Legionnaires' Disease and Pontiac Fever

Legionnaires’ Disease and 232 Pontiac Fever Paul H. Edelstein and Craig R. Roy SHORT VIEW SUMMARY Definition } Pontiac fever is associated with inhalation of highly sensitive in all settings. Urine antigen } Legionnaires’ disease is a noncontagious type Legionellaa spp.–containing water but not testing, the most commonly used test, is about of bacterial pneumonia caused by Legionella necessarily caused by the bacterium. It occurs 70% and 30% sensitive in spp. bacteria, most commonly Legionella in sporadic and epidemic form at apparently community-acquired and nosocomial disease, pneumophila. low incidence but may be more common than respectively. is reported. } Pontiac fever is a several-day-long, Therapy nonpneumonic, febrile, influenza-like illness Microbiology } Macrolides, tetracyclines, and quinolone associated with exposure to Legionellaa spp. } Constituted of more than 60 known species, the antimicrobials can all be used to successfully that resolves spontaneously. Legionellaa bacteria are ubiquitous in the treat the disease, with azithromycin and Legionellosis includes legionnaires’ disease, } aqueous environment and probably moist soils. levofloxacin being the most active. Pontiac fever, and extrapulmonary Legionella } Optimal bacterial growth requires specialized Tetracyclines may not be active for L. spp. infection not associated with pneumonia. media that contain cysteine and iron. longbeachaee–caused disease. Epidemiology } The bacteria are facultative intracellular } For cure, 3 to 14 days’ therapy is required, } Legionnaires’ disease is acquired by inhaling a parasites of free-living amebae and human depending on disease severity, host factors, water aerosol containing Legionellaa spp. monocytes and macrophages that use hostlike and type of therapy used. proteins to masquerade as host and to avail bacteria, and possibly by microaspirating Prevention Legionellaa spp.–containing water. themselves of intracellular resources. } No vaccine is available. } About 20 to 80 cases annually per million Diagnosis } Proper environmental design and maintenance population occur in most developed countries, } Clinical and roentgenographic differentiation reduce disease risk. with the elderly, males, cigarette smokers, and of legionnaires’ disease from common causes immunosuppressed patients most at risk. of pneumonia is not generally possible. } About 1% to 5% of patients hospitalized for } Specific and specialized laboratory testing can community-acquired pneumonia have be helpful for disease diagnosis but is not legionnaires’ disease. HISTORY before, but major advances in technology were required to properly Legionnaires’Legionnaires’ disease (LD) is an acute pneumonic illness caused by determine its cause. gram-negative bacilli of the genus Legionella, the most common of Even with identification of Lp in 1977 as the cause of LD, how best which is Legionella pneumophila (Lp). Pontiac fever (PF) is a febrile, to diagnose the disease and ways to abort epidemics of LD remained nonpneumonic, systemic illness closely associated with, if not caused uncertain for several years. Epidemics of the disease, especially noso- by, Legionella spp. Legionellosis is the term that encompasses all diseases comial ones, commonly lasted for years.16–22 It was discovered that Lp caused by, or presumed to be caused by, the Legionella bacteria, including and other Legionella spp. were naturally occurring aquatic bacteria that LD, focal nonpulmonary infections, and PF. grew in warm water, in cooling towers, water heaters, and potable water LD was first recognized when it caused an epidemic of pneumonia plumbing. These discoveries led to the end of several multiyear outbreaks at a Pennsylvania State American Legion convention in Philadelphia of the disease.23 It is now unusual for LD outbreaks to last more than in 1976; 221 people were affected, and 34 died. Despite intensive labora- a week or two. tory investigation, the cause of the outbreak went undetected for many LD occurs in both sporadic and epidemic forms, sometimes involving months. Epidemiologic investigation concluded that the disease was many hundreds of victims.24–27 The disease, while a relatively rare (1%–5%) most likely airborne, and focused primarily at one convention hotel, cause of community-acquired pneumonia that is often easily treated which closed because of adverse publicity.1,2 About 6 months later, Joseph and relatively mild, can cause severe, and fatal, disease. McDade and Charles Shepard, investigators at the Centers for Disease Control and Prevention, discovered the etiologic agent, a fastidious THE ETIOLOGIC AGENT gram-negative bacillus.3 Because of the historical association with the The LegionellaLegionella spp. aarere ssmallmall ggram-negativeram-neg bacilli with