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Explaining the Rising Tide of Scarlet Fever in the UK with Molecular Epidemiology

Amesh A. Adalja, MD, FACP, FACEP, FIDSA | September 23, 2019


Scarlet fever is often thought of as an infectious disease from another century, but the United Kingdom has been experiencing a record number of cases since 2014. This complication of Streptococcus pyogenes (Group A) infection is caused by the elaboration of the streptococcal pyrogenic exotoxin A (SpeA) and is characterized by rash. It can, in certain contexts, be responsible for severe disease and lethality when septic or toxic scarlet fever occurs. A new paper, published in Lancet Infectious Diseases, explains the molecular epidemiology of this rise.

From 2009 to 2013, noninvasive and invasive S.pyogenes isolates submitted to the Diagnostic Laboratory at Imperial College Healthcare National Health Service Trust and the national reference laboratory (invasive isolates) were emm (M antigen) genotyped. All emm1 genotype isolates (known to be associated with severe disease) underwent whole genome sequencing. SpeA toxin production was also quantified in the isolates.

Emergence of New Toxin Hyper-Producing Lineage

Year-on-year, emm1 genotypes increased to become the dominant strain causing respiratory infections and rose from being responsible for none of the scarlet fever cases in 2014 to 37% of cases in 2016. Single nucleotide polymorphism (SNP) analysis of noninvasive emm1 S.pyogenes isolates revealed the existence of a dominant distinct lineage, M1UK. Beginning in 2015, this lineage represented two-thirds of all noninvasive emm1 genotype isolates from northwest London. Invasive cases of emm1 S.pyogenes also grew to be dominated by the newly identified lineage. Investigators compared the sequence of M1UK to international databases of isolates, finding only 2 isolates outside the UK that matched – 1 in the United States and 1 in Denmark.

The newly identified lineage was characterized by mutations in transcriptional regulators for the SpeA toxin, which conferred a hyperproduction toxin phenotype (9X).

The Value of Molecular Epidemiology

This study is an important concretization of the power of molecular epidemiology, including whole genome analysis, to uncover the causes of important changes in the behavior of common pathogens. Streptococcal infections are very common, and relatively less attention is devoted to noninvasive syndromes, which are not usually reportable. However, spiking numbers of cases of scarlet fever – a disease that diminished even before the advent of antibiotics – led to an investigation that revealed that a new lineage capable of toxin hyperproduction had emerged and grown to dominance. While this strain is not currently prevalent outside the UK, it will be important to track scarlet fever cases in other geographic locations to determine if this lineage has arrived and to advise clinicians accordingly.

Reference

Lynskey NN, Jauneikaite E, Li HK, et al. Emergence of dominant toxigenic M1T1 Streptococus pyogenes clone during increased scarlet fever activity in England: a population-based molecular epidemiological study. Lancet Infect Dis 2019; https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(19)30446-3/fulltext. Accessed September 19, 2019.