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The Lancet Regional Health. Europe Feb 2024Higher-valency pneumococcal vaccines are anticipated. We aimed to describe serotype distribution and risk factors for vaccine-serotype community-acquired pneumonia (CAP)...
BACKGROUND
Higher-valency pneumococcal vaccines are anticipated. We aimed to describe serotype distribution and risk factors for vaccine-serotype community-acquired pneumonia (CAP) in the two years pre-SARS-CoV-2 pandemic.
METHODS
We conducted a prospective cohort study of adults hospitalised with CAP at three UK sites between 2018 and 2020. Pneumococcal serotypes were identified using a 24-valent urinary-antigen assay and blood cultures. Risk factors associated with vaccine-type pneumonia caused by serotypes in the 13-, 15- and 20-valent pneumococcal conjugate vaccines (PCV13, PCV15, PCV20) and 23-valent pneumococcal polysaccharide vaccine (PPV23) were determined from multivariable analysis.
FINDINGS
Of 1921 adults hospitalised with CAP, 781 (40.7%, 95% confidence intervals (CI) 38.5-42.9%) had pneumococcal pneumonia. A single PCV13-serotype was detected in 242 (31.0%, 95% CI 27.8-34.3%) pneumococcal CAP patients, mostly serotype 3 (171/242, 70.7%, 95% CI 64.5-76.0%). The additional two PCV15-serotypes were detected in 31 patients (4%, 95% CI 2.8-5.6%), and PCV20-non13-serotypes in 192 (24.6%), with serotype 8 most prevalent (123/192, 64.1%, 95% CI 57.1-70.5%). Compared to PCV13-serotype CAP, people with PCV20-non13 CAP were younger (median age 62 versus 72 years, p < 0.001) and less likely to be male (44% versus 61%, p = 0.01). PPV23-non13-serotypes were found in 252 (32.3%, 95% CI 29.1-35.6%) pneumococcal CAP patients.
INTERPRETATION
Despite mature infant pneumococcal programmes, the burden of PCV13-serotype pneumonia remains high in older adults, mainly due to serotype 3. PCV20-non13-serotype pneumonia is more likely in younger people with fewer pneumococcal risk factors.
FUNDING
Unrestricted investigator-initiated research grant from Pfizer, United Kingdom; support from National Institute for Health Research (NIHR) Biomedical Research Centre, Nottingham.
PubMed: 38170136
DOI: 10.1016/j.lanepe.2023.100812 -
EBioMedicine Dec 2023Mycoplasma pneumoniae is a common cause of community-acquired pneumonia in school-aged children and can be preceded by asymptomatic carriage. However, its role in...
BACKGROUND
Mycoplasma pneumoniae is a common cause of community-acquired pneumonia in school-aged children and can be preceded by asymptomatic carriage. However, its role in recurrent respiratory tract infections is unclear. We studied the prevalence of M.pneumoniae carriage in children with recurrent respiratory infections and identified associated factors.
METHODS
We tested M.pneumoniae carriage by qPCR in children with recurrent infections and their healthy family members in a cross-sectional study. Serum and mucosal total and M.pneumoniae-specific antibody levels were measured by ELISA and nasopharyngeal microbiota composition was characterized by 16S-rRNA sequencing.
FINDINGS
Prevalence of M.pneumoniae carriage was higher in children with recurrent infections (68%) than their family members without infections (47% in siblings and 27% in parents). M.pneumoniae carriage among family members appeared to be associated with transmission within the household, likely originating from the affected child. In logistic regression corrected for age and multiple comparisons, IgA (OR 0.16 [0.06-0.37]) and total IgG deficiency (OR 0.15 [0.02-0.74]) were less prevalent in M.pneumoniae carriers (n = 78) compared to non-carriers (n = 36). In multivariable analysis, the nasopharyngeal microbiota of M.pneumoniae carriers had lower alpha diversity (OR 0.27 [0.09-0.67]) and a higher abundance of Haemophilus influenzae (OR 45.01 [2.74-1608.11]) compared to non-carriers.
INTERPRETATION
M.pneumoniae carriage is highly prevalent in children with recurrent infections and carriers have a less diverse microbiota with an overrepresentation of disease-associated microbiota members compared to non-carriers. Given the high prevalence of M.pneumoniae carriage and the strong association with H. influenzae, we recommend appropriate antibiotic coverage of M.pneumoniae and H. influenzae in case of suspected pneumonia in children with recurrent respiratory tract infections or their family members.
