ProductClinical REVIEWREVIEW Toxic : causes in people with burn wounds

Toxic shock syndrome (TSS) is a rare of colonisation or by toxin-producing strains of and has often been associated with use, although menstrual-associated TSS has declined over recent years. Non-menstrual-associated TSS can occur in a variety of conditions including small percentage burns in children. Adults with burns are not normally at risk, but there have been a few reported cases. This article will discuss what factors are involved in the development of TSS in people with burn wounds.

Valerie Edwards-Jones

In 1980, after a strict definition of in the incidence of menstrual-related KEY WORDS TSS was devised by the Centers for TSS (MTSS) (Schuchat and Broome, Disease Control and Prevention in 1991) (Figure 1). In addition, details of Toxic shock syndrome Atlanta, USA (Chesney et al, 1981), TSS and symptoms were included in all Staphylococcus aureus there were hundreds of notified TSS packs of , raising awareness of Burn wounds cases in young women associated with the risks with users. Tampons are now menstruation. Epidemiological studies predominantly made of cotton and rayon in the US showed that this sudden (Schuchat and Broome, 1991). increase was due to the introduction of a highly absorbent tampon containing Since carboxymethylcellulose was oxic shock syndrome (TSS) is a carboxymethylcellulose, Rely™, produced removed from tampons, the incidence of rare complication resulting from by Proctor and Gamble (Schlievert et al, MTSS has equalled that of non-menstrual Tcolonisation or infection with a 1984). Subsequently these were shown TSS (NMTSS) (Marples and Wieneke, toxin-producing strain of Staphylococcus to increase production of TSST-1 by 1994). NMTSS occurs in men, women aureus. It was first described in 1978 S. aureus in vitro (Lee et al, 1987) and and children and is associated with a by Todd et al who saw seven cases were recalled and discontinued in 1980 plethora of localised focal of TSS in young children with similar which led to a subsequent decrease involving S. aureus. Foci include surgical symptoms (, , diarrhoea, ) that progressed to disseminated 1500 Rely™ tampons withdraw intravascular coagulation, shock Total and multi-organ failure. It was soon Menstrual confirmed in five of the seven cases, Absorbency lowered Nonmenstrual that the syndrome was a result of infection associated with S. aureus of 1000 phage group 1 (Todd et al, 1978). It was shown that toxic shock syndrome toxin-1 (TSST-1) was involved in the Polyacrylate removed pathogenesis of the syndrome (Bergdoll Number of Cases et al, 1981; Schlievert et al, 1981; 500 Bergdoll and Schlievert, 1984) and since then there have been reported cases associated with other staphylococcal , namely enterotoxin A, B and C (SEA–C) (Yaqoob et al, 1990). 1980 1985 1990 1995 Valerie Edwards-Jones is Assistant Director of Year Research Development, Research Office, St Augustine’s, Manchester Metropolitan University Figure 1. The incidence of TSS per year in the USA 1979–1996 (adapted from Hajjeh et al, 1999).

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5–30% of the T cells can be activated by Antigen Presenting Cell an SAg whereas conventional antigen Table 1. presentation will only stimulate one in Classic criteria for clinical diagnosis of TSS MHC class II 10,000 cells (Marrack and Kappler, 1990) (Figure 2). This causes an overproduction 8 Fever above 38.9˚C Normal of an array of cytokines, such as tumour 8 or orthostatic dizziness Antigen necrosis factor (TNF), interleukin-1 (IL-1), 8 Diffuse or palmar T Cell IL-2, IL-6 and interferon. It appears to be 8 of hands and feet Receptor the over activation of the immune system 8 of conjunctivae and of the mucous by these cytokines that produce some of membranes of the oropharynx or vagina T Cell the clinical symptoms seen in TSS (Kotzin 8 Multisystem dysfunction which must include et al, 1993; Drake and Kotzin, 1992; at least four of the following: Figure 2. A schematic diagram of the interaction Kotb,1995). 8 Diarrhoea and vomiting of a normal antigen (left) and superantigen (right) 8 Alterations in consciousness with the T cell and MHC II on an antigen presenting Studies have implicated 8 Impaired renal function cell. A normal antigen lies within the groove staphylococcal SAgs in other 8 Impaired hepatic function formed within the MHC II after antigen processing. such as neonatal toxic shock syndrome- 8 bind to the outer part of the MHC II like exanthematous disease (NTED) 8 Elevated muscle creatinine phosphokinase without any processing. characterised by skin eruption caused 8 Cardiopulmonary dysfunction by TSST-1 producing strains of S. aureus 8 Decreased serum calcium and phosphate

