New strain of bacteria responsible for rise in cases of scarlet fever, throat infections and sepsis, say scientists

The strain, called M1UK, has an enhanced ability to cause all types of Strep A infection and scientists recommend that its impact on public health is monitored

                            New strain of bacteria responsible for rise in cases of scarlet fever, throat infections and sepsis, say scientists

Scientists have discovered a new strain of bacteria, which is causing a surge in scarlet fever and more serious invasive infections such as bloodstream infections. According to researchers, the emergence of the new strain calls for increased surveillance of the type of strains causing scarlet fever, throat infections, and sepsis, and its impact on public health.

Scarlet fever is a contagious disease that typically infects young children, triggering a high temperature, sore throat, and a pink-red rash that feels like sandpaper. The disease, which peaks around springtime (March to May), is easily treated with antibiotics — but has shown a dramatic surge in recent years, with over 19,000 cases in 2016.

Group A streptococcus (or Strep A) is known to cause scarlet fever, throat infections and — in rare cases — invasive disease, where the bacterium enters the bloodstream or tissue and trigger sepsis and toxic shock.

"When the bacteria infect the body, they release toxins called streptococcal pyrogenic exotoxins (also known as scarlet fever toxins), which are responsible for the disease symptoms in scarlet fever, and promote inflammation in throat infections and invasive disease," say experts.

Now researchers studying scarlet fever have identified a new strain of the disease-causing bacteria, which may explain a rise in more serious Strep A infections in England and Wales, according to results from cases in London and across England and Wales from 2014-2016.

This new strain has increased capacity to produce scarlet fever toxin, says the team. In 2014, England experienced the biggest surge in scarlet fever cases since the 1960s.

Numbers continued to increase, with 15,000 cases in 2014, 17,000 in 2015 and over 19,000 in 2016. "An unprecedented year-on-year increase in scarlet fever notifications has been seen in England since 2014. Among children aged 1-4 years, the incidence of scarlet fever in 2018 reached 1,488 per 100,000," state findings.

The new strain — which has been named M1UK — seems to have emerged in England and Wales since 2010 to become the dominant cause of Strep A infections. The analysis, published in The Lancet Infectious Diseases, suggests that the new strain has increased in numbers among cases of scarlet fever, throat infections, and much rarer invasive infections since 2014.

According to the research team, the spring of 2016 saw the number of laboratory-confirmed invasive Strep A infections increase by 1.5 times, compared to the previous five years. This rise occurred at the same time as scarlet fever cases peaked.

Researchers are now calling for global vigilance to identify further cases of the strain in other countries, and highlight the importance of developing a vaccine against Strep A.

"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," says joint first author, Dr. Nicola Lynskey from Imperial College London, UK, which led the study. 

Researchers explain that the new strain produces more of one type of streptococcal toxin than existing strains, which makes it potentially more likely to cause common throat infections and scarlet fever, and this could account for a rise in invasive infection.

Scarlet fever is a contagious disease that typically infects young children, triggering a high temperature, sore throat, and a pink-red rash. (Getty Images)

What the investigation reveals

The research team — based in the Department of Infectious Disease and affiliated to the NIHR Health Protection Unit in Healthcare Associated Infections and Antimicrobial Resistance at Imperial — decided to investigate whether the bacteria causing the Strep A infections to change in any way.

The researchers studied infections between 2014 and 2016 to identify the main genetic sub-groups causing scarlet fever or common throat infections in London, England, and Wales. These sub-groups are labeled as "emm" due to a type of gene the bacteria carry. 

By analyzing the London data, researchers found that the initial upsurge of scarlet fever in 2014 was caused by strains emm3 and emm4. However, during the spring of 2015 and 2016, emm1 strains became dominant among throat infections.

Infections of emm1 strain increased year-by-year and were responsible for 5% (five of 96) of cases in 2014, 19% (28 of 147) in 2015 and 33% (47 of 144 ) in 2016, thus becoming the single most frequent strain.

The analysis confirmed that emm1 strains also became increasingly dominant among strains causing severe invasive infections more widely within England and Wales. By Spring 2016, 42% (267 of 637) of invasive strains collected in England and Wales were emm1 isolates, up from 31% (183 of 587) in Spring 2015.

Researchers say this suggested that the emm1 strain may have changed in some way — and was potentially getting "fitter". To investigate this, the team analyzed the genomes of all 135 non-invasive emm1 strains, collected in northwest London between 2009 to 2016.

Further, all 552 invasive emm1 isolates collected in England and Wales during the seasonal disease spikes between 2013 and 2016 and compared them with one another.

They assessed how much toxin was produced by different emm1 strains. Researchers found that the majority of emm1 strains from 2015 and 2016 were a distinct, breakaway emm1 clone, which they refer to as M1UK. 

"This unmasked a new strain type (dubbed as M1UK) within the emm1 group of bacteria, which differed from the other emm1 strains by just 27 genetic mutations, some of which were in genes potentially implicated in toxin (streptococcal pyrogenic exotoxin A or SpeA) production," says the study. 

This toxin triggers scarlet fever and may contribute to Strep A pharyngitis and some invasive infections, state the findings. Analysis confirms that the new strain produces nine-times more SpeA than other emm1 strains — possibly providing one explanation for the rise in cases of Strep A.

"The results reveal that 77% of cases of invasive disease caused by emm1 Strep A in England and Wales in spring 2016 were caused by the newly identified M1UK strain. When the analysis expanded to include all emm1 strains (1,240 strains) that had been sequenced over 10 years from across the UK, mainly from invasive cases of the disease, this reached 84% of emm1 samples by 2016," the findings state.

Researchers speculate that the recent increase in activity of Strep A, which coincided with upsurges of scarlet fever, might have provided the conditions required for it to adapt genetically and spread within the UK.

The researchers are now calling for global vigilance to identify further cases of the strain in other countries, and highlight the importance of developing a vaccine against Strep A. (Getty Images)

The team also analyzed 2800 Strep A genome sequences from around the world and found single cases of M1UK in Denmark and the USA. The research team, however, cannot confirm whether the new strain will be suited to environments in other countries, where factors such as climate and management of streptococcal sore throat vary. 

"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," says senior author Professor Shiranee Sriskandan from Imperial College London, UK.

Sriskandan adds, "However, it's also possible that the lineage will not last. In the past, some lineages have appeared and then disappeared quickly. Only further research on recent strains will provide more insights."

The team says since the current work examined strains circulating up until 2016, analysis of the Strep A strains in the years since then is now needed. "There is still uncertainty around the cause of the rise in scarlet fever, and whether it is a result of practice change, population or environmental factors," says Dr. Elita Jauneikaite, first author of the study from Imperial.

Elita adds, "Research investigating the most appropriate way of reducing the burden of Strep A infections is currently underway - including work into developing a vaccine. We may also need to consider whether guidelines for diagnosing and treating throat infections may need to take the evolution of new strains and complications like scarlet fever and invasive infections into account."

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