Yersinia pestis: Infectious substances pathogen safety data sheet

For more information on Yersinia pestis, see the following:

• Plague - Canada.ca

Section I – Infectious agent

Name

Yersinia pestis 

Agent type

Bacteria

Taxonomy

Family

Enterobacteriaceae

Genus

Yersinia

Species

pestis

Synonym or cross-reference

Plague, pestis, Bubonic plague, pestilential fever, Black death, Justinian's Plague, and the plague bacillus^{Footnote 1Footnote 2Footnote 3}.

Characteristics

Brief description

Yersinia pestis is a gram-negative, coccobacillus (1 to 3 µm in length), ovoid in shape with characteristic bipolar staining (safety pin appearance)^{Footnote 3Footnote 4}. It is non-motile, non-spore-forming, facultative anaerobe that can grow between 4 and 40^oC but optimally at 29-30^oC. Y. pestis is an obligate parasite and can not replicate outside of a host. The genome of Y. pestis consists of a 4.6-4.65 Mb chromosome and three plasmids of 96.2, 70.3 and 9.6 kb in size^{Footnote 5}. Y. pestis is classified as a Tier 1 category A bioterrorism agent by the Centers for Disease and Control and a security sensitive biological agent by the Public Health Agency of Canada^{Footnote 6Footnote 7}.

Properties

Y. pestis has a large number of plasmid-borne virulence factors^{Footnote 3Footnote 8}. The 70.3 kb plasmid contains the genes for a type III secretion system (T3SS), the Yersinia outer proteins (Yops), the V antigen and the yersiniabactin siderophore system (ybt)^{Footnote 8}. These genes are thermoregulated and are only induced upon entry into a mammalian host^{Footnote 9}. Yops are secreted into host cells via the T3SS where they have many roles in infection: they inhibit GTPases and disrupt the actin cytoskeleton thereby inhibiting phagocytosis, they downregulate pro-inflammatory cytokines, and they also induce apoptosis^{Footnote 10}. The V-antigen is involved in supressing the host immune system^{Footnote 3}. Ybt aids in growth of Y. pestis in the body by procuring iron from blood and has been shown to be essential for pathogenesis^{Footnote 11}. Plasminogen activator (Pla) is encoded on the 9.6 kb plasmid and is involved in adhesion, invasion, and fibrinolytic activity^{Footnote 3Footnote 12}. While the 100-110 kb plasmid encodes genes that allow for the survival of Y. pestis in the gut of fleas^{Footnote 3Footnote 13}.

Y. pestis can survive and replicate in both neutrophils and macrophages, allowing it to subvert the early immune response and allow time to multiply and to travel to the target organs, either lymph nodes (bubonic plague) or lungs (pneumonic plague)^{Footnote 8Footnote 14Footnote 15}. This ability allows Y. pestis to become a serious infection, progressing to fatal sepsis before symptoms appear.

Section II – Hazard identification

Pathogenicity and toxicity

Y. pestis causes a highly pathogenic infection with clinical characteristics largely dependant on the method of transmission^{Footnote 3}. There are 3 main forms of plague: bubonic, septicaemic, and pneumonic.

Bubonic plague is the most common form of the disease. Transmitted by the bite of a flea, infection leads to acute inflammation of peripheral lymph nodes (buboes). Symptoms of bubonic plague begin 2-10 days after exposure and include swollen glands in the groin, armpit or neck, accompanied with fever, chills, headache, extreme exhaustion, and arthralgias^{Footnote 3Footnote 16}.

Septicaemic plague can be the result of a primary infection or the result untreated bubonic plague progression and bacterial invasion of the bloodstream^{Footnote 3}. Primary septicaemia presents with gastrointestinal symptoms, including nausea, vomiting, diarrhea, hypotension, multiple organ failure, disseminated intravascular coagulation, and septic shock^{Footnote 4}. Secondary septicemia as a result of bubonic plague presents clinically with tachycardia, lethargy, somnolence, hypotension, hepatosplenomegaly, renal failure, disseminated intravascular coagulation, and gangrene of the extremities^{Footnote 3Footnote 4}.

Pneumonic plague is the most virulent and dangerous form of disease^{Footnote 3Footnote 4}. This is an infection of the lungs that develops from either progression of the bubonic form of the disease (secondary) or from inhalation of infected airborne droplets (primary), and is characterized by high fever, cough, bloody sputum, and difficulty breathing. Onset of symptoms from primary plague is usually 1-3 days after exposure to infected droplets.

If untreated, mortality rates are up to 60% for the bubonic form, 100% for septicaemic, and 100% for pneumonic forms. Antibiotic treatment is effective against plague bacteria, so early diagnosis and early treatment can save lives^{Footnote 3Footnote 17}.

Rare forms of Y. pestis infection caused by the ingestion of raw or undercooked meet include pharyngitis, gastrointestinal and tonsillar plague^{Footnote 3Footnote 18}. Cutaneous plague is also described in rare cases and is characterized by the rapid formation of herpes and pustules^{Footnote 19}.

