Gonorrhoea

Gonorrhoea is infection with Neisseria gonorrhoeae, a Gram-negative intracellular diplococcus. It infects columnar and transitional epithelium of the urethra, endocervix, rectum, pharynx and conjunctiva. Over 80 million new cases occur yearly worldwide, with highest rates in people aged 15 to 24 years and in MSM.

Pathogenesis and transmission:

• Attachment by type IV pili and Opa proteins, evasion of immunity by antigenic variation (no lasting immunity, reinfection is common), IgA protease, and lipooligosaccharide-mediated inflammation.
• Transmission by vaginal, anal or oral sex, and perinatal exposure. Transmission risk per act: from man to woman about 50 to 70%, woman to man 20%.
• Incubation 2 to 7 days (up to 14 days).

Risk factors: age under 25, new or multiple partners, MSM, previous STI, inconsistent condom use, substance use, sex work, and partner with gonorrhoea. Co-infection with chlamydia in 20 to 40% (more in heterosexual women).

Antimicrobial resistance:

• Resistance has progressively eliminated penicillins, tetracyclines, fluoroquinolones and (in many settings) macrolides. Ceftriaxone remains the first-line option, with rare treatment failures from strains with mosaic penA genes (FC428, Asia and Europe) and combined ceftriaxone/azithromycin resistance. Surveillance is essential.

Complications:

• Women: pelvic inflammatory disease (10 to 20%), tubo-ovarian abscess, infertility, ectopic pregnancy, chronic pelvic pain, Bartholin abscess, perihepatitis.
• Men: epididymo-orchitis, prostatitis, urethral stricture, and penile oedema.
• Disseminated gonococcal infection (0.5 to 3%): arthritis-dermatitis syndrome or septic arthritis, endocarditis, meningitis, and perihepatitis. Risk factors include complement deficiency (C5 to C9), menstruation, pregnancy, and certain strains.
• Neonates: ophthalmia neonatorum (onset 2 to 5 days), scalp abscess, sepsis, arthritis, with possible blindness.
• Increased risk of HIV acquisition and transmission.

Men (symptomatic in 90% of urethral infections)

• Acute purulent urethral discharge (yellow or green, copious), severe dysuria, meatal erythema, and frequency 2 to 7 days after exposure. Some have mild symptoms or are asymptomatic.
• Complications: unilateral epididymitis, prostatitis, penile lymphangitis, and Tyson gland abscess.

Women (symptomatic in about 50%)

• Increased vaginal discharge, dysuria, intermenstrual bleeding, menorrhagia, lower abdominal pain, and dyspareunia. Examination shows mucopurulent cervicitis with friable cervix. Bartholin or Skene gland abscess.
• Upper tract disease (PID) presents with pelvic pain, fever, and adnexal tenderness.

Extragenital infection

• Rectal: usually asymptomatic. Proctitis (anal discharge, tenesmus, pain, bleeding) in some.
• Pharyngeal: usually asymptomatic. Sore throat in few. A reservoir for transmission and the site where treatment failure is most common.
• Conjunctival: purulent conjunctivitis with corneal ulcer and perforation risk in adults.

Disseminated gonococcal infection

• Triad of tenosynovitis (wrist, fingers, ankles), migratory polyarthralgia and dermatitis (painless pustules or vesicles on erythematous base on extremities), with fever. Septic arthritis (knee, wrist) with purulent joint fluid. Endocarditis (aortic valve) and meningitis are rare.

Neonatal gonococcal infection: purulent conjunctivitis (bilateral, 2 to 5 days of age), with corneal perforation risk.

Differential diagnosis: chlamydia, M. genitalium, trichomonas, herpes, cystitis, prostatitis, bacterial vaginosis, other causes of septic arthritis, meningococcaemia, and reactive arthritis.

Red flags: tubo-ovarian abscess, disseminated infection, pregnancy, child with infection (abuse), treatment failure, and testicular pain.

Laboratory testing

• NAAT (first choice): urine (first void), vulvovaginal or endocervical swab, urethral swab, and rectal and pharyngeal swabs. Sensitivity above 95% at genital sites. Positive pharyngeal NAAT results may be false (cross-reaction with commensal Neisseria), so confirm with a second NAAT targeting a different gene in low-prevalence settings.
• Culture with antimicrobial susceptibility testing (modified Thayer-Martin or chocolate agar in 5% CO2, immediate plating or transport medium): required before treatment in all positive cases where possible (surveillance), and in treatment failure, disseminated infection, and sexual abuse investigations.
• Gram stain of urethral discharge in men: intracellular Gram-negative diplococci with polymorphs (sensitivity 90 to 95%, specificity 95+% in symptomatic men). Less sensitive in women, rectal and pharyngeal samples.
• Disseminated infection: blood cultures, joint fluid culture and Gram stain, skin lesion culture, and cultures from mucosal sites. Synovial fluid white cell count typically above 50,000/µL.
• Screen for chlamydia (NAAT), syphilis, HIV, hepatitis B and C, and trichomonas. Pregnancy test.
• Complement (CH50) in recurrent disseminated or neisserial infection.
• Pelvic ultrasound for suspected tubo-ovarian abscess.

