What is the recommended treatment for syphilis in the Indian population?

Syphilis Treatment in India

For syphilis treatment in India, benzathine penicillin G remains the gold standard: 2.4 million units IM as a single dose for primary, secondary, and early latent syphilis, or three weekly doses (7.2 million units total) for late latent syphilis. 1, 2

Primary and Secondary Syphilis Treatment

• Benzathine penicillin G 2.4 million units IM as a single dose is the recommended first-line treatment for primary and secondary syphilis in adults 1, 2, 3
• This regimen maintains therapeutic penicillin levels (>18 ng/mL) for 18-25 days, well exceeding the required 7-10 days for effective treatment 4
• All patients diagnosed with syphilis must be tested for HIV infection, as co-infection may alter disease progression 1, 2

Early Latent Syphilis

• Benzathine penicillin G 2.4 million units IM as a single dose is recommended for early latent syphilis (acquired within the preceding year) 1, 2
• Early latent syphilis is defined by documented seroconversion, fourfold increase in titer, history of symptoms within the past year, or having a sex partner with documented early syphilis 1

Late Latent Syphilis and Latent Syphilis of Unknown Duration

• Benzathine penicillin G 7.2 million units total, administered as three doses of 2.4 million units IM at weekly intervals is the recommended regimen 1, 2, 3
• CSF examination should be performed before treatment if any of the following are present: neurologic or ophthalmic signs/symptoms, evidence of active tertiary syphilis, treatment failure, HIV infection with late latent syphilis, or serum nontreponemal titer ≥1:32 1

Neurosyphilis

• Aqueous crystalline penicillin G 18-24 million units per day IV (administered as 3-4 million units every 4 hours or continuous infusion) for 10-14 days is the recommended treatment 1, 2
• Procaine penicillin without probenecid does not achieve adequate CSF levels and is inadequate for neurosyphilis treatment 1

Penicillin Allergy Alternatives (Non-Pregnant Adults)

• For primary, secondary, or early latent syphilis: doxycycline 100 mg orally twice daily for 14 days 1, 2, 3
• For late latent syphilis: doxycycline 100 mg orally twice daily for 28 days 1, 2
• Ceftriaxone 1 gram IM/IV daily for 10 days is a reasonable alternative based on randomized trial data showing comparable efficacy to benzathine penicillin 1, 5
• Azithromycin should NOT be used due to widespread macrolide resistance and documented treatment failures 1

Critical Caveat for Ceftriaxone

• Patients with severe penicillin allergy (such as Stevens-Johnson syndrome) may also be allergic to ceftriaxone, as both are beta-lactam antibiotics 1
• Evidence for ceftriaxone in late latent syphilis and tertiary syphilis is extremely limited 1

Pregnancy Considerations

• Pregnant women with syphilis MUST receive penicillin—it is the only therapy proven to prevent maternal transmission and treat fetal infection 1, 2, 3
• Pregnant women with penicillin allergy MUST undergo desensitization followed by penicillin treatment—no alternatives are acceptable 1, 2, 3
• Some experts recommend a second dose of benzathine penicillin 2.4 million units IM administered 1 week after the initial dose for women with primary, secondary, or early latent syphilis 1
• All pregnant women should be screened for syphilis at first prenatal visit, during third trimester, and at delivery 1
• Women treated during the second half of pregnancy are at risk for premature labor and/or fetal distress from Jarisch-Herxheimer reaction; they should seek immediate medical attention if they notice contractions or changes in fetal movements 1

HIV-Infected Patients

• HIV-infected patients should receive the same penicillin treatment regimens as HIV-negative patients for all stages of syphilis 1, 3
• Closer follow-up is mandatory (at 3-month intervals instead of 6-month intervals) to detect treatment failure or disease progression 6, 1
• Limited data suggest no benefit to multiple doses of benzathine penicillin for early syphilis in HIV-infected patients compared to a single dose 1

Follow-Up and Monitoring

• Quantitative nontreponemal serologic tests (RPR or VDRL) should be repeated at 6 and 12 months after treatment for primary/secondary syphilis 1, 2
• For latent syphilis, repeat tests at 6,12, and 24 months 1, 2
• A fourfold decline in titer is expected within 6 months for primary/secondary syphilis and within 12-24 months for late syphilis 1, 2
• Treatment failure is defined as: persistent or recurring signs/symptoms, sustained fourfold increase in nontreponemal titers, or failure of initially high titer to decline at least fourfold within the expected timeframe 1, 2

Management of Treatment Failure

• If treatment failure is suspected, patients should be re-evaluated for HIV infection and undergo CSF examination 1
• Re-treatment typically involves three weekly injections of benzathine penicillin G 2.4 million units IM, unless CSF examination indicates neurosyphilis 2

Management of Sex Partners

• Sex partners exposed within 90 days preceding diagnosis of primary, secondary, or early latent syphilis should be treated presumptively, even if seronegative 1
• Time periods for at-risk partners: 3 months plus duration of symptoms for primary syphilis, 6 months plus duration of symptoms for secondary syphilis, and 1 year for early latent syphilis 1

Critical Pitfalls to Avoid

• Never use oral penicillin preparations—they are completely ineffective for syphilis treatment 1, 3
• Never switch between different nontreponemal test methods (RPR vs VDRL) when monitoring response—results cannot be directly compared 1, 3
• Do not rely solely on treponemal test antibody titers to assess treatment response, as they correlate poorly with disease activity 1
• Remember that 15-25% of successfully treated patients remain "serofast" with persistent low titers (<1:8) that do not indicate treatment failure 1

Jarisch-Herxheimer Reaction

• The Jarisch-Herxheimer reaction is an acute febrile reaction that may occur within 24 hours after any syphilis therapy, especially in early syphilis 1, 2
• Patients should be informed about this possible adverse reaction, which may include headache, myalgia, fever, and other constitutional symptoms 1, 2