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Lecture 21 -Legionella

Lecture 21 -Legionella - Post WWII Changes(1950­1970 Post...

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Unformatted text preview: Post WWII Changes (1950­1970) Post WWII Changes (1950­1970) “The war against infectious diseases has been won.” U.S., Surgeon General, 1969 WHO Reports WHO Reports Since 1967, 39 new pathogens identified – Lyme disease (1970’s) – Ebola (1977) – HIV (1981) – West Nile virus (1999) – SARS (2003) hat happens when there is an outbreak of a novel disease Legionnaire's disease (Aug. 1976) Pennsylvania Department of Health was receiving reports of a puzzling illness from around the state characterized by – Fever – Coughing – Pneumonia­like symptoms CDC sent twenty­three Epidemic Intelligence Officers to Pennsylvania Case Definition (Who to Case Definition (Who to investigate?) Who to investigate: 221 people met these criteria – 34 died – Pneumonia – Cough – Fever of 102o F or higher – Onset after July 1 (incubation time of 2­10 days) What do the sick individuals have in What do the sick individuals have in common? In July, most had The press called the disease Legionnaire’s disease – attended the American Legion’s annual convention at the Bellevue­Statford Hotel in Philadelphia Who was getting sick? Who was getting sick? (risk factors) Age: middle aged and older adults more likely affected than young adults and children Lung disease (smokers) Immunodefficient individuals Diabetics Renal disease Cancer Males 3X more likely to be affected than females What is the cause? What is the cause? Symptoms not unique Could be caused by a variety of Tested tissue samples from autopsies of deceased patients (~15% of patients died) Blood samples from living patients – Toxic agents – microorganisms Testing of samples Testing of samples No consistent presence of toxic chemicals or microorganisms Week two: Exactly where was this Week two mysterious disease coming from? (what is the vector?) Cultured dead pigeons, rodents, droppings swabs of everything including the water supply­­­ NOTHING!! Ruled out Ruled out Person­to­person transmission Food borne outbreak Drinking water Extensive interviews Extensive interviews revealed Ill persons spent more time in the lobby or outside on the sidewalk in front of the hotel Suggests that the disease might be spread through the air Hypothesis and Theories Hypothesis and Theories Elevator hypothesis Old air conditioner unit on roof Toxin Air conditioning vent in lobby directly over registration desk – Nothing found – It was cleaned between time of convention and when CDC was called in – No employees were sick and the air condition vent cleaning repairman did not get sick November November Philadelphia outbreak linked to two other previous outbreaks of unknown cause 1965: St. Elizabeth’s Hospital in D.C. 1966: Pontiac, Michigan – 144 cases, no deaths – 81 patients and staff infected, 14 deaths Silver stained lung specimen from a victim of the 1976 outbreak By December (4 month after outbreak), the cause of the illness was still unknown Dr. Joseph McDade /CDC Dr. Joseph McDade /CDC • • Had inoculated guinea pigs with bacterial isolates from patients found presence of bacteria in gp spleen but could not culture them again “Whenever something like this happens — where you have a very large outbreak investigation — most everybody in the laboratory is involved, one way or another, directly or indirectly,” explained McDade. “At that time, they had asked people who were familiar with diseases that usually had a pneumonia­type component to them to do whatever testing was useful and necessary to try to determine whether or not the outbreak was caused by one of the known pathogens. Well, the organism or the disease that we were asked to rule out was the agent for Q fever,” he said. Q fever is a disease that is found in humans, but transmitted by domestic animals, mostly livestock, such as sheep, goats and cattle. “There wasa fairly low probability at that time [that it was Q fever],” he said, “because obviously, there was no livestock involved in downtown Philadelphia.” The first time McDade tried to isolate the organism, he inoculated guinea pigs and found stray bacterium in the spleens, but he could not grow it in embryonic eggs. “When I tried to grow it in embryonic eggs the first time – remember I’m trying to grow Q fever rickettsiae, which are a special kind of intracellular gram­negative coccobacillary – I actually added antibiotics to the suspension to make sure that no bacterial contamination would occur,” he said. He re­examined slides of the spleen of the guinea pigs that were inoculated in August and found a cluster of organisms. This time, he attempted to isolate them in embryonated eggs, but did not add any antibiotics. Success­bacteria grew December 1976 December 1976 Is this the cause or just an Is this the cause or just