The most common bacterial STIs in the US, in descending order, are chlamydia then gonorrhoea. This tab covers urethritis, the ulcerative and non-ulcerative genital lesions, vaginitis, and the urologic manifestations of HIV/AIDS.
Epidemiology and Screening
Risk factors: number of lifetime partners, unprotected sex (no condom), risky sexual partners, and the effect of alcohol or drugs on sexual decision-making.
CDC screening recommendations:
- Women — annual chlamydia screening for all sexually active women ≤25 and any with new/multiple partners; annual gonorrhoea screening for at-risk women; and syphilis, HIV, and chlamydia for all pregnant women (gonorrhoea for at-risk pregnant women), starting early with repeat testing as needed.
- Men — at least annual syphilis, chlamydia, gonorrhoea, and HIV screening for all sexually active MSM, increasing to every 3–6 months for those with multiple/anonymous partners or drug use.
Reportable in every US state: chlamydia, gonorrhoea, syphilis, chancroid, and HIV/AIDS.
Urethritis
Urethral inflammation is classified as gonococcal or non-gonococcal (NGU).
- Gonococcal — Neisseria gonorrhoeae, a gram-negative diplococcus; an oxidase-positive culture on Thayer-Martin medium is diagnostic. Incubation 3–14 days.
- Non-gonococcal (NGU) — caused by organisms other than N. gonorrhoeae. Chlamydia trachomatis accounts for 15–40%, with less common causes being Mycoplasma genitalium, Trichomonas vaginalis, adenoviruses, and HSV-1.
- Chlamydia — gram-negative; incubation 3–14 days (same as gonorrhoea).
- Mycoplasma genitalium — lacks a cell wall (cannot be Gram-stained) and can become intracellular, establishing chronic infection and evading immunity/antibiotics. Risk factors in men: young age, intercourse in the past month, and a partner with recent STI.
- Ureaplasma — conflicting evidence as a cause.
- Trichomonas vaginalis — a flagellated parasite of the lower genitourinary tract; a common vaginal pathogen that can also cause male urethritis.
Natural history:
- Gonorrhoea — in women causes PID, tubal scarring, infertility, ectopic pregnancy, and chronic pelvic pain; increases HIV transmission risk; disseminated disease (rare) causes arthritis, dermatitis, meningitis, and endocarditis.
- Chlamydia — the major risk in men is transmission to female partners causing PID; male complications include epididymitis and Reiter syndrome (conjunctivitis, urethritis, reactive arthritis); ascending infection in women causes tubal scarring, PID, ectopic pregnancy, pelvic pain, and infertility.
Diagnosis — symptoms are urethral discharge, pruritus, and dysuria. Gonorrhoea is usually symptomatic in men (urethritis, epididymitis, proctitis, prostatitis) though some sources report frequent asymptomatic infection; women are frequently asymptomatic. Chlamydia causes dysuria, discharge, and epididymitis in men, but up to 42% of men with NGU and up to 75% of women are asymptomatic; ~25% of M. genitalium infections are asymptomatic. NAATs on urine are the test of choice for both gonorrhoea and chlamydia — test for both given frequent co-infection — and have replaced urethral swabs, wet mounts, and culture (including for trichomonas; M. genitalium is diagnosed by NAAT/PCR).
Management — ceftriaxone 250 mg IM single dose plus either azithromycin 1 g PO single dose or doxycycline 100 mg PO BID ×7 days. Dual therapy covers both N. gonorrhoeae and chlamydia because of frequent co-infection, and all patients should be tested for other STIs including syphilis and HIV.
Ulcerative Genital Lesions
Genital ulcers are classified as infectious or non-infectious:
| Infectious | Non-infectious |
|---|---|
| Herpes, syphilis, chancroid, lymphogranuloma venereum, donovanosis/granuloma inguinale | Trauma, malignancy, psoriasis, yeast, aphthae, fixed drug eruption |
In sexually active young US men, genital herpes is the most common ulcer, followed by syphilis; chancroid occurs in some areas, LGV is increasing among MSM, and donovanosis is essentially confined to tropical/developing regions. Work-up is history/exam plus targeted labs (HSV culture or NAAT/PCR + serology; syphilis serology ± darkfield; H. ducreyi testing where chancroid is prevalent) and HIV testing. Even after full evaluation, 25% of genital ulcers have no laboratory-confirmed diagnosis; biopsy unusual or non-responding ulcers.
Herpes
The most common cause of genital ulcers, caused by the double-stranded DNA herpes simplex virus. HSV-1 is mainly oral but causes 5–30% of first genital episodes; HSV-2 causes most genital herpes. Women are more susceptible to and more often symptomatic with HSV-2, and most transmission comes from people unaware they are infected; HSV-2 protects against HSV-1, but HSV-1 gives only slight protection against HSV-2.
