1. 3/19/2016 1 Spirochetes (Spiral bacteria) Spirochetes (Spiral bacteria)

2. 3/19/2016 2 Classification Domain: Bacteria Family : Spirochetaceae (free living spirochetes) Treponemataceae (human pathogens) Treponemataceae (human pathogens) Genus: Treponema Genus: Treponema Borrelia Borrelia leptospira leptospira

3. 3/19/2016 3 General Features n All spirochetes have similar morphological appearance n They are all long slender, helically coiled (spiral) gram negative bacilli around 5-250 µm in length n Obligate intracellular parasites n Contain axial filament (endoflagella) which begins at each end of the organism and wind around it, extending and overlapping at the mid point

4. 3/19/2016 4 General Features n Axial filament runs between the bacterial inner and outer membranes in the periplasmic space n Very actively motile n Reproduce by traverse binary fission

5. 3/19/2016 5 Genus : Tryponema n 4 spp (subspecies) T pallidum subspecies pallidum (T pallidum) Syphilis T pallidum subspecies pertenue (T pertenue) Yaws T pallidum subspecies endemicum (T endemicum) Endemic syphilis (bejel) T carateum Pinta

6. 3/19/2016 6 T pallidum subspecies pallidum Morphology Small, about 5-15 µm in length, slender gram negative spiral bacilli Actively motile So thin (very difficult to be seen by gram stain) Can only be seen using dark field illumination or immuno-fluorescent stain

7. 3/19/2016 7 Microaerophilic organisms, survives best in 1-4 % O2 Never been cultured on artificial growth media or tissue culture. Obligate intracellular parasites and therefore cant be transmitted by public surfaces because of its narrow temperature and pH ranges (can not survive in temperature higher than 42 C and their optimal pH range is 7.2 - 7.4) Growth and cultural characteristics

8. 3/19/2016 8 Growth and cultural characteristics Exposure to air, antiseptic or sunlight kill it Invivo generation time very long about 30 hours All spp sensitive to penicillin

9. 3/19/2016 9 Antigenic structures - Not widely characterized - more than 100 protein antigens - Outer membrane lipoproteins - Endoflagellar antigens

10. 3/19/2016 10 Pathogenesis, pathology and clinical findings - T pallidum infection is limited to human host (animals can only be infected experimentally) - Infection with T pallidum cause a disease called Syphilis - Syphilis can be divided into two main types Acquired syphilis Acquired syphilis Congenital syphilis Congenital syphilis

11. 3/19/2016 11 Pathogenesis, pathology and clinical findings Acquired syphilis - Transmitted by sexual intercourse - 3 stages Primary stage Primary stage - Multiply locally at the site of entry - Multiply locally at the site of entry - Painless chancre lesion (painless ulcer) on skin and mucous membrane of external genetalia - Painless chancre lesion (painless ulcer) on skin and mucous membrane of external genetalia

12. 3/19/2016 12 Pathogenesis, pathology and clinical findings - 10-20% of cases the 1ry lesion is intra-rectal or peri-anal or oral - Lasts for 2-6 weeks and then recede even without treatment (you should treat it!!!!) - Highly infectious stage and lesion rich in spirochetes

13. 3/19/2016 13 Secondary stage - Develop 2-10 weeks after the infection - None specific symptoms maculo-papular rash, fatigue, fever sore throat headaches, loss of appetite and lymphadenopathy maculo-papular rash, fatigue, fever sore throat headaches, loss of appetite and lymphadenopathy - Also subsides spontaneously - Like 1ry stage, 2ry lesions are rich in spirochetes and highly contagious Pathogenesis, pathology and clinical findings

14. 3/19/2016 14 Pathogenesis, pathology and clinical findings Tertiary stage - 30 % of patents with syphilis progress to complete cure even without treatment - Another 30% of patents, untreated infections remain latent (evident by positive serological reactions) - About 40 % of patients progress to tertiary syphilis

15. 3/19/2016 15 Pathogenesis, pathology and clinical findings Tertiary stage - Granulmatous lesions (GUMMAS) in skin, bones, joints and liver - Degenerative changes in CNS including syphilitic meningitis, paralysis, difficulties in movements, stroke, numbness and gradual blindness - Cardiovascular syphilitic lesions (aortitis, aortic aneurysm an aortic valve insufficiencies - Not infectious stage, tryponema very rarely isolated and lesions are attributed to hypersensitivity to organism

16. 3/19/2016 16 Congenital syphilis - From pregnant woman to fetus through placenta - Usually begins in the 10 th to 15 th weeks of gestation - Consequences Some of the infected fetuses die and abortion result Some of the infected fetuses die and abortion result Some are stillbirth at delivery Some are stillbirth at delivery Pathogenesis, pathology and clinical findings

