Anthrax is a serious infectious disease that affects both humans and animals. It is caused by exposure to the spores of Bacillus anthracis, a bacterium capable of surviving in the environment for long periods under harsh conditions. Anthrax is primarily a zoonotic disease, occurring most commonly in livestock such as cattle, sheep, and goats, but it can also infect humans through contact with infected animals or contaminated animal products.
Anthrax can manifest in several clinical forms depending on the route of exposure: cutaneous anthrax, the most common form, occurs through breaks in the skin; inhalation anthrax results from breathing in spores; gastrointestinal anthrax arises from ingesting contaminated food; and injection anthrax, a more recently identified form, has been linked to the use of contaminated injectable drugs. The severity of the disease varies by form, with inhalation anthrax being the most lethal if not promptly treated.
The disease is characterized by the production of potent toxins by B. anthracis, which contribute to widespread tissue damage and systemic illness. Symptoms can range from localized skin lesions and fever to severe respiratory distress, shock, and death, especially in untreated cases.
Anthrax continues to be of epidemiological and biodefense significance due to its capacity to cause outbreaks in agricultural environments and its documented application in biological warfare. Preventive measures include animal vaccination, proper handling of animal products, and post-exposure prophylaxis for humans. Early diagnosis and prompt antibiotic treatment are critical to improving outcomes.
Anthrax is a notifiable disease in many countries and is subject to national and international surveillance.
Cause and Pathogenesis
Anthrax is caused by Bacillus anthracis, a spore-forming, Gram-positive bacterium capable of persisting in the environment for extended periods. Disease occurs when dormant spores enter the body through the skin, lungs, gastrointestinal tract, or, more rarely, by injection. Upon exposure to favorable conditions within the host, these spores germinate into metabolically active vegetative cells that multiply and release virulence factors responsible for the clinical manifestations of anthrax.
The pathogenesis of anthrax involves three major components: spore resilience, toxin production, and immune evasion via capsule formation.
Spore Formation and Germination
B. anthracis forms highly durable spores when exposed to nutrient-limited environments. These spores are resistant to heat, desiccation, ultraviolet radiation, and many chemical disinfectants, allowing them to remain viable in soil and animal products for decades. The spore’s protective coat contains proteins that safeguard genetic material and regulate germination based on environmental cues within the host.
Once inside the host, spores detect changes such as temperature, CO₂ concentration, and nutrient availability. These signals trigger germination into vegetative cells, which then begin to produce toxins and proliferate, initiating infection. The ability to remain dormant until reaching a suitable host tissue is a key feature that facilitates both environmental persistence and disease transmission.
Toxin Production
The virulence of B. anthracis is largely attributed to its production of a tripartite exotoxin, encoded on the plasmid pXO1. This toxin consists of three proteins that function synergistically:
- Protective Antigen (PA): Binds to specific receptors on host cells and mediates the entry of the enzymatic toxin components.
- Edema Factor (EF): An adenylate cyclase that increases intracellular cyclic AMP (cAMP), leading to disruption of water homeostasis and tissue edema.
- Lethal Factor (LF): A zinc-dependent metalloprotease that cleaves mitogen-activated protein kinase kinases (MAPKKs), impairing cellular signaling pathways, promoting apoptosis, and disrupting immune responses.
Together, these toxins interfere with host cell function, compromise immune defenses, and contribute to the systemic effects of anthrax, including shock, hemorrhage, and necrosis. The balance and activity of these toxins vary by route of infection and host susceptibility.
Capsule and Immune Evasion
In addition to its toxins, B. anthracis possesses a poly-D-glutamic acid capsule, encoded on the plasmid pXO2. Unlike the polysaccharide capsules seen in many bacteria, this unique capsule is composed entirely of amino acids and is not immunogenic. It plays a critical role in pathogenesis by inhibiting phagocytosis by neutrophils and macrophages, allowing the bacteria to evade the host’s innate immune system.
