Blandford JM, Gift TL, Vasaikar S, Mwesigwa-Kayongo D, Dlali P, Bronzan RN. Cost-effectiveness of on-site antenatal screening to prevent congenital syphilis in rural eastern Cape Province, Republic of South Africa. Sex Transm Dis 2007 Jul;34(7 Suppl):S61-6.
To evaluate the health outcomes and associated costs of on-site screening and same-day treatment of maternal syphilis in low-resource settings.
This modeling study used decision analysis to estimate the incremental cost-effectiveness of two on-site antenatal syphilis screening strategies to avert congenital infections: 1) qualitative RPR (on-site RPR); and 2) treponemal immunochromatographic strip assay (on-site ICS), both compared to the current practice of off-site RPR/TPHA.
The model used data from antenatal clinics (ANCs) in South Africa's Eastern Cape, and the cost-effectiveness analysis was done from the perspective of the Eastern Cape Provincial Department of Health.
Primary data were collected from ANC attendees from December 2001 through March 2002.
Using DATA Pro, the model compared two on-site syphilis testing methods with existing off-site testing methods. The time frame of the analysis was the period of gestation, and the analytic horizon considered pregnancy outcomes through birth. Variables included in the analysis were based on primary data collected during the study, published data, and prices quoted by local suppliers. Syphilis prevalence data among attendees were established through collection of serum specimens from participants and testing at a reference laboratory. Staging of disease was based on results of quantitative RPR and confirmatory TPHA and was characterized as: 1) high-titer active; 2) low-titer active; or 3) past or previously treated disease or biologic false positive. The estimated probability of fetal transmission was 0.94 for high-titer active maternal infection, 0.37 for low-titer active maternal infection, and zero for past infections or biologic false positives. A maternal syphilis infection was estimated to increase the likelihood of spontaneous abortion to three to four times greater than the background rate. The likelihood of cure of maternal syphilis was estimated to be 0.97 and the fetus received full efficacy of therapy (0.97). Additional probabilities incorporated into the model included return rates for subsequent treatment, likelihood of valid test results being received by clinics doing off-site evaluation, and treatment refusal rates. The sensitivity and specificity of the off-site RPR/TPHS was assumed to be perfect. The proportion of live-born infants being diagnosed with syphilis and receiving treatment was estimated at 30%. Costs not considered included medical costs beyond initial treatment of infected infants, long-term direct medical costs of maternal infection, lost productivity, or long-term sequelae of untreated infections.
The primary outcomes for this modeling study were: averted adverse congenital syphilis (CS) events, specified as spontaneous abortion, perinatal death, and infants born infected with syphilis.
With no screening program, the model predicted that 33 CS cases per 1,000 pregnancies would result. Off-site RPR/TPHA was the least expensive screening option, and prevented 18 of 33 cases at a cost of USD$ 2,841 per 1,000 ANC patients screened. On-site RPR would be less effective and more expensive, preventing 15 of 33 cases at a cost of USD$ 2,950. On-site ICS was the most expensive and the most effective screening option, averting 27 of 33 cases at a cost of USD$ 3,779 per 1,000 ANC patients screened.
Incremental cost-effectiveness ratios: Compared to no program, adopting off-site RPR/TPHA would avert 18 of the expected 33 CS cases per 1,000 pregnancies at a cost of USD$ 82 per case. Adoption of on-site ICS would result in the aversion of 27 of the 33 cases per 1,000 pregnancies, or nine additional cases compared to off-site screening, resulting in an incremental cost-effectiveness ratio of USD$ 104 per case.
Sensitivity analyses: Results were stable over a wide range of probability and cost estimates. In one-way analyses, the modeled effectiveness of ANC screening approaches was most affected by test sensitivity of on-site ICS in detecting high- and low-titer maternal infections. Even at lower extremes of test sensitivity, however, the number of averted CS cases exceeded that of other screening approaches. In multi-way analyses, only extreme assumptions would drive effectiveness of on-site ICS below that of other screening approaches. The most influential factors in determining the relative cost-effectiveness were prevalence of maternal syphilis and the relative distribution of active and past disease. As estimates of maternal prevalence increased, on-site ICS became more cost-effective. On-site ICS was sensitive to the prevalence of past disease, implying that relative cost-effectiveness would increase as rates of past disease increased, driven by the costs of unnecessary treatment following misdiagnosis. With the assumption of zero probability of congenital transmission of low-titer infections (as was found in a Tanzanian study(1,2)), on-site ICS would remain the most effective screening approach. Incorporating a further assumption of decreased likelihood of adverse outcomes resulting from high-titer active infections had no significant impact on the relative effectiveness of the screening strategies, but would increase the incremental cost-effectiveness ratios of the strategies.
The authors conclude that implementation of on-site screening with ICS may be a highly effective approach to avert adverse congenital syphilis events and to effectively treat syphilis infections of patients seeking antenatal care in high-prevalence setting,.
As with all cost-effectiveness modeling, the conclusions may be affected by the assumptions used. The authors note that the relative performance of on-site ICS and on-site RPR would improve if the assumed perfect accuracy of the off-site RPR/TPHA strategy decreased, if transportation difficulties increased, or if the models included patient time, costs, and/or lost productivity. The exclusion of user fees would go against the more expensive on-site ICS.
A recent study found that programs offering on-site rapid syphilis testing and treatment in ANCs in South Africa leads to detection and treatment of the majority of maternal syphilis infections, averting a significant number of adverse pregnancy outcomes.(3) Cost-effectiveness analyses are necessary to determine the relative effectiveness of alternative screening methods and to make informed health policy decisions.
While the incremental cost-effectiveness of off-site RPR/TPHA was marginally less than that of on-site ICS, both screening strategies may be considered cost-effective, depending on the available resources of the relevant funding authority and public priorities for syphilis control in mothers and infants. Epidemiologic context is also important and the relative cost-effectiveness of testing strategies will depend on rates and distribution of active and past syphilis infections. Another consideration is the inability of ICS to distinguish active from past infections, leading to over-treatment of some patients.
- Watson-Jones D, Changalucha J, Gumodoka B, Weiss H, Rusizoka M, Ndeki L, et al. Syphilis in pregnancy in Tanzania. I. Impact of maternal syphilis on outcome of pregnancy. J Infect Dis. 2002 Oct 1;186(7):940-7.
- Watson-Jones D, Gumodoka B, Weiss H, Changalucha J, Todd J, Mugeye K, et al. Syphilis in pregnancy in Tanzania. II. The effectiveness of antenatal syphilis screening and single-dose benzathine penicillin treatment for the prevention of adverse pregnancy outcomes. J Infect Dis 2002 Oct 1;186(7):948-57.
- Bronzan RN, Mwesigwa-Kayongo DC, Narkunas D, Schmid GP, Neilsen GA, Ballard RC, et al. On-site rapid antenatal syphilis screening with an immunochromatographic strip improves case detection and treatment in rural South African clinics. Sex Transm Dis 2007 Jul;34(7 Suppl):S55-60.