Invasive Group A Streptococcus Infection Research Articles

Invasive group A Streptococcus infection (Streptococcus pyogenes): Current situation in Spain.

Group A ß-hemolytic Streptococcus (S. pyogenes), also known as GAS, is a Gram-positive bacterium. It can be easily identified in the microbiology laboratory by its ability to hemolyse blood in culture media. This bacterium is highly virulent due to its production of enzymes and toxins, and its ability to cause immunologically mediated diseases such as rheumatic fever and post-streptococcal glomerulonephritis. GAS is the primary cause of bacterial pharyngotonsillitis, although it is typically a benign and non-invasive disease. However, it also has the potential to cause severe skin and soft tissue infections, necrotising fasciitis, bacteraemia and endocarditis, pneumonia and empyema, and streptococcal toxic shock syndrome, without any age or predisposition limits. The term invasive GAS disease (iGAS) is used to refer to this group of conditions. In more developed countries, iGAS disease has declined thanks to improved hygiene and the availability of antibiotics. For example, rheumatic fever has practically disappeared in countries such as Spain. However, recent data suggests a potential increase in some iGAS diseases, although the accuracy of this data is not consistent. Because of this, the COVID and Emerging Pathogens Committee of the Illustrious Official College of Physicians of Madrid (ICOMEM) has posed several questions about invasive GAS infection, especially its current situation in Spain. The committee has enlisted the help of several experts in the field to answer these questions. The following lines contain the answers that we have collaboratively produced, aiming to assist not only the members of ICOMEM but also anyone interested in this topic.

Divergent effects of emm types 1 and 12 on invasive group A streptococcal infections-results of a retrospective cohort study, Germany 2023.

As a potential side effect of the severe acute respiratory syndrome coronavirus type 2 pandemic, invasive group A Streptococcus (iGAS) infections in Europe have increased dramatically in both children and adults in the end of 2022. This epidemiological and molecular study describes the distributions of streptococcal genes encoding the M antigen (emm types) and superantigens in patients with invasive and non-invasive GAS infections. From December 2022 to December 2023, a total of 163 GAS isolates were collected from sterile and non-sterile sites of patients at five hospitals in Germany including two tertiary care centers. Genes encoding M protein and superantigens were determined following the guidelines of CDC Streptococcus laboratory. Patients' characteristics were reviewed retrospectively. Correlations of clinical factors, emm types, and superantigens with rates of invasive infections were analyzed. Of the 163 included GAS cases, 112 (69%) were considered as invasive. In total, 33 different emm types were observed, of which emm1.0 (n = 49; 30%), emm89.0 (n = 15; 9%), and emm12.0 (n = 14; 9%) were most prevalent. In total, 70% of emm1.0 isolates belonged to M1UK lineage. No difference in invasive infections was observed for the M1UK lineage compared with other emm1.0 isolates. However, the emm1.0 type, presence of speA1-3, speG, or speJ, as well as adulthood were significantly associated with invasive infections. In contrast, emm12.0 isolates were significantly less associated with invasive infections. Multivariable analysis confirmed a significant influence of speJ and adulthood on iGAS infections. This study underlines the importance of continuous monitoring of genomic trends and identification of emerging GAS variants. This may aid in delineating pathogenicity factors of Streptococcus pyogenes that propel invasive infections.

Molecular epidemiology of invasive Group A streptococcal infections before and after the COVID-19 pandemic in Switzerland

Group A Streptococcus (GAS, aka Streptococcus pyogenes) poses a significant public health concern, causing a diverse spectrum of infections with high mortality rates. Following the COVID-19 pandemic, a resurgence of invasive GAS (iGAS) infections has been documented, necessitating efficient outbreak detection methods. Whole genome sequencing (WGS) serves as the gold standard for GAS molecular typing, albeit constrained by time and costs. This study aimed to characterize the post-pandemic increased prevalence of iGAS on the molecular epidemiological level in order to assess whether new, more virulent variants have emerged. A total of 66 iGAS strains isolated from nine Swiss hospitals during the COVID-19 post-pandemic increased GAS prevalence were evaluated and compared to 15 strains collected before and 12 during the COVID-19 pandemic. FT-IR measurements and WGS were conducted for network analysis. Demographic, clinical, and epidemiological data were collected. Skin and soft tissue infection was the most common diagnosis, followed by primary bacteremia and pneumonia. Viral co-infections were found in 25% of cases and were significantly associated with more severe disease requiring intensive care unit admission. WGS analysis did not reveal emerging GAS genetic distinct variants after the COVID-19 pandemic, indicating the absence of a pandemic-induced shift. FT-IR spectroscopy exhibited limitations in differentiating genetically distant GAS strains, yielding poor overlap with WGS-derived clusters. The emm1/ST28 genotype was predominant in our cohort and was associated with five of the seven deaths recorded, in accordance with the molecular epidemiological data before the pandemic. Additionally, no notable shift in antibiotic susceptibility patterns was observed. Our data suggest that mainly non-pathogen related factors contributed to the recent increased prevalence of iGAS.

