6.0 Management of Invasive GAS Disease

The public health response to a sporadic case of invasive GAS disease, as described in Section 5.1, includes management of the case, contact identification and tracing, and maintenance of surveillance for further cases. The management of invasive GAS disease is divided into four subsections: the management of cases, contact management, management of cases occurring at LTCFs and management of cases occurring among children attending child care centres. Information about management in the hospital setting can be found in Annex 3.

6.1 Case management

Although this document is not focused on the treatment of GAS disease, where there is a strong clinical suspicion of invasive GAS disease a specimen from a normally sterile site should be obtained for culture, if possible, and empiric therapy started quickly. Confirmatory culture is important to ensure that GAS infection is diagnosed.

Laboratory testing of antimicrobial sensitivity of the GAS strain may be useful for determining appropriate antibiotic therapy. Readers should refer to treatment guidelines that address the clinical management of invasive GAS disease, which is beyond the scope of this document^(24-26).

The case or a proxy for the case should be interviewed to determine close contacts.

6.2 Contact management

The cornerstone of prevention of secondary cases of invasive GAS is aggressive contact tracing to identify people at increased risk of disease (i.e. close contacts). Close contacts of an invasive GAS case may be at increased risk of secondary disease^(17,22,27).Itis important that they should be alerted to signs and symptoms of invasive GAS disease and be advised to seek medical attention immediately should they develop febrile illness or any other clinical manifestations of GAS. Persons who are close contacts of cases are defined in Table 3. The recommendations for contact management in Canada are shown in Table 5. Recommended chemoprophylaxis regimens are discussed in Section 7.0.

The following were considered in determining further management of close contacts: evidence of GAS transmission, reasonable theoretical risk, limited evidence of effectiveness of chemoprophylaxis, risks and benefits of chemoprophylaxis and the number of close contacts who would need to receive chemoprophylaxis to prevent a case. The recommendations for contact management are based on expert opinion and very limited evidence.

• The risk of subsequent infection in household contacts is estimated to range between 0.66 and 2.94per 1,000, and this estimate is based on extremely small numbers of subsequent cases. Most subsequent cases in the Ontario GAS study occurred within 7 days after last contact with an infectious case.

Two population-based studies have estimated that the rate of invasive GAS infection among people living in the same household as a case is much higher than the rate of sporadic disease in the general population. The Ontario Group A Streptococcal Study estimated that the attack rate among household contacts was 2.94 per 1,000 (95% confidence interval [CI]: 0.80-7.50)^(17,27). In comparison, the attack rate among household contacts estimated using data from the US Active Bacterial Core Surveillance (ABCs)/Emerging Infections Program network was 0.66 per 1,000 (95% CI: 0.02-3.67)⁽²²⁾. There are two major limitations of these estimates: first, household contacts and attending physicians were not asked about the use of chemoprophylaxis; and second, these attack rates are based on extremely small numbers of subsequent cases and therefore may be unstable, as exemplified by the large confidence intervals⁽²²⁾.

In a follow-up study of clusters identified through enhanced surveillance in England, Wales and Northern Ireland during 2003, five household clusters were identified. The clusters included two spouse pairs and three mother-neonate pairs, which is in contrast to the clusters identified in the Ontario study (three spouse pairs, one adult sibling pair) and in US ABC surveillance (one father-infant daughter pair). According to the UK data, infections in either the mother or child in the neonatal period (first 28 days of life) were considered as carrying a high risk of further cases in the mother or baby. The risk estimates for other household contacts suggested that over 2,000 close contacts would need chemoprophylaxis to prevent a subsequent case, assuming 100% effectiveness of chemoprophylaxis⁽²⁸⁾.

• The risk of subsequent infection for non-household close contacts has not been quantified, but there is a reasonable theoretical risk that invasive GAS disease can be transmitted to these persons.

