SEROLOGY OF SYPHILIS Assist Prof Dr. Syed Yousaf Kazmi SEROLOGY OF SYPHILIS OBJECTIVES • Perform Rapid Plasma Reagin Test • Understand the principle of screening test of syphilis • Learn different conditions giving rise to false positive serology of screening test of syphilis • Interpret results of screening test in different SYPHILIS INTRODUCTION • The name "syphilis" was coined by Italian physician and poet Girolamo Fracastoro in his Latin written poem “Syphilis sive morbus gallicus” ("Syphilis or The French Disease") in 1530 • The genus name, Treponema, is derived from the Greek term for "turning thread“ • One of the oldest disease known to mankind SYPHILIS INTRODUCTION • Genus Treponema include – Treponema pallidum subspp pallidum (syphilis) – Treponema pallidum subspp pertenue (yaws) – Treponema pallidum subspp endemicum (bejel) – Treponema carateum (pinta) All subspp are indistinguishable serologically from each other SYPHILIS INTRODUCTION • Highly contagious • Penetrate unbroken skin/ through abrasions • Never been cultured on artificial media/ tissue culture • Only human host • Organism survives 4oC temp for 24 hoursimportant for blood transfusion SYPHILIS INTRODUCTION A. ACQUIRED SYPHILIS Primary syphilis Secondary syphilis Latent syphilis Early latent Late latent Tertiary syphilis Yaws, Pinta, Bejel B. CONGENITAL SYPHILIS C. SYPHILIS RELATED DISEASE Yaws PRIMARY SYPHILIS • IP: 9-90 days, usually ~21 days. • Develops at site of contact/inoculation. • Classically: single, painless, clean-based, indurated ulcer, with firm, raised borders • Mostly ano-genital, but may occur at any site (tongue, pharynx, lips, fingers, nipples, etc...) • Non-tender regional adenopathy • Very infectious SECONDARY SYPHILIS • 6 wks to 6 months after primary chancre • Diffuse non-pruritic indurated rash on body including palms & soles. • Fever, malaise, headache, sore throat • Highly infectious LATENT SYPHILIS • Positive syphilis serology without clinical signs of syphilis • begins with the end of secondary syphilis and may last for a lifetime • Early(infectious) and late phase(Non-infectious) • Untreated syphilis – 30% cure – 30% latent – 30% tertiary phase TERTIARY SYPHILIS • Years/ decades later • Granulomatous lesion called Gumma • Skin, bones, liver • Destructive lesions in CNS-stroke, paresis, tabes, neuropsychiatric symptoms etc.) • CVS-Aortitis, aneurysm, valvular insufficiency • Non infectious SEROLOGICAL TESTS • Non Treponemal Tests – VDRL, RPR – Treponemal infection induce formation of two types of antibodies • Reagin (that react with non-treponemal Cardiolipin) • Specific anti-treponemal antibodies • Treponemal Tests – – – – TP-PA (Treponema pallidum particle agglutination) TPHA (Treponema pallidum heam-agglutination) ELISA FTA-ADS test NON-TREPONEMAL SCREENING TESTS Widely available Cheap Easy to perform Rapid results in minutes Correlate with disease activity (become negative with successful treatment) • False positivity-Preg, autoimmune dis, EBV inf, • May be false negative in early Prim syphilis • • • • • NON-TREPONEMAL SCREENING TESTS • Rapid Plasma Reagin test • Cardiolipin-cholesterollecithin acts as antigen • Reagins are mixture of IgG/IgM • Colored compound is attached with antigen • Visible clumping occurs in minutes • Antigen antibody complex visible on card RPR TEST RPR TEST Positive 2-3 weeks in Prim untreated Syphilis Highly positive in secondary syphilis Becomes negative 6-8 months after treatment Quantitative test- response to therapy Positive RPR late after therapy means ineffective treatment/ re-infection • False positivity in viral infections (infectious mononucleosis), bacterial infections (e.g., pneumonia, TB), chronic disease (e.g., RA, SLE), elderly, Pregnancy • • • • • TREPONEMAL TESTS • Use Treponema pallidum antigen • Detects specific antiTreponemal antibodies • Specific tests for syphilis • Once positive-remain positive for life • Do not revert to negative with treatment • Expensive • Laborious, time consuming • Expertise req INTERPRETATION OF SEROLOGICAL TESTS FOR SYPHILIS NonTreponemal tests (RPR/ VDRL) + Treponemal Tests (TP-PA/ FTA-ADS) + + – – + – – Possible Explanation Syphilis - recent or previous Yaws or pinta No syphilis False positive Consistent with previously treated or untreated Syphilis Yaws, Pinta, Bejel No syphilis Syphilis in incubation period