Prevalence, spatial distribution and determinants of complete childhood pneumococcal conjugate vaccination in Ethiopia: spatial and multilevel analyses.

INTRODUCTION: Pneumococcal disease is a serious global public health concern. The primary causative agent of severe illnesses such as pneumonia, meningitis, acute otitis media, and bacteremia is the pneumococcus bacterium. The pneumococcal conjugate vaccine is a key strategy to reduce the burden of pneumococcal disease. Understanding the spatial distribution of complete childhood pneumococcal conjugate vaccine utilization and its associated factors is crucial for designing strategies to improve vaccination implementation. Therefore, this study aimed to determine the spatial distribution of complete childhood pneumococcal conjugate vaccination coverage and identify its determinants in Ethiopia. METHOD: A spatial and multilevel analysis was conducted using data from the 2019 Ethiopian Mini Demographic and Health Survey. The analysis included a total of 2,055 weighted children. The association between the outcome variable and the explanatory variables was determined by calculating adjusted odds ratios at a 95% confidence interval. Explanatory variables were considered significantly associated with the outcome if the p-value was less than 0.05. RESULT: The prevalence of complete childhood pneumococcal conjugate vaccination in Ethiopia was 53.94% (95% CI: 51.77, 56.08). Higher complete childhood pneumococcal vaccination coverage was observed in the Addis Ababa, Tigray, Amhara, Benishangul-Gumuz, and Oromia regions, while lower coverage was seen in the Afar, Somali, and SNNPR regions of Ethiopia. Factors significantly associated with complete childhood pneumococcal conjugate vaccination included maternal age, antenatal care visits, place of delivery, region, community women's literacy level, community poverty level, and community antenatal care utilization. CONCLUSION: The distribution of complete childhood pneumococcal conjugate vaccination exhibited spatial variability across Ethiopia. Approximately half of children aged twelve to thirty-five months received the full dose of the childhood pneumococcal conjugate vaccine in the country. Several factors were identified as statistically significant determinants of complete childhood pneumococcal conjugate vaccination, including maternal age, antenatal care visits, place of delivery, region, community women's literacy level, community poverty level, and community ANC utilization. Therefore, policies and strategies aimed at combating pneumococcal disease should consider these determinants and address areas with low vaccination coverage.

Signal recognition particle RNA is critical for genetic competence and virulence of Streptococcus pneumoniae.

Streptococcus pneumoniae (pneumococcus) causes a wide range of important human infectious diseases, including pneumonia, pneumonia-derived sepsis, otitis media, and meningitis. Pneumococcus produces numerous secreted proteins that are critical for normal physiology and pathogenesis. The membrane targeting and translocation of these secreted proteins are partly mediated by the signal recognition particle (SRP) complex, which consists of 4.5S small cytoplasmic RNA (ScRNA), and the Ffh, and FtsY proteins. Here, we report that pneumococcal ∆scRNA, ∆ffh, and ∆ftsY mutants were significantly impaired in competence induction, competence pili production, exogenous DNA uptake, and genetic transformation. Also, the ∆scRNA mutant was significantly attenuated in the mouse models of bacteremia and pneumonia. Interestingly, unlike the ∆scRNA, both ∆ffh and ∆ftsY mutants had growth defects on Todd-Hewitt Agar, which were alleviated by the provision of free amino acids or serum. Differences in nutritional requirements between ∆ffh and ∆ftsY vs ∆scRNA suggest that Ffh and FtsY may be partially functional in the absence of ScRNA. Finally, the insertase YidC2, which could functionally rescue some SRP mutations in other streptococcal species, was not essential for pneumococcal genetic transformation. Collectively, these results indicate that ScRNA is crucial for the successful development of genetic competence and virulence in pneumococcus. IMPORTANCE: Streptococcus pneumoniae (pneumococcus) causes multiple important infectious diseases in humans. The signal recognition particle (SRP) complex, which comprised 4.5S small cytoplasmic RNA (ScRNA), and the Ffh and FtsY proteins, mediates membrane targeting and translocation of secreted proteins in all organisms. However, the role of SRP and ScRNA has not been characterized during the induction of the competence system for genetic transformation and virulence in pneumococcus. By using a combination of genetic, biochemical, proteomic, and imaging approaches, we demonstrated that the SRP complex plays a significant role in membrane targeting of competence system-regulated effectors important for genetic transformation, virulence during bacteremia and pneumonia infections, and nutritional acquisition.