FUNDING
Wilhelmina Children's Hospital Research Fund, 'Christine Bader Stichting Irene KinderZiekenhuis', Sophia Scientific Research Foundation, ESPID Fellowship funded by Seqirus, Hypatia Fellowship funded by Radboudumc and The Netherlands Organisation for Health Research and Development (ZonMW VENI grant to LM Verhagen).
Topics: Child; Humans; Infant; Streptococcus pneumoniae; Mycoplasma pneumoniae; Pneumococcal Infections; Cross-Sectional Studies; Reinfection; Respiratory Tract Infections; Nasopharynx; Pneumonia; Haemophilus influenzae; Carrier State; Microbiota
PubMed: 37950996
DOI: 10.1016/j.ebiom.2023.104868 -
Cost Effectiveness and Resource... Aug 2023The morbidity and mortality of adult diseases caused by S. pneumoniae increase with age and presence of underlying chronic diseases. Currently, two vaccine technologies...
BACKGROUND
The morbidity and mortality of adult diseases caused by S. pneumoniae increase with age and presence of underlying chronic diseases. Currently, two vaccine technologies against S. pneumoniae are used: the 23-valent pneumococcal polysaccharide vaccine (PPV23) and the pneumococcal conjugate vaccines, one of which is the 20-valent pneumococcal conjugate vaccine (PCV20) that has recently been approved for adults.
OBJECTIVE
This study was conducted to investigate the cost-effectiveness of implementing PCV20 in a reimbursement scheme for Norwegian adults aged 18-99 years at risk of pneumococcal diseases and those aged 65 years and older at low risk compared to PPV23.
METHODS
An established Markov model was adapted to a Norwegian setting to estimate the economic and clinical consequences of vaccinating the Norwegian population in specific age and risk groups against pneumococcal diseases. Inputs for the model were found in Norwegian or Danish real-world evidence or retrieved from available studies. The costs and clinical outcomes were assessed using a health sector perspective and a lifetime time horizon.
RESULTS
The results showed that PCV20 was associated with better health outcomes including fewer disease cases, fewer disease-attributable fatalities, a higher gain of life years and quality-adjusted life years compared to PPV23. In addition, PCV20 had a lower total cost compared to PPV23. Therefore, PCV20 was the dominant vaccination strategy. The base case result was investigated in multiple sensitivity analyses, which showed that the results were robust to changes in input parameters and methodological assumptions, as PCV20 remained the dominant vaccination strategy in almost all scenarios.
CONCLUSION
Results showed that vaccinating the Norwegian adults with PCV20 was cost-effective compared to PPV23. Changes in the hospital cost of pneumonia, the price of PCV 20, the effectiveness of PCV20 against pneumonia, and the pneumonia disease incidence had the highest impact on the ICER, i.e., were the main drivers of the results.
PubMed: 37559118
DOI: 10.1186/s12962-023-00458-4 -
Vaccine Aug 2023Neither indirect protection through use of 13-valent and 10-valent pneumococcal conjugate vaccines (PCV13 and PCV10) in pediatric National Immunization Programs (NIPs)...
BACKGROUND
Neither indirect protection through use of 13-valent and 10-valent pneumococcal conjugate vaccines (PCV13 and PCV10) in pediatric National Immunization Programs (NIPs) nor direct vaccination with the 23-valent polysaccharide vaccine have eliminated vaccine serotype invasive pneumococcal disease (IPD) in older adults. Vaccinating older adults with higher-valency PCV15 and PCV20 could address remaining IPD due to pediatric PCV serotypes plus additional IPD due to serotypes included in these vaccines.
METHODS
We collected serotype-specific IPD data in older adults (≥65 years in most countries), from national or regional surveillance systems or hospital networks of 33 high-income countries. Data were from official government websites, online databases, surveillance system reports, published literature, and personal communication with in-country investigators. Average percentages of IPD serotypes were calculated.
