Chapter 4 Travel-Related Infectious Diseases
Kate Hendricks, Antonio R. Vieira, Chung K. Marston
Aerobic, gram-positive, encapsulated, spore-forming, nonmotile, nonhemolytic, rod-shaped bacterium Bacillus anthracis.
Most human infections with B. anthracis result from handling B. anthracis–infected animals, their carcasses, or their meat, hides, or wool. Products derived from infected animals, such as drumheads and wool clothing, are additional, documented sources of human infection.
Anthrax has 4 main clinical presentations—cutaneous, ingestion, injection, and inhalation. Anthrax meningitis can complicate any of the 4 main clinical presentations. It can also occur with no obvious portal of entry, in which case it is called primary anthrax meningitis.
Spores introduced through the skin can result in cutaneous anthrax; abrasion of the skin increases susceptibility. Eating meat from infected animals can result in ingestion (also called gastrointestinal) anthrax. Reports since 2000 document B. anthracis soft-tissue infections in 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.
Anthrax is a zoonotic disease primarily affecting ruminant herbivores such as cattle, sheep, goats, antelope, and deer that become infected by ingesting contaminated vegetation, water, or soil; humans are generally incidental hosts. Anthrax is most common in agricultural regions in Central and South America, sub-Saharan Africa, central and southwestern Asia, and southern and eastern Europe. Although outbreaks still occur in livestock and wild herbivores in the United States, Canada, and Western Europe, human anthrax in these areas is now rare.
Worldwide, the most commonly 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 (4), ingestion (1), and inhalation (3) anthrax have been reported in people who have handled, played, or made drums; others who have been in the same place as people who participated in these activities have also been infected.
In 2006, a case of travel-associated anthrax (the cutaneous form of the disease) was reported in a woman who traveled with a small group of tourists to Namibia, Botswana, and South Africa. 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 Asia and Africa.
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 taken heroin.
Inhalation exposure was historically associated with the industrial processing of hides or wool (hence, “woolsorters’ disease”). More recently, bioterrorist activities 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.
Cutaneous anthrax usually develops 1–7 days after exposure, but incubation periods as long as 17 days have been reported. Before antimicrobial therapy, almost a quarter of patients with cutaneous anthrax died. The case-fatality ratio is <2% with antimicrobial therapy.
Localized itching, followed by the 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 commonly affected sites. Patients may have malaise and headache; about one-third are febrile.
Ingestion anthrax usually develops 1–7 days after eating contaminated meat; however, incubations as long as 16 days have been reported. Left untreated, more than half of cases will die; with treatment, the case-fatality ratio decreases slightly, to <40%. There are 2 main types of ingestion anthrax: oropharyngeal and intestinal. Fever and chills are usual with either. The oropharyngeal type 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 may be bloody) are more typical of intestinal anthrax; marked ascites may also develop. Later symptoms can include shortness of breath and altered mental status with shock and death occurring 2–5 days after disease onset.
Anthrax in injection drug users usually develops within 1–4 days of exposure; death occurs in more than a quarter of confirmed cases. Cases present with severe soft-tissue infection manifested by swelling, erythema, and excessive bruising at the injection site; pain may be less than anticipated for the degree of swelling. In approximately one-third of cases, patients become septic.
Inhalation anthrax usually develops within a week after exposure, but the incubation period may be prolonged (up to 2 months). Before 2001, fatality ratios for inhalation anthrax were 90%; since then, they have fallen to 45%. During the first few days of illness, most patients exhibit fever, chills, and fatigue. These symptoms may be accompanied by cough, shortness of breath, chest pain, and nausea or vomiting, making inhalation anthrax difficult to distinguish from influenza and community-acquired pneumonia. This is often described as the prodromal period.
Over the next day or so, shortness of breath, cough, and chest pain become more common, and nonthoracic complaints such as nausea, vomiting, altered mental status, diaphoresis, and headache develop in one-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 may develop from hematogenous spread of any of the clinical forms of anthrax, or it may 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. Most, but not all, cases of anthrax meningitis are fatal.
Include anthrax in the differential diagnosis of returning travelers with unexplained fevers or new skin lesions. Ask about recent travel to anthrax-endemic areas (www.cdc.gov/anthrax/specificgroups/travelers.html). Inquire about activities (such as drumming) and souvenir purchases, including animal-hide drums and woolen clothing.
Clinicians can use any of several methods to make a laboratory diagnosis of anthrax infection: bacterial culture and isolation of B. anthracis; detection of bacterial DNA, antigens, or toxins; or detection of a host immune response to B. anthracis. Anthrax lethal toxin can be detected in acute-phase serum, although serologic testing of host antibody responses requires acute- and convalescent-phase sera for diagnosis.
