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PloS One 2024In 2012, Botswana introduced 13-valent pneumococcal conjugate vaccine (PCV-13) to its childhood immunization program in a 3+0 schedule, achieving coverage rates of above...
BACKGROUND
In 2012, Botswana introduced 13-valent pneumococcal conjugate vaccine (PCV-13) to its childhood immunization program in a 3+0 schedule, achieving coverage rates of above 90% by 2014. In other settings, PCV introduction has been followed by an increase in carriage or disease caused by non-vaccine serotypes, including some serotypes with a high prevalence of antibiotic resistance.
METHODS
We characterized the serotype epidemiology and antibiotic resistance of pneumococcal isolates cultured from nasopharyngeal samples collected from infants (≤12 months) in southeastern Botswana between 2016 and 2019. Capsular serotyping was performed using the Quellung reaction. E-tests were used to determine minimum inhibitory concentrations for common antibiotics.
RESULTS
We cultured 264 pneumococcal isolates from samples collected from 150 infants. At the time of sample collection, 81% of infants had received at least one dose of PCV-13 and 53% had completed the three-dose series. PCV-13 serotypes accounted for 27% of isolates, with the most prevalent vaccine serotypes being 19F (n = 20, 8%), 19A (n = 16, 6%), and 6A (n = 10, 4%). The most frequently identified non-vaccine serotypes were 23B (n = 29, 11%), 21 (n = 12, 5%), and 16F (n = 11, 4%). Only three (1%) pneumococcal isolates were resistant to amoxicillin; however, we observed an increasing prevalence of penicillin resistance using the meningitis breakpoint (2016: 41%, 2019: 71%; Cochran-Armitage test for trend, p = 0.0003) and non-susceptibility to trimethoprim-sulfamethoxazole (2016: 55%, 2019: 79%; p = 0.04). Three (1%) isolates were multi-drug resistant.
CONCLUSIONS
PCV-13 serotypes accounted for a substantial proportion of isolates colonizing infants in Botswana during a four-year period starting four years after vaccine introduction. A low prevalence of amoxicillin resistance supports its continued use as the first-line agent for non-meningeal pneumococcal infections. The observed increase in penicillin resistance at the meningitis breakpoint and the low prevalence of resistance to ceftriaxone supports use of third-generation cephalosporins for empirical treatment of suspected bacterial meningitis.
Topics: Humans; Streptococcus pneumoniae; Botswana; Infant; Pneumococcal Infections; Pneumococcal Vaccines; Serogroup; Female; Microbial Sensitivity Tests; Anti-Bacterial Agents; Male; Drug Resistance, Bacterial; Serotyping; Nasopharynx; Prevalence
PubMed: 38787847
DOI: 10.1371/journal.pone.0302400 -
Emerging Infectious Diseases Jun 2024As a follow-up to a previous study, we investigated vaccine effectiveness (VE) of 23-valent pneumococcal polysaccharide vaccine (PPSV23) against invasive pneumococcal...
As a follow-up to a previous study, we investigated vaccine effectiveness (VE) of 23-valent pneumococcal polysaccharide vaccine (PPSV23) against invasive pneumococcal disease (IPD) among 1,254,498 persons >65 years of age as part of a vaccination program in Denmark during April 2020-January 2023. We assessed VE by using a Cox regression model and adjusted for age, sex, and underlying conditions. Using nationwide data, we estimated a VE of PPSV23 against all-type IPD of 32% and against PPSV23-serotype IPD of 41%. Because this follow-up study had more statistical power than the original study, we also estimated VE against IPD caused by PPSV23-serotypes excluding serotype 3; serotype 3; serotype 8; serotype 22F; PPSV23 non-PCV15 serotypes; PPSV23 non-PCV20 serotypes; and IPD over time. Our findings suggest PPSV23 vaccination can protect persons >65 years of age against IPD caused by all serotypes or serotype groupings, except serotype 3.
Topics: Humans; Pneumococcal Vaccines; Pneumococcal Infections; Denmark; Female; Aged; Male; Serogroup; Streptococcus pneumoniae; Follow-Up Studies; Aged, 80 and over; Vaccine Efficacy; Vaccination
PubMed: 38781925
DOI: 10.3201/eid3006.230975 -
Frontiers in Immunology 2024A patient in his 40s with splenic angiosarcoma metastatic to the liver underwent splenectomy, chemotherapy, and partial hepatectomy before being treated on a clinical...
