Definition and epidemiology
Sexually transmitted infections (STIs) encompass more than 30 distinct bacterial, viral, protozoal, and parasitic pathogens transmitted through vaginal, anal, or oral sexual contact. The umbrella ICD-10 code A64 is used for unspecified STI, while most testable conditions have their own specific codes (e.g., gonorrhea A54, chlamydia A56, syphilis A50-A53).
- STIs are among the most common reportable infections worldwide, with hundreds of millions of new curable infections (chlamydia, gonorrhea, syphilis, trichomoniasis) occurring annually per WHO estimates.
- Highest prevalence is in individuals aged 15-24 years, reflecting behavioral risk factors and biologic susceptibility (e.g., cervical ectopy in adolescent females).
- Many infections, particularly chlamydia and HPV, are frequently asymptomatic, contributing to ongoing transmission and underdiagnosis.
- Co-infection is common; diagnosis of one STI should prompt screening for others, including HIV.
- Chlamydia is often asymptomatic in women but is the leading preventable cause of infertility via PID.
- Primary syphilis chancre is classically painless; HSV ulcers are classically painful.
- Co-test for HIV and syphilis whenever another STI is diagnosed.
- Disseminated gonococcal infection presents with the triad of tenosynovitis, dermatitis, and polyarthralgia.
- HPV E6 degrades p53 and E7 inactivates Rb, driving cervical carcinogenesis.
- NAAT is the preferred diagnostic test for chlamydia and gonorrhea.
- Routine dual therapy for gonorrhea and chlamydia is no longer recommended; treat with targeted monotherapy (ceftriaxone for gonorrhea, doxycycline for chlamydia) unless empiric coverage for both is clinically indicated prior to testing results.
- Expedited partner therapy reduces reinfection rates in heterosexual chlamydia/gonorrhea cases.
Etiology and risk factors
Common causative organisms
| Category | Examples |
|---|---|
| Bacterial | Chlamydia trachomatis, Neisseria gonorrhoeae, Treponema pallidum (syphilis) |
| Viral | HSV-2/HSV-1, HPV, HIV, HBV |
| Protozoal | Trichomonas vaginalis |
| Ectoparasitic | Phthirus pubis (pubic lice), Sarcoptes scabiei (scabies) |
Risk factors
- Multiple or new sexual partners, or a partner with multiple partners
- Inconsistent or no condom use
- Age under 25 years
- History of a prior STI
- Men who have sex with men (higher risk for syphilis, gonorrhea, HIV)
- Transactional sex, substance use, incarceration history
- Lack of access to healthcare or sexual health education
Pathophysiology
STIs cause disease through several mechanisms depending on the organism:
- Mucosal invasion: N. gonorrhoeae and C. trachomatis infect columnar epithelium of the urethra, cervix, and rectum, triggering local inflammation (urethritis, cervicitis) that can ascend to cause pelvic inflammatory disease (PID).
- Ulcerative disease: T. pallidum and HSV cause genital ulcers through direct tissue invasion and immune-mediated damage; ulcers also increase HIV acquisition risk by disrupting mucosal barriers and recruiting target CD4 cells.
- Latency and reactivation: HSV establishes latency in sacral dorsal root ganglia with periodic reactivation; HPV persists in basal keratinocytes and can integrate into the host genome, driving oncogenesis via E6/E7 oncoproteins (E6 degrades p53, E7 inactivates Rb).
- Systemic dissemination: Untreated syphilis progresses through primary, secondary, and tertiary stages via hematogenous spread, eventually affecting the cardiovascular and central nervous systems.
- Immune evasion: HIV infects and depletes CD4+ T cells, leading to progressive immunodeficiency.
Clinical features
Presentation depends on the organism and site of infection; a substantial proportion of cases are asymptomatic.
