[Current and new vaccines against pneumococci]. / Aktuelle und neue Impfstoffe gegen Pneumokokken.

Pneumococcal vaccination plays a crucial role in the prevention of bacterial respiratory infections caused by Streptococcus pneumoniae. Pneumococci are responsible for diseases such as pneumonia, sinusitis and acute otitis media and can cause serious invasive infections such as meningitis and bacteraemia. Pneumococcal pneumonia leads to increased morbidity and mortality, particularly in patients with chronic lung diseases such as chronic obstructive pulmonary disease (COPD). The introduction of 13-valent conjugate vaccines (pneumococcal conjugate vaccine 13 [PCV13]) has significantly reduced the burden of disease. However, infections caused by serotypes not covered by PCV13 continue to occur. Current vaccines such as the 20-valent conjugate vaccine (PCV20) provide extended serotype coverage and have shown a robust immune response in clinical trials. The recently updated recommendations of the German Standing Committee on Vaccination (Ständige Impfkommission, STIKO) include the use of PCV20 for all indication categories in adults, which represents a simplified and more effective vaccination strategy. Future developments include vaccines with even broader serotype coverage and improved immunological properties; these are expected to further reduce the burden of pneumococcal disease. Improving vaccination uptake and increasing vaccination rates, particularly among at-risk groups, remain key objectives to protect public health in the long term.

Association Between Pneumococcal Vaccination Uptake and Loneliness Among Regular Patients in Rural Community Hospitals: A Cross-Sectional Study.

Introduction Vaccination is essential for preventing infectious diseases such as pneumonia and seasonal viral infections. The COVID-19 pandemic has underscored the critical role of vaccination in public health. However, vaccination uptake can be influenced by biopsychosocial conditions. Immunocompromised individuals, for instance, face restrictions with live vaccines, and psychosocial factors like loneliness can negatively impact attitudes towards vaccination. This study aims to clarify the association between loneliness and pneumococcal vaccination rate among regular patients in a rural Japanese community. Method A cross-sectional study was conducted at Unnan City Hospital in Unnan City, a rural area in southeastern Shimane Prefecture, Japan. Participants included patients over 40 who regularly visited the general medicine department between September 1, 2023, and November 31, 2023. Data on vaccination rates for pneumococcal pneumonia and loneliness levels assessed using the Japanese version of the three-item University of California, Los Angeles (UCLA) Loneliness Scale were collected. Additional data on demographics, BMI, renal function, and comorbidities were extracted from electronic medical records. Statistical analyses were performed to identify factors associated with vaccination rates, including univariate and multivariate logistic regression. Results Out of 1,024 eligible patients, 647 participated in the study. Participants with higher loneliness had significantly lower vaccination rates for pneumococcal pneumonia (22.3% vs. 34.2%, p = 0.001). The multivariate logistic regression model showed that higher loneliness was significantly associated with lower vaccination likelihood (odds ratio (OR) = 0.54, 95% CI = 0.37-0.78, p = 0.0011). Age was positively associated with vaccination (OR = 1.08, 95% CI = 1.06-1.11, p < 0.001), whereas higher comorbidity scores (Charlson Comorbidity Index (CCI) ≥ 5) and frequent healthy eating practices were associated with lower vaccination rates. Conclusion This study demonstrates a significant association between higher loneliness levels and lower pneumococcal vaccination rates among patients in a rural Japanese community. Addressing psychosocial barriers such as loneliness could enhance vaccination uptake. Public health interventions focused on reducing loneliness and enhancing social support are essential to improving vaccination rates and preventing infectious diseases. Further research should explore the causal mechanisms and develop targeted strategies to mitigate the impact of loneliness on health behaviors.

Immunogenicity and seroefficacy of pneumococcal conjugate vaccines: a systematic review and network meta-analysis.