RESULTS
Among 52,905 cases of IPD with a serotype identified, PCV13 serotypes accounted for 33.7% of IPD (55.8% and 30.6% for countries with PCV10 and PCV13 in the pediatric NIP), most commonly serotypes 3 (14.9%) and 19A (7.0%). PCV15 and PCV20 would cover an additional 10.4% and 32.9% of older adult IPD beyond PCV13 serotypes (PCV10 countries: 7.7% and 23.3%; PCV13 countries: 10.6% and 34.6%). The most common of these additional serotypes were 8 (9.9%), 22F (7.9%), 12F (4.6%), and 11A (3.3%). PPSV23 policies for older adults were not correlated with lower IPD percentages due to PPSV23 serotypes.
CONCLUSIONS
Vaccinating older adults with higher-valency PCVs, especially PCV20, could substantially reduce the remaining IPD burden in high-income countries, regardless of current PCV use in pediatric NIPs and adult PPSV23 policies.
Topics: Child; Humans; Infant; Aged; Serogroup; Streptococcus pneumoniae; Developed Countries; Pneumococcal Infections; Pneumococcal Vaccines; Vaccination; Vaccines, Conjugate
PubMed: 37544825
DOI: 10.1016/j.vaccine.2023.08.001 -
PloS One 2024The Ukrainian Ministerial Order (UMO) recommends pneumococcal vaccine (PCV) in risk groups but not free-of-charge resulting in coverage <5% (crude estimation). In 2022,...
BACKGROUND
The Ukrainian Ministerial Order (UMO) recommends pneumococcal vaccine (PCV) in risk groups but not free-of-charge resulting in coverage <5% (crude estimation). In 2022, the vaccination calendar will include PCV for children <5years. Doctors' pneumococcal knowledge, attitudes and practices (КAP) are paramount to successful roll-out but unexplored. We surveyed doctors aiming to assess their KAP to address gaps and misconceptions and support PCV implementation.
METHODS
In March 2021, we selected and surveyed primary care doctors using simple random sampling and structured self-administered online questionnaire. We measured attitudes (importance, effectiveness, safety) and practices using 5-point Likert-type questions. We defined pneumococcal disease (PD) knowledge as low/moderate (<80%) and high (≥80%), PCV and overall knowledge as low (≤50%) and moderate/high (51-100%) and PCV attitudes and practices as negative/neutral (1.0-3.4) and positive (3.5-5.0). We calculated prevalence ratios (PRs) and 95% confidence intervals (95%CI) using Poisson regression.
RESULTS
The response rate was 46% (286/628). Females represented 85% (243/285); the median age was 47 (interquartile range: 33-59, N = 281) years. Twenty-six percent (72/277) had high PD knowledge associated with age (>47 years: PR = 0.52, 95%CI: 0.30-0.90) and child-related UMO awareness (PR = 1.78, 95%CI: 1.04-3.08); 65% (182/278) had moderate/high PCV knowledge associated with positive attitudes towards PCV effectiveness (PR = 2.08, 95%CI: 1.20-3.59). Overall knowledge was moderate/high in 69% (188/271); 83% (220/265) had positive PCV attitudes; 52% (135/258) had positive practices associated with female sex (PR = 2.11, 95%CI: 1.09-4.09), positive attitudes (PR = 3.40, 95%CI: 1.23-9.39) and perception of vaccine supply as medium/big barrier (PR = 1.66, 95%CI: 1.02-2.72).
CONCLUSION
We observed moderate pneumococcal knowledge, especially in older doctors, positive PCV attitudes and neutral practices. Females and doctors with positive attitudes recommended PCV more. For successful PCV implementation, we recommend proper planning and prior educational activities targeting patients and primary care doctors, especially older males, to improve knowledge, introduce PCV and address concerns while ensuring uninterrupted vaccine supply.
Topics: Humans; Female; Male; Ukraine; Pneumococcal Infections; Health Knowledge, Attitudes, Practice; Pneumococcal Vaccines; Adult; Physicians, Primary Care; Vaccination; Middle Aged; Surveys and Questionnaires; Attitude of Health Personnel
PubMed: 38843200
DOI: 10.1371/journal.pone.0304346 -
Infection and Immunity Sep 2023is a Gram-positive opportunistic pathogen that can colonize the upper respiratory tract. It is a leading cause of a wide range of infectious diseases, including...
