Gonorrhoea

1. Clinical Overview

Summary

Gonorrhoea is a Sexually Transmitted Infection (STI) caused by the Gram-negative diplococcus Neisseria gonorrhoeae. It is the second most common bacterial STI globally, with over 87 million new cases annually worldwide. [1]

The organism is an obligate human pathogen that primarily infects mucosal surfaces lined by columnar or cuboidal epithelium: Urethra, Endocervix, Rectum, Pharynx, and Conjunctiva. Stratified squamous epithelium (vagina, ectocervix) is relatively resistant to infection.

Clinical presentation varies by anatomical site and sex:

• Men: Typically symptomatic with purulent urethral discharge and dysuria (90% develop symptoms within 2-7 days)
• Women: Asymptomatic in 50-80% of cases, which facilitates transmission and increases risk of complications
• Extragenital sites: Pharyngeal (5-10% of cases) and rectal (30-40% in MSM) infections are frequently asymptomatic

Untreated gonorrhoea can ascend to cause Pelvic Inflammatory Disease (PID) in women (10-20% risk) and epididymo-orchitis in men (1-3%). Rarely, haematogenous dissemination occurs, causing Disseminated Gonococcal Infection (DGI) with arthritis-dermatitis syndrome (0.5-3% of cases). [2,3]

The global antimicrobial resistance (AMR) crisis in gonorrhoea represents a major public health threat. N. gonorrhoeae has developed resistance to every first-line antimicrobial class historically used: sulphonamides (1940s), penicillin (1980s), tetracyclines (1980s), fluoroquinolones (2000s), and increasingly to macrolides (azithromycin). Current first-line therapy relies on extended-spectrum cephalosporins (ceftriaxone), but strains with reduced cephalosporin susceptibility and extensively drug-resistant (XDR) strains have been documented globally. [4,5]

Clinical Pearls

"The Great Imitator of STIs": Gonorrhoea can present identically to Chlamydia trachomatis, but typically produces more profuse, purulent discharge. However, distinguishing clinically is unreliable—always test for both.

Asymptomatic Women = Silent Epidemic: Up to 80% of cervical gonorrhoea is asymptomatic. This drives ongoing transmission and presents as "PID of unknown origin" months later. Screen opportunistically in high-risk groups.

"Check All Three Sites" (MSM): In men who have sex with men (MSM), test urethral, pharyngeal, AND rectal sites. Pharyngeal gonorrhoea is asymptomatic in > 90% but serves as a reservoir for transmission and may facilitate resistance development via genetic exchange with commensal Neisseria species. [6]

Antimicrobial Stewardship is Critical: Gonorrhoea is approaching untreatable status in some settings. Extensively drug-resistant (XDR) strains (e.g., FC428 strain in Southeast Asia, A8806 strain in Australia) exhibit resistance to ceftriaxone AND azithromycin. Test of Cure (TOC) is now mandatory in all cases. [7]

Think DGI in Monoarthritis + Skin Lesions: Disseminated Gonococcal Infection presents with the triad of migratory polyarthralgia, tenosynovitis, and pustular skin lesions on extremities. It occurs more frequently in women (especially during menstruation/pregnancy) and individuals with complement deficiencies (C5-C9). [8]

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2. Epidemiology

Global and UK Burden

Gonorrhoea incidence has increased substantially in high-income countries over the past decade, attributed to:

• Reduced condom use (especially in MSM following PrEP availability for HIV)
• Increased screening and NAAT testing (detecting asymptomatic cases)
• Online sexual networking facilitating partner change
• Asymptomatic pharyngeal/rectal reservoirs [1,9]

Demographics and Risk Groups

Sex-specific patterns:

• Men: Higher diagnosed rates (symptomatic presentation drives testing)
• Women: Higher undiagnosed burden (asymptomatic disease)
• MSM: Disproportionately affected (50-60% of male diagnoses in UK) [9,10]

Co-Infection

Chlamydia co-infection is particularly important because:

• Simultaneous infection is common (10-40% of gonorrhoea cases)
• Historical dual therapy (ceftriaxone + azithromycin) covered both
• Current UK guidance uses ceftriaxone monotherapy for gonorrhoea, so separate Chlamydia NAAT is essential [11]

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3. Aetiology and Pathophysiology

Microbiology of Neisseria gonorrhoeae

Organism Characteristics:

• Gram-negative diplococcus (kidney bean-shaped pairs)
• Oxidase-positive, catalase-positive
• Fastidious: Requires enriched media (chocolate agar, Thayer-Martin selective media)
• Obligate human pathogen: No animal reservoir
• Capnophilic: Grows best in 5% CO₂

Key Virulence Factors:

Molecular Pathogenesis

Exam Detail: Phase 1: Attachment (0-6 hours) N. gonorrhoeae attaches to non-ciliated columnar epithelial cells via Type IV pili. Pili undergo antigenic variation through recombination of pilE gene cassettes, generating millions of variants. This prevents antibody-mediated immunity and facilitates reinfection. [12]

Phase 2: Invasion (6-24 hours) Following attachment, opacity proteins (Opa) and porin (PorB) mediate uptake into epithelial cells via receptor-mediated endocytosis. Gonococci transcytose through cells and are released into subepithelial space. PorB inhibits phagolysosome fusion in macrophages, allowing intracellular survival. [13]

Phase 3: Inflammation (24-72 hours) Lipooligosaccharide (LOS) endotoxin triggers TLR4-mediated inflammatory response, recruiting neutrophils. Massive neutrophil influx produces the characteristic purulent discharge. LOS undergoes phase variation and sialylation (mimicking host glycoproteins) to evade complement-mediated lysis.

