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Strep A Sequences Point to Potential Scarlet Fever Culprit in the UK

NEW YORK – A genomic analysis of Streptococcus pyogenes — or group A streptococcus ("Strep A") — isolates collected in England and the UK has uncovered a UK strain with enhanced virulence that is suspected of contributing to a recent rise in scarlet fever cases in England.

"Given that this strain has an apparently enhanced ability to cause all types of Strep A infection, it is important to monitor the bacterium both here and globally," co-first author Nicola Lynskey, an infectious diseases researcher at the Imperial College London's Medical Research Council Centre for Molecular Bacteriology and Infection (CMBI), said in a statement.

Lynskey and colleagues from the UK did genome sequencing on hundreds of S. pyogenes isolates collected in London and other parts of England and Wales between 2014 and 2016, focusing on a highly virulent genotype marked by an M antigen-coding gene called emm1. Their findings, published online today in the Lancet Infectious Diseases, suggested that isolates containing emm3 and emm4 genes were largely replaced by emm1-containing strains in the region by 2015 and 2016.

By taking a closer look at the emm1 isolates in a global S. pyogenes context, the team narrowed in on a strain known as M1UK that appeared more apt to produce a so-called streptococcal pyrogenic exotoxin A (SpeA). That toxin, in turn, is believed to contribute to everything from scarlet fever and sore throats to other dangerous, invasive infections, consistent with the jump in scarlet fever cases documented in the area since 2014.

From these and other findings, the authors suggested that a "dominant new emm1 S. pyogenes lineage characterized by increased SpeA production has emerged during increased S. pyogenes activity in England. The expanded reservoir of M1UK and recognized invasive potential of emm1 S. pyogenes provide plausible explanation for the increased incidence of invasive disease, and rationale for global surveillance."

The number of scarlet fever cases in England reached 15,000 in 2014, the team noted, a level that had not been seen there in decades. In the years since, scarlet fever cases have continued to increase, topping at least 19,000 cases by the spring of 2016.

In an effort to understand this spike, the researchers did genome sequencing on hundreds of invasive or non-invasive S. pyogenes isolates collected in locally or nationally in the UK, comparing these sequences to those previously reported for emm1 isolates collected globally from 2009 to 2016.

Of 96 S. pyogenes isolates collected in northwest London between March and May of 2014, the team identified five emm1 isolates. The following spring, the emm1 gene turned up in 28 of 147 S. pyogenes isolates, rising again in 2016, when 47 of 144 Strep A isolates picked up in northwest London contained emm1.

More broadly, the team found emm1 in 183 of 587, or just over 30 percent of isolates collected across England and Wales in 2015. In 2016, 42 percent of the 637 Strep A isolates collected nationally were emm1-positives.

Within the context of some 2,800 global emm1 Strep A isolates, the researchers identified a M1UK clone that harbored more than two-dozen distinct mutations and showed enhanced SpeA production in their subsequent gene and protein expression analyses. Just two non-UK isolates in the analysis — one in Denmark and another in the US — clustered with M1UK.

"The distinct bacterial clone we have discovered appears so far to be largely limited to the UK, but the fact that we have identified two examples of it elsewhere suggests it has the potential to spread internationally and may already be present in other countries," senior and corresponding author Shiranee Sriskandan, a researcher affiliated with CMBI at Imperial College London and the National Institute for Health Research, said in a statement. "However, it's also possible that the lineage will not last. In the past, some lineages have appeared and then disappeared quickly."

In a related commentary in the Lancet Infectious Diseases, University of Queensland researcher Mark Walker and colleagues from Australia and China noted that scarlet fever cases reported in the UK and beyond have involved several diverse Strep A emm types. Even so, they said the new data "provide a plausible explanation for the increased capacity of M1UK to cause toxin-mediated scarlet fever and invasive infections in the UK."

"The continuing increase in scarlet fever and invasive disease notifications in the UK exemplifies the essential need to install global surveillance systems and address the increased GAS disease activity as a public-health priority," Walker said in a statement, noting that the new study "sends out an important warning for the global public health community."