wounds, pregnancy termination, deep (Iwatsuki et al, 2006), atopic disease (Davis et al, 1980; Chesney et al, 1981) , lacerations, furuncles (an (Michie and Davis, 1996; Baker 2006), infection of a hair follicle) (Reingold et nasal polyposis caused by the effect al, 1982), (Gahrn-Hansen of the SAg on the local nasal mucosa et al, 1989), rhinoplasty (Allen et al, (Tripathi et al, 2005), and sudden infant Egan and Clark, 1988; McAllister et al, 1990) and burns (Frame et al, 1985). death (Newbould et al, 1989; Gordon 1993; Johnson and Pathirana, 2002). Some Cases of TSS associated with wounds et al, 2002). Atopic disease is a common of these cases (usually <10%) resulted are nearly all following injury, primarily sequela of TSS and in one study 16 out of in death where an uneventful recovery small percentage burns (Frame et al, 68 patients recovering from TSS caused would have been expected (McAllister 1985; Egan and Clark, 1988; McAllister et by TSST-1-producing strains of S. aureus et al, 1993). In a typical case of TSS in a al,1993). However, there has been one developed chronic dermatitis compared patient with burns, the patient will present reported case of TSS associated with a with no patients in the group who had with severe pyrexia (40˚C), tachycardia foot ulcer in a male patient with diabetes caused by Gram-negative (200 beats/min), and tachypnoea (51 (Arnold et al, 2001). (Michie and Davis, 1996). breaths/min) quite soon after admission Antibodies to TSST-1 are protective and (mean 2.2 days). This progresses rapidly The symptoms of TSS (Table 1) are they work by preventing the activation to vomiting, diarrhoea, rash, and oliguria. predominantly due to the action of of T cells by the superantigenic TSST-1 Some may also show neurological TSST-1, whose molecular shape makes and overproduction of cytokines (Takei disturbances and if intervention is not it a powerful superantigen (SAg) which et al. 1993). This is a major factor for the implemented at this stage the patient will causes an over-stimulation of T-cells prevention of TSS and work is currently develop multi-organ failure (McAllister in the immune system (Marrack and progressing toward developing vaccines et al, 1993). Specific treatment against Kappler, 1990; Fleischer, 1994). Antigen against some of the virulence factors. the toxin involves the use of passive processing happens when proteins that antibodies present in intravenous human have been endocytosed are degraded Streptococcal pyogenic toxins immunoglobulin, fresh frozen plasma inside the cell by enzymes (usually acid- (SPE) A–C produced by or whole blood as 75% of these fluids dependent proteases) and presented pyogenes can cause a condition very have been shown to contain antibodies via the MHC II complex on the outside similar to TSS and is called toxic shock- for TSST-1 (Childs et al, 1994). These surface so they can be recognised by T like syndrome (TSLS) (Martin and antibodies act by protecting the patient cells, allowing activation of the immune Green, 2006). Typically from day four against the effects of the toxin. Flucloxacillin system. Without any antigen processing, of the streptococcal infection, shock is administered to destroy the S. aureus the SAgs cross-link the variable region and fasciitis are also seen (Roggiani and and prevent any further release of toxin. on the T-cell receptor (TcR) of T cells Schlievert, 1994). The effects of hypovolaemic shock are with the outer groove of the major clinically supported with blood or plasma histocompatibility complex (MHC) II TSS as a complication expanders (McAllister et al, 1993). molecules on the host cells. In normal of a small percentage burn antigen processing, the antigen is Frame et al (1985) described the first Why does TSS develop? presented via the inner groove of the case of TSS in children with burn wounds. Why TSS develops is not clearly MHC II molecule to T cells. Between Several cases followed (Farmer et al, 1985; understood but it appears to be