Management of the vaccination campaign in a population of frail older outpatients affected by cognitive or endocrinological conditions: a pilot study in Italy.

Vaccination, particularly against pneumococcus and influenza, is a low-cost primary prevention, useful to avoid hard complications, particularly among frail older people. In this pilot study, we aimed to assess the effect of a strategy for influenza and pneumococcal vaccination for outpatients mainly affected by cognitive or endocrinological conditions, evaluating what could stimulate or demotivate vaccination among older people. This study was conducted during the 2023-2024 influenza season at the outpatient clinics in Palermo, Italy. A total 76 patients were included. More than half of the patients could be considered as pre-frail and about 20% frail, according to a comprehensive geriatric evaluation. Among patients, 46.05% received only vaccination against pneumococcus, 28.95% both vaccinations, and 25.0% only against influenza. Compared with the previous seasons, a 19.5% increase of influenza and 90.2% of pneumococcal vaccine uptake was observed. Side effects of vaccination were the main reason of the previous rejection, namely 76.9% for influenza and 53.8% for anti-pneumococcal vaccination. In conclusion, our study indicates how a new vaccination strategy in different settings could be feasible. Proposing influenza and pneumococcal vaccination for frail older outpatients could be an effective instrument to improve immunization coverage that is still low among older people.

Natural carriage of Streptococcus pneumoniae is associated with increased experimental pneumococcal carriage but reduced conjugate vaccine efficacy in a human challenge model.

BACKGROUND: In Malawi, the national pneumococcal conjugate vaccine (PCV13) demonstrated less herd immunity than the USA, likely due to higher natural pneumococcal carriage rates. We assessed PCV13 efficacy against experimental pneumococcal carriage in healthy Malawian adults. We explored how natural carriage (pneumococcal carriage of any other serotype apart from 6B) influenced experimental carriage rates and vaccine efficacy. METHODS: Healthy adults aged 18-40 were randomly assigned PCV13 (n=98) or saline (n=106), followed by intranasal SPN 6B inoculation at 20,000 (n=40), 80,000 (n=74), or 160,000 (n=90) CFU/100µl, 28 days post-vaccination. We evaluated natural and experimental pneumococcal carriage before and after vaccination on days 2, 7, and 14 post-inoculation using culture and multiplex qPCR targeting lytA/cpsA genes and compared carriage rates by vaccination status. RESULTS: Of 204 participants, 19.6% (40) exhibited experimental carriage, detected by culture and 25.5% (52) by qPCR. Vaccinated individuals had lower experimental carriage rates (10.2%, n=10/98) compared to the placebo group (28.3%, n=30/106). This difference in vaccine efficacy was more pronounced in participants without natural carriage (PCV13=8% n=6/75 vs. placebo=25.9%, n=21/81) compared to those with natural carriage (PCV13=14.8%, n=4/27 vs. placebo=26.5%, n=9/34). Using a log-binomial model, vaccine effectiveness (VE) was 62%, whether assessed by culture or qPCR. Natural carriers had a lower VE of 52% compared to participants with no natural carriage (VE=69%). CONCLUSION: We have shown that PCV13 VE estimate (62%) is robust whether carriage is assessed by culture or qPCR. PCV13 had lower VE in natural carriers compared to those without natural carriage at the inoculation visit.

Prevalence, Clinical Severity, and Serotype Distribution of Pneumococcal Pneumonia Among Adults Hospitalized With Community-Acquired Pneumonia in Tennessee and Georgia, 2018-2022.