Capsule production is tightly regulated and occurs primarily under in vivo conditions, ensuring energy is conserved until the bacterium is inside a suitable host. Without this capsule, B. anthracis is rapidly cleared and rendered avirulent, highlighting its essential role in bacterial survival during infection.
Transmission and Epidemiology
Anthrax is transmitted through exposure to spores of Bacillus anthracis, which are naturally present in the environment and can remain dormant but viable for decades under favorable conditions. Transmission primarily affects herbivorous animals but can extend to humans via environmental or occupational contact with contaminated soil, animal products, or infected carcasses.
Environmental Reservoirs
The primary natural reservoir of anthrax is soil contaminated with resilient spores of B. anthracis. These spores thrive in alkaline soils with high organic content, elevated calcium levels, and seasonal changes in temperature or rainfall. Favorable conditions allow spores to persist for over 50 years, as documented in several endemic regions, including parts of Sub-Saharan Africa, Central Asia, and the Middle East.
Environmental events such as heavy rainfall, drought, and soil disruption caused by livestock activity or excavation can bring buried spores to the surface. In Siberia (Russia) in 2016, thawing permafrost led to a re-emergence of anthrax spores, causing one child’s death and infecting dozens in a reindeer-herding community. The outbreak was traced to spores released from a 75-year-old infected animal carcass.
Animal Hosts and Spillover
Domestic and wild herbivores including cattle, sheep, goats, deer, elephants, and antelopes serve as primary hosts. Infection typically occurs through ingestion of contaminated vegetation or water, though inhalation of dust containing spores or entry through wounds is also possible.
Animals that die of anthrax release millions of spores into the environment via blood and other bodily fluids. If carcasses are not properly incinerated or buried with care, this contributes to continued environmental contamination and cycles of reinfection. In hyperendemic areas like northern Namibia’s Etosha National Park, annual outbreaks in plains animals such as zebras and springbok are a recurring phenomenon.
Human Exposure and Transmission Routes
Human infection occurs through direct or indirect contact with infected animals or contaminated animal products. Routes of transmission determine the clinical form of anthrax:
- Cutaneous anthrax is the most common form, accounting for about 95% of reported human cases globally. It typically results from spores entering minor cuts or abrasions on the skin. Lesions progress from papules to vesicles to black eschar, hence the name anthrax (from the Greek ánthrax, meaning coal). This form is rarely fatal if treated promptly with antibiotics.
- Inhalation anthrax is rare but highly lethal. It occurs when individuals inhale spores suspended in dust or aerosols, often in industrial settings such as wool-sorting facilities. A notable outbreak occurred in Sverdlovsk, USSR, in 1979, when an accidental release of spores from a military facility led to at least 66 confirmed deaths. The 2001 anthrax letter attacks in the United States caused 22 cases, with 5 deaths, drawing global attention to anthrax’s use as a biological weapon.
- Gastrointestinal anthrax results from consuming meat contaminated with B. anthracis spores. It can involve the oropharynx, esophagus, stomach, or intestines, leading to symptoms such as fever, abdominal pain, vomiting, and bloody diarrhea.
- Injection anthrax has been reported among heroin users in Europe, with cases in Scotland, Germany, and the UK. Between 2009 and 2013, over 100 cases were identified in Europe. This form causes severe soft tissue infections and sepsis, with high mortality even with aggressive treatment.
Human-to-Human Transmission
Anthrax is not considered contagious. There is no documented evidence of direct human-to-human transmission via respiratory droplets, skin contact, or bodily fluids. Therefore, infection control in healthcare settings generally requires only standard precautions, although additional measures may be taken in suspected bioterrorism-related cases.
Epidemiology
Anthrax is found around the world, but how often it occurs and how serious it is can vary depending on the region. This is influenced by factors such as the environment, how livestock are raised, and the strength of local public health systems. Each year, an estimated 2,000 to 20,000 human cases occur globally, mostly in rural areas with limited resources. People who work closely with animals like herders and livestock workers are especially at risk, particularly in parts of Sub-Saharan Africa, Central and South Asia, and the Middle East.
