Bacillus anthracis: Infectious substances pathogen safety data sheet

Section I – Infectious agent

Name

Bacillus anthracis

Agent type

Bacteria

Taxonomy

Family

Bacillaceae

Genus

Bacillus

Species

Anthracis

Synonym or cross-reference

Anthrax, Yamal disease and woolsorters' disease^{Footnote 1Footnote 2Footnote 3}.

Characteristics

Brief description

B. anthracis is a member of the Bacillus cereus group^Footnote 1. B. anthracis are Gram-positive, rod-shaped (1.0 to 1.5 μm by 3 to 8 μm) cells that occur singly or in chains^Footnote 1. B. anthracis is a non-motile, facultative anaerobe that forms metabolically dormant, environmentally resistant endospores under adverse conditions^Footnote 1. Genomic DNA is circular (5.3 to 5.5 Mbp)^Footnote 4. Clades A – E have been defined^Footnote 5. Some strains produce a capsule and/or exotoxins^Footnote 1.

Properties

Upon entering a host, B. anthracis spores are internalized by phagocytes, triggering germination^Footnote 6. The germination process occurs rapidly (2 to 10 min)^Footnote 7. Vegetative cells divide by binary fission and produce virulence factors that aid in the establishment of infection and local tissue damage^Footnote 6. Virulence factors are encoded on two plasmids, pXO1 and pXO2; loss of either plasmid results in a considerable reduction in virulence^Footnote 7. Components of anthrax toxins (lethal toxin and edema toxin) are encoded by pXO1 and are largely responsible for the morbidity and mortality associated with anthrax disease^{Footnote 6Footnote 7}, while pXO2 encodes capsule components.

Section II – Hazard identification

Pathogenicity and toxicity

Bacillus anthracis is the causative agent of anthrax, a toxin-mediated disease affecting humans, livestock, and wildlife. Disease in humans is characterized based on the portal of entry. Cutaneous, ingestion related (oropharyngeal/gastrointestinal), inhalational, and injection-associated forms of anthrax have been described^{Footnote 7Footnote 8}.

Cutaneous form of Bacillus anthracis accounts for about 95% of human anthrax cases^Footnote 7. Disease can be mild to severe. Symptoms include headache, malaise, fever, and bullous lesions on face, neck, hands, and/or arms with localized erythema. Lesions develop into black eschars after 5 to 7 days^Footnote 8. If not treated, dissemination via the bloodstream occurs in 5-20% of cases^Footnote 9. Complications include extensive edema and toxaemic shock^Footnote 10. With treatment, mortality is less than 1%^Footnote 8.

There are two forms of ingestion-associated anthrax. Oropharyngeal anthrax is characterized by lesions affecting the tongue, buccal cavity, tonsils, or posterior pharyngeal wall. Symptoms include sore throat, fever, swelling of neck and anterior chest wall^{Footnote 7Footnote 8}. Gastrointestinal anthrax is characterized by occurrence of ulcers between the jejunum and the cecum and can be mild to severe^Footnote 8. Symptoms include abdominal pain, anorexia, nausea, vomiting, and fever^Footnote 8. In severe cases hematemesis, fluid collection in the abdomen, bloody diarrhoea, and toxic shock may occur^{Footnote 7Footnote 9}. Mortality is estimated to be 4-50%^Footnote 9.

Inhalational anthrax has a biphasic clinical course. Prodromal symptoms include headache, fever, malaise, myalgia, and cough for approximately 4 days^Footnote 8. This is followed by a fulminant phase characterized by high fever, shortness of breath, fluid collection in the chest, and septic shock^Footnote 9. Development of meningoencephalitis occurs in approximately 38% of cases^Footnote 11. Mortality is approximately 45% when treated early, and 97% if patients progress to fulminant phase^Footnote 11.

Intravenous anthrax is associated with tissue edema at the injection site and soft tissue infection^Footnote 8. Papules, vesicles, and eschars are usually absent^Footnote 8. Severe cases develop hemorrhagic meningitis and have a high incidence of septic shock^Footnote 8. Mortality is approximately 34%^{Footnote 8Footnote 12}.