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dependent on several factors (Edwards- burns generally do not receive fluids but it merits further investigation. New Jones and Shawcross, 1997): unless it is clinically indicated. Their technologies (microarrays) are now 8 The person has to be infected or treatment focuses primarily on wound available to allow this to be investigated colonised by a toxin-producing strain management. TSS associated with burns more comprehensively. of S. aureus is more common in people with less 8 The correct environmental than 10% TBSA burns (Edwards-Jones In a number of case reports, dressing conditions must be present to and Shawcross, 1997; Johnson and components have been implicated as stimulate production of TSST-1 (or an Pathirana, 2002), and it is postulated possible environmental factors that equivalent superantigenic toxin) that this group do not receive the stimulate toxin production (Egan and 8 The person must not have protective that is effected via Clark, 1988; Weinzweig et al, 1994). It antibodies to TSST-1 and other blood products. Childs et al (1994) is possible that some dressings provide staphylococcal enterotoxins (Takei et discussed this and showed that 75% of conditions that are favourable for toxin al, 1993) from a previous exposure infused whole blood or fresh-frozen production, perhaps through chelation (typically during transient nasal plasma contained antibodies to TSST-1. of magnesium or other metal ions. colonisation) Some highly absorbent burn dressings 8 The person must be genetically Wound management procedures for contain carboxymethylcellulose (British susceptible to the superantigenic the patient with burns differ between National Formulary, 1994) which was a effects of the toxin. burns units; but the majority use component of the tampons that were ointments and/or impregnated dressings implicated in menstrual-related TSS. Each of these factors will now be in an attempt to prevent infection Sub-lethal levels of silver sulphadiazine r own natural white cell discussed in relation to patients with burns. (Edwards-Jones et al, 2000). have been shown to increase TSST-1 defences. prophylaxis is not part of the normal production in vitro in 45% of strains of S. Colonisation/infection of the burn wound management of burns, but some units aureus although the precise mechanism AQ21 Add this reference in Immediately following injury the wound now administer prophylactic has not yet been determined (Edwards- with Serralta et al. is sterile but within a few hours it to reduce the risk of a patient developing Jones and Foster, 1994). rapidly becomes colonised by a variety TSS (Johnson and Pathirana, 2002; AQ22 of bacteria, usually derived from the Rashid et al, 2005) although there is no A commonly-used silver dressing host, or in some cases from an external consensus among burn centres (Papini et has also been shown to increase TSST- Cooper 2004 can go. source. S. aureus is the most frequently al, 1995; Edwards-Jones et al, 2000). 1 production in vitro in a liquid culture isolated pathogen found in a burn medium as well as in a semi-solid AQ23 wound and the colonisation rate can be Environmental factors influencing toxin production model system (Buck et al, 2002). Sub- as high as 30% (Lawrence, 1992) with Several physical factors in the burn lethal levels of silver sulphadiazine and Costerton 1999 should go in 11% of patients becoming colonised wound, such as the oxygen availability, the silver dressing were also shown to with Costerton 1995 within one day of injury (Childs et al, the pH of surrounding fluid and the inhibit staphylococcal metalloprotease 1994). It has been shown that 55% of availability of trace metal ions create and other virulence factors such as AQ24 S. aureus isolated from patients with a favourable environment for toxin haemolysins (Edwards-Jones and Foster, burn wounds can produce one or more production that normally occurs at the 2002; Buck et al, 2002). Although these Gerson can go. toxins and the incidence of TSST-1 end of the exponential growth phase of in vitro data indicate a risk of developing and SEA–D toxin from these isolates bacteria. Several of these factors have TSS with the use of these ointments and AQ25 Figure 2. were 16.6%, 13%, 12%, 23% and 3.6% been shown to increase TSST-1 toxin dressings, large numbers of cases of TSS

