SPIROCHETES

1. SPIROCHETES Dr.T.V.Rao MD Dr.T.V.Rao MD

2. Spirochetes Spirochetes -are elongated motile, flexible bacteria twisted spirally along the long axis are termed spirochetes Contain – endoflegalla which are polar flagella wound along the helical protoplasmic cylinder and situated between the outer membrane and cell wall Dr.T.V.Rao MD

3. Taxonomy • Order: Spirochaetales • Family: Spirochaetaceae • Genus: Trepanoma • Borrelia • Family: Leptospiraceae • Genus: Leptospira Dr.T.V.Rao MD

4. Human pathogen • Genera Trepanoma • Borreilia • Leptospira Dr.T.V.Rao MD

5. How they appear Dr.T.V.Rao MD

6. What are Trepanoma Trepos – Turn Nema Meaning thread Relatively short and slender With fine spirals pointed and round ends May be pathogenic or commensals in the mouth Dr.T.V.Rao MD

7. Spirochaetales Associated Human Diseases Dr.T.V.Rao MD

8. Venereal Syphilis Venereal Syphilis caused by T.pallidum Endemic syphilis T. pallidum Yaws T.pertune Pinta T.carateum Dr.T.V.Rao MD

9. Discovery“Everything” happened mostly in Germany from 1905 to 1910 !With a short life of 35 years, Fritz Schaudinn (1871-1906) and Paul E. Hoffmann (1868-1959) discovered Treponema pallidum in serumin 1905. Paul Ehrlich, father of immunochemistry and his assistent Hati. Fritz Schaudinn Dr.T.V.Rao MD

10. Syphilis Named from poem published by the Italian physician and poet Girolamo Fracastoro – shepherd from Hispaniola named Syphilis who angered Apollo and was given the disease as punishment Dr.T.V.Rao MD

11. Syphilis Dr.T.V.Rao MD "He who knows syphilis, knows medicine" Sir William Osler

12. Treponema pallidum • Described in 1905 by Schaudinn and Hoffman, Hamburg Dr.T.V.Rao MD

13. Trepanoma pallidumGreek words trepo “turning” & nema “head” • Morphology • Motile, sluggish in viscous environments • Size: 5 to 20 μm in length & 0.09 to 0.5 μm in diameter, with tapered ends • Structure • Multilayer cytoplasmic membrane • Flagella-like fibrils • Cell wall • Outer sheath (outer cell envelope) • Capsule-like outer coat Dr.T.V.Rao MD

14. Treponema pallidum. Spiral spirochete that is mobile of spirals varies from 4 to 14 Length 5 to 20 microns and very thin 0.1 to o.5 microns. Can be seen on fresh primary or secondary lesions by dark field microscopy or fluorescent antibody techniques Dr.T.V.Rao MD

15. General Overview of Spirochaetales • Gram-negative spirochetes • Spirochete from Greek for “coiled hair” • Extremely thin and can be very long • Tightly coiled helical cells with tapered ends • Motile by Periplasmic flagella (a.k.a., axial fibrils or endoflegalla) Dr.T.V.Rao MD

16. General Overview of Spirochaetales • Outer sheath encloses axial fibrils wrapped around protoplasmic cylinder • Axial fibrils originate from insertion pores at both poles of cell • May overlap at centre of cell in Treponema and Borrelia, but not in Leptospira • Differing numbers of endoflegalla according to genus & species Dr.T.V.Rao MD

17. Trepanoma palladium • Physiology • Difficult to culture • Maintained in anaerobic medium with albumin, sodium bicarbonate, pyruvate, cysteine • Microaerophilic Dr.T.V.Rao MD

18. Cross-Section of Spirochete with Periplasmic Flagella Cross section of Borrelia burgdorferi NOTE: a.k.a., endoflegalla, axial fibrils or axial filaments. (Outer sheath) Dr.T.V.Rao MD