INTRODUCTION: Understanding the pneumococcal serotypes causing community-acquired pneumonia (CAP) is essential for evaluating the impact of pneumococcal vaccines. METHODS: We conducted a prospective surveillance study of adults aged ≥18 years hospitalized with CAP at 3 hospitals in Tennessee and Georgia between 1 September 2018 and 31 October 2022. We assessed for pneumococcal etiology with cultures, the BinaxNOW urinary antigen detection test, and serotype-specific urinary antigen detection assays that detect 30 pneumococcal serotypes contained in the investigational pneumococcal conjugate vaccine V116, as well as licensed vaccines PCV15 and PCV20 (except serotype 15B). The distribution of pneumococcal serotypes was calculated based on serotype-specific urinary antigen detection results. RESULTS: Among 2917 hospitalized adults enrolled with CAP, 352 (12.1%) patients had Streptococcus pneumoniae detected, including 51 (1.7%) patients with invasive pneumococcal pneumonia. The 8 most commonly detected serotypes were: 3, 22F, 19A, 35B, 9N, 19F, 23A, and 11A. Among 2917 adults with CAP, 272 (9.3%) had a serotype detected that is contained in V116, compared to 196 (6.7%) patients with a serotype contained in PCV20 (P < .001), and 168 (5.8%) patients with a serotype contained in PCV15 (P < .001). A serotype contained in V116 but not PCV15 or PCV20 was detected in 120 (4.1%) patients, representing 38.0% of serotype detections. CONCLUSIONS: Approximately 12% of adults hospitalized with CAP had S. pneumoniae detected, and approximately one-third of the detected pneumococcal serotypes were not contained in PCV15 or PCV20. Development of new pneumococcal vaccines with expanded serotype coverage has the potential to prevent a substantial burden of disease.

A low-cost culture- and DNA extraction-free method for the molecular detection of pneumococcal carriage in saliva.

Molecular methods have improved the sensitivity of the detection of pneumococcal carriage in saliva. However, they typically require sample culture enrichment and nucleic acid extraction prior to performing the detection assay and may limit scalability for extensive surveillance of pneumococcus, particularly in low-resource settings. We evaluated the performance of a DNA-extraction-free method for the detection of pneumococcus in saliva. We developed a streamlined qPCR-based protocol for the detection of pneumococcus, omitting culture enrichment and DNA extraction. Using saliva samples collected from children attending childcare centers (New Haven, CT, USA), we evaluated the detection of pneumococcus using saliva lysates as compared to purified DNA extracted from culture-enriched aliquots of the paired samples using qPCR targeting the pneumococcal piaB gene. Of the 759 saliva samples tested from 92 children [median age 3.65 years; IQR (2.46-4.78)], pneumococcus was detected in 358 (47.2%) saliva lysates prepared using the extraction-free protocol and in 369 (48.6%) DNA extracted from culture-enriched samples. We observed near-perfect agreement between the two protocols (Cohen's kappa: 0.92; 95% CI: 0.90-0.95). Despite a high correlation between CT values generated by the two methods (r = 0.93, P < 0.0001), the CT values generated from saliva lysates were higher (lower concentration) than those from culture-enriched samples (ΔCT = 6.69, P < 0.00001). The cost of detecting pneumococcus using saliva lysates was at least fivefold lower (US$2.53) compared to the cost of the culture-enriched method (range: US$13.60-US$19.46). For pneumococcal carriage surveillance in children, our findings suggest that a DNA extraction-free approach may offer a cost-effective alternative to the resource-intensive culture-enrichment method.IMPORTANCESurveillance for carriage of pneumococcus is a key component of evaluating the performance of pneumococcal vaccines and informing new vaccination strategies. To improve the scalability of pneumococcal carriage surveillance, we show that molecular detection of pneumococcus in saliva from children can be performed without culture enrichment and DNA extraction. Our findings show that using the extraction-free method can improve surveillance efforts for pneumococcal carriage in children, overcoming the resource-intensive hurdle that comes with the use of molecular methods, particularly in low-resource settings.

RNase R Affects the Level of Fatty Acid Biosynthesis Transcripts Leading to Changes in membrane Fluidity.

Previous studies on RNase R have highlighted significant effects of this ribonuclease in several processes of Streptococcus pneumoniae biology. In this work we show that elimination of RNase R results in overexpression of most of genes encoding the components of type II fatty acid biosynthesis (FASII) cluster. We demonstrate that RNase R is implicated in the turnover of most of transcripts from this pathway, affecting the outcome of the whole FASII cluster, and ultimately leading to changes in the membrane fatty acid composition. Our results show that the membrane of the deleted strain contains higher proportion of unsaturated and long-chained fatty acids than the membrane of the wild type strain. These alterations render the RNase R mutant more prone to membrane lipid peroxidation and are likely the reason for the increased sensitivity of this strain to detergent lysis and to the action of the bacteriocin nisin. Reprogramming of membrane fluidity is an adaptative cell response crucial for bacterial survival in constantly changing environmental conditions. The data presented here is suggestive of a role for RNase R in the composition of S. pneumoniae membrane, with strong impact on pneumococci adaptation to different stress situations.

Oropharyngeal microbial ecosystem perturbations influence the risk for acute respiratory infections in common variable immunodeficiency.

