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Sexually Transmitted Diseases:
doi: 10.1097/01.olq.0000251236.48770.35
Article

Demonstrating Public Health at Work: A Demonstration Project of Congenital Syphilis Prevention Efforts in Bolivia

García, Sandra G. ScD*; Tinajeros, Freddy MPH†; Revollo, Rita MD, MPH†; Yam, Eileen A. MPH*; Richmond, Kara MPH‡; Díaz-Olavarrieta, Claudia PhD*; Grossman, Daniel MD§

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Erratum
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Erratum

An incorrect version of Table 1 was published in Vol. 34, issue 7 Supplement, pages S37–S41. The authors are Sandra García, ScD, Freddy Tinajeros, MPH, Rita Revollo, MD, MPH, Eileen A. Yam, MPH, Kara Richmond, MPH, Claudia Díaz-Olavarrieta, PhD, and Daniel Grossman, MD. The correct version of the table appears below.

Sexually Transmitted Diseases. 34(11):938, November 2007.

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Author Information

From *The Population Council, Mexico City, Mexico; †The Population Council, La Paz, Bolivia; ‡Independent consultant, Albuquerque, New Mexico; and §Ibis Reproductive Health, San Francisco, California

The authors thank the Bill and Melinda Gates Foundation for their generous support of this work. The authors are also grateful to many individuals at the Bolivian Ministry of Health (especially public health officials in the departments of Chuquisaca, Cochabamba, La Paz, and Santa Cruz), and the INLASA—the Bolivian national reference laboratory as well as the study team in Bolivia, and the many women and men who participated in our project. Lastly, the authors thank Davida Becker, Adele Benzaken, Stanley Blanco, Nathalie Broutet, Daniel Chang, Carlos Conde, Juan Díaz, Karina Eguez, Charlotte Ellertson, Terry Elliott, Alissa Fishbane, Patricia Garcia, Monica Gironas, Steve Gloyd, Fernando Gonzales, Carolina de Hilari, Anrudh Jain, Shannon Johnson, Heidi Jones, Ana Langer, Carol Levin, Tom Martin, Carolina Montes, Pablo Montoya, Patricia O’Connor, Sonia Paredes, Gordon Perkin, Diddie Schaff, Matt Steele, Nayrha Villazón, Renato Yucra, and Lourdes Zegarra for their collaboration, sound advice, and moral support along the way.

Correspondence: Sandra G. Garcia, c/o Population Council, One Dag Hammarskjold Plaza, New York, NY 10017. E-mail: sgarcia@popcouncil.org.mx.

Received for publication May 3, 2006, and accepted October 2, 2006.

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Abstract

Objectives: We introduced syphilis immunochromatic strip (ICS) tests into antenatal care (ANC) settings in Bolivia and evaluated feasibility, patient and provider acceptability, and introduction costs. We conducted complementary studies on related topics, strengthened quality of care, and aided the response to sensitive aspects of maternal/congenital syphilis control (e.g., partner notification).

Goal: The goal of this study was to discuss our experience working with Bolivian stakeholders to document potential public health benefits of syphilis ICS test introduction in ANC settings.

Study Design: We trained public health personnel and offered the Abbott Determine Rapid Syphilis TP test in 4 urban maternity hospitals and 37 rural clinics.

Results: Using the ICS test, 11,618 women were tested for syphilis; 5% had positive results and 93.2% received treatment. Women and health personnel found the test acceptable and introduction costs were not prohibitive.

Conclusions: Based on these findings, by mid-2006, the Bolivian Ministry of Health will offer the ICS tests in rural ANC settings.

IN BOLIVIA, LIKE IN MUCH of the developing world, congenital syphilis remains a serious public health problem.1 Bolivia has a relatively high prevalence of syphilis among pregnant women; in 1994, the Bolivian Ministry of Health (MOH) reported 3.1 cases of symptomatic neonatal syphilis per 1,000 live births, and a more recent study in 7 Bolivian hospitals detected maternal syphilis in 4.3% of women who delivered live births and in 26% of women with stillbirths.2,3 In comparison, regional maternal syphilis prevalence is 3.1% in the Latin America and the Caribbean region ranging from 1.0% in Peru to 6.2% in Paraguay.4

