Streptococcus Pneumoniae Research Articles

Excellent antibacterial and anti-inflammatory efficacy of amoxicillin by AgNPs and their conjugates synthesized using Micromeria biflora crude flavonoid extracts

Antibacterial resistance is considered to be one of the major causes for mortality in coming years. In recent years green nanotechnology played a key role in addressing this problem. Biocompatible metal nanoparticles have gained popularity owing to their excellent therapeutic effects and minimal side effects. MethodWe report the synthesis of AgNPs and their amoxicillin conjugates (Ag-amoxi) using Micromeria biflora crude flavonoid extracts. The physicochemical properties of the synthesized NPs and Ag-amoxi conjugates were systematically evaluated using scanning electron microscopy (SEM), energy dispersive X-ray (EDX) and X-ray diffraction (XRD) analysis, Fourier transform infrared (FTIR), and UV–visible (UV–Vis) spectroscopic techniques. ResultsThe average sizes of AgNPs and Ag-amoxi conjugates were 45 and 62 nm, respectively. We have also explored the antibacterial, antioxidant, anti-inflammatory, and analgesic properties of the AgNPs and Ag-amoxi conjugates through in vivo and in vitro analysis. The Ag-amoxi conjugates showed better antibacterial potential against Streptococcus Pneumoniae (S.P), Staphylococcus aureus (S.A), Pseudomonas aeruginosa (P.A), and Methicillin resistance Staphylococcus aureus (MRSA) strain both the drug and AgNPs. Similarly, in vivo anti-inflammatory studies revealed that both Ag-amoxi (68 %) and AgNPs (64 %) had strong anti-inflammatory effects, with (***p < 0.001) significance at a dose of 10 mg kg−1 body weight as compared to standard, amoxicillin (45 %), and flavonoids extract (48 %) at a dose of 100 mg kg−1. The findings of the antinociceptive activities (writhing and hot plate tests) demonstrated that the Ag-amoxi conjugates produced fewer writhing (15 in 20 s) and a shorter latency time of 22 s as compared to vehicle-treated (tramadol) animals, amoxicillin, and P.E at much lower doses. In vitro antioxidant studies revealed that the Ag-amoxi conjugate has the potential to be used as an antioxidant with an IC50 value of 43.58, compared with AgNPs (46.34), amoxicillin (58.17), compared to the standard of ascorbic acid (34.14). ConclusionThese results reveals that these biologically inspired AgNPs and Ag-amoxi conjugate could be used to improve antibiotic efficiency and could play a critical role in addressing the multidrug resistance problem in coming years.

RSV and rhinovirus increase pneumococcal carriage acquisition and density, whereas nasal inflammation is associated with bacterial shedding

Epidemiological studies report the impact of co-infection with pneumococcus and respiratory viruses upon disease rates and outcomes, but their effect on pneumococcal carriage acquisition and bacterial load is scarcely described. Here, we assess this by combining natural viral infection with controlled human pneumococcal infection in 581 healthy adults screened for upper respiratory tract viral infection before intranasal pneumococcal challenge. Across all adults, respiratory syncytial virus (RSV) and rhinovirus asymptomatic infection confer a substantial increase in secondary infection with pneumococcus. RSV also has a major impact on pneumococcal density up to 9days post challenge. We also study rates and kinetics of bacterial shedding through the nose and oral route in a subset. High levels of pneumococcal colonization density and nasal inflammation are strongly correlated with increased odds of nasal shedding as opposed to cough shedding. Protection against respiratory viral infections and control of pneumococcal density may contribute to preventing pneumococcal disease and reducing bacterial spread.

Effect of Childhood Pneumococcal Conjugate Vaccination on Invasive Disease Serotypes in Serbia.

