Objectives. Pre Exposure Vaccines. Disclosure. The Five P s 11/2/2016

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1 Alice C Thornton, MD Kentucky AIDS Education Training Center KAPA 2016 Fall CME Symposium November 4, 2016 Disclosure No Commercial Grant: HRSA, HIV AIDS Bureau (Ryan White Part C, D) Kentucky Cabinet for Health and Family Service, HIV AIDS Branch (Care Coordinator Program RW Part B) Vanderbilt University School of Medicine, Southeast AIDS Education and Training Center (Local Performance Site: Kentucky AIDS Education Center) Objectives Discuss current STI treatments that pertain to adults, inclusive of updates to epidemiology, diagnosis, treatment, and management for STIs Discuss screening and prevention issues relevant to special populations Discuss changes in the partner notification and treatment process as they pertain to STD cases The Five P s Partners Men, women, both? How many in 2 12mo Partners having sex with someone else Practices Vaginal/Anal/Oral Condoms with whom? Prevention of Pregnancy Protection from STDs Not P but important Drug use (IVD, etc) Money or drugs for sex Is there anything else I need to know? Pre Exposure Vaccines Human papillomavirus (HPV) Females up to 26 yrs Males up to 21 yrs HIV and MSM up to 26 yrs Hepatitis A /Hepatitis B MSM, IDU, persons with chronic liver disease, HIV infected Hepatitis B All unvaccinated, uninfected persons 1

2 Promote Condom Use In heterosexual HIV serodiscordant couples in which condoms were consistently used, HIVnegative partners were 80% less likely to become infected Consistent condom use reduces the risk for STDs, including chlamydia, gonorrhea, and trichomoniasis Condom use reduces the risk for HPV, genital herpes, syphilis, and chancroid Weller S, Davis K. Condom effectiveness in reducing heterosexual HIV transmission. Cochrane Database Syst Rev (1):CD std guidelines peer reviewers pdf Other Prevention Methods Abstinence/Reduction of number of sex parnters Male Condoms Female Condoms Cervical Diaphragms Topical Microbicides/Spermicides Male Circumcision Emergency Contraception PEP for HIV/STD Treatment of HIV PREP for HIV Retesting after treatment to Detect Repeat Infection PARTNER STUDY(Partners of People on ART): 75 Clinical Sites in 14 European Countries (9/2010 5/2014) Prospective, observational study 1166 HIV serodiscordant couples condom less sex HIV RNA <200copies/ml Within couple transmission was ZERO Condom 108 MSM and 21 heterosexuals 11 HIV ( ) partners became HIV +: 10 MSM, 1 heterosexual NO phylogenetically linked transmissions Within couple transmission was Zero. Rodger, JAMA 2016,316: STD Screening Annually C. trachomatis/n.gonorrhea All sexually active females aged <25 years Women <35 and men <30 years in correctional facilities MSM HIV all adolescents MSM and who themselves or whose sex partners have had more than one sex partner since most recent HIV test Syphilis MSM Hepatitis B MSM HepB sag Gonorrhea Treatment: A Shrinking Arsenal Epidemiology, content/uploads/2013/05/superbugs.jpg 2

3 Location of Participating Sentinel Sites and Regional Laboratories, Gonococcal Isolate Surveillance Project (GISP), United States, 2013 DRUG Resistant Neisseria Gonorrhoeae NOTE: Austin is a regional laboratory only. report 2013/pdf/ar threats pdf#page=55 Fluoroquinolone Resistance <1% in 1990; 0.4% in 2000 Fluoroquinolones not recommended in Asia/Pacific Island acquisition 2.2% in 2002: rec. extended to Calif. 4.1% in % in 2004: no use in MSM 9.4% in 2005; 13.3% in % in 2007 Honolulu sample Declining Effectiveness of Cephalosporins Gonorrhea has eventually grown resistant to every drug used Sulfonamides, Penicillin, Tetracycline, Fluoroquinlones 2007, Fluoroquinlones no longer recommended Cephalosporins only class left Now CDC s Gonococcal Isolate Surveillance Project (GISP) suggests oral cefixime is becoming less effective to treat Gonorrhea Neisseria gonorrhoeae Percentage of Isolates, with Penicillin, Tetracycline, and/or Ciprofloxacin Resistance, Gonococcal Isolate Surveillance Project (GISP), 2013 Neisseria gonorrhoeae Percentage of Isolates with Elevated Ceftriaxone Minimum Inhibitory Concentrations (MICs) ( μg/ml), Gonococcal Isolate Surveillance Project (GISP), NOTE: PenR=penicillinase producing Neisseria gonorrhoeae and chromosomally mediated penicillinresistant N. gonorrhoeae; TetR=chromosomally and plasmid mediated tetracycline resistant N. gonorrhoeae; and QRNG=quinolone resistant N. gonorrhoeae. 3

