Genomic characterization of <i>Streptococcus pneumoniae</i> isolates among pediatric patients in Addis Ababa, Ethiopia

Abstract

Abstract Background and aims Despite the introduction of pneumococcal conjugate vaccines (PCV), Streptococcus pneumoniae still remains an important cause of morbidity and mortality, especially among children under 5 years in sub-Saharan Africa. We sought to determine the distribution of lineages and antimicrobial resistance genes of S. pneumoniae , 5-6 years after the introduction of PCV10 in Ethiopia. Methods Whole genome sequencing (WGS) was performed on 103 S. pneumoniae (86 from nasopharyngeal swabs, 4 from blood and 13 from middle ear swabs) isolated from children aged &lt; 15 years at three health care facilities in Addis Ababa, Ethiopia from September 2016 to August 2017. Using the WGS data, serotypes were predicted, isolates were assigned to clonal complexes, Global Pneumococcal Sequence Clusters (GPSCs) were inferred and screening for alleles and mutations that confer resistance to antibiotics was performed using multiple bioinformatic pipelines. Results The 103 S. pneumoniae isolates were assigned to 45 different GPSCs. The most common GPSCs were GPSC1 (sequence type (ST) 320, serotype 19A), 14.6%; GPSC268 (ST 6882 and Novel STs; serotypes 16F, 11A and 35A), 8.7% and GPSC10 (STs 2013, 230 and 8804; serotype 19A), 7.7%. Intermediate resistance to penicillin was predicted in 14.6% of the isolates and 27 different Penicillin Binding Protein (PBP) allele combinations were identified. Variations in sulfamethoxazole-trimethoprim ( fol A and/or fol P), tetracycline ( tet M, tet O or tet S/M) and macrolide ( erm B and and/or mef A) resistance genes were predicted in 66%, 38.8% 19.4% of the isolates, respectively. Multidrug resistance (≥ 3 antibiotic classes) was observed in 18.4% (19/103) of the isolates and 78.9% of them were GPSC1 (ST320, serotype 19A). Conclusion Five to six years after introduction of PCV10 in Ethiopia, the population of S. pneumoniae is quite diverse, with the most common lineage an MDR GPSC1 (ST 320, Serotype 19A), which is not covered by the PCV10. Continued assessment of the impact of PCV on the population structure of S. pneumoniae in Ethiopia is warranted. Impact statement This study provides a detailed analysis of the genomic features of carriage and disease Streptococcus pneumoniae isolates from paediatric patients in Addis Ababa Ethiopia collected 5-6 years after introduction of PCV10 in the country. The study describes the distribution of serotypes, lineages, resistance genes and in silico predicted phenotypic antimicrobial resistance. The study highlights the predominance of multidrug resistant serotype 19A expressing GPSC1 (CC320). The findings underline the importance of continued genomic surveillance of pneumococcal carriage and disease to understand the selective pressure of vaccines on lineages and associated antimicrobial resistance. Data Summary Genome sequences are deposited at ENA with accession numbers (ERR9796440-ERR9990857, ERR10419695-ERR10419739). The authors confirm all supporting data have been provided within the article or through supplementary data files.