scholarly journals The Shock of Strep: Rapid Deaths Due to Group a Streptococcus

2018 ◽  
Vol 8 (1) ◽  
pp. 136-149 ◽  
Author(s):  
Katrina M. Thompson ◽  
Alana K. Sterkel ◽  
Joseph A. McBride ◽  
Robert F. Corliss
Keyword(s):  
Streptococcus Pyogenes ◽  
Group A Streptococcus ◽  
Invasive Disease ◽  
Significant Morbidity ◽  
Invasive Group ◽  
Life Threatening ◽  
Group A ◽  
Severe Infections ◽  
Microscopic Findings ◽  
Positive Coccus

Streptococcus pyogenes, also known as group A beta-hemolytic strep, is a Gram positive coccus responsible for several million infections every year. The types of infections vary widely from pharyngitis to myositis, but all can advance to severe life threatening invasive disease. Of those infected, approximately 1100 to 1600 people die each year due to invasive disease. Why certain individuals contract severe infections is not known, but many strains of Streptococcus pyogenes are known to produce toxins and superantigens. Invasive Streptococcus pyogenes infections have been shown to cause significant morbidity and rapid mortality. In many cases, patients expire before full antemortem testing can be performed, causing physicians and families to look to forensic pathologists for answers. Understanding the pathogenesis of invasive group A strep infections, relevant gross and microscopic findings, and proper culturing techniques is critical for forensic pathologists to diagnosis this condition and assist in the education and protection of the communities they serve.

scholarly journals Invasive group A Streptococcus disease in Australian children: 2016 to 2018 – a descriptive cohort study

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Jane Oliver ◽  
◽  
Elise Thielemans ◽  
Alissa McMinn ◽  
Ciara Baker ◽  
...  
Keyword(s):  
Disease Surveillance ◽  
Vaccine Development ◽  
Group A Streptococcus ◽  
Invasive Disease ◽  
Incidence Rates ◽  
Surveillance Systems ◽  
Invasive Group ◽  
Australian State ◽  
Life Threatening ◽  
Group A

Abstract Objectives Invasive group A Streptococcus (iGAS) disease is serious and sometimes life-threatening. The Paediatric Active Enhanced Disease Surveillance (PAEDS) Network collects voluntary notifications from seven major Australian paediatric hospitals on patients with certain conditions, including iGAS disease. Our aims were to: 1) Describe the epidemiological distribution of paediatric iGAS disease in Australia and correlate this with influenza notifications, 2) Identify GAS strains commonly associated with invasive disease in children. Methods IGAS and influenza notification data were obtained (from the PAEDS Network and the Australian Institute of Health and Welfare, respectively, for the period 1 July 2016 to 30 June 2018). Included iGAS patients had GAS isolated from a normally sterile body site. Data were described according to selected clinical and demographic characteristics, including by age group and Australian State, with proportions and minimum incidence rates estimated. Results A total of 181 patients were identified, with most (115, 63.5%) <5 years old. The mean annual minimum incidence rate was 1.6 (95% confidence interval: 1.1–2.3) per 100,000 children across the study period. An epidemiological correlation with the seasonal burden of influenza was noted. Contact prophylaxis was not consistently offered. Of 96 patients with emm-typing results available, 72.9% showed emm-1, −4 or − 12. Conclusions Robust surveillance systems and cohesive patient management guidelines are needed. Making iGAS disease nationally notifiable would help facilitate this. Influenza vaccination may contribute to reducing seasonal increases in iGAS incidence. The burden of disease emphasises the need for ongoing progress in GAS vaccine development.

scholarly journals Streptococcus pyogenes evades adaptive immunity through specific IgG glycan hydrolysis

2019 ◽  
Vol 216 (7) ◽  
pp. 1615-1629 ◽  
Author(s):  
Andreas Naegeli ◽  
Eleni Bratanis ◽  
Christofer Karlsson ◽  
Oonagh Shannon ◽  
Raja Kalluru ◽  
...  
Keyword(s):  
Streptococcus Pyogenes ◽  
Vaccine Development ◽  
Group A Streptococcus ◽  
Invasive Infection ◽  
Invasive Infections ◽  
Life Threatening ◽  
Group A ◽  
Specific Igg

