Suspected sexually transmitted infection

A suspected sexually transmitted infection is a presentation of genital, anorectal or oropharyngeal symptoms or signs, or a sexual exposure, that raises the possibility of infection. Many infections are asymptomatic, so assessment must include screening of exposed sites, other infections (HIV, syphilis, hepatitis B), pregnancy and contraception, and treatment of partners.

Classification by syndrome.

• Urethritis and cervicitis (discharge, dysuria), vaginal discharge, genital ulcer disease, genital warts and lumps.
• Pelvic pain and pelvic inflammatory disease, epididymo-orchitis, proctitis, pharyngitis.
• Systemic illness (acute HIV, secondary syphilis, mpox), and asymptomatic screening after exposure.

Common pathogens. Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, Trichomonas vaginalis, herpes simplex virus, Treponema pallidum, human papillomavirus, HIV, hepatitis B virus. Also Haemophilus ducreyi (chancroid), lymphogranuloma venereum serovars of Chlamydia trachomatis, Klebsiella granulomatis (donovanosis) and mpox virus. Bacterial vaginosis and vulvovaginal candidiasis are not sexually transmitted infections in the strict sense.

Transmission and risk. Risk increases with new or multiple partners, condomless sex, sex between men, partner with infection, sex work, drug use during sex (chemsex), young age, previous infection and sexual violence. Genital ulcer disease and inflammation increase HIV acquisition and transmission.

Incubation.

• Gonorrhoea 2 to 7 days, chlamydia 1 to 3 weeks, herpes 2 to 12 days.
• Primary syphilis 10 to 90 days (usually 3 weeks), chancroid 3 to 10 days.
• Lymphogranuloma venereum 3 to 30 days, warts weeks to months, and acute HIV 2 to 4 weeks.

Key distinctions. Painful grouped vesicles and ulcers suggest herpes. A painless indurated ulcer suggests primary syphilis. A painful ragged ulcer with tender suppurative nodes suggests chancroid. Purulent discharge suggests gonorrhoea, and mucoid discharge suggests chlamydia or Mycoplasma genitalium.

Frothy green discharge with strawberry cervix suggests trichomoniasis.

History

• Symptoms: discharge (colour, amount, odour), dysuria, frequency, genital itch, pain on intercourse, pelvic or testicular pain, ulcers, lumps, rash, anal pain, discharge or bleeding, sore throat, fever, joint pain and eye symptoms.
• Sexual history: number and gender of partners, timing and type of exposure (vaginal, anal, oral), condom use, partners with symptoms, partners from high prevalence areas, injecting drug use, sex work, transactional sex, consent and sexual violence.
• Previous infections and treatment, HIV status, hepatitis B vaccination, human papillomavirus vaccination, last test dates, pre exposure prophylaxis use.
• Gynaecological history: last menstrual period, contraception, pregnancy, breastfeeding, cervical screening, intermenstrual or postcoital bleeding, and previous pelvic infection.
• Medication and allergy history, especially to penicillins, and drugs interacting with treatment.
• Mental health, substance use, safeguarding and partner violence concerns.

Examination

• General: temperature, rash (palms and soles in syphilis), lymphadenopathy (inguinal, generalised), oral and pharyngeal lesions, joints and eyes.
• Abdomen: lower abdominal tenderness, masses, and liver tenderness (Fitz-Hugh-Curtis syndrome).
• Male genitalia: urethral discharge (express by stripping the urethra), meatitis, balanitis, ulcers, warts, scrotal swelling, epididymal tenderness and testicular lie, inguinal nodes.
• Female genitalia: vulval ulcers, warts, vulvitis, Bartholin gland, speculum examination (discharge colour, cervical friability, mucopurulent endocervical discharge, strawberry cervix, ulcers, ectropion), and bimanual examination (cervical motion tenderness, uterine and adnexal tenderness, masses).
• Anorectal: external lesions, proctoscopy (discharge, ulcer, friability), and digital rectal examination.
• Bedside tests:
  • Pregnancy test, urine dipstick, vaginal pH (over 4.5 suggests bacterial vaginosis or trichomoniasis).
  • Wet mount microscopy (clue cells, motile trichomonads, hyphae).
  • Gram stain of urethral smear (5 or more polymorphonuclear leucocytes in each high power field, intracellular Gram negative diplococci), and dark ground microscopy of ulcer exudate.

