Biology 216 - Lect 21
Salmonella
I. Salmonella - range from gastroenteritis to 
	enteric fevers (typhoid)
	A. Bact - Tribe Salmonellae (Most H2S+) - 
		Salmonella (man and animals):
		Arizona (now Salmonella - reptiles and man); 
		Citrobacter (animals and soil)
		1. Classification schemes - 
			Kauffmann/White - O-Ag (2500 species)
			Ewing and CDC - clinical basis (3 species) -
				 S. enteritidis, S. cholerae-suis, S. typhi (man)
				Kauffmann O-Ag as serovar:
				 Ex. S. enteritidis serovar pullorum
			DNA homology - One species, 6 subgroups 
				(no correlation with clinical)
			Zinsser uses one species: S. enterica subspecies xxxx
		2. Biochemical - Lac-, H2S+, very bile resistant 
			(media and gall bladder)
		3. Other - Vi capsule (S. typhi - intracellular survival and 
				antiphagocytic)
			Rough vs smooth associated with virulence 
				(resist complement mediated lysis)
			Enterotoxin - CT related by a few strains.
			S. enteritidis genetics - Ames test.
			Range of hosts: S. typhi (man); others 
				have animal reservoirs.
	B. Pathogenesis virulence: 
		S. enteritidis < S. cholerae-suis < S. typhi
		Genetics of cellular invasion well characterized.
			Chromosomal (invasion) and plasmid 
			(plasmid enhance virulence)
		1. Gastroenteritis - "stomach flu" - 
				food poisoning (infection)
			Estimated 2 million/yr in US
			a. Reservoir - animal GI (normal); fowl, cattle, 
				turtles (300K in 1970), dogs/cats (1 %)
				Subspecies often reflects reservoir: 
					Ex. S. enteritidis serovar pullorum (chicken)
				Subspecies vary in virulence: Ex. serovar Dublin
				Foods contaminated during processing:
					 chicken, milk, eggs. Classic cutting board.
			b. Ingestion:ID50 approx 10(6) - 10(9), 
				colonization (sm and lg);invasion of mucosal cells
			c. Symptoms - 8 - 24 hr incubation, fever,
				 headache, myalgia, diarrhea (mild)
			d. Blood, mucus, pus rare; Self limiting; 
				may secrete for months or years (1 % of cases).
		2. Enteric fevers (typhoid fever is more severe) - 
			invasion not restricted to GI.
			Animal models: mouse and tissue culture.
			a. Reservoir - man only (S. typhi) - controllable 
				by sewage treatment and sanitation.
				1900 - 300K cases in US (35K deaths); 
				Today 400 cases/yr - not endemic.
			b. Transmission - Contaminated food 
				(handlers as carriers; 3 % lifetime carriers)
				Typhoid Mary (Mary Mallon) -
					1900; cook in NY city; 
					offered gall bladder operation, 
					refused, so imprisoned 3 years - 
					200 cases traced to her.
			c. Colonization - ID50 approx 10(6); Multiply -> 
				M-cells -> Macs -> messenteric nodes (Peyer's)
				Note: Macs attached to M-cells 
					stimulate T and B -> IgA -> 
					stimulated B cells at other mucosal surfaces.
				Induced phagocytosis - ruffling 
					cell surface by actin rearrangement.
			d. Invasion - Phagocytosed by Macs 
				(survive ie CMI important) -> 
					liver,spleen, skin,bone
			e. Disease - Gradual onset (2 - 4 weeks); 
				High fever (104 F); delerium, Exhaustion,
				splenomegaly, rose spots (thick, raised, 
					upper abdomen): all LPS mediated.
			f. Liver to gall bladder - reseeding small intesting -> 
					diarrhea, intestinal perforation.
				Colonize gall bladder (survive bile), 
					scarred tissue, stones, 3 % lifetime carrier.
			g. Complications - spleen rupture, abscess in organs, 
				peritonitis, shock (LPS)
				GI perforation.
			h. Duration - 3 - 4 weeks, CMI, 
				10 % fatality w/o treatment, 
				10 % relapse, 3 % carriers.
	C. Diagnosis - Non-typhoidal vs typhoidal
		1. Non-typhoidal - High, moderate and enrichment. 
			Feces in acute, but few later, ID.
		2. Typhoid - History (travel)
			a. Culture - Fecal - early and 3rd week (after reseeding); 
				Blood, urine, rose spots during acute infection (weeks 1 - 4).
			b. ID - biochemical; Serology (Widal agglutination)
	D. Treatment - 
		Non-typhoidal - self limit, rehydrate, pain relief, 
			antibiotics (little effect, may prolong).
		Typhoid - Fever control, fluids (sweating),
		 antiinflammation (LPS), antibiotics.
	E. Prevention and control
		1. Sanitation control - water, sewage, 
			Typhoid Carrier Registry, Bladder removal.
		2. Prevent recontamination of foods, refrigerate.
		3. Vaccine - Typhoid Fever 
			Field trials for new vaccine in 
				endemic countries - Nepal
			Three vaccines: killed, Vi, ty21
			1. Old killed bacteria (phased out)- fever, flu-like
			2. Vi capsule - some protection; 
				Protein capsule conjugate - better.
			3. Live attenuated (ty21a) in capsule; 
				Auxotroph, penetrate, replicate, die, CMI
			   ty21a as delivery for cloned vaccines to other
				 enteropathies: rotavirus, LT-B, ST....
				In trials this has worked to protect from 
					Shigella, not cholera (cloned O-Ag).
				Genes for sIgA against human sperm 
					(works in mice) for birth control