Anthrax is a serious bacterial infection of livestock that occasionally spreads to humans. The most common form of the infection in humans is cutaneous anthrax, which affects the skin. Another form, pulmonary anthrax, affects the lungs and is potentially fatal.


Anthrax is caused by Bacillus anthracis. This bacterium produces spores that can remain dormant for years in soil and animal products and are capable of reactivation. Animals become infected by grazing on contaminated land. Infection can occur in humans via a scratch or a sore if materials from infected animals are handled. Pulmonary anthrax occurs as a result of inhaling spores from infected animal fibres.

Symptoms and treatment

In cutaneous anthrax, a raised, itchy, area develops at the site of entry of the spores, progressing to a large blister and finally a black scab, with swelling of the surrounding tissues. Cutaneous anthrax is treatable in its early stages with antibiotic drugs. Without treatment, infection may spread to lymph nodes and the bloodstream and may be fatal. Pulmonary anthrax causes severe breathing difficulty and may be fatal despite intensive treatment.

Anthrax in detail - technical


Anthrax is primarily a disease of herbivorous mammals, caused by the Gram-positive rod Bacillus anthracis, which causes human infection when its spores enter the body, most commonly from handling infected animals or animal products. The disease occurs in most countries of the world, but not in those where the condition is controlled in livestock by vaccination programmes. Anthrax is a leading agent of biological warfare.

Pathophysiology—after entry into the body, anthrax spores are phagocytosed by macrophages and carried to regional lymph nodes, where they germinate to produce vegetative bacilli that enter the blood stream. These produce anthrax toxin, which has effects including impairment of cellular water homeostasis and of many intracellular signalling pathways.

Clinical features—anthrax occurs in three clinical forms based on the route of exposure. (1) Cutaneous—lesions are usually found on exposed areas of skin; a small papule develops at the site of infection, enlarges and ulcerates, with the painless ulcer becoming covered with a black leathery eschar surrounded by nonpitting oedema before healing in 2 to 6 weeks; associated systemic symptoms are usually mild. (2) Gastrointestinal—acquired by eating contaminated food and comprising (a) oropharyngeal anthrax, presenting with fever, neck swelling, sore throat, oropharyngeal ulcer, and dysphagia, and (b) terminal ileal/caecal anthrax, presenting with fever, nausea, vomiting, and abdominal pain, followed by rapidly developing ascites and bloody diarrhoea. (3) Inhalation—after a nonspecific viral-type prodrome the disease progresses to a fulminant stage of severe respiratory distress, cyanosis, stridor, and profuse sweating; up to half of patients develop anthrax meningitis; shock and death typically follow in less than 24 h.

Diagnosis—may be very difficult in the absence of a known outbreak, particularly for inhalation anthrax, where a clinical clue is widening of the mediastinum due to lymphadenopathy. Confirmation is by laboratory identification of B. anthracis. Serological testing can be used for retrospective diagnosis.

Treatment—this is with supportive care and antibiotics, which are effective against the multiplying (vegetative) form of B. anthracis, but not against the spore form. Mild cases of cutaneous anthrax are usually treated with oral penicillin. For gastrointestinal, inhalational and meningeal anthrax, at least two antibiotics should be given intravenously, e.g. ciprofloxacin or doxycycline along with another antimicrobial expected to be effective (e.g. penicillin, ampicillin, rifampin, vancomycin, chloramphenicol, imipenem, clindamycin, and clarithromycin).

Prognosis—the mortality of untreated cutaneous anthrax is 10 to 20%, but fatalities are rare with appropriate antibiotic treatment. Almost all cases of inhalation anthrax and anthrax meningitis are fatal; initiation of treatment after the start of fulminant disease is rarely effective.

Prevention—routine immunization of livestock should be instituted in endemic areas with continuing cases of animal anthrax. Carcasses of animals suspected of dying from anthrax must be disposed of appropriately. Anthrax vaccines should be offered to members of high-risk groups, e.g. those at occupational risk, laboratory workers and some military groups. Postexposure prophylaxis should be given following suspected exposure to aerosolized anthrax spores (e.g. ciprofloxacin for 60 days).


