To Toxic Shock Syndrome Research Articles

Multisystem Inflammatory Syndrome in Children Associated with COVID-19: An Interim Review

AbstractThe pediatric population is relatively less affected by novel coronavirus disease 2019 (COVID-19) compared with adults, both in numbers and severity. However, evolution of a new entity, named multisystem inflammatory syndrome in children (MIS-C), has led to significant number of children being admitted to hospital, especially to intensive care units. Case definitions of MIS-C have been defined by the World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC) separately. Autoantibodies and antibody-dependent enhancement (ADE) are the key factors proposed in pathogenesis, leading to immune dysregulation, and cytokine storm. Three distinct clinical types are observed as follows: (1) fever and elevated inflammatory markers with no end-organ damage; (2) shock with severe myocardial dysfunction similar to toxic shock syndrome (TSS); and (3) with mucocutaneous features like Kawasaki's disease (KD). Cardiovascular and gastrointestinal symptoms are the predominant presentations. Inflammatory markers like C-reactive protein (CRP), ferritin, and interleukin (IL)-6 are raised along with high D-dimer and lactate dehydrogenase (LDH). Echocardiography may demonstrate low left ventricular ejection fraction (<50%) and/or coronary aneurysms. Reverse-transcription polymerase chain reaction (RT-PCR) for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) is usually negative, with most having antibodies against the virus. KD, KD shock syndrome (KDSS), and toxic shock syndrome (TSS) are the important differential diagnoses to be considered. Immunomodulatory therapy is the cornerstone of the management. Intravenous immunoglobulin (IVIg) is preferred, the next option being steroids. Supportive care, antiplatelet, and anticoagulation medications, when indicated, are also vital aspects of treatment plan. The prognosis is favorable with low mortality but meticulous cardiac monitoring and follow-up by a multidisciplinary team is very important. Being an evolving disease, future research may reveal different manifestations, newer diagnostic modalities, and better treatment options.

The incidence of toxic shock syndrome due to nosocomial methicillin-resistant Staphylococcus aureus infection in burn patients: A four-year retrospective cohort study

Among adult and pediatric patients, concern is growing in regard to toxic shock syndrome (TSS) resulting from methicillin-resistant Staphylococcus aureus (MRSA) nosocomial infection. We investigated the incidence and characteristics of this form of TSS in patients with burn injury who were admitted to our burn care units from January 2008 to December 2011. Of the 244 patients with nosocomial MRSA infection admitted during the study period, TSS occurred in 20 (8.2%) patients whose average age was 42.9 years, average total burn surface area (TBSA) was 31.7%, and average day of TSS appearance was 9.5 days after injury. There were no particular characteristics associated with age, TBSA or day of TSS appearance in these patients. All but 1 patient recovered from TSS within an average of 9.4 days. The incidence of TSS due to nosocomial MRSA infection in these burn patients was higher than expected. TSS due to nosocomial MRSA infection should be considered in burn care.

Novel Tissue Level Effects of the Staphylococcus aureus Enterotoxin Gene Cluster Are Essential for Infective Endocarditis.

BackgroundSuperantigens are indispensable virulence factors for Staphylococcus aureus in disease causation. Superantigens stimulate massive immune cell activation, leading to toxic shock syndrome (TSS) and contributing to other illnesses. However, superantigens differ in their capacities to induce body-wide effects. For many, their production, at least as tested in vitro, is not high enough to reach the circulation, or the proteins are not efficient in crossing epithelial and endothelial barriers, thus remaining within tissues or localized on mucosal surfaces where they exert only local effects. In this study, we address the role of TSS toxin-1 (TSST-1) and most importantly the enterotoxin gene cluster (egc) in infective endocarditis and sepsis, gaining insights into the body-wide versus local effects of superantigens.MethodsWe examined S. aureus TSST-1 gene (tstH) and egc deletion strains in the rabbit model of infective endocarditis and sepsis. Importantly, we also assessed the ability of commercial human intravenous immunoglobulin (IVIG) plus vancomycin to alter the course of infective endocarditis and sepsis.ResultsTSST-1 contributed to infective endocarditis vegetations and lethal sepsis, while superantigens of the egc, a cluster with uncharacterized functions in S. aureus infections, promoted vegetation formation in infective endocarditis. IVIG plus vancomycin prevented lethality and stroke development in infective endocarditis and sepsis.ConclusionsOur studies support the local tissue effects of egc superantigens for establishment and progression of infective endocarditis providing evidence for their role in life-threatening illnesses. In contrast, TSST-1 contributes to both infective endocarditis and lethal sepsis. IVIG may be a useful adjunct therapy for infective endocarditis and sepsis.

Successful Use of Extracorporeal Membrane Oxygenation in an Adult Patient With Toxic Shock-Induced Heart Failure

Cardiomyopathy secondary to toxic shock syndrome (TSS) is an uncommon but potentially life-threatening problem. We report the case of a 51-year-old male who presented with profound cardiogenic shock and multiorgan failure that could not be managed by conventional therapy with intravenous fluids, vasopressors and inotropes. Venoarterial extracorporeal membrane oxygenation (VA ECMO) was instituted as a bridge to recovery. After administration of antibiotics and intravenous immunoglobulin, the patient's condition improved and he was successfully weaned off ECMO after 6 days. The patient recovered from multiorgan failure, and left ventricular ejection fraction improved from <10% pre-ECMO to 65% 8 months after discharge. This case supports the view that VA ECMO can be used successfully to support vital organ perfusion in patients with profound but reversible cardiomyopathy attributed to TSS.

