Legionnaires’ disease: Community, travel and health care acquisition

Issue: December 2015

ByDonald Kaye, MD, MACP

ByMatthew E. Levison, MD, FACP

Once again our attention was drawn to Legionnaires’ disease this summer by a large outbreak in the South Bronx, New York, which involved more than 120 cases, including 12 deaths. The outbreak was attributed to a Legionella-contaminated hotel cooling tower. Other outbreaks this summer also occurred: in a different Bronx neighborhood soon thereafter, involving 13 cases and one death; in a Veterans home in Quincy, Illinois, involving 54 cases and 12 deaths; and in San Quentin State Prison in California, where more than 80 inmates became ill. According to the CDC, cases of Legionnaires’ disease have been increasing dramatically in the United States, with 2,270 in the first 7 months of 2014 and 2,472 cases in the same period this year, whereas only 1,500 cases were being reported annually 15 years ago. Does this represent a true surge in the number of cases of this disease, or is there something else going on?

Disease history

Legionnaires’ disease (LD) was first reported at an American Legion convention in Philadelphia during the hot, humid summer of 1976. About 4,000 delegates from the Pennsylvania chapter of the American Legion met at the Bellevue-Stratford Hotel located on Broad Street for a 4-day annual gathering beginning on July 21. The Bellevue-Stratford had been the most luxurious hotel in the U.S. when it opened in 1904 and was still luxurious in 1976.

A week after the convention ended, hundreds of conventioneers were experiencing pneumonia-like symptoms, and 22 already had died. The final case count totaled 221, including 34 deaths, among both conventioneers (149 cases) and nonconventioneers (72 cases), some of whom had only been at the front of the hotel, but never entered the building. These latter cases were said to have developed “Broad Street pneumonia.”

Epidemiological studies suggested that the disease most probably spread by the airborne route, but the etiology was unknown at the time. Not until 6 months later did Joseph E. McDade, PhD, from the CDC, announce that the causative agent of the outbreak was a previously unknown gram-negative bacterium subsequently named Legionella pneumophila. It was later concluded that the bacteria came from the hotel’s cooling tower and were dispersed as an aerosol throughout the hotel via air conditioning ducts and onto Broad Street in front of the hotel’s lobby. Serology by indirect immunofluorescence was positive in 29 of 33 patients who survived what became known as LD, suggesting they were infected with this organism. Serology done subsequently on serum banked from two earlier unsolved pneumonia outbreaks also was positive for LD.

Since then many other outbreaks, as well as more numerous sporadic cases of LD, have occurred throughout the world, with case fatality rates of 5% to 30%. In the United Kingdom and the U.S., more than 70% of cases are community-acquired, and about 20% are travel-associated. Under 10% are linked to health care facilities. The proportion of community-acquired pneumonias due to Legionella has ranged from 2% to 15%. L. pneumophila ranks among the top five most common causes of community-acquired pneumonia, especially among severe cases admitted to an ICU.

Legionella also causes a milder, nonpneumonic, self-limited flu-like illness (fever, myalgia and headache), called Pontiac fever, which takes its name from an outbreak in 1968 in Pontiac, Michigan. Pontiac fever develops within 72 hours after exposure and attack rates are high; up to 95% of exposed persons become ill (unlike LD, which only develops during outbreaks in 5% of exposed individuals), and symptoms resolve in 2 to 5 days without antibiotic treatment. Because in the U.S. more than 99% of reported cases due to Legionella species are classified as LD, this article concentrates only on LD.

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Risk factors for LD infection

The risk for acquiring LD depends on several factors that include the level of Legionella contamination of the source, the virulence of the strain, the intensity of patient exposure to the source, and the susceptibility of the host. Community-acquired LD occurs predominantly during warm months (summer and early fall) and wet weather. Nosocomial cases occur year-round, with no seasonal pattern.

Host risk factors include being aged older than 50 years, cigarette smoking, diabetes, chronic lung or heart disease and immunosuppression as a result of disease or drugs. Environmental risk factors include residence in a health care facility and proximity to cooling towers, whirlpool spas, decorative fountains, and grocery produce misters. Travel-related cases are associated with exposure in hotels or on cruise ships.

Some studies have identified living in poor neighborhoods as a risk factor, perhaps reflecting less access to medical care or a poorly maintained environment, as well as occupational risk factors, such as driving cars or trucks (exposure to aerosolized contaminated windshield fluid or water on roadways), cleaning and janitorial work, and protective services (ie, police).

Person-to-person transmission does not occur. The diagnosis can be confirmed by culture of respiratory secretions on selective media (buffered charcoal yeast extract with L-cysteine) — preferably before the administration of antibiotics — as well as by direct fluorescent antibody staining, serology, urinary antigen assay for L. pneumophila serogroup 1, and PCR. Antimicrobial therapy includes azithromycin, doxycycline or a fluoroquinolone.

Epidemiology of LD

The genus of Legionella is now known to comprise more than 50 species and many serogroups, but only about 20 Legionella species are linked to human diseases. L. pneumophila serogroup 1 is the most frequent, which may reflect the availability of the Legionella urine antigen test that detects only L. pneumophila serogroup 1. However, of culture-confirmed cases in the U.S. and Europe, more than 80% of LD is caused by L. pneumophila serogroup 1. About 15% of culture-positive cases are caused by other serogroups of L. pneumophila; of the remaining 5%, the most common are Legionella micdadei; Legionella bozemanii, Legionella dumoffii and Legionella long-beachae. However, in Australia and New Zealand, L. long-beachae infection occurs almost as often as L. pneumophila infection and is limited to persons who have had direct contact with unsterilized potting soil or compost. L. long-beachae has been found in soil and potting mix in Australia and New Zealand and, unlike L. pneumophila, is rarely isolated from aquatic environments. Hospital-acquired LD is frequently caused by Legionella other than L. pneumophila serogroup 1.