Red flags

• Lower abdominal pain, fever, cervical motion tenderness or adnexal mass (pelvic inflammatory disease, tubo-ovarian abscess).
• Pregnancy with abdominal pain or vaginal bleeding (ectopic pregnancy).
• Acute scrotal pain with sudden onset in a young man (testicular torsion).
• Neurological, eye or ear symptoms with syphilis (neurosyphilis, ocular and otosyphilis).
• Disseminated gonococcal infection (fever, migratory polyarthralgia, tenosynovitis, pustular rash).
• Mucosal and skin lesions with fever and lymphadenopathy during mpox transmission.
• Sexual assault, child or adolescent patients, and partner violence.
• Immunocompromise or HIV with extensive disease.
• Severe proctitis with fever and bloody discharge, or tenesmus (lymphogranuloma venereum).
• Persistent or treatment resistant symptoms.

Special groups

• Pregnancy: syphilis, chlamydia, gonorrhoea, HIV and hepatitis B need testing and treatment. Avoid doxycycline, and treat herpes near term.
• Adolescents and children: sexual abuse should be considered, and legal reporting obligations apply.
• Men who have sex with men: test every anatomical site exposed (urethra, rectum, pharynx) and include screening for hepatitis A, B and C.
• Sexual assault: forensic documentation, emergency contraception, and prophylaxis.
• Region specific: higher prevalence of chancroid, donovanosis, lymphogranuloma venereum and syphilis in some settings, and widespread antimicrobial resistance in gonorrhoea.

Urethritis, cervicitis and discharge

• Gonorrhoea.
• Chlamydia.
• Mycoplasma genitalium infection.
• Trichomoniasis.
• Nongonococcal urethritis (ureaplasma, adenovirus, herpes simplex virus, Haemophilus species).
• Bacterial vaginosis.
• Vulvovaginal candidiasis.
• Aerobic vaginitis.
• Retained foreign body (tampon).
• Cervicitis from herpes simplex virus.
• Noninfective causes: urethral stricture, allergic reaction to spermicide or latex, chemical irritation, cervical ectropion, cervical cancer.

Genital ulcer and lumps

• Genital herpes.
• Primary syphilis.
• Chancroid.
• Lymphogranuloma venereum.
• Donovanosis.
• Genital warts.
• Molluscum contagiosum.
• Mpox.
• Scabies and pubic lice.
• Fixed drug eruption.
• Behçet disease and aphthous ulcers.
• Trauma and erosive lichen planus.
• Squamous cell carcinoma and vulval intraepithelial neoplasia.
• Candidal balanitis.
• Penile pearly papules and Fordyce spots.

Pelvic and scrotal pain

• Pelvic inflammatory disease and tubo-ovarian abscess.
• Fitz-Hugh-Curtis syndrome.
• Epididymo-orchitis.
• Testicular torsion.
• Acute prostatitis.
• Urinary tract infection.
• Ectopic pregnancy.
• Appendicitis.
• Ovarian torsion and ruptured cyst.
• Endometriosis.

Anorectal and oropharyngeal

• Gonococcal and chlamydial proctitis.
• Lymphogranuloma venereum proctocolitis.
• Herpes proctitis.
• Syphilitic proctitis.
• Shigella, Campylobacter, Giardia and amoebic infection in sexual transmission.
• Inflammatory bowel disease.
• Haemorrhoids and anal fissure.
• Pharyngeal gonorrhoea.
• Streptococcal pharyngitis and mononucleosis.

Systemic

• Acute HIV infection.
• Secondary syphilis.
• Hepatitis A, B and C.
• Disseminated gonococcal infection.
• Mpox.
• Reactive arthritis.
• Cytomegalovirus and Epstein-Barr virus infection.
• Neurosyphilis, ocular syphilis and otosyphilis.

Step 1. Triage and consent. Assess for pregnancy, pelvic inflammatory disease, torsion, sexual assault and safeguarding concerns. Obtain a sexual history in a confidential, nonjudgemental way with chaperone offered.