Anthrax is a zoonotic disease, primarily of herbivorous mammals, caused by Bacillus anthracis. Herbivores are particularly susceptible to anthrax, acquiring the infection via contact with soil-borne spores through oral or gastrointestinal mucosa. The bacteria multiply rapidly to high concentrations and these animals are the common source of exposure to humans. Human infections occur when spores of B. anthracis enter the body, most commonly from handling infected animals or animal products. The disease occurs in three clinical forms based on the route of exposure: cutaneous, gastrointestinal, and inhalation. Septicaemia and meningitis may occur from any primary focus. Other names for anthrax include malignant pustule, Siberian ulcer, charbon, malignant oedema, Milzbrand, and woolsorters’ disease.

Anthrax is present in most countries of the world but has practically disappeared from North America, Western Europe, and Australia since the control of disease in livestock by extensive vaccination programmes. However, it is still prevalent in less developed countries of Asia, Africa, and the Middle East where control programmes are weak or compromised by social disruptions.

Anthrax has gained further importance due to its use as a biological weapon. Evidence exists that at least 13 countries have offensive biological weapons programmes and anthrax is one of the most threatening potential agents (see: bioterrorism). Nonstate groups may attempt to use anthrax as a tool of bioterrorism. Recognition of these threats has led to an increase in resources for development of improved methods of diagnosis, therapy, and prevention.

Historical perspective

Anthrax in agricultural settings has been recognized for more than 2400 years. With the industrial revolution, workers processing animal hides and wool became another risk group. Use as a weapon of biowarfare or bioterrorism is now perceived as the major public health threat posed by anthrax. This was made clear by its accidental release from a Soviet military facility in 1979 and its distribution by letter in the United States of America in 2001.

Industrial exposure to anthrax spores carried by animal hides and wool led to cases of cutaneous and inhalation (‘woolsorters’ disease’) anthrax in industrializing countries at the end of the 19th century. In Liverpool, a disinfection station was established where imported wool and other animal fibres were bathed in formaldehyde. This public health measure led to a marked decrease in industrial anthrax in the United Kingdom.

Anthrax played a central role in the birth of medical microbiology. In the 1870s, Robert Koch and Louis Pasteur carried out complementary studies that proved the causal relation between B. anthracis and the disease anthrax. Koch cultured the organism on artificial media, described the vegetative and spore phases of its life cycle, and demonstrated disease causality by fulfilling ‘Koch’s Postulates’. Pasteur added extensively to the anthrax-based evidence for the germ theory of disease. In the early 1880s, Pasteur in France and Greenfield in England each demonstrated that heat-attenuated strains of B. anthracis protected sheep, goats, and cows from anthrax. This disease of livestock had enormous economic importance and by the mid-1890s millions of sheep and cattle had been given this first animal vaccine. In the 1930s, Sterne developed nonencapsulated strains of B. anthracis that induce protection within weeks after a single injection. This live attenuated vaccine became the main vaccine in the world for domesticated animals and is still used.

Aetiology, genetics, pathogensis, and pathology

Anthrax is caused by B. anthracis, combining a dormant spore phase in the environment with a rapidly multiplying vegetative phase in animals which resists phagocytosis and produces a lethal toxin-mediated disease. The organism is a large nonmotile Gram-positive rod; in clinical specimens it has a large capsule and occurs singly or in short chains that appear as ‘jointed bamboo’ rods. Key to the pathogen’s life cycle and epidemiology is the property of spore formation outside living animals, related to nutrient depletion in its microenvironment. These spores are resistant to heat, desiccation, ultraviolet light, gamma irradiation, and some disinfectants.

