Neisseria gonorrhoeae Nealia House

Neisseria gonorrhoeae

• Nealia House

Gonorrhea

• Topic Overview

• Biology of Neisseria gonorrhoeae

• Survival Within Host

• 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

• Unprotected sex
• Contact with eyes, mouth
• Mother to child during birth

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

• Efficient treatment
• Disease management

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

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