Conway, James H. MD
In 1948, the United Nations (UN) issued the Universal Declaration of Human Rights, reflecting a sense of obligation among the member nations to provide “special care and assistance” to women and children.1 That same year, the World Health Organization (WHO) Constitution stated that to achieve the objective of health for all people, the organization must “promote maternal and child health and welfare.”2 Over the following half-century, a wide array of both international governmental and nongovernmental organizations have offered periodic declarations, summits, conferences, and programs dedicated to improving the health of women and children, with modest results. Nearly 50 years later, despite the interim progress, the UN′s Millennium Development Goals announced in 2000 once again found need to assign high priority to addressing the health of women and children.3
The gains in maternal and child health throughout the world over the past 60 years have been uneven. Interventions aimed at improving nutrition, access to immunizations, and integrated disease management have had measurable benefits toward improving child survival. However, although worldwide mortality of infants and children under 5 years of age has decreased overall, significant regional differences persist, as well as marked disparities between industrialized nations and developing countries. One of the greatest areas deserving more attention is stillbirths and early childhood mortality occurring at birth or within the first 28 days of life. Current WHO estimates suggest that at least 3.3 million babies are stillborn each year, and more than 4 million die within the first 28 days of life.4 According to WHO estimates for 2000 to 2003, the leading cause of mortality in children under age 5 consistently remains neonatal issues, and the leading causes of deaths in neonates are severe infection and prematurity.4 Maternal and congenital syphilis infections likely represent a significant proportion of these deaths.
The Role of Syphilis in Newborn and Infant Mortality and Morbidity
Accurate estimates for the role of particular diseases in newborn mortality have been difficult to obtain. With only 43% of mothers and newborns worldwide receiving any perinatal care, there are concerns with the accuracy of perinatal mortality calculations.4 Using published data, Schmid et al. have attempted to determine an accurate estimate of maternal syphilis rates in developing countries and then calculate the burden of congenital syphilis from previously documented attack rates. Their findings suggest that there are approximately 2 million cases of maternal syphilis each year, with the majority occurring in sub-Saharan Africa, and between 728,547 and 1,527,560 cases of congenital syphilis annually.5
Previous studies have shown that the case-fatality rate for symptomatic congenital syphilis is at least 15% to 38% in developing countries.6 Of course, there are also significant costs that are difficult to calculate for surviving infants with congenital syphilis, because of the morbidity associated with infection, especially neurodevelopmental effects. Analysis of stillbirths, specifically, is complicated by variations in definitions and reporting systems between countries. A thorough systematic review of the literature by DiMario et al. found limited data from developing countries on specific causes of stillbirths, but concluded that conditions significantly linked to stillbirth include maternal syphilis and lack of antenatal care.7 These papers support the substantial contributing factor of syphilis in the failure of many pregnancies to produce viable offspring and for newborns to even reach infancy. Certainly, further study examining the substantial morbidity in congenital syphilis survivors is needed, and would be valuable in calculations assessing the costs and benefits of various interventions.
Approaching the Problem—Assessing Antenatal Testing Interventions
Clearly, efforts to increase capacity and access to antenatal care for pregnant women are considered critical for improving maternal–infant health conditions.4 For the control of syphilis, the key components are the availability of cost-effective rapid simple testing methods for diagnosing syphilis and provision of prompt effective treatment. Although the traditional rapid plasma reagin (RPR) has been used successfully in many settings, it does require access to basic laboratory materials and appropriately trained personnel, and for accuracy, is often coupled with a treponemal hemagglutination (TPHA) or particle agglutination assay.
