Legionella pneumophila : Infectious substances pathogen safety data sheets

Section I – Infectious agent

Name

Legionella pneumophila

Agent type

Bacteria

Taxonomy

Family

Legionellaceae

Genus

Legionella

Species

pneumophila

Synonym or cross-reference

Legionellosis, Legionnaires' disease, Legionnaires' pneumonia, legion fever, Pontiac fever, nonpneumonic legionellosis^{Footnote 1}.

Characteristics

Brief description

Legionella pneumophila is a gram negative, intracellular, aerobic bacteria in the family Legionellaceae. There are 3 subspecies: L. pneumophila subsp. fraseri, L. pneumophila subsp. pascullei, and L. pneumophila subsp. Pneumophila^{Footnote 2}. L. pneumophila is further divided into serogroups based on antigenic characterization; 16 serogroups are currently recognized^{Footnote 3Footnote 4}. L.pneumophila stains poorly and can appear in different forms. In clinical lung and sputum specimens, L. pneumophila is a short rod 3-5 µm in length, whereas when cultured, L. pneumophila may produce filamentous forms of 10-25 µm in length. Motility is limited in L. pneumophila, and some strains are completely non-motile^{Footnote 4}.

Properties

L. pneumophila is an intracellular bacteria. In aquatic environments, L. pneumophila infects and multiplies in free-living amoebae, ciliated protozoa and slime moulds^{Footnote 5Footnote 6}. Within mammalian hosts, L. pneumophila infects and multiplies in macrophages and monocytes^{Footnote 4Footnote 7} . The infection process involves the injection of pathogenicity effectors into host cells via a type IV secretion system^{Footnote 3}. L. pneumophila is also able to survive extracellularly in aquatic systems within biofilms. Within these settings, L. pneumophila is protected from environmental stressors such as biocides and heat^{Footnote 3Footnote 5Footnote 8}. L. pneumophila can multiply at temperatures ranging from 20-42°C^{Footnote 3}.

Section II – Hazard identification

Pathogenicity and toxicity

There are two distinct forms of L. pneumophila-associated disease in humans: a non-pneumonic form, commonly referred to as Pontiac fever, and a pneumonic form, which is known as Legionnaires' disease (LD)^{Footnote 1Footnote 3Footnote 8}. Collectively, these 2 diseases are known as legionellosis. LD accounts for the majority of reported cases of legionellosis^{Footnote 9}.

Pontiac fever manifests as an acute, self-limiting influenza-like illness that lasts for 2 to 5 days^{Footnote 4}. The primary symptoms of disease include fever, chills, headache, malaise, muscle pain, cough, nausea, and sore throat^{Footnote 10}. Other symptoms such as dyspnea, thoracic pain, vomiting and diarrhea have also been described. No deaths have been associated with Pontiac fever. The cause of Pontiac fever is not well understood; it may be caused by the inhalation of bacterial toxins, such as endotoxin, or an acute allergic reaction to L. pneumophila^{Footnote 1Footnote 3}.

Legionnaires' disease presents initially with symptoms of fever, loss of appetite, headache, malaise, and lethargy^{Footnote 3}. Abdominal pain, nausea, vomiting and diarrhea may also be present^{Footnote 1Footnote 3Footnote 11}. A cough then develops, and as many as 50% of patients may have sputum production. Headache, obtundation, seizures, and focal neurological findings may also be present. In some patients, primarily immunocompromised patients, extra-pulmonary infections can occur, such as splenomegaly, pericarditis, myocarditis, wound infections, endocarditis, arthritis, and central nervous system (CNS) infections^{Footnote 11}. Symptoms from CNS infection may include confusion, delirium, depression, disorientation, hallucinations, tremors, hyperactive or reduced reflexes, and cerebral dysfunction^{Footnote 4}. Severe cases of LD can lead to respiratory failure, shock, brain sequelae, acute kidney failure, multi-organ failure, and ultimately death. The overall LD death rate is in the range of 5-15%^{Footnote 1Footnote 3Footnote 4Footnote 8}. In untreated immunosuppressed patients, the death rate can be as high as 40-80%, but can be reduced to 5-30% with appropriate treatment^{Footnote 8}.

In rare instances, L. pneumophila has been reported as the cause of wound infections following the immersion of a wound in contaminated water^{Footnote 12Footnote 13}.

Although serological surveys among wild and domestic animals have confirmed widespread exposure to and infection with L. pneumophila, there is a lack of clinical reports of L. pneumophila associated disease in animals^{Footnote 7}. L. pneumophila infection in animals does not generally result in the development of disease; however, LD has been reported in a calf.

