Listeria monocytogenes: Infectious substances Pathogen Safety Data Sheet

For more information on Listeria monocytogenes, see Listeriosis (Listeria).

Section I: Infectious agent

Name

Listeria monocytogenes

Agent type

Bacteria

Taxonomy

Family

Listeriaceae

Genus

Listeria

Species

monocytogenes

Synonym or cross reference

Listeria, listeriosis, listeriasis, listerellosis, silage disease, and circling disease^{Footnote 1Footnote 2Footnote 3Footnote 4Footnote 5Footnote 6Footnote 7Footnote 8Footnote 9Footnote 10Footnote 11}.

Characteristics

Brief description

Listeria monocytogenes is a facultatively anaerobic, Gram-positive, non-spore forming, rod-shaped coccobacillus, typically measuring 0.5 to 2μm long and 0.5μm in diameter^{Footnote 1Footnote 2Footnote 3Footnote 8Footnote 12Footnote 13}. L. monocytogenes has the ability to grow at a wide range of pH values (between 4.3 and 9.6), and can reproduce at temperatures between 1 and 45°C^{Footnote 1Footnote 2Footnote 13}. L. monocytogenes strain EGDe was the first to be sequenced; its genome is 2,944,528 base pairs with an average G+C content of 38%^{Footnote 14}.

L. monocytogenes is a very diverse species divided into 4 evolutionary lineages (I–IV), 4 serogroups (IIa, IIb, IIc, and IVb), and 13 serotypes based on characterization of the somatic (O) and flagellar (H) antigens; all of these serotypes can cause listeriosis, but most human and animal cases are caused by serotypes 1/2a, 1/2b, and 4b^{Footnote 12}.

Properties

Virulence factors are either scattered across the genome (e.g., the inlA-inlB locus, bsh, inlC, lap) or clustered in pathogenicity islands LIPI-1, LIPI-3, and LIPI-4^{Footnote 15}. The inlA-inlB locus and LIPI-1 produce several virulence factors necessary for adhesion, internalization, intracellular survival, and dissemination. These virulence factors include listeriolysin O, bacteriocins such as listeriolysin S (LLS) and Lmo2776, phospholipases A and B, ActA protein, and internalins InlA and InlB. Upon internalization of L. monocytogenes by receptor-mediated endocytosis or phagocytosis, listeriolysin O (LLO), a cholesterol-dependent cytolysin, enables L. monocytogenes to escape from the vacuole by creating large pores in the vacuolar membrane^{Footnote 15}. L. monocytogenes acts as an environmental saprophyte in soil, but when present within a host organism, can transition to a facultative intracellular pathogen by up-regulation of several virulence genes^{Footnote 14Footnote 15}.

Section II: Hazard identification

Pathogenicity and toxicity

L. monocytogenes was first described as a human pathogen in the 1920s; it is the etiological agent of listeriosis^{Footnote 1Footnote 6}. Although relatively rare, human listeriosis cases are often severe and mortality rates can approach 50%^{Footnote 1Footnote 2}. Most commonly, listeria causes a mild febrile illness; however, several types of disease manifestations are recognised, including listeriosis in pregnancy, listeriosis of the central nervous system (CNS), febrile gastroenteritis, glandular listeriosis, local listeriosis, typhoid listeriosis, and atypical listeriosis^{Footnote 11}.

Listeriosis in pregnancy occurs mostly during the third trimester, and is characterised by a "flu like" illness with symptoms such as fever, chills, malaise, arthralgia, back pain, and diarrhoea^{Footnote 2Footnote 5Footnote 11Footnote 16}. In many cases the infection is subclinical; however, intrauterine infection of the foetus can lead to foetal death, spontaneous abortion, premature delivery, or the birth of a foetus that dies shortly after birth^{Footnote 5Footnote 6Footnote 11}. Surviving newborns with listeriosis are often classified as "early onset" or "late onset". Early onset neonatal listeriosis due to transplacental infection often presents as pneumonia and/or sepsis^{Footnote 8Footnote 16}. Severe disease can result in widespread granulomas (granulomatosis infantisepticum)^{Footnote 8Footnote 16}. Late onset neonatal listeriosis occurs from infection during birth, with neonates showing symptoms of meningitis one to several weeks after birth^{Footnote 2Footnote 8}. In both early and late onset neonatal listeriosis, the mortality rate ranges from 20 to 30%^{Footnote 8}.