The number of anthrax cases differs widely between countries. For example, Ghana has reported about 0.03 cases per 100,000 people, while Georgia reported 1.4 per 100,000. In China, between 2005 and 2014, there were 3,379 reported cases, with most happening in rural areas and affecting young men under the age of 34.
In Odisha, India, there were 325 cases reported between 2010 and 2015, and another 81 in a separate year. The death rate was relatively low, around 4%. These figures show that anthrax continues to spread in certain high-risk environments.
In Europe, anthrax is very rare. In 2022, only 22 cases were reported in the EU/EEA, mostly in Croatia, Romania, and Spain. Most of these were cutaneous anthrax, the mildest form, which affects the skin.
How deadly anthrax is depends on the type of infection and how quickly treatment is given:
- Cutaneous anthrax (affecting the skin) is the most common and least deadly form. Without treatment, it can kill up to 20–25% of patients, but with antibiotics, the risk drops to below 1%.
- Inhalational anthrax (from breathing in spores) is very serious. It was once fatal in up to 90% of untreated cases. Today, with intensive medical care, about 45–50% survive, though the death rate can still reach 75–97% in severe cases.
- Gastrointestinal anthrax (from eating contaminated food) has a death rate ranging from 25–60%, but treatment can lower it to under 40%.
- Injection anthrax, seen mainly among heroin users in Europe, is rare but has a high fatality rate even with treatment.
Notable Outbreaks
- In Sverdlovsk, USSR (1979), a laboratory accident released anthrax spores into the air, causing at least 60 deaths. This remains one of the most serious inhalational anthrax outbreaks on record.
- In the U.S. (2001), anthrax spores were sent through the mail in a bioterrorism attack. This led to 22 cases (11 inhalational and 11 cutaneous), and 5 people died.
- In Thailand (May 2025), four people were infected after slaughtering an infected animal. One person died—the first anthrax death in the country in 25 years.
- In Zambia (2023), 684 suspected human cases were reported, with 4 deaths. Most cases were in rural areas, highlighting how the disease spreads from animals to people.
- In Virunga National Park, Democratic Republic of Congo, about 50 hippos died during a wildlife outbreak, showing that wild animals can also carry and spread anthrax.
Symptoms of Anthrax
Anthrax presents in distinct clinical forms depending on the route of infection. Each form varies in symptoms, severity, and fatality risk, necessitating prompt identification and treatment.
Cutaneous Anthrax
Cutaneous anthrax is the most common form, accounting for approximately 95% of cases. It begins as a painless, itchy papule at the site of spore entry.
Within 1 to 2 days, the lesion develops into a vesicle and then a characteristic black eschar surrounded by edema. Regional lymphadenopathy and malaise may occur.
If untreated, it can progress to systemic infection, but mortality remains under 20% with appropriate antibiotic therapy. Early antibiotic treatment typically results in a favorable outcome.
Inhalation Anthrax
Inhalation anthrax results from inhaling aerosolized spores. Initial symptoms resemble a flu-like illness with fever, cough, and malaise.
Within a few days, severe respiratory distress, mediastinal widening on chest X-ray, and shock develop. Without treatment, the mortality rate approaches 85%.
It often progresses rapidly to septicemia and meningoencephalitis. Aggressive supportive care combined with antibiotics is required for survival.
Gastrointestinal Anthrax
Gastrointestinal anthrax occurs after ingestion of contaminated meat. Symptoms include nausea, vomiting, abdominal pain, and severe diarrhea often with blood.
Oral or esophageal lesions may be present along with regional lymphadenopathy. The disease course frequently includes septicemia and shock.
Fatality rates range from 25% to 60% depending on the promptness of diagnosis and treatment. Antibiotics can reduce mortality if begun early.
Injectional Anthrax
Injectional anthrax has emerged among intravenous drug users exposed to spore-contaminated heroin. It presents with rapidly spreading soft tissue infection.