Epidemiology

Y. pestis is maintained in over 200 mammalian species but the main reservoir is rodents, specifically rats^{Footnote 3Footnote 16}. From 2010-2019, there have been 4547 reported cases of the plague reported worldwide from 21 countries in the Americas, Africa and Asia^{Footnote 3Footnote 20Footnote 21}. 94% of the reported cases were found in either the Democratic Republic of Congo or Madagascar^{Footnote 20}. Where plague is endemic, it is a seasonal infection with a defined geographic distribution correlating with that of the rodent reservoirs and the flea vectors^{Footnote 22}. The most recent large outbreak of the plague occurred in Madagascar between August and November of 2017^{Footnote 20}. During this outbreak 597 cases of plague were reported with 418 (84%) being pneumonic plague and 55 (9%) deaths occurring. In North America, plague is found on the western side of the continent (from British Columbia to Alberta, Pacific Coast east to the western Great Plains, and Southward from Canada to Mexico). Most human cases occur in the western United States New Mexico, Arizona, Colorado, and California^{Footnote 3}.

Population risk factors of plague infection include people working with animals such as farming, butchery or animal husbandry^{Footnote 23}.

Host range

Natural host(s)

Humans, more than 200 species and subspecies of rodents (including mice, ground squirrels, rock squirrels, prairie dogs), other small mammals, such as rabbits, hares, dogs and cats; and wild carnivores that prey on these animals^{Footnote 3Footnote 16}. The primary host is the rat, Rattus rattus and Rattus norvegicus^{Footnote 16}.

Other host(s)

Nonhuman primates used as experimental hosts include rhesus macaques, cynomolgus macaques, and African green monkeys^{Footnote 24}.

Infectious dose

Laboratory animal studies have shown the lethal and infectious doses to be quite low, less than 100 colony-forming units, with some estimates being as low as 1-10 organisms^{Footnote 4Footnote 25}.

Incubation period

Bubonic plague: 2 to 10 days. Pneumonic plague: 1 to 3 days^{Footnote 3}. Septicaemic plague : no information available.

Communicability

Y. pestis causes a highly pathogenic infection that is most commonly acquired through the bite of infected rodent fleas^{Footnote 3}. The most commonly involved rodents are Rattus rattus and Rattus norvegicus, though more than 200 species of mammals can be infected by Y. pestis.^{Footnote 3Footnote 16}. The flea Xenopsylla cheopsis is most commonly associated with and most efficient at transmitting Y. pestis.^{Footnote 16}. Y. pestis can also be transmitted through direct contact/bites with infected animals, or in rare cases by ingestion of contaminated meat and other animal products^{Footnote 3Footnote 18}. Contact with the corpses of infected humans and carcasses of infected animals (mountain lions, coyotes, camels, rats, goats, marmots, Tibetan sheep, rabbits, and guinea pigs) can transmit Y. pestis ^{Footnote 3Footnote 26}. Pneumonic plague can be transmitted by the inhalation of respiratory droplets expelled by the coughing of an infected person or animal^{Footnote 3}. Direct exposure to domestic pets (e.g., cats and dogs), as well as plague-infected fleas on these animals, is another route of transmission^{Footnote 27}.

Section III – Dissemination

Reservoir

Primarily wild rodents (prairie dogs, rock squirrels)^{Footnote 3}. Commensal rats may be important in some places, and fleas may also be considered part of the reservoir, thus the natural reservoir is an arthropod-vertebrate complex.

Zoonosis

Y. pestis is transmitted from rodents to animals and humans via fleas and to humans directly from infected animals^{Footnote 3}.

Vectors

Y. pestis is transmitted primarily by wild rodent fleas, most often the oriental rat flea Xenopsylla cheopis.^{Footnote 4}. Occasionally it can be transmitted by human fleas Pulex irritans and Pediculus humanis or other ectoparasites such as camel fleas, lice, mites, and ticks^{Footnote 4Footnote 28}.

Section IV – Stability and viability

Drug susceptibility/resistance

Y. pestis is sensitive to a wide range of antibiotics and effective treatment has been shown with aminoglycosides, sulfonamides, tetracycline, and fluroquinolones^{Footnote 29}. β-lactams have been shown to lack efficacy and are therefore not recommended. Drug resistance is a growing concern^{Footnote 30}. In 1995, a multi-drug resistant strain was identified from a Madagascar plague epidemic^{Footnote 30}. The strain was resistant to at least 8 anti-microbial drugs, including streptomycin, ampicillin, kanamycin, spectinomycin, sulfonamides, tetracycline, minocycline, and chloramphenicol. There have also been four strains identified showing resistance to streptomycin and one strain resistant to doxycycline.

Susceptibility to disinfectants

Susceptible to many disinfectants, including 1% sodium hypochlorite, 70% ethanol, 2% glutaraldehyde, iodines, phenolics, formaldehyde, and vaporous hydrogen peroxide^{Footnote 31Footnote 32Footnote 33}. In potable water, a 2-log₁₀ (99%) or 3-log₁₀ (99.9%) inactivation was found with 0.03 and 0.04 mg/min/liter free active chlorine, respectively, at both 5^oC and 25^oC^{Footnote 34}.

