Anthrax

Article Author:
Kari Simonsen
Article Editor:
Kingshuk Chatterjee
Updated:
3/24/2019 10:14:32 PM
PubMed Link:
Anthrax

Introduction

The bacteria Bacillus anthracis causes anthrax. The bacteria is a small aerobic or facultatively-anaerobic, gram-positive or gram-variable, encapsulated, spore-forming rod. The organism produces toxins which are important for clinical virulence. It grows well on blood agar resulting in large, irregular-shaped colonies. The origin of the name comes from the Greek word "anthrakis," meaning black, in reference to the necrotic lesion seen in cutaneous anthrax.[1][2][3]

Although B. anthracis is generally an environmentally-stable and ubiquitous organism in nature, it has also been recognized as a potential pathogen that could be used as a biologic weapon.

Etiology

Bacillus anthracis is environmentally stable in spore form and may contaminate soil worldwide, resulting in infections of herbivores while grazing. Spores can remain dormant and viable in the environment for decades. Animal cases of anthrax tend to occur in summer and fall seasons and are most frequent in grazing mammals including domestic sheep, goat, and cattle and wild deer and antelope. Human transmission occurs via contact with infected animals through butchering and working with hides or ingestion of raw or undercooked meat. Skin contact results in cutaneous anthrax while inhalation or ingestion of the spores leads to inhalational or gastrointestinal (GI) anthrax.[4]

Epidemiology

Anthrax occurs worldwide, and the world health organization (WHO) estimates the annual global incidence of between 2000 and 20,000 cases. It is rare in the United States, although in the year 2000, an outbreak of anthrax occurred in the ranches of North Dakota. Skin contact results in cutaneous anthrax while inhalation or ingestion of the spores leads to inhalational, pharyngeal, or GI anthrax.[5]

Anthrax is categorized as a category A priority pathogen by the Centers for Disease Control and Prevention because it is potentially capable of being disseminated as a bioweapon.

Pathophysiology

The pathogenesis of anthrax follows the route of infection with three primary forms in humans: cutaneous, GI, and inhalational.

Inhalational anthrax leads to accumulation of B. anthracis spores within the lung alveoli. The spores are engulfed by immune cells (macrophages, neutrophils, dendritic cells) and transported to regional lymph nodes where the bacteria germinate, multiply, and begin toxin production.  This results in systemic clinical illness, and pathologically to toxin-induced cell damage and cell death.  As the disease progresses, bloodstream infection occurs leading to septic shock.  Patients can present suddenly and may deteriorate rapidly.   

Cutaneous anthrax results from inoculation of B. anthracis spores through the abraded skin into subcutaneous tissues. The bacteria subsequently germinate and multiply locally and begin toxin production.  This leads to the characteristic edema and cutaneous ulceration. 

GI anthrax occurs due to ingestion of contaminated meat, with spores introduced into the gastrointestinal tract, causing bacterial replication, mucosal ulcerations, and bleeding. 

Recently, injection anthrax has been described in northern European injection drug users, resulting in symptoms similar to cutaneous anthrax but with a deeper infection which may include myositis.[6]

Histopathology

One classic feature of anthrax is the presence of the bacteria in the capillaries at the infection site. Other features include hemorrhage, necrosis, and submucosal thrombosis.

History and Physical

Inhalational anthrax presents following an incubation period of approximately 1 to 6 days post-exposure, with a non-specific prodromal phase including fever, sweats, nausea, vomiting, malaise, chest pain and nonproductive cough. The second stage of illness occurs as bacterial replication in mediastinal lymph nodes results in hemorrhagic lymphadenitis and mediastinitis, and progression to bacteremia. Fever, dyspnea, and stridor from increasing lymphadenopathy impacting the airways, and ultimately respiratory failure and hemodynamic collapse occur. Meningitis also occurs in up to 50% of inhalational cases, with a headache, confusion, and progression to coma. Chest x-rays classically demonstrate a widened mediastinum (the result of significant lymphadenopathy) without pulmonary infiltrates, though pleural effusions and/or pulmonary infiltrates both of which may be hemorrhagic can also be seen. The time from onset of symptoms to death ranges from 1 to 10 days.

GI anthrax results from ingestion of contaminated, undercooked meat or ingestion of spores inhaled into the nasopharynx and can include oropharyngeal and/or intestinal symptoms. Patient with oropharyngeal anthrax develops ulcers of the posterior oropharynx and associated dysphagia, cervical swelling, and regional lymphadenopathy. Patients with intestinal anthrax develop fever, nausea, vomiting, and diarrhea. They can progress to an acute abdomen-like presentation with bloody diarrhea, hematemesis, and massive ascites. Intestinal involvement more frequently involves the terminal ileum and cecum. Untreated patients will progress to septicemia. Mortality ranges from 25% to 60%.