Streptococcus pyogenes (Group A streptococcus; GAS) is a human pathogen causing diseases from uncomplicated tonsillitis to life-threatening invasive infections. GAS secretes EndoS, an endoglycosidase that specifically cleaves the conserved N-glycan on IgG antibodies. In vitro, removal of this glycan impairs IgG effector functions, but its relevance to GAS infection in vivo is unclear. Using targeted mass spectrometry, we characterized the effects of EndoS on host IgG glycosylation during the course of infections in humans. Substantial IgG glycan hydrolysis occurred at the site of infection and systemically in the severe cases. We demonstrated decreased resistance to phagocytic killing of GAS lacking EndoS in vitro and decreased virulence in a mouse model of invasive infection. This is the first described example of specific bacterial IgG glycan hydrolysis during infection and thereby verifies the hypothesis that EndoS modifies antibodies in vivo. This mechanisms of immune evasion could have implications for treatment of severe GAS infections and for future efforts at vaccine development.

scholarly journals Survey of the bp/tee genes from clinical group A streptococcus isolates in New Zealand – implications for vaccine development

2014 ◽  
Vol 63 (12) ◽  
pp. 1670-1678 ◽  
Author(s):  
John D. Steemson ◽  
Nicole J. Moreland ◽  
Deborah Williamson ◽  
Julie Morgan ◽  
Philip E. Carter ◽  
...  
Keyword(s):  
New Zealand ◽  
Vaccine Development ◽  
Group A Streptococcus ◽  
Invasive Disease ◽  
T Antigen ◽  
Clinical Group ◽  
Wide Range ◽  
Life Threatening ◽  
Group A ◽  
The Individual

Group A streptococcus (GAS) is responsible for a wide range of diseases ranging from superficial infections, such as pharyngitis and impetigo, to life-threatening diseases, such as toxic shock syndrome and acute rheumatic fever (ARF). GAS pili are hair-like extensions protruding from the cell surface and consist of highly immunogenic structural proteins: the backbone pilin (BP) and one or two accessory pilins (AP1 and AP2). The protease-resistant BP builds the pilus shaft and has been recognized as the T-antigen, which forms the basis of a major serological typing scheme that is often used as a supplement to M typing. A previous sequence analysis of the bp gene (tee gene) in 39 GAS isolates revealed 15 different bp/tee types. In this study, we sequenced the bp/tee gene from 100 GAS isolates obtained from patients with pharyngitis, ARF or invasive disease in New Zealand. We found 20 new bp/tee alleles and four new bp/tee types/subtypes. No association between bp/tee type and clinical outcome was observed. We confirmed earlier reports that the emm type and tee type are associated strongly, but we also found exceptions, where multiple tee types could be found in certain M/emm type strains, such as M/emm89. We also reported, for the first time, the existence of a chimeric bp/tee allele, which was assigned into a new subclade (bp/tee3.1). A strong sequence conservation of the bp/tee gene was observed within the individual bp/tee types/subtypes (>97 % sequence identity), as well as between historical and contemporary New Zealand and international GAS strains. This temporal and geographical sequence stability provided further evidence for the potential use of the BP/T-antigen as a vaccine target.

scholarly journals Prevalence and Characterization of Invasive Isolates of Streptococcus pyogenes with Reduced Susceptibility to Fluoroquinolones

2005 ◽  
Vol 49 (5) ◽  
pp. 2130-2132 ◽  
Author(s):  
Jeff Powis ◽  
Allison McGeer ◽  
Carla Duncan ◽  
Ryan Goren ◽  
Joyce C. S. de Azavedo ◽  
...  
Keyword(s):  
Streptococcus Pyogenes ◽  
Susceptibility Testing ◽  
Group A Streptococcus ◽  
Invasive Group ◽  
Group A

ABSTRACT Fluoroquinolone susceptibility testing was performed on invasive group A streptococcus isolates from 1992-1993 and 2003 from Ontario, Canada. None were nonsusceptible to levofloxacin. Two of 153 (1.3%) from 1992-1993 and 7 of 160 (4.4%) from 2003 had a levofloxacin MIC of 2 μg/ml; all nine had parC mutations, and eight were serotype M6.

scholarly journals Canada-Wide Epidemic of emm74 Group A Streptococcus Invasive Disease

2018 ◽  
Vol 5 (5) ◽  
Author(s):  
Sarah Teatero ◽  
Allison McGeer ◽  
Gregory J Tyrrell ◽  
Linda Hoang ◽  
Hanan Smadi ◽  
...  
Keyword(s):  
Group A Streptococcus ◽  
Invasive Disease ◽  
Drug Usage ◽  
Rare Type ◽  
Invasive Group ◽  
Intravenous Drug Usage ◽  
Clinical Data Analysis ◽  
Invasive Infections ◽  
Group A ◽  
Canadian Provinces