In Serbia, PCV10 was introduced into the routine immunization for children under 2 in 2018 and replaced by PCV13 in 2022. We evaluated their impact on the distribution of invasive pneumococcal disease (IPD) serotypes across all age groups. Overall, 756 isolates were obtained from patients with IPD between 2010 and 2023 through laboratory surveillance. In the post-vaccination period, serotypes 14, 19F, 23F, and 6A significantly declined, while 3 and 19A considerably increased. This was especially evident in the ≤2 years group, making these serotypes the most prevalent among them. Serotype 3 dominated, representing 19.1% of all invasive isolates prior to 2018 and 33.1% thereafter. While serotype coverage of PCV10 has significantly decreased in the ≤2 years group (from 74.2% before 2018 to 29.5% after 2018), PCV13 coverage was 63.9% after 2018. In the post-PCV period, non-PCV13 serotypes, such as 9N, 10A, 15A, 15B, 15C, 22F, 6C, 6D, and 7C, increased across all isolates. Antibiotic non-susceptibility considerably decreased after 2018. MLST analysis showed shifts in sequence type prevalence, with pre-PCV lineages replaced and ongoing serotype 3 persistence, alongside potential capsule-switching events. These findings emphasize a noticeable shift in the distribution of serotypes and adaptability of pneumococcal populations, highlighting the importance of ongoing surveillance and the requirement for the urgent introduction of higher valent vaccines into the National Immunization Program.

Indirect impact of childhood 13-valent pneumococcal conjugate vaccine (PCV13) in Canadian older adults: a Canadian Immunization Research Network (CIRN) retrospective observational study

Background13-valent pneumococcal conjugate vaccine (PCV13) has been part of publicly funded childhood immunisation programmes in Ontario and British Columbia (BC) since 2010. We assessed the indirect impact of infant PCV13...

Associations of mental health with vaccination readiness in informal caregivers and the vaccination status of their care recipients during the Covid-19 pandemic – A cross sectional analysis

IntroductionVaccinations are important for informal caregivers and their care recipients. Mental health problems are common among care givers. The aim of this study was to investigate vaccination readiness in informal caregivers and associations with mental health issues. Associations between vaccination readiness in informal caregivers and the vaccination status of their aged care recipients were examined. MethodsWithin the multicenter prospective registry study ‘Bavarian ambulatory Covid-19 Monitor (BaCoM) ‘, informal caregivers were asked for symptoms of depression (PHQ-9), burden of caretaking (BSFC-s), psychological antecedents of vaccination readiness (5C model) and previous Covid-19 infections of their care recipients. The vaccination status against Covid-19, seasonal influenza and pneumococcal disease was determined via vaccination certificates. Data analysis was performed using ordinal regressions and Mann-Whitney-U tests. ResultsData of n = 91 informal caregivers, associated with n = 84 care recipients were collected. Symptoms of depression were associated with reduced vaccination readiness (Calculation: p = 0.026, OR = 1.18), as well as the perceived burden of caretaking (Confidence: p = 0.006, OR = 0.88). A previous Covid-19 infection of the care recipients was associated with decreased vaccination readiness of informal caregivers (Median (Q1–Q3) Confidence: 5.0 (4.5–6.0) vs. 4.0 (3.0–5.0); Calculation: 5.0 (3.0–6.0) vs. 4.0 (1.0–5.0)). The vaccination status of the care recipients interrelated significantly with vaccination readiness of their informal caregivers (Confidence: p < 0.001; Complacency: p < 0.01; Constraints p < 0.05). No significant interrelations between vaccination readiness and the vaccination status against seasonal influenza or pneumococcal disease occurred. ConclusionMental health issues of informal caregivers seem to be associated with the actual vaccination status against Covid-19 in their care recipients. Target group specific counselling as well as an active involvement of informal caregivers in shared decision-making processes can be of relevance, but even more attention should be paid to the protection of mental health for informal caregivers.Trial registration number: German Register of Clinical Studies DRKS 26039.

Pneumococcal Vaccination Rates and Associated Meningitis Events in Patients With Acute Cerebrospinal Fluid Leak.