A patient in his 40s with splenic angiosarcoma metastatic to the liver underwent splenectomy, chemotherapy, and partial hepatectomy before being treated on a clinical trial with CTLA4 and PD1 inhibitors. He had received pneumococcal and meningococcal vaccines post-splenectomy. On week 10, he developed grade 3 immune-related colitis, successfully treated with the anti-tumor necrosis factor-alpha inhibitor infliximab and steroids. After 4 cycles of treatment, scans showed partial response. He resumed anti-PD1 therapy, and 6 hours after the second dose of anti-PD1 he presented to the emergency room with hematemesis, hematochezia, hypotension, fever, and oxygen desaturation. Laboratory tests demonstrated acute renal failure and septicemia (). He died 12 hours after the anti-PD1 infusion from overwhelming post-splenectomy infection (OPSI). Autopsy demonstrated non-viable liver tumors among other findings. In conclusion, patients undergoing immunotherapy and with prior history of asplenia should be monitored closely for OPSI as they may be at increased risk.
Topics: Humans; Splenectomy; Male; Hemangiosarcoma; Splenic Neoplasms; Fatal Outcome; Liver Neoplasms; Immune Checkpoint Inhibitors; Immunotherapy; Adult; Pneumococcal Infections; Programmed Cell Death 1 Receptor; CTLA-4 Antigen
PubMed: 38779675
DOI: 10.3389/fimmu.2024.1366271 -
EClinicalMedicine Jun 2024Bacille Calmette-Guérin (BCG) vaccination has off-target (non-specific) effects that are associated with protection against unrelated infections and decreased all-cause...
BACKGROUND
Bacille Calmette-Guérin (BCG) vaccination has off-target (non-specific) effects that are associated with protection against unrelated infections and decreased all-cause mortality in infants. We aimed to determine whether BCG vaccination prevents febrile and respiratory infections in adults.
METHODS
This randomised controlled phase 3 trial was done in 36 healthcare centres in Australia, Brazil, the Netherlands, Spain, and the United Kingdom. Healthcare workers were randomised to receive BCG-Denmark (single 0.1 ml intradermal injection) or no BCG in a 1:1 ratio using a web-based procedure, stratified by stage, site, age, and presence of co-morbidity. The difference in occurrence of febrile or respiratory illness were measured over 12 months (prespecified secondary outcome) using the intention-to-treat (ITT) population. This trial is registered with ClinicalTrials.gov, NCT04327206.
FINDINGS
Between March 30, 2020, and April 1, 2021, 6828 healthcare workers were randomised to BCG-Denmark (n = 3417) or control (n = 3411; no intervention or placebo) groups. The 12-month adjusted estimated risk of ≥1 episode of febrile or respiratory illness was 66.8% in the BCG group (95% CI 65.3%-68.2%), compared with 63.4% in the control group (95% CI 61.8%-65.0%), a difference of +3.4 percentage points (95% CI +1.3% to +5.5%; p 0.002). The adjusted estimated risk of a severe episode (defined as being incapacitated for ≥3 consecutive days or hospitalised) was 19.4% in the BCG group (95% CI 18.0%-20.7%), compared with 18.8% in the control group (95% CI 17.4%-20.2%) a difference of +0.6 percentage points (95% CI -1.3% to +2.5%; p 0.6). Both groups had a similar number of episodes of illness, pneumonia, and hospitalisation. There were three deaths, all in the control group. There were no safety concerns following BCG vaccination.
INTERPRETATION
In contrast to the beneficial off-target effects reported following neonatal BCG in infants, a small increased risk of symptomatic febrile or respiratory illness was observed in the 12 months following BCG vaccination in adults. There was no evidence of a difference in the risk of severe disease.
FUNDING
Bill & Melinda Gates Foundation, Minderoo Foundation, Sarah and Lachlan Murdoch, the Royal Children's Hospital Foundation, Health Services Union NSW, the Peter Sowerby Foundation, SA Health, the Insurance Advisernet Foundation, the NAB Foundation, the Calvert-Jones Foundation, the Modara Pines Charitable Foundation, the UHG Foundation Pty Ltd, Epworth Healthcare, the National Health and Medical Research Council, the Swiss National Science Foundation and individual donors.
PubMed: 38774675
DOI: 10.1016/j.eclinm.2024.102616 -
Nature Communications May 2024Resolving inflammation is thought to return the affected tissue back to homoeostasis but recent evidence supports a non-linear model of resolution involving a phase of...
Resolving inflammation is thought to return the affected tissue back to homoeostasis but recent evidence supports a non-linear model of resolution involving a phase of prolonged immune activity. Here we show that within days following resolution of Streptococcus pneumoniae-triggered lung inflammation, there is an influx of antigen specific lymphocytes with a memory and tissue-resident phenotype as well as macrophages bearing alveolar or interstitial phenotype. The transcriptome of these macrophages shows enrichment of genes associated with prostaglandin biosynthesis and genes that drive T cell chemotaxis and differentiation. Therapeutic depletion of post-resolution macrophages, inhibition of prostaglandin E2 (PGE) synthesis or treatment with an EP4 antagonist, MF498, reduce numbers of lung CD4/CD44/CD62L and CD4/CD44/CD62L/CD27 T cells as well as their expression of the α-integrin, CD103. The T cells fail to reappear and reactivate upon secondary challenge for up to six weeks following primary infection. Concomitantly, EP4 antagonism through MF498 causes accumulation of lung macrophages and marked tissue fibrosis. Our study thus shows that PGE signalling, predominantly via EP4, plays an important role during the second wave of immune activity following resolution of inflammation. This secondary immune activation drives local tissue-resident T cell development while limiting tissue injury.