Step 2. Samples by site and syndrome

• Women:
  • Self taken or clinician taken vulvovaginal swab for nucleic acid amplification tests for Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis and Mycoplasma genitalium.
  • Endocervical swab for gonorrhoea culture and resistance testing when positive.
  • Speculum examination and high vaginal swab for bacterial vaginosis (Gram stain Nugent score, or Amsel criteria: 3 of 4 of homogeneous discharge, pH over 4.5, clue cells, positive amine test) and candida.
• Men: first void urine (first 20 mL, at least 1 hour after last urination) for nucleic acid amplification tests for chlamydia, gonorrhoea, Mycoplasma genitalium and Trichomonas. Urethral Gram stain and culture when discharge.
• Rectal and pharyngeal swabs for nucleic acid amplification tests in anyone with receptive anal or oral exposure.
• Ulcers: swab for herpes simplex virus PCR, and for Treponema pallidum PCR, dark ground microscopy when available, and Haemophilus ducreyi culture or PCR. Swab for lymphogranuloma venereum genotyping when chlamydia positive from rectum.
• Mpox: lesion swab PCR with infection control.
• Genital warts: clinical diagnosis, with biopsy for atypical, pigmented or persistent lesions.

Step 3. Blood tests

• HIV fourth generation antigen and antibody test (window period about 4 weeks, repeat at 4 to 12 weeks after exposure) with HIV RNA in suspected acute infection.
• Syphilis serology: a treponemal enzyme immunoassay as the first test, then a nontreponemal test (RPR or VDRL, with titre) and a second treponemal test (Treponema pallidum particle agglutination) for confirmation. Early primary syphilis may be seronegative, so repeat at 2 to 4 weeks when suspicion remains.
• Hepatitis B (surface antigen, core antibody, surface antibody), hepatitis C antibody, and hepatitis A immunity where indicated.
• Pregnancy test and cervical screening status.
• Renal function when drugs with renal dosing are planned.

Step 4. Targeted tests

• Pelvic inflammatory disease: pelvic ultrasound for abscess and ectopic pregnancy, CRP, white count, and laparoscopy for diagnostic uncertainty.
• Neurosyphilis, ocular or otosyphilis: lumbar puncture (CSF white cells over 5/microlitre, raised protein, reactive VDRL), ophthalmology and audiology.
• Treatment failure: culture and antimicrobial susceptibility testing for gonorrhoea, and macrolide and fluoroquinolone resistance testing for Mycoplasma genitalium.
• Epididymo-orchitis: urine culture, Doppler ultrasound when torsion is possible.

Interpretation. Serological follow up of syphilis: a fourfold (two dilution) fall in nontreponemal titre by 6 to 12 months (12 to 24 months in late disease) indicates response. Treponemal tests remain positive for life. A positive screening test in a low risk patient needs confirmation. Biological false positive nontreponemal tests occur in pregnancy, autoimmune disease and infection.

Limits. Nucleic acid amplification tests can remain positive for weeks after treatment (do not test for cure earlier than 3 to 4 weeks unless symptoms persist). Window periods limit early testing. Dark ground microscopy requires skilled staff. Self swabs perform nearly as well as clinician swabs.

Immediate. Treat on the day when the patient is likely to be lost to follow up or has a clear syndrome. Treat pelvic inflammatory disease, epididymo-orchitis and suspected gonorrhoea empirically before results. Admit unstable patients, and manage suspected ectopic pregnancy or torsion as emergencies.

Urethritis and cervicitis (empirical, before results)

• Doxycycline 100 mg orally twice daily for 7 days (avoid in pregnancy, and with photosensitivity, oesophageal strictures, and antacids or iron within 2 hours).
• Add ceftriaxone 1 g intramuscularly once for suspected or confirmed gonorrhoea (a single dose treats pharyngeal infection as well).
• Gonorrhoea: ceftriaxone 1 g intramuscularly once (2 g for resistant strains under specialist advice). Alternatives in cephalosporin allergy: gentamicin 240 mg intramuscularly once with azithromycin 2 g orally once, under specialist advice. Test of cure after 2 weeks when pharyngeal infection, resistance, or symptoms persist.
• Chlamydia: doxycycline 100 mg orally twice daily for 7 days. Pregnancy and breastfeeding: azithromycin 1 g orally once, then test of cure at 4 weeks. Rectal and lymphogranuloma venereum infection: doxycycline 100 mg twice daily for 21 days.
• Mycoplasma genitalium:
  • Doxycycline 100 mg twice daily for 7 days, followed by moxifloxacin 400 mg once daily for 7 days when macrolide resistance is present or unknown.
  • Or, when macrolide sensitive, follow the doxycycline with azithromycin 1 g orally then 500 mg daily for 2 days.
  • Check QT, tendon and neuropsychiatric risks of moxifloxacin, and test of cure at least 5 weeks after.
• Trichomoniasis: metronidazole 400 to 500 mg orally twice daily for 7 days (a single 2 g dose is less effective in women). Avoid alcohol during and for 48 hours after treatment, and screen partners.
• Bacterial vaginosis: metronidazole 400 to 500 mg orally twice daily for 7 days, or clindamycin 2% cream 5 g intravaginally at night for 7 days.
• Vulvovaginal candidiasis: fluconazole 150 mg orally once (avoid in pregnancy; use clotrimazole 500 mg pessary once), with fluconazole 150 mg every 72 hours for 3 doses for complicated or recurrent disease.