To characterize the institutional utilization of pneumococcal vaccination during an index hospital admission for acute cerebrospinal fluid (CSF) leakage and associated infectious and clinical outcomes. This retrospective cohort study included patients hospitalized and treated for an acute CSF leak from January 2017 to June 2022. The primary outcome evaluated the incidence of pneumococcal vaccination during the index admission in patients without prior vaccination. Secondary outcomes evaluated the incidence of meningitis, time from CSF leak identification to meningitis, and mortality within 1 year of the index admission. A total of 94 patients were included. Nineteen (20.2%) patients received pneumococcal vaccination prior to admission. Of the 75 patients without prior vaccination, 4 (5.3%) patients received vaccination during the admission. Meningitis occurred in 5/94 (5.3%) patients and occurred 4-24 days from CSF leak identification. Mortality was observed in 9/94 (9.6%) patients. None of the meningitis cases were attributed to culture-positive findings of pneumococcal disease. The results of this study demonstrate an overall low institutional utilization of pneumococcal vaccination in patients with an acute CSF leak. Infectious and clinical outcomes reflected comparable to previous reported literature. Further evaluation into the risk-benefit relationship of vaccination omission is warranted in this patient population.

Potential impact of replacing the 13-valent pneumococcal conjugate vaccine with 15-valent or 20-valent pneumococcal conjugate vaccine in the 1 + 1 infant schedule in England: a modelling study

Paediatric pneumococcal conjugate vaccine (PCV) programmes in England using seven-valent PCV (PCV7) in 2006 and 13-valent PCV (PCV13) in 2010 have reduced vaccine-type invasive pneumococcal disease, but the overall effect has been reduced by an increase in invasive pneumococcal disease due to non-vaccine serotypes and serotype 3. We developed pneumococcal transmission models to investigate the potential effect on invasive pneumococcal disease of higher valency PCVs covering an additional two (ie, 15-valent PCV [PCV15]) or seven serotypes (ie, 20-valent PCV [PCV20]) in England. We conducted a modelling study using realistic, age-structured, and compartmental deterministic models fitted to carriage data from before the introduction of PCVs and invasive pneumococcal disease data from before and after the introduction of PCV7 and PCV13 in England from the UK Heath Security Agency invasive pneumococcal disease surveillance system. We estimated key parameters, including PCV7 and PCV13 efficacy against vaccine-type carriage and invasiveness of PCV7 serotypes; the additional serotypes in PCV13, PCV15 and PCV20; and non-vaccine serotypes. We simulated the effect of transitioning from PCV13 to PCV15 or PCV20 in infants under the current 1 + 1 vaccination schedule and investigated the effect of reduced carriage protection against PCV13 serotypes due to attenuation of immunogenicity in higher valency vaccines. Our results suggest that PCV15 might increase overall invasive pneumococcal disease as the reduction in vaccine-type invasive pneumococcal disease would be counterbalanced by an increase in non-PCV15 invasive pneumococcal disease. By contrast, PCV20 is projected to have a substantial impact on overall invasive pneumococcal disease due to higher invasiveness of the additional serotypes covered by PCV20 than the replacing non-vaccine serotypes. Reduced carriage protection against PCV13 serotypes with higher valency vaccines would amplify these effects. Replacing PCV13 with PCV20 is likely to have a substantial public health benefit, but PCV15 could potentially increase the overall burden of disease. UK Health Security Agency and National Institute of Health Research.

Assessing the Impact of Pneumococcal Conjugate Vaccine Immunization Schedule Change From 3+0 to 2+1 in Australian Children: A Retrospective Observational Study.

In mid-2018, the Australian childhood 13-valent pneumococcal conjugate vaccine schedule changed from 3+0 to 2+1, moving the third dose to 12 months of age, to address increasing breakthrough cases of invasive pneumococcal disease (IPD), predominantly in children aged >12 months. This study assessed the impact of this change using national IPD surveillance data. Pre- and postschedule change 3-dose 13-valent pneumococcal conjugate vaccine breakthrough cases were compared by age group, serotype, and clinical syndrome. Annual rates of breakthrough cases were calculated (per 100 000) using respective birth cohort sizes and 3-dose vaccine coverage. Using time-series modelling, observed IPD rates in children aged <12 years were compared to that expected if the 3+0 schedule were continued. Over 2012-2022, rate of 3-dose breakthrough cases in children aged >12 months was 2.8 per 100 000 (n = 557; 11 birth cohorts). Serotype 3 replaced 19A as predominant breakthrough serotype (respectively, 24% and 65% in 2013 to 60% and 20% in 2022) followed by 19F. In breakthrough cases, the most frequent clinical phenotype was bacteremic pneumonia (69%), with meningitis accounting for 3%-4%. In cohorts eligible for 2+1 versus 3+0 schedules, rate of breakthrough cases was lower for all vaccine serotypes, except type 3 (incidence rate ratio, 0.50 [95% confidence interval, .28-.84] and 1.12 [0.71-1.76], respectively). Observed compared to expected IPD was 51.7% lower (95% confidence interval, -60.9 to -40.7%) for vaccine serotypes, but the change for nonvaccine types was not significant 12% (-9.6 to 39.7). The 2+1 schedule is likely superior to 3+0 for overall IPD control, a finding that may be worth consideration for other countries considering or using 3+0 PCV schedules.

