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Legionella

UPDATE OF NOVEMBER 18, 2019: NCCID Disease Debriefs provide Canadian public health practitioners, clinicians and advisors with up-to-date reviews of essential information on prominent infectious diseases for Canadian public health practice. While not a formal literature review, information is gathered from key sources including peer reviewed literature, the Public Health Agency of Canada (PHAC), the USA Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO).

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What are important characteristics of Legionella infection?

CAUSE

Legionellosis is caused by Legionella species, small, gram-negative, aerobic bacilli that are found in natural and man-made environments such as cooling towers, potable water systems, lakes, rivers, and streams. Legionella spp. can also be found in soil.

Legionellosis derives its name from an American Legion convention held in Philadelphia in 1976 where an outbreak of a previously unrecognized disease affected 182 delegates. Of these, 146 required hospitalization and 29 (16%) died. Although the original source of the bacterium was not found, epidemiologic analysis suggested potential exposure from the lobby of the hotel or the surrounding area. Following the outbreak, a new microorganism, Legionella pneumophila, was identified and “Legionnaires’ Disease” was recognized in 1977.

Since 1977, 60 different Legionella species have been described to date, with 26 of them having been linked to disease in humans. However, infections occur primarily due to L. pneumophila (especially L. pneumophila Serogroup 1) and, less often, due to the non-pneumophila organisms such as L. micdadei, L. bozemanae, or L. longbeachae.

SIGNS AND SYMPTOMS

Legionellosis can manifest as 2 distinct syndromes: Legionnaires’ disease (a form of atypical bacterial pneumonia) and Pontiac fever.

Legionnaires’ disease typically develops within 2 to 14 days following infection. Symptoms often resemble those caused by typical bacterial pathogens, and include cough, fever, headache, diarrhoea, chills, shortness of breath, myalgias, hyperacute presentation, septic shock, initial upper respiratory illness followed by acute deterioration, white blood cell count >15,000 or 6,000 cells/cubic ml, or dense or segmental lobar consolidation.

Pontiac fever is characterized by a flu-like illness that features fever, chills, and malaise but notably occurs without pneumonia. The illness is typically shorter in duration, lasting an average of 3 days.

SEVERITY

Legionnaires’ disease is associated with a high frequency of hospitalization and intensive care admissions. Occasionally, extra-pulmonary symptoms including mental status changes, ataxia, seizures, or encephalitis develop. There is an approximate 10% case-fatality rate among confirmed, inpatient cases.

In contrast to Legionnaires’ disease, Pontiac fever rarely requires hospitalization. There is a shorter time of incubation, ranging from 1 to 3 days, and symptoms typically last an average of 3 days.

Epidemiologic risk factors include chronic diseases such as diabetes, renal disease, lung disease and malignancy, smoking, age greater than 50, and a weakened immune system (due to disease or from exposure to immunosuppressive drugs, especially anti-tumour necrosis factor agents). Legionella disproportionately affects males. Risk of acquiring Legionella is also increased following recent exposure to hot tubs, repairs or maintenance of domestic plumbing, and overnight stays in a healthcare facility.

INCUBATION PERIOD

The incubation period for Legionnaires’ disease is approximately 2 to 10 days. For Pontiac fever, the incubation period is approximately 36 hours.

RESERVOIR AND TRANSMISSION

Transmission most commonly occurs from inhalation of aerosolized water containing the bacteria. Aspiration of contaminated water may also cause infection in susceptible hosts. Though previously unrecognized, person-to-person transmission has been reported in a single case (1).

In water, Legionella associates with biofilm communities and protozoan species, such as amoeba. Legionella parasitize protozoa, allowing them to grow and replicate inside their host where they are protected from unfavourable environments including extreme temperatures, biocides, and chlorine. Since protozoa look and function similarly to human alveolar macrophages in the lungs, Legionella may mistake macrophages for their natural host, invading these incidental hosts and resulting in extensive disease.

Although Legionella are usually in water sources, bacterial concentrations are generally too low to cause disease in healthy patients. Most relevant exposures occur in buildings where conditions favour growth of bacteria and their biofilms, including the stagnant, warm water found in cooling towers, plumbing systems, and humidifiers.

LABORATORY TESTING

Diagnostic testing should be considered for: outpatients who have failed antibiotic therapy; individuals requiring intensive care admission; immunocompromised patients; individuals with pneumonia in the setting of known Legionellosis outbreak; and those with a recent travel history. In addition, testing should be considered if there have been recent changes in water quality that may promote Legionella growth.

