1. Global Congenital Syphilis Elimination Mary L. Kamb 1, Nathalie Broutet 2, Jennifer Mark 1, Ken Wind-Anderson 2, and John M. Douglas 1 CDC Division of STD Prevention, Atlanta WHO Department of Reproductive Health and Research, Geneva Update on the New Global Public Health Initiative

2. Global Congenital Syphilis Elimination What is our commitment (as a world)? Global burden of disease How estimates reached Cost-benefit studies Why is a global initiative justified? Why now? New global health goals Program tools Future directions, next steps

3. New Global Initiative October 2007: WHO launched a new Initiative for the “Global Elimination of Congenital Syphilis as a Public Health Problem” Women Deliver Conference, London Ministers of Health of Nigeria and Mongolia presided at launch, several other Ministers of Health were present for the inauguration Letter of Commitment signed by 26 nations and international agencies

4. Congenital Syphilis Elimination: 4 Pillars

5. I. Ensure sustained political commitment and advocacy National policies Financial resources Policies "enforced" Congenital Syphilis Elimination: 4 Pillars

6. I. Ensure sustained political commitment and advocacy II. Increase access to, and quality of, maternal and newborn health services National policies Financial resources Policies "enforced" Accessibility of services (location, cost, waiting time) Education of women Quality of services (friendly, value to women) Congenital Syphilis Elimination: 4 Pillars

7. I. Ensure sustained political commitment and advocacy II. Increase access to, and quality of, maternal and newborn health services III. Screen and treat all pregnant women National policies Financial resources Policies "enforced" Accessibility of services (location, cost, waiting time) Education of women Quality of services (friendly, value to women) Presence/type of test Treatment PN Training of HCWs Congenital Syphilis Elimination: 4 Pillars

8. I. Ensure sustained political commitment and advocacy II. Increase access to, and quality of, maternal and newborn health services III. Screen and treat all pregnant women IV. Surveillance, monitoring and evaluation systems (includes lab QA systems) National policies Financial resources Policies "enforced" Accessibility of services (location, cost, waiting time) Education of women Quality of services (friendly, value to women) Presence/type of test Treatment PN Training of HCWs Congenital Syphilis Elimination: 4 Pillars

9. Four Guiding Principles The process should be country-driven An integrated approach should be adopted A rights-based approach should be applied Partnership and collaboration

10. Four Guiding Principles The process should be country-driven An integrated approach should be adopted A rights-based approach should be applied Partnership and collaboration

11. Why is such an Initiative Justified?

12. (i) Consequences of untreated maternal syphilis and (ii) New information

13. Why is such an Initiative Justified? Globally, each year there are an estimated 750,000 – 1.5 million congenital syphilis cases (i) Consequences of untreated maternal syphilis and (ii) New information

14. Why is such an Initiative Justified? Globally, each year there are an estimated 750,000 – 1.5 million congenital syphilis cases Major cause of stillbirth globally (i) Consequences of untreated maternal syphilis and (ii) New information

15. Why is such an Initiative Justified? Globally, each year there are an estimated 750,000 – 1.5 million congenital syphilis cases Major cause of stillbirth globally Important cause of preterm delivery, low birth weight, neonatal death (i) Consequences of untreated maternal syphilis and (ii) New information

16. Why is such an Initiative Justified? Globally, each year there are an estimated 750,000 – 1.5 million congenital syphilis cases Major cause of stillbirth globally Important cause of preterm delivery, low birth weight, neonatal death Perinatal mortality on par with that of HIV or malaria (i) Consequences of untreated maternal syphilis and (ii) New information

17. Why is such an Initiative Justified? Globally, each year there are an estimated 750,000 – 1.5 million congenital syphilis cases Major cause of stillbirth globally Important cause of preterm delivery, low birth weight, neonatal death Perinatal mortality on par with that of HIV or malaria Easily and cheaply prevented : among the most cost-effective public health interventions (i) Consequences of untreated maternal syphilis and (ii) New information

18. Global Estimates of Maternal Syphilis Seroprevalence* Overall prevalence 1.76% Estimation of 2,156,304 women Estimated # of infants born with congenital syphilis: 750,000 to 1,500,000 *Schmid et al 2007

