scholarly journals 1200. Risk of group A streptococcal Transmission Among the Pediatric Population in the Houston Area

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S621-S622
Author(s):  
zain I Alamarat ◽  
Lauren Sommer ◽  
Jonathon C McNeil ◽  
Anthony R Flores
Keyword(s):  
Group A Streptococcus ◽  
Medical Center ◽  
Pediatric Population ◽  
National Level ◽  
Invasive Disease ◽  
Streptococcal Toxic Shock Syndrome ◽  
Passive Surveillance System ◽  
Superficial Skin ◽  
Group A ◽  
Index Cases

Abstract Background Disease due to group A Streptococcus (GAS) occurs frequently in children and usually manifests as pharyngitis or superficial skin infections. However, invasive disease (iGAS) such as necrotizing fasciitis or streptococcal toxic shock syndrome is responsible for significant morbidity and mortality. National-level surveillance at the Centers for Disease Control and Prevention (CDC) estimates >10,000 cases and ~1,500 deaths due to iGAS occur annually in the US. Much interest revolves around the ability to detect potential transmission events (PTEs) of GAS disease using surveillance data as such information may change recommendations for chemoprophylaxis of close contacts. Studies by the CDC have shown a secondary attack rate from 66.1 to 102 /100,000, primarily occurring among older adults with co-morbidities. However, previous studies were limited in that the GAS surveillance was limited to iGAS disease. Methods Retrospective study using a comprehensive GAS passive surveillance system. GAS isolates and associated metadata were obtained from 2 hospital systems in the Texas Medical Center from 2017-2019. Molecular emm typing of GAS isolates was performed using the CDC protocol. PTEs were defined based on GAS disease isolates originating from the same zip code, occurring within 30 days of each other, and of the same emm type. Results A total of 1291 isolates were included in the study – 94 PTEs were identified representing 168 individual GAS isolates of which 74 were defined as index cases. The 4 most common GAS emm types identified among PTEs were emm1 (43/94, 45.7%), emm12 (30/94, 31.9%), emm4 (6/94, 6.4%), and emm6 (5/94, 5.3%). Index cases most frequently resulted in a single PTE (n=74) with an average number of PTEs per index case of 1.3 (range 1 to 3 PTEs). From index cases, 10 GAS isolates were derived from invasive disease (10/74, 13.5%) and 6 from skin and soft tissue infections (SSTI; 6/74, 8.1%). A substantial proportion of PTEs resulted in iGAS (9/94, 9.5%) and SSTI (10/94, 10.6%). Conclusion Using comprehensive local surveillance, we were able to identify several potential GAS transmission events. Further analysis – including whole genome sequencing on index and PTE isolates – is needed to better define transmission events. Disclosures Jonathon C. McNeil, MD, Nabriva (Research Grant or Support, I serve as the site investigator on a multicenter clinical trial sponsored by Nabriva)

scholarly journals A Two-Component Regulatory System Impacts Extracellular Membrane-Derived Vesicle Production in Group A Streptococcus

mBio ◽  
2016 ◽  
Vol 7 (6) ◽  
Author(s):  
Ulrike Resch ◽  
James Anthony Tsatsaronis ◽  
Anaïs Le Rhun ◽  
Gerald Stübiger ◽  
Manfred Rohde ◽  
...  
Keyword(s):  
Lipid Composition ◽  
Secretory Pathway ◽  
Group A Streptococcus ◽  
Regulatory System ◽  
Surface Proteins ◽  
Streptococcal Toxic Shock Syndrome ◽  
Gram Positive ◽  
Gram Positive Bacteria ◽  
Two Component ◽  
Group A

ABSTRACT Export of macromolecules via extracellular membrane-derived vesicles (MVs) plays an important role in the biology of Gram-negative bacteria. Gram-positive bacteria have also recently been reported to produce MVs; however, the composition and mechanisms governing vesiculogenesis in Gram-positive bacteria remain undefined. Here, we describe MV production in the Gram-positive human pathogen group A streptococcus (GAS), the etiological agent of necrotizing fasciitis and streptococcal toxic shock syndrome. M1 serotype GAS isolates in culture exhibit MV structures both on the cell wall surface and in the near vicinity of bacterial cells. A comprehensive analysis of MV proteins identified both virulence-associated protein substrates of the general secretory pathway in addition to “anchorless surface proteins.” Characteristic differences in the contents, distributions, and fatty acid compositions of specific lipids between MVs and GAS cell membrane were also observed. Furthermore, deep RNA sequencing of vesicular RNAs revealed that GAS MVs contained differentially abundant RNA species relative to bacterial cellular RNA. MV production by GAS strains varied in a manner dependent on an intact two-component system, CovRS, with MV production negatively regulated by the system. Modulation of MV production through CovRS was found to be independent of both GAS cysteine protease SpeB and capsule biosynthesis. Our data provide an explanation for GAS secretion of macromolecules, including RNAs, lipids, and proteins, and illustrate a regulatory mechanism coordinating this secretory response. IMPORTANCE Group A streptococcus (GAS) is a Gram-positive bacterial pathogen responsible for more than 500,000 deaths annually. Establishment of GAS infection is dependent on a suite of proteins exported via the general secretory pathway. Here, we show that GAS naturally produces extracellular vesicles with a unique lipid composition that are laden with proteins and RNAs. Interestingly, both virulence-associated proteins and RNA species were found to be differentially abundant in vesicles relative to the bacteria. Furthermore, we show that genetic disruption of the virulence-associated two-component regulator CovRS leads to an increase in vesicle production. This study comprehensively describes the protein, RNA, and lipid composition of GAS-secreted MVs and alludes to a regulatory system impacting this process.