There is little evidence that GAS has been transmitted to non-household close contacts after unprotected direct contact, prolonged mucous membrane contact or contact with oral or nasal secretions of a case; however, this was felt to be biologically plausible and was therefore included. Direct mucous membrane contact should be prolonged for a person to be considered this type of non-household close contact. This would include close contact, such as mouth-tomouth resuscitation or open mouth kissing, but exclude kissing with closed mouths and sharing of utensils, water bottles or cigarettes. A firefighter developed toxic shock syndrome and cellulitis within 24 hours of performing cardiopulmonary resuscitation on a child with STSS using a bag-valve mask apparatus. The close temporal relation and the isolation of the same GAS strain from the child's blood and CSF and from the hand wound of the firefighter suggest the transmission of GAS during resuscitation or while cleaning secretions from the resuscitation equipment⁽²⁹⁾.

Three Swiss studies have demonstrated the occurrence of clusters of clonal strains causing endemic or epidemic infection among injection drug users living or purchasing drugs in the same region^(30-32). A case report from Israel reported the occurrence of invasive GAS isolates of the same serotype in a couple who regularly shared needles for injecting drugs⁽³³⁾.

Several studies have shown that, compared with rates in the general population, rates of pharyngeal carriage of the same strain of GAS are higher among close contacts spending at least 24 hours with an index case in the week preceding onset of illness⁽³⁴⁾,among residents and staff at the LTCF of the case^(35,36) and among children sharing the same room as a case in a child care centre^(37-39). Asymptomatic pharyngeal carriage or acute streptococcal pharyngitis among such persons may contribute to the spread of invasive infection.

• Decisions about chemoprophylaxis must take into account the individual and population risks and benefits of this intervention.

While prophylaxis of close contacts may be intuitively attractive, there is limited evidence that such prophylaxis is effective, and it is possible that prophylaxis may not be uniformly effective because of widespread transmission of S. pyogenes in the community.

The consequences of prophylaxis must also be considered. Serious adverse effects associated with the antibiotics used for prophylaxis are very rare but do occur. In addition, use of antibiotics clearly selects for antibiotic resistance and may have an impact on antibiotic resistance patterns. Finally, contact tracing and follow-up affect public health resources, which are scarce and must be directed to where they have the greatest benefit.

Based on an estimate that approximately 300 close contacts of an invasive GAS case would need to receive chemoprophylaxis to prevent one secondary case, that there would be an average of 10 contacts per case, a retail cost of $30 per person for antibiotics and approximately 3 hours of public health nurse follow-up time per case, at $50 per hour, the cost-effectiveness has been estimated to be $13,500 CAD in direct health care costs per secondary case prevented. This cost-effectiveness is within the range of other recommended public health preventive measures⁽⁴⁰⁾.

On the basis of these considerations, the working group consensus is that chemoprophylaxis is indicated only for contacts at the highest risk of acquisition of the organism and of subsequent severe disease. This explains why prophylaxis is not routinely recommended for contacts of cases that are not severe (see Table 2) (e.g. bacteremia or septic arthritis). Such cases have milder disease than others with invasive GAS, and their contacts are also likely to have milder disease, as there is some degree of consistency in the type and severity of disease caused by a particular GAS strain. The level of risk may vary for different groups, and there may be individual circumstances under which different decisions regarding chemoprophylaxis may be made.

The approach for contact management and recommended chemoprophylaxis varies by country^(27,28). The uncertainties in this decision-making process also explain why recommendations from various authorities will continue to differ, and as additional evidence becomes available these guidelines may need to be revisited.

Table 5. Recommendations for Contact Management

Follow-up of contacts

Cultures for GAS have no role in the identification of asymptomatic close contacts of sporadic cases occurring in the community. The only reason for obtaining cultures for GAS is in the diagnosis of suspected infection. There is no role for routine culture for a test of cure for contacts receiving antibiotic chemoprophylaxis.

