Author(s): Kate Hendricks, Antonio Vieira, Rita Traxler, Chung Marston

Infectious Agent

Anthrax is caused by aerobic, gram-positive, encapsulated, spore-forming, nonmotile, nonhemolytic, rod-shaped bacterium, Bacillus anthracis.

Transmission

Most human infections with B. anthracis result from handling B. anthracis–infected animals or their carcasses, meat, hides, or wool. Products derived from infected animals (e.g., drumheads, wool clothing) are additional documented sources of human infection.

Anthrax infection can occur via cutaneous, ingestion, injection, and inhalation routes. Spores introduced through the skin can result in cutaneous anthrax; breaks in the skin increase susceptibility. Eating meat from infected animals can result in ingestion (also called gastrointestinal) anthrax. Since 2000, injection transmission has been reported in cases of B. anthracis soft-tissue infections among intravenous heroin users in northern Europe. Aerosolized spores from contaminated hides or wool can cause inhalation anthrax. Anthrax in humans generally is not considered contagious; person-to-person transmission of cutaneous anthrax has been reported only rarely and only in instances of extremely close contact with an infected person (e.g., breastfeeding, dressing a wound, direct skin contact with the blood from a patient with anthrax).

Epidemiology

Anthrax is a zoonotic disease primarily affecting ruminant herbivores (e.g., antelope, cattle, deer, goats, sheep) that become infected by ingesting vegetation, soil, or water that has been contaminated with B. anthracis spores; humans are generally incidental hosts. Anthrax is most common in agricultural regions in sub-Saharan Africa, Central and South America, central and southwestern Asia, and southern and eastern Europe. Although outbreaks still occur in livestock and wild herbivores in Canada, the United States, and western Europe, human anthrax in these areas is now rare.

Worldwide, the most reported form of anthrax in humans is cutaneous anthrax (95%–99%). Anthrax can occur after playing or handling drums made from contaminated goatskins. Although the risk of acquiring anthrax from drums imported from anthrax-endemic countries appears low, life-threatening or fatal disease is possible. Cases of cutaneous (n=4), ingestion (n=1), and inhalation (n=3) anthrax have been reported in people who have handled, played, or made such drums; bystanders to such indoor activities have rarely been infected.

Outbreaks of cutaneous and ingestion anthrax have been associated with handling infected animals and butchering and eating meat from those animals. Most of these outbreaks have occurred in endemic areas in Africa and Asia. A handful of cutaneous cases have been reported in travelers with direct or indirect contact with animals or their byproducts. One instance occurred in a tourist who traveled to Namibia, Botswana, and South Africa in 2006; another, in a traveler to Turkey in 2018. A third case happened in a scientist who was conducting anthrax fieldwork in Namibia, also in 2018.

Severe soft-tissue infections, including cases complicated by sepsis and systemic infection, are suspected to be due to recreational use of heroin contaminated with B. anthracis spores. No associated cases have been identified in people who have not injected heroin.

Inhalation exposure was historically associated with the industrial processing of hides or wool. More recently, bioterrorist activities directed toward the American public were implicated as a source of inhalation exposure. Occasional anthrax cases have occurred in the United States and elsewhere, in which the exposure source remains unidentified.

Travelers are at greatest risk for infection in areas where the disease is more prevalent. Destination categories that increase risk for infection include safari areas where direct contact with animals or carcasses might occur; regions with limited meat inspections and processing capacity; and areas where travelers are exposed to livestock byproducts (e.g., souvenirs). Immigrants and refugees in areas of low socioeconomic development and limited food availability also might be at increased risk of contracting anthrax due to lack of proper inspection of meat and animal products.

Clinical Presentation

Anthrax has 4 main clinical presentations—cutaneous, ingestion, injection, and inhalation. Anthrax meningitis can complicate any of the 4 main clinical presentations and can occur with no obvious portal of entry, in which case it is called primary anthrax meningitis.

Cutaneous Anthrax

Cutaneous anthrax usually develops 1–7 days after exposure, but incubation periods up to 17 days have been reported. Before antimicrobial therapy became available, almost a quarter of patients with cutaneous anthrax died. The case-fatality ratio is <2% with antimicrobial therapy.

Localized itching, followed by development of a painless papule, heralds cutaneous anthrax. The papule then turns into a vesicle that enlarges and ulcerates, ultimately becoming a depressed black eschar 7–10 days after the appearance of the initial lesion. Edema around lesions is characteristic, sometimes with secondary vesicles, hyperemia, and regional lymphadenopathy. Head, neck, forearms, and hands are the most common sites affected. Patients might have malaise and headache; about one-third are febrile.

Ingestion Anthrax

Ingestion anthrax usually develops 1–7 days after eating contaminated meat; incubation periods up to 16 days have been reported, however. Left untreated, more than half of cases will die; with treatment, the case-fatality ratio decreases slightly, to <40%. Ingestion anthrax has 2 main types: oropharyngeal and intestinal. Patients with either form usually have fever and chills.

Oropharyngeal anthrax is characterized by severe sore throat, difficulty swallowing, swelling of the neck, and regional lymphadenopathy; airway compromise and death can occur. Nausea, vomiting, and diarrhea, which might be bloody, are more typical of intestinal anthrax; marked ascites or coagulopathy also can develop. Later symptoms can include shortness of breath and altered mental status, with shock and death occurring 2–5 days after disease onset.

