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Chlamydia and Chlamydophila (Chlamydia)

Chlamydia and Chlamydophila (Chlamydia). Family: Chlamydiaceae. Genus: Chlamydia C. trachomatis - Urogenital infections, trachoma, conjunctivitis, pneumonia and lymphogranuloma venerium (LGV) Genus: Chlamydophila C. psittaci - Pneumonia (psittacosis)

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Chlamydia and Chlamydophila (Chlamydia)

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  1. Chlamydia and Chlamydophila (Chlamydia)

  2. Family: Chlamydiaceae • Genus: Chlamydia • C. trachomatis - Urogenital infections, trachoma, conjunctivitis, pneumonia and lymphogranuloma venerium (LGV) • Genus: Chlamydophila • C. psittaci - Pneumonia (psittacosis) • C. pneumoniae - Bronchitis, sinusitis, pneumonia and possibly atherosclerosis Note: New taxonomy, previously three species in one genus - Chlamydia

  3. Chlamydiaceae- Microbiology • Small obligate intracellular parasites • Contain DNA, RNA and ribosomes (so not viruses) • Inner and outer membrane (like Gram - bacteria) • Lipopolysacchride (LPS) but no peptidoglycan • Cell wall not well characterized • LPS has weak endotoxin activity • Energy parasites • Can’t make ATP

  4. Physiology and Structure • Elementary bodies (EB) • Small (0.3 - 0.4 µm) • Extracellular form • Rigid outer membrane • Major outer membrane protein (MOMP) unique to species and variations result in serovars • Disulfide linked proteins (OMP2), highly conserved in family, gives stability • Resistant to harsh conditions (spore-like) • Non-replicating, non-metabolically active form • Infectious form • Bind to columnar epithelial cells (and macrophages in LGV)

  5. Physiology and Structure • Reticulate bodies (RB) • Larger (0.8 - 1 µm) • Intracellular form • Fragile membrane • Fewer disulfide bonds (missing OMP2) • Metabolically active form • Replicating form • Non-infectious

  6. Developmental Cycle of Chlamydia • EB bind to host cells • Epithelial cells • Macrophage (LGV) • Internalization • Endocytosis • Phagocytosis • Inhibition of phagosome-lysosome fusion (if EB outer membrane intact) • Reorganization into RB • Breakdown of disulfide bonds • Growth of RB (binary fission)

  7. Developmental Cycle of Chlamydia • Reorganization into EB • Inclusion bodies (one way to distinguish between species) • Release of EB • Lysis -C. psittaci • Extrusion - C. trachomatis and C. pneumoniae

  8. Chlamydia trachomatis • Trachoma • Inclusion conjunctivitis • Infant pneumonia • Ocular lymphogranuloma venerium • Urogenital infections • Reactive arthritis (Reiter’s syndrome) • Lymphogranuloma venerium

  9. C. trachomatis • Biovars - biological variants • Trachoma • LGV • Mouse pneumonitis (mouse model of disease) • Serovars - serological variants • Different Major outer membrane proteins • A through L

  10. C. trachomatis - Serovars and associated disease Serovars Diseases A, B, Ba, C Trachoma (trachoma biovar) D - K Urogenital tract disease (trachoma biovar) L1, L2, L2a, L2b, L3 Lymphogranuloma venereum (LGV biovar)

  11. C. trachomatis-Pathogenesis and Immunity • Infects nonciliated columnar, cuboidal, and transitional epithelial cells (and macrophages in LGV) • Down regulation of Class I MHC • Infiltration of PMNs and lymphocytes • Lymphoid follicle formation • Fibrosis • Disease results from destruction of cells and host immune response • No long lasting immunity; reinfection results in inflammatory response and tissue damage

  12. C. trachomatis - Epidemiology • Ocular infections - Biovar: trachoma • Worldwide • Poverty and overcrowding • Endemic in Africa, Middle East, India, SE Asia • United States - American Indians • Infection of children • Transmission: droplets, hands, contaminated clothing, flies, contaminated birth canal • Damage to eyes is not seen immediately

  13. C. trachomatis - Epidemiology • Genital tract infections • Biovar: trachoma • Most common STD in US • 2006: USA = 1,030,911; SC = 22,351 • 2007: USA = 1,025208; SC = 31,086 (612 reported /100,000 population in SC, only MS, AL, DC had higher rates) • ~ 50 million new cases/year worldwide • Biovar: LGV • Humans are only natural host • Prevalent in Africa, Asia and South America • Sporadic in USA • 300 -500 cases/year • Male homosexuals are major reservoir

  14. Clinical Syndrome -trachoma(C.trachomatis biovar: trachoma) • Chronic or repeated infection (A - C serovar) • Follicle formation on conjunctiva • Scarring of the conjunctiva

  15. Clinical Syndrome -Trachoma • Eyelids turn in and abrade cornea • Ulceration • Scarring • Blood vessel formation

  16. Clinical Syndrome -Trachoma • Flow of tears impeded • Secondary infections occur

  17. Clinical Syndrome -Trachoma From: G. Wistreich, Microbiology Perspectives, Prentice Hall

  18. Clinical Syndrome -Trachoma

  19. Clinical Syndrome -Trachoma

  20. Clinical Syndrome - Inclusion Conjunctivitis(C. trachomatis biovar: trachoma) • Associated with genital chlamydia (Serovars D -K) • Mucopurulent discharge • Corneal infiltrates, vascularization and scarring can occur • In neonates infection results from infected birth canal • Apparent 5-12 days after birth • Ear infection and rhinitis often accompany ocular disease

