Biology 216 - Lect 23 - Plague
I. Y. pestis - plague (refers to any pandemic, 
	but medically refers to this organism)
	A. History - 6th century 100 million deaths 
			in North Africa;
		1350 AD (4 years, 1/4 or Europe) 
			Black Death 25 million in Europe 
			Kaffa (Jaffa) trade route (by Black Sea) 
				war over control:
			Doorway to East. Mongols catapulted bodies 
				which may be introduction to Europe.
			LPS + toxin 
				- hemorrhage subcutaneous -> dark spots
			Treatment: Bath in urine, 
				place dead animals in homes.
			Doctors: Bird beak with filter and 
				perfume to disinfect
		Today approx 1000/yr worldwide
	Oct94 MMWR - India epidemic.
		5150 cases, 53 deaths, several hundred 
			pneumonic, shipped tetracycline
		1 % fatality suggests: not true cases; 
			deaths underrepresented; antibiotics early.
      B. Bacteriiology
	1. LPS - Endotoxemia 
		(Fever, chills, weight loss, shock)
	2. 70 kb plasmid - code Yops 
		(affect signal transduction and 
			cytoskeleton of host cells)
		Yops regulated by V-Ag (LcrV)
		Fraction 1 (Fra1) - antiphagocytic capsule.
		Pla1 - protease that activates plasminogen -> 
			plasmid -> dissolve clots.
	B. Pathogenesis
		1. Transmission - Endemic in mammals 
				(even developed countries - SF in 1900)
			Approx 50 cases/yr in US: outdoor activity.
			Highest in SE Asia (rats in rice fields) - 
				vaccine given to military in these areas
			a. Ecology of transmission - Vector - 
					certain fleas (dog/cat flea poor vector)
				Transmitted in animal population by
					 flea, urine, feces
				Flea ingests Yersinia 
					(rodent may have 10(8)/ml blood)
				Yersinia coagulase in midgut -> 
					blocks gut few weeks, multiply.
				Regurgitate and defecate into wound - 
					less selective about host.
				Fleas may live for years in soil 
					around rodent burrow.
			b. Urban plague - enzootic in urban rats 
					(Xenopsylla cheopis - rat flea)
				Not problem in US due to sanitation
				Problem when ships comes into port 
					(genetically and immu susceptible populat)
				No herd immunity; Rat dies; 
					Fleas seek another warm body.
			c. Sylvatic plague - Enzootic in wild rodents 
				(ground squirrels, chipmonk, prairie dog)
				This is reservoir of concern in US (CA, NY, Ariz)
				Animal disease - asympt to severe, 
					depends on immunity and genetic factors.
				Epizootic - susceptible population. 
					High mortality.... Sierras, SF.
			Human infection - flea bite; 
				Ex. Child comes across dead or dying animal.
		2. Local multiplication - No V & W or Yop,
				 so intracellular killing.
			Some begin to express Yop,
				 and survive in Macs.
		3. Drain to local node - 2 - 6 days
			Further multiplication;
				 hemorrhagic inflammation.
 	 4.  Drainage to local nodes.
		LPS - Hemorrhagic inflammation, 
				chill, fever, pain in area.
			Hemorrhage -> black gangrenous areas
		Bubos - Inflammation of draining node 
			(ie bubonic plague).
		Node - swollen, tender, painful, may 
			suppurate to surface (size of orange)
		Inguinal most common (groin)
		May be hemorrhagic and painful at 
			site of bite. Conjunctivitis
    	5. Low level bacteremia - progressive 
		infection of internal organs.
    	6. Systemic phenomena - fever, edema, DIC, shock. 
		Not communcable at this stage.
   	7. Extension to lung (5 - 20 % of cases) -> 
			pneumonic plague.
		Only form contagious w/o flea 
			(droplet transmission)
		Bloody, edematous pneumonia -> 
			poor gas exchange, dissemination, shock
 	8. Mortality: 50 - 80 % untreated; 10 % treated; 
		25 % average, since often not suspected.
B. Diagnosis
     1. Clinical picture: History; exposure to animal; 
		Rapid onset (bubos, conjunctivitis)
	Similar to tularemia (Francisella tularensis) - 
		ticks, skinning rabbits, ulcer, bubo.
	Immediate treatment
     2. Isolation and ID - usually Public Health Lab 
		contained (gloves, hood, SFSU outbreak)
	Specimen - bubo aspirate, sputa, blood
	ID - biochemicals, Fl-Ab
      3. Serology - not done; patient dead by 
		time of seroconversion.
C. Treatment - Quarantine patient and contacts.
	Antibiotics: Streptomycin (also covers tularemia)
		1997: Plasmid-mediated multiple 
			drug resistance in Madigascar.
D. Prevention
      1. Avoidance of animal burrows.
	Close public camping during epizootic
		 outbreaks (rodent serologic surveys)
       2. Flea and rodent control (Flea first)
	Impossible to eradicate sylvatic.
       3. Quarantine and treat patient and contacts.
       4. Vaccine - formalin killed for high risk groups 
	(researchers, Donna Murrill, 
		travel to endemic, Vietnam)
	Side effects, low protection, 
		short term protection.
        5. Ship docking practices to prevent 
		escape of rats and fleas - fumigation.