Global Burden of Congenital Syphilis
Congenital syphilis (CS) continues to appear in both developed and developing countries despite the availability of feasible, cost-effective interventions to detect, treat, and monitor this preventable infection.1,2 Although estimates of the global burden of CS and maternal syphilis vary, the levels are consistently high. Spontaneous abortion, stillbirth or CS in pregnancies of 12 weeks gestation or more are estimated in 50–80% of maternal syphilis cases.3 CS may also account for 21% of perinatal deaths in sub-Saharan Africa alone,4 where approximately 2 million women with active syphilis become pregnant. According to the 2000 Global Burden of Disease estimates, CS may also be attributable to 1.3% of deaths among children under the age of 5.5 Estimates for the annual global number of CS cases range from 713,600 to 1,575,000.6 These and other estimates suggest that the incidence and burden of CS among neonates may exceed that of HIV.7 In 2001, approximately 2.6 million HIV infected women became pregnant and 720,000 HIV-infected infants were born.8,9
Consequently, the elimination of CS is an important global objective that is not only technically achievable, but also impacts the more broad-ranging targets of the UN Millennium Development Goals including: (goal 4) Reduce infant mortality; (goal 5) Improve maternal health; and (goal 6) Combat HIV/AIDS and other diseases.10
Lessons Learned From the History of Syphilis Control
Records of early attempts to understand and control syphilis can be found as early as the 15th century.11 Throughout Europe, legislation once penalized infected individuals who knowingly infected others or did not complete treatment.11–14 The introduction of the Wasserman test in 190715 helped to increase the momentum of “venereal disease” control efforts, and public health efforts began to adapt to the changing epidemiologic nature and social perception of a stigmatized infection.16,17 By 1943, “rapid treatment centers” were available in the United States with 5–10 days of arsenical therapy18 and in Europe, venereal disease clinics opened providing free and confidential treatment with Ehrlich’s salvarsan treatment.19 Countries such as the United States saw a 90% decline in CS between 1941 and 1972 with the widespread availability of screening and penicillin, the promotion of partner treatment, and blood donor screening.18,20,21
Other examples of successful early syphilis control policies have been noted in several Scandinavian countries. The incidence of syphilis in the general population decreased between 1919 and 1933 from 119 to 20 per 100,000 in Denmark, 97 to 7 per 100,000 in Sweden, and 360 to 30 per 100,000 in Norway. (Details on tests used to measured incidence for these reported figures were not available.) These accomplishments have been credited to policies providing free treatment, case finding and control, and public education. A high degree of political will and cooperation between medical professionals and the national health department, a homogenous population, low levels of diagnosis and treatment by untrained individuals, and prompt and adequate treatment have been attributed to its success.22 Initial public health efforts to combat this preventable infection in pregnancy arose in the 1940s in the form of antenatal syphilis screening and surveillance programs.19
Historically, the approaches and concepts developed by syphilis-control strategies over a century ago have provided a valuable model used by current sexually transmitted infection (STI) control programs, including HIV/AIDS.18 The original syphilis-control model included: early identification, effective treatment of the index case and partner, follow-up, and behavioral modification of risky sexual practices—-all components of modern-day STI control based on an individual approach.23 Although the historical lessons of syphilis control are applicable to CS control policies today and also provide insights for HIV/AIDS control, more attention could be paid to the delivery of a comprehensive public health approach for controlling and eliminating CS. A higher level of programmatic success is likely if CS control is integrated alongside programs to reduce overall levels of syphilis (and other genital ulcer diseases) in the adult population. Notably, many of the building blocks of a successful CS elimination program—-such as high antenatal care attendance levels, cost-effective diagnostic testing, and the widespread availability of penicillin—-are already in place across most countries.
Creating the WHO Action Plan
With many countries already working towards controlling or eliminating CS, in 2003 the World Health Organization (WHO) commissioned a series of reviews and consultations on maternal and CS highlighting the continuing problem of CS worldwide. Based upon the evidence of the reviews, a general framework was created that could be tailored to the resource and disease burden in individual countries. WHO identified 4 pillars that form the basis of the proposed action plan:
* Pillar 1: Ensure advocacy and sustained political commitment for a successful health initiative;
* Pillar 2: Increase access to and quality of maternal and newborn health services;
* Pillar 3: Screen and treat all pregnant women and partners; and
* Pillar 4: Establish surveillance, monitoring, and evaluation systems.6
The proposed WHO action plan is designed to be adapted to local contexts but operates under common guiding implementation principles. These include (1) the creation of a country-driven process that encourages the commitment and participation at the national and local level; (2) the coordination and integration of CS elimination efforts with existing national interventions (i.e., safe motherhood, reproductive health, HIV/PMCT, STI control, etc.); (3) a rights-based approach to diagnosis and treatment where patients have the right to information for prevention as well as the right to seek and receive high-quality treatment; (4) the use of existing tools and technologies; and (5) improving access to and the quality of antenatal care and other health services.
