iGAS Infections Research Articles

A protracted iGAS outbreak in a long-term care facility 2014–2015: control measures and the use of whole-genome sequencing

In 2014, two residents of a long-term care facility (LTCF) developed invasive group A streptococcal (iGAS) infections with identical typing (emm 11), resulting in one death. The second resident recovered but had a subsequent episode of emm 11 iGAS infection 10 months later. This second episode was linked to a third case, within 12 days, leading to a further outbreak investigation. To combine different techniques to establish whether this was a protracted outbreak, understand transmission pathways and inform appropriate control measures. Following a routine response to the first cluster, the second investigation included a care record review. This informed network analysis of case interactions with staff and visitors during 10 days prior to infection. These data were combined with post-outbreak whole-genome sequencing (WGS) using isolates from cases, and staff and resident screening (44 GAS isolates: 11 outbreak-related and 33 sporadic isolates). Two of the three confirmed iGAS cases died (one suffered two episodes). All iGAS cases, and six non-invasive isolates from 2015, were emm 11 (monophylogenetic WGS clade). Network analysis highlighted only indirect contact through staff-visitor interactions between iGAS cases in 2015. This suggested a common source and transmission propagation through carriage and/or environmental contamination over an 11-month period. This outbreak highlighted benefits of staff/resident screening and typing as part of routine response. Network analysis and highly discriminatory WGS clarified the protracted nature of the outbreak, supporting findings of hygiene and infection control issues and adding to our understanding of the epidemiology.

462. Prospective Surveillance of Invasive Group A Streptococcal Infections in Toronto, Ontario, Canada: 1992–2017

Background. BackgroundInvasive Group A streptococcal (iGAS) infections remain a substantial source of morbidity and mortality. We explore the clinical and molecular epidemiology of iGAS infections in Toronto, Ontario, Canada over a 26-year period.MethodsThe Toronto Invasive Bacterial Diseases Network has performed population-based surveillance for iGAS infections in metropolitan Toronto and Peel regions since 1992. Participating microbiology laboratories report and submit sterile site specimens for central processing. M typing was performed on iGAS isolates until September 2006; thereafter emm typing was performed. Clinical information was collected by chart review using standardized collection forms.ResultsOver the 26-year period there were 2819 iGAS infections, representing an average incidence of 2.85 per 100,000 residents with a nadir of 1.65 in 1993 and a peak of 4.52 in 2014. Nosocomial infections occurred in 8.9% (251/2,819). There was substantial variation in annual incidence rates over the study period with increases from 1992 until 2002 and then 2004 until 2014 (analysis for trend, P < 0.001). Skin and soft-tissue infections were the most common clinical presentation, accounting for 33.2% (936/2,819), followed by bacteremia without a focus in 15.4% (435/2,819). Necrotizing fasciitis was observed in 7.4% (208/2,819) and criteria for toxic shock syndrome were met in 17.6% (497/2,819). Overall case fatality within 30 days of hospitalization was 15.3% (95% confidence interval 14.0 to 16.6) and did not change over time. M serotype distribution varied yearly with the most common type being M1 at 22.2% (626/2,189) followed by M12 at 8.2% (230/2,189), then M89 at 5.8% (163/2,189). Antibiotic susceptibility was available from 1998 onwards with overall clindamycin susceptibility at 92.3% (1,957/2,121) and erythromycin susceptibility at 87.9% (1864/2,121).ConclusionThe incidence of iGAS in Toronto, Ontario has varied over time, with no recent increase apparent. Similar to worldwide observations, M1 serotype was the most commonly isolated; most common serotypes demonstrated cyclical variation. Case fatality rates have remained relatively constant making the development of a vaccine imperative. Disclosures All authors: No reported disclosures.