an experimental artifact? Tested serum specimens of Legionnaires’ disease patients who survived for antibodies to the bacterium More than 90% of the patients had high serum levels of antibodies to the bacterium bacterium Serum from patients Serum affected by the two previous outbreaks also showed high levels of antibodies to the bacterium bacterium Lecture 21 Legionella Lecture 21 Legionella Classification Classification Family Genus Species Legionellaceae Legionella > 48 species L. pneumophila Legionella pneumophilia Legionella pneumophilia Genus Legionella Genus Mildly gram negative bacillus Motile (monotrichious ), temp. sens. expression (less expressed at 37C) Aerobic Non­fermentative and derive energy from the metabolism of amino acids 48 species have been identified – Difficult to stain – Stain best with silver staining techniques ~ 50% have been associated ~ 50% have been associated with human disease L. Pneumophila accounts for 85% Of all Legionella infections Growth Conditions Growth Conditions Growth temperature Growth media (unusual) – Prefers elevated temperatures (>37) – High levels of the amino acid cysteine – Inorganic iron – Low sodium – Charcoal 3­5 days to grow (to absorb free radicals) BCYE selective agar Some species distinguished by Some species distinguished by fluorescence under UV light Legionella pneumophila Legionella bozemanii Where does it live? Where does it live? Found in non­marine, aquatic environments Can survive in tap water at room temperature for more than a year Tends to live as a biofilm associated with certain species of algae and protozoa Legionella biofilm Legionella Biofilm is found on Consists of – Surfaces of lakes and ponds – internal surfaces of pipes – heat exchange surfaces – Water cooling towers – Variety of bacteria – Algae (provide nutrients) – Fungi – Variety of protozoa Legionella Life Cycle Legionella Most common host are a variety of amoebae (nature’s macrophages) Human is accidental host Coiling Phagocytosis Coiling Phagocytosis Legionella Life Cycle Legionella http://www.nature.com/nrmicro/animation/index.html Clinical Diseases Clinical Diseases Asymptomatic Legionella infections are believed to be relatively common Two forms of symptomatic infections :Legionellosis – Legionnaires disease (more severe) – Non­pneumonic form of Legionellosis / Pontiac fever Legionnaires’ Disease Pathogenesis Pathogenesis – 2­10 day incubation – Fever , anorexia, headache (sometime diarrhea and confusion) – Recruited neutrophiles and monocytes, as well as, bacterial enzymes (proteases), produce destructive alveolar inflammation – Severe pneumonia; Respiratory failure if left untreated – Mortality rates vary between 20­50% ! Pathogenesis Non­pneumonic Legionellosis / Pontiac fever (first discovered in Pontiac, Michigan) – Up to 48 hr incubation period – flu like symptoms that self resolve lasting 2­5 days – No deaths Mode of Transmission Mode of Transmission No person­to­person­transmission Infection from air conditioner vent From an aerosolized water source An average relative humidity of 65% – Shower heads – Pipes – Whirlpools – Humidifiers – Respiratory therapy devices (hospitals) – Grocery store misters Laboratory Diagnosis Laboratory Diagnosis Growth on Buffered Charcoal Yeast Extract agar (BCEY) agar Direct fluorescent antibody (DFA) test – Not very sensitive (25%­75%) Urine antigen test Antibodies are serotype specific Need a high concentration of bacteria to detect (difficult due to intracellular nature of Legionella) Nucleic Acid Amplification (NAA) assays: PCR Indirect Fluorescent Antibody (IFA) test to detect antibodies to Legionella (4x increase is considered diagnostic) – Antigen persists in urine for several months Epidemiology (USA) Epidemiology (USA) 8,000 to 18,000 people hospitalized with Legionnaires disease Many infections go undiagnosed Epidemiology: USA Epidemiology: USA Epidemiology Epidemiology People most at risk of getting sick are older people (usually 65 years of age or older) smokers those who have a chronic lung disease (like emphysema). Immunosuppressed Individuals Nosocomial infections! Treatment (Pontiac Fever) Treatment is symptomatic No antimicrobial therapy Treatment (Legionellosis) Treatment (Legionellosis) If untreated may becomes fatal β ­Lactam antibiotics are ineffective because Legionella produces β ­ lactamases Most effective antibiotics are: Erythromycin/Azithromycin (Macrolides) Fluoroquinolones (ciprofloxacin) also used – able to penetrate macrophages Prevention Prevention Identification of the source Monitor water supply in Hospitals/Nursery Homes (most susceptible population) Difficult to kill in water supply Treat water supply with UV (expensive) Working on the development of various biocides (early stages of development) Vaccine development (early stages of development) – – Live inside amoebae Formation of biofilm ...
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