19. Staining with special stains Staining by Giemsa and Fontana Dr.T.V.Rao MD

20. Antigenic structure • The Antigens are complex • Infection with Treponema will induce 3 types of Antigens • Reagin Antibodies – STS • Detected by Standard tests for Syphilis • 1 Wasserman Test, 2 Kahn Test • VDRL Test Dr.T.V.Rao MD

21. Beef Heart Extracts - Antigen Lipid Hapten – Cardiolipin Chemically Dipphostidyl glycerol Cardiolipin present in the Trenonems ? Or a product of tissue Damage ? Dr.T.V.Rao MD

22. Second Group Antigen T.pallidum • Present in T.pallidum and Non pathogenic cultivable treponemes • Reiter's Trenonems Dr.T.V.Rao MD

23. Third Antigen Polysaccharide species specific Positive only in sera of patients infected with pathogenic Treponema Dr.T.V.Rao MD

24. Dark field Microscopy Dr.T.V.Rao MD

25. Treponema cannot be cultivated in Culture Media The inability to grow most pathogenic Treponema in vitro, coupled with the transitory nature of many of the lesions, makes diagnosis of Treponema infection impossible by routine bacteriological methods Dr.T.V.Rao MD

26. Cultivation of .. ? Although the Treponemes are distantly related to Gram-negative bacteria, they do not stain by Gram's method, and modified staining procedures are used. Moreover, the pathogenic Treponemes cannot be cultivated in laboratory media and are maintained by subculture in susceptible animals. Dr.T.V.Rao MD

27. Trepanoma pallidum • Clinical Infection: Syphilis • Transmission • Usually through sexual contact from an infected individual by invading intact mucous membranes or abraded skin • Pathogenesis • Disease of blood vessel & perivascular areas • Primary lesion due to inflammation at site of inoculation • Secondary lesion due to inflammation of ectodermal tissues • Tertiary lesion due to diffuse chronic inflammation to organ systems Dr.T.V.Rao MD

28. Trepanoma pallidum • Clinical Infection: Syphilis • Clinical Manifestations • Primary Disease • Chancre: single lesion, non-tender & firm with a clean surface, raised border & reddish color • Usually on the cervix, vaginal wall, anal canal • Draining lymph nodes enlarged & non-tender Dr.T.V.Rao MD

29. Pathogenesis of T. pallidum • Tissue destruction and lesions are primarily a consequence of patient’s immune response • Syphilis is a disease of blood vessels and of the perivascular areas • In spite of a vigorous host immune response the organisms are capable of persisting for decades • Infection is neither fully controlled nor eradicated • In early stages, there is an inhibition of cell-mediated immunity • Inhibition of CMI abates in late stages of disease, hence late lesions tend to be localized Dr.T.V.Rao MD

30. Pathogenesis 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 Dr.T.V.Rao MD

31. Pathology • The bacteria rapidly enter the lymphatic's, are widely disseminated via the bloodstream and may lodge in any organ. The exact infectious dose for man is not known, but in experimental animals fewer than ten organisms are sufficient to initiate infection. Dr.T.V.Rao MD

32. Pathology The bacteria multiply at the initial entry site forming a chancre, a lesion characteristic of primary syphilis, after an average incubation period of 3 weeks Dr.T.V.Rao MD

33. STAGES OF SYPHILIS • Primary • Secondary • Latent • Early latent • Late latent • Late or tertiary • May involve any organ, but main parts are: • Neurosyphilis • Cardiovascular syphilis • Late benign (gumma) Dr.T.V.Rao MD

34. Basic lesion of syphilis The chancre is painless and most frequently on the external genitalia, but it may occur on the cervix, perianal area, in the mouth or anal canal. Dr.T.V.Rao MD

35. Stages of syphilis Untreated syphilis may be a progressive disease with primary, secondary, latent and tertiary stages. T. pallidum enters tissues by penetration of intact mucosae or through abraded skin. Dr.T.V.Rao MD