Genital ulcer disease

• Genital herpes:
  • First episode: aciclovir 400 mg orally three times daily for 7 to 10 days, or valaciclovir 500 mg twice daily for 5 to 10 days.
  • Adjust at creatinine clearance 30 to 49 mL/min to 1 g every 12 hours for valaciclovir 1 g regimens.
  • Recurrence: aciclovir 400 mg three times daily for 3 to 5 days, or valaciclovir 500 mg twice daily for 3 days started at prodrome.
  • Suppression for 6 or more episodes each year: aciclovir 400 mg twice daily or valaciclovir 500 mg once daily, reviewed annually.
  • Maintain hydration, give analgesia, topical lidocaine 5% and saline bathing.
  • Treat from 36 weeks in pregnancy with a primary episode in late pregnancy, and suppress with aciclovir 400 mg three times daily from 36 weeks for women with recurrent disease.
• Early syphilis (primary, secondary, early latent under 1 year): benzathine benzylpenicillin 2.4 million units intramuscularly once (a second dose 1 week later in pregnancy and in HIV with advanced disease under specialist direction).
• Penicillin allergy in early syphilis: doxycycline 100 mg orally twice daily for 14 days (not in pregnancy; desensitise and give penicillin in pregnancy).
• Late latent or unknown duration syphilis: benzathine benzylpenicillin 2.4 million units intramuscularly weekly for 3 weeks, or doxycycline 100 mg twice daily for 28 days.
• Neurosyphilis, ocular syphilis and otosyphilis:
  • Benzylpenicillin 18 to 24 million units daily intravenously (3 to 4 million units every 4 hours) for 10 to 14 days.
  • Or procaine benzylpenicillin 2.4 million units intramuscularly daily with probenecid 500 mg orally four times daily for 10 to 14 days.
  • Give prednisolone 40 to 60 mg daily for 3 days starting 24 hours before treatment when the Jarisch-Herxheimer reaction is a concern (neurosyphilis, cardiovascular syphilis, pregnancy).
  • Warn all patients about the Jarisch-Herxheimer reaction (fever, myalgia within 24 hours).
• Chancroid: azithromycin 1 g orally once, or ceftriaxone 250 mg intramuscularly once, or ciprofloxacin 500 mg twice daily for 3 days (not in pregnancy). Aspirate buboes.
• Lymphogranuloma venereum: doxycycline 100 mg twice daily for 21 days (azithromycin 1 g weekly for 3 weeks in pregnancy).
• Donovanosis: azithromycin 1 g orally weekly (or 500 mg daily) for at least 3 weeks and until healed.
• Mpox: supportive care and isolation until lesions have crusted. Tecovirimat is considered for severe or high risk disease with evidence being limited.

Pelvic inflammatory disease and epididymo-orchitis

• Pelvic inflammatory disease:
  • Ceftriaxone 1 g intramuscularly once, doxycycline 100 mg orally twice daily and metronidazole 400 to 500 mg orally twice daily for 14 days.
  • Admit for severe illness, pregnancy, tubo-ovarian abscess, failure of oral therapy, or when surgical emergency cannot be excluded. Give ceftriaxone 2 g intravenously daily with doxycycline and metronidazole until 24 hours after improvement.
  • Remove an intrauterine device only when there is no improvement at 72 hours, with emergency contraception when needed.
• Epididymo-orchitis in sexually active men under 35 years or with urethritis: ceftriaxone 1 g intramuscularly once plus doxycycline 100 mg orally twice daily for 10 to 14 days.
• Epididymo-orchitis in older men or with enteric risk: levofloxacin 500 mg orally once daily for 10 days (or ofloxacin 200 mg twice daily for 14 days). Scrotal support and analgesia, and exclusion of torsion.

Proctitis. Ceftriaxone 1 g intramuscularly once with doxycycline 100 mg twice daily for 7 days (21 days when lymphogranuloma venereum is suspected, or confirmed in the rectum with positive chlamydia).