4 Neisseria gonorrhoeae Percentage of Isolates with Elevated Cefixime Minimum Inhibitory Concentrations (MICs) ( 0.25 μg/ml), Gonococcal Isolate Surveillance Project (GISP), Cefixime The percentage of isolates with elevated cefixime MICs increased from 0.1% in 2006 to 1.7% in 2011, a 17 fold increase. No documented treatment failures in the US yet International reports of cefixime treatment failures(asia, Europe, South Africa and Canada) Concern: Gonorrhea s history of evolving antibiotic resistant increases the likelihood of cephalosporin resistance *Isolates not tested for cefixime susceptibility in 2007 and Robert D. Kirkcaldy, MD, MPH, Aug 13, Uncomplicated Gonorrhea ( Cervix, Urethra and Rectum) STD Guidelines Recommended Alternative Ceftriaxone 250mg IM plus Azithromycin 1 gram If azithromycin allergy: Doxycycline 100mg bid for 7 days Cefixime 400mg plus Azithromycin 1gram Ceftriaxone Single dose of 250mg: sustained, high bactericidal levels Cures 99.2% of uncomplicated urogenital and anal/rectal and 98.9% of pharyngeal infections 250mg over 125mg dose Wide geographic distribution of isolates with decreased susceptibility to cephalosporins in vitro Reports of ceftriaxone treatment failures Improved efficacy of ceftriaxone 250mg in pharyngeal infection Simple/consistent recommendation regardless of anatomic site MMWR/Aug 10, 2012/ vol. 61. no 31. MMWR, Sexually Transmitted Disease Treatment Guidelines, 2010 Two New Promising Treatment Regimens for Gonorrhea (NCT ) Gentamycin 240mg IM +Azithromycin 2gm % effective 28% nausea, 19% diarrhea, 7% abdominal discomfort/pain or vomiting R Kirkcaldy, ISSTDR, July 2013 Gemifloxacin 320mg + Azithromycin 2gm % effective 37% nausea, 23% diarrhea, 11% abdominal discomfort/pain When Treatment Alternatives are Used Cephalosporin allergic Consider Azithromycin 2 g If use alternatives including cefixpime 1 week test of cure Source: CDC/NCHSTP/Division of STD Prevention, STD Clinical Slides 4

5 Chlamydia Chlamydia Rates by Reported Cases by Region, United States, Chlamydia Rates of Reported Cases by Age and Sex, United States, 2013 Treatment: Uncomplicated Genital Chlamydial Infections Recommended regimens Azithromycin 1 g orally in a single dose, Doxycycline 100 mg orally twice daily for 7 days Alternative regimens Erythromycin base 500 mg orally 4 times a day for 7 days, Erythromycin ethylsuccinate 800 mg orally 4 times a day for 7 days, Ofloxacin 300 mg orally twice a day for 7 days Levofloxacin 500 mg orally once a day for 7 days Expedited Partner Therapy (EPT) Unless prohibited by law, offer EPT to heterosexual patients with gonorrhea or chlamydial infection when the provider cannot y assure that all sex partners from the prior 60 days will be treated Sex partners Evaluated, tested, and treated if sexual contact with the patient 60 days prior Most recent sex partner should be evaluated and treated even if the time of the last sexual contact was >60 days. to use/chlamydia.htm; MMWR, Sexually Transmitted Disease Treatment Guidelines, std guidelines peer reviewers pdf 5