36. Primary syphilis a) One or more painless chancres (indurated raise edges & clear bases) that erupt in the genitalia, anus, nipples, tonsils or eyelids. b) Starts as papule and then erode c) Disappear after three to six weeks even without treatment. d) Lymphadenopathy that is either unilateral or bilateral Dr.T.V.Rao MD

37. Trepanoma pallidum • Clinical Infection: Syphilis • Clinical Manifestations • Latent disease • Early latent (1st 4 years) • No signs & symptoms of active syphilis but remain seroactive • Late latent (after 4 years) • If untreated, 60% continue to be asymptomatic while 40% progress to tertiary stage Dr.T.V.Rao MD

38. Pathology The chancre is painless and most frequently on the external genitalia, but it may occur on the cervix, peri-anal area, in the mouth or anal canal. Chancres usually occur singly, but in immunocompromised individuals, Dr.T.V.Rao MD

39. Chancre • The chancre usually heals spontaneously within 3-6 weeks, and 2-12 weeks later the symptoms of secondary syphilis develop. These are highly variable and widespread but most commonly involve the skin where macular or pustular lesions develop, particularly on the trunk and extremities. The lesions of secondary syphilis are highly infectious. Dr.T.V.Rao MD

40. Progress of Disease • Relapse of the lesions of secondary syphilis is common, and latent syphilis is classified as early (high likelihood of relapse) or late (recurrence unlikely). Individuals with late latent syphilis are not generally considered infectious, but may still transmit infection to the fetus during pregnancy and their blood may remain infectious. Dr.T.V.Rao MD

41. Trepanoma pallidum • Clinical Infection: Syphilis • Clinical Manifestations • Primary Disease • Chancre: single lesion, non-tender & firm with a clean surface, raised border & reddish color • Usually on the cervix, vaginal wall, anal canal • Draining lymph nodes enlarged & non-tender Dr.T.V.Rao MD

42. PRIMARY SYPHILIS(The Chancre) • Incubation period 9-90 days, usually ~21 days. • Develops at site of contact/inoculation. • Classically: single, painless, clean-based, indurated ulcer, with firm, raised borders. Atypical presentations may occur. • Mostly anogenital, but may occur at any site (tongue, pharynx, lips, fingers, nipples, etc...) • Non-tender regional adenopathy • Very infectious. • May be darkfield positive but serologically negative. • Untreated, heals in several weeks, leaving a faint scar. Dr.T.V.Rao MD

43. Primary Syphilis Dr.T.V.Rao MD

44. Clinical Manifestations Primary Syphilis- Penile Chancre Dr.T.V.Rao MD Source: CDC/ NCHSTP/ Division of STD Prevention, STD Clinical Slides

45. Primary Syphilis Dr.T.V.Rao MD

46. Primary Syphilis - Chancre Dr.T.V.Rao MD

47. Primary Syphilis - Chancre Dr.T.V.Rao MD

48. Pathogenesis of T. pallidum (cont.) Secondary Syphilis • Secondary disease 2-10 weeks after primary lesion • Widely disseminated mucocutaneous rash • Secondary lesions of the skin and mucus membranes are highly contagious • Generalized immunological response Dr.T.V.Rao MD

49. Treponema pallidum • Clinical Infection: Syphilis • Clinical Manifestations • Tertiary Disease • Gummas (3-10 years after secondary disease) • Non-progressive, localized dermal lesions • Benign tertiary syphilis • Pronounced immunologic host reaction • Neurosyphilis (>5 years after primary disease) • Paralytic dementia, tabes dorsalis, amyotropic lateral sclerosis, meningovascular syphilis, seizures, optic atrophy, gummatous changes of the cord Dr.T.V.Rao MD

50. Secondary Syphilis • Secondary syphilis at 6-8 weeks – diffuse symptoms: • Fever • Headache • Skin pustules • Usually disappears even without treatment Dr.T.V.Rao MD