Abstract
Background Since 2022, many countries reported an upsurge in invasive group A streptococcal (iGAS) infections. We explored whether changes in S. pyogenes carriage rates or emergence of more virulent strains, such as emm1 variants M1UK and M1DK, contributed to the 2022/2023 surge in the Netherlands.MethodsWe determined emm (sub)type distribution for 2,698 invasive and 351 S. pyogenes carriage isolates collected between January 2009 - March 2023. Genetic evolution of emm1 was analyzed by whole-genome sequencing of 497 emm1 isolates. FindingsThe nationwide iGAS upsurge coincided with a sharp increase of emm1.0 from 18% (18/100) of invasive isolates in Q1 2022 to 58% (388/670) in Q1 2023 (p<0.0001). M1UK became dominant among invasive emm1 isolates in 2016 and further expanded from 72% in Q1 2022 to 96% in Q1 2023. Phylogenetic comparison revealed evolution and clonal expansion of four new M1UK clades in 2022/2023. DNase Spd1 and superantigen SpeC were acquired in 9% (46/497) of emm1 isolates. S. pyogenes carriage rates and emm1 proportions in carriage isolates remained stable during this surge and the expansion of M1UK in iGAS was not reflected in carriage isolates.Interpretation During the 2022/2023 iGAS surge in the Netherlands, expansion of four new M1UK clades was observed among invasive isolates but not carriage isolates, suggesting increased virulence and fitness of M1UK compared to contemporary M1 strains. The emergence of more virulent clades has important implications for public health strategies such as antibiotic prophylaxis for close contacts of iGAS patients.
Competing Interest Statement
NMvS reports fee for service and presentations from MSD, GSK and grants from the Dutch Health Council (ZonMW; all directly paid to the institution), contract research with Argenx (unrelated to this work), a patent on vaccine development against S. pyogenes (licensee: University of California San Diego, inventors Nina van Sorge and Victor Nizet; licensed by Vaxcyte; personal revenue), participation in the science advisory board of the ItsME foundation (no honorarium; https://itsme-foundation.com/en/) and Rapua te me ngaro ka tau, a project facilitating Strep A vaccine development for Aotearoa New Zealand (honorarium paid directly to the institution). Other authors have nothing to disclose.
Funding Statement
The study has been funded by a European Society of Clinical Microbiology and Infectious Diseases (ESCMID) research grant to LWR in 2022, St. Antonius hospital research grant in 2020, and Amsterdam UMC Innovation Grant (2023-26) in 2023, and by the DRESSCODE project (project number 09150181910001) of the Vici Talent program to NMvS, which is financed by ZonMW.
Author Declarations
I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.
Yes
The details of the IRB/oversight body that provided approval or exemption for the research described are given below:
Invasive S. pyogenes isolates were collected as part of routine care. Carriage isolates were collected after written informed consent from all adults and parents or legal guardians of the included children. Ethical approval was obtained from The Central Committee on Research Involving Human Subjects (CCMO), the Netherlands (OKIDOKI-1; NL24116.000.08), the Medical Ethics Testing Committee (METC Noord-Holland), The Netherlands (OKIDOKI-3; NL40288.094.12 and OKIDOKI-4; NL53027.094.15) and Medical Research Ethics Committees United (MEC-U), Nieuwegein, The Netherlands (OKIDOKI-5; NL65919.100.18). Ethical approval was waived for OKIDOKI-2 performed in 2009 by Stichting Therapeutische Evaluatie Geneesmiddelen (STEG), Arnhem, The Netherlands (NVI-257) and for OKIDOKI-6 by the Centre for Clinical Expertise at the RIVM, Bilthoven, the Netherlands (ISRCTN31549735) because these studies do not fulfill both conditions stated in the law for medical research involving human subjects (WMO) and therefore were exempted for further approval by the ethical research committee. All were conducted in accordance with the European Statements for Good Clinical Practice and the Declaration of Helsinki of the World Medical Association. Only fully anonymized data was used.
I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.
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I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).
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I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.
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Data Availability
Whole genome sequence data will be publically available through the PubMLST database: https://pubmlst.org/organisms/streptococcus-pyogenes
FAQs
The bacitracin test, along with the Lancefield antigen A test, is used for greater specificity in the identification of S. pyogenes, since other β-hemolytic strains of streptococci that may contain the group A antigen are resistant to bacitracin.
What disease does Streptococcus pyogenes cause? ›
Streptococcus pyogenes (group A Streptococcus)
GAS causes infections such as strep throat and impetigo. These bacteria also cause approximately 11,000–24,000 cases of severe (invasive) GAS disease, such as necrotizing fasciitis, in the United States each year.
