Klebsiella pneumoniae peptide hijacks a Streptococcus pneumoniae permease to subvert pneumococcal growth and colonization.

Treatment of pneumococcal infections is limited by antibiotic resistance and exacerbation of disease by bacterial lysis releasing pneumolysin toxin and other inflammatory factors. We identified a previously uncharacterized peptide in the Klebsiella pneumoniae secretome, which enters Streptococcus pneumoniae via its AmiA-AliA/AliB permease. Subsequent downregulation of genes for amino acid biosynthesis and peptide uptake was associated with reduction of pneumococcal growth in defined medium and human cerebrospinal fluid, irregular cell shape, decreased chain length and decreased genetic transformation. The bacteriostatic effect was specific to S. pneumoniae and Streptococcus pseudopneumoniae with no effect on Streptococcus mitis, Haemophilus influenzae, Staphylococcus aureus or K. pneumoniae. Peptide sequence and length were crucial to growth suppression. The peptide reduced pneumococcal adherence to primary human airway epithelial cell cultures and colonization of rat nasopharynx, without toxicity. We identified a peptide with potential as a therapeutic for pneumococcal diseases suppressing growth of multiple clinical isolates, including antibiotic resistant strains, while avoiding bacterial lysis and dysbiosis.

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.

Retrospective study on the health and economic burden of hospitalized patients due to pneumonia and invasive pneumococcal infections in Belgium settings.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Cost-effectiveness and impact on infections and associated antimicrobial resistance of 20-valent pneumococcal conjugate vaccine in US children previously immunized with PCV13.

AIM: The US Food and Drug Administration approved the 20-valent pneumococcal conjugate vaccine (PCV20) to prevent pneumococcal disease. In the context of routine PCV20 vaccination, we evaluated the cost-effectiveness and public health and economic impact of a PCV20 catch-up program and estimated the number of antibiotic prescriptions and antibiotic-resistant infections averted. MATERIALS AND METHODS: A population-based, multi-cohort, decision-analytic Markov model was developed using parameters consistent with previous PCV20 cost-effectiveness analyses. In the intervention arm, children aged 14-59 months who previously completed PCV13 vaccination received a supplemental dose of PCV20. In the comparator arm, no catch-up PCV20 dose was given. The direct and indirect benefits of vaccination were captured over a 10-year time horizon. RESULTS: A PCV20 catch-up program would prevent 5,469 invasive pneumococcal disease cases, 50,286 hospitalized pneumonia cases, 218,240 outpatient pneumonia cases, 582,302 otitis media cases, and 1,800 deaths, representing a net gain of 30,014 life years and 55,583 quality-adjusted life years. Furthermore, 720,938 antibiotic prescriptions and 256,889 antibiotic-resistant infections would be averted. A catch-up program would result in cost savings of $800 million. These results were robust to sensitivity and scenario analyses. CONCLUSIONS: A PCV20 catch-up program could prevent pneumococcal infections, antibiotic prescriptions, and antimicrobial-resistant infections and would be cost-saving in the US.

Cost-effectiveness of an in-development adult-formulated 21-valent pneumococcal conjugate vaccine in US adults aged 50 years or older.

