Staphylococcal Toxic Shock Research Articles

Toxic shock syndrome toxin-1 (TSST-1) antibody levels in Japanese children

Children with burns have a greater risk of developing toxic shock syndrome (TSS) than adults. This risk is thought to be associated with colonisation by toxic shock syndrome toxin-1 (TSST-1)-producing Staphylococcus aureus in children with insufficient antibody titers. The diagnosis of TSS is difficult because, in the early stages, its signs and symptoms resemble those of other common childhood illnesses such as scarlet fever. If the condition is not treated promptly, the mortality rate is high. This study was designed to determine the titers of TSST-1 serum antibody in Japanese children, in order to prevent TSS and facilitate its early diagnosis. Between May 2006 and May 2007, we studied 119 patients who were treated in the Department of Plastic and Reconstructive Surgery of Kanazawa Medical University Hospital. An enzyme-linked immunosorbent assay (ELISA) was used to test the level of the IgG antibody to TSST-1 in the patients’ serum samples. The percentage of cases testing for TSST-1 antibody in the patients under 6 months old was 78.6%, and it was lowest (21.3%) in the age group from 6 to 12 months old. The group of patients older than 41 years showed the highest rate of positivity (100.0%) for TSST-1 antibody. Higher titers of TSST-1 antibody were found within the first 6 months after birth, and lower titers were found between 6 months and 2 years old. The titers began to increase again after age three. The high morbidity of TSS in children around 2 years of age was proven to be related to changes in the titers of TSST-1 antibody. Infants under 6 months old are protected from TSS because of the high level of TSST-1 antibody they receive from their mother. Children are at risk of developing staphylococcal toxic shock syndrome when their immune system is immature and they have no protective circulating anti-TSS antibodies.

Staphylococcal Toxic Shock Syndrome Erythroderma Is Associated with Superantigenicity and Hypersensitivity

Staphylococcal toxic shock syndrome (TSS) has rarely been reported without rash and desquamation. This study describes a patient who met all criteria for TSS except erythroderma and desquamation. The associated staphylococcal superantigen was enterotoxin B. We demonstrate that erythroderma depends on preexisting T cell hypersensitivity amplified by superantigenicity.

Reduction inStaphylococcus aureusGrowth and Exotoxin Production and in Vaginal Interleukin 8 Levels Due to Glycerol Monolaurate in Tampons

Staphylococcal menstrual toxic shock syndrome depends on vaginal production of exotoxins. Glycerol monolaurate (GML) inhibits Staphylococcus aureus exotoxin production in vitro. The purpose of this study was to determine whether GML, as a tampon fiber finish, inhibits production of exotoxins and the cytokine interleukin 8 (IL-8) during normal tampon use. On day 2 of menstruation, when vaginal S. aureus counts are high in colonized women, study participants exchanged their own preferred tampons, after wearing them for 2-6 h, for study tampons with or without GML (assigned randomly and blindly), which they then wore for 4-6 h. The women's own tampons and the study tampons with or without GML were assayed for S. aureus, the exotoxins toxic shock syndrome toxin 1 and alpha-toxin, and IL-8. A total of 225 women completed the study. S. aureus was present in the tampons of 41 women (18%). Lower numbers of S. aureus and the exotoxins were detected in study tampons with or without GML than in women's own tampons; lower amounts of the exotoxins were present in study tampons with GML than study tampons without GML. The IL-8 level was lower in tampons from women without vaginal S. aureus compared with women with S. aureus and was lower in study tampons with GML than in study tampons without GML. Tampons that contain GML reduce S. aureus exotoxin production. S. aureus increases vaginal IL-8 levels, and GML reduces production of this proinflammatory cytokine. These results suggest that GML added to tampons provides additional safety relative to menstrual toxic shock syndrome as well as benefits for vaginal health generally, thus supporting the addition of GML to tampons.

Tigecycline attenuates staphylococcal superantigen-induced T-cell proliferation and production of cytokines and chemokines

The purpose of this study is to examine the in vitro modulatory effect of tigecycline on staphylococcal superantigen-induced T-cell activation and cytokines and chemokines production by human peripheral blood mononuclear cells (PBMC). Isolated human PBMC from ten healthy volunteers were stimulated by staphylococcal enterotoxin B (SEB) and Staphylococcal toxic shock syndrome toxin-1 (TSST-1) superantigens with varying concentrations of tigecycline. Cytokines IL-1β, IL-6, TNF-α, and chemokines MIP-1α and MIP-1β concentrations were measured along with T cell proliferation. Results demonstrated that tigecycline alters cytokine production and reduces T-cell proliferation in vitro suggesting an immunomodulatory activity independent of its antimicrobial effect.