- Pathophysiology — HSV replicates in epithelial cells at the entry site, then travels up peripheral sensory nerves to lie latent in the nerve cell body; reactivation (triggered by local trauma/surgery/UV light, immunosuppression, or fever) sends virus back to the surface. Incubation 4–7 days.
- Presentation — pain, burning, or itching, with dysuria in 80% of women, plus flu-like symptoms; complications include aseptic meningitis and autonomic dysfunction causing urinary retention. The classic primary lesion is clusters of erythematous papules and vesicles that do NOT follow a neural distribution, with tender inguinal/femoral nodes; over 2–3 weeks 75% develop new lesions that vesiculate, pustulate, coalesce into ulcers, then crust and heal. HSV-1 and HSV-2 cannot be told apart clinically.
- Labs — NAAT (preferred) or cell culture of a lesion; the Tzanck preparation is non-specific and insensitive; with no active lesions, type-specific IgG serology distinguishes HSV-1 from HSV-2.
- Course/management — genital HSV-1 recurs far less than HSV-2, and recurrences decrease after the first year. Treat the first episode on clinical grounds before confirmation; antivirals (acyclovir, valacyclovir, famciclovir — the "-ciclovir" agents) reduce signs/symptoms and new lesions but do not eradicate the virus. Acyclovir is used for neurologic complications, inability to take oral medication, or widespread disease (immunocompromised). Treat 7–10 days (extend if not healed); untreated lesions heal in 5–10 days.
Syphilis
Caused by Treponema pallidum.
- Primary — incubation 2–3 weeks (range 9–90 days); the lesion is a chancre at the inoculation site (glans/corona/perineum in men; labia/perianal in women), usually single and painless (up to 25% painful) with non-tender local lymphadenopathy. Untreated lesions heal in 3–8 weeks.
- Secondary — systemic bacteraemia appearing 3–5 months after infection, with a maculopapular rash involving the palms and soles, condyloma lata, fever, malaise, weight loss, patchy alopecia, and ocular inflammation; ~10% develop a broad vasculitis (hepatitis, iritis, nephritis, cranial-nerve involvement — especially CN VIII). Relapses occur mainly in the first year, then the infection becomes latent (seroreactive, no clinical disease).
- Tertiary/late — ~35% of late-latent patients develop neurosyphilis, cardiovascular syphilis, or gummatous syphilis.
- Diagnosis — culture is not possible; direct darkfield microscopy identifies T. pallidum. Serology has two classes: non-treponemal (RPR, VDRL, TRUST — directed against phospholipids; used to monitor activity but need treponemal confirmation, as they false-positive in viral infection, pregnancy, malignancy, autoimmune disease, and advanced age) and treponemal (FTA-ABS, MHA-TP, TP-HA, TP-PA). Test all patients for HIV.
- Management — benzathine penicillin G for all stages (dose/duration set by stage). The Jarisch-Herxheimer reaction (fever, malaise, nausea, vomiting ± chills and rash flare) is not a penicillin allergy but a reaction to treponeme death, most common in early syphilis — manage with bed rest and NSAIDs.
Chancroid
Caused by H. ducreyi (gram-negative coccobacilli): a papule progresses to painful anogenital ulceration with lymphadenitis and bubo formation; incubation 3–10 days, most often on the prepuce. Definitive diagnosis needs culture on media not routinely available; the CDC allows a probable diagnosis with one or more painful ulcers, no T. pallidum on darkfield/serology ≥7 days after onset, typical ulcers/adenopathy, and negative HSV testing. It is an HIV-transmission risk factor — test for HIV. Treatment: azithromycin 1 g once, ceftriaxone 250 mg IM once, ciprofloxacin 500 mg BID ×3 days, or erythromycin base 500 mg TID ×7 days.
Lymphogranuloma Venereum
Caused by chlamydia: a self-limited (often already-gone) genital ulcer/papule is followed by the common secondary stage — tender, typically unilateral inguinal/femoral lymphadenopathy (more common in men, since cervical/vaginal drainage is retroperitoneal). LGV proctocolitis can mimic IBD, with chronic colorectal fistulas and strictures. Diagnosis: swab/bubo aspirate for culture, direct immunofluorescence, or nucleic acid detection. Treatment: doxycycline 100 mg BID ×21 days.
Donovanosis / Granuloma Inguinale
Caused by Klebsiella granulomatis (intracellular gram-negative); rare in the US. It causes painless, slowly progressive beefy-red, easily bleeding ulcers on the genitals and perineum; despite the name, inguinal involvement is uncommon (10%, tender if present). Diagnosis: Donovan bodies on crush preparation or biopsy. Treatment: doxycycline 100 mg PO BID for at least 3 weeks and until all lesions heal.
