Public/Private Partnerships: Intervening in the Spread of Syphilis

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1 Public/Private Partnerships: Intervening in the Spread of Diana Torres-Burgos MD, MPH Gerard Castaneda, BSN Alana Thomas, BS STD/HIV Update Conference Grand Rapids, MI 3/11/2014 Outline overview Stages of Screening and testing CDC recommended treatment regime Congenital syphilis (CS) Prevention - Public Health and Healthcare provider partnership. Pathogenesis 3 Etiologic agent: Treponema pallidum Transmission: Sexual contact- vaginal, rectal, oral Transmitted via placenta from infected mother to fetus during pregnancy The Stages of Early Latent Late Latent Exposure Primary Secondary Tertiary 6 months 12 months INFECTIOUS Clinical Manifestations 5 Primary Primary lesion or "chancre" develops at the site of inoculation about 3 weeks (range days) after exposure. Primary Chancre Clinical manifestations: Macule - Papule - Ulcer Typically painless, indurated with clean base Heals within 3-6 weeks without treatment Serologic tests: May not be positive during early primary syphilis. 1

2 Primary Chancre Darkfield microscopy Secondary Secondary syphilis lesions occur about 4-10 weeks after the primary chancre appears. Primary and secondary stages may over lap. Can be recurrent. Clinical manifestations: Rash -most common Lymphadenopathy Malaise Mucous patches Condylomata lata Alopecia Uveitis Serologic tests: RPR/VDRL always positive Usually highest in titer during this stage. Possibility of prozone effect in very high titers Secondary Stage of syphilis- Rash Secondary Mucous patch Alopecia Clinical Manifestations 11 Secondary Condylomata lata Perianal and Vulvar Warts Clinical Manifestations12 Source: CDC/ NCHSTP/ Division of STD Prevention, STD Clinical Slides Source: Seattle STD/HIV Prevention Training Center at the University of Washington/ UW HSCER Slide Bank Source: Reprinted with permission of Gordon D. Davis, MD. 2

3 Clinical Manifestations13 Latent, Tertiary, & Neurosyphilis Latent Patient infected but asymptomatic Positive serological test is the only evidence of infection Tertiary Approximately 30% of untreated patients progress to the tertiary stage within 1 to 20 years. Rare because of the widespread availability and use of antibiotics Neurosyphilis May occur at any stage of syphilis Can be asymptomatic Screening Females and Males No routine screening recommendation. Consider in high risk groups. Pregnant Women Screen 1 st prenatal visit and at delivery; retest during 3 rd trimester if at high risk MSM Serology at least annually HIV-infected Serology at baseline and at least annually Serological Testing Non-treponemal Tests RPR, VDRL Non-specific Quantitative (titer) Reactivity declines with time Traditional Testing Algorithm Reflex to Treponemal Tests FTA-Abs, TP-PA Specific Qualitative EIA Reactivity persists over lifetime Serological Testing Reverse Sequence Testing Algorithm Treponemal Tests Non-Treponemal Tests (EIA, CIA) Specific to TP Qualitative Reactivity persists over lifetime Reflex to (RPR, VDRL) Non-specific to TP Quantitative Reactivity declines with time MMWR. Discordant results from Reverse Sequence Screening- Five Laboratories, U.S., Feb. 11,2011/Vol. 60/No.5: MMWR. Discordant results from reverse sequence syphilis screening- Five Laboratories, US, February 11, Vol.60/No. 5: CDC Recommended algorithm for Reverse Sequence Testing Initial Screen IgG Positive Negative Reflex Testing RPR Not Positive Negative Confirmation with TPPA Confirmatory Positive Confirmatory Negative Old syphilis infection Previously treated syphilis False positive IgG Reverse Sequence Testing Advantages Highly automated Less occupational hazard (no pipette) Less costly No prozone effect Disadvantages Does not distinguish between treated/current disease Significantly increases number of persons requiring f/u evaluations How to deal with EIA+/RPR-, esp.in HIV, early untreated, false + EIA, or previously treated syphilis. Few studies compare test performance with other serological tests 3

