Clinical overview
Each sexually transmitted infection produces a characteristic pathological lesion, and the lesion explains the clinical presentation. This chapter walks through the major STIs by pathogen, linking pathology to symptoms, signs, and the implications for treatment failure and complications. The clinical management of discharge and ulcer syndromes is in discharge-and-ulcers — here we cover what each organism does to tissue, why it presents the way it does, and how the pathology shapes diagnostic and treatment choices.
Core knowledge
Chlamydia trachomatis (serotypes D–K — urogenital)
Cervicitis can ascend through the endometrium to the fallopian tube, leaving tubal scarring that explains infertility and ectopic risk.
Pathology:
- Obligate intracellular bacterium; infects columnar and transitional epithelium.
- Two-phase life cycle (elementary body — extracellular infectious form; reticulate body — intracellular replicating form).
- Causes follicular cervicitis with intense lymphoid infiltration.
- Ascends to endometrium → endometritis (often silent), then tubes → silent salpingitis.
Clinical correlate:
- Often asymptomatic (60–70% of women) — pathology proceeds silently.
- Cervicitis with mucopurulent discharge, contact bleeding, friable cervix.
- Intermenstrual or postcoital bleeding.
- PID with often relatively mild symptoms (vs gonorrhoea) but significant tubal damage.
- Long-term sequelae from indolent tubal damage — infertility, ectopic, chronic pelvic pain.
Diagnosis: NAAT/PCR (endocervical swab or self-collected vaginal swab); urine for men. Culture obsolete.
Neisseria gonorrhoeae
Pathology:
- Gram-negative diplococcus; pili attach to columnar epithelium.
- Intracellular survival in neutrophils — paradoxically not killed by neutrophil response in the early stages.
- Causes acute purulent inflammation with neutrophil infiltrate.
- Ascends similarly to chlamydia but tends to produce more acute clinical syndromes.
Clinical correlate:
- More acute presentation: dysuria, frequent purulent cervical discharge, severe pelvic pain in PID.
- Disseminated gonococcal infection (DGI): septic arthritis, dermatitis (small pustules), tenosynovitis. Septic arthritis often monoarticular.
- Pharyngitis, conjunctivitis (neonatal ophthalmia in vertical transmission).
Diagnosis: NAAT/PCR + culture (essential for sensitivity given resistance patterns).
Mycoplasma genitalium
Pathology:
- Smallest free-living bacterium; lacks cell wall (so beta-lactams ineffective).
- Causes cervicitis and urethritis with chronic inflammation.
Clinical correlate:
- Persistent or recurrent cervicitis/urethritis after standard treatment.
- Associated with PID and tubal damage.
- Increasingly recognised in non-gonococcal, non-chlamydial PID.
Diagnosis: PCR; macrolide resistance testing where available.
Treatment: azithromycin (resistance rising), moxifloxacin, pristinamycin — challenging.
Trichomonas vaginalis
Pathology:
- Flagellated protozoan.
- Infects squamous epithelium of vagina; not cervical canal.
- Inflammatory infiltrate of polymorphs.
- Causes punctate haemorrhages of cervical epithelium → "strawberry cervix" (colpitis macularis).
Clinical correlate:
- Frothy, often profuse, yellow-green discharge.
- Intense vulval itch and dyspareunia.
- Strawberry cervix (15–25% of cases on careful inspection).
- Coexists frequently with BV.
- Associated with preterm birth and HIV acquisition.
Diagnosis: motile flagellates on wet mount (low sensitivity), PCR (high sensitivity), culture (Diamond's medium).
Bacterial vaginosis (BV)
Not a single organism but a disturbed vaginal microbial ecosystem.
Pathology:
- Loss of Lactobacillus crispatus dominance.
- Overgrowth of anaerobic and facultative bacteria: Gardnerella vaginalis, Atopobium vaginae, Mobiluncus, Prevotella.