Phase 4: Tissue Damage Neutrophil degranulation releases proteases and reactive oxygen species, causing epithelial damage. In women, infection can ascend from endocervix → endometrium → fallopian tubes, causing PID. LOS-induced tubal damage leads to scarring, ciliary dysfunction, and infertility. [14]

Phase 5: Dissemination (Rare) In less than 1% of cases, gonococci enter the bloodstream, causing Disseminated Gonococcal Infection (DGI). Strains causing DGI are typically:

• Serum-resistant (due to sialylated LOS)
• PorB1A phenotype (resistant to complement-mediated killing)
• More common in individuals with terminal complement deficiencies (C5-C9) [8]

Immune Evasion Mechanisms

N. gonorrhoeae is a "master of immune evasion":

1. Antigenic Variation: Pili, Opa proteins, and LOS undergo phase and antigenic variation at high frequency, generating immunologically distinct variants within hours
2. Molecular Mimicry: Sialylated LOS resembles host glycoproteins, reducing complement activation
3. IgA Protease: Cleaves secretory IgA1, the predominant antibody at mucosal surfaces
4. Intracellular Survival: Survives within neutrophils and macrophages by inhibiting phagolysosome fusion
5. Suppression of Adaptive Immunity: Inhibits T-cell proliferation and dendritic cell maturation

Clinical Consequence: No protective immunity develops after natural infection. Individuals can be reinfected repeatedly with the same strain. This contrasts with other bacterial infections (e.g., Streptococcus pyogenes) where immunity develops. [15]

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4. Antimicrobial Resistance

Historical Evolution of Resistance

Current Resistance Landscape

Cephalosporin Resistance:

• Mediated primarily by mosaic penA alleles (altered penicillin-binding protein 2) acquired through horizontal gene transfer from commensal Neisseria species
• First ceftriaxone-resistant strain (H041) identified in Japan (2009), then France (F89), Australia (A8806)
• Extensively Drug-Resistant (XDR) strains resistant to ceftriaxone AND azithromycin reported globally (FC428 strain, Singapore 2018) [4,5,7]

Global Surveillance:

• UK (GRASP - Gonococcal Resistance to Antimicrobials Surveillance Programme): Monitors resistance trends, guides national policy
• WHO (GASP - Gonococcal Antimicrobial Surveillance Programme): Coordinates global surveillance
• USA (GISP - Gonococcal Isolate Surveillance Project): Sentinel surveillance in 25-30 STI clinics

Current Resistance Rates (UK 2019 GRASP):

• Ciprofloxacin: > 35% (not recommended)
• Azithromycin (high-level, MIC ≥256 mg/L): 3-5%
• Ceftriaxone (MIC ≥0.125 mg/L): less than 1% (but rising)
• Penicillin: > 10% (not used)

Future Threats

"Untreatable Gonorrhoea": Scenarios where no single antimicrobial reliably achieves cure:

• Pan-resistant strains to all oral and IM options
• Already documented in case reports (FC428, A8806 strains requiring multi-drug IV regimens)
• Threatening return to pre-antibiotic era complications (widespread PID, infertility, neonatal blindness) [16]

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5. Clinical Presentation

Male Urogenital Infection

Anterior Urethritis (95% of male cases):

• Incubation: 2-7 days (range 1-14 days)
• Symptoms (90% symptomatic):
  • "Urethral discharge: Profuse, purulent (thick, creamy, yellow-green). Volume greater than Chlamydia"
  • "Dysuria: Burning sensation, typically at meatus"
  • "Urethral irritation: Discomfort, pruritus"
• Signs:
  • Mucopurulent/purulent meatal discharge (expressible or spontaneous)
  • Meatal erythema, edema
• Timing: Symptoms develop rapidly (80% within 5 days)

Asymptomatic Urethral Infection (10% of men):

• More common in MSM
• Detected by screening or partner notification
• Equally infectious and can progress to complications

Complications in Men:

• Epididymo-orchitis (1-3%): Scrotal pain, swelling, fever. Risk of subfertility
• Urethral stricture (rare, chronic untreated disease)
• Prostatitis (rare)
• Tysonitis (inflammation of Tyson's glands)

Female Urogenital Infection

Endocervicitis (Primary site in 80-90%):

• Asymptomatic in 50-80% (CRITICAL for public health control)
• Symptoms (when present):
  • "Vaginal discharge: Mucopurulent (less profuse than male urethral discharge)"
  • Dysuria: Can mimic UTI ("urethral syndrome")
  • Intermenstrual bleeding (IMB)
  • Post-coital bleeding (PCB)
  • Lower abdominal pain (suggests ascending infection)
• Signs (on speculum examination):
  • "Mucopurulent cervicitis: Yellow/green discharge from os"
  • "Cervical friability: Bleeds easily on contact (e.g., with swab)"
  • Cervical erythema, edema

Urethritis (co-exists in 70-90% of cervical infections):

• Contributes to dysuria
• Can be sole site in post-hysterectomy women

Bartholin's Gland Abscess (1-2%):

• Acute painful labial swelling
• Requires incision and drainage + antimicrobials

Ascending Infection:

• Pelvic Inflammatory Disease (PID): 10-20% of untreated cases ascend
  • Endometritis → salpingitis → tubo-ovarian abscess
  • Presents with lower abdominal pain, fever, cervical excitation tenderness
  • "Complications: Tubal scarring (infertility 10-20%), ectopic pregnancy risk (×7-10), chronic pelvic pain (18%)"
• Fitz-Hugh-Curtis Syndrome (Perihepatitis): 5-10% of PID cases
  • Right upper quadrant pain (can mimic cholecystitis)
  • "Violin string" adhesions between liver capsule and peritoneum
  • Diagnosed via laparoscopy or clinical suspicion [17]

Extragenital Infection

Pharyngeal Gonorrhoea (5-10% heterosexuals, 10-20% MSM):

• Asymptomatic in > 90%
• Symptoms (rare): Sore throat, pharyngitis (clinically indistinguishable from viral pharyngitis)
• Importance:
  • Reservoir for onward transmission (via oral sex)
  • Difficult to eradicate (biofilm formation, lower antimicrobial penetration)
  • Site of horizontal gene transfer with commensal Neisseria (facilitates resistance development)
  • Spontaneous clearance in 80% by 12 weeks (but infectious in interim) [6]

Rectal Gonorrhoea (5-10% women, 30-40% MSM):

• Asymptomatic in 80-90%
• Symptoms (when present):
  • Anal discharge (purulent)
  • Rectal pain, pruritus
  • Tenesmus, urgency
  • Rectal bleeding (proctitis)
• Signs (on proctoscopy):
  • Mucopurulent anal discharge
  • Rectal mucosal erythema, friability
  • Ulceration (severe cases)
• Routes of infection:
  • Direct (receptive anal intercourse)
  • Indirect (contamination from vaginal discharge in women)

Conjunctival Gonorrhoea (Adult):

• Acute purulent conjunctivitis
• Unilateral or bilateral
• Copious purulent discharge
• Risk of corneal ulceration → perforation → blindness if untreated
• Acquired via autoinoculation (contaminated fingers) or direct contact
• Medical emergency: Requires urgent ophthalmology review + systemic antimicrobials

Disseminated Gonococcal Infection (DGI)

Incidence: 0.5-3% of gonococcal infections (rare but important)

Risk Factors:

• Female sex (3× higher risk)
• Menstruation, pregnancy (immunological changes)
• Terminal complement deficiencies (C5, C6, C7, C8, C9): 10-20× risk
• Pharyngeal gonorrhoea (serum-resistant strains)
• SLE, HIV (immunosuppression)

Clinical Syndromes:

1. Arthritis-Dermatitis Syndrome (Classic DGI):

   • Triad:
     • Migratory polyarthralgia: Affects multiple joints sequentially (wrists, ankles, knees)
     • Tenosynovitis: Inflammation of tendon sheaths (wrists, fingers, ankles, toes). Classic sign
     • Dermatitis: Sparse pustular or vesiculopustular skin lesions (5-40 lesions) on acral surfaces (hands, feet, forearms)
   • Fever (50-80%)
   • Blood cultures positive in 20-30%
   • Genital/pharyngeal culture positive in 80%

2. Septic Arthritis:

   • Monoarticular (80%): Knee > ankle > wrist > elbow
   • Purulent joint effusion
   • Synovial fluid culture positive in 50%
   • Can cause cartilage destruction if untreated

3. Rare Manifestations:

   • Endocarditis (less than 1%): Aortic valve most common; high mortality
   • Meningitis (less than 1%): Purulent meningitis, similar to meningococcal
   • Osteomyelitis: Rare
   • Perihepatitis (Fitz-Hugh-Curtis): Part of PID spectrum

Diagnostic Clues:

• Young sexually active adult with monoarthritis + pustular rash
• Tenosynovitis (uncommon in other septic arthritides)
• Positive sexual health screen
• Complement deficiency (recurrent DGI) [8,18]

Neonatal Gonorrhoea

Ophthalmia Neonatorum:

• Vertical transmission during passage through infected birth canal (30-50% transmission rate)
• Incubation: 2-5 days after birth (earlier than Chlamydial ophthalmia, which occurs at 5-14 days)
• Presentation:
  • Bilateral purulent conjunctivitis
  • Profuse discharge (more severe than Chlamydia)
  • Lid edema, chemosis
• Complications:
  • Corneal ulceration → perforation → blindness (if untreated)
  • Rapid progression (hours to days)
• Prevention:
  • Maternal screening in pregnancy
  • Neonatal ocular prophylaxis (varies by country; UK does not routinely use)
  • Treatment of maternal infection before delivery
• Treatment:
  • Ceftriaxone 25-50 mg/kg IM/IV (single dose, max 125 mg)
  • Saline irrigation of eyes
  • Ophthalmology review
  • Test mother and partner

Disseminated Neonatal Gonorrhoea (Rare):

• Sepsis, arthritis, meningitis
• High mortality if untreated [19]

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6. Differential Diagnosis

Urethritis (Male)

Cervicitis (Female)

Disseminated Gonococcal Infection (DGI)

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7. Investigations

First-Line Diagnostic Tests

Nucleic Acid Amplification Test (NAAT) - Gold Standard:

NAAT Advantages:

• Non-invasive (urine, self-swabs)
• Higher sensitivity than culture
• Stable at room temperature (transport logistics)
• Detects non-viable organisms

NAAT Limitations:

• No antimicrobial susceptibility testing (requires culture)
• Risk of false-positives (cross-reaction with commensal Neisseria in pharynx)
• Cannot distinguish viable from dead organisms (not suitable for Test of Cure less than 7 days post-treatment)