468. Epidemiologic Features of Invasive Methicillin-Resistant Staphylococcus aureus and Group A Streptococcus Infections among Adults Who Inject Drugs in the San Francisco Bay Area, 2008–2017

BackgroundInjection drug use has been associated with infection with invasive methicillin-resistant Staphylococcus aureus (iMRSA) and invasive group A Streptococcus (iGAS). In light of the ongoing opioid epidemic, we sought to describe the epidemiologic features of iGAS and iMRSA infections among persons who inject drugs (PWID) in the San Francisco Bay Area.MethodsActive, population-based surveillance for iMRSA and iGAS was conducted in three California counties during 2008–2017. We defined a case as recovery of MRSA or GAS from a normally sterile site in a surveillance area resident ≥18 years of age. We collected demographic and clinical information and history of injection drug use (IDU) in the past 12 months. Trends in the incidence of infection were assessed using the Cochran-Armitage test for trend. Odds ratios (OR) and 95% Confidence Intervals (CI) were calculated comparing PWID and non-PWID.ResultsOf the 6,705 iMRSA and 1,691 iGAS cases identified during 2008–2017, 764 (11%) and 241 (14%), respectively, were among PWID. The proportion of iMRSA cases reporting IDU increased from 9.6% in 2008 to 12.9% (P = 0.017) in 2017 (Figure 1); no significant trend was observed for iGAS cases (Figure 2). Among iMRSA and iGAS cases, PWID cases were younger than non-PWID cases (iMRSA median 46 vs. 63 years, P < 0.0001; iGAS 41 vs. 57 years, P < 0.0001) and were more likely to be homeless (iMRSA OR 8.3, CI 6.7–10.2; iGAS OR 5.4, CI 4.0–7.2), and diagnosed with endocarditis (iMRSA OR 5.9, CI 4.8–7.3; iGAS OR 2.8, CI 1.3–6.4) and internal abscesses (iMRSA OR 4.3, CI 3.5–5.3; iGAS OR 3.4, CI 2.1–5.5) (Table 1). For iMRSA, PWID cases were more likely than non-PWID cases to be community-associated, (OR 2.5, CI 2.1–2.9) and diagnosed with septic arthritis (OR 2.4, CI 1.9–3.0).ConclusionThe proportion of iMRSA cases reporting IDU significantly increased between 2008 and 2017, in the San Francisco Bay Area. iMRSA and iGAS cases among PWID are younger, more likely to be homeless, and diagnosed with endocarditis and internal abscesses. Prevention measures targeting this younger population who are experiencing homelessness and/or are injecting drugs, may limit severe manifestations of iMRSA and iGAS. These prevention measures should include support of safe injection practices. Disclosures All authors: No reported disclosures.

Screening asymptomatic households for Streptococcus pyogenes pharyngeal carriage as a part of in-hospital investigation of puerperal sepsis

Invasive group A streptococcal (iGAS) infection in the peripartum setting is a rare but devastating disease occasionally occurring as a health care-associated infection (HAI). Current guidelines suggest enhanced surveillance and streptococcal isolate storage after a single case of iGAS, as well as a full epidemiological investigation that includes screening health care workers (HCWs) from several sites after 2 cases. Current guidelines do not recommend routine screening of household members of a patient with iGAS. We conducted studies of 3 patients with iGAS puerperal sepsis and related epidemiologic and molecular investigations. Identical GAS emm gene types were found in pharyngeal cultures of 3 asymptomatic spouses of patients with iGAS puerperal sepsis. HCWs screened negative for GAS, and emm typing indicated that other iGAS cases from this hospital were sporadic and not related to the puerperal cases. The concurrent presence of the same emm type in a household member practically excludes the option of an inadvertent HAI or facility outbreak. Hence, we suggest that screening close family members for asymptomatic GAS carriage should be performed early as a part of infection prevention measures, as doing so would have significant utility in saving time and resources related to a full epidemiological inquiry.

P033: Clinical and laboratory characteristics of patients presenting to a tertiary care centre emergency department with invasive Group A Streptococcus infections

