Which sexually transmitted infection (STI) laboratory tests should I order for an asymptomatic sexually active adult with risk factors such as multiple partners and unprotected intercourse?

STI Laboratory Testing for Asymptomatic Sexually Active Adults with Risk Factors

Order nucleic acid amplification tests (NAATs) for chlamydia and gonorrhea on urine (or vaginal swab for women), serologic testing for both treponemal and nontreponemal syphilis antibodies, and HIV antigen/antibody testing as your core screening panel, with site-specific testing based on sexual practices and screening frequency every 3-6 months for ongoing high-risk behavior. 1

Core Laboratory Panel (All Asymptomatic High-Risk Patients)

Bacterial STI Testing

• Chlamydia and gonorrhea NAAT: First-catch urine specimen for men; vaginal swab (preferred, can be self-collected) or urine for women 1, 2
• Syphilis serologic testing: Both nontreponemal test (RPR or VDRL) AND treponemal test (EIA, CIA, or TP-PA) are required—a single positive test is not diagnostic 3, 1
• These tests detect infection even within 72 hours of exposure, making them appropriate for immediate screening 1

Viral STI Testing

• HIV testing: Laboratory-based antigen/antibody combination test as the initial screen 1
• Hepatitis B serology: Test for surface antigen and antibodies if patient has not been previously vaccinated 1

Additional Testing for Women

• Trichomonas: Vaginal NAAT is the recommended test 1, 2

Site-Specific Testing Based on Sexual Practices

For Receptive Anal Intercourse

• Rectal swab NAAT for both chlamydia and gonorrhea—failing to test rectal sites misses a substantial proportion of infections, particularly in men who have sex with men 1, 4

For Receptive Oral Sex

• Pharyngeal swab for gonorrhea only (NAAT or culture)—pharyngeal chlamydia testing is not routinely recommended 1, 4
• This is particularly important for men who have sex with men, who should receive annual pharyngeal gonorrhea screening at minimum 4

Comprehensive Testing for Men Who Have Sex with Men

• Urine/urethral NAAT for chlamydia and gonorrhea 1
• Rectal NAAT for chlamydia and gonorrhea when receptive anal intercourse occurs 1
• Pharyngeal NAAT for gonorrhea when receptive oral intercourse occurs 1
• Annual screening at all sites of sexual contact is the minimum standard 4

Screening Frequency Algorithm

Every 3-6 Months (High-Risk Indicators Present)

Screen more frequently if the patient has ANY of the following: 3, 1

• Multiple or anonymous partners
• Substance use during sex (especially methamphetamine)
• Prior STI diagnosis
• Engagement in sex work or transactional sex
• Partners who engage in high-risk behaviors
• Men who have sex with men

Annual Minimum (Standard Risk)

• All sexually active individuals with new or multiple partners should receive at least yearly screening for chlamydia, gonorrhea, syphilis, and HIV 1
• All persons aged 13-64 should be screened routinely for HIV, with high-risk individuals requiring annual rescreening at minimum 1

Critical Follow-Up Testing

Reinfection Screening at 3 Months

• Mandatory retesting at 3 months for any patient with positive chlamydia or gonorrhea results, even if partners were treated—reinfection rates are 25-40% 1, 2
• This applies to all anatomical sites that were initially positive 4

HIV and Syphilis Window Period Considerations

• HIV follow-up: Repeat testing at 4-6 weeks and definitive testing at 12 weeks post-exposure if initial test was negative, due to the window period for detection 1
• Syphilis follow-up: Repeat serologic test at 6-12 weeks if initial test was negative, as early infection may not be detected immediately 1

Common Pitfalls to Avoid

Testing Errors

• Do not rely on urinalysis alone in sexually active patients under 25 with urinary symptoms—STI testing is mandatory regardless of urinalysis findings 2
• Do not use Gram stain for pharyngeal specimens—it has insufficient sensitivity and is not recommended 4
• Do not test only urogenital sites in men who have sex with men—extragenital sites (pharynx, rectum) must be tested based on sexual practices 1, 4

Interpretation Errors

• A single positive syphilis test is not diagnostic—both treponemal and nontreponemal results are required along with clinical evaluation 3
• Testing too early and stopping there is critical—bacterial STIs need repeat testing at 2 weeks if initially negative and no presumptive treatment was given 1

Follow-Up Errors

• Never skip the 3-month retest after positive chlamydia or gonorrhea—high reinfection rates make this mandatory even with partner treatment 1, 2

Evidence Quality Note

These recommendations are derived from CDC guidelines published in high-quality sources and the American Academy of Pediatrics guidelines 3, 1. While one recent European review questions the benefit of frequent chlamydia and gonorrhea screening due to antimicrobial resistance concerns 5, current U.S. guidelines prioritize detection and treatment to prevent complications including HIV transmission, tubal factor infertility, and congenital syphilis 3, 6.