Current UK Guidance: All NAAT-positive samples should be reflex-tested with culture (from residual sample or repeat swab) to enable antimicrobial susceptibility testing for surveillance. [20]

Microscopy and Culture

Gram Stain Microscopy:

• Urethral discharge (men): Sensitivity 90-95%, Specificity > 95%
  • "Pathognomonic finding: Gram-negative intracellular diplococci (GNID) within polymorphonuclear leukocytes (PMNs)"
  • Appearance: "Kidney bean" or "coffee bean" pairs inside neutrophils
  • Requires > 5 PMNs per high-power field for diagnosis of urethritis
• Endocervical smear (women): Sensitivity 45-65%, Specificity 90-95%
  • Lower sensitivity due to lower bacterial load, normal vaginal flora
  • Not recommended for diagnosis in women (use NAAT)
• Rectal/pharyngeal: Not recommended (low sensitivity; commensal Neisseria cause false-positives)

Culture:

• Media: Chocolate agar (non-selective) or modified Thayer-Martin agar (selective: vancomycin, colistin, nystatin inhibit normal flora)
• Atmosphere: 5% CO₂, 35-37°C, humid
• Growth: 24-48 hours; grey, mucoid colonies
• Identification:
  • "Oxidase test: Positive (purple color)"
  • "Gram stain: Gram-negative diplococci"
  • "Carbohydrate utilization: Ferments glucose only (not maltose, sucrose, lactose)"
  • MALDI-TOF mass spectrometry (rapid identification)
• Antimicrobial Susceptibility Testing (AST):
  • "Agar dilution (gold standard): Determines minimum inhibitory concentration (MIC)"
  • "E-test: Gradient diffusion method"
  • "Disc diffusion: Not recommended (poor correlation with MIC)"

Culture Indications:

• All NAAT-positive cases (where feasible) for AMR surveillance
• Pharyngeal gonorrhoea (confirm NAAT-positive; exclude commensal Neisseria)
• Treatment failure (suspected resistance)
• Medico-legal cases (sexual assault, child abuse)

Culture Limitations:

• Fastidious organism: Requires rapid transport (less than 6 hours), appropriate media, controlled temperature
• Lower sensitivity than NAAT (60-85% for endocervical specimens)
• Not viable in urine samples

Test of Cure (TOC)

Indications (UK BASHH 2019): MANDATORY for ALL gonorrhoea cases due to AMR concerns

Timing:

• NAAT: ≥14 days (2 weeks) post-treatment (to avoid false-positives from dead organisms)
• Culture: ≥3-5 days post-treatment (viable organisms only)

Sample Site:

• Re-test all initially infected sites (e.g., if pharyngeal + urethral positive, re-test both)

Interpretation:

• Negative TOC: Cure confirmed; discharge from follow-up
• Positive TOC:
  • Treatment failure (resistance) vs. reinfection (new exposure)
  • Repeat culture with AST
  • Consider alternative regimen (e.g., gentamicin 240 mg IM + azithromycin 2 g PO, or IV ceftriaxone 1 g daily × 3 days)
  • Partner notification review [20]

Screening for Co-Infections

Mandatory at gonorrhoea diagnosis:

Investigations for Disseminated Gonococcal Infection (DGI)

If DGI suspected:

• Blood cultures (×3 sets): Positive in 20-30%
• Synovial fluid aspiration:
  • Gram stain (positive in 25%)
  • Culture (positive in 50%)
  • Cell count (> 50,000 WBC/μL, > 90% PMNs)
• Skin lesion swab/biopsy: Low yield
• Urogenital/pharyngeal/rectal NAAT: Positive in 80% (confirms source)
• Echocardiography (if suspected endocarditis)
• Complement assay (if recurrent DGI): C5-C9 levels

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8. Management

Management Algorithm

SUSPECTED GONORRHOEA
         ↓
NAAT Testing (All Exposed Sites)
- Urethral/Vaginal/Urine
- Pharyngeal (if oral sex exposure)
- Rectal (if receptive anal sex)
         ↓
NAAT POSITIVE
         ↓
Simultaneous Actions:
1. TREAT IMMEDIATELY (Epidemiological Treatment)
   - Ceftriaxone 1g IM STAT
2. SEND FOR CULTURE + AST (before/at treatment)
3. SCREEN FOR CO-INFECTIONS (CT, HIV, Syphilis)
         ↓
PATIENT COUNSELLING
- Abstinence for 7 days post-Tx
- Avoid sex until partner(s) treated
- Return for Test of Cure (TOC)
         ↓
PARTNER NOTIFICATION
- All partners in last 3 months (asymptomatic)
  or 2 weeks (symptomatic)
- Partners receive epidemiological treatment
         ↓
TEST OF CURE (TOC)
- NAAT at 2 weeks (all sites)
- Culture at 1 week (if available)
         ↓
┌──────────────┬──────────────┐
TOC Negative   TOC Positive
Discharge      Treatment Failure
               - Repeat culture + AST
               - Alternative regimen
               - Review partner notification

First-Line Treatment (Uncomplicated Gonorrhoea)

UK (BASHH 2019), Europe (IUSTI 2020): [20,21]

• Ceftriaxone 1 g IM single dose
  • Dilute in 1% lidocaine (reduces injection pain)
  • Inject into gluteus maximus or lateral thigh (vastus lateralis)
  • Observe for 20 minutes (rare anaphylaxis risk)

