5.1. ADAPTATION, IMPLEMENTATION AND MONITORING
These guidelines provide recommendations for syphilis screening and treatment for pregnant women, based on the best global evidence available at the time of compilation. However, the epidemiology and antimicrobial resistance (AMR) of STIs vary by geographical location and are constantly changing, sometimes rapidly. It is recommended that countries conduct good-quality studies to gather the information needed to adapt these guidelines to the local STI situation as they update their national guidelines. In areas lacking local data as a basis for adaptation, the recommendations in this guideline can be adopted as presented here.
For further guidance on adaptation, implementation and monitoring of national guidelines, please refer to Introducing WHO’s reproductive health guidelines and tools into national programmes: principles and processes of adaptation and implementation (14).
5.2. CONSIDERATION ON THE IMPLEMENTATION OF ANTENATAL SYPHILIS SCREENING AND TREATMENT
A decision on whether to continue the current antenatal syphilis screening algorithm or to introduce a new syphilis screening strategy that includes treponemal-based rapid syphilis tests (RSTs) into the national system should be based on a careful assessment of the screening coverage, treatment rate, and quality of the existing system of testing. The following points should be taken into consideration.
Coverage: An assessment should be made of the proportion of all persons at risk and pregnant women who have access to syphilis testing.
Quality of testing: The quality of testing should be assessed to ensure accuracy of results.
Treatment of seropositive individuals: The proportion of all persons tested who subsequently receive test results and obtain treatment in a timely manner.
If the coverage of testing of pregnant women and the rate of treatment of seropositive individuals are not at least 95% each, consistent with the targets presented in the Global guidance on criteria and processes for validation: elimination of mother-to-child transmission of HIV and syphilis (15), then efforts should be made to rectify the inadequacies in the system. If the problems cannot be resolved, consideration should be given to introducing new screening and treatment strategies, following the decision-making flowchart presented in Figure 1.
Figure 1
Decision-making flowchart for maintaining or introducing new syphilis screening and treatment strategies. RPR: rapid plasma reagin test; RST: rapid syphilis (treponemal) test; TPHA: Treponema pallidum haemagglutination assay; TPPA: Treponema pallidum (more...)
A decision will also be based on the resources available. Country-level decision-makers should consider whether existing laboratory testing facilities meet the required standards, and the availability of other resources such as electricity for refrigeration of reagents, rotator and blood centrifuge, and if these resources are not available on-site at the point of care, then the costs of transporting laboratory samples will also need to be considered. In most settings, RSTs are less expensive than on-site and laboratory-based rapid plasma reagin (RPR) tests.
It will be essential to have accurate baseline data on the prevalence of syphilis among pregnant women, based on RPR test results which have been subsequently confirmed by Treponema pallidum haemagglutination assay (TPHA) or Treponema pallidum particle agglutination assay (TPPA). This guideline defines low syphilis prevalence as a rate that is below 5%, and high syphilis prevalence as a rate of 5% or above.
The interpretation of results and decisions about subsequent treatment regimen, based on recommendations 5, 6, 7 and 8 for the treatment of early and late syphilis in pregnant women (see section 4.3) should be specified.
5.3. SCREENING AND TREATMENT STRATEGIES AND FLOWCHARTS
STRATEGY A: SINGLE ON-SITE RST FOLLOWED BY TREATMENT IF POSITIVE
The on-site RST can be provided as a single test and treatment provided during the same visit based on the results. The RST does not, however, distinguish between the presence of previously adequately treated syphilis and untreated syphilis. Therefore, pregnant women who test positive on the RST and are treated adequately for syphilis will likely still test positive on a subsequent RST (e.g. during a subsequent pregnancy). Pregnant women who tested positive on a previous RST (e.g. during a previous pregnancy) could therefore be treated again for syphilis without repeating the RST if the risk of re-infection is considered high. Alternatively, a quantitative RPR test could be performed in these women instead of an RST (i.e. to determine the titre).
STRATEGY B: SINGLE ON-SITE RPR TEST FOLLOWED BY TREATMENT IF POSITIVE
The RPR test in this strategy is provided on-site as a single test and the results are available rapidly such that treatment can be provided the same day. This means that (as with the single on-site RST strategy), a pregnant woman can receive both testing and treatment during the same visit. If the RPR is negative, it can be repeated after approximately one month to obtain a correct (positive) diagnsosis for persons with early syphilis whose first RPR test was still negative. Women with early syphilis will be detectable by RPR test approximately a month after the onset of the primary chancre. Provision of on-site RPR will require a rotator, a blood centrifuge and a refrigerator for reagents, as well as electricity to operate this equipment.