This paper compares a sample of existing national-level maternal and CS control policies against the 4 strategic pillars of the proposed WHO action plan. The objective of the review was to identify areas of commonality or divergence between the national strategies and the WHO plan, thereby helping to target the development of national-level policies in light of the forthcoming recommendations of the proposed WHO action plan to eliminate CS.
The included policies represent a sample of countries with a range of resources and CS prevalence levels. They represent a convenience sample and are not intended to reflect all existing policies.
Policy documents and national treatment protocols were compiled through a desk-based review. When original documents could not be located, national strategies were extracted from published literature. The policies were derived from the following types of sources: (1) government health care policies addressing maternal syphilis or CS prevention, control, or elimination; or (2) maternal syphilis or CS pilot programs conducted in conjunction with individual Ministry/Department of Health offices. Surveillance data from published or unpublished sources and epidemiologic studies for maternal syphilis and CS, antenatal care (ANC) attendance, screening rates among pregnant women, and treatment rates were considered. Where possible, data were corroborated from 2 or more sources. With the exception of policy documents from Haiti (French) and Brazil (Portuguese), English or translated versions of the policies were used.
Search Strategy for Existing Policies, Guidelines, and Supporting Data
Original policy documents were located through available national health Internet sites; electronic correspondence with national coordinators of STIs or Ministry/Department of Health offices; citations in published literature; and electronic searching of policy-related sites, grey-literature (information produced in formats not controlled by commercial publishing) gateway sites, and nongovernmental sites. Inquiries through government offices were made but did not yield a high response rate.
Due to the limited availability of national-level evaluation data, a systematic search for studies related to existing maternal syphilis and CS policies was conducted. For each country strategy, records from 6 major medical databases (PubMed, Popline, CAB Abstracts, ISI Web of Knowledge, Cochrane Library, SciELO) were also searched using a set of terms based on combinations of the word syphilis with some or all of the words—-congenital, women, pregnancy, screening, antenatal, prenatal, policy, elimination, management, strategy, diagnosis, plan, testing, screening, service utilization, delivery, partner treatment, contact tracing, prevention, control, treponemal, STD, or STI. MeSH terms, key words, and free-text approaches were utilized, and database dependent. Reference lists and both regional and specialist journals were searched for relevant citations. Additional references were obtained through experts at WHO that provided advice on possible resources. Studies were excluded if they described drug therapies only, evaluated high-risk populations only, did not include a valid comparison group, or described only socioeconomic risk factors. Studies were considered to be outside the scope of this report if they were not relevant to primary care or an antenatal population, unrelated to the current policy, or conducted before policy implementation.
Eleven possible variables were extracted to identify policy goals and policy activities including: national syphilis screening policy goals, CS definition, policy implementation years, national targets, national strategy, ANC coverage, ANC syphilis screening rates, follow-up policy, partner treatment strategy health promotion goals, surveillance agency, and funding source.
Using the proposed WHO action plan as a comparative framework, each country’s policies were assessed against the pillars and selected key implementation indicators. Policies were considered to have met a WHO-defined indicator if a policy document, national guidelines or protocols, or a research study with government involvement stated a similar policy goal or implementation measure. The degree of implementation of the identified policies was not evaluated.
Maternal syphilis or CS control policies from 14 countries were identified and compared to the proposed WHO action plan for the elimination of CS. The policy sources included 19 official policy or guideline documents, 4 additional country policy descriptions found through published peer-reviewed studies, 14 documents describing national surveillance figures, and 71 peer-reviewed operational research studies. The 14 country policies included: Australia, Canada, England, New Zealand, and the United States (countries with a low CS prevalence level), as well as Bolivia, Brazil, Ethiopia, Haiti, Kenya, Malawi, Mozambique, the Russian Federation and Tanzania (countries with a mid- to-high CS prevalence level).