19. Extent and Type of Perinatal Morbidity & Mortality 1917 Harman 1951 Ingraham 1987 Schulz 1990 Hira 2002* Watson- Jones Stillbirth17%22%30-40%22%25% Perinatal Death 23%12%10-20%No data Infected Infant 21%33%10-20%2%No data Preterm/ LBW No data --33%25% Any adverse Outcome 61%67%50-80%57%49% * * Restricted to high-titer seroreactive mothers (RPR ≥1:8), which represented 73% of all women with active syphilis Studies among Syphilis-Infected Pregnant Women*

20. Extent and Type of Perinatal Morbidity & Mortality 1917 Harman 1951 Ingraham 1987 Schulz 1990 Hira 2002* Watson- Jones Stillbirth17%22%30-40%22%25% Perinatal Death 23%12%10-20%No data Infected Infant 21%33%10-20%2%No data Preterm/ LBW No data --33%25% Any adverse Outcome 61%67%50-80%57%49% * * Restricted to high-titer seroreactive mothers (RPR ≥1:8), which represented 73% of all women with active syphilis Studies among Syphilis-Infected Pregnant Women*

21. Cost Benefit of Maternal Syphilis Screening Country (Publication) Maternal Σ Prevalence $ per ♀ Screened $ per ♀ Treated $ per P erinatal Outcome Averted $ per DALY Saved Zambia* (Hira, 1990) 9%$1 (RPR) $22$181$11 Kenya* (Jenniskens, 1995) 6%$2 (RPR) $34$280$17 Kenya* (Fonck, 2001) 3%$1 (RPR) $40$300$19 Tanzania* (Terris-Prestholt, 2003) 7%$1 ( RPR) $20$187$11 Haiti (Schackman, 2007) used 2004 USD 3.5% urban 3.8% rural $1.5 (RPR) $2 (rapid) Not available $7 (rural) $9 (urban) Summary of Published Studies * Adjusted to 2001 USD

22. Cost Benefit of Maternal Syphilis Screening Country (Publication) Maternal Σ Prevalence $ per ♀ Screened $ per ♀ Treated $ per P erinatal Outcome Averted $ per DALY Saved Zambia* (Hira, 1990) 9%$1 (RPR) $22$181$11 Kenya* (Jenniskens, 1995) 6%$2 (RPR) $34$280$17 Kenya* (Fonck, 2001) 3%$1 (RPR) $40$300$19 Tanzania* (Terris-Prestholt, 2003) 7%$1 ( RPR) $20$187$11 Haiti (Schackman, 2007) used 2004 USD 3.5% urban 3.8% rural $1.5 (RPR) $2 (rapid) Not available $7 (rural) $9 (urban) Summary of Published Studies * Adjusted to 2001 USD

23. How does maternal syphilis screening compare with other perinatal interventions? PMTCT (Rapid HIV CT) and Prophylaxis (Nevirapine) of positives Maternal HIV Prevalence$ per Perinatal Outcome Averted*$ per DALY Saved 13 – 18%$2284 - $4292$77 - $140 *adjusted to 2000 US dollars Sweat et al. AIDS 2004 Zambia, Kenya, Tanzania

24. How does maternal syphilis screening compare with other perinatal interventions? Maternal Σ Prevalence$ per Perinatal Outcome Averted**$ per DALY Saved* 3 – 9%$181 - $300$11-19 Maternal Syphilis Screening (RPR) and Treatment (Penicillin) of positives PMTCT (Rapid HIV CT) and Prophylaxis (Nevirapine) of positives Maternal HIV Prevalence$ per Perinatal Outcome Averted**$ per DALY Saved 13 – 18%$2284 - $4292$77 - $140 *adjusted to 2000 US dollars **adjusted to 2001 US dollars Hira et al 1990, Jenniskens et al 1995, Fonck et al 2001, Terris-Prestholt 2003 Sweat et al. AIDS 2004 Zambia, Kenya, Tanzania

25. How does maternal syphilis screening compare with other perinatal interventions? Maternal Σ Prevalence$ per Perinatal Outcome Averted**$ per DALY Saved* 3 – 9%$181 - $300$11-19 Maternal Syphilis Screening (RPR) and Treatment (Penicillin) of positives PMTCT (Rapid HIV CT) and Prophylaxis (Nevirapine) of positives Maternal HIV Prevalence$ per Perinatal Outcome Averted**$ per DALY Saved 13 – 18%$2284 - $4292$77 - $140 *adjusted to 2000 US dollars **adjusted to 2001 US dollars Hira et al 1990, Jenniskens et al 1995, Fonck et al 2001, Terris-Prestholt 2003 Sweat et al. AIDS 2004 Zambia, Kenya, Tanzania

