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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 -
Therapeutic Advances in Respiratory... 2024A significant decline in pulmonary exacerbation rates has been reported in CF patients homozygous for F508del treated with lumacaftor/ivacaftor. However, it is still...
BACKGROUND
A significant decline in pulmonary exacerbation rates has been reported in CF patients homozygous for F508del treated with lumacaftor/ivacaftor. However, it is still unclear whether this reduction reflects a diminished microbiological burden.
OBJECTIVES
The aim of this study was to determine the impact of lumacaftor/ivacaftor on the bacterial and fungal burden.
DESIGN
The study is a prospective multicenter cohort study including 132 CF patients homozygous for F508del treated with lumacaftor/ivacaftor.
METHODS
Clinical parameters as well as bacterial and fungal outcomes 1 year after initiation of lumacaftor/ivacaftor were compared to data from 2 years prior to initiation of the treatment. Changes in the slope of the outcomes before and after the onset of treatment were assessed.
RESULTS
Lung function measured as ppFEV1 ( < 0.001), body mass index (BMI) in adults ( < 0.001), and BMI -score in children ( = 0.007) were improved after initiation of lumacaftor/ivacaftor. In addition, the slope of the prevalence of ( = 0.007) and ( < 0.001) shifted from positive to negative, that is, became less prevalent, 1 year after treatment, while the slope for ( = 0.009), spp ( = 0.026), and ( < 0.001) shifted from negative to positive.
CONCLUSION
The current study showed a significant improvement in clinical parameters and a reduction of some of CF respiratory microorganisms 1 year after starting with lumacaftor/ivacaftor. However, no significant changes were observed for , or , key pathogens in the CF context.
Topics: Humans; Cystic Fibrosis; Male; Prospective Studies; Female; Aminophenols; Benzodioxoles; Child; Adult; Young Adult; Adolescent; Drug Combinations; Aminopyridines; Quinolones; Sweden; Treatment Outcome; Mycoses; Respiratory Tract Infections; Cystic Fibrosis Transmembrane Conductance Regulator; Lung; Chloride Channel Agonists; Time Factors; Fungi; Bacterial Infections
PubMed: 38780228
DOI: 10.1177/17534666241254090 -
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 -
Frontiers in Cellular and Infection... 2024Periodontal diseases are known to be associated with polymicrobial biofilms and inflammasome activation. A deeper understanding of the subgingival cytological (micro)...
INTRODUCTION
Periodontal diseases are known to be associated with polymicrobial biofilms and inflammasome activation. A deeper understanding of the subgingival cytological (micro) landscape, the role of extracellular DNA (eDNA) during periodontitis, and contribution of the host immune eDNA to inflammasome persistence, may improve our understanding of the mechanisms underlaying severe forms of periodontitis.
METHODS
In this work, subgingival biolfilms developing on biologically neutral polyethylene terephthalate films placed in gingival cavities of patients with chronic periodontitis were investigated by confocal laser scanning microscopy (CLSM). This allowed examination of realistic cytological landscapes and visualization of extracellular polymeric substances (EPS) including amyloids, total proteins, carbohydrates and eDNA, as well as comparison with several single-strain model biofilms produced by oral pathogens such as , , , , and . Fluorescence hybridization (FISH) analysis was also used to identify eDNA derived from eubacteria, streptococci and members of the (BPP) group associated with periodontitis.
RESULTS
Analysis of subgingival biofilm EPS revealed low levels of amyloids and high levels of eDNA which appears to be the main matrix component. However, bacterial eDNA contributed less than a third of the total eDNA observed, suggesting that host-derived eDNA released in neutrophil extracellular traps may be of more importance in the development of biofilms causing periodontitis.
DISCUSSION
eDNA derived from host immunocompetent cells activated at the onset of periodontitis may therefore be a major driver of bacterial persistence and pathogenesis.
Topics: Biofilms; Humans; Periodontitis; Microscopy, Confocal; DNA; In Situ Hybridization, Fluorescence; Bacteria; DNA, Bacterial; Inflammasomes; Extracellular Polymeric Substance Matrix; Gingiva; Chronic Periodontitis
PubMed: 38779563
DOI: 10.3389/fcimb.2024.1374817 -
Frontiers in Cellular and Infection... 2024Competence development is essential for bacterial transformation since it enables bacteria to take up free DNA from the surrounding environment. The regulation of...
Competence development is essential for bacterial transformation since it enables bacteria to take up free DNA from the surrounding environment. The regulation of teichoic acid biosynthesis is tightly controlled during pneumococcal competence; however, the mechanism governing this regulation and its impact on transformation remains poorly understood. We demonstrated that a defect in lipoteichoic acid ligase (TacL)-mediated lipoteichoic acids (LTAs) biosynthesis was associated with impaired pneumococcal transformation. Using a fragment of regulatory probe as bait in a DNA pulldown assay, we successfully identified several regulatory proteins, including ComE. Electrophoretic mobility shift assays revealed that phosphomimetic ComE, but not wild-type ComE, exhibited specific binding to the probe. DNase I footprinting assays revealed the specific binding sequences encompassing around 30 base pairs located 31 base pairs upstream from the start codon of . Expression of was found to be upregulated in the Δ strain, and the addition of exogenous competence-stimulating peptide repressed the transcription in the wild-type strain but not the Δ mutant, indicating that ComE exerted a negative regulatory effect on the transcription of . Mutation in the JH2 region of upstream regulatory sequence led to increased LTAs abundance and displayed higher transformation efficiency. Collectively, our work identified the regulatory mechanisms that control LTAs biosynthesis during competence and thereby unveiled a repression mechanism underlying pneumococcal transformation.
