Genetic evolution of invasive emm28 Streptococcus pyogenes strains and significant association with puerperal infections in young women in Finland

Abstract

<p><strong>Objectives: </strong>Streptococcus pyogenes or group A streptococcus (GAS) is a human specific pathogen that annually infects over 700 million individuals. GAS strains of type emm28 are an abundant cause of invasive infections in Europe and North America.</p><p><strong>Methods: </strong>We conducted a population-based study on bacteraemic emm28 GAS cases in Finland, from 1995 to 2015. Whole-genome sequencing (WGS) was used to genetically characterize the bacterial isolates. Bayesian analysis of the population structure was used to define genetic clades. Register-linkage analysis was performed to test for association of emm28 GAS with delivery- or postpartum-related infections. A genome-wide association study was used to search for DNA sequences associated with delivery or puerperal infections.</p><p><strong>Results: </strong>Among 3060 bacteraemic cases reported during the study period, 714 were caused by emm28. Women comprised a majority of cases (59 %, 422/714), and were significantly over-represented (84.4 %, 162/192, p < 0.0001) among cases in the childbearing age group (20-40 years). Register-linkage analysis revealed strong association (p < 0.0001) of emm28 bacteraemias with delivery and puerperium. In this register-linkage analysis, 120 women with GAS bacteraemia were identified and linked to delivery, infections during delivery or puerperium time. Among these the proportion of cases caused by emm28 was significantly higher than any other emm type (55.8%, 67/120, p < 0.0001). Among the four genetic subclades identified, SC1B has dominated among the bacteraemic cases since 2000. Altogether 620 of 653 (94.9%) isolates belonged to SC1B. No specific sequence or genetic clade was found nonrandomly associated with delivery or puerperal infections.</p><p><strong>Conclusions: </strong>Women of childbearing age were significantly overrepresented among bacteraemic emm28 GAS cases, and in particular were strongly associated with delivery and puerperium cases over the 21 years studied. The molecular mechanisms behind these associations are unclear and warrant further investigation.</p>