Toxic shock syndrome explained

Toxic shock syndrome
Field:	Infectious disease
Symptoms:	Fever, rash, skin peeling, low blood pressure
Complications:	Shock, kidney failure
Onset:	Rapid
Types:	Staphylococcal (menstrual and nonmenstrual), streptococcal
Causes:	Streptococcus pyogenes, Staphylococcus aureus, others
Risks:	Very absorbent tampons, skin lesions in young children
Diagnosis:	Based on symptoms
Differential:	Septic shock, Kawasaki's disease, Stevens–Johnson syndrome, scarlet fever
Treatment:	Antibiotics, incision and drainage of any abscesses, intravenous immunoglobulin
Prognosis:	Risk of death: ~50% (streptococcal), ~5% (staphylococcal)
Frequency:	Staphylococcal: 0.3 to 0.5 cases per 100,000 population Streptococcal: 2 to 4 cases per 100,000 population

Toxic shock syndrome (TSS) is a condition caused by bacterial toxins.^[1] Symptoms may include fever, rash, skin peeling, and low blood pressure.^[1] There may also be symptoms related to the specific underlying infection such as mastitis, osteomyelitis, necrotising fasciitis, or pneumonia.^[1]

TSS is typically caused by bacteria of the Streptococcus pyogenes or Staphylococcus aureus type, though others may also be involved.^{[1] [2]} Streptococcal toxic shock syndrome is sometimes referred to as toxic-shock-like syndrome (TSLS).^[1] The underlying mechanism involves the production of superantigens during an invasive streptococcus infection or a localized staphylococcus infection.^[1] Risk factors for the staphylococcal type include the use of very absorbent tampons, skin lesions in young children characterized by fever, low blood pressure, rash, vomiting and/or diarrhea, and multiorgan failure.^{[1] [3]} Diagnosis is typically based on symptoms.^[1]

Treatment includes intravenous fluids, antibiotics, incision and drainage of any abscesses, and possibly intravenous immunoglobulin.^{[1] [4]} The need for rapid removal of infected tissue via surgery in those with a streptococcal cause, while commonly recommended, is poorly supported by the evidence.^[1] Some recommend delaying surgical debridement.^[1] The overall risk of death is about 50% in streptococcal disease, and 5% in staphylococcal disease.^[1] Death may occur within 2 days.^[1]

In the United States, the incidence of menstrual staphylococcal TSS declined sharply in the 1990s, while both menstrual and nonmenstrual cases have stabilized at about 0.3 to 0.5 cases per 100,000 population. Streptococcal TSS (STSS) saw a significant rise in the mid-1980s and has since remained stable at 2 to 4 cases per 100,000 population. In the developing world, the number of cases is usually on the higher extreme. TSS was first described in 1927. It got associated with very absorbent tampons that were removed from sale soon after.

Signs and symptoms

Symptoms of toxic shock syndrome (TSS) vary depending on the underlying cause. TSS resulting from infection with the bacterium Staphylococcus aureus typically manifests in otherwise healthy individuals via signs and symptoms including high fever, accompanied by low blood pressure, malaise and confusion, which can rapidly progress to stupor, coma, and multiple organ failure. The characteristic rash, often seen early in the course of illness, resembles a sunburn (conversely, streptococcal TSS will rarely involve a sunburn-like rash), and can involve any region of the body including the lips, mouth, eyes, palms and soles of the feet. In patients who survive, the rash desquamates (peels off) after 10–21 days.

STSS caused by the bacterium Streptococcus pyogenes, or TSLS, typically presents in people with pre-existing skin infections with the bacteria. These individuals often experience severe pain at the site of the skin infection, followed by rapid progression of symptoms as described above for TSS.^[5]

Pathophysiology

In both TSS (caused by S. aureus) and TSLS (caused by S. pyogenes), disease progression stems from a superantigen toxin. The toxin in S. aureus infections is TSS Toxin-1, or TSST-1. The TSST-1 is secreted as a single polypeptide chain. The gene encoding toxic shock syndrome toxin is carried by a mobile genetic element of S. aureus in the SaPI family of pathogenicity islands.^[6] The toxin causes the non-specific binding of MHC II, on professional antigen presenting cells, with T-cell receptors, on T cells.