The Thousand Faces of Invasive Group A Streptococcal Infections: Update on Epidemiology, Symptoms, and Therapy.

Invasive infections caused by Streptococcus pyogfenes (iGAS), commonly known as Group A Streptococcus, represent a significant public health concern due to their potential for rapid progression and life-threatening complications. Epidemiologically, invasive GAS infections exhibit a diverse global distribution, affecting individuals of all ages with varying predisposing factors. The pathogenesis of invasive GAS involves an array of virulence factors that contribute to tissue invasion, immune evasion, and systemic dissemination. In pediatrics, in the last few years, an increase in iGAS infections has been reported worldwide becoming a challenging disease to diagnose and treat promptly. This review highlights the current knowledge on pathogenesis, clinical presentations, and therapeutic approaches for iGAS in children.

Effects of Acipenserid herpesvirus 2 on the outcome of a Streptococcus iniae co-infection in white sturgeon (Acipenser transmontanus)

Acipenserid herpesvirus 2 (AciHV-2) is a large double-stranded DNA virus in the family Alloherpesviridae that causes catastrophic outbreaks in young naive white sturgeon (Acipenser transmontanus) populations, with mortalities of up to 80%. Survivors of these infections are suspected to remain latently infected. The gram-positive zoonotic bacterium Streptococcus iniae is another important sturgeon pathogen that causes severe myositis and up to 50% mortality during natural outbreaks. Throughout the last decade, co-infections of AciHV-2 and S. iniae have been reported in cultured white sturgeon in California resulting in severe presentations of piscine streptococcosis. This phenomenon of herpesvirus and streptococcus co-infection appears to span multiple taxa since in humans, it is recognized that a Human herpesvirus 3 infection (VZV) is a negative prognostic indicator for pediatric Invasive Group A Streptococcal infections (IGASI). While a decrease in humoral immunity caused by VZV has been hypothesized as a potentially important factor in IGASI cases, no natural animal model exists to study this process. Moreover, no studies have investigated these reported co-infections in white sturgeon. Therefore, the goal of this study was to investigate the effects of a recent AciHV-2 infection on the outcome of a subsequent S. iniae challenge in white sturgeon fingerlings. When fish were infected with 108 colony forming units (CFU) of S. iniae intramuscularly (IM), a statistically significant decrease in survival of 41% was detected in the co-infection group compared to the S. iniae group (p-value < 0.001). This difference was not observed when fish were infected with 106 CFU of S. iniae IM. At this lower infection dose, however, a statistically significant downregulation of tnfα was observed in the spleen of fish in the co-infection group compared to the S. iniae group (p-value = 0.0098). Analysis of serum from survivors revealed a statistically significant reduction in anti-S. iniae serum IgM and serum serotransferrin in fish from the co-infection group compared to the S. iniae group (p-value = 0.0134 and p-value = 0.0183, respectively). Further studies are indicated to determine what interactions lead to the decreased production of pathogen-specific IgM, serotransferrin, and TNFα in the host.