Identifying a more practical test for use in rural areas is important. Bronzan et al. compared 3 different screening strategies at a clinic in rural South Africa. In their population, 6.3% of pregnant women were found to have active syphilis. They demonstrated that an on-site treponemal immunochromatographic strip (ICS) test had high sensitivity (89.4%) and specificity (92.9%), after giving additional training to the testing personnel. They reported issues with an on-site RPR having lower sensitivity and specificity compared with the ICS, largely due to inherent difficulties reported by the personnel with performing the more technically demanding test. In addition, problems with an off-site RPR were also encountered owing to issues with client return rates and lost opportunities for treatment.8 Although the ICS does not allow easy differentiation between past and current infections, given the low morbidity of penicillin treatment and the high cost of missed syphilis cases, the possibility of “overtreatment” for some women seems acceptable.
A cost analysis for implementation of these strategies in rural South Africa lends further strength to both the use of on-site testing and the role for ICS testing. Using decision-analytic cost-effectiveness modeling, Blandford et al. demonstrated that an off-site RPR/TPHA combination was the least-expensive testing strategy, but led to prevention of just over 50% of expected congenital syphilis cases. On-site RPR testing prevented less than 50% of expected congenital syphilis cases, and was also significantly more expensive than the off-site RPR/TPHA techniques. Finally, on-site ICS testing proved to be the most expensive strategy in this setting, but prevented over 80% of predicted cases of congenital syphilis. Most importantly, the cost-effectiveness of ICS improves as the prevalence of maternal syphilis increases.9 Compared with no program and the costs of neonatal mortality or survivor morbidity from congenital syphilis, these costs still should prove to be acceptable, especially in high-prevalence regions.
Analysis of the relative costs associated with introducing these testing techniques has been performed in both Bolivia and Mozambique. Levin et al. showed that using either RPR or ICS testing individually resulted in a range of 23% to 35% false-positives from RPR testing and a consistent 29% false-positive rate from ICS testing. Fortunately, the cost of treatment with a single dose of penicillin in these cases proved to be insignificant. Implementing these testing programs cannot be done without some capital investment, and approximately 80% to 90% of the costs associated with implementing these tests were primarily related to personnel and supplies, including training. Higher costs were actually associated with sites not having laboratories, and reflected higher initial training costs for sites that had not previously offered syphilis testing. Overall, in both Bolivia and Mozambique, although the ICS test was more expensive than the RPR for unit cost ($0.40 vs. $0.20), the overall cost for screening women was comparable between the two.10 Most importantly, the ICS offers an affordable, sensitive, and simple on-site screening option for rural health clinics that do not have ready access to laboratories.
Implementing Comprehensive Programs
Experience in the implementation of such antenatal screening and treatment programs in resource-poor countries offers many lessons and identifies many more challenges. Estimates from 22 countries in sub-Saharan Africa suggest that although 73% of pregnant women receive some antenatal care, only about 35% were screened for syphilis, with the costs and organization of services being the principal barriers identified.11 These can be overcome, though, and the progress of interventions made in countries like Mozambique, Bolivia, and others is a credit to determination, innovation, and the benefits of collaborative implementation.