Indirect effects of childhood pneumococcal conjugate vaccines (PCV) have diminished the cost-effectiveness of current adult vaccine recommendations. An in-development adult-formulated 21-valent pneumococcal conjugate vaccine (PCV21) may play a critical role in reducing pneumococcal illness by targeting a larger number of serotypes responsible for adult pneumococcal infections. This study assesses the cost-effectiveness of PCV21 in US adults aged 50 years or older compared with currently recommended pneumococcal vaccines, from both the societal and healthcare perspectives. A Markov model evaluated the lifetime cost-effectiveness of PCV21 (given at age 50 years only, at ages 50/65 years, and risk-based at ages < 65 years plus age-based at age 65 years) compared to no vaccination and to currently recommended pneumococcal vaccines given either as currently recommended or routinely at ages 50/65 years. The analysis was conducted in hypothetical Black and non-Black cohorts aged 50 years or older, with and without considering childhood pneumococcal vaccination indirect effects. Model parameters were based on US data. Parameter uncertainty was assessed using 1-way and probabilistic sensitivity analyses. From the societal perspective, PCV21 at ages 50/65 years compared to PCV21 at age 50 years cost $7,410 per quality adjusted life year (QALY) gained in Black cohort analyses and $85,696/QALY gained in the non-Black cohort; PCV21 at ages 50/65 years had the most favorable public health outcomes. From the healthcare perspective, compared to no vaccination, PCV21 at age 50 years cost $46,213/QALY gained in the Black cohort and $86,629/QALY in non-Blacks. All other strategies were dominated in both cohorts and from both perspectives. When considering childhood pneumococcal vaccination indirect effects, costs of PCV21 at ages 50/65 years remained less than $140,000/QALY gained from the societal perspective in both populations. PCV21 is potentially cost-effective compared to currently approved pneumococcal vaccines in adults aged 50 years or older from both the societal and healthcare perspectives.

Uptake of pneumococcal vaccines in older Australian adults before and after universal public funding of PCV13.

BACKGROUND: In 2020 Australia changed the funded universal older adult pneumococcal vaccination program from use of the 23-valent pneumococcal polysaccharide vaccine (PPV23) at age 65 to the 13-valent pneumococcal conjugate vaccine (PCV13) at age 70 years. We investigated uptake of both PCV13 and PPV23 in older adults before and after the program change. METHODS: We analysed a national dataset of records of patients attending general practices (GPs). We included regular attendees aged 65 or above in 2020. Cumulative uptake of PCV13 and monthly uptake of PPV23 was compared for the two periods before (January 2019 to June 2020) and after (July 2020 to May 2021) the program change on 1 July 2020, by age groups and presence of comorbid conditions. RESULTS: Our study included data from 192,508 patients (mean age in 2020: 75.1 years, 54.2 % female, 46.1 % with at least one comorbidity). Before July 2020, for all adults regardless of underlying comorbidities, the cumulative uptake of PCV13 was < 1 % but by May 2021, eleven months after the program changes, cumulative uptake of PCV13 had increased among those aged 70-79 years (without comorbidity: 16.3 %; with comorbidity: 21.1 %) and 80 + years (without comorbidity: 13.5 %; with comorbidity: 17.7 %), but not among those aged 65-69 years (without comorbidity: 1.3 %; with comorbidity: 3 %). Monthly uptake of PPV23 dropped following the program change across all age groups. CONCLUSIONS: Changes in uptake of PCV13 and PPV23 among those aged 70 + years were consistent with program changes. However, PCV13 uptake was still substantially lower in individuals aged 65-69 years overall and in those with comorbidities.

Protective effect of PCV13 against all-cause hospitalized pneumonia in children in Beijing, China: real-world evidence.

BACKGROUND: The study evaluated the protective effect of 13-valent pneumococcal polysaccharide conjugate vaccine (PCV13) against all-cause hospitalized pneumonia in children in Beijing. METHODS: Based on the vaccination record and inpatient medical record database of Beijing, children born in 2017 in Beijing, matched by age, gender, and district of the children with the ratio of 1:4, were selected as the vaccinated and unvaccinated groups according whether if vaccinated with PCV13. The incidence rate and 95 % confidence interval (95 %CI), vaccine effectiveness (VE) and direct medical costs of all-cause hospitalized pneumonia were calculated and compared within the same period of 12 months, 18 months, 24 months and 30 months after the birth of the child. RESULTS: The decreased incidence rates of all-cause hospitalized pneumonia were observed at the four points in the PCV13 vaccinated group compared to the unvaccinated group, which were significant at the points of 12 months (0.42 % vs. 0.72 %, P = 0.001), 18 months (0.90 % vs. 1.26 %, P = 0.002) and 24 months (1.37 % vs. 1.65 %, P = 0.046). The VE of PCV13 against all-cause hospitalized pneumonia within 12 months was the highest as 41.9 % (95 % CI 19.6 %, 58.0 %), followed by 29.3 % (95 % CI 11.4 %, 43.5 %) within 18 months, 17.1 % (95 % CI 0.3 %, 31.1 %) within 24 months and it almost disappeared within 30 months. The VE of 4-dose vaccination within 18 months and 24 months were 39.9 % (95 % CI 20.3 %, 54.7 %) and 27.2 % (95 % CI 8.6 %, 42.0 %), respectively. The median hospitalization cost of the children in the vaccinated group was higher at the four points but without significance. CONCLUSIONS: PCV13 had a certain protective effect on all-cause hospitalized pneumonia, and the booster immunization strategy had the best protective effect with great public health significance to enter the immunization program.