Epidemiology

Cases of legionellosis are reported globally^{Footnote 3}. The annual global disease incidence of LD is reported to be between 4-20 cases per million population^{Footnote 3}, representing 2-9% of all cases of community-acquired pneumonia^{Footnote 11}. The number of cases of LD is likely underreported due to difficulty in distinguishing LD from other forms of pneumonia, lack of awareness among clinicians, and limited availability and shortcomings of available diagnostic tests^{Footnote 14}. In recent years, the incidence of LD has been increasing in the United States and in Europe^{Footnote 15}. Canadian data also demonstrates a similar increasing trend in the number of reported cases of legionellosis^{Footnote 16}. In Canada, there are generally less than 100 cases of LD reported annually^{Footnote 17}.

Along with L. pneumophila, L. micdadei, L. bozemanae, L. longbeachae, and L. dumoffii can also cause legionellosis in humans; however, L. pneumophila is by far the most clinically relevant species, causing greater than 90% of cases. L. pneumophila serogroup 1 is the most virulent and prevalent disease causing serogroup^{Footnote 11}. Co-infection with multiple serogroups has been recognized. Cases of legionellosis are commonly reported in the summer and fall; however, cases can occur throughout the year^{Footnote 6}. Sporadic cases and outbreaks of legionellosis have been reported^{Footnote 18}. Outbreaks of Pontiac fever can have an explosive presentation with attack rates as high as 95%, while outbreaks of LD can be much more difficult to detect due to lower attack rates of 0.1-5%^{Footnote 1Footnote 4Footnote 19}.

Of the reported cases of LD, 75-80% occur in individuals over 50 years of age, and 60-70% of those infected are male^{Footnote 8}. The likelihood of development of disease following exposure is related, in part, to host risk factors such as being immunocompromised (for example, organ transplant recipients, cancer patients, corticosteroid treatment), smoking, heavy drinking, pulmonary disease, and chronic respiratory, cardiac or renal illness. In nosocomial cases, risk factors for development of disease include recent surgery, intubation, mechanical ventilation, aspiration, nasogastric tubes, and the use of respiratory therapy equipment.

LD is very rare in cattle, and predisposing factors such as poor hygiene, poor diet, and bad animal management practices likely contribute to the development of disease^{Footnote 7}.

Host range

Natural host(s)

Amoebae, ciliated protozoa, slime moulds, and humans are the primary natural hosts for L. pneumophila^{Footnote 5}.

Other host(s)

Natural infection of calves with L. pneumophila has been reported, although disease is rare^{Footnote 7Footnote 20}. L. pneumophila antibodies have been detected in various wild and domestic animals including horses^{Footnote 20Footnote 21Footnote 22}, cattle^{Footnote 20Footnote 21Footnote 23}, pigs^{Footnote 21}, sheep^{Footnote 20Footnote 21Footnote 23}, dogs^{Footnote 21}, goats^{Footnote 21Footnote 23}, camels^{Footnote 20Footnote 23}, antelopes^{Footnote 20}, buffaloes^{Footnote 20}, and poultry^{Footnote 24}. Guinea pigs, horses, rhesus macaques, mice, and rats are susceptible to experimental infection^{Footnote 25Footnote 26Footnote 27Footnote 28}.

Infectious dose

Unknown^{Footnote 8}.

Incubation period

Pontiac fever usually develops within 48 hours of exposure^{Footnote 4}. The incubation period of LD ranges from 2-14 days, with a median onset of symptoms of 4 days^{Footnote 3}.

Communicability

L. pneumophila is most commonly transmitted to humans and animals through the inhalation of aerosolized water containing the bacteria, and aspiration of contaminated water^{Footnote 1Footnote 3}. Less commonly, direct contact of infectious material with broken skin can result in infection in humans^{Footnote 11Footnote 12Footnote 13}. Most cases of legionellosis occur following environmental exposure. Although previously unrecognized, a probable case of human-to-human transmission of LD was reported following close and sustained contact in a poorly ventilated space^{Footnote 14Footnote 29}. There are no reports of animal-to-animal transmission, or zoonotic transmission.

Section III – Dissemination

Reservoir

L. pneumophila is ubiquitous worldwide in natural and artificial aquatic environments^{Footnote 8Footnote 11}. It is found in most fresh water sources including lakes, ponds, rivers and creeks; however, these natural aquatic environments are rarely identified as sources of human infection^{Footnote 6}. Common exposure sources of L. pneumophila are artificial aquatic environments such as the water found in plumbing systems, water heaters, spas, and cooling towers^{Footnote 3Footnote 6Footnote 11}. Rainwater and soil may also be sources of L. pneumophila^{Footnote 30}.

Zoonosis

None.

Vectors

None.