Figure 3. respectively (Edwards-Jones et al, 1996). production in vitro (Kass et al, 1987; have not been reported associated with Harrison-Balstra can also go. This shows that not all isolates of S. Sarafian and Morse, 1987; Reeves, 1989; their use (Edwards-Jones et al, 2000). aureus produce the toxins equally. In the Wong et al, 1990). The presence of both AQ26 same study, 20.7% of patients carried blood and protein is also known to Protective antibodies more than one strain of S. aureus. increase the amount of TSST-1 produced Antibodies to TSST-1 are usually absent Mertz should be kept, put it in by S. aureus (Todd et al, 1987). Topical from the sera of patients with TSS, in with Serralta. The extent of the burn (total body antimicrobial agents (Edwards-Jones and contrast to age-matched control subjects surface area [TBSA]), the depth of Foster, 1994; 2002), wound dressings (Bonventre et al, 1984) and patients who AQ27 the burn or evidence of infection will (Buck et al, 2000) and the mixed suffer recurrent TSS do not produce effect the subsequent management of population of bacteria found growing antibodies to either TSST-1 and other Thorn goes. the patient in terms of administration together in a wound can affect the levels enterotoxins (Crass and Bergdoll, 1986). of antibiotics, dressing protocol and of extra-cellular enzymes and TSST-1 TSST-1 antibodies are protective and AQ28 intravenous fluids. Patients with more produced by S. aureus in vitro (Sergent can prevent the development of TSS than 10% TBSA burns are usually and Edwards-Jones, 1996). In a study by in animal models when given passive In the references with Chaw, infused with intravenous fluids or Holland et al (1998), supernatant fluid immunisation with TSST-1 monoclonal Akiyama on the first page. Add plasma expanders to replace fluid of S. epidermidis was shown to reduce antibodies (Best et al, 1988). A study in White RJ (2005) The benefits losses (Muir and Barclay, 1962), whereas TSST-1 production. It is not known if undertaken in 1983 showed that TSST-1 of honey in wound management. patients with less than 10% TBSA the same effects occur at wound sites; antibodies develop with age and that

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47%, 58%, 70%, 88%, 96% and 99% of DR in normal human keratinocytes bacterial strain (Balaban et al, 1995; Ji the population have antibodies at the (Morishita et al, 1999), and very recent et al, 1995). When the concentration ages of one, five, 10, 20, 30, and 50 years studies have shown that there are reaches an optimal level, an array of respectively (Vergeront et al, 1983). This differences in binding and presentation virulence factors/secondary metabolites was confirmed in children admitted to of the staphylococcal SAg staphylococcal (including toxins and enzymes) are a paediatric burns unit in Manchester enterotoxin A by different HLA-DR produced (Novick et al, 1993). This where 49% of children possessed alleles (Llewelyn et al, 2006). If this is the phenomenon is termed quorum sensing antibodies to TSST-1 (Childs et al, 1994; case then this subtle difference could and is dependent on the concentration 1999). This implies that the children account for the severity of disease of organisms. The cells signal to each under five years are at greater risk of in different patient groups. It may be other and communicate using these developing TSS because of the lack of that binding of the different SAgs with molecules. Furthermore it has become protective antibodies to TSST-1. different HLA-DR allelic types can more apparent that bacteria grow ultimately affect levels of expression of in communities as biofilms therefore The occurrence of antibodies to cytokines. requiring a very sophisticated system of other enterotoxins, such as SEA–E, varies communication (Lyon and Novick, 2004). within the population (Notermans et al, The increase in knowledge is leading 1983). The risk of developing TSS for a to improvements in diagnosing TSS, which In vitro studies have shown that person aged over 50 years is extremely has always