Background: Vaccination of infants with pneumococcal conjugate vaccines is recommended by the World Health Organization. Evidence is mixed regarding the differences in immunogenicity and efficacy of the different pneumococcal vaccines. Objectives: The primary objective was to compare the immunogenicity of pneumococcal conjugate vaccine-10 versus pneumococcal conjugate vaccine-13. The main secondary objective was to compare the seroefficacy of pneumococcal conjugate vaccine-10 versus pneumococcal conjugate vaccine-13. Methods: We searched the Cochrane Library, EMBASE, Global Health, MEDLINE, ClinicalTrials.gov and trialsearch.who.int up to July 2022. Studies were eligible if they directly compared either pneumococcal conjugate vaccine-7, pneumococcal conjugate vaccine-10 or pneumococcal conjugate vaccine-13 in randomised trials of children under 2 years of age, and provided immunogenicity data for at least one time point. Individual participant data were requested and aggregate data used otherwise. Outcomes included the geometric mean ratio of serotype-specific immunoglobulin G and the relative risk of seroinfection. Seroinfection was defined for each individual as a rise in antibody between the post-primary vaccination series time point and the booster dose, evidence of presumed subclinical infection. Each trial was analysed to obtain the log of the ratio of geometric means and its standard error. The relative risk of seroinfection ('seroefficacy') was estimated by comparing the proportion of participants with seroinfection between vaccine groups. The log-geometric mean ratios, log-relative risks and their standard errors constituted the input data for evidence synthesis. For serotypes contained in all three vaccines, evidence could be synthesised using a network meta-analysis. For other serotypes, meta-analysis was used. Results from seroefficacy analyses were incorporated into a mathematical model of pneumococcal transmission dynamics to compare the differential impact of pneumococcal conjugate vaccine-10 and pneumococcal conjugate vaccine-13 introduction on invasive pneumococcal disease cases. The model estimated the impact of vaccine introduction over a 25-year time period and an economic evaluation was conducted. Results: In total, 47 studies were eligible from 38 countries. Twenty-eight and 12 studies with data available were included in immunogenicity and seroefficacy analyses, respectively. Geometric mean ratios comparing pneumococcal conjugate vaccine-13 versus pneumococcal conjugate vaccine-10 favoured pneumococcal conjugate vaccine-13 for serotypes 4, 9V and 23F at 1 month after primary vaccination series, with 1.14- to 1.54-fold significantly higher immunoglobulin G responses with pneumococcal conjugate vaccine-13. Risk of seroinfection prior to the time of booster dose was lower for pneumococcal conjugate vaccine-13 for serotype 4, 6B, 9V, 18C and 23F than for pneumococcal conjugate vaccine-10. Significant heterogeneity and inconsistency were present for most serotypes and for both outcomes. Twofold higher antibody after primary vaccination was associated with a 54% decrease in risk of seroinfection (relative risk 0.46, 95% confidence interval 0.23 to 0.96). In modelled scenarios, pneumococcal conjugate vaccine-13 or pneumococcal conjugate vaccine-10 introduction in 2006 resulted in a reduction in cases that was less rapid for pneumococcal conjugate vaccine-10 than for pneumococcal conjugate vaccine-13. The pneumococcal conjugate vaccine-13 programme was predicted to avoid an additional 2808 (95% confidence interval 2690 to 2925) cases of invasive pneumococcal disease compared with pneumococcal conjugate vaccine-10 introduction between 2006 and 2030. Limitations: Analyses used data from infant vaccine studies with blood samples taken prior to a booster dose. The impact of extrapolating pre-booster efficacy to post-booster time points is unknown. Network meta-analysis models contained significant heterogeneity which may lead to bias. Conclusions: Serotype-specific differences were found in immunogenicity and seroefficacy between pneumococcal conjugate vaccine-13 and pneumococcal conjugate vaccine-10. Higher antibody response after vaccination was associated with a lower risk of subsequent infection. These methods can be used to compare the pneumococcal conjugate vaccines and optimise vaccination strategies. For future work, seroefficacy estimates can be determined for other pneumococcal vaccines, which could contribute to licensing or policy decisions for new pneumococcal vaccines. Study registration: This study is registered as PROSPERO CRD42019124580. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 17/148/03) and is published in full in Health Technology Assessment; Vol. 28, No. 34. See the NIHR Funding and Awards website for further award information.