Genetically, B. anthracis consists of a 5.2-Mbp chromosome and two plasmids, pXO1 (182 kbp) and pXO2 (96 kbp), which contain hundreds of predicted protein-coding sequences. The nucleotide sequences are highly conserved, with interisolate identity typically greater than 99%. This genetic homogeneity complicates the strain typing needed for molecular epidemiology. Based on the variable copy numbers of tandem repeat markers, six distinct genetic groups have been identified. Since spores long dormant in the environment will cause new disease outbreaks, revision of this initial typing system is expected. Genetic typing of isolates from bioterrorist events has special forensic importance.

Transmission of anthrax to humans is via spores entering the skin or gastrointestinal or respiratory tracts. In the skin, entry is enhanced by abrasion and germination may occur in extracellular tissue fluid. In the respiratory tract, airborne spores reach the alveoli where they are phagocytosed by macrophages and potentially dendritic cells, and are carried to regional lymph nodes. Intracellular spores germinate, producing vegetative bacilli that multiply and activate genes carried on plasmids pXO1 and pXO2 which are the basis of its virulence. pXO1 expresses anthrax toxin, which is made up of three proteins, protective antigen (PA), lethal factor (LF), and oedema factor (EF), expressed from the genes pag, lef, and cya, respectively. pXO2 expresses poly-D-glutamic acid that forms a capsule resistant to phagocytosis. LF and EF impair leucocyte function, and contribute to tissue necrosis, oedema, and relative absence of leucocytes. Multiplying bacteria enter the blood stream, reaching bacteraemias of 107 to 108 bacilli/ml.

Anthrax toxin causes the massive oedema, organ failure, and immune compromise seen in severe anthrax. Transfer of sterile plasma containing anthrax toxin was shown in the 1950s to be lethal in a guinea pig model. The toxicology of the binding (PA) and active (LF and EF) proteins is complex. PA (83 kDa) binds to cell surface receptors, is cleaved by a furin protease which releases a 20-kDa segment, and oligomerizes into heptamers on cell surface lipid rafts. The final step in forming the toxin–receptor complex is the additional binding of three EF and/or LF proteins. The surface-bound structures are internalized by endocytosis; PA is degraded and EF/LF protected while transported to, and released into, the cytoplasm. EF, a calmodulin-dependent adenylate cyclase, increases intracellular cAMP levels and interferes with water homeostasis. LF, a zinc metalloprotease, cleaves key protein kinases on pathways linking surface receptors to transcription of specific nuclear genes resulting in cellular dysfunction. These toxins also interfere with immune responses, including production of inflammatory cytokines and phagocyte function.

When spores of B. anthracis are introduced cutaneously they germinate and multiply, protected by the antiphagocytic capsule. EF and LF impair leucocyte function and contribute to tissue necrosis, oedema, and the paucity of leucocytes in the skin lesion. Spread to draining lymph nodes results in haemorrhagic, oedematous, and necrotic lymphadenitis. Gastrointestinal anthrax follows ingestion of food contaminated with B. anthracis. Localization and multiplication of bacilli in the oropharynx and the draining lymph nodes causes oropharyngeal ulcers and neck swelling. Localization and multiplication in the stomach, duodenum, ileum, or caecum cause mucosal inflammation, ulcers, and ascites. Bacteria drain to mesenteric lymph nodes causing haemorrhagic adenitis. Inhalation anthrax follows deposition of spores in alveoli, phagocytosis and transport to tracheobronchial and mediastinal lymph nodes, and intracellular germination. Production of toxins leads to haemorrhagic, oedematous, and necrotic lymphadenitis in the mediastinum.

All primary forms of anthrax can be complicated by septicaemia and, at times, haemorrhagic meningitis. This is especially common with inhalation anthrax; autopsies of untreated cases reveal numerous bacteria in blood vessels, lymph nodes, and multiple organs.