is a Gram-positive opportunistic pathogen that can colonize the upper respiratory tract. It is a leading cause of a wide range of infectious diseases, including community-acquired pneumonia and meningitis. Pneumococcal infections cause 1-2 million deaths per year, most of which occur in developing countries. Here, we focused on three choline-binding proteins (CBPs), i.e., PspC, PspA, and LytA. These pneumococcal proteins have different surface-exposed regions but share related choline-binding anchors. These surface-exposed pneumococcal proteins are in direct contact with host cells and have diverse functions. We explored the role of the three CBPs on adhesion and pathogenicity in a human host by performing relevant imaging and functional analyses, such as electron microscopy, confocal laser scanning microscopy, and functional quantitative assays, targeting biofilm formation and the hemolytic capacity of . biofilm formation assays and electron microscopy experiments were used to examine the ability of knockout mutant strains lacking the lytA, pspC, or pspA genes to adhere to surfaces. We found that LytA plays an important role in robust synthesis of the biofilm matrix. PspA and PspC appeared crucial for the hemolytic effects of on human red blood cells. Furthermore, all knockout mutants caused less damage to endothelial cells than wild-type bacteria, highlighting the significance of each CPB for the overall pathogenicity of . Hence, in addition to their structural function within the cell wall of , each of these three surface-exposed CBPs controls or mediates multiple steps during bacterial pathogenesis.
Topics: Humans; Streptococcus pneumoniae; Carrier Proteins; Endothelial Cells; Choline; Bacterial Proteins; Pneumococcal Infections; Membrane Proteins; Erythrocytes
PubMed: 37551971
DOI: 10.1128/iai.00154-23 -
G3 (Bethesda, Md.) Jun 2024Streptococcus pneumoniae (the pneumococcus) is a globally distributed, human obligate opportunistic bacterial pathogen which, although often carried commensally, is also...
Streptococcus pneumoniae (the pneumococcus) is a globally distributed, human obligate opportunistic bacterial pathogen which, although often carried commensally, is also a significant cause of invasive disease. Apart from multi-drug resistant and virulent clones, the rate and direction of pneumococcal dissemination between different countries remains largely unknown. The ability for the pneumococcus to take a foothold in a country depends on existing population configuration, the extent of vaccine implementation, as well as human mobility since it is a human obligate bacterium. To shed light on its international movement, we used extensive genome data from the Global Pneumococcal Sequencing project and estimated migration parameters between multiple countries in Africa. Data on allele frequencies of polymorphisms at housekeeping-like loci for multiple different lineages circulating in the populations of South Africa, Malawi, Kenya, and The Gambia were used to calculate the fixation index (Fst) between countries. We then further used these summaries to fit migration coalescent models with the likelihood-free inference algorithms available in the ELFI software package. Synthetic datawere additionally used to validate the inference approach. Our results demonstrate country-pair specific migration patterns and heterogeneity in the extent of migration between different lineages. Our approach demonstrates that coalescent models can be effectively used for inferring migration rates for bacterial species and lineages provided sufficiently granular population genomics surveillance data. Further, it can demonstrate the connectivity of respiratory disease agents between countries to inform intervention policy in the longer term.
Topics: Streptococcus pneumoniae; Humans; Pneumococcal Infections; Gene Frequency; Africa; Kenya
PubMed: 38507601
DOI: 10.1093/g3journal/jkae058 -
Expert Review of Vaccines 2024Next-generation, higher-valency pneumococcal conjugate vaccines (PCVs), 15-valent PCV V114 and 20-valent PCV (PCV20), have been assessed by comparing their immune...
BACKGROUND
Next-generation, higher-valency pneumococcal conjugate vaccines (PCVs), 15-valent PCV V114 and 20-valent PCV (PCV20), have been assessed by comparing their immune responses across serotypes shared with the 13-valent PCV (PCV13). Without efficacy or real-world vaccine effectiveness (VE) it becomes important to relate IgG titers to VE to aid in the interpretation of the immune response elicited by V114 and PCV20.
METHODS
We estimated the protective antibody concentrations for each serotype in 7-valent PCV (PCV7) and PCV13 which were then used to predict the serotype-specific VE for each PCV7 and PCV13 non PCV7 serotype present in V114 and PCV20.