Topics: Teichoic Acids; Bacterial Proteins; Lipopolysaccharides; Gene Expression Regulation, Bacterial; Streptococcus pneumoniae; Transformation, Bacterial; Transcription, Genetic; Promoter Regions, Genetic; DNA Transformation Competence; Mutation; Protein Binding; Ligases
PubMed: 38779562
DOI: 10.3389/fcimb.2024.1375312 -
The Lancet Regional Health. Southeast... Jul 2024The WHO Global Antimicrobial Resistance Surveillance System (GLASS) aims to describe antimicrobial resistance (AMR) patterns and trends in common bacterial pathogens,...
BACKGROUND
The WHO Global Antimicrobial Resistance Surveillance System (GLASS) aims to describe antimicrobial resistance (AMR) patterns and trends in common bacterial pathogens, but data remain limited in many low and middle-income countries including Indonesia.
METHODS
We systematically searched Embase, PubMed and Global Health Database and three Indonesian databases for original peer-reviewed articles in English and Indonesian, published between January 1, 2000 and May 25, 2023, that reported antimicrobial susceptibility for the 12 GLASS target pathogens from human samples. Pooled AMR prevalence estimates were calculated for relevant pathogen-antimicrobial combinations accounting for the sampling weights of the studies (PROSPERO: CRD42019155379).
FINDINGS
Of 2182 search hits, we included 102 papers, comprising 19,517 bacterial isolates from hospitals (13,647) and communities (5870). In hospital settings, 21.6% of isolates, 18.3% of isolates, 35.8% of isolates and 70.7% of isolates were carbapenem-resistant; 29.9% of isolates were penicillin-resistant; and 22.2% of isolates were methicillin-resistant. Hospital prevalence of carbapenem-resistant and , and penicillin-resistant increased over time. In communities, 28.3% of isolates and 15.7% of isolates were carbapenem-resistant, 23.9% of isolates were penicillin-resistant, and 11.1% of isolates were methicillin-resistant. Data were limited for the other pathogens.
INTERPRETATION
AMR prevalence estimates were high for critical gram-negative bacteria. However, data were insufficient to draw robust conclusions about the full contemporary AMR situation in Indonesia. Implementation of national AMR surveillance is a priority to address these gaps and inform context-specific interventions.
FUNDING
Wellcome Africa Asia Programme Vietnam.
PubMed: 38778837
DOI: 10.1016/j.lansea.2024.100414 -
BMC Complementary Medicine and Therapies May 2024Medicinal plants play a major role in the delivery of healthcare, particularly among the rural population of Ethiopia. Plant extracts and their bioactive compounds have...
BACKGROUND
Medicinal plants play a major role in the delivery of healthcare, particularly among the rural population of Ethiopia. Plant extracts and their bioactive compounds have been utilized for the treatment of several diseases. This study was aimed at evaluating the antibacterial activity, antioxidant capacity, and phytochemical content of selected medicinal plants used in Dibatie district, western Ethiopia.
METHODS
Study plants were collected, shade dried, pulverized, extracted by maceration in 80% ethanol, and subjected to antibacterial, antioxidant, and phytochemical tests. Minimum inhibitory concentration (MIC) was determined using 96-well microplates and nutrient broth microdilution. Antioxidant activity was evaluated using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assay. Phytochemical screening was conducted using standard test methods.
RESULTS
The ethanolic extract of Polystachya steudneri Rchb.f. pseudobulbs was the most active against gram-negative Proteus mirabilis, Salmonella typhimurium, Klebsiella pneumoniae, Escherichia coli, and Shigella flexneri, with MIC values of 8 ± 0, 11 ± 5, 3 ± 1, 3 ± 1, and 2 ± 0 mg/mL, respectively. The ethanolic extract of P. steudneri was also the most effective against gram-positive Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus agalactiae, and Enterococcus faecalis, with MIC values of 8 ± 0, 8 ± 0, 3 ± 1, and 16 ± 0 mg/mL, respectively. Ethanolic extracts of Gnidia involucrata Steud. ex A.Rich. stems and roots were effective antioxidants, with respective 50% DPPH free radical inhibitory concentrations (IC) of 168.68 and 181.79 µg/mL, followed by that of P. steudneri (IC = 203.11 µg/mL). The study plants contained alkaloids, anthocyanins, anthraquinones, cardiac glycosides, coumarins, flavonoids, phenols, saponins, steroids, tannins, and terpenoids.
CONCLUSIONS
This study confirmed the antibiotic, antioxidant, and phytochemical constituents of the investigated plants and suggested further investigations that may lead to bioactive lead compounds.
Topics: Ethiopia; Plants, Medicinal; Anti-Bacterial Agents; Antioxidants; Plant Extracts; Microbial Sensitivity Tests; Phytochemicals; Medicine, African Traditional; Humans; Bacteria
PubMed: 38773522
DOI: 10.1186/s12906-024-04499-x -
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