Burkholderia mallei: Infectious substances Pathogen Safety Data Sheet

Section I: Infectious agent

Name

Burkholderia mallei

Agent type

Bacteria

Taxonomy

Family

Burkholderiaceae

Genus

Burkholderia

Species

mallei

Synonym or cross reference

Glanders, Glanders bacillus, farcy, malleus, droes^{Footnote 1}

Formally known as Bacillus mallei, Actinobacillus mallei, Pfeifferella mallei, Malleomyces mallei, Loefferella mallei, Acinetobacter mallei, Pseudomonas mallei, Corynebacterium mallei, Mycobacterium mallei ^{Footnote 2Footnote 3}.

Characteristics

Brief description

Gram-negative, bipolar staining, aerobic, non-motile, nonpigmented, encapsulated, intracellular slender rod with rounded ends, 2-5 µm long^{Footnote 2Footnote 4Footnote 5}.

There is significant genetic homology (99%) between B. pseudomallei and B. thailandensis ^{Footnote 6Footnote 7}.

Properties

B. mallei is naturally aerobic, however, it will grow under anaerobic conditions in a complex medium containing nitrates^{Footnote 2}.

B. mallei encodes type III secretion systems to deliver bacterial proteins, known as effector molecules, into the plasma membrane and cytoplasm of eukaryotic cells^{Footnote 8}. B. mallei expresses genes for capsule production, actin-based intracellular motility, and type VI secretion (T6S). Together, these components are used to escape phagocytosis, spread intra- and intercellularly via actin-based motility and avoid detection by the host humoral immune response^{Footnote 9}. The virulence genes and pathway are not currently known^{Footnote 8Footnote 9}.

Section II: Hazard identification

Pathogenicity and toxicity

B. mallei is the etiological agent of glanders or farcy, which is primarily an animal disease. Infected animals present a variety of signs and symptoms dependent on the route of infection. B. mallei infection commonly presents as either a chronic and latent form, common in horses, or an acute form, common in mules and donkeys^{Footnote 3Footnote 10}. The chronic, or pulmonary form, presents with cough, mucopurulent nasal discharge, lung lesions, and nodules involving the liver and spleen. The acute, or septicemic form, presents with fever, chills, and prostration and death within 7-10 days. Farcy presents primarily through skin lesion and can spread into the lymphatic system, while glanders presents as nodules and ulcerations mainly in the nostrils, lungs and other internal organs^{Footnote 2}.

As with animals, symptoms of disease in humans are dependent on the route of exposure. Direct contact of B. mallei with the skin can lead to a farcy, a localized cutaneous infection. Inhalation of aerosol or dust containing B. mallei can lead to septicemic, pulmonary or chronic infections of the muscle, liver and spleen. Entry into the body can occur through the eyes, nose, mouth or breaks in the skin. Glanders in humans is characterized by an initial onset of fever, followed by rigors and malaise. Without treatment, there is usually a rapid onset of pneumonia, bacteremia, pustules and abscesses, which will lead to death within 7–10 days^{Footnote 2Footnote 11}. The disease has a 95% case fatality rate for untreated septicemia infections and a 50% case fatality rate in antibiotic-treated individuals^{Footnote 3Footnote 11}.

Predisposing factors

There are no reported predisposing factors; however, individuals that work in close contact with solipeds are at an increased risk of exposure^{Footnote 4Footnote 12}.

Communicability

In humans, the routes of infection include direct contact with infected animals, or aerosols of B. mallei, through the eyes, nose, mouth or breaks in the skin. Inhalation may also lead to deep lung deposition and infection by bacterial invasion of the nasal, oral, and conjunctival mucous membranes may occur^{Footnote 13}. Human-to-human transmission is very rare, however it may occur during occupational exposure through medical practices or at autopsies; most often through exposed skin, particularly the hands, arms, neck, and face. Transmission has been reported in a home setting, where the care of a glanders infected individual led to the infection of other family members^{Footnote 3Footnote 12}.

In animals, the most common routes of infection are direct contact with nasal secretion of infected animals, inhalation of aerosols, or consumption of feed or water contaminated with nasal discharges of infected animals^{Footnote 3}.