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 Dextromethorphan Efficiently Increases Bactericidal Activity, Attenuates Inflammatory Responses, and Prevents Group A Streptococcal Sepsis

2011 ◽  
Vol 55 (3) ◽  
pp. 967-973 ◽  
Author(s):  
Ming-Han Li ◽  
Yueh-Hsia Luo ◽  
Chiou-Feng Lin ◽  
Yu-Tzu Chang ◽  
Shiou-Ling Lu ◽  
...  
Keyword(s):  
Bactericidal Activity ◽  
Inflammatory Responses ◽  
Group A Streptococcus ◽  
Wide Spectrum ◽  
Serum Levels ◽  
Streptococcal Toxic Shock Syndrome ◽  
Necrosis Factor Alpha ◽  
Bacterial Killing ◽  
Air Pouch ◽  
Group A

ABSTRACTGroup A streptococcus (GAS) is an important human pathogen that causes a wide spectrum of diseases, ranging from mild throat and skin infections to severe invasive diseases such as necrotizing fasciitis and streptococcal toxic shock syndrome. Dextromethorphan (DM), a dextrorotatory morphinan and a widely used antitussive drug, has recently been reported to possess anti-inflammatory properties. In this study, we investigated the potential protective effect of DM in GAS infection using an air pouch infection mouse model. Our results showed that DM treatment increased the survival rate of GAS-infected mice. Bacterial numbers in the air pouch were lower in mice treated with DM than in those infected with GAS alone. The bacterial elimination efficacy was associated with increased cell viability and bactericidal activity of air-pouch-infiltrating cells. Moreover, DM treatment prevented bacterial dissemination in the blood and reduced serum levels of the proinflammatory cytokines interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and IL-1β and the chemokines monocyte chemotactic protein 1 (MCP-1), macrophage inflammatory protein 2 (MIP-2), and RANTES. In addition, GAS-induced mouse liver injury was reduced by DM treatment. Taken together, DM can increase bacterial killing and reduce inflammatory responses to prevent sepsis in GAS infection. The consideration of DM as an adjunct treatment in combination with antibiotics against bacterial infection warrants further study.

scholarly journals Identification of Group A Streptococcus Antigenic Determinants Upregulated In Vivo

2005 ◽  
Vol 73 (9) ◽  
pp. 6026-6038 ◽  
Author(s):  
Kowthar Y. Salim ◽  
Dennis G. Cvitkovitch ◽  
Peter Chang ◽  
Darrin J. Bast ◽  
Martin Handfield ◽  
...  
Keyword(s):  
Murine Model ◽  
Vibrio Vulnificus ◽  
Group A Streptococcus ◽  
Hypothetical Protein ◽  
Invasive Disease ◽  
Antigenic Determinants ◽  
Expression Library ◽  
Group A

ABSTRACT Group A Streptococcus (GAS) causes a range of diseases in humans, from mild noninvasive infections to severe invasive infections. The molecular basis for the varying severity of disease remains unclear. We identified genes expressed during invasive disease using in vivo-induced antigen technology (IVIAT), applied for the first time in a gram-positive organism. Convalescent-phase sera from patients with invasive disease were pooled, adsorbed against antigens derived from in vitro-grown GAS, and used to screen a GAS genomic expression library. A murine model of invasive GAS disease was included as an additional source of sera for screening. Sequencing DNA inserts from clones reactive with both human and mouse sera indicated 16 open reading frames with homology to genes involved in metabolic activity to genes of unknown function. Of these, seven genes were assessed for their differential expression by quantitative real-time PCR both in vivo, utilizing a murine model of invasive GAS disease, and in vitro at different time points of growth. Three gene products—a putative penicillin-binding protein 1A, a putative lipoprotein, and a conserved hypothetical protein homologous to a putative translation initiation inhibitor in Vibrio vulnificus—were upregulated in vivo, suggesting that these genes play a role during invasive disease.