6 Partner Delivered Partner Therapy (PDPT) Emphasize importance of medical evaluations for any symptoms of STD Some states prohibit PDPTwww.cdc.gov/std/ept Gonorrhea, chlamydia and trichomoniasis NOT Syphilis Can be considered in heterosexual patients PDPT is not routinely recommended for MSM because of a high risk for coexisting infections, especially HIV MMWR, Sexually Transmitted Disease Treatment Guidelines, Trichomonas Epidemiology, Trichomoniasis Treatment Recommended Metronidazole 2g orally in a single dose or Tinidazole 2 g orally in a single dose Alternative Metronidazole 500mg oraly bid for 7 days Recent trial demonstrated that a single dose of metronidazole in women with HIV and trich was not as effective as bid for 7 days stuffed plush toy.html Kissinger P, et al.. J Acquir Immune Defic Syndr 2010;55:

7 HPV 101 Cutaneous or mucosa Mucosa: Anogenital epithelium (cervix, vagina, vulva, rectum, urethra, penis and anus) Low Risk Types Benign associated with genital warts (6, 11,40 etc.) High Risk Types Associated with cervical, vulvar, penile and anal cancer(16, 18, 31, etc) 16 and 18 are associated with 99% of cervical cancers, LSIL,HSIL and abnormal Pap tests MMWR, (No. RR 2) HPV associated cancers United States, Anatomic Area Average annual number of cases* Estimated + HPV attributable HPV 16/18 attributable Cervix 11,967 11,500 9,100 Vagina Vulva 3,136 1,600 1,400 Anus (F) 3,089 2,900 2,700 Oropharynx (F) 2,370 1,500 1,400 Total (Females) 21,291 18,000 15,000 Penis 1, Anus (M) 1,678 1,600 1,500 Oropharynx (M) 9,356 5,900 5,600 Total (Males) 12,080 7,900 7,400 * Defined by histology and anatomic site; Watson M et al. Cancer Data source: National Program of Cancer Registries and SEER, covering 100% coverage of US population. + Gillison ML, et al. Cancer Ref: Human Papillomavirus- Associated Cancers MMWR 2012;61(15): Clinical Manifestations and Sequelae In most cases, genital HPV infection is transient and has no clinical manifestations or sequelae. Clinical manifestations of genital HPV infection include Genital warts,* Cervical cellular abnormalities detected by Pap tests,* Some anogenital squamous cell cancers, Some oropharyngeal cancers, and Recurrent respiratory papillomatosis. *Two most common clinically significant manifestations of genital HPV infection Transmission Skin to skin contact Most HPV infections are asymptomatic and resolve without treatment 70% spontaneously clear within 1 st year 90% within 2 years No evidence that treatment prevents transmission Persistent infection with high risk types is risk for cervical cancer. HPV Vaccines: 3 Types Bivalent (Cervarix)(HPV2): HPV 16 and 18 asso cervical precancers. Quadrivalent (Gardasil)(HPV4): HPV 6, 11, 16, and 18 assoc. genital warts, cervical vulvar, vaginal and anal precancers Now Gardasil 9 Valent MMWR, (No. RR 2) 7

8 HPV Vaccine Administration HPV 2/4: females 11 12yrs. HPV4: males yrs. Can give at 9 10yrs Females yrs and Males yrs who have not had any or all the doses when younger MSM : through 26 yrs Immunocompromised: through 26 yrs Gardasil Quadrivalent HPV Vaccine Protects against 6,11,16, 18 (responsible for 70% of cervical cancer and 90% of genital warts) Made from non infectious HPV like particles (VLP) No thimersol or mercury MMWR 2007;56(No. RR 2) HPV vaccines: protection pre teens can grow into now for girls and boys Gardasil is also licensed, safe, and effective for males ages 9 through 26 years to prevent genital warts, and anal cancer. Both females and males, 3 doses (shots) are needed vac/hpv/vac faqs.htm. hpv preteens.doc Human Papillomavirus Vaccine Schedule Females 9 through 26 years of age Routine schedule is 0, 2, and 6 months Minimum intervals: 4 weeks between doses 1 and 2 12 weeks between doses 2 and 3 Source: MMWR 2007;56(No. RR 2) HPV Vaccination ACIP (Advisory Committee on Immunization Practices) Recommendations Routine vaccination of females years of age with three doses of quadrivalent HPV vaccine The vaccination series can be started as young as 9 years of age at the clinician s discretion HPV Vaccination ACIP Recommendations Vaccination is recommended for females years of age not previously vaccinated Vaccine should be administered before onset of sexual activity, if possible Females who are sexually active should be vaccinated Source: MMWR 2007;56(No. RR 2) Source: MMWR 2007;56(No. RR 2) 8