Rationale for Monotherapy:

• Azithromycin co-therapy no longer recommended in UK/Europe (2019 update) due to:
  • Rapidly increasing azithromycin resistance (high-level resistance 3-5%)
  • Preserving azithromycin efficacy for Mycoplasma genitalium (emerging pathogen)
  • Ceftriaxone 1 g monotherapy cure rate > 95% for urogenital gonorrhoea

USA (CDC 2020): [22]

• Ceftriaxone 500 mg IM single dose (≥150 kg: 1 g IM)
• No routine azithromycin (updated 2020; previously recommended dual therapy)

Site-Specific Treatment

Pharyngeal gonorrhoea is particularly challenging:

• Lower cure rates than urogenital (90-95% vs > 99%)
• Biofilm formation, lower antimicrobial penetration
• Do not use oral regimens (e.g., ciprofloxacin) even if susceptible
• Mandatory Test of Cure at 2 weeks [6]

Alternative Regimens

If Ceftriaxone Unavailable or Contraindicated:

Cephalosporin Allergy:

• True IgE-mediated allergy (anaphylaxis, urticaria): Use gentamicin 240 mg IM + azithromycin 2 g PO
• Non-IgE reactions (rash): Can cautiously use ceftriaxone under observation
• Consult infectious diseases/sexual health specialist

Disseminated Gonococcal Infection (DGI) / Complicated Gonorrhoea

Initial Treatment (Inpatient):

• Ceftriaxone 1-2 g IV daily OR
• Ceftriaxone 1 g IM daily (if IV access difficult)
• Continue for 24-48 hours after clinical improvement

Step-Down Therapy (after 24-48h improvement):

• Cefixime 400 mg PO BD (if susceptible) OR
• Continue IM ceftriaxone 1 g daily
• Total duration: 7 days (arthritis), 14 days (endocarditis), 10-14 days (meningitis)

Adjunctive Measures:

• Septic arthritis: Joint drainage (aspiration or arthroscopic washout)
• Endocarditis: Cardiothoracic surgical review (valve replacement may be needed)

Special Populations

Pregnancy and Breastfeeding:

• Ceftriaxone 1 g IM is safe (Category B)
• Azithromycin safe if needed
• Avoid: Fluoroquinolones, tetracyclines
• Screen all pregnant women in high-prevalence areas or with risk factors
• Treat before delivery to prevent neonatal ophthalmia

Neonatal Ophthalmia Neonatorum:

• Ceftriaxone 25-50 mg/kg IM/IV single dose (max 125 mg)
• Saline irrigation of conjunctival sac
• Ophthalmology review (risk of corneal ulceration)
• Test and treat parents

HIV-Positive Individuals:

• Same treatment regimen (no dose adjustment)
• Higher risk of DGI
• Ensure dual HIV/STI partner notification

Pelvic Inflammatory Disease (PID) with Gonorrhoea:

• Ceftriaxone 1 g IM PLUS
• Doxycycline 100 mg BD PO for 14 days (covers Chlamydia, anaerobes)
• Metronidazole 400 mg BD PO for 14 days (covers anaerobes)
• Consider hospital admission if severe, pregnancy, tubo-ovarian abscess

Epididymo-orchitis with Gonorrhoea:

• Ceftriaxone 1 g IM PLUS
• Doxycycline 100 mg BD PO for 10-14 days (covers Chlamydia)
• Scrotal support, analgesia

Treatment Failure

Definition: Positive NAAT or culture at Test of Cure (≥14 days post-treatment)

Approach:

1. Distinguish reinfection vs resistance:
   • Sexual history (new exposure?)
   • Partner treatment status
   • Culture with AST (essential)
2. If resistance confirmed:
   • Gentamicin 240 mg IM + Azithromycin 2 g PO (UK second-line)
   • High-dose ceftriaxone 1-2 g IV daily × 3 days (case reports)
   • Ertapenem, carbapenem (XDR gonorrhoea; specialist advice)
3. Notify Public Health England / CDC (resistance surveillance)
4. Repeat TOC after alternative treatment [23]

Partner Notification and Contact Tracing

Principle: Break transmission chain; prevent reinfection; detect asymptomatic cases

Lookback Period:

• Symptomatic patients: All partners in preceding 2 weeks
• Asymptomatic patients: All partners in preceding 3 months

Methods:

1. Patient referral: Patient informs partners directly
2. Provider referral: Healthcare worker contacts partners (with patient consent)
3. Conditional referral: Patient referral first; provider referral if unsuccessful

Partner Management:

• Epidemiological treatment (treat presumptively without waiting for test results)
• Test for gonorrhoea and co-infections (even if treated empirically)
• Avoid sex for 7 days post-treatment

Expedited Partner Therapy (EPT): Providing antimicrobial prescriptions for partners without clinical assessment

• Not recommended for gonorrhoea (need for culture, TOC, AMR monitoring)
• Legal status varies by jurisdiction

Safeguarding:

• Under-16 s: Consider child protection issues, sexual exploitation
• Vulnerable adults: Domestic abuse, commercial sex work

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9. Complications

Female Complications

PID Risk Factors:

• Young age (less than 25 years)
• Multiple sexual partners
• Non-barrier contraception
• IUD insertion (transient risk in first 3 weeks)
• Bacterial vaginosis
• Previous PID [17]

Male Complications

Disseminated Complications (Both Sexes)

