2. Spirochetes Thin-walled Spiral rods Flexible Motile Having an axial filament under the outer memberane

3. Motility  Spirochetes are motile through the undulation of an axial filament that lies under the outer sheath.

5. Treponema  - Seen only by darkfield microscopy, silver impregnation, or immunofluorescence.  - No growth in bacteriologic media or in cell culture except nonpathogenic treponems which are part of the normal flora of human mucous membranes. Leptospira  Seen only by darkfield microscopy, silver impregnation, or immunofluorescence.  Growth in bacteriologic media Borrelia  - Larger than two others  Seen by Giemsa’s and other blood stains  Seen in the standard light microscope  Growth in bacteriologic media

6. If you notice delays in slide effects or a decrease in performance, you may want to remove the reproduction instructions in the Slide Notes. To remove the instructions from a particular slide: 1.Place your cursor in the Slide Notes. 2.Press CTRL + A, and then press DELETE. To print the reproduction instructions in this file: 1.Select the slide that you want to reproduce. 2.Place your cursor in the Slide Notes. 3.Press CTRL + A, and then Copy the text. 4.Open a new document in Microsoft Word. 5.Then Paste the text into the Word documentdocument. For your reference, the steps required to reproduce each of these slides have been included in the Slide Notes. Treponema 1 Leptospira 2 Borrelia 3

10. Treponema pallidum  Causes syphilis

11. Treponema pallidum pallidum (The bacterial agent of syphilis) Subspecies pallidum (not bejel, pinta, yaws).  A worldwide STD  The incidence is increasing

12. Transmission  From spirochete-containing lesions of the skin or mucous membranes  From pregnant women to their fetuses  Blood transfusion during early syphilis.

13. Antibodies  The antigenes of T. pallidum induce specific antibodies, which can be detected by immunofluorescence tests.  They also induce nonspecific antibodies (reagin), which can be detected by the flocculation of lipids (cardiolipin) extracted from normal mammalian tissues, eg. Beef heart.

14. Pathogenesis  No important toxins or enzymes.

16. Clinical finding  Primary stage  Secondary stage  Tertiary stage

17. Primary stage  Chancre  Chancre in 2 – 10 weeks (average 21 days) after exposure.  A single firm, painless, non itchy skin ulceration with a clean base and sharp borders between 0.3 and 3 cm in size. The ulcer heals spontaneously after 3 to 6 weeks without treatment, but spirochetes spread widely in tissues.

22. Secondary stage  Secondary syphilis occurs approximately 4 to 10 weeks after the primary infection.  Lesions as maculopapular rash or moist papules on skin and mucous membranes. Or organ involvement (meningitis, nephritis, hepatitis….). rich in spirochetes  Secondary lesions are rich in spirochetes and highly infectious but heal spontaneously.

27. Tertiary stage  One-third of early syphilis cases progress to cure without treatment.  Another third remain latent; i.e. no lesions appear, but positive serologic tests indicating continuing infections (Asymptomatic).  In the remainder, the disease progresses to the late, tertiary stage.

28. Tertiary stage - Granulomas (gummas) ( Gummas in skin, bones, central nervous system, cardiovascular lesions, e.g. aortitis, aneurysm). - Paralysis (also tabes and paresis), Blindness, Insanity, Death - In tertiary stage, the treponemes are very rare.

34. Congenital syphilis Fetus infection through transplacental passage after the third month of pregnancy.transplacental Unless treated promptly, multiple fetal abnormalities.

35. Congenital syphilis  Early congenital syphilis Occurs in children between 0 and 2 years old  Late congenital syphilis Late congenital syphilis Starts to occurs after 2 years old

36. Congenital syphilis  Early congenital syphilis - - Born premature - Active mucocutaneous syphilis - Enlargement of the liver, spleenliverspleen - Skeletal abnormalities - Pneumonia

39.  Symptoms can develop two weeks to three months after birth:  anemia  fever  rashes  skin sores  weak/hoarse crying sounds  yellowish skin (jaundice)

41. Late congenital syphilis Late congenital syphilis  Malformations and damage to:Bones Brain Brain (neurologic changes)EyesEars Teeth Teeth (Hutchinson's teeth)

47. Immunity  Immunityincomplete  Immunity to syphilis is incomplete: Antibodies are produced but not stop the progression of the disease. early syphilis can contract syphilis again  Patients with early syphilis treated can contract syphilis again. late syphilis resistant  Patients with late syphilis are relatively resistant to reinfection.