Pneumococcal disease is a serious illness caused by a bacterial infection that can result in death. Children in the United Kingdom receive a vaccine to prevent this disease that protects against 13 different types of pneumococcal diseases. It is very effective, but other vaccines are also available, such as one that contains 10 types of pneumococcal diseases. Vaccines in the United Kingdom are bought by the government and the choice of which vaccine to provide is based on the cost of the vaccine as well as the benefits to our health. However, there is very little information comparing different vaccines and it is often assumed they are the same. We did a large analysis combining all studies of the two main licensed pneumococcal vaccines to determine which vaccine provides better protection against infection and how this affects costs. We used information from studies published in medical journals, and also data from studies done by the companies that own the vaccines. Our results showed that pneumococcal conjugate vaccine-13 vaccine provided better protection than pneumococcal conjugate vaccine-10 for 5 of the 10 serotypes that are contained in both vaccines. When we used these results to model what might have happened had either of these vaccines been introduced into the United Kingdom vaccination programme in 2006, we found that both vaccines caused a rapid decrease in the amount of disease, but that the decrease in disease was faster with pneumococcal conjugate vaccine-13 than pneumococcal conjugate vaccine-10. This resulted in 2808 cases of diseases prevented over a 25-year time frame with pneumococcal conjugate vaccine-13 compared with pneumococcal conjugate vaccine-10. Our methods can be used to compare other vaccines and we recommend this type of study be done in future when making decisions on vaccine product choice.

Monogenic Inborn Errors of Immunity with impaired IgG response to polysaccharide antigens but normal IgG levels and normal IgG response to protein antigens.

In patients with severe and recurrent infections, minimal diagnostic workup to test for Inborn Errors of Immunity (IEI) includes a full blood count, IgG, IgA and IgM. Vaccine antibodies against tetanus toxoid are also frequently measured, whereas testing for anti-polysaccharide IgG antibodies and IgG subclasses is not routinely performed by primary care physicians. This basic approach may cause a significant delay in diagnosing monogenic IEI that can present with an impaired IgG response to polysaccharide antigens with or without IgG subclass deficiency at an early stage. Our article reviews genetically defined IEI, that may initially present with an impaired IgG response to polysaccharide antigens, but normal or only slightly decreased IgG levels and normal responses to protein or conjugate vaccine antigens. We summarize clinical, genetic, and immunological findings characteristic for these IEI. This review may help clinicians to identify patients that require extended immunologic and genetic evaluations despite unremarkable basic immunologic findings. We recommend the inclusion of anti-polysaccharide IgG antibodies as part of the initial routine work-up for possible IEI.

Effectiveness of 13-valent pneumococcal conjugate vaccine for prevention of invasive pneumococcal disease among children in the United States between 2010 and 2019: An indirect cohort study.

BACKGROUND: A U.S. case-control study (2010-2014) demonstrated vaccine effectiveness (VE) for ≥ 1 dose of the thirteen-valent pneumococcal conjugate vaccine (PCV13) against vaccine-type (VT) invasive pneumococcal disease (IPD) at 86 %; however, it lacked statistical power to examine VE by number of doses and against individual serotypes. METHODS: We used the indirect cohort method to estimate PCV13 VE against VT-IPD among children aged < 5 years in the United States from May 1, 2010 through December 31, 2019 using cases from CDC's Active Bacterial Core surveillance, including cases enrolled in a matched case-control study (2010-2014). Cases and controls were defined as individuals with VT-IPD and non-PCV13-type-IPD (NVT-IPD), respectively. We estimated absolute VE using the adjusted odds ratio of prior PCV13 receipt (1-aOR x 100 %). RESULTS: Among 1,161 IPD cases, 223 (19.2 %) were VT cases and 938 (80.8 %) were NVT controls. Of those, 108 cases (48.4 %; 108/223) and 600 controls (64.0 %; 600/938) had received > 3 PCV13 doses; 23 cases (17.6 %) and 15 controls (2.4 %) had received no PCV doses. VE ≥ 3 PCV13 doses against VT-IPD was 90.2 % (95 % Confidence Interval75.4-96.1 %), respectively. Among the most commonly circulating VT-IPD serotypes, VE of ≥ 3 PCV13 doses was 86.8 % (73.7-93.3 %), 50.2 % (28.4-80.5 %), and 93.8 % (69.8-98.8 %) against serotypes 19A, 3, and 19F, respectively. CONCLUSIONS: At least three doses of PCV13 continue to be effective in preventing VT-IPD among children aged < 5 years in the US. PCV13 was protective against serotypes 19A and 19F IPD; protection against serotype 3 IPD did not reach statistical significance.

[Vaccination against influenza, pneumococcus and herpes zoster in the elderly Survey of prescribing physicians: assessment of knowledge and identification of obstacles to the prescription of vaccination]. / Vaccination contre la grippe, le pneumocoque et le zona chez les sujets âgés Enquête menée autour des médecins prescripteurs : état des lieux des connaissances et identification des freins à la prescription de la vaccination.

