The Emergence and Impact of the M1UK Lineage on Invasive Group A Streptococcus Disease in Aotearoa New Zealand.

M1UK is associated with current surges in invasive infection globally, partly due to increased production of superantigen streptococcal pyrogenic exotoxin A. We show that M1UK is now the dominant invasive emm1 lineage in Aotearoa New Zealand and is genomically related to community infections, suggesting that measures that effectively prevent group A Streptococcus pharyngitis in children could reduce invasive disease.

Group A Streptococcal Toxic Shock Syndrome With Portal Vein Thrombosis: A Rare Presentation in Newborns.

Invasive disease due to group A Streptococcus infection results in a large spectrum of clinical manifestations. In the neonatal period, the occurrence is rare and potentially serious. We present a case of a term male newborn on the 9th day of life who was admitted to the emergency room with moaning and poor feeding. The patient was hemodynamically unstable needing mechanical ventilation and inotropic support. Mother and father had clinical symptoms of pharyngitis. Blood samples revealed high serum C-reactive protein and procalcitonin, leucopenia, thrombocytopenia, hyponatremia, hepatic cytolysis, and cholestasis. He started on IV ampicillin, gentamicin, and cefotaxime. Due to an abdominal distension, an ultrasound was done showing a heterogenous hepatic lobe. A color Doppler scan completed the study revealing a left hepatic thrombosis. Enoxaparin was started. The newborn's blood culture and mother's milk were positive for the same strain of group A Streptococcus. Intravenous immunoglobulin and clindamycin were added to the treatment. On day 5 of treatment, inotropic support was ceased and extubation took place on day 6. Neonatologists should be aware of rare complications of group A Streptococcus infection such as thrombotic events.

A Diagnostic Dilemma: Clindamycin-Resistant Group A Streptococcal Toxic Shock Syndrome Leading to Acute Respiratory Distress Syndrome (ARDS) With Multiple Possible Sources.

Group A Streptococcal (GAS) infections can potentially progress into streptococcal toxic shock syndrome (STSS) with multiorgan failure. Even with a benign presentation, GAS can rapidly lead to fatal necrotizing infections. While myositis and cutaneous infections are the typical initial presentation of STSS, genitourinary infections are a less common source. This report presents a case of a previously healthy woman with the chief complaint of ankle pain who subsequently developed streptococcal toxic shock syndrome and multiorgan failure from a Group A streptococcus infection of the genitourinary tract. She was treated with antibiotics and medical management for her septic shock and required prone ventilation for her acute respiratory distress syndrome (ARDS) but eventually recovered without surgery. This case highlights the importance of recognizing unusual presentations of Group A Strep infections, which have the potential to lead to rapid deterioration in patients. Also described are antibiotic and ventilator strategies that can be used to treat these severe systemic infections.

Evaluation of the efficacy of MONTANIDE™ GR01, a new adjuvant for feed-based vaccines, on the immune response and protection against Streptococcus agalactiae in oral vaccinated Nile tilapia (Oreochromis niloticus) under laboratory and on-farm conditions.

Streptococcosis, an emerging infectious disease caused by Streptococcus agalactiae, has had adverse effects on farmed tilapia. Several vaccines have been developed to prevent this disease and induce a specific immune response against S. agalactiae infection. In this study the use of MONTANIDE™ GR01, a new adjuvant for oral vaccination, was optimized for use in tilapia under laboratory and field studies. In the laboratory trial the immune response and protective efficacy of two doses of MONTANIDE™ GR01, 20 % (w/w) and 2 % (w/w), included into the feed-based adjuvanted vaccines were assessed comparatively. Following immunization, the innate immune parameters studied in serum, including lysozyme, myeloperoxidase, catalase and glutathione peroxidase activity, were all increased significantly. Furthermore, specific IgM antibodies against S. agalactiae were induced significantly in serum post-vaccination, with higher levels observed in both groups that received the feed-based adjuvanted vaccine. Under both injection and immersion challenge conditions, the relative percent survival for the feed-based adjuvanted vaccine groups ranged from 78 % to 84 %. Following use of the low dose concentration of MONTANIDE™ GR01 for oral vaccination of tilapia in cage culture systems, several innate immune parameters were effectively enhanced in the immunized fish. Similarly, the levels of specific IgM antibodies in the serum of feed-based vaccinated fish were significantly enhanced, reaching their highest levels 2-5 months post-vaccination. Cytokines associated with innate and adaptive immunity were also examined, and the expression levels of several genes showed significant up-regulation. This indicates that both cellular and humoral immune responses were induced by the feed-based adjuvanted vaccine. The economic impact of a feed-based adjuvanted vaccine was examined following vaccination, considering the growth performance and feed utilization of the fish. It was found that the Economic Performance Index and Economic Conversion Ratio were unaffected by vaccination, further demonstrating that there are no negative impacts associated with administering a feed-based vaccine to fish. In conclusion, the data from this study indicate that MONTANIDE™ GR01 is a highly valuable adjuvant for oral vaccination, as demonstrated by its ability to induce a strong immune response and effectively prevent streptococcal disease in Nile tilapia.