Clinical and economic burden of acute otitis media caused by Streptococcus pneumoniae in European children, after widespread use of PCVs-A systematic literature review of published evidence.

BACKGROUND: Acute otitis media (AOM) is a common childhood disease frequently caused by Streptococcus pneumoniae. Pneumococcal conjugate vaccines (PCV7, PCV10, PCV13) can reduce the risk of AOM but may also shift AOM etiology and serotype distribution. The aim of this study was to review estimates from published literature of the burden of AOM in Europe after widespread use of PCVs over the past 10 years, focusing on incidence, etiology, serotype distribution and antibiotic resistance of Streptococcus pneumoniae, and economic burden. METHODS: This systematic review included published literature from 31 European countries, for children aged ≤5 years, published after 2011. Searches were conducted using PubMed, Embase, Google, and three disease conference websites. Risk of bias was assessed with ISPOR-AMCP-NPC, ECOBIAS or ROBIS, depending on the type of study. RESULTS: In total, 107 relevant records were identified, which revealed wide variation in study methodology and reporting, thus limiting comparisons across outcomes. No homogenous trends were identified in incidence rates across countries, or in detection of S. pneumoniae as a cause of AOM over time. There were indications of a reduction in hospitalization rates (decreases between 24.5-38.8% points, depending on country, PCV type and time since PCV introduction) and antibiotic resistance (decreases between 14-24%, depending on country), following the widespread use of PCVs over time. The last two trends imply a potential decrease in economic burden, though this was not possible to confirm with the identified cost data. There was also evidence of an increase in serotype distributions towards non-vaccine serotypes in all of the countries where non-PCV serotype data were available, as well as limited data of increased antibiotic resistance within non-vaccine serotypes. CONCLUSIONS: Though some factors point to a reduction in AOM burden in Europe, the burden still remains high, residual burden from uncovered serotypes is present and it is difficult to provide comprehensive, accurate and up-to-date estimates of said burden from the published literature. This could be improved by standardised methodology, reporting and wider use of surveillance systems.

Understanding healthcare providers' preferred attributes of pediatric pneumococcal conjugate vaccines in the United States.

As higher-valent pneumococcal conjugate vaccines (PCVs) become available for pediatric populations in the US, it is important to understand healthcare provider (HCP) preferences for and acceptability of PCVs. US HCPs (pediatricians, family medicine physicians and advanced practitioners) completed an online, cross-sectional survey between March and April 2023. HCPs were eligible if they recommended or prescribed vaccines to children age <24 months, spent ≥25% of their time in direct patient care, and had ≥2 y of experience in their profession. The survey included a discrete choice experiment (DCE) in which HCPs selected preferred options from different hypothetical vaccine profiles with systematic variation in the levels of five attributes. Relative attribute importance was quantified. Among 548 HCP respondents, the median age was 43.2 y, and the majority were male (57.9%) and practiced in urban areas (69.7%). DCE results showed that attributes with the greatest impact on HCP decision-making were 1) immune response for the shared serotypes covered by PCV13 (31.4%), 2) percent of invasive pneumococcal disease (IPD) covered by vaccine serotypes (21.3%), 3) acute otitis media (AOM) label indication (20.3%), 4) effectiveness against serotype 3 (17.6%), and 5) number of serotypes in the vaccine (9.5%). Among US HCPs, the most important attribute of PCVs was comparability of immune response for PCV13 shared serotypes, while the number of serotypes was least important. Findings suggest new PCVs eliciting high immune responses for serotypes that contribute substantially to IPD burden and maintaining immunogenicity against serotypes in existing PCVs are preferred by HCPs.

