1. University of Alabama at Birmingham Jefferson County Depart. Of Health
Back Again: Recurring Epidemics of Syphilis in the U.S. – A Syphilis Management Update
Edward W. Hook III M. D.
University of Alabama at Birmingham
And
Jefferson County Depart. Of Health
Birmingham, Alabama

4. Treponema pallidum Morphology Spiral, 8-13x0.15 m
Motility Corkscrew, Flexing
Division Time 33 hours - 5 days
In vitro Cultivation No
(Culture)

6. Principles of STD Management
Accurate Diagnosis
Effective Therapy
Dose
Duration
Compliance
Concomitant Infections
Management of Partners

7. SYPHILIS MANAGEMENT GOALS
Resolution of clinical signs/symptoms
Prevention of disease progression
Prevention of transmission to others
Prevention of HIV transmission/acquisition

8. EPIDEMIOLOGICAL CHARACTERISTICS OF SYPHILIS
Rates highest during social upheaval
War time
Economic stress
Most common in developing nations
Disease most common in marginalized groups
Lower socio-economic classes
Racial / ethnic minorities
Limited access to health care
Commercial sex workers and drug users

9. Syphilis—Reported Cases by Stage of Infection, United States, 1941–2011
2011-Fig 36. SR

10. Primary and Secondary Syphilis—by Sex and Sexual Behavior, 33 Areas
*32 states and Washington, DC reported sex of partner data for ³70% of cases of P&S syphilis for each year during
†MSM=men who have sex with men; MSW=men who have sex with women only.
2011-Fig 37. SR

11. Primary and Secondary Syphilis—Rates by Age and Sex, United States, 2011
2011-Fig 42. SR

12. Selected STD Rates, 2007 – U.S., Canada, U.K. and Sweden
N. Gonorrhoeae
118.9
36.1
30.6
7.0
C. Trachomatis
370.2
224.4
200.3
458.4
Early (P, S & EL Syphilis)
7.4
3.7
4.3
2.6
CDC, STD Surveillance
Public Health Agency of Canada, Reported cases of STI
WHO 2009

13. SYPHILIS CONTROL
CURRENTLY AVAILABLE TOOLS HAVE BEEN USED WITH SUCCESS THROUGHOUT MOST OF THE DEVELOPED WORLD

14. Features Favoring Syphilis Control
No animal reservoir
Reliable diagnostic tests
Safe, effective curable and preventative therapy
Relatively long, non-infectious incubation period
Low or declining disease rates

15. National Plan for Syphilis Elimination
Cross-Cutting Strategies
Enhanced surveillance
Strengthened community involvement and partnerships
Intervention Strategies
Rapid outbreak response
Expanded clinical and laboratory services
Enhanced health promotion
Syphilis nearly non-existent in Europe. One of the reasons: Better access to care. Syphilis not reported from the vast majority of counties. Assume – as stated by Garnett/ others – improvements additional pressure from almost any source would be sufficient to push it over the edge. Basic philosophy – regarded it as a “sentinenl event” – some public health deficiency that could be improved by greater involvement of community groups, improving access to care. Etc.

16. Progress on Syphilis Elimination (1997-2001)
Reduction
1997
1998
1999
2000
2001
P&S syphilis cases
Congenital syphilis cases
Counties responsible for 50%
Black:White rate ratio
8,556
1,078 31
44:1
7,007
840 28
34:1
6,617
575 25
30:1
5,979
554 22
24:1
6,103
441 21
16:1
29%
60%
32%
63%
In fact disparities were even greater earlier in the decade.