Assessing the influence of the COVID-19 pandemic on the incidence, clinical presentation, and clindamycin resistance rates of Streptococcus pyogenes infections

ObjectivesStreptococcus pyogenes (group A Streptococcus [GAS]) is a prevalent cause of community-acquired bacterial infections, with invasive GAS (iGAS) infections presenting severe morbimortality. Clindamycin is generally used based on its antitoxin effect. This study investigates changes in iGAS incidence, clinical presentation, outcomes, and clindamycin resistance in an adult cohort. MethodsThis is a retrospective analysis of S. pyogenes episodes from a tertiary adult hospital in Barcelona (Spain) between 2015 and 2023. The pre-pandemic period includes data from 2015-2019. The pandemic period, from 2020-2021, and post-pandemic period comprised 2022 to the first semester of 2023. ResultsThe global incidence of GAS infections in the pre-pandemic and post-pandemic periods were 2.62 and 2.92 cases per 10.000 hospital admissions, whereas for iGAS cases, they were 1.85 and 2.34. However, a transient decrease was observed during the pandemic period: 1.07 and 0.78 per 10.000 hospital admissions. There was a significant decrease in GAS and iGAS infections during the pandemic period compared with the pre-pandemic incidence (P <0.001 for GAS infections and P = 0.001 for iGAS cases) and the post-pandemic incidence (P = 0.032 for GAS infections and P = 0.037 for iGAS cases). The most common source of infection was skin and soft tissue infections with 264 (54%) cases. Skin and soft tissue infections and cases of necrotizing fasciitis increased during the pandemic. Clindamycin resistance occurred in 13.5% of isolations during the pre-pandemic and 17.5% in post-pandemic period (P = 0.05). ConclusionsOur study revealed a temporary reduction in iGAS infections, followed by resurgence in the post-pandemic period. The observed rise in clindamycin resistance emphasizes the importance of monitoring local resistance patterns for tailored treatment.

Interplay between group A Streptococcus and host innate immune responses.

SUMMARYGroup A Streptococcus (GAS), also known as Streptococcus pyogenes, is a clinically well-adapted human pathogen that harbors rich virulence determinants contributing to a broad spectrum of diseases. GAS is capable of invading epithelial, endothelial, and professional phagocytic cells while evading host innate immune responses, including phagocytosis, selective autophagy, light chain 3-associated phagocytosis, and inflammation. However, without a more complete understanding of the different ways invasive GAS infections develop, it is difficult to appreciate how GAS survives and multiplies in host cells that have interactive immune networks. This review article attempts to provide an overview of the behaviors and mechanisms that allow pathogenic GAS to invade cells, along with the strategies that host cells practice to constrain GAS infection. We highlight the counteractions taken by GAS to apply virulence factors such as streptolysin O, nicotinamide-adenine dinucleotidase, and streptococcal pyrogenic exotoxin B as a hindrance to host innate immune responses.

Polymeric Nanoparticles as Oral and Intranasal Peptide Vaccine Delivery Systems: The Role of Shape and Conjugation.

Mucosal vaccines are highly attractive due to high patient compliance and their suitability for mass immunizations. However, all currently licensed mucosal vaccines are composed of attenuated/inactive whole microbes, which are associated with a variety of safety concerns. In contrast, modern subunit vaccines use minimal pathogenic components (antigens) that are safe but typically poorly immunogenic when delivered via mucosal administration. In this study, we demonstrated the utility of various functional polymer-based nanostructures as vaccine carriers. A Group A Streptococcus (GAS)-derived peptide antigen (PJ8) was selected in light of the recent global spread of invasive GAS infection. The vaccine candidates were prepared by either conjugation or physical mixing of PJ8 with rod-, sphere-, worm-, and tadpole-shaped polymeric nanoparticles. The roles of nanoparticle shape and antigen conjugation in vaccine immunogenicity were demonstrated through the comparison of three distinct immunization pathways (subcutaneous, intranasal, and oral). No additional adjuvant or carrier was required to induce bactericidal immune responses even upon oral vaccine administration.

Insights gained from sequencing Australian non-invasive and invasive Streptococcus pyogenes isolates.

Epidemiological data have indicated that invasive infections caused by the Gram-positive cocci Streptococcus pyogenes (group A streptococcus, GAS) have increased in many Australian states over the past two decades. In July 2022, invasive GAS (iGAS) infections became nationally notifiable in Australia via public-health agencies. Surveillance for S. pyogenes infections has been sporadic within the state of New South Wales (NSW). This has led to a lack of genetic data on GAS strains in circulation, particularly for non-invasive infections, which are the leading cause of GAS's burden on the Australian healthcare system. To address this gap, we used whole-genome sequencing to analyse the genomes of 318 S. pyogenes isolates collected within two geographical regions of NSW. Invasive isolates were collected in 2007-2017, whilst non-invasive isolates were collected in 2019-2021. We found that at least 66 different emm-types were associated with clinical disease within NSW. There was no evidence of any Australian-specific clones in circulation. The M1UK variant of the emm1 global pandemic clone (M1global) has been detected in our isolates from 2013 onwards. We detected antimicrobial-resistance genes (mainly tetM, ermA or ermB genes) in less than 10 % of our 318 isolates, which were more commonly associated with non-invasive infections. Superantigen virulence gene carriage was reasonably proportionate between non-invasive and invasive infection isolates. Our study adds rich data on the genetic makeup of historical S. pyogenes infections within Australia. Ongoing surveillance of invasive and non-invasive GAS infections within NSW by whole-genome sequencing is warranted to inform on outbreaks, antimicrobial resistance and vaccine coverage.