In herbivores, sudden death is often the first sign of anthrax^Footnote 13. Death may be preceded by fever, dyspnea, edematous swelling in neck, or abdomen^Footnote 13. Mortality rates in herbivores are highly variable, can be up to 90% for some unvaccinated species under certain environmental conditions^{Footnote 7Footnote 14Footnote 15}. Pigs, dogs, and carnivorous species are more resistant but can still die from infection^{Footnote 7Footnote 13}. Anthrax in birds is relatively rare; disease course is similar to that in herbivorous mammals^Footnote 13.

Epidemiology

B. anthracis inhabits every continent except Antarctica^{Footnote 7Footnote 16}. Some regions have been characterized as hyperendemic, while other endemic regions can go years or decades without an anthrax outbreak^{Footnote 16Footnote 17Footnote 18Footnote 19}. At least 2,000 cases of human anthrax occur annually worldwide^Footnote 20. Approximately 95% of human anthrax cases are the cutaneous form acquired during the handling or processing of infected meat or animal products (e.g., hides, wool, bones)^{Footnote 7Footnote 9}. Sporadic anthrax outbreaks associated with consumption of insufficiently cooked infected meat account for less than 5% of human cases^{Footnote 7Footnote 8}. Several intravenous drug use-associated anthrax cases have been reported in which drugs were contaminated with B. anthracis spores^Footnote 12. A recent incident involving the malicious use of B. anthracis spores in 2001 in the United States where spores were mailed to several individuals resulted in 22 anthrax cases and 5 fatalities^Footnote 7.

Introduction of livestock vaccines in the 1930s and other control measures drastically reduced anthrax incidence^Footnote 13. Anthrax outbreaks affecting livestock, particularly cattle, and herbivorous wildlife populations (e.g., bison, reindeer, hippopotami) are still reported in endemic and hyperendemic regions^{Footnote 13Footnote 15Footnote 16Footnote 21}. Seasonality of outbreaks varies according to affected species and ecosystem^{Footnote 16Footnote 17Footnote 22}. Some sporadic outbreaks have been attributed to soil disturbance such as digging, dredging, or erosion-related exposure of sites previously used for carcass disposal or processing of animal products (e.g., tanneries)^{Footnote 7Footnote 13}.

Unknown for humans. Seroprevalence studies indicate that herbivores are more severely affected than carnivorous wildlife, with the exceptions of mink and cheetahs^{Footnote 13Footnote 17}. Some herbivore species (e.g., white-tailed deer, bison, and reindeer) are particularly prone to B. anthracis infection^{Footnote 3Footnote 17}. Animal stress has been suggested to play an important role in disease susceptibility^{Footnote 3Footnote 22}.

Host range

Natural host(s)

Humans, cattle, sheep, goats, swine, poultry^Footnote 13. Various herbivorous mammals including bovines (e.g., buffalo^Footnote 23, bison^Footnote 24), equines (e.g., horses, zebra^Footnote 13), hippopotami^{Footnote 15Footnote 23}, elephants^Footnote 25, rhinos^Footnote 26, antelopes^{Footnote 15Footnote 22Footnote 26}, elks, and deers^{Footnote 27Footnote 28} are susceptible hosts. Other hosts include felines^{Footnote 13Footnote 29}, canines^{Footnote 13Footnote 17}, ostriches^Footnote 13, and snakes^Footnote 30.

Other host(s)

Non-human primates, rabbits, guinea pigs, and rodents have been experimentally infected^{Footnote 17Footnote 31}.

Infectious dose

The infectious dose for anthrax varies from species to species and is dependent on route of exposure and the strain^Footnote 31. The infectious dose for humans is unknown but in the absence of skin lesions (which lowers the infectious dose for cutaneous anthrax), the 50% infective doses (ID₅₀) are in the thousands or tens of thousands of spores^Footnote 9. The infectious doses for cutaneous and injection-associated anthrax are considerably lower^Footnote 31.

Incubation period

In humans, the incubation period for anthrax ranges from 12 hours to 7 days for cutaneous anthrax; 2 to 5 days for ingestion-associated anthrax; 1 to 6 days for inhalational anthrax; and 1 to 10 days for intravenous anthrax^Footnote 9. For trade purposes, the World organisation for Animal Health (WOAH- founded as OIE) incubation period for animals is up to 20 days^Footnote 7.

Communicability

Anthrax occurs from human exposure to B. anthracis spores via contact with mucous membranes or broken skin, ingestion, inhalation, or injection^{Footnote 7Footnote 8}. Human exposure commonly occurs due to handling or consumption of animal meat or handling of animal products (e.g., hides, hair, bones, wool) containing B. anthracis spores^Footnote 7. Human-to-human transmission is rare and has not been reported for gastrointestinal or inhalation anthrax. Maternal-fetal transmission is possible^{Footnote 32Footnote 33}.