Memory B cell responses induced by pneumococcal conjugate vaccine schedules with fewer doses: analysis of a randomised-controlled trial in Viet Nam

The use of pneumococcal conjugate vaccine (PCV) schedules with fewer doses are being considered to reduce costs and improve access, particularly in low- and middle-income countries. While several studies have assessed their immunogenicity, there are limited data on their potential for long-term immune protection, as assessed by pneumococcal serotype-specific memory B cell (Bmem) responses. This current study reports secondary outcome data that aims to compare Bmem responses following reduced-dose (0 + 1 and 1 + 1) schedules of PCV10 and PCV13 in Vietnamese infants from our randomised-controlled trial (trial registration number NCT03098628). Following vaccination at 12 months of age, Bmem levels for most serotypes peaked seven days post-vaccination and were higher in magnitude for the 1 + 1 than 0 + 1 schedules and for PCV13 than PCV10. Furthermore, Bmem did not wane as rapidly as IgG levels by 24 months of age. Further studies are needed to assess the use of Bmem as markers of long-term protection against pneumococcal carriage and disease, which is crucial to generate data for immunisation program decision-making.

Sex-based difference in immune responses and efficacy of the pneumococcal conjugate vaccine.

Vaccine-mediated protection and susceptibility to Streptococcus pneumoniae (pneumococcus) infections are influenced by biological sex. The incidence of invasive pneumococcal disease remains higher in males compared to females even after the introduction of the pneumococcal conjugate vaccine (PCV). However, sex-based differences in the immune response to this conjugate vaccine remain unexplored. To investigate those differences, we vaccinated adult male and female mice with PCV and assessed cellular and humoral immune responses. Compared to females, male mice displayed lower levels of T follicular helper cells, germinal center B cells and plasmablasts, which are all required for antibody production following vaccination. This was linked to lower IgG and IgM levels against pneumococci and lower isotype switching to IgG3 in vaccinated males. Due to lower antibody levels, sera of vaccinated male mice had lower efficacy in several anti-pneumococcal functions including neutralization of bacterial binding to pulmonary epithelial cells as well as direct cytotoxicity against S. pneumoniae. Importantly, while the vaccine was highly protective in females, vaccinated males succumbed to infection more readily and were more susceptible to both lung-localized infection and systemic spread following S. pneumoniae challenge. These findings identify sex-based differences in immune responses to PCV that can inform future vaccine strategies.

Experimental Human Pneumococcal Carriage using Streptococcus pneumoniae serotype 3 in Malawi: a dose ranging and reproducibility human infection study

Background Streptococcus pneumoniae is a major cause of morbidity and mortality from respiratory tract infections, pneumonia, meningitis, and sepsis. Nasopharyngeal carriage of pneumococcus is a prerequisite for pneumococcal disease and transmission. Since the global introduction of pneumococcal conjugated vaccines, rates of pneumococcal disease have declined for many vaccine type serotypes but serotype 3 (SPN3) continues to cause significant disease. The Experimental Human Pneumococcal Challenge (EHPC) model is a unique method of determining pneumococcal colonisation, understanding the impact of colonisation on acquired immunity and for testing pneumococcal vaccines. This study will develop a serotype 3 EHPC model to address some pertinent questions on the burden of pneumococcal disease in Malawi. Methods Healthy adults aged 18-50 years will be recruited, with a maximum target of 83 participants to complete all study visits. The study will consist of a dose ranging and safety study, followed by a reproducibility study. Sequential cohorts of 10 healthy participants will be challenged with escalating doses of SPN3 in the dose ranging study. Samples will be collected before inoculation and on days 2, 7, 13, 16, 21 and 28 following inoculations, for determination of carriage. A total of 33 participants will be enrolled in the reproducibility part and will use a dose that established ≥60% of carriage, and with a high safety profile. Samples will be collected for determination of both local and systemic immunological responses to pneumococcal challenge. Upon completion of study visits, participants will complete a questionnaire establish acceptability. Interpretations We expect to establish an optimal SPN3 dose required to establish nasopharyngeal colonisation in healthy adults in an EHPC model. The model can then be used to evaluate pneumococcal vaccines in both healthy and at-risk populations.

