1. The Great Imitator

2. Why a lecture on syphilis? syphilis is an treatable disease control of syphilis is vital because of its interactions with HIV

3. Outline History Microbiology Epidemiology Diagnosis Pathophysiology Clinical Manifestations Treatment Syphilis and HIV

4. Pre-Penicillin Era Highly prevalent in many countries/societies in pre-penicillin era Highly prevalent in many countries/societies in pre-penicillin era Dramatic drop in incidence/prevalence after introduction of penicillin in mid- 1940s Dramatic drop in incidence/prevalence after introduction of penicillin in mid- 1940s

5. Epidemiological Synergy HIV and syphilis co-facilitate transmission of each other HIV and syphilis co-facilitate transmission of each other  Despite CDC campaign to eradicate in 2000s total cases per year continue to increase  EPIDEMIOLOGY: Worldwide; primarily involving young people between 20-35 years  HOST RANGE: Humans

6. Microbiology Treponema pallidum, causative agent isolated 1905 Treponema pallidum Family Spirochaetacaeae

7. Treponema Gram-negative have an outer membrane motile microaerophilic to anaerobic found in the oral cavity, intestinal tract, genital areas of man and some animals

8. The primary mode of transmission is via sexual contact. Syphilis is passed from person to person through direct contact with a syphilis sore. Sores occur mainly on the external genitals, vagina, anus, or in the rectum. Sores also can occur on the lips and in the mouth. blood transfusion Syphilis is also transmitted congenitally from an infected mother to her infant. Syphilis is also transmitted congenitally from an infected mother to her infant.

9. Congenital Syphilis Syphilis is transmissible from mother to infant Syphilis is transmissible from mother to infant Transmission usually occurs during early stages, but may occur at any stage in an untreated mother Transmission usually occurs during early stages, but may occur at any stage in an untreated mother

10. Clinical Stages Syphilis is conventionally divided into several stages: – Primary – Secondary – Latent – Late, or tertiary

11. Untreated, syphilis progresses through a primary and secondary stage before becoming latent. Untreated, syphilis progresses through a primary and secondary stage before becoming latent. Up to 1/3 of people with untreated syphilis develop tertiary disease late in life, primarily cardiovascular and neurologic. Up to 1/3 of people with untreated syphilis develop tertiary disease late in life, primarily cardiovascular and neurologic.

12. Natural History of Untreated Syphilis

13. Pathophysiology Transmission, usually sexual, requires direct contact lesion, incubation period 21 days PRIMARY : Initial lesion develops at site of transmission, cellular response/perivascular infiltrate. SECONDARY : Treponemes disseminate, cleared by macrophages. TERTIARY : Result of chronic inflammation, hypersensitivity reaction and end organ damage

14. Primary syphilis incubation period - 10-90 days(3weeks) lesion at the site of inoculation – chancre (hard chancre) lesion not infectious lesion spontaneously disappears in 2-6 weeks bacteria enter blood stream

15. Primary Syphilis Chancre appears within 3 weeks of infection Single painless papule at site of inoculation distinct indurated borders and ulcerated center Spontaneously heals Discreet, firm painless lympadenopathy

16. Primary syphilis

17. Secondary Syphilis Defined by disseminated symptoms and positive serology – Bilateral symmetric rash, palms/soles – Fever, sore throat, malaise – Arthalgias – Condyloma lata Usually 2-8 weeks after appearance of chancre. Even if untreated, eventually macrophage clearance and treponemicidal complement leads to resolution.

18. Rash is never vesicular except in congenital form

21. Period of asymptomatic infection, however serologic test continue to be positive. – Early Latent: documented within one(4) year of acquisition, very infectious. – Late Latent: greater than 1(4) year since transmission

23. Tertiary Syphilis 30% of untreated P&SS progresses to tertiary. Combination of treponemal invasion of end organs and delayed type hypersensitivity response in skin, CVS, CNS. GUMMA : late benign granulomas to skin/viscera CVS: endarteritis obliterans to vaso vasorum

24. Involvement may occur as soon as 1 yr post acquisition. Asymptomatic: 15% of PS and 40% SS have abnormal CSF findings Acute Meningitis: typical meningeal findings dx via PCR, VDRL Meningovascular: diffuse inflammation/ syphilitic endarteritis eventual vascular occlusion of cerebral vessels. – General paresis: chronic infection cerebral cortex/meninges – Tabes Dorsalis: demyelination of posterior columns, dorsal roots, and dorsal root ganglia.