Since the mid-1990s, the Bolivian MOH has made a concerted effort to prevent and control maternal and congenital syphilis. Since 1998, the Bolivian Maternal–Child Universal Insurance program (Seguro Universal Materno Infantil [SUMI]) has covered maternal syphilis screening (mostly with rapid plasma reagin [RPR] testing and, to a lesser degree, with Venereal Disease Research Laboratory [VDRL] testing) and treatment. Nevertheless, despite more than 10 years of noteworthy government efforts, routine testing during antenatal care (ANC) has been deficient. Although the 1998 Demographic and Health Survey (DHS) indicated that nearly 70% of all pregnant Bolivian women present for at least one ANC visit,5 a maternal syphilis study conducted 2 years earlier by Southwick et al found that although 76% of participants reported having received ANC, only 17% had undergone syphilis testing during the current pregnancy.2 Although Southwick et al’s study uses a convenience sample,2 national estimates from the MOH’s national surveillance database are similar, documenting that only 19.7% of 2002 ANC attendees received a laboratory-based syphilis test.6 The lack of testing during pregnancy is especially tragic because syphilis is not only the most preventable of the congenital infections, but also the most affordably treatable—with penicillin, a broad-spectrum antibiotic on the list of essential drugs of the World Health Organization (WHO).7 In Bolivia, like elsewhere, successful strategies for the elimination of congenital syphilis will require not only timely diagnosis among pregnant women, but also treatment of positive women and their male sexual partners. Although SUMI covers syphilis treatment for pregnant women, neither diagnosis nor treatment of male partners is covered by SUMI, other public sector health insurance plans, or vertical programs such as the National Program for STI-HIV-AIDS.

The logistic and technical challenges of relying solely on laboratory tests such as RPR or VDRL for syphilis screening may undermine a government’s best efforts to effectively prevent and treat maternal and congenital syphilis, particularly in developing countries with large pockets of rural and other low-resource settings. Difficulties associated with these tests include their substantial laboratory and reagent storage requirements, risk of interreader variability, lack of access to quality supplies, and transport requirements of specimens and results. When such difficulties translate into long turnaround times between initial testing and the availability of results, the opportunity to treat syphilis-positive women may be lost, especially in rural clinics that send RPR blood samples to laboratories in neighboring cities, often hours away by car.

Syphilis experts worldwide have recognized the need for improved screening tools and capacity to overcome these persistent barriers to effective maternal syphilis screening.8–10 One such diagnostic device that could greatly improve Bolivian antenatal syphilis screening is an immunochromatographic strip (ICS) test. The syphilis ICS test requires just a few drops of whole blood obtained from a fingerstick, it does not require a laboratory, and patients can obtain results in approximately 20 minutes. With such a quick diagnosis, initial treatment may be offered on-site during the same visit, even in rural health centers. By 2002, one such ICS test, the Abbott Determine Rapid Syphilis TP test (Abbott Laboratories, Abbott Park, IL), was commercially available in Brazil, Chile, and Peru, and evaluations had documented adequate test performance characteristics (sensitivity from 92–100% and specificity of 93–100%).11–13

Recognizing the ICS test’s potential to improve maternal syphilis screening in Bolivia, the Population Council, working closely with the Program for Appropriate Technology in Health (PATH), collaborated with the Bolivian MOH to introduce the Abbott Determine Rapid Syphilis TP test in select urban and rural ANC settings. After 2 years of extensive planning alongside members of the Bolivian MOH and other stakeholders, in January 2004, we launched an ambitious and multifaceted demonstration project to document the feasibility, acceptability, and costs of introducing syphilis ICS tests into existing Bolivian ANC services in two settings: 1) rural clinics that lacked traditional testing capacity and 2) large urban maternity hospitals where barriers to syphilis screening existed despite the capacity to perform RPR.

This article describes the experience of planning and carrying out this challenging demonstration project with a particular focus on those elements that contributed to its success; we do not present detailed study results, because these will be presented in subsequent papers (see Table 1.) As we discuss our collaboration with the public sector, the volatile Bolivian political environment in which the project took place, and the implications for scale-up, we also aim to share the lessons learned and discuss remaining challenges.

Table 1
Table 1
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Project Description and Overview
Partners, Funding, and Early Planning.