Staphylococcal enterotoxin genes are common inStaphylococcus aureusintestinal flora in Sudden Infant Death Syndrome (SIDS) and live comparison infants

Pathological and epidemiological findings in sudden infant death syndrome (SIDS) suggest an infectious aetiology with indications of involvement of staphylococcal enterotoxins (SEs). While SEA, SEB and SEC have been found in the sera and tissues of SIDS cases, little is known about the role of intestinal Staphylococcus aureus or the roles of later-described toxins SEE, SEG, SEH, SEI and SEJ in SIDS. We used a molecular-based approach to define whether the intestinal tract could be a source of SEs to support the staphylococcal toxic shock hypothesis for SIDS. Intestinal contents from 57 SIDS infants and faeces from 79 age- and gender-matched live comparison infants were cultured and tested for S. aureus and sea-b-c-e-g-h-j and TSST using PCR. High proportions of infants in both groups carried toxigenic and nontoxigenic S. aureus. Significantly greater proportions of SIDS compared with comparison babies were positive for S. aureus (68.4% vs. 40.5%) and for SE genes (43.8% vs. 21.5%), suggesting a possible role in SIDS. The results indicate that colonization by S. aureus with SE genes is common in infants; however, their detection is unlikely to be a strong predictive tool for SIDS. Other factors (including immune response) may reveal a specific susceptibility to SEs in SIDS infants.

How could improvement in the management of T-cell acute lymphoblastic leukemia be achieved? Experience of Princess Nourah Oncology Center, National Guard Hospital, Jeddah, Saudi Arabia

10048 Background: T-cell acute lymphoblastic leukemia (T-ALL) is representing 10–15% of pediatric ALL. The use of more intensive treatments and risk adapted therapy have significantly improved the outcome of patients with T-ALL and event-free survival rate of 60–70% are now reported in children. Our published data showed that T-ALL phenotype patients fared poorly with 5 year survival of 27% versus 83% for precursor B-ALL (Recent Advances Research Update: 2006, 7; 1, P 51–56). Objectives: We reviewed all patients diagnosed with T-ALL to assess risk classification according to NCI criteria, type of therapy received, overall survival and causes of mortality. Methods: Retrospective review of all patients files diagnosed with T-ALL from 1989 until now with data collection including; sex, age, white cell count (WBCs), CNS disease, type of protocol used, length of survival, overall survival, cause of death (toxic, disease). Results: Over the last 20 years, T-ALL cases registered were 52/460 (11%) of all ALL cases, Male:Female ratio 42:10 (4.2:1), median age 7 year (range: 1.5–12 yrs). Median WBCs 50,000/Cmm (range: 1.500–619,000/Cmm) and positive CNS at diagnosis 10/52 (20%). NCI risk classification criteria showed SR 24/52 (46%) and HR 28/52 (54%). Protocols used were UKALL ( n = 21; 3 UKALL X-B, 4 UKALL X-D, 10 UKALL XI and 4 MRC-97 ). BFM (n = 8); and CCG 1961 (n = 23). Overall survival 27/52 (52%) and 25 pts. died (48%); 15 secondary to disease recurrence (9 on UKALL, 4 BFM, 2 CCG 1961); 4 during induction, 1 fulminant hepatic failure, 1 tumor lysis syndrome, and 4 due to toxicities (mucormycosis, staphylococcal toxic shock syndrome, CMV pneumonia, pseudomonas sepsis). Survival for different regimen; UKALL: 5/21=31%, BFM: 4/8=50%, CCG: 18/23=78%, while overall cohort survival 52%. Mean length of survivors 4 year (range 4–140 month) and mean length for non-survivors 1 year (range 0.1–40 months). Conclusions: This review showed the improvement of T-ALL survival from 27% to 56%. Using augmented therapy based on CCG1961 was associated with better outcome. Further risk and response stratification in addition to intensification of therapy for T-cell ALL in our center may prove to be beneficial. Therapy remains an important prognostic factor. No significant financial relationships to disclose.

Evaluation of Surveillance Methods for Staphylococcal Toxic Shock Syndrome

We compared passive surveillance and International Classification of Diseases, 9th Revision, codes for completeness of staphylococcal toxic shock syndrome (TSS) surveillance in the Minneapolis–St. Paul area, Minnesota, USA. TSS-specific codes identified 55% of cases compared with 30% by passive surveillance and were more sensitive (p = 0.0005, McNemar χ2 12.25).