Sensory neurons regulate stimulus-dependent humoral immunity.

Sensory neurons sense pathogenic infiltration, serving to inform immune coordination of host defense. However, sensory neuron-immune interactions have been predominantly shown to drive innate immune responses. Humoral memory, whether protective or destructive, is acquired early in life - as demonstrated by both early exposure to streptococci and allergic disease onset. Our study further defines the role of sensory neuron influence on humoral immunity in the lung. Using a murine model of Streptococcus pneumonia pre-exposure and infection and a model of allergic asthma, we show that sensory neurons are required for B-cell and plasma cell recruitment and antibody production. In response to S. pneumoniae, sensory neuron depletion resulted in a larger bacterial burden, reduced B-cell populations, IgG release and neutrophil stimulation. Conversely, sensory neuron depletion reduced B-cell populations, IgE and asthmatic characteristics during allergen-induced airway inflammation. The sensory neuron neuropeptide released within each model differed. With bacterial infection, vasoactive intestinal polypeptide (VIP) was preferentially released, whereas substance P was released in response to asthma. Administration of VIP into sensory neuron-depleted mice suppressed bacterial burden and increased IgG levels, while VIP1R deficiency increased susceptibility to bacterial infection. Sensory neuron-depleted mice treated with substance P increased IgE and asthma, while substance P genetic ablation resulted in blunted IgE, similar to sensory neuron-depleted asthmatic mice. These data demonstrate that the immunogen differentially stimulates sensory neurons to release specific neuropeptides which specifically target B-cells. Targeting sensory neurons may provide an alternate treatment pathway for diseases involved with insufficient and/or aggravated humoral immunity.

Epidemiology and Management of Pediatric Group A Streptococcal Pneumonia With Parapneumonic Effusion: An Observational Study.

During autumn/winter 2022, UK pediatricians reported an unseasonal increase in invasive group A streptococcal infections; a striking proportion presenting with pneumonia with parapneumonic effusion. Clinicians across the United Kingdom were requested to submit pseudonymized clinical data using a standardized report form for children (<16 years) admitted between September 30, 2022 and February 17, 2023, with microbiologically confirmed group A streptococcal pneumonia with parapneumonic effusion. From 185 cases submitted, the median patient age was 4.4 years, and 163 (88.1%) were previously healthy. Respiratory viral coinfection was detected on admission for 101/153 (66.0%) children using extended respiratory pathogen polymerase chain reaction panel. Molecular testing was the primary method of detecting group A streptococcus on pleural fluid (86/171; 50.3% samples). Primary surgical management was undertaken in 171 (92.4%) children; 153/171 (89.4%) had pleural drain inserted (96 with fibrinolytic agent), 14/171 (8.2%) had video-assisted thoracoscopic surgery. Fever duration after admission was prolonged (median, 12 days; interquartile range, 9-16). Intravenous antibiotic courses varied in length (median, 14 days; interquartile range, 12-21), with many children receiving multiple broad-spectrum antibiotics, although evidence for additional bacterial infection was limited. Most cases occurred with viral coinfection, a previously well-recognized risk with influenza and varicella zoster, highlighting the need to ensure routine vaccination coverage and progress on vaccines for other common viruses (eg, respiratory syncytial virus, human metapneumovirus) and for group A streptococcus. Molecular testing is valuable to detect viral coinfection and confirm invasive group A streptococcal diagnosis, expediting the incorporation of cases into national reporting systems. Range and duration of intravenous antibiotics administered demonstrated the need for research on the optimal duration of antimicrobials and improved stewardship.

Novel manufacturing process of pneumococcal capsular polysaccharides using advanced sterilization methods.