When planning for our project launch, we were very fortunate to have the full support of the Bolivian MOH and other national public health and policy stakeholders. The Bolivian government had a strong track record of positive actions and policies to help encourage syphilis screening during pregnancy with RPR. In addition, the Population Council had worked with the Bolivian MOH, local nongovernmental organizations and special projects (such as MotherCare), and bilateral (USAID) and multilateral (Pan American Health Organization, WHO) organizations to help expand access to RPR services for pregnant women. We believe that 3 key factors help explain the Bolivian government’s strong interest in ANC syphilis screening services: 1) the burden of disease, particularly neonatal morbidity and mortality; 2) the country’s large rural areas with relatively low coverage of antenatal syphilis screening or treatment; and 3) the importance of following up on the significant financial investments and policy reforms made in the recent past to improve ANC syphilis screening (such as the reform of SUMI and the expansion of RPR services nationwide).

Given the history of fruitful collaboration with Bolivian colleagues to address these challenges, in 2002, Mexico-based Population Council researchers began exploring the possibility of bringing the Abbott Determine Rapid Syphilis TP test to Bolivian ANC settings. Introducing this particular rapid test made sense because: 1) the test was commercially available in neighboring countries; 2) it was affordable (for study purposes, Abbott Laboratories offered it to us for US $1.00 per test), and easy to import; and 3) Bolivian healthcare workers found it easy to use compared with other candidate ICS tests. Additionally, preliminary results from a WHO multicountry field study comparing the performance characteristics of different ICS tests became available, supporting our selection of the Abbott Determine Rapid Syphilis TP test. In 2002, we received funding from the Bill and Melinda Gates Foundation as part of a proposal on the use of simple, inexpensive technologies to prevent bacterial sexually transmitted infections.

In addition to the project activities outlined in the main study protocol, we carried out a number of complementary and/or nested studies (see Table 1). Likewise, inspired by the work of colleagues like Kerrigan et al,14,15 through grounded formative research, we involved the main beneficiaries of this research—in this case, Bolivian women, their male partners, and health/laboratory personnel—in crafting a culturally appropriate intervention responsive to their needs. The pilot phase of this project also helped us identify and troubleshoot problems that were difficult to identify in the abstract, thus helping our research team become familiar with procedures, forms, and the nuances of interacting with patients/study participants. Finally, to address gaps in needed support activities for the demonstration project as a whole, we also carried out the following: 1) a rapid assessment of existing syphilis testing services in selected public health establishments nationally (results determined that 60% of these health establishments relied on RPR and 40% on VDRL); 2) RPR/VDRL and ICS training for project laboratory and health personnel; 3) the design of a national informational and media campaign to encourage pregnant women to seek early ANC services; and 4) the development of MOH-endorsed manuals and technical guides on syphilis testing during ANC that were made available to all interested health personnel regardless of their participation in our project.

In June 2003, the main study protocol (including procedures for informed consent) was approved by the Population Council’s Institutional Review Board and a research subcommittee of the Bolivian MOH (this committee would become the MOH’s official Institutional Review Board during the course of our study). Protocols for complementary and nested studies were approved subsequently. By April 2004, after gradually phasing in the fieldwork (beginning with La Paz and following suit in Chuquisaca, Cochabamba, and Santa Cruz), data collection in all 4 study departments was underway. Fieldwork ran 16 months from January 2004 to May 2005.

Throughout project planning and implementation, the involvement of key staff within the Bolivian MOH and other stakeholders was critical for building rapport and ensuring early commitment from these individuals as well as for making important project decisions (such as where to field the project and how to handle procurement, importation, and stocking of rapid tests and other supplies) and other strategic decisions such as how to best present results to key stakeholders. By engaging in frequent (on average monthly) communication with our MOH collaborators at the central level, our goal was to involve them not merely as interested bystanders, but as active endorsers of the project.

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Participants and Methods

Study participants were chosen from a random sample of rural health clinics and urban maternity hospitals that met a set of predefined research and practical criteria (such as sufficiently high numbers of women seeking ANC, adequate road infrastructure, and observed syphilis prevalence was 3.0% or higher). We selected 4 large maternity hospitals (those with the highest patient volume—2 in La Paz department and one each in the departments of Santa Cruz and Cochabamba) and 37 rural centers across the 4 study provinces (La Paz, Santa Cruz, Cochabamba, and Chuquisaca).