The primary route of infection with B. anthracis in herbivores is via inhalation or ingestion of spores while grazing or via ingestion of contaminated feed^Footnote 13. In some areas, transmission may be aided by flies^{Footnote 13Footnote 17}. Carnivorous and omnivorous animals can become infected via consumption of B. anthracis-infected animals^Footnote 13.

Section III – Dissemination

Reservoir

B. anthracis spores can remain viable in animal carcasses, animal products, and soil for many years^Footnote 7.

Zoonosis

Anthrax is primarily a disease of herbivorous mammals. It can be transmitted to humans via contact with infected animal meat and animal products^Footnote 7.

Vectors

Insects (e.g., tabanids) may play a role as a mechanical vector capable of transmitting B. anthracis in some ecosystems^{Footnote 17Footnote 22Footnote 31Footnote 34Footnote 35Footnote 36}.

Section IV – Stability and viability

Drug susceptibility/resistance

B. anthracis is susceptible to penicillin^Footnote 7; ampicillin^Footnote 7; amoxicillin^Footnote 7; fluoroquinolones (e.g., ciprofloxacin, levofloxacin, gatifloxacin, ofloxacin)^{Footnote 7Footnote 37}; macrolides (e.g., clindamycin, clarithromycin, erythromycin)^Footnote 7; aminoglycosides (e.g., streptomycin, gentamicin)^{Footnote 1Footnote 7}; tetracyclines (e.g., doxycycline, omadacycline)^{Footnote 7Footnote 38Footnote 39}; vancomycin^{Footnote 7Footnote 40}; and rifampin^{Footnote 7Footnote 41Footnote 42}. Other promising antimicrobial agents effective against B. anthracis include daptomycin and dalbavancin^Footnote 37.

Naturally occurring penicillin-resistant B. anthracis strains have been isolated occasionally^{Footnote 43Footnote 44Footnote 45}. Many B. anthracis strains are resistant to some cephalosporins (e.g., cefuroxime, ceftriaxone, ceftazidime)^{Footnote 45Footnote 46Footnote 47}.

Susceptibility to disinfectants

Vegetative cells are highly susceptible to a range of disinfectants, including ethanol and chlorine, whereas B. anthracis spores require high doses and/or extensive contact time to achieve adequate reduction of viable spores^{Footnote 48Footnote 49}. Ozone gas (9,800-12,000 ppm for 6 to 12 hours, 85% relative humidity)^Footnote 49; hydrogen peroxide vapour treatment for 90 minutes^{Footnote 49Footnote 50}; iodine vapour (2.1 mg/L for 24 hours, 90% relative humidity)^Footnote 51; chlorine dioxide gas (100-300 ppm for 3 to 12 hours, 75% relative humidity)^Footnote 52; formaldehyde gas (10.5 g solid paraformaldehyde per m³)^Footnote 49; methyl bromide gas (300 mg/L for 18 hours, 75% relative humidity)^Footnote 49; methyl iodide gas (100-400 mg/L, 12 to 48 hours)^Footnote 53; and metam sodium^Footnote 54 completely inactivated or achieved ≥6-log reduction of B. anthracis (or surrogate) spores. Sodium hypochlorite (2%)^Footnote 49, formaldehyde (5-38%)^{Footnote 49Footnote 55}, and peracetic acid (2%)/0.2% surfactant^{Footnote 49Footnote 56} also effectively inactivated B. anthracis spores.

Physical inactivation

Heat treatment (75-80 °C, 70-90% relative humidity) for 7 days resulted in a 7-log reduction of surrogate spores on surfaces^Footnote 57. Gamma irradiation (>30 kGy) has been used to achieve 6-log reduction in B. anthracis spores^Footnote 58.

Survival outside host

B. anthracis spores can persist for years on various materials, particularly under dry conditions^{Footnote 7Footnote 59}. B. anthracis spores can remain viable in dry soil for 60 years^Footnote 60. Viable B. anthracis spores were recovered from bones that were over 200 years old^Footnote 7.