In the United States, anthrax is a nationally notifiable disease. Laboratory Response Network reference laboratories can perform confirmatory testing, such as isolate identification, and CDC laboratories—in addition to performing isolate identification—are capable of conducting other complex tests such as mass spectrometry for toxin, quantitative serology, and antigen detection in tissues. Internationally, relevant national reference laboratories should perform testing. CDC provides specimen collection and submission guidelines and algorithms for laboratory diagnosis at www.cdc.gov/anthrax/lab-testing/index.html. 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, as it removes a nidus for toxin. Unless contraindicated, lumbar puncture should be performed to rule out meningitis in all patients with systemic illness.
Treat naturally occurring localized or uncomplicated cutaneous anthrax with 7–10 days of a single oral antibiotic. First-line agents include ciprofloxacin (or an equivalent fluoroquinolone) or doxycycline; clindamycin is an alternative, as are penicillins if the isolate is penicillin susceptible. Treat systemic anthrax with combination broad-spectrum intravenous antibiotics pending the results of confirmatory testing; delays in initiating therapy may prove fatal.
Online recommendations for the treatment and prevention of anthrax are available:
- Adults: wwwnc.cdc.gov/eid/article/20/2/13-0687_article
- Pregnant, postpartum, and lactating women: wwwnc.cdc.gov/eid/article/20/2/13-0611_article
- Children: http://pediatrics.aappublications.org/content/133/5/e1411
In 2010, CDC published updated recommendations from the Advisory Committee on Immunization Practices for preexposure use of anthrax vaccine and for postexposure management of previously unvaccinated people (www.cdc.gov/mmwr/preview/mmwrhtml/rr5906a1.htm). Vaccination against anthrax is not recommended for the majority of travelers.
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. No tests are available to determine if animal products 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 may be found in the following references:
- Yellow Book 2020, Appendix E, Taking Animals & Animal Products Across International Borders (www.cdc.gov/importation/animal-products.html)
- US Department of Agriculture, Animal and Plant Health Inspection Service, import-export regulations (www.aphis.usda.gov/aphis/ourfocus/importexport)
- World Organisation for Animal Health, Terrestrial Animal Health Code, Anthrax (www.oie.int/en/animal-health-in-the-world/animal-diseases/anthrax)
A map of anthrax-endemic countries and guidance for travelers visiting those countries can be found at www.cdc.gov/anthrax/specificgroups/travelers.html.
CDC website: www.cdc.gov/anthrax
- Bales ME, Dannenberg AL, Brachman PS, Kaufmann AF, Klatsky PC, Ashford DA. Epidemiologic response to anthrax outbreaks: field investigations, 1950–2001. Emerg Infect Dis. 2002 Oct;8(10):1163–74.
- Beatty ME, Ashford DA, Griffin PM, Tauxe RV, Sobel J. Gastrointestinal anthrax. Arch Int Med. 2003 Nov;163:2527–31.
- Bradley JS, Peacock G, Krug S, et al. Pediatric anthrax clinical management. Pediatrics. 2014 May;133(5):e1411–36.
- CDC. Gastrointestinal anthrax after an animal-hide drumming event—New Hampshire and Massachusetts, 2009. MMWR Morb Mortal Wkly Rep. 2010 Jul 23;59(28):872–7.
- 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. 2014 Feb;20(2). Available from: wwwnc.cdc.gov/eid/article/20/2/13-0687_article.
- Holty JEC, Bravata DM, Liu H, Olshen RA, McDonald KM, Owens DK. Systematic review: a century of inhalational anthrax cases from 1900 to 2005. Ann Intern Med. 2006;144:270–80.
- Katharios-Lanwermeyer S, Holty JE, Person M, et al. Identifying meningitis during an anthrax mass casualty incident: systematic review of systemic anthrax since 1880. Clin Infect Dis. 2016 June;62:1537–45.
- Meaney-Delman D, Zotti ME, Creanga AA, Misegades LK, Wako E, Treadwell TA, et al. Special considerations for prophylaxis for and treatment of anthrax in pregnant and postpartum women. Emerg Infect Dis. 2014 Feb;20(2). Available from: wwwnc.cdc.gov/eid/article/20/2/13-0611_article.
- National Anthrax Outbreak Control Team. An outbreak of anthrax among drug users in Scotland, December 2009 to December 2010. Health Protection Scotland, 2011.
- Van den Enden E, Van Gompel A, Van Esbroeck M. Cutaneous anthrax, Belgian traveler. Emerg Infect Dis. 2006 Mar;12(3):523–5.