25. Meningeal neurosyphilis – includes acute syphilitic meningitis – headache, fever, CSF abnormalities Meningovascular neurosyphilis – “syphilitic stroke” – hemiparesis, hemiplegia, aphasia, seizure Parenchymatous neurosyphilis – general paresis – tabes dorsalis

26. Parenchymatous neurosyphilis General paresis (dementia paralytica) – T. pallidum directly invades cerebrum memory loss, personality changes, headache, delusions, seizure – neurologic findings include: Argyll Robertson pupils slurred speech expressionless face tremors

27. Parenchymatous neurosyphilis Tabes dorsalis – occurs after long latent period (20-25 yrs.) early features: lightning pains, paresthesias, diminished DTRs, poor pupillary responses late features: ataxia, bladder and rectal disturbances, Charcot joints, “visceral crises” – “tabetic facies” due to ptosis and flabbiness of facial muscles

28. Tertiary syphilis

31. Syphlitic Aortic Aneurysm

32. Aortic Aneurysm

33. Ruptured Aortic Aneurysm Tree-barking Clot

34. Stenosis of Coronary Arteries

35. Charcot Joint

36. Gumma of Face

37. Gummas of the Nose

38. Gumma - Nose

39. Gmmas of Arm u

40. Gummas - Arm

41. Ulcerating Gumma

42. Late complications of syphilis occurred in about 1/3 of patients in the preantibiotic era Prompt penicillin therapy of early disease not only prevents infection in others, but also prevents late complications Neurosyphilis may present and progress rapidly in patients co-infected with HIV

43. - perinatal death -premature delivery -Low birth weigth -congenital anomalies

44. Syphilis in newborns Congenital syphilis : - Transplacental: beginning 9 - 10 weeks analogous to secondary adquired syphilis affects bone, brain, liver, lung placenta: large and thickened, hypercellular villi, UC abscess-like necrotic foci - Vertical transmission: more freq. primary and secondary. Risk diminishes with after 4 years of infection

45. Clinical manifestations of early CS The earliest sign of CS is nasal discharge (snuffles) that occurs 1-2 weeks before the onset of the rash. Treponemes abound in the discharge, providing a definitive means of diagnosis.

46. Secondary lesions on face; they first appeared during the fourth postnatal week.

47. The vesiculobullous eruption, known as pemphigus syphiliticus, is highly distinctive when present. When the bullae rupture, they leave a macerated, dusky red surface that readily dries and crusts

48. Other stigmata seen before the age of 2 years include maculopapular rash, hepatosplenomegaly and jaundice.

49. Congenital syphilis. Diaphysitis with abundant callus formation secondary to pathologic fractures through the metaphyseal lesions. The lesions healed, and there were no sequelae

51. Laboratory Examination Since the treponeme is too small to be visualized under light microscopy, oblique light dark field microscopy is required to identify organisms. Serology: – Non-Treponemal: RPR, VDRL – Treponemal Test: MHA-TP, FTA-ABS

52. Laboratory Diagnosis Blood serum for antibodies detection a.Non-specific: non-treponemal tests (lipoidal antibody) Rapid Plasma Reagin RPR Venereal Disease Reference Laboratory VDRL Autamate reagin test ART b.Specific: treponemal tests Treponema pallidum HemAgglutination assay TPHA Treponema pallidum Particle Agglutination assay TPPA FTA abs

53. DIAGNOSIS Diagnostic testing involves a two-step process, beginning with a nonspecific test and concluding with a treponeme- specific test for patients screening positive. The non-treponemal screening tests include the VDRL (Venereal Disease Research Laboratory), RPR (rapid plasma reagin), or ART (automated reagin test). Nontreponemal test antibody titers usually correlate with disease activity and should be reported with a quantitative titer. On the other hand, other disease states or physiologic states, such as pregnancy, can yield false-positive results. Because the current incidence of syphilis is so low, the majority of positive screening tests are not due to treponemal infection.

54. The FTA-ABS test (Fluorescent Treponemal Antibody Absorption Test) for syphilis is an example of an indirect fluorescent antibody procedure. This is a confirming test for syphilis In this test, killed T. pallidum,(the known antigen), is fixed on a slide. The patient's serum is added to the slide. If the patient has syphilis, antibodies against the T. pallidum will react with the antigen on the slide.

57. Penicillin G, in benzathine, aqueous procaine, or aqueous crystalline form, is the drug of choice for treatment of all stages of syphilis, and is the only effective treatment for the prevention of congenital syphilis in pregnancy. Erythromycin may be curative in the mother, but may not prevent congenital syphilis because of the variability of transplacental passage of the antibiotic. Ceftriaxone may prove useful in adults as an alternative regimen for patients who have penicillin allergy azithromycin in the penicillin-allergic pregnant woman has not been adequately evaluated.

60. Within hours after treatment, patients can develop an acute complication called the Jarisch-Herxheimer reaction. Symptoms include fever, chills, myalgias, headache, tachycardia, hyperventilation, vasodilation, and mild hypotension. Although the reaction occurs in 10% to 25% of patients overall, it is most common in the treatment of early syphilis.

61. All children born to mothers who were sero-positive during pregnancy: A single intramuscular dose of benzathine benzylpenicillin 50,000 IU/kg

64. THNAK YOU !