Though several diagnostic tests are available, culture of lower respiratory secretions and the Legionella urinary antigen test are preferred. The most commonly utilized test is the urinary antigen test, however, although rapid, this test can only identify L. pneumophila serogroup 1 (the most common cause of Legionellosis). Since the urinary antigen test has low sensitivity for the other Legionella species, culture of lower respiratory secretions is recommended and should be ordered concurrently.

Isolation of Legionella from clinical specimens (including sputum, bronchoalveolar lavage, pleural fluid, or lung tissue) allows for the identification of species and serogroup, which may help identify exposure sources and prevent further outbreak of disease.

Other diagnostic tests are not ordered in routine practice due to technical challenges and inherent limitations. Serology, for instance, requires paired sera (requiring collection 3 to 6 weeks following initial sampling). Direct fluorescent antibody staining is highly specific but technically difficult as it is typically performed on lung tissue. Finally, polymerase chain reaction (PCR) is rapid and can be performed on lung tissue; however, assay quality varies via laboratory and so overall sensitivity and specificity remain unknown.

PREVENTION

The major key to prevention of Legionellosis outbreaks is proper maintenance of water systems to prevent Legionella growth. In the healthcare setting, this requires routine maintenance and frequent testing of the healthcare facility’s water system. In the event of positive testing, official infection control protocols should be in place to reduce bacteria and minimize risk to patients.  In private settings, proper maintenance of mist-producing devices, including shower heads and humidifiers, may reduce the risk of Legionella transmission. Home water heaters should be kept at a minimum temperature of 60°C to help reduce the risk of Legionella growth.

There is no vaccine for the prevention of Legionellosis.

TREATMENT

Cases limited to non-pneumonic disease (i.e., Pontiac fever) usually last only 2-5 days, and do not typically require antibiotic treatment. However, supportive treatments to ease symptoms may help.  No deaths have been reported with this type of infection.

For confirmed pneumonic disease (Legionnaires’ disease), newer macrolides and quinolones may be used as monotherapy. There are no randomized studies on the treatment of patients with confirmed Legionella; however, uncontrolled retrospective analyses have suggested fewer complications and a more rapid response in patients treated with quinolones. For transplant patients, quinolones are often favoured, as macrolides may interact with some immunosuppressive agents such as tacrolimus and cyclosporine. For intensive-care patients, combination therapy may include a macrolide, a quinolone, and rifampin, however, for most patients monotherapy is sufficient. For immunosuppressed patients, a longer course of treatment is generally recommended.

In practice, treatment is often initiated if Legionella is suspected, even if a diagnostic confirmation is still pending. For outpatients, azithromycin (or a quinolone such as levofloxacin or moxifloxacin) alone are usually sufficient while, for inpatients, azithromycin (or levofloxacin or moxifloxacin) may be combined with initial beta-lactam therapy.

What is happening with current outbreaks of Legionella?

Legionella incidence is on the rise in Canada and across North America.

In Canada, the number of reported cases of Legionnaires’ Disease is generally less than 100 per year although the actual number of cases is suspected to be much higher as many patients are often treated empirically and not tested for Legionella.

Although person-to-person transmission of Legionellosis is rare, it can occur and was reported for the first time in 2016 (1). Much more commonly, infections occur sporadically or in outbreaks which are typically due to exposure to a contaminated water supply via cooling towers or complex plumbing systems.

In the United States, approximately 5000 cases of Legionellosis are reported annually. Outbreaks continue to be reported in connection with long-term care facilities, resorts, and in municipal water supplies.

What measures should be taken for a suspected Legionella case?

The Public Health Agency of Canada provides clinical guidance on Legionella. Clinicians should also refer to provincial/territorial guidelines.

Clinical suspicion and prompt treatment initiation are critical for favourable outcomes when dealing with Legionella infections. Therefore, Legionella should be considered when an individual presents with community acquired pneumonia, and if signs and symptoms are compatible with typical bacterial pathogens (hyperacute presentation, septic shock, absence of upper respiratory symptoms, or dense or segmental lobar consolidation) then these agents should strongly be considered. Case confirmation requires objective confirmation including via Legionella urinary antigen as well as culture of lower respiratory tract secretions.

In Canada, Legionellosis has been a nationally reportable disease since 1986.

In health-care associated cases, Infection Control should be notified immediately and involved in subsequent decision-making. Outbreaks should be investigated to localize the source of infection and prevent further exposures. Public notification should be coordinated with regional Public Health officials.

WORKS CITED

(1) Correia AM, Ferreira JS, Borges V, et al. Probable Person-to-Person Transmission of         Legionnaires’ Disease. New England Journal of Medicine. 2016;374(5):497- 498. doi:10.1056/NEJMc1505356.