The associations between invasive group A streptococcal disease and infection with influenza, varicella, or hepatitis C viruses: A data linkage study, Victoria, Australia.

OBJECTIVES: To quantify the associations between invasive group A streptococcal disease (iGAS) incidence and influenza, varicella, and chronic hepatitis C virus (HCV). METHODS: We used individual-level linked data of iGAS cases from Victoria, Australia (2007-2017) to assess associations between these viral infections and iGAS. A self-controlled case series method was used to estimate the relative incidence of iGAS following an influenza or varicella infection, while the relative incidence of iGAS among HCV cases, and HCV cases who inject drugs, was estimated using population-level data and a negative binomial regression model. RESULTS: Of the 1949 individuals with at least one iGAS diagnosis, 82 were diagnosed with influenza at least once, 30 with varicella, and 118 with HCV during the study period. The relative incidence of iGAS increased substantially following infection with influenza (incidence rate ratio [IRR]: 34.5, 95% confidence interval [CI]: 21.3-55.8) or varicella (IRR: 22.4, 95% CI: 10.3-48.8). iGAS incidence was higher among HCV cases (IRR: 5.7, 95% CI: 4.4-7.3) compared to individuals without HCV. iGAS incidence was also higher among HCV cases who inject drugs (IRR: 17.9, 95% CI: 13.0-24.4) compared to individuals without HCV who did not inject drugs. CONCLUSIONS: We found a significantly higher risk of iGAS following an influenza or varicella infection and for chronic HCV cases, particularly those who inject drugs. These findings are relevant to public health practice and support the timely identification of iGAS cases.

Narcolepsy type 1 and Sydenham chorea - Report of 3 cases and review of the literature.

OBJECTIVES/BACKGROUND: Narcolepsy type 1 (NT1) is an immune-mediated disorder characterized by excessive daytime sleepiness, cataplexy, low levels of hypocretin-1 in the cerebrospinal fluid, and a strong association with the HLA DQB1*06:02 allele. There is evidence for streptococcal infections as one pathogenic factor that may lead to NT1 as part of a multifactorial pathogenesis. Elevated titers of Antistreptolysin-O antibodies and increased inflammatory activity in response to streptococci antigens have been described in patients with NT1. Sydenham chorea (SC) results from a post-streptococcal autoimmune process targeting basal ganglia neurons. Despite this common trigger, SC has been interpreted as a misdiagnosis in a few described cases of patients who were first diagnosed with SC and later with NT1. Our goal was to analyze the association between SC and NT1. PATIENTS/METHODS: We reviewed the literature and report three patients from three European sleep centers who were diagnosed with both SC and NT1 within a few months. RESULTS: We describe the cases of one male (age 10) and two female (age 22 and 10) patients. CONCLUSIONS: We argue that in those cases both diagnoses are justified, unlike reports of previous cases in which SC was considered a misdiagnosis in patients with NT1. It remains, however, unclear if the conditions occur independently or if there is an overlap disorder- an SC-like subtype of narcolepsy with a particular sequence of symptoms. Further studies need to clarify the causality of the relationship and the pathophysiology of the reported rare association.

Higher body mass index after intrapartum antibiotic exposure in children persists over 10-years.

Exposure to intrapartum antibiotic prophylaxis to reduce perinatal group B streptococcal disease was associated with increased childhood body mass index (BMI) persisting to age 10 years compared to no exposure (Δ BMI at 10 years: vaginal delivery 0.14 kg/m2 , caesarean 0.40 kg/m2 ).

Increasing Incidence of Invasive Group A Streptococcus Disease, Idaho, USA, 2008-2019.

