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Vaccine Jul 2023CDC pneumococcal vaccination recommendations for older adults now include either 15- or 20-valent pneumococcal conjugate vaccine (PCV15/PCV20). However, an...
INTRODUCTION
CDC pneumococcal vaccination recommendations for older adults now include either 15- or 20-valent pneumococcal conjugate vaccine (PCV15/PCV20). However, an in-development 21-valent vaccine (PCV21), formulated based on adult pneumococcal disease epidemiology, could substantially increase coverage of disease-causing pneumococcal serotypes, particularly in Black older adults, who are at greater risk. The potential public health impact and cost-effectiveness of PCV21 compared to currently recommended vaccines in older adults is unclear.
METHODS
A Markov decision model compared current pneumococcal vaccination recommendations to PCV21 use in Black and non-Black 65-year-old cohorts. CDC Active Bacterial Core surveillance data informed population and serotype-specific pneumococcal disease risk. Vaccine effectiveness was estimated using Delphi panel estimates and clinical trial data, with variation in sensitivity analyses. Potential indirect effects on adult disease from PCV15 childhood vaccination were examined. All model parameters were varied individually and collectively in sensitivity analyses. Scenarios with decreased PCV21 effectiveness and potential COVID-19 pandemic effects were also examined.
RESULTS
In the Black cohort, the PCV21 strategy cost $88,478 per quality adjusted life-year (QALY) gained without and $97,952/QALY with childhood PCV15 indirect effects. PCV21 in the non-Black cohort cost $127,436/QALY gained without and $141,358/QALY with childhood PCV15 effects. Current recommendation strategies were economically unfavorable, regardless of population or indirect childhood vaccination effects. Results favoring PCV21 use were robust in sensitivity analyses and alternative scenarios.
CONCLUSION
An in-development PCV21 vaccine would likely be economically and clinically favorable compared to currently recommended pneumococcal vaccines in older adults. While PCV21 was more favorable in Black cohort analyses, results for both Black and non-Black populations were economically reasonable, highlighting the potential importance of adult-specific pneumococcal vaccine formulations and, pending further investigation, potentially justifying a future general population recommendation for PCV21 use in older adults.
Topics: Humans; Aged; Adult; Middle Aged; Pneumococcal Vaccines; Cost-Benefit Analysis; Pandemics; COVID-19; Streptococcus pneumoniae; Pneumococcal Infections; Vaccination; Vaccines, Conjugate
PubMed: 37316409
DOI: 10.1016/j.vaccine.2023.06.007 -
The Lancet. Infectious Diseases Aug 2023Interest in reduced-dose pneumococcal conjugate vaccine (PCV) schedules is growing, but data on their ability to provide direct and indirect protection are scarce. We... (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy against pneumococcal carriage and the immunogenicity of reduced-dose (0 + 1 and 1 + 1) PCV10 and PCV13 schedules in Ho Chi Minh City, Viet Nam: a parallel, single-blind, randomised controlled trial.
BACKGROUND
Interest in reduced-dose pneumococcal conjugate vaccine (PCV) schedules is growing, but data on their ability to provide direct and indirect protection are scarce. We evaluated 1 + 1 (at 2 months and 12 months) and 0 + 1 (at 12 months) schedules of PCV10 or PCV13 in a predominately unvaccinated population.
METHODS
In this parallel, single-blind, randomised controlled trial, healthy infants aged 2 months were recruited from birth records in three districts in Ho Chi Minh City, Vietnam, and assigned (4:4:4:4:9) to one of five groups: PCV10 at 12 months of age (0 + 1 PCV10), PCV13 at 12 months of age (0 + 1 PCV13), PCV10 at 2 months and 12 months of age (1 + 1 PCV10), PCV13 at 2 months and 12 months of age (1 + 1 PCV13), and unvaccinated control. Outcome assessors were masked to group allocation, and the infants' caregivers and those administering vaccines were not. Nasopharyngeal swabs collected at 6 months, 12 months, 18 months, and 24 months were analysed for pneumococcal carriage. Blood samples collected from a subset of participants (200 per group) at various timepoints were analysed by ELISA and opsonophagocytic assay. The primary outcome was the efficacy of each schedule against vaccine-type carriage at 24 months, analysed by intention to treat for all those with a nasopharyngeal swab available. This trial is registered at ClinicalTrials.gov, NCT03098628.