Section V – First aid/medical

Surveillance

B. anthracis can be isolated from clinical samples using culture-based methods^{Footnote 7Footnote 8}. Blood smears can be stained and examined microscopically for presence of capsulated, Gram-positive bacilli^Footnote 7. Gamma phage susceptibility assay, PCR, and immunoassays can also be used to confirm presence of B. anthracis^{Footnote 8Footnote 61Footnote 62}. Xenodiagnosis has also been used^Footnote 22.

Note: The specific recommendations for surveillance in the laboratory should come from the medical surveillance program, which is based on a local risk assessment of the pathogens and activities being undertaken, as well as an overarching risk assessment of the biosafety program as a whole. More information on medical surveillance is available in the Canadian Biosafety Handbook (CBH).

First aid/treatment

Human anthrax can be treated successfully with appropriate antibiotics and supportive care to manage symptoms^Footnote 7. Duration of treatment can range from 3 to 60 days^{Footnote 7Footnote 9}. Some licensed immunoglobulin products have been approved in Canada for use in combination with antibiotics for the treatment of toxaemia associated with inhalational anthrax, including Anthrasil® (AIGIV, Emergent BioSolutions, Winnipeg, MB)^{Footnote 9Footnote 63}. Surgical treatment to remove damaged/necrotic tissue and reconstructive surgery may be necessary in some cases^{Footnote 12Footnote 64}.

Similarly, animals can be treated successfully with appropriate antibiotics, particularly when administered early in the course of infection^Footnote 7.

Note: The specific recommendations for first aid/treatment in the laboratory should come from the post-exposure response plan, which is developed as part of the medical surveillance program. More information on the post-exposure response plan can be found in the CBH.

Immunization

Human vaccines include BioThrax® (Anthrax Vaccine Adsorbed, Emergent Biosolutions, Winnipeg, MB) approved in the United States and Canada, Anthrax Vaccine Precipitated in the United Kingdom^Footnote 7, Russian live attenuated anthrax vaccine, and live attenuated strain A16R in China^{Footnote 7Footnote 65Footnote 66}.

Most veterinary vaccines use a live attenuated, toxigenic, non-capsulating B. anthracis Sterne strain 34F₂ or an analogous strain^Footnote 7. About 200 million doses of anthrax vaccine are used for livestock globally every year^Footnote 16.

Note: More information on the medical surveillance program can be found in the CBH, and by consulting the Canadian Immunization Guide.

Prophylaxis

In the United States and Canada, BioThrax® is licensed for post-exposure prophylaxis of anthrax in combination with antimicrobial drugs (e.g., ciprofloxacin, doxycycline) for up to 60 days^{Footnote 7Footnote 8Footnote 67}.

Note: More information on prophylaxis as part of the medical surveillance program can be found in the CBH.

Section VI – Laboratory hazard

Laboratory-acquired infections

Prior to 1975, forty-five cases of laboratory-acquired anthrax were reported^Footnote 68. Five of the infections were fatal^Footnote 68. In 2002, a laboratory worker in the United States developed cutaneous anthrax after handling a contaminated vial with bare hands^Footnote 69.

Note: Please consult the Canadian Biosafety Standard (CBS) and CBH for additional details on requirements for reporting exposure incidents. A Canadian biosafety guideline describing notification and reporting procedures is also available.

Sources/specimens

Blood, skin lesion exudates, cerebrospinal fluid, pleural fluid, sputum, feces^Footnote 8.

Primary hazards

Primary hazards in a laboratory setting are exposure of broken skin or mucous membranes to infectious material (e.g., cultures, contaminated laboratory surfaces), autoinoculation, and exposure to infectious aerosols^Footnote 70.

Special hazards

None.

Section VII – Exposure controls/personal protection

Risk group classification

B. anthracis is a Risk Group 3 (RG3) Human Pathogen, a RG3 Animal Pathogen, and a Security Sensitive Biological Agent (SSBA)^{Footnote 71Footnote 72}. B. anthracis Sterne strain, Weybridge strain, and Ames35 strain are RG2 human pathogens and RG2 animal pathogens^Footnote 72.

Containment requirements

Containment Level 3 facilities, equipment, and operational practices outlined in the CBS are required for work involving infectious or potentially infectious materials, animals, or cultures.

Containment Level 2 facilities, equipment, and operational practices outlined in the CBS are required for work involving B. anthracis Sterne strain, Weybridge strain, and Ames35 strain.

Note: There are additional security requirements, such as obtaining a Human Pathogens and Toxins Act Security Clearance, for work involving SSBAs.