In typical T-cell recognition, an antigen is taken up by an antigen-presenting cell, processed, expressed on the cell surface in complex with class II major histocompatibility complex (MHC) in a groove formed by the alpha and beta chains of class II MHC, and recognized by an antigen-specific T-cell receptor. This results in polyclonal T-cell activation. Superantigens do not require processing by antigen-presenting cells but instead, interact directly with the invariant region of the class II MHC molecule.^[7] In patients with TSS, up to 20% of the body's T-cells can be activated at one time. This polyclonal T-cell population causes a cytokine storm,^[4] followed by a multisystem disease.

Risk factors

A few possible causes of toxic shock syndrome are:^{[8] [9]}

• Having strep throat or a viral infection like the flu or chickenpox
• Using tampons, especially if super-absorbent or left in longer than recommended
• Using contraceptive sponges, diaphragms or other devices placed inside the vagina
• History of a recent birth, miscarriage, or abortion
• Having a skin infection like impetigo or cellulitis
• Cuts or open wounds on the skin
• Surgical wounds
• Previously having TSS

Diagnosis

For staphylococcal toxic shock syndrome, the diagnosis is based upon CDC criteria defined in 2011, as follows:^[10]

1. Body temperature > 38.9°C
2. Systolic blood pressure < 90 mmHg
3. Diffuse macular erythroderma
4. Desquamation (especially of the palms and soles) 1–2 weeks after onset
5. Involvement of three or more organ systems:
   • Gastrointestinal (vomiting, diarrhea)
   • Muscular: severe myalgia or creatine phosphokinase level at least twice the upper limit of normal for laboratory
   • Mucous membrane hyperemia (vaginal, oral, conjunctival)
   • Kidney failure (serum creatinine > 2 times normal)
   • Liver inflammation (bilirubin, AST, or ALT > 2 times normal)
   • Low platelet count (platelet count < 100,000 / mm³)
   • Central nervous system involvement (confusion without any focal neurological findings)
6. Negative results of:
   • Blood, throat, and CSF cultures for other bacteria (besides S. aureus)
   • Negative serology for Rickettsia infection, leptospirosis, and measles

Cases are classified as confirmed or probable as follows:

• Confirmed: All six of the criteria above are met (unless the patient dies before desquamation can occur)
• Probable: Five of the six criteria above are met

Treatment

The severity of this disease frequently warrants hospitalization. Admission to the intensive care unit is often necessary for supportive care (for aggressive fluid management, ventilation, renal replacement therapy and inotropic support), particularly in the case of multiple organ failure.^[11] Treatment includes removal or draining of the source of infection—often a tampon—and draining of abscesses. Outcomes are poorer in patients who do not have the source of infection removed.^[11]

Antibiotic treatment should cover both S. pyogenes and S. aureus. This may include a combination of cephalosporins, penicillins or vancomycin. The addition of clindamycin^[12] or gentamicin^[13] reduces toxin production and mortality.

In some cases doctors will prescribe other treatments such as blood pressure medications (to stabilize blood pressure if it is too low), dialysis, oxygen mask (to stabilize oxygen levels), and sometimes a ventilator. These will sometimes be used to help treat side effects of contracting TSS.^[8]

Prognosis

With proper treatment, people usually recover in two to three weeks. The condition can, however, be fatal within hours. TSS has a mortality rate of 30–70%. Children who are affected by TSS tend to recover easier than adults do.^[14]

Complications

• Amputation of fingers, toes, and sometimes limbs^[15]
• Death^[16]
• Liver or kidney failure^[17]
• Heart problems
• Respiratory distress
• Septic shock^{[8] [18]}
• Other abnormalities may occur depending on the case

Prevention

During menstruation:^[19]

• Use pads at night instead of tampons
• Try to keep up with changing a tampon every 4 to 8 hours
• Use low absorbent tampons
• Follow directions when using vaginal contraceptives (sponges or diaphragms)
• Make sure to maintain good hygiene during a menstrual cycle

For anyone:^[20]

• Keep open wounds clean
• Watch wounds and cuts for signs of infection (e.g. pus, redness, and warm to touch)^[8]
• Keep personal items personal (e.g.towels, sheets, razors)
• Wash clothing and bedding in hot water