Test for herpes and syphilis.

Genital warts.

• Podophyllotoxin 0.15% cream or 0.5% solution applied twice daily for 3 days then 4 days off, for up to 4 weeks (not in pregnancy).
• Imiquimod 5% cream 3 times weekly at night for up to 16 weeks.
• Cryotherapy every 1 to 2 weeks, or surgical excision.
• Immunocompromised and large lesions need specialist care. Offer human papillomavirus vaccination.

Hepatitis B, A and HIV prevention

• Hepatitis B vaccination (0, 1 and 6 months, or accelerated schedules) for all non immune patients, and hepatitis A vaccination for men who have sex with men, injecting drug users and others at risk.
• Post exposure prophylaxis for HIV within 72 hours of a high risk exposure: tenofovir disoproxil 300 mg with emtricitabine 200 mg once daily plus dolutegravir 50 mg once daily for 28 days (adjust tenofovir at creatinine clearance under 50 mL/min).
• Do baseline HIV, hepatitis B and creatinine tests, with follow up HIV tests at 4 to 6 weeks and 3 months.
• Pre exposure prophylaxis: tenofovir disoproxil 300 mg with emtricitabine 200 mg once daily, or on demand dosing for men who have sex with men (2 tablets 2 to 24 hours before sex, then 1 tablet at 24 hours and 1 at 48 hours).
• Monitor kidney function every 3 to 6 months, with HIV, STI and creatinine testing every 3 months.
• Evidence supports doxycycline 200 mg orally within 72 hours of condomless sex as post exposure prophylaxis for bacterial infection in men who have sex with men (limit to 200 mg each 24 hours), with concerns about resistance.
• Emergency contraception after unprotected sex: levonorgestrel 1.5 mg orally once within 72 hours (less effective with weight over 70 kg), ulipristal acetate 30 mg orally once within 120 hours, or copper intrauterine device within 120 hours.

Sexual assault. Document findings and obtain consent for forensic sampling.

• Give HIV post exposure prophylaxis (tenofovir disoproxil 300 mg with emtricitabine 200 mg and dolutegravir 50 mg once daily for 28 days) when risk is present.
• Give hepatitis B vaccine with immunoglobulin when indicated, emergency contraception, and tetanus when needed.
• Presumptive treatment: ceftriaxone 1 g intramuscularly once, azithromycin 1 g orally once (or doxycycline 100 mg twice daily for 7 days) and metronidazole 2 g orally once.
• Offer counselling and mental health support, and follow up at 2 weeks, 6 weeks, 3 months and 6 months.

Partner management. Notify and treat partners from the preceding 3 months (6 months for gonorrhoea in some settings and 90 days for primary syphilis, longer for secondary and latent disease), with epidemiological treatment where results cannot be obtained. Advise abstinence from sex until 7 days after both partners complete treatment and symptoms resolve (until lesions heal for herpes). Monitoring.

• Test of cure for gonorrhoea at 2 weeks (pharyngeal infection, resistance), chlamydia at 4 weeks (pregnancy), and Mycoplasma genitalium after at least 5 weeks.
• Check syphilis titres at 3, 6 and 12 months (and at 24 months for late disease, or for HIV positive patients at 3 month intervals).
• Retest all infections at 3 months because reinfection is frequent.

Referral and escalation.

• Sexual health or genitourinary medicine for complicated infection, treatment failure and partner notification.
• Gynaecology for pelvic inflammatory disease, abscess and ectopic pregnancy.
• Urology or surgery for torsion.
• HIV services for confirmed HIV (start antiretroviral therapy early).
• Neurology, ophthalmology or ENT for neurosyphilis, ocular syphilis or otosyphilis.
• Safeguarding and legal services for children and assault.
• Public health notification where required (syphilis, gonorrhoea, chlamydia, HIV, hepatitis B, mpox).

Admission criteria. Pelvic inflammatory disease with severe features or pregnancy, tubo-ovarian abscess, disseminated gonococcal infection, neurosyphilis requiring intravenous therapy, torsion, severe mpox, immunocompromise with extensive disease, and inability to take oral therapy.

Discharge and follow up. Provide counselling on condom use, HIV and other testing, vaccination, partner treatment and abstinence. Safety net advice: return for persistent symptoms after 7 days of treatment, fever, abdominal or scrotal pain, rash, neurological or eye symptoms, or new partners with symptoms.