Syphilis and other STD s

1. Syphilis and other STD’s DH Duckworth ID Class

2. Common Features of All STD’s Human only Transmission Virulence Mechanism Inapparent Infection Prevention Abstinance Monogamy Epidemics Sexual Promiscuity

3. Two Major Presentations “Drips” Urethritis or Cervicitis Gonorrhea Non-gonoccal urethritis Vaginitis Trichomoniasis “Bumps” Warts Swollen lymph glands AIDS Chancroid LGV Genital ulcer disease Herpes Syphilis Chancroid LGV

4. Most Common STD’s Non-gonococcal urethritis Gonorrhea Genital herpes Genital warts Trichomoniasis

5. Less Common STD’s Common AIDS Syphilis Uncommon Chancroid LGV

6. Gonorrhea Causative agent – Neisseria gonorrhoea Major Symptoms Many asymptomatic Male; urethritis with painful urination, purulent discharge; proctitis Female; cervicitis, urethritis, both asymptomatic or with minor discharge; salpingitis; PID Both sexes; pharyngitis, septic arthritis Disseminated gonococcal infection (DGI) Pustular skin lesions Septic arthritis Newborns; conjunctivitis, opthalmia neonatorum

7. Gonorrhea Diagnosis intracellular Gram negative diplococci in discharge growth on selective media, oxidase positive colonies flourescent antibody Treatment Penicillin, ciprofloxacin, ceftriaxone, tetracycline for probable association of C. trachomatis

8. Gram-negative Intracellular Diplococci

9. Gonorrhea -- Pathogenesis Encounter – from other humans only Entry – genital contact – NOT fomites Spread – can spread hematogenously and also through the uterus to Fallopian tubes and pelvic cavity Multiplication – can multiply extracellularly or intracellularly Avoid Host Immune Response – adhesins, antigenic variation, phase variation, sialation of LOS, IgA-ase Damage -- inflammation Transmission – sexual contact; vertical (mother to newborn)

10. Non-gonococcal Urethritis Infectious agents Chlamydia trachomatis Ureaplasma urealyticum Symptoms of Chlamydial infection Often inapparent in men Watery or mucopurulent discharge Dysuria In women, mucopurulent cervicitis, salpingitis, premature labor In newborns may cause conjunctivitis or pneumonia

11. Chlamydial Life Cycle

12. Non-gonococcal urethritis (Chlamydia) Pathogenesis Encounter – from infected humans Entry – direct sexual contact; NOT fomites Spread Multiplication – intracellular in columnar epithelial cells; elementary body is infectious form, reticulate body is replicative form Avoid Host Immune Response – prevents phagolysozome fusion by “hijacking” membrane trafficking system; grows intracellularly Damage -- inflammation Transmission

13. Non-gonococcal urethritis (Chlamydia) Diagnosis – grow in fibroblasts, detect with flourescein-labeled antibody PCR Treatment tetracycline doxycycline erythromycin

14. Other Common STD’s Genital herpes Caused by HHV 1 Causes painful ulcers and (with a primary infection) asceptic meningitis Can be treated with acyclovir Genital warts Caused by papilloma virus May cause cervical cancer Trichomoniasis Caused by Trichomonas vaginalis Asymptomatic in men Causes severe vaginal itching and a blood-tinged discharge in women Treated with metronidazole

15. Less Common STD’s Aids Syphilis Chancroid Lymphogranuloma venereum

16. Syphilis

17. Treponema pallidum:Dark Field

18. Treponema pallidum: EM

19. Stages of Syphilis

20. Symptoms of Syphilis Primary Single, painless, genital ulcer Regional lymphadenopathy (swollen lymph nodes) Secondary Headache Fever Whole-body rash Generalized lymphadenophathy Tertiary Neurological damage Heart damage Bone and joint damage Congenital Fetal death Birth defects

21. Primary Syphilis -- chancre

22. Secondary Syphilis -- rash

23. Syphilis -- Pathogenesis Encounter – humans only Entry – horizontal, sexual contact; NOT fomites Entry – vertical, acquired in utero Spread – to virtually any organ Multiplication – multiplies very rapidly extracellularly Avoid Host Immunity -- ? Damage – inflammation, cell death, autoimmunity (?) Transmission

24. Syphilis……Note Only infection that is Bacterial STD Congenital Causes bone changes

25. Syphilis Diagnosis VDRL Dark-field microscopy Anti-treponemal tests Treatment Penicillin Mercury (before penicillin)

26. Other Diseases Caused by T. pallidum Bejel or endemic syphilis Affects the skin and bones. Begins with ulcer on the leg The sore heals, but soft nodules of tissue (granulomas) erupt on the face, arms, legs, and buttocks. Painful open sores may develop on the soles of the feet (crab yaws). Areas of the shinbones may be destroyed, and other disfiguring growths, especially around the nose, may develop. Occurs in arid countries of the eastern Mediterranean and West Africa.

