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Syphilis , Chlamydia and Gonorrhea : Bacteriology, Epidemiology, Pathogenesis, Clinical Manifestations, Diagnosis and Treatment. Group B6. Epidemiology - Syphilis. Epidemiology - Syphilis. Epidemiology - Syphilis. Epidemiology - Syphilis. Epidemiology - Syphilis. Epidemiology - Syphilis.

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slide1

Syphilis, Chlamydia and Gonorrhea: Bacteriology, Epidemiology, Pathogenesis, Clinical Manifestations, Diagnosis and Treatment

Group B6

transmission t pallidum
Transmission - T. pallidum
  • “teeming with spirochetes”
  • Transmission
    • Sexually engaging a person with lesions
    • Mother  Baby
      • In utero
      • Congenital syphilis
pathogensis t pallidum
Pathogensis – T. pallidum

3-6 wks post-incubation

pathogensis t pallidum1
Pathogensis – T. pallidum

Chancres resolve w/in wks even w/o treatment

Some move directly to 2 syphilis

Period in which organism replicates & spreads throughout body

4-10 wks after first signs of primary lesions

If left untreated, can move to 3 syphilis

Latent Period

2 syphilis
2 Syphilis

Sites of replication

Lymph nodes, mucous membranes, liver, joints, muscle, skin

  • Spirochete replication  dissemination
  • Manifestations(variable)
    • Malaise & Fever
    • Myalgias & Arthralgias
    • Lymphadenopathy
    • Rash & Lesions
      • Rash present on ENTIRE body (inc. palms & soles)
      • Lesions present in different stages (macular, papular, pustular)
        • Contains treponemes

Condylomatalata

gray/white lesions

painless

highly infectious

warm/moist areas

2 syphilis will heal w/in weeks w/o treatment; if left untreated  latent &/or 3 syphilis

latent syphilis
Latent Syphilis
  • Early Latent Syphilis
    • Less than 1 yr after 2 syphilis
    • Relapse possible
      • PT may have relapse of 2 syphilis lesions/symptoms
    • CONTAGIOUS
  • Late Latent Syphilis
    • Less than 1 yr after 2 syphilis
    • No symptoms
    • Not as contagious

PT is seropositive during latent phase, thus blood test is required for diagnoses.

Latent stage may persist for years (10-20yrs); if left untreated  3 syphilis

3 syphilis
3 Syphilis
  • Rare  ~1/3 of untreated PTs
  • Slow, chronic inflammatory damage d/t to reaction of spirochetes in tissue
  • 3 categories
    • Gummatous syphilis
    • Cardiovascular syphilis
    • Neurosyphilis
  • Gummatous syphilis
    • Granulomatous lesions
    • Center = necrotic tissue
    • Form in (but not limited to) liver, bones, ski
  • Cardiovascular syphilis
    • Aneurysm formation in ascending aorta
  • Neurosyphilis
    • CNS invasion  syphilitic meningitis
    • Damage to blood vessels in CNS  meningovascular syphilis
    • Parenchymalneurosyphilis tabesdorsalis & general paresis
clinical syphilis
Clinical - Syphilis
  • Aka The Great Imitator
  • Primary syphilis characterized by a firm, round, small, PAINLESS, chancre
  • Usually a single lesion but there may be multiple
  • Occurs at the site where the treponeme invaded
  • The chancre lasts 3 to 6 weeks
clinical syphilis1
Clinical - Syphilis
  • Secondary syphilis is characterized via a skin rash and mucous membrane lesions
  • Presents as rough, red/brownish spots on palms and soles
  • Other symptoms are fever, lymphadenopathy, myalgias, weight loss, and fatigue
  • These symptoms will disappear with or without treatment
clinical syphyilis
Clinical - Syphyilis
  • Tertiary syphilis occurs many years after the secondary phase
  • Treponemes damage the brain, eyes, heart, vessels, bones, joints, and many internal organs
  • Patients may develop aortitis, hoarseness, Argyll Robertson’s pupil, gummas, and TabesDorsalis
diagnosis t pallidum
Diagnosis – T. pallidum
  • Dark Field microscopy serology tests:
    • Fluorescent Treponemal Antibody Absorption (FTA-ABS)
      • Specific
    • Veneral Disease Research Lab (VDRL)
      • Nonspecific
      • detects reaginAb against cardiolipin
diagnosis t pallidum1
Diagnosis – T. pallidum
  • Serology
    • Non-treponemal antibodies
      • VDRL & PRP
  • Serology
    • Treponemal antibodies
      • FTA-ABS & MHA-TP
treatment t pallidum
Treatment – T. pallidum
  • Drugs:
    • Benzathine penicillin G
virulence factors chlamydia
Virulence Factors – Chlamydia
  • Intracellular organism
  • Downregulates MHC-I
  • LPS
    • Promotes inflammation via TLR-4 activation (inducing IL-1 & -8 secretion)
  • Prevents fusion of endosome with lysosome
    • Provides a “home”
  • Persistent state
    • Allows Chlamydia to persist in face of IFN-gamma
  • Nutrient up-take
    • Via Type 3 secretion system which serves as a “transport channel”
clinical chlamydia
Clinical - Chlamydia
  • Clamydia trachomatis
    • A,B,C serotypes induce chronic infections and blindness due to follicular conjunctivitis
    • D,K serotypes cause urethritis/PID, ectopic pregnancy, neonatal pneumonia(staccato cough), or neonatal conjunctivitis
    • L1,L2,L3 result in lymphogranulomavenereum
clinical chlamydia1
Clinical - Chlamydia
  • Known as the silent STD since many are asymptomatic
  • Women may have burning upon urination or vaginal discharge
  • Untreated infections may lead to PID or ectopic pregnancy
  • Leading cause of pneumoniae and conjunctivitis in neonates
clinical chlamydia2
Clinical - Chlamydia
  • Men may have discharge from penis or burning upon urination
  • Rarely, Reiter’s syndrome may occur including arthritis, skin lesions, and inflammation of the eye and urethra
diagnosis c trachomatis
Diagnosis – C. trachomatis
  • Cell culture
  • Non-culture Direct Detection methods:
    • Direct Fluorescent Antibody tests (DFA) test) – direct at elementary bodies
    • Enzyme Immunoassays (EIA)
    • Nucleic Acid Hybridization Tests
    • Nucleic Acid Amplification Tests – most sensitive
  • Serologic Tests
treatment c trachomatis
Treatment – C. trachomatis
  • Drugs
    • Azithromycin
    • Ceftriaxone + Doxycycline = concurrent N. gonorrhea
    • Erythromycin (oral) = Neonates
virulence factors n gonorrhea
Virulence Factors – N. gonorrhea
  • Adherence/Uptake
    • Pili
    • Opa proteins
      • Antigen variation/antigen phase variation
    • Porin 1
  • Enzymes/Toxins
    • LOS
    • IgA protease
pathogenesis n gonorrhea
Pathogenesis – N. gonorrhea
  • Virulence Factors
  • Adherence/Uptake
    • Pili
    • Opa proteins
      • Antigen variation
      • Movement across cell
    • Porin 1
  • Enzymes/Toxins
    • LOS
    • IgA protease
clinical gonorrhea
Clinical - Gonorrhea
  • Men may have burning upon urination and white, yellow, or green discharge
  • Painful or swollen testes may also occur as well as epidydimitis leading to infertility
  • Women are often asymptomatic but could experience burning upon urination
  • Untreated infections lead to PID in women and septic arthritis in both sexes
  • Pregnant women may also transmit gonorrhea to their baby via passage through birth canal resulting in blindness and joint infections
diagnosis n gonorrhoeae
Diagnosis – N. gonorrhoeae
  • Nucleic acid amplification tests (NAAT) – most sensitive (PCR)
  • Nucleic acid hybridization test (co-infection Chlamydia)
  • Culture: Thayer Martin agar / chocolate agar
  • Gram stain: diplococci within neutrophils
treatment n gonorrhoeae
Treatment – N. gonorrhoeae
  • Drugs:
    • Ceftriaxone + Azithromycin
    • Ceftriaxone + Doxycycline = concurrent Chlamydia
    • Erythromycin (eye gtts) = prophylaxis in neonates
    • Resistance:
      • Penicillin
      • Fluoroquinolones – Ciprofloxacin or Levofloxacin (Levaquin)
  • Vaccines:
    • NONE (varied pili antigens)
antibiotic resistance n gonorrhoeae
Antibiotic Resistance – N. gonorrhoeae
  • Beta-lactamases
  • Efflux pumps
  • Mutations:
    • Penicillin-binding proteins
    • DNA gyrase and topoisomerase
    • Porins
slide50
Q1