Eligible participants were women aged 18 and over seeking ANC in participating health clinics and hospitals who had not had a prior syphilis test during the current pregnancy. Every consenting woman in our study received the ICS test and the decision to offer treatment was based on ICS test results; in the 4 urban hospitals, however, in addition to receiving the ICS test, participants also provided an intravenous blood specimen to process the RPR test usually offered by the hospital (RPRhosp) as well as to send a second sample (RPRref) to the INLASA, a national reference laboratory located in La Paz. Finally, the INLASA carried out Treponema pallidum particle agglutination assay (TPPA) confirmation of all positive RPRref results. All women testing positive for syphilis by ICS were offered treatment that consisted of 3 doses (one per week) of benzathine penicillin G 2.4 million units intramuscularly in accordance with Bolivia MOH and WHO guidelines. Alternative treatment (500 mg erythromycin 4 times per day for 7 days) was available for participants who tested positive for penicillin allergy. Women who consented to treatment were offered the first dose of penicillin immediately and asked to return for the following 2 doses. If they consented, these women were provided with notification cards requesting that their male sex partners visit the health facility for free presumptive treatment (following the same treatment protocols established for the women). We decided to treat males presumptively for ethical reasons to avoid the possibility of diagnosing couples with discordant syphilis results. We offered participating women a modest gift (a swaddling blanket for their newborns), and treatment was free for women and their partners.

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Informational Campaign

Shortly after clinical training, we designed and launched a multimedia informational campaign to raise public awareness about the benefits of early ANC and maternal syphilis testing. After a rigorous selection process led by a multidisciplinary group of experts (the head of communication of the MOH SUMI division, the director of UNICEF–Bolivia’s sexually transmitted infection program, the technical manager of communications at the USAID/Bolivia mission, and Population Council investigators), we chose a marketing agency to spearhead the campaign. MOH officials approved and agreed to include their logo on all materials, and the MOH was explicitly mentioned in all radio spots.

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Results

Informational Campaign

Informed by formative research, agency staff produced 5,000 posters for use in rural and urban areas as well as 12 radio ads that aired in the 4 study departments, each with distinct, tailored messages of 30 seconds’ duration in Spanish and the local dialects of Aymara, Quechua, and Camba. Three radio networks with national coverage and 54 local networks across the 4 departments aired the campaign from April to November 2004.

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Clinical Findings of the Main Project

We tested 11,618 women with the ICS test; 2,718 women (23.4%) were tested at rural clinics and 8,900 (76.6%) were tested at the urban maternity hospitals. The average age of women in both settings was 25, and 82.3% of rural and 80.7% of urban women were married or cohabiting. Of the 11,618 participants, 577 (5.0%) tested positive by the ICS test. Nearly all of these women (n = 538 [93.2%]) received at least a single dose of penicillin, and most of them (n = 470 [81.5%]) received all 3 recommended doses. Of the 577 women who tested positive by the ICS test, 9 (1.6%) tested positive for penicillin allergy and 498 (86.3%) identified a male partner at the time of testing. A total of 383 (76.9%) male partners presented at a participating health facility for treatment. Among these 383 men, 7 (1.8%) tested positive for penicillin allergy, 376 (98.2%) received a single dose of treatment, and 325 (84.9%) received all 3 doses. Female and male study participants, clinicians, and laboratory technicians indicated on questionnaires that they found the test highly acceptable and supported its introduction into the SUMI program in Bolivia.

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Cost Analysis and Other Complementary Studies

We are pleased that this issue of Sexually Transmitted Diseases also includes papers from 2 of our complementary studies. Table 2 provides the page references for these 2 papers and also highlights key findings from additional project components.

Table 2
Table 2
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Policy Outcomes

In addition to the clinical outcomes described here, our study directly influenced Bolivian health policy regarding maternal syphilis screening. The MOH added syphilis screening with rapid ICS tests to the national maternal health guidelines, and at our September 2005 end-of-project meeting, the Bolivian Minister of Health announced that the SUMI package of care would include ICS tests for pregnant women in rural clinics with no laboratory infrastructure. The MOH has continued to make this policy a reality and PAHO will donate approximately 11,000 ICS tests to the MOH to create a “startup” supply with which to launch the syphilis screening in rural areas. In urban health establishments with sufficient laboratory infrastructure, the MOH has committed to strengthening the quality of RPR and VDRL services. In addition, this year, our project field team is also exploring financial mechanisms with UNICEF to offer presumptive treatment to male partners of syphilis-positive pregnant women. Furthermore, the National Program for STI-HIV-AIDS is considering covering 2,500 treatment doses for male partners during 2006. Lastly, as a result of the high quality of services demonstrated in this project, the Bolivian MOH has requested ongoing technical support from project staff to develop work plans for the elimination of congenital syphilis as part of a WHO multicountry initiative.

