Single dose treatment of syphilis is effective and cost-effective
Maternal syphilis, left untreated, continues to be an important risk factor for adverse pregnancy outcome in Tanzania (Watson-Jones et al. 2002b; Terris-Prestholt et al. 2003). This risk is especially high in mothers with high RPR test titres, observed in earlier stages of infection (Watson-Jones et al. 2002a), and is consistent with an earlier African study (Schultz et al. 1987). There remain no data from randomized trials comparing single with triple dose benzathine penicillin therapy, but our data suggest that single dose treatment is effective in preventing stillbirth and LBW in women with syphilis, including those with HTS, the stage of untreated syphilis most strongly associated with poor birth outcome (Watson-Jones et al. 2002b).
Our cost analysis of syphilis screening and treatment in Tanzania also shows that this is a highly cost-effective intervention (Terris-Prestholt et al. 2003). Earlier studies estimated that the cost of antenatal syphilis screening compared well with other childhood interventions (Schultz et al. 1992). In the context of the HIV epidemic in Africa, the cost of syphilis screening and treatment ($10.56 per DALY saved) compares favourably to that of nevirapine treatment for HIV-PMTCT in Uganda ($11.19) (Marseille et al. 1999).
Routine implementation faces operational obstacles
The reality, however, is that antenatal syphilis screening is failing across sub-Saharan Africa. Based on the limited coverage from 22 African countries (Gloyd et al. 2001), it has been estimated that with these coverage levels and a mean 8.3% prevalence of active syphilis, approximately 630 000 women are screened and treated while another 1 640 000 seropositive pregnant women remain untreated, of whom 1 030 000 (63%) will have attended antenatal services. Assuming RPR-positive women would have similar rates of HTS as in Mwanza (27%) and that they would experience a similar rate of adverse outcomes as observed in untreated women in Mwanza (49%) (Watson-Jones et al. 2002a), a total of 136 269 adverse birth outcomes could potentially be averted by screening and treatment.
In principle, a single visit for on-site testing and same-day treatment should improve the uptake of syphilis screening (Watson-Jones et al. 2002a). This is important in the context of sub-Saharan Africa where women frequently fail to re-attend for treatment (Jenniskens et al. 1995; Fonck et al. 2001). Despite the fact that Tanzania has decided to implement a decentralised screening service, however, a disappointingly low proportion of ANC attenders are successfully screened and treated at PHC level.
Screening and single-dose treatment are clinically effective and cost-effective, and the procedures are simple, implying that antenatal syphilis screening should be feasible and affordable. What remain to be addressed, however, are the operational barriers at the ANC level, as well as the political will and financial constraints within the health system.
Obstacles to successful implementation include the organization of services, costs of treatment, transport costs to health facilities performing testing and low priority at government level (Gloyd et al. 2001), as well as staff training, monitoring, quality control and logistics. Improvements can be effective, as shown by an evaluation of the antenatal syphilis screening programme in Nairobi, which currently has a 3.4% RPR seroprevalence. Overall, 91% of RPR-positive women received prompt treatment (Fonck et al. 2001). The programme started with an intensive monitoring and evaluation phase in 1993 but, over time, observed a decline in the quality of RPR testing (Fonck et al. 2001). The authors concluded that maintaining a high level of quality control and supervision was difficult, and may be impossible in some remote settings, and that in Nairobi mass treatment with penicillin in pregnancy may be equally cost-effective. However, the acceptability and effectiveness of this strategy are unproven.
Further research is needed on several specific components of syphilis screening programmes. The simple and cheap RPR test, recommended as a suitable screening test for syphilis (World Health Organisation 2001; Centers for Disease Control and Prevention 2002), is time-consuming, subjective to interpret and therefore requires some experience to recognize a positive test. Although the RPR antigen is relatively stable at room temperature (van Dyck et al. 2001), storage between 2 and 8 °C is recommended, which is difficult at the PHC level. It is unclear how much this affects test performance as there are few sites implementing regular quality control exercises. Our observations in Tanzania also highlight the difficulties in ensuring that HCW actually perform this test and show that there are basic misunderstandings about the testing procedure. In Nairobi, there was also wide variation in performance at different clinics within the city (Jenniskens et al. 1995). Wide variations are likely in other countries where refresher training and quality assurance of programme activities are infrequent.
There has long been an urgent need for simple rapid screening tests for syphilis and other STI. Several dipstick-type Treponema-specific serological tests for syphilis are now on the market (Mabey and Peeling 2002). These new tests, whose advantages and limitations are shown in Table 3, could greatly simplify ANC syphilis screening, because of their ease of use even under the most rudimentary conditions. Like other Treponema-specific tests, however, they do not distinguish between previously treated and untreated infections and, in areas of high syphilis prevalence, these tests may best be used in conjunction with RPR results.
