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Vaccine Apr 2022We used an indirect cohort analysis in children under 5 years-old from 2002 to 2018 to examine vaccine effectiveness (VE) of the 7-valent pneumococcal conjugate vaccine...
We used an indirect cohort analysis in children under 5 years-old from 2002 to 2018 to examine vaccine effectiveness (VE) of the 7-valent pneumococcal conjugate vaccine (PCV) (3 + 1 doses in most regions) and the 13-valent PCV (2 + 1 doses in all regions) against invasive pneumococcal disease (IPD) caused by vaccine serotypes in children in Canada. Cases were identified from the Canadian Immunization Monitoring Program ACTive (IMPACT), a national active surveillance network of 12 tertiary care pediatric hospitals that represent about 90% of tertiary care hospital beds in Canada. There were 1477 children evaluated for PCV7 VE and 489 for PCV13 VE. PCV7 VE in children with vaccination up to date for their age was 96% (95% CI: 67-99%) after a single dose and 95% (95% CI: 92-97%) after ≥2 doses. The VE was 91% (95% CI: 85-94%) in children who had received doses but were not up to date for their age. PCV13 VE in children with vaccinations up to date for their age was 55% (95% CI: 28-72%) after ≥2 doses. The PCV13-vaccine serotypes causing breakthrough IPD in children up to date for their age with 2+ doses of PCV13 were 3 (13/27, 48.2%),19A (11/27, 40.7%), and 19F (3/27, 11.1%). When serotype 3 and 19A were excluded, the VE of PCV13 against the remaining vaccine serotypes was 89% (95% CI: 64-97%) in children with ≥2 doses. The lower VE of PCV13 may be due to lower effectiveness against serotypes 3 and 19A, which could be influenced by the change in dosing schedule from 4 to 3 total doses with the introduction of PCV13, combined with vaccine uptake of 80%. However, PCV13 still provides the benefit of protection against more serotypes than PCV7, and good VE against all serotypes except 3 and 19A.
Topics: Canada; Child; Child, Preschool; Heptavalent Pneumococcal Conjugate Vaccine; Humans; Infant; Pneumococcal Infections; Pneumococcal Vaccines; Serogroup; Streptococcus pneumoniae; Vaccination; Vaccine Efficacy; Vaccines, Conjugate
PubMed: 35351324
DOI: 10.1016/j.vaccine.2022.03.048 -
The Lancet. Microbe Sep 2023The effect of childhood pneumococcal conjugate vaccine implementation in Malawi is threatened by absence of herd effect. There is persistent vaccine-type pneumococcal... (Randomized Controlled Trial)
Randomized Controlled Trial
Effect of 13-valent pneumococcal conjugate vaccine on experimental carriage of Streptococcus pneumoniae serotype 6B in Blantyre, Malawi: a randomised controlled trial and controlled human infection study.
BACKGROUND
The effect of childhood pneumococcal conjugate vaccine implementation in Malawi is threatened by absence of herd effect. There is persistent vaccine-type pneumococcal carriage in both vaccinated children and the wider community. We aimed to use a human infection study to measure 13-valent pneumococcal conjugate vaccine (PCV13) efficacy against pneumococcal carriage.
METHODS
We did a double-blind, parallel-arm, randomised controlled trial investigating the efficacy of PCV13 or placebo against experimental pneumococcal carriage of Streptococcus pneumoniae serotype 6B (strain BHN418) among healthy adults (aged 18-40 years) from Blantyre, Malawi. We randomly assigned participants (1:1) to receive PCV13 or placebo. PCV13 and placebo doses were prepared by an unmasked pharmacist to maintain research team and participant masking with identification only by a randomisation identification number and barcode. 4 weeks after receiving either PCV13 or placebo, participants were challenged with 20 000 colony forming units (CFUs) per naris, 80 000 CFUs per naris, or 160 000 CFUs per naris by intranasal inoculation. The primary endpoint was experimental pneumococcal carriage, established by culture of nasal wash at 2, 7, and 14 days. Vaccine efficacy was estimated per protocol by means of a log-binomial model adjusting for inoculation dose. The trial is registered with the Pan African Clinical Trials Registry, PACTR202008503507113, and is now closed.
FINDINGS
Recruitment commenced on April 27, 2021 and the final visit was completed on Sept 12, 2022. 204 participants completed the study protocol (98 PCV13, 106 placebo). There were lower carriage rates in the vaccine group at all three inoculation doses (0 of 21 vs two [11%] of 19 at 20 000 CFUs per naris; six [18%] of 33 vs 12 [29%] of 41 at 80 000 CFUs per naris, and four [9%] of 44 vs 16 [35%] of 46 at 160 000 CFUs per naris). The overall carriage rate was lower in the vaccine group compared with the placebo group (ten [10%] of 98 vs 30 [28%] of 106; Fisher's p value=0·0013) and the vaccine efficacy against carriage was estimated at 62·4% (95% CI 27·7-80·4). There were no severe adverse events related to vaccination or inoculation of pneumococci.