Background: The respiratory tract microbiome is essential for human health and well-being and is determined by genetic, lifestyle, and environmental factors. Patients with Common Variable Immunodeficiency (CVID) suffer from respiratory and intestinal tract infections, leading to chronic diseases and increased mortality rates. While CVID patients' gut microbiota have been analyzed, data on the respiratory microbiome ecosystem are limited. Objective: This study aims to analyze the bacterial composition of the oropharynx of adults with CVID and its link with clinical and immunological features and risk for respiratory acute infections. Methods: Oropharyngeal samples from 72 CVID adults and 26 controls were collected in a 12-month prospective study. The samples were analyzed by metagenomic bacterial 16S ribosomal RNA sequencing and processed using the Quantitative Insights Into Microbial Ecology (QIME) pipeline. Differentially abundant species were identified and used to build a dysbiosis index. A machine learning model trained on microbial abundance data was used to test the power of microbiome alterations to distinguish between healthy individuals and CVID patients. Results: Compared to controls, the oropharyngeal microbiome of CVID patients showed lower alpha- and beta-diversity, with a relatively increased abundance of the order Lactobacillales, including the family Streptococcaceae. Intra-CVID analysis identified age >45 years, COPD, lack of IgA, and low residual IgM as associated with a reduced alpha diversity. Expansion of Haemophilus and Streptococcus genera was observed in patients with undetectable IgA and COPD, independent from recent antibiotic use. Patients receiving azithromycin as antibiotic prophylaxis had a higher dysbiosis score. Expansion of Haemophilus and Anoxybacillus was associated with acute respiratory infections within six months. Conclusions: CVID patients showed a perturbed oropharynx microbiota enriched with potentially pathogenic bacteria and decreased protective species. Low residual levels of IgA/IgM, chronic lung damage, anti antibiotic prophylaxis contributed to respiratory dysbiosis.

Invasive pneumococcal disease surveillance in Canada, 2021-2022.

Background: Invasive pneumococcal disease (IPD, Streptococcus pneumoniae) has been a nationally notifiable disease in Canada since 2000. The use of conjugate vaccines has caused a shift in the distribution of serotypes over time. This report is a summary of the demographics, serotypes and antimicrobial resistance of IPD isolates collected in Canada in 2021 and 2022. Methods: The National Microbiology Laboratory (NML) of the Public Health Agency of Canada in Winnipeg, Manitoba collaborates with provincial and territorial public health laboratories to conduct national surveillance of IPD. There were 1,999 isolates reported in 2021 and 3,775 isolates in 2022. Serotype was determined by the Quellung reaction or whole-genome sequencing (WGS). Antimicrobial susceptibilities were determined by WGS methods, broth microdilution, or data shared by collaborators in the Canadian Antimicrobial Resistance Alliance program at the University of Manitoba. Population-based IPD incidence rates were obtained through the Canadian Notifiable Disease Surveillance System. Results: The incidence of IPD in Canada was 5.62 cases per 100,000 population in 2021, decreasing from the peak of 10.86 cases per 100,000 population in 2018. Serotypes with increasing trends (p<0.05) between 2018 and 2022 included: 4 (6.1%-12.4%), 9V (1.0%-5.1%) and 12F (4.8%-5.4%). The overall prevalence of PCV13 serotypes increased over the same period (31.2%-41.5%, p<0.05) while the prevalence of non-vaccine types decreased significantly (27.3%-21.5%, p<0.0001). The highest rates of antimicrobial resistance in 2021 and 2022 were seen with clarithromycin (21%, 2021; 24%, 2022) and erythromycin (22%, 2021; 24%, 2022). Multidrug-resistant IPD continued to increase from 2018 to 2022 (6.7%-12.6%, p<0.05). Conclusion: The number of cases of IPD continued to decrease in 2021 in comparison to previous years, however, 2022 saw a return to pre-COVID-19 levels. Disease due to PCV13 serotypes 3, 4, 9V and 19F, as well as non-PCV13 serotypes 12F and 20, is increasing in prevalence. Surveillance of IPD to monitor changing serotype distribution and antimicrobial resistance is essential.

[Mortality in bacterial pneumonia due to pneumococcus]. / Mortalidad en neumonía bacteriémica por neumococo.