STRATEGY C: ON-SITE RST FOLLOWED (IF POSITIVE) BY FIRST DOSE AND RPR TEST
In this strategy, an on-site RST (treponemal test) is provided to the pregnant women first. If the result is seronegative, it can be interpreted as no syphilis infection and no treatment or further testing are given. If the on-site RST is positive, immediate treatment should be given to prevent adverse outcomes of pregnancy. A single dose of benzathine penicillin will be sufficient to prevent such adverse outcomes. The woman can then proceed to further testing with an RPR test (which may be conducted on- or off-site, depending on available resources), and if this test is also positive then she should be treated appropriately for syphilis according to the determined duration of her infection (see section 4.3). If the duration is less than two years then another dose is not needed, but if the duration is unknown or greater than two years then a second dose is needed a week after the first and a third dose a week later. If the RPR is negative, however, it can be repeated after approximately one month to obtain a correct (positive) diagnosis for persons with early syphilis whose first RPR test was still negative. Women with early syphilis will become detectable by RPR test approximately a month after the onset of the primary chancre. It should be noted that as with Strategy D, this strategy may also require the pregnant woman to make two visits to the clinic if her first test was positive (i.e. to receive the results of the second [RPR] test if it was not available on-site and for further treatment if indicated), but in this strategy she will have already received her first test results and first dose of treatment (if positive) on the first visit, whereas with Strategy D she will not receive any test results or treatment on the first visit.
STRATEGY D: STANDARD LABORATORY-BASED SCREENING STRATEGY: OFF-SITE RPR OR VDRL FOLLOWED (IF POSITIVE) BY TPPA OR TPHA TEST AND FOLLOWED (IF POSITIVE) BY TREATMENT
The standard screening strategy is an RPR or VDRL test, followed (if positive) by confirmation testing using TPHA or TPPA with the same blood sample; both tests are usually conducted at an off-site laboratory. Treatment is based on confirmed syphilis. Since confirmation takes 2–3 days, this strategy typically requires the pregnant woman to make two visits to the clinic: first to provide the blood sample for testing, and second to receive the final test results and appropriate treatment.
5.4. INTERPRETATION OF SYPHILIS TEST RESULTS
Figure 2 shows an overview of the reactivity of non-treponemal and treponemal serological tests for syphilis and the effect of successful treatment. Serological tests for syphilis give only a presumptive diagnosis of syphilis and their interpretation must be made together with a good sexual history of the individual, a physical examination, information about the stage of the disease and about any other underlying diseases or infections, and considering the possibility of false-positive or false-negative reactions. If possible, positive non-treponemal tests (i.e. RPR or VDRL) should be quantified (i.e. the titres should be determined). Above all, performance of RSTs require proficiency testing of providers and ongoing performance monitoring and quality assurance with negative and positive control specimens.
Figure 2
Reactivity of serological tests by stage of syphilis and effect of treatment. Source: Unemo et al., 2013 (4).
The non-treponemal tests, such as RPR or VDRL, become positive within four to six weeks after infection, or some one to four weeks after the appearance of the chancre of primary syphilis. The tests are reactive almost without exception in secondary syphilis. As the duration of the early and late latent stages of syphilis increases, the antibody titre decreases and may eventually give a negative result in late syphilis (late latent and tertiary stages), even without treatment. With treatment, syphilis serology test may revert to negative depending on the stage of syphilis when treatment is instituted. This is more likely to happen if the individual is treated during the primary or secondary stage of syphilis. If the disease is diagnosed in late syphilis, non-treponemal tests remain positive for life.
The specific treponemal tests, including the TPHA, TPPA, FTA-ABS or RST, may become positive earlier than the non-treponemal tests. Once an individual tests positive on a treponemal test, most (85%) remain positive on subsequent treponemal tests even with successful treatment of the infection.
5.5. LABORATORY PROCEDURES AND QUALITY ASSURANCE
For details about the procedures for performing RSTs and RPR tests, refer to the WHO manual on Laboratory diagnosis of sexually transmitted infections, including human immunodeficiency virus (4).
It is essential that the quality of laboratory-based syphilis testing is maintained as part of the overall maintenance of laboratory operations. Staff performing the tests should be adequately trained and standard operating procedures should be developed. An internal quality assurance and external quality assessment system should be established, including periodic proficiency testing of staff syphilis testing skills. Consistent availability of test kits and treatment should be ensured.