Discharge syndromes
- Gonorrhea/chlamydia: urethral or cervical discharge, dysuria, intermenstrual bleeding; often asymptomatic in women
- Trichomoniasis: frothy, malodorous yellow-green vaginal discharge with vulvar irritation; "strawberry cervix" on exam
Ulcerative syndromes
- Primary syphilis: single, painless, indurated ulcer (chancre) with regional lymphadenopathy
- Genital herpes: multiple painful vesicles/ulcers, often with systemic symptoms (fever, malaise) on first episode
- Chancroid (Haemophilus ducreyi): painful, ragged-edged ulcer with suppurative lymphadenopathy (less common in US/Europe)
Other presentations
- HPV: genital warts (condyloma acuminata) or subclinical infection detectable on cervical cytology
- Secondary syphilis: diffuse maculopapular rash including palms and soles, condylomata lata
- PID (ascending chlamydia/gonorrhea): lower abdominal pain, cervical motion tenderness, fever
- Disseminated gonococcal infection: tenosynovitis, dermatitis, polyarthralgia (triad)
Diagnosis
Diagnosis combines history, risk assessment, physical exam, and targeted laboratory testing.
Testing approach
- Nucleic acid amplification testing (NAAT): first-line for chlamydia and gonorrhea on urine, vaginal, or extragenital (pharyngeal/rectal) swabs
- Serology: nontreponemal tests (RPR, VDRL) for syphilis screening with confirmatory treponemal tests (FTA-ABS, TP-PA); HIV screened with combination antigen/antibody immunoassay
- Microscopy: wet mount for trichomoniasis (motile trophozoites), though NAAT is more sensitive
- Viral culture or PCR: for HSV from an active lesion; HPV typically diagnosed clinically or via cervical cytology/co-testing
- Dark-field microscopy: historically used for primary syphilis chancre, rarely available now
Screening recommendations
- Annual chlamydia/gonorrhea screening for sexually active women under 25 and older women with risk factors
- HIV screening at least once for all adults; more frequent in high-risk groups
- Syphilis screening in pregnancy and high-risk populations
- All patients diagnosed with one STI should be tested for others, including HIV and syphilis
Differential diagnosis
- Genital ulcers: syphilis vs. HSV vs. chancroid vs. lymphogranuloma venereum vs. Behçet disease vs. fixed drug eruption
- Vaginal discharge: bacterial vaginosis vs. candidiasis vs. trichomoniasis vs. cervicitis (gonorrhea/chlamydia) — note bacterial vaginosis and candidiasis are not classically sexually transmitted
- Dysuria: urinary tract infection vs. urethritis (gonococcal or non-gonococcal)
- Pelvic pain: PID vs. ectopic pregnancy vs. ovarian torsion vs. appendicitis
- Genital lesions: HPV warts vs. molluscum contagiosum vs. seborrheic keratosis vs. skin tags
Management
Treatment is organism-specific; guidelines from the CDC, WHO, and European IUSTI are broadly concordant but may differ on specific regimens or dosing strategies.
Antimicrobial therapy by organism
| Organism | First-line agent(s) |
|---|---|
| Chlamydia trachomatis | Doxycycline (preferred); azithromycin as alternative |
| Neisseria gonorrhoeae | Ceftriaxone (single-agent regimens now preferred given resistance trends) |
| Treponema pallidum | Benzathine penicillin G |
| Trichomonas vaginalis | Metronidazole or tinidazole |
| HSV | Acyclovir, valacyclovir, or famciclovir (suppressive or episodic) |
| HIV | Combination antiretroviral therapy |
General principles
- Per current CDC guidance, routine empiric dual therapy for gonorrhea and chlamydia together is no longer universally recommended. Empiric treatment of suspected cervicitis or non-gonococcal urethritis is typically doxycycline alone; empiric gonorrhea coverage (ceftriaxone) is added only for specific high-risk patients, high-prevalence settings, or when Gram stain shows Gram-negative diplococci. Targeted monotherapy guided by NAAT results is preferred once available.
- Partner notification and treatment (expedited partner therapy where legally permitted) is essential to prevent reinfection
- Advise abstinence from sexual activity until treatment is completed and symptoms resolve (typically 7 days after single-dose therapy)
- Re-testing ("test of cure" or routine rescreen) at 3 months is recommended for chlamydia and gonorrhea given high reinfection rates
- HPV vaccination is a key primary prevention strategy, recommended for adolescents before sexual debut
- Pre-exposure prophylaxis (PrEP) for HIV should be discussed with patients at substantial ongoing risk
- Condom use remains the most effective barrier method for reducing transmission of most STIs
Complications and prognosis
Most bacterial and protozoal STIs are curable with prompt treatment, but delayed or missed diagnosis can lead to significant morbidity.