The natural life cycle of anthrax involves vegetative multiplication in susceptible animals and dormancy of spore forms in soil. Anthrax in animals is usually acquired by exposure of mucous membranes of the mouth and gastrointestinal tract to soil contaminated with spores of B. anthracis. Once internalized, the spores germinate to yield vegetative cells which multiply and produce either localized or systemic infection. Animal species vary in susceptibility to infection and disease severity. Herbivores such as horses, sheep, goats, and cattle are most susceptible, dying with overwhelming bacteraemias. They often bleed from the nose, mouth, and bowel, and thereby contaminate soil with vegetative B. anthracis which sporulate and can persist for decades. Carcasses of infected animals are additional sources of contamination. B. anthracis spores in soil may undergo bursts of vegetative multiplication that increase the local concentration of organisms in the soil of ‘hot’ zones. The factors controlling this ex vivo multiplication of anthrax are poorly understood, but seem associated with major shifts in soil microenvironment after droughts and floods.

Human anthrax may occur in agricultural or industrial settings, or by the intentional use of anthrax spores as biological weapons. Agricultural cases result from direct contact with infected animals, generally by herders, butchers, and slaughterhouse workers. Industrial cases involve workers in contact (direct or via aerosol) with contaminated animal products such as hides, wool, goat’s hair, or bone. No human-to-human transmission of anthrax has been reported. Cutaneous anthrax typically follows skin exposure to infected animals or animal products. Gastrointestinal anthrax follows ingestion of B. anthracis-contaminated food, usually meat, and may be more common than appreciated in endemic regions of Asia and Africa. Inhalation anthrax is a result of alveolar deposition of the 1- to 2-µm-diameter spores. Historically, woolsorters and those working with herbivore hides in industrial mills were at risk, but naturally occurring inhalation anthrax is now rare.

The worldwide incidence of human anthrax is not known, but is estimated to be 2000 to 20 000 cases annually, of which some 95% are cutaneous. Based on reporting of anthrax outbreaks in animals, the World Health Organization (WHO) characterizes several countries in Africa, the Middle East, and Asia as hyperendemic/epidemic. Many other countries in these regions, as well as in southern Europe and the Americas, have an endemic level of anthrax, while most remaining countries have at least sporadic cases. The largest reported outbreak of agricultural anthrax occurred in Zimbabwe in the late 1970s during the civil war. Most of the estimated 10 000 human cases were cutaneous and a small number gastrointestinal. Disruption of veterinary health services, especially anthrax vaccination, led to epizootic anthrax in cattle and the associated epidemic in humans.

An outbreak of the oropharyngeal variant of anthrax occurred in Thailand in 1982 when 24 people developed anthrax after eating poorly cooked meat from infected cattle and buffalo. In Switzerland in 1991, 25 workers in one textile factory contracted anthrax, 24 had cutaneous disease and one had inhalation disease. The factory had imported contaminated goat hair from Pakistan. An unnatural outbreak of inhalation anthrax occurred among residents of Sverdlovsk in the former Soviet Union in 1979. Spores accidentally released into the atmosphere from a military laboratory were carried downwind and caused at least 79 cases of inhalation anthrax and 68 deaths. In the United Kingdom and Europe in 2000 and again in 2009, there were infections and deaths among parenteral drug users due to anthrax-contaminated heroin.

State-sponsored biological weapons programmes have often selected anthrax as an ideal organism for tactical use (see: bioterrorism). It is easily obtained and cultured, and spores are very stable and small enough to reach alveoli when aerosolized; inhalation infections are usually fatal. In the early 1970s, more than 140 countries signed or ratified the Biological Weapons Convention, agreeing to terminate offensive weapons programmes and destroy existing weapons stockpiles. Monitoring compliance of this convention remains problematic.

Anthrax has also been used by terrorist groups. In the early 1990s, members of the Aum Shinrikyo cult dispersed aerosols of B. anthracis (Sterne strain) spores over a Japanese city but caused no disease. In 2001, at least five letters containing anthrax spores (Ames strain) were mailed in the United States of America to several government and news offices, leading to 11 cases of inhalation anthrax with five deaths, and another 11 cases of suspected or confirmed cutaneous anthrax. Thus, in industrialized countries, the threat of human infection due to agricultural and industrial anthrax has lessened while that due to biological warfare has increased.