Epidemiology

Staphylococcal toxic shock syndrome is rare and the number of reported cases has declined significantly since the 1980s. Patrick Schlievert, who published a study on it in 2004, determined incidence at three to four out of 100,000 tampon users per year; the information supplied by manufacturers of sanitary products such as Tampax and Stayfree puts it at one to 17 of every 100,000 menstruating females, per year.^{[21] [22]}

TSS was considered a sporadic disease that occurred in immunocompromised people. It was not a more well-known disease until the 1980s, when high-absorbency tampons were in use. Due to the idea of the tampons having a high absorbency this led users to believe that they could leave a tampon in for several hours. Doing this allowed the bacteria to grow and led to infection. This resulted in a spike of cases of TSS.^[23]

Philip M. Tierno Jr. helped determine that tampons were behind TSS cases in the early 1980s. Tierno blames the introduction of higher-absorbency tampons in 1978. A study by Tierno also determined that all-cotton tampons were less likely to produce the conditions in which TSS can grow; this was done using a direct comparison of 20 brands of tampons including conventional cotton/rayon tampons and 100% organic cotton tampons from Natracare. In fact, Dr Tierno goes as far to state, "The bottom line is that you can get TSS with synthetic tampons, but not with an all-cotton tampon."^[24]

A rise in reported cases occurred in the early 2000s: eight deaths from the syndrome in California in 2002 after three successive years of four deaths per year, and Schlievert's study found cases in part of Minnesota more than tripled from 2000 to 2003.^[21] Schlievert considers earlier onset of menstruation to be a cause of the rise; others, such as Philip M. Tierno and Bruce A. Hanna, blame new high-absorbency tampons introduced in 1999 and manufacturers discontinuing warnings not to leave tampons in overnight.^[21]

In Japan, Cases of streptococcal toxic shock syndrome (STSS) reached 1,019 from January to June 2024, as compared to the 941 cases reported in 2023.^{[25] [26]}

TSS is more common during the winter and spring and occurs most often in the young and old.^[2]

Toxic shock syndrome is commonly known to be an issue for those who menstruate, although fifty percent of Toxic Shock Syndrome cases are unrelated to menstruation. TSS in these cases can be caused by skin wounds, surgical sites, nasal packing, and burns.^[19]

History

Initial description

The term "toxic shock syndrome" was first used in 1978 by a Denver pediatrician, James K. Todd, to describe the staphylococcal illness in three boys and four girls aged 8–17 years.^[27] Even though S. aureus was isolated from mucosal sites in the patients, bacteria could not be isolated from the blood, cerebrospinal fluid, or urine, raising suspicion that a toxin was involved. The authors of the study noted reports of similar staphylococcal illnesses had appeared occasionally as far back as 1927, but the authors at the time failed to consider the possibility of a connection between toxic shock syndrome and tampon use, as three of the girls who were menstruating when the illness developed were using tampons. Many cases of TSS occurred after tampons were left in after they should have been removed.^[28]

Rely tampons

Following controversial test marketing in Rochester, New York, and Fort Wayne, Indiana,^[29] in August 1978, Procter and Gamble introduced superabsorbent Rely tampons to the United States market^[30] in response to demands for tampons that could contain an entire menstrual flow without leaking or replacement.^[31] Rely used carboxymethylcellulose (CMC) and compressed beads of polyester for absorption. This tampon design could absorb nearly 20 times its own weight in fluid.^[32] Further, the tampon would "blossom" into a cup shape in the vagina to hold menstrual fluids without leakage.^{[33] [34]}

In January 1980, epidemiologists in Wisconsin and Minnesota reported the appearance of TSS, mostly in those menstruating, to the CDC.^[35] S. aureus was successfully cultured from most of the subjects. The Toxic Shock Syndrome Task Force was created and investigated the epidemic as the number of reported cases rose throughout the summer of 1980.^[36] In September 1980, CDC reported users of Rely were at increased risk for developing TSS.^[37]

On 22 September 1980, Procter and Gamble recalled Rely^[38] following release of the CDC report. As part of the voluntary recall, Procter and Gamble entered into a consent agreement with the FDA "providing for a program for notification to consumers and retrieval of the product from the market".^[39] However, it was clear to other investigators that Rely was not the only culprit. Other regions of the United States saw increases in menstrual TSS before Rely was introduced.^[40]