Neonatal Complications

Oncological Association

Cervical Cancer: Gonorrhoea (and Chlamydia) co-infection with HPV increases risk of:

• Persistent HPV infection (reduced viral clearance)
• Cervical intraepithelial neoplasia (CIN) progression
• Invasive cervical cancer (2-3× relative risk in some studies)
• Mechanism: Chronic inflammation, immune dysregulation [24]

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10. Prognosis and Outcomes

With Appropriate Treatment

Without Treatment (Historical / Current Untreated Cases)

Long-Term Sequelae

Infertility (Women):

• Mechanism: Tubal scarring from PID → tubal occlusion
• Risk after 1 PID episode: 10-12%
• Risk after 2 PID episodes: 25-30%
• Risk after 3+ PID episodes: 50-75%
• Time to infertility recognition: Often years (when attempting conception)

Ectopic Pregnancy:

• 7-10× increased risk after PID
• Life-threatening if rupture occurs
• Accounts for 3-4% of maternal mortality in developed countries

Chronic Pelvic Pain:

• Affects 18% of women after PID
• Mechanism: Adhesions, nerve sensitization
• Significantly impacts quality of life

Reinfection:

• 10-20% reinfection rate within 12 months
• Risk factors: Untreated partners, new partners, resumed high-risk behavior
• Each reinfection increases PID risk incrementally [25]

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11. Prevention and Public Health

Primary Prevention

Barriers to Prevention:

• Asymptomatic infection (unrecognized transmission)
• PrEP-associated behavioral disinhibition (reduced condom use)
• Online sexual networking (rapid partner change)

Secondary Prevention (Screening)

UK Screening Recommendations (BASHH/PHE):

• Universal screening in sexual health clinics
• Opportunistic screening:
  • "MSM: Annually (or 3-6 monthly if high-risk)"
  • Under-25 s: Annually if sexually active
  • Asymptomatic individuals with new partners
  • Partners of index cases

Screening Sites:

• Sexual health clinics (GUM)
• General practice (GP)
• Community services (young people's services, pharmacies)
• Online self-sampling (e.g., SH:24 in UK)

Tertiary Prevention (Reducing Complications)

• Early diagnosis and treatment: Prevents PID, DGI
• Partner notification: Breaks transmission chain
• Test of Cure: Confirms eradication (AMR detection)

Vaccine Development

Challenges:

• Antigenic variation: Pili and Opa proteins constantly change
• No protective immunity after natural infection
• No animal model (obligate human pathogen)

Current Approaches:

• Outer membrane vesicle vaccines (OMV) from Neisseria meningitidis (cross-protection observed in observational studies)
• Conserved epitopes (e.g., MetQ, NGO2054)
• Still in early-phase trials; no licensed vaccine available [26]

Antimicrobial Resistance Mitigation

Strategies:

• Surveillance: GRASP (UK), GISP (USA), GASP (WHO)
• Culture-based AST: All NAAT-positive cases
• Monotherapy: Preserve azithromycin for M. genitalium
• Test of Cure: Detect treatment failures early
• Reporting: Notify resistant cases to public health authorities
• Research: Novel antimicrobials (e.g., zoliflodacin—first-in-class spiropyrimidinetrione) [27]

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12. Evidence and Guidelines

Key Guidelines

Landmark Studies and Evidence

Antimicrobial Resistance Evolution:

1. Ohnishi et al. (2011): First report of ceftriaxone-resistant N. gonorrhoeae H041 strain (Japan). MIC 2-4 mg/L. Demonstrated mosaic penA allele. [4]
2. Unemo et al. (2016): First report of extensively drug-resistant (XDR) gonorrhoea FC428 strain (Japan, France). Resistant to ceftriaxone AND azithromycin. [7]
3. Whiley et al. (2018): Ceftriaxone-resistant A8806 strain (Australia) in heterosexual male. Highlights global spread. [5]

Dual vs Monotherapy Debate:

1. Bignell & Fitzgerald (2011): Advocated dual therapy (ceftriaxone + azithromycin) to prevent resistance emergence.
2. Fifer et al. (2018): UK GRASP data showed rising azithromycin resistance (3-5% high-level). Recommended ceftriaxone monotherapy to preserve azithromycin. [28]
3. CDC (2020): Updated US guidelines to ceftriaxone monotherapy (500 mg) after evidence of high cure rates and azithromycin resistance concerns. [22]

Pharyngeal Gonorrhoea:

1. Chow et al. (2016): Pharyngeal gonorrhoea is harder to treat (90-95% cure vs > 99% urogenital) and may facilitate AMR development via horizontal gene transfer with commensal Neisseria. [6]

Disseminated Gonococcal Infection:

1. Ram et al. (2014): Review of DGI cases; complement deficiency found in 10-20% of recurrent DGI cases. Screening for C5-C9 deficiency recommended. [8]

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13. Examination Focus

High-Yield Exam Topics

Microbiology:

• Gram-negative intracellular diplococci (GNID)
• Oxidase-positive
• Ferments glucose only (not maltose—cf. N. meningitidis)

Clinical Scenarios:

1. Young man with purulent urethral discharge → Gonorrhoea vs NGU; test for both GC and CT
2. Asymptomatic woman with mucopurulent cervicitis on speculum exam → Screen for GC/CT; high PID risk if untreated
3. MSM with pharyngeal gonorrhoea → Importance of multi-site testing; AMR reservoir
4. Monoarthritis + pustular rash + recent sexual exposure → DGI; test complement levels