WHO Pillar 1: Ensure Advocacy and Sustained Political Commitment for a Successful Health Initiative
Evidence for ensuring advocacy and sustained political commitment for a successful health initiative varied. CS elimination goals were noted in only 3 countries—-Bolivia, Brazil, and the United States—-using similar strategy goals and components, including enhanced surveillance and testing during ANC and delivery.24–27 Bolivia and Brazil have based their broad universal strategies upon PAHO’s (Pan-American Health Organization) recommendations to reduce the rate of CS to <0.5 cases per 1000 live births through an increase in ANC, routine serological syphilis testing during ANC and delivery, and the rapid treatment of seropositive pregnant women.28 The United States has adopted detailed elimination efforts targeting high-risk populations.26 Canada, on the other hand, has defined its efforts to control infectious syphilis cases among the general population with a specified maintenance goal of 0.5 per 100,000 population infectious syphilis cases. It has continued to provide universal antenatal screening due to a recent resurgence of infectious syphilis.29
Universal screening policies existed in all 14 countries. Two countries with a high CS prevalence, Haiti and Malawi, have specified antenatal syphilis screening as a part of their overall HIV/AIDS strategy for the prevention of mother-to-child transmission (PMTCT).30–32 Although recommended in the low CS prevalence countries examined, recent research suggests that provider adherence varied in Australia, England, New Zealand, and the United States, where screening is not necessarily performed during routine antenatal care visits.33–40 Nine countries had evidence of programs primarily funded with committed government funds. Eleven countries, with both low and high CS prevalence levels, have incorporated CS control policies (i.e., ANC screening and testing) into national maternal-newborn health (MNH), PMTCT of HIV, or STI prevention or treatment policies.27,29–32,37,41–45 Kenya, Malawi, Mozambique, Ethiopia, and Tanzania have partnered with foreign donors to strengthen their antenatal screening policies.31,32,43,46–52
WHO Pillar 2: Increase Access to, and Quality of, Maternal and Newborn Health Services
The proposed WHO action plan was designed to reflect differences between areas with accessible services and those without. Evidence for increasing access to, and quality of, health services varied by country resource level. Eight countries recommended measures to ensure all pregnant women were screened and treated,27,29,37,53–58 which included standardized protocols and guidelines, with 7 of these having high national ANC coverage (83–100%).59–68
Four country policies mention improvements to the quality of MNH care.27,42,50,51 Of the 8 countries with limited resources or in the early stages of their control effort, 6 had formed partnerships with international research, community or nongovernmental organizations (NGOs) in order to pilot test the efficacy of point-of-care testing and/or treatment for policy and programming purposes.42,43,46,47,56,69–71 Three low-CS prevalence countries provided information on health promotion programs.26,29,36,41 No information was available on strategies specific to maternal or CS for increasing access in areas where service accessibility was limited.
WHO Pillar 3: Screen and Treat Pregnant Women and Partners
Three of the 14 countries recommended or had recently pilot-tested point-of-care testing for all pregnant women.43,44,46,47,69,72,73 Kenya and Haiti are examples of countries where the efficacy and feasibility of decentralized testing and treatment were evaluated with the intention of developing national policy and programming.
ANC syphilis screening varied greatly both between and within countries with ranges from 17% to 88% in Bolivia,28,46,54 63.6% to 79.7% in Brazil,24 51% to 81% in Kenya,47,74 43.2% in Malawi,75 <5% to 40% in Mozambique,48 83.2% in Tanzania,76 and 32% to 98.2% in the United States.77–80 Among the few existing studies documenting provider adherence, the range was wide, with no country documenting screening 100% of pregnant women receiving antenatal care.28,35,43,47,54,75–81
In addition, despite national-level recommendations and protocols, regional screening and treatment practices varied. The United States has an active national plan for syphilis elimination, but only 46 of the 50 states recommend screening during pregnancy or delivery.40
The WHO-recommended treatment for syphilis in pregnant women includes a single dose treatment (2.4 U intramuscularly benzathine penicillin) for the effective prevention of CS.82 Treatment guidelines, which included recommendations for a single-dose treatment, were noted in Australia, New Zealand,83 United States,26 Kenya,46 Canada,29 Brazil,84 England,85 and Tanzania.86 In addition, recommendations for partner treatment were noted in 9 policies.37,70,84,87–91
WHO Pillar 4: Establish Surveillance, Monitoring, and Evaluation Systems
Details on comprehensive monitoring and evaluation components were lacking in nearly all countries and an essential component—-prevalence data on syphilis cases in pregnancy and CS—-was limited. In addition, a uniform definition has yet to be decided as CS case definitions for reporting varied between countries. Although evidence for active surveillance programs was noted in 10 countries, national statistics on CS cases were accessible from only 6 (Australia,92 Canada,93,94 New Zealand,95,96 England,97 Russian Federation,98 and the United States99). Other countries such as Brazil have only recently implemented national surveillance systems.45 Sentinel surveillance sites were noted among 4 countries (Brazil,45 Kenya,100 Malawi,101 and Tanzania44,102).