It was shown later that higher absorbency of tampons was associated with an increased risk for TSS, regardless of the chemical composition or the brand of the tampon. The sole exception was Rely, for which the risk for TSS was still higher when corrected for its absorbency.^[41] The ability of carboxymethylcellulose to filter the S. aureus toxin that causes TSS may account for the increased risk associated with Rely.^[32]

Notable cases

• Clive Barker, fully recovered, contracted the syndrome after visiting the dentist.^[42]
• Lana Coc-Kroft, fully recovered, contracted the syndrome due to group A streptococcal infection.^[43]
• Jim Henson, d. 1990, contracted the syndrome due to group A streptococcal infection and subsequently died from it.^{[44] [45]}
• Nan C. Robertson, d. 2009, the 1983 winner of the Pulitzer Prize for Feature Writing for her medically detailed account of her struggle with toxic shock syndrome, a cover story for The New York Times Magazine which at that time became the most widely syndicated article in Times history.^{[46] [47]}
• Barbara Robison, lead vocalist for the psychedelic rock band the Peanut Butter Conspiracy, was performing in Butte, Montana on 6 April 1988; during the concert, she fell ill and was transported to a hospital. She did not recover, and died sixteen days later on 22 April from toxic shock poisoning at the age of 42.^[48]
• Mike Von Erich, d. 1987, developed the syndrome after shoulder surgery: he made an apparent recovery but experienced brain damage and weight loss as a result of the condition; he died by suicide later.^[49]

External links

• Stevens DL . Streptococcal toxic-shock syndrome: spectrum of disease, pathogenesis, and new concepts in treatment . . 1 . 3 . 69–78 . 1995 . 8903167 . 2626872 . 10.3201/eid0103.950301 .
• Web site: Toxic Shock Syndrome (TSS): The Facts . Toxic Shock Syndrome information service . tssis.com .

