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31 Cards in this Set
- Front
- Back
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Characteristics of Chlamydia
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- gram-negative
- obligate intracellular - unique developmental cycle - ubiquitous - taxonomy (a) new genus = chlamydophila (b) human species = C. tracomatis, C. pneumoniae (c) other ones infect animals |
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Describe the developmental cycle of Chlamydia
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@ 0 hrs: attachment and entry =>
@ 2-5 hrs: redistribution to nuclear periphery => @ 5-8 hrs: early differentiation => @ 8-20 hrs: contact dependent replication => @ 20-40 hrs: detachment and asynchronous late differentiation => @ 40+ hrs: lysis and release of infectious progeny - single elementary body => 500-1000 in 40+ hrs - Basic particle of chlamydia attaches to mucosal surface of epithelial cell => migrates from cellular to nuclear periphery => differentiates to replicated body (like a bacteria that grows and divide) => replicated bodies replicate by binary fission; back wall/membrane called inclusion (bound to periphery of this inclusion) => inclusion occupies most of space in cytosol of infected cell => when no more space available, chlamydia fall off (later differentiation but not infectious) => exocytosis to outside |
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Chlamydia: Differentiate b/w EB and RB
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- Elementary Body (EB):
*0.2-0.4 um diameter (smaller) *1.21 g/ml density (higher) *late developmental stage *infectious *not replicative (no intracellular multiplication) *OM proteins linked by disulfides *compacted DNA w/ histones *doesn't make ATP, doesn't have ATP/ADP exchange system or undergoes protein synthesis - Replicated Body (RB): *0.5-1.5 um diameter (larger) *1.18 g/mL (lower density) *early developmental stage *not infectious *replicative (undergoes intracellular multiplication) *OM proteins not linked by disulfides *more dispersed/translucent DNA w/ no histones *loosely defined cell wall *makes ATP, has ATP/ADP exchange system, and undergoes protein synthesis |
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Chlamydia Genomics
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- 1.0-1.2 mB; 40% G+C; no repeat sequences
- highly conserved genome (a) ~900-1,100 genes; 800 shared in all species (b) reductive evolution (gene loss) - shattered dogmas (a) Chlamydia CAN make ATP (b) Chlamydia HAVE peptidoglycan *closing in on the Chlamydia gene pool (at least 50 more in progress...) |
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List 4 Virulence Factors of Chlamydia
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- non-specific adherence
- tryptophan synthase - type III secretion (molecular 'syringes' that inject virulence factors directly into cytosol of infected cell) - cytotoxins related to clostridial cytotoxins *chlamydia often goes unnoticed for many years (asymptomatic infection) |
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Paradigm of Chlamydial Infection and Disease
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- infection starts asymptomatically or not severe
- mucosal surface of eye => localized infection (self-limited; can be cured w/ antibiotic) => *often times ends here; sometimes progresses further - chronic/repeated infection leads to scarring & sequelae at local site => - disseminated infection leads to scarring and sequelae at remote site |
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Distinguish b/w Primary and Chronic Ocular Chlamydia trachomatis Infection
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- primary = inclusion conjunctivitis
(a) caused by serovars A-C (b) readily treated w/ antibiotics - chronic = trachoma (a) causes preventable blindness (b) ~500 million infected in rural, sub-tropical regions (~5 million blind) (c) transmission by direct contact (house flies) (d) enhanced by poor hygienic conditions (e) antibiotic therapy has no effect past childhood |
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Newborn Infections: ophthalmia neonatorum & pneumonia syndrome of newborn
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- Ophthalmia neonatorum =
(a) incubation: 5-12 days post-natal (b) hospitals required to administer antibiotic eye drops immediately after delivery - Pneumonia syndrome of newborn (a) incubation: 3-16 wks (b) interstitial pneumonitis (c) chronic if untreated - Treatment: (a) erythromycin base 50mg/kg/day orally for 14 days (b) macrolides, less data but probably equally effective |
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Characteristics of Genital Chlamydia trachomatis
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- most common bacterial STI in U.S. (~4-5 million cases/yr - gone UP over the yrs)