Vaccination coverage is insufficient for influenza, pneumococcus, and herpes zoster in people over the age of 65 in France, even though these are common infectious diseases. Using a computerised questionnaire, the aim of our study was to assess the knowledge of general practitioners, geriatricians, infectious diseases specialists and interns in the Loire region about the vaccination against these three diseases in elderly subjects, to identify the obstacles to vaccination, and to evaluate whether the provision of knowledge modifies the prescriptions and vaccination recommendations made to patients. Of the 125 responses from doctors and interns, 90.2 % are correct for influenza, 69.2 % for pneumococcus, and 32.8 % for herpes zoster, with no significant difference between specialities. By providing information, practitioners are more willing to vaccinate their patients against influenza (99 %), pneumococcus (93 %), and herpes zoster (39 %). The main obstacles to vaccination are the patient's refusal (85 %), the doctor's lack of knowledge and time (70 % and 41 % respectively), doubts about the vaccine's effectiveness (28 %), and fear of side effects (21 %).

Penicillin Prophylaxis in Patients With Sickle Cell Disease Beyond Age 5 Years.

OBJECTIVE: Patients with sickle cell disease (SCD) are at increased risk for invasive pneumococcal disease (IPD) caused by Streptococcus pneumoniae. Immunization and antimicrobial prophylaxis may prevent this complication, and landmark clinical trials support discontinuation of antimicrobial prophylaxis at age 5 years. However, antimicrobial prophylaxis continues in some patients indefinitely. The objective of this study was to evaluate the incidence of culture-positive IPD and other infections in the setting of penicillin prophylaxis in the pediatric SCD population. METHODS: This was a single-center, retrospective cohort study of patients with SCD who continued antimicrobial prophylaxis with penicillin, compared with those whose antimicrobial prophylaxis was discontinued. Included patients were aged 5 to 18 years during the study period and had no history of IPD or surgical splenectomy. Patient charts were reviewed for demographics, immunizations, penicillin prescription history, and microbiologic culture data. RESULTS: Antimicrobial prophylaxis continued beyond age 5 years in 65% of patients, a higher percentage of whom had hemoglobin SS or S beta-zero disease. No patients whose antimicrobial prophylaxis was discontinued experienced IPD; 1 patient who continued antimicrobial prophylaxis died of S pneumoniae sepsis. Rates of other infections were comparable between groups (21% in prophylaxis versus 18% in no prophylaxis). CONCLUSIONS: These results support appropriate de-prescribing of antimicrobial prophylaxis in patients with SCD who are not at high risk for IPD. Further multicenter studies are needed to evaluate consequences of antimicrobial prophylaxis with alternative agents on antibiotic resistance, examine provider rationale for continuation of antimicrobial prophylaxis, and assess quality of life effects (e.g., medication adherence, adverse drug reactions) of antimicrobial prophylaxis.

Highly Resistant Serotype 19A Streptococcus pneumoniae of the GPSC1/CC320 Clone from Invasive Infections in Poland Prior to Antipneumococcal Vaccination of Children.

INTRODUCTION: The introduction of pneumococcal conjugate vaccines (PCV) into the national immunization programs (NIPs) has significantly reduced the number of pneumococcal infections. However, infections caused by isolates of non-vaccine serotypes (NVT) started spreading shortly thereafter and strains of NVT 19A have become the main cause of invasive pneumococcal disease burden worldwide. The aim of the study was to characterize serotype 19A invasive pneumococci of GPSC1/CC320 circulating in Poland before the introduction of PCV into the Polish NIP in 2017 and to compare them to isolates from other countries where PCVs were implemented much earlier than in Poland. METHODS: All the GPSC1/CC320 isolates were analyzed by serotyping, susceptibility testing, and whole genome sequencing followed by analyses of resistome, virulome, and core genome multilocus sequence typing (cgMLST), including comparative analysis with isolates with publicly accessible genomic sequences (PubMLST). RESULTS: During continuous surveillance the NRCBM collected 4237 invasive Streptococcus pneumoniae isolates between 1997 and 2016, including 200 isolates (4.7%) of serotype 19A. The most prevalent among 19A pneumococci were highly resistant representatives of Global Pneumococcal Sequence Cluster 1/Clonal Complex 320, GPSC1/CC320 (n = 97, 48.5%). Isolates of GPSC1/CC320 belonged to three sequence types (STs): ST320 (75.2%) ST4768 (23.7%), and ST15047 (1.0%), which all represented the 19A-III cps subtype and had complete loci for both PI-1 and PI-2 pili types. On the basis of the cgMLST analysis the majority of Polish GPSC1/CC320 isolates formed a group clearly distinct from pneumococci of this clone observed in other countries. CONCLUSION: Before introduction of PCV in the Polish NIP we noticed an unexpected increase of serotype 19A in invasive pneumococcal infections, with the most common being representatives of highly drug-resistant GPSC1/CC320 clone, rarely identified in Europe both before and even after PCV introduction.