This review examined a sample of policies in 14 countries to gain an overview of current national-level maternal and CS control and elimination efforts. The policies represent each nation’s commitment to their individual goal of reducing or eliminating CS and provide the working guidelines around which each national health system operates. Based upon the policy comparison with the proposed WHO action plan to eliminate CS, the evidence highlights areas where countries can target the development of national-level policies in light of the forthcoming WHO action plan.
Several limitations existed for this review. First, policies were obtained through electronic means rather than country site visits. This method potentially skews the policies towards countries with greater research or outside donor involvement as health officials may not have had the resources to respond to policy queries or provide translations of relevant documents. Second, the majority of documents were restricted to English thereby limiting the geographical focus of the review. Third, as a result of the above mentioned, we were unable to ensure that the policies compared include all of the relevant indicators. This study sought to use all available evidence, but we acknowledge that in many cases there may have been relevant policy documents that we were unable to access via our search methodology. Fourth, we did not aim to quantify the implementation or impact of each policy compared as a multitude of factors influence a program’s success including operational barriers, demographic, economic, and political trends.
Pillar 1—-strong political commitment—-is crucial for a successful health initiative. The global commitment to mitigating the effects of HIV/AIDS offers one example of an initiative with strong political commitment. Uganda, Thailand, and Senegal are representative of countries where political will has significantly contributed to reducing the potential morbidity and mortality burden of the HIV/AIDS epidemic.103 However, political commitment is difficult to measure, and it is well recognized that the existence of a policy does not directly translate into implementation.104 In this review, evidence for political commitment was considered through the existence of defined elimination goals, universal screening guidelines or recommendations, committed government funding, evidence of national and international partnerships, and linkages with appropriate case-management services. Varying levels of support were noted, with only 3 countries defining CS elimination goals, although all had policies for the promotion of universal screening among pregnant women. Although an essential element to CS elimination, a universal screening policy does not necessarily ensure that all mothers and partners will be treated. We also attempted to assess political commitment in terms of budget allocation for public funding and found that 9 countries had CS-related funding, but we had no access to information showing whether committed funds were disbursed to their intended programs. Such information can only be garnered through in-country assessments. Budgetary commitments may reflect political commitment at the national level, but commitment to implementation is reflected by the views and actions of key stakeholders further down the policy chain. We were not able to capture the commitment (or possible lack thereof) of key stakeholders at the subnational level, but we recommend this type of analysis be undertaken to provide a more comprehensive picture of sustained commitment across all levels of health service delivery.
WHO further recommends the incorporation of CS elimination interventions into programs that work towards increasing access to high-quality maternal and newborn health services, such as Making Pregnancy Safer (MPS) programs. The synergy between CS and MPS programs could be exploited to maximize the opportunities for achieving the goal of universal coverage of CS interventions. In our review, although linkages to STI and MPS programs were noted, the functional and budgetary relationship between the various agencies involved and responsible agency for oversight was not easily delineated. Similarly, the agencies responsible for monitoring and evaluation were not clearly defined. This suggests a need for stronger partnerships between programs and interventions that aim to address the control of syphilis in the general population and those that provide antenatal syphilis screening. In several settings, antenatal syphilis screening policies were incorporated into national HIV/AIDS policy documents.
Political commitment to CS elimination or control varied, irrespective of resource or prevalence level, but appears to impact subsequent policy recommendations in the other 3 pillars. For example, pillar 4 surveillance, monitoring, and evaluation systems helps to quantify the extent of the problem, thereby promoting sustained political commitment. Likewise, political commitment can help to drive surveillance, monitoring, and evaluation programs.
Pillar 2—-increasing and improving access to health services—-was unsurprisingly weak in resource-poor settings. One analysis remarked that the “issue for the developing world is … not whether to screen but how to screen more efficiently.”105 Partnerships with community organizations represent a cost-effective method to improve and extend the coverage of CS elimination efforts. Donor involvement is likely to be an influential factor but due to limited data it was not clear whether donor involvement is a prerequisite for success.
Pillar 3—-effective screening and treatment of pregnant women and partners—-may be achieved through point-of-care testing and availability of logistical supplies. Point-of-care testing recommendations were noted primarily in low-resource settings; US policy also recommends point-of-care testing in situations where prenatal care may be difficult. Ensuring adequate screening and treatment requires a commitment to increasing both capacity (i.e., of health workers to undertake the screening tests, and to provide counseling inputs), and ensuring the availability of sufficient resources (e.g., human, drug, financial, etc.). It was beyond the scope of this paper to address issues of program implementation, including reviewing the logistical and support requirements necessary for program efficiency. However, our review highlighted the central nature of this pillar in the majority of countries surveyed, and reinforced its position in the proposed WHO action plan.