A 34-year-old male presents to your ofice with a painless penile ulcer several weeks after an episode of unprotected sexual intercourse.(bad luck?!) Which of the following is most useful in diagnosing Treponemapallidum infection in this patient?

  • Ulcer exudate microscopy after Gram staining
  • Ulcer exudate microscopy with darkfield illumination
  • Ulcer eudate cultures on enrichment media
  • Blood culture on differential media
  • Antitoxin detection in the serum
slide51
Q2

A 22-year-old female presents with severe pain and swelling in her right knee, left elbow, and left wrist. Joint aspiration of the knee reveals an opaque exudate with high neutrophil content and intracellular organisms. This patient’s symptoms could have most likely been prevented by

  • Methotrexate therapy
  • Proper sore throat threatment
  • Timely vaccination
  • Barrier contraception
  • Avoiding intravenous drug abuse
slide52
Q3

Neurosyphillis might present in all of the following form except:

  • Meningitis
  • Meningovascular syphilis
  • Tabesdorsalis
  • Condylomatalata
  • Argyll Robertson pupil
slide53
Q4

Genital examination of a 31-year-old female reveal yellow discharge from the cervical os that demonstrates abundant neutrophils on light microscopy. The patient will most likely experience which of the following as a sequela of this disease?

  • Endometrial hyperplasia
  • Hydatidiform mole
  • Ovarian cancer
  • Polycystic ovary syndrome
  • Infertility
slide54
Q5

Which of the following regarding Chlamydia life cycle is false?

  • Elementary bodies are infectious
  • Reticulate bodies are metabolically active
  • Presence of IFN-beta will shut down chlamydia growth and falsely make body believe infection is gone
  • All of the above (do not choose this one)
  • None of the above
slide55

Q #1,2,4 are from Qbank-USMLE

  • Q#3,5 are from lecture notes
references
References
  • http://www.cdc.gov/std/stats10/gonorrhea-figs.htm
  • http://www.cdc.gov/std/stats10/chlamydia-figs.htm
  • http://www.cdc.gov/std/stats10/syphilis-figs.htm
  • Dr. Buxton’s “Bacteria That Do Not Gram Stain” lecture
  • Dr. Buxton’s “Microbial Causes of Genital Discharges” lecture
  • Dr. Buxton’s “Microbial Causes of Genital Ulcers or Growths” lecture
  • Dr. Gregg’s “Gram(-) Bacteria” lecture
  • E-Medicine
  • PubMed Health