Chlamydia,
Rickettsia,
and
Mycoplasma Infections
kkelly@mednet.ucla.edu
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