Meningitis is the most frequently recognised listerial infection of the CNS^{Footnote 5}. Symptoms include high fever, nuchal rigidity, tremor and/or ataxia, and seizures^{Footnote 5}. The most common form of non-meningitic form of CNS listeriosis is encephalitis involving the brainstem (rhombencephalitis)^{Footnote 5}.

Febrile gastroenteritis is a non-invasive form of foodborne listeriosis that manifests as symptoms typical of gastroenteritis, such as, fever, diarrhoea, and vomiting^{Footnote 5Footnote 8Footnote 11}. Glandular listeriosis resembles infectious mononucleosis with swelling of the salivary glands and nuchal lymph nodes^{Footnote 11}. Cutaneous listeriosis (or local listeriosis) can manifest as papules and pustules on the hands and arms following direct contact with infectious material, and can be accompanied by constitutional symptoms (fever, myalgia, and/or headache)^{Footnote 10Footnote 17Footnote 18}. Typhoid listeriosis is characterised by high fever and is particularly frequent in immunocompromised individuals^{Footnote 11}. Rare cases of atypical listeriosis have been described with symptoms such as endocarditis, purulent (mononuclear) pleural exudates, pneumonia, urethritis, and abscesses^{Footnote 11}.

L. monocytogenes infects a vast range of animals^{Footnote 10Footnote 19} and intestinal carriage in animals is common^{Footnote 20}. Infection is usually subclinical, and disease is most common in sheep, cattle, and goats^{Footnote 10}. Listeriosis in animals was first described as "circling disease" based on the behaviour observed in infected sheep^{Footnote 1Footnote 10}. Listerial encephalitis/meningoencephalitis is the most common presentation of the disease and is characterized by elevated temperatures, refusal to eat or drink, grinding of teeth, difficulty swallowing, facial paralysis, strabismus, and ataxia; symptoms eventually progress to the characteristic circling (i.e. the animal moves in circles to the left or right depending on the affected side of the brain)^{Footnote 1Footnote 9Footnote 10}. During the advanced stages of encephalitis, vision and movement are impaired, the animal becomes irritable, and eventually enters a coma from which death occurs within 1 to 2 days^{Footnote 10}. The disease typically lasts 1 to 2 weeks^{Footnote 9Footnote 10}. Vertical transmission of L. monocytogenes from pregnant ewes and cows to the fetus has been reported and resulted in abortion, stillbirths, or delivery of septic animals^{Footnote 9Footnote 10}. Clinical signs of septicemia include fever, loss of appetite and diarrhoea^{Footnote 10}. L. monocytogenes can be shed in the milk of lactating ewes and cows, although mastitis is rare^{Footnote 9Footnote 10}. Uveitis and keratoconjunctivitis have also been reported in cattle^{Footnote 9}.

Listeriosis is uncommon in pigs; septicemia is the most common presentation, although there have been a few reports of encephalitis and abortion^{Footnote 9Footnote 10}. Listeriosis has also been described in both domestic and wild birds and many are considered asymptomatic carriers^{Footnote 9Footnote 10}. Disease in birds is rare and usually secondary to other conditions or infections; septicemia is the most common presentation of the disease^{Footnote 9Footnote 10}.

Predisposing factors

Certain factors predispose individuals to infection with L. monocytogenes, such as neonates, pregnancy, leukemia, Hodgkin's disease, diabetes mellitus, alcoholism or cirrhosis, and immunosuppressive or cytostatic therapy^{Footnote 11}. Similarly, baby, pregnant and older animals are more susceptible to listeriosis^{Footnote 9Footnote 10}.

