Legionella pneumophila

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Legionella pneumophila

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Introduction:
Legionella pneumophila are gram-negative rods. They are very difficult to culture because of their complex nutrient requirements, such as cysteine, high concentrations of iron, and the use of activated charcoal agar. They survive as intracellular pathogens of either protozoa or human macrophages. They are most often found in stagnant water reservoirs like air conditioning cooling towers, whirlpool spas, humidifiers, faucets and shower heads, and are infectious when inhaled. L. pneumophila was first identified and named after the American Legion convention of 1976, held in Philadelphia, PA. 182 people became infected, and 29 died (most of which were older men or cigarette smokers). Although this organism was named in the 70’s, retrospective studies showed cases since 1943.

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Diseases:
L. pneumophila has a very wide range of effects. Healthy individuals usually go through an asymptomatic seroconversion, while less healthy people may undergo Pontiac Fever or Legionnaires’ Disease (LD). In 1968, employees at the county health department in Pontiac, Michigan came down with a fever, but the responsible pathogen was not identified at the time. It was frozen and later diagnosed as L. pneumophila. Pontiac Fever, being milder than LD, generally does not need treatment. Infected individuals will show fever, muscle aches, and headaches, and usually recover between 2-5 days. Pontiac Fever will present symptoms anywhere from a couple of hours to a couple of days after exposure, while LD takes 2-10 days to incubate. LD patients have fever, chills and a cough, with x-rays showing pneumonia. This more severe form usually prevails in elderly, cigarette smokers, people with chronic lung disease, or those who are immunocompromised, such as cancer or AIDS patients.

Virulence:
Being a gram-negative bacterium, L. pneumophila has lipopolysaccharides (LPS) that act as endotoxin within a human host. The presence of a flagella is thought to mediate adherence to human lung cells, thereby causing infection, since flagella-less strains do not cause disease. Once attached to human cells, the organism is engulfed by a macrophage where is utilizes the internal environment to multiply.

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Gene clusters, or pathogenicity islands, have been found that enhance the organism’s ability to grow inside macrophages. Mutations to these genes result in the organisms’ loss of ability to survive. These genes regulate trafficking of the phagosome and inhibit lysosome fusion. L. pneumophila continues to multiply within a macrophage until either space or nutrients are depleted. It uses a two-component regulatory system (Let A/S) that helps the bacteria escape the old cell and move on to another to repeat its growth cycle.

Epidemiology:
In the U.S. there is an incidence of 8,000 to 18,000 cases reported per year. Approximately only 5-10% of the total L. pneumophila cases are actually reported. Worldwide, there is an estimated incidence of 25,000 to 35,000 cases per year. Cases are seen more in the summer, when air conditioning is being used most often. Out of the individuals who come down with Legionnaires’ Disease, 5-30% will die. If untreated, mortality can reach 80%.

Treatment/Prevention:
Erythromycin is the classic antibiotic of choice, with Rifampin being prescribed as well in severe cases. More recently it has been found that flouroquinolones and macrolides are more superior to erythromycin because they can get inside macrophages faster and they have a longer half-life, which decreases the number of necessary doses.
Because there is no person to person transmission, keeping water supplies clean will greatly reduce the risk of infection. There are many useful techniques for destroying L. pneumophila in water reservoirs. Superheating the water to temperatures above 70º C will generally kill the bacteria. Exposure to UV light will damage the bacterial DNA. Copper-silver ionizing puts metallic ions in the water that disrupt bacterial cell walls. Hyper-chlorination of the water is not widely used because L. pneumophila are somewhat resistant to chlorine. Adjustments to the design of water towers and plumbing systems have also helped to suppress growth of L. pneumophila. Most often, these techniques are used in conjunction with each other to ensure clean water and prevent outbreaks of Legionnaires' Disease.

Sources:

Schaechter, Moselio, N. Cary Engleberg, Barry I. Eisenstein, and Gerald Medoff.
Mechanisms of Microbial Disease. 3rd ed. Baltimore, MD: Lippencott Williams & Wilkens, 1999 (218-222).

http://www.med.umich.edu/microbio/faculty/mswanson.html

http://www.cdc.gov/ncidod/dbmd/diseaseinfo/legionellosis_g.htm

http://www.channing.harvard.edu/14.htm

http://author.emedicine.com/MED/topic1273.htm

http://www.merck.com/mrkshared/CVMHighLight?

file=/mrkshared/mmanual/section6/chapter73/73g.jsp%3Fregion%3Dmerckcom&word=Legionnaires&
domain=www.merck.com#hl_anchor


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