RESULTS
The predicted effectiveness of V114 was comparable to PCV7 and PCV13 for 11 of the 13 shared serotypes (1, 4, 5, 6B, 7F, 9 V, 14, 18C, 19A, 19F, and 23F), with improved effectiveness against serotype 3 and decreased effectiveness against serotype 6A. PCV20 had predicted effectiveness comparable to PCV7 and PCV13 for 7 of the 13 shared serotypes (5, 6A, 7F, 9 V, 18C, 19F, and 23F), with decreased effectiveness against the remaining serotypes (1, 3, 4, 6B, 14, and 19A).
CONCLUSIONS
Prediction of serotype-specific VE values suggests that V114 retains greater effectiveness than PCV20 toward most serotypes present in PCV7 and PCV13.
Topics: Child; Humans; Infant; Serogroup; Heptavalent Pneumococcal Conjugate Vaccine; Pneumococcal Vaccines; Streptococcus pneumoniae; Pneumococcal Infections; Antibodies, Bacterial; Vaccines, Conjugate
PubMed: 38073483
DOI: 10.1080/14760584.2023.2292773 -
BMJ Global Health Aug 2023Pneumonia due to (pneumococcus) is a major cause of mortality in infants (children under 1 year of age), and pneumococcal conjugate vaccines (PCVs), delivered during... (Review)
Review
Pneumonia due to (pneumococcus) is a major cause of mortality in infants (children under 1 year of age), and pneumococcal conjugate vaccines (PCVs), delivered during the first year of life, are available since the year 2000. Given those two premises, the conclusion follows logically that favourable impact reported for PCVs in preventing pneumococcal disease should be reflected in the infant mortality rates (IMRs) from all causes. Using publicly available datasets, country-level IMR estimates from UNICEF and PCV introduction status from WHO, country-specific time series analysed the temporal relationship between annual IMRs and the introduction of PCVs, providing a unique context into the long-term secular trends of IMRs in countries that included and countries that did not include PCVs in their national immunisation programmes. PCV status was available for 194 countries during the period 1950-2020: 150 (77.3%) of these countries achieved nationwide PCV coverage at some point after the year 2000, 13 (6.7%) achieved only partial or temporary PCV coverage, and 31 (15.9%) never introduced PCVs to their population. One hundred and thirty-nine (92.7%) of countries that reported a decreasing (negative) trend in IMR, also reported a strong correlation with decreasing maternal mortality rates (MMRs), suggesting an improvement in overall child/mother healthcare. Conversely, all but one of the countries that never introduced PCVs in their national immunisation programme also reported a decreasing trend in IMR that strongly correlates with MMRs. IMRs have been decreasing for decades all over the world, but this latest decrease may not be related to PCVs.
Topics: Child; Infant; Female; Humans; Pneumococcal Vaccines; Pneumococcal Infections; Streptococcus pneumoniae; Pneumonia; Infant Mortality; Vaccines, Conjugate
PubMed: 37550006
DOI: 10.1136/bmjgh-2023-012752 -
Diseases (Basel, Switzerland) Apr 2024Globally, sepsis and pneumonia account for significant mortality and morbidity. A complex interplay of immune-molecular pathways underlies both sepsis and pneumonia,... (Review)
Review
Globally, sepsis and pneumonia account for significant mortality and morbidity. A complex interplay of immune-molecular pathways underlies both sepsis and pneumonia, resulting in similar and overlapping disease characteristics. Sepsis could result from unmanaged pneumonia. Similarly, sepsis patients have pneumonia as a common complication in the intensive care unit. A significant percentage of pneumonia is misdiagnosed as septic shock. Therefore, our knowledge of the clinical relationship between pneumonia and sepsis is imperative to the proper management of these syndromes. Regarding pathogenesis and etiology, pneumococcus is one of the leading pathogens implicated in both pneumonia and sepsis syndromes. Growing evidence suggests that pneumococcal pneumonia can potentially disseminate and consequently induce systemic inflammation and severe sepsis. Streptococcus pneumoniae could potentially exploit the function of dendritic cells (DCs) to facilitate bacterial dissemination. This highlights the importance of pathogen-immune cell crosstalk in the pathophysiology of sepsis and pneumonia. The role of DCs in pneumococcal infections and sepsis is not well understood. Therefore, studying the immunologic crosstalk between pneumococcus and host immune mediators is crucial to elucidating the pathophysiology of pneumonia-induced lung injury and sepsis. This knowledge would help mitigate clinical diagnosis and management challenges.
PubMed: 38667530
DOI: 10.3390/diseases12040072