been difficult because the biofilm formation has been inhibited by rare (1%), but not totally unknown. Two early stages resemble many common ribonucleic-acid-III-inhibiting peptide (RIP) cases of TSS have been described in infectious diseases and TSS is not often that enhances the effects of antibiotics adult patients with burns. The first case, confirmed until the latter stages when the and cationic peptides. RIP is part of in 1999, was a 38-year-old woman with patient has gone into multi-organ failure the regulatory system and has been 25% flame burns who was colonised and shock. Recent studies have shown extracted and purified. This compound by an S. aureus-producing enterotoxin that the expansion of T-cell V2 families thus has potential as a new molecule B (Withey et al, 1999) and the second in peripheral blood can be used as a that may have a use in prevention was a 64-year-old man with 15% scald rapid diagnostic test for TSS using a flow or treatment of colonistion/infection in whom the focus of infection was not cytometer (Matsuda et al, 2003). and ultimately toxin expression (Lyon determined (Masaki et al, 2004). These and Novick, 2004). This may result in two cases confirm that the development Future research suppression of virulence factors and may of TSS does not depend upon one TSS is a complex disease and in order have an impact on wound healing as well single factor. Studies by Jacobson et al to unravel how it develops in the as the development of TSS. This complex (1989) showed that patients infected susceptible host, a full understanding of sequence of events can be confounded with a TSST-1-producing strain of S. the interaction of the bacteria and the by alteration of the wound environment aureus who also lacked the antibodies host has to fully elucidated. and subsequent gene expression by to TSST-1 did not develop TSS. This was topical antimicrobial agents and dressings. later substantiated by Childs et al (1994) We know that it is not a single toxin- Now with new technologies and the in a prospective study undertaken on producing strain of S. aureus causing ability to examine gene expression at children with burns. TSS in patients with burns. This is slightly the molecular level using microarrays different to that seen in menstrual TSS we may eventually unravel some of Genetic susceptibility where Musser et al (1990) showed these complex interactive events. In S. aureus can cause local infections as that it was predominantly a single clone addition, further information on host well as toxin-mediated disease and causing TSS in this group of patients. susceptibility to TSS and the role of the can be lethal in the case of sepsis and Non-menstrual TSS is caused by a HLA type warrants further investigation. associated shock (Astiz and Rackhow, number of staphylococcal SAgs (TSST- Understanding exactly how a disease is 1998). Genetic predisposition to this has 1, SEA, SEB, SEC) and all of these have caused may allow the use of some of the been increasingly recognised (Holmes et been described in burn-associated TSS. molecules as potential new treatments. al, 2003). Inherent genetic susceptibility Expression of these SAgs and a variety of to the superantigenic effects of the enzymes are coordinated and controlled Questions that need answering toxins may be a contributory factor in by complex multi-level regulatory systems include: the development of TSS and has been within the genome of the staphylococcus 8 What happens at a local level (i.e. to investigated (Llewelyn et al, 2006) but (Arvidson and Tegmark, 2001). Small the wound healing process) when there is still much information to be molecules identified as octapeptides superantigenic toxins produced by determined before a full understanding in staphylococcal species and N acyl- S. aureus are released into the local is forthcoming. Staphylococcal homoserine lactone molecules in Gram- wound environment? enterotoxins A and B (both SAgs) have negative bacteria (Williams et al, 2000) 8 Do they cause an overstimulation been shown to stimulate expression of can be secreted into the surrounding of the inflammatory process in the intracellular adhesion molecule (ICAM) environment by one strain and have an wound bed? and human leucocyte antigen (HLA)- effect on gene expression by another 8 Could superantigens be used at

