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Anthrax is a rare but serious bacterial infection caused by the Gram-positive, spore-forming, bacterium Bacillus anthracis. Spores are very resistant to damage and can remain dormant in the soil for decades. It is primarily a disease of herbivorous mammals. The disease occurs most often in wild and domestic animals in Asia, Africa and parts of Europe. Humans generally acquire the disease through contact with infected animals or contaminated animal products. Symptoms usually develop within two days of exposure for inhalation anthrax and 1-7 days with cutaneous anthrax.
- Cutaneous anthrax: direct contact with the skins or tissues of infected animals - eg, among people working with animal products such as hides from abroad.
- Inhalation anthrax: breathing in anthrax spores, usually in industrial processes such as the tanning of animal skins and the processing of wool or bones from abroad.
- Intestinal anthrax: this is very rare and is caused by swallowing spores in contaminated meats.
- Injection anthrax: since December 2009, anthrax infection has been identified in a signficant number of drug users in Scotland, probably contracted from using heroin contaminated by anthrax spores.
Person-to-person infection is very rare. Airborne transmission from one person to another does not occur and skin infection from direct contact with anthrax lesions is uncommon.
Deliberate release of anthrax
- Bioterrorism: terrorists may use anthrax as a 'biological weapon' by releasing large quantities of spores in an aerosol.
- The threat is considered serious, as the organism is relatively easy to cultivate from environmental sources and the inhalation form of disease has a high mortality rate.
- Human anthrax is rare in the UK. In England and Wales only 30 possible cases of anthrax were notified between 1981 and 2015.
- Historically human anthrax in the UK has been almost entirely an occupational disease affecting those handling imported infected animal products or working with infected animals.
- However, since December 2009 there has been an ongoing outbreak of anthrax among heroin users in the UK.
- In Scotland, between December 2009 and December 2010, there were 119 drug-using patients who were classed as anthrax cases. 14 of these cases died.
- Infections are more common in countries where the disease is common in animals - eg, South and Central America, southern and eastern Europe, Asia, and Africa.
- Anthrax spores have also been released deliberately as biological weapons.
The incubation period is usually 48 hours but may be up to seven days. Clinical presentation depends on the route of entry (direct contact, ingestion, injection or aerosol) with symptoms ranging from isolated skin infections to more severe manifestations such as cardiac or pulmonary shock, meningitis and death.
Typically, there are three forms of the disease, depending on the mode of infection. However, 'injection anthrax' can be considered to be a fourth disease form characterised by soft tissue infection.
Cutaneous (95% of cases)
- Areas affected are usually the hands, forearms, face and neck.
- Usually 2-3 days after exposure (but there may be a much longer incubation), an inflamed itchy pimple develops, which enlarges and becomes vesicular and then ulcerates; 2-6 days later a black eschar develops - 'malignant pustule').
- Local erythema and induration, with local lymphadenopathy.
- Oedema may be striking and there may be hepatosplenomegaly.
- There is associated systemic malaise with headache and sore throat, but often afebrile.
- Contact with skin lesions can transmit cutaneous infection.
- Pulmonary anthrax: ID50 (ID50 is the dose required to infect 50% of exposed individuals) for inhalation anthrax is approximately 10,000 spores.
- Symptoms usually develop within 48 hours of exposure.
- Initially, there is a flu-like illness with a nonproductive nausea, vomiting, sore throat, cough, sweats, fever, confusion, headache and myalgia. Patients also develop pallor or cyanosis, dyspnoea, tachycardia, abdominal pain and pleuritic chest pain.
- Abrupt onset of respiratory failure may develop 2-4 days later.
- Antibiotic treatment (see 'Treatment', below) should be given immediately after exposure (in the prodromal stage), as it may not prevent a fatal outcome if delayed until pulmonary or bacteraemic symptoms develop.
- This is rare - characterised by severe abdominal pain, nausea and vomiting with watery or bloody diarrhoea.
- If bacteraemia develops it is usually fatal, with massive gastrointestinal haemorrhage and sometimes meningoencephalitis.
- Soft tissue infection may present as swelling, redness and pain around injection sites.
- Abscess or ulcers at an injection site, often with marked oedema.
- Possible late presentation with sepsis and meningitis.
- As well as antimicrobials, prompt surgical management of the soft tissue infection is likely to be needed for good outcomes.
Anthrax in drug users
The presentation depends on the way in which the heroin is taken by the user. Most commonly this leads to injection anthrax but symptoms of inhalational anthrax may occur if contaminated heroin has been smoked.
Public Health England (PHE) provides an algorithm for the clinical evaluation and management of drug users with possible anthrax.
Laboratory staff should be warned of possible anthrax in specimens so that appropriate laboratory biohazard precautions can be followed.
- FBC shows raised white cells (predominantly neutrophils); LFTs show raised transaminases.