17. THE NEXT GREAT PLAGUE TO GO Thomas Parran’s 5-Point Program For Syphilis Control – 1936
Case Finding – Serologic Screening Programs
Prompt Therapy
Contact Identification, Testing, and Therapy
Mandatory Serological Evaluations – Premarital and Early Pregnancy
Public Education = Symptoms, Complications, Treatment

18. Principles of STD Management
Accurate Diagnosis
Effective Therapy
Dose
Duration
Compliance
Concomitant Infections
Management of Partners

19. NATURAL HISTORY OF SYPHILIS
20-50%
Exposure … 1°
Latent 3
33% 25% % 2°

21. Parenthetical Comment: Rethinking Genital Herpes

22. Etiology of Genital Ulcers In 516 STD Clinic Patients
515 patients recruited from STD Clinics in 10 U.S Cities With High Syphilis Rates
PCR Result Number (%)
HSV (62%)
Syphilis (10%)
HSV and Syphilis (3%)
Chancroid (3%)
PCR Negative (22%)
Mertz K et al JID 1998: 178:

24. Back To Syphilis

25. NATURAL HISTORY OF SYPHILIS
20-50%
Exposure … 1°
Latent 3
33% 25% % 2°

26. Secondary syphilis

31. NATURAL HISTORY OF SYPHILIS
20-50%
Exposure … 1°
Latent 3
33% 25% % 2°

34. Serologic Tests for Syphilis
Nontreponemal Tests (VDRL, RPR)
Antigen -
cardiolipin-lecithin-cholesterol
Quantitative
Treponemal Tests (FTA-ABS, MHA-TP, EIAs)
Treponemal Antigens
Qualitative

36. Interpretation of Changing STS Titers
Error of RPR VDRL Tests dilution
Meaningful change is 2 dilution (or 4-fold) change in titer
e.g. 1:2  1:4 or 1:1, no meaningful change
1:2  1:8, meaningful change
Quantitative RPR or VDRL test, results are not interchangeable
Two dilution decline in titer indicates response to therapy however, failure to decline > 2 dilutions does not necessarily mean patient has failed treatment

37. SYPHILIS SERODIAGNOSIS: Why Use Confirmatory Tests?
Imagine the results of false positive tests (BFPs) when 100,000 people without syphilis are tested. Assume BFP rates of 1.5% for the non-treponemal and 1% for treponemal tests used
Screening
Non-treponemal Test Treponemal Test
100, ,000
x x
Confirmatory Testing
Treponemal Test Non-treponemal Test
1, ,000
x x 015

38. PITFALLS ENCOUNTERED IN SYPHILIS SERODIAGNOSIS AND FOLLOW-UP
Biologic False Positives
False Negative or Delayed STS Reactivity
Delayed or Partial Response to Therapy
Interpretation of Test Results in Pregnant Patients
Interpretation of Test Results in Patients with Prior Syphilis

39. EIA Serologic Tests for Syphilis
EIA= Enzyme Immuno- Assay
Pro’s
Cloned Treponemal Antigens
Easy to do in large numbers.
Inexpensive
Con’s
Limited data on specificity
Positives need quantitative test to assess response to therapy and perhaps for confirmation

40. EIA (ELISA) Serologic Tests for Syphilis Suggested Evaluation of Positive Tests
Clinical Evaluation and Record Search. Significance of positive test unknown in persons with prior syphilis.
Confirm result with RPR/VDRL.
If positive, use for monitoring response to therapy.
If negative- ?? Possible longstanding infection vs.. false positive. Clinical evaluation/correlation required

41. HIV/STD Potential Interactions
STDs as markers for HIV risk
STDs as risk factors for HIV/acquisition transmission
Alterations of clinical +/or laboratory manifestations of STDs due to coexistent HIV infection
Decreases susceptibility to STD therapy due to coexistent HIV infection
Acceleration of HIV natural history due to coexistent or intercurrent STDs

42. Syphilis Therapy: Goals
Cure of disease: improvement of clinical signs and symptoms; prevention of disease progression
Prevention of disease transmission
Reduction of risk for HIV acquisition

43. NATURAL HISTORY OF SYPHILIS
20-50%
Exposure … 1°
Latent 3
33% 25% % 2°

44. Recommend Treatment For Gonorrhea and Syphilis, 1935 - 2006
Gonorrhea Syphilis
Sulfonilamide
Penicillin Penicillin
Ampicillin
Tetracycline
Spectinomycin
Ceftriaxone
Fluoroquinolones
Cefixime