Protective clothing

The applicable Containment Level 2 or Containment Level 3 requirements for personal protective equipment (PPE) and clothing outlined in the CBS to be followed for work involving RG2 and RG3 B. anthracis strains, respectively. At minimum, use of full body coverage dedicated protective clothing, dedicated protective footwear and/or additional protective footwear, gloves when handling infectious materials or animals, face protection when there is a known or potential risk of exposure to splashes or flying objects, respirators when there is a risk of exposure to infectious aerosols, and an additional layer of protective clothing prior to work with infectious materials or animals.

A local risk assessment will identify the appropriate hand, foot, head, body, eye/face, and respiratory protection, and the personal protective equipment requirements for the containment zone and work activities must be documented.

Other precautions

All activities involving open vessels of pathogens are to be performed in a certified biological safety cabinet (BSC) or other appropriate primary containment device. The use of needles, syringes, and other sharp objects are to be strictly limited. Additional precautions must be considered with work involving animals or large-scale activities.

Additional information

For diagnostic laboratories handling primary specimens that may contain B. anthracis, the following resources may be consulted:

• Human Diagnostic Activities Biosafety Guideline
• Local Risk Assessment Biosafety Guideline

Section VIII – Handling and storage

Spills

Allow aerosols to settle. Wearing personal protective equipment, gently cover the spill with absorbent paper towel and apply suitable disinfectant, starting at the perimeter and working towards the centre. Allow sufficient contact time before clean up (CBH).

Disposal

All materials/substances that have come in contact with the regulated materials should be completely decontaminated before they are removed from the containment zone or standard operating procedures (SOPs) to be in place to safely and securely move or transport waste out of the containment zone to a designated decontamination area / third party. This can be achieved by using decontamination technologies and processes that have been demonstrated to be effective against the regulated material, such as chemical disinfectants, autoclaving, irradiation, incineration, an effluent treatment system, or gaseous decontamination (CBH).

Storage

The applicable Containment Level 2 or Containment Level 3 requirements for storage outlined in the CBS are to be followed for work involving RG2 and RG3 B. anthracis strains, respectively. Primary containers of regulated materials removed from the containment zone to be stored in a labelled, leak-proof, impact-resistant secondary container, and kept either in locked storage equipment or within an area with limited access.

Containers of SSBAs stored outside the containment zone must be labelled, leakproof, impact resistant, and kept in locked storage equipment that is fixed in place (i.e., non-movable) and within an area with limited access.

An inventory of RG3 and SSBA in long-term storage, to be maintained and to include:

• specific identification of the pathogens, toxins, and other regulated materials
• a means to allow for the detection of a missing or stolen sample in a timely manner

Section IX – Regulatory and other information

Canadian regulatory information

Controlled activities with B. anthracis require a Human Pathogens and Toxins licence, issued by the Public Health Agency of Canada^Footnote 71. Anthrax is a World organisation for Animal health (WOAH) listed disease (founded as OIE), and a nationally notifiable disease and a reportable disease in Canada^{Footnote 71Footnote 73}.

The following is a non-exhaustive list of applicable designations, regulations, or legislations:

• Human Pathogen and Toxins Act and Human Pathogens and Toxins Regulations
• Health of Animals Act and Health of Animals Regulations
• National notifiable disease (human)
• Reportable disease (animal)
• Transportation of Dangerous Goods Regulations

Last file update

2020

Prepared by

Centre for Biosecurity, Public Health Agency of Canada.

Disclaimer

The scientific information, opinions, and recommendations contained in this Pathogen Safety Data Sheet have been developed based on or compiled from trusted sources available at the time of publication. Newly discovered hazards are frequent and this information may not be completely up to date. The Government of Canada accepts no responsibility for the accuracy, sufficiency, or reliability or for any loss or injury resulting from the use of the information.

Persons in Canada are responsible for complying with the relevant laws, including regulations, guidelines and standards applicable to the import, transport, and use of pathogens in Canada set by relevant regulatory authorities, including the Public Health Agency of Canada, Health Canada, Canadian Food Inspection Agency, Environment and Climate Change Canada, and Transport Canada. The risk classification and related regulatory requirements referenced in this Pathogen Safety Data Sheet, such as those found in the Canadian Biosafety Standard, may be incomplete and are specific to the Canadian context. Other jurisdictions will have their own requirements.

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