State of pneumococcal vaccine immunity.

Like the other invasive encapsulated bacteria, Streptococcus pneumoniae is also covered with a polysaccharide structure. Infants and elderly are most vulnerable to the invasive and noninvasive diseases caused by S. pneumoniae. Although antibodies against polysaccharide capsule are efficient in eliminating S. pneumoniae, the T cell independent nature of the immune response against polysaccharide vaccines renders them weakly antigenic. The introduction of protein conjugated capsular polysaccharide vaccines helped overcome the weak immunogenicity of pneumococcal polysaccharides and decreased the incidence of pneumococcal diseases, especially in pediatric population. Conjugate vaccines elicit T cell dependent response which involve the interaction of specialized CD4+ T cells, called follicular helper T cells (Tfh) with germinal center B cells in secondary lymphoid organs. Despite their improved immunogenicity, conjugate vaccines still need to be administered three to four times in infants during the first 15 month of their life because they mount poor Tfh response. Recent studies revealed fundamental differences in the generation of Tfh cells between neonates and adults. As the portfolio of pneumococcal conjugate vaccines continues to increase, better understanding of the mechanisms of antibody development in different age groups will help in the development of pneumococcal vaccines tailored for different ages.

Pneumococcal vaccination and primary care presentations for acute respiratory tract infection and antibiotic prescribing in older adults.

BACKGROUND: While the 23-valent pneumococcal polysaccharide vaccine (PPV23) has demonstrated its role in preventing severe pneumococcal disease, its impact on more non-specific conditions like acute respiratory tract infection (ARI) and lower respiratory tract infections (LRTI) remains unclear. We aimed to investigate the role of PPV23 in prevention of presentations for ARI and LRTI and related antibiotic prescriptions among older adults in primary care. METHODS: Using a nationwide general practice dataset, we followed a cohort of regularly attending patients aged ≥65 years from 1 January 2014 until 31 December 2018 for presentations for ARI, LRTI, and related antibiotic prescriptions. Associations between PPV23 receipt and each outcome were assessed using a multiple failures survival model to estimate hazard ratios (HR) adjusted for age, sex, socioeconomic status, and various health measures. RESULTS: A cohort of 75,264 patients aged ≥65 years (mean 75.4, 56% female) in 2014 was followed. The incidence of presentations for ARI, ARI-related antibiotic prescription, LRTI, and LRTI-related antibiotic prescription was 157.6, 76.0, 49.6, and 24.3 per 1000 person-years, respectively. Recent PPV23 vaccine receipt was associated with a small reduction in ARI presentations (adjusted HR vaccinated vs. unvaccinated 0.96; 95%CI 0.94-0.98; p = 0.002); however, there was no reduction in ARI-related antibiotic prescription, LRTI presentation, nor LRTI-related antibiotic prescription (adjusted HR were 0.99[95%CI 0.96-1.03], 1.04[95%CI 0.99-1.09], 1.07[95%CI 1.00-1.14]). CONCLUSION: PPV23 vaccination in older adults may result in a small reduction in the incidence of total ARI presentations in primary care. However, the effect is small and residual confounding cannot be excluded.

