Scarlet Fever Is Caused By a Limited Number of Streptococcus pyogenes Lineages and Is Associated with the Exotoxin Genes ssa, speA and speC

Background: Several outbreaks of scarlet fever caused by Streptococcus pyogenes were recently reported. Scarlet fever is historically considered a toxin-mediated disease, dependent on the production of the exotoxins SpeA and SpeC, but a strict association between scarlet fever and these exotoxins is not always detected. The aims of this study were to characterize the scarlet fever bacterial isolates recovered from patients in a Lisbon hospital and to identify any distinctive characteristics of such isolates. Methods: We characterized a collection of 303 pharyngeal S. pyogenes collected between 2002 and 2008. One-hundred and one were isolated from scarlet fever patients and 202 were associated to a diagnosis of tonsillo-pharyngitis. Isolates were characterized by T and emm typing, pulsed field gel electrophoresis profiling and superantigen gene profiling. Results: The diversity of the scarlet fever isolates was lower than that of the pharyngitis isolates. Specific lineages of emm87, emm4 and emm3 were overrepresented in scarlet fever isolates but only 1 pulsed field gel electrophoresis major lineage was significantly associated with scarlet fever. Multivariate analysis indicated associations of ssa, speA and speC with scarlet fever. Conclusions: In nonoutbreak conditions, scarlet fever is caused by a number of distinct genetic lineages. The lower diversity of these isolates and the association with specific exotoxin genes indicates that some lineages are more prone to cause this presentation than others even in nonoutbreak conditions.