What antibiotic is used to treat Streptococcus pyogenes? ›
The drug of choice for treatment of bacterial pharyngitis is oral penicillin for 10 days or IM benzathine penicillin. This treatment is cost-effective and has a narrow spectrum of activity. Severe invasive S. pyogenes infections can be treated with vancomycin or clindamycin.
What is a sequelae of Streptococcus pyogenes infection? ›
Infection with S pyogenes (but not S pneumoniae ) can give rise to serious nonsuppurative sequelae: acute rheumatic fever and acute glomerulonephritis. These sequelae begin 1-3 weeks after the acute illness, a latent period consistent with an immune-mediated rather than pathogen-disseminated etiology.
How do you treat Streptococcus pyogenes skin infection? ›
Treatment of streptococcal skin infection
Flucloxacillin is more appropriate than simple penicillin as it treats both Staphylococcus (staph) and strep. If the laboratory has confirmed streptococcal infection, then the most appropriate antibiotic is usually penicillin.
What is the autoimmune disease caused by Streptococcus pyogenes? ›
Poststreptococcal disorder is a group of autoimmune disorders that occur after an infection with the bacteria Streptococcus pyogenes, also known as group A Streptococcus (GAS). An autoimmune disorder occurs when your immune system mistakes your healthy cells as foreign and begins to attack them.
What kills Streptococcus bacteria in the gut? ›
Group A streptococcus bacteria can be treated with common, inexpensive antibiotics. Penicillin is the drug of choice for both mild and severe disease. For penicillin-allergic patients with mild illness, erythromycin can be used, although occasional resistance has been seen.
What is the most serious infection caused by streptococci? ›
Two of the most severe, but less common, forms of invasive Group A Strep disease are called "necrotizing fasciitis" (a destructive infection of muscle and fat tissue) and "Streptococcal Toxic Shock Syndrome" (a rapidly progressing infection causing low blood pressure/shock and injury to organs such as the kidneys, ...
Is strep A usually serious? ›
Strep A infections are more common in children, but adults can also sometimes get them. Most strep A infections are not serious and can be treated with antibiotics. But rarely, the infection can cause serious problems. This is called invasive group A strep (iGAS).
What are the symptoms of Streptococcus? ›
Symptoms of group A streptococcal infection
- sore, red throat or tonsils.
- pus on throat or tonsils.
- pain on swallowing.
- fever and chills.
- swollen and tender lymph nodes (glands) in the neck.
- vomiting, nausea and abdominal pain.
- headache and muscle aches.
- general feeling of unwell (malaise)
Penicillin or amoxicillin are considered the best first-line treatments for Strep throat. According to the CDC (Centers for Disease Control and Prevention) “There has never been a report of a clinical isolate of group A strep that is resistant to penicillin”.
What disinfectant kills Streptococcus pyogenes? ›
Susceptibility to disinfectants
Sodium hypochlorite (1%), glutaraldehyde (2%), and ethanol (70%) are effective against S. pyogenes 29 30.
How long does it take to recover from Streptococcus pyogenes? ›
It could take between three to five days until you start to feel better after taking antibiotics to treat a group A streptococcal infection. Symptoms should reduce after a few days if you have a mild infection. Severe infections could take up to two weeks until you start to feel better.
Where do Streptococcus bacteria come from? ›
Streptococcal bacteria are contagious. They can spread through droplets when someone with the infection coughs or sneezes, or through shared food or drinks. You can also pick up the bacteria from a doorknob or other surface and transfer them to your nose, mouth or eyes.
How serious is strep in the bloodstream? ›
The most serious infections linked to GAS come from invasive group A strep, known as iGAS. These infections are caused by the bacteria getting into parts of the body where it is not normally found, such as the lungs or bloodstream. In rare cases an iGAS infection can be fatal.
Which test can be used to detect a prior infection with Streptococcus pyogenes? ›
Antistreptolysin O (ASO) titer is a blood test to measure antibodies against streptolysin O, a substance produced by group A streptococcus bacteria. Antibodies are proteins our bodies produce when they detect harmful substances, such as bacteria.
What is the quick test for Streptococcus pyogenes? ›
Rapid strep test.
These antigens are substances in the Strep A bacteria that trigger your immune system to fight the virus. A rapid strep test can provide results in 10-20 minutes. If a rapid test is negative, but your health care provider thinks you or your child has strep throat, they may order a throat culture.
How is Staphylococcus pyogenes diagnosed? ›
Definitive diagnosis depends on demonstrating streptococci in throat swab cultures. Antibodies to streptolysin O appear in the blood of 80% of reconvalescents after 2 weeks or later. It is important to follow the rise of the titer of these antibodies because they may be high from a previous infection.
What antibody is used to diagnose streptococcal skin disease? ›
Streptococcal antibody tests are used for the diagnosis of antecedent infections caused by the group A streptococcus (GAS) and are particularly useful for the diagnosis of acute rheumatic fever and acute post-streptococcal glomerulonephritis.