Control of anthrax in animals limits human exposure. Routine immunization of livestock should be instituted in endemic areas with continuing cases of animal anthrax. The most widely used animal vaccine is a live nonencapsulated strain of B. anthracis developed in the United States of America by Sterne in the 1930s. Cases of animal and human anthrax should be reported to the appropriate authorities. Carcasses of animals, domestic or wild, suspected of dying from anthrax should be incinerated in a manner that also sterilizes the underlying soil, or buried intact to a depth of six feet and covered with lime to avoid sporulation. Gastrointestinal anthrax can be prevented by public education about proper cooking of meat and avoidance when contamination is suspected. Anthrax vaccines should be offered to members of high-risk groups, such as those at occupational risk, laboratory workers, and some military groups.

Current anthrax vaccines for humans are all produced from attenuated strains of B. anthracis that are nonencapsulating. In the United Kingdom and the United States of America vaccines made from cell-free culture supernatants are used to induce antitoxin immunity, PA being the main immunizing antigen. In Russia and China, live spore vaccines have been developed. The licensed vaccine in the United States of America is anthrax vaccine adsorbed (AVA); it is given intramuscularly at 0, 1, 6, 12, and 18 months, with yearly boosters. More than 95% of vaccinees are seropositive after the first three doses. The licensed vaccine in the United Kingdom is anthrax vaccine precipitated (AVP); it is given intramuscularly at 0, 3, 6, and 26 weeks, with yearly boosters. The Russian anthrax vaccine is a suspension of live spores (strain STI-1) in use since 1953; it is given by scarification through a drop of vaccine containing 108 spores or subcutaneously at 0 and 3 weeks, with yearly boosters. The Chinese anthrax vaccine is a live spore (strain A16R) product in use since the 1960s; it is given by scarification with a dose of 108 colony-forming units and boosted at 6 to 12 months.

Drawbacks of the current cell-free vaccines are the incomplete characterization of the vaccine and the complex immunization regimens. These, along with the increased risk of B. anthracis use as a biological weapon, have stimulated renewed efforts to develop improved vaccines. A recombinant PA vaccine is in clinical development. Additional approaches under investigation include antigen and adjuvant modification, live vaccines, and DNA and vectored constructs.

Postexposure prophylaxis is given following suspected exposure to aerosolized anthrax spores. Ciprofloxacin has been approved for this indication in the United States of America (500 mg every 12 h). A 60-day course is recommended because antibiotics are not effective against the spore form that may be dormant in alveoli for many weeks. Antibiotics protect against multiplying organisms, but prevent development of protective immune responses. Therefore, disease may occur if the strain is drug resistant, after cessation of antibiotics, or when compliance is poor. For these reasons, concurrent vaccination may become part of the recommendation.

Clinical features

Cutaneous anthrax

Anthrax acquired its name from the Hippocratic description of the skin lesion’s characteristic eschar as being the colour of coal (Greek anthrakos = coal). These cutaneous lesions are usually found on exposed areas of skin, such as the face, neck, arms, or hands, and may be single or multiple depending on the type of exposure. The incubation period ranges from 1 to 12 days, usually 2 to 7 days. Initially a small papule develops at the site of infection, and it then enlarges and ulcerates. The depressed ulcer becomes covered with a black leathery eschar surrounded by nonpitting oedema  that is occasionally massive (‘malignant oedema’). Established lesions are characteristically painless and may be hypaesthetic. Small satellite vesicles, containing many organisms and few white cells, may surround the original lesion; regional lymphadenitis is common. Associated systemic symptoms are usually mild; lesions heal without scarring, although slowly (2–6 weeks), after eschar separation. In 10 to 20% of patients the disease becomes systemic, with bacteraemia and toxaemia. Cutaneous anthrax should be considered in patients with painless ulcers associated with oedema and vesicles, and who have had prior contact with animals or animal products. Differential diagnosis includes staphylococcal or streptococcal skin infections, ulceroglandular tularaemia, bubonic plague, bites of brown recluse spiders, orf, rickettsial pox, and scrub typhus.