fastidious growth American Legion convention, this disease is now called “legionnaires’ requirements. Amino acids are the main energy source for extracellular disease,” and the etiologic agents belong to the family Legionellaceae, growth, with glycerol or glucose used during intracellular growth.28 with Lp being the agent responsible for the 1976 Philadelphia epidemic. Obligate aerobes, the bacteria grow at temperatures ranging from 20°C Several past unsolved outbreaks of pneumonia in the 1950s to the early to 42°C. Coxiella burnetii, an obligate intracellular parasite and the 1970s had been LD.4–6 An unsolved epidemic of a nonpneumonic febrile etiologic agent of Q fever, is the closest relative of the Legionellaceae. illness in Pontiac, Michigan, was found to be associated with Lp exposure; l-Cysteine is required for the growth of all but one of the clinically this illness was termed “Pontiac fever”.7,8 Prior epidemics of PF occurred important Legionella spp., and this amino acid is needed for the initial as early as 1949.9 Bacterial isolates from the 1940s through the 1960s, growth of all described Legionella spp. from environmental or clinical previously thought to be rickettsial agents, were found to be Legionella sources. Soluble iron is required for optimal growth, and for initial bacteria.10–15 Both the organism and the disease had been studied decades isolation of the bacterium from both clinical and environmental sources. 2807 2808 s ent g ic A g tiolo E A B FIG. 232.1 Cultures of Legionella pneumophila. (A) Typical opal-like colony of L. pneumophila grown on BCYEα agar. (B) Gram stain of L. pneumophila taken from culture plate. Basic fuchsin should be used as the counter-stain as safranin stains the bacterium poorly. ectious Diseases and Their f In I A yeast extract agar containing iron, l-cysteine, α-ketoglutarate, and Part II charcoal and buffered with an organic buffer (buffered charcoal-yeast extract [BCYEα] agar) is the preferred growth medium for clinical isolation. Clinically important Legionella spp. grow best at 35°C in humidified air on BCYEα medium, usually in 3 to 5 days after inoculation of plates. Up to 14 days’ incubation may very rarely be required for the isolation of unusual Legionella spp. More than 60 different Legionella spp. have been described, about half of which have been reported to infect humans.29 Lp serogroup 1 (Lp1) caused the 1976 Philadelphia outbreak, and is the cause of 65% to 90% of all cases of LD for which there is a bacterial isolate.30–32 Lp1 dominance is not universal. For example, Lp1 constituted only 66% of Legionella spp. isolates in LD patients in Ontario Province, Canada, with Lp serogroup 6 being a relatively common isolate in that province.32 Also, L. longbeachae (Llb) causes 50% to 85% of LD cases in New Zealand, and a similar fraction in Australia.33 Lp1 can be divided into multiple subtypes using a variety of serologic, other phenotypic, and genetic FIG. 232.2 Gimenez stain of L. pneumophila growing in an ameba. methods. One particular subtype of Lp1 causes 55% to 76% of cases of Note that the bacteria are much smaller and more uniform in morphology LD due to Lp, and 85% of cases due to Lp1. This “Pontiac” subtype than when the bacteria are taken from a culture plate (see Fig. 232.1B). reacts with a specific monoclonal antibody and contains the lag-1 gene encoding a lipopolysaccharide acetyl transferase.34,35 The most common non-Lp species that are isolated from humans are Llb, L. micdadei, L. In addition to intraamebal survival, free-living Legionella bacteria bozemanae, and L. dumoffii,31 which, with the exception of Australasia, can enter a low metabolic state termed “viable but not cultivatable”, constitute fewer than 5% of culture-proven cases.36,37 making them difficult to recover from the environment and biocide- Most clinical microbiology laboratories should be able to identify resistant.42 The Legionella bacteria, amebae, and other microorganisms Legionella bacteria to the genus level (Fig. 232.1). Identification of Lp constantly escape from the biofilm because of pressure fluxes into a and Lp1 can be accomplished by sophisticated laboratories. Identification freely moving phase. Environmental changes that disrupt the biofilm of other Lp serogroups and other Legionella spp. is more difficult, can result in the sudden and massive release of Legionella bacteria into requiring molecular testing for accurate identification.38 Matrix-assisted the surrounding water. If this water is then aerosolized or aspirated, laser desorption/ionization time-of-flight (MALDI-TOF) mass spec- the bacteria can cause illness in a susceptible host. Almost all cases of trometry identification of bacterial colonies can be useful for the LD result from Legionella

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