Screening

• Women under 25 and older women at risk annually. MSM at all exposed sites at least annually (3 to 6 monthly if at risk). Pregnant women at risk. People with HIV.

Test of cure

• Recommended for pharyngeal infection (NAAT at 7 to 14 days, culture if NAAT positive), persistent symptoms, pregnancy, treatment failure, and when non-ceftriaxone regimens are used. NAAT may remain positive up to 2 weeks (repeat no earlier than 14 days), so use culture for early assessment.

Uncomplicated urogenital, rectal, pharyngeal infection (adults and adolescents)

• Ceftriaxone 500 mg IM as a single dose (1 g if weight 150 kg or more). In the UK and Europe, 1 g IM single dose is used. If chlamydia has not been excluded, add doxycycline 100 mg twice daily for 7 days.
• Alternative regimens (cephalosporin allergy, or when ceftriaxone is not available):
• Gentamicin 240 mg IM single dose plus azithromycin 2 g orally single dose (poor tolerability, 2 g azithromycin causes gastrointestinal upset).
• Cefixime 800 mg orally single dose (urogenital and rectal only, not recommended for pharyngeal infection).
• Spectinomycin 2 g IM single dose (not effective for pharyngeal infection).
• Newer drugs: zoliflodacin 3 g oral single dose and gepotidacin (urogenital) have shown non-inferiority to ceftriaxone and are recently approved in some regions.
• Penicillin allergy: low cross-reactivity to ceftriaxone (under 2%), so use ceftriaxone unless there has been a severe immediate reaction.

Conjunctivitis: ceftriaxone 1 g IM single dose and saline lavage of the eye.

Pelvic inflammatory disease and epididymitis: as in the chlamydia article, with ceftriaxone 500 mg IM single dose plus doxycycline 100 mg twice daily for 14 days (10 to 14 days for epididymitis) plus metronidazole 400 to 500 mg twice daily (PID).

Disseminated gonococcal infection

• Hospitalise. Ceftriaxone 1 g IM or IV every 24 hours (some use 2 g daily), continued for 24 to 48 hours after improvement, then switch to an oral agent per susceptibility (cefixime 400 mg twice daily, ciprofloxacin 500 mg twice daily if susceptible) to complete at least 7 days. Add doxycycline for chlamydia. Joint drainage by repeated aspiration or arthroscopy.
• Endocarditis: ceftriaxone 1 to 2 g IV every 12 hours for at least 4 weeks. Meningitis: ceftriaxone 1 to 2 g IV every 12 hours for 10 to 14 days.

Neonatal

• Ophthalmia neonatorum or disseminated disease: ceftriaxone 25 to 50 mg/kg IV or IM single dose (maximum 125 mg) for conjunctivitis, or 25 to 50 mg/kg daily for 7 days (10 to 14 days for meningitis) for disseminated infection. Avoid ceftriaxone in hyperbilirubinaemic neonates and those receiving calcium-containing IV products (use cefotaxime 50 mg/kg every 12 hours). Saline irrigation of eyes. Treat the mother and partners, and screen for chlamydia and other STIs.
• Prophylaxis: erythromycin 0.5% ophthalmic ointment (or povidone-iodine 2.5%) to all newborns.

Treatment failure

• Confirm by culture and susceptibility testing, exclude reinfection (most common), and re-treat with ceftriaxone 1 g IM plus azithromycin 2 g orally, or gentamicin 240 mg plus azithromycin 2 g, guided by susceptibility. Consult an expert and public health authorities for suspected resistance. Newer agents (zoliflodacin, gepotidacin) or ertapenem 1 g IM daily for 3 days for ceftriaxone-resistant strains.

Partner management and prevention

• Notify and treat all sexual partners from the preceding 60 days (14 days for symptomatic men with urethral symptoms in some guidelines), with presumptive treatment. Abstain from sexual contact for 7 days after treatment and until partners are treated.
• Retest at 3 months after treatment regardless of partner treatment (reinfection is common).
• Complete HIV, syphilis, hepatitis B and C screening, offer HIV PrEP (cabotegravir 600 mg every 2 months, tenofovir/emtricitabine 300/200 mg daily), vaccination (hepatitis A and B, HPV), and consider doxycycline PEP (not effective for gonorrhoea in most settings, with resistance concerns). The 4CMenB vaccine offers 30 to 40% protection against gonorrhoea and is recommended in some countries for people at high risk.
• Condom use and regular screening.

Follow-up

• Review at 1 to 2 weeks for symptoms (or in 7 to 14 days for test of cure), and again for retest at 3 months. Report to public health authorities per local regulation. Counsel on the risks of antimicrobial resistance and the importance of completing treatment.