- 10% of sexually active population infected - highest incidence in adolescents - predominantly caused by serovars D-K - most often asymptomatic or mild, hence unreported, untreated - men function as a reservoir *different serovars that cause genital vs. ocular infections *men have much lower level (but probably not true) |
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Primary Infection of Genital Chlamydia trachomatis
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- often mild/asymptomatic
- men = non-gonococcal urethritis - women = urethritis, cervicitis - treatment (a) azithromycin single dose or doxycycline for 7 days (b) altern.: erythromycin or ofloxacin or levofloxacin |
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Genital Chlamydia trachomatis: Sequelae of chronic infection in women
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- Pelvic Inflammatory Disease (PID) = chronic infection and damage in reproductive tract; blockage of fallopian tube
(a) difficult to diagnose (easily confused w/ other diseases) (b) mild-severe symptoms (fever, abdominal pain, pain upon urination, intercourse) (c) scar tissue may cause tubal obstruction (d) rate of infertility ~10% after single case (e) rate 2x w/ each succeeding infection - ectopic pregnancy - infertility - endometritis - salpingitis |
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Treatment of PID
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- should be effective against gonococcal and chlamydial PID
- treatment of sex partners - parenteral = (a) cefoxitin + doxycycline (b) clindamycin + gentamicin - oral = (a) levofloxacin (b) ceftriaxone + doxycycline - cephalosporin + doxycycline - special consideration = pregnancy, HIV infection |
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Lymphogranuloma venereum
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- caused by serotypes L1-L3
- shallow ulcer on genitalia - invasive = lymphadenopathy of inguinal lymph nodes - potentially severe complications - risk factor for HIV - current increases in LGV proctitis in women and homosexual men (in Netherlands and other European countries) = recto-vaginal fistulae in women; substantial urethral destruction - treatment: doxycycline for 21 days; altn: erythromycine |
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Reiter's Syndrome
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- triad of urethritis, conjunctivitis, and arthritis
- occurs in ~6% of individuals following chlamydia genital infection - chlamydial antigen can be detected in synovium - common in HLA B-27 haplotype |
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How do you diagnose Reiter's Syndrome?
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- urethral or cervical swab (must obtain cells; exudate insufficient)
- culture - PCR - direct stain w/ monoclonal Ab's (DFA or EIA) - urine can be used especially in males - serum antibody not useful |
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Immunity in genital infections
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- both antibody and cell-mediated immunity required
- immunity short-lived - no vaccine - vaccine made more difficult b/c disease is host-mediated |
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Chlamydia pneumoniae
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- worldwide distribution, >50% sero-prevalence
- probably recently 'jumped' from animal host to humans - primary infection ranges from common cold-like symptoms to atypical, community acquired pneumonia |
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Chlamydia pneumoniae (sequelae of chronic infection vs. sequelae of disseminated chronic infection)
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- sequelae of chronic infection =
*chronic bronchitis *asthma *exacerbation of COPD - sequelae of disseminated chronic infection = *reactive arthritis *abdominal aortic aneurysm *stroke *MS, Alzheimer disease *strongest association w/ atherosclerosis |
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Chlamydia pneumoniae
- diagnosis - treatment |
- diagnosis = usually not attempted
- treatment = minimum 10-14 days *doxycycline *erythromycin *quinolones, e.g. levofloxacin |
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avian Chlamydia psittaci
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- Psittacosis (ornithosis) = C. psittaci zoonosis from infected birds
- Flu-like illness to severe pneumonia - Occupational hazard for people exposed to exotic birds or poultry, BGE engineers - 30-95% infection rates in pigeons in Sarajevo, chicken in Beijing, duck farms in France, poultry farms in Germany, etc - Rarely diagnosed in humans > vastly under-reported? - Treatment: doxycycline, tetracycline - B list bioweapon [b/c transmitted thru air] |
