ToxCard: Anthrax

Authors: Oriane Longerstaey, MD  (Emergency Medicine Resident, Carolinas Medical Center, Charlotte, NC), Kathryn T Kopec, DO (Emergency Medicine Attending; Medical Toxicologist, Carolinas Medical Center) // Reviewed by: Cynthia Santos, MD (@Cynthia Santos, MD); Alex Koyfman, MD (@EMHighAK); and Brit Long, MD (@long_brit)

 

What is Anthrax?

Anthrax is a spectrum of disease caused by Bacillus anthracis, an aerobic or facultatively-anaerobic, gram-positive or gram-variable encapsulated spore forming rod. (1) This bacterium is commonly found in nature. Spores can be dormant in soil for decades and are very resistant to environmental changes or attempts at disinfection. (2) Anthrax is primarily a livestock disease for which humans are incidental hosts, who cannot further transmit the infection. (3) Exposure in humans can occur from contact with animals, such as sheep, cattle, and goats, who ingest the spores in the soil or direct contact with contaminated soil. (4) Although cases are less common with animal vaccination and tracking, they still occur. Furthermore, there is concern about anthrax possible use as a biological weapon.

The method of exposure determines clinical presentation, and the majority of exposures are inhalational or via ingestion. (2) Virulence comes from two plasmids that encode the protein capsule and the exotoxin.

The exotoxin is made up of three proteins: (5)

  • Protective antigen – facilitates the other 2 factors entering cell
  • Edema factor – increasing intracellular cAMP leading to massive edema
  • Lethal factor – stimulates release TNF alpha and interleukin-1-beta

Edema factor and lethal factor produce the subunits of the toxin. (6) This toxin works by targeting immune cells to decrease host response and delaying protein clearance to prolong toxin presence in the host. (6)


Clinical Presentation:

There are 4 types of exposure/infections, all vary in time from exposure to onset of symptoms as well as the type of symptoms at presentation.

  • Gastrointestinal
  • Cutaneous
  • Inhalational
  • Injectional

 

Cutaneous anthrax (>95% cases): (1,2,7)

  • Spores enter through break in the skin such as laceration or abrasion
  • Incubation: 1-7 days
  • Presents as a papule that becomes vesicular. Multiple vesicles may form around the initial site. The vesicle then ulcerates and forms an eschar. There will also be pitting edema in the area. However, this will be painless and non-tender.
  • Other symptoms can include headache, fever, and general malaise
  • Uncomplicated lesions can take 2-3 weeks to heal
  • Can lead to disseminated disease and death in 5-20% cases
  • Best prognosis overall

 

Injectional Anthrax: (1)

  • Associated with intravenous drug use
  • Presents as group of vesicles around injection side with progression to ulcerative lesion with severe edema
  • Lesions can be painful but often not as painful as expected
  • Higher risk of systemic infection than cutaneous form
  • Up to 30% mortality

 

Inhalational anthrax (< 5% cases): (1,2)

  • Has been called “wool sorter’s disease”
  • Incubation 2-10 days, up to 1 month
  • Most likely form for a biological attack
  • Two Stages:
    • First Stage: non-specific influenza-like illness that includes fever, chest pain and non-productive cough with a short period of improvement prior to development of second stage
    • Second Stage: fever, dyspnea, hemorrhagic lymphadenitis and mediastinitis, stridor, meningitis, cyanosis and shock.
  • High mortality: 50% of patients die within 72 hours of symptoms onset.

 

Gastrointestinal anthrax: (1,2,7)

  • Two forms:
    • Oropharyngeal
    • Gastrointestinal
  • Incubation 1-6 days
  • Oropharyngeal:
    • Ulcers in mouth and pharynx
    • Symptoms include dysphagia, cervical swelling and regional lymphadenopathy
  • Gastrointestinal:
    • Superficial ulcers in gastrointestinal epithelium
    • Symptoms include fever, abdominal pain, nausea, vomiting. It can progress to severe gastrointestinal bleeding, peritonitis and sepsis.
  • ~ 50% of patient with oropharyngeal anthrax die

Diagnosis: 

For any patient in which anthrax is suspected you should obtain (1,2):

  • Laboratory testing includes CBC, CMP, LFTs, coagulation studies, ESR, CRP, troponin, and BNP
  • Fluid samples should be sent for gram stain, culture and toxin assay
  • Cardiac monitoring and EKG are recommended
  • For cutaneous anthrax, obtain culture of the lesion, serology or punch biopsy

 

Diagnosis of inhalational anthrax does not require sputum culture or gram stain although these are recommended (1,2,8).

Imaging such as chest x-ray and computed tomography of the chest may also be indicated.

  • Chest X-ray findings include widened mediastinum, hilar adenopathy and pleural effusions
    • These are not always present and are non-specific.
  • CT of the chest is more sensitive for widened mediastinum and can also evaluate for pericardial effusion or pulmonary embolism.
  • If pleural fluid is present and sampled, these can be tested for anthrax sero-markers. (4)

 

Gastrointestinal anthrax can be diagnosed by PCR and culture of ascitic fluid, stool samples or rectal swab.

