Neisseria gonorrhoeae Nealia House


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Neisseria gonorrhoeae

  • Nealia House


Gonorrhea

  • Topic Overview

  • Biology of Neisseria gonorrhoeae

  • Screening

  • Treatment

  • Control/Surveillance



Gonorrhea

  • Sexually transmitted disease

  • Infection Rate

    • socioeconomic class
    • Age
  • Very common infectious disease

    • STI second only to chlamydia
  • Increasing antibacterial resistance

  • Increases efficiency of HIV transmission



Affected Populations



Gonorrhea

  • Humans only natural host

    • Reproductive tract
  • Infection can be asymptomatic

    • Infertility
  • Several tests available for detection of gonorrhea



Gonorrhea

  • Topic Overview

  • Biology of Neisseria gonorrhoeae

    • Survival Within Host
  • Screening

  • Treatment

  • Control/Surveillance



Transmission

  • Does not survive in the environment, must be transmitted through contact



Transmission

  • Transmissibility dependent on:

    • Strain
    • Male to female transmission more effective
      • Higher number of organisms present in male urethral discharge than female vaginal secretions


Structure

  • Diplococcus

  • Gram-negative

  • Fimbriae extend several micrometers from cell surface





Systemic Infection



Infection

  • N. gonorrhoeae attaches to mucosal cells via pili and other surface proteins

  • Induces production of inflammatory cytokines by epithelial cells



Infection



Survival Within Host

  • Evades host immune system by changing surface proteins

    • Often asymptomatic infection
  • The RdgC protein is required for efficient pilin antigenic variation



Antigenic Variation

  • Pilus promotes attachment of gonococcal cell to host epithelial cell

    • Must retain some consistency
  • Conserved N-terminal and variable C-terminal regions

    • Constant regions
    • Semi-variable regions
    • Hypervariable regions
  • Phase variation from piliated to non-piliated



Immune Memory

  • Infection history did not alter antibody levels in patients with current infection

    • Suggests immunological memory not induced by uncomplicated gonococcal infections
  • Local and systemic immune responses to gonococci extremely modest

    • Slight increase in serum immunoglobulin G (IgG) in infected males
    • Slight increase in serum IgA1 antibodies in infected females


Survival Within Host

  • Pili, outer membrane proteins, lipopolysaccharides

    • Binding to epithelial surfaces
    • Passage through epithelium
    • Interaction with phagocytes
  • Variations in outer membrane protein (P1, Por)

  • Requires

    • Carbon dioxide
    • Sulfur in form of cysteine
    • Iron


Antimicrobial Resistance

  • Gonococcal strains resistant to:

    • Penicillins
    • Tetracyclines
    • Spectinomycin
    • Fluoroquinolones
  • Presently, ciprofloxacin and ofloxacin recommended by CDC for treatment



Biotechnology

  • Oligonucleotide chips now used to screen for antimicrobial resistance

    • Point mutations in the gyrA and parC genes
      • Determine the prevalence of ciprofloxacin-resistant strains
  • Results identical to sequencing results

  • Rapid and reliable analysis



Gonorrhea

  • Topic Overview

  • Biology of Neisseria gonorrhoeae

    • Survival Within Host
  • Screening

  • Treatment

  • Control/Surveillance



Screening

  • “Gold Standard”

    • Nucleic acid amplification assays
      • Polymerase chain reaction
  • Cell culture to confirm diagnosis

    • Oxidase positive


Types of Tests

  • Gram-Stained Smear

    • Sensitivity reduced in asymptomatic infections
    • Less that 50% sensitive as cell culture
    • Not useful in rectal infections


Types of Tests

  • Culture Based Systems

    • High degree of specificity
    • Expensive
    • Trained personnel
    • Media requirements
    • Presumptive identification
      • Growth on selective GC agar, gram stain, oxidase and superoxol positivity


Types of Tests

  • Antigen Detection and Enzyme Immunoassays

    • Extensively investigated
      • Low/high prevalence
      • Symptomatic/asymptomatic
    • Few to no situations for which this assay recommended
      • Because of antigenic variation


Types of Tests

  • DNA Probe Hybridization

    • Specific chemiluminescent label on probe
    • Available commercially
    • 85% sensitivity
    • 99% specificity


Types of Tests

  • Nucleic Acid-Based Amplification Assays (NAAT)

    • 95% accurate
    • False positives due to specimen cross-contamination, environmental contamination


Current Screening

  • No test for samples from all major sites of gonococcal infection

    • Rapid
    • Inexpensive
    • Reliable
  • Such a test would improve case-finding



Gonorrhea

  • Topic Overview

  • Biology of Neisseria gonorrhoeae

    • Survival Within Host
  • Screening

  • Treatment

  • Control/Surveillance



Treatment



Treatment

  • Fluoroquinolones



Treatment

  • Ceftriaxone (Rocephin®)

    • Single dose intramuscularly
    • Introduced as treatment in 1985
      • Retained resistance
    • Beta-lactam antibiotic
    • Action against penicillinase


Treatment

  • Possible co-infection with Chlamydia trachomatis



Vaccine

  • Hard to develop

    • No animal model
  • No immune memory to Neisseria gonorrhoeae

    • Antigenic variation strategy
  • Difficulty finding target common to all strains

  • Research continues to identify possible vaccine targets

    • DNA vaccines
    • Mucosal immunization


Gonorrhea

  • Topic Overview

  • Biology of Neisseria gonorrhoeae

    • Survival Within Host
  • Screening

  • Treatment

  • Control/Surveillance



Prevention

  • Abstinence

  • Safe/”smart” sex

  • Barrier contraceptives

  • Educational programs

  • Reduce misuse of antimicrobials



Governmental Programs

  • Health Canada

    • Educational plans
    • STD Screening
    • Free STD clinics


Governmental Programs

  • CDC Gonococcal Isolate Surveillance Project (GISP)



Conclusions

  • More research

    • Reliable, fast screening
    • Preventative therapeutics
  • Non-biotechnological interventions

  • Prudent antimicrobial use



References

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  • Centers for Disease Control and Prevention, 2005. STD facts and information Gonorrhea. National Center for HIV, STD, and TB Prevention, Division of Sexually Transmitted Diseases Prevention. http://www.cdc.gov/nchstp/dstd/GonorrheaInfo.htm last accessed: 3/29/05.

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