INTRODUCTION: Despite improvements in health care, pneumonia-associated mortality remains high. The objective of this study was to analyze the factors associated with mortality in bacteremic pneumonia caused by pneumococcus. METHODS: Retrospective cohort study in adult patients with pneumonia diagnosis and isolation of pneumococcus in blood cultures, between January 2012 and May 2021, was carried out. Clinical and laboratory variables, radiological involvement, evolution and mortality during hospitalization were analyzed. The group of deceased patients was compared with that of survivors. RESULTS: 152 patients were included. Median age: 58 years; men: 58.9%; 33% presented a CURB-65 > than 2 at admission. Overall mortality: 34% (n=52). Deceased patients were more tachypneic on admission (respiratory rate 26 vs. 22; p=0.003), presented sensory alteration more frequently (58% vs. 14%; p< 0.001), PaO2/fraction of inspired oxygen ratio < 250 (58% vs. 22%; p<0.001), bilateral radiological compromise (50% vs. 32%; p=0.03), needed mechanical ventilation (50% vs 12%; p< 0.001), higher blood creatinine values (1.6 vs. 1.15; p=0.01), lower white blood cell count (10 900 vs 17 400; p=0.002), a lower glucose dosage (111 vs. 120; p=0.01), and fewer days of hospital stay (6 vs. 9; p=0.015). In logistic regression model, significant differences were maintained in the following factors associated with mortality: mechanical ventilation (OR=3.54), altered mental status (OR=5.95), chest X-ray with bilateral compromise (OR 3.20) and PAFI less than 250 (OR=3.62). CONCLUSION: In our series, the factors related to mortality, despite the presence of bacteremia, do not differ from those published in the literature and which are part of the different prognostic scores used in routine practice.

Introducción: A pesar de las mejoras en los cuidados de la salud, la mortalidad asociada a neumonía continúa siendo alta. El objetivo de este estudio fue analizar los factores asociados a mortalidad en neumonía bacteriémica por neumococo. Métodos: Estudio de cohorte retrospectiva en pacientes adultos con diagnóstico de neumonía y neumococo aislado en hemocultivos, entre enero 2012 y mayo 2021. Se analizaron: variables clínicas y de laboratorio, compromiso radiológico, evolución y mortalidad durante la internación. Se comparó el grupo de pacientes fallecidos con el de sobrevivientes. Resultados: Se incluyeron 152 pacientes. La mediana de edad fue de 58 años y el 58.9% fueron hombres. El 33% presentó un CURB-65 mayor a 2 al momento de internación. La mortalidad global fue 34% (n=52). Los pacientes fallecidos se encontraban más frecuentemente taquipneicos al ingreso (frecuencia respiratoria 26 vs. 22; p=0.003), presentaban más frecuentemente alteración del sensorio (58% vs. 14%; p< 0.001), PaO2/fracción inspirada de oxígeno (PAFI) < 250 (58% vs. 22%; p<0.001), compromiso radiológico bilateral (50% vs. 32%; p=0.03), necesidad de asistencia respiratoria mecánica (ARM) (50% vs. 12%; p< 0.001), mayor valor de creatinina en sangre (1.6 vs. 1.15; p=0.01), menor recuento de glóbulos blancos (10 900 vs. 17 400; p=0.002), menor valor de glucemia (111 vs. 120; p=0.01) y menos días de estancia hospitalaria (6 vs. 9; p=0.015). En el análisis de regresión logística multivariable se mantuvieron diferencias significativas en los siguientes factores asociados a mortalidad: ventilación mecánica (OR=3.54), confusión (OR=5.95), radiografía con compromiso bilateral (OR= 3.20) y PAFI < 250 (OR=3.62). Conclusión: Los factores relacionados con mortalidad, a pesar de la presencia de bacteriemia, no difieren de los publicados en la literatura y forman parte de los scores pronósticos de práctica habitual.

Activating A1 adenosine receptor signaling boosts early pulmonary neutrophil recruitment in aged mice in response to Streptococcus pneumoniae infection.