FINDINGS
2501 infants were enrolled between March 8, 2017, and July 24, 2018 and randomly assigned to study groups (400 to 0 + 1 PCV10, 400 to 0 + 1 PCV13, 402 to 1 + 1 PCV10, 401 to 1 + 1 PCV13, and 898 to control). Analysis of the primary endpoint included 341 participants for 0 + 1 PCV10, 356 0 + 1 PCV13, 358 1 + 1 PCV10, 350 1 + 1 PCV13, and 758 control. At 24 months, a 1 + 1 PCV10 schedule reduced PCV10-type carriage by 58% (95% CI 25 to 77), a 1 + 1 PCV13 schedule reduced PCV13-type carriage by 65% (42 to 79), a 0 + 1 PCV10 schedule reduced PCV10-type carriage by 53% (17 to 73), and a 0 + 1 PCV13 schedule non-significantly reduced PCV13-type carriage by 25% (-7 to 48) compared with the unvaccinated control group. Reactogenicity and serious adverse events were similar across groups.
INTERPRETATION
A 1 + 1 PCV schedule greatly reduces vaccine-type carriage and is likely to generate substantial herd protection and provide some degree of individual protection during the first year of life. Such a schedule is suitable for mature PCV programmes or for introduction in conjunction with a comprehensive catch-up campaign, and potentially could be most effective given as a mixed regimen (PCV10 then PCV13). A 0 + 1 PCV schedule has some effect on carriage along with a reasonable immune response and could be considered for use in humanitarian crises or remote settings.
FUNDING
Bill & Melinda Gates Foundation.
TRANSLATION
For the Vietnamese translation of the abstract see Supplementary Materials section.
Topics: Infant; Humans; Pneumococcal Infections; Vietnam; Single-Blind Method; Streptococcus pneumoniae; Pneumococcal Vaccines; Vaccines, Conjugate; Nasopharynx
PubMed: 37062304
DOI: 10.1016/S1473-3099(23)00061-0 -
Vaccine Apr 2024Pneumococcal conjugate vaccines (PCVs) significantly reduced pneumococcal disease burden. Nevertheless, alternative approaches for controlling more serotypes are needed.... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Pneumococcal conjugate vaccines (PCVs) significantly reduced pneumococcal disease burden. Nevertheless, alternative approaches for controlling more serotypes are needed. Here, the safety, tolerability, and immunogenicity of a 24-valent (1/2/3/4/5/6A/6B/7F/8/9N/9V/10A/11A/12F/14/15B/17F/18C/19A/19F/20B/22F/23F/33F) pneumococcal vaccine based on Multiple Antigen-Presenting System (MAPS) technology (Pn-MAPS24v) was assessed in toddlers.
METHODS
In this phase 1, blinded, dose-escalation, active-controlled multicenter study conducted in the United States (September/2020-April/2022), 12-15-month-old toddlers primed with three doses of 13-valent PCV (PCV13) were randomized 3:2 to receive a single dose of one of three Pn-MAPS24v dose levels (1 μg/2 μg/5 μg per polysaccharide) or PCV13 intramuscularly. Reactogenicity (within 7 days), treatment-emergent adverse events (TEAEs, within 180 days), serious/medically attended adverse events (SAEs/MAAEs, within 180 days), and immunogenicity (serotype-specific anti-capsular polysaccharide immunoglobulin G [IgG] and opsonophagocytic activity [OPA] responses at 30 days post-vaccination) were assessed.