9 HPV Vaccine Special Situations Females 26 years of age or younger with equivocal or abnormal Pap test, positive HPV DNA, or genital warts may be vaccinated Vaccine will have no effect on existing disease or infection HSV Source: MMWR 2007;56(No. RR 2) Characteristics of HSV Genital Lesions Early lesions are vesicular Blisters rupture leaving painful shallow ulcers Primary HSV usually presents with bilateral lesions, while reactivation disease presents as unilateral and localized lesions Lesions then crust and may have secondary bacterial overgrowth Presentation Asymptomatic in many First outbreak: 2 weeks after exposure Flu like symptoms Can have fever and lymphadenopathy First outbreak: expect 5 6 reoccurrences within the first year 9

10 Diagnosis of HSV Clinical Diagnosis Should be confirmed when possible Sensitivity declines as lesions heal Standard: culture with typing or PCR Recurrence 1 st year: HSV 1 (60%) /HSV 2 (90%) With time, reductions in recurrences Antibody serologic tests Not indicated in general population Type specific glycoprotein for G1 and G2 (HerpeSelect) Treatment of HSV Primary: Treat all Episodic Suppressive >6 episodes/yr or distress Decreases recurrences by >75% Decreases viral shedding Nucleoside Analogs Acyclovir CDC does NOT recommend topical Famciclovir Valacyclovir Treatment First Episode Recommended Regimens* Acyclovir 400 mg orally three times a day for 7 10 days Acyclovir 200 mg orally five times a day for 7 10 days Famciclovir 250 mg orally three times a day for 7 10 days Valacyclovir 1 g orally twice a day for 7 10 days *Treatment can be extended if healing is incomplete after 10 days of therapy Workowski, 2010 Treatment Recurrence Recurrence: HSV 2 > HSV 1 Asymptomatic shedding common (HSV 2) 2 treatment strategies Suppressive Episodic, symptomatic If disseminated and/or severe: IV acyclovir 5 10 mg/kg IV every 8 hours for 2 7 days or until clinical improvement is observed, followed by oral antiviral therapy to complete at least 10 days of total therapy Treatment Suppressive Recommended Regimens* Acyclovir 400 mg orally twice a day Famiciclovir 250 mg orally twice a day Valacyclovir 500 mg orally once a day* Valacyclovir 1 g orally once a day * Valacyclovir 500 mg once a day might be less effective than other valacyclovir or acyclovir dosing regimens in patients who have very frequent recurrences (i.e., 10 episodes per year). Workowski, 2010 Workowski,

11 Treatment Episodic, Recommended Regimens Symptomatic Acyclovir 400 mg orally three times a day for 5 days Acyclovir 800 mg orally twice a day for 5 days Acyclovir 800 mg orally three times a day for 2 days Famciclovir 125 mg orally twice daily for 5 days Famciclovir 1000 mg orally twice daily for 1 day Famciclovir 500 mg once, followed by 250 mg twice daily for 2 days Valacyclovir 500 mg orally twice a day for 3 days Valacyclovir 1 g orally once a day for 5 days Special Scenario The Pregnant Female HSV can be devastating to newborn Highest risk transmission if primary infection during pregnancy Mom may not realized infected If lesions seen, indication for c section (primary or reactivation) Workowski, 2010 Syphilis Primary and Secondary Syphilis Reported Cases by Sex and Sexual Behavior, 33 Areas*, *32 states and Washington, DC reported sex of partner data for 70% of cases of P&S syphilis for each year during MSM=men who have sex with men; MSW=men who have sex with women only. warns gay men of syphilis with horror film parody.html Primary and Secondary Syphilis Rates of Reported Cases by Sex and Male to Female Rate Ratios, United States, Primary and Secondary Syphilis Rates of Reported Cases by Age and Sex, United States,