Notes and References

1. Low . Donald E. . July 2013 . Toxic Shock Syndrome: Major Advances in Pathogenesis, But Not Treatment . . en . 29 . 3 . 651–675 . 10.1016/j.ccc.2013.03.012 . 23830657 . Elsevier.
2. Gottlieb. Michael. Long. Brit. Koyfman. Alex. June 2018. The Evaluation and Management of Toxic Shock Syndrome in the Emergency Department: A Review of the Literature. . 54. 6. 807–814. 10.1016/j.jemermed.2017.12.048. 29366615. 1812988.
3. Khajuria. A. Nadam. HH. Gallagher. M. Jones. I. Atkins. J. Pediatric Toxic Shock Syndrome After a 7% Burn: A Case Study and Systematic Literature Review. Ann. Plast. Surg.. 2020. 84. 1. 35–42. 10.1097/SAP.0000000000001990. 31192868. 189815024.
4. Wilkins. Amanda L.. Steer. Andrew C.. Smeesters. Pierre R.. Curtis. Nigel. 2017. Toxic shock syndrome – the seven Rs of management and treatment. Journal of Infection. en. 74. S147–S152. 10.1016/S0163-4453(17)30206-2. 28646955.
5. Web site: Bush . Larry Marc . March 2023 . Toxic Shock Syndrome . live . https://web.archive.org/web/20240323061029/https://www.msdmanuals.com/en-sg/home/infections/bacterial-infections-gram-positive-bacteria/toxic-shock-syndrome . 2024-03-23 . 2024-06-23 . The Merck Manuals.
6. Lindsay. JA. Ruzin, A. Ross, HF. Kurepina, N. Novick, RP. July 1998. The gene for toxic shock toxin is carried by a family of mobile pathogenicity islands in Staphylococcus aureus. Molecular Microbiology. 29. 2. 527–43. 10.1046/j.1365-2958.1998.00947.x. 9720870. 30680160. free.
7. Book: Principles of Bacterial Pathogenesis . . 2001 . 978-0-12-304220-0 . Groisman . Eduardo Abraham . San Diego, Calif . 740 . en . 15. Pathogenic Mechanisms in Streptococcal Diseases . 10.1016/B978-0-12-304220-0.X5000-6 . Superantigens are proteins that have the ability to bind to an invariant region of the class II major histocompatibility complex (MHC) on an antigen-presenting cell and to crosslink this receptor to a T cell through binding to the variable region of the β-chain of the T cell antigen receptor. . https://www.sciencedirect.com/science/article/abs/pii/B9780123042200500169 . 22 June 2024 . 22 June 2024 . https://web.archive.org/web/20240622062117/https://www.sciencedirect.com/book/9780123042200/principles-of-bacterial-pathogenesis . live .
8. Web site: 2024-06-18 . Sepsis and Toxic Shock Syndrome . live . https://web.archive.org/web/20240624072247/https://www.sepsis.org/sepsisand/toxic-shock/ . 2024-06-24 . 2024-06-24 . . en.
9. Web site: The Basics of Toxic Shock Syndrome . 27 December 2023 . WebMD . 27 December 2023 . https://web.archive.org/web/20231227085813/https://www.webmd.com/women/understanding-toxic-shock-syndrome-basics . live .
10. Web site: Toxic shock syndrome (other than Streptococcal) (TSS): 2011 Case Definition. 8 May 2014. 9 February 2021. Centers for Disease Control and Prevention. live. https://web.archive.org/web/20201102183953/https://wwwn.cdc.gov/nndss/conditions/toxic-shock-syndrome-other-than-streptococcal/case-definition/2011/. 2 November 2020. dmy-all.
11. The Pediatric Infectious Disease Journal. 18. 12. 1096–1100. Improved outcome of clindamycin compared with beta-lactam antibiotic treatment for invasive Streptococcus pyogenes infection. Zimbelman J, Palmer A, Todd J. 10.1097/00006454-199912000-00014. 1999. 10608632. 16 February 2009. 11 January 2020. https://web.archive.org/web/20200111104126/https://journals.lww.com/pidj/pages/articleviewer.aspx?year=1999&issue=12000&article=00014&type=abstract. live.
12. Clindamycin-induced suppression of toxic-shock syndrome-associated exotoxin production. Schlievert PM, Kelly JA . . 149. 3. 471. 1984. 6715902. 10.1093/infdis/149.3.471.
13. Antimicrobial Agents and Chemotherapy. 1 August 1997. 1682–5. 41. 8. Combination of flucloxacillin and gentamicin inhibits toxic shock syndrome toxin 1 production by Staphylococcus aureus in both logarithmic and stationary phases of growth. van Langevelde P, van Dissel JT, Meurs CJ, Renz J, Groeneveld PH. 9257741. 163985. 10.1128/AAC.41.8.1682.