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Discussion

The elimination of congenital syphilis has become a global priority in the international public health community,16–19 and through our project, we demonstrated that effective maternal syphilis screening during ANC can function well using a mix of rapid diagnostic tests (the ICS) and traditional screening tests (RPR, VDRL) when there is strong political will; when key stakeholders (including women and their male partners) are involved at all levels of a project; when training, monitoring, and supervision is continuous and of high quality; when support systems are in place for women (especially counseling on communication strategies for notifying male partners about a positive syphilis diagnosis and referral services for women who live in fear of intimate partner violence) and for health practitioners (e.g., a guarantee of adequate stocking of supplies); when treatment is made available to women and their partners; and when information-sharing and progress updates to public health officials are frequent, transparent, and evidence-based.

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Study Limitations

Despite the comprehensiveness of this project, our study has several limitations and we recognize that it could have been stronger with regard to both design and outcome measures. The study did not include a control group; however, we made this decision to provide services to a greater number of persons. Another limitation is that we could not link data from women with their sex partners. Last, we did not follow our participants through to delivery, so we have no data on repeat syphilis infections, on sexual practices with partners after a positive syphilis diagnosis, or on birth outcomes. Such data would have been ideal for calculating the true cost-effectiveness of our intervention. Resource constraints made it impossible to collect data on the prevalence of maternal syphilis in all departments. Furthermore, the data we did collect is only representative of women presenting for ANC. However, one of our complementary studies is more generalizable to all pregnant women (see study of congenital syphilis in Table 2).

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Challenges

Perhaps the greatest challenge faced during the 3-year study period was the extraordinary political instability in Bolivia characterized by frequent disruptive government turnover and civil disorder in La Paz and departmental capital cities. During the course of this project, there were 4 Bolivian presidents and 5 Ministers of Health, which translated into steady and unpredictable turnover among stakeholders at the MOH. Bolivian investigators often had to forge new ties with new appointees while the study was underway. Being able to work effectively under these circumstances required consistent and frequent communication (more often than not, face-to-face interaction) with the different MOH officials at federal, provincial, and city levels as well as careful nurturing of relationships with whoever held decision-making power at the time. We can only speculate, but the fact that our project carried on successfully in the face of political instability is perhaps the result of the broad public health appeal of the elimination of congenital syphilis campaign coupled with the delicate persistence of our project managers on the ground.

Working in the 37 remote rural areas was also challenging, given the long distances, the poor road infrastructure, and the greater risks of losing syphilis-positive women to follow up during the treatment phase (because of the long distances from their homes to the clinics). Finally, we faced an unexpected challenge in setting up and providing quality counseling and referral services to victims of intimate partner violence.

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Recommendations

On the whole, we consider this project to have been a public health success because of its breadth, quality, and policy impact. The MOH has been our partner from the outset, and we hope that this project has built up a critical mass of committed stakeholders to guide the MOH in its next phase of project expansion and scale-up. Although we consider the uptake of ICS syphilis screening in rural ANC settings to be a very positive step toward eliminating congenital syphilis in Bolivia, it is not sufficient by itself. We strongly encourage the MOH and other stakeholders to also focus attention and resources on improving the quality of RPR and VDRL services in urban health facilities, including the development of stringent quality control standards for the purchase of reagents and other measures. The problem of frequent treatment and supply stockouts must be addressed not only so as to treat as many women as possible, but also to maintain provider engagement with the testing program. Similarly, treatment must be guaranteed to pregnant women and their male partners. In Bolivia, SUMI will cover treatment for syphilis-positive women, but not their male partners (because, by definition, it is a public insurance package for pregnant women and infants). Even if a pregnant woman complies with treatment, if male sex partners continue to be ignored, reinfection is probable and imminent. We recommend that traditionally “vertical” public health programs (maternal health and STI-HIV-AIDS) begin exploring ways to work together and complement efforts to address congenital syphilis. Finally, this project has taught us the importance of having strong data systems in place. We hope to build on the lessons we learned and challenges we overcame during the course of this project as we continue to work with MOH partners in strengthening syphilis surveillance and monitoring systems.