26. Why CS Elimination Now? World focus on health for women and children Millennium Development Goals (MDGs) MDG 4: reduce child mortality MDG 5: improve maternal health MDG 6: combat HIV, malaria, and other diseases Making Pregnancy Safer Initiative (WHO) Better measures of infant mortality (e.g., repeated DHS) Increased recognition in countries (e.g., almost universal support for universal maternal syphilis screening)

27. Why CS Elimination Now? Possible shared resources in antenatal health – several existing programmatic efforts are scaling up Childhood Immunization Programs Enhanced Malaria Control Prevention of Maternal-to-Child HIV Transmission (PMTCT) Family Planning and Reproductive Health Services Better data on cost-benefits of maternal syphilis screening Cheaper, easier tests available Why not? (right thing to do)

28. Why CS Elimination Now? Possible shared resources in antenatal health – several existing programmatic efforts are scaling up Childhood Immunization Programs Enhanced Malaria Control Prevention of Maternal-to-Child HIV Transmission (PMTCT) Family Planning and Reproductive Health Services Better data on cost-benefits of maternal syphilis screening Cheaper, easier tests available Why not? (right thing to do)

29. Mission: To promote the development, evaluation and application of STI diagnostic tests appropriate for use in developing countries settings Sexually Transmitted Diseases Diagnostics Initiative (SDI)

30. Global Vision of Controlling STIs is ASSURED J. Clin. Path. 2007;60:376 Ideal Test A A ffordable S S ensitive S S pecific U U ser-friendly R R apid E E quipment-free D D elivered CT S

31. SDI Evaluation Sites LAB SITES LAB SITES FIELD SITES Africa: Madagascar Mwanza, Tz Fajara, Gambia Cotonu, Benin Americas: Manaus,Brazil Port au Prince, Haiti Birmingham, USA Asia: China Sri Lanka Europe: Moscow, Russia SYPHILIS SYPHILISCTNG SDI Network – Rapid Syphilis Tests

32. Rapid Syphilis Tests are Affordable Currently available rapid tests are treponemal tests (any syphilis in lifetime) Promising dual tests under development WHO/SDI bulk procurement scheme allows low-income nations to purchase tests at affordable prices Costs $.19 - $1.00 per test

33. Rapid Syphilis Test (Bioline) CT 1. Add serum or whole blood

34. Rapid Syphilis Test (Bioline) CTCT 1. Add serum or whole blood2. Add buffer 3. Wait 5 minutes

35. Rapid Syphilis Test (Bioline) CTCT 1. Add serum or whole blood2. Add buffer 3. Wait 5 minutes CTCT Negative resultPositive result

37. S ame-visit T esting a nd T reatment STAT!! Women get testing, results and (if positive) treatment at same visit without need to return Pilot studies in Haiti and Mozambique suggest STAT can increase screening/treatment to > 90% Could be RPR in some settings, or rapid treponemal test If rapid tests -- CE studies suggest over-treatment of positive treponemal tests adds little to cost. Over-treatment also has very low morbidity for women.

38. With international partners: Develop integrated framework for surveillance & monitoring Build on existing evidence: scale up successful interventions Establish recommendations on treatment; testing algorithms Support operations research to introduce rapid tests and other practical technologies Ensure congenital syphilis information is adequately addressed in clinical guidelines, tools, etc. Identify resources – “Investment Case” Moving Forward, Next Steps (WHO)

39. Investment Case for CS Elimination Document compelling reasons for investing in CSE - Participants Consortium of nations & agencies supporting the initiative, working together to identify donor funding Dec 2007 meeting in Atlanta (WHO/CDC) with USAID, universities, international NGOs and CDC Foundation - Identified models/strategies - Clarified areas where additional funding needed - Developing an Investment Case paper for dissemination Major goal: Country-wide “scale up projects” What does it take to implement universal screening in a nation?

40. The Global Elimination of Congenital Syphilis: Rationale and Strategy for Action For more information: http://www.who.int/reproductive-health/stis/syphilis.html

41. More information on CS Elimination Also See Poster # 99 “Are national policies, services and indicators ready for the global initiative to eliminate congenital syphilis as a public health problem?” Facilitator: Jennifer Mark, MPH