We investigated invasive group A Streptococcus epidemiology in Idaho, USA, during 2008-2019 using surveillance data, medical record review, and emm (M protein gene) typing results. Incidence increased from 1.04 to 4.76 cases/100,000 persons during 2008-2019. emm 1, 12, 28, 11, and 4 were the most common types, and 2 outbreaks were identified. We examined changes in distribution of clinical syndrome, patient demographics, and risk factors by comparing 2008-2013 baseline with 2014-2019 data. Incidence was higher among all age groups during 2014-2019. Streptococcal toxic shock syndrome increased from 0% to 6.4% of cases (p = 0.02). We identified no differences in distribution of demographic or risk factors between periods. Results indicated that invasive group A Streptococcus is increasing among the general population of Idaho. Ongoing surveillance of state-level invasive group A Streptococcus cases could help identify outbreaks, track regional trends in incidence, and monitor circulating emm types.

The epidemiology of invasive group A streptococcal disease in Victoria, 2007-2017: an analysis of linked datasets.

OBJECTIVE: To describe the incidence and severity of invasive group A streptococcal disease (iGAS) in Victoria, Australia. METHODS: Retrospective analysis of iGAS cases identified in linked datasets, 2007-2017: laboratory data from the Victorian Hospital Pathogen Surveillance Scheme; hospitalisation data from the Victorian Admitted Episodes Dataset; and deaths reported by the Australian Coordinating Registry. RESULTS: There were 1,369 confirmed and 610 probable cases of iGAS identified from 2007 to 2017 in Victoria, Australia. The median annual incidence was 3.1 (range 2.4-5.2) per 100,000 population. The incidence was highest in 2017, with 5.2 (95%CI: 4.6-5.8) cases per 100,000 population. The median length of stay in hospital was 10 days, with 33.1% (578/1,744) of cases admitted to the intensive care unit, of whom 49.5% (286/578) were mechanically ventilated. The case fatality rate was 5.6% (110/1,979), reaching 13.5% (51/378) among those aged 75 years or older. CONCLUSIONS: There was an increased incidence of iGAS in 2017 in Victoria, with substantial healthcare utilisation and a high case fatality rate among older Victorians. IMPLICATIONS FOR PUBLIC HEALTH: These data support mandatory notification of iGAS, which will enable better characterisation of the disease, rapid identification of changes in epidemiology and targeted public health responses.

Public health response following an iGAS outbreak in a residential aged care facility in Queensland.

Abstract: During an 18-day period, beginning in April 2020, three residents with invasive group A streptococcal infections (iGAS) were reported at a single residential aged care facility (RACF) in Brisbane's northern geographical region. All three cases were hospitalised with severe illness; two of the cases died as a result of the illness. The Metro North Public Health Unit (PHU) led the public health investigation and response, targeting infection control measures and offering chemoprophylaxis to all 142 staff and 119 residents at the facility. The outbreak was declared over in June, after 30 days of no new cases. Isolates from all three cases were shown to have identical strain typing, emm89. The benefits and challenges of implementing mass chemoprophylaxis in this setting are discussed.

The cost of care for children hospitalised with Invasive Group A Streptococcal Disease in Australia.

BACKGROUND: Invasive Group A Streptococcal (iGAS) disease exerts an important burden among Australian children. No Australian hospitalisation cost estimates for treating children with iGAS disease exist, so the financial impact of this condition is unknown. AIM: To determine the minimum annual healthcare cost for children (< 18 years) hospitalised with iGAS disease in Australia from a healthcare sector perspective. METHODS: A cost analysis including children with laboratory-confirmed iGAS disease hospitalised at the Royal Children's Hospital (Victoria, Australia; July 2016 to June 2019) was performed. Results were extrapolated against the national minimum iGAS disease incidence. This analysis included healthcare cost from the 7 days prior to the index admission via General Practitioner (GP) and Emergency Department (ED) consultations; the index admission itself; and the 6 months post index admission via rehabilitation admissions, acute re-admissions and outpatient consultations. Additional extrapolations of national cost data by age group, Aboriginal and Torres Strait Islander ethnicity and jurisdiction were performed. RESULTS: Of the 65 included children, 35% (n = 23) were female, 5% (n = 3) were Aboriginal and Torres Strait Islander, and the average age was 4.4 years (SD 4.6; 65% aged 0-4). The iGAS disease related healthcare cost per child was $67,799 (SD $92,410). These costs were distributed across the 7 days prior to the index admission via GP and ED consultations (0.2 and 1.1% of total costs, respectively), the index admission itself (88.7% of the total costs); and the 6 months post index admission via rehabilitation admissions, acute re-admissions and outpatient consultations (5.3, 4.5 and 0.1% of total costs, respectively). Based on a national minimum paediatric incidence estimation of 1.63 per 100,000 children aged < 18 (95%CI: 1.11-2.32), the total annual healthcare cost for children with iGAS in 2019 was $6,200,862. The financial burden reflects the overrepresentation of Aboriginal and Torres Strait Islander people in the occurrence of iGAS disease. Costs were concentrated among children aged 0-4 years (62%). CONCLUSION: As these cost estimations were based on a minimum incidence, true costs may be higher. Strengthening of surveillance and control of iGAS disease, including a mandate for national notification of iGAS disease, is warranted. TRIAL REGISTRATION: The current study is a part of ongoing iGAS surveillance work across seven paediatric health services in Australia. As this is not a clinical trial, it has not undergone trial registration.

