Introduction

Group A Streptococcus (GAS) are gram-positive cocci that produce an obvious zone of hemolysis (β) on blood agar, distinguishing them from other streptococci that produce partial hemolysis (α) and non-hemolytic (γ) streptococci [1]. Within GAS, only Streptococcus pyogenes exhibits clinical significance. GAS is typed serologically based on unique surface proteins and critical virulence factors, such as a hyaluronic acid capsule that shields GAS from phagocytosis [2].

GAS can colonize the anogenital tract, skin, and throat. GAS can be transmitted through direct skin contact, respiratory droplets, and close personal touch. Additionally, it can spread through touch with infected things like towels or bedding as well as eating the food that has been infected by a carrier. While some people who carry the bacterium in their bodies may not feel well or exhibit any signs of infection but are still capable of transmitting it to others, the risk of dissemination is significantly higher when a person is ill [1, 2].

Tonsillitis, pharyngitis, scarlet fever, impetigo, erysipelas, cellulitis, and pneumonia are the non-invasive diseases it can cause. Rheumatic fever and glomerulonephritis are two unusual post-streptococcal sequelae that individuals may experience [3, 4]. The invasion ability of the bacterium comes from multiple virulence factors such as the attachment to the epithelium with the aid of the surface proteins like M and M like proteins which play a role in the escape from the immune system by interfering with the complement system with different mechanisms and enzymes such as streptokinase, hyaluronidase, and DNases which are secreted from this type of bacterium. An infection known as invasive GAS (iGAS) occurs when bacteria are isolated from a typically sterile bodily location, like the blood [5, 6]. The diagnosis of the iGAS is mainly based on the isolation of the bacterium from a sterile site, and by the results, the clinicians can confirm that the causative agent of the presenting symptoms is the GAS and one of the severe manifestations of the GAS is the streptococcal toxic shock syndrome (STSS), which requires diagnostic criteria such as the criterion that was developed by Breiman et al. (Figure 1) [7].

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Figure 1. 

The diagnostic criterion that can be used for the diagnosis of STSS. There must be hypotension with two or more of the other findings

The burden of GAS was estimated in the last five years as 14,000 to 25,000 cases of the invasive group A streptococcal disease in the USA with an estimated death from 1,500 to 2,300 cases per year due to iGAS, and as per the World Health Organization (WHO), the disease is considered to be more apparent in the winter and early spring with an estimated death of 50,000 cases annually in the world [8–10]. According to reports, the greatest burden of GAS disease is placed on children between the ages of 0 and 4 [8].

The incidence of iGAS is recorded by the active bacterial core surveillance system (ABCs) tracked and generated by the Centers for Disease Control and Prevention (CDC), which shows a change in the ratio between survived and death cases between 1997 and 2020 [11]. As per the WHO report in mid-December, it was reported that there is an increase in the incidence of iGAS and scarlet fever, especially among children who are younger than 10 years old in France, Ireland, Netherlands, Sweden, and the United Kingdom (UK) [8–10]. The different syndromes that are caused by iGAS are shown in Figure 2, in the form of the percentage of cases that are infected with each type which shows that cellulitis is at the top percentage among the other diseases.

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Figure 2. 

Percentage of cases that occurred with each of the five disease types caused by the iGAS as per ABCs bact facts interactive data dashboard [11]

Note. Reprinted from “ABCs Bact Facts Interactive Data Dashboard” by CDC (https://www.cdc.gov/abcs/bact-facts-interactive-dashboard.html). CC0. The use of the material on the CDC websites does not imply endorsement by CDC or the United States Government.

The management of iGAS patients mainly focuses on the supportive management of the case by preventing dehydration, especially in the case of toxic shock syndrome when the patient is experiencing life-threatening hypotension with sufficient monitoring for the kidney markers as they may develop renal failure [7]. The antibacterial agents are considered the main core in the management of the cases as the first line drug of penicillin in the initial period. Therefore the patient should take a broad-spectrum antibiotic that covers the Staphylococcus aureus till the culture results become available. If there is a suspected infection with methicillin-resistant Staphylococcus aureus (MRSA), the patient should take vancomycin to cover it so the type of administered antibacterial differs according to the presenting case [12].

Clindamycin is considered to be an adjunctive antibiotic to penicillin, especially in cases of toxic shock syndrome and necrotizing fasciitis [12]. The management of the disease also includes the early removal of the infected tissues, especially in severe cases such as necrotizing fasciitis as this is correlated with a lower mortality rate, besides the other management tools such as the intravenous immunoglobulin in which the clinician must weigh between the benefits and the risks, and it is advisable to avoid the use of non-steroidal anti-inflammatory drugs (NSAIDs) in case of any presenting fever without a known cause as it may mask the initial manifestations which will be associated with a delayed identification of the case [3].

In the UK, Scarlet fever and iGAS infection are both notifiable diseases. Medical professionals are required to alert the local health system if any suspected cases are documented and follow the defined policies for managing scarlet fever outbreaks in educational settings as well as iGAS cases in the community and clinical settings [13].

Recent development

Global GAS outbreaks cause major illness, necessitating continuous monitoring and continuing attempts to define pathogenic GAS populations’ evolutionary trajectories. Based on the gene sequence of the amino terminus of the surface-exposed M protein, GAS may be epidemiologically divided into more than 220 encoding mature M protein gene (emm) type 2. Multiclonal outbreaks of scarlet fever have been found in Asia and the UK, with the UK epidemic coinciding with a rise in invasive infections. The development of novel GAS clones, typically with new virulence features or antimicrobial characteristics that better fit the infection niche or avoid human immunity, characterizes worldwide GAS epidemiology. Clinical GAS isolates with first-step PBP2x mutations and rising macrolide resistance endanger the frontline and role of penicillin-adjunctive antibiotic treatment. WHO has come up with a GAS research and technology roadmap and has emphasized the vaccine qualities taking into account safe and effective GAS vaccinations [14, 15].