Epidemiología molecular de la colonización nasofaríngea neumocócica en niños de Sevilla, tras la implementación del programa de vacunación con VNC13 en Andalucía (España) / Molecular epidemiology of pneumococcal carriage in children from Seville, following implementation of the PCV13 immunization program in Andalusia, Spain

Introducción: El programa de vacunación universal con la vacuna antineumocócica conjugada 13-valente (VNC13) se implantó en Andalucía en diciembre de 2016. Métodos: Estudio transversal de colonización nasofaríngea por Streptococcus pneumoniae. Se seleccionó a 397 niños sanos en centros de atención primaria de Sevilla durante los periodos 1/4/2018-28/2/2020 y 1/11/2021-28/2/2022 (periodo VNC13). Se utilizó una colección histórica de un estudio de colonización desarrollado en niños sanos y con infección respiratoria superior entre el 1/01/2006 y el 30/06/2008 (periodo VNC7) para comparar las distribuciones de serotipos/genotipos y las tasas de resistencias antibióticas. Resultados: Un total de 76 (19%) niños estaban colonizados con S. pneumoniae en el periodo VNC13 y se dispuso de 154 aislamientos del periodo VNC7. La colonización por serotipos incluidos en VNC13 disminuyó significativamente entre los periodos VNC13 y VNC7 (11 vs. 38%; p=0,0001); los serotipos 19F (8%), 3 (1%) y 6B (1%) fueron los únicos serotipos vacunales circulantes. Los serotipos 15B/C y 11A fueron los serotipos no VNC13 más prevalentes durante el periodo VNC13 (14% y 11%, respectivamente); este último se incrementó de forma significativa entre periodos de tiempo (p=0,04). El serotipo 11A solo se asoció en el periodo VNC13 con variantes resistentes a la ampicilina del clon Spain9V-ST156 (ST6521 y genéticamente relacionado ST14698), no detectados en el periodo anterior. Conclusiones: Hubo una circulación muy residual de los serotipos vacunales durante el periodo VNC13, con excepción del serotipo19F. El serotipo 11A se incrementó de forma significativa entre los periodos VNC13 y VNC7 por expansión clonal del genotipo resistente a la ampicilina ST6521.(AU)

Background: The 13-valent pneumococcal conjugate vaccine (PCV13) universal vaccination program was introduced in December 2016 in Andalusia. Methods: A cross-sectional study was conducted on the molecular epidemiology of pneumococcal nasopharyngeal colonization. A total of 397 healthy children were recruited from primary healthcare centres in Seville for the periods 1/4/2018 to 28/2/2020 and 1/11/2021 to 28/2/2022 (PCV13 period). Data from a previous carriage study conducted among healthy and sick children from 1/01/2006 to 30/06/2008 (PCV7 period) were used for comparison of serotype/genotype distributions and antibiotic resistance rates. Results: Overall, 76 (19%) children were colonized with S. pneumoniae during the PCV13 period and there were information available from 154 isolates collected during the PCV7 period. Colonization with PCV13 serotypes declined significantly in the PCV13 period compared with historical controls (11 vs. 38%, P=0.0001), being serotypes 19F (8%), 3 (1%) and 6B (1%) the only circulating vaccine types. Serotypes 15B/C and 11A were the most frequently identified non-PCV13 serotypes during the PCV13 period (14% and 11%, respectively); the later one increased significantly between time periods (P=0.04). Serotype 11A was exclusively associated in the PCV13 period with ampicillin-resistant variants of the Spain9V-ST156 clone (ST6521 and genetically related ST14698), not detected in the preceding period. Conclusions: There was a residual circulation of vaccine types following PCV13 introduction, apart from serotype 19F. Serotype 11A increased between PCV13 and PCV7 periods due to emergence and clonal expansion of ampicillin-resistant genotype ST6521.(AU)

Progresión temporal de la distribución de los serotipos de Streptococcus pneumoniae productores de enfermedad neumocócica invasiva en Galicia (España) y su relación con la resistencia a antibióticos (periodo 2011-2021) / Temporal progression of the distribution of Streptococcus pneumoniae serotypes causing invasive pneumococcal disease in Galicia (Spain) and its relationship with resistance to antibiotics (period 2011-2021)

