<prompt> Most sensitive test for Treponema -VDRLRPRFTA-ABSKahn  <response>: Ans. isc i.e., FTA-ABS test Most sensitive test in SyphilisThe nonspecific tests VDRLRPR test can be easily ruled out:-Their sensitivity is comparable to that of specific tests in primary and secondary syphilis but in latent or late syphilis they have quite low sensitivity.Specific Tests TPIIn its time TPI was the most specific test available for diagnosis of syphilis and was considered gold standard in syphilis serology.However because of its extreme complexity it was available only in few laboratories.The TPI test has now been supplanted by other tests such as FTA-ABS and TPHA which are quite as specific and much simpler.FTA-ABS testFTA-ABS test is as specific as the TPI test and is now accepted as the standard reference testHowever it can be done only in suitably equipped laboratories, it is not available for routine testing.TPHA testTPHA test is just as specific as FTA-ABS and almost as sensitive except in the primary stage.It is also much simple and more economical.These advantages have made TPHA a standard confirmations test.TPPA testThe TPHA test has been replaced by the serodia TP-PA test which is more sensitive for primary syphilis.TPHA is widely available in Europe but not used in U.S.A.From the discussion above, and from the table reproduced from Harrison, it seems, the TPPA is the most sensitive test for syphilis.Both FTA-ABS and TP-PA are equally sensitive in secondary and latent syphilis.TP-PA has higher sensitivity in Primary syphilis.The problem is that enough datas for TP-PA are not available.Sensitivity of Serodiagnostic tests in SyphilisTestPrimarySecondaryLatentTertiary VDRLRPR78 74-871009588-10071 37-94 FTA-ABS84 70-10010010096 TP-PA89100100NADiagnosis of syphilis:-Treponema pallidum cannot be isolated by routine culture methods therefore detection is either by direct visualization of the organisms in material from the lesion or indirectly by immunologicalserological methods.Each stage of the treponematoses requires a particular testing modality.Absolute diagnosis during the first and second stages can be made by direct examination under dark field microscopy of a specimen from primary chancre, the maculopapular rash, or the condyloma latum.Since the direct visualization of spirochetes is effective only during the active stages of primary and secondary syphilis, serologic tests were developed.Serological tests in syphilis are of two typesNonspecific treponemal testsSpecific treponemal tests Nonspecific treponemal tests : -Infection with syphilis results in cellular damage and the release into the serum of a number of lipids including cardiolipin and lecithin.The body produces antibodies against these antigens.Nonspecific treponemal tests detects the presence of these antibodies to lipoprotein material from damaged cells and cardiolipin from treponemes and as a consequence are not specific for Treponema. Reactivity in these tests indicates host tissue damage.If the patient has these antibodies it is assumed that he or she has syphilis.These tests are used for screening of syphilis.If these tests are positive presence of the disease should be confirmed by specific tests.The tests commonly employed are: -Venereal disease Research laboratory test VDRL TESTRapid plasma Regain Test RPR testWhy are these tests nonspecific??These tests measure antibodies directed against cardiolipin antigen that results from interaction of host tissues with Treponema Pallidum or spirochete itself. They do not detect the antibodies against Treponema itself.Cardiolipin is a phospholipid and it is possible that a similar substance present in the treponemal cell or released from damage host cells damaged by the stimulate antibody production.Assays for nonspecific antibody, because of their low cost and technical simplicity have routinely been used as screening test for evidence of syphilis since these tests have relatively low specificity positive results are confirmed by detection of specific anti Treponemal antibody.Antibody develops in 70 of patients within 2 weeks of developing chancre and in 100 of patients with secondary syphilis.The important point about nonspecific treponemal tests is that they can be used quantitatively: -Quantitative result of these tests tends to correlate with disease activity thus they are very helpful for screening. A fourfold or greater rise in the titre may be seen during the evolution of early syphilis. In secondary syphilis, test results are always positive and often at a high titre.The nonspecific treponemal tests should become nonreactive one year after successful therapy in primary syphilis and 2 years after successful therapy in late syphilis.Therefore these tests can be used to monitor response to treatment. - After successful treatment there would be sustained four fold decrease in antibody titre.Similarly a fourfold increase in titre following therapy suggests reinfection or relapse and necessitates re- evaluation.Nonspecific Treponemal tests for syphilis VDRL TestThe VDRL test is a nonspecific serological test for syphilis.It uses a mixture of cardiolipin, cholesterol and lecithin as antigen. With the use of these antigens, IgG or IgM antibodies present in the serum or C.S.F. in case of neurosyphilis are detected.This test can be used quantitatively and increase in VDRL titre with time can be used to confirm a diagnosis of syphilis.R.P.R.It is also a nonspecific test which uses cardiolipin as antigen.Treponemal specific testsWhile the nonspecific tests look for anti lipoidal antibodies the specific treponemal tests look for antibodies against the spirochete itself.The tests included in this category are: -Indirect immunofluorescence treponemal antibody-absorption test FTA-ABS test.Treponema Pallidum hemagglutination assay TPHA or microhemagglutination test MHA-TPTreponema Pallidum immobilization test TPI.Enzyme immune assay ELISA.TPPA testThese tests are used to confirm a positive nontreponemal reaginic test.Treponema specific tests are not completely specific for syphilis because false positive reactions can occur with other spirochetal diseases e.g., Yaws, pinta leptospirosis, rat bite fever, relapsing fever, Lyme disease.An important point about these tests is that they do not correlate with disease activity.These test findings become positive soon after infection and typically remain positive for life despite adequate treatment. 