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appropriate doses as possible Baker BS (2006) The role of microorganisms Davis JP, Chesney PJ, Wand PJ, La- modulators of the inflammatory in atopic dermatitis. Clin Exp Immunol Ventre M (1980) Toxic shock syndrome: process? 144(1): 1–9 Epidemiological features recurrence risk factors and prevention. New Eng J Med 303: Balaban N, Novick RP (1995) Autocrine 8 Could they have a role to play in 1429–35 chronic wounds? regulation of toxin synthesis by Staphylococcus. Proc Natl Acad Sci USA 92 Drake CG, Kotzin BL (1992) Superantigens: (5): 1619–23 Biology, Immunology and potential role in Conclusion disease. J Clin Immun 12: 149–62 How bacteria either in isolation or in Balaban N, Stoodley P, Fux CA, Wilson S, Costerton JW, Dell’Acqua G (2005) mixed culture cause the over-stimulation Edwards-Jones V, Foster HA (1994) The Prevention of staphylococcal biofilm- effect of topical antimicrobial agents on the of the immune system via cytokines associated infections by the quorum sensing production of toxic shock syndrome toxin-1. J and genetic predisposition leading to inhibitor RIP. Clin Orthop Relat Res 437: Med Microbiol 41(6): 408–13 TSS needs to be determined. New 48–54 Edwards-Jones V, Childs C, Foster HA (1996) technologies are becoming available Bergdoll MS, Crass BA, Reiser RF, Robbins A comparison of isolates of S. aureus from to unravel some of these events at a RN, Davis JP (1981) A new staphylococcal burned patients and other patient groups. molecular level and with detailed clinical enterotoxin, enterotoxin F, associated with Burns 22: 384–9 studies we may be able to identify Toxic Shock Syndrome Staphylococcus aureus isolates. Lancet 1: 1017–21 Edwards-Jones V, Shawcross S (1997) Toxic susceptible patients more rapidly. With shock syndrome in the burned patient. Br J appropriate vaccination or prophylactic Bergdoll MS, Schlievert PM (1984) Toxic Biomed Sci 54: 110–7 shock syndrome toxin. Lancet 2: 691 treatment it may be possible to eradicate Edwards-Jones V, Dawson MM, Childs CA this rare complication of burn wounds in Best GK, Scott DF, Kling MJ, Thompson MR, (2000) Survey into TSS in UK Burn Units. Adinolfe LE, Bonventre PF (1988) Protection the future. WUK Burns 26: 323–3 of rabbits in an infection model of toxic shock syndrome (TSS) by a TSS Toxin-1, specific Edwards-Jones V, Foster HA (2002) The monoclonal antibody. Infect Immun 56: 998–9 effects of silver sulphadiazine on the Key Points production of exoproteins by S. aureus. J Med Bonventre PF, Linnemann C, Weckback LS et Micro 51(1): 50–5 al (1984) Antibody responses to toxic shock syndrome (TSS) toxin by patients with TSS Egan WC, Clark WR (1988) The Toxic Shock 8 Toxic shock syndrome is a rare and by healthy staphylococcal carriers. J Infect Syndrome in a burned victim. Burns 14: 135–8 complication of minor burns in Dis 150: 662–6 Farmer BA, Bradley JS, Smiley PW (1985) children. British National Formulary (1994) Toxic shock syndrome in a scald burn victim. British National Formulary Number 28. J Trauma 25: 1004–6 8 The superantigenic toxins British Medical Association and the Royal Hajjeh RA, Reingold A, Weil A, Shutt K, of Staphylococcus aureus Pharmaceutical Society of Great Britain, Schuchat A, Perkins BA (1999) Toxic shock are responsible for the London: 464–5 syndrome in the : surveillance development of the syndrome. Buck R, Dawson MM, Shawcross SG, update, 1979–1996. Emerg Infect Dis 5: Edwards-Jones V (2000) The Effect of 807–10 8 Topical antiseptics and Wound Dressings on Production by Iwatsuki K, Yamasaki O, Morizane S, Oono T Staphylococcus Aureus. Proceedings of the 9th dressings have been implicated (2006) Staphylococcal cutaneous infections; International Symposium of Staphylococci Invasion, evasion and aggression. J Dermatol as possible risk factors. and , Kolding Sci 42: 203–14 Denmark. 