CDC recommends traditional vs. reverse sequence screening for syphilis

The CDC continues to recommend the use of nontreponemal testing for syphilis screening and that treponemal testing should only be used to confirm syphilis as the cause of nontreponemal reactivity, according to data published in Morbidity and Mortality Weekly Report.

“Although CDC continues to recommend the traditional algorithm with reactive nontreponemal tests confirmed by treponemal testing, in this report, the CDC offers additional recommendations if reverse sequence syphilis screening is used,” researchers wrote.

According to the CDC, some laboratories have adopted reverse sequence screening, permitting for high throughput testing, to reduce time and labor required for syphilis screening.

For this reason, data from five studies conducted between 2006 and 2010 were assessed from five laboratories utilizing reverse sequence screening for syphilis. Officials evaluated the use of Treponema pallidum particle agglutination and fluorescent treponemal antibody absorbed tests for identifying false-positive enzyme and chemiluminescence immunoassay screening tests.

According to the report, discordant testing results may be caused by:

lPrevious syphilis infection, treated or untreated, with persistence of treponemal antibodies but seroreversion of nontreponemal antibodies;

• A false-positive treponemal test result;
• Early primary syphilis in a person who has yet to develop nontreponemal antibodies.

Of 140,176 specimens screened with an automatable treponemal enzyme and chemiluminescence test, 4,834 had a reactive test result, of which 56.7% had nonreactive nontreponemal results and 31.6% were nonreactive with the use of another treponemal test.

Further, the percentage of reactive automatable treponemal enzyme and chemiluminescence test results were 6.3 times the rate (14.5%) of those with a low prevalence for syphilis (2.3%). The low-prevalence population had higher discordant results when compared with high-prevalence population (60.6% vs. 50.6%).

In an accompanying editorial, CDC researchers wrote that: “Results from all serologic testing should be reported promptly and concurrently to the clinician and public health department. When making management decisions, clinicians should consider data other than the results of serodiagnostic tests. An assessment is needed of the patient’s sexual risk factors and medical history, especially history of previous treatment for syphilis. If the traditional algorithm is used and the initial nontreponemal test is nonreactive, patients with suspected syphilis should be treated and then retested with a nontreponemal test in several weeks.” – by Ashley DeNyse

For more information:

• Radolf JD. MMWR. 2011;60:133-137.

Screening for syphilis has always been a clinical challenge as there is no single test available for definitively diagnosing syphilis. Clinicians must use multiple sources of information for making a diagnosis which include using information from risk assessments, physical examination, multiple serologic test results, medical history of previous syphilis tests results and treatment, and any history of recently infected partners. The traditional screening algorithm for syphilis has always used two types of serologic tests: an initial nontreponemal test (e.g. RPR or VDRL) and, if positive, followed by a treponemal test (e.g. TP-PA, FTA-ABS and various EIAs or CIAs).

More recently, laboratories have been increasingly using the highly automated treponemal EIA/CIA tests as the initial test and, if positive, followed by a nontreponemal test; thus the name “reverse sequence syphilis screening.” The recent MMWR provides data on the results from five laboratories using the “reverse sequence syphilis screening” algorithm. These data highlight what we have already known: that the use of only one type of serologic test is insufficient for diagnosis, because each type of test has limitations, including the possibility of false-positive results in persons without syphilis.

The clinical implications of the MMWR data pertain to clinicians using the reverse sequence syphilis screening algorithm. For those using this algorithm, a third serologic test (the TP-PA) is recommended by CDC if the initial treponemal test is positive and the second nontreponemal test is negative. Clinical management of these patients remains the same as for those using the traditional screening algorithm. In addition to the serologic tests results, providers must consider the information from the risk assessment, physical exam and previous syphilis history to inform their clinical management decisions. Further details on the clinical management of patients with a possible diagnosis of syphilis are outlined in the recently published 2010 STD Treatment Guidelines.

– Kevin A. Fenton, MD, PhD, FFPH

Infectious Disease News Editorial Board member

Director, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, CDC

Disclosure: Dr. Fenton reports no relevant financial disclosures