Section IV – Stability and viability

Drug susceptibility/resistance

L. pneumophila is sensitive to most macrolides, tetracyclines, ketolides and quinolones^{Footnote 3Footnote 11}. LD is commonly treated with azithromycin, doxycycline, levofloxacin and fluoroquinolone^{Footnote 3Footnote 4Footnote 11}.

L. pneumophila is resistant to β-lactams and aminoglycosides^{Footnote 3Footnote 11}. Fluoroquinolone-resistant L. pneumophila strains have been identified among patients treated with these antibiotics, leading to treatment failure and poor prognosis^{Footnote 15Footnote 31}.

Susceptibility to disinfectants

Ethanol (70%), sodium hypochlorite (1%), phenol (2%), glutaraldehyde (2%), and hydrogen peroxide (6%) are effective against L. pneumophila^{Footnote 32}.

Physical inactivation

L. pneumophila can be inactivated by autoclaving at 121°C for 15 minutes^{Footnote 33}. In water systems, L. pneumophila inactivation can be achieved by UV light exposure at 254 nm for 320 minutes at 30 mW-s/cm², heat exposure at 80°C for 0.4 minutes, ozonation, and copper-silver ionization^{Footnote 34}.

Survival outside host

L. pneumophila is able to grow at temperatures between 20°C and 42°C, with optimal growth observed at 35-37°C^{Footnote 3}. There is little to no growth of L. pneumophila at temperatures below 20°C^{Footnote 4}. It can be isolated from aquatic environments up to 70°C, but is rapidly destroyed at temperatures above 70°C^{Footnote 4Footnote 11}. It was found to survive up to 139 days in distilled water, and for 415 days in tap water^{Footnote 35Footnote 36}. L. pneumophila has the ability to persist outside of a host in biofilms^{Footnote 4}.

Section V – First aid/medical

Surveillance

Diagnostic methods for L. pneumophila include culture, antigen detection in urine (for serogroup 1 only), paired serology tests, detection of bacteria by immunofluorescent staining, and molecular polymerase chain reaction (PCR) testing^{Footnote 11Footnote 14}.

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

Azithromycin, doxycycline, and levofloxacin are considered first-line antibiotics for the treatment of LD^{Footnote 3Footnote 11}. For severe LD, the use of fluoroquinolone is recommended^{Footnote 8}. Treatment typically lasts for 10-14 days in immunocompetent patients, and 21 days in immunocompromised patients^{Footnote 4}. LD can be resolved in 95-99% of cases in otherwise healthy patients with timely and appropriate antibiotic treatment^{Footnote 3}. Less than half of patients may respond favourably if there is a delay in the initiation of treatment, in immunosuppressed patients, and in cases of respiratory failure. Pontiac fever does not usually require treatment.

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

Immunization

None^{Footnote 8}.

Note: More information on the medical surveillance program can be found in the CBH^{Footnote 37}, and by consulting the Canadian Immunization Guide.

Prophylaxis

No known post-exposure prophylaxis.

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

One presumed case of laboratory acquired infection with L. pneumophila has been reported in association with aerosol or droplet exposure during animal challenge studies^{Footnote 37}.

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

Sputum and lower respiratory tract specimens are the most common clinical sources of L. pneumophila^{Footnote 3}. Other less common sources include pleural fluid, blood, pericardial fluid, tissue samples, infected wounds, peritoneal fluid, heart valves, joint fluids, bone marrow and intestine. Soil, and water samples from natural and artificial water environments may also be a source of L. pneumophila^{Footnote 6Footnote 30}.

Primary hazards

Inhalation of aerosolized infectious material is the primary hazard associated with exposure to L. pneumophila^{Footnote 1Footnote 3}. Exposure of broken skin to infectious material is another hazard associated with exposure to L. pneumophila.

Special hazards

None.

Section VII – Exposure controls/personal protection

Risk group classification

L. pneumophila is a Risk Group 2 Human Pathogen and Risk Group 1 Animal Pathogen^{Footnote 38Footnote 39}.

Containment requirements

Containment Level 2 facilities, equipment, and operational practices outlined in the CBS 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 CBS to be followed. The personal protective equipment could include the use of a labcoat and dedicated footwear (e.g., boots, shoes) or additional protective footwear (e.g., boot or shoe covers) where floors may be contaminated (e.g., animal cubicles, PM rooms), 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

A biological safety cabinet (BSC) or other primary containment devices to be used for activities with open vessels, based on the risks associated with the inherent characteristics of the regulated material, the potential to produce infectious aerosols or aerosolized toxins, the handling of high concentrations of regulated materials, or the handling of large volumes of regulated materials.

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.

For diagnostic laboratories handling primary specimens that may contain Legionella pneumophila, 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 requirements for storage outlined in the CBS 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 information

Controlled activities with Legionella pneumophila 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, regulations, or legislations:

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

Last file update

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 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, 2021, Canada