8 Antibodies to the toxins are Fleischer B (1994) Superantigens. Beh Inst Buck R, Dawson MM, Shawcross SG, Miett 94: 104–12 protective. Edwards-Jones V (2002) The Development of A Semi-solid System to Assess the Effect of Wound Frame JD, Eve MD, Hackett MEJ, et al Dressings on TSST-1 Production. Proceedings (1985) The Toxic Shock Syndrome in burned of the British Burns Association conference, children. Burns 11: 234–41 Birmingham UK Gahrn-Hansen B, Lundicvist L, Nielson E References Chesney PJ, Davis JP, Purdy WK, Wand PJ, (1989) Pyomyositis and probable toxic shock Allen ST, Liland JB, Nichols CG, Glew RH Chesney RW (1981) Clinical manifestations syndrome caused by a toxin-1 producing (1990) Toxic shock syndrome associated with of Toxic Shock Syndrome. JAMA 246: 741–8 strain of Staphylococcus aureus. Eur J Clin the use of nasal packing. Arch Int Med 150: Micro Infect Dis 8: 89–90 Childs C, Edwards-Jones V, Heathcote DM et 2587–8 al (1994) Patterns of S. aureus colonisation, Gordon AE, MacKenzie DA, El Ahmer OR et Arnold J, Lucarelli M, Cutrona AF, toxin production, immunity and illness in al (2002) Evidence for a genetic component DiDomenico LA, Karlock L (2001) Toxic burned children. Burns 20: 514–21 in sudden infant death syndrome. Child Care Shock Syndrome originating from the foot. J Health Dev 28 Suppl 1: 27–9 Childs C, Dawson MM, Edwards-Jones Foot Ankle Surg 40: 411–3 V (1999) Toxic shock syndrome toxin-1 Holland KT, Timmins B, Wright J, Davis Arvidson S, Tegmark K (2001) Regulation antibodies in burned children. Burns 25: W (1998) Does the microflora of the of virulence determinants in Staphylococcus 473–6 vagina modulate expression of tst by S. aureus. Int J Med Microbiol 291: 159–70 aureus? In: Arbuthhnott J, Furman B eds. Crass BA, Bergdoll MS (1986) Toxin European Conference on Toxic Shock Syndrome Astiz ME, Rackhow EC (1998) Septic shock. involvement in Toxic Shock Syndrome. J Inf International Congress and Symposium series Lancet 351: 1501–5 Dis 153: 918–26 229. RSM Press, London: 118–20

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Holmes CL, Russell JA, Walley KR (2003) McAllister RMR, Mercer NSG, Mercer 1 (TSST-1) synthesis. J Med Microbiol 24: Genetic polymorphisms in sepsis and septic BDG, Sanders R (1993) Early diagnosis of 75–81 shock; role and potential for staphylococcal toxaemia in burned children. Schlievert PM, Shands KN, Dan BB, Schmid therapy. Chest 124: 1103–15 Burns 19: 22–5 GP, Nishimura RD (1981) Identification Jacobson JA, Kasworm E, Daly JA (1989) Michie CA, Davis T (1996) Atopic dermatitis and characterisation of an exotoxin from Risk of developing toxic shock syndrome and staphylococcal superantigens. Lancet Staphylococcus aureus associated with Toxic associated with toxic shock syndrome toxin- 347(8997): 324 Shock Syndrome. J Infect Dis 143: 509–16 1 following non-genital staphylococcal Morishita Y, Tada J, Sato A, et al (1999) Schlievert PM, Blomster DA, Kelly JA (1984) infection. Rev Infect Dis 11(Suppl 1): S8–S13 Possible influences of Staphylococcus aureus Effect of tampons on growth and production Ji GY, Beavis RC, Novick RP (1995) Cell- on atopic dermatitis — the colonizing of TSS exotoxin. Obstet Gynecol 64: 666–74 density control of staphylococcal virulence features and the effects of staphylococcal Sergent P, Edwards-Jones V (1996) The effect mediated by an octapeptide pheromone. Proc enterotoxins. Clin Exp Allergy 29: 1110–7 of mixed culture on the production of toxins Natl Acad Sci USA 92: 12055–9 Muir IFK, Barclay TL (1962) Burns and Their by Staphylococcus aureus. In: Proceedings Johnson D, Pathirana PDR (2002) Toxic Treatment. Lloyd-Luke, London of the 8th International Symposium on Staphylococci and Staphylococcal Infections. Shock Syndrome following cessation of Musser JM, Schlievert PM, Chow AW et al Aix les Bains, France prophylactic antibodies in a child with a 2% (1990) A single clone of S. aureus causes the scald. Burns 28: 181–4 majority of cases of toxic shock syndrome. Schuchat A, Broome CV (1991) Toxic shock Kass EH, Kendrick MI, Tsai YC Parsonnet J Proc of the Natl Acad Sci USA 87: 225–9 syndrome and tampons. Epidemiol Rev 13: 99–112 (1987) Interaction of magnesium ion, oxygen Newbould MJ, Malam J, McIllmurray tension and temperature in the production of JM, Morris JA, Telford DR, Barson AJ Takei S, Arora YK, Walker SM (1993) toxic shock syndrome toxin-1 by S. aureus. J (1989) Immunohistological localisation of Intravenous immunoglobulin contains Infect Dis 155: 812–5 staphylococcal toxic shock syndrome toxin specific antibodies inhibitory to activation of Kotzin BL, Leung DYM, Kappler J, Marrack P (TSST-1) antigen in sudden infant death T cells by