Introduction: According to the Public Health Agency of Canada, the rate of invasive Group A Streptococcus (iGAS) has more than doubled since it first became a notifiable disease in 2000. Our objectives were to describe the clinical and laboratory characteristics of iGAS in a geographic area that sees a relatively high volume of cases annually. Methods: We conducted a retrospective chart review of all adult and pediatric patients presenting to the Thunder Bay Regional Health Sciences Centre Emergency Department from January 2016 to December 2017 with a hospital discharge diagnosis of iGAS infection using ICD-10 codes. Patient demographics, host characteristics, triage vital signs, laboratory values, culture sites, and disposition were analyzed using univariate and bivariate statistics. Results: Forty-five cases of iGAS were identified over 2 years, with a mean age of 45 years (SD 18). The most prevalent associations were male sex (69%), diabetes mellitus (44%), current or previous alcohol abuse (38%), and current or previous intravenous drug use (33%). Prevalence of iGAS was roughly two times the national average in 2016 (11.5 per 100,000) and four times the national average in 2017 (25.5 per 100,000). Mean triage vital signs included a systolic blood pressure of 126 mmHg (SD 24), diastolic blood pressure of 73 mmHg (SD 16), temperature of 37.3°C (SD 1.4), oxygen saturation of 97% (SD 2), heart rate of 113 beats per minute (SD 22), and respiratory rate of 22 breaths per minute (SD 7). Mean laboratory values revealed a white blood cell count of 17,500 cells/μL (SD 9,800) and C-reactive protein of 243 mg/L (SD 144). A higher Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score was positively correlated with longer hospital length of stay (r = 0.46, p &amp;lt; 0.01). Conclusion: Despite its morbidity and mortality, iGAS infections often present insidiously with only mild abnormalities in triage vital signs, and require a high index of suspicion by the emergency physician for a prompt diagnosis, particularly in at-risk populations such as patients with diabetes mellitus or those who misuse alcohol or drugs.

Increased Risk for Invasive Group A Streptococcus Disease for Household Contacts of Scarlet Fever Cases, England, 2011-2016.

The incidence of scarlet fever in England and Wales is at its highest in 50 years. We estimated secondary household risk for invasive group A Streptococcus (iGAS) disease within 60 days after onset of scarlet fever. Reports of scarlet fever in England during 2011–2016 were matched by residential address to persons with laboratory-confirmed iGAS infections. We identified 11 iGAS cases in ≈189,684 household contacts and a 60-day incidence rate of 35.3 cases/100,000 person-years, which was 12.2-fold higher than the background rate (2.89). Infants and contacts >75 years of age were at highest risk. Three cases were fatal; sepsis and cellulitis were the most common manifestations. Typing for 6 iGAS cases identified emm 1.0 (n = 4), emm 4.0 (n = 1), and emm 12.0 (n = 1). Although absolute risk in household contacts was low, clinicians assessing household contacts should be aware of the risk to expedite diagnosis and initiate life-saving treatment.

Invasive group A streptococcal infection outbreaks of typeemm118 in a long-term care facility, and of type emm74 in the homeless population, Montréal, Quebec.

BackgroundTwo invasive group A streptococcus (iGAS) infection outbreaks occurred in Montreal in 2016 and 2017; one in a long-term care facility (type emm118) and one in the community, primarily involving homeless people (type emm74).ObjectiveTo describe two recent iGAS outbreaks in Montréal and highlight the challenges in dealing with these outbreaks and the need to tailor the public health response to control them.MethodologyAll cases of iGAS were investigated and the isolates were sent to the laboratory for emm typing. In both outbreaks, cases of superficial group A streptococcus (GAS) infection were identified, through 1) systematic case detection accompanied by screening for asymptomatic carriers among residents and employees of the long-term care facility and 2) sentinel surveillance among homeless people. Visits were made to community organizations providing homeless services (including shelters) and social networks were analyzed to establish whether there were any links among cases of GAS infection (both invasive and noninvasive) and locations frequented. In both outbreaks, recommendations were made to service providers regarding enhancement of infection prevention and control measures.ResultsIn the long-term care facility, five cases of type emm118 iGAS were identified over a 22-month period, one of which resulted in death. All residents were screened and no carriers were identified. Among the employees, 81 (65%) were screened and fourcarriers were identified. Of those, one was a carrier of type emm118 GAS. All carriers were treated, and subsequent follow-up sampling on three carriers (including the one with emm118) was negative.In the community, 23 cases of type emm74 iGAS were detected over a 16-month period, four of which resulted in death. Half of the cases (n=12) were described as homeless, and six others were users of services for the homeless. Sentinel surveillance of superficial infections yielded 64 cultures with GAS, chiefly on the skin, including 51 (80%) of type emm74. An analysis of the social networks revealed the large number and variety of resources for the homeless used by the cases. Visits to the community organizations providing homeless services revealed the heterogeneity and precariousness of some of these services, the difficulties encountered in applying adequate health and hygiene measures, and the high degree of mobility amongst those who use these services.ConclusionThe detection and control of iGAS outbreaks in both long-term care establishments and among community organizations providing homeless services are very complex. An outbreak of iGAS can develop in the background over a long time and be easily overlooked despite cases being admitted to the hospital. Emm typing and systematic research of previous cases of iGAS are essential tools for the detection and characterization of outbreaks. Close cooperation among public health agencies, clinical teams, community organizations and laboratories is essential for proper monitoring and the reduction of GAS transmission in the community and health care settings.