14. Web site: 23 November 2021 . Streptococcal Toxic Shock Syndrome: For Clinicians CDC . 2 April 2022 . www.cdc.gov . en-us . 23 December 2022 . https://web.archive.org/web/20221223185356/https://www.cdc.gov/groupastrep/diseases-hcp/Streptococcal-Toxic-Shock-Syndrome.html . live .
15. Web site: 2019-11-19 . Toxic Shock Syndrome (TSS) . live . https://web.archive.org/web/20220129110243/https://www.hopkinsmedicine.org/health/conditions-and-diseases/toxic-shock-syndrome-tss . 2022-01-29 . 2022-03-31 . . en.
16. Web site: 2022-03-23 . Toxic shock syndrome . live . https://web.archive.org/web/20230306012522/https://www.mayoclinic.org/diseases-conditions/toxic-shock-syndrome/symptoms-causes/syc-20355384 . 2023-03-06 . 2023-03-15 . Mayo Clinic.
17. Web site: 2009-04-08 . Toxic Shock Syndrome . live . https://web.archive.org/web/20220324003737/https://rarediseases.org/rare-diseases/toxic-shock-syndrome/ . 2022-03-24 . 2022-03-31 . . en.
18. Book: Ferri . Fred F. . Ferri's Differential Diagnosis: A Practical Guide to the Differential Diagnosis of Symptoms, Signs, and Clinical Disorders . . 2010 . 978-0-323-07699-9 . 2nd . . 478 . en .
19. Web site: Toxic Shock Syndrome (TSS): Causes, Symptoms & Treatment . 1 April 2022 . Cleveland Clinic . 24 March 2022 . https://web.archive.org/web/20220324022531/https://my.clevelandclinic.org/health/diseases/15437-toxic-shock-syndrome . live .
20. Web site: Staph infections – Symptoms and causes . 1 April 2022 . Mayo Clinic . en . 1 June 2021 . https://web.archive.org/web/20210601055650/https://www.mayoclinic.org/diseases-conditions/staph-infections/symptoms-causes/syc-20356221 . live .
21. News: Julie Sevrens . Lyons . A New Generation Faces Toxic Shock Syndrome . Knight Ridder Newspapers . . 25 January 2005 . 11 September 2017 . 11 September 2017 . https://web.archive.org/web/20170911162601/http://www.seattletimes.com/seattle-news/health/a-new-generation-faces-toxic-shock-syndrome/ . live . first published as "Lingering Risk", San Jose Mercury News, 13 December 2004
22. Web site: 2006 . Stayfree — FAQ About Toxic Shock Syndrome (TSS) . 13 October 2006 . dead . https://web.archive.org/web/20070323054438/http://www.stayfree.com/faq_TSS.jsp . 23 March 2007 . dmy-all .
23. Mishra . Gita . 2014 . Australian Longitudinal Study on Women's Health . 2 April 2022 . UQ eSpace. 10.14264/uql.2016.448 .
24. News: Welcome to the cotton club. Emma. Lindsey. 6 November 2003. The Guardian. live. https://web.archive.org/web/20161109224602/https://www.theguardian.com/world/2003/nov/07/gender.uk. 9 November 2016.
25. Web site: 21 June 2024. Japan is dealing with a 'flesh-eating bacteria' outbreak. Here's what we know about STSS and how to avoid infection. 22 June 2024. ABC News. Elissa. Steedman.
26. News: A deadly bacterial infection is on the rise in Japan. What is STSS?. The Washington Post. 19 June 2024. Niha. Masih. Frances. Vinall. 21 June 2024. 19 June 2024. https://web.archive.org/web/20240619155207/https://www.washingtonpost.com/health/2024/06/19/japan-stss-flesh-eating-bacteria/. live.
27. Todd J, Fishaut M, Kapral F, Welch T . Toxic-shock syndrome associated with phage-group-I staphylococci . . 2 . 8100 . 1116–8 . 1978 . 82681 . 10.1016/S0140-6736(78)92274-2. 54231145 .
28. Todd J . Toxic shock syndrome—scientific uncertainty and the public media . . 67 . 6 . 921–3 . 1981 . 10.1542/peds.67.6.921 . 7232057. 3051129 .
29. Web site: Finley, Harry. Rely Tampon: It Even Absorbed the Worry!. Museum of Menstruation. 20 March 2006. live. https://web.archive.org/web/20060414012958/http://www.mum.org/Rely.htm. 14 April 2006.
30. Hanrahan S. Historical review of menstrual toxic shock syndrome. . 21. 2–3. 141–65. 1994. 8073784. 10.1300/J013v21n02_09. Submission. Haworth Continuing Features.
31. Web site: Citrinbaum, Joanna . 14 October 2003 . The question's absorbing: 'Are tampons little white lies?' . . 27 December 2015 . live . https://web.archive.org/web/20170620095544/http://www.collegian.psu.edu/archives/article_452b372f-0f54-5d7b-a034-ffff9d824503.html . 20 June 2017 . dmy-all .
32. Web site: Vitale, Sidra. 1997. Toxic Shock Syndrome. Web by Women, for Women. 20 March 2006 . https://web.archive.org/web/20060316030919/http://www.io.com/~wwwomen/menstruation/tss.html . 16 March 2006.
