Browsing 500 Presentations
POOR ANTIBODY RESPONSE POST-PNEUMOCOCCAL VACCINATION IN YOUNG CHILDREN WITH RECURRENT WHEEZING EXACERBATIONS (ID 108)
STUDY OF INTERACTIONS OF PNEUMOCOCCAL CAPSULAR POLYSACCHARIDES WITH ANTISERUM BY DIFFUSION NMR (ID 116)
PNEUMOCOCCAL SURFACE PROTEIN A VACCINE DOES NOT PROTECT HIGHLY SUSCEPTIBLE MICE AGAINST INFECTION WITH A SEROTYPE 3 PNEUMOCOCCAL STRAIN (ID 117)
IMPACT OF THE PNEUMOCOCCAL CONJUGATE VACCINE ON PNEUMONIA MORTALITY IN SOUTH AFRICA, 1999-2016: A RETROSPECTIVE OBSERVATIONAL STUDY (ID 118)
EXPLORATORY COST-EFFECTIVENESS ANALYSIS OF IN-DEVELOPMENT AND HYPOTHETICAL HIGHER-VALENCY PNEUMOCOCCAL CONJUGATE VACCINES IN OLDER ADULTS: BARKING UP THE WRONG TREE? (ID 120)
Abstract
Background
Higher-valency pneumococcal conjugate vaccines (PCV) are under development; their potential cost-effectiveness in older adults (≥65 years) is unknown.
Methods
A Markov model estimated the cost-effectiveness of current US recommendations and sole pneumococcal polysaccharide vaccine (PPSV23) use compared to: in-development PCV15 and PCV20, and a hypothetical vaccine (HypoPCV20) adding the 7 commonest non-PCV13 serotypes in older adults (all with/without PPSV23). Sensitivity analyses and alternative scenarios were examined.
Results
In analyses considering only existing and in-development vaccines, sole PCV20 use cost $176,500 per quality-adjusted life-year (QALY) gained compared to current US recommendations, while dual PCV20/PPSV23 use cost $4,050,000/QALY when equal serotype effectiveness and no childhood vaccination indirect effects on added serotypes were assumed. PCV15 strategies were dominated. When PCV13/PCV20 were assumed ineffective against serotype 3 and PCV15 was fully effective, PCV15 cost $209,000/QALY and PCV15/PPSV23 cost $1,403,000/QALY. Adding childhood vaccination indirect effects or alternative serotype effectiveness assumptions decreased PCV15/PCV20 cost-effectiveness. When HypoPCV20 was considered, HypoPCV20 cost $152,700/QALY gained, and HypoPCV20/PPSV23 cost $2,480,000/QALY; other strategies were dominated.
Conclusions
In exploratory analyses, PCV15/PCV20 may not be economically reasonable in older adults, regardless of serotype effectiveness assumptions, particularly when potential indirect effects were considered. Adult vaccines containing higher-risk serotypes not contained in childhood vaccines may be more promising.
STREPTOCOCCUS PNEUMONIAE SEROTYPE 8 IS MAINLY A PROBLEM FOR THE ELDERLY IN DENMARK (ID 121)
EFFICIENT DISSEMINATION OF INTEGRATIVE AND CONJUGATIVE ELEMENTS CONFERRING MULTIDRUG RESISTANCE IN STREPTOCOCCUS PNEUMONIAE IN AN EX VIVO HUMAN NASOPHARYNGEAL BIOFILM (ID 125)
Abstract
Background
Multidrug resistance in Streptococcus pneumoniae (Spn) has been increasingly attributed to dissemination of integrative and conjugative elements (ICEs), such as Tn2009 (23.5kb). The mechanism for Spn ICE dissemination has not been defined.
Methods
Recombination frequency (rF) for Tn2009 was investigated utilizing in vitro transformation or an ex vivo nasopharyngeal biofilm bioreactor. Recombinant lineage and extracellular DNA (eDNA) concentrations were determined by serotype-specific qPCR. Whole genome sequencing (WGS) identified putative junctions for Tn2009 recombination.