Epidemiology

B. mallei animal infection has been effectively eradicated from Canada, the United States, and many European countries through the systematic destruction of infected animals and strict quarantine measures^{Footnote 3}. Sporadic cases in humans in Western countries are attributed to contact with infected equines and laboratory-acquired infections. Glanders is still considered endemic in Africa, Asia, the Middle East and Central and South America^{Footnote 2Footnote 14}.

Host range

Natural host(s)

Solipeds, including horses, mules and donkeys are the primary hosts. Humans are considered accidental hosts^{Footnote 3Footnote 10}.

Other host(s)

Felines, camels and goats^{Footnote 9}. Experimentally, glanders has been demonstrated in camels, bears, wolves and dogs. Carnivores may be infected through the ingestion of infected meat. Small ruminants may be infected if kept in close contact with infected animals^{Footnote 15}.

Infectious dose

Unknown. B. mallei is highly infectious when experimentally aerosolized, and infection requires only a few organisms^{Footnote 3}.

Incubation period

In humans, acute glanders has a typical incubation period of 1-14 days, while chronic glanders has an incubation period of up to 12 weeks. Localized infection typically follows within 1-5 days of exposure. Symptoms from acute pulmonary infections can take 10-14 days to appear^{Footnote 1Footnote 12}. Septicemia may develop immediately or up to two weeks after initial infection^{Footnote 1}. Pneumonic disease usually has a rapid onset and, if untreated, is lethal between 10-30 days^{Footnote 16}.

In animals, the incubation period varies from 6 days to several months. This variability is attributed to species susceptibility, strain virulence, site of infection, and routes of transmission^{Footnote 17}. In experimental studies, clinical signs were reported within 3 days post-exposure^{Footnote 4Footnote 17}.

Section III: Dissemination

Reservoir

Horses are the main reservoir^{Footnote 3}; mules and donkeys are also susceptible^{Footnote 2}.

Control programmes indicate that soil and water are not reservoirs for B. mallei, unlike its sister strain, Burkholderia pseudomallei.

Zoonosis/Reverse zoonosis

Zoonosis is prevalent; cases have been reported in several countries such as Cameroon, Curaçao, Sri Lanka, Turkey, and the United States. Infection is usually related to direct or indirect contact of mucous membrane with lesion discharges of infected animals^{Footnote 4}. No cases of reverse zoonosis have been reported.

Vectors

None

Section IV: Stability and viability

Drug susceptibility

Sensitive to ceftazidime, imipenem, doxycycline, minocycline, ciprofloxacin, and gentamicin^{Footnote 18}.

Drug resistance

Ampicillin, cefuroxime, chloramphenicol, sulfamethoxazole, and co-trimoxazole resistance has been shown. In addition, strains resistant to ceftazidime have been shown in clinical settings^{Footnote 19}. Aminoglycosides and other antibiotics that are incapable of penetrating host cells are most likely not useful for the treatment of B. mallei infections^{Footnote 18}.

Susceptibility to disinfectants

Susceptible to 1% sodium hypochlorite, 70% ethanol, 2% glutaraldehyde, quaternary ammonia, and glycolic acid^{Footnote 20Footnote 21}.

Physical inactivation

Inactivated by heating at 55°C for 10 minutes^{Footnote 22} or by moist heat (121° C for at least 15 min), and sensitive to UV irradiation^{Footnote 23}.

Survival outside host

B. mallei survives in water at room temperature up to 30 days^{Footnote 2}. Primary infection routes include consumption of feed or water contaminated with nasal discharges of infected animals, indicating B. mallei can survive for a period outside the host; however, the survival time is unknown^{Footnote 3}.

Section V: First aid/medical

Surveillance

Monitor for symptoms and isolate affected patients. The mallein test, an allergic hypersensitivity test involving the injection of B. mallei proteins in the eyes, is used strictly in animals; however, it has fallen out of favour for less stressful and more accurate tests. Current testing methods include biochemical phenotyping, Matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) spectra, genome sequencing, complement fixation tests, polymerase chain reaction (PCR), and real-time PCR assays^{Footnote 17Footnote 24}.

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

Commonly, symptomatic cases are treated concurrently with an intensive intravenous (IV) therapy and oral eradication therapy. IV medications commonly used are imipenem, meropenem or ceftazidime with or without trimethoprim-sulfamethoxazole (TMP-SMX), while the oral therapy uses doxycycline^{Footnote 25}.

