Sexually Transmitted Infections

Organisms grouped by mechanism of tissue injury

• Pyogenic mucosal invaders: Neisseria gonorrhoeae attaches via pili to columnar epithelium and drives a neutrophil-rich exudate — hence frank pus. Antigenic variation of pilin and Opa proteins prevents durable immunity, so reinfection is the rule.
• Obligate intracellular pathogens: Chlamydia trachomatis replicates within an inclusion, producing indolent, low-grade inflammation; damage comes from delayed hypersensitivity to chlamydial antigens with fibrosis rather than from acute suppuration.
• Spirochetal disseminators: Treponema pallidum is too thin for light microscopy and invades perivascular tissue, producing obliterative endarteritis — the unifying lesion behind chancre, gumma, and aortitis.
• Latency-establishing viruses: HSV (sensory ganglia), HPV (basal keratinocytes with oncogene integration), HIV (integrated provirus in CD4+ cells). Latency explains lifelong recurrence and why cure is not a treatment goal.
• Protozoal/other: Trichomonas vaginalis (flagellate, direct cytotoxicity), Haemophilus ducreyi (toxin-mediated ulceration).

Modifiable risk factors (what the stem plants)

• Inconsistent barrier use and new or multiple partners within the preceding months — the single most commonly seeded clue.
• Partner with known STI or untreated symptoms, including nontreatment of partners after a prior episode.
• Substance use and transactional sex, which reduce condom negotiation and increase partner turnover.
• Not being screened: USPSTF recommends chlamydia and gonorrhea screening in all sexually active women 24 and younger and older women at increased risk, HIV screening once for ages 15–65, and syphilis screening in pregnancy and in persons at increased risk.
• Douching, which disrupts protective lactobacilli and facilitates ascending infection.

Non-modifiable / fixed factors

• Age 15–24, where cervical ectopy exposes columnar epithelium directly to the vaginal vault.
• Prior STI, the strongest single predictor of a new one.
• Men who have sex with men, especially for syphilis, LGV, and HIV; anatomic female sex for asymptomatic carriage and upper-tract sequelae.
• Immunosuppression (HIV, transplant), which worsens HSV and HPV severity.
• Incarceration and limited healthcare access, markers of network prevalence rather than individual behavior.

Bacterial STIs (Gonorrhea, Chlamydia, Syphilis)

• Neisseria gonorrhoeae produces IgA protease that cleaves secretory IgA, evading mucosal immunity; inflammatory response causes urethritis and cervicitis with characteristic purulent discharge
• Chlamydia trachomatis (serovars D-K) exhibits obligate intracellular replication in columnar epithelial cells; causes chronic inflammation with tissue damage, scarring, and tubal obstruction
• Treponema pallidum disseminates hematogenously after initial inoculation; organisms invade multiple organ systems with varying manifestations depending on stage (primary, secondary, latent, tertiary)

Viral STIs (HSV, HPV, HIV)

• Herpes simplex virus establishes latency in sensory ganglia via retrograde axonal transport; recurrent disease results from reactivation triggered by stress, immunosuppression, or sexual activity
• Human papillomavirus integrates viral oncogenes (E6, E7) into host genome, disrupting p53 and Rb tumor suppressor pathways leading to malignant transformation (HPV-16, HPV-18)
• HIV directly targets CD4+ T cells via gp120/gp41 envelope proteins; progressive immunosuppression increases opportunistic infection risk

Parasitic/Protozoal STIs

• Trichomonas vaginalis causes mechanical tissue damage and inflammatory response; produces proteases that degrade IgA and epithelial cells, generating characteristic frothy discharge
• Haemophilus ducreyi produces cytolethal distending toxin causing progressive ulcerative lesions with severe pain

Gonorrhea (N. gonorrhoeae)

• Males: Acute urethritis with dysuria, purulent urethral discharge ("yellow or green discharge"), urinary frequency; may progress to epididymitis or prostatitis
• Females: Cervicitis with purulent cervical discharge, dysuria, pelvic pain; often asymptomatic (40-50% of cases), increasing transmission risk
• Anorectal involvement: Rectal discharge, tenesmus, anal pain; often asymptomatic
• Pharyngeal: Usually asymptomatic; may cause pharyngitis
• Disseminated gonococcal infection (DGI): Migratory polyarthritis, tenosynovitis, skin lesions (pustular rash on extremities), bacteremia—occurs in 1-3% of untreated urogenital infections

Chlamydia trachomatis

• Urethritis: Dysuria, urinary frequency; often with mucopurulent discharge (less purulent than gonorrhea)
• Cervicitis: Mucopurulent cervical discharge, postcoital bleeding, pelvic pain
• Asymptomatic infection: Present in 50% of infected women and 25% of men—major epidemiologic concern
• Lymphogranuloma venereum (L1-L3 serovars): Small painless papule progressing to deep bubo formation with severe inguinal lymphadenopathy
• Proctocolitis: Rectal pain, discharge, tenesmus
• Reactive arthritis: Triad of urethritis, arthritis, and conjunctivitis (Reiter syndrome)