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Closing Comments

Although the cornerstone of our project was the introduction of ICS syphilis testing in ANC settings, our project offers a demonstration of effective public health through well-coordinated, grounded, comprehensive, and evidence-based activities. The WHO has identified Bolivia as one of the countries in which congenital syphilis can be eliminated in the near future, and the MOH has shown a commitment to addressing this public health problem since the early 1990s through the application of WHO recommendations and guidelines, the expanded availability of RPR services, reforms in social programs such as SUMI to offer universal syphilis screening and treatment to pregnant women, willingness to test new models of care (such as this demonstration project), and the willingness to improve health services based on such evidence-based models. Although our project was not without challenges, and although many challenges remain, we feel that the Bolivian experience can serve as a model for other developing countries within and beyond Latin America.

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References

1. Hook EW III, Peeling RW. Syphilis control—A continuing challenge. N Engl J Med 2004; 351:122–124.

2. Southwick K, Blanco S, Santander A, et al. Congenital and maternal syphilis in Bolivia, 1996: Prevalence and risk factors. Bull World Health Organ 2001; 79:33–42.

3. Deperthes BD, Meheus A, O’Reilly K, et al. Maternal and congenital syphilis programmes: Case studies in Bolivia, Kenya, and South Africa. Bull World Health Organ 2004; 82:439–446.

4. Valderrama J, Zacarías F, Mazin R. Sífilis materna y sífilis congénita en América Latina: Un problema grave de solución sencilla. Rev Panam Salud Publica 2004; 16:211–217.

5. Macro International. Bolivia, 1998: Demographic and Health Survey. La Paz: Macro International, 1998.

6. Sistema Nacional de Información en Salud. Annual Report of Antenatal Care Coverage, 2002. La Paz: Ministry of Health and Sports, 2003.

7. Wendel GD Jr, Sheffield JS, Hollier LM, et al. Treatment of syphilis in pregnancy and prevention of congenital syphilis. Clin Infect Dis 2002; 35(suppl 2):S200–209.

8. Peeling R, Ye H. Diagnostic tools for preventing and managing maternal and congenital syphilis: An overview. Bull World Health Organ 2004; 82:410–416.

9. Deperthes BD, Meheus A, O’Reilly K, et al. Maternal and congenital syphilis programmes: Case studies in Bolivia, Kenya, and South Africa. Bull World Health Organ 2004; 82:439–446.

10. West B, Walraven G, Morison L, et al. Performance of the rapid plasma reagin and the rapid syphilis screening tests in the diagnosis of syphilis in field conditions in rural Africa. Sex Transm Infect 2002; 78:282–285.

11. Lien TX, Tien NT, Chanpong GF, et al. Evaluation of rapid diagnostic tests for the detection of human immunodeficiency virus types 1 and 2, hepatitis B surface antigen, and syphilis in Ho Chi Minh City, Vietnam. Am J Trop Med Hyg 2000; 62:301–309.

12. Juarez-Figueroa LA, Gonzalez CC. Field and laboratory evaluation of a new reagent for syphilis diagnosis. Presented at the 9th International Congress on Infectious Diseases, Buenos Aires, Argentina, April 10–13, 2000. Abstract #19.012.

13. Abbott Laboratories. Reference catalog: 7D24-33, Abbott Determine Syphilis Whole Blood Assay, Determine syphilis TP test card, Treponema pallidun antigen coated.

14. Kerrigan D, Moreno L, Rosario S, et al. Adapting the Thai 100% condom programme: Developing a culturally appropriate model for the Dominican Republic. Cult Health Sex 2001; 3:221–240.

15. Kerrigan D, Ellen JM, Moreno L, et al. Environmental–structural factors significantly associated with consistent condom use among female sex workers in the Dominican Republic. AIDS 2003; 17:415–423.

16. Saloogee H, Velaphi S, Goga Y, et al. The prevention and management of congenital syphilis: An overview and recommendations. Bull World Health Organ 2004; 82:424–432.

17. Hawkes S, Miller S, Reichenbach L, et al. Antenatal syphilis control: People, programmes, policies and politics. Bull World Health Organ 2004; 82:417–423.

18. Eliminating Congenital Syphilis. Geneva: World Health Organization, 2005. Available at: www.who.int/reproductive-health/stis/syphilis.html. Accessed May 1, 2006.

19. Sexually Transmitted Infections and Other Reproductive Tract Infections: A Guide to Essential Practice. Geneva: World Health Organization, 2005.

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