Staphylococcal Toxic Shock Syndrome
by Stephanie Cunningham
Streptococcal Toxic Shock Syndrome (TSS) is caused by the bacterium Staphylococcus aureus (S. aureus). TSS is not a transmissible disease from an infected to an uninfected person, though the bacterium, S. aureus, is found naturally occurring on the skin and can be found in the warm wet mucous membranes of the body, such as the mucous membranes of the airway and the vagina (1)(2)(3). TSS can present in women, men, or children of any age, and less than half of present cases are tied to menstruation (3). Regarding natural reservoirs, humans are the largest for S. aureus.
TSS was described in 1927 by Franklin Stevens who referred to it as “staphylococcal scarlet fever” but the name Toxic Shock Syndrome wasn’t attached until 1978 by James Todd and colleagues (first described in children presenting S. aureus infections). Even now, pediatric burn patients and surgical patients can experience rapid onset (around 48 hours) and can quickly deteriorate, especially children (5). However, the greatest incident, or perhaps the most infamous, occurred in the 1980s. A brand of tampons called Rely were made of synthetic synthetic resulting in peak occurrence of the menstrual form of TSS, prompting feminine care products to utilize cotton absorbent and required information to be available to women who purchased these feminine care items (6). The estimated incidence for all forms during this time was 13.7/100,000; though public awareness and labeling significantly reduced that within a decade to 0.53/100,000 (5) and the CDC estimates that since the 1980s, cases of TSS associated with menstruation in women have decreased 55%. Global numbers are not easy to identify. Today, inserted contraception (sponge, diaphragm, etc) and contraction of TSS post-delivery or following surgery or abortion play a role still. Men and women who have a S. aureus infection elsewhere on their body are at higher risk though women who use tampons or inserted contraception do still fall into the higher risk category (1).
Symptoms commonly include high fever (greater than 102 degrees), rash, hypotension, and desquamation (flaking of skin, particularly on the hands and feet)(6). There is no specific test for TSS, though blood or urine sample or swabs from the vagina, cervix, or throat may be swabbed for presence of staph (S. aureus) or strep (S. pyogenes)-which can also produce a variant of TSS (2). Desquamation typically presents late (1-2 weeks) but is a key identifying symptom. Additional tests are often performed, though not at the expense of delayed treatment, to rule out diseases such as measles or Rock Mountain spotted fever (R. rickettsia). Negative lab tests performed are bacterial or viral cultures or RT-PCR from blood specimen (6).
The progression of toxic shock syndrome occurs when toxins produced by S. aureus are able to enter general circulation, typically through small cuts (believed to be the case in the use of tampons) or in cases of surgical or ongoing S. aureus infections. Superantigens (SAgs) are potent exotoxins, unique in that they deliberately target the immune system, initiating T-cell activation. More than 20 distinct SAgs are known to exist for S. aureus, TSST-1, distinct evolutionarily from other forms, is often categorized as the major, or possibly only cause of menstrual form of TSS. Non-menstrual forms have been attributed to SEB and SEC (staphylococcal enterotoxin forms B and C). In SEB and SEC forms the patient characteristically presents with vomiting, which is absent in TSST-1 cases (5).
The level of T-cell activation that presents in TSS is extremely higher than what would occur under normal activation pathways and this is where the problem lies. Activated T cells flood the body with cytokines – proinflammatory molecules, which, as is the case in TSS initiated a positive feedback loop between cytokines and the immune cells–a “cytokine storm”- that if proceeded unchecked can result inevitably in systemic septic shock (4) which could prove fatal (with treatment, fatality rate of Staphylococcal TSS is 2-4% (1)). “T cell anergy” is the condition of where T cells no longer respond to stimulation and has been the proposed tactic of S. aureus when it releases SAgs – which otherwise would not make sense; the bacterium would normally not profit or benefit from intentional stimulation of the host organism’s immune system (5). Research investigating the mechanisms of T cell activation is currently being studied.
Treatment relies on removing the source of infection (if applicable: tampon, diaphragm, etc) or cleaning wounds that the patient currently or has had. Any secondary symptoms, such as hypertension or fever are treated as they would normally be: IV fluids or fever reducers/NSAIDs. Antibiotics are given once the presence of the bacteria is confirmed (1). Prevention follows common sense based on high-risk: monitoring use of inserted feminine care items, proper wound care and sterile technique in hospital and home settings. Recurrence of TSS can also be a problem, so those that have had a previous infection should take even more cautious action.
As antibiotic-resistant forms of the S. aureus bacteria (MRSA) become a greater problem in the United States and globally, one might expect this to become a considerable factor for future treatment, especially with the way TSS progresses. Epidemiological studies by DeVries and colleagues investigated this potential; only 7% of cases (n=4) investigated resulted in isolated MRSA from 2000-2006 (7). Knowledge and prevention –the basics– are the best measures for all.
1 Staphylococcal (Toxic Shock Syndrome) Fact Sheet. Virginia Department of Health, Office of Epidemiology. Published 9/2001, Updated 9/28/2011. Accessed 3/4/2013. http://www.vdh.state.va.us/epidemiology/factsheets/pdf/Staphylococcal.pdf
2 Toxic Shock Syndrome. Mayo Clinic staff. Revision 5/7/2011. Accessed 3/4/2013. http://www.mayoclinic.com/health/toxic-shock-syndrome/DS00221
3 Toxic shock syndrome. National Library of Medicine, National Institutes of Health. Updated 8/15/12. Accessed 3/4/13. http://www.nlm.nih.gov/medlineplus/ency/article/000653.htm
4 Septic shock. US National Library of Medicine. Last reviewed 1/14/10. Accessed 3/4/13. http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001689/
5 Xu SX, McCormick JK (2012). Staphylococcal superantigens in colonization and disease. Front Cell Infect Microbiol 2(52), 1-11. Accessed 3/9/2013. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3417409/pdf/fcimb-02-00052.pdf
6 Vostral SL (2011) Rely and Toxic Shock Syndrome: A Technological Health Crisis. Yale J Biol Med 84(4), 447-459. Accessed 3/10/2013. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3238331/
7 DeVries AS, Lesher L, Schlievert PM, Rogers T, Villaume LG, et al. (2011) Staphylococcal Toxic Shock Syndrome 2000–2006: Epidemiology, Clinical Features, and Molecular Characteristics. PLoS ONE 6(8): e22997. doi:10.1371/journal.pone.0022997 Accessed 3/10/2013.