BACKGROUND: Streptococcus pneumoniae (pneumococcus) is a leading cause of pneumonia in older adults. Successful control of pneumococci requires robust pulmonary neutrophil influx early in infection. However, aging is associated with aberrant neutrophil recruitment and the mechanisms behind that are not understood. Here we explored how neutrophil recruitment following pneumococcal infection changes with age and the host pathways regulating this. RESULTS: Following pneumococcal infection there was a significant delay in early neutrophil recruitment to the lungs of aged mice. Neutrophils from aged mice showed defects in trans-endothelial migration in vitro compared to young controls. To understand the pathways involved, we examined immune modulatory extracellular adenosine (EAD) signaling, that is activated upon cellular damage. Signaling through the lower affinity A2A and A2B adenosine receptors had no effect on neutrophil recruitment to infected lungs. In contrast, inhibition of the high affinity A1 receptor in young mice blunted neutrophil recruitment to the lungs following infection. A1 receptor inhibition decreased expression of CXCR2 on circulating neutrophils, which is required for trans-endothelial migration. Indeed, A1 receptor signaling on neutrophils was required for their ability to migrate across endothelial cells in response to infection. Aging was not associated with defects in EAD production or receptor expression on neutrophils. However, agonism of A1 receptor in aged mice rescued the early defect in neutrophil migration to the lungs and improved control of bacterial burden. CONCLUSIONS: This study suggests age-driven defects in EAD damage signaling can be targeted to rescue the delay in pulmonary neutrophil migration in response to bacterial pneumonia.

Qualification of a 21-valent pneumococcal urine antigen detection assay and development of clinical positivity cutoffs.

Aim: Serotype-specific assays detecting pneumococcal polysaccharides in bodily fluids are needed to understand the pneumococcal serotype distribution in non-bacteremic pneumonia.Methods: We developed a urine antigen detection assay and using urine samples from adult outpatients without pneumonia developed positivity cutoffs for both a previously published 15-valent and the new 21-valent assay. Clinical sensitivity was confirmed with samples from patients with invasive pneumococcal disease.Results: Total assay precision ranged from 7.6 to 17.8% coefficient of variation while accuracy ranged between 80 and 150% recovery, except for three serotypes where recoveries ranged from 32 to 60%. Clinical sensitivity was 86.4% and specificity was 96.5% across all 30 serotypes.Conclusion: The assay could potentially assess serotype-distribution in non-infected and infected participants with pneumococcal disease.

[Box: see text].

Clinical and Microbial Determinants of Upper Respiratory Colonization with Streptococcus pneumoniae and Native Microbiota in People with HIV-1 and Control Adults.

BACKGROUND: The substantial risk for respiratory and invasive infections with Streptococcus pneumoniae (Spn) among people with HIV-1 (PWH) begins with asymptomatic colonization. The frequency of Spn colonization among U.S. adults with and without HIV-1 infection is not well-characterized in the conjugate vaccine era. METHODS: We determined Spn colonization frequency by culture and specific lytA gene QPCR and microbiota profile by 16S rRNA gene sequencing in nasopharyngeal (NP) and oropharyngeal (OP) DNA from 138 PWH and 93 control adults and associated clinical characteristics. RESULTS: The frequencies of Spn colonization among PWH and controls did not differ (11.6% vs 8.6%, respectively; p=0.46) using combined results of culture and PCR, independent of vaccination or behavioral risks. PWH showed altered microbiota composition (i.e., beta-diversity. NP: p=0.0028, OP: p=0.0098), decreased alpha-diversity (NP: p=0.024, OP: p=0.0045), and differences in the relative abundance of multiple bacterial taxa. Spn colonization was associated with altered beta-diversity in the NP (p=0.011), but not OP (p=0.21). CONCLUSIONS: Despite widespread conjugate vaccine and antiretroviral use, frequencies of Spn colonization among PWH and controls are currently consistent with those reported in the pre-conjugate era. The persistently increased risk of pneumococcal disease despite ART may relate to behavioral and immunologic variables other than colonization.

Decline in pneumococcal vaccine serotype carriage, multiple-serotype carriage, and carriage density in Nepalese children after PCV10 introduction: A pre-post comparison study.

