What are the guideline sources, guidelines and references for Syphilis infection ?
Guideline sources The following summarized guidelines for the evaluation and management of syphilis infection are prepared by our editorial team based on guidelines from the U.S. Preventive Services Task Force (USPSTF 2018; 2016), the International Union Against Sexually Transmitted Infections (IUSTI 2014), and the AIDSinfo Society (AIDSInfo 2009). 1 2 3 4 Guidelines 1. Screening and diagnosis Indications for screening (patients at increased risk): screen for syphilis infection in patients who are at increased risk for infection. A Indications for screening (pregnant women): screen all women for syphilis infection during early pregnancy. A 2. Classification and risk stratification https://web.pathway.md/diseases/recRgmaGBKhlZ6zrn 1/6 6/24/23, 3:14 PM Syphilis infection Pathway Staging of active disease: diagnose primary syphilis in patients with serological evidence of syphilis infection presenting with an ulcer (chancre). The chancre of syphilis is primarily super cial, single, painless and indurated with a clean base discharging clear serum, most often located in the anogenital region. However, lesions are often atypical in appearance and may be multiple, painful, deep and indistinguishable from herpes. Show 3 more Classification of latent disease: Diagnose latent syphilis in patients with serological evidence of syphilis infection and no clinical evidence of treponemal infection. Classify latent syphilis into early latent (if within the rst year of infection) and late (or undetermined duration) after > 1 year (on the basis of clinical signs in patient and partners). 3. Diagnostic investigations Types of serological tests for syphilis: Treponemal tests detect IgG and/or IgM antibodies. These become positive around 6 weeks after infection and remain positive for life in most patients. These tests include the following: treponemal enzyme immunoassay (EIA) treponemal chemiluminescence immunoassay (CIA) treponema pallidum hemagglutination test (TPHA) treponema pallidum passive particule agglutination test (TPPA) treponema pallidum IgG immunoblot test (TPIB). Non-treponemal tests detect a mixture of heterophile IgG and IgM antibodies. These become positive 6 weeks after infection, correlate grossly with disease activity, and are useful to monitor disease activity and the efficacy of treatment. These tests include the following: venereal disease research laboratory RPR toluidine red unheated serum test (TRUST). Initial testing: Use one of the following approaches for primary screening: A treponemal test alone (TPHA, MHA-TP, TPPA or EIA/CIA) A non-treponemal test alone (RPR or VDRL) both a treponemal test and a non-treponemal test. Confirmatory testing: Use a second treponemal test of a different type as confirmatory testing in patients in whom a treponemal test alone was used as a primary screening test (TTPA or TPHA, if EIA or CIA was used for screening, and vice-versa), and obtain a quantitative non-treponemal test if the second treponemal test is positive. Use a treponemal test as confirmatory testing in patients in whom a non-treponemal test was used as a primary screening test, and obtain a quantitative non-treponemal test if not performed https://web.pathway.md/diseases/recRgmaGBKhlZ6zrn 2/6 6/24/23, 3:14 PM Syphilis infection Pathway initially. Evaluation for neurosyphilis: perform a complete clinical examination (neurological, ocular and otologic) in every patient with positive syphilis screening test. Show 3 more 4. Medical management Antibiotic therapy, early-stage disease (HIV-): Use benzathine penicillin G (2.4 million units intramuscularly, for one dose) as preferred therapy for patients with early syphilis. B Use procaine penicillin (600 000 units intramuscularly once daily, for 10-14 days) as alternative therapy for patients with early syphilis, if benzathine penicillin G is not available. B Antibiotic therapy, early-stage disease (HIV+): use benzathine penicillin G (2.4 million units intramuscularly, for 1 dose) as preferred therapy for patients with early-stage syphilis (primary, secondary, and early-latent). B Show 2 more Antibiotic therapy, late-latent disease (HIV-): Use benzathine penicillin G (2.4 million units intramuscularly once weekly, for 3 weeks) as the preferred therapy in patients with late-latent syphilis. B Use procaine penicillin (600 000 units intramuscularly daily, for 17-21 days) as alternative therapy in patients with late-latent syphilis, if benzathine penicillin G is not available. B Antibiotic therapy, late-latent disease (HIV+): use benzathine penicillin G (2.4 million units intramuscular every week, for 3 weeks) as the preferred therapy for patients with late-latent syphilis. B Show 2 more Antibiotic therapy, neurological, otic, or ocular disease (HIV-): use benzyl penicillin (3-4 million units IV every 4 hours, for 10-14 days) as preferred therapy for patients with neurosyphilis, ocular, and auricular syphilis. B Show 3 more Antibiotic therapy, neurological, otic, or ocular disease (HIV+): Use the following regimen as preferred therapy for patients with neurosyphilis, otic or ocular disease: aqueous crystalline penicillin G - 18-24 million units per day, as 3-4 million units IV every 4 hours or by continuous IV infusion, for 10-14 days B with or without benzathine penicillin G - 2.4 million units intramuscularly every week, for 1 to 3 doses after completion of intravenous therapy B Show 3 more Prevention of Jarisch-Herxheimer reactions: Corticosteroids may help to prevent severe deterioration due to Jarisch-Herxheimer reactions in patients with early syphilis with optic neuritis and uveitis. https://web.pathway.md/diseases/recRgmaGBKhlZ6zrn 3/6 6/24/23, 3:14 PM Syphilis infection Pathway Consider using prednisolone (20-60 mg PO once daily for 3 days) for the prevention of Jarisch- Herxheimer reactions, if indicated; start antitreponemal treatment after 24 hours of initiating prednisolone. C 