Gastrointestinal anthrax

Gastrointestinal anthrax is acquired by eating contaminated food, and thus may occur in familial clusters. The disease has an incubation period of 2 to 5 days and occurs in two forms. Oropharyngeal anthrax follows deposition of bacteria in the oropharynx. Patients present with fever, neck swelling, sore throat, and dysphagia. The neck swelling is caused by enlargement of the jugular lymph nodes together with subcutaneous oedema as in diphtheria. The lesion in the oral cavity or oropharynx starts as inflamed mucosa, progressing through necrosis and ulceration to formation of a pseudomembrane (no eschar) covering the ulcer. In severe cases, the subcutaneous oedema extends to the anterior chest wall and axilla, with the overlying skin showing signs of inflammation. Death may result from systemic toxaemia or local airway obstruction. Oropharyngeal anthrax should be considered in patients who present with fever, neck swelling, sore throat, and oropharyngeal ulcer, and who give a history of eating raw or undercooked meat. The differential diagnosis includes diphtheria and peritonsillar abscess.

In the other form of gastrointestinal anthrax, organisms are deposited in the terminal ileum or caecum, and occasionally in more proximal parts of the gastrointestinal tract. Disease onset is nonspecific with fever, nausea, vomiting, and abdominal pain, followed by rapidly developing ascites and bloody diarrhoea. Haematemesis, melaena, haematochezia, and/or profuse watery diarrhoea may occur. In severe cases, toxaemia, shock, and death follow. Early diagnosis is difficult, except in an epidemic setting, and the disease is likely under reported.

Inhalation anthrax

Inhalation anthrax has an incubation period of 1 to 43 days. A prodrome consists of malaise, myalgia, fever, and nonproductive cough, nonspecific symptoms similar to those of viral respiratory diseases. In some patients there is transient improvement after 2 to 4 days. A fulminant stage follows which begins with severe respiratory distress, cyanosis, stridor, and profuse sweating. Subcutaneous oedema of the chest and neck may develop. A characteristic radiographic finding is mediastinal widening with or without pleural effusion. By CT, nearly all patients have mediastinal enlargement secondary to lymphadenopathy, as well as pleural effusions. Blood cultures collected before the start of antibiotics will grow B. anthracis. Up to one-half of patients develop anthrax meningitis. Shock and death typically follow in less than 24 h. During the prodrome, and in the absence of a known outbreak, the disease is very difficult to diagnose. Advanced disease may be suspected in the presence of a characteristically widened mediastinum despite otherwise normal chest radiographic findings. Inhalation anthrax must be distinguished from pneumonic plague.

Meningeal anthrax

Anthrax meningitis, associated with overwhelming B. anthracis bacteraemia, may complicate any primary form of anthrax. Rarely, a case of anthrax meningitis has been reported in which the primary site was not identified. Within a few days of the primary lesion the patient suddenly develops confusion, loss of consciousness, and focal neurological signs. The cerebrospinal fluid may be haemorrhagic, but of note is the high concentration of organisms. The disease is almost always fatal.

Criteria for diagnosis

Diagnosis of anthrax may be suspected on clinical and epidemiological grounds, and is confirmed by laboratory identification of B. anthracis. Clinical signs and symptoms are discussed above. Clinical specimens containing large Gram-positive rods, singly and in short chains of 2 to 4 cells, should be interpreted as possible Bacillus spp. Demonstration of encapsulation of these bacilli by India ink, Giemsa’s, or polychrome methylene blue stain leads to a presumptive identification of B. anthracis. Culture isolates are identified by classic biochemical and morphological characteristics: Gram-positive broad spore-forming rods, the spores do not swell the vegetative cell and are oval shaped; nonmotile; colonies have a ground-glass appearance and are (nearly always) nonhaemolytic. Standard confirmatory tests include lysis by gamma phage and direct immunofluorescent assays for cell wall or capsular antigens.