Summary of Ulcerative STIs
| Disease | Agent | Lesion | Lymphadenopathy | Systemic | Testing | Treatment |
|---|---|---|---|---|---|---|
| Genital herpes | HSV-1/2 | Painful shallow vesicles, usually multiple | Tender, bilateral inguinal | During primary infection | NAAT/culture; serology for subtype | "-ciclovir" agents |
| Primary syphilis | T. pallidum | Painless, indurated, clean base, usually single | Non-tender, rubbery, non-suppurative, bilateral | None | Darkfield, serology | Benzathine penicillin G |
| Chancroid | H. ducreyi | Painful papule → undermined purulent ulcer | Tender, regional, suppurative | None | Culture (special media) | Azithromycin |
| LGV | Chlamydia | Small, painless vesicle/papule → ulcer | Tender, matted, with fistulous tracts | After genital lesion heals | NAAT/culture of aspirate | Doxycycline |
| Donovanosis | Klebsiella | Painless, multiple, slowly progressive | Usually absent | — | Donovan bodies | Doxycycline |
Other Genital Lesions
Human Papillomavirus (HPV)
A double-stranded DNA virus. Non-oncogenic types 6 and 11 cause ≈90% of anogenital warts (condyloma acuminata); oncogenic types 16 and 18 cause cervical and other anogenital cancers (penile, vulvar, vaginal, anal) — type 16 is most important for penile cancer.
- Epidemiology/natural history — >50% of sexually active people are infected at least once; ~70% clear within 1 year and 90% within 2 years, with persistence in the rest. Transmission occurs from asymptomatic/subclinical infection. Risk factors: foreskin, more partners, no condom use, smoking. Urethral warts can cause haematuria, dysuria, or voiding difficulty.
- Management — the goal is removal of warts; treatment does not eradicate infection, and is guided by wart size, number, location, and preference.
- Patient-applied: imiquimod cream 3.75%/5% (8 h daily ×2 weeks; max 8 weeks for 3.75% vs 16 weeks every other day for 5%); podofilox 0.5% (BID ×3 consecutive days/week, up to 4 weeks); sinecatechins 15% ointment (TID up to 16 weeks).
- Provider-administered: podophyllin, trichloroacetic acid, cryotherapy, and surgery (scissor/shave excision, curettage, CO₂ laser).
- Vaccine — prevents infection but does not clear established infection; recommended for females and males under 26, ideally before sexual debut. Gardasil is quadrivalent (6, 11, 16, 18); Cervarix is bivalent (16, 18).
Scabies
Caused by the mite Sarcoptes scabiei — the female lays eggs in the skin, transmitted by skin-to-skin contact; incubation 2–6 weeks. The main symptom is rash with itching, especially at night; diagnosis is by microscopy of a skin scraping for mites, eggs, or faeces (scybala). Treatment: permethrin cream or oral ivermectin 200 μg/kg.
Pediculosis Pubis (Crab Louse, Phthirus pubis)
An obligate bloodsucking parasite spread by close contact, presenting with pruritus (delayed hypersensitivity) worse at night and after baths. Treatment: permethrin 5% rinse or pyrethrins with piperonyl butoxide, each washed off after 10 minutes.
Molluscum Contagiosum
A poxvirus infection that can be sexually transmitted, with characteristic small, waxy, umbilicated papules 3–5 mm across. Usually self-limited (resolves in 6–12 months, up to 4 years), but more severe and extensive in immunocompromised/HIV patients.
Candidal Balanitis
C. albicans causes burning and pruritus with erythema of the glans/prepuce and subpreputial discharge. Risk factors: diabetes, HIV, iatrogenic immunosuppression, foreskin, and widespread antibiotic use. Treatment is not standardised — topical antifungals (± systemic), usually azoles (clotrimazole, miconazole, econazole, fluconazole, itraconazole).
Vaginitis
Vaginal infections present with discharge, itching, or odour; the three most associated with discharge are bacterial vaginosis, trichomoniasis, and candidiasis, of which bacterial vaginosis is the most common.
Bacterial Vaginosis
A handy mnemonic: "I have no CLUE why there are FISH in my GARDEN." BV is caused by replacement of normal hydrogen-peroxide-producing Lactobacillus with anaerobes (Prevotella, Mobiluncus, Gardnerella vaginalis, Ureaplasma, Mycoplasma, and other fastidious anaerobes). It is not sexually transmitted and the partner is not treated. Most women with BV are asymptomatic; diagnosis rests on clue cells and a fishy odour. Treatment: metronidazole.
Trichomoniasis
Caused by the protozoan T. vaginalis and is sexually transmitted. Discharge is diffuse, malodorous, and yellow-green with vulvar irritation, sometimes with a strawberry cervix. Diagnosis is by microscopy of vaginal secretions. Treatment: metronidazole — the partner must be treated.