In 1992 Mozambique had emerged from over a decade of civil strife with approximately 8% of the population infected with syphilis, as well as endemic malaria and HIV. Despite stated objectives for national antenatal care and syphilis screening, less than 5% of women were screened. Significant problems included a lack of qualified or trained staff, as well as overburdened and inadequate healthcare facilities. As described by Gloyd et al., with strong governmental policy support, including informational and educational interventions, screening rates gradually increased to >50%, but only with procedural changes in laboratory testing did testing rates exceed 90%. Treatment rates still lagged behind until the Ministry of Health managed to provide free therapy. In a relatively short period, however, by continued strengthening of the antenatal care system and changing of the norms for both the healthcare personnel and patients, testing and treatment rates in 1999 were consistently over 90%.12
Similar success is related by Garcia et al. in selected Bolivian provinces where as late as 2002 only 19.2% of antenatal clinic attendees had been tested for syphilis despite an endemic rate estimated at over 4%.13,14 With support from the Bolivian Ministry of Health and numerous other stakeholders, a program using the rapid ICS tests was implemented in 2002. Critical to the success of this program was the development of culturally appropriate materials for dissemination of information, as well as close communication with partners at all levels.13 Besides confirming a baseline 5% seropositivity rate, these investigators also demonstrated success in both rural and urban settings in providing some treatment to 93.2% of women. In addition, they were also able to identify male partners and 76.9% presented for treatment as well. On the basis of this documented success using the ICS test, the Bolivian Ministry of Health has subsequently proceeded to further expand the program for rural clinics nationwide, though still requiring extensive technical and financial support.13
As with all sexually transmitted infections, the identification of such diseases has significant impact on the social dynamic of the patient’s relationships. Reinfection is a significant risk if sexual partners of women diagnosed with syphilis are not treated as well.12 One component of the Bolivian project involved implementing a partner notification strategy that might reduce the risk of violence to the woman identified with maternal syphilis. As described by Diaz-Olavarrieta et al., women who did not fear a violent reaction from their partners were more likely to notify them of their diagnosis. In addition, the reactions by the men to these notifications were less traumatic than originally feared. This may be explained by the counseling provided to each woman in anticipation of notification, though without a control group this is unclear. Certainly, these findings suggest that screening for domestic violence and counseling about partner notification should be integrated into screening programs, to increase treatment of men and minimize the re-infection of women.15
As such successful programs grow, their success can be challenged by the complications of progress. In Mozambique, increased utilization of services leads to supply shortages, and the development of interventions for malaria and HIV lead to a strain on the organization of the antenatal system. Only by carefully managing the workforce, healthcare system, and facilities, and enlisting community involvement, leadership, and outside financial support could these challenges be met.12 Other challenges derive from the root cause of much of the turmoil and poverty seen in these affected countries. In Bolivia, political instability and ongoing civil disorder required frequent adjustments to changing personnel and effective communication skills. Remote clinics and logistics related to travel remain a challenge in many areas, where the overall infrastructure requires extensive improvements.13
Setting Policy and Priorities to Eliminate the Burden
Recognizing that syphilis is a fully treatable and curable condition, the WHO has proposed a strategy for prevention and control with the goal to eliminate congenital syphilis. These 4 “pillars” include sustained political commitment and advocacy, increased access to quality maternal and newborn health services, screening and treatment of all pregnant women, and establishing improved surveillance systems with comprehensive monitoring and evaluation. Besides identifying syphilis eradication as a priority, suggested principles to achieve success include integrated partnerships both within and between nations that provide a rights-based approach for women.5,16 Establishing national programs that integrate these 4 pillars into practice will likely not only impact congenital syphilis but also address the Millennium Development Goals of reducing infant mortality, improving maternal health, and combating HIV/AIDS and other diseases.3
Yet Hossain et al. have found implementation of these pillars quite variable among 14 countries analyzed. National policies and strategies were identified and compared with the WHO congenital syphilis elimination strategy. As expected, the gap between stated objectives and implementation of programs is wide, and there is considerable variation within countries as to the effectiveness of programs. Interestingly, financial resources do not appear to be the sole limiting factor, though affordability for national programs is a concern. Industrialized countries with low prevalence rates for syphilis have neglected to prioritize syphilis control, with antenatal screening programs inconsistent.16 As the incidence of disease diminishes, the cost-effectiveness of programs similarly declines, though still remaining cost-effective. A reemergence of syphilis in such a setting is not only possible but well documented in many more developed countries.17 It is essential for policymakers to appreciate that on-site antenatal syphilis screening and treatment is just as cost-effective as prevention of maternal-to-child HIV transmission, and that there can be synergy between such programs that improve the economy of each.18
Given the limited resources available in areas where rates of maternal syphilis remain high, cost-effective strategies must be utilized and implemented with urgency to control the burden of congenital syphilis. Improved quality and access to antenatal screening clinics where rapid syphilis testing and treatment are available is critical. Screening for domestic violence risks, counseling, and partner notification for treatment cannot be underestimated as crucial in breaking the cycle of reinfection. Ongoing disease surveillance must continue, and be expanded, to better appreciate the ramifications of syphilis infections and to allow continued modification and improvements of interventions.