Serological testing is not helpful for diagnosis at the onset of symptoms but can be used for retrospective diagnosis. Specific IgG antibodies are detectable by enzyme-linked immunosorbent assay (ELISA), with testing of paired samples preferred. In 2004, the United States Food and Drug Administration approved a rapid blood test for confirmatory diagnosis of anthrax based on antibodies to the anthrax toxin. Delayed-type hypersensitivity is assessed by antigen skin test (Anthraxin) in the former Soviet Union for diagnosis of former infection or response to vaccination. Other technologies include immunohistochemistry, polymerase chain reaction (PCR), and genetic sequencing.

Antibiotics are effective against the multiplying (vegetative) form of B. anthracis, but not against the spore form. They should be used in combination for all severe anthrax disease. Most strains of B. anthracis are susceptible to penicillin, and mild cases of cutaneous anthrax may be treated with oral penicillin at the dosage of 250 mg 6-hourly for 5 to 7 days. For extensive lesions, parenteral penicillin G, 2 million units every 6 h, should be given for a total treatment period of 7 to 10 days. Ciprofloxacin, erythromycin, doxycycline, or chloramphenicol can be used in penicillin-sensitive patients. Antibiotics decrease the likelihood of systemic disease and thus mortality, but the time to resolution of skin lesions is unchanged. The skin lesion should be covered with a sterile dressing and used dressings should be decontaminated.

In gastrointestinal, inhalational, and meningeal anthrax, at least two antibiotics should be given intravenously. If naturally acquired, penicillin G (4 million units every 4 h) has been the drug of choice; ciprofloxacin (400 mg every 12 h) or doxycycline (100 mg every 12 h) are currently recommended in the United States of America. Of note, doxycycline should not be used for meningitis which should be assumed in the management of inhalation anthrax. Many patients will require intensive supportive care.

Anthrax caused by a biological weapon will generally be acquired by inhalation. In this setting, drug resistance due to genetic modification is of concern and drug sensitivity testing is imperative. Treatment should begin intravenously with ciprofloxacin (400 mg every 12 h) or doxycycline (100 mg every 12 h), along with one or two other antimicrobials expected to be effective (penicillin, ampicillin, rifampicin, vancomycin, chloramphenicol, imipenem, clindamycin, and clarithromycin are candidates). Factors associated with lower mortality are initiation of treatment during the prodrome phase, drainage of pleural fluid, and use of multidrug regimens. Initiation of treatment after the start of fulminant disease is rarely effective.


The mortality of untreated cutaneous anthrax is 10 to 20%. With appropriate antibiotic treatment, fatalities are rare. Almost all cases of inhalation anthrax and anthrax meningitis are fatal. An exception to this is suggested by the recent experience in the United States of America where initiation of multidrug treatment during the prodromal stage, along with drainage of pleural effusions and extensive supportive measures, resulted in a reduction of mortality to about 50%. Mortality of oropharyngeal anthrax is about 15% in treated patients; mortality of the other form of gastrointestinal anthrax is uncertain, but high if disease becomes systemic.

Other issues

The WHO has estimated that 50 kg of B. anthracis spores released over a city of 5 million people would infect 250 000 people, killing 40% of them. Numbers would be influenced by the quality of the aerosol, dispersal method, and ambient weather conditions. Cases would be largely inhalation and intensive medical care would be required. Most cities would not have the required medical surge capacity. Antibiotics and vaccine would be needed in great quantities for postexposure prophylaxis. These realities are among the challenges to preparedness planning.

Areas of uncertainty

Specificity of environmental assays will remain challenging, since true-positives will be rare and false-positives disruptive and expensive. The increasing capacity to genetically modify anthrax strains may lead to biological weapons that are resistant to antibiotics or have altered vaccine target sites.

Likely future developments

Methods for detection of spores in the atmosphere will improve. The mechanisms by which anthrax toxins compromise immune responses and cause rapid death will become clear and result in improved therapies. New vaccines with simpler immunizing regimens will become available.