Swelling, pain, and extensive edema occur without the classic eschar seen in cutaneous anthrax. Systemic symptoms including fever and shock often develop quickly.
Because of delayed diagnosis and rapid progression, mortality can be high. Surgical intervention alongside antibiotic therapy is often necessary.
Diagnosis
The diagnosis of anthrax relies on a combination of clinical evaluation and laboratory testing to detect the presence of Bacillus anthracis or evidence of the host’s immune response. Laboratory confirmation is critical due to the disease’s potential severity and its overlap with other infections in early stages.
Laboratory Identification
Initial laboratory diagnosis typically involves direct examination of clinical specimens. Microscopic analysis using Gram staining may reveal large, Gram-positive rod-shaped bacteria arranged in chains. When present, a capsule surrounding the bacilli visible with special stains can help distinguish Bacillus anthracis from related species.
Culture remains a cornerstone of diagnosis. Specimens are commonly grown on blood agar, where B. anthracis forms distinctive gray-white, non-hemolytic colonies with a ground-glass appearance. The organism is non-motile, and capsule formation is often observed in vivo but not in routine culture. These traits, along with catalase positivity and susceptibility to gamma phage lysis, assist in distinguishing it from other Bacillus species.
Molecular Detection Methods
Molecular diagnostic methods offer faster and more specific identification. Polymerase chain reaction (PCR) assays are commonly used to detect genes located on the bacterium’s plasmids, such as pagA (protective antigen) and cap (capsule formation), which are considered unique markers for anthrax. Real-time PCR enables rapid diagnosis—often within hours—directly from clinical specimens, which is particularly valuable for early intervention.
Other nucleic acid-based methods, such as loop-mediated isothermal amplification (LAMP), provide simplified alternatives suitable for field settings with limited laboratory infrastructure. Whole-genome sequencing can further confirm diagnosis and provide strain-level data useful in epidemiological investigations.
Serological Testing
Serological tests detect antibodies produced in response to infection, particularly against the protective antigen component of anthrax toxins. Enzyme-linked immunosorbent assay (ELISA) is the most commonly employed method to measure antibody titers. However, since antibody responses typically take days to weeks to develop, serology is more useful for retrospective diagnosis or population-level surveillance than for early clinical detection.
Additional assays, including complement fixation and Western blot, may be used for confirmatory purposes. However, serological results must be interpreted cautiously, as they may not reliably differentiate between vaccination and natural infection without supporting clinical and epidemiological information.
Treatment Strategies
Antibiotics are the cornerstone of anthrax treatment and should be initiated as soon as anthrax is suspected, ideally before laboratory confirmation. The choice of antibiotic and duration of treatment depend on the form of anthrax and its severity.
For cutaneous anthrax, oral antibiotics such as ciprofloxacin or doxycycline are typically effective. Treatment duration is usually 7–10 days for uncomplicated cases, though extended therapy (up to 60 days) may be recommended if exposure to spores is ongoing or uncertain.
Inhalational anthrax, a life-threatening condition, requires intravenous (IV) antibiotics and intensive supportive care. Recommended first-line agents include:
- Ciprofloxacin (IV), combined with one or two additional agents such as clindamycin, meropenem, or linezolid to ensure broad-spectrum coverage and potential antitoxin effects. Penicillin may also be used, especially in confirmed susceptible strains.
- Antitoxins, such as raxibacumab and oblitoxaximab, are monoclonal antibodies that target anthrax toxins and may be used as adjunctive therapy. These agents are especially beneficial in advanced cases where bacterial toxins drive systemic illness.
Treatment for inhalational anthrax typically continues for 60 days due to the potential for delayed germination of inhaled spores.