Table 3. Advantages and limitations of Treponema-specific rapid diagnostic tests for on-site antenatal syphilis screening
| Simplicity and speed (some tests can use whole blood rather then serum)|
| Reduces the time-consuming procedure of serum separation|
| Avoids 8-min shaking procedure required for RPR test|
| Shorter waiting time for patient to receive results|
| In most cases these tests are easier to read than agglutination tests|
| May reduce need for staff training and quality control that is essential to maintain screening performance using subjective RPR test|
| Less subjective therefore improves the performance of on-site syphilis testing|
| Less expensive (Some tests can use a finger-prick specimen of capillary blood)|
| Lancets are cheaper than needle and syringes or vacutainer systems|
| No RPR test cards or test-tubes or racks required|
| Reagents can in most cases be stored at room temperature|
| Treatment costs for women with biological false positive RPR reactions would be avoided|
| Finger prick blood can be messy to handle|
| Patient's preference for venous blood collection which appears more ‘serious’ in some settings|
| Cannot distinguish between past and present infections|
| Lifetime positivity means difficulty in interpretation in subsequent tests – may require ‘confirmatory’ RPR test|
| Cost of tests still high|
Treatment of sexual partners is a recommended component of syphilis programmes in order to prevent congenital syphilis because of maternal re-infection (World Health Organization 2001; Centers for Disease Control and Prevention 2002). The CE of this strategy has never been rigorously evaluated in sub-Saharan Africa (Mathews et al. 2001). First, there are few data on its actual efficacy. One study in Nairobi found that RPR-positive women whose partners attended for treatment had a better pregnancy outcome than those whose partners did not attend (Gichangi et al. 2000). However, this analysis was not adjusted for other variables that might have influenced birth outcome. Secondly, the effectiveness of the intervention would depend on its coverage. In Tanzania, uptake of treatment by partners has proved to be low (Watson-Jones et al. 2002b), as in other countries where it varies between 15 and 75% (Jenniskens et al. 1995; Gichangi et al. 2000; Fonck et al. 2001). Barriers to successful partner notification in Africa include inadequate counselling, short-term or casual relationships and fear of informing partners (St Louis 1996; Fonck et al. 2001). Thirdly, doubts have been raised as to whether partner notification has any practical impact on syphilis transmission because those most at risk of infection may not be traceable or may not choose to attend for treatment (Andrus et al. 1990; St Louis 1996). Certainly, both in Mwanza and South Africa (Donders et al. 1997), over 60% of contacts presenting to the clinic were syphilis seronegative. In our study, overall 42 of 203 (21%) attending male contacts with complete serology results were RPR and TPHA positive. The rate of seropositivity was significantly higher among partners of women with HTS (32%), but a strategy targeting partners of women with a confirmed RPR test (either HTS or LTS), or indeed only women with HTS, would fail to identify a high proportion of truly infected men: 7% (3/42) in the former group, 62% (26/42) in the latter. In summary, there are insufficient data from developing countries on the quality of partner notification, the consequences for the infected index case and their contacts, the CE and overall impact on syphilis transmission of any contact tracing strategy, but there is some evidence that it identifies a significant number of men who otherwise would be left untreated.
Despite these uncertainties, it is important that policy makers and HCW recognize that syphilis screening is an essential component of antenatal care. Moreover, we know that syphilis is capable of re-emerging in populations extremely rapidly when prevention efforts decline or collapse (Nanda et al. 1990; Imperato 1991; Cossa et al. 1994; Borisenko et al. 1999). There is an array of cheap and simple screening tests, an effective treatment, and the cost per DALY saved is at least comparable with that of HIV-PMTCT. Furthermore, there is evidence that antenatal syphilis screening may help to reduce the heterosexual transmission of syphilis as the prevalence of syphilis is declining in sites such as Nairobi where screening and partner notification have been implemented for some years (Temmerman et al. 1999).
Integration and sharing lessons learned
Syphilis screening as a routine antenatal intervention must not be neglected in the context of initiatives to prevent maternal transmission of HIV. Syphilis might not carry the same stigma associated with HIV, given the relatively high rate of women accepting the tests, and of their male partners coming forward, and because syphilis is a curable disease. Indeed, HIV surveillance and interventions have often been piggy-backed onto antenatal syphilis screening services. Conversely, efforts to provide wide-scale HIV-PMTCT programmes would provide an excellent opportunity to strengthen antenatal syphilis screening. Both interventions are aimed at the same target population, are sited in the same facilities, face similar logistical challenges, involve the same HCW and require a blood sample to be taken after pre-test discussion. At present, however, HIV prevention and treatment services are often organized vertically, and this is likely to lead over time to increased costs and fragmentation as observed in other vertical programmes. The need to develop models of integration must be addressed now, while PMTCT initiatives are still in their developmental phase.
Studies in South Africa, Nairobi and Mwanza have demonstrated that effective syphilis screening programmes can be implemented through the PHC system if these programmes are given sufficient support through training, adequate supervision and availability of resources, and that these programmes are capable of significantly reducing adverse pregnancy outcomes attributable to syphilis (Wilkinson & Sach 1998; Temmerman et al. 2000; Watson-Jones et al. 2002b). Data on the implementation of PMTCT programmes suggest that there are a number of problems related to achieving coverage and retention of patients, and that costs are much higher than in pilot or trial conditions (Stringer et al. 2003). Experience from syphilis screening also highlights the potential problems faced by new PMTCT programmes as they try to increase coverage. Adequate training, continuity of supplies of testing kits, consumables and drugs, supervision and quality control are all essential if the quality of the intervention is to be sustained.
There is a need for genuine recognition by donors and policy makers that syphilis control and PMTCT of HIV are complementary. PMTCT programmes have a much larger funding base and their system requirements are greater but they will likely remain poorly implemented in areas where there are currently no sustainable systems for syphilis screening and management. PMTCT of HIV, maternal syphilis screening and other ANC interventions would benefit greatly from closer collaboration as part of an integrated reproductive health programme. As governments grapple with decentralization of health services, integration would help to ensure that evidence-based ANC interventions such as syphilis screening, malarial prophylaxis and vitamin supplementation do not drop off the agenda in the face of pressure to implement HIV-PMTCT through vertical programmes.