Lecture No. 12 T. pallidum-2

Based upon CDC educational materials for STDs:

Based upon CDC educational materials for STDs All copyrighted materials belongs to CDC Syphilis curriculum 2

History:

3 History Stan Carter is a 19-year-old male who presents to the STD clinic Chief complaint: penile lesion x 1 week Last sexual exposure was 3 weeks prior, without a condom No history of recent travel Predominantly female partners (3 in the last 6 months), and occasional male partners (2 in the past year) Last HIV antibody test (2 months prior) was negative Case Study

Physical Exam :

4 Physical Exam No oral, perianal , or extra-genital lesions Genital exam: Lesion on the ventral side near/at the frenulum . Lesion is red, indurated , clean-based , and non-tender. Case Study

Physical Exam :

5 Physical Exam Two enlarged tender right inguinal nodes, 1.5 cm x 1 cm Scrotal contents without masses or tenderness No urethral discharge No rashes on torso, palms, or soles. No alopecia. Neurologic exam within normal limits. Case Study

Stan’s Sex Partners:

6 Stan’s Sex Partners Lucy – last sexual exposure 3 weeks ago Danielle – last sexual exposure 6 weeks ago Jonathan – last sexual exposure 1 month ago Tony – last sexual exposure 8 months ago Carrie – last sexual exposure 6 months ago Case Study

Spirochaetales responsible for human disease:

Spirochaetales responsible for human disease Treponema Borrelia Leptospira Thin, helical, gram-negative bacteria 7

Syphilis :

8 Syphilis Treponema pallidum

Syphilis Definition :

9 Syphilis Definition Sexually acquired infection Etiologic agent: Treponema pallidum Disease progresses in stages May become chronic without treatment Epidemiology

Transmission:

10 Transmission Sexual and vertical Most contagious to sex partners during the primary and secondary stages Epidemiology

Disease Trends in the U.S.:

11 Disease Trends in the U.S. Distributed widely throughout the U.S. in the 1940s Declined rapidly after introduction of penicillin therapy and broad-based public health programs 1986-90: 85% increase in the incidence of primary and secondary syphilis During the 1990s, reported cases of syphilis decreased approximately 15% per year to an all-time low in 2000 Rates remain high in: Rural areas in the South Some urban areas throughout the U.S Recent outbreaks have occurred among subpopulations of men who have sex with men (MSM) Epidemiology

Syphilis — Reported cases by stage of infection: United States, 1941–2003 :

12 Syphilis — Reported cases by stage of infection: United States, 1941–2003 Source : CDC/NCHSTP 2003 STD Surveillance Report Epidemiology

Primary and secondary syphilis — Rates by state: United States and outlying areas, 2003:

13 Primary and secondary syphilis — Rates by state: United States and outlying areas, 2003 Note: The total rate of primary and secondary syphilis for the United States and outlying areas (Guam, Puerto Rico and Virgin Islands) was 2.5 per 100,000 population. The Healthy People 2010 target is 0.2 case per 100,000 population. Source : CDC/NCHSTP 2003 STD Surveillance Report Epidemiology

Primary and secondary syphilis — Rates by sex: United States, 1981–2003 and the Healthy People 2010 target :

14 Primary and secondary syphilis — Rates by sex: United States, 1981–2003 and the Healthy People 2010 target Note: The Healthy People 2010 target for P&S syphilis is 0.2 case per 100,000 population. Source : CDC/NCHSTP 2003 STD Surveillance Report Epidemiology

Primary and secondary syphilis — Male-to-female rate ratios: United States, 1981–2003:

15 Primary and secondary syphilis — Male-to-female rate ratios: United States, 1981–2003 Source : CDC/NCHSTP 2003 STD Surveillance Report Epidemiology

Primary and secondary syphilis — Rates by race and ethnicity: United States, 1981–2003 and the Healthy People 2010 target:

16 Primary and secondary syphilis — Rates by race and ethnicity: United States, 1981–2003 and the Healthy People 2010 target Note: The Healthy People 2010 target for P&S syphilis is 0.2 case per 100,000 population. Source : CDC/NCHSTP 2003 STD Surveillance Report Epidemiology

Congenital syphilis — Reported cases for infants <1 year of age and rates of primary and secondary syphilis among women: U.S., 1970–2003:

17 Congenital syphilis — Reported cases for infants <1 year of age and rates of primary and secondary syphilis among women: U.S., 1970–2003 Note: The surveillance case definition for congenital syphilis changed in 1988. Source : CDC/NCHSTP 2003 STD Surveillance Report Epidemiology

Pathogenesis:

18 Pathogenesis

Microbiology:

19 Microbiology Etiologic agent: Treponema pallidum , subspecies pallidum Corkscrew-shaped, motile microaerophilic bacterium Cannot be cultured in vitro Cannot be viewed by normal light microscopy Pathogenesis

Treponema pallidum:

20 Treponema pallidum Pathogenesis Source : CDC/NCHSTP/Division of STD Prevention, STD Clinical Slides Electron photomicrograph, 36,000 x.

Treponema pallidum on darkfield microscopy:

21 Treponema pallidum on darkfield microscopy Pathogenesis Source : CDC/NCHSTP/Division of STD Prevention, STD Clinical Slides

Pathology:

22 Pathology Penetration: T. pallidum enters the body via skin and mucous membranes through abrasions during sexual contact Also transmitted transplacentally Dissemination: Travels via the lymphatic system to regional lymph nodes and then throughout the body via the blood stream Invasion of the CNS can occur during any stage of syphilis Pathogenesis

Clinical Manifestations:

23 Clinical Manifestations

Primary Syphilis :

24 Primary Syphilis Primary lesion or "chancre" develops at the site of inoculation Chancre: Progresses from macule to papule to ulcer Typically painless, indurated, and has a clean base Highly infectious Heals spontaneously within 1 to 6 weeks 25% present with multiple lesions Regional lymphadenopathy: classically rubbery, painless, bilateral Serologic tests for syphilis may not be positive during early primary syphilis Clinical Manifestations

Primary Syphilis- Penile Chancre:

25 Primary Syphilis- Penile Chancre Clinical Manifestations Source : CDC/ NCHSTP/ Division of STD Prevention, STD Clinical Slides

Primary Syphilis – Labial Chancre:

26 Primary Syphilis – Labial Chancre Clinical Manifestations Source : CDC/ NCHSTP/ Division of STD Prevention, STD Clinical Slides

Primary Syphilis – Perianal Chancre:

27 Primary Syphilis – Perianal Chancre Clinical Manifestations Source : CDC/ NCHSTP/ Division of STD Prevention, STD Clinical Slides

Syphilis Lesion - Tongue:

28 Syphilis Lesion - Tongue Source : CDC/ NCHSTP/ Division of STD Prevention /STD Clinical Slides Clinical Manifestations

Secondary Syphilis :

29 Secondary Syphilis Secondary lesions occur 3 to 6 weeks after the primary chancre appears; may persist for weeks to months Primary and secondary stages may overlap Mucocutaneous lesions most common Manifestations: Rash (75%-100%) Lymphadenopathy (50%-86%) Malaise Mucous patches (6%-30%) Condylomata lata (10%-20%) Alopecia (5%) Serologic tests are usually highest in titer during this stage Clinical Manifestations

Secondary Syphilis - Papulosquamous Rash:

30 Secondary Syphilis - Papulosquamous Rash Clinical Manifestations Source : CDC/ NCHSTP/ Division of STD Prevention, STD Clinical Slides

Secondary Syphilis: Palmar/Plantar Rash:

31 Secondary Syphilis: Palmar/Plantar Rash Clinical Manifestations Source : Seattle STD/HIV Prevention Training Center at the University of Washington, UW HSCER Slide Bank Source : CDC/NCHSTP/Division of STD Prevention, STD Clinical Slides

Secondary Syphilis: Generalized Body Rash:

32 Secondary Syphilis: Generalized Body Rash Clinical Manifestations Source : Cincinnati STD/HIV Prevention Training Center Source : CDC/NCHSTP/Division of STD Prevention, STD Clinical Slides

Secondary Syphilis – Papulo-pustular Rash:

33 Secondary Syphilis – Papulo-pustular Rash Clinical Manifestations Source : CDC/ NCHSTP/ Division of STD Prevention, STD Clinical Slides

Secondary Syphilis - Condylomata lata:

34 Secondary Syphilis - Condylomata lata Clinical Manifestations Source : CDC/ NCHSTP/ Division of STD Prevention, STD Clinical Slides

Secondary Syphilis – Nickel/Dime Lesions:

35 Secondary Syphilis – Nickel/Dime Lesions Clinical Manifestations Source : CDC/ NCHSTP/ Division of STD Prevention, STD Clinical Slides

Secondary Syphilis - Alopecia:

36 Secondary Syphilis - Alopecia Clinical Manifestations Source : CDC/ NCHSTP/ Division of STD Prevention, STD Clinical Slides

Latent Syphilis :

37 Latent Syphilis Host suppresses the infection enough so that no lesions are clinically apparent Only evidence is positive serologic test for syphilis May occur between primary and secondary stages, between secondary relapses, and after secondary stage Categories: Early latent: <1 year duration Late latent:  1 year duration Clinical Manifestations

Neurosyphilis :

38 Neurosyphilis Occurs when T. pallidum invades the CNS May occur at any stage of syphilis Can be asymptomatic Early neurosyphilis occurs a few months to a few years after infection Clinical manifestations include acute syphilitic meningitis, meningovascular syphilis, ocular involvement Late neurosyphilis occurs decades after infection and is rarely seen Clinical manifestations include general paresis, tabes dorsalis, ocular involvement Clinical Manifestations

Neurosyphilis - Spirochetes in Neural Tissue:

39 Neurosyphilis - Spirochetes in Neural Tissue Clinical Manifestations Source : CDC/ NCHSTP/ Division of STD Prevention, STD Clinical Slides Silver stain, 950x

Tertiary (Late) Syphilis :

40 Tertiary (Late) Syphilis Approximately 30% of untreated patients progress to the tertiary stage within 1 to 20 years Rare because of the widespread availability and use of antibiotics Manifestations Gummatous lesions Cardiovascular syphilis Clinical Manifestations

Late Syphilis - Serpiginous Gummata of Forearm:

41 Late Syphilis - Serpiginous Gummata of Forearm Clinical Manifestations Source : CDC/ NCHSTP/ Division of STD Prevention, STD Clinical Slides

Late Syphilis - Ulcerating Gumma:

42 Late Syphilis - Ulcerating Gumma Clinical Manifestations Source : CDC/ NCHSTP/ Division of STD Prevention, STD Clinical Slides

Late Syphilis--Cardiovascular :

43 Late Syphilis--Cardiovascular Clinical Manifestations Source : CDC/ NCHSTP/ Division of STD Prevention, STD Clinical Slides

Congenital Syphilis :

44 Congenital Syphilis Occurs when T. pallidum is transmitted from a pregnant woman with syphilis to her fetus May lead to stillbirth, neonatal death, and infant disorders such as deafness, neurologic impairment, and bone deformities Transmission to the fetus in pregnancy can occur during any stage of syphilis; risk is much higher during primary and secondary syphilis Fetal infection can occur during any trimester of pregnancy Wide spectrum of severity exists; only severe cases are clinically apparent at birth Early lesions (most common): Infants <2 years old; usually inflammatory Late lesions: Children >2 years old; tend to be immunologic and destructive Clinical Manifestations

Congenital Syphilis - Mucous Patches:

45 Congenital Syphilis - Mucous Patches Clinical Manifestations Source : CDC/ NCHSTP/ Division of STD Prevention, STD Clinical Slides

Congenital Syphilis - Hutchinson’s Teeth:

46 Congenital Syphilis - Hutchinson’s Teeth Clinical Manifestations Source : CDC/ NCHSTP/ Division of STD Prevention, STD Clinical Slides

Congenital Syphilis - Perforation of Palate:

47 Congenital Syphilis - Perforation of Palate Clinical Manifestations Source : CDC/ NCHSTP/ Division of STD Prevention, STD Clinical Slides

Syphilis Diagnosis:

48 Syphilis Diagnosis

Aspects of Syphilis Diagnosis:

49 Aspects of Syphilis Diagnosis Clinical history Physical examination Laboratory diagnosis Diagnosis

Clinical History:

50 Clinical History Assess: History of syphilis Known contact to an early case of syphilis Typical signs or symptoms of syphilis in the past 12 months Most recent serologic test for syphilis Diagnosis