Therapeutic Inhibition of Pro-Inflammatory Signaling and Toxicity to Staphylococcal Enterotoxin B by a Synthetic Dimeric BB-Loop Mimetic of MyD88

Staphylococcal enterotoxin B (SEB) exposure triggers an exaggerated pro-inflammatory cytokine response that often leads to toxic shock syndrome (TSS) associated with organ failure and death. MyD88 mediates pro-inflammatory cytokine signaling induced by SEB exposure and MyD88−/− mice are resistant to SEB intoxication, suggesting that MyD88 may be a potential target for therapeutic intervention. We targeted the BB loop region of the Toll/IL-1 receptor (TIR) domain of MyD88 to develop small-molecule therapeutics. Here, we report that a synthetic compound (EM-163), mimic to dimeric form of BB-loop of MyD88 attenuated tumor necrosis factor (TNF)- α, interferon (IFN)-γ, interleukin (IL)-1β, IL-2 and IL-6 production in human primary cells, whether administered pre- or post-SEB exposure. Results from a direct binding assay, and from MyD88 co-transfection/co-immunoprecipitation experiments, suggest that EM-163 inhibits TIR-TIR domain interaction. Additional results indicate that EM-163 prevents MyD88 from mediating downstream signaling. In an NF-kB-driven reporter assay of lipopolysaccharide-stimulated MyD88 signaling, EM-163 demonstrated a dose-dependent inhibition of reporter activity as well as TNF-α and IL-1β production. Importantly, administration of EM-163 pre- or post exposure to a lethal dose of SEB abrogated pro-inflammatory cytokine responses and protected mice from toxic shock-induced death. Taken together, our results suggest that EM-163 exhibits a potential for therapeutic use against SEB intoxication.

Neutralization of Multiple Staphylococcal Superantigens by a Single‐Chain Protein Consisting of Affinity‐Matured, Variable Domain Repeats

Staphylococcus aureus secretes various toxins that act as superantigens by stimulating a large fraction of the host's T cells. Toxin binding to variable domains of T cell receptor beta chains (Vbeta) leads to massive release of inflammatory molecules and potentially to toxic shock syndrome (TSS). Previously, we generated soluble forms of different Vbeta domains with a high affinity for binding superantigens. However, a broader spectrum antagonist is required for the neutralization of multiple toxins. In the present study, we expressed Vbeta domains in tandem as a single-chain protein and neutralized the clinically important superantigens staphylococcal enterotoxin B and TSS toxin-1 with a single agent.

Structural basis of T-cell specificity and activation by the bacterial superantigen TSST-1

Superantigens (SAGs) bind simultaneously to major histocompatibility complex (MHC) and T-cell receptor (TCR) molecules, resulting in the massive release of inflammatory cytokines that can lead to toxic shock syndrome (TSS) and death. A major causative agent of TSS is toxic shock syndrome toxin-1 (TSST-1), which is unique relative to other bacterial SAGs owing to its structural divergence and its stringent TCR specificity. Here, we report the crystal structure of TSST-1 in complex with an affinity-matured variant of its wild-type TCR ligand, human T-cell receptor beta chain variable domain 2.1. From this structure and a model of the wild-type complex, we show that TSST-1 engages TCR ligands in a markedly different way than do other SAGs. We provide a structural basis for the high TCR specificity of TSST-1 and present a model of the TSST-1-dependent MHC-SAG-TCR T-cell signaling complex that is structurally and energetically unique relative to those formed by other SAGs. Our data also suggest that protein plasticity plays an exceptionally significant role in this affinity maturation process that results in more than a 3000-fold increase in affinity.

Expanding disease spectrum associated with puerperal mastitis

Background Staphylococcus aureus and the β-hemolytic streptococci are the commonest causes of puerperal mastitis which tends to be a localized disease process. This report describes 2 cases attributable to these bacteria that resulted in extramammary involvement and augmented morbidity. Cases: Two cases of postpartum mastitis are described, one leading to necrotizing fasciitis caused by group A streptococci and the other leading to toxic shock syndrome (TSS) caused by S. aureus. Conclusion The spectrum of disease commonly attributed to mastitis occurring in this setting should be expanded. Infect. Dis. Obstet. Gynecol. 5:376–379, 1997. © 1998 Wiley-Liss, Inc.

Expanding Disease Spectrum Associated With Puerperal Mastitis

Background: Staphylococcus aureus and the β-hemolytic streptococci are the commonest causes of puerperal mastitis which tends to be a localized disease process. This report describes 2 cases attributable to these bacteria that resulted in extramammary involvement and augmented morbidity. Cases: Two cases of postpartum mastitis are described, one leading to necrotizing fasciitis caused by group A streptococci and the other leading to toxic shock syndrome (TSS) caused by S. aureus. Conclusion: The spectrum of disease commonly attributed to mastitis occurring in this setting should be expanded.