LB9. Rising High Rate of Invasive Group A Streptococcus Infections Among Persons Experiencing Homelessness in San Francisco, 2010–2017

BackgroundRates of invasive group A Streptococcus (iGAS) disease in the United States have risen since 2014; reasons remain unclear. Outbreaks of iGAS infection among persons experiencing homelessness (PEH) and persons who inject drugs in Europe, Canada, and the United States have been described. Using active, population-based surveillance data from California’s Emerging Infections Program, we describe incidence trends and characteristics of iGAS infection among PEH and persons not experiencing homelessness (PNEH) in San Francisco (SF) County during 2010–2017.MethodsWe defined an iGAS case as infection with GAS isolated from a normally sterile site (e.g., blood) in an SF resident. We calculated annual iGAS disease incidence rates (cases per 100,000 population) for PEH and PNEH using denominators from SF’s Department of Homelessness and Supportive Housing and the State of California Department of Finance. Demographic, clinical, and exposure characteristics of PEH and PNEH were compared by chi-square or t-test.ResultsWe identified 673 iGAS cases in SF during 2010–2017. Among these, 34% (229/673) were among PEH. Annual iGAS incidence among PEH rose from ~300 (2010–2014) to 547 (95% CI: 379–714) per 100,000 in 2017 (P < 0.001, Cochran-Armitage trend test); rates peaked at 758 (95% CI: 561–955) in 2016. Annual iGAS incidence in PNEH rose from a mean of 5 in 2010–2013 to 9.3 (95% CI: 7.3–11.4) per 100,000 in 2017 (P < 0.001). Annual iGAS incidence in PEH was 42–72 times that in PNEH. PEH with iGAS infections were significantly younger and more likely to be male, white, and uninsured or enrolled in Medicaid (P < 0.05 for each) compared with PNEH with iGAS disease. Case fatality ratios, ICU admission, infection type, and length of hospital stay did not differ significantly. Smoking, current injection drug use, current alcohol abuse, and AIDS diagnosis were significantly more common among PEH with iGAS. Obesity, diabetes, and cancer were significantly more common among PNEH with iGAS.ConclusionIn San Francisco, iGAS rates among both PEH and PNEH have risen significantly. Incidence of iGAS is strikingly higher in PEH than in PNEH and exposures differed between PEH and PNEH with iGAS. This information could inform development of disease control and prevention strategies.Disclosures All authors: No reported disclosures.

685. Correlation Between Hospitalized Influenza and Group A Streptococcus Infections in Minnesota, 2010–2016

BackgroundOutbreaks of influenza can result in significant morbidity, including secondary bacterial infections. Invasive group A streptococcal (iGAS) infections are associated with a 12% case fatality rate. We used surveillance data to examine if there was a correlation between hospitalized influenza and GAS cases.MethodsMinnesota Department of Health conducts population-based surveillance for hospitalized lab-confirmed influenza and iGAS (sterile site isolation) cases in the Minneapolis–St. Paul area as part of the CDC Emerging Infections Program. Cases were categorized by week during October–April of each year for 2010–2016, based on specimen collection date. Using STATA (v15), the correlation between the number of influenza (N = 11,768), and overall iGAS (N = 687), iGAS septic shock (n = 104), and iGAS pneumonia cases (n = 59) was assessed in weekly time periods using the Granger causality test.ResultsThe number of hospitalized influenza cases was associated with an increase in the overall number of iGAS cases (Wald χ2 = 10.22, P = 0.04). Hospitalized influenza cases were associated with an increase in iGAS septic shock cases; every 1,000 increase in case counts were associated with one case of iGAS septic shock 1 week later (P = 0.02). Similarly, every 1,000 increase in hospitalized influenza cases were associated with one case of iGAS pneumonia 1 week later (P < 0.01). While the effect of Granger causality is cumulative when describing the causal relationship between hospitalized influenza and total iGAS, the correlation between influenza and the iGAS subgroups is best described with a 1-week lag.ConclusionGranger causality tests are commonly used in economic modeling but have not been routinely applied to infectious diseases. Using this test, we found a strong correlation between weekly cases of hospitalized influenza and iGAS cases, with a 1-week lag between influenza and iGAS septic shock or pneumonia. This approach can provide insight into the potential impact of developing prevention interventions for infections with strong correlation. Further exploration of Granger tests in infectious disease modeling should be considered.Disclosures All authors: No reported disclosures.