17. 3/19/2016 17 Congenital syphilis Some fetuses born life but die soon after birth Some fetuses born life but die soon after birth Some fetuses born life but develop signs of congenital syphilis in childhood, these include Some fetuses born life but develop signs of congenital syphilis in childhood, these include - Varity of CNS anomalies - Varity of CNS anomalies - Deafness - Deafness - Teeth deformities - Teeth deformities - Saddle nose - Saddle nose Pathogenesis, pathology and clinical findings

18. 3/19/2016 18 Laboratory Diagnosis Specimen Specimen - Tissue fluid expressed from early surface lesions for identification of spirochetes - Blood or serum for serology Direct testing Direct testing - Dark - field examination (should be before the starting of antibiotic treatment) - Dark - field examination (should be before the starting of antibiotic treatment) - IF - IF

19. 3/19/2016 19 Laboratory Diagnosis Serology Serology - Two types : - None treponemal serological tests (detect none trponemal antigens or antibodies) - None treponemal serological tests (detect none trponemal antigens or antibodies) - Treponemal serological tests (detect treponemal antigens or antibodies) - Treponemal serological tests (detect treponemal antigens or antibodies)

20. 3/19/2016 20 None treponemal serological tests - None specific tests - Used for screening - Look for cardiolipins ( Indirect indications of the infection with T pallidum - Cardiolipin shares some antigenic determinants with T pallidum - They indicate either active infection or healed but not treated infection Laboratory Diagnosis

21. 3/19/2016 21 - Two types VDRL (Venereal Disease Research Laboratory) test VDRL (Venereal Disease Research Laboratory) test RPR (Rapid Plasma Reagin) test RPR (Rapid Plasma Reagin) test - The only difference between the two the later does not need a microscope to read the result Laboratory Diagnosis

22. 3/19/2016 22 - Positive test is indicated by the formation of clusters - If positive, go with treponemal serological tests Laboratory Diagnosis - Ve VDRL test + Ve VDRL test + Ve VDRL test

23. 3/19/2016 23 Disadvantages of None treponemal serology Disadvantages of None treponemal serology - Not specific (false positive can occur with other conditions such us pregnancy, HIV, TB, and rheumatoid arthritis - Not very sensitive in early syphilis, specially in the first 2-3 weeks after the infection (false negative) Laboratory Diagnosis

24. 3/19/2016 24 Disadvantages of None treponemal serology Disadvantages of None treponemal serology - Not specific (false positive can occur with other conditions such us pregnancy, HIV, TB, rheumatoid arthritis - Not very sensitive in early syphilis, specially in the first 2-3 weeks after the infection (false negative)

25. 3/19/2016 25 Treponemal serological tests - Indicated if non treponemal serological tests are positive - Detect treponemal antigens or antibodies - Remains positive for life (not useful for screening) - Many types: Fluorescent treponemal antibody (FTA) Fluorescent treponemal antibody (FTA) Treponema pallidum particle agglutination Treponema pallidum particle agglutination ELISA ELISA Laboratory Diagnosis

26. 3/19/2016 26 - Sensitive to penicillin ( treatment of choice) - If patient is allergic, tetracycline and erythromycin can be substituted but they are generally less effective than penicillin - No permanent immunity. If the disease is treated, the individual again becomes fully susceptible to re-infection Treatment and Immunity

27. 3/19/2016 27 T pallidum subspecies pertenue Yaws T pallidum subspecies pertenue Yaws T pallidum subspecies endimicum Bejel T pallidum subspecies endimicum Bejel - Non sexually transmitted diseases - Non sexually transmitted diseases - Affect children in hot tropical countries - Affect children in hot tropical countries - 1ry lesion is an ulcerating macule or papule on arms and legs. Complications rare - 1ry lesion is an ulcerating macule or papule on arms and legs. Complications rare - Yaws is a variant of syphilis (????) - Yaws is a variant of syphilis (????) - Sensitive to penicillin ( treatment of choice) - Sensitive to penicillin ( treatment of choice) Other Treponema subspecies

28. 3/19/2016 28 T carateum Pinta T carateum Pinta - Non sexually transmitted disease - Non sexually transmitted disease - Affect all age groups in Mexico and South America (restricted to dark skinned people) - Affect all age groups in Mexico and South America (restricted to dark skinned people) - 1ry lesion is non ulcerating macule on exposed areas changes later on to hyperpigmented lesions. Complications rare - 1ry lesion is non ulcerating macule on exposed areas changes later on to hyperpigmented lesions. Complications rare - Diagnosis and treatment like syphilis - Diagnosis and treatment like syphilis Other Treponema subspecies