BACKGROUND: Carriage studies are an efficient means for assessing pneumococcal conjugate vaccine effect in settings where pneumococcal disease surveillance programmes are not well established. In this study the effect of 10-valent pneumococcal conjugate vaccine (PCV10) introduction on pneumococcal carriage and density among Nepalese children using a bacterial microarray and qPCR was examined. METHODS: PCV10 was introduced into the Nepalese infant immunisation schedule in August 2015. Nasopharyngeal swabs were collected from healthy Nepalese children in Kathmandu between April 2014 and December 2021. Samples were plated on blood agar, incubated overnight, and DNA extracted from plate sweeps. Pneumococcal serotyping was done using the Senti-SPv1.5 microarray (BUGS Bioscience, UK). DNA was extracted from swab media and qPCR performed for pneumococcal autolysin (lytA). RESULTS: A significant decline in prevalence of PCV10 serotypes was observed when comparing pre-PCV10 with post-PCV10 collection periods (36.5 %, 454/1244 vs 10.3 %, 243/2353, p < 0.0001). Multiple-serotype carriage was also observed to significantly decline when comparing pre-PCV10 with post-PCV10 periods (31.4 %, 390/1244 vs 22.2 %, 522/2353, p < 0.0001). Additionally, a significant decline in median pneumococcal density was observed when comparing pre-PCV10 with post-PCV10 periods (3.3 vs 3.25 log10 GE/ml, p = 0.0196). CONCLUSIONS: PCV10 introduction was associated with reduced, prevalence of all PCV10 serotypes, multiple serotype carriage, and pneumococcal carriage density.

Prior pneumococcal vaccination improves in-hospital mortality among elderly population hospitalized due to community-acquired pneumonia.

BACKGROUND: Pneumococcal vaccination is a preventive method to reduce pneumonia related mortality. However, real-world data on efficacy of the pneumococcal vaccine in reducing mortality is lacking, especially in elderly patients. This study was conducted to assess the effects of prior pneumococcal vaccination in elderly pneumonia patients. METHODS: The data was procured from the Health Insurance Review and Assessment and Quality Assessment database. Hospitalized patients who met the criteria of community-acquired pneumonia (CAP) were included and they were grouped according to vaccination state. Patients were aged ≥ 65 years and treated with beta-lactam, quinolone, or macrolide. Patients were excluded when treatment outcomes were unknown. RESULTS: A total of 4515 patients were evaluated, and 1609 (35.6%) of them were vaccinated prior to hospitalization. Mean age was 77.0 [71.0;82.0], 54.2% of them were male, and mean Charlson comorbidity index (CCI) was 3.0. The patients in the vaccinated group were younger than those in the unvaccinated group (76.0 vs. 78.0 years; P < 0.001), and showed higher in-hospital improvement (97.6 vs. 95.0%; P < 0.001) and lower 30-day mortality (2.6 vs. 5.3%; P < 0.001). After adjusting confounding factors such as age, gender, CURB score and CCI score, the vaccinated group demonstrated a significant reduction in 30-day mortality (hazard ratio [HR] 0.58, 95% confidence interval [CI] 0.41-0.81; P < 0.01) and in-hospital mortality (HR 0.53, 95% CI0.37-0.78; P < 0.001) compared to the unvaccinated group in multivariate analysis. Vaccinated group showed better 30-day survival than those in non-vaccinated group (log-rank test < 0.05). CONCLUSIONS: Among elderly hospitalized CAP patients, prior pneumococcal vaccination was associated with improved in-hospital mortality and 30-day mortality.

Diabetes Mellitus and Pneumococcal Pneumonia.

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.

The Uptake of Pneumococcal and Seasonal Influenza Vaccinations Based on Perceptions and Attitudes Toward the COVID-19 Vaccine Among Patients With Diabetes.

Objective In this study, we aimed to assess the rates of pneumococcal and seasonal influenza vaccinations among elderly and nonelderly diabetes patients and examine their perceptions and attitudes toward the coronavirus disease 2019 (COVID-19) vaccine. Methods A single-center study was conducted among patients with diabetes, employing a structured survey encompassing sociodemographic data, vaccination records, and the COVID-19 vaccine perception and attitude scale. Results Among the 280 diabetes patients in our study, the vaccination rates for COVID-19, seasonal influenza, and pneumococcal vaccines were 96.1%, 16.8%, and 17.5%, respectively. A higher cumulative dosage of the COVID-19 vaccine was associated with older age (r = 0.463; p<0.001), increased safety score (r = 0.479; p<0.001), and lower conspiracy theory score (r = -0.336; p<0.001). Participants who had received COVID-19 and influenza vaccines were observed to have significantly higher safety scores related to COVID-19 vaccines (p<0.001; d = 2.381 and p = 0.008; d = 0.525, respectively). Notably, vaccination rates for influenza and pneumococcus were significantly different between nonelderly and elderly patients (8.7% vs. 29.6%; p<0.001 and 13.4% vs. 24.1%; p = 0.022). Elderly patients with diabetes were 3.3 times more likely to receive the influenza vaccine than nonelderly participants [odds ratio (OR) = 3.319; 95% confidence interval (CI) = 1.592 - 6.920; p = 0.001] and had a higher safety score related to COVID-19 vaccines (OR = 1.076; 95% CI = 1.011 - 1.146; p = 0.021). Conclusions Both influenza and pneumococcal vaccination rates were below the desired targets in this study. The vaccination rates among the nonelderly diabetes population suggest that this group may be more likely to neglect to receive vaccination compared to the elderly diabetes population. The association between vaccination rates and post-pandemic safety perceptions highlights the critical need to implement public health strategies specifically designed to address and improve safety-related information dissemination.

