Jayne Howard Clinical Coordinator HIV Ambulatory Care The Alfred SYPHILIS Jayne Howard Clinical Coordinator HIV Ambulatory Care The Alfred

Current situation / epidemic 1st quarter 199 cases of syphilis total, of which 102 were infectious syphilis - 98 were male, 89 (90%) indicated a male partner - among males reporting male partner, 85% reported from casual partner, 10% from a regular partner 2nd quarter 97 Source: Victorian Infectious Diseases Bulletin, DHS, June 2007.

Syphilis serology - Alfred Number of tests Courtesy Jenny (micro) and Denis Spelman.

Syphilis serology - Alfred Number of positives Courtesy Denis Spelman and VIDRL. *2007 to end July

A bacteria A member of the spirochete family Treponema Pallidum www.cdc.gov/phil/home.asp

Transmission Direct contact with infectious lesions of skin and mucous membranes Most commonly occurs during sexual activity Unprotected vaginal, anal or oral intercourse Rarely occurs during non sexual activity Blood transfusions Vertical transmission from mother to child during pregnancy Direct contact with an infectious lesion

Clinical stages of syphilis Primary Syphilis Chancre (sore) develops between 10-90 days after exposure (3 weeks) at the site of infection Most are painless Can often go undetected Usually heals within few weeks(3-6 weeks) Occasionally more than 1 sore may develop (HIV +ve individuals) Lymphadenopathy (swollen glands) Infectious period The stages of syphilis can produce symptoms or be asymptomatic. These stages can often overlap. Chancre can be found in or around the vagina, the glans penis, tongue, lips or fingers Fairfield Hospital and MSHC Photo Collection.

Secondary syphilis Rash Infection spreads through the blood and lymph system Usually between 2-6 week weeks after the chancre Common symptoms include- Fever and a rash Rash dark pink or copper coloured palms of hands Soles of the feet Abdomen Also lymphadenopathy, headache, malaise, anorexia Lesions in mucous membranes e.g. mouth,vagina snail track ulcers and condyloma lata Chancre may still be present

Secondary syphilis Less common symptoms include- Hair loss (alopecia) with a moth eaten appearance Hepatitis, GI ulceration Arthritis and joint problems Renal symptoms Neurologic abnormalities, headaches,memory loss (common in HIV+ve individuals) Eye and ear abnormalities Symptoms usually resolve around 3-12 weeks 25% of symptoms will recur in the 1st year (some up to 4 years) Infectious period

Secondary syphilis Fairfield Photo Collection, Up to Date, MSHC collection

Latent and Tertiary Syphilis Asymptomatic infection, no clinical signs of illness with positive serology (blood tests) Divided into- Early latent: Within the first 2 years from transmission Based on possibility of relapses, potentially infectious Late Latent: Greater than 2 years duration (US Public Health Service, CDC: > 1 year) Non infectious period, however transmission from mother to child can occur up to 4 years Tertiary Non infectious period. 2-30 years 1/3 patients will develop cardiovascular involvement, neurosyphilis, gummatous syphilis Untreated syphilis – 10% developed cardiovascular syphilis, 16% gummatous syphilis, 6.5% symptomatic neurosyphilis.

Clinical stages of syphilis Acquisition (~30%) 1o 2o 2o 3o 2 years 1 to 30 years: If untreated occurs in 40%, 25% clinically recognisable Incubation period 10-90 days (average 21 days) Weeks to few months Episodes may recur (occurs in 25%) Early syphilis (infectious) Late syphilis (non-infectious)

Syphilis and HIV Similar mode of transmission Often more than 1 chancre (up to 70%) May be larger and deeper HIV +ve individuals may present with both primary and secondary lesions (approx 25%) Transient increase in HIV viral load and decrease in CD4 count Resolves after the infection is treated Neurological symptoms are more common in the early stages of syphilis in HIV+ve individuals Zetola and Klausner. Syphilis and HIV Infection: An Update. CID 2007;44:1222-1228.

Syphilis and HIV Presence of one is risk factor for acquiring the other Presence of one increases the risk of transmission of the other All patients with syphilis should have a HIV test All patients with HIV infection should have syphilis testing- upon entry to care / diagnosis annually more often if risk factors

STIGMA GUIDELINES NSW,2005

Diagnosis and Testing Syphilis is known as the “Great Mimicker” Good sexual history and examination Identification of the bacteria (treponeme) from infectious lesion(ability to recognize from other spirochetes) Most cases rely on specific blood tests Serological testing VDRL=Venereal Disease Research Laboratory RPR=Rapid Plasma Reagin Beware of false positive results from other illness +ve in 75% primary 100% secondary