12 Primary and Secondary Syphilis Reported Cases* by Stage, Sex, and Sexual Behavior, United States, 2013 Primary and Secondary Syphilis Reported Cases* by Sex, Sexual Behavior, and Race/Ethnicity, United States, 2013 *Of the reported male cases of primary and secondary syphilis, 16.9% were missing sex of sex partner information. MSW=men who have sex with women only; MSM=men who have sex with men. *Of the reported male cases of primary and secondary syphilis, 16.9% were missing sex of sex partner information; 2.9% of reported male cases with sex of sex partner data were missing race/ethnicity data. MSW=men who have sex with women only; MSM=men who have sex with men. Epidemiology Epidemiology Syphilis Definition Sexually acquired infection Etiologic agent: Treponema pallidum Disease progresses in stages May become chronic without treatment Transmission Sexual and vertical Most contagious to sex partners during the primary and secondary stages Epidemiology The rate of P&S Syphilis decreased during the 1990s to 2000 Rate declined by 89.7% In 2000, the rate was lowest since 1941 In 2012, rate increased (5.0 cases/100,000) Men s rates: 8. 1 cases (2001 ) to 9.3 cases (2012) per 100,000 Women s rates: 0.8 cases (2004) to 1.5 cases (2008 )per 100,000 In 2005, CDC requested reporting of the sex of sex partners for person with syphilis P&S syphilis cases attributable to MSM increased from 7% in 2000 to 64% in MSM accounted for 75% of P&S syphilis cases in 2005 Pathology Penetration: T. pallidum enters the body via skin and mucous membranes through abrasions during sexual contact Transmitted transplacentally from mother to fetus Dissemination: Via the circulatory system ( lymphatic system and regional lymph nodes) throughout body Invasion of the central nervous system (CNS) can occur during any stage of syphilis 12

13 Treponema pallidum Pathogenesis Pathogenesis Treponema pallidum on Darkfield Microscopy Electron photomicrograph, 36,000 x. Source: CDC/NCHSTP/Division of STD Prevention, STD Clinical Slides 73 Source: CDC/NCHSTP/Division of STD Prevention, STD Clinical Slides 74 Diagnosis of Treponema pallidum Cannot be cultured: relies on serology Ideally early syphilis diagnosis Direct visualization of spirochete dark field Fluorescent antibodies DFA TP PCR not readily available clinically Most persons present without signs/symptoms Healed early lesions/inapparent lesions/latent infection Serologic Tests for Syphilis Two types Treponemal (qualitative) Nontreponemal (qualitative and quantitative) The use of only one type of serologic test is insufficient for diagnosis Nontreponemal Tests Principles Measure antibody directed against a cardiolipin lecithincholesterol antigen Not specific for T. pallidum Titers usually correlate with disease activity and results are reported quantitatively May be reactive for life, referred to as serofast Nontreponemal tests: VDRL (Veneral Disease Research Laboratory), RPR (Rapid Plasma Reagin), TRUST (Toluidine red unheated serum test) Nontreponemal Serologic Tests Advantages Rapid and inexpensive Easy to perform and can be done in clinic or office Quantitative Used to follow response to therapy Can be used to evaluate possible reinfection Disadvantages May be insensitive in certain stages False positive reactions may occur Prozone effect may cause a false negative reaction (rare) 13

14 Treponemal Serologic Tests Principles Measure antibody directed against T. pallidum antigens Qualitative Usually reactive for life Titers should not be used to assess treatment response Treponemal tests include TP PA, FTA ABS, EIA, and CIA Trep0nemal TP PA (T. pallidum particle agglutination) FTA ABS (Fluorescent Treponemal Antibody Absorbed) MHA TP (Microhemagglutination assay for T.pallidum) EIA (Enzyme immunoassays) Trep Check Trep Sure CLIA (Chemiluminescence) Liaison/Architect Microbead immunoassay Bioplex Qualitative Confirmatory Which Algorithm? Webinar Slides.pdf Presenters: Hoover and Park Hoover and Parks Hoover and Parks 14