RESULTS
Of 75 toddlers enrolled, 74 completed the study (Pn-MAPS24v 1 μg/2 μg/5 μg: 15/14/16, PCV13: 29). Frequencies of local (60 %/67 %/31 %) and systemic events (67 %/67 %/75 %) in the Pn-MAPS24v 1 μg/2 μg/5 μg and the PCV13 (55 %, 79 %) groups were in similar ranges. TEAEs were reported by 47 %/40 %/63 % of Pn-MAPS24v 1 μg/2 μg/5 μg recipients and 52 % of PCV13 recipients. No vaccine-related SAE was reported. At 30 days post-vaccination, for each of the 13 common serotypes, ≥93 % of participants in each group had IgG concentrations ≥0.35 μg/mL; >92 % had OPA titers ≥lower limit of quantitation (LLOQ), except for serotype 1 (79 %). For 7/11 unique serotypes (2/8/9N/11A/17F/22F/33F), at all dose levels, ≥78 % of Pn-MAPS24v recipients in each group had IgG concentrations ≥0.35 μg/mL and 80 %-100 % had OPA titers ≥LLOQ.
CONCLUSIONS
In 12-15-month-old toddlers, a single dose of Pn-MAPS24v showed an acceptable safety profile, regardless of dose level; AEs were reported at similar frequencies by Pn-MAPS24v and PCV13 recipients. Pn-MAPS24v elicited IgG and OPA responses to all common and most unique serotypes. These results support further clinical evaluation in infants.
Topics: Humans; Infant; Antibodies, Bacterial; Immunogenicity, Vaccine; Immunoglobulin G; Pneumococcal Infections; Pneumococcal Vaccines; Polysaccharides; Streptococcus pneumoniae; Vaccines, Conjugate
PubMed: 38360475
DOI: 10.1016/j.vaccine.2024.02.001 -
Cell Chemical Biology Feb 2024Streptococcus pneumoniae is a remarkably adaptable and successful human pathogen, playing dual roles of both asymptomatic carriage in the nasopharynx and invasive... (Review)
Review
Streptococcus pneumoniae is a remarkably adaptable and successful human pathogen, playing dual roles of both asymptomatic carriage in the nasopharynx and invasive disease including pneumonia, bacteremia, and meningitis. Efficacious vaccines and effective antibiotic therapies are critical to mitigating morbidity and mortality. However, clinical interventions can be rapidly circumvented by the pneumococcus by its inherent proclivity for genetic exchange. This leads to an underappreciated interplay between vaccine and antibiotic pressures on pneumococcal populations. Circulating populations have undergone dramatic shifts due to the introduction of capsule-based vaccines of increasing valency imparting strong selective pressures. These alterations in population structure have concurrent consequences on the frequency of antibiotic resistance profiles in the population. This review will discuss the interactions of these two selective forces. Understanding and forecasting the drivers of antibiotic resistance and capsule switching are of critical importance for public health, particularly for such a genetically promiscuous pathogen as S. pneumoniae.
Topics: Humans; Streptococcus pneumoniae; Pneumococcal Infections; Anti-Bacterial Agents; Pneumococcal Vaccines; Vaccination; Vaccines, Conjugate
PubMed: 38052216
DOI: 10.1016/j.chembiol.2023.11.003 -
Journal of Clinical GastroenterologyGuidelines for inflammatory bowel disease (IBD) patients receiving immunosuppression encouraged both the pneumococcal polysaccharide vaccine (PPSV23) and the...
BACKGROUND
Guidelines for inflammatory bowel disease (IBD) patients receiving immunosuppression encouraged both the pneumococcal polysaccharide vaccine (PPSV23) and the pneumococcal conjugate vaccine (PCV13). We aimed to evaluate which pneumococcal vaccines are recommended and administered, and to understand provider and IBD patient knowledge regarding pneumococcal vaccinations.
METHODS
We performed a retrospective, cross-sectional analysis of 357 adult IBD patients on immunosuppression in our health care system. Patient demographics and clinical characteristics were collected. The primary outcome was rate of documented vaccinations recommended by providers; the secondary outcome was rate of receipt of the vaccines. We identified factors associated with receipt of any pneumococcal vaccine through multivariable logistic regression. We also performed provider and IBD patient surveys to understand provider and patient knowledge regarding pneumococcal vaccines. We used χ 2 and Fisher exact tests to assess survey responses.
