#17,567
Over the past year we've seen a sharp rise in viral and bacterial respiratory illnesses around the world, including RSV (see ECDC: Risk Assessment On Intensified Circulation of RSV In The EU/EEA), Whooping Cough (see Denmark SSI Reports Sharp Increase In Pertussis), and Scarlet Fever (see below).
Eurosurveillance: Increase in Invasive Group A Streptococcal (IGAS) Infections & Emergence of Novel, Rapidly Expanding Sub-lineage, Denmark 2023
EID Journal: Increase of Severe Pulmonary Infections in Adults Caused by M1UK Streptococcus pyogenes, Central Scotland, UK
CDC HAN #0484: Increase in Pediatric Invasive Group A Streptococcal Infections
WHO Risk Assessment On Rise Of Strep A Infections In Europe & UKHSA Weekly Update
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) or GAS, which indicates infection of the bloodstream, deep tissues, or lungs, and may result in severe (and frequently fatal) cases of necrotizing fasciitis, streptococcal toxic shock syndrome, and (rarely) bacterial meningitis.
Just as we see with viruses, bacteria can evolve over time creating more infectious, drug-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.
Since 2019 we've been following the emergence of 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.
Last month we looked at report on dominance of this highly aggressive M1UK lineage of S. pyogenes in Scotland over last winter (see EID Journal: Increase of Severe Pulmonary Infections in Adults Caused by M1UK Streptococcus pyogenes, Central Scotland, UK).
Yesterday the CDC's EID Journal published the following research letter, which describes a 21-fold increase in the incidence of GAS Meningitis in Denmark last winter (compared to the previous 7 years), and the dominance of the M1UK strain.
Volume 29, Number 9—September 2023
Research Letter
Group A Streptococcus Meningitis in Adults, Denmark
Henrik NielsenComments to Author , Merete Storgaard, Jannik Helweg-Larsen, Lykke Larsen, Micha P.G. Jepsen, Birgitte R. Hansen, Lothar Wiese, and Jacob Bodilsen
Abstract
We report a 21-fold increase in group A Streptococcus meningitis in adults in Denmark during October 13, 2022–April 12, 2023, concurrent with an outbreak of invasive streptococcal disease. We describe clinical characteristics of the outbreak cases and prognosis for patients in comparison to those for previous sporadic cases.
Emergence of increased group A Streptococcus (GAS) disease, initially expressed as activity of scarlet fever in childhood, has been observed in multiple countries; some countries reported the toxigenic M1UK clone (1–3). A report from the Netherlands suggested an increase in GAS meningitis cases, mainly from the toxicogenic M1UK lineage (4). This increase is likely result of the rise in invasive GAS infections (5), because ≈1% of invasive GAS manifests as meningitis (6). However, it is unclear if this outbreak differs clinically from previous sporadic cases, as acknowledged by van der Putten et al. (4). To address this limitation, we compared all cases of GAS meningitis in adults in Denmark during 2015–2022 with cases during the outbreak, October 2022–April 2023.
The Danish Study Group for Infections of the Brain (DASGIB) has performed active, real-time nationwide surveillance of community-acquired bacterial meningitis in adults (>18 years of age) since January 1, 2015, as described previously (7). In brief, data on demographics, comorbidities, clinical signs and symptoms, microbiology and biochemical examinations, radiology, treatment, and outcome are aggregated in an online platform. The legal department of the North Denmark Region (record no. 2023-012693) and the Danish Board of Health (record nos. 3-3013-2579/1 and 3-3013-3168/1) approved the DASGIB database. Patient consent or permission from an ethical committee is not required.
For this study, a definition of GAS meningitis required (7) clinical symptoms suggestive of bacterial meningitis (e.g., headache, neck stiffness, fever, altered mental status) and either of the following criteria: positive culture or bacterial DNA/antigen analysis of cerebrospinal fluid (CSF); positive blood culture and CSF leukocytes >10 × 106 cells/L; or culture-confirmed otitis or mastoiditis and CSF leukocytes >10 × 106 cells/L. Incidence was computed as no. cases/no. adults in Denmark during each study period.
During January 1, 2015–October 12, 2022, we observed a total of 8 cases of GAS meningitis, corresponding to a mean of 0.11/1 million adults/6 months (Figure). Because of the increase in invasive GAS in Denmark beginning in October 2022 (8), we then assessed the incidence of GAS meningitis during October 13, 2022–April 12, 2023. We observed 11 cases of GAS meningitis in adults, corresponding to 2.32/1 million/6 months, an increase in incidence by a factor of 21. The diagnosis was confirmed by culture in 9 patients, whereas it was established by PCR in 2 patients for whom antimicrobial treatment began before lumbar puncture. We examined isolates of emm-1.0 type in 4 cases, emm-12.0 in 2 cases, and emm-87.0 in 1 case; isolate type was not available in 2 cases.
Patients with GAS meningitis had lower Glasgow Coma Scale scores at admission and higher CSF leukocyte counts in the last 6 months of the study than overall (Table); otherwise, clinical characteristics and prognosis did not differ between the 2 study periods. We observed a high percentage of patients with streptococcal infection in the upper respiratory tract (Table). We observed 2 serious complications, endophthalmitis (1 case) and subdural empyema (1 case), but no increase in deaths in the second study period.
We conclude that in October 2022–April 2023, an outbreak of GAS meningitis occurred in Denmark, showing a 21-fold increase in incidence compared with the baseline in previous years. The baseline incidence agrees with earlier findings in Denmark (9). Our case definition included cases confirmed by positive PCR of CSF, positive blood cultures or other cultures combined with CSF pleocytosis, and clinical manifestations of bacterial meningitis, in addition to positive CSF culture, which may explain why our incidence is higher than that recently reported for adults from the Netherlands (4).
The rise in invasive GAS infections was initially seen in children (5), but our study indicates an increase of severe infections in adults as well. The toxicogenic emm-1.0 type is currently the predominant strain in Denmark (8) and other countries (4,5). However, we found no differences in clinical characteristics or prognosis for GAS meningitis during this surge compared with those of previous years.
Dr. Nielsen is a clinical professor of infectious diseases at Aalborg University Hospital, Aalborg, Denmark. His research interest is infections in the brain, including bacterial meningitis.
Given its enhanced virulence, rapid growth in the UK, and recent spread to Denmark, this is something that doctors here in the United States, and around the world, will now need to be aware of.
