What are the recommended testing and treatment protocols after exposure to syphilis?

Syphilis Exposure: Testing and Treatment Protocols

Immediate Management After Exposure

Persons exposed within 90 days of a partner diagnosed with primary, secondary, or early latent syphilis should receive presumptive treatment with benzathine penicillin G 2.4 million units IM as a single dose, even if their initial serologic testing is negative. 1

Risk-Based Treatment Algorithm

For exposures within 90 days:

• Treat presumptively regardless of serology status, as infected persons may still be seronegative during the incubation period 1
• Administer benzathine penicillin G 2.4 million units IM immediately 2, 3

For exposures >90 days before partner's diagnosis:

• Treat presumptively if serologic results cannot be obtained immediately AND follow-up is uncertain 1
• If serologic testing is available and follow-up is reliable, base treatment on test results 1

For partners of patients with high-titer syphilis (≥1:32) of unknown duration:

• Assume early syphilis and treat presumptively 1

For long-term partners of patients with late latent syphilis:

• Evaluate clinically and serologically, then treat based on findings 1

Testing Timeline After Exposure

Initial Testing

• Perform both nontreponemal (RPR or VDRL) and treponemal tests at initial evaluation 1, 3
• Critical caveat: Seronegative results do not exclude infection in the first 3-4 weeks after exposure, as antibodies may not yet be detectable 4, 5

Follow-Up Testing Schedule

• If initial testing is negative and infection in the source cannot be ruled out: Repeat serologic testing at 4-6 weeks and 3 months post-exposure 1
• Treponemal antibodies typically appear 1-4 weeks after infection, while nontreponemal antibodies appear by 4-6 weeks 4
• Testing at 9-13 weeks is adequate to definitively exclude syphilis if infection had occurred 4

Special Populations and Considerations

HIV-Infected Individuals

• Use the same treatment regimens as HIV-negative patients for post-exposure management 1, 2
• Screen for syphilis at baseline and at least annually, with more frequent screening (every 3-6 months) for those with high-risk behaviors 1
• Consider CSF examination if CD4 count <350 cells/mm³ or nontreponemal titer >1:32 1

Pregnant Women

• Parenteral penicillin G is the ONLY therapy with documented efficacy for preventing maternal transmission 1, 2
• Pregnant women with penicillin allergy MUST undergo desensitization followed by penicillin treatment 2
• Screen at first prenatal visit, during third trimester, and at delivery 2, 5

Penicillin-Allergic Non-Pregnant Adults

• For presumptive treatment of early syphilis exposure: Doxycycline 100 mg orally twice daily for 14 days 2, 3
• Important limitation: Doxycycline has less robust evidence than penicillin and should only be used when penicillin is contraindicated 2

Clinical Monitoring After Treatment

Expected Serologic Response

• Quantitative nontreponemal tests should be repeated at 3,6, and 12 months after treatment 2, 3
• A fourfold decline in titer is expected within 6 months for early syphilis 2, 3, 4

Treatment Failure Indicators

• Failure of nontreponemal titers to decline fourfold within 6 months 2, 3
• Persistence or recurrence of clinical signs/symptoms 3, 4
• Sustained fourfold increase in nontreponemal titer 4

Critical Pitfalls to Avoid

Do not delay treatment while awaiting serology results in high-risk exposures (<90 days). The window period for seroconversion means negative tests do not exclude early infection. 1

Do not use oral penicillin preparations—they are ineffective for syphilis treatment. Only parenteral penicillin G formulations are appropriate. 1, 2

Do not switch between different nontreponemal test methods (RPR vs VDRL) when monitoring response, as results cannot be directly compared. 2, 4

Do not substitute alternative antibiotics in pregnant women—penicillin desensitization is mandatory as only penicillin prevents congenital syphilis. 2

Jarisch-Herxheimer Reaction

• Occurs within 24 hours of treatment in up to 50% of patients with early syphilis 1
• Presents as acute fever, headache, myalgia, and constitutional symptoms 1, 2
• Counsel all patients about this expected reaction before treatment 1, 2
• In pregnant women, may precipitate premature labor or fetal distress but should not delay therapy 1, 2
• Antipyretics may be used but have not been proven to prevent the reaction 1