28. Other Diseases Caused by T. pallidum, ctd. Yaws Transmitted by skin contact, mainly between children Begins with a slimy patch in the mouth Followed by blisters on the trunk, arms, and legs. Bone infection develops later, mainly in the legs. Occurs in humid equatorial countries. Pinta Involves only the skin Skin loses pigmentation in patches Occurs in Mexico, South and Central America

29. Other Diseases Caused by T. pallidum All caused by organisms that cannot be distinguished By antibodies By DNA hybridization DNA sequence?????

30. HISTORY OF SYPHILIS

37. HISTORY OF SYPHILIS……Facts 1495 – Severe epidemic of (possibly) new disease Starts in Naples, Italy, during siege of city Ends war due to illness of soldiers Soldiers return to all countries of Europe Disease had no name – called French or Spanish or German or Polish disease…note…NOT called Indian disease Disease turns up in far flung places Aberdeen, Scotland, 1497: For protection of disease from “France and strange parts” all prostitutes cease work or be branded with hot poker Edinburgh, Scotland, 1498: Individuals with French disease banished to Island of Inchkeith 1539 – Spanish doctor says Columbus’ men returned from America with the disease

38. HISTORY OF SYPHILIS……Facts Evidence of epidemic from Letters Legal documents Literary and art works Medical treatises Evidence that Columbus started the epidemic None Nada Zilch

39. Were Indians afflicted? Conflicting Evidence Strictest criteria in bones (caries sicca) none in 12,000 6 in 4500 Looser criteria – some bone changes

40. If not Columbus….where? Subacute,smoldering disease in Europe Not much evidence from bones Was leprosy really syphilis? Evolved from Yaws or Bejel after being brought from Africa

41. Bones rewrite syphilis history: 2001 The remains of a medieval woman found in Essex could change medical history by disproving the theory that Christopher Columbus brought syphilis to Europe. Experts estimate the bones, which show signs of syphilis, are aged between 1296 and 1445 The roughness of the bones and the pitted surface indicate she had syphilis. (?) Work including DNA tests will now continue on this and related specimens.

42. Did Syphilis Exist in Europe before 1492? China, 2000BC ms claims ulcer “may happen if a woman meets a man whose blood has the virus. This virus will then spread throughout the entire volume of blood.” Mercury is treatment. Japan 808 AD. “After ulcer (of genital tract) has been cured there is fever and the bones and joints become painful.” Vedic books of the Hindus… “Disease transmitted by copulation causes destruction of the nose, affects the blood and contaminates the seed.” Called leprosy! Vedic books of the Hindus…”shameful disease cause ulcers on the soles of the feet and palms of the hands”

43. Was “leprosy” really syphilis? Lepers very feared even though leprosy not very contagious Leprosy is not congenital but ancient references refer to it as such Leprosy described (14th cent) as a disease that “will break forth in him who lies with a woman who has lain with a leper” Mercury thought to be a cure for leprosy 1321 …English cardinal bought a brothel as an investment for the church to protect against “great pox” Woodcut from14th cent pictures leper with spots on hands and dragging one leg as people with tertiary syphilis sometimes do.

45. Unitarian Hypothesis Syphilis, yaws, bejel, pinta are all same disease Yaws originated in Sub-Saharan Africa Spread around the world and adapted to different climates Slave trade brought disease to Europe “Superior hygiene….eliminated opportunities for transmission between children”

46. EMERGING DISEASES CAUSED BY A CHANGE……to pathogen reservoir vector host EXAMPLES acquisition of new gene (pathogen changed) diseases migrating to new areas (reservoir moved) diseases caused by human technologies (new vectors) diseases caused by disruption of animal habitats ( reservoir or vector moved) immune deficiency diseases (host changed)

47. SOLUTION Will come from DNA studies to show differences between the four treponematoses (done) Will be able to show whether syphilis was in New World before 1492 or in the Old World prior to then (maybe)