Topics: Animals; Pneumonia, Pneumococcal; Disease Models, Animal; Mice; Dinoprostone; Mice, Inbred C57BL; Streptococcus pneumoniae; Receptors, Prostaglandin E, EP4 Subtype; Macrophages; Lung; Macrophages, Alveolar; Integrin alpha Chains; Female; Antigens, CD; T-Lymphocytes
PubMed: 38773113
DOI: 10.1038/s41467-024-48138-y -
ACS Infectious Diseases Jun 2024Serotypes 6C and 6D of are two major variants that cause invasive pneumococcal disease (IPD) in serogroup 6 alongside serotypes 6A and 6B. Since the introduction of the...
Serotypes 6C and 6D of are two major variants that cause invasive pneumococcal disease (IPD) in serogroup 6 alongside serotypes 6A and 6B. Since the introduction of the pneumococcal conjugate vaccines PCV7 and PCV13, the number of cases of IPD caused by pneumococcus in children and the elderly population has greatly decreased. However, with the widespread use of vaccines, a replacement effect has recently been observed among different serotypes and lowered the effectiveness of the vaccines. To investigate protection against the original serotypes and to explore protection against variants and replacement serotypes, we created a library of oligosaccharide fragments derived from the repeating units of the capsular polysaccharides of serotypes 6A, 6B, 6C, and 6D through chemical synthesis. The library includes nine pseudosaccharides with or without exposed terminal phosphate groups and four pseudotetrasaccharides bridged by phosphate groups. Six carbohydrate antigens related to 6C and 6D were prepared as glycoprotein vaccines for immunogenicity studies. Two 6A and two 6B glycoconjugate vaccines from previous studies were included in immunogenicity studies. We found that the conjugates containing four phosphate-bridged pseudotetrasaccharides were able to induce good immune antibodies and cross-immunogenicity by showing superior activity and broad cross-protective activity in OPKA bactericidal experiments.
Topics: Streptococcus pneumoniae; Oligosaccharides; Serogroup; Pneumococcal Vaccines; Pneumococcal Infections; Antibodies, Bacterial; Animals; Mice; Bacterial Capsules; Humans; Female
PubMed: 38770797
DOI: 10.1021/acsinfecdis.4c00147 -
Open Forum Infectious Diseases May 2024Global use of pneumococcal conjugate vaccines (PCVs) with increasingly broader serotype coverage has helped to reduce the burden of pneumococcal disease in children and... (Review)
Review
Global use of pneumococcal conjugate vaccines (PCVs) with increasingly broader serotype coverage has helped to reduce the burden of pneumococcal disease in children and adults. In clinical studies comparing PCVs, higher-valency PCVs have met noninferiority criteria (based on immunoglobulin G geometric mean concentrations and response rates) for most shared serotypes. A numeric trend of declining immunogenicity against shared serotypes with higher-valency PCVs has also been observed; however, the clinical relevance is uncertain, warranting additional research to evaluate the effectiveness of new vaccines. Novel conjugation processes, carriers, adjuvants, and vaccine platforms are approaches that could help maintain or improve immunogenicity and subsequent vaccine effectiveness while achieving broader protection with increasing valency in pneumococcal vaccines.
PubMed: 38770212
DOI: 10.1093/ofid/ofae220 -
PloS One 2024Streptococcus pneumoniae is a leading cause of morbidity and mortality globally, causing bacteremic pneumonia, meningitis, sepsis, and other invasive pneumococcal... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Streptococcus pneumoniae is a leading cause of morbidity and mortality globally, causing bacteremic pneumonia, meningitis, sepsis, and other invasive pneumococcal diseases. Evidence supports nasopharyngeal pneumococcal carriage as a reservoir for transmission and precursor of pneumococcal disease.
OBJECTIVES
To estimate the pneumococcal nasopharyngeal burden in all age groups in Latin America and the Caribbean (LAC) before, during, and after the introduction of pneumococcal vaccine conjugate (PVC).
METHODS
Systematic literature review of international, regional, and country-published and unpublished data, together with reports including data from serotype distribution in nasopharyngeal carriage in children and adults from LAC countries following Cochrane methods. The protocol was registered in PROSPERO database (ID: CRD42023392097).