Disease burden due to Group B Streptococcus in the Indian population and the need for a vaccine - a narrative review.

Streptococcus agalactiae, a Gram-positive bacterium, causes invasive infection known as Group B streptococcal disease (GBS). It is a leading cause of neonatal death and complications prior to delivery. The burden of GBS is unknown in India despite the high incidence of preterm and stillbirths. In this study, we performed a narrative review of the available literature (published in the last 10 years) on the epidemiology of GBS, using PubMed and Google Scholar, to understand its impact in India and evaluate potential strategies to prevent the disease in the high-risk population, that is, neonates. The review showed that the incidence of early- and late-onset GBS in neonates (per 1000 live births) was in the ranges of 0.090-0.68 and 0.0-0.07 respectively. The overall case fatality rate reported in only one study was 0.63. In pregnant women, the prevalence of GBS colonization was 2-62% and its transmission to their newborns varied from 6.7% to 11.1%. The serotype distribution of GBS is unclear, but some studies reported the distribution of types Ia, Ib, II, III, V, VII among pregnant women in India. The associated risk factors for GBS colonization in pregnant women are unclear but a few studies suggest the role of age and multigravida, while the risk factors in neonates include preterm birth, prolonged rupture of membrane (⩾18 h), maternal fever, obstetric complications, and prolonged labor >18 h. Screening of GBS is not a routine practice in India and intrapartum antibiotics prophylaxis is limited to only in risk conditions to prevent neonatal disease transmission. A few studies also suggest that high birth rate, poor detection methods, and financial constraints limit routine GBS screening in a developing country such as India. Hence, maternal vaccination is the most promising strategy to prevent neonatal GBS and Pfizer's hexavalent GBS conjugate vaccine (GBS6) is being developed for GBS neonatal disease.

Uncovering Infant Group B Streptococcal (GBS) Disease Clusters in the United Kingdom and Ireland Through Genomic Analysis: A Population-based Epidemiological Study.

BACKGROUND: The true frequency of hospital outbreaks of invasive group B streptococcal (iGBS; Streptococcus agalactiae) disease in infants is unknown. We used whole genome sequencing (WGS) of iGBS isolates collected during a period of enhanced surveillance of infant iGBS disease in the UK and Ireland to determine the number of clustered cases. METHODS: Potentially linked iGBS cases from infants with early (<7 days of life) or late-onset (7-89 days) disease were identified from WGS data (HiSeq 2500 platform, Illumina) from clinical sterile site isolates collected between 04/2014 and 04/2015. We assessed time and place of cases to determine a single-nucleotide polymorphism (SNP) difference threshold for clustered cases. Case details were augmented through linkage to national hospital admission data and hospital record review by local microbiologists. RESULTS: Analysis of sequences indicated a cutoff of ≤5 SNP differences to define iGBS clusters. Among 410 infant iGBS isolates, we identified 7 clusters (4 genetically identical pairs with 0 SNP differences, 1 pair with 3 SNP differences, 1 cluster of 4 cases with ≤1 SNP differences) of which 4 clusters were uncovered for the first time. The clusters comprised 16 cases, of which 15 were late-onset (of 192 late-onset cases with sequenced isolates) and 1 an early-onset index case. Serial intervals between cases ranged from 0 to 59 (median 12) days. CONCLUSIONS: Approximately 1 in 12 late-onset infant iGBS cases were part of a hospital cluster. Over half of the clusters were previously undetected, emphasizing the importance of routine submission of iGBS isolates to reference laboratories for cluster identification and genomic confirmation.

