[Question #9272] Syphilis Reverse Algorithm testing

34 months ago

My husband before we got married had sex with numerous FSWs - so I got tested for STDs recently - I was negative for everything - but one test (syphilis) was incredibly confusing. I took the reverse algorithm test for Treponema pallidum antibodies here is link to the test: https://testdirectory.questdiagnostics.com/test/test-detail/90349/syphilis-antibody-cascading-reflex?cc=MASTER

I am assuming that this test is an a TPA/EIA and it tests for both IGM & IGG or at least IGG antibodies - I tried to verify with Quest but they were very unhelpful and would only refer me to the link above. I have been with my husband a long time and I am concerned if he had syphilis it would be very latent - so I am assuming that the test would need to test for IGG to tell if I also had a latent infection. My question is would all TPA/EIA tests look for both IGG and IGM antibodies or just IGG, they wouldn't ever just look for IGM, correct? Since Quest and my GP were not helpful, I thought I would ask the forum to take a look at the link I sent and then answer this question: Would a TPA/EIA screen always look for both IGG & IGM antibodies or just IGG - NEVER ONLY IGM? Also, with my negative test does that mean I don't need any other screening for syphilis? My husband has ED so we haven't had sex in years, so I assuming I am well out of the window period - I also never had any symptoms - so would this test be definitive? Thanks in advance for your help.

H. Hunter Handsfield, MD

34 months ago

Welcome to the forum. Thank you for your confidence in our services.

You needn't be at all worried about syphilis. Your test results rule it out with 100% certainty. All of the initial blood tests used to screen for syphilis -- either a negative RPR or VDRL (the traditional algorithm) or an EIA ("reverse algorithm") is conclusive if done more than several weeks after the last possible exposure. You're a bit too focused on IgG versus IgM antibody -- but in any case, every EIA available on the market or used by any and all labs is for IgG antibody, with or without IgM. In other words, to answer your specific question, never IgM alone. Stated another way, the reverse algorithm always is equally effective in excluding syphilis as the traditional one.

From your description, it seems your husband never was at high risk for syphilis: the large majority of female sex workers in the US have syphilis, and it was even less common in past years than now; and their clients typically are at low risk. But even if he had been exposed to a known-infected partner, his negative EIA proves he wasn't infected.

I hope these comments are helpful. Let me know if anything isn't clear.

HHH, MD

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34 months ago

Thank you for the reply Dr. Handsfield.

I have a couple of follow-ups please. I’m unsure if I had an EIA, all I know is that I had the reverse algorithm with a TPA immunoassay. It could be an EIA, a CIA or some other immunoassay, so I would like to check that your statement about every EIA available on the market and used by labs is for IgG antibody with or w/o IgM is applicable for all TPA immunoassays? I’m assuming it is but I just wanted to check because I’m worried about late syphilis and wanted to verify that your confidence of 100% includes late syphilis.

I also have one other question about HIV testing, I just took a 4^th generation test that was negative so I know I am fine, but I was wondering if I should get my husband to get tested because he was last tested about ten years ago. He had three negative fingerstick antibody tests that I think were 2^nd generation – are those tests accurate enough that he is definitely negative (the tests were years after his risk factors)? I know he has been faithful since we got married so he has no risk factors since the tests, is there any reason he should get tested again or are his past tests definitive?

Thank you for your help.

H. Hunter Handsfield, MD

34 months ago

Reverse algorithm means the initial test is EIA; they are the same thing. (CIA is technologically basically the same as EIA.) Every EIA (or CIA) used for syphilis is for IgG antibody, whether or not IgM antibody is also included. It is 100% certain you do not have late syphilis.

All HIV blood tests in use in the United States, whether fingerstick or venous blood, and regardless of test "generation", are equally accurate in detecting HIV infection more than 8-12 weeks in duration. Thus, it is also 100% certain neither you nor your husband has HIV.

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34 months ago

Thank you so much Dr. H - its wonderful what you do in this forum, I was so embarrassed to ask my GP questions like this, but felt very safe asking you - so thanks again for your prompt responses.

34 months ago

Sorry one last thing so I understand when they say TPA Immunoassay - that means treponemal Pallidum Antibody - the TPA is the syphilis antibody the test looks for and the EIA/CIA is the immunoassay method they use to detect it - correct? Are these immunoassays as accurate as the manual trepenomal tests (TPPA, FTA-ABs)? This is just for my own knowledge and again thank you for creating a safe space to discuss very private matters - thanks again.

H. Hunter Handsfield, MD

34 months ago

Almost certainly they did not do the TPA on your specimen. If the initial test (RPR in the historical algorithm, EIA on the reverse algorithm) is negative, that's all that's done. The next test only is done to confirm the first, if it is positive. ---

34 months ago

OK I understand now - and are the EIA immunoassays as accurate or close in accuracy to the manual treponomial tests TPPA, FTS-ab?

H. Hunter Handsfield, MD

34 months ago

How "accurate" the tests are has to be understood in how they are supposed to be employed. Their accuracy isn't really comparable because the tests have different purposes. In general, EIA and RPR are highly sensitive, but nonspecific: i.e. a positive result often is false. The opposite is true for TPPA, FTA-ABS, etc: their main purpose is to provide specificity, and they are never used in a way intended to determine how sensitive they are (i.e. how well they would work if used as the only test, which is never done and not their intended use). This is getting into the weeds about how test accuracy is defined and measured -- and we haven't even got into the equally important concepts of negative and positive predictive value.

For purposes of your question, TPPA, FTA-ABS and similar tests are never done as stand-alone tests to diagnose syphilis; they should only be done in people with positive RPR, EIA, etc.

That will have to complete this thread -- we're already past the normal two follow-up exchanges included with each question. Please just accept the bottom line: your and your husband's test result prove unequivocally neither of you has syphilis, no matter what risks you may have faced in past years when one or the other (or both?) might potentially have been exposed.

I hope the discussion has been helpful. Best wishes.

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