The U.S. Food and Drug Administration (FDA) is alerting clinical laboratory staff and healthcare providers that false reactivity Rapid Plasma Reagin (RPR) test results, when using the Bio-Rad Laboratories BioPlex 2200 Syphilis Total & RPR kit, can occur in some people who received a COVID-19 vaccine.
Bio-Rad Laboratories said the RPR false reactivity—or “false-positive”–was observed in some individuals for at least five months following a COVID-19 vaccination.
More research is underway to determine the extent of the issue. It is not known if other RPR tests may be affected similarly. Treponemal testing for syphilis such as Treponema pallidum particle agglutination (TP-PA) and treponemal immunoassays do not appear to be impacted by this issue.
The FDA says healthcare providers should make patients who received a reactive RPR result using the Bio-Rad BioPlex 2200 Syphilis Total & RPR test kit aware that they may need to be retested for syphilis with another test to confirm results.
The FDA recommends clinical laboratory staff and health care providers who use the Bio-Rad BioPlex 2200 Syphilis Total & RPR kit should do the following:
- Perform confirmatory testing for all reactive results. Use of only one type of serologic test (non-treponemal or treponemal) for people without an earlier syphilis diagnosis is insufficient for diagnosis.
- In individuals with a negative treponemal test (e.g., TP-PA) but reactive RPR result on the BioPlex 2200 Syphilis Total & RPR kit, repeat RPR testing is not necessary unless otherwise clinically indicated.
- For people previously treated for syphilis in whom treponemal tests will remain persistently positive, and who are being evaluated for possible new syphilis infection, a reactive RPR should be interpreted in the context of the patient’s medical history (including COVID-19 vaccination status), risk factors and clinical presentation.
- Ensure your patients are aware of the importance of getting vaccinated against COVID-19 and are aware that the COVID-19 vaccines do not cause syphilis. Millions of people in the United States have already received a COVID-19 vaccine.
- Encourage patients who are sexually active to get tested for sexually transmitted infections to protect their health.
A person is considered positive for syphilis when the non-treponemal (RPR) and treponemal antibody tests (e.g., TP-PA, or enzyme immunoassay) are both reactive. The Bio-Rad BioPlex 2200 Syphilis Total & RPR kit is a multiplex test used to detect antibodies to Treponema pallidum—the bacteria that causes syphilis—and non-treponemal reagin antibodies in human serum or plasma.
The clinical community is aware that false-reactive RPR test results have been observed in people with systemic infections unrelated to syphilis, such as tuberculosis, rickettsial diseases, and endocarditis. False reactive RPR testing has been previously observed following immunization (specifically following smallpox vaccine). False reactivity with RPR can also occur during pregnancy.
The FDA is continuing to investigate whether this issue is specific to the Bio-Rad BioPlex 2200 Syphilis Total & RPR test or if other tests may also be affected. The FDA will continue to keep clinical laboratory staff, health care providers, and the public informed of significant new information.
The FDA encourages healthcare providers to report adverse events or suspected adverse events experienced with medical devices, including in vitro diagnostic tests.
Featured image: Analyst prepares blood plasma samples for RPR test.