[Vaccination status and factors associated with pneumococcal vaccination in geriatric short-stay care]. / Statut vaccinal et facteurs associés à la vaccination antipneumococcique en court séjour gériatrique.

Nearly two-thirds of geriatric short-stay patients were eligible for pneumococcal vaccination. Among patients eligible for vaccination, less than 5 % had received at least one injection of pneumococcal vaccine on admission. We found no modifiable factors associated with vaccination status, but several avenues for improving vaccination coverage.

The prostaglandin D2 antagonist asapiprant ameliorates clinical severity in young hosts infected with invasive Streptococcus pneumoniae.

Streptococcus pneumoniae (pneumococcus) remains a serious cause of pulmonary and systemic infections globally, and host-directed therapies are lacking. The aim of this study was to test the therapeutic efficacy of asapiprant, an inhibitor of prostaglandin D2 signaling, against pneumococcal infection. Treatment of young mice with asapiprant after pulmonary infection with invasive pneumococci significantly reduced systemic spread, disease severity, and host death. Protection was specific against bacterial dissemination from the lung to the blood but had no effect on pulmonary bacterial burden. Asapiprant-treated mice had enhanced antimicrobial activity in circulating neutrophils, elevated levels of reactive oxygen species (ROS) in lung macrophages/monocytes, and improved pulmonary barrier integrity indicated by significantly reduced diffusion of fluorescein isothiocyanate (FITC)-dextran from lungs into the circulation. These findings suggest that asapiprant protects the host against pneumococcal dissemination by enhancing the antimicrobial activity of immune cells and maintaining epithelial/endothelial barrier integrity in the lungs.

Poor association between 13-valent pneumococcal conjugate vaccine-induced serum and mucosal antibody responses with experimental Streptococcus pneumoniae serotype 6B colonisation.

BACKGROUND: Pneumococcal carriage is the primary reservoir for transmissionand a prerequisite for invasive pneumococcal disease. Pneumococcal Conjugate Vaccine 13 (PCV13) showed a 62% efficacy in protection against experimental Streptococcus pneumoniae serotype 6B (Spn6B) carriage in a controlled human infection model (CHIM) of healthy Malawian adults. We, therefore, measured humoral responses to experimental challenge and PCV-13 vaccination and determined the association with protection against pneumococcal carriage. METHODS: We vaccinated 204 young, healthy Malawian adults with PCV13 or placebo and nasally inoculated them with Spn6B at least four weeks post-vaccination to establish carriage. We collected peripheral blood and nasal lining fluid at baseline, 4 weeks post-vaccination (7 days pre-inoculation), 2, 7, 14 and > 1 year post-inoculation. We measured the concentration of anti-serotype 6B Capsular Polysaccharide (CPS) Immunoglobulin G (IgG) and IgA antibodies in serum and nasal lining fluid using the World Health Organization (WHO) standardised enzyme-linked immunosorbent assay (ELISA). RESULTS: PCV13-vaccinated adults had higher serum IgG and nasal IgG/IgA anti-Spn6B CPS-specific binding antibodies than placebo recipients 4 to 6 weeks post-vaccination, which persisted for at least a year after vaccination. Nasal challenge with Spn6B did not significantly alter serum or nasal anti-CPS IgG binding antibody titers with or without experimental pneumococcal carriage. Pre-challenge titers of PCV13-induced serum IgG and nasal IgG/IgA anti-Spn6B CPS binding antibodies did not significantly differ between those that got experimentally colonised by Spn6B compared to those that did not. CONCLUSION: This study demonstrates that despite high PCV13 efficacy against experimental Spn6B carriage in young, healthy Malawian adults, robust vaccine-induced systemic and mucosal anti-Spn6B CPS binding antibodies did not directly relate to protection.