M2012003Chlamydia
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Transcript M2012003Chlamydia
Chlamydia,
Rickettsia,
and
Mycoplasma Infections
[email protected]
206-5562
Chlamydia, Rickettsia,
and Mycoplasma
Microbiology
Infectious disease presentations
Treatment
Chlamydiacea
Three organisms cause human disease
– Chlamydia trachomatis (genus = Chlamydia)
– Chlamydia pneumoniae (genus = Chlamydophila)
– Chlamydia psittaci (genus = Chlamydophila)
Recent taxonomy changed based on the 16S
rRNA sequence
Chlamydial Biology
Prokaryotes
Gram negative with LPS
Lack peptidoglycans?
Obligate intracellular life cycle
Chlamydia
Developmental Cycle
Elementary body;
– Infectious form, metabolically inert
– Extracellular spore-like state
Reticulate body;
– Non-infectious form, metabolically active
– obligate intracellular form in eukaryotic cells
48-72 hour cycle
Chlamydia Developmental Cycle
1-6 hrs
12-16 hrs
24-72 hrs
Attachment & Internalization to
Epithelial Cells
Chlamydial Inclusion
Type III Secretion System Contact with Host Cell ?
Chlamydial Genome
1.043 million base pairs
Contains genes for LPS, glycolysis, fatty
acid and phospholipid synthesis and,
peptidoglycan synthesis
Missing genes for amino acid and purinepyrimidine biosynthesis, anaerobic
fermentation, and transformation
competence proteins
Chlamydia trachomatis:
Disease Presentations
Genitourinary tract infections
Perinatal infections
Trachoma
Chlamydia trachomatis &
Sexually Transmitted Infections
Urogenital infections: cervicitis,
urethritis, PID, epididymitis/prostatitis
4-6 million cases/year, U.S.
Prevalence highest in young women,
3-11% (age 15-24)
Lymphogranuloma venereum (LGV)
Urethritis
Non purulent discharge
Cervicitis
Serious Consequences of
C. trachomatis STI's
Tubal infertility
Pelvic inflammatory disease
Ectopic pregnancy
Reactive arthritis (Reiter's syndrome)
* Recent studies showed that 50% of infections occurred in
15-19 year old individuals.
Acute Inflammation
in the Cervix
Chronic Inflammation in the
Cervix
Fallopian Tube Pathology
Normal Cross-section
Tubal dilation and
epithelial cell destruction
C. trachomatis
Perinatal Infections
Neonatal inclusion conjunctivitis
(20-45% of infants from infected mothers)
Infant pneumonia
(10-20% of infants from infected
mothers)
C. trachomatis and
Trachoma
Blinding conjunctival infection
600 million cases worldwide
Develops over years,
chronic inflammation
Endemic in Middle East, Asia & Africa
Trachomatis Inflammation
Thickening on the tarsal conjunctiva appears red, rough and thickened.
Usually associate with numerous follicles (aggregates of immune cells).
Cornea Scarring
& Trichiasis
Scars (white streaks) visible on cornea. Trichiasis = Eyelashes rub the eyeball
Tryptophan Starvation by
Indoleamine 2,3 dioxygenase
Genital isolates (D-K)
Use trp B gene to form tryptophan
from indole
Ocular isolates (A-C)
Can NOT metabolize indole
J. Biol. Chem., Vol. 277, 26893-26903, 2002
Molecular Basis Defining Human Chlamydia trachomatis
Tissue Tropism
POSSIBLE ROLE FOR TRYPTOPHAN SYNTHASE*
Christine Fehlner-Gardiner, et al
C. trachomatis: Diagnosis
Serology
(MIF=microimmunofluorescence)
Culture
EIAs/DFA (direct fluorescent antibody)
Direct hybridization
Nucleic acid amplification
(PCR, LCR, others)
Fluorescent inclusion
(green) inside cell (red)
Stary sky appearance of green
fluorescent chlamydiae detected
by DFA in smear
NAATS; Nucleic Acid
Amplification Tests
Routine clinical use 1990s
Major impact of epidemiology of
Chlamydia infections
C. trachomatis: NA
Amplification
Improved Sensitivity, 90%+, specificity
>99%
– Use of novel specimens: urine, vaginal swabs,
patient collect tampons and cervical/urethral
specimens
Access difficult patient populations:
male cases
Performed in diverse clinical settings
C. trachomatis: Treatment
Azithromycin,
(single 1000 mg dose acceptable)
Tetracyclines (Doxycycline)
– (erythromycin for pregnant women and
neonates/children)
Chlamydia pneumoniae
1983, described as a distinct
chlamydial pathogen
Approximately 50% of US
population is seropositive
Less than 10% DNA homology with
C. trachomatis
Similar life cycle but different cell
wall construction
C. pneumoniae:
Disease Presentations
Pharyngitis, bronchitis
Pneumonia (7-10% of cases)
Other syndromes
(otitis media, endocarditis)
C. pneumoniae and
Chronic Diseases
Atherosclerosis (seroepidemiologic
studies, experimental disease)
Asthma
Neurological disease?
