Sex, Sores, Science, and Surveillance: Syphilis in the 21 st Century (U046)

Sex, Sores, Science, and Surveillance: Syphilis in the 21 st Century (U046) Kenneth A. Katz, MD, MSc, MSCE Dermatologist, Kaiser Permanente, San Francisco, CA AAD Annual Meeting, Orlando, FL March 4, 2017

Conflict of Interest Disclosure Prevention Health Labs, Inc.: Co-Founder Arrowhead Pharmaceuticals Corp.: Shareholder Synta Pharmaceuticals, Inc.: Shareholder Madrigal Pharmaceuticals, Inc.: Shareholder

Syphilis in the 21 st Century Epidemiology of syphilis in the USA Reverse-sequence serologic testing algorithm Syphilis screening recommendations Management recommendations

Epidemiology of syphilis in the USA

https://www.cdc.gov/std/stats15/slides/stds-survrpt-2015-all-slides.pdf

Primary and secondary cases 1999: 6,617 1999: National Plan to Eliminate Syphilis https://www.cdc.gov/std/stats15/slides/stds-survrpt-2015-all-slides.pdf

Primary and secondary cases 1999: 6,617 1999: National Plan to Eliminate Syphilis 2000: 5,979 https://www.cdc.gov/std/stats15/slides/stds-survrpt-2015-all-slides.pdf

Primary and secondary cases 1999: 6,617 1999: National Plan to Eliminate Syphilis 2000: 5,979 2015: 23,872 https://www.cdc.gov/std/stats15/slides/stds-survrpt-2015-all-slides.pdf

https://www.ncbi.nlm.nih.gov/pubmed/?term=25487961

Methamphetamine use: 19% Use of Internet to meet sex partner(s): 36% Meth and Internet users had more sex partners than non-users https://www.ncbi.nlm.nih.gov/pmc/articles/pmc4007854/pdf/ajph.2012.300808.pdf

https://www.ncbi.nlm.nih.gov/pubmed/?term=25487961

https://www.cdc.gov/std/stats15/msm.htm; https://www.ncbi.nlm.nih.gov/pubmed/?term=25487961 High rates of coinfection among MSM MSM with P&S syphilis at STD clinics HIV co-infection in 21% 59%

Pre-exposure prophylaxis for HIV (PrEP) 2010: NEJM publishes iprex trial 2012: FDA approves PrEP 2015: High rates of STDs among MSM on PrEP in California (but no new HIV infections!) https://www.ncbi.nlm.nih.gov/pubmed/?ter m=25487961; http://www.nejm.org/doi/full/10.1056/nej Moa1011205; http://www.fda.gov/newsevents/newsroo m/pressannouncements/ucm312210.htm; https://academic.oup.com/cid/article/61/10 /1601/302937/No-New-HIV-Infections- With-Increasing-Use-of-HIV

https://www.cdc.gov/std/stats15/slides/stds-survrpt-2015-all-slides.pdf

388 cases (0.6% of total syphilis cases) 69% MSM 51% living with HIV 28% with primary or secondary syphilis 22% had other neurosyphilis symptoms Symptoms: blurry vision (64%), vision loss (33%), eye pain or red eye (14%) https://www.cdc.gov/mmwr/volumes/65/wr/pdfs/mm6543a2.pdf

Screen syphilis patients for visual complaints Test all syphilis patients for HIV if not known to be HIV-positive Perform neuro exam including cranial nerves in all syphilis patients Refer syphilis patients with ocular complaints for ophtho exam and LP Treat ocular syphilis according to neurosyphilis recommendations Report ocular syphilis cases to health department within 24 hours https://www.cdc.gov/std/syphilis/clinicaladvisoryos2015.htm

https://www.cdph.ca.gov/programs/std/documents/neurosyphilisguide.pdf

https://www.cdc.gov/std/stats15/slides/stds-survrpt-2015-all-slides.pdf

CDC: Congenital syphilis increasing Late or limited prenatal care Failure of healthcare providers to adhere to syphilis screening recommendations https://www.cdc.gov/std/stats15/womenandinf.htm; https://www.cdc.gov/std/stats15/slides/stds-survrpt-2015-all-slides.pdf

https://www.cdc.gov/std/stats15/slides/stds-survrpt-2015-all-slides.pdf

Reverse-sequence serologic testing algorithm

Reverse-sequence serologic testing Starts with treponemal before nontreponemal tests Uses new treponemal tests that are less expensive than RPR or VDRL Enzyme immunoassay (EIA) Chemiluminescent immunoassay (CLIA)