Pneumococcal disease is caused by Streptococcus pneumoniae, including pneumonia, meningitis and sepsis. Capsular polysaccharides (CPSs) have been shown as effective antigens to stimulate protective immunity against pneumococcal disease. A major step in the production of pneumococcal vaccines is to prepare CPSs that meet strict quality standards in immunogenicity and safety. The major impurities come from bacterial proteins, nucleic acids and cell wall polysaccharides. Traditionally, the impurity level of refined CPSs is reduced by optimization of purification process. In this study, we investigated new aeration strategy and advanced sterilization methods by formaldehyde or β-propiolactone (BPL) to increase the amount of soluble polysaccharide in fermentation supernatant and to prevent bacterial lysis during inactivation. Furthermore, we developed a simplified process for the CPS purification, which involves ultrafiltration and diafiltration, followed by acid and alcohol precipitation, and finally diafiltration and lyophilization to obtain pure polysaccharide. The CPSs prepared from formaldehyde and BPL sterilization contained significantly lower level of residual impurities compared to the refined CPSs obtained from traditional deoxycholate sterilization. Finally, we showed that this novel approach of CPS preparation can be scaled up for polysaccharide vaccine production.

Changes in the Pneumococcal Vaccination Uptake and Its Determinants before, during, and after the COVID-19 Pandemic among Community-Living Older Adults in Hong Kong, China: Repeated Random Telephone Surveys.

Pneumococcal vaccination (PV) is effective in preventing vaccine-type pneumococcal diseases. This study investigated the changes in PV uptake and its determinants before, during, and after the Coronavirus Disease 2019 (COVID-19) pandemic among community-living older adults aged ≥65 years in Hong Kong, China. Three rounds of random telephone surveys were conducted every two years from May 2019 to October 2023. Multivariate logistic regression models were fitted to examine the between-round differences in PV uptake rate and factors associated with PV uptake in each round. This study included 1563 participants. The standardized PV uptake rate in Round 1, 2, and 3 was 17.3%, 28.3%, and 35.5%, respectively. A significant difference in the PV uptake rate was found between Rounds 2 and 1 (p = 0.02), but not between Rounds 3 and 2 (p = 0.98). Perceived barriers, cue to action and self-efficacy, were significant determinants of PV uptake in all rounds. Perceived benefits were significant determinants of PV uptake in the first and second rounds, but not in the third round. Continuous monitoring of PV uptake and its determinants, and evaluating and adjusting the PV program, might contribute to the success of such a vaccination program in the post-pandemic era.

Non-pharmaceutical interventions for COVID-19 transiently reduced pneumococcal and Haemophilus influenzae carriage in a cross-sectional pediatric cohort in Southampton, UK.

The Southampton pneumococcal carriage study of children under 5 years old continued during the coronavirus disease 2019 (COVID-19) pandemic. Here, we present data from October 2018 to March 2023 describing prevalence of pneumococci and other pathobionts during the winter seasons before, during, and after the introduction of non-pharmaceutical interventions (NPIs) to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission. Nasopharyngeal swabs were collected from children attending outpatient clinics at a secondary care hospital and community healthcare sites. Pre-NPIs, in 2019/2020, the carriage prevalence of pneumococci at the hospital site was 32% (n = 161 positive/499 participants). During NPIs, this fell to 19% (n = 12/64), although based on fewer participants compared to previous years due to COVID-19 restrictions on health-care attendance. In 2021/2022, after NPIs had eased, prevalence rebounded to 33% (n = 15/46) [compared to NPIs period, χ2 (1, N = 110) =2.78, P = 0.09]. Carriage prevalence at community healthcare sites fell significantly from 27% (n = 127/470) in 2019/2020 to 19% during the NPI period (n = 44/228) in 2020/2021 [χ2 (1, N = 698) =4.95, P = 0.026]. No rebound was observed in 2021/2022 [19% (n = 56/288)]. However, in a multivariate logistic regression model, neither site had a significantly lower carriage prevalence during the NPI period compared to the post NPI period. A reduction in serotype diversity was observed in 2020/2021. Carriage of Haemophilus influenzae was particularly affected by NPIs with a significant reduction observed. In conclusion, among children under 5 years of age, transient, modest, and statistically non-significant alterations in carriage of both Streptococcus pneumoniae and H. influenzae were associated with SARS-CoV-2 NPIs.IMPORTANCEStreptococcus pneumoniae (the pneumococcus) continues to be a major contributor to global morbidity and mortality. Using our long-running pediatric study, we examined changes in pneumococcal carriage prevalence in nearly 3,000 children under the age of 5 years between the winters of 2018/2019 and 2022/2023. This period coincided with the severe acute respiratory syndrome coronavirus 2 pandemic and, in particular, the implementation of national strategies to limit disease transmission in the UK. We observed a transient reduction of both Streptococcus pneumoniae and Haemophilus influenzae in these populations during this period of non-pharmaceutical interventions. This aligned with the reduction in invasive pneumococcal disease seen in the UK and is therefore a likely contributor to this phenomenon.