4 Serologic Interpretation RPR -NonReactive / FTA-ABS NonReactive No Diagnosis Incubating syphilis infection Very Early Primary RPR -Reactive / FTA-ABS NonReactive Biologic False Positive False-negativeTreponemal Test (rare) RPR -NonReactive / FTA-ABS- Reactive Very Early Primary Secondary w/ Prozone Late untreated syphilis w/ sero-reversal of RPR History of Treated Rxed inadvertently in past False-negative Non-Treponemal test False-positive Treponemal Test (rare) RPR -Reactive / FTA-ABS Reactive Positive Diagnosis Lyme disease Endemic (non-sexual) treponemal dz Causes of False Positive serology tests Connective tissue diseases Autoimmune diseases Acute and chronic infections Viral infections Malignancies Drug dependence Pregnancy Vaccinations Treatment Stage Recommended Regime Alternative Regimen Primary, Secondary, and Early Latent Late latent and Latent of unknown duration 2.4 million units IM x million units, administered as doses of 2.4 million units IM each at one week intervals x 3 weeks. Doxycyline 100 mg BID x 14 days Tetracycline 500 mg QID x 14 days Ceftriaxone 1 gm IM or IV x days Doxycyline 100 mg BID x 28 days Tetracycline 500 mg QID x 28 days Treatment in Pregnancy Primary, Secondary, and Early Latent Late latent and Latent of unknown duration Recommended Regime 2.4 million units IM x million units, administered as doses of 2.4 million units IM each at one week intervals x 3 weeks. Alternative Regimen None. Desensitize and treat. None. Desensitize and treat. Some evidence suggests that additional therapy can be beneficial for pregnant women in some settings (e.g., a second dose of benzathine penicillin 2.4 million units IM administered 1 week after the initial dose for women who have primary, secondary, or early latent syphilis) Jarisch-Herzheimer(J-H) Reaction Treatment of early syphilis may trigger the J-H reaction Acute febrile reaction with myalgias and headache within 24 hrs of treatment. May induce premature labor and fetal distress in pregnant women. Response to Therapy by Stage * Primary, Secondary Resolution of symptoms By 6-12 months- Fall in RPR titer by 2 titers * Early Latent, Late Latent If RPR titer </= 1:32 - Fall in RPR titer by 2 titers within months??? HIV-infected Patients *Test persons with syphilis for HIV 4

5 1:128 1: 64 1: 32 1: 16 1: 8 1: 4 SEROFAST RPR 1: 2 1: 1 Approach to Inadequate Serologic Response to Treatment Evaluate for possible re-infection Re-screen for HIV Consider suboptimal treatment Incorrect staging of infection Non-compliance with oral therapy Rule out Neurosyphilis (CSF exam) Re-treat with Bicillin 2.4 mu IM x 3 Treatment 3 mo. 6 mo. 9 mo. 12 mo. 1.5 yrs Indications for CSF exam Neurologic or Ophthalmic signs/symptoms Inadequate Serologic Response to Treatment Treatment failure without evidence of reinfection Latent syphilis -Although associated with clinical and CSF abnormalities c/w neurosyphilis - no data that CSF exam improved outcomes Consider - HIV+ and CD4 count < 200 Follow up and partner management Test persons with syphilis for HIV. Monitor RPR/VDRL tests 3-6 months based on risk factors. Contact, treat, and evaluate all sexual partners. Increases the number of persons with STIs to access treatment Prevents reinfections Interferes with transmission networks Local Health Department partner notification 2010 CDC STD Treatment Guidelines is a consequence of untreated or inadequately treated maternal syphilis. Prevention is feasible! Prevention, early diagnosis and treatment will prevent fetal and newborn infections. Transmission Rates of Untreated in Pregnancy Primary/secondary syphilis: % Early latent: 40% Late latent: 10% Tertiary disease: 10% Doroshenko, A., Sherrard, J., Pollard, A., in pregnancy and the neonatal period, International Journal of STD & AIDS, 2006; 17: Norwitz, E., in pregnancy, UpToDate retrieved 10/8/2013 from 5

6 Outcomes for Inadequate treatment Spontaneous miscarriage Stillbirth or fetal demise Premature labor and/or fetal distress Intrauterine growth restriction/low birth weight Congenital anomalies Early and late congenital stigmata in infants and children Neonatal death Clinical Manifestations of Early Snuffles Newborn with congenital syphilis. Desquamating rash Centers for Disease Control and Prevention Clinical Manifestations of Early Mucous patches Perforated palate Clinical Manifestations of Late Interstitial keratitis Hutchinson s teeth Eight nerve deafness Severely affected new born Plantar rash CDC, Red Book online image library Cutaneous syphilis Hutchinson s triad Clinical Manifestations of Late Clutton s joints Saber shins Clinical Guidelines Rhagades Frontal Bossing & Saddle nose Prevention/Partnership Management of in Clinical Practice 6

7 Thank you! Diana Torres-Burgos, MD, MPH Gerard Castaneda, BSN Alana Thomas, BS 7