1681. Persistent Increased Invasive Pediatric Streptococcus pyogenes (Group A Streptococcus) Infections with Correlated Increase in Superficial Infection and Pharyngitis

Abstract Background Children's Hospital of Philadelphia (CHOP) clinicians observed an increase in invasive group A Streptococcus infections (iGAS) in November 2022. In December 2022, the Centers for Disease Control and Prevention published an investigation of increased iGAS. At CHOP iGAS remain increased, even after peak respiratory viral season. Our objective was to compare pre-pandemic and current case counts and to investigate if the increase in iGAS correlates with an increase in non-invasive GAS infections (nGAS). Methods Data for positive Streptococcus pyogenes results at CHOP from January 2018 to April 2023 was collected from the electronic medical record (n=466). Results were classified by source and specimen type as pharyngitis, superficial, and invasive, then further classified as non-invasive (pharyngitis and superficial) or invasive. For infection events with multiple results only one result was included, giving preference to the most aggressive classification (invasive &amp;gt;pharyngitis &amp;gt;superficial). Fisher's exact test was used to assess association between the increase in nGAS and iGAS prior to and after the start of the COVID-19 pandemic (2018-2019 vs. 2021-2023). Fisher's exact test, with Monte Carlo simulation, was used to assess association between the increase in nGAS and iGAS infections by year. Results There was a statistically significant association in the increase in pharyngitis, superficial, and invasive group A Streptococcus infections (GAS) (p-value &amp;lt; 0.0001) and in nGAS and iGAS (p-value = 0.0001), when comparing pre- and post-2020. We found statistically significant associations in the increase of pharyngitis, superficial, and invasive GAS cases (p-value = 0.0005) and of nGAS and iGAS cases (p-value = 0.0005). Conclusion Our data shows a significant increase in cases from pre-pandemic years for nGAS and iGAS infections. iGAS is correlated with nGAS, even with further stratification of nGAS into pharyngitis and superficial. Notably, increases in nGAS were significantly more than the increase in iGAS, which has unexpectedly persisted beyond the typical winter viral infection peak. Continued monitoring or GAS, particularly iGAS, is justified. Disclosures All Authors: No reported disclosures

Streptococcus pyogenes emm98.1 variants activate inflammatory caspases in human neutrophils

ABSTRACT The human pathogen Streptococcus pyogenes (Group A Streptococcus, GAS) is responsible for invasive disease characterized by inflammation and tissue destruction. Inflammatory symptoms of invasive disease may be attributed to the neutrophil response during the early stages of infection. Here, the human neutrophil response to GAS was characterized in vitro using emm98.1 type covS mutant GAS strain NS88.2 (isolated from invasive infection) and avirulent variant NS88.2rep. NS88.2 was shown to resist phagocytic killing and proliferate in the presence of human neutrophils, where neutrophil antimicrobial defence through the production of reactive oxygen species was reduced compared with NS88.2rep. In the presence of NS88.2, neutrophil death was delayed compared with NS88.2rep. Infection with either GAS strain induced expression of inflammatory caspases-1 and -4 in neutrophils, with increased detection of activated inflammatory caspases in response to NS88.2rep compared with NS88.2. NS88.2 infection caused differential expression of cell-surface CD66b, CD16, and CD31, when compared to NS88.2rep. We conclude that the neutrophil response to NS88.2 promotes inflammation and may be a contributing factor to the severity of invasive GAS infections. Abbreviations CovRS, control of virulence regulatory system; GAS, Group A Streptococcus; PMN, polymorphonuclear leukocyte.

Naturally acquired functional antibody responses to group A Streptococcus differ between major strain types.