Further reading

Abrami L, Reig N, Gisou van der Goot F (2005). Anthrax toxin: the long and winding road that leads to the kill. Trends Microbiol, 13, 72–8. [Good review of anthrax toxicology.]
Beatty ME, et al. (2003). Gastrointestinal anthrax: review of the literature. Arch Intern Med, 163, 2527–31. [Review of gastrointestinal anthrax, clinical, microbiological, and epidemiological aspects.]
Brachman PS, Friedlander AM, Grabenstein JD (2008). Anthrax vaccine. In: Plotkin SL, Orenstein WA, Offit PA (eds) Vaccines, pp. 111–126. Saunders, Philadelphia. [Comprehensive and expert review of anthrax vaccines.]
Brachman PS, et al. (1962). Field evaluation of a human anthrax vaccine. Am J Public Health, 52, 632–45. [Report of controlled human efficacy study of vaccine against anthrax.]
Brittingham KC, et al. (2005). Dendritic cells endocytose Bacillus anthracis spores: implications for anthrax pathogenesis. J Immunol, 174, 5545–52. [Evidence for potential role of dendritic cells in pathogenesis.]
Centers for Disease Control and Prevention (2006). Inhalation anthrax associated with dried animal hides: Pennsylvania and New York City, 2006. MMWR Morb Mortal Wkly Rep, 55, 280–2. [Report of first case of naturally acquired inhalation anthrax in the United States of America in 30 years.] 
Davies JCA (1982). A major epidemic of anthrax in Zimbabwe, part 1. Cent Afr J Med, 28, 291–8. [First of three articles describing the largest known anthrax outbreak.]  
Holty J-EC, et al. (2006). Systematic review: a century of inhalational anthrax cases from 1900 to 2005. Ann Intern Med, 144, 270–80. [Retrospective case review of inhalation anthrax showing factors associated with survival.]
Inglesby TV, et al. (2002). Anthrax as a biological weapon, 2002: updated recommendations for management. JAMA, 287, 2236–52. [Comprehensive review of bioweapons-related concerns.]
Keim P, et al. (2000). Multiple-locus variable-number tandem repeat analysis reveals genetic relationships within Bacillus anthracis. J Bacteriol, 182, 2928–36. [Description of genetic groupings of B. anthracis.]
Maguina C, et al. (2005). Cutaneous anthrax in Lima, Peru: retrospective analysis of 71 cases, including four with a meningoencephalic complication. Rev Inst Med Trop Sao Paulo, 47, 25–30. [Large retrospective review of cutaneous cases.]
Marano N, et al. (2008). Effects of reduced dose schedule and intramuscular administration of anthrax vaccine absorbed on immunogenicity and safety at 7 months. JAMA, 300, 1532–43. [Basis for shift to IM administration of vaccine and drop of dose at 2 weeks.]
Meselson M, et al. (1994). The Sverdlovsk anthrax outbreak of 1979. Science, 266, 1202–8. [Description of the bioweapons-related outbreak in the former Soviet Union.]
Perl DP, Dooley JR (1976). Anthrax. In: Binford CH, Connor DH (eds) Pathology of tropical and extraordinary diseases, vol. 1, pp. 118–23. Armed Forces Institute of Pathology, Washington. [Description and illustrations of gross and microscopic human pathology.]
Plotkin SA, et al. (1960). An epidemic of inhalation anthrax, the first in the twentieth century: I. Clinical features. Am J Med, 29, 992–1001. [Landmark description of industrial anthrax.]
Read TD, et al. (2002). Comparative genome sequencing for discovery of novel polymorphisms in Bacillus anthracis. Science, 296, 2028–33. [Development of genetic typing of isolates, spurred on by the 2001 outbreak in the United States of America.]
Sirisanthana T, et al. (1984). Outbreak of oral-pharyngeal anthrax: an unusual manifestation of human infection with Bacillus anthracis. Am J Trop Med Hyg, 39, 144–50. [Largest reported outbreak of an unusual variant of gastrointestinal anthrax.]
Vietri NJ, et al. (2006). Short-course post-exposure antibiotic prophylaxis combined with vaccination protects against experimental inhalational anthrax. Proc Natl Acad Sci, 103, 7813–6. [Evidence from primates showing benefit of postexposure vaccination with antibiotics.]