INTERPRETATION
This is, to our knowledge, the first human challenge study to test the efficacy of a pneumococcal vaccine against pneumococcal carriage in Africa, which can now be used to establish vaccine-induced correlates of protection and compare alternative strategies to prevent pneumococcal carriage. This powerful tool could lead to new means to enhance reduction in pneumococcal carriage after vaccination.
FUNDING
Wellcome Trust.
Topics: Adult; Child; Humans; Malawi; Streptococcus pneumoniae; Vaccines, Conjugate; Serogroup; Pneumococcal Vaccines
PubMed: 37659418
DOI: 10.1016/S2666-5247(23)00178-7 -
The Pan African Medical Journal 2022Vaccines are considered as a therapeutic area for children; the scientific community focuses mainly on managing chronic disease when it comes to adults. There currently... (Review)
Review
Vaccines are considered as a therapeutic area for children; the scientific community focuses mainly on managing chronic disease when it comes to adults. There currently is an increase in the burden of vaccine preventable illnesses in adults. Adult vaccination has been shown to dramatically increase the health and quality of life of older populations. Therefore, adult vaccinations need to be approached as a public health issue, similar to smoking cessation programs, for example. According to the Kenya Non-Communicable Diseases and injuries poverty commission report, 2018. Kenya has a high percentage of disability adjusted life years (DALYs) from communicable diseases at 63%, while non-communicable diseases (NCDs) contribute 30% of the DALYs. Specific to pneumococcal pneumonia (PP) in adults, the Global burden of disease (GBD) study in 2016 found that 2,377,697 people of all ages died from lower respiratory tract infections (LRTI) in 2016. Of these, more people died from Streptococcus pneumonia(SP) than from all other studied respiratory pathogens combined. While the incidence of LRTIs in children under five years old was reducing, partly as a result of well-established vaccination programs in children, the incidence, morbidity and mortality of PP was increasing in older populations. The expert recommendations included the following; i) all individuals 65 years of age and above, and individuals with a predisposing comorbidity regardless of age, should receive the pneumococcal vaccine; ii) several systemic modules can be emulated from the successful childhood vaccines programs onto an adult vaccine program; iii) formulation of an effective vaccine program will require collaboration from the public, the government, healthcare providers, and the media, to create awareness; iv) stakeholders who need to be involved in vaccine policy development and implementation include medical professional associations, nurses, pharmacists, clinical officers, payers (private and public insurances), government, medical learning institutions and faith-based medical organizations.
Topics: Adult; Aged; Child; Child, Preschool; Humans; Expert Testimony; Kenya; Pneumococcal Vaccines; Pneumonia, Pneumococcal; Quality of Life
PubMed: 35317473
DOI: 10.11604/pamj.2022.41.51.31849 -
The Journal of Laryngology and Otology Jul 2022This study aimed to investigate whether children with cochlear implants received the recommended vaccinations according to New Zealand national immunisation guidelines... (Review)
Review
OBJECTIVE
This study aimed to investigate whether children with cochlear implants received the recommended vaccinations according to New Zealand national immunisation guidelines and to report the incidence of meningitis in this population after intervention.
METHOD
A retrospective review of the vaccination coverage of paediatric patients receiving cochlear implants between 2005 and 2019 was performed.
RESULTS
Data were collected on 203 children. Evidence of immunisation against B was documented in 94.1 per cent of this cohort and 21.2 per cent received the seasonal influenza vaccine. The pneumococcal conjugate vaccine was fully administered in 81.8 per cent of children; however, only 16.9 per cent of eligible children had received the pneumococcal polysaccharide vaccine There was marked improvement in compliance to the pneumococcal conjugate vaccine once it became fully funded for cochlear implant patients.
CONCLUSION
Despite established guidelines, the paediatric vaccination rates were less than expected. Work is in progress to address this.
Topics: Child; Cochlear Implantation; Cochlear Implants; Humans; Pneumococcal Vaccines; Vaccination; Vaccines, Conjugate
PubMed: 34698004
DOI: 10.1017/S0022215121003133 -
Clinical Infectious Diseases : An... Apr 2020Cambodia introduced the 13-valent pneumococcal conjugate vaccine (PCV13) in January 2015 using a 3 + 0 dosing schedule and no catch-up campaign. We investigated the...
BACKGROUND
Cambodia introduced the 13-valent pneumococcal conjugate vaccine (PCV13) in January 2015 using a 3 + 0 dosing schedule and no catch-up campaign. We investigated the effects of this introduction on pneumococcal colonization and invasive disease in children aged <5 years.
