Bacteriology-47 Neisseria gonorrhoeae Infections*
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- What diseases are caused by Neisseria gonorrhoeae
- Urethritis, cervicitis, proctitis, pharyngitis, conjunctivitis, epididymitis, endometritis, salpingitis, pelvic inflammatory disease, perihepatitis, bartholinitis, disseminated gonococcal infection
- What are the general characteristics of Neisseriaceae
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Gram negative diplococci, oxidase positive, nonmotile. Require iron and 2-8% CO2 for growth
Naturally competent for DNA transformations - How is Neisseria gonorrhoeae transmitted
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Viral contact between mucosal surfaces and infected tissue or secretion. Non-sexual transmission is rare
ID50 for men is 10^3
Attack rate from infected persons is 20-50% - What is the clinical spectrum of Neisseria gonorrhoeae
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Asymptomatic infection
Urethritis
Cervicits
Rectal infection
Pharyngeal infection
Ophthalmia neonatorum
Localized dissemination in the reproductive tract
Disseminated gonococcal infection (DGI) - Describe urethritis caused by Neisseria gonorrhoeae
- Males and females. Frequent, urgent and painful urination and yellow mucopurulent discharge containing neutrophils and gram-negative diplococci
- Describe cervicitis caused by Neisseria gonorrhoeae
- Inflammation of the endocervical canal with mucopurulent discharge. Infection of paracervical glands, Bartholin's glands resulting in abscesses. Presents as vulvovaginitis rather than cervicitis in pre-adolescent girls and hysterectomized women
- Describe rectal infection from Neisseria gonorrhoea
- Usually asymptomatic, but may have tenesmus, discharge or pain on defecation
- Describe pharyngeal infection from Neisseria gonorhoeae
- Usually asymptomatic, but may have very sore throat. From orogenital sex. In patients with gonorrhea, gonococcal pharyngitis is found
- Describe Ophthalmia neonatorum caused by Neisseria gonorhoeae
- Acute purulent conjunctivitis in the newborn which was once a common cause on blindness in the US
- Describe localized dissemination in the reproductive tract caused by Neisseria gonorrhoeae
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Males: Epididymitis, prostitis. Can lead to infertility
Females: Endometritis, salpingitis, pelvic inflammatory disease. Damage to the fallopian tubes during salpingitis can cause post-infection complications like chronic pelvic pain, infertility, and ectopic pregnancy. Dissemination into the peritoneum from the fallopian tubes can lead to perihepatitis (Curtis-Fitx-Hugh syndrome) - Describe disseminated gonococcal infection (DGI) caused by Neisseria gonorrhoeae
- Hematogenous spread with a predilection for skin and joints, resulting in dermatitis and arthritis. Dermatitis manifests as hemorrhagic papular lesions. Gonococcal arthritis is the leading cause of septic arthritis in young adults and usually involves the large joints. DGI can cause endocarditis or meningitis
- What is the pathogenesis of Neisseria gonorrhoeae
- Upon entry into the lower urogenital tract, gonocci adhere to epithelial cells via colonization pili. Invasion of epithelial cells also occurs. Vigorous inflammatory response can occur. Discharge contains neutrophils, exfoliated epithelial cells and diplococci
- What is the connection between gonorrhea in females and hormonal status
- Gonococcal Disseminated gonococcal infection and Pelvic inflammatory disease tend to occur during or shortly after menses; women are more heavily colonized in the proliferative stage
- How does pH of the lower female genital tract affect gonorrhea
- Neisseria gonorrhoeae is sensitive to low pH. The occurrence of vulvovaginitis in prepubescent and post-hysterectomy females rather that cervicitis may be due to the higher vaginal pH in these females
- How does the onset of menstrual blood affect gonorrhea
- Ascension to the upper reproductive tract may be facilitated by the reflux of menstrual blood. High amounts of iron bound to hemoglobin may stimulate gonococcal growth or up-regulate virulence genes
- In the fallopian tubes, what do gonococci specifically adhere to
- Nonciliated epithelial cells. Damage to columnar epithelial cells and ciliated cells is mediated by gonococcal lipooligosaccharide (LOS) and peptidoglycan fragments
- Disseminated gonococcal infections (DGI) is associated with what types of strains
- Those that express porins that bind to complement regulatory proteins C4 binding protein (C4bp) and factor H (fH). Binding to these will cause down-regulation of complement activation, and decrease complement-mediated killing
