Why is syphilis important? Treponema pallidum. Attributions. Much Ado About Syphilis

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1 Much Ado About Syphilis Sean Schafer, MD, MPH Medical Epidemiologist Oregon Health Division HIV/STD/TB Section (I have no financial conflicts to disclose.) Attributions Mary Ann Ware Sexually Transmitted Diseases, 4 th Ed. Holmes et al. eds. McGraw Hill Medical ES Theel. Accessed May 16, 2015 Various and sundry internet resources otherwise unattributed here (think Wikipedia, others presentations, etc.) Some actual peer reviewed literature Why is syphilis important? Disability & death Aortic aneurysm, coronary artery disease, aortic insufficiency Meningovascular syphilis (strokes, seizures) General paresis (progressive dementing illness) Tabes dorsalis (parenchymal infection of the spinal cord) Facilitates HIV transmission Increases transmission of HIV virus 2-5 x Congenital infection of fetus Stillbirth, infant death, developmental delays, bone and tooth deformities, general paresis in adolescence, meningitis Treponema pallidum Bacterium Spirochete Motile ( corkscrew ) Can t culture in lab wadsworth.org Transmission Sexual Trans-placental Percutaneous following contact with infectious lesions Bloodborn Extremely rare

2 Syphilis a few key concepts Highly infectious Infectious Dose~57 organisms Attack rate 1/3 3 clinical stages Primary: Painless sore (chancre) at inoculation site Secondary: Rash, fever, lymphadenopathy, malaise Symptomatic Late/Tertiary: Dementia, tabes dorsalis, cardiovascular disease Golden, M. R. et al. JAMA 2003 Natural History of Untreated Syphilis in Immunocompetent Individuals Copyright restrictions may apply. Argyll Robertson pupils Medical school revisited what are Argyll Robertson pupils? Vision preserved Small, fixed, don t respond to strong light Accommodate (constrict with convergence on near object) Mydriatics fail to dilate Do not dilate on painful stimuli

3 Early Syphilis Cases In Oregon Per Year by Date of Report year Rates of early* syphilis by sex and year Oregon, Cases of syphilis, all stages by year Deschutes County, Men 19.3** Overall 10.6** Women 2.0** *includes primary, secondary and early latent within 12 months of exposure **for 10 months.will be higher by 25 30% Year *includes primary, secondary and early latent within 12 months of exposure **for 10 months.will be higher by 25 30% Year

4 Syphilis Regional Trainings STD Prevention Program conducting four regional trainings for local health departments on syphilis case investigations, case follow up & partner testing/tx. Training materials and additional provider resources related to syphilis are available at: Each local health department has an assigned state STD Disease Intervention Specialist who can assist with unique and challenging cases and offer technical assistance. State DIS Assigned Counties Columbia Washington Clatsop Sherman Gilliam Hood River Multnomah Umatilla Tillamook Wallowa Morrow Union Yamhill Clackamas Wasco Polk Marion Wheeler Baker Jefferson Linn Grant Crook Lane Deschutes Coos Douglas Harney Malheur Lake Curry Josephine Klamath Jackson Last updated 1/25/2016 Patrick Phone & fax numbers Patrick Dinwiddie (Portland office) Desk Fax Cell Abdon Correa (Salem office) Desk Fax Cell Kym Coleman (Cottage Grove office) Desk No fax Cell Multnomah County DIS Staff Desk Fax Rates of early* syphilis by sex and year NY City, Seattle, Portland, Rates of early* syphilis and gonorrhea by sex and year Oregon, NY City Gonorrhea 61.0* Seattle Portland Syphilis 10.6** *includes primary, secondary and early latent within 12 months of exposure **for 10 months.will be higher by 25 30% Year *includes primary, secondary and early latent within 12 months of exposure **for 10 months.will be higher by 25 30% Year

5 Rates of HIV by sex and year Oregon, * *for 10 months.will be higher by 25 30% Year Seropreference Viral suppression prevents transmission Decreasing condom use LA county mascot for syphilis prevention Stop the sores campaign Phil the syphilis sore