Injection Anthrax

Anthrax in injection drug users usually develops within 1–4 days of exposure; death occurs in more than a quarter of confirmed cases. Case-patients present with severe soft-tissue infection manifested by swelling, erythema, and excessive bruising at the injection site; pain might be less than anticipated for the degree of swelling. Most patients become septic.

Inhalation Anthrax

Inhalation anthrax usually develops within a week after exposure, but the incubation period could be prolonged, up to 2 months. Before 2001, fatality ratios for inhalation anthrax were 90%; since then, ratios have fallen to 45% with improved treatment. During the first few days of illness (the prodromal period), most patients exhibit fever, chills, and fatigue. These symptoms can be accompanied by cough, shortness of breath, chest pain, and nausea or vomiting, making inhalation anthrax difficult to distinguish from influenza, coronavirus disease 2019 (COVID-19), or community-acquired pneumonia.

Over the next day or so, shortness of breath, cough, and chest pain become more common, and nonthoracic complaints (e.g., nausea, vomiting, altered mental status, diaphoresis, headache) develop in a third or more of patients. Upper respiratory tract symptoms occur in only a quarter of patients, and myalgias are rare. Altered mental status or shortness of breath generally brings patients to the attention of the medical establishment and heralds the fulminant phase of illness.

Anthrax Meningitis

Anthrax meningitis can develop from hematogenous spread of any of the clinical forms of anthrax, or it can occur alone; half of all reported cases are sequelae of cutaneous anthrax. The condition should be suspected in patients with anthrax who have severe headache, altered mental status (including confusion), meningeal signs, or neurologic deficits of any kind. Intracranial bleeding occurs in about two-thirds of patients with anthrax meningitis. Most cases of anthrax meningitis are fatal.

Diagnosis

Include anthrax in the differential diagnosis of travelers returning with unexplained fevers or new skin lesions. Ask about recent travel to anthrax-endemic areas and inquire about activities, such as direct contact with animals and animal products, drumming, and souvenir purchases, including animal-hide drums, leather, and hides.

Any of several methods can be used to make a laboratory diagnosis of anthrax infection: bacterial culture with isolation of B. anthracis; detection of bacterial DNA, antigens, or toxins; or detection of a host immune response to B. anthracis. Although lethal toxin can be detected in a single acute-phase serum, detection of a host immune response requires paired acute- and convalescent-phase serum samples.

In the United States, anthrax is a nationally notifiable disease. Laboratory Response Network reference laboratories can perform confirmatory testing (e.g., isolate identification). Laboratories at the Centers for Disease Control and Prevention (CDC) can perform isolate identification and conduct other complex tests (e.g., mass spectrometry for toxin, quantitative serology, antigen detection in tissues). Internationally, relevant national reference laboratories should perform testing.

For diagnostic support and specimen submission guidance, contact the state, local, territorial, or tribal public health department. Public health departments should urgently notify CDC of any suspected anthrax cases through the CDC Emergency Operations Center (770-488-7100). CDC’s Bacterial Special Pathogens Branch can coordinate testing needs in conjunction with the public health department and other CDC programs; specimen collection and submission guidelines and algorithms for laboratory diagnosis are available. Collect specimens for culture before initiating antimicrobial therapy.

Diagnostic procedures for inhalation anthrax include thoracic imaging studies to detect a widened mediastinum or pleural effusion. Drainage of pleural effusions can be useful for diagnosis and can increase survival because it removes a nidus for toxin. Regardless of route of infection, patients with systemic anthrax should have a diagnostic evaluation to rule out meningitis.

Treatment

Treat naturally occurring localized or uncomplicated cutaneous anthrax with 7–10 days of a single oral antibiotic. First-line agents include ciprofloxacin (or levofloxacin or moxifloxacin) or doxycycline; clindamycin is an alternative, as is penicillin if the bacterial isolate is penicillin-susceptible. Pending results of confirmatory testing, treat systemic anthrax with combination broad-spectrum intravenous antimicrobial drugs and one of the anthrax antitoxins approved for use by the US Food and Drug Administration; delays in initiating therapy can be fatal. Online recommendations for the treatment and prevention of anthrax are available for the following groups:

• Adults
• People who are pregnant, postpartum, and lactating
• Children

Prevention

In 2019, CDC published updated recommendations from the Advisory Committee on Immunization Practices (ACIP) for preexposure use of anthrax vaccine and for postexposure management of previously unvaccinated people. Vaccination against anthrax is not recommended for most travelers, except for researchers working in anthrax-endemic areas who could be at high risk for direct contact with animals and animal products. Vaccine is also recommended to members of the military traveling to these areas.

To prevent anthrax exposures while visiting anthrax-endemic countries, travelers should avoid direct and indirect contact with animal carcasses and should not eat meat from animals butchered after having been found dead or ill. Cooking contaminated meats does not eliminate the risk of contracting anthrax. Thus, travelers should determine the provenance of the meat they are being served in rural areas, and ask for meat that has been inspected by health authorities.

No tests are available to determine if animal byproducts are free from B. anthracis spore contamination; travelers should be aware of regulations concerning and restrictions against the importation of prohibited animal products, trophies, and souvenirs. Additional information regarding import regulations can be found in Sec. 4, Ch. 9, Bringing Animals & Animal Products into the United States; at the US Department of Agriculture, Animal and Plant Health Inspection Service website, Import-Export Regulations; and the World Organization for Animal Health website, Terrestrial Animal Health Code, Anthrax.

CDC website: Anthrax