48. Laboratory diagnosis Microscopy - Microscopy darkfield immunofluorescence Demonstrating spirochetes by darkfield or immunofluorescence microscopy. - Nonspecific serologic tests - Specific serologic tests - Specific serologic tests

49.  Antibodies agains Treponema palidum: - Nonspecific reagin - Specific antitreponemal antibody  Nonspecific serologic tests - Nontreponemal antigens - Nontreponemal antigens (extracts of Cardiolipin from beef heart) react with “reagin” antibodies in serum samples from patients with syphilis. These antibodies are a mixture of IgG and IgM.

50. - VDRL (Venereal Disease Research Laboratory)/RPR (Rapid plasma reagin) (a simplified version of VDRL test) - The reagin antibody binds with the antigen (Antigen is composed of a complex of cardiolipin, lecithin and cholesterol particles with activated charcoal). - Flocculation or clumping - Flocculation or clumping of the particles is read as a positive test. The test can be quantitated by examining serial dilutions of serum.

51. The ASI RPR test is in an 8-minute

54. Nonspecific antibodies (cont.)  Detectable in the majority of patients at the time the primary syphilis and are always present in secondary syphilis.  False-positive reactions may occur (in hepatitis and infectious mononucleosis and autoimmune diseases).  So, positive results have to be confirmed by specific tests.

55. Specific serologic tests treponemal antigens  Using treponemal antigens  T. pallidum extracted from experimentally infected rabbits.  Reacts in FTA-ABS (fluorescent treponemal antibody absorbed) test or TPHA (treponema pallidum hemagglutination)  Specific antitreponemal antibodies arise within 2-3 weeks of syphilitic infection.

56. Specific serologic tests  Treponemal antibody tests are specific for treponematoses but: - expensive - remain positive after treatment

57. Treatment  Penicillin G (A single injection of benzathin penicillin G) can eradicate T pallidum and cure early syphilis.

58. Prevention  Administration of antibiotic after suspected exposure.  The presence of any sexually transmitted disease makes testing for syphilis mandatory.  No vaccine is available.

59. Borrelia  Borrelia species are irregular, loosly coiled spirochetes which stain with Giemsa’s and other stains.  Culturable in bacteriologic media containing serum or tissue extracts.  Transmitted by arthropods.  Cause 2 major disease: relapsing fever and lyme disease.

61. Borrelia recurrentis  Causing relapsing fever  During infection, the antigens of these organisms undergo variation.  As antibodies develop against one antigen, variants emerge and produce relapses of the illness repeating 3-10 times.  Transmission from person to person by human body louse.  Humans are the only hosts

62. Borrelia hermsii  Causing relapsing fever  During infection, the antigens of these organisms undergo variation.  Transmission to humans by ticks  Rodents and other small animals are the main reservoirs.  These borrelia are passed transovarially in the ticks.

63. Clinical finding  Cyclic Fever, chills, headaches  Multiple organ dysfunction

64. Lab Diagnosis - Microscopy (large spirochetes in stained smears of peripheral blood) - Culture in special media - Serological tests

66. Treatment & Prevention  Tetracycline may be beneficial early in the illness and may prevent relapses.  Avoidance of arthropod vectors

67. Borrelia burgdorferi  Causes Lyme disease  Transmission by tick bite (genus Ixodes)Ixodes  The main reservoirs: Mice and deer Incidence of Lyme Disease in the United States, 1991-2006. Lyme disease is the most prevalent tick- borne illness in the United States.

71. Clinical finding  Early in disease  Early in disease: erythema chronicum migrans Fever, severe headache, myalgia, fatigue, depression, stiff neck, and a typical skin rash called ‘erythema chronicum migrans [ECM]’ If untreated, neurologic and cardiac abnormalities ensue weeks later and arthritis follows months to years later. Immune complexes are found in the affected joints.

75. Erythema migrans

77. Lab diagnosis  Serology: Detecting IgM antibodies by immunofluorescence tests or ELISA  Culture are not typically done.

79. Treatment & Prevention  Penicillin or Tetracycline  Prevention includes avoiding tick bites.

80. Leptospira  Tightly coiled, fine spirochetes that are not stained with dyes.  They are seen by darkfield microscopy.  They grow in bacteriologic media containing serum.