15 Sensitivity of Tests in Untreated Syphilis Stage of Disease (Percent Positive [Range]) Test Primary Secondary Latent Tertiary VDRL 78 (74 87) (88 100) 71 (37 94) RPR 86 (77 99) (95 100) 73 FTA-ABS* 84 (70 100) Treponemal Agglutination* 76 (69 90) (97 100) 94 EIA *FTA-ABS and TP-PA are generally considered equally sensitive in the primary stage of disease. Key Points: Syphilis Screening Some clinical laboratories: reverse screening algorithm treponemal test (EIA) then reactive samples confirmed by rapid plasma reagin (RPR) Reverse Screening Algorithm Automated, generates an objective interpretation of results and may facilitate the identification of patients with late/latent or early syphilis May identify a higher number of reactive patients Samples with discordant Treponemal reactive, RPRnonreactive results should be tested by a second treponemal assay (TP PA) Stephen Nelson 41 yo African from South Africa DX in 2001: RPR was 1:8 2/21/2001 with negative TPPA Here for follow up, new partner (had not had sex for 7years). Female partner visiting from Africa Penile lesion found not painful RPR 1:64 Thoughts? Binnicker, CurrOpin Infect Dis 2012,25:79 85 Primary Syphilis Clinical Manifestations Primary lesion or "chancre" develops at the site of inoculation. Chancre Progresses from macule to papule to ulcer; Typically painless, indurated, and has a clean base; Highly infectious Heals spontaneously within 3 to 6 weeks; and Multiple lesions can occur Regional lymphadenopathy: classically rubbery, painless, bilateral Serologic tests for syphilis may not be positive during early primary syphilis. David Smith 26 yo m, comes in July 2013 HIV+ since 2008 On Atripla, He is an RN at a rural hospital Here for HIV f/u but has concerns 1 week: sore throat, sore on mouth/lip, more tired than usual Last CD4: 205, 35% and viral load<20 In a monogamous relationship with male partner for 5 years ½ pck cig/day. No alcohol nor drugs Allergies: pcn rash 89 15

16 David, continued Pharynx cobblestone Lower lip: apthous ulcer No adenopathy Scrotum 3 hypopigmented areas He denies any new partners His partner in the room avoids looking you in the eye and does not deny new partners His RPR is 1:64 (Always negative ) Secondary Syphilis Clinical Manifestations Secondary lesions occur several weeks after the primary chancre appears; and may persist for weeks to months. Primary and secondary stages may overlap Mucocutaneous lesions most common Clinical Manifestations: Rash (75% 100%) Lymphadenopathy (50% 86%) Malaise Mucous patches (6% 30%) Condylomata lata (10% 20%) Alopecia (5%) Liver and kidney involvement can occur Splenomegaly is occasionally present Serologic tests are usually highest in titer during this stage. 92 Jack Andrews 28 yo wm Here for f/u on July 2013 Dx in 2007 Atripla ROS tired for 2 weeks, insominia Has been working overtime No substance use CD % and viral load <20 July RPR: NR July 23, 2013 RPR : 1:64 Finally admits: sexual enounter outside of the relationship Previous syphilis but RPR has been negative since ~ 2010 Became ill with pcn injection felt faint and his bp dropped a little ( 134/82 then 123/77) Jarisch Herxheimer Reaction Management Self limited reaction to antitreponemal therapy Fever, malaise, nausea/vomiting; may be associated with chills and exacerbation of secondary rash, tachycardia, hyperventilation, vasodilation flushing, mild hypotension Occurs within 24 hours after therapy Not an allergic reaction to penicillin More frequent after treatment with penicillin More common with secondary but can occur at any stage Can last 12 to 24 hours and has been correlated with the release of heat stable protein from the spirochetes Antipyretics can be used to manage symptoms, but don t prevent Warn pregnant women that the reaction may precipitate early labor, and to call obstetrician if problems develop 94 Therapy for Primary, Secondary, and Early Latent Syphilis Benzathine penicillin G 2.4 million units intramuscularly in a single dose (Bicillin L A ) If penicillin allergic Doxycycline 100 mg orally twice daily for 14 days, or Tetracycline 500 mg orally 4 times daily for 14 days Source: Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines MMWR 2010;59 (No. RR-12). Management 95 Primary and Secondary Syphilis, HIV+ Guidelines, 2006 Guidelines, 2010 Some specialists recommend additional treatments (e.g., benzathine penicillin G administered at 1 week intervals for 3 weeks, as recommended for late syphilis) in addition to benzathine penicillin G 2.4 million units IM. additional doses of benzathine penicilling, amoxicilin or other antibiotics in early syphilis do not result in enhanced efficacy, regardless of HIV status 16

