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Latent Syphilis
Latent syphilis is defined as syphilis characterized by seroreactivity without other evidence of primary, secondary, or tertiary disease. Persons who have latent syphilis and who acquired syphilis during the preceding year are classified as having early latent syphilis (early nonprimary, nonsecondary). Persons can receive a diagnosis of early latent syphilis if, during the year preceding the diagnosis, they had a documented seroconversion or a sustained (>2 weeks) fourfold or greater increase in nontreponemal test titers in a previously treated person; unequivocal symptoms of primary or secondary syphilis; or a sex partner documented to have primary, secondary, or early latent syphilis. In addition, for persons with reactive nontreponemal and treponemal tests whose only possible exposure occurred during the previous 12 months, early latent syphilis can be assumed.
In the absence of these conditions associated with latent syphilis, an asymptomatic person should be considered to have latent syphilis of unknown duration or late latent syphilis (>1 year’s duration). Nontreponemal serologic titers usually are higher early in the course of syphilis infection. However, early latent syphilis cannot be reliably diagnosed solely on the basis of nontreponemal titers. All persons with latent syphilis should have careful examination of all accessible mucosal surfaces to evaluate for mucosal lesions (primary or secondary syphilis) before making a latent syphilis diagnosis. Physical examination should include the oral cavity, perianal area, perineum, rectum, and genitals (vagina and cervix for women; scrotum, penis, and underneath the foreskin for uncircumcised men).
Treatment
Because latent syphilis is not transmitted sexually, the objective of treating persons in this disease stage is to prevent medical complications of syphilis. Latent syphilis can also be vertically transmitted to a fetus; therefore, the goal of treating a pregnant woman is to prevent congenital syphilis. Although clinical experience supports the effectiveness of penicillin in achieving this goal, limited evidence is available for guiding choice of specific regimens or duration. Available data demonstrate that additional doses of benzathine penicillin G, amoxicillin, or other antibiotics in early latent syphilis do not enhance efficacy, regardless of HIV status (592,593,609).
Early Latent Syphilis: Benzathine penicillin G 2.4 million units IM in a single dose
Late Latent Syphilis: Benzathine penicillin G 7.2 million units total, administered as 3 doses of 2.4 million units IM each at 1-week intervals
* Recommendations for treating syphilis in persons with HIV and pregnant women are discussed elsewhere in this report (see Syphilis in Persons with HIV; Syphilis During Pregnancy).
Infants and children aged ≥1 month with diagnosed latent syphilis should be managed by a pediatric infectious disease specialist and receive a CSF examination. In addition, birth and maternal medical records should be reviewed to assess whether these infants and children have congenital or acquired syphilis. For those with congenital syphilis, treatment should be undertaken as described (see Congenital Syphilis). Those with acquired syphilis should be evaluated for sexual abuse (e.g., through consultation with child protection services) (see Sexual Assault or Abuse of Children). These regimens are for children who are not allergic to penicillin who have acquired syphilis and who have normal CSF examinations.
Doxy-PEP as an STI Prevention Strategy: Considerations for individuals and healthcare providers of gay or bisexual men or transgender women
Other Management Considerations
All persons who have latent syphilis should be tested for HIV at the time of diagnosis or treatment. Those persons whose HIV test results are negative should be offered HIV PrEP. In geographic areas in which the prevalence of HIV infection is high or among populations vulnerable to HIV acquisition, persons who have early latent or late latent syphilis should be offered PrEP and retested for HIV in 3 months if the first HIV test result was negative.
Persons who receive a diagnosis of latent syphilis and have neurologic or ocular signs and symptoms (e.g., cognitive dysfunction, motor or sensory deficits, ophthalmic or auditory symptoms, cranial nerve palsies, or symptoms or signs of meningitis or stroke) should be evaluated for neurosyphilis, ocular syphilis, or otosyphilis according to their clinical presentation (see Neurosyphilis, Ocular Syphilis, and Otosyphilis).