Management Pearls:

• Current first-line UK: Ceftriaxone 1 g IM (monotherapy)
• Historical dual therapy: Ceftriaxone + azithromycin (no longer recommended UK/Europe/USA)
• Test of Cure: Mandatory at 2 weeks (NAAT)
• Partner notification: 2 weeks (symptomatic) or 3 months (asymptomatic)

Antimicrobial Resistance:

• Sequential resistance: Sulphonamides → Penicillin → Tetracycline → Ciprofloxacin → Azithromycin → (Ceftriaxone)
• XDR strains (FC428, A8806): Resistant to ceftriaxone AND azithromycin
• GRASP surveillance (UK), GISP (USA), GASP (WHO)

Common Viva Questions

Q1: What is the organism that causes gonorrhoea? Describe its appearance on Gram stain. A: Neisseria gonorrhoeae, a Gram-negative diplococcus (appears as kidney bean-shaped pairs). On Gram stain of urethral discharge, it is characteristically seen as Gram-negative intracellular diplococci (GNID) within polymorphonuclear leukocytes (neutrophils). It is oxidase-positive and grows on chocolate agar or selective Thayer-Martin media.

Q2: Why is gonorrhoea in women a public health concern despite often being asymptomatic? A: 50-80% of women with cervical gonorrhoea are asymptomatic, leading to:

1. Delayed diagnosis: Women do not seek care, allowing prolonged infectivity
2. Ongoing transmission: Asymptomatic women unknowingly infect partners
3. Ascending infection: 10-20% develop PID, causing tubal scarring, infertility (10-20% post-PID), ectopic pregnancy (7-10× risk), and chronic pelvic pain (18%)
4. Reservoir: Maintains community prevalence

This necessitates opportunistic screening in high-risk groups and partner notification to identify asymptomatic cases.

Q3: A 25-year-old MSM presents with mild pharyngitis. Sexual history reveals recent unprotected oral sex. What is your diagnostic approach and why? A: Test for pharyngeal gonorrhoea (and Chlamydia) via pharyngeal NAAT.

Rationale:

• Pharyngeal gonorrhoea is asymptomatic in > 90% (this case has mild symptoms, but GC may be coincidental)
• MSM have high prevalence (10-20%) of pharyngeal GC
• Pharynx is a reservoir for onward transmission (via oral sex)
• Pharyngeal GC is difficult to eradicate (90-95% cure vs > 99% urogenital)
• Site of horizontal gene transfer with commensal Neisseria → facilitates AMR development
• If positive: Treat with ceftriaxone 1 g IM + mandatory Test of Cure at 2 weeks

Q4: What is Disseminated Gonococcal Infection (DGI)? Describe the classic presentation. A: DGI occurs when N. gonorrhoeae enters the bloodstream (0.5-3% of infections), causing:

Classic Triad (Arthritis-Dermatitis Syndrome):

1. Migratory polyarthralgia: Multiple joints (wrists, ankles, knees) affected sequentially
2. Tenosynovitis: Inflammation of tendon sheaths (wrists, fingers, ankles)—highly characteristic
3. Dermatitis: Sparse (5-40 lesions) pustular or vesiculopustular skin lesions on acral surfaces (hands, feet, distal extremities)

Additional Features:

• Fever (50-80%)
• Can progress to septic arthritis (monoarticular, purulent joint effusion)
• Rarely: Endocarditis, meningitis

Risk Factors: Female sex, menstruation, pregnancy, complement deficiency (C5-C9), HIV

Diagnosis: Blood cultures (20-30% positive), synovial fluid culture (50% positive), urogenital/pharyngeal NAAT (80% positive)

Q5: Explain the evolution of antimicrobial resistance in gonorrhoea and the rationale for current treatment. A: N. gonorrhoeae has sequentially developed resistance to every first-line agent:

• 1940s: Sulphonamides
• 1976: Penicillin (β-lactamase plasmid—PPNG)
• 1980s: Tetracyclines
• 2000s: Fluoroquinolones (ciprofloxacin > 20% resistance UK; withdrawn as first-line)
• 2010s: Azithromycin (high-level resistance 3-5%)
• 2009-present: Ceftriaxone (H041, FC428, A8806 XDR strains)

Current UK Treatment (BASHH 2019):

• Ceftriaxone 1 g IM monotherapy
• Rationale:
  • Ceftriaxone cure rate > 99% urogenital, 90-95% pharyngeal
  • "Azithromycin no longer co-prescribed to:"
    • Preserve azithromycin for Mycoplasma genitalium (emerging pathogen)
    • Reduce selection pressure for azithromycin resistance
  • Mandatory Test of Cure (2 weeks) to detect treatment failures
  • All NAAT-positive cases undergo culture + AST for surveillance

Threat: XDR gonorrhoea approaching "untreatable" status; novel agents (e.g., zoliflodacin) in development.

Q6: What is the management of a neonate born to a mother with untreated gonorrhoea? A:

Immediate Assessment:

• Examine for ophthalmia neonatorum (purulent conjunctivitis at 2-5 days)
• If present:
  • Ceftriaxone 25-50 mg/kg IM/IV single dose (max 125 mg)
  • Saline irrigation of conjunctivae
  • Urgent ophthalmology review (risk of corneal ulceration → blindness)
• If asymptomatic but mother has gonorrhoea:
  • Prophylactic ceftriaxone 25-50 mg/kg IM (single dose)
  • Monitor for conjunctivitis

Additional:

• Test mother and partner (if not already done)
• Screen for other STIs (Chlamydia, HIV, Syphilis)
• Counsel on safer sex and partner notification

Prevention: Maternal screening in pregnancy (high-risk women); treatment before delivery

OSC E/Clinical Case Scenarios

Scenario 1: Partner Notification Counselling A 22-year-old man diagnosed with gonorrhoea asks, "Do I have to tell my girlfriend?"