Physical inactivation

Killed by a 15 minute exposure to 55°C^{Footnote 30}. Y. pestis is very susceptible to UV light, temperatures exceeding 40°C, and intensive desiccation^{Footnote 35}.

Survival outside host

One study demonstrated survival of Y. pestis for 16 months in soil. It has been isolated from the undisturbed burrow of an infected animal 11 months after the animal's death^{Footnote 3}. On steel or glass, Y. pestis is much less resilient, surviving less than 72 hours.

Section V – First aid/medical

Surveillance

Early diagnosis is important, as starting treatment in the early stages of infection greatly increases survival rates. The gold standard for diagnosis is the isolation, culturing, and detection of Y. pestis from clinical samples (bubo aspirates, sputum, blood, pharyngeal swabs, and urine)^{Footnote 3}. Cultures are grown on Cefsulodin-Irgasan-Novobiocin (CIN) agar to reduce the growth of contaminant bacteria^{Footnote 3Footnote 4}. Rapid F1 antigen detection kits and both conventional and real-time PCR diagnostic methods are also available^{Footnote 3Footnote 36}. Recombinase polymerase assays and loop mediated isothermal amplification (LAMP) assays are also available, simpler, and more efficient than conventional PCR^{Footnote 29}.

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

Antibiotic therapy should be performed as soon as possible (8 to 20 hours after onset of pneumonic plague) with either streptomycin, gentamicin, doxycycline, ciprofloxacin, levofloxacin, or moxiloxacin^{Footnote 4Footnote 37}. Supportive treatment consists of intravenous fluids, oxygen and respiratory support^{Footnote 33}.

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

A licensed, inactivated, whole cell vaccine was available until 1998, but is no longer being produced. No vaccine is currently available, although new alternatives are under development^{Footnote 4Footnote 38}.

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

Prophylaxis

Antibiotic therapy is recommended for close contact with confirmed or suspected pneumonic plague cases, including medical personnel^{Footnote 3Footnote 4}. Individuals present in places where a plague outbreak is occurring should also take antibiotics. For individuals potentially exposed during laboratory work ciprofloxacin for 7 days is recommended^{Footnote 39}.

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 1970 at least 10 laboratory-acquired infections have been reported, with 4 deaths^{Footnote 40}. Since then, there has been a reported death with exposure thought to have occurred due to inconsistent glove wearing and exposure through a cut or skin abrasion^{Footnote 41Footnote 42}. In an other report, there were two fatal accidental exposures; one was a wildlife biologist, who carried out an autopsy on an infected mountain lion in Arizona in 2007, and another a geneticist with subclinical hemochromatosis in Chicago, who was handling an avirulent strain of Y. pestis in 2009^{Footnote 43Footnote 44}.

Note: Please consult the Canadian Biosafety Standard (CBS) and CBH for additional details on requirements for reporting exposure incidents.

Sources/specimens

Bubo fluid, blood, sputum, tracheal/lung aspirate, nasal swab, lymph node aspirate, cerebrospinal fluid, faeces, urine, post-mortem lymphoid tissues, lung, and bone marrow samples^{Footnote 3Footnote 4}.

Primary hazards

Direct contact with cultures and infectious materials from humans or rodents. Infectious aerosols or droplets generated during manipulation of cultures, and infected tissues, necropsy of rodents, accidental auto-inoculation, and ingestion^{Footnote 45}.

Special hazards

Bites by infected fleas collected from rodents^{Footnote 3}.

Section VII – Exposure controls/personal protection

Risk group classification

Yersinia pestis is a Risk Group 3 Human Pathogen and Risk Group 3 Animal Pathogen^{Footnote 46}. Yersinia pestis 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 are 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 are to be strictly limited. Additional precautions must considered for work involving animals or large scale activities.

Proper precautions should be considered when working with infected arthropods. This might include implementing a program to prevent escapes and monitor any escaped arthropods, as well as using suitable personal protective equipment (PPE), among other measures^{Footnote 47Footnote 48}.

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

Regulated materials, as well as all items and waste, to be decontaminated at the containment barrier prior to removal from the containment zone, animal room, animal cubicle, or post mortem room. 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. 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 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.

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

• specific identification of the regulated materials
• a mechanism that allows 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 Yersinia pestis require a Human Pathogen and Toxins licence issued by the Public Health Agency of Canada (PHAC). Yersinia pestis is a terrestrial animal pathogen in Canada; therefore, importation of Yersinia pestis requires an import permit under the authority of the Health of Animals Regulations (HAR). The PHAC issues a Pathogen and Toxin licence which includes a Human Pathogen and Toxin licence and an HAR importation permit.

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

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

• Human Pathogen and Toxins Act and Human Pathogens and Toxins Regulations
• Quarantine Act
• Transportation of Dangerous Goods Act and Transportation of Dangerous Goods Regulations
• National Notifiable Disease (human)

Last file update

February, 2024

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.

Copyright ^© Public Health Agency of Canada, 2024, Canada

References