Lyme Disease
Family: Spirochaetaceae - long slender, coiled, motile, 
	grow slowly, systemic ->Treponema, Borrelia
Family: Leptospriaceae - Leptospira
Genera: Treponema - syphilis; Leptospira - liver, meninges, 
		kidney; Borrelia - Lyme, Replasing fever.
	Large (30 um), darkfield of lesion, axial filament 
		(flagella wrapped in sheath), linear x-some/plasmids
I. Lyme Disease - Borrelia burgdorferi
		 (#1 reportable tick-borne disease over RMSF; 
			16,000 reported every year to CDC)
	Slow growth, several animal models (rabbits)
	Penetrate capillary endothelia -> long term survival in host
	Virulence correlates w/ OspB (mutants less
		 invasive and less inflammatory)
	A. General - First in 1975 in Lyme Co Connecticut;
		 Mother called health dept on kids w/arthritis 
		12  cases/town of 5000, bulls-eye rash (>5 cm),
			 tick exposures; 
			Blood sent to Rocky Mtn  NIH in Montana (Rickettsial?) 
		Described before in Europe, thought to 
			be bacterial (antibiotics); US thought viral.
		1978 reported in CA. Old disease now understood 
			due to increase white tail deer population in Lyme
	B. Epidemiology - East (Ixodes dammini -deer tick); 	
		West (Ixodes pacifica - western black legged tick)
		Not Dermicentor (dog tick); Both ticks very small. (nymph <1 mm)
		1. Cycle in nature - tick-> mouse -> 
				tick (2 year life span - not transovarial)
				Disease in deer, dog, horse, cat, human 
					(human due to nymph and adult stages)
				Nymph - 1 mm undetectable; 
					Engorged detectable (10 hours)
			     Up to 80 % ticks infected in endemic areas 
				(tested by FA of tick mdigut pools)(capture w/ flannel bags)
				Some cross reactivity with B. hermsii
		2. Geographical distribution of tick dictates disease - 
				43 states in US; 16,000 in 1996; 90 % east coast (NY #1)
				Notifiable in 1990
		3. Butte Co (50 cases/yr) - 1000-2000ft Berry/Loafer creek, 
				Concow (chapparal/Ponderosa Pine).
				Approx 5 % tick carriage in lower Ponderosa Pine
				2 % of dogs tested seropositive (dogs as sentinels)
		4. Increase due to: increase deer population in Lyme Co, 
				human encroachment; awareness elsewhere
	C. Pathogenesis  - Animals; Swollen joints, arthritis, Bell's palsy
			Symptoms soley from inflammation (no exotoxins) - 
				due to Osp and lipoproteins.
		1. Transmission - tick bite(questing in grasses/bushes); 
					often inapparent (only 30 % recall tick bite)
				Never person->person (except transplacental - 
					rare for bacterial infections; also Treponem)
				Spring and early fall in Butte Co 
				(Low questing in summer heat)
				Several transplacental cases per year.
		2. Three stages (most spirochete infections; Ex. Syphilis) - 
				early easiest to treat; Later immune sequela.
				Like syphilis: Invade between cells into tissues
				 (OspB correlates); transplacental; 
			   Stage 1 - 
				Erythema chronicum migrans (ECM) - 
					85 % pathognomonic, Bull's eye rash
				Slowly expands, appears 1 week after bite.
				Large (several cm) spreads, clear in center, site of bite, 
					disappear in few weeks.
				Not yet seropositive (low level IgM); 25 % self resolve.
				Overlap with stage 2
				Killed by Ab + complement
		     Stage 2 - Hematogenous spread -> arthritis (knee most common)
				Several weeks, Flu-like(fever, myalgia, chills) (several days); 
				Myocarditis - heart congestion (arrhythmia) - 10 % of cases
				Neurologic - headache, Bell's palsy (rare in CA lyme cases)
				(10 % of cases)
				Few cases of in utero transmission -> stillbirth
		    Stage3 - Chronic debilitating arthritis, numbness, muscle pain - 
				60 % of untreated cases.
				Possibly autoimmune
				 (anti flagellin x-reacts w/nerve and cardiac), 
					correlates with high Abtiter 
				May reside in endothelia of capillaries or coat self w/host Ag
				Bacteria not recovered.
				Larger joints affected.
				10 % of 3rd stage develop chronic arthritis 
				(associated with rheumatoid arthritis HLA-MHC II type).
	D. Diagnosis 
		1. History - tick bite, endemic area, ECM, 
				May mistake allergic rxn to tick bite.
		2. Culture - unreliable - recovered from skin lesions
		3. Serodiagnosis - not reliable yet - Low IgM in stage 
				1 - 50 % positive (Possibly due to Ag masking).
				Many false positive and especially negatives.
				Humans slow to respond to OspA and OspB 
				(these are protective Ab, but too late to control).
				Test Ag is flagellin and internal antigens. 
				Higher titer in stages 2 & 3
				IFA and ELISA many false positive
				 (cross react with Ab to normal flora Treponema)
		4. Exptl - PCR
	E. Treat - Antibiotics effective in stages 1 & 2 (less so in stage 2)
		Antiinflammatory for stage 3 (immune sequela)
	F. Prevention
		1. Protective clothing; socks in pants; repellants
		2. Careful removal of ticks
		3. Pet flea/tick collars
		4. Dog vaccine recently approved, 
				but efficacy is controversial.
		5. Human vaccine: Recombinant Osp
	G. Future - Better diagnostic tests - PCR of lesion
		Vaccine development
		OspA has multiple serotypes
		Research at NIH in Hamilton, MT
II. Relapsing Fever - Borrelia recurrentis, Ag shift, 
		Tick associated, 4 - 10 relapses.