Abstract
Serotype 1 is an important cause of invasive pneumococcal disease in South Africa and has declined following the introduction of the 13-valent pneumococcal conjugate vaccine in 2011. We genetically characterized 912 invasive serotype 1 isolates from 1989 to 2013. Simpson's diversity index (D) and recombination ratios were calculated. Factors associated with sequence types (STs) were assessed. Clonal complex 217 represented 96% (872/912) of the sampled isolates. Following the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13), ST diversity increased in children <5 years (D, 0.39 to 0.63, P = 0.002) and individuals >14 years (D, 0.35 to 0.54, P < 0.001): ST-217 declined proportionately in children <5 years (153/203 [75%] versus 21/37 [57%], P = 0.027) and individuals >14 years (242/305 [79%] versus 96/148 [65%], P = 0.001), whereas ST-9067 increased (4/684 [0.6%] versus 24/228 [11%], P < 0.001). Three subclades were identified within ST-217: ST-217C1 (353/382 [92%]), ST-217C2 (15/382 [4%]), and ST-217C3 (14/382 [4%]). ST-217C2, ST-217C3, and single-locus variant (SLV) ST-8314 (20/912 [2%]) were associated with nonsusceptibility to chloramphenicol, tetracycline, and co-trimoxazole. ST-8314 (20/912 [2%]) was also associated with increased nonsusceptibility to penicillin (P < 0.001). ST-217C3 and newly reported ST-9067 had higher recombination ratios than those of ST-217C1 (4.344 versus 0.091, P < 0.001; and 0.086 versus 0.013, P < 0.001, respectively). Increases in genetic diversity were noted post-PCV13, and lineages associated with antimicrobial nonsusceptibility were identified.
Highlights
A recent epidemiological study in South Africa [5] reported two spatially and temporarily distinct serotype 1 clusters in 2003 to 2004 and 2008 to 2012; a decrease in serotype 1 incidence was reported in all age groups following PCV13 introduction, even compared to years without clusters
We aimed to genetically characterize a comprehensive collection of invasive serotype 1 isolates, spanning 25 years, including whole-genome analyses of a subset of isolates to analyze temporal and/or vaccine pressure-associated genomic changes that may not be revealed by multilocus sequence typing (MLST)
Since 1979, the former South African Institute for Medical Research served as the national reference center for pneumococcal serotyping and monitoring of antimicrobial resistance [24,25,26]
Summary
Streptococcus pneumoniae serotype 1 is one of the commonest causes of invasive pneumococcal disease (IPD) in Africa, Asia, and South America [1, 2]. Serotype 1 is associated with bacteremia, empyema, and peritonitis and has a lower risk of mortality relative to other serotypes [5, 9,10,11]. It has high invasive potential and is rarely detected in colonization studies, remaining predominantly susceptible to antimicrobial agents [12, 13].
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