Full-Genome Dissection of an Epidemic of Severe Invasive Disease Caused by a Hypervirulent, Recently Emerged Clone of Group A Streptococcus

2012 ◽  
Vol 180 (4) ◽  
pp. 1522-1534 ◽  
Author(s):  
Nahuel Fittipaldi ◽  
Stephen B. Beres ◽  
Randall J. Olsen ◽  
Vivek Kapur ◽  
Patrick R. Shea ◽  
...  
Keyword(s):  
Group A Streptococcus ◽  
Invasive Disease ◽  
Full Genome ◽  
Group A

scholarly journals Genetic Relatedness and Superantigen Expression in Group A Streptococcus Serotype M1 Isolates from Patients with Severe and Nonsevere Invasive Diseases

2000 ◽  
Vol 68 (6) ◽  
pp. 3523-3534 ◽  
Author(s):  
Sonia Chatellier ◽  
Nahla Ihendyane ◽  
Rita G. Kansal ◽  
Farukh Khambaty ◽  
Hesham Basma ◽  
...  
Keyword(s):  
Disease Severity ◽  
Genetic Relatedness ◽  
Group A Streptococcus ◽  
Phenotypic Expression ◽  
Invasive Disease ◽  
Banding Patterns ◽  
Clinical Criteria ◽  
Group A ◽  
High Degree ◽  
Culture Supernatants

ABSTRACT The relatedness of group A streptococcal (GAS) strains isolated from 35 Canadian patients with invasive disease of different severity was investigated by a variety of molecular methods. All patients were infected with M1T1 strains and, based on clinical criteria, were classified as severe (n = 21) and nonsevere (n = 14) invasive GAS infection cases. All the M1 strains studied had the emm1.0 allele and the same streptococcal pyrogenic exotoxin (Spe) genotype,speA+ speB+ speC speF+speG+ speH smeZ+ ssa. All isolates had the same speA allotype, speA2. The randomly amplified polymorphic DNA banding pattern with two different primers was identical for all strains, and pulsed field gel electrophoresis analysis showed that 33 and 30 isolates had identical banding patterns after DNA digestion with SfiI or SmaI, respectively; the nonidentical isolates differed from the main pattern by only one band. A relatively high degree of polymorphism in specific regions of the sic gene was observed among isolates; however, this polymorphism was not associated with disease severity. Likewise, although the phenotypic expression of SpeA, SpeB, and SpeF proteins varied among the M1T1 isolates, there was no correlation between the amount of Spe expressed and disease severity. Importantly, mitogenic and cytokine responses induced by partially purified bacterial culture supernatants containing a mixture of expressed superantigens were very similar for isolates from severe and nonsevere cases (P > 0.1). Together, the data indicate that highly related invasive M1T1 isolates, some indistinguishable, can cause disease of varying severity in different individuals. These findings underscore the contribution of host factors to the outcome of invasive GAS infections.

An Outbreak of Severe Group A Streptococcus Infections Associated with Podiatric Application of a Biologic Dermal Substitute

2015 ◽  
Vol 37 (3) ◽  
pp. 306-312 ◽  
Author(s):  
Lauren A. Ibrahim ◽  
John A. Sellick ◽  
Elaine L. Watson ◽  
Lisa M. McCabe ◽  
Karen A. Schoenhals ◽  
...  
Keyword(s):  
Cohort Study ◽  
Group A Streptococcus ◽  
Medical Center ◽  
Laboratory Data ◽  
Case Definition ◽  
Graft Material ◽  
Dermal Substitute ◽  
Number Of Patients ◽  
Severe Group ◽  
Group A

OBJECTIVETo describe an outbreak of severe Group A Streptococcus (GAS) infections that appeared to be associated with use of a biologic dermal substitute on foot woundsDESIGNRetrospective cohort study of cases and similar uninfected patientsSETTING/PATIENTSPatients attending the podiatry clinic at a Veterans Affairs Medical Center between July 2011 and November 2011INTERVENTIONSMicrobiology laboratory data were reviewed for the calendar year, a case definition was established and use of the biologic dermal substitute was discontinued. Staff were cultured to identify potentially colonized employees. A case–cohort study was designed to investigate risk factors for disease. Emm typing and pulsed field gel electrophoresis (PFGE) were performed to identify strain similarity.RESULTSIn 10 months, 14 cases were identified, and 4 of these patients died. All strains were emm type 28 and were identical according to PFGE. Discontinuation of biologic dermal substitute use halted the outbreak. A prior stroke was more common in the case cohort vs uninfected patient cohorts. The number of patients attending the clinic on 13 probable transmission days was significantly higher than on nontransmission days. We identified 2 patients who were present in the clinic on all but 1 probable transmission day. Surveillance cultures of podiatry clinic staff and cultures of the same lot of retained graft material were negative.CONCLUSIONSA carrier was not identified, and we believe the outbreak was associated with inter-patient transmission likely due to lapses in infection control techniques. No additional cases have been identified in >3 years following the resumption of dermal substitute use in May 2012.Infect. Control Hosp. Epidemiol. 2016;37(3):306–312

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