Bio216 Lecture - Syphilis (Treponema pallidum)
Syphilis - Treponema pallidum - Spirochete, 3 stages, 
	penetrate between cells... similar to Lyme.
A. Bacteriology - Diameter too small to resolve by 
		light microscope - darkfield or phase contrast.
	Little known, because never grown in lab. Reports of 
		replication in tissue culture. High titer rabbit testes.
B. Disease - 25K/yr in US (Increased in mid 1980s, 
		then decline - probably due to AIDS scare)
	1. Origins - Migration from Africa to Europe, new population, 	
			acute, 25 % fatality; or Columbus' crew.
		(Based on pre-1492 bone lesions in America), 
			1495 epidemic in Europe.
		Currently - balance, chronic, but still devastating
		1927 - Nobel prize to Julius Wagner-Jauregg for malarial
				 treatment of syphilis, then cure with quinine.
		1930s treatment withheld from 100s of blacks to follow 
				progression of disease in Macon, GA
		Ehrlich's arsphenamine 606 treatment used for years, 
			then discontinued.
	2. Transmission - Direct contact (susceptible to drying), 
				human only, low transmission rate 10%
		Venereal from primary or secondary; 
				Open sore or mucus membrane
		Transplacental (4th month on) -> congenital syphilis
		High incidence in homosexual men, AIDS, 
				due to hidden rectal lesions.
	3. Clinical 3 stages - note similarities with Lyme - 
				30 hour generation time.
		a. Primary - 2 - 10 weeks; usually symptomatic
				 (may be overlooked in women - cervix, vaginal) 
			Local infection of capillary endothelial cells -> 
				obstruction inflammation, edema,
				necrosis from decreased blood flow, 
				raised border, non-painful  ---> CHANCRE
			Indurated, non-painful, last few weeks, then spontaneously heals. 
			Exudate full of spirochetes, resolves by fibrosis in weeks -> scar
			Bilateral inguinal lymphadenopathy, ie systemic at this point.
			Invades between endothelial cells -> invasion; 
				CMI arrests infection in 75 % of cases.
		b. Secondary - 6 - 8 weeks following primary. 
				1/3 perianal/vaginal warts (condylomata)
				Flu-like, generalized lymphadenitis, skin rash
				 (trunk, palm, sole), white patches in mouth.
				Highly infectious stage - Many treponemes 
					in lesions and mucosa.
				Heal in several weeks: Probably survive in endothelial cells; 
					50 % develop symptomatic tertiary
		c. Tertiary - 3 - 30 years later (10 % of all untreatd cases) -
				 Immune sequela, non-infectious
				    (Immune complex most likely, but may be autoimmune)
				Gumma - benign or destructive granuloma of 
					internal organs, bone, skin, 
				    (vascular occlusion and necrosis)
				Neurosyphilis - Cortical degeneration, pain in 
					arms or legs, loss of motor coordination
					(ataxia), blindness, memory loss, 
					hallucination, psychosis.
				Cardiovascular syphilis - vascular damage
					 (endothelial inflammation), arteritis,
					loss elastacity -> aneurysm of aorta (ballooning), 
					valve thickening, occlusion, clot, heart attack
		d. Congenital - transplacental after 4th month 
				(chorion degenerates, organisms enter)
				Placental endothelial barrier breached.
				Reason for marriage blood test, not required 
					after 1996 (no blood test for marriage)
				Transmission during primary or secondary -> 
					arrested development; >1000 live births/yr in US
				25 % stillborn; 25 % death soon after; 
					40 % survive w/defects (deaf, mental retard, learning 
					disability long bone deformity (bones don't connect), 
					blindness, Hutchinson's teeth, 
					saddle nose); 10 %healthy
				Preventable by treating mother. 
				Teeth and nose apparent by 2 years age.
C. Lab diagnosis - serology most important	
	1. Direct exam - darkfield, Fl-Ab
	2. No culture
	3. Serology -
		a.  Non-treponemal - test reagin, Ab which react 
				with cardiolipin (autoAb); Negative in 2 years,
				so measure of cure.
		Wasserman (CF); Originally syphlitic fetus Ag
				 thought to be Treponeme, 
				1906 fetal liver + serum -> flocullaton. 
				Ab was to cardiolipin (mitochontrial lipid).
				Control (non-infected) fetal liver also gave positive.
		Mechanism - tissue damage releases cardiolipin from cells -> 
				Ab response.
		VDRL (flocculation); RPR card agglutination 
				(Rapid plasma reagin) - black particles on white card
		Problems: Prozone; biological false + (autoimmune, 
				mononucleosis, hepatitis, malaria, pregnancy....
		b. Treponemal (if positive non-treponemal) - 
				Use treponemal Ag; 
				Negative IgM if treatment; IgG + for life,
				so not measure of cure.
				Ex. TPHA: RBC w/ treponema coating + serum -> HA
				        FTA (fluoresecent treponemal Ab): 
				        IFA using serum absorbed w/Reiter strain (FTA-ABS)
					to remove group Ag (to normal flora treponemes)
D. Treatment - Penicillin for primary or secondary (become 
				reagin negative in one year)
		Jarisch-Herxheimer - Therapeutic shock - flu-like due to 
				sudden release of Ag (24 hours later)
			Due to LPS release, IL-1, TNF. 50 % ofprimary and  
				90 % of secondary.
		Tertiary - Antiinflammatory therapy
E. Prevention - Condoms; Vaccine - none since
	 not grown (several surface Ag cloned into E. coli)