Neisseria gonorrhoeae
last authored: July 2011, David LaPierre
last reviewed: Nov 2011, Vidya Beharry
Introduction
Neisseria gonorrhoeae, also known as gonococcus (GC), is a gram-negative diplococcus which is one of the most common sexually transmitted microorganisms, and causes gonorrhea.
Gonorrhea cervicitis, courtesy of CDC PHIL #4087
Humans are the only natural reservoir of N. gonorrhoeae, and transmission is primarily sexual.
GC infections include cervicitis, urethritis, pharyngitis, proctitis, conjunctivitis, arthritis, meningitis, and sepsis.
N. gonorrhoeae continues to evolve, and we are increasingly limited in the antiobiotics available to treat infections - a sigmificant public health issue.
The Case of Jules W
Jules is a 19 year-old man who develops painful, purulent discharge from his penis. It is accompanied by fever. He comes to you for treatment.
- how would you diagnose his condition?
- what other sites of infection would you inquire into?
- how would you treat him?
Epidemiology
Rates of gonorrhea are extremely high and represent a serious public health concern. In the US, there are over 300,000 cases reported yearly, an increase of 10% per year, with the highest rates of increase seen in teenages and young adults. Spread is influenced by reluctance to seek medical care.
Risk factors include:
- under 25 y old
- homelessness
- new/ multiple sexual partners
- non-barrier contraception
Prevention is important to reduce spread; condoms can be very effective. Contact tracing is essential but may be difficult.
Classification and Characteristics of N. gonorrhoeae
Neisseria are aerobic, gram negative diplococci, typically ocurring in kidney bean-shaped pairs. On gram stains, they often appear intracellular, ie inside the cytoplasm of polymorphonuclear neutrophils.
Like other gram negatives, their walls have a peptidoglycan layer and an outer membrane containing endotoxic glycolipid.
Virulence factors
pili extend beyond the outer membrane and are Neisseria's most important virulence factor. They are essential for adhesion to mucosal surfaces and inhibit neutrophil killing.
The outer membrane is composed of phospholipids and other outer membrane proteins. These proteins facilitate adhesion and promote invasion.
Lipo-oligosaccharides have endotoxin activity.
Transmission and Infection
Intracellular GC, courtesy of CDC PHIL #4085
Infection with N. gonorrhoeae occurs with genital contact, usually from asymptomatic patients. Male-to-female transmission risk is ~50% per episode, while female-to-male is 20%. Nonsexual transmission is extremely rare.
The presence of gonococci in children raises strong suspicion of sexual abuse.
Anal sex also has high risk of transmission. Perinatal transmission during vaginal delivery typically involves eyes of the newborn.
GC primarily infects columnar or cuboidal (not squamous) epithelium, with attachment mediated by pili and outer membrane proteins onto nonciliated cells. Endocytosis is followed by passage through the cell and exit through the basement membrane to enter the submucosa, where infection takes hold. Antibody production and activity are low, even with repeated infections.
Infection is established in subepithelial space. A vigorous neutrophil response to GC infection leads to sloughing of epithelium and pus exudation after 2-5 day incubation. Receptors scavenge iron, and gonococci create their own capsule by binding host sialic acid to prevent complement C3b deposition. Pili resist phagocytosis, and the production of catalase inhibits phagocyte activity.
Spread to the fallopian tubes can occur via pili binding to sperm. Salphingitis often begins during or following menstruation.
Clinical Manifesations
Urethritis, with accompanying pyoderma
courtesy of CDC PHIL, #4065
Gonorrhea initially affects mucosal surfaces, causing urethritis or cervicitis 2-7 days after infection. This leads to dysuria and purulent discharge, primarily of the urethra in men and of the cervix in women.
Up to 50% of women with the infection do not show serious symptoms, though approximately 95% of men do. After a few weeks, symptoms subside, and the person then becomes a carrier.
Rectal gonorrhea can cause tenesmus, discharge, and rectal bleeding.
Pharyngitis can occur with oral-genital contact.
Ophtalmia neonatorium, courtesy of CDC PHIL, #3766
Conjunctival contact can lead to severe, acute, purulent infection. This can seriously affect neonates during childbirth.
Ascending disease can lead to salphingitis/pelvic inflammatory disease, a serious infection of the pelvis that can lead to sterility or ectopic pregnancy. It occurs in 10-20% of women. Males can uncommonly develop prostatitis or epididymitis.
Septic arthritis, courtesy of CDC PHIL, # 6805
Disseminated gonococcal infection (DGI) may also spread via the bloodstream, causing bacteremia/sepsis, rash (petechial, maculopapular, or pustular), septic arthritis, meningitis, or endocarditis.
Diagnosis
A Gram stain reveals multiple gram-negative, bean-shaped diplococci. It is very sensitive and specific in men, but isless than 50% sensitive in women due to the abundance of normal flora. A cervical, not vaginal, swab must be done. Confirmation of infection must include the isolation of N. gonorrhoeae on culture media for both men and women.
Culture requires an aerobic atmosphere with added carbon dioxide and enriched medium (eg Martin-Lewis agar: chocolate agar + antibiotics). For men, a urethral swab is ideal; for women, again, a cervical, not vaginal, swab must be done.
N. gonorrhoeae are very fastidious. They do not survive drying and die rapidly during transport, and as such should be innoculated directly onto culture medium or transported in the appropriate medium. Samples collected on transport swabs must be sent to the lab without delay. The organisms may die if not innoculated onto culture medium within 24 hours of collection.
Colonies appear after 1-2 days in CO2 at 35 C. N. gonorrhoeae are catalase and oxidase positive. N. gonorrhoeae oxidizes glucose; N. meningitis oxidizes glucose and maltose; N. lactamica oxidizes glucose, maltose, and lactose. Newer methods of distinguishing Neisseria species include immunofluoresence, coagglutination, and EIA. The identification of the organism should rely on two different methods of identification for accurate and precise confirmation.
Polymerase chain reaction (PCR) is increasingly being used to screen for N. gonorrhoeae, at the same time as for Chlamydia.
Serology is not helpful in diagnosing N. gonorrhoeae.
Treatment
Treatment includes the public as much as it does the individual. As patients often stop treatment once symptoms subside, definitive treatment at time of initial visit is ideal.
Gonorrhea and chlamydia are often treated concurrently, as it can be difficult to distinguish between the two clinically.
Treatment initially was intramuscular penicillin G, though rampant antiobitic resistance, often mediated by plasmids coding for beta-lactamase, has made penicillin useless.
The current recommendation is a third generation cephalosporin such as oral cefixime or intramuscular ceftriaxone. Other options include fluoroquinolones such as ciprofloxacin, azythromycin, or doxycycline. Resistance to tetracycline and fluoroquinolones is unfortunately increasing.
Prevention
For reasons that are poorly understood, vaccine trials against GC have been unsuccessful. Chemoprohylaxis is typically ineffective, other than prevention of eye infections in newborns with silver nitrate, tetracycline, or eryhtromycin.
Education of society re: safer sex practices, as well as thorough identification and treatment of sexual contacts, are some of the most effective strategies for addressing GC infection.
Resources and References
Wong B. 2009. Gonoccocal Infections. eMedicine
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