84. Leptospira interrogans  The causative of leptospirosis  Divided into serogroups (occurring in different animals and geographic locations)  Each serogroup is subdivided into serovars by response to agglutination tests.  Leptospira infects various animals including rats and other rodents, domestic livestock and household pets.

85. Transmission  Animals excrete leptospiras in urine, which contaminates water and soil.  Swimming in contaminated water or consuming food or drink results human infection.  Miners, farmers and people who work in sewers are at high risk.  Person-to-person transmission is rare.

87. Pathogenesis  Leptospira are ingested or pass through mucous membranes or skin.  They circulate in the blood and multiply in various organs.

88. Clinical finding  Fever  Dysfunction of the liver (jundice, hemmorrhage), kidneys (uremia), and central nervous system (aseptic meningitis)  Subclinical infection is common.  Serovar-specific immunity develops with infection.

94. Lab Diagnosis Clinical Diagnosis is based on history of exposure.  Serology: Marked rise in agglutinating antibodies.  Occasionally leptospira is isolated from blood and urine cultures.

95. Treatment & Prevention  Tetracycline  Prevention: - Avoiding contact with the contaminated environment. - Doxycycline in exposed persons.

96. Rickettsiae  Very short rods and barely visible in the light microscope  Gram-negative but poorly stain with gram stain

97. Rickettsiae  Non-motile coccobacillus  Obligate intracellular parasites, so normally must be grown in cell culture.  Against chlamydiae divide by binary division not by a distinctive intracellular cycle.

99. Transmission  They maintained in nature in certain arthropods: ticks, lice, fleas and mites  The exception to arthropod transmission is C. burnetii, transmitted by aerosol and inhaled into the lungs. epidemic typhus only in humans  All rickettsial diseases are zoonoses with the exception of epidemic typhus which occurs only in humans.

101. Coxiella burnetii  Q fever (inhalation, contact with the milk, urine, feces, vaginal mucus, or semen of infected animalsinhalation

102. R. prowazekii  Epidemic Typhus (by lice)  R. typhi  Murine or endemic typhus (by fleas, commonly rat flea)fleas  Orientia (formerly Rickettsia) tsutsugamushi  Scrub typhus (by mite)  Rickettsia rickettsii  Rocky mountain spotted fever (by ticks)

103. R. prowazekii  Growth in the louse's gut  Excretion in its feces.feces  Transmition to an uninfected human who scratches the louse bite (which itches) and rubs the feces into the wound.

104. R. prowazekii  The incubation period: 1-2 weeks.incubation period  R. prowazekii can remain viable and virulent in the dried louse feces for many days.  Typhus will eventually kill the louse, though the disease will remain viable for many weeks in the dead louse.

107. Clinical findings  Severe headache, a sustained high fever (39 °C, common to all forms of typhus), cough, rash, severe muscle pain, chills, falling blood pressure, stupor, sensitivity to light, and delirium.rashmuscle painchillsblood pressurestuporsensitivity to light delirium  A rash begins on the chest about five days after the fever appears, and spreads to the trunk and extremities.

109. Brill-Zinsser disease  A mild form of epidemic typhus  It occurs when the disease re-activates in a person who was previously infected.  More common in the elderly

110. R. typhi (Murine/Endemic typhus) By bite of certain fleas Rash and other manifestations are similar to epidemic typhus: High fever, severe headaches, a red rash, chills, myalgia, nausea, vomiting, and cough. myalgianauseavomiting

111. Typhus rashes

112. Laboratory diagnosis of rickettsial infections  A complete blood count (CBC) may show anemia and low platelets.CBC anemiaplatelets Other tests:  High level of typhus antibodiesantibodies  Low level of albuminalbumin  Low sodium levelsodium  Mild kidney failure  Mildly high liver enzymes

113. Laboratory diagnosis of rickettsial infections  Weil-Felix test: (based on a cross-reaction of proteus vulgaris with R. prowazekii, R. tsutsugamushi, R. ricketsii, …) Detection of antirickettsial antibodies by agglutination of the antigenes of OX strain of proteus vulgaris

114. Treatment  Mortality rate 10% to 60% in untreated cases  Close to zero if intracellular antibiotics, such as tetracycline. tetracycline  Can prevented by vaccination.  Intravenous fluids  Intravenous fluids and oxygen may be needed to stabilize the patient.oxygen