Compiled by Simon Wright NUM Sydney Sexual Health Centre The basic test for syphilis is an Elisa Antibody test which detects antibodies to syphilis. This is a very sensitive test Negative Elisa will indicate that the person has not been infected with syphilis up until three months ago (there is a window period similar to HIV window period) The presence of positive Elisa antibodies indicate that the patient has been infected with Syphilis The lab will automatically test all new positive Elisa antibody tests and TPPA, FTa antibody, and RPR test will be done Elisa Ab TPPA FTa Ab RPR Positive Positive Positive Negative Elisa Ab TPPA FTa Ab RPR Positive Positive Positive Positive Elisa Ab TPPA FTa Ab RPR Positive Negative Negative Negative Elisa Ab TPPA FTa Ab RPR Positive Positive Positive Negative An old infection that has been treated (proven record of treatment from notes or patient history) In the absence of any history of previous treatment or negative syphilis serology in the past two years a diagnosis of Late Latent Syphilis is made If there is a proven history of negative syphilis serology in the past 2 years a diagnosis of early latent syphilis is made Late Latent syphilis is treated currently with 3 shots of antibiotics over 3 weeks and no further follow-up is needed as the RPR is already negative As Syphilis infection is only infectious for the first 6 months, PN should go back as far as possible to ensure as many partners are aware and screened This will include all current partners who are long-term partners. A diagnosis of early latent syphilis can only be made with a Negative RPR and history of negative syphilis serology within the past two years. This will be treated with one shot of antibiotics and again if RPR is negative, no further follow-up is needed as the RPR is already negative PN should go back two years to ensure as many sexual partners are informed and are screened. There must be proven history of treatment for past syphilis infection. WARNING Re-infection of syphilis can not be ruled out unless regular Syphilis serology tests are done as re-infection will cause the RPR to become positive again with high titres but with time the titres will drop and RPR may go negative again even without further treatment. In a very sexually active person with many sexual partners and no history of resent negative syphilis serology, reinfection must be considered and such cases discussed with senior doctor Gay men and commercial sex workers are at risk of reinfection Syphilis Antibody TPPA RPR FTa Ab Positive Positive Positive (with titres) Positive These may be negative in a primary syphilis This would indicate resent infection of Syphilis especially if the RPR titres are high i.e. 1:38 The presents of any symptoms will determine the stage of infection: Ulcer or chancre present would possibly indicate Primary infection of Syphilis Presents of rash on trunk, hands or soles of feet might indicate secondary syphilis infection Primary Syphilis Infection Treated with one shot of antibiotics. PN would need to go back 3 months to ensure all sexual partners are advised to be screened. Patient should be reviewed by the doctor two weeks post treatment and further blood test done at one month and repeated monthly until sero-fast or Negative RPR Sero-Fast means that the RPR has not changed or increased over a three month period indicating that treatment has been successful What is the significance of an RPR that remains positive? If the RPR remains Positive (neat) this is as good as negative What are the titres and what are their significance? In the case of the RPR test for syphilis, the sample is tested neat (undiluted) if that is positive it is then diluted with a diluents of the same volume and if that is still positive it is said to be positive 1:2. That sample is then diluted again and if remains positive it is said to be positive 1:4 and so on so could be 1:8, 1:16, 1:32 and so on If 1:32 is still positive and it is diluted again and this time is negative, the result will be 1:32 (as 1:64 would mean the sample is too diluted to pick up and give a positive result It could be argued that a an RPR that is positive neat is the same as negative as one dilution is enough to produce a negative result. EXIT In the case of Syphilis, the titres that are expressed with the RPR result indicates the strength of the positive result. The blood is tested neat, if that is positive, it is diluted with a diluents of the same volume and retested, if that diluted sample is also neat, the result will be expressed as 1:2, That sample will then be diluted again and retested and if positive will be expressed as 1:4 and so on. Each time the sample is diluted again and remains positive it is expressed as 1:8, 1:16, 1:32 until the sample is diluted enough to not produce a positive