5. Specific circumstances Pregnant patients (HIV-): Use benzathine penicillin G (2.4 million units intramuscularly, for one dose) as the preferred therapy in pregnant patients with early syphilis. B Consider using procaine penicillin (600,000 units intramuscularly once daily, for 10-14 days) as alternative therapy for pregnant patients with early syphilis, if benzathine penicillin G is not available. C Pregnant patients (HIV+): Use benzathine penicillin, following desensitization, in all pregnant women with syphilis who are allergic to penicillin. Consider administering a second dose of benzathine penicillin G (2.4 million units intramuscularly, one week after the first dose) in pregnant women with early syphilis. C Patients with penicillin allergy (HIV-): Consider using one of the following regimens in patients with early syphilis who are allergic to penicillin or refuse parenteral treatment: doxycycline - 100 mg PO BID for 14 days C azithromycin - 2 g PO as a single dose B Consider using doxycycline (100 mg PO BID, for 21-28 days) in patients with late-latent syphilis who are allergic to penicillin or refuse parenteral treatment. C Patients with penicillin allergy (HIV+): recognize that the efficacy of non-penicillin alternatives has not been well evaluated in patients with human immunodeficiency virus infection and should be undertaken only with close clinical and serologic monitoring. Show 5 more Patients with transplant-induced syphilis: Use benzathine penicillin G (2.4 million units intramuscularly every week, for 3 weeks) as preferred therapy for patients with syphilis acquired via solid organ transplantation. B Use doxycycline (100 mg PO BID, for 21-28 days) as preferred therapy for patients with syphilis acquired via solid organ transplantation who are penicillin-allergic. 6. Patient education Counseling on treatment reactions: counsel patients regarding the Jarisch-Herxheimer reaction, an acute febrile reaction accompanied by headache and myalgias that can occur within the first 24 hours after the initiation of treatment for syphilis. It occurs more frequently in patients with early https://web.pathway.md/diseases/recRgmaGBKhlZ6zrn 4/6 6/24/23, 3:14 PM Syphilis infection Pathway syphilis, high non-treponemal antibody titers, and prior penicillin treatment. Inform patients that this reaction does not represent an allergic reaction to penicillin. 7. Follow-up and surveillance Tracing of sexual contacts: Ensure sexual contact noti cation is performed in all patients with syphilis (noti cation by the patient: patient referral; by a health department: provider referral). Sexual contacts should include all those individuals who have had oral, vaginal or anal intercourse with infected individuals, whether or not barrier protection was used. Notify sexual contacts within the past 3 months for patients with early syphilis, as the incubation period is up to 90 days. Partner noti cation may have to extend up to 2 years for patients in secondary syphilis with clinical relapse or in early latent syphilis. Longer periods may be required in those with late latent and late syphilis. Treatment of sexual contacts: Administer presumptive treatment for early syphilis in patients who have had sexual contact with a person diagnosed with primary, secondary, or early latent syphilis within 90 days preceding the diagnosis, even if serologic test results are negative. B Administer presumptive treatment for early syphilis in patients who have had sexual contact with a person who diagnosed with primary, secondary, or early latent syphilis > 90 days before the diagnosis, if serologic test results are not immediately available and the opportunity for follow-up is uncertain. B Follow-up blood testing: Measure non-treponemal test titers at 1, 3 and every 6 months subsequently, using the same assay, performed in the same laboratory. Continue follow-up until the non-treponemal test becomes negative, attains a low plateau (1:1-1 :4, sustained for 1 year and in the absence of ongoing risk). B Consider using either quantitative VDRL or RPR tests to monitor disease progression and effectiveness of treatment at follow-up visits. Obtain baseline titers on the very first day of treatment in order to accuarely measure a decrease in antibody titers. Follow-up CSF testing: obtain follow-up examination of cerebrospinal uid within 6 weeks to 6 months of treatment in patients with neurosyphilis. References 1. Janier M, Hegyi V, Dupin N et al. 2014 European guideline on the management of syphilis. J Eur Acad Dermatol Venereol. 2014 Dec;28 12 1581 93. Open 2. Kaplan JE, Benson C, Holmes KK et al. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of https://web.pathway.md/diseases/recRgmaGBKhlZ6zrn 5/6 6/24/23, 3:14 PM Syphilis infection Pathway Health, and the HIV Medicine Association of the Infectious Diseases Society of America. MMWR Recomm Rep. 2009 Apr 10;58 RR 4 1 207. Open 3. US Preventive Services Task Force. Screening USPSTF for Syphilis Infection in Pregnant Women US Preventive Services Task Force Reaffirmation Recommendation Statement. JAMA. 2018;320 9 911 917. Open 4. US Preventive Services Task Force USPSTF , Bibbins-Domingo K, Grossman DC et al. Screening USPSTF for Syphilis Infection in Nonpregnant Adults and Adolescents: US Preventive Services Task Force Recommendation Statement. JAMA. 2016 Jun 7;315 21 2321 7. Open 5. M Janier, M Unemo, N Dupin et al. 2020 European guideline on the management of syphilis. J Eur Acad Dermatol Venereol. 2021 Mar;35 3 574 588. Open 6. Panel on Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. Department of Health and Human Services. 2023. Open 7. Naokatsu Ando, Daisuke Mizushima, Kazumi Omata et al. Combination of Amoxicillin 3,000 mg and Probenecid versus 1,500 mg Amoxicillin Monotherapy for Treating Syphilis in Patients with HIV an Open- Label, Randomized, Controlled, Non-Inferiority Trial. Clin Infect Dis. 2023 May 9;ciad278. Open https://web.pathway.md/diseases/recRgmaGBKhlZ6zrn 6/6