Introducción: Streptococcus pneumoniae causa enfermedades graves en la población susceptible. La vacuna neumocócica conjugada (PCV) 13-valente (PCV13) se incluyó en el calendario infantil en 2011. Este estudio analiza la evolución de los serotipos de neumococo y de sus resistencias tras la PCV13. Métodos: Se incluyeron los neumococos serotipados en Galicia en 2011-2021. Se estudió la sensibilidad antibiótica siguiendo criterios EUCAST. Se analizaron los datos en 3 subperíodos: inicial (2011-2013), medio (2014-2017) y final (2018-2021). Se calcularon las prevalencias de los serotipos y el porcentaje de resistencia a los antibióticos más representativos. Resultados: Se incluyeron 2.869 aislados. Inicialmente el 42,7% presentaba tipos capsulares incluidos en la PCV13, frente al 15,4% al final. Los incluidos en la PCV20 y no en la PCV13 y PCV15 fueron el 12,5% inicialmente y el 41,3% al final. El 26,4% de los serotipos a lo largo del estudio no estaban incluidos en ninguna vacuna. La prevalencia del serotipo 8 se multiplicó casi por 8 y la del 12F se triplicó. El serotipo 19A fue el más resistente inicialmente. La resistencia de los serotipos 11A y 15A aumentó a lo largo del estudio. Conclusiones: La introducción de la PCV13 en la población infantil determinó un cambio en los serotipos de neumococo hacia los incluidos en la PCV20 y los no incluidos en ninguna vacuna. El serotipo 19A inicialmente fue el más resistente, y el 15A, no incluido en ninguna vacuna, merece un especial seguimiento. El serotipo 8, que fue el que más se incrementó, no mostró resistencia destacable.(AU)

Introduction: Streptococcus pneumoniae causes serious diseases in the susceptible population. The 13-valent pneumococci conjugate vaccine (PCV13) was included in the children's calendar in 2011. The objective of the study was to analyze the evolution of pneumococcal serotypes and their resistance after PCV13. Methods: This study included the pneumococci serotyped in Galicia in 2011-2021. Antibiotic susceptibility was analyzed following EUCAST criteria. The data was analyzed in 3 sub-periods: initial (2011-2013), middle (2014-2017) and final (2018-2021). The prevalence of serotypes and their percentage of resistance to the most representative antibiotics were calculated. Results: A total of 2.869 isolates were included. Initially, 42.7% isolates presented capsular types included in PCV13, compared to 15.4% at the end. Those included in PCV20 and not in PCV13 and PCV15 were 12.5% at baseline and 41.3% at the end; 26.4% of the isolates throughout the study had serotypes not included in any vaccine. The prevalence of serotype 8 multiplied almost by 8 and that of 12F tripled. The 19A serotype was initially the most resistant, while the resistance of serotypes 11A and 15A increased throughout the study. Conclusions: The introduction of PCV13 in the pediatric population determined a change in pneumococcal serotypes towards those included in PCV20 and those not included in any vaccine. Serotype 19A was initially the most resistant and the 15A, not included in any vaccine, deserves special follow-up. Serotype 8, which increased the most, did not show remarkable resistance.(AU)

Streptococcus pneumoniae serotype 3 population structure in the era of conjugate vaccines, 2001-2018.

Background. Despite use of highly effective conjugate vaccines, invasive pneumococcal disease (IPD) remains a leading cause of morbidity and mortality and disproportionately affects Indigenous populations. Although included in the 13-valent pneumococcal conjugate vaccine (PCV13), which was introduced in 2010, serotype 3 continues to cause disease among Indigenous communities in the Southwest USA. In the Navajo Nation, serotype 3 IPD incidence increased among adults (3.8/100 000 in 2001-2009 and 6.2/100 000 in 2011-2019); in children the disease persisted although the rates dropped from 5.8/100 000 to 2.3/100 000.Methods. We analysed the genomic epidemiology of serotype 3 isolates collected from 129 adults and 63 children with pneumococcal carriage (n=61) or IPD (n=131) from 2001 to 2018 of the Navajo Nation. Using whole-genome sequencing data, we determined clade membership and assessed changes in serotype 3 population structure over time.Results. The serotype 3 population structure was characterized by three dominant subpopulations: clade II (n=90, 46.9 %) and clade Iα (n=59, 30.7 %), which fall into Clonal Complex (CC) 180, and a non-CC180 clade (n=43, 22.4 %). The proportion of clade II-associated IPD cases increased significantly from 2001 to 2010 to 2011-2018 among adults (23.1-71.8 %; P<0.001) but not in children (27.3-33.3 %; P=0.84). Over the same period, the proportion of clade II-associated carriage increased; this was statistically significant among children (23.3-52.6 %; P=0.04) but not adults (0-50.0 %, P=0.08).Conclusions. In this setting with persistent serotype 3 IPD and carriage, clade II has increased since 2010. Genomic changes may be contributing to the observed trends in serotype 3 carriage and disease over time.