Diagnosis and Testing Specific treponemal tests FTA Antibody-Fluorescent treponemal antibody absorption TPHA test- Treponemal pallidum haemagglutination assay TPPA test- Treponemal pallidum particle agglutination assay Treponemal 1gG EIA- Recombinant based IgG & IgM EIA Beware of false positive results Treponemal tests do not differentiate between other treponeme species Neurosyphilis testing includes- Positive serology (blood tests) Clinical neurological symptoms (headache, confusion, memory loss) +/- findings in the cerebrospinal fluid (CSF) following lumbar puncture Decisions to perform a lumbar puncture may vary between specialists

Treatment recommendations – Early syphilis (Primary, Secondary, Early Latent) Sexual Health Guidelines – Royal Australasian College Physicians, Sexual Health Chapter, 2004 Therapeutic Guidelines, 2006 MSHC Treatment Guidelines, 2005

Treatment recommendations – Late syphilis (syphilis > 2 years or unknown duration) Sexual Health Guidelines – Royal Australasian College Physicians, Sexual Health Chapter, 2004 Therapeutic Guidelines, 2006 MSHC Treatment Guidelines, 2005

Treatment recommendations – Neurosyphilis Sexual Health Guidelines – Royal Australasian College Physicians, Sexual Health Chapter, 2004 Therapeutic Guidelines, 2006 MSHC Treatment Guidelines, 2005 “Seek Specialist Advice”

Penicillin treatment issues Penicillin is the treatment of choice Jarisch-Herxheimer reaction An acute reaction to penicillin treatment (not an allergy ) fever, headache, myalgia and other symptoms Usually occurs within 24 hours (6-12 hours) of therapy for syphilis Resolves after 24 hours Prednisolone may be used to reduce the likelihood of a reaction Penicillin allergy A potential risk Desensitization to penicillin can be undertaken CAUTION

Clinical follow-up All patients should return to the clinic at 3, 6 and 12 months. Up to 24 months for HIV+ve individuals Repeat blood tests and a clinical examination will be performed RPR should drop 4 fold by 6 months(Test of cure) Will become negative in approx 70% primary 55% secondary Re-treatment may be necessary (re-infection must be excluded) Health education and safe sex counselling Neurosyphilis Seek specialist advice CSF abnormalities may persist for longer in HIV+ individuals

Management of contacts Syphilis is a notifiable infection Contact tracing (partner notification) should be undertaken- Notify all sexual contacts for the past 3 months for patients with primary syphilis Patients with secondary syphilis should notify all contacts within the last 2 years Treatment of contacts Treat all sexual contacts of patients with primary and secondary syphilis (infectious period) even if the blood test is negative Sexual contacts greater than 12 months ago require treatment if their blood test is positive for syphilis Health education and safe sex counselling

Case 1 45yo MSM HIV June 2006 CD4 495, 24%. HIV VL 1600 Feb 2007, visited his GP for HIV monitoring and sexual health screen No clinical signs of illness Syphilis blood tests positive,EIA +, RPR 1024 Last recorded syphilis test was neg, June 06

Case 1 Single dose of benzathine penicillin was given intramuscular (IM) Repeat blood tests were performed at 3,6 months (test of cure) May 07, RPR 16 August 07, RPR 16 Treatment successful to date..

Case 2 50 yo train driver, MSM October 2006 patient referred to Alfred HIV diagnosed Oct 05 CD4 count 510, 25%. HIV VL >100,000 Syphilis testing performed, EIA +, RPR 64 No clinical signs or symptoms Treated with a single dose of benzathine penicillin IM Lost to follow up October 2006 patient referred to Alfred 12 month history multiple non-tender genital ulcers 4 month history of bilateral hearing impairment 4 week history of mouth ulcers S.J.Aitchison, K.M. Watson, A.M. Mijch. IAS Poster

Case 2 Syphilis testing repeated EIA +, RPR 512 Lumbar puncture was performed CSF Syphilis serology was positive Swabs from penile and oral lesions Negative Treated with intravenous (iv) benzylpenicillin and oral prednisolone Following treatment Hearing improved Ulcers healing Unfortunately was lost to follow up. Unable to perform test of cure S.J.Aitchison, K.M. Watson, A.M. Mijch. IAS Poster

Conclusion Alternate treatments Azithromycin Ceftriaxone Penicillin best treatment no resistance allergy Alternate treatments Azithromycin Ceftriaxone resistance HIV and syphilis Both conditions increasing in incidence Often occur together Variety of clinical presentations In general diagnosis and treatment similar as in HIV-uninfected patients Some studies have shown treatment failures are common in HIV and syphilis so treat with caution and close follow up

Acknowledgements Further reading: Dr Jonathan Darby, Infectious Diseases Registrar at The Alfred HIV Data Team at The Alfred Further reading: Sexual Health Medicine, 2005 Australasian Contact Tracing Manual 3rd Ed, 2006 National Management Guidelines for Sexually Transmissible Infections, 2002