Streptococcus pyogenes: Infectious substances Pathogen Safety Data Sheet

Section I: Infectious agent

Name

Streptococcus pyogenes

Agent type

Bacteria

Taxonomy

Family

Streptococcaceae

Genus

Streptococcus

Species

pyogenes

Synonym or cross reference

Group A Streptococcus (GAS) ^{Footnote 1}

Characteristics

Brief description

S. pyogenes is a gram-positive, β-hemolytic, group A streptococcus. Cells are spherical, non-motile, non-spore forming, measure 0.5 to 1.0 µm in diameter, and usually occur in chains ^{Footnote 2}. More than 150 serotypes have been identified based on antigenic differences in the M-protein ^{Footnote 1}. The genome is circular and approximately 1.85 Mbp ^{Footnote 3}.

Properties

Most strains produce multiple toxins and virulence factors including the M-protein, streptolysin O, streptolysin S, and pyrogenic exotoxins (e.g., SpeA, SpeB) ^{Footnote 1}. S. pyogenes is a facultative anaerobe and is catalase-negative.

Section II: Hazard identification

Pathogenicity and toxicity

While S. pyogenes can colonize and infect various body sites, the most common infection caused by S. pyogenes is streptococcal pharyngitis, also known as strep throat ^{Footnote 1}. The carriage rate in children can be up to 20%, but is much lower in adults ^{Footnote 1}. Initial symptoms of streptococcal pharyngitis include sore throat, malaise, fever, and headache ^{Footnote 1}. Children may also experience nausea, vomiting, and abdominal pain ^{Footnote 1}. In the absence of complications, symptoms often resolve within one week without treatment; however, antibiotic treatment helps prevent acute rheumatic fever (an immune-mediated sequelae), and can decrease the duration of symptoms and the potential for transmission to close contacts ^{Footnote 1 Footnote 4}. Scarlet fever manifests as a blanching rash on the trunk, neck, and limbs ^{Footnote 5}. Usually, the tongue is initially coated with a white film before becoming bright red. Disease can be mild and self-limiting, with rash resolving within one week without treatment, or severe and require hospitalization ^{Footnote 5}. Another non-invasive (i.e., non-spreading) skin and soft tissue infection caused by S. pyogenes is streptococcal pyoderma, which is characterized by discrete, purulent lesions affecting the face or lower limbs. Invasive skin and soft tissue infections caused by S. pyogenes include erysipelas (i.e., bright red, raised lesions with clear lines of demarcation); streptococcal cellulitis (i.e., an inflammation of the skin and subcutaneous tissue appearing as pink, non-raised lesions with indistinct border); necrotizing fasciitis (i.e., an infection of the deeper subcutaneous tissues and fascia, characterised by necrosis and rapid spread); and myositis (i.e., a purulent infection of muscle tissue which is only rarely caused by S. pyogenes but which can occur concurrently with necrotizing fasciitis and streptococcal toxic shock syndrome [STSS]) ^{Footnote 1}. STSS is a severe complication associated primarily with invasive S. pyogenes infection, which is characterised by an initial period with flu-like symptoms followed by a rapid onset of hypotension and organ failure. The incidence of invasive S. pyogenes infection varies globally, with higher rates occurring in low-resource settings; since 2000, there have been fewer than nine cases per 100,000 population in Canada annually ^{Footnote 6 Footnote 7}. S. pyogenes is occasionally isolated from blood (i.e., bacteremia), which can be either benign or cause serious disease. Other infections include pneumonia, endocarditis, and lymphangitis, which is characterized by long red streaks that lead to swollen, sore regional lymph nodes, fever, and headache ^{Footnote 1}. Post-infection immune sequelae include glomerulonephritis, and acute rheumatic fever, which can result in rheumatic heart disease. In industrialized countries, the mortality rate for severe S. pyogenes-associated disease is 10 to 20%, although the mortality rates for STSS and necrotizing fasciitis are typically higher ^{Footnote 8 Footnote 9 Footnote 10 Footnote 11}.