Temporally Associated Invasive Pneumococcal Disease and SARS-CoV-2 Infection, Alaska, USA, 2020-2021.

Streptococcus pneumoniae can co-infect persons who have viral respiratory tract infections. However, research on S. pneumoniae infections that are temporally associated with SARS-CoV-2 infections is limited. We described the epidemiology and clinical course of patients who had invasive pneumococcal disease (IPD) and temporally associated SARS-CoV-2 infections in Alaska, USA, during January 1, 2020-December 23, 2021. Of 271 patients who had laboratory-confirmed IPD, 55 (20%) had a positive SARS-CoV-2 test result. We observed no major differences in age, race, sex, or underlying medical conditions among IPD patients with and without SARS-CoV-2. However, a larger proportion of IPD patients with SARS-CoV-2 died (16%, n = 9) than for those with IPD alone (4%, n = 9) (p<0.01). IPD patients with SARS-CoV-2 were also more likely to be experiencing homelessness (adjusted OR 3.5; 95% CI 1.7-7.5). Our study highlights the risk for dual infection and ongoing benefits of pneumococcal and COVID-19 vaccination, especially among vulnerable populations.

Safety and immunogenicity of 15-valent pneumococcal conjugate vaccine in Japanese healthy infants: A phase III study (V114-033).

BACKGROUND: This phase III study evaluated safety, tolerability, and immunogenicity of V114 (15-valent pneumococcal conjugate vaccine) in Japanese infants. V114 contains all 13 serotypes in PCV13 plus additional serotypes 22F and 33F. METHODS: Healthy Japanese infants were randomized to receive three primary doses of V114 or PCV13 (dose 1 at 2-6 months of age; doses 2 and 3 ≥ 27 days after prior dose), plus a toddler dose at 12-15 months of age. Adverse events (AEs) were collected on Days 1-14 following each vaccination. Serotype-specific anti-pneumococcal immunoglobulin G (IgG) was measured 30 days post-dose 3, pre-dose 4, and 30 days post-dose 4. Primary objectives included non-inferiority of V114 to PCV13 for the 13 shared serotypes based on serotype-specific IgG response rates (IgG ≥ 0.35 µg/mL) and geometric mean concentration (GMC) ratios, and for serotypes 22F and 33F based on IgG response rates and compared with the lowest response of any serotype in the PCV13 group, at 30 days post-dose 3. RESULTS: Overall, 694 infants were randomized to V114 (n = 347) or PCV13 (n = 347). Proportions of participants with solicited and serious AEs were comparable between vaccination groups. V114 met non-inferiority criteria for all 13shared serotypes, based on difference in proportion of responders (lower bound of two-sided 95 % confidence interval [CI] > -10.0) and IgG GMC ratios (V114/PCV13, lower bound of two-sided 95 % CI > 0.5) at 30 days post-dose 3. The non-inferiority criterion based on IgG response rates was met for serotype 22F, but narrowly missed for serotype 33F (90.9 %, lower bound of two-sided 95 % CI -10.6). CONCLUSION: In Japanese infants, a four-dose series of V114 was generally well tolerated. Compared with PCV13, V114 provided non-inferior immune responses to the 13 shared serotypes and higher immune responses to serotype 22F and 33F post-primary series. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04384107; EudraCT 2019-003644-68.

Safety and immunogenicity of a 15-valent pneumococcal conjugate vaccine in Japanese healthy infants: A Phase I study (V114-028).