Hospital clusters of invasive Group B Streptococcal disease: A systematic review.

OBJECTIVES: To characterize outbreaks of invasive Group B Streptococcal (iGBS) disease in hospitals. METHODS: Systematic review using electronic databases to identify studies describing iGBS outbreaks/clusters or cross-infection/acquisition in healthcare settings where 'cluster' was defined as ≥2 linked cases. PROSPERO CRD42018096297. RESULTS: Twenty-five references were included describing 30 hospital clusters (26 neonatal, 4 adult) in 11 countries from 1966 to 2019. Cross-infection between unrelated neonates was reported in 19 clusters involving an early-onset (<7 days of life; n = 3), late-onset (7-90 days; n = 13) index case or colonized infant (n = 3) followed by one or more late-onset cases (median serial interval 9 days (IQR 3-17, range 0-50 days, n = 45)); linkage was determined by phage typing in 3 clusters, PFGE/MLST/PCR in 8, WGS in 4, non-molecular methods in 4. Postulated routes of transmission in neonatal clusters were via clinical personnel and equipment, particularly during periods of crowding and high patient-to-nurse ratio. Of 4 adult clusters, one was attributed to droplet spread between respiratory cases, one to handling of haemodialysis catheters and two unspecified. CONCLUSIONS: Long intervals between cases were identified in most of the clusters, a characteristic which potentially hinders detection of GBS hospital outbreaks without enhanced surveillance supported by genomics.

The distribution of clones of Streptococcus agalactiae (group B streptococci) among herdspersons and dairy cows demonstrates lack of host specificity for some lineages.

Streptococcus agalactiae (Group B streptococcus, GBS) is a commensal of the human intestinal tract and vagina and is also an opportunistic pathogen causing serious, potentially lethal, infections preferentially in newborns and in the elderly. In cattle, it is considered an udder-specific pathogen and a common cause of mastitis. Here we investigated the host specificity of GBS by examining their colonization at various anatomical sites in both cattle and humans, as well as the possible cross-species transmission in closed barn environments. We collected more than 800 swab samples from dairy cows and herdspersons at eight dairy farms in Denmark. GBS was isolated from 12% of the samples. The GBS strains (N = 105) were characterized by biochemical test, serology, and Pulsed-Field Gel Electrophoresis (PFGE). Based on the PFGE patterns, 25 strains were selected for whole genome sequencing followed by phylogenetic analyses. The genomes were compared to each other and to a collection of publicly available GBS genomes. The study revealed that GBS clones were shared by cows and herdspersons. In phylogenetic analyses, these shared clones clustered with GBS strains from persons with no relation to farming. Horizontal cross-species transmission of the contagion in both directions was found to be highly likely within the same environment; thus, some cases of bovine mastitis are probably antrophonotic.

Prolonged and large outbreak of invasive group A Streptococcus disease within a nursing home: repeated intrafacility transmission of a single strain.

OBJECTIVES: Multiple invasive group A Streptococcus (GAS) infections were reported to public health by a skilled nursing facility (facility A) in Illinois between May 2014 and August 2016. Cases continued despite interventions including antibiotic prophylaxis for all residents and staff. Two other geographically close facilities reported contemporaneous outbreaks of GAS. We investigated potential reasons for ongoing transmission. METHODS: We obtained epidemiologic data from chart review of cases and review of facility and public health records from previous investigations into the outbreak. Infection control practices at facility A were observed and evaluated. Whole genome sequencing followed by phylogenetic analysis was performed on available isolates from the three facilities. RESULTS: From 2014 to 2016, 19 invasive and 60 noninvasive GAS infections were identified at facility A occurring in three clusters. Infection control evaluations during clusters 2 and 3 identified hand hygiene compliance rates of 14% to 25%, appropriate personal protective equipment use in only 33% of observed instances, and deficient wound-care practices. GAS isolates from residents and staff of all three facilities were subtype emm89.0; on phylogenetic analysis, facility A isolates were monophyletic and distinct. CONCLUSIONS: Inadequate infection control and improper wound-care practices likely led to this 28-month-long outbreak of severe infections in a skilled nursing facility. Whole genome sequencing and phylogenetic analysis suggested that intrafacility transmission of a single highly transmissible GAS strain was responsible for the outbreak in facility A. Integration of genomic epidemiology tools with traditional epidemiology and infection control assessments was helpful in investigation of a facility-wide outbreak.