Supportive Care
In addition to antibiotics, supportive care is vital—especially for systemic anthrax involving respiratory failure, sepsis, or multi-organ dysfunction. Common interventions include:
- Mechanical ventilation for respiratory distress
- Vasopressors to maintain blood pressure in septic shock
- Intravenous fluids for hydration and perfusion
- Analgesia for pain management
- Surgical debridement or drainage in cases of large necrotic skin lesions or soft tissue abscesses
Patients with meningeal anthrax—a rare but fatal complication—require immediate administration of high-dose IV antibiotics capable of crossing the blood-brain barrier, such as meropenem or linezolid, alongside antitoxins.
Admission to an intensive care unit (ICU) is often required for patients with inhalational or gastrointestinal anthrax, or when severe complications arise. In high-resource settings, ICU-level monitoring has been shown to significantly reduce mortality through timely management of systemic effects.
Post-Exposure Prophylaxis
Post-exposure prophylaxis is recommended for individuals who have been exposed to Bacillus anthracis spores, particularly during occupational incidents, laboratory accidents, or bioterrorism events. PEP aims to prevent infection by eliminating spores before they germinate and cause illness.
PEP consists of:
- 60-day oral antibiotic regimen with ciprofloxacin (500 mg twice daily) or doxycycline (100 mg twice daily)
- Anthrax Vaccine Adsorbed (AVA), administered as a 3-dose series over 4 weeks (days 0, 14, and 28), enhances protection when given alongside antibiotics
The Centers for Disease Control and Prevention (CDC) recommends initiating PEP within 48 hours of exposure for maximum effectiveness. During the 2001 U.S. anthrax attacks, over 10,000 individuals received PEP, which played a key role in preventing additional cases.
PEP is particularly indicated for:
- Individuals with confirmed or suspected exposure to aerosolized spores
- Laboratory personnel and emergency responders involved in high-risk investigations
- Workers in animal industries where exposure to infected materials is possible
Although rare, adverse effects of long-term antibiotic use or vaccination (e.g., gastrointestinal discomfort, rash, injection-site reactions) are typically mild and self-limiting.
Prevention and Control Measures
Effective prevention and control of Bacillus anthracis involves coordinated efforts in immunization, strict laboratory and field safety protocols, and proper management of livestock and contaminated environments. These strategies target reducing infection risks in both humans and animals.
Vaccination Programs
Vaccination remains one of the most effective strategies for preventing anthrax in livestock and at-risk human populations. In animals, the Sterne vaccine, a live attenuated spore-based vaccine, is widely used and has significantly reduced outbreaks in endemic areas when applied regularly. Annual vaccination of susceptible species particularly cattle, sheep, goats, and horses is recommended in regions with recurring outbreaks.
For humans, the Anthrax Vaccine Adsorbed (AVA) is approved for use in countries such as the United States. It is recommended for:
- Laboratory personnel handling Bacillus anthracis cultures
- Military personnel deployed to high-risk areas
- Workers who process animal hides, wool, or bone products
The AVA schedule typically involves five intramuscular doses over 18 months, followed by annual boosters. While the vaccine is not licensed for general public use due to limited exposure risk, it is a critical component of post-exposure prophylaxis during bioterrorism events.
Biosafety Practices
Handling Bacillus anthracis in laboratory settings necessitates strict Biosafety Level 3 (BSL-3) protocols due to the risk of airborne spore transmission. These practices include:
- Use of Class II or III biological safety cabinets
- HEPA-filtered ventilation systems to prevent aerosol dispersal
- Comprehensive personal protective equipment (PPE), including gowns, gloves, and respirators
- Routine disinfection with sporicidal agents such as sodium hypochlorite or peracetic acid
Laboratory-acquired infections, though rare, have been documented, reinforcing the need for rigorous biosafety.
