Chlamydia, Rickettsia, and Mycoplasma Infections

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  hour cycle

Chlamydia Developmental Cycle 1-6 hrs hrs hrs

Attachment & Internalization to Epithelial Cells

Chlamydial Inclusion

Type III Secretion System - Contact with Host Cell ?

Chlamydial Genome  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

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 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 J. Biol. Chem., Vol. 277, , 2002 Molecular Basis Defining Human Chlamydia trachomatis Tissue Tropism POSSIBLE ROLE FOR TRYPTOPHAN SYNTHASE** Christine Fehlner-Gardiner, et al Genital isolates (D-K) Use trp B gene to form tryptophan from indole Ocular isolates (A-C) Can NOT metabolize indole

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) (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

 Three human pathogens –Mycoplasma pneumoniae –M. hominis –Ureaplasma urealyticum Mycoplasma and Ureaplasma

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

PathogenicityPathogenicity  Attachment via P1  Host receptors –Sialoglycoproteins –Sialoglycolipids H & O 2- 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