Physical Examination:

51 Physical Examination Oral cavity Lymph nodes Skin of torso Palms and soles Genitalia and perianal area Neurologic examination Diagnosis

Laboratory Diagnosis:

52 Laboratory Diagnosis Identification of Treponema pallidum in lesions Darkfield microscopy Direct fluorescent antibody - T. pallidum (DFA-TP) Serologic tests Nontreponemal tests Treponemal tests Diagnosis

Darkfield Microscopy:

53 Darkfield Microscopy What to look for: T. pallidum morphology and motility Advantage: Definitive immediate diagnosis Disadvantages: Requires specialized equipment and an experienced microscopist Possible confusion with other pathogenic and nonpathogenic spirochetes Must be performed immediately Generally not recommended on oral lesions Possibility of false-negatives Diagnosis

Direct Fluorescent Antibody-- T. pallidum (DFA-TP):

54 Direct Fluorescent Antibody-- T. pallidum (DFA-TP) Identifies T. pallidum in direct lesion smear by immunofluorescence Advantages: Commercially available Compares favorably with darkfield microscopy Disadvantages: Turnaround time 1-2 days Diagnosis

Serologic Tests for Syphilis:

55 Serologic Tests for Syphilis Two types Treponemal (qualitative) Nontreponemal (qualitative and quantitative) The use of only one type of serologic test is insufficient for diagnosis. Diagnosis

Nontreponemal Serologic Tests:

56 Nontreponemal Serologic Tests Principles Measure antibody directed against a cardiolipin-lecithin-cholesterol antigen Not specific for T. pallidum Titers usually correlate with disease activity and results are reported quantitatively May be reactive for life Nontreponemal tests include VDRL, RPR, TRUST, USR Diagnosis

Jarisch-Herxheimer Reaction :

57 Jarisch-Herxheimer Reaction Self-limited reaction to anti-treponemal therapy Fever, malaise, nausea/vomiting; may be associated with chills and exacerbation of secondary rash Occurs within 24 hours after therapy Not an allergic reaction to penicillin More frequent after treatment with penicillin and treatment of early syphilis Pregnant women should be informed of this possible reaction, that it may precipitate early labor, and to call obstetrician if problems develop Management

Prevention:

58 Prevention

Reporting:

59 Reporting Laws and regulations in all states require that persons diagnosed with syphilis are reported to public health authorities by clinicians, labs, or both. The follow-up of patients with early syphilis is a public health priority. Prevention

Questions about the case:

60 Questions about the case What are the possible etiologic agents that should be considered in the differential diagnosis? What is the most likely diagnosis? Which laboratory tests would be appropriate to order or perform? Case Study

Stat Lab Results:

61 Stat Lab Results The results of stat laboratory tests showed the following: RPR: Nonreactive Darkfield examination of penile lesion: Positive for T. pallidum What is the diagnosis? What is the appropriate treatment? Case Study

Reference Lab Results:

62 Reference Lab Results RPR: Nonreactive FTA-ABS: Reactive HSV culture: Negative Gonorrhea culture: Negative Chlamydia DNA-probe: Negative HIV antibody test: Negative Do the reference laboratory results change the diagnosis? Who is responsible for reporting this case to the local health department? Case Study

Stan’s Sex Partners:

63 Stan’s Sex Partners Lucy – last sexual exposure 3 weeks ago Danielle – last sexual exposure 6 weeks ago Jonathan – last sexual exposure 1 month ago Tony – last sexual exposure 8 months ago Carrie – last sexual exposure 6 months ago Which of Stan’s partners should be evaluated and treated prophylactically , even if their test results are negative? Case Study

Sex Partner Follow-Up:

64 Sex Partner Follow-Up Stan’s partner, Lucy , is found to be infected and is diagnosed with primary syphilis. She is also in her second trimester of pregnancy and is allergic to penicillin. 9. What is the appropriate treatment for Tracy? Case Study

Follow-Up:

65 Follow-Up Stan returned to the clinic for a follow-up exam 1 week later. Results were as follows: His penile lesion was almost completely healed. He had not experienced a Jarisch-Herxheimer reaction. The RPR (repeated at the follow-up visit because the initial one was negative) was 1:2. 10. What type of follow-up evaluation will Stan need? Case Study