Finally, if a patient has a headache, altered mental status or other neurologic symptoms, it is recommended to perform a lumbar puncture unless contraindicated to evaluate for meningeal involvement. (7)


Specific Treatment Recommendations:

The goal is to kill the bacteria before it can release the toxins systemically. (4) Once the toxin causes systemic effects, antibiotics will do little to prevent clinical worsening.

Per CDC recommendations, treatment will depend on whether or not meningitis is suspected: (9)

  • If meningitis is suspected, a combination of three or more antibiotics with CNS penetration should be used for at least 2 weeks.
    • CDC recommends IV ciprofloxacin, a carbapenem (meropenem preferred, unless the strain is susceptible to penicillin), and linezolid.
  • If meningitis is ruled out, at least 2 antibiotics are required for at least 14 days
    • IV penicillin or a fluoroquinolone combined with either clindamycin or linezolid are recommended.
    • Doxycycline can be used if linezolid or clindamycin cannot be used.
  • Once the initial treatment of systemic disease is completed, patients who were exposed to aerosolized spores will be transitioned to a single oral agent to prevent relapse.
    • Ciprofloxacin or doxycycline are recommended for 60-day course from onset of illness.
  • Uncomplicated cutaneous anthrax can be treated with either fluoroquinolones or doxycycline for 7-10 days.
  • All patients should also be vaccinated as quickly as possible.
  • Vaccination consists of three injections each two weeks apart. This vaccine is only approved for patients over the age of 18.
    • Prophylactic vaccination is available for high-risk individuals, such as, members of the military.

 

The FDA has approved ciprofloxacin, levofloxacin and doxycycline for post-exposure prophylaxis although ciprofloxacin and doxycycline are used primarily since treatment for 60 days is required. (7)

Otherwise, standard guidelines for treating sepsis and septic shock should be followed including intravenous fluid resuscitation, vasopressors, and mechanical ventilation. (7)


Clinical Pearls:

  • Anthrax spores are very stable in the environment and can persist despite weather changes and attempts at disinfection.
  • Clinical presentation will vary based on type of exposure: cutaneous, injection, inhalational, or gastrointestinal.
  • Inhalational or gastrointestinal variants have the highest rates of mortality
  • A high clinical suspicion is important to make the diagnosis
  • Antibiotic treatment choices depend on whether or not there is suspicion for meningitis.
  • Treatment often requires at least 2 antibiotics and lasts for 60 days plus vaccination
  • Uncomplicated cutaneous anthrax can be treated with either fluoroquinolones or doxycycline for 7-10 days.

References:

  1. Simonsen KA, Chatterjee K. Anthrax. In: StatPearls. Treasure Island, FL: StatPearls Publishing; 2020.
  2. Savransky V, Ionin B, Reece J. Current Status and Trends in Prophylaxis and Management of Anthrax Disease. Pathogens. 2020;9(5):370. Published 2020 May 12. doi:10.3390/pathogens9050370
  3. Chugh T. Bioterrorism: Clinical and public health aspects of anthrax. Curr Med Res Pract. 2019;9(3):110-111. doi:10.1016/j.cmrp.2019.05.004
  4. Jessica Chambers, Siva Naga S. Yarrarapu, Josephin K. Mathai. Anthrax Infection Chambers J, Yarrarapu SNS, Mathai JK. Anthrax Infection. [Updated 2020 Aug 25]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan
  5. Suchard JR. Biological Weapons. In: Nelson LS, Howland M, Lewin NA, Smith SW, Goldfrank LR, Hoffman RS. eds. Goldfrank’s Toxicologic Emergencies, 11e. McGraw-Hill; Accessed February 18, 2021. https://accessemergencymedicine-mhmedical-com.libproxy.lib.unc.edu/content.aspx?bookid=2569&sectionid=210264982
  6. Friebe S, van der Goot FG, Bürgi J. The Ins and Outs of Anthrax Toxin. Toxins (Basel). 2016;8(3):69. Published 2016 Mar 10. doi:10.3390/toxins8030069
  7. Ozer V, Gunaydin M, Pasli S, Aksoy F, Gunduz A. Gastrointestinal and cutaneous anthrax: Case series. Turk J Emerg Med. 2018;19(2):76-78. Published 2018 Nov 14. doi:10.1016/j.tjem.2018.10.002
  8. Hendricks KA, Wright ME, Shadomy SV, Bradley JS, Morrow MG, Pavia AT, et al. Centers for Disease Control and Prevention expert panel meetings on prevention and treatment of anthrax in adults. Emerg Infect Dis [Internet]. 2014 Feb. http://dx.doi.org/10.3201/eid2002.130687
  9. Cdc.gov. 2021. Anthrax Vaccination | What You Should Know | CDC. [online] Available at: <https://www.cdc.gov/vaccines/vpd/anthrax/public/index.html#:~:text=There%20is%20one%20anthrax%20vaccine,at%20increased%20risk%20of%20exposure.> [Accessed 17 February 2021].

 

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