Epidemiology and Impact of Anti-Pneumococcal Vaccination and COVID-19 on Resistance of Streptococcus pneumoniae Causing Invasive Disease in Piedmont, Italy.

The international surveillance of antimicrobial resistance (AMR) reports S. pneumoniae as one of leading causes of death associated with AMR. Against invasive disease, several vaccinations are available and a reduction in AMR in S. pneumoniae has been observed. Here, we evaluated the impact of anti-pneumococcal vaccination policy and the SARS-CoV2 outbreak on AMR in S. pneumoniae causing invasive disease. We collected all strains of S. pneumoniae causing invasive disease from 2008 in the Piedmont region (Italy). Each strain was typed in order to identify the serogroup and data about AMR were collected. The population under surveillance was classified as infants, children, adults, and the old population. We collected n = 2076 S. pneumoniae strains, with 21.9% and 40.3% being resistant to penicillin G and erythromycin, respectively. We reported an increased risk of infection with penicillin-resistant S. pneumoniae among all populations and evaluated whether the infection was caused by a serotype included in the vaccine formulation. A similar increase was observed after the SARS-CoV2 outbreak. In the Piedmont region, subsequently to the introduction of anti-pneumococcal vaccination, a significant increase in the risk of penicillin G-resistant invasive pneumococcal disease among infants and old population was reported. No significant impact was found for the SARS-CoV2 outbreak.

Impact of twelve immunization-preventable infectious diseases on population health using disability-adjusted life years (DALYs) in Spain

BackgroundThe objective of this study is to estimate the burden of selected immunization-preventable infectious diseases in Spain using the Burden of Communicable Diseases in Europe (BCoDE) methodology, as well as focusing on the national immunization programme and potential new inclusions.MethodsThe BCoDE methodology relies on an incidence and pathogen-based approach to calculate disease burden via disability-adjusted life year (DALY) estimates. It considers short and long-term sequelae associated to an infection via outcome trees. The BCoDE toolkit was used to populate those trees with Spanish-specific incidence estimates, and de novo outcome trees were developed for four infections (herpes zoster, rotavirus, respiratory syncytial virus [RSV], and varicella) not covered by the toolkit. Age/sex specific incidences were estimated based on data from the Spanish Network of Epidemiological Surveillance; hospitalisation and mortality rates were collected from the Minimum Basic Data Set. A literature review was performed to design the de novo models and obtain the rest of the parameters. The methodology, assumptions, data inputs and results were validated by a group of experts in epidemiology and disease modelling, immunization and public health policy.ResultsThe total burden of disease amounted to 163.54 annual DALYs/100,000 population. Among the selected twelve diseases, respiratory infections represented around 90% of the total burden. Influenza exhibited the highest burden, with 110.00 DALYs/100,000 population, followed by invasive pneumococcal disease and RSV, with 25.20 and 10.57 DALYs/100,000 population, respectively. Herpes zoster, invasive meningococcal disease, invasive Haemophilus influenza infection and hepatitis B virus infection ranked lower with fewer than 10 DALYs/100,000 population each, while the rest of the infections had a limited burden (< 1 DALY/100,000 population). A higher burden of disease was observed in the elderly (≥ 60 years) and children < 5 years, with influenza being the main cause. In infants < 1 year, RSV represented the greatest burden.ConclusionsAligned with the BCoDE study, the results of this analysis show a persisting high burden of immunization-preventable respiratory infections in Spain and, for the first time, highlight a high number of DALYs due to RSV. These estimates provide a basis to guide prevention strategies and make public health decisions to prioritise interventions and allocate healthcare resources in Spain.