Severe group A streptococcal infections in mothers and their newborns in London and the South East, 2010-2016: assessment of risk and audit of public health management.

We describe cases of invasive group A Streptococcus (iGAS) in mothers or neonates and assess management according to national guidelines, which recommend administering antibiotics to both mother and neonate if either develops iGAS infection within 28days of birth and investigation of clusters in maternity units. Cross-sectional retrospective study. Notified confirmed iGAS cases in either mothers or neonates with onset within 28days of birth in London and the South East of England between 2010 and 2016 METHOD: Review of public health records of notified cases. Incidence and onset time of iGAS in postpartum mothers and babies, proportion given prophylaxis, maternity unit clusters within 6months. We identified 134 maternal and 21 neonatal confirmed iGAS infections. The incidence (in 100 000 person years) of iGAS in women within 28days postpartum was 109 (95% CI 90-127) compared with 1.3 in other females aged 15-44. For neonates the incidence was 1.5 (95% CI 9-23). The median onset time was 2days postpartum [interquartile range (IQR) 0-5days] for mothers and 12days (IQR 7-15days) for neonates. All eligible mothers and most (109, 89%) eligible neonates received chemoprophylaxis. Of 20 clusters (59 cases of GAS and iGAS) in maternity units, two clusters involved possible transmission. However, in 6 of 15 clusters, GAS isolates were not saved for comparison even after relevant guidance was issued. iGAS infection remains a potential postpartum risk. Prophylaxis among neonates and storage of isolates from maternity cases can be improved. Are public health guidelines being followed in the management of mothers and their newborns to reduce the risk of iGAS infection?

Epidemiology of an upsurge of invasive group A streptococcal infections in Ireland, 2012–2015

Group A streptococcus (GAS) is responsible for mild to very severe disease. The epidemiology of an upsurge in invasive GAS (iGAS) infections in Ireland, 2012-2015 was investigated. Epidemiological typing of iGAS (n = 473) isolates was performed and compared to non-invasive (n = 517) isolates. Clinical data of notified iGAS was obtained from the national infectious disease information system. Annual incidences of iGAS cases (n = 561) were 2.33-3.66 per 100,000 population. Bacteraemia was the most common clinical presentation (75%) followed by focus without bacteraemia (19%) and necrotizing faciitis (7%). Streptococcal toxic shock syndrome occurred in 19% of presentations. The main invasive emm types in rank order were emm1, emm3, emm28, emm12 and emm89 whereas emm4, emm28, emm3, emm12, emm89 and emm1 predominated in non-invasive infections. Invasive emm1 and emm3 showed annual fluctuations (15-48% and 4-37%, respectively) and predominated in most clinical presentations of iGAS. Superantigens speA, speG, speJ was associated with iGAS disease and, speC, speI and ssa with non-invasive infections. There was 4.3% erythromycin and 5.6% tetracycline resistance. The main resistant types were emm11, emm28 and emm77. Cyclic increases in emm1 and emm3 occurred during the iGAS upsurge. Continued surveillance of GAS is therefore essential given the epidemiological changes that occur in a short time period.

Canada-Wide Epidemic of emm74 Group A Streptococcus Invasive Disease.