METHODS
There were 6 colonization surveys done between January 2014 and January 2018 in children attending the outpatient department of a nongovernmental pediatric hospital in Siem Reap. Nasopharyngeal swabs were analyzed by phenotypic and genotypic methods to detect pneumococcal serotypes and antimicrobial resistance. Invasive pneumococcal disease (IPD) data for January 2012-December 2018 were retrieved from hospital databases. Pre-PCV IPD data and pre-/post-PCV colonization data were modelled to estimate vaccine effectiveness (VE).
RESULTS
Comparing 2014 with 2016-2018, and using adjusted prevalence ratios, VE estimates for colonization were 16.6% (95% confidence interval [CI] 10.6-21.8) for all pneumococci and 39.2% (95% CI 26.7-46.1) for vaccine serotype (VT) pneumococci. There was a 26.0% (95% CI 17.7-33.0) decrease in multidrug-resistant pneumococcal colonization. The IPD incidence was estimated to have declined by 26.4% (95% CI 14.4-35.8) by 2018, with a decrease of 36.3% (95% CI 23.8-46.9) for VT IPD and an increase of 101.4% (95% CI 62.0-145.4) for non-VT IPD.
CONCLUSIONS
Following PCV13 introduction into the Cambodian immunization schedule, there have been declines in VT pneumococcal colonization and disease in children aged <5 years. Modelling of dominant serotype colonization data produced plausible VE estimates.
Topics: Asian People; Cambodia; Child; Child, Preschool; Heptavalent Pneumococcal Conjugate Vaccine; Humans; Infant; Pneumococcal Infections; Pneumococcal Vaccines; Serogroup; Vaccines, Conjugate
PubMed: 31175819
DOI: 10.1093/cid/ciz481 -
Expert Review of Vaccines 2023Despite the introduction of effective pneumococcal conjugate vaccines (PCV), Streptococcus pneumoniae remains a major cause of acute otitis media (AOM) worldwide. New,... (Review)
Review
Acute otitis media pneumococcal disease burden and nasopharyngeal colonization in children due to serotypes included and not included in current and new pneumococcal conjugate vaccines.
INTRODUCTION
Despite the introduction of effective pneumococcal conjugate vaccines (PCV), Streptococcus pneumoniae remains a major cause of acute otitis media (AOM) worldwide. New, higher valency vaccines that offer broader serotype coverage have been recently developed and others are in development. However, given the capsular serotypes expressed by pneumococci causing AOM, it is unclear to what extent differing or higher valency PCVs will provide additional protection.
AREAS COVERED
We conducted a systematic literature search of the MEDLINE database to identify articles published from January 2016 to September 2021 in 4 low and middle income and 10 high-income countries. We searched PubMed with terms: () OR pneumococcal AND serotype AND (conjugate vaccine). We evaluated serotype distribution and the actual or projected coverage of pneumococcal serotypes by PCV10 (GlaxoSmithKline), PCV13 (Pfizer), PCV10SII (Serum Institute of India) PCV15 (Merck) and PCV20 (Pfizer).
EXPERT OPINION
Our review highlights the important epidemiological differences in serotype distribution and coverage by existing and higher valency vaccines to protect against AOM in children. These data provide support for further evaluation of serotype-independent vaccines for optimal control of pneumococcal AOM disease worldwide.
Topics: Child; Humans; Infant; Streptococcus pneumoniae; Serogroup; Vaccines, Conjugate; Heptavalent Pneumococcal Conjugate Vaccine; Pneumococcal Infections; Pneumococcal Vaccines; Otitis Media
PubMed: 36565291
DOI: 10.1080/14760584.2023.2162506 -
Frontiers in Immunology 2022VSA-1 is a semisynthetic saponin adjuvant prepared from naturally occurring saponin and capable of stimulating antigen-specific humoral and cellular immune responses....
VSA-1 is a semisynthetic saponin adjuvant prepared from naturally occurring saponin and capable of stimulating antigen-specific humoral and cellular immune responses. Its immunostimulating activity in enhancing the immune responses induced by the clinical glycoconjugate pneumococcal vaccine PCV13 is compared with QS-21 in female BALB/c mice. Both VSA-1 and QS-21 boosted IgG and opsonic antibodies titers against seven selected serotypes, including serotypes 3, 14, and 19A that are involved in most PCV13 breakthroughs. Since VSA-1 is much more accessible and of lower toxicity than QS-21, it can be a practical saponin immunostimulant to be included in a new glycoconjugate pneumococcal vaccine formulation.