6 Lab Diagnosis uncommon methods Rabbit Infectivity Test (RIT) Dark field microscopy Immunostaining CDC/NCHSTP/Dividion of STD Prevention Lab Diagnosis common methods Serology (tests for antibodies produced upon syphilis infection) Mainstay for syphilis testing Two kinds Non-treponemal Treponemal textbookofbacteriology.net Polymerase Chain Reaction (PCR) Non-treponemal serologic tests RPR and VDRL are agglutination assays T. pallidum causes cells to release cardiolipin Reagin = antibody to cardiolipin Non-treponemal tests measure levels of reagin: Test solution contains carbon particles+cardiolipin No reagin present, no agglutination Rapid Plasma Reagin (RPR) Venereal Disease Research Laboratory (VDRL) Toluidine red unheated serum test (TRUST) Cardiolipin Charcoal

7 Reagin present.agglutination of the charcoal Reagin Non-Treponemal Test Advantages Rapid turnaround time minutes Inexpensive No specialized instrumentation required Usually revert to negative following therapy Can be used to monitor response to therapy Treponemal serologic tests Syphilis Antibodies against T. pallidum Tests detect treponeme specific antibodies Fluorescent treponemal antibody absorbtion test (FTA-ABS) Microhemagglutination assay (MHA) T. pallidum particle agglutination (TP-PA) Enzyme Immunoassay (EIA) Immunochromatographic strips (ICS point of care tests) 12 FTA-ABS ICS

8 Treponemal Test Advantages Few false positives (high specificity) Fewer false negatives (more sensitive) especially during early and late syphilis Objective result interpretation Automation option High throughput = batchable High reproducibility/precision Treponemal Test Limitations Remain positive for life Cannot be used to monitor response to therapy Conventional (older) versions (e.g. FTA-ABS, TP-PA) Subjective interpretation like non-treponemal tests Newer versions Expensive instrumentation Higher cost/test Traditional Algorithm Non-treponemal test (e.g., RPR) Reactive Non-reactive Syphilis Screening Algorithms: Traditional versus Reverse Reactive Treponemal test (e.g., FTA) Non-reactive Not syphilis Syphilis Not syphilis

9 Traditional algorithm pros and cons Pros Familiar One confirmation test, typically done reflexively, leads to clear result Rapid, inexpensive Recommended by CDC Cons Manual Subjective interpretation False-positives False negatives, especially late syphilis Reverse Algorithm Treponemal test (eg, EIA) Reactive Non-reactive Non-Treponemal test (eg, RPR) Not syphilis Reactive Non-reactive Syphilis Second Treponemal Test (e.g., FTA) Reactive Non-reactive Probably syphilis Not syphilis Reverse algorithm pros and cons Pros Objective Can be batched for high volume labs Recommended by public health agencies in Europe and Canada More sensitive and more specific more cases of syphilis diagnosed and treated Cons Unfamiliar Cost Complexity often second confirmatory test needed, not yet typically done reflexively Disfavored by CDC VDRL RPR FTA -ABS TP -PA MHA -TP Syphilis Antibody Alphabet venereal disease research laboratory non-treponemal antibody reactive plasma reagin non-treponemal antibody fluorescent treponemal antibody absorbed treponemal antibody treponema pallidum particle agglutination ; treponemal antibody microhemagglutinin treponema pallidum treponemal antibody

10 The Syphilitic Albrecht Durer 1496 Early syphilis in women, Oregon, Self reported risk factors among female early syphilis cases (80), Oregon, (October) Drug use 20 (17 meth) Exchange sex for money/drugs 2 Past reported chlamydia or gonorrhea or HIV (28) None of above (40) Year