If a person receives a delayed dose of penicillin in a course of weekly therapy for late latent syphilis or syphilis of unknown duration, the course of action that should be recommended is unclear. Clinical experience indicates that an interval of 10–14 days between doses of benzathine penicillin for latent syphilis might be acceptable before restarting the sequence of injections (i.e., if dose 1 is administered on day 0, dose 2 is administered on days 10–14). Pharmacologic considerations indicate that an interval of 7–9 days between doses, if feasible, might be preferred (610–612). Delayed doses are not optimal for pregnant women receiving therapy for latent syphilis (613). Pregnant women who have delays in any therapy dose >9 days between doses should repeat the full course of therapy.
Follow-Up
Quantitative nontreponemal serologic tests should be repeated at 6, 12, and 24 months. These serologic titers should be compared with the titer at the time of treatment. Persons with at least a fourfold sustained increase in nontreponemal test titer persisting for >2 weeks or who experienced signs or symptoms attributable to primary or secondary syphilis were likely reinfected or experienced treatment failure. These persons should be retreated and reevaluated for HIV infection. Among persons who have neurologic findings after a thorough neurologic examination or among persons with no neurologic findings and no sexual exposure during the previous year, a CSF examination is recommended. Treatment should be guided by CSF findings. Among persons with no neurologic findings after neurologic examination and who are sexually active, treatment with weekly injections of benzathine penicillin G 2.4 million units IM for 3 weeks is recommended.
Optimal management of persons who have less than a fourfold decrease in titers 24 months after treatment (i.e., an inadequate serologic response) is unclear, especially if the initial titer was <1:8. At a minimum, these persons should receive additional clinical and serologic follow-up and be evaluated for HIV infection. If neurologic symptoms or signs are identified, a CSF evaluation is recommended, with the findings guiding management. If additional follow-up cannot be ensured or if an initially high titer (>1:32) does not decrease at least fourfold 24 months after treatment, retreatment with weekly injections of benzathine penicillin G 2.4 million units IM for 3 weeks is recommended. Because treatment failure might be the result of unrecognized CNS infection, CSF examination can be considered in such situations where follow-up is uncertain or initial high titers do not decrease after 24 months.
If the CSF examination is negative, repeat treatment for latent syphilis is recommended. Serologic titers might not decrease despite a negative CSF examination and a repeated course of therapy, especially if the initial nontreponemal titer is low (<1:8); in these circumstances, the need for additional therapy or repeated CSF examinations is unclear but is usually not recommended. Serologic and clinical monitoring at least annually should continue to monitor for any sustained increases in nontreponemal titer.
Management of Sex Partners
See Syphilis, Management of Sex Partners.
Special Considerations
Penicillin Allergy
The effectiveness of alternatives to penicillin in treating latent syphilis has not been well documented. Nonpregnant patients allergic to penicillin who have clearly defined early latent syphilis should respond to antibiotics recommended as alternatives to penicillin for treating primary and secondary syphilis (see Primary and Secondary Syphilis). The only acceptable alternatives for treating late latent syphilis or syphilis of unknown duration are doxycycline (100 mg orally 2 times/day) or tetracycline (500 mg orally 4 times/day), each for 28 days. The efficacy of these alternative regimens among persons with HIV infection has not been well studied. These therapies should be used only in conjunction with close serologic and clinical follow-up, especially among persons with HIV infection. On the basis of biologic plausibility and pharmacologic properties, ceftriaxone might be effective for treating latent syphilis. However, the optimal dose and duration of ceftriaxone therapy have not been defined; treatment decisions should be discussed in consultation with a specialist. Persons with a penicillin allergy whose compliance with therapy or follow-up cannot be ensured should be desensitized and treated with benzathine penicillin G. Skin testing for penicillin allergy might be useful in circumstances in which the reagents and expertise are available for performing the test adequately (see Management of Persons Who Have a History of Penicillin Allergy).
Pregnancy
Pregnant women who are allergic to penicillin should be desensitized and treated with penicillin G. Skin testing for penicillin allergy might be useful in circumstances in which the reagents and expertise are available for performing the test adequately (see Management of Persons Who Have a History of Penicillin Allergy; Syphilis During Pregnancy).
HIV Infection
Persons with HIV infection who have latent syphilis should be treated similarly to persons who do not have HIV (see Syphilis Among Persons with HIV Infection).