Legionnaires’ disease

Synonyms

2

Overview

Legionnaires' disease (also known as legionellosis or Legion fever), is a form of atypical pneumonia caused by any type of Legionella bacteria. Over 90% of cases of Legionnaires' disease are caused by Legionella pneumophila.

Other causative species include L. longbeachae, L. feeleii, L. micdadei, and L. anisa. These species cause a less severe infection known as Pontiac fever, which resembles acute influenza. These bacterial species can be water-borne or present in soil, whereas L. pneumophila has only been found in aquatic systems, where it is symbiotically present in aquatic-borne amoebae. It thrives in temperatures between 25 and 45 °C (77 and 113 °F), with an optimum temperature of 35 °C (95 °F). During infection, the bacterium invades macrophages and lung epithelial cells and reproduces within the infected cells.

Symptoms

The length of time between exposure to the bacteria and the appearance of symptoms is generally two to 10 days, but can rarely extend to as much as 20 days. For the general population, among those exposed between 0.1 to 5% develop disease, while among those in hospital between 0.4 to 14% develop disease.

Those with Legionnaires' disease usually have fever, chills, and a cough, which may be dry or may produce sputum. Almost all with Legionnaires' experience fever, while approximately half have cough with sputum, and one third cough up blood or bloody sputum. Some also have muscle aches, headache, tiredness, loss of appetite, loss of coordination (ataxia), chest pain, or diarrhea and vomiting. Up to half of those with Legionnaires' have gastrointestinal symptoms, and almost half have neurological symptoms, including confusion and impaired cognition. "Relative bradycardia" may also be present, which is low or low-normal heart rate despite the presence of a fever.

Laboratory tests may show that kidney functions, liver functions and electrolyte levels are abnormal, which may include low sodium in the blood. Chest X-rays often show pneumonia with consolidation in the bottom portion of both lungs. It is difficult to distinguish Legionnaires' disease from other types of pneumonia by symptoms or radiologic findings alone; other tests are required for definitive diagnosis.

Persons with Pontiac fever experience fever and muscle aches without pneumonia. They generally recover in two to five days without treatment. For Pontiac fever the time between exposure and symptoms is generally a few hours to two days.

Causes

Legionella enters the lung either by aspiration of contaminated water or inhalation of aerosolized contaminated water or soil. In the lung, the bacteria are consumed by macrophages, a type of white blood cell, inside of which the Legionella bacteria multiply causing the death of the macrophage. Once the macrophage dies, the bacteria are released from the dead cell to infect other macrophages. Virulent strains ofLegionella kill macrophages by blocking the fusion of phagosomes with lysosomes inside the host cell; normally the bacteria are contained inside the phagosome, which merges with a lysosome, allowing enzymes and other chemicals to break down the invading bacteria.

Prevention

Outbreaks of Legionnaire's disease are preventable, but prevention requires meticulous cleaning and disinfection of water systems, pools and spas.

Avoiding smoking is the single most important thing you can do to lower your risk of infection. Smoking increases the chances that you'll develop Legionnaires' disease if you're exposed to legionella bacteria.

Diagnosis

People of any age may suffer from Legionnaires' disease, but the illness most often affects middle-aged and older persons, particularly those who smoke cigarettes or have chronic lung disease. Immunocompromised people are also at higher risk. Pontiac fever most commonly occurs in persons who are otherwise healthy.

The most useful diagnostic tests detect the bacteria in coughed up mucus, find Legionella antigens in urine samples, or allow comparison of Legionella antibody levels in two blood samples taken 3 to 6 weeks apart. A urine antigen test is simple, quick, and very reliable, but it will only detect Legionella pneumophila serogroup 1, which accounts for 70 percent of disease caused by L. pneumophila which means use of the urine antigen test alone may miss as many as 40% of cases. This test was developed by Richard Kohler in 1982. When dealing with Legionella pneumophila serogroup 1, the urine antigen test is useful for early detection of Legionnaire's disease and initiation of treatment, and has been helpful in early detection of outbreaks. However, it will not identify the specific subtypes, so it cannot be used to match the person with the environmental source of infection. The Legionella bacteria can be cultured from sputum or other respiratory samples. Legionella stains poorly with Gram stain, stains positive with silver, and is cultured on charcoal yeast extract with iron and cysteine (CYE agar).

A significant under-reporting problem occurs with legionellosis. Even in countries with effective health services and readily available diagnostic testing, about 90 percent of cases of Legionnaires' disease are missed. This is partly due to Legionnaires' disease being a relatively rare form of pneumonia, which many clinicians may not have encountered before and thus may misdiagnose. A further issue is that people with legionellosis can present with a wide range of symptoms, some of which (such as diarrhea) may distract clinicians from making a correct diagnosis.

Prognosis

The fatality rate of Legionnaires' disease has ranged from 5% to 30% during various outbreaks and approaches 50% for nosocomial infections, especially when treatment with antibiotics is delayed. According to the journal Infection Control and Hospital Epidemiology, hospital-acquired Legionella pneumonia has a fatality rate of 28%, and the principal source of infection in such cases is the drinking-water distribution system.

Treatment

Effective antibiotics include most macrolides, tetracyclines, ketolides, and quinolones. Legionella multiply within the cell, so any effective treatment must have excellent intracellular penetration. Current treatments of choice are the respiratory tract quinolones (levofloxacin, moxifloxacin, gemifloxacin) or newer macrolides (azithromycin,clarithromycin, roxithromycin). The antibiotics used most frequently have been levofloxacin, doxycycline, and azithromycin.

Macrolides (azithromycin) are used in all age groups, while tetracyclines (doxycycline) are prescribed for children above the age of 12 and quinolones (levofloxacin) above the age of 18. Rifampicin can be used in combination with a quinolone or macrolide. It is uncertain whether rifampicin is an effective antibiotic to take for treatment. The Infectious Diseases Society of America does not recommend the use of rifampicin with added regimens. Tetracyclines and erythromycin led to improved outcomes compared to other antibiotics in the original American Legion outbreak. These antibiotics are effective because they have excellent intracellular penetration in Legionella-infected cells. The recommended treatment is 5–10 days of levofloxacin or 3–5 days of azithromycin, but in people who are immunocompromised, have severe disease, or other pre-existing health conditions, longer antibiotic use may be necessary. During outbreaks, prophylactic antibiotics have been successfully used to prevent Legionnaires' disease in high-risk individuals who have possibly been exposed.

The mortality at the original American Legion convention in 1976 was high (34 deaths in 180 infected individuals ) because the antibiotics used (including penicillins, cephalosporins, and aminoglycosides) had poor intracellular penetration. Mortality has plunged to less than 5% if therapy is started quickly. Delay in giving the appropriate antibiotic leads to higher mortality.