The number of invasive group A Streptococcus (iGAS) infections due to hitherto extremely rare type emm74 strains has increased in several Canadian provinces since late 2015. We hypothesized that the cases recorded in the different provinces are linked and caused by strains of an emm74 clone that recently emerged and expanded explosively. We analyzed both active and passive surveillance data for iGAS infections and used whole-genome sequencing to investigate the phylogenetic relationships of the emm74 strains responsible for these invasive infections country-wide. Genome analysis showed that highly clonal emm74 strains, genetically different from emm74 organisms previously circulating in Canada, were responsible for a country-wide epidemic of >160 invasive disease cases. The emerging clone belonged to multilocus sequence typing ST120. The analysis also revealed dissemination patterns of emm74 subclonal lineages across Canadian provinces. Clinical data analysis indicated that the emm74 epidemic disproportionally affected middle-aged or older male individuals. Homelessness, alcohol abuse, and intravenous drug usage were significantly associated with invasive emm74 infections. In a period of 20 months, an emm74 GAS clone emerged and rapidly spread across several Canadian provinces located more than 4500 km apart, causing invasive infections primarily among disadvantaged persons.

Have reducing tonsillectomy rates in England led to increasing incidence of invasive Group A Streptococcus infections in children?

To determine whether there is a correlation between falling tonsillectomy numbers and increasing numbers of tonsillitis admissions and invasive Group A β-haemolytic streptococcus (iGAS) infection in children aged 14 and under in England. An observational cross-sectional study was performed. The data extracted covered the period from 1991 until 2014. Hospital admissions for tonsillectomies, tonsillitis/pharyngitis and all diagnoses of iGAS in children aged 14 and under who had a tonsillectomy. Correlation between trends in tonsillectomies, tonsillitis/pharyngitis and iGAS. Across all age groups, there was a dramatic reduction in the total number of tonsillectomies performed in England from 28 309 in 1990/1991, down to 6327 in 2013/2014 (77.7% reduction). The numbers of hospital admissions for management of acute tonsillitis and pharyngitis have risen dramatically. iGAS numbers have increased steadily over this time period and more than doubled in children aged 14 and under. There are significant negative correlations between the trend in iGAS infections and numbers of tonsillectomies in all ages. There are also strong positive correlations between the trend in numbers of tonsillitis episodes and the number of iGAS infections in all under 14-year groups; the strongest correlation was seen in the 1- to 4-year age group (+0.92 Pearson correlation coefficient). There appears to be a correlation between falling tonsillectomy numbers, increasing hospital admissions with tonsillitis and rising iGAS infection in England. Further studies are required to assess the aetiological role of tonsillitis in predisposing to iGAS infection and the potential societal benefit of tonsillectomies.

Invasive and non-invasive group A β-haemolytic streptococcal infections in patients attending public sector facilities in South Africa: 2003–2015

Background: The burden of disease caused by group A streptococcus (GAS) in Africa is largely unknown. The aim of this study was to determine the incidence of invasive (iGAS) and non-invasive GAS (non-iGAS) infections in patients attending the public health sector of South Africa.Methods: iGAS and non-iGAS infection was defined as GAS isolated in culture from sterile and non-sterile sites respectively. Using annual census data, we calculated incidence rates (IR) of iGAS and non-iGAS infection by reviewing cases from the National Health Laboratory Service (NHLS) database derived from the 9 provinces of South Africa between 2003 and 2015.Results: About 50% of the samples were collected in the Eastern Cape province which had data for all the years under observation; missing data from the other eight provinces precluded analysis of annual incidence. A multi-modal distribution of 5 256 GAS cases was observed in the Eastern Cape province. iGAS cases (n = 428) showed an annual mean IR of 0.48 (Range: 0.15–1.12) cases per 105 per year (py) with a marginal decrease from 2003 to 2015 (Rate Difference (RD), 0.23/105 py; 95% CI: 0.02–0.44/105 py). The mean annual IR for non-iGAS infection (n = 4828) was 5.48 (Range: 0.19–11.55) cases/105py; IR showed a decrease (RD, 11.36/105 py; 95% CI: 10.53–12.19/105 py). The Mann-Kendall test and the Theil-Sen estimator showed a decreasing trend in the incidence of non-iGAS infection (p = 0.002) over the study period.Conclusions: The incidence of non-iGAS infection in the Eastern Cape province of South Africa declined from 2003 to 2015. The trends from the Eastern Cape and incomplete data from other provinces indicate the need for a detailed prospective evaluation of GAS infection in South Africa to verify this trend and provide information for planning appropriate interventions.

