According to a new study on cases of scarlet fever and other Streptococcus A infections in England and Wales, the recent rise in cases is due to a newly identified strain. This accounted for the great increase in the number of cases of scarlet fever that occurred in 2014. The last such outbreak was way back in the 1960s.
Moreover, the cases continue to increase, from 15,000 in 2014, 17, 000 in 2015 and 19,000 or more in 2016. Moreover, since 2016, this rise has been associated with an increase in the frequency of serious Strep A infections that enter the bloodstream to cause invasive infections and sepsis.
Close up of petri dish with colony of Streptococcus bacteria. Image Credit: Stastny_Pavel / Shutterstock
What is scarlet fever?
Scarlet fever is a condition that affects young children, caused by S. pyogenes, part of the group of streptococci called Strep A. It is so called because of the characteristic pinkish-red sandpapery rash on the skin that accompanies the symptoms of a high temperature and sore throat. The rash is due to the toxin called Streptococcal pyrogenic exotoxin A (SpeA) released by the bacterium. Most cases occur from March to May, but rapidly respond to antibiotics. Though very common and deadly in children until the 20th century, it showed a rapid decline, both in intensity and in numbers, since then, though the reasons are not clear.
The study shows that the new S. pyogenes strain is capable of producing more toxin and triggering scarlet fever in vulnerable children. It is also more capable of producing all types of infection other than scarlet fever. Therefore, says researcher Nicola Lynskey, “It is important to monitor the bacterium both here and globally.”
How the discovery was made
The researchers started to examine the different S. pyogenes strains behind the scarlet fever scourge and other infections, first in London and then in the rest of England and Wales. They looked at the emm gene expression and found significant differences in the type of gene found in different years.
According to them the 2014 upturn in scarlet fever was due to S. pyogenes bacteria carrying emm3 and emm4 genes, but this changed to lemm1-positive strains which were causing throat infections, in the spring of 2015 and 2016. This strain accounted for only 5% of strains in northwest London in the spring of 2014, but in the next two years, its contribution went up to 19% and 33%. In effect, the emm1 strain became the single most commonly found isolate in 2016.
The same trend was seen with respect to severe invasive infections caused by S. pyogenes. In 2015 and 2016, an astounding 31% and 42% of these infections were caused by emm1 strains, not just in London, but in England and Wales.
Moving in for the kill
Now the researchers analysed all the strains from scarlet fever outbreaks in London and invasive infections in England and Wales. Both were emm1 isolates, but the first category contained samples from 2009 to 2016, while the second had only isolates from the spring outbreaks in 2013- 2016. They performed genomic sequencing of all the strains and compared them with each other.
The findings were stunning. Firstly, most emm1 strains from the 2015/2016 outbreaks belonged to a single clone called M1UK, unlike earlier emm1 outbreaks. The signature of this clone was 27 unique mutations, along with a higher production of the scarlet fever toxin SpeA. This is also involved in producing throat infection and other invasive infections as well. The researchers found that this clone produces 9 times as much of the toxin than any other emm1 strain, at an average of 190 ng/mL compared to 21 ng/mL for other strains.
Moreover, this clone first appeared in 2010. Over the next 6 years, it proliferated widely, to the point that it now comprises 84% of all emm1 isolates n England and Wales from 2006 to 2016. This is therefore the chief culprit in serious S. pyogenes infections due to an emm1 strain. And when it is linked to increased scarlet fever cases, which are the more common forms of S. pyogenes infection, an increase in serious invasive infections is also potentially around the corner.
According to researcher Shiranee Sriskandan, “Scarlet fever is a very visible signal of how much Strep A is circulating in the wider community, and causing sore throats. Strains of Strep A that cause these commoner throat infections and scarlet fever are the same strains that cause rarer invasive diseases - and therefore a rise in these commoner throat infections including scarlet fever could lead to increases in all forms of Strep A infection.”
Why did this sudden increase in M1UK activity occur?
Scientists do not know precisely what set off this sudden wave of M1UK spread. It could be that an increased number of cases of scarlet fever (NOT due to this strain) occurring at the same time as the upsurge in the activity of this clone allowed it to spread its genetic matter to other strains and become the dominant clone. This strain is genetically unique and different from all the other 2800 strains that carry the emm1 gene.
The main lesson is that this strain will have to be monitored more closely since it produces more of the SpeA toxin which has been held responsible for the 1980s rise in severe streptococcal invasive infections. Further analysis of isolates from 2016 to date are also needed. The researchers will now have to examine whether the climate and treatment of sore throat in the UK have any effect on this spread, since one isolate each of this highly invasive strain has been found in the US and in Denmark.
Moreover, many other factors must be considered, including changes in the way a sore throat is treated, whether other factors like population or environmental changes are implicated, and whether a vaccine can be developed to prevent S. pyogenes infection. It could therefore spread over the world, or it could fade out, as other clones have done in the past.
Researcher Elita Jauneikaite says, “We may also need to consider whether guidelines for diagnosing and treating throat infections may need to take evolution of new strains and complications like scarlet fever and invasive infections into account.”
This emphasizes the importance of Mark Walker’s comment on the report: “The continuing increase in scarlet fever and invasive disease notifications in the UK exemplifies the essential need to install global surveillance systems. The report by Lynskey and colleagues sends out an important warning for the global public health community - recently emerging scarlet fever GAS [Group A Streptococcus] strains have enhanced invasive potential which may have profound implications for the future global health burden.”
The study was published in the journal The Lancet Infectious Diseases on September 10, 2019.
Emergence of dominant toxigenic M1T1 Streptococcus pyogenes clone during increased scarlet fever activity in England: a population-based molecular epidemiological study. Nicola N Lynskey, Elita Jauneikaite, Ho Kwong Li, Xiangyun Zhi, Claire E Turner, Mia Mosavie, Max Pearson, Masanori Asai, Ludmila Lobkowicz, J. Yimmy Chow, Julian Parkhill, Theresa Lamagni, Victoria J. Chalker, & Shiranee Sriskandan. The Lancet Infectious Diseases. https://doi.org/10.1016/S1473-3099(19)30446-3. https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(19)30446-3/fulltext