Candidiasis
Usually C. albicans. Diagnosis is by wet prep (saline or KOH) or Gram stain showing yeast/hyphae/pseudohyphae, or culture — do wet mounts first for all patients, reserving culture for symptomatic patients with negative wet mounts. Treatment of uncomplicated disease: OTC intravaginal azoles (butoconazole, clotrimazole, miconazole, or tioconazole).
HIV/AIDS
HIV is a single-stranded RNA retrovirus infecting CD4 helper T cells and dendritic cells; its envelope precursor gp160 is cleaved into gp120 and gp41. After a needle-stick, seroconversion risk rises with deep exposure, visible blood on the device, prior placement of the device in an artery/vein, and the source patient dying within 2 months.
Diagnosis — the initial screen is an antibody enzyme immunoassay (EIA) (result in 30 minutes); a reactive screen must be confirmed by a supplemental antibody test (Western blot, IFA) or virologic HIV-1 RNA assay. HIV is detectable in 95% within 3 months; during the "window" period the screen may be negative while the person is infected, so a viral-load assay is the best test in acute infection. AIDS is diagnosed with a CD4 count <200 cells/mm³ or a serious opportunistic infection, neoplasm, or other life-threatening condition.
Urologic manifestations:
- General — test for HIV in anyone with or at risk for an STI; bleeding genital ulcers increase infectiousness.
- Kidney infections — higher risk of clinical TB (renal/extrapulmonary); mycobacterial renal infection is found at autopsy in 6–23% of AIDS patients; also CMV, aspergillus, toxoplasma.
- Prostatitis — may be more common; usually E. coli, but many other organisms occur (S. aureus, K. pneumoniae, P. aeruginosa, S. marcescens, Salmonella Typhi, M. tuberculosis, M. avium intracellulare, CMV, fungi — especially with T cells <200/μL), so culture broadly.
- UTI — bacteriuria incidence tracks CD4 count and viral load; unusual organisms (e.g. CMV) occur.
- Testis/epididymis/seminal vesicles — semen is the main transmission vector (persists despite ART); the most common intrascrotal finding is testicular atrophy; HIV is cytotoxic to germ and Sertoli cells, and testosterone falls with disease progression.
- Erectile dysfunction — more prevalent than in uninfected men; start PDE5 inhibitors at the lowest dose because protease inhibitors and NNRTIs inhibit CYP3A and markedly raise PDE5i levels.
- Renal function — HIV-associated nephropathy (HIVAN): rapidly progressive azotaemia with severe (often nephrotic) proteinuria and little peripheral oedema; APOL1 polymorphism is associated with HIVAN in African-American patients.
- Voiding/haematuria — increased LUTS and microscopic haematuria (evaluate haematuria as in anyone else).
- Stones — protease inhibitors (especially indinavir) cause stones; indinavir stones are typically radiolucent on plain film and CT (but can appear radiopaque if mixed with calcium); newer agents (lopinavir, atazanavir, amprenavir, nelfinavir) less so. Manage protease stones with drug cessation and hydration first; ammonium acid urate stones are also more common (chronic diarrhoea/malnutrition).
- Neoplasms — AIDS-defining cancers are Kaposi sarcoma, non-Hodgkin lymphoma, and invasive cervical cancer. Kaposi sarcoma (caused by HHV-8 in >90%) is most relevant to urology for penile lesions. HIV also raises the risk of testicular tumours (including testicular non-Hodgkin lymphoma), kidney cancer, and penile cancer (though the 2018 EAU guidelines state penile cancer is not linked to HIV/AIDS), but not prostate or bladder cancer. Use caution with intravesical BCG in HIV-positive patients, as its efficacy depends on a functioning immune system.
Self-Test
1. List the ulcerative genital lesions and their pathogens. Herpes — HSV; syphilis — Treponema pallidum; chancroid — H. ducreyi; lymphogranuloma venereum — chlamydia; donovanosis/granuloma inguinale — Klebsiella (granulomatis).
2. Which ulcerative lesions are painful? Herpes and chancroid.
3. Which ulcerative lesions present with lymphadenopathy? Herpes (tender), syphilis (non-tender), chancroid (tender), and LGV (tender).
4. Which HPV subtypes cause penile warts? Types 6 and 11 (the non-oncogenic subtypes responsible for ~90% of anogenital warts). Types 16 and 18 are the oncogenic subtypes that cause cancer, not warts.
5. What are the treatment options for penile HPV? Patient-applied: imiquimod, podofilox, sinecatechins. Provider-administered: podophyllin, trichloroacetic acid, cryotherapy, and surgery (excision, shave, curettage, or CO₂ laser).
6. What pathogen causes Kaposi sarcoma? Human herpesvirus 8 (HHV-8).
7. Which urologic malignancies are associated with HIV? Testicular cancer, kidney cancer, and penile cancer.