This Phase I study evaluated the safety, tolerability, and immunogenicity of V114, a 15-valent pneumococcal conjugate vaccine (PCV), via subcutaneous (SC) or intramuscular (IM) administration, in healthy Japanese infants 3 months of age. A total of 133 participants were randomized to receive four doses (3 + 1 regimen) of V114-SC (n = 44), V114-IM (n = 45), or 13-valent PCV (PCV13)-SC (n = 44) at 3, 4, 5, and 12-15 months of age. Diphtheria, tetanus, and pertussis-inactivated poliovirus (DTaP-IPV) vaccine was administered concomitantly at all vaccination visits. The primary objective was to assess the safety and tolerability of V114-SC and V114-IM. Secondary objectives were to assess the immunogenicity of PCV and DTaP-IPV at 1-month post-dose 3 (PD3). On days 1-14 following each vaccination, the proportions of participants with systemic adverse events (AEs) were comparable across interventions, whereas injection-site AEs were higher with V114-SC (100.0%) and PCV13-SC (100.0%) than with V114-IM (88.9%). Most AEs were mild or moderate in severity and no vaccine-related serious AEs or deaths were reported. Serotype-specific immunoglobulin G (IgG) response rates at 1-month PD3 were comparable across groups for most shared serotypes between V114 and PCV13. For additional V114 serotypes 22F and 33F, IgG response rates were higher with V114-SC and V114-IM than with PCV13-SC. DTaP-IPV antibody response rates at 1-month PD3 for V114-SC and V114-IM were comparable with PCV13-SC. Findings suggest that vaccination with V114-SC or V114-IM in healthy Japanese infants is generally well tolerated and immunogenic.

Pneumococcal bacteraemia in adults over a 10-year period (2011-2020): a clinical and serotype analysis.

BACKGROUND: Streptococcus pneumoniae (pneumococcus) is a human nasopharyngeal tract coloniser responsible for invasive pneumococcal disease, which is largely vaccine preventable. Vaccination is recommended from birth for all, and through adulthood for those with risk conditions. AIMS: To describe the clinical and serotype analysis of pneumococcus bacteraemia over a 10-year period. METHODS: A 10-year (February 2011-December 2020) retrospective review was performed on all adult (age ≥18 years) pneumococcus bacteraemia presenting to the four public hospitals in Western Sydney, Australia. Comorbidities and risk factors were recorded. RESULTS: Three hundred unique episodes of S. pneumoniae bloodstream infection (SPBI) were identified during the study period. The median age for SPBI was 63 years with 31.7% aged 70 years or older. A 94.7% had one or more risks factors for SPBI. Pneumonia was reported in 80% of all SPBI, whereas meningitis was reported in 6% and infective endocarditis in <1%. Asplenia was noted in 2.4%. Seven- and 30-day mortality was 6.6% and 11.9%, with a higher 30-day mortality in those aged ≥70 years (24.4%). The serotype distribution showed 7-valent conjugate vaccine covered 11.0% of all isolates, whereas 13-valent conjugate vaccine (13vPCV) and a 23-valent polysaccharide vaccine (23vPPV) covered 41.7% and 69.0% respectively. Immunisation details were available for 110 individuals, of whom, only 7.3% had received pneumococcal vaccination. CONCLUSIONS: Most patients with pneumococcal bacteraemia had age- or comorbidity-related risk factors but were not vaccinated. Two-thirds of cases occurred in people aged <70 years. 13vPCV and 23vPPV covered 41.7% and 69.0% of bacteraemic isolates.

Safety, tolerability, and immunogenicity of V114 pneumococcal vaccine compared with PCV13 in a 2+1 regimen in healthy infants: A phase III study (PNEU-PED-EU-2).