(MS, Alzheimer’s)
C. pneumoniae:
Diagnosis
Serology
(MIF = microimmunofluorescence)
Culture
PCR
C. pneumoniae:
Treatment
Azithromycin/clarithromycin
(macrolides)
Erythromycin
Tetracycline (Doxycycline)
Chlamydophila psittaci
Recently distinguished as a separate
genus using sequence phylogeny
Zoonosis, typically from pet birds,
occupational exposure
80 cases/year in the U.S
Chlamydophila psittaci:
Clinical Disease/Dx/Tx
Severe pneumonia
Endocarditis, other systemic
presentations
Diagnosis by serology, culture
Prolonged therapy with tetracycline
Rickettsia Family
Includes the genera:
Rickettsia, Orientia, Coxiella, Ehrlichia,
Bartonella
Intracellular Gram negative bacteria
Diseases Caused by
Rickettsiae Family
Spotted fever group (R. rickettsii)
Typhus group
(R. prowazekii, R. typhi)
Scrub typhus group
(Orientia tsutsugamushi)
Q fever group (C. burnetti)
Rocky Mountain Spotted
Fever
More common in midwest, south
central states
Ixodid tick transmission
Infects vascular endothelial cells
Rocky Mountain Spotted
Fever: Clinical Presentation
Skin rash, extremities
Fever
High mortality if untreated
Rocky Mountain
Spotted Fever: Dx/Tx
Culture (blood or biopsy should
be frozen, -70 degrees C.)
Direct immunofluorescence
Serology
PCR
Doxycycline/Chloramphenicol
Ciprofloxacin
– within 5 days of onset
Epidemic Typhus
Unsanitary conditions
Spread by the human louse
Also infects endothelial cells
Epidemic Typhus: Clinical
Presentation
Intense fever, headache
Rash, axillary folds, trunk
Mortality as high as 40% due to
clinical complications
Epidemic Typhus: Dx/Tx
Serology (no longer use Weil-Felix)
Culture
PCR
Tx: Doxycycline/Chloramphenicol
Q Fever
Tick (animals), aerosols, infected milk
Animal exposure
(skins, dust, excreta, POC
– poc = products of conception, ie placenta)
Q Fever: Clinical Presentation
Highly contagious
Febrile illness, rash is rare
Primarily pneumonia
Granulomatous hepatitis,
bacterial endocarditis
Q Fever: Dx/Tx
Culture
Serology (Antigenic variation)
PCR
Ehrlichiosis
Emerging infectious disease
– monocytic
– granulocytic
Similar to Rocky Mountain
Spotted Fever - but no rash
Dx: Serology
Tx: Doxycycline/Chloramphenicol
Mycoplasma and
Ureaplasma
Three human pathogens
– Mycoplasma pneumoniae
– M. hominis
– Ureaplasma urealyticum
Mycoplasma &
Ureaplasma Biology
Lack a rigid cell wall
Very small genome, limited
metabolic capabilities
Requires sterol for growth
Most closely related to lactobacilli
Morphology “Fried egg”
Mycoplasma pneumoniae:
Clinical Disease
Atypical pneumonia
(2 million cases/yr)
Bronchitis
Older children, young adults
Insidious onset
Pathogenicity
Attachment via
P1
Host receptors
– Sialoglycoproteins
– Sialoglycolipids
H202 & O2- produced as a
metabolic by product from
Mycoplasma can damage
host cells.
Mycoplasma hominis and
Ureaplasma urealyticum
Isolated from genital tracts of both
men and women
Uncertain associations with
urethritis, amniotic infections,
abortion
Mycoplasma: Dx/Tx
Culture (identification based on use of
glucose, arginine, urea)
Typical "fried egg" colonies
Nucleic acid based tests
(hybridization, PCR)
Tx with doxycycline/tetracycline