Biology 216 - Lect 33 - Chlamydia
I. Chlamydia in General
	A. Bacteriology - Obligate intracellular (Induce phagocytosis 
			by all cell types (epithelia, phagocytes))
		Grow within phagosome (inhibit phago/lysosome 
			fusion or escape lysosomal contents).
		Degenerative evolution: 
			Use host ATP, enzymes, nucleic acids.
		Developmental cycle - differentiate into two forms.
			1. Elementary body - extracellular 
				infectious stage (small than bacteria) 
				Attach to host cells (tropism for columnar 
					epithelial cells of mucus membranes) - 
					Basis of Ag tests
			2. Reticulate body - metabolically active; 
				Multiply into colony in cell (Membrane bound inclusion)
				Many infectious elementary body progeny
					 produced and released upon cell 
					rupture or exocytosis
	B. Diagnosis
		1. Direct exam -  Iodine or Giemsa stain for inclusion body 
			(not easy to find) - Stain glycogen coat of retic body
			Old way - Culture in McCoy cells (egg, tissue culture)
				 48 hours - look for inclusion (amplified)
		2. Antigen detection - Fluorescent antibody for 
			elementary body (Microtrak); ELISA
		3. Serodiagnosis - not routine since most surface; 
			Only with invasive C. psittaci; C. trach serology does exist.
		4. DNA probes available and widely accepted.
II. C. trachomatis (misleading name since many serovars
			 and disease - TRIC Agents)
	A. Trachoma - keratoconjunctivitis (inflammation of cornea) -> 
			partial or total blindness (millions)
		1. Pathogenesis - high virulence serovar (A - C); Person -> 
				person clothing, towels -> eye.
			Local infection - inflammation (pyogenic); 
			Neovascularization and hypertrophy.
			Single infection is mild; Chronic -> opacity, ulceration,
				secondary infection. Progressive damage over years
			Scaring of conjuctiva -> pebbly appearance
		2. Diagnosis - Clinical picture; Inclusions in epithelia of eyelid
			 and pebbly appearance; Fl-Ab
		3. Treatment (local antibiotics); 4. Prevention - personal hygiene.
	B. Inclusion conjunctivitis - lower virulence serovar (D - K)
		1. Pathogenesis - Adults (unchlorinated pools and direct); 
			Neonate from birth canal.
			Local inflammation and inclusions. Problem if chronic. 
			Also mild pneumonia 
	C. Non-gonococcal urethritis (NGU) - 
		Same serovar as inclusion conjunctivitis
		NGU - 50 % Chlamydia. Remainder Mycoplasma, Ureaplasma, 
		1992 reportable to CA State Dept not CDC. 
		Estimated 4 million/yr in US; 1/2 million PID;
		Reportable nationally 1996
		1. Pathogenesis - STD, Local colonization, 
			Most asymptomatic, 
			Same as GC including complications
		2. Diagnosis - Clinical suspect GC or NGU. 
			Direct smear PMN w/o Gm negative intracellular diplococci
			Ag detection: ELISA (Chlamydiazyme); Fl-Ab (Microtrak)
			No culture (Used to inoculate McCoy cells); DNA probe to rRNA
		3. Treatment - antibiotics.
		4. Prevention - Erythromycin in eye of neonate 1 hour after birth.
III. C. psittaci - zoonosis in bird populations (crowding/stress) - 
		parrot fever, ornithosis, psittacosis; Reportable
	A. Pathogenesis - 100 cases/yr; From secretion of 
			infected birds (parrots, turkey....)
		Birds - respiratory or diarrhea (most severe in parrots, 
			asymptomatic in others)
		Human - Inhalation, lung and systemic multiplication
			 (2 week incubation)
			Lung - Edema, exudate, hemorrhage, 
				bloody sputum, consolidation, anoxia.
			Systemic - Granulomatous liver/spleen, endocarditis, 
				fever, headache, myalgia
			Lasts few weeks; Mortality 20 % w/o treatment, 5 % with.
	B. Diagnosis - History (bird handlers); Lab serodiagnosis.
	C. Treatment - antibiotics
IV. TWAR (Taiwan Acute Respiratory) - 
     A. Chlamydia pneumoniae - similar to Mycoplasmal pneumonia.
        Sequenced 2000
     B. Role in Atherosclerosis?
        1. Correlation between C. pneumoniae and atherosclerosis
           Fl-antibody analysis of plaque material (strong correlation)
        2. Other evidence: Antibody titer, PCR, culturable.
        3. In vitro endothelial cell response to C. pneumoniae
           - Release coagulation factors
           - Release of inflammatory cytokines
        4. Conclusion:
           - Strong correlation
           - Cause or effect?
           - Initiate or contribute?