The Bolivian MOH recommends a minimum sensitivity of 81% for screening tests for detecting active syphilis in pregnant women. The Determine Syphilis TP test is 91.85% sensitive and 98.5% specific in pregnant women when compared to RPR confirmed by TPPA performed by a reference laboratory. The performance of the Determine rapid syphilis test therefore meets the national standards for it to be used as a prenatal screening tool. Previous retrospective studies observed similar or slightly higher measures of accuracy,5,6,7,8
particularly sensitivity. The manufacturer notes that use of whole blood may lower sensitivity from that observed with serum,4
which may account for this small difference.
Furthermore, we found that the Determine Syphilis TP test was more sensitive than RPR performed in a hospital (75.7%). This means if 20 people have syphilis, five will not be detected or receive treatment using the hospital‐based RPR. It is not clear why the sensitivity of the RPR performed in the hospital was so low compared to the gold standard tests performed by the reference laboratory. We hypothesise that the laboratories in the hospitals might use outdated or poor quality reagents or suboptimal equipment, and the staff might not be adequately trained to perform the test or might have insufficient experience performing the test. This suggests that a simple POC test such as the Determine Syphilis TP test may be appropriate even in settings with laboratory capacity by minimising the dependence on reagents, equipment and staff training.
The positive predictive value of the Determine Syphilis TP test was 71.0%, suggesting that the test may over‐diagnose syphilis cases. While this is true, it is useful to put this into perspective by considering the number of congenital syphilis cases averted versus the potential risks of over‐diagnosis. In our study, there were 342 cases of maternal syphilis diagnosed by the reference laboratory, of which 259 were detected by the hospital laboratory RPR. The Bolivian surveillance system estimates that 50% of pregnant women never return to the clinic to obtain their RPR results,2
meaning that with standard testing only 130 of the hospital‐RPR‐positive women would obtain treatment. Therefore, with standard RPR testing, only 38% (130/342) of maternal syphilis cases would have been detected and treated. In comparison, with the Determine Syphilis TP test, 92% (314/342) of the true syphilis cases were detected and immediately treated. Assuming that congenital syphilis occurs in approximately 30% of cases,9
an additional 61 cases ((314−130)/3) of congenital syphilis were averted by using the Determine Syphilis TP test compared to using hospital‐based RPR testing.
At the same time, 128 (1.4% of the tested population) were falsely diagnosed as syphilis‐positive using the Determine Syphilis TP test when RPR confirmed by TPPA was used as the reference standard. The rate of biological false positive treponemal tests has been estimated at 1% or less. Thus, among these 128 women, it is likely that only 1–2 were true false positive cases; the remainder were women with a past history of syphilis. Re‐treatment of pregnant women with a history of syphilis may be beneficial as these women may have been inadequately treated or re‐infected. The risks of a misdiagnosis are primarily adverse reaction to treatment, including anaphylaxis, and stigma and other social consequences, including possible domestic violence from their partner. While it is difficult to estimate the risk of the social sequelae, the incidence of anaphylaxis after parenteral penicillin has been reported to be 32 per 100
000 exposed patients.10
Based on these limited data, it seems that the benefits of the Determine Syphilis TP test's improved sensitivity and ability to provide treatment immediately outweigh the risks of over‐treatment.
Treponemal tests including the Abbott Determine Syphilis TP test continue to detect antibodies and react positively even after successful treatment. This limits the use of treponemal tests as an accurate screening tool, especially in high‐risk populations that have access to adequate care. This study shows that the treponemal POC test is a reasonable alternative testing method, particularly if the priorities are to: (1) increase uptake of testing by simplifying the process; (2) introduce testing in locations with no laboratory infrastructure; and (3) ensure treatment delivery. Use of this test can facilitate implementation of WHO's recommendation to build capacity on‐site for ANC screening,1
particularly in locations that do not have the capital to construct laboratories or conduct routine technical training.
This study showed that using Abbott's Determine Syphilis TP test can improve case detection when committed laboratory staff in urban hospitals performed each test. A study assessing performance of a different POC syphilis test observed a 97.2% agreement between POC test results obtained by clinic staff in basic health facilities and POC test results obtained by reference laboratory staff.11
This suggests that these accuracy measures may also represent test performance when the Abbott test is conducted by clinic staff in simple clinic settings such as rural Bolivia.
Our study had several limitations. One is that we defined the gold standard for syphilis diagnosis as a reactive RPR confirmed by TPPA. While this makes sense from a clinical standpoint, it is possible that there were false negative cases among the RPR results performed by the reference laboratory that would have been detected if we had used TPPA alone as the gold standard. We performed TPPA on a random sample of 3% of the RPR‐negative samples (216 cases) and found only one positive result. This suggests that the results would not have been significantly different if we had used TPPA as the gold standard. Another limitation of our study relates to how generalisable the results are. In other settings with highly efficient and accessible laboratories that perform RPR, the performance of the Abbott Determine Syphilis TP might not be superior to standard testing procedures. In general, however, the results are likely to be applicable to many low‐resource settings in the developing world where hospital laboratories frequently are under‐funded, understaffed and generally concentrated in urban centres.
This study has shown that Abbott Determine Syphilis TP rapid tests can perform well when used among pregnant women, for whom prevention of congenital syphilis is a primary consideration. This study has also shown that use of traditional screening tests in locations with laboratory capacity may result in substandard results. Introducing a POC test is one option. Addressing the inadequacies (insufficient supplies, poor quality reagents, irregular quality control and assurance opportunities, and lack of routine technical training) is another option, particularly in locations with laboratory capacity. Taking this indirect approach may improve the quality of syphilis screening as well as enhance overall laboratory capacity.
- When used in a real‐world setting in antenatal clinics in Bolivia, the Abbott Determine Syphilis TP test was more sensitive than standard rapid plasma reagin performed in an urban hospital and equally specific
- The accuracy of the Abbott Determine Syphilis TP test in this prospective study was similar to that reported in other retrospective studies
- Because the Abbott Determine Syphilis TP test is a simple, point‐of‐care test, its use in low‐resource settings could dramatically increase the proportion of pregnant women tested and treated for syphilis and could have a significant impact on the prevention of congenital syphilis
Based on our findings, several strategies can be taken to improve ANC syphilis screening. We understand that the contexts for delivery of syphilis diagnosis and treatment are heterogeneous and require a portfolio of complementary solutions and recommend the following actions to the Bolivian MOH:
- Implement a POC syphilis test to improve the diagnostic coverage, especially in health care facilities where traditional syphilis tests cannot be performed.
- Improve the quality of RPR results in maternity hospitals by implementing quality control and quality assurance procedures.
- Refine the purchasing system for RPR and VDRL kits and supplies so they fulfill a minimum standard of quality and accuracy.
New developments in POC syphilis tests are on the horizon. Of particular interest is a single test that has non‐treponemal and treponemal reactivity. Availability of such a test will broaden the populations for which POC syphilis tests are appropriate. Future research interests include evaluation of such new technologies as well as the review, standardisation, and implementation of operational procedures that improve overall laboratory capacity.