Regulatory Focus™ > News Articles > Update of Blood and Plasma Guidance Calls for Revised Syphilis Screening Procedures

Update of Blood and Plasma Guidance Calls for Revised Syphilis Screening Procedures

Posted 27 February 2013

A new draft guidance published by the US Food and Drug Administration (FDA) recommends revised screening procedures to guard against the threat of syphilis contamination in donated blood and plasma, taking a multi-pronged approach emphasizing redundant testing and risk mitigation methods.


The draft guidance, Recommendations for Screening, Testing, and Management of Blood Donors and Blood and Blood Components Based on Screening Tests for Syphilis, notes that the transfer of syphilis is a rare event, but one more common than the transmission of some other viruses like HIV. In between 2007 and 2008, for example, 324 cases of syphilis were detected by the American Red Cross, an entity that oversees much of the blood and plasma supply in the US.

That figure was "several times higher than the numbers of repeat allogeneic donors identified with human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), and human T-cell lymphotropic virus (HTLV) infections, which were 92, 47, 127 and 9, respectively, during the same time period," FDA wrote.

The problem lies within how syphilis manifests itself. It is a three-stage disease transmitted by a spirochete bacterium, T. pallidum. The bacterium is most commonly transmitted through sexual contact or by birth. While symptoms are exhibited during the first, second and third stages of the disease, the disease generally enters a period of latency without visible symptoms after its second stage.

It is this phase that FDA said it is particularly worried about, as some studies have shown that the disease can still be transmitted during this stage through blood donations.


FDA's guidance is intended to supersede a June 2003 one entitled, Guidance for Industry: Revised Recommendations for Donor and Product Management Based on Screening Tests for Syphilis, and notes a number of requirements.

At its most basic level, the guidance notes that donation facilities are required to perform a serological screening test on each donation of blood for the presence of syphilis. Donors must be tested upon their first plasmapheresis, and then every four months thereafter so long as they do not fail the first test. Donors may later be requalified if the test is found to be a false-positive, and every 12 months regardless.

FDA recommends using both nontreponemal assays and treponemal assays to test for the bacteria, though the latter are noted as being somewhat less useful than the former since they do not monitor the progression of the disease or its response to antibiotics, whereas the former does. When used together, the tests offer a measure of redundancy.

However, neither is particularly useful in catching the disease in its most critical stage: early infection, when antibodies are not yet present.

To catch donors within this "window period,"-and all periods-FDA advises sponsors utilize a multi-pronged approach including questionnaires to assess risk factors, frequent donor screening (every four months) using FDA-approved test methods, and redundant retesting of all positive results.

Positive Developments

Despite FDA's acknowledgement that syphilis is more commonly found than HIV, HBV, HCV and HTLV-combined-it's still a lot less common than it was historically, it said.

One reason why lies in changes in how blood and plasma donations are handled. FDA explains that "universal testing of blood donors may have played a role in the [relative] disappearance of transfusion-transmitted syphilis."

Other factors have also played a positive role, such as the elimination of direct donor-to-donor transfusions (refrigeration of blood and plasma typically inactivates the disease), self-deferral of donors through questionnaires and the wide use of antibiotics in recipients of transfusions, which may naturally treat the disease.


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