Group A Streptococcus (GAS) is a leading human pathogen for which there is no licensed vaccine. Infections are most common in young children and the elderly suggesting immunity accumulates with exposure until immune senescence in older age. Though protection has been postulated to be strain type specific, based on the M-protein (emm-type), the antigenic basis of population-level immunity remains poorly understood. Naturally acquired GAS antibody responses were investigated using intravenous immunoglobulin (IVIG), which contains pooled immunoglobulins from thousands of healthy human donors, as a surrogate for population immunity. Functional opsonophagocytic killing assays were conducted with GAS strains (n = 6) representing the three major emm-pattern types (emm12, A-C pattern; emm53, D-pattern; and emm75, E-pattern). While IVIG induced opsonophagocytic killing of all GAS strains tested, specificity assays showed the profile of protective antibodies differed considerably between emm-types. Antibodies targeting the M-protein were a major component of the functional IVIG antibody response for emm12 and emm53 strains but not for emm75 strains. The striking differences in the contribution of M-protein specific antibodies to killing suggest naturally acquired immunity differs between strains from the major emm-patterns. This challenges the dogma that M-protein is the primary protective antigen across all GAS straintypes. IMPORTANCE Group A Streptococcus (GAS) is a globally important pathogen. With the surge of invasive GAS infections that have occurred in multiple countries, contemporaneous with the relaxation of COVID-19 pandemic restrictions, there is increased interest in the mechanisms underpinning GAS immunity. We utilized intravenous immunoglobulin (IVIG), pooled immunoglobulins from thousands of healthy donors, as a surrogate for population-level immunity to GAS, and explored the contribution of strain-specific (M-type specific) antibodies to GAS immunity using functional killing assays. This revealed striking differences between major strain types as to the contribution of strain specific antibodies to killing. For GAS strains belonging to the E pattern group, M-type specific antibodies do not mediate killing and immunity, which contrasts with strains belonging to pattern A-C and D groups. This challenges the historical dogma, originally proposed by Rebecca Lancefield in the 1950-1960s, that the M-protein is the major protective antigen across all GAS strain types.

The many faces of Group A Streptococcal infections, case-series of invasive infections in children in Iceland

In recent months the incedence of invasive group A streptococcal infections (Streptococcus pyogenes) has increased worldwide. In the Children's Hospital Iceland 20 such cases were admitted during a four month period, until which time the avarage was one or two children admitted with an invasive GAS infection per year. To demonstrate the variability in the presentation of these invasive infections four cases were chosen for discussion in this case-series. Empyema with toxic shock syndrome, meningitis, orbital abscess and fascitis of the leg are reviewed.

Invasive Streptococcus pyogenes: A Short Literature Review

Abstract Objective Streptococcus pyogenes also called Group A streptococci (GAS) is an important pathogen known since past years and infects millions of people around the world every year and can cause death. Although it often causes pharyngitis and skin infections, it can also spread to the bloodstream and cause invasive GAS (iGAS) infections. In this review, studies on the epidemiology of GAS and iGAS and vaccine studies were reviewed. Methods A comprehensive search of databases was conducted up to April 1, 2023 to related studies, in English using the following terms: S. pyogenes, GAS, invasive S. pyogenes infections, iGAS, S. pyogenes vaccine. The data extraction was conducted by two investigators using the same methodology. Results There has been an increase in iGAS infections in various countries in the last year and they have been followed closely. Although the reason for the increase in iGAS cases cannot be determined exactly, it is thought that the recent removal of coronavirus disease 2019 restrictions and the increase in the number of individuals susceptible to GAS and to viral respiratory pathogens is thought to have caused this situation. Another important issue with GAS is the vaccine studies. Vaccines are based on two different targets: M protein-based and non-M protein-based. Phase-I clinical trials have been initiated for some vaccines. Conclusion The increase in recent iGAS infections will draw attention to this agent and accelerate vaccine studies.

HLA-II-Dependent Neuroimmune Changes in Group A Streptococcal Necrotizing Fasciitis.