Results
In vitro transformation yielded no Tn2009-containing D39 recombinants (rF<10-9) while mutation-mediated streptomycin resistance was obtained (rF 10-6). However, in the bioreactor, Tn2009 transference from donor GA16833Tet/Ery (ST19F) to recipient D39Str (ST2) generated >90% D39Tet/Str recombinants with variably sized donor DNA fragments encompassing intact Tn2009 (rF 10-4), indicating varied recombination junctions. Tn2009 transference was prevented by DNaseI addition (rF<10-7). D39 competence mutants (ΔcomC/D/E) with GA16833 yielded reduced rFs (10-8-10-6) and nearly 100% ST19F recombinants acquiring Str resistance. Similar bacterial densities and eDNA concentrations from each strain were detected. D39ΔcomC with GA16833ΔcomC yielded no recombinants (rF<10-7).
Conclusions
Efficient Tn2009 dissemination among Spn strains occurs in an ex vivo nasopharyngeal biofilm and requires recipient competence development. Further, there is a com-mediated dominance for a specific Spn strain to acquire resistance.
DEVELOPMENT AND VALIDATION OF A MACHINE LEARNING PREDICTION MODEL FOR PNEUMONIA MORTALITY IN CHILDREN AGED UNDER FIVE YEARS IN RURAL GAMBIA (ID 126)
Abstract
Background
Pneumonia accounts for many deaths in children aged under 5 years in developing countries. A reliable and generalizable tool to predict mortality and thus assess the severity of pneumonia would aid patient management.
Methods
We used a dataset of 11,012 children admitted with clinical pneumonia to develop a model to predict mortality. Using a High Performance Computing platform, we generated multiple models for all possible feature combinations, applying support vector machine, neural networks, random forests and logistic regression to 2/3 of the dataset with repeated cross-validation (5 repetitions, 10 folds). We chose the final model based on its performance and on the number of and measurement reliability of the included features to increase generalizability. In the validation stage, we applied the selected model to the held-out dataset to test its performance on unseen cases.
Results
Not only did the selected model have good sensitivity and specificity (both >80%) on the training set, but more importantly, it had promising performance when applied to the test set.
Conclusions
Our predictive model performed well not only in cross-validated data, but also in our test dataset, increasing our confidence in its generalizability.
PNEUMOCOCCAL SEROTYPES ASSOCIATED WITH MORTALITY AMONG CHILDREN LESS THAN 5 YEARS IN SOUTH AFRICA IN THE POST-VACCINATION ERA (ID 163)
Abstract
Background
Mortality due to S. pneumoniae is particularly high amongst children. We assessed the association of serotype with mortality in ages below 5 years in invasive pneumococcal disease (IPD) in the post-vaccine era in South Africa (SA).
Methods
We conducted surveillance for laboratory-confirmed IPD at 28 hospitals in SA during 2012-2018. We used multivariable logistic regression to compare the association of serotype with in-hospital outcome.
Results
Of 825 IPD cases with pneumococcal serotype, age and outcome data, 212(26%) died (31%(79/254) with meningitis, 21% (109/513) with bacteremia and 41%(24/58) from other invasive disease). Overall among IPD, compared to patients infected with serotype 8 (the most common serotype identified) and after adjusting for age, HIV status and specimen type, those with serotypes 15A (OR:5.0, 95%CI:2.0-12.1), 6A (OR:4.8, 95%CI:1.8-12.9), 19F (OR:3.3, 95%CI:1.3-8.6), 22F (OR:6.8, 95%CI:1.5-31.7), 17F (OR:3.8, 95%CI:1.2-12.2), 11A (OR:6.0, 95%CI:1.2-28.7), 13 (OR:4.1, 95%CI:1.2-14.7) and 35B (OR:2.6, 95%CI:1.1-6.2) were more likely to die. In meningitis cases, those with serotype 6A (OR:13.1, 95%CI:1.2-139.5) were more likely to die compared to serotype 8.
Conclusions
In the vaccine era in children aged <5 years, of the serotypes associated with increased mortality, the majority (15A, 22F, 17F, 11A, 13, 35B) are not included in the current conjugate vaccines.