Dataset Information

Impact of Antibiotic Resistance on Treatment of Pneumococcal Disease in Ethiopia: An Agent-Based Modeling Simulation.

ABSTRACT: Antimicrobial resistance (AMR) is a growing threat to global health. Although AMR endangers continued effectiveness of antibiotics, the impact of AMR has been poorly estimated in low-income countries. This study sought to quantify the effect of AMR on treatments for pediatric pneumococcal disease in Ethiopia. We developed the DREAMR (Dynamic Representation of the Economics of AMR) model that simulate children younger than 5 years who acquire pneumococcal disease (pneumonia, meningitis, and acute otitis media) and seek treatment from various health facilities in Ethiopia over a year. We examined the AMR levels of three antibiotics (penicillin, amoxicillin, and ceftriaxone), treatment failures, and attributable deaths. We used the cost-of-illness method to assess the resulting economic impact of AMR from a societal perspective by estimating the direct and indirect treatment costs and productivity losses. Findings showed that AMR against antibiotics that were used to treat pneumococcal disease led to 195,763 treatment failures per year, which contributed to 2,925 child deaths annually in Ethiopia. Antimicrobial resistance resulted in a first-line treatment failure rate of 29.4%. In 1 year, the proportion of nonsusceptible Streptococcus pneumoniae bacteria increased by 2.1% and 0.5% for amoxicillin and penicillin, and reduced by 0.3% for less commonly used ceftriaxone. Annual costs of AMR to treat pneumococcal disease were around US$15.8 million, including US$3.3 million for ineffective first-line treatments, US$3.7 million for second-line treatments, and US$8.9 million for long-term productivity losses. Antibiotic stewardship to reduce misuse and overuse of antibiotics is essential to maintain the effectiveness of antibiotics, and lessen the health and economic burden of AMR.

SUBMITTER: Chen HH

PROVIDER: S-EPMC6838571 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Impact of Antibiotic Resistance on Treatment of Pneumococcal Disease in Ethiopia: An Agent-Based Modeling Simulation.

Chen Hui-Han HH Stringer Andrew A Eguale Tadesse T Rao Gauri G GG Ozawa Sachiko S

The American journal of tropical medicine and hygiene 20191101 5

Antimicrobial resistance (AMR) is a growing threat to global health. Although AMR endangers continued effectiveness of antibiotics, the impact of AMR has been poorly estimated in low-income countries. This study sought to quantify the effect of AMR on treatments for pediatric pneumococcal disease in Ethiopia. We developed the DREAMR (Dynamic Representation of the Economics of AMR) model that simulate children younger than 5 years who acquire pneumococcal disease (pneumonia, meningitis, and acute ...[more]

PMID: 31516111

Similar Datasets

Project description:BackgroundPneumococcal conjugate vaccines have reduced the incidence of invasive pneumococcal disease, caused by vaccine serotypes, but non-vaccine-serotypes remain a concern. We used whole genome sequencing to study pneumococcal serotype, antibiotic resistance and invasiveness, in the context of genetic background.MethodsOur dataset of 13,454 genomes, combined with four published genomic datasets, represented Africa (40%), Asia (25%), Europe (19%), North America (12%), and South America (5%). These 20,027 pneumococcal genomes were clustered into lineages using PopPUNK, and named Global Pneumococcal Sequence Clusters (GPSCs). From our dataset, we additionally derived serotype and sequence type, and predicted antibiotic sensitivity. We then measured invasiveness using odds ratios that relating prevalence in invasive pneumococcal disease to carriage.FindingsThe combined collections (n = 20,027) were clustered into 621 GPSCs. Thirty-five GPSCs observed in our dataset were represented by >100 isolates, and subsequently classed as dominant-GPSCs. In 22/35 (63%) of dominant-GPSCs both non-vaccine serotypes and vaccine serotypes were observed in the years up until, and including, the first year of pneumococcal conjugate vaccine introduction. Penicillin and multidrug resistance were higher (p < .05) in a subset dominant-GPSCs (14/35, 9/35 respectively), and resistance to an increasing number of antibiotic classes was associated with increased recombination (R2 = 0.27 p < .0001). In 28/35 dominant-GPSCs, the country of isolation was a significant predictor (p < .05) of its antibiogram (mean misclassification error 0.28, SD ± 0.13). We detected increased invasiveness of six genetic backgrounds, when compared to other genetic backgrounds expressing the same serotype. Up to 1.6-fold changes in invasiveness odds ratio were observed.InterpretationWe define GPSCs that can be assigned to any pneumococcal genomic dataset, to aid international comparisons. Existing non-vaccine-serotypes in most GPSCs preclude the removal of these lineages by pneumococcal conjugate vaccines; leaving potential for serotype replacement. A subset of GPSCs have increased resistance, and/or serotype-independent invasiveness.