There is no treatment regime recommended for animals. Common recourse to infection is the elimination of contaminated animals, combined with the testing and quarantining of suspected infections, and imported livestock^{Footnote 24}.

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

Currently, there is no approved animal or human vaccine against B. mallei infection^{Footnote 3}.

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

Prophylaxis

Post-exposure prophylaxis drug recommendations are trimethoprim/sulfamethoxazole or co-amoxiclav^{Footnote 26}.

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

Section VI: Laboratory hazards

Laboratory-acquired infections

Nine fatal glanders infections occurred between 1905 and 1925^{Footnote 27}. An accident involving a centrifuge infected four people, three of whom died. A fatal infection in Prague was associated with the inoculation of a guinea pig with material from a horse with glanders. A U.S. fatality occurred in 1914, apparently as a result of smoking while autopsying an infected guinea pig.

Eight cases of laboratory-acquired B. mallei infection have been reported between 1943 and 2013 at research centers in the United States^{Footnote 28}. The first six cases occurred in 1947 during the performance of normal laboratory procedures that generated aerosols^{Footnote 16}. The seventh case is not well described in published literature^{Footnote 29} and the eighth case may have resulted from inconsistent use of personal protective equipment particularly latex gloves^{Footnote 30}.

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

Primarily nasal secretions, blood, and wound exudate^{Footnote 3Footnote 12}. B. mallei has also been shown in lung, spleen, and liver of mice experimentally infected through inhalation^{Footnote 31}. In a deceased camel B. mallei was only recovered from the lungs, choanae, and nasal septae. It was not found in other organs^{Footnote 32}.

Primary hazards

Direct contact with infectious materials from human or animals; exposure to infectious aerosols and droplets; ingestion; parenteral inoculation^{Footnote 3Footnote 12Footnote 33}. Handling cultures of B. mallei puts laboratory workers at a high risk for infection due to the increased concentration and ease of aerosolization^{Footnote 28}.

Special hazards

Infected laboratory animals^{Footnote 3}.

Section VII: Exposure controls/personal protection

Risk group classification

B. mallei is a Risk Group 3 Human Pathogen and Risk Group 3 Animal Pathogen^{Footnote 34Footnote 35}. B. mallei is a Security Sensitive Biological Agent (SSBA).

Containment requirements

Containment Level 3 facilities, equipment, and operational practices outlined in the CBS for work involving infectious or potentially infectious materials, animals, or cultures. Note that 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 3 requirements for personal protective equipment and clothing outlined in the CBS to be followed. 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.

Note: 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 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 to be strictly limited. Additional precautions must be considered with work involving animals or large scale activities.

Section VIII: Handling and storage

Spills

Allow aerosols to settle. Wearing protective clothing, 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 infectious agent must be completely decontaminated before they are removed from the containment zone. This can be achieved by using decontamination technologies and processes that have been demonstrated to be effective against the infectious material, such as chemical disinfectants, autoclaving, irradiation, incineration, an effluent treatment system, or gaseous decontamination (CBH).

Storage

The applicable Containment Level 3 requirements for storage outlined in the CBS are to be followed. Containers of security sensitive biological agents (SSBA) 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.

SSBA: Inventory of Risk Group 4 (RG4) pathogens and security sensitive biological agent (SSBA) in long-term storage to be maintained and to include:

• specific identification of the pathogens, toxins, and other regulated infectious material; and
• 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 context

Controlled activities with B. mallei require a Human Pathogens and Toxins Licence issued by the Public Health Agency of Canada^{Footnote 35}. B. mallei is a non-indigenous animal pathogen in Canada; therefore, importation of B. mallei requires an import permit issued by the Canadian Food Inspection Agency. The following is a non-exhaustive list of applicable designations, regulation, or legislation:

• Human Pathogen and Toxins Act and Human Pathogens and Toxins Regulations
• Health of Animals Act and Health of Animals Regulations
• Transportation of Dangerous Goods Regulations
• Immediately Notifiable Disease (animal)

Updated

September, 2021

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 Biosecurity Standard, may be incomplete and are specific to the Canadian context. Other jurisdictions will have their own requirements.

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