Infections due to Gram-Positive Cocci

The gram-positive cocci that produce infection include pneumococci, group A streptococci, non?group A streptococci (including groups B, C, D, G, and nongroupable streptococci), anaerobic streptococci, enterococci, and staphylococci. This chapter discusses the pathogenesis, diagnosis, and treatment of infections associated with each of these gram-positive cocci, including methicillin-resistant Staphylococcus aureus (MRSA). The clinical infections caused by each of these organisms are reviewed. Tables describe the incidence of pneumococcal disease according to age and underlying disease, factors associated with adverse outcomes in pneumococcal pneumonia; medically important streptococci and enterococci; antibiotic treatment for penicillin-resistant Streptococcus pneumoniae, enterococcal infections, and staphylococcal infections; laboratory tests for streptococcal pharyngitis; clinical manifestations and antibiotic treatment for staphylococcal toxic-shock syndrome (TSS); revised Jones criteria for the diagnosis of acute rheumatic fever, and drug treatment of acute rheumatic fever. This review contains 105 references.

Characterization of Staphylococcus aureus Isolated from Dairy Animals in Ireland

Enterotoxigenic Staphylococcus aureus frequently contaminate milk and milk products causing food poisoning. Staphylococcus aureus were isolated from bovine, ovine and caprine milk and milk filters from 78 dairy production holdings supplying the farmhouse cheese sector in Ireland, using standard culture methods. Molecular methods were applied to study the distribution of genes encoding staphylococcal enterotoxins and toxic shock syndrome toxin in the collection. Multilocus variable number tandem repeat analysis was used to subtype the collection. One hundred and two Staphylococcus aureus (54 milk filters and 48 bulk milk) were recovered from apparently healthy animals; half of the isolates were toxigenic. Our findings are discussed in light of the risks posed to public health.

Biological characterization of the zinc site coordinating histidine residues of staphylococcal enterotoxin C2

The bacterial toxin staphylococcal enterotoxin C2 (SEC2) can cause staphylococcal toxic shock syndrome and food poisoning. Although the previously determined crystal structure of SEC2 revealed that some histidine residues (His47, His118 and His122) contribute to the binding of zinc ions, little is known about their biological roles in SEC2. This prompted us to investigate the role of the zinc site coordinating histidine residues in the biological activities of SEC2. The mutants with substitutions at positions 118 and 122 all retained T-cell stimulatory activity, whereas the histidine mutants at position 47 were defective in the ability to stimulate T-cell proliferation. Further toxicity assays in vivo indicated that mutants SEC2-H118A and SEC2-H122A were defective in emetic and febrile activities. However, mutant SEC2-H47A could cause significant emetic and febrile responses in comparison with the other two histidine mutants. These findings suggested that the zinc-coordinating histidine residues play significant roles in superantigen and toxic activities of SEC2 and further implied that superantigen and febrile activities could be separable in staphylococcal enterotoxins. The results also show that it should be possible to design new SEC2 immunotherapeutic agents that have superantigen activity and low toxicity.

An alternative approach to combination vaccines: intradermal administration of isolated components for control of anthrax, botulism, plague and staphylococcal toxic shock

BackgroundCombination vaccines reduce the total number of injections required for each component administered separately and generally provide the same level of disease protection. Yet, physical, chemical, and biological interactions between vaccine components are often detrimental to vaccine safety or efficacy.MethodsAs a possible alternative to combination vaccines, we used specially designed microneedles to inject rhesus macaques with four separate recombinant protein vaccines for anthrax, botulism, plague and staphylococcal toxic shock next to each other just below the surface of the skin, thus avoiding potentially incompatible vaccine mixtures.ResultsThe intradermally-administered vaccines retained potent antibody responses and were well- tolerated by rhesus macaques. Based on tracking of the adjuvant, the vaccines were transported from the dermis to draining lymph nodes by antigen-presenting cells. Vaccinated primates were completely protected from an otherwise lethal aerosol challenge by Bacillus anthracis spores, botulinum neurotoxin A, or staphylococcal enterotoxin B.ConclusionOur results demonstrated that the physical separation of vaccines both in the syringe and at the site of administration did not adversely affect the biological activity of each component.The vaccination method we describe may be scalable to include a greater number of antigens, while avoiding the physical and chemical incompatibilities encountered by combining multiple vaccines together in one product.

