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Legionella sp. Legionnaire’s Disease Pontiac Fever Genus Legionella • Best-studied species is L. pneumophila • accounts for ~ 85% of infections • motile, Gram-negative, aerobic rod • complex nutritional requirements • ~ 50 species in genus, > half implicated in human disease – L. micdadei: mild, febrile, flu-like illness called Pontiac fever • self-limiting, little or no tissue damage Ecology • There are 40 species in the family of legionella bacteria in the world. Of these species, 12 have been implicated in human disease. 90% of these disease cases are caused by Legionella Pneumophila. • There are 15 serogroups of L. Pneumophila and most cases are associated with serogroup 1. There are 5 subgroups in this serogroup which have different degrees of virulence. Ecology • Legionella are usually found in the freshwater of streams, lakes, warm springs, rivers, and riverbanks. • In their natural aquatic environment, legionella feed on various nutrients from the water, but are most adept in the role of an intracellular parasite on other bacteria. • Once it is uptaken by a larger bacterium, it resists bacterial defenses and then multiplies. Ecology • Environmental conditions which promote the growth of legionella are: • • • • Water temperature between 20 – 50 ºC. Stagnant water. pH range of 2.0 – 8.5 Sediment in water which supports the growth of supporting microbiota. • Presence microbiota including algae, protozoa, and others. • L-Cysteine-HCL and Iron salts to promote growth. Ecology • The range of temperatures within which legionella survives and thrives: Pathogenesis • In their usual aquatic environment, legionella do not cause infections. But, when transferred to water supplies and air conditioning units, they are able to cause large outbreaks of disease. • Legionnaires’ Disease is caused by inhaling L. pneumophila bacteria dispersed in aerosols of contaminated water from the environment. • These aerosols are provided by devices in which warm water can stagnate, such as A/C cooling towers, humidifiers, shower heads, decorative fountains, and water misters in grocery stores. RISK AREAS • • • • • • • Hot & cold water systems Cooling Towers & Air Conditioning Storage Cisterns Calorifiers Deadlegs Showers Spa pools Nemco U T I L I T I E S SHOWERS Operate at desired temps Poor hygiene Infrequently used Prone to scaling Create aerosol Nemco U T I L I T I E S DEAD LEGS Stagnant water Ambient temps Breeding ground Nemco U T I L I T I E S STORAGE TANKS Over capacity Stagnation Out of site Poor flow Ambient temps Nemco U T I L I T I E S CALORIFIERS Can run at critical temps Thermal stratification Sludge build up Nemco U T I L I T I E S COOLING TOWERS Run at ideal temps Open to elements Contamination via water supply Intermittent use Drift affects wide area Nemco U T I L I T I E S Virulence Factors • Environmental survival – free living – intracellular parasites of amoebae (Acanthamoeba sp, Naegleria sp), ciliated protozoa, slime molds • more resistant than free-living bacteria to biocides • Biofilms – more resistant to disinfectants (very slow growth rate in the biofilm) Virulence Factors • Phospholipase C – hydrolyzes phosphatidylcholine – may injure phagocytes and lung tissue – could allow escape from phagosome • Protein kinases – phosphorylate tyrosine, serine, threonine residues in eucaryotic signaling proteins Pathogenesis • L. Pneumophila enters a human host by penetrating into the alveolar region of the lungs; the size of the bacterium allows its entrance in the human respiratory tract. • Alveolar macrophages attempt to ingest the invader. Instead of being destroyed within the macrophage, they grow and replicate , eventually killing the macrophage. Many new legionella are released into the lungs and worsen the infection. • Legionnaires’ Disease develops 2 – 10 days after exposure to the bacteria. Exposure doesn’t necessarily lead to infection. About 5 – 10% of the American population show serologic evidence of exposure, but never develop symptoms of an infection. Legionnaire’s Disease • Susceptibility – healthy are relatively resistant – impairment of respiratory defenses (heavy alcohol use, smoking, old age) increases susceptibility – hospital patients with underlying immune defects also susceptible Damage to the Lung • Phagocytes, T cells – attracted to lung, do not kill bacteria – release cytokines, other toxic products • Zinc metalloprotease – intranasal, intratracheal challenge of guinea pigs produces compatible lesions – similar to Pseudomonas aeruginosa elastase • enzymatically inactivates IL-2, CD4 receptors on T cells: could inhibit T cell activation • antibodies are protective Symptoms • Early symptoms include lethargy, headaches, high fever, chills, muscle aches, and anorexia. • As the disease progresses, a dry, hacking cough develops. Half of the people who develop Legionnaires’ Disease suffer shortness of breath and a third complain of chest pain. • Although the pneumonia affects the lungs, the disease is accompanied by symptoms that affect other areas of the body such as diarrhea, nausea, and vomiting. Diagnosis • Clinically, the early stages of Legionnaires’ Disease resemble influenza. The advanced symptoms are common to many types of pneumonia. Routine laboratory tests will not detect the presence of legionella bacteria. Patients who have been misdiagnosed as having pneumococcal pneumonia will fail to respond to the usual penicillin therapy given. • If a pneumonia case involves multi-system symptoms, such as diarrhea and vomiting, Legionnaires’ Disease can be suspected. The diagnosis depends on very specialized lab tests involving culture of the patient’s sputum, detection of specific antibodies in the patient’s sera, or detecting the organism in urine. Diagnosis • Culture Live bacterial cells • Fluorescent antibody staining bacterial antigens • Gene probes bacterial DNA • PCR bacterial DNA • Clinical tests (urine, antigen, serology) antigens/antibodies Who Gets Legionnaires’ Disease? • Factors influencing susceptibility include the elderly, those with suppressed immune systems, heavy smokers & alcoholics, and others with weak lungs. Males are over twice as susceptible as females. • Estimates of the number of cases vary from 25,000 to 50,000 a year in the U.S., mostly in the summer. Between 5 – 15% of those who contract the disease die from it. There have been over 50 separate outbreaks. Treatment • Most cases show improvement within 12 – 48 hours of starting antibiotic therapy. The antibiotic of choice has been erythromycin and for best results, it is prescribed together with rifampicin. • Other antibiotics have been used successfully to combat the disease, such as doxycycline and clarithromycin. The type of antibiotic prescribed by the doctor depends on the severity of the infection, potential allergies, etc. Prevention • Elimination of L. Pneumophila from the environment is impossible. However, elimination or reduction of the number of organisms in closed systems, such as hospital and hotel water supplies and cooling towers, have been achieved by means of hyperchlorination or the use of disinfectants. • Studies have shown that high heating of the hot water supplies and removal of contaminated shower heads and gaskets also have temporarily reduced the number of organisms. Prevention • Legionella outbreaks are inevitably linked to neglected A/C cooling towers. They are difficult to keep clean and usually operate at about 35 ºC, within the bacteria’s optimal growth range. • Two critical factors for domestic water services are water cleanliness and water temperature: dirty water provides a food supply for the bacteria. Colonization is most likely between 35 – 40 ºC. It is important to avoid long-term storage of water. • Cooling towers and humidifiers should be examined and cleaned regularly. Cooling towers must be registered with the local authority and biocides may be added to the water. RISK MANAGEMENT • • • • • • • Risk assessment Regular monitoring Temperature control Water Treatment Maintenance & Cleaning Annual review Awareness Nemco U T I L I T I E S