Literature review > Issue_2 > Review Zarakolu et al. 

The recent outbreaks of syphilis in the US and Europe, and the continuing high rates of infection in other parts of the world, confirm that the current mechanisms for identifying and treating persons infected with syphilis are inadequate. Prenatal screening is one important example of an effective proactive approach for identifying infected women and preventing infection in their newborns. In settings other than prenatal care, however, most health authorities find themselves in a reactive position in response to evidence of increased transmission in their communities. New tools are needed to facilitate rapid screening of high risk individuals in small rural clinics in developing countries and in non-medical settings (e.g. bath houses, bars) in the US and Europe. Such tests should be specific, sensitive, and should require neither specialized technical training nor equipment. The Immunochromatographic Strip (ICS) test developed by PATH may be a first step in fulfilling that need. This paper describes a preliminary evaluation of the ICS test in a small number of patients with and without syphilis.

In this patient sample, the ICS test performs as well as the standard, but technically complicated, FTA-ABS test for identifying persons with anti-treponemal antibody. However, the limited number of syphilis patients in this study and the complete lack of information about their stages of infection and past syphilis histories makes extrapolation of these results to the "real world" difficult. For example, all 30 patients were reactive in the ICS at diagnosis. If all or most of the 30 syphilis patients in this study had secondary or early latent syphilis, this sensitivity is not particularly impressive given that all such patients should have significant amounts of antibody. It is stated that all known syphilis patients were seropositive in RPR and FTA-ABS at the time of diagnosis; this suggests that patients had infection of = 4-6 weeks duration. How does the ICS test perform in patients with early primary lesions (confirmed by darkfield microscopy) but nonreactive RPR tests? Such persons are likely to be highly infectious to others and should be a primary target of screening strategies.

The specificity of the test, compared to FTA-ABS, is 100%. However, the FTA-ABS and other treponemal tests remain reactive in patients with past treated syphilis. This feature of the ICS limits its utility in identifying the active syphilis cases that would be the targets of control efforts. The authors recognize this limitation and address the practical utility of the ICS test in various settings. The question remains, however, as to which screening strategy is the most effective in identifying persons who need treatment. The best test may be different dependent upon local conditions. For example, use of the RPR (which can be used as a screening test in field settings, with hand rotation) would result in unnecessary treatment of persons with BFP reactions and would miss some persons with very early syphilis. The magnitude of the BFP issue is dependent upon the prevalence of BFP reactors in the local population; this may be affected by the amount of IV drug use or the burden of malaria in the population. On the other hand, RPR reactivity is thought to correlate better with current disease activity than treponemal tests and is more likely to be nonreactive following treatment. In contrast, the use of a treponemal test, such as the ICS, would result in unnecessary treatment of persons with past treated syphilis. Because persons with past syphilis are at higher risk for acquiring syphilis again, however, this latter approach may be preferable in high-risk populations. A treponemal test also may have the advantage of detecting primary infections earlier, although this point was not directly addressed for the ICS in this study.

While this preliminary evaluation suggests that the ICS test is quite promising, there are several other issues to consider. The choice of antigen in the ICS test deserves comment. While the 47kd antigen used in this test is certainly one of the antigens that is readily recognized during syphilis infection, other antigens (or combinations of antigens) have been shown to have useful characteristics in terms of high sensitivity during primary syphilis [1, 2] and loss of antibody following effective treatment [3[. The ICS test may be improved by the consideration of other antigens. The nature of the clinical sample and test logistics are also important. In this study, sera were tested; collection of serum requires venipuncture, time for clotting, and serum separation. How does the test perform with plasma, which is easier and less time-consuming to obtain? Can the test be adapted to use finger-stick blood? How stable is the ICS test upon storage in high temperatures? Does the test perform equally well in testing conditions of high and low ambient temperature?

In summary, this preliminary study suggests that the simple-to use ICS test performs well with a small number of sera. Although many questions remain to be answered, this study is encouraging with regard to development of a rapid field test for use in populations at high risk and in non-traditional testing settings.

References:

1. Young H, Moyes A, Seagar L, McMillan A. Novel recombinant-antigen enzyme immunoassay for serological diagnosis of syphilis. J Clin Microbiol 36:913-7, 1998

2. Van Voorhis WC, Barrett LK, Lukehart SA, Schmidt B, Schriefer M, Cameron CE. Serodiagnosis of syphilis: antibodies to recombinant Tp0453, Tp92, and Gpd proteins are sensitive and specific indicators of Treponema pallidum infection. J Clin Microbiol, in press.

3. Ijsselmuiden OE, Schouls LM, Stolz E, Aelbers GN, Agterberg CM, Top J, van Embden JD. Sensitivity and specificity of an enzyme-linked immunosorbant assay using the recombinant DNA-derived Treponema pallidum protein TmpA for serodiagnosis of syphilis and the potential use of TmpA for assessing the effect of antibiotic therapy. J Clin Microbiol 27(1):152-7, 1989.

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