17 Debbie Thomas 43 yo wf 6 7 mo ago, black spot with bright lights around it in r eye, then blurred vision and left eye blurred 1 month later Saw ophthalmologist, who did hiv and syphilis test now seeing UK ophtalm: Uveitis ROS: rash on both arms noticed 2 months ago,; husband had rash similar last year and it resolved on its own PMH: eczema dx after rash on palms with skin desquamation (2010). Resolved with steroids Married 18 yrs but separated Both have had multiple sexual partners Eczema dx after she got back with her husband Wears a wig, had patches of baldness so she shaved her head and bought a wig. She also has her eyebrows penciled in, does have macular, papular rash arms, legs, back Shoddy lymph nodes : cervical inguinal and axillary Debbie Thomas HIV Elisa and WB + RPR 1:256 and + TPPA Serum glucose 115 CSF 54 nucleated cells, 84% lymph, 17 rbc VDRL + 1:2 Cbc and cmp normal Cd4 828 and 41% and viral load 562 Tsh 1,312 Debbie Thomas Secondary Syphilis Palmar/Plantar Rash Clinical Manifestations Source: Seattle STD/HIV Prevention Training Center at the University of Washington, UW HSCER Slide Bank Source: CDC/NCHSTP/Division of STD Prevention, STD Clinical Slides 100 Neurosyphilis Occurs when T. pallidum invades the central nevous system (CNS) May occur at any stage of syphilis Can be asymptomatic Clinical Manifestations Early neurosyphilis occurs a few months to a few years after infection Clinical manifestations can include acute syphilitic meningitis, meningovascular syphilis, and ocular involvement Neurologic involvement can occur decades after infection and is rarely seen Clinical manifestations can include general paresis, tabes dorsalis, and ocular involvement Ocular involvement can occur in early or late neurosyphilis. 101 CNS Disease Diagnostic Issues Diagnosis CNS disease can occur during any stage of syphilis. Conventional therapy is effective for the vast majority of immuno competent patients with asymptomatic CNS involvement in primary and secondary syphilis

18 Diagnosis Diagnosis Indications for CSF Examination Patients with syphilis who demonstrate any of the following criteria should have a prompt CSF evaluation: Neurologic or ophthalmic signs or symptoms Evidence of active tertiary syphilis (e.g., gummatous lesions) Treatment failure HIV infection with a CD4 count 350 and/or a nontreponemal serologic test titer of 1: Diagnosis of CNS Disease No test can be used alone to diagnose neurosyphilis. VDRL CSF: highly specific, but insensitive Diagnosis usually depends on the following factors: Reactive serologic test results Abnormalities of CSF cell count or protein A reactive VDRL CSF with or without clinical manifestations CSF leukocyte count usually is elevated (>5 WBCs/mm 3 ) in patients with neurosyphilis. The VDRL CSF is the standard serologic test for CSF, and when reactive in the absence of contamination of the CSF with blood, it is considered diagnostic of neurosyphilis. However, in early syphilis it can be of unknown prognostics significance. 104 Neurosyphilis Probable Any stage with a negative VDRL test in CSF and either 1.) a reactive treponemal serologic test for syphilis (e.g., FTA ABS, TP PA, EIA, CIA,) 2.) a reactive non treponemal serologic test for syphilis (VDRL, RPR, ) AND both the following: Elevated CSF protein or WBC in the absence of other known causes of these Abnormalities AND Clinical symptoms or signs consistent with neurosyphilis without other causes Confirmed Syphilis of any stage that meets the laboratory criteria for neurosyphilis CSF protein >50 mg/dl,> 5 white blood cells/cubic millimeter CSF; 4 in HIV positive individuals Neurosyphilis Infection of the central nervous system with T. pallidum Syphilitic meningitis, meningovascular syphilis, optical involvement (interstitial keratitis and uveitis) General Paresis including dementia Delusions, tabes dorsalis, change in mental function, mood changes, personality changes, etc. Tabes Dorsalis: demylination in the dorsal columns of the spinal cord Weakness, decreased reflexes, parasthesias, hypoesthesias, ataxia,personality changes, deafness, Laboratory criteria for diagnosis +VDRL CSF AND either 1.) +treponemal serologic test for syphilis (e.g., FTA ABS, TP PA, EIA, CIA, or equivalent serologic methods) 2.) + nontreponemal serologic test for syphilis (VDRL, RPR,) Therapy for Neurosyphilis Aqueous crystalline penicillin G million units per day, administered as 3 4 million units intravenously every 4 hours or continuous infusion for 10 to14 days intravenously Alternative regimen (if compliance can be ensured) Procaine penicillin 2.4 million units intramuscularly once daily PLUS Probenecid 500 mg orally 4 times a day, both for 10 to14 days JIM BOB Husband of Debbie 44 yo WM, IVDU Dx when wife was dx HIV She has also been dx with neurosyphilis He has a +RPR 1:256 He is asympotmatic Source: Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines MMWR 2010;59 (No. RR-12). 18