- What types of gonococcal strains are epidemiologically associated with DGI
- Strains that contain the porin serotypes that bind C4bp and fH. Strains that express serum-sensitive porin types are associated with localized mucosal infections
- What allows the gonococcus to evade the immune response or provide functionally different phenotypes
- Antigenically and phase variable surface proteins, such as pili, opacity proteins, and lipooligosaccharide
- Why might repeated gonococcal infection be common
- The antigenically variable nature of the gonococcal surface
- Define phase variation in gonococci
- The ability to turn the expression of a gene on or off; can be reversible or nonreversible, depending on the mechanism
- What two variations provide for the variable nature of gonococcal surfaces
- Antigenic variation and phase variation
- What is the major subunit of gonococcal pili
- The antigenically variable protein called pilin. Antigenic variation of pilin is probably a major mechanism by which the gonococcus evades the immune response
- What does the pili (fimbriae) of gonococci do
- Mediates adherence to epithelial cells and spermatozoa
- What is the probable function of Opacity (Opa) proteins in Neisseria gonorrhoeae
- Mediate adherence to, and invasion of, epithelial cells and non-opsonic uptake by neutrophils
- What are opacity (Opa) proteins in gonococci
- Family of variable outer membrane proteins (up to 12 of them). Each individual Opa protein undergoes phase variation via a frame shift mechanism
- What does Neisseria sp express instead of the lipopolysaccharide found in enteric gram negative bacteria
- Lipooligosaccharide (LOS) (short carbohydrate chains)
- How does gonococcal LOS undergo phase and antigenic variation
- Via frameshift mechanisms that occur in glycosyltransferase genes. The gonococcus also produces a sialyltransferase that catalyzes the addition of host sialic acid residues to its LOS
- What is the significance of sialylated LOS
- Gonococci with sialylated LOS are more resistant to complement-mediated lysis due to this capsule-like modification
- What are three less common gonococcal virulence factors
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Iron-binding proteins: response to low iron. Compete with human transferrin, hemoglobin and lactoferrin
IgA1 protease: cleaves IgA1
P.I. protein-major porin: serological classification only - Why is Neisseria gonorhoeae able to persist during periods of intense inflammation
- It has multiple mechanisms by which it evades complement-mediated and phagocytic killing
- What is the epidemiology of Neisseria gonorrhoeae
- High incidence; Regional differences in the US; high incidence in adolescents; more common in men; frequent in African Americans
- How is laboratory diagnosis of Neisseria gonorrhoeae made
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Males: Gram stain of urethral discharge. Look for gramneg diplococci within neutrophils. PCR if asymptomatic
Females: PCR of urine or cervical discharge. Also rectal swabs - How is Neisseria gonorrhoeae cultured
- Chocolate agar; modified Thayer Martin or Martin Lewis agar
- For gonococcal infections in children, what must be considered
- Sexual abuse. Genital, anal, and pharyngeal cultures should be obtained from all patients before antibiotic therapy is initiated
- Why is penicillin no longer the first choice for Neisseria gonorrhoeae
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Penicillinase-producing N. gonorrhoeae carry penicillinase on a small plasmid, probably acquired from H. ducreyi.
Penicillin resistance due to altered penicillin-binding proteins can also occur and is chromosomally encoded - What is tetracycline resistance in Neisseria gonorrhoeae due to
- Insertion of a transposon carrying the tetM gene into the large conjugative plasmid. Can join with the penicillinase-producing plasmid
- What is the antibiotic of choice against Neisseria gonorrhoeae
- Ceftriaxone. Fluoroquinolones (ciprofloxacin and ofloxacin) are usually effective too
- When treating for Neisseria gonorrhoeae, what else should be treated for
- Chlyamidia trachomatis, since coinfection is common. Use doxycycline
- How should gonococcal conjunctivitis be treated
- With erythromycin or tetracyclin ophthalmic ointment or silver nitrate drops
- Why is there no vaccine for Neisseria gonorrhoeae
- Unlike most serogroups of N. meningitidis, the gonococcus lacks a capsule to which a protective immune response can be induced