Model Answer: "Yes, it's very important for two reasons:

1. Her health: She may have gonorrhoea too, often without symptoms in women. Untreated, it can cause serious problems like pelvic infection and difficulty getting pregnant in the future.
2. Your health: If she's infected and doesn't get treated, you could catch it again even after your treatment works.

We recommend telling all sexual partners in the last 3 months. They should get tested and treated. We can help you with this—you can tell them yourself, or we can contact them confidentially without using your name (provider referral).

You should avoid sex for 7 days after your treatment and until your partner has been treated and completed 7 days too."

Scenario 2: Treatment Failure Discussion A patient returns with positive Test of Cure at 2 weeks. Culture shows ceftriaxone MIC 0.5 mg/L (elevated).

Model Answer: "Your follow-up test shows the gonorrhoea is still there. This could mean:

1. Reinfection: New sexual contact since treatment
2. Treatment resistance: The gonorrhoea strain didn't respond fully to the antibiotic

We'll treat you with a different antibiotic combination today: gentamicin injection plus azithromycin tablets.

We also need to:

• Re-check your recent sexual contacts (have they been treated?)
• Repeat the test 2 weeks after this new treatment
• Report this to Public Health (gonorrhoea resistance is a serious concern; this helps track and control resistant strains)

Have you had any new sexual partners since your last treatment?"

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14. Patient and Layperson Explanation

What is Gonorrhoea?

Gonorrhoea (sometimes called "the clap") is a common sexually transmitted infection (STI) caused by bacteria called Neisseria gonorrhoeae. It is passed through vaginal, anal, or oral sex with someone who has the infection.

It is the second most common bacterial STI in the UK, with over 70,000 cases diagnosed each year.

What are the Symptoms?

Men:

• Thick yellow or green discharge from the penis (usually appears 2-7 days after infection)
• Pain or burning when urinating
• Symptoms are usually obvious, so most men seek treatment quickly

Women:

• Often no symptoms at all (50-80% of women don't know they have it)
• Some women have unusual vaginal discharge, pain when urinating, or bleeding between periods
• Because it's often "silent," women may not realize they have it until complications develop

Other Sites:

• Throat: Usually no symptoms (may have sore throat)
• Rectum (back passage): Often no symptoms (may have discharge or discomfort)
• Eyes: Severe eye infection with discharge (can cause blindness if untreated)

Why is it Important to Treat?

If gonorrhoea is not treated:

Women:

• It can spread up into the womb and fallopian tubes, causing a serious infection called Pelvic Inflammatory Disease (PID)
• This can lead to infertility (difficulty getting pregnant), ectopic pregnancy (pregnancy outside the womb—life-threatening), and long-term pelvic pain

Men:

• It can spread to the testicles, causing pain, swelling, and rarely, reduced fertility

Both:

• Rarely, gonorrhoea can spread in the bloodstream, causing joint infections, skin rashes, and sepsis
• It makes you more likely to catch or pass on HIV

Babies:

• If you're pregnant and have gonorrhoea, it can be passed to your baby during birth, causing a severe eye infection that can lead to blindness

How is it Diagnosed?

• Simple urine test (men) or swab test (women can often do this themselves)
• Swabs from throat or rectum if you've had oral or anal sex
• Results usually available within a few days

How is it Treated?

• Single injection of an antibiotic called ceftriaxone (into your buttock or thigh muscle)
• The injection cures gonorrhoea in over 99% of cases
• You must avoid all sex for 7 days after treatment (and until your partner has been treated too)
• You will need a follow-up test 2 weeks later to make sure the treatment worked (called "Test of Cure")

Important: Gonorrhoea is becoming resistant to many antibiotics. This is why the follow-up test is essential.

What About My Partner(s)?

• All recent sexual partners must be tested and treated (even if they have no symptoms)
• We recommend telling partners from the last 3 months if you had no symptoms, or last 2 weeks if you had symptoms
• The clinic can help you contact them confidentially if needed
• If your partner isn't treated, they can pass gonorrhoea back to you even after your treatment works

Can I Get it Again?

• Yes. Having gonorrhoea once does not protect you from getting it again
• You can be reinfected if you have sex with someone who has gonorrhoea
• Using condoms correctly every time is the best way to prevent gonorrhoea

When Can I Have Sex Again?

• Wait 7 days after your treatment
• Make sure your partner has also been treated and completed 7 days
• If you have sex too soon, you risk catching it again or passing it to someone else

Will This Affect My Future?

• If treated quickly, gonorrhoea does not cause long-term problems
• If left untreated (especially in women), it can cause infertility, chronic pain, and pregnancy complications
• This is why testing and early treatment are so important

How Can I Protect Myself?

• Use condoms (male or female) every time you have vaginal, anal, or oral sex
• Get tested regularly if you have new or multiple sexual partners
• Tell partners if you have an STI, so they can get treated too
• Attend follow-up appointments (Test of Cure) to make sure treatment worked

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Primary Sources

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Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists and follow local guidelines.