RESULTS
Fifty seven percent of IBD patients had any pneumococcal vaccination recommended and 35% had recommendations for both PPSV23 and PCV13. Forty percent received any pneumococcal vaccine and 18% received both vaccines. In multivariable analyses, increasing age (adjusted odds ratio: 1.03, 95% CI: 1.01-1.05) was associated with receipt of any pneumococcal vaccine, after adjusting for gender, race, insurance, disease activity, and time seen in our gastroenterology clinics. In the survey study, on average, 59% of providers correctly answered questions regarding pneumococcal vaccination indications.
CONCLUSION
In our health care system, while recommendation for any pneumococcal vaccination was >50%, receipt of both PPSV23 and PCV13 was low. Simplified vaccine regimens (ie, PCV20) will likely improve vaccination rates.
Topics: Adult; Humans; Retrospective Studies; Cross-Sectional Studies; Vaccination; Pneumococcal Vaccines; Inflammatory Bowel Diseases
PubMed: 36728018
DOI: 10.1097/MCG.0000000000001783 -
International Journal of Epidemiology Feb 2024Despite the general consensus on the safety of pneumococcal conjugate vaccine (PCV), safety concerns unveiled during post-licensure surveillance need to be addressed. We...
BACKGROUND
Despite the general consensus on the safety of pneumococcal conjugate vaccine (PCV), safety concerns unveiled during post-licensure surveillance need to be addressed. We investigated whether there is a transient increased risk following a three-dose series of pneumococcal conjugate vaccine (PCV) administered at 2, 4 and 6 months of age.
METHODS
This was a population-based cohort study using the Korea immunization registry data linked to nationwide administrative claims data. Self-controlled risk interval analysis was conducted for PCV recipients who had an outcome of interest within pre-defined risk and control intervals between 2018 and 2022. The outcomes were anaphylaxis, asthma, encephalopathy, febrile seizure, Kawasaki disease and thrombocytopenia. We used conditional Poisson regression model to estimate the incidence rate ratios (IRRs) and 95% confidence intervals (CIs) comparing the outcomes in the risk and control intervals.
RESULTS
Of 1 114 096 PCV recipients, 8661 had outcomes either in the risk or control intervals. Their mean age at Dose 1 was 10.0 weeks, 58.3% were boys, and 85.3% received 13-valent PCV. PCV was not associated with an increased risk of any outcomes except for febrile seizure. There were 408 (56.0%) cases of febrile seizure in the risk interval, corresponding to an IRR of 1.27 (95% CI 1.10-1.47).
CONCLUSIONS
It is reassuring to note that there was no increased risk of the potential safety concerns following PCV administration. Despite the transient increased risk of febrile seizure, absolute numbers of cases were small. Febrile seizure is generally self-limiting with a good prognosis, and should not discourage parents or caregivers from vaccinating their children.
Topics: Female; Humans; Infant; Male; Cohort Studies; Pneumococcal Infections; Pneumococcal Vaccines; Routinely Collected Health Data; Seizures, Febrile; Vaccination; Vaccines, Conjugate
PubMed: 38302750
DOI: 10.1093/ije/dyae010 -
Vaccine Jul 2023The spleen is responsible for blood filtration and mounting an immune response against pathogens. In some people the spleen must be surgically removed because of...