Communicability

The predominant mode of L. monocytogenes transmission is ingestion of contaminated food^{Footnote 1Footnote 2Footnote 3Footnote 4Footnote 6Footnote 10Footnote 11Footnote 21}. L. monocytogenes can also be transmitted transplacentally from mother to child during pregnancy, and via the birth canal during birth^{Footnote 2Footnote 8Footnote 10Footnote 11Footnote 16}. Direct contact with diseased animals may lead to transmission to farmers and veterinarians during the birthing of domestic farm animals^{Footnote 17Footnote 18}. Nosocomial infections and person-to-person transmission (excluding vertical) are recognised but rare^{Footnote 1}. Animal-to-animal transmission occurs through the fecal-oral route and through vertical transmission^{Footnote 20}.

Epidemiology

Listeriosis occurs worldwide, but is seen mostly in industrialised countries^{Footnote 2Footnote 3}. Although L. monocytogenes was described as a human pathogen in the 1920s (mistakenly thought to be the cause of infectious mononucleosis), the first documented outbreak of food-borne listeriosis was in 1979 and involved 23 patients in a Boston hospital^{Footnote 2Footnote 6}. The first confirmed outbreak in Canada, and first definitive link of listeriosis cases to food, was in 1981 in the Maritime Provinces and was due to consumption of contaminated cabbage in coleslaw^{Footnote 6}. Further outbreaks occurred during subsequent years and were often associated with a particular food type, from vegetable products in the early 1980s, to dairy products in the mid 1980s and early 1990s, to ready-to-eat meat and poultry products in the late 1990s to early 2000s^{Footnote 4Footnote 6}. Indeed, ready-to-eat meat and poultry products were responsible for a multi-state outbreak in the United States in 1999 that resulted in 101 cases of illness and 21 fatalities. One of the largest outbreaks ever recorded in South Africa between 2017 and 2018 involved 937 reported cases of illness and 193 fatalities^{Footnote 4Footnote 22}. One of the deadliest listeriosis outbreaks occurred in Canada in 2008^{Footnote 23}. This multi-province outbreak was linked to contaminated deli meat that was consumed primarily in long-term care facilities or hospitals; a total of 57 individuals were infected, and 24 (42%) of these individuals died. The annual rate of listeriosis ranges between 2 to 15 cases per million population^{Footnote 9}.

Cumulatively, 2,652 cases of human listeriosis were reported in Canada from 1990 to 2020^{Footnote 24}. However, it should be noted that listeriosis was removed from the list of national notifiable diseases after 1999 and was reinstated in 2007. Canadian epidemiological data is available at Notifiable Diseases Online.

In animals, listeriosis occurs worldwide and is observed primarily from winter to spring in feedlot or housed ruminants, often associated with the seasonal feeding of poor quality silage^{Footnote 9Footnote 20}.

Host range

Natural host(s)

Humans, sheep, cattle, and goats are the primary natural hosts for L. monocytogenes^{Footnote 2Footnote 6Footnote 9Footnote 10Footnote 20}.

Other host(s)

Many other animal hosts are susceptible to listeriosis including chickens, turkeys, ducks, partridges, eagles, parrots, canaries, starlings, mice, voles, rats, rabbits, guinea pigs, chinchillas, lemmings, primates, hyraxes, mink, skunks, horses, llamas, dogs, cats, fox, deer, buffalo, giraffes, bats, frogs, turtles^{Footnote 10Footnote 19}. In addition, L. monocytogenes has been isolated from fish and crustaceans.

Infectious dose

The approximate infective dose of L. monocytogenes is estimated to be 10 to 100 million colony forming units (CFU) in healthy hosts, and 0.1 to 10 million CFU in individuals at high risk of infection^{Footnote 21}.