Effect of pneumococcal conjugate vaccine six years post-introduction on pneumococcal carriage in Ulaanbaatar, Mongolia

Limited data from Asia are available on long-term effects of pneumococcal conjugate vaccine introduction on pneumococcal carriage. Here we assess the impact of 13-valent pneumococcal conjugate vaccine (PCV13) introduction on nasopharyngeal pneumococcal carriage prevalence, density and antimicrobial resistance. Cross-sectional carriage surveys were conducted pre-PCV13 (2015) and post-PCV13 introduction (2017 and 2022). Pneumococci were detected and quantified by real-time PCR from nasopharyngeal swabs. DNA microarray was used for molecular serotyping and to infer genetic lineage (Global Pneumococcal Sequence Cluster). The study included 1461 infants (5–8 weeks old) and 1489 toddlers (12–23 months old) enrolled from family health clinics. We show a reduction in PCV13 serotype carriage (with non-PCV13 serotype replacement) and a reduction in the proportion of samples containing resistance genes in toddlers six years post-PCV13 introduction. We observed an increase in pneumococcal nasopharyngeal density. Serotype 15 A, the most prevalent non-vaccine-serotype in 2022, was comprised predominantly of GPSC904;9. Reductions in PCV13 serotype carriage will likely result in pneumococcal disease reduction. It is important for ongoing surveillance to monitor serotype changes to potentially inform new vaccine development.

Abstract We063: CD73 EXPRESSION ON NEUTROPHILS PROTECTS AGAINST CARDIOMYOCYTE DAMAGE DURING INVASIVE STREPTOCOCCUS PNEUMONIAE INFECTION

In recent years, Streptococcus pneumoniae (pneumococcus)-induced cardiac events have emerged as one of the most serious and life-threatening infection outcomes of invasive pneumococcal disease (IPD), leading to major adverse cardiac events (MACE) with high mortality rates. S. pneumoniae has the ability to invade myocardium and damage cardiomyocytes through the release of bacterial factors and formation of bacterial-filled cardiac microlesions. We previously found that polymorphonuclear cells (PMNs) or neutrophils are crucial for host defense against S. pneumoniae lung infection and that extracellular adenosine (EAD) production, by the exonucleosidase CD73, controlled the anti-bacterial functions of these cells. The objective of this study was to explore the role of PMNs and CD73 in cardiac damage during invasive pneumococcal infection. Upon intra-peritoneal ( i.p .) injection with TIGR4, an invasive pneumococcal strain, C57BL/6 mice showed an increased influx of PMNs into the cardiac tissue as determined by flow cytometry. However, the increased PMN numbers failed to contain bacterial burden in the heart and showed a positive correlation with serum levels of the cardiac damage marker Troponin-1 as determined through ELISA. Depletion of PMNs prior infection reduced pneumococcal burden in the heart and lowered the Troponin-1 levels suggesting that PMNs induce cardiac damage during infection. While exploring the mechanisms underlying the detrimental PMN response, we found that the late stage of IPD was associated with reduced CD73 expression on PMNs. The role of CD73 in regulating cardiac damage was tested in vivo using CD73 -/- mice which had significantly higher bacterial burden and cardiac damage compared to wild-type mice despite similar PMN numbers. The role of CD73 expression on PMNs was also tested ex vivo using the HL-1 cardiomyocyte cell line which showed increased LDH release upon S. pneumoniae infection in presence of CD73 -/- PMNs, a phenotype reversed by supplementation of exogenous adenosine. Similar iincreased damage in presence of CD73 -/- PMNs was seen with C57BL/6 Mouse Primary Cardiac Microvascular Endothelial Cells which lead to increased migration of beads across endothelium. Our findings suggest that dysregulation of CD73 on PMNs during invasive pneumococcal infection leads to an inability to control bacterial numbers and increased cardiac damage, and that the EAD-pathway can be a potential pharmacological target to limit disease severity.