46. 2010 CDC STD TREATMENT GUIDELINES Early Syphilis
Recommended
Benzathine Penicillin G, 2.4 Mu IM
Penicillin Allergy
Doxycyline 100 mg PO, BID x 14d
Limited Data
Ceftriaxone 1.0 g IM or IV x 8-10d
Azithromycin 2.0g PO

47. SYPHILIS THERAPY: RESPONSE TO THERAPY
Primary or Secondary Syphilis – Fourfold (2 dilution) or greater decline in RPR or VDRL titers by time of 3 month follow-up
Early Latent Syphilis – Fourfold (2 dilution) or greater decline in RPR or VDRL titers by time of 6 month follow-up

48. MANIFESTATIONS OF SYPHILIS TREATMENT FAILURE
Clinical Relapse (Recurrent or New Signs)
Serologic Failure
Relapse following initial response
Serologic progression despite therapy
Serologic non-response
N.B. Treatment failure must be differentiated from reinfection

49. TREATMENT OF EARLY SYPHILIS IN HIV-INFECTED AND UNINFECTED PERSONS
Proportion of Subjects with RPR Decline <2 Dilutions
3 Mo.
6 Mo.
12 Mo.
Treatment Group
Usual
25% (175)
24% (157)
18% (137)
Enhanced
29% (189)
19% (172)
17% (144)
Rolfs et al, NEJM

50. 2010 STD TREATMENT GUIDELINES Syphilis in Pregnant Patients
Serological Screening for All Women in Early Pregnancy; Repeat Screening at Weeks and at Delivery in High Risk Patients or High Prevalence Communities
Treat as Recommended for Non-Pregnant Patients
No Infant Should Leave the Hospital Without Maternal Serologic Status having Been Determined at Least Once During Pregnancy

51. HIV/STD Potential Interactions
STDs as markers for HIV risk
STDs as risk factors for HIV/acquisition transmission
Alterations of clinical +/or laboratory manifestations of STDs due to coexistent HIV infection
Decreases susceptibility to STD therapy due to coexistent HIV infection

52. TREATMENT OF EARLY SYPHILIS IN HIV-INFECTED AND UNINFECTED PERSONS
Proportion of Subjects with RPR Decline <2 Dilutions
3 Mo.
6 Mo.
12 Mo.
Treatment Group
Usual
25% (175)
24% (157)
18% (137)
Enhanced
29% (189)
19% (172)
17% (144)
HIV-Status
Positive
38% (76)*
28% (69)
21% (61)
Negative
24% (287)
19% (259)
16% (219)
*P < 0.05
Rolfs et al, NEJM

53. 2010 STD TREATMENT GUIDELINES Syphilis in HIV Infected Patients
Treat as Recommended for Patients Without HIV Infection
Closer Follow-up
(3, 6, 9, 12, and 24 mos)

54. 2010 STD TREATMENT GUIDELINES Early vs. Late Latent Syphilis
Early Latent Syphilis
Documented Seroconversion Past Year Unequivocal history of 1°, 2° syphilis symptoms, past year
Sex partner with 1°, 2°, or EL syphilis, past year
Late Latent Syphilis
All others
(STD Titers Do Not Differentiate Early vs. Late Latent Syphilis)

55. 2010 CDC STD TREATMENT GUIDELINES Late Latent and Tertiary Syphilis
Benzathine Penicillin G 2.4 Mu IM weekly x 3
Penicillin Allergy
Doxycycline 100 mg PO, BID x 28

56. Syphilis Therapy: Response To Therapy
Late Latent or Tertiary Syphilis Other Than Neurosyphilis – Follow-up at 6 and 12 months. If titers increase fourfold, if an initially high (> 1:32) fails to decrease, or if signs or symptoms progress or develop, re-evaluate for neurosyphilis and re-treat.

57. Latent Syphilis: Response To Therapy

58. SYPHILIS MANAGEMENT GOALS
Resolution of clinical signs/symptoms
Prevention of disease progression
Prevention of transmission to others
Prevention of HIV transmission/acquisition