S. pyogenes-associated infections are relatively rare in animals, but skin and soft tissue infections have been reported in cattle, sheep, rabbits, and hedgehogs ^{Footnote 12 Footnote 13 Footnote 14}. S. pyogenes has been implicated, albeit rarely, in conjunctivitis and respiratory illness in domestic dogs and cats ^{Footnote 15 Footnote 16 Footnote 17} . In addition, S. pyogenes has been isolated from the throats of mice that later died from systemic disease ^{Footnote 18}. Furthermore, a fatal case of S. pyogenes-associated STSS has been reported in a captive, pregnant rhesus monkey ^{Footnote 19}.

Predisposing factors

Most diseases caused by S. pyogenes predominantly affect otherwise healthy individuals; however, individuals who are immunocompromised or who have recently sustained a skin injury (e.g., burns, varicella-zoster virus infection, blunt or penetrating trauma, and/or surgical wounds) are generally more susceptible to invasive infections, including those caused by S. pyogenes ^{Footnote 8 Footnote 11 Footnote 20}. Other potential predisposing factors for severe S. pyogenes disease include injection drug use and chronic medical conditions (e.g., malignancy, diabetes, and heart disease) ^{Footnote 10 Footnote 11 Footnote 21}.

Communicability

S. pyogenes is transmitted primarily through direct person-to-person contact via respiratory droplets or contaminated surfaces ^{Footnote 1 Footnote 22}. The main portals of entry for pyoderma and pharyngitis are damaged skin and a damaged respiratory tract, respectively ^{Footnote 8}. Transmission via the consumption of S. pyogenes-contaminated food (e.g., premade foods containing eggs, unpasteurized milk) has been reported ^{Footnote 12 Footnote 23 Footnote 24 Footnote 25}.

Epidemiology

S. pyogenes diseases and associated sequelae occur in all countries, but are more prevalent in socioeconomically disadvantaged regions ^{Footnote 6 Footnote 22}. More than 600 million cases of S. pyogenes-associated pharyngitis occur globally each year ^{Footnote 6}. S. pyogenes-associated pharyngitis most commonly affects children aged 5 to 15 years ^{Footnote 26}. S. pyogenes-associated pyoderma affects an estimated 111 million individuals globally ^{Footnote 6}. Localised outbreaks of S. pyogenes infection attributed to contaminated food are reported occasionally ^{Footnote 23 Footnote 24}. Localized outbreaks of S. pyogenes disease in crowded or close-contact settings (e.g., hospitals, military camps, prisons, and daycares) have been reported ^{Footnote 4 Footnote 8}. Rheumatic heart disease causes the greatest burden of all S. pyogenes-associated illnesses and is responsible for 233,000 deaths annually ^{Footnote 6}. The estimated total global burden of severe S. pyogenes-associated disease is 517,000 deaths annually ^{Footnote 6}.

Host range

Natural host(s)

Humans are the primary hosts. S. pyogenes infection has been reported in animals, albeit rarely; infected species include cattle, sheep, rabbits, wild hedgehogs, domestic cats and dogs, captive rhesus monkeys, and captive mice ^{Footnote 12 Footnote 13 Footnote 14 Footnote 16 Footnote 18 Footnote 19 Footnote 27}.

Other host(s)

Wax worms (Galleria mellonella larvae) have been experimentally infected ^{Footnote 28}.

Infectious dose

Unknown

Incubation period

Usually 2 to 4 days ^{Footnote 1}

Section III: Dissemination

Reservoir

Humans ^{Footnote 4}

Zoonosis/Reverse zoonosis

S. pyogenes transmission between animals and humans is rare. S. pyogenes infections have been reported in commercially farmed animals (e.g., cattle, rabbits, and sheep) and captive animals (e.g., monkeys) that have had contact with humans ^{Footnote 12 Footnote 13 Footnote 19}.

Vectors

None

Section IV: Stability and viability

Drug susceptibility

S. pyogenes is universally sensitive to penicillin ^{Footnote 8}. Most strains are susceptible to macrolides (e.g., erythromycin, azithromycin, and clarithromycin), cephalosporins, and lincosamides (e.g., clindamycin) ^{Footnote 4 Footnote 8}.

Drug resistance

Resistance to macrolides, lincosamides, tetracyclins and fluoroquinolones has been described in some regions ^{Footnote 4}.

Susceptibility to disinfectants

Sodium hypochlorite (1%), glutaraldehyde (2%), and ethanol (70%) are effective against S. pyogenes ^{Footnote 29 Footnote 30}.

Physical inactivation

S. pyogenes is susceptible to moist heat treatment at 121° C for 15 minutes or dry heat treatment at 170 °C for 1 hour ^{Footnote 31}.

Survival outside host

Viable S. pyogenes was recovered from heavily contaminated dust collected from the clothing of patients with hemolytic streptococcal infections and stored at room temperature for 195 days ^{Footnote 32}. Viable S. pyogenes (initial cell count 100,000 colony forming units per ml) was recovered from sterile distilled water 15 days after inoculation and storage at room temperature ^{Footnote 32}. Viable S. pyogenes (initial cell count 5,000 colony forming units per gram) was recovered from commercial butter two days after inoculation and storage at room temperature ^{Footnote 32}. S. pyogenes has been shown to persist for hours to days in cold salads, particularly those containing eggs ^{Footnote 33}.

Section V: First aid/medical

Surveillance

The gold standard for S. pyogenes identification in throat specimens is isolation using culture-based methods ^{Footnote 1}. Rapid antigen detection tests that target the group A carbohydrate antigen can also be used to diagnose S. pyogenes pharyngitis. Cultures of other types of clinical samples for diseases caused by S. pyogenes other than pharyngitis are not always useful.

Note: The specific recommendations for surveillance in the laboratory should come from the medical surveillance program, which is based on a local risk assessment of the pathogens and activities being undertaken, as well as an overarching risk assessment of the biosafety program as a whole. More information on medical surveillance is available in the Canadian Biosafety Handbook.

First aid/treatment

S. pyogenes-associated infection can be treated with a suitable antibiotic (e.g., penicillin, macrolide, or cephalosporin) ^{Footnote 1}; penicillin is the treatment of choice ^{Footnote 8}. In some cases of severe invasive disease, intensive supportive care and/or debridement of necrotic tissues may be necessary ^{Footnote 1}.

Note: The specific recommendations for first aid/treatment in the laboratory should come from the post-exposure response plan, which should be developed as part of the medical surveillance program. More information on the post-exposure response plan can be found in the Canadian Biosafety Handbook.

Immunization

Although no vaccine is currently available, several vaccines are in development ^{Footnote 8}.

Note: More information on the medical surveillance program can be found in the Canadian Biosafety Handbook, and by consulting the Canadian Immunization Guide.

Prophylaxis

Primary prophylaxis for close contacts of patients with severe invasive S. pyogenes infection may be recommended ^{Footnote 8}. Secondary prophylaxis for some individuals with previous acute rheumatic fever or rheumatic heart disease is recommended to prevent recurrence ^{Footnote 8}.

Note: More information on prophylaxis as part of the medical surveillance program can be found in the Canadian Biosafety Handbook.

Section VI: Laboratory hazards

Laboratory-acquired infections

In the early 1980s, a researcher who infected mice intranasally with S. pyogenes developed symptoms consistent with pharyngitis ^{Footnote 34}. This individual recovered fully after antibiotic treatment. No laboratory-acquired infections associated with S. pyogenes have been reported in recent decades.

Note: Please consult the Canadian Biosafety Standard and Canadian Biosafety Handbook for additional details on requirements for reporting exposure incidents. A Canadian biosafety guideline on notification and reporting procedures is also available.

