A Review and Update on Adult Syphilis,with Particular Reference to its Treatment

Abstract

Syphilis has become less common in Europe in the last decade, but has once again become a major problem in the USA, and remains so in many developing countries. Several treponemal genes have now been cloned and expressed in Escherichia coli, allowing study of treponemal proteins. The importance of cell mediated immunity in syphilis has been demonstrated in animal models.

A diagnosis of syphilis is usually confirmed by dark-field microscopy or serological tests. Seroconversion may be delayed in HIV infected individuals. A positive reaginic test in cerebrospinal fluid (CSF) has a high specificity but low sensitivity in the diagnosis of neurosyphilis. Indeed, virulent treponemes can be identified in CSF samples which have negative reaginic tests, normal cell counts and protein levels. In the CSF, the FTA-Abs test has a high sensitivity but low specificity for neurosyphilis.

Penicillin remains the treatment of choice for all stages of syphilis, although it penetrates the blood brain barrier poorly. Treatment with intramuscular benzathine penicillin 2.4 million units stat, or 600,000 units procaine penicillin daily does not produce treponemicidal levels within the CSF. However, the incidence of neurosyphilis is low in immunocompetent patients treated with such regimens during early syphilis. Acceptable alternatives in penicillin-allergic patients include ceftriaxone and doxycycline. Erythromycin is not recommended as it has produced unacceptably high rates of treatment failure. Recently, a strain of macrolide-resistant Treponema pallidum was isolated from a patient with secondary syphilis. For the treatment of neurosyphilis, treponemicidal levels of penicillin can be achieved in the CSF using 2.4 million units procaine penicillin daily with concurrent probenecid 500 mg 4 times a day, or an intravenous infusion of benzyl penicillin 12–24 million units daily. Early syphilis can be treated adequately over 10 days, but 21 to 28 days is appropriate for late syphilis.

In HIV-infected patients syphilis may present atypically with initially negative serological tests. Treatment of early syphilis in HIV-positive patients has been associated with the early development of neurosyphilis. It is advisable to treat all patients co-infected with HIV with an antibiotic regimen that achieves adequate levels within the CSF.