6.3 Long-term care facilities

Residents of LTCF are at increased risk of morbidity and mortality due to invasive GAS disease because of their older age and higher prevalence of underlying conditions^(36,41-43). When a culture-confirmed case of invasive GAS disease occurs in an LTCF, there is a 38% likelihood that a second, positive blood culture-confirmed case of the same strain will be detected in the facility within 6 weeks (Dr. A. McGeer, Mount Sinai Hospital, Toronto: personal communication, July 2005). A number of outbreaks of invasive GAS infections have been documented in LTCF ^{(23,36,42-46)}. Infection is often spread through person-to-person contact, with clustering of cases by room or care unit in some instances^{(23,36,42,43,46)}. Staff may be a source of or conduit of infection either through poor infection control practices or asymptomatic carriage^{(35,42,44,45)}. However, hospital staff who are carriers are more likely to be the source of infection in outbreaks in acute care facilities, whereas outbreaks in LTCF are more often patientpropagated⁽²³⁾. In LTCF outbreaks, the implicated strain is usually widespread within the facility, and limited provision of chemoprophylaxis to close contacts is not the optimal approach.

In addition to strict enforcement of standard infection control practices, the following approach may be useful in the investigation and control of invasive GAS disease in LTCF:

• When a confirmed case of invasive GAS disease (as described in Section 5.1) occurs in an LTCF such as a nursing home, the facility should
  • report the case to the local health authorities
  • conduct a retrospective chart review of the entire facility's residents over the previous 4 to 6 weeks for culture-confirmed cases of GAS disease and any suggested cases of noninvasive or invasive GAS infection, including skin and soft tissue infections (e.g. pharyngitis and cellulitis) and excluding pneumonia and conjunctivitis not confirmed by culture. An excess of GAS infection, or an LTCF outbreak, is defined in Table 4;
  • assess the potential for a source of infection from outside the facility (e.g. regular visits from children who have recently been ill).
• If an excess of GAS infection is identified, the following actions should be considered:
  • all patient care staff should be screened for GAS with throat, nose and skin lesion cultures. In LTCF with < 100 beds, all residents should be screened for GAS. In LTCF with 100 beds or greater, screening can be limited to all residents within the same care unit as the infected case and contacts of the case if necessary, unless patient and care staff movement patterns or epidemiologic evidence (e.g. from the chart review) suggest that screening should be conducted more broadly;
  • anyone colonized with GAS should receive chemoprophylaxis (see Section 7.0)
  • non-patient care staff should be asked about possible recent GAS infections. Those with a positive history should be screened for GAS, and those who are positive should be treated with antibiotics as per the recommended regimen;
  • all GAS isolates should have further typing (see Annex 2: Laboratory Support for Outbreak Investigation of Invasive GAS, for further details). Culture for a test of cure is recommended for individuals found to have the outbreak-related strain, particularly if there is epidemiologic evidence indicating that contact with the individual is significantly related to illness. Culture for a test of cure is not necessary for individuals infected with a strain of GAS not related to the outbreak
  • all GAS positive residents and staff should be re-screened, including throat and skin lesion(s), 14 days after chemoprophylaxis has been started; this should be followed by screening at 2 weeks and at 4 weeks after the first re-screening. If the person is found to be positive, a second course of chemoprophylaxis should be offered. If the person is still colonized after the second course, discontinue chemoprophylaxis unless the facility has an ongoing problem with GAS infection;
  • active surveillance for GAS infection should be initiated and continued for 1 to 2 months;
  • appropriate specimens should be taken for culture to rule out GAS when suspected infections are detected by active surveillance.
• If no excess is identified, especially if there is evidence of an outside source of infection for the index case, then active surveillance alone for 2 to 4 weeks to establish the absence of additional cases is warranted.

Disease control measures for invasive GAS disease occurring in other health care settings are described in Annex 3.

6.4 Child Care Centres

For the purposes of these guidelines, child care centres include group or institutional child care centres (day care), family or home day care and pre-schools. Non-invasive GAS infection can spread easily in child care centres (CCC)⁽³⁸⁾; however, outbreaks of invasive GAS disease occurring among children attending CCC are rare. The recommendations for invasive GAS disease in CCC are therefore based on expert opinion and very limited evidence.

In two CCC outbreaks in the United States, GAS infection or carriage of the same serotype as the index case was detected in 8% to 18% of other attendees. The risk of GAS infection or carriage was associated with sharing a room with the index case and spending a greater number of hours per week at the CCC. GAS prevalence among staff was low in both outbreaks, suggesting that they did not contribute to the spread of infection^(37,39).