- Biofilm formation on vaginal epithelial cells → "clue cells."
- Raised pH (>4.5) due to loss of lactic acid production.
Clinical correlate:
- Thin grey-white discharge with fishy odour (volatile amines from anaerobes).
- Worsens after intercourse (alkaline semen) and during menses (alkaline blood).
- Often asymptomatic.
- Increases risk of: STI acquisition (including HIV), preterm birth, PID after instrumentation, post-hysterectomy cuff cellulitis.
Diagnosis: Amsel criteria (≥3 of 4): thin grey discharge, pH >4.5, positive whiff test, clue cells. Or Nugent score on Gram stain (7–10 = BV).
Candida albicans (and other Candida species)
Pathology:
- Yeast/hyphal dimorphism.
- Adheres to vaginal epithelium via candidal adhesins.
- Inflammatory response — erythema, oedema, fissuring.
- Recurrent disease may involve C. glabrata (more antifungal-resistant).
Clinical correlate:
- Thick, white, "cottage cheese" discharge.
- Intense itch, vulval erythema, fissures.
- Dyspareunia, dysuria (vulval).
- Normal vaginal pH (<4.5).
- Recurrent in immunocompromised, diabetes, antibiotic use.
See candidiasis for full management.
Herpes simplex virus (HSV-1, HSV-2)
Pathology:
- Double-stranded DNA virus.
- Infects mucosal/cutaneous epithelium → multinucleate giant cells, ballooning degeneration, intranuclear inclusions (Cowdry type A).
- Establishes latency in sensory dorsal root ganglia; reactivates periodically.
Clinical correlate:
- Primary infection: prodromal tingling/burning → vesicles → ulcers; bilateral, multiple, painful; inguinal lymphadenopathy; systemic features (fever, malaise, dysuria).
- Recurrence: unilateral, fewer lesions, milder, no systemic features; recurrences decline over years.
- HSV-2 more frequent genital recurrences than HSV-1.
- Severe disease in immunocompromised; aciclovir resistance rare but possible (foscarnet).
- Vertical transmission: highest risk with active lesions at delivery — caesarean delivery.
Diagnosis: PCR from ulcer base; serology for type-specific antibodies.
Syphilis (Treponema pallidum)
Pathology:
- Spirochete; penetrates mucosa or microabrasions.
- Endarteritis obliterans is the histological hallmark — perivascular plasma cell infiltrate.
- Stages:
- Primary: chancre — painless, indurated, single ulcer with rolled edges.
- Secondary (6 weeks to 6 months later): widespread skin rash (palms and soles), condylomata lata (broad-based wart-like genital lesions — moist, infectious), mucous patches, generalised lymphadenopathy, alopecia.
- Latent: serology positive, no clinical features. Early (<1 year) and late.
- Tertiary (years later): gummata, cardiovascular syphilis (aortic aneurysm), neurosyphilis (tabes dorsalis, general paresis).
- Congenital syphilis: vertical transmission can occur from any stage but highest in primary/secondary; fetal effects — hepatosplenomegaly, rash, snuffles, bone changes, hutchinson teeth, mulberry molars, neurologic damage.
Diagnosis: dark-field microscopy of chancre (early); serology — RPR/VDRL (non-treponemal, follows treatment response) + TPHA/EIA (treponemal, lifelong positive after exposure).
Treatment: penicillin (intramuscular benzathine penicillin G); penicillin desensitisation in pregnancy if allergic — no other proven treatment for congenital syphilis prevention.
Chancroid (Haemophilus ducreyi)
Pathology:
- Gram-negative coccobacillus.
- Painful, soft-edged ulcers (non-indurated) with purulent base.
- Tender suppurative inguinal lymphadenitis (bubo).
Clinical correlate:
- Multiple painful ulcers (typically 2–10).
- Fluctuant inguinal nodes that may rupture and discharge pus.
- More common in tropical settings.