Incubation period

Can vary depending on the mode of transmission and dose received, but typically ranges from 1 to 4 weeks, and can be as long as 2 to 3 months^{Footnote 3Footnote 11}. Febrile gastroenteritis as a result of L. monocytogenes has a short incubation period, typically 18 to 20 hours^{Footnote 4Footnote 8}. The incubation period for cutaneous listeriosis ranges from 6 hours to 7 days with an average of 2 days^{Footnote 18}. The median incubation periods for listeriosis presenting as bacteremia, CNS cases, and pregnancy-associated are 2 days, 9 days, and 27.5 days respectively^{Footnote 25}.

Section III: Dissemination

Reservoir

Soil, manure, decaying vegetable matter, silage, water, animal feed, fresh and frozen poultry, fresh and processed meats, raw milk, cheese, slaughterhouse waste, and asymptomatic human and animal carriers^{Footnote 3Footnote 19}.

Zoonosis/Reverse zoonosis

Zoonosis has been reported to occur through consumption of food containing infected animal products, manure contaminated vegetables, and by direct contact with animal tissues during birthing and butchering^{Footnote 1Footnote 2Footnote 3Footnote 4Footnote 6Footnote 8Footnote 11Footnote 16}.

Vectors

L. monocytogenes has been isolated from ticks and flies^{Footnote 10Footnote 19}. However, arthropod-mediated transmission has not been reported.

Section IV: Stability and viability

Drug susceptibility

Most broad spectrum and gram-positive spectrum antibiotics, except the cephalosporins and first generation of quinolones, are active against L. monocytogenes in vitro^{Footnote 7Footnote 13}. In vivo, the most active antibiotics are ampicillin and amoxicillin^{Footnote 7}.

Drug resistance

Some strains of L. monocytogenes show antibiotic resistance to nalidixic acid, streptomycin, clindamycin, meropenem, and sulfamethoxazole-trimethoprim^{Footnote 13Footnote 26}. Resistance to ampicillin, gentamicin, and tetracycline, the drugs most frequently used to treat listeriosis in humans and animals, have also been reported^{Footnote 13}.

Susceptibility to disinfectants

L. monocytogenes is susceptible to sodium hypochlorite, iodophor compounds, and quaternary ammonium compounds^{Footnote 12Footnote 27Footnote 28}. The concentration of disinfectant required is influenced by temperature, surface type, and organic load in the sample.

Physical inactivation

L. monocytogenes can be inactivated by ozone, high pressure (500MPa), and high temperatures (at least 70°C for 2 minutes)^{Footnote 27Footnote 29}.

Survival outside host

L. monocytogenes is commonly found in nature, particularly in association with soil, is relatively heat resistant, can tolerate cold temperature environments well, and can survive at low pH^{Footnote 8Footnote 29}. It can survive in soil, pond and river water, fecal matter, and animal feed for more than a year depending on the moisture content of the material^{Footnote 19}.

Section V: First aid/medical

Surveillance

Listeriosis can be identified by monitoring for symptoms. Diagnosis is made in the laboratory by cultivation of the bacteria, and demonstration of the infectious agent or its products in tissues or body fluids^{Footnote 1Footnote 11}. Several commercially available kits based on ELISA and PCR technology exist for the detection of L. monocytogenes^{Footnote 3Footnote 4Footnote 9}.

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.

First aid/treatment

Treatment for human listeriosis with ampicillin or amoxicillin together with gentamicin or erythromycin is the primary choice of therapy^{Footnote 7Footnote 9}. The recommended course of treatment is ampicillin for 2 to 4 weeks^{Footnote 11}. The addition of gentamicin for 2 weeks should be considered for immunocompromised patients^{Footnote 11}. An alternative therapy for individuals allergic to β-lactams is intravenous co-trimoxazole^{Footnote 11}.

Chlortetracycline for 5 days and penicillin for 1 – 2 weeks are administered in cattle diagnosed with listerial encephalitis^{Footnote 9Footnote 10}. Tetracycline for 1 week is used in the treatment of infected birds^{Footnote 10}.