Traditional Algorithm RPR or VDRL (nontreponemal) Newer Algorithm EIA/CLIA (treponemal) Nonreactive STOP Reactive Nonreactive Generally do not get these combinations TPPA or other of results with STOP treponemal testthe traditional algorithm Reactive RPR or VDRL (nontreponemal) Nonreactive Reactive Nonreactive Reactive Biologic false positive Syphilis (new or previously treated) Tiebreaker test(s) Syphilis (new or previously treated) Note: Algorithms are slightly simplified

Newer Algorithm Discordant Results from Reverse-Sequence Syphilis Screening Five Laboratories, United States, 2006 2010 140,176 specimens Nonreactive 96% STOP EIA Reactive 4% RPR or VDRL Nonreactive Reactive 57% 43% Tiebreaker test(s) Syphilis (new or previously treated) http://www.cdc.gov/mmwr/pdf/wk /mm6005.pdf 32% nonreactive, 68% reactive

Syphilis screening recommendations

Syphilis screening recommendations: CDC and USPSTF Group Pregnant women MSM and HIV-infected Others at increased risk Agency and Recommendation CDC: 1 st prenatal visit. Repeat in 3 rd trimester and at delivery if risk USPSTF: 1 st prenatal visit. Repeat in 3 rd trimester and at delivery if risk CDC: Screen at least annually; every 3 6 months if at increased risk USPSTF: Screen. Optimal frequency not clear; every 3 months more effective than annually USPSTF: Risk factors include history of incarceration or commercial sex work; geography; race/ethnicity; men < 29 years. Screen. Optimal frequency not clear; every 3 months more effective than annually https://www.uspreventiveservicestaskforce.org/page/document/recommendationstatementfinal/syphilis-infection-in-pregnancy-screening; https://www.uspreventiveservicestaskforce.org/page/document/recommendationstatementfinal/syphilis-infection-in-nonpregnant-adults-andadolescents; http://www.cdc.gov/std/tg2015/screening-recommendations.htm

Management recommendations

Treatment of primary and secondary syphilis in adults without neurosyphilis or ocular syphilis Benzathine penicillin G 2.4 million units intramuscular, single dose Penicillin-allergic Non-Pregnant: Doxycycline 100 mg orally twice per day for 14 days Pregnant: Desensitize, treat with penicillin G benzathine 2.4 MU IM once Treatment of other stages/children/neurosyphilis/ocular syphilis See CDC Guidelines http://www.cdc.gov/std/tg2015/syphilis.htm Clement ME, Okeke NL, Hicks CB. Treatment of syphilis: a systematic review. JAMA.2014;312:1905-17.

Jarisch-Herxheimer reaction Acute febrile reaction to dying treponemes Flu-like symptoms Usually occurs within 24 hours after treatment in high-titer syphilis Not a penicillin (or doxycycline) allergy Can treat with acetaminophen Pregnant women: might induce labor or cause fetal distress, but do not delay therapy http://www.cdc.gov/std/tg2015/syphilis.htm

Other Management Pearls Report case to local or state health authority Provider AND laboratory are BOTH required to report in all states Inform patient that public health workers might follow up Address other sexual health needs HIV/STD testing, vaccinations, pre- and post-exposure prophylaxis for HIV Assess clinical response No sex until clinically resolved Assess serologic response Four-fold decline in nontreponemal test titer (RPR/VDRL) (e.g., 1:64 1:16) Need day-of-treatment titer http://cdc.gov/std/treatment/2010/genital-ulcers.htm#syphilis

Follow-up: CDC recommendations Stage HIV Status Follow-up after treatment Primary or secondary HIVuninfected 6 and 12 months Typical timeframe for 4-fold titer decline 6 12 months HIVinfected 3, 6, 9, 12, 24 months 6 12 months Latent HIVuninfected 6, 12, 24 months 12 24 months HIVinfected 6, 12, 18, 24 months 12 24 months http://www.cdc.gov/std/tg2015/syphilis.htm

Follow-up: a practical approach Stage HIV Status Follow-up after treatment Primary or secondary HIVuninfected Every 3 6 months Typical timeframe for 4-fold titer decline 6 12 months HIVinfected Every 3 6 months 6 12 months Latent HIVuninfected Every 3 6 months 12 24 months HIVinfected Every 3 6 months 12 24 months

Repeat syphilis among MSM 7% within 1 year among MSM with HIV 12% within 2 years among MSM with HIV 6% within 2 years among MSM with HIV, Blacks, MSM with multiple sex partners