Syphilis

• Primary: Single hard chancre (indurated, painless ulcer) at inoculation site with regional lymphadenopathy; heals spontaneously in 3-6 weeks even without treatment
• Secondary: Occurs 4-10 weeks after primary; systemic manifestations including rash (maculopapular, involving palms and soles), condyloma lata, mucous patches, generalized lymphadenopathy, fever, malaise
• Latent: Asymptomatic period lasting years to lifetime; positive serology without clinical signs
• Tertiary (15-30% of untreated cases): Neurosyphilis (tabes dorsalis with posterior column degeneration, argyll-robertson pupils), general paresis of the insane (dementia, ataxia), cardiovascular syphilis (aortic aneurysm), gummas (granulomatous lesions)
• Congenital syphilis: Affects infants born to untreated mothers; early manifestations (hepatosplenomegaly, rash, rhinitis), late manifestations (interstitial keratitis, saddle nose deformity, saber shins)

Herpes Simplex Virus (HSV-1/HSV-2)

• Primary infection: Severe dysuria, painful vesicular eruptions, inguinal lymphadenopathy, systemic symptoms (fever, malaise), viral meningitis possible
• Recurrent infection: Milder vesicular lesions; preceded by prodrome (tingling, pain) at site of reactivation
• Atypical presentations: Small fissures, erythema without vesicles; commonly mistaken for other conditions
• Severe manifestations: HSV proctitis (severe pain, tenesmus, discharge), disseminated disease in immunocompromised hosts

Human Papillomavirus (HPV)

• Genital warts: Caused by low-risk types (HPV-6, HPV-11); flesh-colored, exophytic papillomas on genitals, perianal area, or intra-anal region
• Asymptomatic infection: Most common presentation; high-risk types (HPV-16, HPV-18, HPV-31, HPV-33) often unrecognized until abnormal cervical cytology
• Cervical dysplasia/cancer: Progressive from CIN I → CIN II/III → invasive carcinoma over years to decades
• Anogenital cancers: Anal, penile, vulvar, vaginal malignancies associated with high-risk types

Trichomonas vaginalis

• Females: Frothy, yellow-green, malodorous vaginal discharge, vulvar itching and erythema, dysuria, dyspareunia, urinary frequency
• Males: Often asymptomatic; may present with urethritis or prostatitis
• Increased risk: Bacterial vaginosis, pelvic inflammatory disease

Haemophilus ducreyi (Chancroid)

• Painful ulcers: Multiple deep, purulent, ragged-edged ulcers with surrounding erythema (unlike syphilis chancre which is painless)
• Severe inguinal lymphadenopathy: Often unilateral "bubo" with overlying erythema and potential drainage
• Associated pain: Often severe, limiting sexual activity

HIV

• Acute retroviral syndrome: Occurs 2-4 weeks post-infection; fever, fatigue, rash, lymphadenopathy, pharyngitis, myalgia (often mistaken for flu)
• Chronic asymptomatic phase: Lasting 8-10 years without treatment; CD4+ count gradually declines
• AIDS-defining illnesses: When CD4 <200 cells/mm³; include PCP, toxoplasmosis, CMV, candidiasis, tuberculosis, Cryptococcus, progressive multifocal leukoencephalopathy (PML)

Gonorrhea

• Nucleic acid amplification test (NAAT): Gold standard; sensitivity >95%, specificity >99%; testing of urine, urethral swab, cervical swab, or rectal/pharyngeal swabs
• Gram stain: Gram-negative diplococci in polymorphonuclear leukocytes (PMNs); useful for male urethritis but insensitive in females and extragenital sites
• Culture: Less sensitive

Stabilize first when systemic

• Disseminated gonococcal infection, gonococcal meningitis/endocarditis, PID with tubo-ovarian abscess, or neonatal HSV: admit for IV therapy, blood cultures, and imaging before outpatient regimens are considered.

First-line therapy by organism

• Gonorrhea: third-generation cephalosporin — ceftriaxone 500 mg IM once (1 g if ≥150 kg). CDC abandoned routine dual therapy in 2020; add doxycycline 100 mg PO BID for 7 days only if chlamydia has not been excluded.
• Chlamydia: tetracycline — doxycycline 100 mg PO BID × 7 days, now preferred over single-dose azithromycin because of superior rectal cure.
• Syphilis: benzathine penicillin G 2.4 million units IM once for primary, secondary, and early latent disease; three weekly doses for late latent or unknown duration; IV aqueous crystalline penicillin G for neurosyphilis, ocular, or otic syphilis.
• HSV: nucleoside analogs — acyclovir, valacyclovir, or famciclovir; episodic for recurrences, daily suppression if frequent outbreaks or serodiscordant partner.
• Trichomoniasis: nitroimidazole — metronidazole, multiday dosing in women, single 2 g dose acceptable in men.
• Chancroid: azithromycin or ceftriaxone. LGV: doxycycline for 21 days.
• PID: ceftriaxone IM plus doxycycline plus metronidazole.