staphylococcal toxin superantigen. (1993) Superantigens and their potential role syndrome. J Clin Pathol 42: 935–9 J Clin Invest 91: 602–7 in human disease. Adv Immun 54: 99–166 Notermans S, Van Leeuwen WJ, Dufrenne Todd JK, Fishalt M, Kapral F, Welch T Kotb M (1995) Bacterial pyrogenic exotoxins J, Tips PD (1983) Serum antibodies to (1978) Toxic Shock Syndrome associated as superantigens. Clin Microbiol Rev 8: enterotoxins produced by S.aureus with with phage group 1 staphylococci. Lancet ii: 411–26 special reference to enterotoxin F and toxic 1116–8 shock syndrome. J Clin Microbiol 18: 1055–60 Lawrence JC (1992) Burn bacteriology Todd JK, Todd H, Franco-Buff A, Smith CM, during the last 50 years. Burns 18(suppl2): Novick RP, Kornblum J, Krieswirth BN, Lawellin DW (1987) Influence of focal growth S23–29 Projan S, Ross H (1989) Agr: a complex locus conditions on the pathogenesis of toxic shock regulating post exponential phase exoprotein syndrome. J Infect Dis 155: 673–81 Lee AC, Crass BA, Bergdoll MS (1987) synthesis in S.aureus. In: Butler LO, Harwood Investigation by syringe method of effect C, Moseley BEB eds. Genetic Transformation Tripathi A, Kern R, Conley DB et al (2005) of tampons on production in vitro of toxic and Expression. Intercept Ltd, Andover: Staphylococcal exotoxins and nasal shock syndrome toxin-1 by S.aureus. J Clin 495–510 polyposis: analysis of systemic and local Microbiol 25: 87–90 responses. Am J Rhinol 19: 327–33 Novick RP, Ross HF, Projan SJ, Kornblum J, Llewelyn M, Sriskandan S, Terrazzini N, Kreiswirth B, Moghazeh S (1993) Synthesis of Vergeront JM, Stolz SJ, Crass BA, Nelson Cohen J, Altmann DM (2006) The TcR Vb staphylococcal virulence factors is controlled DB, Davis JP, Bergdoll MS (1983) Prevalence signature of bacterial superantigens spreads by a regulatory RNA molecule. EMBO J 12: of serum antibody to Staphylococcal stimulus strength. Int Immunol 18: 1433–41 3967–75 enterotoxin F among Wisconsin residents: implications for toxic shock syndrome. J Lyon GJ, Novick RP (2004) Peptide signaling Papini RPG, Wilson APR, Steer JA, Infect Dis 148: 692–8 in Staphylococcus aureus and other Gram- McGrouther DA, Parkhouse N (1995) Wound positive bacteria. Peptides 25: 1389–403 management in burn centres in the United Weinzweig J, Gottlieb LJ, Krizek TI (1994) Kingdom. Br J Surg 82: 505–9 Toxic shock syndrome associated with the Marples RR, Weineke AA (1994) Toxic shock use of Biobrane in a scald burn victim. Burns syndrome and related conditions in the Rashid A, Brown AP, Khan K (2005) On the 20: 180–1 United Kingdom 1992–1993. CDR 4: R1 use of prophylactic antibiotics in prevention of Toxic Shock Syndrome. Burns 31: 981–5 Williams P, Camara M, Hardman A et al Martin JM, Green M (2006) Group A (2000) Quorum sensing and the population- streptococcus. Semin Pediatr Infect Dis 17: Reeves MW (1989) Effect of trace metals on dependent control of virulence. Philos Trans 140–8 the synthesis of toxic shock syndrome toxin- R Soc Lond B Biol Sci 29: 667–80 1. Rev Infect Dis 11(Suppl 1): 145–50 Marrack P, Kappler J (1990) The Withey SJ, Carver N, Frame JD, Walker staphylococcal enterotoxins and relatives. Reingold AL, Hargrett NT, Dan DB, Shands CC (1999) Toxic Shock Syndrome in adult Science 248: 705–11 KN, Strickland BY, Broome CV (1982) Non- burns. Burns 25: 659–62 menstrual toxic shock syndrome. A review of Masaki F, Gozo N, Yuichi H et al (2004) Fatal 130 cases. Ann Intern Med 96(part 2): 871–4 Wong ACL, Bergdoll MS (1990) Effect of possible toxic shock syndrome in an adult environmental conditions on production of following 15% scald burn. Burns 30: 181–4 Roggiani M, Schlievert PM (1994) toxic shock syndrome toxin 1 by S. aureus. Streptococcal toxic shock syndrome, Infect Immun 58: 1026–9 Matsuda Y, Kato H, Yamada R et al (2003) including and myocitis Early and definitive diagnosis of toxic shock Curr Opin Infect Dis 7: 423–6 Yaqoob M, McClelland P, Murray AE, syndrome by detection of marked expansion Mostafa SM, Ahmad R (1990) Staphylococcal of T-cell receptor Vb2-postive T cells. Emerg Sarafian SK, Morse BA (1987) Environmental enterotoxin-A and enterotoxin-C causing Infect Dis 3: 387–9 factors affecting toxic shock syndrome toxin- toxic shock syndrome. J Infect 20: 176–8

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