BACKGROUND: This phase III study evaluated safety, tolerability, and immunogenicity of V114 (15-valent pneumococcal conjugate vaccine) in healthy infants. V114 contains all 13 serotypes in PCV13 and additional serotypes 22F and 33F. METHODS: Healthy infants were randomized to two primary doses and one toddler dose (2+1 regimen) of V114 or PCV13 at 3, 5, and 12 months of age; diphtheria, tetanus, pertussis (DTaP), inactivated poliovirus (IPV), Haemophilus influenzae type b (Hib), hepatitis B (HepB) vaccine was administered concomitantly. Adverse events (AEs) were collected on Days 1-14 following each vaccination. Serotype-specific anti-pneumococcal immunoglobulin G (IgG) was measured 30 days post-primary series, immediately prior to toddler dose, and 30 days post-toddler dose. Primary objectives included non-inferiority of V114 to PCV13 for 13 shared serotypes and superiority of V114 to PCV13 for serotypes 22F and 33F. RESULTS: 1191 healthy infants were randomized to V114 (n = 595) or PCV13 (n = 596). Proportions of participants with solicited AEs and serious AEs were comparable between groups. V114 met non-inferiority criteria for 13 shared serotypes, based on difference in proportions with serotype-specific IgG ≥0.35 µg/mL (lower bound of two-sided 95% confidence interval [CI] >-10.0) and IgG geometric mean concentration (GMC) ratios (lower bound of two-sided 95% CI >0.5) at 30 days post-toddler dose. V114 met superiority criteria for serotypes 22F and 33F, based on response rates (lower bound of two-sided 95% CI >10.0) and IgG GMC ratios (lower bound of two-sided 95% CI >2.0) at 30 days post-toddler dose. Antibody responses to DTaP-IPV-Hib-HepB met non-inferiority criteria, based on antigen-specific response rates. CONCLUSION: A two-dose primary series plus toddler dose of V114 was well-tolerated in healthy infants. Compared with PCV13, V114 provided non-inferior immune responses to 13 shared serotypes and superior immune responses to additional serotypes 22F and 33F.

A cost-effectiveness analysis of pneumococcal conjugate vaccines in infants and herd protection in older adults in Colombia.

BACKGROUND: Pneumococcal diseases have a clinical and economic impact on the population. Until this year, a 10-valent pneumococcal vaccine (PCV10) used to be applied in Colombia, which does not contain serotypes 19A, 3, and 6A, the most prevalent in the country. Therefore, we aimed to assess the cost-effectiveness of the shift to the 13-valent pneumococcal vaccine (PCV13). RESEARCH DESIGN AND METHODS: A decision model was used for newborns in Colombia between 2022-2025 and adults over 65 years. The time horizon was life expectancy. Outcomes are Invasive Pneumococcal Diseases (IPD), Community-Acquired Pneumonia (CAP), Acute Otitis Media (AOM), their sequelae, Life Gained Years (LYGs), and herd effect in older adults. RESULTS: PCV10 covers 4.27% of serotypes in the country, while PCV13 covers 64.4%. PCV13 would avoid in children 796 cases of IPD, 19,365 of CAP, 1,399 deaths, and generate 44,204 additional LYGs, as well as 9,101 cases of AOM, 13 cases of neuromotor disability and 428 cochlear implants versus PCV10. In older adults, PCV13 would avoid 993 cases of IPD and 17,245 of CAP, versus PCV10. PCV13 saves $51.4 million. The decision model shows robustness in the sensitivity analysis. CONCLUSION: PCV13 is a cost-saving strategy versus PCV10 to avoid pneumococcal diseases.

Enfermedad invasiva por Streptococcus pneumoniae, en pacientes adultos. Periodo 2016 al 2018

Introducción: En Paraguay y en otras partes del mundo el Streptococcus pneumoniae es el principal agente causante de neumonía bacteriana, otitis media, meningitis y septicemia. Objetivo: Describir las características clínico-epidemiológicas de pacientes con enfermedad invasiva por Streptococcus pneumoniae atendidos en el Instituto de Medicina Tropical (IMT) durante los años 2016 al 2019. Metodología: Estudio observacional, descriptivo, transversal. Se incluyeron a todos los pacientes con enfermedad invasiva por Streptococcus pneumoniae confirmada. Resultados: Fueron incluidos 34 pacientes, la edad promedio fue de 44años, 76% fueron varones, 61% diagnóstico de infección por VIH. El foco infeccioso predominante fue el pulmonar. De las muestras biológicas con cultivos positivos, el 73% fueron aislados en sangre, y los restantes distribuidos entre muestras de esputo, líquido ceflorraquideo y liquido pleural. El 24% de los pacientes presentaron complicaciones, entre falla orgánica (15%) y empiema (9%). El 59% de los pacientes recibió tratamiento con cefalosporinas. La mortalidad intrahospitalaria registrada fue del 18%.Conclusión: Los pacientes con enfermedad invasiva que acudieron al IMT durante los años 2016 al 2019 fueron en su mayoría adultos jóvenes, inmunosuprimidos, con neumonía.