Diagnosis: difficult to grow on culture; clinical diagnosis often.
Lymphogranuloma venereum (LGV — Chlamydia trachomatis L1–L3)
Pathology:
- Same organism as urogenital chlamydia but different serovars with greater virulence.
- Three stages:
- Primary: small painless papule or ulcer that often passes unnoticed.
- Secondary: tender inguinal/femoral lymphadenopathy ("groove sign" — both above and below the inguinal ligament).
- Tertiary: chronic genital ulceration, lymphatic obstruction (elephantiasis), strictures.
- Proctitis if anal exposure (rectal LGV).
Diagnosis: PCR with LGV typing.
Treatment: doxycycline 100 mg PO 12-hourly × 21 days.
Granuloma inguinale (donovanosis — Klebsiella granulomatis)
Pathology:
- Gram-negative encapsulated bacterium.
- Causes painless beefy-red, friable, slowly progressive ulcers.
- Donovan bodies on histology (bipolar-stained bacteria within macrophages).
Clinical correlate:
- Painless ulcers that gradually expand.
- Tropical climates.
- Rare in modern SA but reported.
Treatment: azithromycin or doxycycline for ≥3 weeks until healed.
Human papillomavirus (HPV)
See hpv-pathology for full coverage. Key points:
- DNA virus; >100 types; ~40 anogenital.
- Low-risk types (6, 11) cause genital warts (condyloma acuminata).
- High-risk types (16, 18, others) cause cervical, vulval, vaginal, anal, oropharyngeal cancers.
- HPV vaccines (Cervarix, Gardasil, Gardasil-9) prevent infection.
Hepatitis B and C
Sexually transmissible. Routine screening at first HIV testing or first ANC visit. Vaccination for HBV. HCV: increasingly recognised in MSM and IV drug users; new antivirals highly effective.
Assessment
Assessment of the symptomatic patient is detailed in discharge-and-ulcers and acute-pelvic-infection.
Management
Pathology-driven management implications:
- Chlamydia in young woman → silent ascent → screen and treat early to prevent tubal damage.
- Gonorrhoea → resistance to oral agents requires ceftriaxone IM.
- Mycoplasma genitalium → don't assume treatment-failure cervicitis is non-compliance; consider resistance, send PCR.
- Trichomonas → treat partner (often missed).
- BV → recurrence common; address concurrent issues (douching, scented products).
- HSV → suppressive treatment if frequent recurrences; consider delivery planning if active in pregnancy.
- Syphilis → adequate treatment by stage; penicillin only proven treatment in pregnancy.
- LGV → 21 days doxycycline.
- Chancroid, donovanosis → recognise; treat empirically.
- HPV → vaccinate eligible girls and boys (SA national programme for girls 9–14; expanding); screen for cervical disease in HIV-positive.
Red flags / pitfalls
- Treating cervicitis without identifying organism — appropriate where syndromic, but follow-up with PCR for partner and re-screen.
- Missing painless ulcer = syphilis or LGV until proven otherwise.
- Persistent ulcer >2 weeks — biopsy (malignancy).
- Treating HSV without considering immune status — HIV testing.
- Inadequate syphilis treatment in pregnancy — congenital syphilis still occurs in SA.
- Failure to test all partners — re-infection.
- Not vaccinating against HPV when eligible.
- Forgetting hepatitis B/C screening.
- Mycoplasma not considered in chronic cervicitis.
Evidence anchors
- South African National Department of Health STI Management Guidelines (latest).
- CDC STI Treatment Guidelines (2021).
- WHO STI Treatment Guidelines.
- BASHH UK National Guidelines for individual STIs.
- IUSTI Europe STI Guidelines.
- Workowski KA, et al. — CDC STI guideline reviews.
- Holmes KK, Sparling PF, et al. Sexually Transmitted Diseases (textbook, 4th ed.).
- South African HIV Clinicians Society Adult ART Guidelines (2023).