#15,705
Over the past year we've been closely watching the sharp rise in Strep A - primarily scarlet fever - along with Invasive Group A Strep (aka iGAS) in the UK, the United States, and other parts of Europe (see partial list below).
Scarlet fever is caused by the same bacteria that causes `strep throat’ - Streptococcus pyogenes - and is characterized by fever, a very sore throat, a whitish coating or sometimes `strawberry’ tongue, and a `scarlet rash’ that first appears on the neck and chest.
Far less common, albeit considerably more serious, is a related illness called iGAS (invasive Group A Strep), which indicates infection of the bloodstream, deep tissues, or lungs, and may result in severe (and frequently fatal) cases of necrotizing fasciitis and streptococcal toxic shock syndrome.
While Scarlet fever can generally be successfully treated with antibiotics, iGAS carries a substantial fatality rate. In their most recent update, the UKHSA reported:
So far this season 60 deaths have been recorded within 7 days of an iGAS infection diagnosis (from any cause), with 38% (n=23) of the recorded deaths being in those aged 75 years and over, and 17% (n=10) in children aged 10 years and under (Table 3).
While this latest surge may be due to increased social contacts following the end of pandemic lockdowns, scarlet fever has been on the ascendant for more than a decade - starting first in Asia (see Hong Kong: Scarlet Fever In 2012) - but centered in recent years in the UK and Europe.
Bacteria can evolve over time creating more infectious, antibiotic resistant, or more pathogenic strains. Strep A strains are identified by changes in their M-protein gene sequence (emm types) – and within these types new variants can emerge.
In 2019 we looked at a new and aggressive emm type from the UK described in The Lancet (see Lancet: Emergence of Dominant Toxigenic M1T1 Streptococcus pyogenes Clone in England), which identified it as a new variant showing an increased capacity to produce scarlet fever toxin.
Today we have a dispatch published in the CDC's EID Journal that documents the near complete dominance over the past winter of this highly aggressive M1UK lineage of S. pyogenes in Scotland, and its apparent link to influenza A co-infection.
Given its enhanced virulence, and rapid growth in the UK, this is something that doctors here in the United States, and around the world, will now need to be aware of. Due to its length, I've only posted some excerpts from the report.
Follow the link to read it in its entirety.
Volume 29, Number 8—August 2023
Dispatch
Increase of Severe Pulmonary Infections in Adults Caused by M1UK Streptococcus pyogenes, Central Scotland, UKPeter J.B. Davies, Clark D. Russell, Anna-Rose Morgan, Surabhi K. Taori, Diane Lindsay, Roisin Ure, Derek Brown, and Andrew Smith
Abstract
We characterized the epidemiology, host–pathogen characteristics, and outcomes of severe adult pulmonary Streptococcus pyogenes infections that coincided with a high community caseload in central Scotland, UK. The pulmonary infections had high illness and death rates and were associated with socioeconomic deprivation, influenza A co-infection, and the M1UK lineage of S. pyogenes.
The association between respiratory viruses and secondary invasive pulmonary bacterial disease is recognized, but the proportion of pulmonary invasive group A Streptococcus (PiGAS) infections after seasonal influenza is low compared with those for other bacterial pathogens (e.g., Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus) (1,2). However, PiGAS has been shown to complicate epidemics of measles and, notably, the 1918–1919 influenza pandemic (3).
Winter 2022–23 saw a marked increase in influenza and associated group A Streptococcus (GAS) infections in the United Kingdom as well as globally (link). In autumn 2022, an unusually high number of pediatric GAS pleural empyema cases associated with human metapneumovirus co-infection was described in Scotland (4). After similar cases were observed in adults, we aimed to characterize the burden of PiGAS in adults and contrast it to published and local historical data.
(SNIP)
Conclusions
Europe is experiencing an increased incidence of invasive GAS disease (4). We report an unusually high incidence of severe PiGAS in adults from central Scotland. We also note an additional strong association with influenza A co-infection and the near-complete dominance of M1UK, contrasting with local and published precedent. M1 comprised 38% of adult and 58% of pediatric invasive GAS referrals in England during 2022–23, in contrast to the 96% we report (LINK)
The pathophysiology of PiGAS after a respiratory viral infection (influenza A in our cohort) is incompletely understood. In vitro and in vivo studies suggest prior influenza A infection increases both GAS adherence and internalization by binding to viral hyaluronic acid on the infected host cell surface, which is followed by increases in the abundance of, and access to, bacterial receptors and the GAS ligands fibrinogen and fibronectin (13). Influenza B is also implicated, both in the literature and locally during 2017–2018 (14).
M1 has an established association with severe disease (7). In particular, the M1UK strain appears to have an enhanced capability for transmission and virulence and is now the predominant strain in the United Kingdom (6). This strain exhibits a hypervirulent phenotype because of greater expression of streptococcal pyrogenic exotoxin A than global M1 strains. Case reports of severe rapidly fatal M1 PiGAS in young healthy patients echo outcomes seen in our cohort (15).
Modern molecular techniques have revolutionized our ability to investigate patterns of disease (e.g., widespread availability of rapid point-of-care tests for COVID-19 and influenza). We are experiencing a major outbreak of S. pyogenes infections with an unusual predilection for severe pulmonary disease in addition to the usual manifestations of disease by this pathogen, including distinctive viral and M-type associations in the winter and spring of 2022–23. The PiGAS phenotype we describe is similar to those from more sporadic reports identified from a review of published case series of severe pulmonary infections from S. pyogenes (Appendix).
Historical outbreaks probably underreported coexistent viral infections because of a lack of accessible point-of-care tests. Similarly, only half of patients had an extended viral respiratory screen, and we therefore risk underreporting metapneumovirus cases, an agent notable locally in GAS empyema in children immediately before December 2022 (4). Although our cohort is small, it is comparatively large compared with the few described in the literature and notable for the short timeframe of cases captured.
Our study highlights a new aggressive pattern of S. pyogenes infections linked to the dominant circulating M1UK strain, manifesting as severe pulmonary disease and having a strong association with influenza A co-infection. Clinicians and public health officials need to be vigilant of such clinical manifestations while rates of iGAS remain high.
Dr. Davies is an infectious diseases and microbiology specialist trainee at the National Health Service Greater Glasgow and Clyde in Scotland. His primary research interests are GAS disease and microbiology diagnostic pathways.
