Emily J. Erbelding, M.D., M.P.H. and Khalil G. Ghanem, M.D.
- Recent national survey from Zambia found syphilis prevalence 6.5% for women and 7.4% for men; Copperbelt, Eastern and Lusaka provinces had higher rates for both men and women (no data on rates of HIV coinfection).
- Given synergy between syphilis and HIV, all pts Dx'd with syphilis should be referred for HIV testing, and all pts Dx'd with HIV should be screened for syphilis.
- Dx and management of syphilis in Zambia similar to that in other countries.
- RPR is test of choice, as darkfield examination, DFA, and FTA not readily available.
- Rx recommendations in this module are same as in Zambia's National Guidelines on Management and Care for HIV/AIDS.
- Rx for children in Zambia: benzathine penicillin 50,000 units/kg IM (up to adult dose of 2.4 million units IM weekly x 3 doses).
Zambia Information Author: David Riedel, M.D.
Treponema pallidum: a spirochete
- HIV+ pts may have abnormal serologic results (unusually high titers, false negatives, delayed seroreactivity, higher rates of serologic failure after therapy), but serology can usually be interpreted in usual manner. Occurs at any CD4 count.
- Staging at time of Dx determines therapy; clinical stages may overlap and manifestations are protean; neurologic manifestations can occur with any stage.
- Primary: Usually evident 14-21 days after exposure; indurated ulcer at site of inoculation (chancre); most commonly anogenital or oral.
- Secondary: Usually 4-10 weeks after chancre; maculopapular or papulosquamous eruption, often involves palms/soles (60%); other: fever, alopecia, mucous patches, condyloma lata; rarely arthritis, glomerulonephritis, hepatitis.
- Tertiary: 1/3 of those left untreated develop late sequelae, including cardiovascular syphilis, gummas, paresis, tabes dorsalis.
- Latent: No clinical findings but reactive serology; early latent <1 yr duration; late latent >1 yr duration.
- Neurosyphilis should be considered in DDx when neurologic signs or symptoms in HIV+ pts; ocular syphilis should be considered in DDx of visual loss.
- Early neurosyphilis (i.e. occurring within the first year after infection) is frequent in HIV+ patients
- Worsening of lab markers of HIV stage (decline in CD4 count and increased VL) with early stage syphilis.
- Parenteral penicillin is drug of choice in ALL stages of syphilis; no resistance observed despite decades of PCN use.
- Higher risk of neurosyphilis with HIV+, CD4 < 350, and RPR > 1:32. Consider LP with any of these factors, and also with any neuro findings or serologic treatment failure.
- Immune reconstitution using ART may help decrease risk of serological failure and neurosyphilis
- Definitive: visualization of motile T. pallidum (darkfield examination) or positive DFA test in fluid from clinically compatible lesion or on histopathology
- Serologic testing: Nontreponemal serology (RPR, VDRL) followed by reflex treponemal testing (FTA-Abs or MHA-TP) establishes presumptive Dx; EIA testing (followed by nontreponemal test titer) becoming more common.
- Neurosyphilis: Reactive CSF VDRL (30-70% sensitive) or elevated WBC (>5) or protein (>) 50; treatment for neurosyphilis indicated if reactive FTA-Abs in CSF and CSF WBC >5 or CSF protein >45, OR reactive CSF VDRL.
- Preferred: benzathine PCN G 2.4 million units IM x1.
- Alternative (PCN allergic): doxycycline 100 mg twice-daily x 14 days
- Early latent syphilis (<1 yr duration): benzathine PCNG 2.4 million units IM x1
- Late latent (>1 yr duration), latent of unknown duration, or tertiary syphilis, excluding neurosyphilis: benzathine PCN G-2.4 million units IM q wk x 3 doses. Experts recommend LP to evaluate for asymptomatic neurosyphilis.
- Alternative: doxycycline 100 mg twice-daily x 28 days
- Preferred: aqueous crystalline PCN G 18-24 million units daily as 3-4 million units q4 hrs (or continuously) x10-14 d.
- Alternative: procaine PCN 2.4 million units IM once-daily x10-14 d (along with probenecid 500 mg four times a day).
- Alternative: ceftriaxone 2 gm IM/IV once-daily x 10-14 d (less clinical experience than with PCN regimens)
Doxycycline not recommended.
- Some experts recommend benzathine PCN G 2.4 million units q wk for 1-3 doses after completion of IV PCN regimen.
- Use should generally be avoided. Azithromycin 1 or 2 gm single dose effective in preventing syphilis in exposed contacts, but macrolide resistance documented.
| Azithromycin ||Data suggest equivalence to PCN in preventing syphilis infection in partners of infectious cases; resistance to macrolides reported, causing concern for use in both incubating syphilis and syphilis infection.
| Doxycycline ||Has been used for years as alternative when PCN contraindicated, though no data to support use in treating neurosyphilis; use in HIV infection not studied.
|Penicillin||Preferred drug for treatment of all stages of syphilis; only therapy indicated for treatment of syphilis in pregnancy.
|Ceftriaxone||More limited clinical experience compared to PCN, but may be more effective and more convenient parenteral therapy for neurosyphilis.
- Resolution of clinical Sx and appropriate serologic response (decline in nontreponemal titer) are best measures of therapeutic response.
- RPR (or other non-treponemal test titer) at 3, 6, 9, 12, 24 mos; 4-fold decline from baseline titer 6 mos after therapy expected. Treatment failure requires LP and re-treatment with 3 weekly doses of benzathine PCN G if LP is negative.
- RPR (or other non-treponemal test titer) at 6, 12, 24 mos; 4-fold decline from initially high baseline titer (>1:32) at 12-24 mos after therapy expected.
- If follow-up RPR (or other non-treponemal test titer) fails to decline as above, or declines then rises, evaluate for reinfection and for neurosyphilis, then re-treat.
- Neurosyphilis: repeat LP every 6 mos until cell count normal. Consider retreatment if cell count has not decreased after 6 mos or if not entirely normal after 2 yrs.
- Errors in Bicillin formulation (use of benzathine penicillin G/procaine penicillin G rather than benzathine penicillin G) have led to inadequate treatment of syphilis cases and FDA alert.
- Centers for Disease Control and Prevention ;
Sexually transmitted diseases treatment guidelines 2006. Centers for Disease Control and Prevention.;
MMWR Recomm Rep;
Basis for recommendation
Comments:These consensus panel guidelines should provide a basis for managing nearly all syphilis cases encountered.