Screening recommendations varied and were often difficult to assess as variations between national and regional guidelines exist. Australia, England, and the United States are examples of where regional bodies regulate screening practices. One Australian region discontinued general syphilis screening due to low prevalence levels despite national guidelines,33 while England recently evaluated the need to continue universal screening.35,106 Provider adherence is also difficult to evaluate as syphilis in pregnancy is often not a notifiable disease or is underreported. Kenya, Tanzania, Malawi, and Brazil require reporting from sentinel surveillance sites only, while in other settings, such as the Russian Federation, private clinics may not be required to report cases in pregnancy.
Pillar 4—-surveillance monitoring, and evaluation systems—-is an integral component of any STI control program. Reliable surveillance and evaluation data aid in guiding control efforts as well as evaluating effectiveness. Ten countries in this review had national baseline surveillance data available but due to differences in collection methods and case definitions, comparisons between and within settings were not possible. In resource-limited settings, much of the available surveillance data were based on local or regional prevalence studies. Countries with passive surveillance systems, which rely on health facility reporting, can lead to low incidence reporting, particularly in low-resource settings, due to underdetection, misclassification, and underreporting.107 In the Russian Federation, a 26-fold increase in reported CS cases in the early 1990s occurred following the breakdown of the Soviet Union; however, by the late 1990s, an increased use of private health providers corresponded to a decrease in reported CS cases.108 In other settings, sentinel surveillance data alone may not accurately represent syphilis prevalence in the ANC population as reported results include false-positive and false-negative results, different types of screening tests (e.g., RPR, VDRL, TP-EIA) are utilized, and confirmatory testing is not always performed.109 The proposed WHO action plan offers a common definition and recommends a standardized testing procedure for a more efficient evaluation of policy effectiveness between settings. A standardized case definition of CS would improve prevalence estimates and enable comparisons of the effectiveness of CS control or elimination programs across settings for best practices.
The limited amount of data in national trends limits evaluation of the policy and is especially common in low-resource settings. Mullick et al. speculate that the “lack of convincing evidence of antenatal syphilis as a public health problem” contributes to its status as a low health care priority110 and further emphasize the necessity of a comparable data with comprehensive monitoring and evaluation efforts.
Among the 14 countries, proxy CS measurements was noted in only 2 countries and comprehensive monitoring and evaluation efforts were found primarily among low-CS prevalence and high-resource settings. Successful monitoring and evaluation is dependent upon a synergistic relationship between all of the agencies involved. WHO recommends that CS control programs use all available national resources of STI and MPS-related programs as well as create a system with clear oversight to ensure that the necessary programmatic components are addressed.
Our review highlighted a number of areas where there are points of convergence and disparity between the existing national-level policies and the proposed WHO action plan recommendations. Analysis of national-level policies suggests 4 key points for those charged with controlling STIs and maternal-child health to consider:
1. Sustained political commitment and advocacy were often associated with defined policy activities across the remaining 3 pillars (improving and increasing access to health services; screening and treatment; surveillance, monitoring, and evaluation). Such commitment could be reinforced by pillar 4 surveillance, monitoring and evaluation systems to assess the CS disease burden and policy impact. The use of media and information dissemination outlets are methods of promoting political and stakeholder commitment.
2. Financial resources, while being a limiting factor, are not an insurmountable barrier to improvement. The creation of clearly defined goals, responsibilities and programmatic links between agencies responsible for STIs, HIV/AIDS and Making Pregnancy Safer initiatives can be achieved at relatively low cost utilizing existing infrastructure.
3. Without a standardized surveillance method, it is difficult to assess the magnitude of the epidemic, policy effectiveness between settings, and appropriately assign resources, suggesting the need for a common CS definition and standardized testing procedure.
4. All countries, to varying extents, would benefit from targeting policies to meet the detailed indicators of the 4 pillars. The WHO plan is applicable across settings, and can be adopted if no policies currently exist.
CS continues to be an entirely preventable disease whose burden is inflicted on those who are most vulnerable and unable to defend their own health and wellbeing. We believe that, working in conjunction with other health programs (such as MPS, child and adolescent health programs, PMTCT of HIV), the elimination of CS is an achievable goal not only within countries who have established policies, but also within those countries that have yet to articulate health service goals in this area.
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