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Rickettsia genera
(general characteristics) |
- gram-negative
- obligate intracellular - NO developmental cycle - transmission primarily thru arthropods (lice, fleas, ticks) |
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Rickettsia Rickettsiae
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- Small cocci
- Gram-negative cell wall, but stain poorly with GS - Heterogeneous group - Weil-Felix test based on antigenic relatedness of Rickettsia and Proteus sp. - Slow growing: g = 8-12 hrs - Induces own phagocytosis - Cell-to-cell spread (à la Listeria) |
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Rickettsial disease
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- Rocky Mountain Spotted Fever, Ehrlichiosis, Anaplasmosis, Rickettsialpox, Scrub typhus, Epidemic typhus, Murine typhus, Q fever
- various vectors: tick, mite, louse, and flea - Q fever is esp. dangerous pathogen; no vector; farm animals carry it |
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Famous Louse - Strigiphilus garylarsoni
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- biting louse of a genus only found on owls
- member of the Mallophaga order and Philopteridae family - no common name; named for cartoonist Gary Larson |
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Rickettsial disease = Rocky Mountain Spotted Fever (general characteristics)
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- Rickettsia rickettsii
- Most severe rickettsial disease - Most prevalent rickettsial disease in US - Common in tick season (spring-summer) - People outdoors most susceptible - Clinical diagnosis *History of tick bite or tick exposure *Severe headache *High fever (up to 105F) *Rash [characteristics but typically doesn't appear until several days after fever onset] *Myalgia, photophobia, thrombocytopenia -Incubation period: 5-7 days -lab diagnosis = several assays based on serology -treatment = doxycycline, tetracycline; no vaccine -development of immunity important b/c antibiotics are bacteriostatic |
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Rickettsial disease = Q Fever (general characteristics)
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- Coxiella burnetii
- Grows in macrophage phagolysosomes - Aerosol transmission - Reservoir: domestic animals (livestock) - People in slaughterhouses, dairy farms, etc., most susceptible - Clinical symptoms *Flu-like illness *Chronic form associated with endocarditis - Treatment *Doxycycline *Chloramphenicol - Vaccine used in countries with high incidence - Potential bioweapon |
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Mycoplasma
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- wall-less pleiomorphic bacteria, evolved from Gram-positive by mutational loss
- broad group, few pathogenic to humans - fastidious organisms, difficult to manipulate in vitro - can grow outside host cell - can undergo protein synthesis - don't have a rigid cell wall - are antibiotic susceptible - can have RNA & DNA - require cholesterol - undergo pleiomorphism - fried egg colony morphology [notable exception: mycoplasma pneumoniae] |
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5 species of Mycoplasma that cause diseases in humans?
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*Mycoplasma pneumoniae
-Mycoplasma hominis -Mycoplasma genitalium -Mycoplasma fermentens *Ureaplasma urealyticum |
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Virulence Determinants of Mycoplasma
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- Hemolysins = alpha or beta hemolysin
- Surface structures = organelles thought to mediate attachment to the surface of ciliated epithelial cells of the respiratory tract - Capsule = polysaccharidic, may be involved in attachment or may have toxic effects |
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Mycoplasma pneumoniae
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- 2 million cases yearly in US
*persistent cough, malaise, fever *community-acquired pneumonia *diagnosis by serology and PCR *leading cause of pneumonia in school-age children and young adults - Immune Response to M. pneumoniae Infection *Beneficial: early IgM, late IgG, IgA and CMI may play a role in protection *Deleterious: 50% develop cold agglutinins, IgM Abs that agglutinate erythrocytes at 4deg - Diagnosis = *difficult to grow (20 days) *round mulberry colonies *mostly serology - cold agglutinins, older test, poor sensitivity - IgG or IgM by ELISA - Treatment = doxycycline, ciproflaxicin, erythromycin, azithromycin, levoflaxin - no vaccine |
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Mycoplasma and STI
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- M. hominis, M. genitalium & U. urealyticum
*members of normal flora *opportunistic pathogens - M. fermentans or M. penetrans *association with HIV infection |