Infectious purpura fulminans associated with pneumococcal septicaemia in a patient with unacknowledged functional asplenia.

Purpura fulminans (PF) is a life-threatening complication of septic shock that can occur due to disseminated infections with Streptococcus pneumoniae The spleen is an important organ in the immunisation process against encapsulated bacteria. Patients with asplenia, either functional or anatomical, are therefore at increased risk of developing serious infections and complications, such as PF, if infected with such bacteria.This case report presents a woman in her late 40s with unacknowledged functional asplenia who was admitted to the hospital with signs of an acute disseminated infection causing septic shock, signs of disseminated intravascular coagulation and infectious PF. A few days after admission, the blood cultures showed growth of S. pneumoniae With early sepsis treatment, the patient survived although with some complications. Clinical presentation, investigations, differential diagnosis, treatment and outcome are presented. Treatment and early recognition of PF are presented and discussed. Relevant recognition and preventative treatment strategies for patients with asplenia are also reviewed and discussed.This case demonstrates the importance of early recognition and treatment of PF in septic patients and the importance of preventive treatment strategies for patients with asplenia to avoid serious infections and complications.

Potential serotype-specific effectiveness against IPD of pneumococcal conjugate vaccines V114 and PCV20 in children given a 2+1 dosing regimen.

BACKGROUND: Next generation, higher valency pneumococcal conjugate vaccines (PCVs) are assessed and licensed by comparing the immune response across serotypes shared with the PCVs that are standard of care for prevention of pneumococcal disease. METHODS: Using a previously qualified method we predicted the serotype-specific vaccine effectiveness (VE) against invasive pneumococcal disease of V114 and PCV20 for the serotypes shared with PCV13 in an EU, Russian, and Australian pediatric population that is recommended to receive a 2 + 1 dosing regimen. RESULTS: The estimated protective antibody concentrations ranged from 0.03 (serotype 23F) to 1.49 µg/mL (serotype 19F). Predicted VE values for V114 ranged from 79% (serotype 5) to 100% (serotype 23F). V114 had comparable effectiveness to PCV13 for all but one of shared serotypes, with predicted higher effectiveness (in V114) against serotype 3 (93% vs. 65%). Predicted VE values for PCV20 ranged from 47% (serotype 3) to 91% (serotype 14). PCV20 predicted VE was lower than PCV13's for serotypes 4, 19F, 23F, 1, 3, 5, 6A, 7F, and 19A. CONCLUSIONS: Predicted serotype-specific VE values suggest that, with a 2 + 1 dosing regimen, V114 will have greater effectiveness than PCV20 against PCV13 serotypes, particularly for the still-prevalent serotype 3. Real-world VE studies will ultimately provide clarity on the effectiveness of novel PCVs and support further confidence in and/or improvements to modeling efforts.

Pediatric pneumococcal conjugate vaccines (PCVs) were first introduced in Europe in the early 2000s and their incorporation into national immunization programs has helped decrease the incidence of invasive pneumococcal disease (IPD) in Europe and globally. However, some IPD persists, due both to the emergence of non-vaccine pneumococcal serotypes and to the persistence of certain vaccine-targeted serotypes. Higher valency vaccines have been developed to help prevent IPD arising from these serotypes. The goal of the present study is to employ a previously developed model to predict the serotype-specific vaccine effectiveness of higher valency PCVs in a pediatric population that is recommended to receive a 2 + 1 dosing schedule.