33. Book: Vostral, Sharra Louise . Sharra L. Vostral . Toxic Shock: A Social History . 2018-11-27 . . 978-1-4798-7784-3 . . 140 . en . 5. Health Activism and the Limits of Labeling . 10.18574/nyu/9781479877843.001.0001 . 2018012210 . 1031956695 . Pursettes blossom out to absorb more fully, more effectively. . https://chooser.crossref.org/?doi=10.18574%2Fnyu%2F9781479877843.003.0006.
34. July 1963 . No bulky applicator—Prelubricated tip . . 18 . 9 . 44 . On contact with moisture, new Pursettes blossom out to absorb more fully, more effectively. . Internet Archive.
35. CDC . Centers for Disease Control and Prevention . Toxic-shock syndrome—United States . . 29 . 20 . 229–230 . 23 May 1980 . live . https://web.archive.org/web/20141020044053/http://stacks.cdc.gov/view/cdc/1434 . 20 October 2014 .
36. News: Dennis Hevesi . Bruce Dan, Who Helped Link Toxic Shock and Tampons, Is Dead at 64 . . 10 September 2011 . 12 September 2011 . live . https://web.archive.org/web/20110911170623/http://www.nytimes.com/2011/09/11/health/research/11dan.html . 11 September 2011 . Dennis Hevesi .
37. CDC . Centers for Disease Control and Prevention . Follow-up on toxic-shock syndrome . . 29 . 37 . 441–5 . 19 September 1980 . live . https://web.archive.org/web/20160304025425/http://stacks.cdc.gov/view/cdc/1460/ . 4 March 2016 .
38. Hanrahan S. Historical review of menstrual toxic shock syndrome. . 21. 2–3. 141–165. 1994. 8073784. 10.1300/J013v21n02_09. Submission. Haworth Continuing Features.
39. Web site: Kohen, Jamie . 2001 . The History of the Regulation of Menstrual Tampons . LEDA at Harvard Law School . 5 March 2017 . live . https://web.archive.org/web/20161020060908/https://dash.harvard.edu/bitstream/handle/1/8852185/Kohen.html?sequence=2 . 20 October 2016 .
40. Petitti D, Reingold A, Chin J . The incidence of toxic shock syndrome in Northern California. 1972 through 1983. . 255 . 3 . 368–72 . 1986 . 3941516. 10.1001/jama.255.3.368.
41. Berkley S, Hightower A, Broome C, Reingold A . The relationship of tampon characteristics to menstrual toxic shock syndrome . . 258. 7. 917–20. 1987. 3613021 . 10.1001/jama.258.7.917.
42. Clive Barker recovering from 'near fatal' case of toxic shock syndrome. Entertainment Weekly. 7 February 2012. 11 November 2014. live. https://web.archive.org/web/20141111003549/http://news-briefs.ew.com/2012/02/07/clive-barker-toxic-shock/. 11 November 2014.
43. News: Lana's leap outside her comfort zone. Lang. Sarah. 15 February 2009. The New Zealand Herald. https://archive.today/20130223032919/http://www.nzherald.co.nz/entertainment/news/article.cfm?c_id=1501119&objectid=10556979&pnum=0. 23 February 2013. 26 January 2010. dead.
44. News: Altman. Lawrence. The Doctor's World; Henson Death Shows Danger of Pneumonia. The New York Times. 29 May 1990. 10 June 2017. live. https://web.archive.org/web/20071016193259/http://query.nytimes.com/gst/fullpage.html?res=9C0CE7D6133BF93AA15756C0A966958260&sec=health&spon=. 16 October 2007. dmy-all.
45. Book: Ryan . KJ . Ray . CG . Sherris Medical Microbiology . 4th . McGraw Hill . 2004 . 276–286 . 0-8385-8529-9.
46. Web site: Toxic Shock . Robertson . Nan . The New York Times . 19 September 1982 . 9 November 2022 . 9 November 2022 . https://web.archive.org/web/20221109143513/https://www.nytimes.com/1982/09/19/magazine/toxic-shock.html . live .
47. Book: Rupp, Carla Marie. http://www.atariarchives.org/deli/times_goes_computer.php. Digital Deli. The Times Goes Computer. Steve. Ditlea. Atari Archives. 12 October 2013. live. https://web.archive.org/web/20130827201631/http://atariarchives.org/deli/times_goes_computer.php. 27 August 2013.
48. Book: Rock Obituaries – Knocking On Heaven's Door. 978-0-85712-117-2. 29 January 2015. Talevski. Nick. 7 April 2010. Omnibus Press .
49. Book: Mercer, Bill. Play-by-Play: Tales from a Sportscasting Insider. 12 October 2013. 2007. Taylor Trade Publishing. 978-1-4617-3474-1. 277–. live. https://web.archive.org/web/20131015170021/http://books.google.com/books?id=zb4VAAAAQBAJ&pg=PA277. 15 October 2013.