Neisseria gonorrhoeae

Question 1

Important properties

Answer 1

• no polysaccharide
  capsule
• multiple serotypes based on pilus protein antigenicity.
• marked antigenic
  variation in gonococcal pili-> chromosomal rearrangement
• 100+ serotypes known.
• 3 outer membrane proteins (I, II, & III).
• Protein II plays role in attachment of organism to cells & varies antigenically

Question 2

Pathogenesis & Epidemiology

Answer 2

• only humans.
• transmitted sexually
• newborns infected birth.
• sensitive to dehydration & cool conditions, sexual transmission favors survival.
• symptomatic in men; asymptomatic in
  women.
• Genital tract, anorectal & pharyngeal infections
• Pili-> virulence factor,
• mediate attachment to mucosal cell surfaces
  & antiphagocytic.
• Piliated -> virulent
• Nonpiliated-> avirulent
• 2 virulence factors in cell wall -> endotoxin (lipooligosaccharide,
  LOS) & outer membrane proteins.
• IgA protease hydrolyze secretory IgA preventing blocking of attachment to mucosa.
• no capsules.
• main host defenses-> antibodies (IgA & IgG), complement, & neutrophils.
• repeated infections common-> antigenic changes of pili & outer membrane proteins.

Question 3

Pathogenesis: Disseminated infections

Answer 3

• infect mucosal surfaces
  (urethra & vagina), but dissemination occurs.
• dissemination strains-> resistance to being killed by antibodies & complement.
• presence of porin A in cell wall inactivates C3b component of
  complement.

Risk increases-> deficiency of late-acting complement components (C6–C9) & women during menses
& pregnancy

Arise from asymptomatic infections->local inflammation deter dissemination

Question 4

Clinical findings

Answer 4

• localized infections in genital tract
• disseminated infections with seeding of organs through bloodstream.

Men -> urethritis
accompanied by dysuria & purulent discharge & Epididymitis.

Women-> endocervix, purulent vaginal discharge & intermenstrual bleeding (cervicitis).
- ascending infection of uterine tubes (salpingitis, PID)-> sterility or ectopic
pregnancy->scarring of tubes.

Disseminated gonococcal infections (DGI) -> arthritis, tenosynovitis, pustules in skin, septic arthritis in sexually active adults.

• difficult to confirm using lab tests-> not cultured

Anorectal-> women &
homosexual men.
- asymptomatic, bloody or purulent discharge (proctitis).

Throat-> pharyngitis, asymptomatic.

Newborn infants-> purulent conjunctivitis (ophthalmia neonatorum) from mother during
passage through birth canal.
- declined-> prophylactic erythromycin eye ointment (silver nitrate) applied shortly after birth.
- occurs in adults-> transfer of organisms from genitals to eye.

Other sexually transmitted infections can coexist with gonorrhea, appropriate
diagnostic & therapeutic measures taken

Question 5

Lab Diagnosis

Answer 5

• Men-> gram-negative diplococci within
  PMNs in a urethral discharge specimen.
• Women-> Gram stain alone difficult to interpret; cultures done.
  Gram stains on cervical specimen can be falsely positive-> presence of
  gram-negative diplococci in normal flora & inability to see small numbers
  of gonococci when using oil immersion lens.

Cultures-> pharyngitis
or anorectal infections.

Specimens from mucosal sites (urethra & cervix) cultured on Thayer-Martin medium-> chocolate agar containing antibiotics (vancomycin, colistin,
trimethoprim, & nystatin) to suppress normal flora.

• oxidase-positive colony of gram-negative diplococci sufficient to identify isolate as member of Neisseria.

Specific identification->
fermentation of glucose (but not maltose) or by fluorescentantibody
staining.

Specimens from sterile sites (blood or joint fluid) cultured on chocolate
agar without antibiotics -> no competing normal flora.

Nucleic acid amplification tests-> detect presence of gonococcal nucleic acids in
patient specimens.
- produce results rapidly, & highly sensitive & specific.
- used on urine samples,
obviating need for more invasive collection techniques.

• Serologic tests determine presence of antibody
  to gonococci in patient’s serum not useful for
  diagnosis.
• Isolates resistant to
  fluoroquinolones (ciprofloxacin)-> problem so not recommended.

Question 6

Treatment

Answer 6

Ceftriaxone -> uncomplicated infections.

Penicillin or Cephalosporins allergy-> Azithromycin or ciprofloxacin

Mixed infections with C. trachomatis->azithromycin or doxycycline

follow-up culture performed 1 week after completion of treatment to determine whether
gonococci still present.

Complicated infections, (PID)-> hospitalization.

Question 7

How resistance formed

Answer 7

• Prior to mid-1950s, all gonococci highly penicillin sensitive.
  Isolates with lowlevel penicilin tetracycline & chloramphenicol resistance emerged-> encoded by bacterial chromosome due to
  reduced uptake of drug or altered binding sites than enzymatic degradation of drug.
• 1976-> penicillinase-producing (PPNG) strains exhibited high-level resistance isolated from
  patients. Penicillinase is plasmid-encoded.
• PPNG strains now common.

Question 8

Prevention

Answer 8

• use condoms & treatment of symptomatic patients &
  their contacts.
• Cases reported to public health department to ensure proper follow-up.
• Problem -> asymptomatic carriers.
• Gonococcal conjunctivitis in newborns -> erythromycin ointment. Silver nitrate drops used less frequently.

No vaccine is available