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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 -
Human Vaccines & Immunotherapeutics Dec 2024Pneumonia, predominantly caused by , remains a leading cause of global mortality. The 23-valent Pneumococcal polysaccharide vaccine (PPSV23) and conjugate vaccines...
Pneumonia, predominantly caused by , remains a leading cause of global mortality. The 23-valent Pneumococcal polysaccharide vaccine (PPSV23) and conjugate vaccines (PCVs) are vital measures to fight against it. This paper discussed the changes in pneumococcal vaccination strategies, particularly for older adults, as vaccine effectiveness and epidemiological patterns shift. While PPSV23 maintains effectiveness against invasive pneumococcal disease (IPD), its effectiveness against pneumococcal pneumonia is declining. Conversely, PCV13 consistently demonstrates effectiveness against both IPD and pneumonia. Consequently, the US Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices recommends using PCVs, notably PCV20 and PCV15, over PPSV23. Japanese studies indicate a change in the efficacy/effectiveness of PPSV23 following PCV introduction in children, likely owing to serotype replacement and herd immunity. Additionally, recent data reveals a plateau in the reduction of PCV13 and PPSV23-covered serotypes, posing a challenge to current strategies. This paper indicates a paradigm shift in pneumonia management, acknowledging its chronic nature and potential to exacerbate other diseases. The future of pneumococcal vaccination lies in broader serotype coverage through PCVs, adapting to serotype changes driven by childhood vaccination programs. Furthermore, continuous research and vaccine development are crucial in this evolving field.
Topics: Child; Humans; Aged; Streptococcus pneumoniae; Pneumonia, Pneumococcal; Pneumococcal Infections; Vaccination; Pneumococcal Vaccines; Serogroup; Vaccines, Conjugate
PubMed: 38517265
DOI: 10.1080/21645515.2024.2328963 -
Pneumonia (Nathan Qld.) Aug 2023Pneumococcal pneumonia remains a significant global public health issue. Malaysia has recently added the 10 valent pneumococcal conjugate vaccine to its national... (Review)
Review
Pneumococcal pneumonia remains a significant global public health issue. Malaysia has recently added the 10 valent pneumococcal conjugate vaccine to its national immunisation programme. Data on pneumococcal serotype epidemiology is vital for informing national vaccination policy. However, there remains a lack of representative population-based pneumococcal surveillance in Malaysia to help both the assessment of vaccine effectiveness in the country and to shape future vaccine policy. This review explores the history of pneumococcal vaccination, the burden of pneumococcal disease in Malaysia, and offers an insight into the prospects for reducing pneumococcal disease in Malaysia.
PubMed: 37620925
DOI: 10.1186/s41479-023-00114-8 -
Seminars in Hematology Apr 2024Chronic lymphocytic leukemia (CLL) is characterized by immune dysfunction resulting in heightened susceptibility to infections and elevated rates of morbidity and... (Review)
Review
Chronic lymphocytic leukemia (CLL) is characterized by immune dysfunction resulting in heightened susceptibility to infections and elevated rates of morbidity and mortality. A key strategy to mitigate infection-related complications has been immunization against common pathogens. However, the immunocompromised status of CLL patients poses challenges in eliciting an adequate humoral and cellular immune response to vaccination. Most CLL-directed therapy disproportionately impairs humoral immunity. Vaccine responsiveness also depends on the phase and type of immune response triggered by immunization. In this review, we discuss the immune dysfunction, vaccine responsiveness, and considerations for optimizing vaccine response in patients with CLL.
Topics: Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Vaccination; Immunocompromised Host; Immunity, Humoral
PubMed: 38302313
DOI: 10.1053/j.seminhematol.2024.01.003 -
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 -
Australian Prescriber Dec 2023
Review
PubMed: 38152312
DOI: 10.18773/austprescr.2023.026 -
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 -
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 -
Frontiers in Immunology 2023is one of the main causes of community-acquired infections in the lung alveoli in children and the elderly. Alveolar macrophages (AM) patrol alveoli in homeostasis and...
INTRODUCTION
is one of the main causes of community-acquired infections in the lung alveoli in children and the elderly. Alveolar macrophages (AM) patrol alveoli in homeostasis and under infectious conditions. However, the molecular adaptations of AM upon infections with are incompletely resolved.
METHODS
We used a comparative transcriptomic and proteomic approach to provide novel insights into the cellular mechanism that changes the molecular signature of AM during lung infections. Using a tandem mass spectrometry approach to murine cell-sorted AM, we revealed significant proteomic changes upon lung infection with
RESULTS
AM showed a strong neutrophil-associated proteomic signature, such as expression of CD11b, MPO, neutrophil gelatinases, and elastases, which was associated with phagocytosis of recruited neutrophils. Transcriptomic analysis indicated intrinsic expression of CD11b by AM. Moreover, comparative transcriptomic and proteomic profiling identified CD11b as the central molecular hub in AM, which influenced neutrophil recruitment, activation, and migration.
DISCUSSION
In conclusion, our study provides novel insights into the intrinsic molecular adaptations of AM upon lung infection with and reveals profound alterations critical for effective antimicrobial immunity.
Topics: Animals; Mice; Integrins; Lung; Macrophages, Alveolar; Pneumonia, Pneumococcal; Proteomics; Streptococcus pneumoniae; Transcriptome; CD11b Antigen
PubMed: 37790937
DOI: 10.3389/fimmu.2023.1227191 -
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