Chlamydia, Rickettsia, and Mycoplasma Infections

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Chlamydia,Rickettsia, and Mycoplasma Infections
kkelly_at_mednet.ucla.edu206-5562
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Chlamydia, Rickettsia, and Mycoplasma

• Microbiology
• Infectious disease presentations
• Treatment

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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

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Chlamydial Biology

• Prokaryotes
• Gram negative with LPS
• Lack peptidoglycans?
• Obligate intracellular life cycle

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ChlamydiaDevelopmental 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

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Chlamydia Developmental Cycle
1-6 hrs
12-16 hrs
24-72 hrs
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Attachment Internalization to Epithelial Cells
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Chlamydial Inclusion
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Type III Secretion System - Contact with Host
Cell ?
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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
  purine-pyrimidine biosynthesis, anaerobic
  fermentation, and transformation competence
  proteins

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Chlamydia trachomatis Disease Presentations

• Genitourinary tract infections
• Perinatal infections
• Trachoma

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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)

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UrethritisNon purulent discharge
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Cervicitis
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Serious Consequences of C. trachomatis STI's

• Tubal infertility
• Pelvic inflammatory disease
• Ectopic pregnancy
• Reactive arthritis (Reiter's syndrome)

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Recent studies showed that 50 of infections
occurred in 15-19 year old individuals.
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Acute Inflammationin the Cervix
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Chronic Inflammation in the Cervix
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Fallopian Tube Pathology
Tubal dilation and epithelial cell destruction
Normal Cross-section
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C. trachomatis Perinatal Infections

• Neonatal inclusion conjunctivitis (20-45 of
  infants from infected mothers)
• Infant pneumonia (10-20 of infants from
  infected mothers)

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C. trachomatis and Trachoma

• Blinding conjunctival infection
• 600 million cases worldwide
• Develops over years,
  chronic inflammation
• Endemic in Middle East, Asia Africa

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Trachomatis Inflammation
Thickening on the tarsal conjunctiva appears
red, rough and thickened. Usually associate with
numerous follicles (aggregates of immune cells).
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Cornea Scarring Trichiasis
Scars (white streaks) visible on cornea.
Trichiasis Eyelashes rub the eyeball
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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
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C. trachomatis Diagnosis

• Serology (MIFmicroimmunofluorescence)
• Culture
• EIAs/DFA (direct fluorescent antibody)
• Direct hybridization
• Nucleic acid amplification (PCR, LCR, others)

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Fluorescent inclusion (green) inside cell (red)
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Stary sky appearance of green fluorescent
chlamydiae detectedby DFA in smear
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NAATS Nucleic Acid Amplification Tests

• Routine clinical use 1990s
• Major impact of epidemiology of Chlamydia
  infections

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C. trachomatis NA Amplification

• Improved Sensitivity, 90, specificity gt99
• 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

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C. trachomatis Treatment

• Azithromycin,
• (single 1000 mg dose acceptable)
• Tetracyclines (Doxycycline)
• (erythromycin for pregnant women and
  neonates/children)

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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

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C. pneumoniae Disease Presentations

• Pharyngitis, bronchitis
• Pneumonia (7-10 of cases)
• Other syndromes (otitis media,
  endocarditis)

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C. pneumoniae and Chronic Diseases

• Atherosclerosis (seroepidemiologic studies,
  experimental disease)
• Asthma
• Neurological disease? (MS, Alzheimers)

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C. pneumoniae Diagnosis

• Serology (MIF microimmunofluorescence
  )
• Culture
• PCR

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C. pneumoniae Treatment

• Azithromycin/clarithromycin (macrolides)
• Erythromycin
• Tetracycline (Doxycycline)

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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

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Chlamydophila psittaci Clinical Disease/Dx/Tx

• Severe pneumonia
• Endocarditis, other systemic presentations
• Diagnosis by serology, culture
• Prolonged therapy with tetracycline

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Rickettsia Family

• Includes the genera
• Rickettsia, Orientia, Coxiella, Ehrlichia,
  Bartonella
• Intracellular Gram negative bacteria

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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)

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Rocky Mountain Spotted Fever

• More common in midwest, south central states
• Ixodid tick transmission
• Infects vascular endothelial cells

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Rocky Mountain Spotted Fever Clinical
Presentation

• Skin rash, extremities
• Fever
• High mortality if untreated

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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

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Epidemic Typhus

• Unsanitary conditions
• Spread by the human louse
• Also infects endothelial cells

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Epidemic Typhus Clinical Presentation

• Intense fever, headache
• Rash, axillary folds, trunk
• Mortality as high as 40 due to clinical
  complications

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Epidemic Typhus Dx/Tx

• Serology (no longer use Weil-Felix)
• Culture
• PCR
• Tx Doxycycline/Chloramphenicol

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Q Fever

• Tick (animals), aerosols, infected milk
• Animal exposure (skins, dust, excreta, POC
• poc products of conception, ie placenta)

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Q Fever Clinical Presentation

• Highly contagious
• Febrile illness, rash is rare
• Primarily pneumonia
• Granulomatous hepatitis, bacterial endocarditis

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Q Fever Dx/Tx

• Culture
• Serology (Antigenic variation)
• PCR

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Ehrlichiosis

• Emerging infectious disease
• monocytic
• granulocytic
• Similar to Rocky Mountain Spotted Fever - but no
  rash
• Dx Serology
• Tx Doxycycline/Chloramphenicol

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Mycoplasma and Ureaplasma

• Three human pathogens
• Mycoplasma pneumoniae
• M. hominis
• Ureaplasma urealyticum

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Mycoplasma Ureaplasma Biology

• Lack a rigid cell wall
• Very small genome, limited metabolic capabilities
• Requires sterol for growth
• Most closely related to lactobacilli

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Morphology Fried egg
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Mycoplasma pneumoniae Clinical Disease

• Atypical pneumonia (2 million cases/yr)
• Bronchitis
• Older children, young adults
• Insidious onset

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Pathogenicity

• Attachment via P1
• Host receptors
• Sialoglycoproteins
• Sialoglycolipids

H202 O2- produced as a metabolic by product
from Mycoplasma can damage host cells.
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Mycoplasma hominis and Ureaplasma urealyticum

• Isolated from genital tracts of both men and
  women
• Uncertain associations with urethritis, amniotic
  infections, abortion

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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

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