Abstract Background 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. Methods 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. Results 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 &gt;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. Conclusions 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.

scholarly journals Streptococcus pyogenes prtFII, but not sfbI, sfbII or fbp54, is represented more frequently among invasive-disease isolates of tropical Australia

2002 ◽  
Vol 128 (3) ◽  
pp. 391-396 ◽  
Author(s):  
A. DELVECCHIO ◽  
B. J. CURRIE ◽  
J. D. McARTHUR ◽  
M. J. WALKER ◽  
K. S. SRIPRAKASH
Keyword(s):  
Streptococcus Pyogenes ◽  
Group A Streptococcus ◽  
Invasive Disease ◽  
Host Cells ◽  
Non Invasive ◽  
Invasive Diseases ◽  
Genetic Endowment ◽  
Group A ◽  
Tropical Australia

Streptococcus pyogenes (group A streptococcus) strains may express several distinct fibronectin-binding proteins (FBPs) which are considered as major streptococcal adhesins. Of the FBPs, SfbI was shown in vitro to promote internalization of the bacterium into host cells and has been implicated in persistence. In the tropical Northern Territory, where group A streptococcal infection is common, multiple genotypes of the organism were found among isolates from invasive disease cases and no dominant strains were observed. To determine whether any FBPs is associated with invasive disease propensity of S. pyogenes, we have screened streptococcal isolates from bacteraemic and necrotizing fasciitis patients and isolates from uncomplicated infections for genetic endowment of 4 FBPs. No difference was observed in the distribution of sfbII, fbp54 and sfbI between the blood isolates and isolates from uncomplicated infection. We conclude that the presence of sfbI does not appear to promote invasive diseases, despite its association with persistence. We also show a higher proportion of group A streptococcus strains isolated from invasive disease cases possess prtFII when compared to strains isolated from non-invasive disease cases. We suggest that S. pyogenes may recruit different FBPs for different purposes.

scholarly journals Rapid Emergence of a New Clone Impacts the Population at Risk and Increases the Incidence of Type emm89 Group A Streptococcus Invasive Disease

2017 ◽  
Vol 4 (2) ◽  
Author(s):  
Sarah Teatero ◽  
Brenda L. Coleman ◽  
Stephen B. Beres ◽  
Randall J. Olsen ◽  
Christopher Kandel ◽  
...  
Keyword(s):  
Group A Streptococcus ◽  
Invasive Disease ◽  
Population Based ◽  
Invasive Group ◽  
Clonal Variant ◽  
Clinical Presentations ◽  
Group A ◽  
Tract Infections ◽  
Rapid Shift ◽  
Rapid Emergence

Abstract Background Invasive group A Streptococcus (iGAS) disease caused by type emm89 strains has been increasing worldwide, driven by the emergence of an epidemic clonal variant (clade 3 emm89). The clinical characteristics of patients with emm89 iGAS disease, and in particular with clade 3 emm89 iGAS disease, are poorly described. Methods We used population-based iGAS surveillance data collected in metropolitan Toronto, Ontario, Canada during the period 2000–2014. We sequenced the genomes of 105 emm89 isolates representing all emm89 iGAS disease cases in the area during the period and 138 temporally matched emm89 iGAS isolates collected elsewhere in Ontario. Results Clades 1 and 2 and clade O, a newly discovered emm89 genetic variant, caused most cases of emm89 iGAS disease in metropolitan Toronto before 2008. After rapid emergence of new clade 3, previously circulating clades were purged from the population and the incidence of emm89 iGAS disease significantly increased from 0.14 per 100000 in 2000–2007 to 0.22 per 100000 in 2008–2014. Overall, emm89 organisms caused significantly more arthritis but less necrotizing fasciitis than strains of the more common type emm1. Other clinical presentations were soft tissue and severe respiratory tract infections. Clinical outcomes did not differ significantly between emm89 clades overall. However, clade 3 emm89 iGAS disease was more common in youth and middle-aged individuals. Conclusions The rapid shift in emm89 iGAS strain genetics in metropolitan Toronto has resulted in a significant increase in the incidence of emm89 iGAS disease, with noticeably higher rates of clade 3 disease in younger patients.

scholarly journals Antibiotic Treatment, Mechanisms for Failure, and Adjunctive Therapies for Infections by Group A Streptococcus