Invasive GAS disease in children frequently occurs secondary to varicella infection^(20,47-52).Two population-based Canadian studies have shown that 15% to 25% of pediatric cases of invasive GAS disease are associated with antecedent varicella infection^(20,50). The risk is significantly increased during the 2-week period after the onset of varicella infection and may be due to a breakdown in the skin barrier, infection through another less apparent portal, such as lesions on the oral mucosa or the respiratory tract, or immunosuppression⁽⁵⁰⁾.The National Advisory Committee on Immunization (NACI) recommends varicella vaccination for children between 12 and 18 months of age and for susceptible persons ≥ 12 months of age⁽⁵³⁾. It has been estimated that the full implementation of universal childhood varicella vaccination could prevent at least 10% of pediatric invasive GAS cases in Canada⁽⁵⁰⁾. Outbreaks of invasive GAS and varicella have been previously reported to occur concurrently among children^(37,49,54). According to NACI guidelines, post-exposure use of varicella vaccine should be considered during an outbreak of varicella in a child care facility⁽⁵³⁾. Varicella vaccination of susceptible attendees may help prevent the further spread of a concurrent outbreak of invasive GAS disease^(37,49).

In addition to strict enforcement of standard infection control practices⁽⁵⁵⁾, staff from the affected CCC must report to local health authorities when a confirmed case of invasive GAS disease (as described in Section 5.1) occurs in a child attending the CCC. This may be required by legislation in some provinces and territories.

Health authorities should investigate when one severe case of invasive GAS disease (see Table 2) occurs in a child attending a CCC. Investigators should take into consideration the following:

1. the nature of the CCC (e.g. type of centre, including the size and physical structure, number and ages of the children, type of interaction of the children);
2. the characteristics of the case (e.g. if the case occurred secondary to a varicella infection);
3. the potential for a source of infection from within the CCC:
   1. whether there has been any suggested non-invasive or invasive GAS infections
      (e.g. other cases of invasive GAS, pharyngitis, impetigo);
   2. potential of a point source of infection (foodborne outbreaks of pharyngitis have occurred and are a consequence of human contamination of food in conjunction with improper preparation or refrigeration procedures⁽²⁵⁾ );
4. the presence of varicella cases within the CCC in the previous 2 weeks;
5. the potential for a source of infection from outside the CCC (e.g. exposure to a family member with suggested non-invasive or invasive GAS infection).

The following approach should be considered in the investigation and control of invasive GAS disease when one severe case of invasive GAS disease (see Table 2) occurs in a child attending a CCC:

• Parents and/or guardians of attendees should be informed of the situation, alerted to the signs and symptoms of invasive GAS disease and be advised to seek medical attention immediately should their child develop febrile illness or any other clinical manifestations of GAS.
• In family or home day care settings, chemoprophylaxis should be recommended for all children and staff (see Section 7.0).
• In group or institutional CCC and pre-schools, chemoprophylaxis is generally not warranted but may be considered in certain situations, including the occurrence of > 1 case of invasive GAS disease in children or staff of the CCC within 1 month or a concurrent varicella outbreak at the CCC. Cases of invasive GAS occurring among children or staff of a CCC within 1 month should be considered as part of the same cluster. Consideration could be given to testing isolates from invasive GAS cases occurring in a CCC more than 1 month apart, to determine strain relatedness.If a case of varicella has occurred in the CCC within the 2 weeks before onset of GAS symptoms in the index case, all attendees should be assessed for varicella vaccination history. Two weeks was chosen as the time interval on the basis of findings that risk of GAS was significantly increased 2 weeks after onset of varicella infection⁽⁵⁰⁾.Varicella vaccination should be recommended for those without a history of prior varicella infection or vaccination as per the NACI guidelines⁽⁵³⁾.
• A test of cure is not warranted for persons receiving chemoprophylaxis.
• It should be emphasized that staff of the CCC must notify local public health officials if further cases of invasive GAS infection occur. This may be required by legislation in some provinces and territories.
• Appropriate specimens can be taken for culture to rule out GAS when suspected infections are detected during this period; however routine screening of attendees is not recommended.

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