Analysis of superantigenic toxin Vβ T-cell signatures produced during cases of staphylococcal toxic shock syndrome and septic shock

Most clinical isolates of Staphylococcus aureus harbour genes encoding superantigenic toxins that bind the Vbeta domain of T-cells, but little information is available concerning superantigenic toxin production during staphylococcal toxic shock syndrome (TSS) and septic shock. This prospective study investigated 14 patients with staphylococcal TSS or septic shock; the toxin gene profile of each isolate was determined and flow-cytometry was used to identify the discriminant Vbeta signature (DVbetaS) of each superantigenic toxin in vitro. Attempts were also made to identify in-vivo production of superantigenic toxin DVbetaS in patients' blood. The DVbetaS identified in vitro were: toxic shock syndrome toxin (TSST)-1, Vbeta 2; staphylococcal enterotoxin (SE), Vbeta 9, Vbeta 22; SEB, Vbeta 3, Vbeta 14, Vbeta 17; SED, Vbeta 1, Vbeta 8; egc, Vbeta 5.3, Vbeta 7.1, Vbeta 9, Vbeta 23; and SElK, Vbeta 5.1. The DVbetaS of TSST-1 and SEB were detected in patients with menstrual and non-menstrual TSS, respectively, whereas no Vbeta signature was detected during septic shock. All patients with septic shock (but only one patient with TSS) had lymphopenia and/or impaired cellular immunity. Detection of a superantigenic toxin DVbetaS may help to show which toxin is produced during staphylococcal TSS, thus confirming the diagnosis and hastening the administration of anti-toxin therapy. In contrast, this approach failed to demonstrate superantigenic toxin involvement in cases of septic shock. In this latter condition, a superantigenic toxin may not be produced by S. aureus, or its production may occur without expansion of targeted T-cells because of T-cell apoptosis and/or anergy.

Staphylococcal scalded skin syndrome and toxic shock syndrome after tooth extraction

Staphylococcus aureus may cause cutaneous and systemic infections such as staphylococcal scalded skin syndrome (SSSS) and toxic shock syndrome (TSS). Although exfoliative toxins A and B, which cause SSSS, and TSS toxin-1 may be produced by different strains of S aureus, the two syndromes rarely occur simultaneously. We describe a patient admitted to the intensive care department with an exfoliative generalized erythroderma, signs of shock, and biopsy specimen findings consistent with SSSS. This patient presented after a tooth extraction. Symptoms recurred after dismissal, and he was readmitted. Subsequent test results were positive for exfoliative toxin B and TSS toxin-1, suggesting concurrent SSSS and TSS. For patients with acute, exfoliative, generalized erythroderma, TSS and SSSS should be considered. Although rare, it is possible to see both syndromes present concurrently.

The Role of Superantigens in Chronic Rhinosinusitis with Nasal Polyps

Recent reports suggest that staphylococcal exotoxins, acting as superantigens, activate T cells with subsequent massive proliferation, thereby contributing to the etiology of chronic rhinosinusitis with nasal polyps (CRSwNP). The objectives of this study are (1) to demonstrate directly the presence of staphylococcal exotoxins in nasal mucosa and sinonasal polyp tissue, and (2) provide indirect evidence of the effect of superantigens on the T cells expressing the target of superantigen, i.e., the β variable chain receptor (TCRBV) in polyp tissue and peripheral blood of patients with CRSwNP. Sinonasal polyp tissue and peripheral blood specimens were obtained from 37 patients with chronic rhinosinusitis (22 patients with bilateral nasal polyps, 15 without nasal polyps) and 12 normal subjects for comparative negative controls. Tissue specimens were assayed by enzyme-linked immunosorbent assay (ELISA) for the most common staphylococcal exotoxins (A–D) and toxic shock syndrome toxin type 1. Fresh tissue and blood samples were analyzed by flow cytometry to determine the expression of TCRBV. In the CRSwNP subjects 12 of 22 samples (54.54%) demonstrated reactivity for at least 1 staphylococcal exotoxin, while 2 of the 12 were positive for 2 toxins. There were no positive results in the CRS without nasal polyps or control groups. There was a clear trend of increased TCRBV expression in the ELISA-positive group both for tissue and blood specimens. Staphylococcal superantigens were present in the nasal cavity of patients with CRSwNP with a high percentage of TCRBV, which suggests the possibility of superantigens as etiological agents of CRSwNP.

Symmetrical peripheral gangrene complicating staphylococcal toxic shock syndrome

Sudden onset symmetrical peripheral gangrene (SPG) is a relatively uncommon clinical entity which was initially described in 1981 by Hutchison. It is defined as symmetric distal ischemic damage in two or more sites in the absence of major vascular occlusive disease [1, 2, 3]. It is a manifestation of many systemic disorders and accompanies infectious disease of various etiologies, shock, drugs and malignancy [1, 2, 3]. Toxic shock syndrome (TSS) is an acute life threatening inflammatory response characterized by fever, rash, hypotension, constitutional symptoms and multiorgan involvement [4, 5]. The disease first described in 1978, is typically associated with tampon use in healthy menstruating women. The disease also exists in men, neonates and non-menstruating women. TSS is a toxin mediated disease caused by coagulase - positive staphylococci (S aureus) and group A beta- hemolytic streptococci (S pyogenes) [4, 5]. We report a case of staphylococcal TSS, complicated by rapid onset SPG involving the toes and fingers.

