CAP TODAY Pathology/Laboratory Medicine/Laboratory Management
LaDow
With automation coming to RPR testing, LaDow says, it will serve the high throughput needs of laboratories doing several hundred tests per night. “Because of the high costs of treponemal tests, they will serve their original purpose of verifying the nontreponemal result.”
He predicts a “tidal wave” of large companies working to develop automated nontreponemal assays to accommodate laboratories returning to the traditional algorithm.
“The nontreponemal system is an algorithm that has been used for 70 years, and a lot of people would agree it’s superior in terms of results for the clinician,” LaDow says. “If an RPR test for screening had been automated 12 to 15 years ago, treponemal tests would probably still only be used for confirmatory testing. The nontreponemal test is a better screening test.”
LaDow points to the fact that nontreponemal testing is required by the FDA for syphilis screening of all organ and tissue donations as further evidence that RPR testing produces better results.
Joanne Starkey, laboratory manager at VRL-Eurofins Laboratories in Denver, agrees that nontreponemal assays produce more accurate results. “You’re better able to distinguish between somebody who does not have a current, acute infection and somebody who has had the infection in the past. They are usually not going to be reactive using the nontreponemal whereas they could possibly come up with a reactive result on the treponemal test if they ever had the infection. A reactive result using a treponemal test doesn’t do you much good unless it’s paired with clinical information as far as does this person have any active symptoms or does their history indicate the possibility of an infection?”
Starkey
The problem with nontreponemal assays, though, is the risk of false-positives, she says. “There is a long list of parasitic infections or disease states or even autoimmune diseases that can cause a false-positive result with nontreponemal tests. They are relatively rare, but that is one of the hang-ups with the nontreponemal test; it is just throwing a net and catching what’s out there.”
Due to the nonspecific nature of nontreponemal tests, pregnant women and those with autoimmune disease and with some other infections that are not syphilis may have antibodies that can be picked up by a nontreponemal assay, Dr. Fakile of the CDC says. “If you are reactive to a nontreponemal assay, it does not mean you have syphilis. It could be a nonspecific reaction. And if you use a trep-only test and it comes up reactive, it could be past infection, or it could be recent infection. So you have to investigate further.”
Starkey’s reference laboratory is running more than 200 syphilis tests per day, mostly from cadaveric samples for organ and tissue donation screening, on the FDA-approved ASiManager assay. Reactive results for syphilis infection are confirmed with the Trinity Biotech Captia Syphilis (T. pallidum)-G.
“Moving away from the subjective assays and more toward the objective assays like Captia is something I think the industry would like to see,” she says.
As far as which syphilis testing algorithm is preferred, “I don’t think there’s an easy answer to that, unfortunately,” Dr. Schmitz of UNC says.
“We’ve done some comparison studies here on reverse versus traditional algorithms, and we certainly do pick up more positives using a reverse algorithm approach,” he says. “I can’t draw a firm conclusion yet about performance, but we certainly pick up more positives that are confirmed by a second, different treponemal assay.”
The sensitivity of the treponemal assay, performed first, gives it the ability to detect latent infection that might be missed using the traditional screening algorithm. “It’s been pretty clearly demonstrated that the treponemal screening test may be slightly more sensitive in very early infection, and certainly more sensitive in latent syphilis, where the sensitivity of the nontreponemal test can decline over time,” Dr. Schmitz says.
The lack of specificity in the treponemal test can be a drawback, though. “It presents the clinician with the scenario of having to determine if that confirmed reactive treponemal test and nonreactive nontreponemal test is due to past treated or untreated syphilis.” If a laboratory has a positive treponemal assay result followed by nonreactive nontreponemal assay result, a second, different treponemal assay must be performed.
Dr. Schmitz
Nontreponemal assays are also preferred for monitoring therapeutic efficacy, Dr. Schmitz says. “We don’t want to use a treponemal screen or reverse algorithm in those cases. We want to go to a nontreponemal test and do titers to look for declines in titer with effective treatment.”
In higher prevalence populations, the nontreponemal test is used to assess whether a patient has been re-infected by looking for an increase in titer, Dr. Schmitz says. “That isn’t going to be typically detected with a treponemal antibody screen, because those are qualitative tests.”
test, Dr. Fakile says, “where if I test an individual sample, I can tell you, ‘This is it, the person has active syphilis.’”
“We are very focused on trying to find new tests that can be developed to get to the bottom of this diagnostic challenge, and then find tests that are much more rapid, closer to the patient, and do have good sensitivity and specificity.”
In the U.S., there is only one rapid point-of-care test, Dr. Fakile says, the Syphilis Health Check (SHC) by Trinity Biotech. “The CDC is still looking at rapid point-of-care testing with a lot of interest and trying to gather as much data as we can, trying to reach out to people or programs that may be using this test,” Dr. Fakile says. Another rapid test is the DPP Syphilis Screen and Confirm assay, from Chembio Diagnostic Systems, which is a dual nontreponemal and treponemal POC test. It does not have FDA clearance.
“We are considering a lot of other new assays which are just entering the U.S. market,” Dr. Fakile says, “and trying to understand the performance characteristics so we can properly identify the patients early, treat them and their contacts, and stem the rise of syphilis.”
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Amy Carpenter Aquino is CAP TODAY senior editor.