Escalation / alternatives

• Cephalosporin allergy in gonorrhea: gentamicin IM plus high-dose azithromycin; consult infectious diseases. True IgE penicillin allergy cross-reacts with cephalosporins in only about 1–3%, driven by shared R1 side chains, not the beta-lactam ring.
• Penicillin allergy with syphilis in pregnancy: penicillin desensitization is mandatory — no alternative is adequate (CDC/ACOG).
• HIV: start antiretroviral therapy promptly; offer PrEP and PEP within 72 hours of exposure.

Contraindicated / avoid

• Fluoroquinolones for gonorrhea — resistance; doxycycline in pregnancy; alcohol with metronidazole (disulfiram-like reaction).
• Treat partners and offer expedited partner therapy where legal; retest at 3 months.

Ascending and reproductive complications

• Pelvic inflammatory disease: gonococcal or chlamydial ascent through the cervical os; cervical motion tenderness with adnexal tenderness. Scarring of tubal cilia produces infertility and ectopic pregnancy — the reason chlamydia is screened even when asymptomatic.
• Tubo-ovarian abscess: adnexal mass with fever and leukocytosis; rupture causes peritonitis and septic shock — a surgical emergency.
• Fitz-Hugh–Curtis syndrome: transperitoneal spread to the liver capsule; right upper quadrant pain with violin-string adhesions at laparoscopy.
• Epididymitis in men; scrotal pain that must be distinguished from torsion by Doppler.

Disseminated and late complications

• Disseminated gonococcal infection: bacteremic seeding producing the triad of tenosynovitis, migratory polyarthralgia, and pustular acral rash, or purulent monoarthritis. Endocarditis and meningitis are rare but emergent.
• Tertiary syphilis: obliterative endarteritis of the vasa vasorum yields ascending aortic aneurysm with aortic regurgitation; rupture or dissection is an emergency. Neurosyphilis gives tabes dorsalis and Argyll Robertson pupils.
• HPV-driven malignancy: E6/E7 inactivation of p53 and Rb; detected by abnormal cytology or high-risk HPV testing long before symptoms.
• HIV acquisition: mucosal ulceration from any ulcerative STI markedly increases transmission risk in both directions.

Neonatal and pregnancy complications

• Ophthalmia neonatorum: gonococcal conjunctivitis in the first days of life with purulent discharge and possible corneal perforation — an emergency; AAP supports universal erythromycin ointment prophylaxis at birth.
• Chlamydial neonatal pneumonia: staccato cough with eosinophilia at 1–3 months.
• Neonatal HSV: skin/eye/mouth, CNS, or disseminated disease — emergency; risk is highest with maternal primary infection, and ACOG advises cesarean delivery for active lesions or prodrome at labor.
• Congenital syphilis: stillbirth, hydrops, snuffles, saber shins.

Treatment-related

• Jarisch–Herxheimer reaction: fever, chills, and myalgia hours after penicillin from spirochete lysis and cytokine release; supportive care, not an allergy.
• Doxycycline: photosensitivity, esophagitis; anaphylaxis with any beta-lactam requires epinephrine 0.3 mg IM.

• Painless versus painful ulcer is the discriminator: a solitary indurated painless chancre is syphilis; painful grouped vesicles on an erythematous base are HSV; painful ragged purulent ulcers with a suppurative bubo are chancroid ("you do cry with *ducreyi*"). LGV gives a painless, often-missed ulcer followed by painful inguinal nodes and the groove sign.
• Best next step in gonococcal urethritis or cervicitis: ceftriaxone 500 mg IM once, plus doxycycline for 7 days if chlamydia has not been excluded by NAAT. The common distractor is adding azithromycin reflexively — CDC dropped routine dual therapy.
• Penicillin is the only acceptable syphilis therapy in pregnancy. A pregnant patient with reported penicillin allergy gets skin testing and desensitization, never doxycycline. Doxycycline is also contraindicated in pregnancy for chlamydia — azithromycin is used instead, with test of cure.
• Fever and myalgias hours after the first penicillin dose is the Jarisch–Herxheimer reaction, not anaphylaxis. Do not stop or switch the antibiotic.
• Serology sequence matters: nontreponemal tests (RPR/VDRL) titer with disease activity and are used to follow treatment response; treponemal tests stay positive for life. A negative RPR in florid secondary syphilis suggests the prozone phenomenon — dilute the sample.
• The classic association examiners test: reactive arthritis after chlamydial urethritis — conjunctivitis, urethritis, and arthritis, HLA-B27–associated, and sterile joints. Contrast with disseminated gonococcal infection, where the joint may actually be infected.
• Trichomonas gives frothy yellow-green discharge with a strawberry cervix and motile trichomonads; treat the partner, and warn about alcohol with metronidazole.
• Every new STI diagnosis triggers HIV and syphilis testing, partner treatment, and retesting at about 3 months — reinfection, not treatment failure, is the usual cause of a positive repeat test.