result. So if at 1:32 is positive and at further dilution of 1:64 was negative, the result will be 1:32 as 1:64 was too diluted to give a positive result. If the sample is positive neat and with one dilution 1:2 is negative this indicates a very weak positive and could argued to be the same as negative, What are the tests for Syphilis? • Syphilis Antibody Elisa Assay • TPPA Treponema Palladium Particle Agglutination • (TPHA) Treponema Pallidum Haemagglutination Assay (no longer in use) • RPR Rapid Plasma Regain (often expressed as titres) • FTA Ab Fluorescent Treponemal Antibody Absorption Test TPPA & FTA Ab in the vast majority of patients infected and treated for Syphilis will remain positive for life, but a very small number of patients may lose these positive markers The Elisa Antibody test is very sensitive and will nearly always remain positive for life Primary Syphilis Signs & Symptom 1. Chancre, usually a solitary, painless, clean ulcer with an indurated base. 2. Regional lymphadenopathy, discrete, painless, rubbery Diagnosis 1. Dark ground microscopy x 3 to identify Trepnema pallidum spirochaetes 2. Serological tests for syphilis (STS). May be negative at this stage Treatment & Management 1. Benzathine penicillin 2.4 MU IM - single dose 2. Doxycycline P.O. 100 mg bd for 14 days (contraindicated in pregnancy) Procaine penicillin IM 600,000 units daily for 10 days 3. Complications of treatment 1. Painful injection 2. Jarisch-Herxheimer reaction. Warn patients; advise bed rest, paracetamol or aspirin or ibuprofen. This is caused by toxins released from dead spirochetes causing an immune response and high fever and malaise Secondary Syphilis, Signs & Symptoms 1. 2. 3. 4. Skin lesions, non-itchy macular papular rash, may involve palms and soles of feet. Pink or copper coloured condylomata in moist areas. Pustular lesions and patchy alopecia. Mucous membrane lesions, painless erosions on genitals or in mouth Generalised lymphadenopathy Fever , malaise, arthralgia Diagnosis 1. Dark ground microscopy from mucous patches 2. Syphilis serology, all tests likely to be positive Treatment & Management 1. 1 shot of antibiotics 2. All patients to see HA for PN going back 3-4 months 3. Review by doctor 2 weeks post treatment 4. Monthly blood test to ensure successful treatment until RPR is negative or serofast Classic symptoms of Secondary Syphilis Classic symptoms of Secondary Syphilis Some classic chancres seen in primary syphilis Spirochetes as seen at dark ground microscopy Syphilis Antibody TPPA RPR FTa Ab Positive Positive Negative Positive The above serology result could indicate the following: 1. A past treated infection (documentation of past treatment should be made) 2. An old infection that has not been treated (no past history of syphilis treatment) This will be diagnosed as either Early Latent or Late Latent Syphilis * It is important to remember that if a patient has been treated for syphilis many years ago but has not had regular Syphilis serology done, it is possible that the patient may have been re-infected at some time and possibly gone undiagnosed and the RPR has returned to negative over the passage of time. This is particularly worth thinking about in a patient who is very sexually active (Gay men are more at risk of syphilis infection) How is a diagnosis of Early or late latent syphilis made? Early or Late Latent Syphilis? • In the absence of any symptoms such as Chancre or Rash indicating primary or secondary Syphilis and serology consistent with infection being present for some time i.e. Negative RPR (or positive with titre of neat), a diagnosis or early latent or late latent has to be made. • For a diagnosis of Early Latent Syphilis to be made, there must be proven negative serology within the past 2 years. If the patient was negative 2 or less years ago, then we know that this infection was acquired since the last negative serology. • Late Latent Syphilis will be made if there is no proven negative serology within the past 2 years. This means that it is very difficult to pinpoint when the infection was acquired and therefore how long the patient has been infected. Syphilis Antibody TPPA RPR FTa Ab Positive Negative Negative Negative The above serology could mean one of the following: 1. A false biological positive. This test must be repeated and blood may be sent to the reference laboratory for definitive diagnosis. (The serology lab will make the decision about sending specimens to the reference lab). 2. In some cases, a person who has had Syphilis in the past, may lose their positive TPPA and Fta Ab, it is unusual but not impossible. It is for this reason these results must be checked and followed up carefully. The Antibody test is very sensitive and is more reliable than TPPA and Fta Ab. Take me to the clinic guide for more information