In clinical and field settings, frontline health workers and veterinarians are advised to:
- Avoid direct contact with suspected animal carcasses or cutaneous lesions
- Use disposable protective gear
- Apply sterilization procedures for surgical instruments and sample containers
- Implement quarantine measures in the event of animal outbreaks
Animal and Environmental Management
Anthrax spores can persist in the soil for decades, making environmental control essential in endemic regions. Key strategies include:
- Prompt reporting and disposal of infected animal carcasses by incineration or deep burial (at least 2 meters deep with lime)
- Avoiding opening carcasses, which can release large numbers of spores
- Fencing off contaminated pastures to prevent animal exposure
- Decontaminating soil using formalin, quicklime, or solar irradiation where practical
In Zambia, the 2023 anthrax outbreak involving over 680 suspected human cases was linked to exposure to infected animal meat in rural areas. The government implemented livestock quarantine, carcass disposal, and mass animal vaccination to contain the outbreak.
Additionally, vector control is essential. Biting flies and scavengers such as vultures or wild dogs can spread spores between carcasses and pastures. Reducing mechanical transmission through insect control and safe waste management lowers outbreak risk.
Proper handling and processing of animal products such as hides, wool, and bones are crucial to prevent occupational exposure. Workers in the leather, textile, and bone meal industries should undergo regular health checks and ensure materials are heat-treated or chemically sterilized before processing.
Bacillus anthracis in Bioterrorism
Bacillus anthracis is recognized as one of the most potent biological warfare agents due to its high lethality, spore resilience, and capacity to cause widespread panic. Its spores are capable of surviving in the environment for decades, making them ideal for long-term storage and potential deployment. These properties have made B. anthracis a focal point in biodefense strategies and international biosecurity discussions.
Historical Incidents
One of the most infamous bioterrorism incidents involving B. anthracis occurred in the United States in 2001, when anthrax spores were mailed in envelopes to media outlets and government offices. This event resulted in five deaths, 17 additional infections, and significant public anxiety. It exposed vulnerabilities in national security and postal systems, leading to heightened surveillance and investment in biodefense infrastructure.
Earlier, in World War II, several countries, including the United Kingdom, Japan, and the Soviet Union, explored anthrax for military use. Japan’s Unit 731 is reported to have conducted human experimentation with anthrax and other pathogens. The UK tested anthrax bombs on Gruinard Island, rendering the island contaminated for decades.
The 1979 Sverdlovsk incident in the former Soviet Union also highlighted the dangers of accidental release. A leak from a military microbiology facility released anthrax spores into the air, killing at least 66 people. Though not an act of terrorism, it underscored the consequences of handling anthrax in weaponized form.
Preparedness and Response
Governments worldwide have developed comprehensive plans to detect and respond to anthrax attacks. These include rapid identification protocols, medical countermeasures such as vaccination and antibiotics, and public communications strategies to minimize panic.
Stockpiles of antibiotics—ciprofloxacin, doxycycline, and amoxicillin—along with anthrax vaccines (e.g., BioThrax), are maintained in national medical reserves like the Strategic National Stockpile (SNS). Routine simulations and response drills are conducted for first responders, public health officials, and hospital personnel to maintain readiness.
Specialized procedures are in place to disinfect buildings, equipment, and clothing following an anthrax exposure, often involving chlorine dioxide, formaldehyde, or hydrogen peroxide vapor.
Risk Assessment
Risk assessments of anthrax as a bioweapon consider several key factors:
- Spore Durability: Spores can persist in soil, clothing, or surfaces for decades, making cleanup and containment difficult after an attack.
- Ease of Production: While culturing B. anthracis is technically straightforward for someone with microbiological training, producing spores in sufficient quantity and purity for effective aerosol dissemination requires specialized equipment and expertise.
- Modes of Dissemination: Inhalational anthrax is the most lethal form and the primary concern in bioterrorism scenarios. However, spores must be aerosolized into particles of 1–5 microns to reach the alveoli, a technically complex process.
- Limited Person-to-Person Transmission: Anthrax does not typically spread between individuals, limiting its pandemic potential but concentrating its effects among directly exposed populations.
- Global Biosecurity Regulations: The Biological Weapons Convention (BWC) prohibits the development and stockpiling of biological weapons, including anthrax. However, enforcement relies on national compliance and intelligence sharing.