- Infertility: ascending chlamydia/gonorrhea infection causing PID can lead to tubal scarring, infertility, and ectopic pregnancy risk
- Chronic pelvic pain: sequela of recurrent or untreated PID
- Neonatal transmission: congenital syphilis, neonatal conjunctivitis/pneumonia (chlamydia, gonorrhea), neonatal herpes — can cause severe morbidity and mortality
- Oncogenesis: persistent high-risk HPV infection is the necessary cause of cervical cancer and is linked to anal, oropharyngeal, vulvar, and penile cancers
- Increased HIV acquisition: ulcerative and inflammatory STIs significantly increase susceptibility to HIV transmission
- Tertiary syphilis: untreated syphilis can progress over years to neurosyphilis (tabes dorsalis, general paresis) or cardiovascular syphilis (aortitis)
- Viral STIs (HSV, HPV, HIV) are generally not curable but are manageable with suppressive therapy and monitoring
- Prognosis is excellent for curable STIs when diagnosed and treated early with appropriate partner management
"SIX P's" of STI history-taking: Partners, Prevention of pregnancy, Protection from STIs, Practices, Past history of STIs, (Pregnancy intentions).
Practice questions
1. A 19-year-old woman presents for a routine wellness visit. She is sexually active with one partner and uses condoms inconsistently. She reports no symptoms. Pelvic exam is unremarkable. Which of the following is the most appropriate next step?
2. A 28-year-old man presents with a single, painless ulcer on the penile shaft with firm, nontender inguinal lymphadenopathy. He had unprotected intercourse 3 weeks ago. Which test is most appropriate to confirm the diagnosis?
3. A 24-year-old woman presents with fever, lower abdominal pain, and cervical motion tenderness on exam. She was treated for chlamydia 8 months ago but did not ensure her partner was treated. Which long-term complication is she now at increased risk for?
Frequently asked questions
What causes sexually transmitted infections?
STIs are caused by a range of bacteria (chlamydia, gonorrhea, syphilis), viruses (HPV, HSV, HIV, hepatitis B), protozoa (trichomoniasis), and ectoparasites (pubic lice, scabies), all transmitted through vaginal, anal, or oral sexual contact. Some can also spread via skin-to-skin contact (HSV, HPV) or from mother to child during pregnancy or delivery.
What are the first symptoms of an STI?
Early symptoms vary widely and many STIs cause no symptoms at all, especially chlamydia and HPV in women. When present, common early signs include genital discharge, burning with urination, genital sores or ulcers, itching, and pelvic or testicular pain. Because symptoms are unreliable, routine screening is recommended for sexually active individuals rather than waiting for symptoms.
How are STIs diagnosed?
Diagnosis typically involves nucleic acid amplification testing (NAAT) on urine or swab samples for chlamydia and gonorrhea, blood tests (serology) for syphilis and HIV, and clinical examination with swabs for herpes or trichomoniasis. The right test depends on the suspected organism and exposure site, so a clinician will tailor testing to symptoms and sexual history.
Are STIs curable?
It depends on the organism: bacterial and protozoal STIs like chlamydia, gonorrhea, syphilis, and trichomoniasis are curable with appropriate antibiotics. Viral STIs such as herpes, HIV, and HPV are not curable but are manageable with antiviral therapy, suppressive treatment, or the immune system's own clearance (common with HPV).
Chlamydia vs gonorrhea — what is the difference?
Both are bacterial infections causing similar urethritis/cervicitis symptoms and are frequently tested together, but they are caused by different organisms (Chlamydia trachomatis vs Neisseria gonorrhoeae) and treated with different antibiotics (doxycycline vs ceftriaxone). Gonorrhea is more likely to cause purulent discharge and has greater concern for antibiotic resistance, while chlamydia is more often silent.
Key drugs
Related conditions and differentials
Sources and further reading
StatPearls (NCBI Bookshelf)MedlinePlusWHO ICD-10: A64
Educational content for medical students, prepared by the WhiteCoat Pro editorial team with AI assistance; every page is reviewed by a second AI model for factual errors. It is not medical advice and does not replace the product label, local guidelines or a clinician.