19 Clinical Manifestations Latent Syphilis Host suppresses infection, but no lesions are clinically apparent Only evidence is a positive serologic test May occur between primary and secondary stages, between secondary relapses, and after secondary stage Categories: Early latent: <1 year duration Late latent: 1 year duration Diagnosis of Latent Syphilis Early latent syphilis, if within the year preceding the evaluation Documented seroconversion or 4 fold increase in comparison with a serologic titer Unequivocal symptoms of primary or secondary syphilis reported by patient Contact to an infectious case of syphilis Only possible exposure occurred within past 12 months Latent syphilis of unknown duration should be managed clinically as if they have late latent syphilis. Public health laws require that all cases of syphilis be reported to the state/local health department. 109 Syphilis, Late Latent Clinical A subcategory of latent syphilis (a stage of infection caused by T. pallidum in which organisms persist in the body of the infected person without causing symptoms or signs) when initial infection has occurred >12 months previously. Probable No signs/symptoms of syphilis with one of the following: No past diagnosis of syphilis, AND a reactive nontreponemal test (e.g., VDRL, RPR,), AND a reactive treponemal test ( FTA ABS, TP PA, EIA,) Past titer 4 =fold higher than last test AND no sx in 12 mo Therapy for Late Latent Syphilis Management Benzathine penicillin G 7.2 million units total, administered as 3 doses of 2.4 million units intramuscularly each at 1 week intervals If penicillin allergic Doxycycline 100 mg orally twice daily for 28 days or Tetracycline 500 mg orally 4 times daily for 28 days Source: Centers for Disease Control and Prevention. Sexually transmitted pdfP diseases treatment guidelines MMWR 2010;59 (No. RR-12). 112 Therapy for Tertiary Syphilis Benzathine penicillin G 7.2 million units total, administered as 3 doses of 2.4 million units intramuscularly each at 1 week intervals If penicillin allergic Doxycycline 100 mg orally twice daily for 28 days or Tetracycline 500 mg orally 4 times daily for 28 days Follow Up Management Primary or secondary syphilis Reexamine at 6 and 12 months. Follow up titers should be compared to the maximum or baseline nontreponemal titer obtained on day of treatment. Latent syphilis Reexamine at 6, 12, and 24 months. HIV infected patients 3, 6, 9, 12 and 24 months for primary or secondary syphilis 6, 12, 18, and 24 months for latent syphilis Neurosyphilis Serologic testing as above Repeat CSF examination at 6 month intervals until normal Source: Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines MMWR 2010;59 (No. RR-12)

20 Therapy for Late Latent Syphilis Management Benzathine penicillin G 7.2 million units total, administered as 3 doses of 2.4 million units intramuscularly each at 1 week intervals If penicillin allergic Doxycycline 100 mg orally twice daily for 28 days or Tetracycline 500 mg orally 4 times daily for 28 days A PATHOLOGICAL MOCKING BIRD "Know syphilis in all its manifestations and relations," says Sir Wm. Osler, M.D., "and all other things clinical will be added unto you." He called "syphilis" the "Great Imitator," because, to use the words of Dr. Thomas Parran, Surgeon General of The U. S. Public Health Service, "in its late stages it simulates almost every disease known to man." Osler added, "Know syphilis and the whole of medicine is opened to you." Source: Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines MMWR 2010;59 (No. RR-12) syphilis/020134syphilis ch3.htm Things I ve Learned about Syphilis Always think of it Folks can get it through oral sexual activity Amazing folks who say they never have sex get it HA! Rash on trunk, palms, weight loss, lymphadenopathy, bump in LFTs, tiredness, weight loss People get it. AGAIN When folks have a positive RPR bring them back in: look in mouth, genitalia and between buttocks I look up the treatment EVERTYTIME References Workowski, KA and Berman S. Sexually Transmitted Diseases Treatment Guidelines, MMWR, 59:RR 12 MMWR, STD Treatment Guidelines, june