  21. Clinical Syndrome - Infant Pneumonia (C. trachomatis biovar: trachoma) • Associated with genital chlamydia (serovars D - K) • Infection arises from contaminated birth canal • Wheezing cough and pneumonia but no fever • Often preceded by conjunctivitis

  22. Clinical Syndrome - Ocular Lymphogranuloma Venereum (C. trachomatis biovar: LGV) • Associated with LGV serovars (L1 - L3) • Conjunctivitis and associated lymphadenopathy (can infect macrophages)

  23. Clinical Syndrome - Urogenital Infections (C.trachomatis biovar: trachoma) • Females • Asymptomatic (80%) • Cervicitis, urethritis and salpingitis (fallopian tubes) • Postpartum fever • Increased rate • Premature delivery • Ectopic pregnancy

  24. Clinical Syndrome - Urogenital Infections (C.trachomatis biovar: trachoma) • Males • Symptomatic (75%) • Urethritis, dysuria and pyuria • Cause of nongonococcal urethritis (35 - 50%) • Common cause of postgonococcal urethritis (might have both bacteria and so both will need to be treated)

  25. Time Course of Untreated Chlamydial Urethritis in Males

  26. Clinical Syndrome - Reactive arthritis* • Conjunctivitis, polyarthritis and genital or gastrointestinal inflammation • Associated with HLA-B27 (MHC class I surface antigen associated with certain autoimmune diseases) • 50 - 65% have C. trachomatis infection • 80% have antibodies to C. trachomatis *AKA Reiter syndrome. Why replace with reactive arthritis? See Panush et al. (2007) Arthritis and Rheumatism, 56:693-694.

  27. Clinical Syndrome - Lymphogranuloma VenereumC. trachomatis (biovar: LGV) • First stage • Small painless vesicular lesion at infection site • Fever, headache and myalgia • Second stage • Inflammation of draining lymph nodes • Fever, headache and myalgia • Buboes (rupture and drain) • Proctitis • Ulcers or Elephantiasis

  28. Patient with LGV Bilateral inguinal buboes (arrows)

  29. C. trachomatis - Diagnosis Iodine-stained inclusion bodies • Cytology • Iodine-staining inclusions (glycogen) • Need tissues to see this not just pus • Not sensitive • Culture • Iodine staining inclusions • Infect cell lines • Most specific

  30. C. trachomatis - Diagnosis • Antigen detection (ELISA or IF) • Group specific LPS • Strain specific outer membrane proteins (to identify serovar) • Serology • Can’t distinguish between current or past infection • Detection of high titer IgM antibodies can be helpful to diagnose current infection • Nucleic acid probes • Several kits available • May eventually replace culture

  31. C. trachomatis - Treatment and Prevention • Tetracycline, erythromycin, and sulfonamides • Vaccines are of little value since there is no immunity with infection • Treatment coupled with improved sanitation • Safe sexual practices • Treatment of patients and their sexual partners

  32. Chlamydophila psittaci • Psittacosis (Parrot fever) • Ornithosis (since all birds can carry)

  33. Pathogenesis - C. psittaci • Inhalation of organisms in bird droppings • Person to person transmission is rare • Hematogenous spread to spleen and liver • Local necrosis of tissue • Hematogenous spread to lungs and other organs • Lymphocytic inflammatory response • Edema, infiltration of macrophages, necrosis and occasionally hemorrhage • Mucus plugs may develop in alveoli • Cyanosis and anoxia • Atypical type of pneumonia

  34. Epidemiology - C. psittaci • 50 - 100 cases per year in USA • Organisms present in birds (symptomatic or asymptomatic) • Tissue, feces, feathers • Primarily an occupational disease • Veterinarians, poultry workers, zoo keepers, pet shop workers

  35. Clinical Syndrome - OrnithosisUncomplicated Infection • Incubation period • 1-2 weeks • Fever, chills, headache, nonproductive cough, mild pneumonitis • Recovery • 5-6 weeks

  36. Clinical Syndrome - OrnithosisComplicated Infection • Incubation period • 1-2 weeks • Fever, chills, headache, nonproductive cough, mental confusion, pneumonitis, cyanosis, jaundice • Prolonged Recovery • 7-8 weeks

  37. Laboratory Diagnosis - C. psittaci • Serology (Complement fixation test) • fourfold rise in titer • requires paired samples

  38. Treatment and Prevention - C. psittaci • Tetracycline or erythromycin (sulfonamides do not work) • Quarantine of imported birds • Control of bird infection • Antibiotic supplementation of food but this may lead to resistant strains

  39. Chlamydophila pneumoniae • TWAR agent • Two isolates that ended up being identical: Taiwan (TW-183) and acute respiratory isolate (AR-39) • Atypical pneumonia • Atherosclerosis ?

  40. Pathogenesis - C. pneumoniae • Person to person spread • Respiratory droplets • Bronchitis, sinusitis, and pneumonia

  41. Epidemiology - C. pneumoniae • Common infection (200,000 - 300,000 cases per year) • Primarily in adults • Most infections are asymptomatic • Associated with crowded conditions • Schools, military bases, etc. • Association with atherosclerosis • Organisms in arterial lesions • Antibodies to C. pneumoniae

  42. Clinical Syndrome - C. pneumoniae • Mild or asymptomatic disease • Pharyngitis, bronchitis, persistent cough, and malaise • Atypical pneumonia may develop • Usually a single lobe

  43. Laboratory Diagnosis - C. pneumoniae • Serology • Fourfold rise in titer in paired samples

  44. Treatment and Prevention - C. pneumoniae • Tetracycline or erythromycin (not sulfonamides) • Difficult to prevent transmission • No vaccine

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