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Latent syphilis
Last reviewed: 04.07.2025
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Latent syphilis is defined as the period after infection with T. pallidum when the patient has no signs of the disease but has positive serological reactions.
Patients with latent syphilis, as well as patients with a disease duration of no more than 1 year, are classified as patients with early latent syphilis. Early latent syphilis is diagnosed if, during the previous year, patients:
- documented seroconversion was observed,
- symptoms and signs of primary or secondary syphilis were identified,
- had sexual contact with partners who had primary, secondary or latent syphilis.
Almost all other patients with an unknown duration of latent syphilis should be managed as having late latent syphilis. Nontreponemal serologic test titers are higher in early latent than in late latent syphilis. However, nontreponemal titers alone should not be used to reliably differentiate early from late latent syphilis. Patients who do not have features consistent with early latent syphilis should be treated as having late latent syphilis, regardless of nontreponemal titer levels. All sexually active women with positive nontreponemal serologic tests should undergo intravaginal examination to evaluate mucosal lesions before syphilis is diagnosed. All patients with syphilis should be tested for HIV.
Treatment of latent syphilis
Treatment of latent syphilis is aimed at preventing the development or progression of late complications. Although clinical experience confirms the effectiveness of penicillin for the treatment of this form of syphilis, there is little data on the choice of a specific treatment regimen. There are also few data on the use of non-penicillin drugs.
Recommended treatment regimens for latent syphilis in adults
These regimens are used in patients without allergies and with normal CSF values (if such a study was performed).
Early latent syphilis
Benzathine penicillin G 2.4 million units intramuscularly once
[ 3 ], [ 4 ], [ 5 ], [ 6 ], [ 7 ], [ 8 ]
Late latent syphilis or latent syphilis of unknown duration
Benzathine penicillin G, total 7.2 million units, administered 3 times
2.4 million units intramuscularly with a 1-week interval.
Recommended treatment regimens for latent syphilis in children
After the neonatal period, children diagnosed with syphilis should have CSF examination to exclude neurosyphilis and a careful medical history to determine whether syphilis is congenital or acquired (see Congenital Syphilis). Older children with acquired latent syphilis are evaluated as adults and given the appropriate treatment regimens recommended for children (see Child Sexual Abuse or Rape). These regimens are used in children with acquired syphilis and normal CSF who are not allergic to penicillin.
Early latent syphilis
Benzathine penicillin G, 50,000 U/kg IM to adult dosage
2.4 million IU single dose Late latent syphilis or latent syphilis of unknown duration
Benzathine penicillin G, from 50,000 U/kg IM to the adult dose of 2.4 million U 3 times with a break of 1 week (total from 150,000 U/kg to the adult dose of 7.2 million U).
[ 9 ]
Other issues in the management of patients with latent syphilis
All patients with latent syphilis should be examined for signs of tertiary syphilis (aortitis, neurosyphilis, gumma, and iritis). In patients with syphilis, if any of the following criteria are met, CSF examination should be performed before treatment:
- Neurological or ophthalmological symptoms or signs;
- Other evidence of active tertiary syphilis (eg, aortitis, gumma, iritis);
- Ineffective treatment;
- HIV infection combined with late latent syphilis or syphilis of unknown duration).
In certain circumstances, and at the patient's request, CSF testing may be performed in other patients who do not meet the above criteria. If CSF testing results indicate abnormalities consistent with neurosyphilis, the patient should be treated for neurosyphilis (see Neurosyphilis). All patients with syphilis should be tested for HIV.
Follow-up observation
Quantitative nontreponemal serologic tests should be repeated at 6 and then 12 months. There are limited data on treatment response in patients with latent syphilis. If titers increase 4-fold, or if initially high titers (t1:32) do not decrease at least 4-fold (two dilutions) within 12 to 24 months, or the patient develops symptoms or signs consistent with syphilis, the patient should be tested for neurosyphilis and re-treated appropriately.
[ 10 ], [ 11 ], [ 12 ], [ 13 ]
Special Notes
Allergy to penicillin
Men and non-pregnant women with penicillin allergy should be treated according to the following regimens.
[ 14 ], [ 15 ], [ 16 ], [ 17 ], [ 18 ]
Recommended schemes
Doxycycline 100 mg orally 2 times a day
Or Tetracycline 500 mg orally 4 times a day.
Both drugs are used for 2 weeks if the infection is known to have lasted more than 1 year; in all other cases, for 4 weeks.
Pregnancy
Pregnant patients with penicillin allergy should be treated with penicillin after desensitization (see Management of Patients with Penicillin Allergy and Syphilis in Pregnancy).