EARLY DIAGNOSIS OF STAPHYLOCOCCAL TOXIC SHOCK SYNDROME BY DETECTION OF THE TSST-1 VBETA SIGNATURE IN PERIPHERAL BLOOD OF A 12-YEAR-OLD BOY

We report the case of a 12-year-old boy who developed staphylococcal toxic shock syndrome associated with S. aureus pharyngeal colonization or infection. The diagnosis was rapidly confirmed by detecting the Vbeta signature of the toxic shock syndrome toxin-1 in peripheral blood, based on transient T cell depletion rapidly followed by massive expansion of Vbeta 2-positive T cells.

The Potency of Anti-Oxidants in Attenuating Superantigen-Induced Proinflammatory Cytokines Correlates with Inactivation of NF-κB

Excessive release of proinflammatory cytokines and chemokines mediates the toxic effects of superantigenic staphylococcal exotoxins (SE). We evaluated the potency of two anti-oxidants, N-acetyl-cysteine (NAC) and pyrrolidine dithiocarbamate (PDTC) in inhibiting the staphylococcal enterotoxin B and staphylococcal toxic shock syndrome-1-induced activation of human peripheral blood mononuclear cells (PBMC). Both NAC and PDTC dose-dependently inhibited SE-stimulated T-cell proliferation (by 98%), production of cytokines and chemokines by PBMC and expression of SE-induced cell surface activation markers. The potency of both NAC and PDTC corresponded to their ability to inhibit NF-κB activation. Our results suggest that anti-oxidants might be useful to mitigate the pathogenic effects of SE by blocking transcriptional signaling activated by superantigens.

Staphylococcal Toxic Shock Syndrome Toxin‐1 Induces the Translocation and Secretion of High Mobility Group‐1 Protein from Both Activated T Cells and Monocytes

High mobility group box-1 (HMGB-1) is a DNA-binding protein secreted by activated monocytes and has been identified as a key late mediator of endotoxic shock. We investigated the regulation of HMGB-1 in human peripheral blood mononuclear cells (PBMCs) following stimulation with the staphylococcal superantigen, toxic shock syndrome toxin-1 (TSST-1), and found that TSST-1, like LPS, induced the secretion of HMGB-1 from human PBMC. However, unlike monocyte-driven sepsis caused by endotoxin, translocation and secretion of HMGB-1 mediated by TSST-1 was dependent on the presence of both activated T cells and monocytes. Furthermore, we show that nuclear HMGB-1 is released from TSST-1 stimulated T cells. This finding presents a basis for investigating the potential of targeting HMGB-1 for the treatment of toxic shock syndrome, and provides further insight on the role of HMGB-1 in the cross-talk between activated monocytes and T cells.

Clinical and microbiological characteristics of staphylococcal toxic shock syndrome presenting to a paediatric intensive care unit

Background: Staphylococcal toxic shock syndrome (STSS) is a toxin-mediated disease which presents with fever, rash, hypotension and multi-organ dysfunction. This study describes the clinical characteristics, intensive care management and characterisation (including toxin gene profiles) of staphylococcal isolates from cases presenting to a paediatric intensive care unit in London.

Analysis of Twin-Arginine Translocation Pathway Homologue in Staphylococcus aureus

Staphylococcus aureus releases a large number of exoproteins, including membrane-active proteins and toxins with superantigenic activity involved in pathogenicity. However, the export pathways of exoproteins in S. aureus have not been reported. We analyzed the function of the staphylococcal twin-arginine translocation (Tat) pathway homologue, the presence of which was recently discovered according to the genome database. The amino-acid sequences of the Tat homologues of S. aureus do not have a high similarity with those of Escherichia coli and other bacteria. Constructed tatC-deficient mutants from distinct parent strains showed the same patterns of exoproteins compared with those of parent strains on two-dementional gel electrophoresis, and the amounts of secreted staphylococcal enterotoxins and toxic shock syndrome toxin-1, of which signal peptides have some features often seen in signal sequences of Tat-dependent proteins, did not change with Western blotting analyses. Therefore, it seems that the Tat pathway does not play a major role in the secretion system of S. aureus, but other export pathways may play an important role in toxin secretion. This is the first experimental report showing the influence of the Tat pathway on the secretion of S. aureus.