Whole-genome sequencing in the investigation of recurrent invasive group A streptococcus outbreaks in a maternity unit

The clinical manifestations of group A streptococcus (GAS) (Streptococcus pyogenes) are diverse, ranging from asymptomatic colonization to devastating invasive disease. Maternity-related clusters of invasive GAS (iGAS) infection are complex to investigate and control, especially if recurrent. To investigate three episodes of emm 75 GAS/iGAS infection in maternity patients at one hospital site over a four-year period (two with monophyletic ancestry). The episodes are described, together with whole-genome sequence (WGS) isolate analyses. Single nucleotide polymorphism differences were compared with contemporaneous emm 75 genomes. Over the four-year study period, seven mothers had emm 75 GAS/iGAS and one mother had emm 3 iGAS (in year 4) (subsequently discounted as linked). Three (clinical/screening samples) of the seven babies of emm-75-positive mothers and three screened healthcare workers were positive for emm 75 GAS. WGS similarity suggested a shared ancestral lineage and a common source transmission, but directionality of transmission cannot be inferred. However, the findings indicate that persistence of a particular clone in a given setting may be long term. Occupational health procedures were enhanced, staff were screened, and antibiotic therapy was provided to GAS-positive staff and patients. The definitive source of infection could not be identified, although staff-patient transmission was the most likely route. The pattern of clonal GAS transmission over the four-year study period suggests that long-term persistence of GAS may have occurred.

Prevalent emm Types among Invasive GAS in Europe and North America since Year 2000.

Streptococcus pyogenes or group A streptococcus (GAS) is an important human pathogen responsible for a broad range of infections, from uncomplicated to more severe and invasive diseases with high mortality and morbidity. Epidemiological surveillance has been crucial to detect changes in the geographical and temporal variation of the disease pattern; for this purpose the M protein gene (emm) gene typing is the most widely used genotyping method, with more than 200 emm types recognized. Molecular epidemiological data have been also used for the development of GAS M protein-based vaccines. The aim of this paper was to provide an updated scenario of the most prevalent GAS emm types responsible for invasive infections in developed countries as Europe and North America (US and Canada), from 1st January 2000 to 31st May 2017. The search, performed in PubMed by the combined use of the terms ("emm") and ("invasive") retrieved 264 articles, of which 38 articles (31 from Europe and 7 from North America) met the inclusion criteria and were selected for this study. Additional five papers cited in the European articles but not retrieved by the search were included. emm1 represented the dominant type in both Europe and North America, replaced by other emm types in only few occasions. The seven major emm types identified (emm1, emm28, emm89, emm3, emm12, emm4, and emm6) accounted for approximately 50-70% of the total isolates; less common emm types accounted for the remaining 30-50% of the cases. Most of the common emm types are included in either one or both the 26-valent and 30-valent vaccines, though some well-represented emm types found in Europe are not. This study provided a picture of the prevalent emm types among invasive GAS (iGAS) in Europe and North America since the year 2000 onward. Continuous surveillance on the emm-type distribution among iGAS infections is strongly encouraged also to determine the potential coverage of the developing multivalent vaccines.

Streptococcal toxic shock syndrome caused by the dissemination of an invasive emm3/ST15 strain of Streptococcus pyogenes

BackgroundStreptococcus pyogenes (group A Streptococcus [GAS]) is a major human pathogen that causes a wide spectrum of clinical manifestations. Although invasive GAS (iGAS) infections are relatively uncommon, emm3/ST15 GAS is a highly virulent, invasive, and pathogenic strain. Global molecular epidemiology analysis has suggested that the frequency of emm3 GAS has been recently increasing.Case presentationA 14-year-old patient was diagnosed with streptococcal toxic shock syndrome and severe pneumonia, impaired renal function, and rhabdomyolysis. GAS was isolated from a culture of endotracheal aspirates and designated as KS030. Comparative genome analysis suggested that KS030 is classified as emm3 (emm-type) and ST15 (multilocus sequencing typing [MLST]), which is similar to iGAS isolates identified in the UK (2013) and Switzerland (2015).ConclusionsWe conclude that the global dissemination of emm3/ST15 GAS strain has the potential to cause invasive disease.

Estimating the risk of invasive group A Streptococcus infection in care home residents in England, 2009-2010.