Streptococcus pyogenes (Group A Streptococcus, GAS) bacteria cause a spectrum of human diseases ranging from self-limiting pharyngitis and mild, uncomplicated skin infections (impetigo, erysipelas, and cellulitis) to highly morbid and rapidly invasive, life-threatening infections such as streptococcal toxic shock syndrome and necrotizing fasciitis (NF). HLA class II allelic polymorphisms are linked with differential outcomes and severity of GAS infections. The dysregulated immune response and peripheral cytokine storm elicited due to invasive GAS infections increase the risk for toxic shock and multiple organ failure in genetically susceptible individuals. We hypothesized that, while the host immune mediators regulate the immune responses against peripheral GAS infections, these interactions may simultaneously trigger neuropathology and, in some cases, induce persistent alterations in the glial phenotypes. Here, we studied the consequences of peripheral GAS skin infection on the brain in an HLA-II transgenic mouse model of GAS NF with and without treatment with an antibiotic, clindamycin (CLN). Mice expressing the human HLA-II DR3 (DR3) or the HLA-II DR4 (DR4) allele were divided into three groups: (i) uninfected controls, (ii) subcutaneously infected with a clinical GAS strain isolated from a patient with GAS NF, and (iii) GAS-infected with CLN treatment (10 mg/kg/5 days, intraperitoneal). The groups were monitored for 15 days post-infection. Skin GAS burden and lesion area, splenic and hippocampal mRNA levels of inflammatory markers, and immunohistochemical changes in hippocampal GFAP and Iba-1 immunoreactivity were assessed. Skin GAS burden and hippocampal mRNA levels of the inflammatory markers S100A8/A9, IL-1β, IL-33, inflammasome-related caspase-1 (Casp1), and NLRP6 were elevated in infected DR3 but not DR4 mice. The levels of these markers were significantly reduced following CLN treatment in DR3 mice. Although GAS was not detectable in the brain, astrocyte (GFAP) and microglia (Iba-1) activation were evident from increased GFAP and Iba-1 mRNA levels in DR3 and DR4 mice. However, CLN treatment significantly reduced GFAP mRNA levels in DR3 mice, not DR4 mice. Our data suggest a skin-brain axis during GAS NF, demonstrating that peripherally induced pathological conditions regulate neuroimmune changes and gliotic events in the brain.

Incidence and clinical and microbiological features of invasive and probable invasive streptococcal group A infections in children and adults in the Brussels-Capital Region, 2005–2020

Assess the incidence, risk factors, clinical and microbiological features, and outcome of both probable invasive and invasive group A Streptococcus (GAS) infections in children and adults in the BrusselsCapital Region between 2005 and 2020. A retrospective, multicentric study was performed in three university hospitals in Brussels. Patients were identified through the centralized laboratory information system. Epidemiological and clinical data were collected from patients' hospital records. A total of 467 cases were identified. Incidence has increased from 2.1 to 10.9/100,000 inhabitants between 2009 and 2019 in non-homeless adults while it was above 100/100,000 on homeless in years with available denominators. Most of GAS were isolated from blood (43.6%), and the most common clinical presentation was skin and soft tissue infections (42.8%). A third of all the patients needed surgery, a quarter was admitted to the intensive care unit, and 10% of the adult patients died. Wounds and chickenpox disease were the main risk factors for children. Tobacco, alcohol abuse, wounds or chronic skin lesion, being homeless, and diabetes were identified as major predisposing factors for adults. The most common emm clusters were D4, E4, and AC3; 64% of the isolates were theoretically covered by the 30-valent M-protein vaccine. The burden of invasive and probable invasive GAS infections is on the rise in the studied adult population. We identified potential interventions that could contribute to decrease this burden: appropriate care of wounds, specifically among homeless and patients with risk factors such as diabetes and systematic chickenpox vaccination for children.

Scarlet fever and the dental team

Scarlet fever is a mild, but highly contagious disease caused by Group A Streptococcus (GAS) bacteria. Scarlet fever begins with flu-like symptoms and, within the first 12-48 hours, it is common for a rash to develop that feels like sandpaper to the touch. In rare cases, GAS bacteria can cause an invasive infection that can be fatal. Invasive GAS (iGAS) infection occurs when the bacteria are in a place of the body where they are not normally found, such as the blood stream. Scarlet fever is usually treated with antibiotics, which can reduce the chances of the patient developing iGAS and reduce the risk of them spreading the infection to others. The World Health Organization and UK Health Security Agency have announced that the number of scarlet fever and iGAS cases observed in children has been several times higher than pre-pandemic levels for the equivalent period of time. As healthcare professionals, it is important that the dental team understand key aspects of scarlet fever. Here, scarlet fever symptoms, transmission, clinical manifestations, antibiotic treatment, and risks to the dental team are reviewed. CPD/Clinical Relevance: To describe epidemiology of scarlet fever and discuss the implications for the dental team.