Project description:Introduction Antibiotics are commonly prescribed to young children for treating bacterial infections such as invasive pneumococcal disease (IPD) caused by Streptococcus pneumoniae. Despite the obvious benefits of antibiotics, little is known about their possible side effects on children’s nasopharyngeal microbiota. In other ecological niches, antibiotics have been described to perturb the balanced microbiota with short- and long-term effects on children’s health. The present study aims to evaluate and compare the nasopharyngeal microbiota of children with IPD and different degree of antibiotic exposure. Methods We investigated differences in nasopharyngeal microbiota of two groups of children <18 years with IPD: children not exposed to antibiotics before sample collection (n=27) compared to children previously exposed (n=54). Epidemiological/clinical data were collected from subjects, and microbiota was characterized by Illumina sequencing of V3-V4 amplicons of the 16S rRNA gene. Results Main epidemiological/clinical factors were similar across groups. Antibiotic-exposed patients were treated during a median of 4 days (IQR: 3–6) with at least one beta-lactam (100.0%). Higher bacterial richness and diversity were found in the group exposed to antibiotics. Different streptococcal amplicon sequence variants (ASVs) were differentially abundant across groups: antibiotic use was associated to lower relative abundances of Streptococcus ASV2 and Streptococcus ASV11 (phylogenetically close to S. pneumoniae), and higher relative abundances of Streptococcus ASV3 and Streptococcus ASV12 (phylogenetically close to viridans group streptococci). ASVs assigned to typical bacteria from the oral cavity, including Veillonella, Alloprevotella, Porphyromonas, Granulicatella, or Capnocytophaga, were associated to the antibiotic-exposed group. Common nosocomial genera such as Staphylococcus, Acinetobacter, and Pseudomonas were also enriched in the group exposed to antibiotics. Conclusion Our results point toward a reduction of S. pneumoniae abundance on the nasopharynx of children with IPD after antibiotic treatment and a short-term repopulation of this altered niche by oral and nosocomial bacteria. Future research studies will have to evaluate the clinical implications of these findings and if these populations would benefit from the probiotic/prebiotic administration or even from the improvement on oral hygiene practices frequently neglected among hospitalized children.

Project description:BackgroundInvasive pneumococcal disease remains an important health priority owing to increasing disease incidence caused by pneumococci expressing non-vaccine serotypes. We previously defined 621 Global Pneumococcal Sequence Clusters (GPSCs) by analysing 20 027 pneumococcal isolates collected worldwide and from previously published genomic data. In this study, we aimed to investigate the pneumococcal lineages behind the predominant serotypes, the mechanism of serotype replacement in disease, as well as the major pneumococcal lineages contributing to invasive pneumococcal disease in the post-vaccine era and their antibiotic resistant traits.MethodsWe whole-genome sequenced 3233 invasive pneumococcal disease isolates from laboratory-based surveillance programmes in Hong Kong (n=78), Israel (n=701), Malawi (n=226), South Africa (n=1351), The Gambia (n=203), and the USA (n=674). The genomes represented pneumococci from before and after pneumococcal conjugate vaccine (PCV) introductions and were from children younger than 3 years. We identified predominant serotypes by prevalence and their major contributing lineages in each country, and assessed any serotype replacement by comparing the incidence rate between the pre-PCV and PCV periods for Israel, South Africa, and the USA. We defined the status of a lineage as vaccine-type GPSC (≥50% 13-valent PCV [PCV13] serotypes) or non-vaccine-type GPSC (>50% non-PCV13 serotypes) on the basis of its initial serotype composition detected in the earliest vaccine period to measure their individual contribution toward serotype replacement in each country. Major pneumococcal lineages in the PCV period were identified by pooled incidence rate using a random effects model.FindingsThe five most prevalent serotypes in the PCV13 period varied between countries, with only serotypes 5, 12F, 15B/C, 19A, 33F, and 35B/D common to two or more countries. The five most prevalent serotypes in the PCV13 period varied between countries, with only serotypes 5, 12F, 15B/C, 19A, 33F, and 35B/D common to two or more countries. These serotypes were associated with more than one lineage, except for serotype 5 (GPSC8). Serotype replacement was mainly mediated by expansion of non-vaccine serotypes within vaccine-type GPSCs and, to a lesser extent, by increases in non-vaccine-type GPSCs. A globally spreading lineage, GPSC3, expressing invasive serotypes 8 in South Africa and 33F in the USA and Israel, was the most common lineage causing non-vaccine serotype invasive pneumococcal disease in the PCV13 period. We observed that same prevalent non-vaccine serotypes could be associated with distinctive lineages in different countries, which exhibited dissimilar antibiotic resistance profiles. In non-vaccine serotype isolates, we detected significant increases in the prevalence of resistance to penicillin (52 [21%] of 249 vs 169 [29%] of 575, p=0·0016) and erythromycin (three [1%] of 249 vs 65 [11%] of 575, p=0·0031) in the PCV13 period compared with the pre-PCV period.InterpretationGlobally spreading lineages expressing invasive serotypes have an important role in serotype replacement, and emerging non-vaccine serotypes associated with different pneumococcal lineages in different countries might be explained by local antibiotic-selective pressures. Continued genomic surveillance of the dynamics of the pneumococcal population with increased geographical representation in the post-vaccine period will generate further knowledge for optimising future vaccine design.FundingBill & Melinda Gates Foundation, Wellcome Sanger Institute, and the US Centers for Disease Control.

Dataset Information

Impact of Antibiotic Resistance on Treatment of Pneumococcal Disease in Ethiopia: An Agent-Based Modeling Simulation.

Publications

Impact of Antibiotic Resistance on Treatment of Pneumococcal Disease in Ethiopia: An Agent-Based Modeling Simulation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets