Invasive Group A Streptococcal Disease
Queensland Health Guidelines for Public Health Units
|1.0||April 2017||Initial guideline|
|2.0||August 2017||Revision of guideline|
|3.0||October 2018||Revision of guideline|
Period of Communicability
Susceptibility and Resistance
Invasive Group A Streptococcal Disease
The infectious agent is Group A Streptococcus pyogenes (GAS) a Gram positive, ß-haemolytic bacteria (1).
Group A Streptococcus and Infection Definitions
- GAS: Group A streptococcus
- Severe GAS infection: An infection where GAS has been isolated from a normally non-sterile site, in conjunction with severe clinical illness including streptococcal toxic shock syndrome (strep TSS) or necrotising fasciitis (2)
- iGAS: Invasive Group A Streptococcus
- iGAS infection: illness associated with the isolation of GAS from a normally sterile site such as blood cerebrospinal fluid, joint aspirate, pericardial/peritoneal/pleural fluids, bone, endometrium, deep tissue or abscess at operation or post mortem. It also includes severe iGAS infection (2)
- Severe iGAS infection: iGAS infection presenting as pneumonia (pneumonia is not in itself a diagnosis of severe iGAS), meningitis, necrotising fasciitis, streptococcal toxic shock syndrome (strep TSS) or any other manifestation requiring admission to intensive care or causing death (3)
Note: While clinical evidence of necrotising fasciitis and strep TSS is required for classification, reporting and response purposes, necrotising fasciitis is not clinically notifiable under the Public Health Act.
Laboratory definitive evidence
Isolation of Group A Streptococci (Streptococcus pyogenes) by culture from a normally sterile site (e.g. blood, cerebrospinal fluid, joint aspirate, peritoneal fluid, pleural fluid or pericardial fluid)
Laboratory suggestive evidence (for strep TSS and necrotising fasciitis):
Isolation of GAS from a non-sterile site which includes isolation of GAS from an intraoperative specimen or a specimen labelled ‘deep tissue’, or where the requesting clinician has made a clinical note suggesting the presence of necrotising fasciitis.
Clinical evidence (necrotising fasciitis):
Soft tissue necrosis.
Clinical evidence (strep TSS):
An illness that meets the definition of strep TSS and includes both hypotension AND multi-organ involvement. See the Appendix for further information.
To notify on confirmation of laboratory definitive evidence by usual means.
Note: While clinical evidence is required to meet the definitions of GAS necrotising fasciitis and strep TSS, clinical notifications are not required under the Public Health Act.
Reporting to NoCS
Report confirmed and probable cases (GAS necrotising fasciitis and strep TSS).
- Confirmed case: A confirmed case requires laboratory definitive evidence
- Probable case: A probable case of strep TSS GAS necrotising fasciitis requires laboratory suggestive evidence and clinical evidence.
Objectives of Surveillance
- Identify, respond to and manage the public health risks associated with outbreaks
- Identify clusters of iGAS and at-risk contacts
- Monitor and regularly report the epidemiology of invasive Group A disease in Queensland, including surveillance of emm types.
Public Health Significance and Occurrence
The Invasive Group A Streptococcal Disease Guidelines Working Group was established in 2016 to develop Queensland guidelines for iGAS. The group identified wide variation in national and international guidelines for public health follow up of iGAS. Recommendations ranged from nil routine follow up of individual cases to chemoprophylaxis and information for contacts of severe cases (3-9). Several guidelines recommend follow up of the mother or baby if either develops iGAS in the neonatal period (first 28 days of life)(3, 4).
Based on the evidence available, the group has taken a pragmatic, risk-based approach to the development of this guideline. Continuous review is necessary to optimise the public health response in the Queensland context.
GAS colonises the throat, skin and anogenital tract and can cause diseases ranging from pharyngitis and impetigo to life-threatening invasive disease (10). iGAS infection occurs when GAS breaches epithelial barriers to migrate to normally sterile sites including blood, meninges, articular spaces, pericardium, peritoneum, pleural cavity, bone and endometrium (11). GAS may also cause toxic shock and necrotising fasciitis. The overall mortality of iGAS in Australia is 7%, reaching 23% in individuals with streptococcal toxic shock syndrome (12,13).
GAS strains are classified mainly on the basis of variation in a cell-surface molecule known as M protein, encoded by the emm gene. M protein is a critical virulence factor and a major site of the human antibody response against GAS. M type–specific immunity develops in persons recovering from some GAS infections. Over 240 emm types are recognised worldwide (1).
Household, institutional and childcare contacts of iGAS cases have an increased risk of iGAS(3). Incidence risk ratios in household contacts, compared with the general population, range from 18 (95% confidence interval 0.5–101) to 165 (95% CI 34–487) (8, 14-17).
Antibiotics are effective in eradicating nasopharyngeal carriage of Streptococcus pyogenes in individuals with GAS pharyngitis. Queensland isolates are currently (2015) penicillin and vancomycin sensitive with low erythromycin resistance (2.2%). Evidence for antibiotic chemoprophylaxis to prevent secondary transmission of iGAS is limited(16).
Between 2006 and 2015, there were 4.5 iGAS notifications per 100,000 per year in Queensland (18). Similar to published reports (12), Indigenous people had higher notification rates (25.3 per 100,000 per year) than non-Indigenous people (3.3 per 100,000 per year). Children less than 5 years of age (7.4 per 100,000 per year) and adults ≥60 years of age (9.5 per 100,000 per year) also had higher notification rates than the 5-59 year age group (3.5 per 100,000 per year)(12).
For the period 2004/2005 to 2014/2015, there were 152, 1,470 and 1,131 admissions to Queensland hospitals, respectively, for toxic shock syndrome (TSS), necrotising fasciitis and sepsis due to iGAS (19). The proportions of TSS and necrotising fasciitis due to GAS and other organisms are uncertain.
Outbreaks of tonsillopharyngitis have been reported following consumption of food contaminated with GAS. These outbreaks are usually of sudden onset and have a high attack rate but low complication rate.
The spectrum of disease caused by GAS includes:
- Superficial infections such as pharyngitis, impetigo and pyoderma
- Scarlet and puerperal fever
- Severe invasive disease such as septicaemia, meningitis, necrotising fasciitis and toxic shock syndrome
- Post-streptococcal immunological sequelae including acute rheumatic fever and acute glomerulonephritis (1).
Necrotising Fasciitis (Streptococcal Gangrene)
Necrotising fasciitis is an infection of the deeper subcutaneous tissues and fascia, characterised by extensive and rapidly spreading necrosis and by gangrene of the skin and underlying structures. Characteristically, it begins at a site of trivial or even unapparent trauma or in an operative incision. The initial lesion may appear only as an area of mild erythema but over the next 24 to 72 hours undergoes a rapid evolution. Bacteraemia is frequently present, and metastatic abscesses may occur. By the fourth to fifth day, frank gangrenous changes are evident and this is followed by extensive sloughing. The process may march inexorably over large bodily areas unless measures are taken to contain it. The patient with streptococcal gangrene appears perilously ill, with high fever and extreme prostration. Mortality rates are high (20 to 70%) even with appropriate treatment (20).
Streptococcal Toxic Shock Syndrome
The first phase of streptococcal toxic shock syndrome (strep TSS) begins with prodromal flu-like illness (fever, chills, myalgia, nausea, vomiting and diarrhoea) that precedes hypotension by 24 to 48 hours. Confusion may be present. The second phase of strep TSS is characterised by tachycardia, rapid breathing, persistent fever and in patients who subsequently develop necrotising fasciitis, increasingly severe pain at the site of infection. The third phase includes sudden onset of shock and organ failure. Shock may be present at admission or a few hours after admission (20).
Mortality for strep TSS is high and can reach 50% in both affluent and resource-poor settings (21). Other microbial causes of toxic shock syndrome are Staphylococcus aureus, and group B, C and G beta-hypolytic streptococci. Staphylococcal TSS can be associated with tampon use during menstrual periods in women (22).
Bacteraemia may not have a focus of infection, or there may be a focal infection such as meningitis, pneumonia, peritonitis, puerperal sepsis, osteomyelitis, septic arthritis, myositis and surgical wound infection. In children the infection may emanate from an upper respiratory infection, but it is more commonly associated with cutaneous foci, including burns and varicella.
Elderly patients with streptococcal bacteraemia often have an underlying chronic illness such as diabetes mellitus or peripheral vascular disease. The portal of entry in older adults is usually the skin.
Malignancy and immunosuppression are risk factors in both children and the elderly. Although Group A Streptococcal bacteraemia may at times be transient and relatively benign, it is more often fulminant. The onset is abrupt, with chills, high fever, and prostration. Rarely, patients may present with acute abdominal pain. Bacteraemia associated with strep TSS and necrotising fasciitis has significant morbidity and mortality (20, 23).
Meningitis due to GAS occurs in ~2% of people with systemic infection with GAS. Predisposing factors include otitis and sinusitis. Clinical features include fever, neck stiffness, seizures, focal neurological findings and hyponatremia. GAS meningitis can have a fulminant course. Neurological sequelae can be significant in surviving patients (24).
Mode of Transmission
Transmission of GAS is usually from person to person, via droplet spread or direct contact with patients or carriers (1).
Nosocomial outbreaks of GAS infection, particularly following surgical or obstetric procedures, have been traced to asymptomatic carriers. The site of carriage may be the skin, throat, anus, or vagina.
Outbreaks of GAS infection may occur as a result of ingestion of contaminated foods such as milk, milk products and eggs.
GAS infection is rarely transmitted by indirect contact through objects.
In cases of pharyngitis, the incubation period is usually 1 to 3 days, rarely longer (1). Cases with impetigo have a longer incubation of 7 to 10 days (1).
Period of Communicability
Cases are infectious from 7 days before onset of symptoms until 24 hours after initiation of antibiotic treatment.
Susceptibility and Resistance
Few people who acquire GAS will develop invasive disease. Individuals at an increased risk of invasive disease include the elderly and those with chronic disease, including diabetes mellitus, cardiac disease, chronic obstructive pulmonary disease, HIV, cancer, paralysis, regular use of NSAIDs, use of corticosteroids as well as history of injecting drug use (1, 25).
Individuals with acute GAS infection develop very strong lasting immunity to the infecting serotype (26). This immunity prevents further suppuratives (pus-forming) infections, although the same M type may persist or recolonise asymptomatic carrier states(26). While there are no licensed GAS vaccines yet, development of GAS vaccines is biologically feasible (27).
Begin the follow-up investigation within 1 working day of notification of iGAS.
Liaise with the hospital Infection Control Nurse and/or treating Clinician to obtain demographic and clinical details.
The case is generally considered infectious from the onset of the acute illness until completion of 24 hours treatment with effective systemic antibiotics (1). During this period the case should be managed using droplet precautions.
The case should be advised of the nature of the infection and its mode of transmission, and of appropriate precautions necessary to prevent others from becoming infected from the same source. A Queensland Health iGAS fact sheet should be made available to the case and their close contacts (see definition in Contacts below).
If the case is a resident at a facility (e.g. child care centre, aged care facility, prison) the fact sheet should be provided to a supervising staff member for distribution to contacts within the facility. In addition, infection control at the facility should be reviewed and additional cases excluded.
Refer to latest edition of Therapeutic Guidelines: Antibiotic for management of Streptococcus pyogenes bacteraemia.
All household contacts should receive a fact sheet. Antibiotic prophylaxis is recommended for mother-baby pairs in the neonatal period. Routine screening and chemoprophylaxis are not recommended for other household contacts. See below for recommended follow-up in the outbreak setting.
A close contact is defined as someone who has had prolonged close contact with the case in a household type setting in the 7 days before onset of illness. Someone who has also been directly exposed to larger particle droplet/secretions should be considered a close contact (e.g. healthcare workers who have provided resuscitation to the case without adequate PPE).
Contact Tracing: Mother-baby pair in the neonatal period:Routine contact tracing is recommended if the case is either a mother or neonate in the neonatal period (first 28 days of life).
If either a mother or baby develops iGAS infection in the neonatal period, antibiotics should be offered to the other of the pair, together with, in the case of a multiple birth, any other neonate(s) in the family.
Liaise with the treating Clinician and advise of the Public Health response management recommendation.
The Queensland Health iGAS fact sheet should be made available to the mother.
Antibiotic prophylaxis is recommended for mother/neonate (and neonatal twin) of the index case (see Table 1 below). Administer antibiotics as soon as possible and preferably within 24 hours of case identification(7). Prophylaxis is recommended for up to 7 days after the last contact with a severe invasive case (7).
Table 1: Recommended chemoprophylaxis for iGAS contacts (3, 28)
Adult: 500 mg orally, 12-hourly for 10 days
Child: 15 mg/kg up to 500mg orally, 12-hourly for 10 days
Adult: 900 mg IM as a single dose
Child (single dose):
3 to 6 kg: 225 mg IM
6 to 10 kg: 337.5 mg IM
10 to 15kg: 450 mg IM
15 to 20kg: 675 mg IM
20 kg or more: 900 mg IM
NB: Dose may be difficult to obtain and administration may be challenging
Adult: 1 g orally, 12 hourly for 10 days
Child: 25 mg/kg up to 1 g orally, 12 hourly for 10 days
Adult: 500 mg orally, daily for 5 days
Child: 12 mg/kg orally, daily for 5 days
|Clindamycin||Adult: 300 mg orally, 12 hourly for 10 days|
Other contact tracing: Single Case
- Household contacts of the iGAS case should be provided with a fact sheet.
- If a single case of iGAS is identified in the institutional setting (e.g. aged care facility), the following should be completed:
- The facility should rule out additional cases.
- Infection control should be reviewed.
- The iGAS fact sheet should be provided to the facility.
- If a single case of iGAS is identified in an Early Education and Care Centre, the iGAS fact sheet should be provided to the centre for distribution to staff and parents. Infection control at the centre (particularly hand hygiene) should be reviewed.
Restriction of asymptomatic contacts is generally not indicated.
Suspected iGAS outbreak: two or more cases of invasive Group A Streptococcal disease that are epidemiologically linked (particularly aged care, child care, hospitals or maternity wards) that occur within a 3 month period.
An epidemiological link exists where cases occur in a physical or geographical context and a plausible mode of transmission accounts for infection spreading between people, AND when one person is likely to have been infectious AND at least one person has an illness which starts within the incubation period after contact with the infectious person.
Confirmed iGAS outbreak: two or more cases of invasive Group A Streptococcal disease that are epidemiologically linked (particularly aged care, child care, hospitals or maternity wards) that occur within a 3 month period and are identical on molecular typing.
Investigate suspected and confirmed outbreaks to identify the likely source of infection.
Failure to control iGAS outbreaks in institutional settings has been attributed to persistent environmental contamination that has not been detected or to a serious breach in infection control. Measures to prevent and control iGAS outbreaks in institutional settings include:
- Vigilant infection prevention and control practices, particularly hand hygiene, and the cleaning of shared equipment and the environment
Note: mass prophylaxis in institutional settings may not be effective if infection control practices are inadequate (29, 30)
- Early identification of further cases of iGAS infection through surveillance and communication (29, 30)
- Patients with serious, invasive disease should be managed under droplet precautions (and contact precautions if skin infections, infected wounds or burns without dressing or where drainage is unable to be contained are involved) until 24 hours after effective antibiotic treatment is commenced
- Where patients with iGAS have been isolated, the isolation room, furniture, and equipment should be cleaned with detergent and water
- Ensure high touch items and communal facilities such as baths and showers are thoroughly cleaned between all patients (2).
Identify any other linked cases. Provide information on preventive measures for any defined community population identified to be at risk.
Household: If there are 2 or more cases of iGAS within a 30 day time period then the entire household should be issued chemoprophylaxis (refer to Table 1 above) and be provided with the iGAS fact sheet.
Institutional Setting: An Outbreak Control Team should be convened if two or more cases have been reported within a 30 day period.
If outbreak criteria are met, all asymptomatic residents and staff should be offered chemoprophylaxis simultaneously (refer to Table 1 above). In the situation where all of the iGAS cases occur within a subdivision of the facility and there is negligible crossover of residents and patient-care staff between subdivisions, chemoprophylaxis can be restricted to those within the affected subdivision.
Screening for iGAS carriage is not routinely recommended in the institutional setting. If a staff member working in an institutional setting has been screened and identified as a GAS carrier, the staff member should be excluded until they have received 48 hours of appropriate antibiotic therapy (29).
The Queensland Health iGAS fact sheet should be provided to all contacts.
Restriction of asymptomatic contacts, screening for asymptomatic GAS carriage and treating asymptomatic carriers of GAS are generally not indicated (see Appendix). If a staff member of an institutional setting is screened and found to be a GAS carrier, restriction and treatment should take place as noted above.
The iGAS fact sheet should be provided to all contacts.
Educate public on the importance of wound hygiene (including attention to hand hygiene and keeping wounds clean and dry).
Someone who becomes unwell after being in contact with a confirmed iGAS case should seek medical advice as soon as practicable.
Development of a Group A Streptococcus vaccine
The variable surface M-protein has been the focus of much vaccine research as these vaccines elicit robust M type specific immune responses. However the large number of different M types has made development of a broadly protective vaccine challenging. There are also concerns around the potential role of M-protein induced immunity in rheumatic fever pathogenesis.
Other researchers have been working on vaccines using other more conserved antigen components of the organism and a variety of conserved cell surface proteases, which have shown promising results in pre-clinical development.
Complete case report form for local unit file and fax to the Communicable Diseases Branch, Prevention Division, Department of Health.
Prepare a summary report of any outbreak investigation for the Communicable Diseases Branch, Prevention Division, Department of Health, on request.
Streptococcal Toxic Shock Syndrome
- Hypotension defined by a systolic blood pressure less than or equal to 90 mm Hg for adults or less than the fifth percentile by age for children aged less than 16 years.
- Multi-organ involvement characterized by two or more of the following:
- Renal impairment: Creatinine greater than or equal to 177 µmol/L for adults or greater than or equal to twice the upper limit of normal for age. In patients with pre-existing renal disease, a greater than twofold elevation over the baseline level.
- Coagulopathy: Platelets less than or equal to 100 x 106/L or disseminated intravascular coagulation, defined by prolonged clotting times, low fibrinogen level, and the presence of fibrin degradation products.
- Liver involvement: Alanine aminotransferase, aspartate aminotransferase, or total bilirubin levels greater than or equal to twice the upper limit of normal for the patient's age. In patients with pre-existing liver disease, a greater than twofold increase over the baseline level.
- Acute respiratory distress syndrome: defined by acute onset of diffuse pulmonary infiltrates and hypoxemia in the absence of cardiac failure or by evidence of diffuse capillary leak manifested by acute onset of generalized oedema, or pleural or peritoneal effusions with hypoalbuminemia.
- A generalized erythematous macular rash that may desquamate.
- Soft-tissue necrosis, including necrotizing fasciitis or myositis, or gangrene (31).
Treatment of GAS Carriage
Most international guidelines recommend that GAS throat carriage is not treated in most circumstances. For further information please refer to the Infectious Disease Society of America recommendations (32, 33).
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