2021 ◽  
Vol 12 ◽  
Author(s):  
Anders F. Johnson ◽  
Christopher N. LaRock
Keyword(s):  
Streptococcus Pyogenes ◽  
Disease Burden ◽  
Group A Streptococcus ◽  
Human Pathogen ◽  
Invasive Infections ◽  
Group A ◽  
Severe Infections ◽  
Treatment Mechanisms ◽  
Antibiotic Failure ◽  
Global Disease Burden

Group A Streptococcus (GAS; Streptococcus pyogenes) is a nearly ubiquitous human pathogen responsible for a significant global disease burden. No vaccine exists, so antibiotics are essential for effective treatment. Despite a lower incidence of antimicrobial resistance than many pathogens, GAS is still a top 10 cause of death due to infections worldwide. The morbidity and mortality are primarily a consequence of the immune sequelae and invasive infections that are difficult to treat with antibiotics. GAS has remained susceptible to penicillin and other β-lactams, despite their widespread use for 80 years. However, the failure of treatment for invasive infections with penicillin has been consistently reported since the introduction of antibiotics, and strains with reduced susceptibility to β-lactams have emerged. Furthermore, isolates responsible for outbreaks of severe infections are increasingly resistant to other antibiotics of choice, such as clindamycin and macrolides. This review focuses on the challenges in the treatment of GAS infection, the mechanisms that contribute to antibiotic failure, and adjunctive therapeutics. Further understanding of these processes will be necessary for improving the treatment of high-risk GAS infections and surveillance for non-susceptible or resistant isolates. These insights will also help guide treatments against other leading pathogens for which conventional antibiotic strategies are increasingly failing.

scholarly journals IgG Protease Mac/IdeS Is Not Essential for Phagocyte Resistance or Mouse Virulence of M1T1 Group A Streptococcus

mBio ◽  
2013 ◽  
Vol 4 (4) ◽  
Author(s):  
Cheryl Y. M. Okumura ◽  
Ericka L. Anderson ◽  
Simon Döhrmann ◽  
Dan N. Tran ◽  
Joshua Olson ◽  
...  
Keyword(s):  
Group A Streptococcus ◽  
Living Organism ◽  
Immune Defense ◽  
Common Disease ◽  
Invasive Infection ◽  
Invasive Infections ◽  
Life Threatening ◽  
Group A ◽  
Severe Infections ◽  
Human Infections

ABSTRACT The Mac/IdeS protein of group A Streptococcus (GAS) is a secreted cysteine protease with cleavage specificity for IgG and is highly expressed in the GAS serotype M1T1 clone, which is the serotype most frequently isolated from patients with life-threatening invasive infections. While studies of Mac/IdeS with recombinant protein have shown that the protein can potentially prevent opsonophagocytosis of GAS by neutrophils, the role of the protein in immune evasion as physiologically produced by the living organism has not been studied. Here we examined the contribution of Mac/IdeS to invasive GAS disease by generating a mutant lacking Mac/IdeS in the hyperinvasive M1T1 background. While Mac/IdeS was highly expressed and proteolytically active in the hyperinvasive strain, elimination of the bacterial protease did not significantly influence GAS phagocytic uptake, oxidative-burst induction, cathelicidin sensitivity, resistance to neutrophil or macrophage killing, or pathogenicity in pre- or postimmune mouse infectious challenges. We conclude that in the highly virulent M1T1 background, Mac/IdeS is not essential for either phagocyte resistance or virulence. Given the conservation of Mac/IdeS and homologues across GAS strains, it is possible that Mac/IdeS serves another important function in GAS ecology or contributes to virulence in other strain backgrounds. IMPORTANCE Group A Streptococcus (GAS) causes human infections ranging from strep throat to life-threatening conditions such as flesh-eating disease and toxic shock syndrome. Common disease-associated clones of GAS can cause both mild and severe infections because of a characteristic mutation and subsequent change in the expression of several genes that develops under host immune selection. One of these genes encodes Mac/IdeS, a protease that has been shown to cleave antibodies important to the immune defense system. In this study, we found that while Mac/IdeS is highly expressed in hypervirulent GAS, it does not significantly contribute to the ability of the bacteria to survive white blood cell killing or produce invasive infection in the mouse. These data underscore the importance of correlating studies on virulence factor function with physiologic expression levels and the complexity of streptococcal pathogenesis and contribute to our overall understanding of how GAS causes disease.

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