The spleen is responsible for blood filtration and mounting an immune response against pathogens. In some people the spleen must be surgically removed because of traumatic events or oncological and hematological conditions. These patients are at higher risk of developing diseases caused by encapsulated bacteria throughout their lives. Thus, immunisations are advised for splenectomised persons to prevent infection caused by Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae type b (Hib). This study assessed vaccination coverage (VC) among Norwegian patients with surgical asplenia. Using the Nomesco Classification of Surgical Procedures codes, patient information (age, sex, date of initial diagnosis and date of surgery) was acquired from the Norwegian Patient Registry. The National Immunization Register provided information on vaccination status and data of any subsequent invasive bacterial infections were obtained from the Norwegian Surveillance System for Communicable Diseases. From the total population of Norway, 3155 patients who had undergone complete splenectomy were identified. Of these, 914 (29.0%) had received at least one dose of pneumococcal conjugate vaccine (PCV), 1324 (42.0%) at least one dose of pneumococcal polysaccharide vaccine and 589 (18.7%) had received both. Only 4.2% of the patients had received two doses of a meningococcal ACWY conjugate vaccine, while 8.0% of 1467 patients splenectomised after 2014 had received at least two doses of a serogroup B meningococcal vaccine. The VC for Hib was 18.7%. Nearly all splenectomised children under the age of 10 were vaccinated with Hib and PCV as these vaccines are included in the childhood immunisation program. For all vaccines, VC decreased with age. Twenty-nine invasive bacterial infections were registered post-splenectomy in 25 patients. Vaccination according to national recommendations could have prevented at least 8 (28%) of these infections. Our study showed that efforts are required to increase VC of splenectomised individuals in Norway.
Topics: Child; Humans; Bacterial Infections; Haemophilus influenzae type b; Haemophilus Vaccines; Meningococcal Vaccines; Norway; Pneumococcal Vaccines; Splenectomy; Vaccination; Vaccines, Conjugate; Guideline Adherence; Vaccination Coverage
PubMed: 37336662
DOI: 10.1016/j.vaccine.2023.06.034 -
Microbial Genomics Sep 2023() is a leading vaccine-preventable cause of childhood invasive disease. Nigeria has the second highest pneumococcal disease burden globally, with an estimated...
() is a leading vaccine-preventable cause of childhood invasive disease. Nigeria has the second highest pneumococcal disease burden globally, with an estimated ~49 000 child deaths caused by pneumococcal infections each year. Ten-valent pneumococcal conjugate vaccine (GSK; PCV10) was introduced in December 2014 in a phased approach. However, few studies have characterized the disease-causing pneumococci from Nigeria. This study assessed the prevalence of serotypes, antibiotic susceptibility and genomic lineages using whole genome sequencing and identified lineages that could potentially escape PCV10 (GSK). We also investigated the potential differences in pneumococcal lineage features between children with and without sickle cell disease. A collection of 192 disease-causing pneumococcal isolates was obtained from Kano (=189) and Abuja (=3) states, Nigeria, between 1 January 2014 and 31 May 2018. The majority (99 %, 190/192) of specimens were recovered from children aged 5 years or under. Among them, 37 children had confirmed or traits of sickle cell disease. Our findings identified 25 serotypes expressed by 43 Global Pneumococcal Sequence Clusters (GPSCs) and 85 sequence types (STs). The most common serotypes were 14 (18 %, =35), 6B (16 %, =31), 1 (9 %, =17), 5 (9 %, =17) and 6A (9 %, =17); all except serotype 6A are included in PCV10 (GSK). PCV10 (SII; PNEUMOSIL) and PCV13 formulations include serotypes 6A and 19A which would increase the overall coverage from 67 % by PCV10 (GSK) to 78 and 82 %, respectively. The pneumococcal lineages were a mix of globally spreading and unique local lineages. Following the use of PCV10 (GSK), GPSC5 expressing serotype 6A, GPSC10 (19A), GPSC26 (12F and 46) and GPSC627 (9L) are non-vaccine type lineages that could persist and potentially expand under vaccine-selective pressure. Approximately half (52 %, 99/192) of the pneumococcal isolates were resistant to the first-line antibiotic penicillin and 44 % (85/192) were multidrug-resistant. Erythromycin resistance was very low (2 %, 3/192). There was no significant difference in clinical manifestation, serotype prevalence or antibiotic resistance between children with and without traits of or confirmed sickle cell disease. In summary, our findings show that a high percentage of the pneumococcal disease were caused by the serotypes that are covered by currently available vaccines. Given the low prevalence of resistance, macrolide antibiotics, such as erythromycin, should be considered as an option to treat pneumococcal disease in Nigeria. However, appropriate use of macrolide antibiotics should be vigilantly monitored to prevent the potential increase in macrolide resistance.