Cutaneous anthrax presents 1 to 10 days post-inoculation with a pruritic papular lesion that progresses over several days into a painless ulcer. The lesion may have associated satellite vesicles and will progress into a necrotic and blackened center with surrounding non-pitting edema.  The painlessness of the lesion is characteristic of cutaneous anthrax and a distinguishing feature from other diagnoses. As the lesion heals, the eschar will dry, and slough off after 1 to 2 weeks. Without appropriate treatment, the mortality rate can approach 20%.

Injection drug anthrax presents as a grouping of small vesicles or papules at the injection site, with progression to painless ulcerative lesion similar to cutaneous anthrax. Injection anthrax may make it more difficult to recognize and may progress more rapidly to systemic illness than cutaneous anthrax.

Evaluation

The CDC has developed detailed recommendations for patient evaluation by suspected anthrax exposure and clinical syndrome. Depending on the clinical features, relevant specimens include PCR, gram stain, and cultures, from blood, pleural fluid, site of ulceration, cerebrospinal fluid, and stool. Patients may also need routine diagnostic evaluations such as complete blood count (CBC) and chest x-ray. Testing for relevant pathogens on the differential diagnosis may need to be incorporated into the evaluation as well.[7][8]

Treatment / Management

The CDC has concise treatment recommendations based upon anthrax disease manifestations, including multiple alternative agents that may be considered in select patients.[7][9][8]

In brief, treatment for inhalational anthrax requires a multidrug regimen with one bactericidal agent + 1 protein-synthesis inhibitor. Intravenous ciprofloxacin + clindamycin or linezolid are the preferred agents. In patients with meningitis, a 3-drug regimen comprised of 2 bactericidal agents from different drug classes (fluoroquinolone + beta-lactam) + 1 protein-synthesis inhibitor are recommended. For cutaneous anthrax, oral ciprofloxacin or doxycycline are effective, except in cases with extensive edema or head and neck involvement, when a multidrug intravenous regimen is recommended.

An antitoxin product may be recommended as a treatment adjunct together with a multidrug antimicrobial regimen, and there are multiple products that have been developed including both monoclonal and polyclonal antitoxins.

Anthrax immune globulin should also be considered with CDC consultation as adjunctive therapy for systemic anthrax treatment.

Anthrax vaccines for humans and animals are available. Animal vaccination has greatly reduced, but not eliminated animal cases. Human vaccination is not recommended for the general US population but is recommended for high-risk professions having occupational contact with animal hides and fur including some veterinarians, certain laboratory workers who may work directly with the organism, and some members of the US military.

The vaccine may also be recommended more broadly to exposed community members as a component of a public health response after a bioterrorism event.

Differential Diagnosis

The differential diagnosis of inhalational anthrax includes community-acquired pneumonia, influenza, respiratory syncytial virus, pneumonic plague, and tularemia. The differential diagnosis of cutaneous anthrax includes staphylococcal skin abscess, cat scratch disease, tularemia, spider bite, and ecthyma gangrenosum. Additional GI anthrax differential diagnostic considerations include ulceroglandular tularemia or bubonic plague.

Pearls and Other Issues

A bioterrorist attack occurred in the United States in 2001, resulting in inhalational anthrax in 11 people and 5 deaths, and cutaneous anthrax in another 11 people. In response, the United States has prepared a medical countermeasures strategic national stockpile of antimicrobials, antitoxins, and vaccine.

Enhancing Healthcare Team Outcomes

Anthrax is a serious infection which can rapidly prove fatal. Anthrax is very rare and when it occurs, one should suspect bioterrorism. All healthcare workers including nurses, pharmacists, physician assistants, and physicians must be aware that anthrax has the potential to be used as an agent of terrorism. The multidisciplinary team should be vigilant in evaluating for the possibility of anthrax when multiple patients present with similar symptoms.

In the event of a bioterrorism attack, mass post-exposure prophylaxis with ciprofloxacin or doxycycline may be recommended with public health guidance. As a preventive for inhalational anthrax post-exposure, duration of antibiotic therapy is 60 days to prevent relapse from ungerminated spores in the lungs.

When caring for anthrax patients, the team should work together to maintain standard hospital universal precautions should be utilized with attention to using contact precautions for draining cutaneous lesions.[10][11]


References

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[7] O'Leary ST,Kimberlin DW,Maldonado YA, Update From the Advisory Committee on Immunization Practices. Journal of the Pediatric Infectious Diseases Society. 2018 May 15     [PubMed PMID: 29741721]
[8] Banerjee D,Chakraborty B,Chakraborty B, Anthrax: Where Margins are Merging between Emerging Threats and Bioterrorism. Indian journal of dermatology. 2017 Sep-Oct     [PubMed PMID: 28979006]
[9] Vietri NJ, Does anthrax antitoxin therapy have a role in the treatment of inhalational anthrax? Current opinion in infectious diseases. 2018 Jun     [PubMed PMID: 29570493]
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[11] Denk A,Tartar AS,Ozden M,Demir B,Akbulut A, Cutaneous anthrax: evaluation of 28 cases in the Eastern Anatolian region of Turkey. Cutaneous and ocular toxicology. 2016 Sep     [PubMed PMID: 26293781]