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 Canadian Biosafety Handbook.

Immunization

No vaccine is currently available.

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

Prophylaxis

Trimethoprim-sulfamethoxazole is a suitable prophylactic agent in HIV patients and in patients undergoing chemotherapy for leukemia or lymphoma^{Footnote 30}. Precautions for immunocompromised individuals or pregnant women include the avoidance of raw food and vegetables, undercooked meat, soft cheeses, and cheeses prepared from unpasteurised milk^{Footnote 11}.

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

Section VI: Laboratory hazards

Laboratory-acquired infections

A case of cutaneous listeriosis from an unknown source of exposure was reported in a laboratory technician in 1957, characterized by papules and vesicles, and accompanying systemic symptoms including headache, fever, swollen lymph nodes, and vomiting^{Footnote 18}. There is documentation of cutaneous listeriosis in veterinarians and farmers resulting from occupational exposure to infected animals^{Footnote 31}.

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

Sources/specimens

Soil, food, blood, cerebrospinal fluid, faeces, placenta, skin lesions, pus, amniotic fluid, menstrual blood, lochia, respiratory secretions, meconium, gastric aspirate, animal tissues/specimens, and infected organs such as brain and liver^{Footnote 3}.

Primary hazards

Ingestion of infectious material is the primary hazard associated with exposure to L. monocytogenes^{Footnote 3Footnote 31}. Exposure of mucous membranes and skin to infectious materials could also result in infection^{Footnote 3Footnote 31}. In addition, naturally and experimentally infected animals are another source of exposure for laboratory workers^{Footnote 17Footnote 18}.

Special hazards

Pregnant women and immunocompromised individuals are at an increased risk of infection with L. monocytogenes, and should take special caution when working with L. monocytogenes in laboratory settings^{Footnote 11}.

Section VII: Exposure controls/personal protection

Risk group classification

L. monocytogenes is a Risk Group 2 Human Pathogen and Risk Group 2 Animal Pathogen^{Footnote 32Footnote 33}.

Containment requirements

Containment Level 2 facilities, equipment, and operational practices outlined in the Canadian Biosafety Standard for work involving infectious or potentially infectious materials, animals, or cultures.

Protective clothing

The applicable Containment Level 2 requirements for personal protective equipment and clothing outlined in the Canadian Biosafety Standard to be followed. At minimum, use of a labcoat and closed-toes cleanable shoes, gloves when direct skin contact with infected materials or animals is unavoidable, and eye protection where there is a known or potential risk of exposure to splashes.

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 and work activities must be documented.

Other precautions

All activities that may produce aerosols, or involve high concentrations or large volumes are to be conducted in a biological safety cabinet (BSC) or other primary containment devices.

Use of needles and syringes to be strictly limited. Bending, shearing, re-capping, or removing needles from syringes to be avoided, and if necessary, performed only as specified in standard operating procedures (SOPs). Additional precautions are required with work involving animals or large scale activities.

Additional information

For diagnostic laboratories handling primary specimens that may contain L. monocytogenes, 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 (Canadian Biosafety Handbook).

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 (Canadian Biosafety Handbook).

Storage

Containment Level 2: The applicable Containment Level 2 requirements for storage outlined in the Canadian Biosafety Standard are to be followed. Primary containers of regulated materials removed from the containment zone to be labelled, leakproof, impact resistant, and kept either in locked storage equipment or within an area with limited access.

Section IX: Regulatory and other information

Canadian regulatory context

Controlled activities with L. monocytogenes require a Human Pathogens and Toxins Licence issued by the Public Health Agency of Canada.
The following is a non-exhaustive list of applicable designations, regulation, or legislations:

• 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
• National Notifiable Disease (human)
• Annually Notifiable Disease (animal)

OIE-listed disease (please contact the Canadian Food Inspection Agency)

Updated

April 2023

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.

Copyright^©Public Health Agency of Canada, 2023, Canada