BM) in children. It's an infectious sickness that kills and severely mobilizes children. For a variety of reasons, bacterial meningitis remains a global public health concern; most cases and deaths are found in Sub-Saharan Africa, particularly in Ethiopia. Even though vaccination has made BM more preventable, children worldwide are still severely harmed by this serious illness. Age, sex, and co-morbidity are among the risk variables for BM that have been found. Therefore, the main objective of this study was to identify the variables influencing the time to recovery for children with bacterial meningitis at Jigjiga University referral hospital in the Somali regional state of Ethiopia. Method: A retrospective cohort of 535 children with bacterial meningitis who received antibiotic treatment was the subject of this study. Parametric Shared Frailty ty and the AFT model were employed with log likelihood, BIC, and AIC methods of model selection. The frailty models all employed the patients' kebele as a clustering factor. Results: The number of cases of BM declined in young children during the duration of the 2 year, 11 month study period, but not in the elderly. Streptococcus pneumonia (50%), hemophilic influenza (30.5%), and Neisseria meningitides (15%) were the most frequent causes of BM. The time to recovery of patients from bacteria was significantly influenced by the covariates male patients (ϕ = 0.927; 95% CI (0.866, 0.984); p-value = 0.014), patients without a vaccination history (ϕ = 0.898; 95% CI (0.834, 0.965); P value = 0.0037), and patients who were not breastfeeding (ϕ = 0.616; 95% CI (0.404, 0.039); P-value = 0.024). The recovery times for male, non-breastfed children with bacterial patients are 7.9 and 48.4% shorter, respectively. In contrast to children with comorbidity, the recovery time for children without comorbidity increased by 8.7%. Conclusion: Age group, sex, vaccination status, co-morbidity, breastfeeding, and medication regimen were the main determinant factors for the time to recovery of patients with bacterial meningitis. Patients with co-morbidities require the doctor at Jigjiga University Referral Hospital to pay close attention to them. [ABSTRACT FROM AUTHOR]