Invasive group A streptococcal (iGAS) infections cause severe disease and death, especially in residents of long-term care facilities (LTCFs). In order to inform iGAS prevention, we compared the risk of iGAS in LTCF residents and community residents. We identified LTCF residents among cases of iGAS from national surveillance (2009-2010) using postcode matching, and cases of hospital-acquired infections via hospital admission records. We used Poisson regression to calculate incidence rate ratios (IRR) and logistic regression to explore factors associated with case fatality rate (CFR). A total of 2741 laboratory-confirmed iGAS cases were matched to a hospital admission: 156 (6%) were defined as hospital-acquired. Out of the total cases, 96 (3·5%) were LTCF residents. Compared with community residents, LTCF residents over 75 years of age had a higher risk of iGAS infection (IRR=1·7; 95% CI 1·3-2·1) and CFR (OR=2·3; 95% CI 1·3-3·8). Amongst community-acquired cases, the risk of iGAS in LTCF residents between 75 and 84 years of age doubled (IRR=2·7; 95% CI 1·8-3·9) compared with their community counterparts. The CFR among community-acquired cases was higher in LTCF residents than community residents (21% vs. 11%). Age remained associated with death in our final model. Our study showed that, even controlling for age, LTCF residents have a higher risk of acquiring and dying from iGAS. Whilst existing co-morbidities may explain this, it is reasonable to assume that the institutional setting may facilitate transmission. Therefore, cases in LTCF require prompt investigation together with a better understanding of factors contributing to the acquisition of infection.

Epidemiological and Molecular Characterization of an Invasive Group A Streptococcus emm32.2 Outbreak.

ABSTRACTAn emm32.2 invasive group A streptococcus (iGAS) outbreak occurred in Liverpool from January 2010 to September 2012. This genotype had not previously been identified in Liverpool, but was responsible for 32% (14/44) of all iGAS cases reported during this time period. We performed a case-case comparison of emm32.2 iGAS cases with non-emm32.2 control iGAS cases identified in the Liverpool population over the same time period to assess patient risk factors for emm32.2 iGAS infection. The emm32.2 iGAS cases were confined to the adult population. We show that homelessness, intravenous drug use, and alcohol abuse predisposed patients to emm32.2 iGAS disease; however, no obvious epidemiological linkage between the patients with emm32.2 iGAS could be identified. Comparative whole-genome sequencing analysis of emm32.2 iGAS and non-emm32.2 control isolates was also performed to identify pathogen factors which might have driven the outbreak. We identified 19 genes, five of which had previously been implicated in virulence, which were present in all of the emm32.2 iGAS isolates but not present in any of the non-emm32.2 control isolates. We report that a novel emm32.2 genotype emerged in Liverpool in 2010 and identified a specific subset of genes, which could have allowed this novel emm32.2 genotype to persist in a disadvantaged population in the region over a 3-year period.

High Incidence of Invasive Group A Streptococcal Infections in Remote Indigenous Communities in Northwestern Ontario, Canada.

BackgroundWorldwide, indigenous populations appear to be at increased risk for invasive group A streptococcal (iGAS) infections. Although there is empirical evidence that the burden of iGAS disease is significant among remote First Nations communities in Northwestern Ontario, Canada, the epidemiology of iGAS infections in the area remains poorly characterized.MethodsIndividuals that met case definition for iGAS disease and whose laboratory specimens were processed by Meno Ya Win Health Centre in Sioux Lookout, Canada or who were reported to Thunder Bay District Health Unit, Canada were identified for the period 2009 to 2014. Case demographics, clinical severity, comorbidities, and risk factors were collected through chart review. Strain typing and antibiotic susceptibility were determined when possible. Basic descriptive statistics were calculated.ResultsSixty-five cases of iGAS disease were identified, for an annualized incidence of 56.2 per 100 000. Primary bacteremia was present in 26.2% of cases, and cellulitis was identified in 55.4% of cases. The most common comorbidities identified were diabetes (38.5%) and skin conditions (38.5%). Prevalent risk factors included alcohol dependence (25%). Fourteen different emm types were identified among 42 isolates, with the most common being emm114 (17.4%), emm11 (15.2%), and emm118 (13.0%). Resistance to erythromycin and clindamycin was found in 24.6% of isolates.ConclusionsRural and remote First Nations communities in Northwestern Ontario experience iGAS infections at a rate 10 times the provincial and national average. Compared with other North American series, a lower proportion of isolates causing infection were of emm types included in candidate GAS vaccines.