Topics: Humans; Child; Streptococcus pneumoniae; Nigeria; Anti-Bacterial Agents; Drug Resistance, Bacterial; Macrolides; Pneumococcal Infections; Erythromycin; Anemia, Sickle Cell; Protein Synthesis Inhibitors
PubMed: 37712828
DOI: 10.1099/mgen.0.001094 -
Vaccine: X Dec 2023To compare the vaccine prices per vaccinated child under 18 and vaccine funding and procurement systems in the national vaccination programmes (NVPs) in Europe.
OBJECTIVE
To compare the vaccine prices per vaccinated child under 18 and vaccine funding and procurement systems in the national vaccination programmes (NVPs) in Europe.
METHODS
The on-line survey targeted to NVP managers collected data referred to the information available on 31 December 2016. The prices of vaccines were categorised into three groups. The price per child 1) fully vaccinated comprised all vaccines and doses offered in the NVP; 2) vaccinated with standard vaccines comprised the vaccines included in the NVP in all countries; 3) vaccinated with recent vaccines comprised the pneumococcal conjugate, human papillomavirus and rotavirus vaccines.
RESULTS
In the 23 out of 32 countries that answered the survey, 17 funded the vaccines by taxes and six by social insurance. 18 countries procured the vaccines through public tenders or negotiations. Five countries purchased the vaccines by healthcare providers and reimbursed from the health insurance system.In the countries with vaccine procurement through public tenders the price per child vaccinated with standard vaccines ranged from €59 to €117 when using pentavalent and from €98 to €220 when using hexavalent vaccines. The mean price per child vaccinated with recent vaccines was €130 for the countries that offered pneumococcal conjugate and human papillomavirus vaccines and €142 for the countries that in addition included rotavirus vaccine.In the countries that purchased the vaccines by healthcare providers and reimbursed from the health insurance system the price per child vaccinated with standard vaccines ranged from €136 to €427.
CONCLUSIONS
The vaccine prices differ notably in Europe. Prices were lower in countries where vaccines in the NVP were tax-funded and nationally or regionally procured. Improved procurement systems could lead to substantial savings or possibilities to introduce more vaccines into the NVP.
PubMed: 37779660
DOI: 10.1016/j.jvacx.2023.100392 -
Antibiotics (Basel, Switzerland) Sep 2023Antimicrobial resistance (AMR) is a significant global health concern, causing an estimated 700,000 deaths annually. Although immunisation has been shown to... (Review)
Review
BACKGROUND
Antimicrobial resistance (AMR) is a significant global health concern, causing an estimated 700,000 deaths annually. Although immunisation has been shown to significantly reduce AMR, the role of vaccines as part of antimicrobial stewardship (AMS) practices is often overlooked.
OBJECTIVE
To identify and examine the available literature on the role of vaccines as part of AMS practices.
METHOD
A scoping review was conducted in the following databases: MEDLINE, Embase, Scopus, CINAHL, CCRCT, IPA, and WoS, along with grey literature sources. The review was conducted using the JBI Methodology for Scoping Reviews and reported in line with the PRISMA-SCr checklist.
RESULTS
Among the 1711 records identified, 34 met the inclusion criteria; 8 discussed only the concept, while 26 discussed both the concept and the vaccine implementation method in AMS practices. There were eight recommended and/or utilised types of AMS activities identified involving vaccines, under four key themes of vaccine-related AMS strategies: Education, Screening, Vaccination, and Monitoring. Influenza and pneumococcal vaccines had the most evidence for inclusion.
CONCLUSION
Overall, the evidence supports the role of vaccines as part of AMS practices and the value of their inclusion in creating improved and comprehensive AMS strategies to further combat the development of AMR.
PubMed: 37760725
DOI: 10.3390/antibiotics12091429