11 Congenital Syphilis, Oregon, Congenital Syphilis, Case Histories 2014 Douglas County. 21 y/o, White, bipolar, methamphetamine use, chlamydia. First prenatal ~10 weeks when RPR negative. Tested positive and treated at 18 weeks, after exposure. Still birth at 22 weeks. Hydrops but no positive staining for T. pallidum 2014 Marion County 20 y/o G2P1. Black. Sex partner is meth user. First prenatal care at 8 weeks when RPR negative. Positive RPR at 33.5 weeks after fetal ascites, splenomegaly, microcephaly, IUGR on ultrasound. Treated at 34 weeks, delivered at 35 weeks. Infant had radiographic stigmata, hepatosplenomegaly, positive CSF- VDRL and elevated CSF protein. Infant treated with IV Pen G. CDC, ACOG Prenatal Syphilis Screening Recommendations In communities and populations in which the risk for congenital syphilis is high, serologic testing and a sexual history also should be obtained at 28 weeks gestation and at delivery. Should we or shouldn t we recommend additional screening for syphilis in pregnancy: Cost effectiveness modeling additional prenatal screening in third trimester Albright, Obstetrics and Gynecology 2015 Decision analysis Assumptions seroconversion during pregnancy.012 Cost effectiveness threshold: $285,000 to prevent one congenital case Base case $419,842 to prevent one congenital case (not cost-effective by this model) Cost-effective if seroconversion.017

12 What is Oregon s syphilis seroconversion rate in pregnant women? Do we meet Albright s threshold? The denominator: how many pregnant women on any day in Oregon? Prevalence = Incidence * Duration Oregon Birth cohort ( incidence ): 40,000/52 weeks Duration: 40 weeks Size of population ( prevalence ) = (40,000/52 weeks) * 40 weeks = 30,769 The numerator; how many incident infections in women 12 to 32 weeks gestation in 2015? 6/11 mos ~ 7/12 mos Seroconversion pregnancy: 7/30,769 =.00023, 1 in 4286 pregnant women per year: 73-fold lower than Albright s threshold What exactly is a uvea*? Is this a polite word in mixed company? Uveitis or vision loss + syphilis any stage 2014 & 2015 cases Washington 4 cases, 4/4 MSM, 3/4 HIV+ San Francisco 8 cases, 6/8 MSM, 7/8 male, 7/8 HIV+ Estimated baseline 6 12 cases per year in US Diagnoses Uveitis, ischemic optic neuropathy, retinal detachment Uveitis ~ intraocular inflamation Anterior (front) Iritis or iridocyclitis Posterior (back) Vitritis, intermediate uveitis, pars plantitis, choroiditis, retinitis, chorioretinitis, retinochoroiditis Pan (front and back) Uva (Latin) = grape (English)

13 Ocular Syphilis in Oregon Case definition Vision loss, ophthalmia, physician diagnosis of uveitis Serological evidence of syphilis, any stage 35 cases 2014: 10, 2015: male 19 treated for neurological involvement; 11 secondary, 3 early latent, 21 late syphilis; 16 HIV+ 18 msm Suspected Ocular Syphilis Contact your local health department or Oregon Health Division STD Program (Sean Schafer, MD, MPH sean.schafer@state.or.us or ) to report Oregon Health Division would like frozen samples of whole blood and csf for testing Ask patients with syphilis about ocular symptoms Conduct careful neurologic exam including cranial nerves Conduct a lumbar puncture Treat as neurosyphlis with IV aqueous Pen G Most effective step to reduce syphilis transmission Recommend that sexually active men who have sex with men get a serologic test for syphilis every 3 months Consider adding routine syphilis serology to regular CD4 and viral loads in men who have sex with men who have HIV

14 Provider Outreach Screening recommended at least annually, 4 times a year if sexually active multiple partners Men who have sex with men Illicit drugs, including cocaine, methamphetamines, heroin Sex workers all genders Other sexually transmitted infections, including HIV Exposure to syphilis Take a sexual history on all patients, including sex of partners Provider resources at healthoregon.org/std Letter, county rates, congenital syphilis summary, ocular syphilis summary, testing algorithms, investigative guidelines, CDC STD treatment guidelines