Introduction: In Paraguay and in other parts of the world, Streptococcus pneumoniae is the main causative agent of bacterial pneumonia, otitis media, meningitis and septicemia. Objective: To describe the clinical-epidemiological characteristics of patients with invasive disease due to Streptococcus pneumoniae treated at the Institute of Tropical Medicine (IMT) during the years 2016 to 2019. Methodology: Observational, descriptive, cross-sectional study. All patients with confirmed invasive disease due to Streptococcus pneumoniae were included. Results: 34 patients were included, the average age was 44 years, 76% were male, 61% diagnosed with HIV infection. The predominant infectious focus was the lung. Of the biological samples with positive cultures, 73% were isolated from blood, and the rest distributed among samples of sputum, cerebrospinal fluid, and pleural fluid. 24% of the patients presented complications, between organic failure (15%) and empyema (9%). 59% of the patients received treatment with cephalosporins. The registered intrahospital mortality was 18%. Conclusion: The patients with invasive disease who attended the IMT during the years 2016 to 2019 were mostly young adults, immunosuppressed, with pneumonia.

Cost-effectiveness of 20-valent pneumococcal conjugate vaccine in Denmark compared with PPV23.

BACKGROUND: A new 20-valent pneumococcal conjugate vaccine (PCV20) provides protection against 20 pneumococcal serotypes. The vaccine has the potential to decrease the impact of pneumococcal diseases in society and to increase health among vulnerable persons. AIM: This study investigates the cost-effectiveness of vaccinating Danish adults in different age groups and risk of pneumococcal disease with PCV20 compared to the 23-valent pneumococcal polysaccharide vaccine (PPV23) - either as PCV20 compared to PPV23 or as PPV23 followed by PCV20 compared to PPV23. METHODS: A Markov model adapted to the Danish setting was developed to estimate clinical outcomes and costs of vaccinating the Danish population in specific age and risk groups. The model used a restricted societal perspective and estimated outcomes and costs using a lifetime time horizon. To estimate the clinical outcomes and costs, inputs on vaccine effectiveness and waning were retrieved from other studies whereas data on risk groups, coverage and costs were based on real-world data. RESULTS: The results showed that in all scenarios the incidence and mortality of pneumococcal disease were reduced when vaccinating with PCV20, resulting in lower costs. For the vaccine target group of adults aged ≥18 years at moderate or high risk and all adults aged ≥65 years both in the case of PPV23+PCV20 compared to PPV23 and in case of PCV20 compared to PPV23 vaccination with PCV20 was found to be a dominant strategy gaining 1,350 or 5,821 quality-adjusted life years (QALYs), respectively, and reducing total costs by 60 or 396 million EUR, respectively, as compared to PPV23 vaccination alone. Similar results of dominant PCV20 strategy were found for other age and risk group comparisons. Both deterministic and probabilistic sensitivity analyses confirmed the results being robust to changes in input parameters and applied assumptions. LIMITATIONS: Like other modelling studies, this analysis has limitations such as lack of detailed data for some inputs. CONCLUSION: Vaccination with PCV20 reduced the incidence and mortality of pneumococcal diseases in Danish adults compared to PPV23. This reduction has the potential to reduce the financial burden related to managing diseases while also increasing public health.

Predicting effectiveness of the V114 vaccine against invasive pneumococcal disease in children.

BACKGROUND: The potential impact of new pneumococcal conjugate vaccines (PCVs) is assessed by using immune responses to predict their effectiveness against invasive pneumococcal disease (IPD). This analysis predicted the serotype-specific effectiveness against IPD of a new 15-valent PCV (V114) for the serotypes shared with a 13-valent PCV (PCV13), in a US pediatric population given a 3 + 1 dosing regimen. METHODS: Beginning with the known serotype-specific antibody concentrations after vaccination with placebo, 7-valent PCV (PCV7) and PCV13, reverse cumulative distribution curves were used, along with published serotype-specific vaccine effectiveness of PCV7 and PCV13, to derive a protective antibody concentration (Cp) for each PCV13 serotype in V114. Serotype-specific effectiveness was predicted using the Cp estimates and the respective serotype-specific antibody concentrations of placebo and V114 recipients in recent pediatric clinical trials. RESULTS: Predicted serotype-specific V114 effectiveness values ranged from 86% to 99% for PCV7 serotypes and from 59% to 97% for (non-PCV7) PCV13 serotypes. CONCLUSIONS: V114 serotype-specific effectiveness against IPD in a US pediatric population was predicted to be largely comparable to that of PCV7 and PCV13 for shared serotypes, with models suggesting likelihood of high overall benefit gained from increased serotype 3 effectiveness, and additional protection against serotypes 22 F and 33 F.