RESULTS
We included 54 studies with data on nasopharyngeal pneumococcal carriage and serotypes from 31,803 patients. In children under five years old, carriage was found in 41% and in adults over 65, it was 26%. During the study period, children under five showed a colonization proportion of 34% with PCV10 serotypes and 45% with PCV13 serotypes. When we analyze the carriage prevalence of PCV serotypes in all age groups between 1995 and 2019, serotypes included in PCV10 and those included in PCV13, both showed a decreasing trend along analysis by lustrum.
CONCLUSION
The data presented in this study highlights the need to establish national surveillance programs to monitor pneumococcal nasopharyngeal carriage to monitor serotype prevalence and replacement before and after including new pneumococcal vaccines in the region. In addition, to analyze differences in the prevalence of serotypes between countries, emphasize the importance of approaches to local realities to reduce IPD effectively.
Topics: Humans; Streptococcus pneumoniae; Latin America; Caribbean Region; Nasopharynx; Pneumococcal Infections; Carrier State; Pneumococcal Vaccines; Serogroup; Child, Preschool; Adult; Child; Prevalence
PubMed: 38768099
DOI: 10.1371/journal.pone.0297767 -
Vaccine Jul 2024Pneumococcal disease, presenting as invasive pneumococcal disease (IPD) or community-acquired pneumonia (CAP) is an important cause of illness and hospitalisation in the...
Pneumococcal disease, presenting as invasive pneumococcal disease (IPD) or community-acquired pneumonia (CAP) is an important cause of illness and hospitalisation in the elderly. To reduce pneumococcal burden, since 2003, 65-year-olds in England have been offered a 23-valent pneumococcal polysaccharide vaccine (PPV23). This study compares the impact and cost-effectiveness (CE) of vaccination with the existing PPV23 vaccine to the new 15-and 20-valent pneumococcal conjugate vaccines (PCV15 and PCV20), targeting adults aged 65 or 75 years old. We developed a static Markov model for immunisation against pneumococcal disease, capturing different vaccine effectiveness and immunity waning assumptions, projecting the number of IPD/CAP cases averted over the thirty years following vaccination. Using an economic model and probabilistic sensitivity analysis we evaluated the CE of the different immunisation strategies at current vaccine list prices and the willingness-to-pay at a median threshold of £20,000/QALY and an uncertainty threshold of 90% of simulations below £30,000/QALY. PCV20 averted more IPD and CAP cases than PCV15 or PPV23 over the thirty years following vaccination: 353(360), 145(159) and 150(174) IPD and 581(673), 259(485) and 212(235) CAP cases at a vaccination age of 65(75) under base vaccine effectiveness assumptions. At the listed prices of PCV20 and PPV23 vaccines as of May 2023, both vaccines were cost-effective when vaccinating 65- or 75-year-olds with an ICER threshold of £20,000 per QALY. To achieve the same cost-effectiveness as PPV23, the additional cost of PCV20 should be less than £44(£91) at an ICER threshold of £20,000/QALY (£30,000/QALY) if vaccination age is 65 (or £54(£103) if vaccination age is increased to 75). We showed that both PPV23 and PCV20 were likely to be cost-effective. PCV20 was likely to avert more cases of pneumococcal disease in elderly adults in England than the current PPV23 vaccine, given input assumptions of a higher vaccine effectiveness and slower waning for PCV20.
Topics: Humans; Pneumococcal Vaccines; Cost-Benefit Analysis; Aged; England; Pneumococcal Infections; Male; Female; Vaccination; Aged, 80 and over; Vaccines, Conjugate; Community-Acquired Infections; Markov Chains; Quality-Adjusted Life Years
PubMed: 38763851
DOI: 10.1016/j.vaccine.2024.05.001 -
The Pediatric Infectious Disease Journal Feb 2024We evaluated whether the quantification of IgG to pneumococcal capsular polysaccharides is an accurate diagnostic test for pneumococcal infection in children with...
Evaluation of Acute and Convalescent Antibody Concentration Against Pneumococcal Capsular Polysaccharides for the Diagnosis of Pneumococcal Infection in Children with Community-Acquired Pneumonia.
We evaluated whether the quantification of IgG to pneumococcal capsular polysaccharides is an accurate diagnostic test for pneumococcal infection in children with pneumonia in Nepal. Children with pneumococcal pneumonia did not have higher convalescent, or higher fold change, IgG to pneumococcal polysaccharides than children with other causes of pneumonia. Caution is needed in interpreting antibody responses in pneumococcal infections.
Topics: Humans; Antibodies, Bacterial; Child, Preschool; Polysaccharides, Bacterial; Immunoglobulin G; Infant; Streptococcus pneumoniae; Pneumonia, Pneumococcal; Community-Acquired Infections; Male; Female; Child; Nepal; Bacterial Capsules
PubMed: 38758207
DOI: 10.1097/INF.0000000000004185