Topics: Animals; Mice; Female; Pneumococcal Vaccines; Adjuvants, Immunologic; Adjuvants, Pharmaceutic; Immunoglobulin G; Saponins
PubMed: 36578488
DOI: 10.3389/fimmu.2022.1079047 -
Applied Health Economics and Health... Jul 2022Cost-effectiveness analyses (CEAs) are often prepared to quantify the expected economic value of potential vaccination strategies. Estimated outcomes and costs of...
Cost-effectiveness analyses (CEAs) are often prepared to quantify the expected economic value of potential vaccination strategies. Estimated outcomes and costs of vaccination strategies depend on numerous data inputs or assumptions, including estimates of vaccine efficacy and disease incidence in the absence of vaccination. Limitations in epidemiologic data can meaningfully affect both CEA estimates and the interpretation of those results by groups involved in vaccination policy decisions. Developers of CEAs should be transparent with regard to the ambiguity and uncertainty associated with epidemiologic information that is incorporated into their models. We describe selected data-related challenges to conducting CEAs for vaccination strategies, including generalizability of estimates of vaccine effectiveness, duration and functional form of vaccine protection that can change over time, indirect (herd) protection, and serotype replacement. We illustrate how CEA estimates can be sensitive to variations in specific epidemiologic assumptions, with examples from CEAs conducted for the USA that assessed vaccinations against human papillomavirus and pneumococcal disease. These challenges are certainly not limited to these two case studies and may be relevant to other vaccines.
Topics: Cost-Benefit Analysis; Humans; Pneumococcal Infections; Pneumococcal Vaccines; Uncertainty; Vaccination
PubMed: 35138601
DOI: 10.1007/s40258-022-00718-z -
Human Vaccines & Immunotherapeutics Nov 2020Immunocompromising conditions increase the risk of invasive pneumococcal disease (IPD). Vaccine uptake in patients with these conditions may be low in part because of... (Review)
Review
Immunocompromising conditions increase the risk of invasive pneumococcal disease (IPD). Vaccine uptake in patients with these conditions may be low in part because of concerns about decreased immunogenicity and safety in these high-risk groups. We conducted a literature search to identify publications describing antibody responses to 13-valent pneumococcal conjugate vaccine (PCV13) in immunocompromised individuals recommended for PCV13 vaccination by the US Advisory Committee on Immunization Practices (ACIP). This review summarizes immunogenicity data from 30 publications regarding the use of PCV13 comprising 2406 individuals considered at high risk for IPD by the ACIP. Although antibody responses to PCV13 in individuals with immunocompromising and high-risk conditions were variable and generally lower compared with healthy controls, the vaccine was immunogenic and was largely well tolerated. Based on these findings, concerns regarding immunogenicity and safety of PCV13 are not supported and should not be barriers to vaccination in high-risk populations.
Topics: Advisory Committees; Humans; Immunocompromised Host; Immunogenicity, Vaccine; Pneumococcal Infections; Pneumococcal Vaccines; Vaccination; Vaccines, Conjugate
PubMed: 32530360
DOI: 10.1080/21645515.2020.1735224 -
Human Vaccines & Immunotherapeutics Aug 2023Pneumococcal serogroups consist of structurally related serotypes, and serotype-specific antibodies can cross-react against other serotypes within the same serogroup....
Pneumococcal serogroups consist of structurally related serotypes, and serotype-specific antibodies can cross-react against other serotypes within the same serogroup. Cross-reactivity of vaccine-induced serotype 6A antibodies, and, to a lesser extent, serotype 6B antibodies, to serotype 6C has been demonstrated following receipt of the 13-valent pneumococcal conjugate vaccine (PCV13), which contains serotypes 6A and 6B. V114 is a 15-valent PCV containing the 13 PCV13 serotypes plus two additional serotypes, 22F and 33F. This study assessed cross-reactivity to serotype 6C in recipients of V114 and PCV13 as well as specificity of opsonophagocytic activity (OPA) responses in serogroup 6. Following receipt of V114 or PCV13, the observed OPA geometric mean titers to serotypes 6A, 6B, and 6C were comparable across both vaccination groups (post-single dose in adults ≥50 years of age [ = 250] and from pre- to post-dose 4 in pediatric participants 12-15 months of age [ = 150]). Based on OPA inhibition studies, V114 induced cross-reactive antibodies to serotype 6C in adult and pediatric populations that were specific and comparable to those induced by PCV13. Based on experience with PCV13, V114 may also provide comparable protection against pneumococcal disease caused by serotype 6C; however, this will have to be evaluated in real-world studies.
Topics: Adult; Humans; Child; Serogroup; Vaccines, Conjugate; Antibodies, Bacterial; Streptococcus pneumoniae; Pneumococcal Vaccines; Pneumococcal Infections
PubMed: 37529944
DOI: 10.1080/21645515.2023.2235238