Legionella are intracellular parasites of environmental amebae. They are distributed throughout the world in natural, freshwater environments but are thought to be present in insufficient numbers to cause disease. They tend to grow in biofilms and are not easily eradicated by the chlorination methods typically employed to purify domestic water systems. Low levels of the organism that colonize a water source can grow to high concentrations under certain conditions in water systems of large buildings such as domestic hot-water systems with water heaters that operate below 60°C (140°F), dental water lines that are frequently maintained at temperatures above 20°C (68°F), water storage tanks, pipes, cooling towers, evaporative condensers, decorative fountains or hot tubs. These sites, if not properly cleaned, maintained and disinfected, can provide optimal conditions for their growth. Growth requires inorganic iron and L-cysteine and is enhanced by organic sediments and the presence of other microorganisms. They grow best in warm, stagnant water at temperatures between 32°C to 40°C (90°F to 104°F). However, the infective dose of Legionella for humans is unknown and likely varies with the mode of transmission, susceptibility of the host and virulence of the strain. Water stored below 20°C (68°F) is generally not a source for high L. pneumophila levels.

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LD can occur if contaminated water (or potting soil in the case of L. long-beachae) is aerosolized and then inhaled by susceptible individuals. Aerosols can be generated in homes and in institutions (such as hotels, health care facilities, cruise ships, supermarkets, dental offices and spas), originating from cooling towers, showers, misters in salad bars and grocery produce sections, warmed dental water lines, decorative fountains and whirlpool baths. LD also can be transmitted by aspiration of contaminated water, especially in health care settings by patients who are prone to aspirate. Underwater birthing, which has been promoted as a means of decreasing maternal discomfort during childbirth, has resulted in LD in newborns following aspiration of Legionella.

In the U.S. there have been a total of 42,877 cases of legionellosis reported to the CDC from 1990 through 2011. In 2011, more than 75% of cases were reported along the East Coast, especially the Mid-Atlantic region, plus the East North Central region (Illinois, Indiana, Michigan, Ohio and Wisconsin). The incidence rates increase with age. Rates per 100,000 population by age category were 0.4 (< 50 years), 2.5 (50-64 years), 3.6 (65-79 years), and 4.7 ( 80 years), and about 64% of cases were male. Most cases were reported in the summer or fall. The number of cases remained under 1,500 each year (except for a small spike in 1994), with an annual incidence rate of about 0.4 per 100,000 until 2003, when the number increased abruptly by 70% — from 1,310 cases in 2002 to 2,223 cases in 2003, with an incidence rate of 0.78. The number of cases has continued to increase almost every year to reach 4,202 cases, with an incidence rate of 1.36 cases per 100,000 in 2011.

However, the incidence rates reported in the U.S. are likely underestimated, in part because LD surveillance is passive, dependent on health care providers and laboratories reporting cases. Indeed, a population-based study of community-acquired pneumonia requiring hospitalization in 1991 in the U.S. estimated that Legionella species likely caused 8,000 to 18,000 pneumonia cases annually, at a time when the reported number was about 1,500 cases annually. Outbreaks among travelers can be difficult to detect because of the low attack rate, long incubation period, and the dispersal of people from the source of an outbreak. Health care-acquired LD also likely is underestimated.

Similar to the U.S., the incidence of LD in the European Union increased from about 4 to 5 cases per million residents in the years before 2000 to about 12 per million in 2005; the increase was primarily due to older EU member countries that report the most cases. The incidence in the EU, however, stabilized after 2005, which was attributed to the addition of countries mainly from Eastern Europe that joined the EU after 2004 and reported few cases — perhaps because of limited laboratory capacity and underreporting to health authorities. However, the annual incidence rate in the EU since 2005 (between approximately 11 and 12 per million) is actually very similar to the rate in the U.S. of 13.6 per million in 2011.

Vulnerable populations

Increased awareness of the disease and improved diagnostic testing and reporting likely have contributed in part to an upsurge in reported LD cases in the U.S. and many of the EU member countries. For example, urine antigen tests are easy to perform and provide rapid, accurate results for detecting L. pneumophila serogroup 1, the most common cause of LD cases, and they are used to confirm most suspected cases in the U.S. and the EU. However, urine antigen testing has been available since 1980s; its use is unlikely to account for the entire increase in legionellosis cases since 2000. A true increase in incidence might reflect an increasing number of vulnerable people. There are more elderly people today, some of whom are prone to aspirate, and people with weakened immune systems who are at high risk for LD. Other host factors might include increasing travel on cruise ships or hotel stays, residency in health care facilities or rundown buildings with aging cooling towers and plumbing systems in need of repair, or occupations that place the vulnerable in proximity to environments where growth of Legionella has been promoted. Climate change may have resulted in prolonged spells of hot or wet weather that also may have promoted growth of Legionella.

The key to preventing LD is maintenance of the water systems in which Legionella tend to grow, including drinking water systems, hot tubs, decorative fountains, and cooling towers. If Legionella are found, facilities should be prepared to eliminate them, especially if they serve people at higher risk for LD.

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For more information:

Donald Kaye, MD, is a professor of medicine at Drexel University College of Medicine, associate editor of ProMED-mail, section editor of news for Clinical Infectious Diseases and an Infectious Disease News Editorial Board member.

Matthew E. Levison, MD, is a ProMED-mail bacterial disease moderator, professor of public health, Drexel University School of Public Health, and adjunct professor of medicine and former chief of the division of infectious diseases, Drexel University College of Medicine.

Disclosures: Kaye and Levison report no relevant financial disclosures.