Biology 216 - Lect 34 - Legionella
I. Legionaires Disease - historical
	A. 1976 - Legionaires Convention (Philadelphia)
		221 cases of severe pneumonia (21 % fatality); 
		Most had attended convention at hotel.
		Remainder - Broadstreet pneumonia (walked by hotel)
		Hotel closed until cause discovered.
	B. Etiology - no infectious agents cultured or 
			observed in tissues
		No bacteria; No transmission to family members; 
		Histology similar to toxic agent: 
			Tested for cadmium, nickel.....
	C. What would you do? 6 months later: Lung -> 
			guinea pig -> same disease,
		Recover bacteria from blood (very rich media, stains poorly)
		How to show human disease due to this bact? 
			Ab in convalescent serum to bact.
	D. Retrospective studies: Past mysterious outbreaks
		1968 - Pontiac Fever: 95 % Health Dept workers 
			developed fever, headache, diarrhea, chest pain
				No fatalities; All sera tested positive.
		1965 - St Elizabeth Hosp (East Coast) - 
			20 % fatalities; Sera test positive.
		Unexplained outbreaks in 1940's: Sera test positive.
II. Legionella pneumophila (14 serotypes and 29 species now): 
		L. pn serogroup 1 most common.
	A. Bacteriology - long Gm negative rods, stain poorly 
			(counter with fuchsin)
		Very fastidious - Cys auxotroph;  inhibited by unsaturated FA; 
		Buffered Charcoal YE (CYE) + Antibiotics
		Products: Chromosomal B-lactamase; 
			Cytotoxin block O2 burst during phagocytosis (No H2O2)
			Protease: purified -> lung damage, 
				but mutants still virulent. Significance inconclusive.
		Facultative intracellular in PMN, Mac, epithelia; 
			Grow in phagosome; CMI protects
		In nature: survive in distilled water years; 
			Grow in algae and amoeba; 
			Found in most water supplies, rusty water
	B. Pathogenesis - Serotesting epidemiology -> 
		2 - 22 % seropositive adults; most asymptomatic.
		Estimated 50K pneumonia/yr in US; 
			Outbreaks continue to occur (isolated from Hosp shower head
			Hottub outbreak; Incidence increasing due 
				to central AC in large offices; 
			Contamination of inhalation therapy
		1. Reservoir - water (tanks, cooling systems, shower heads, streams, 
			Holt Hall roof 10(3)/ml serogp 1), biofilms
			Grow intracellular in acanthamoeba and Naegleria  
				and survive in amoeba cysts (resist chlorine treatment)
		2. Transmission - Never person-> person; 
			Aerosol (ex cooling system) -> lung (small droplets).
			(Ex. Humidifiers, hotels, factories, hospitals)
			Peak - July - Sept (opposite of other pneumonias) - air coolers
			Predisposition - Legionaires were 55 - 60, 
				smoked, drank, COPD
			Estimated 20 % of nosocomial pneumonias
			Environmental monitering: 
			Filtration of large volumes of water.
		3. Clinical - asymptomatic (most) -> acute pneumonia
			a. Pontiac Fever - healthier host, fewer bugs, 
				less virulent serovar.
				5 day incubation, flu-like, meningeal signs 
				(stiff neck, photophobia), self limit 5 days.
			b. Legionaires disease - compromised host, 
				more bugs, serovar .
				Acute lobar consolidation pneumonia, 
					pulmonary failure by fibrosis, disseminate
				Fever, chill, cough, gasp for air
	C. Diagnosis - Clinical (x-ray, season, age)
		1. Direct Exam - Fl-Ab (50 % sensitive, 95 % specific)
		2. Isolation and ID - Sputum/bronchial wash -> 
			CYE, 3 - 5 day, ID with Fl-Ab
		3. Ag detection in urine early (ELISA)
		4. Serodiagnosis (seroconversion by take weeks) - 
			IFA, ELISA
		5. DNA hybridization being developed to 
			Legionella specific sequences
	D. Treatment - Antibiotics (erythro, rif, few others) - 
		Portland rif resistance for genetics.
	E. Prevention - 
		1. Disinfection of cooling and water systems
			 (quaternary ammonium compounds)
			Chlorine and heat.
		2. Hospital surveillance to control nosocomial
		3. Other - ubiquitous, so impossible to completely control
                 Survive in protozoans