Most important is the integration of these programs with other interventions and public health initiatives, with adequate financial support, to increase the number of pregnancies where antenatal and perinatal care is available. Almost as essential, though, is the continuation of such programs when disease rates fall, since despite the perception of diminishing cost-effectiveness, this is the only means by which eradication of syphilis can be achieved. And eradication is both feasible and necessary.
Only by making a unified, well-financed, sustained, and concerted effort to incorporate and enact the pillars of syphilis eradication into routine healthcare and national health policy will the burden of congenital syphilis be lifted from the women and children of the world. And only when that happens can we begin to fulfil the UN and WHO promises of 1948, and truly improve the health of women and children.
The time is now.
4. World Health Organization. The World Health Report 2005: Make Every Mother and Child Count. Geneva, Switzerland: WHO Press, 2005.
5. Schmid GP, Stoner B, Hawkes S, et al. The need and plan to eliminate congenital syphilis. Sex Transm Dis 2007; 34 Supplement:S5–S10.
6. Saloojee H, Velaphi S, Goga Y, et al. The prevention and management of congenital syphilis: An overview and recommendations. Bull World Health Organ 2004; 82:424–430.
7. DiMario S, Say L, Lincetto O. The multiple origins of stillbirth in developing countries: A systematic review of the literature. Sex Transm Dis 2007; 34 Supplement:S11–S21.
8. Bronzan RN, Mwesigwa-Kayongo DC, Narkunas D, et al. Onsite rapid antenatal syphilis screening with an immunochromatographic strip improves case detection and treatment in rural South African clinics. Sex Transm Dis 2007; 34 Supplement:S55–S60.
9. Blandford JM, Gift TL, Vasaikar S, et al. Cost-effectiveness of on-site antenatal screening to prevent congenital syphilis in rural eastern Cape Province, Republic of South Africa. Sex Transm Dis 2007; 34 Supplement:S61–S66.
10. Levin C, Steele M, Atherly D, et al. Analysis of operational costs of using rapid syphilis tests for the detection of maternal syphilis in Bolivia and Mozambique. Sex Transm Dis 2007; 34 Supplement:S47–S54.
11. Gloyd S, Chai S, Mercer MA. Antenatal syphilis in sub-Saharan Africa: Missed opportunities for mortality reduction. Health Policy Plan 2001; 16:29–34.
12. Gloyd S, Montoya P, Floriano F, et al. Scaling up antenatal syphilis screening in Mozambique. Sex Transm Dis 2007; 34 Supplement:S31–S36.
13. Garcia SG, Tinajeros F, Revollo R, et al. Demonstrating public health at work: A demonstration project of congenital syphilis prevention efforts in Bolivia. Sex Transm Dis 2007; 34 Supplement:S37–S41.
14. Southwick KL, Blanco S, Santander A, et al. Maternal and congenital syphilis programmes: Case studies in Bolivia, Kenya and South Africa. Bull World Health Organ 2001; 79:33–42.
15. Diaz-Olavarrieta C, Garcia SG, Feldman BS, et al. Maternal syphilis and domestic violence in Bolivia: A gender-based analysis of implications for partner notification and universal screening. Sex Transm Dis 2007; 34 Supplement:S42–S46.
16. Hossain M, Broutet N, Hawkes S. The elimination of congenital syphilis: A comparison of national policies to the World Health Organization proposed action plan for the elimination of congenital syphilis. Sex Transm Dis 2007; 34 Supplement:S22–S30.
17. Walker DG, Walker GJA. Forgotten but not gone: The continuing scourge of congenital syphilis. Lancet Infect Dis 2002; 2:432–436.
18. Terris-Prestholt F, Watson-Jones D, Mugeye K, et al. Is antenatal syphilis screening still cost-effective in sub-Saharan Africa. Sex Transm Infect 2003; 79:375–381.