Incidence of pneumococcal disease in children ≤48 months old in the United States: 1998-2019.

BACKGROUND: Pneumococcal disease (PD) is a major cause of morbidity and mortality among children, particularly in the youngest age groups. This study aimed to assess the incidence of PD over time by age group in young children with commercial or Medicaid coverage in the US. METHODS: Episodes of invasive pneumococcal disease (IPD), all-cause pneumonia (ACP), and acute otitis media (AOM) were identified in the MarketScan® Commercial and Medicaid claims databases using diagnosis codes among children aged ≤ 48 months with confirmed date of birth (DoB), at any time during the study period (1998-2019). DoB was assigned using diagnosis codes for birth or delivery using the child's or mother's medical claims to ensure accurate age determination. Annual incidence rates (IRs) were calculated as number of disease episodes/100,000 person-years (PY) for IPD and ACP and episodes/1,000 PY for AOM, for children aged 0-6, 7-12, 12-24, and 25-48 months. RESULTS: Annual IPD IRs declined from 53 to 7 episodes/100,000 PY between 1998 and 2019 in commercially-insured and 58 to 9 episodes/100,000 PY between 2001 and 2019 in Medicaid-insured children. Annual ACP IRs declined from 5,600 to 3,952 episodes/100,000 PY, and from 6,706 to 4,521 episodes/100,000 PY, respectively, over these periods. In both populations, children aged 0-6 months had the highest incidence of IPD and inpatient ACP. Annual AOM IRs declined from 1,177 to 738 episodes/1,000 PY (commercially-insured) and 633 to 624 episodes/1,000 PY (Medicaid-insured), over these periods. IRs were higher in rural vs. urban areas for all disease manifestations. CONCLUSIONS: Incidence rates of IPD, ACP, and AOM decreased in children with commercial insurance and Medicaid coverage from 1998 to 2019. However, burden of disease remained substantial, with higher annual IRs for IPD and ACP for Medicaid-insured vs. commercially-insured children. IPD and inpatient ACP were most common in the youngest children 0-6 months old, followed by the 7-12-month age group.

Streptococcus pneumoniae as a colonizing agent of the Nasopharynx - Oropharynx in adults: A systematic review and meta-analysis.

BACKGROUND: Streptococcus pneumoniae (Spn) is a commensal pathogen that usually colonizes the upper respiratory tract of children. Likewise, Spn colonization has been considered a critical factor in the development of pneumococcal invasive disease. However, Spn prevalence in adults remains unclear. This study performs a systematic review and meta-analysis to explore the prevalence of Spn Nasopharynx - Oropharynx Colonization (NOC) in adults. METHODS: A Systematic review of scientific databases was utilized to identify eligible studies that follow strict selection criteria. Subsequently, a meta-analysis was conducted to establish NOC prevalence in adults (≥18 years old). The heterogeneity and sensitivity analyses were assessed using the microorganism identification technique, sample type, and age subgroups. RESULTS: Initial selection includes 69 studies, with 37 selected for the meta-analysis, involving 23,724 individuals. The overall prevalence (95 % CI) of Spn NOC among adults was 6 % (5-9). The subgroup analysis revealed that young adults (YA), 18-64 years old, had a prevalence of 10 %, whereas older adults (OA), ≥65 years old, had a prevalence of 2 %. The identification of Spn NOC may vary depending on the method of diagnosis used. High heterogeneity (I2 > 90 %) was observed but diminished to 70 % when the analysis was restricted to oropharyngeal swabs as an identification method. Furthermore, heterogeneity decreased to 58 % when exclusively employing traditional culture as the identification method. CONCLUSIONS: This study found a low prevalence of Spn NOC in adults. Notably, the prevalence of Spn NOC was higher in younger adults than in older adults. It is essential to highlight a significant heterogeneity among studies, which indicates there is no standardized method of Spn NOC identification.