Sources/specimens

Saliva, blood, throat swabs, and/or biopsy tissues from infected sites ^{Footnote 4}

Primary hazards

Inhalation of aerosolized infectious material and exposure of mucous membranes/damaged skin to infectious material ^{Footnote 35}

Special hazards

None

Section VII: Exposure controls/personal protection

Risk group classification

S. pyogenes is a Risk Group 2 human pathogen and a Risk Group 1 animal pathogen ^{Footnote 36 Footnote 37}.

Containment requirements

Containment Level 2 facilities, equipment, and operational practices outlined in the Canadian Biosafety Standard for work involving infectious or potentially infectious materials, animals, or cultures.

Protective clothing

The applicable Containment Level 2 requirements for personal protective equipment and clothing outlined in the Canadian Biosafety Standard to be followed. At minimum, use of a labcoat and closed-toes cleanable shoes, gloves when direct skin contact with infected materials or animals is unavoidable, and eye protection where there is a known or potential risk of exposure to splashes.

Note: A local risk assessment will identify the appropriate hand, foot, head, body, eye/face, and respiratory protection, and the personal protective equipment requirements for the containment zone must be documented.

Other precautions

All activities that may produce aerosols, or involve high concentrations or large volumes, are to be conducted in a biological safety cabinet (BSC) or other primary containment devices. The use of needles, syringes, and other sharp objects to be strictly limited. Additional precautions must be considered with work involving animals or large scale activities.

Section VIII: Handling and storage

Spills

Allow aerosols to settle. Wearing protective clothing, gently cover the spill with absorbent paper towel and apply suitable disinfectant, starting at the perimeter and working towards the centre. Allow sufficient contact time before clean up (Canadian Biosafety Handbook).

Disposal

All materials/substances that have come in contact with the infectious agent should be completely decontaminated before they are removed from the containment zone. This can be achieved by using decontamination technologies and processes that have been demonstrated to be effective against the infectious material, such as chemical disinfectants, autoclaving, irradiation, incineration, an effluent treatment system, or gaseous decontamination (Canadian Biosafety Handbook).

Storage

The applicable Containment Level 2 requirements for storage outlined in the Canadian Biosafety Standard are to be followed. Containers of infectious material or toxins stored outside the containment zone must be labelled, leakproof, impact resistant, and kept either in locked storage equipment or within an area with limited access.

Section IX: Regulatory and other information

Canadian regulatory context

Controlled activities with S. pyogenes require a Human Pathogens and Toxins Licence issued by the Public Health Agency of Canada. The following is a non-exhaustive list of applicable designations, regulation, or legislation:

• Human Pathogen and Toxins Act and Human Pathogens and Toxins Regulations
• Transportation of Dangerous Goods Regulations
• National Notifiable Disease (human)

Updated

August, 2021

Prepared by

Centre for Biosecurity, Public Health Agency of Canada.

Disclaimer

The scientific information, opinions, and recommendations contained in this Pathogen Safety Data Sheet have been developed based on or compiled from trusted sources available at the time of publication. Newly discovered hazards are frequent and this information may not be completely up to date. The Government of Canada accepts no responsibility for the accuracy, sufficiency, or reliability or for any loss or injury resulting from the use of the information.

Persons in Canada are responsible for complying with the relevant laws, including regulations, guidelines and standards applicable to the import, transport, and use of pathogens in Canada set by relevant regulatory authorities, including the Public Health Agency of Canada, Health Canada, Canadian Food Inspection Agency, Environment and Climate Change Canada, and Transport Canada. The risk classification and related regulatory requirements referenced in this Pathogen Safety Data Sheet, such as those found in the Canadian Biosecurity Standard, may be incomplete and are specific to the Canadian context. Other jurisdictions will have their own requirements.

Copyright^© Public Health Agency of Canada, 2021, Canada