New Strep A Strain Linked to Scarlet Fever, and Sepsis

Nicky Broyd

September 11, 2019

A new strain of group A streptococcus bacteria called M1UK linked to scarlet fever and sepsis has been identified in England and Wales.

The discovery was made by researchers led by Imperial College London who report their findings in the Lancet Infectious Diseases journal.

Professor Shiranee Sriskandan, senior author from the Department of Infectious Disease at Imperial told Medscape News UK: "In a nutshell, a previously, already dominant bacterial strain has changed in a few small genetic places … and the only biological change we can see in the bug is that it's making more of a particular type of toxin." 

So far cases appear to be restricted to the UK but the study authors wrote that their discovery "underlines a need for global surveillance and increased vigilance".

Scarlet Fever Outbreaks

Major increases in scarlet fever cases were seen in recent years: more than 15,000 cases in 2014, over 17,000 in 2015, and more than 19,000 in 2016.

Cases of invasive infections caused by the same bacterium, Streptococcus pyogenes (S pyogenes), also rose during 2016 compared to the previous 5 years.

Cases were assessed by emm genotypes.

The initial rise in scarlet fever cases in 2014 was associated with Strep A strain types emm3 and emm4. However, 2015-2016 saw emm1 strains becoming dominant in throat infections.

The emm1 strains also became more dominant across England and Wales.

By Spring 2016, 42% of invasive strains collected were emm1 compared with 31% the previous year.

The researchers say the new strain of Streptococcus pyogenes offers an explanation for the rise in invasive cases.

Prof Sriskandan told us: "The strain that has emerged is related to this previously dominant strain called emm1. And it's changed in a very small way in that it has acquired 27 quite small mutations. And yet, having done that, then become quite successful. It seems to have got an aptitude to expand within the population in terms of causing both throat infections, and also the much rarer invasive infection.

"What's interesting, from a science point of view, is that whatever has happened to this bacterium, it has made it more 'fit', or has better aptitude to cause throat infections in a population.

"One of the ways it has manifested biologically is that it can make more of one particular type of toxin called SpeA, or scarlet fever toxin." 

Genome Sequencing

The new strain type was identified after the genomes were sequenced of all 135 non-invasive emm1 isolates collected in northwest London between 2009 and 2016. The same was done with 552 invasive emm1 isolates collected in England and Wales during the seasonal disease increases from 2013-2016.

These were compared and assessed for toxin production by different strains of emm1.

The majority of emm1 strains from 2015 and 2016 were found to be phylogenetically distinct, which the researchers called M1UK.

This M1UK clone produced nine times more streptococcal pyrogenic exotoxin A (SpeA) than other emm1 strains (190 ng/mL vs 21 ng/mL).

This strain was found to have been circulating in England as far back as 2010.

By 2016, M1UK represented 84% of all emm1 genomes that were analysed from cases in England and Wales.

Prof Sriskandan says the M1UK strep type can be treated with penicillin and alternatives to penicillin as well.

An analysis was also made of 2800 Strep A genome sequences cases from around the world. Single isolates of M1UK were found in the US and Denmark.

However, M1UK was not a major part of the initial 2014 UK scarlet fever outbreak. Neither was it the strain involved in the Strep A outbreak in Essex earlier this year.

More Research

Prof Sriskandan says: "This particular strain type has been dominant across developed countries for quite a long time now, 20 years, so this change that it's undergone that we've detected in the UK might have more implications than just par for the normal course. We just don't know as yet. It's too early to say whether it's going to stick around or whether it's just going to die off.

"Should we be doing more about it? I'm a hospital physician, so I see the much more serious side of the infectious disease the bacteria cause … but it seems that the bacterial infections that cause sore throats do seem to target the youngest children. Children who get scarlet fever are largely aged between 4 and 6-years old. We also see a surge in strep throat around the same time of the year. So, my personal view is that we should look at whether slightly more targeted diagnosis and treatment of strep sore throats in that age group might reduce the reservoir of infection in the community.

"The much rarer infectious diseases, invasive diseases that as a hospital physician I see, are really, really rare, but clearly if one could reduce the burden of strep throat and scarlet fever we're very likely to reduce the burden of those more invasive serious infections too."

She acknowledges that further research is needed: "We don't know if we had conducted the study this year rather than 2016 whether we would have found the same things. That's work yet to be done."

'Plausible Clue'

Reacting to the findings through the Science Media Centre, Prof Jimmy Whitworth, professor of international public health, London School of Hygiene and Tropical Medicine, said: "This important study gives us a plausible clue to the worrying recent increase in cases of scarlet fever in children in England."

He continued: "The researchers rightly call for more surveillance to confirm these findings, as these streptococcal infections are highly sensitive to antibiotics, unlike most other types of sore throat in children. The researchers also call for development of a vaccine, but perhaps more achievable in the short-term would be to re-evaluate and refine existing desk-top diagnostic tests which could greatly help GPs to accurately and rapidly identify streptococcal sore throats in the future."

‘Emergence of dominant toxigenic M1T1 Streptococcus pyogenes clone during increased scarlet fever activity in England: a population-based molecular epidemiological study’ by Lynskey et al. The Lancet Infectious Diseases, Tuesday 10th September. DOI: 10.1016/S1473-3099(19)30446-3


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