- The diagnosis of cutaneous anthrax is usually suggested by the characteristic appearance of skin lesions. Gram stain of any tissue or fluid will reveal large numbers of the bacilli. B. anthracis can be cultured from blood, ascitic fluid, cerebrospinal fluid, pleural effusion or skin lesion. Blood culture is almost always positive. Culture of skin lesion is positive in only 60-65% of cases.
- CXR and/or chest CT scan are indicated if inhalation anthrax is suspected. CXR often shows a widened mediastinum (lymphadenopathy and haemorrhagic mediastinitis), pleural effusion and pulmonary infiltrates.
- Enzyme-linked immunosorbent assay (ELISA) serological diagnosis is also available.
- Polymerase chain reaction (PCR) can amplify specific markers of B. anthracis or of the Bacillus cereus group and specific virulence plasmid markers carried by different strains.
Inhalation or gastrointestinal anthrax should be treated initially with either ciprofloxacin (not licensed for gastrointestinal anthrax) or doxycycline (unlicensed indication) combined with one or two other antibacterials - eg, amoxicillin, benzylpenicillin, chloramphenicol, clarithromycin, clindamycin, imipenem with cilastatin, rifampicin (unlicensed indication) and vancomycin. When the condition improves and the sensitivity of the B. anthracis strain is known, treatment may be switched to a single antibacterial. Treatment should continue for 60 days because germination may be delayed.
Clinical guidelines for the treatment of systemic anthrax recommend antitoxin therapy in combination with intravenous antibiotics. However, a large-scale or mass anthrax incident may exceed antitoxin availability.
Cutaneous anthrax should be treated with either ciprofloxacin (unlicensed indication) or doxycycline (unlicensed indication) for seven days. Treatment may be switched to amoxicillin if the infecting strain is susceptible. Treatment may need to be extended to 60 days if exposure is due to aerosol. A combination of antibacterials for 14 days is recommended for cutaneous anthrax with systemic features, extensive oedema, or lesions of the head or neck.
Management is multidisciplinary with timely surgical debridement to remove the primary source of toxin, with a combination of antibacterials.
Anthrax is treatable if antibiotics are administered promptly and continued for 60 days. However, if treatment is delayed or administered improperly, the patient's chances of survival are drastically decreased.
- Cutaneous anthrax is readily treatable with antibiotics if diagnosed early.
- Mortality is often high for inhalation and gastrointestinal anthrax because of delayed diagnosis and also the lack of readily available treatment in developing countries.
- The anthrax vaccine is inactivated, does not contain the live organism and cannot cause the disease.
- Anthrax immunisation is indicated for individuals at high risk of occupational exposure. These include those who handle infected animals (eg, farm workers, vets and zoo keepers), for those exposed to imported infected animal products and for laboratory staff who work with B. anthracis.
- A four-dose regimen is used for primary immunisation; booster doses should be given annually to workers at continued risk of exposure to anthrax.
- Post-exposure immunisation may be indicated, in addition to antibiotic prophylaxis. Ciprofloxacin or doxycycline should continue for 60 days (may be switched to amoxicillin after 10-14 days if the strain of B. anthracis is susceptible). Vaccination against anthrax may allow the duration of antibacterial prophylaxis to be shortened.
- Immunisation of animals at risk, and enforcement of sound food-handling and carcass hygiene policies.
Further reading and references
Shooting Up: Infections among people who inject drugs in the UK 2011. An update: November 2012; Health Protection Agency (archived content).
Notifiable diseases and causative organisms: how to report; Public Health England, 2010
Friebe S, van der Goot FG, Burgi J; The Ins and Outs of Anthrax Toxin. Toxins (Basel). 2016 Mar 108(3). pii: E69. doi: 10.3390/toxins8030069.
Anthrax: guidance, data and analysis; Public Health England
Immunisation against infectious disease - the Green Book (latest edition); Public Health England
Anthrax; Health Protection Scotland.
Head BM, Rubinstein E, Meyers AF; Alternative pre-approved and novel therapies for the treatment of anthrax. BMC Infect Dis. 2016 Nov 316(1):621.
Hicks CW, Sweeney DA, Cui X, et al; An overview of anthrax infection including the recently identified form of disease in injection drug users. Intensive Care Med. 2012 Jul38(7):1092-104. doi: 10.1007/s00134-012-2541-0. Epub 2012 Apr 24.
Kamal SM, Rashid AK, Bakar MA, et al; Anthrax: an update. Asian Pac J Trop Biomed. 2011 Dec1(6):496-501. doi: 10.1016/S2221-1691(11)60109-3.
British National Formulary; NICE Evidence Services (UK access only)
Huang E, Pillai SK, Bower WA, et al; Antitoxin Treatment of Inhalation Anthrax: A Systematic Review. Health Secur. 2015 Nov-Dec13(6):365-77. doi: 10.1089/hs.2015.0032.
Grunow R, Verbeek L, Jacob D, et al; Injection anthrax--a new outbreak in heroin users. Dtsch Arztebl Int. 2012 Dec109(49):843-8. doi: 10.3238/arztebl.2012.0843. Epub 2012 Dec 7.
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