Should Linezolid Replace Clindamycin as the Adjunctive Antimicrobial of Choice in Group A Streptococcal Necrotizing Soft Tissue Infection and Toxic Shock Syndrome? A Focused Debate.

Group A Streptococcus (GAS) necrotizing soft tissue infections and toxic shock syndrome remain high-mortality conditions. In vitro and animal model data, as well as multiple observational studies, suggest adjunctive clindamycin (ie, given with a beta-lactam) reduces invasive GAS infection mortality by inhibiting exotoxin production. Unfortunately, clindamycin resistance in GAS has been rapidly increasing in the United States since the mid-2010s, although the clinical significance of this remains unclear. Linezolid is a promising alternative adjunctive agent to which US GAS isolates remain near-universally susceptible, with a similar mechanism of action and similar in vitro evidence of GAS virulence factor attenuation. However, the clinical data supporting linezolid's value in severe GAS infections are far more limited. Here the authors review the data and reasoning behind a general preference for clindamycin or linezolid in a focused, pro-con debate format.

The effects of air pollutants exposure on the transmission and severity of invasive infection caused by an opportunistic pathogen Streptococcus pyogenes

Currently, urbanization is associated with an increase in air pollutants that contribute to invasive pathogen infections by altering the host's innate immunity and antimicrobial resistance capability. Streptococcus pyogenes, also known as Group A Streptococcus (GAS), is a gram-positive opportunistic pathogen that causes a wide range of diseases, especially in children and immunosuppressed individuals. Diesel exhaust particle (DEP), a significant constituent of particulate matter (PM), are considered a prominent risk factor for respiratory illness and circulatory diseases worldwide. Several clinical and epidemiological studies have identified a close association between PM and the prevalence of viral and bacterial infections. This study investigated the role of DEP exposure in increasing pulmonary and blood bacterial counts and mortality during GAS M1 strain infection in mice. Thus, we characterized the upregulation of reactive oxygen species production and disruption of tight junctions in the A549 lung epithelial cell line due to DEP exposure, leading to the upregulation of GAS adhesion and invasion. Furthermore, DEP exposure altered the leukocyte components of infiltrated cells in bronchoalveolar lavage fluid, as determined by Diff-Quik staining. The results highlighted the DEP-related macrophage dysfunction, neutrophil impairment, and imbalance in pro-inflammatory cytokine production via the toll-like receptor 4/mitogen-activated protein kinase signaling axis. Notably, the tolerance of the GAS biofilms toward potent antibiotics and bacterial resistance against environmental stresses was also significantly enhanced by DEP. This study aimed to provide a better understanding of the physiological and molecular interactions between exposure to invasive air pollutants and susceptibility to invasive GAS infections.

AR-12 Has a Bactericidal Activity and a Synergistic Effect with Gentamicin against Group A Streptococcus.

Streptococcus pyogenes (group A Streptococcus (GAS) is an important human pathogen that can cause severe invasive infection, such as necrotizing fasciitis and streptococcal toxic shock syndrome. The mortality rate of streptococcal toxic shock syndrome ranges from 20% to 50% in spite of antibiotics administration. AR-12, a pyrazole derivative, has been reported to inhibit the infection of viruses, intracellular bacteria, and fungi. In this report, we evaluated the bactericidal activities and mechanisms of AR-12 on GAS infection. Our in vitro results showed that AR-12 dose-dependently reduced the GAS growth, and 2.5 μg/mL of AR-12 significantly killed GAS within 2 h. AR-12 caused a remarkable reduction in nucleic acid and protein content of GAS. The expression of heat shock protein DnaK and streptococcal exotoxins was also inhibited by AR-12. Surveys of the GAS architecture by scanning electron microscopy revealed that AR-12-treated GAS displayed incomplete septa and micro-spherical structures protruding out of cell walls. Moreover, the combination of AR-12 and gentamicin had a synergistic antibacterial activity against GAS replication for both in vitro and in vivo infection. Taken together, these novel findings obtained in this study may provide a new therapeutic strategy for invasive GAS infection.