Lecture 8 Treponema Pallidum (Syphilis)

Urogenital System Microbiology… Lecture 8 Treponema pallidum (Syphilis) 1 _ First: general features: I. II. Treponema pallidum is the causative agent of syphilis Gram negative, Spirochete spiral (spiral bacteria “corkscrew shape) III. Rotating motility (due to axial filaments) IV. Extremely susceptible to drying, disinfectant and temperature (41-42o C; fever therapy, let the patient with his fever to treat himself) V. Lack enzymes (e.g. catalase, oxidase), lack ATP, and lack LPS in outer membrane. VI. They are too thin & slowly growing. So, Stain poorly VII. The morphology of Spirochetes is achieved by a flexible peptidoglycan cell wall VIII. surrounded by axial fibrils and covered by an outer bilayer membrane IX. The medically important genera of Spirochetes: - Treponema (described in this lecture) - Leptospira - Borrelia _ Second: Epidemiology: I. II. III. IV. Exclusively human disease and pathogenic only in human Acquired by direct sexual contact with patients with primary or secondary syphilitic lesions…Tertiary syphilis is not infectious via needles, contact with an infected lesions and trans-placental (from infected mother to the fetus, EVEN if the disease IS LATENT!) Lesions, that are formed by syphilis, are port for HIV transmission, Syphilis was controlled for a long time, but the emergence of HIV leads to re-emergence of the disease again. So that, when you do a test for syphilis you must do a test for HIV and vice versa _Third: Pathogenesis: I. II. III. IV. Entrance through unapparent skin and mucus membrane breaks They Multiply in submucosa, which makes them spread rapidly ( in hours ) The organisms disseminate via lymph nodes and bloodstream They enter the LATENT phase for many years 2 _fourth: Immunity: I. II. III. IV. Both humoral and CMI, but Slow and imperfect Resistance is proportional to anti-treponemal antibodies (those Abs immobilize & kill organism) You will find CD4 and CD8 T cells + macrophages in the lesions More severe disease in AIDS occurs. _fifth: Clinical diseases: I. Primary Syphilis: - The lesions: chancres: 1. Start with Endarteritis (inflammation of the inner lining/endothelium of an artery) 2. the artery lumen closed by inflammation process (edema, proliferation...etc. ) 3. then necrotic ulcers appears at the site of infection ( chancre) 4. Those lesions are: • In external genitalia or cervix; also, anal or oral • Painless, but sensitive to touch - Firm, non-suppurative and painless lymphoadenopathy (enlargement of lymph nodes) develop 1 week after lesions’ appearance...(diagnostic) - I.P. = 3 weeks (3 -90 days) - Heal spontaneously after 4 -6 weeks, BUT spirochetes disseminate. - become silent until secondary stage II. Secondary (disseminated) Syphilis: - The lesions: mucocutaneous maculopapular rash: 1. Develops 2 – 8 weeks after chancre 2. Symmetric, on the trunk & extremities; often on palms, soles & face 3. many organisms are in lesions, makes it the most infectious phase! - Comes with non-tender generalized lymphadenopathy, fever, malaise and others. - Condylomata Lata: painless cutaneous mucosal watery erosions develop in 1/3 of the cases (on genitalia and perineum) , look to the picture - the highly infectious lesions; resolve spontaneously after few days to weeks, but infection persists in 2/3. 3 III. Latent Syphilis : - No clinical manifestations - low antigenicity and slow growth assist this latency - Latency extends to > 5 years up to decades (15 – 20 years) - Mother can transmit disease to fetus during latency - 1/3 of cases do not progress beyond this stage IV. Tertiary Syphilis (in the organs): - Neurosyphilis: 1. meningovasculitis + degenerative parenchymal changes 2. Chronic meningitis 3. Cortical degeneration of the brain (mental manifestations occur) - Tabes dorsalis: spinal cord cord demyelination of posterior column, dorsal roots, dorsal root ganglia: 1. Ataxia and Loss of sensation 2. Wide-based gait (the patient can't balance if his feet are close together) 3. Foot drop 4. PARESIS: Neurologic deficit + Behavior disturbances (Personality, Affect, Reflexes, Eyes, Sensorium, Intellect, Speech) 5. Delayed Type Hypersensitivity (DTH) reaction - Cardiovascular syphilis 1. Eyesue to arteritis involving vasa vasorum (small blood vessels that supply the Walls of large vessels) of aorta causing medial necrosis & loss of elastic fibers, Dilatation of Aorta and Aortic Ring, leading to Aneurysms of ascending & transverse aortic segments or aortic valve incompetence - Gumma: Localized granulomatous reaction in skin, bones, joints, or other organs leading to mass-related destruction V. Congenital Syphilis: - Fetuses are susceptible after 4th month of gestation - analogue to secondary syphilis in adults - Prior treatment for mother and Screen in early pregnancy and last trimester prevent it - Usually asymptomatic - Snuffles , rhinitis, maculo-papular rash - Bone changes: Saddle nose, Saber shins - Hutchinson’s teeth (small, separated, notched).. diagnostic - Anemia, thrombocytopenia & liver failure 4 _sixth: Lab Diagnosis: I. Detection: Immunofluorescent, dark-field microscopy orsilver impregnation histologically - Dark field microscopy: In primary & secondary lesions (serous transudate from below ulcers): 1. Shape and motility are characteristics 2. Negative result does not exclude syphilis II. III. IV. V. DFA method: Is done in only certain centers Can not be grown in culture; only in animals, so we inject it in animal Sluggish growth (generation time > 30 hours) Serologic tests: - Non-treponemal tests (NTT) : 1. Antibodies against Cardiolipin (which is a lipid complex), this Anticardiolipin antibody called Reagin which is Originally extracted from beef heart 2. Test is an immune flocculation type. 3. Most common tests: • Rapid Plasma Reagin (RPR) • Venereal Disease Research Laboratory (VDRL) • They’re Positive in early stages of primary lesions and always in secondary stage • In neurosyphilis CSF is VDRL positive, while serum VDRL is reverted to negative 4. But NTT non-specific tests: Positive in SLE, viral hepatitis, infectious mononucleosis & malaria. Also false + result may be in pregnancy & HIV infection. So, If positive confirm by TT 5. Usually, used for screening and follow up, e.g. with antibiotic therapy become negative 5 - Treponemal tests (TT) : Detect antibodies (Ab) specific to T. pallidum 1. Fluorescent Treponemal Antibody (FTA-ABS): • Spirochetes appears on fixed slides • ABS: ABSorbance of non-specific Ab 2. Microhemagglutination test for T. pallidum (MHA-TP) • Ag attached to RBC to agglutinate Ab 3. Not useful for screening or follow up, because if they are positive once, they remain so for a the whole life - In congenital syphilis : Treponemal IgM tests (since IgG is from the mother) _seventh: Treatmen and Prevention: I. II. III. PENICILLIN; for primary, secondary or latent syphilis If patient has an allergy to penicillin: Doxycycline is alternative For neurosyphilis and congenital syphilis desensitize patients for penicillin rather than using alternatives. IV. For prevention: Safe sex practice, because VACCINE IS NOT AVAILABLE❌ 6 This is a summary from osmosis _past years’ questions: – Not true about syphilis : Answer: non treponemal is confirm diagnosis – A 53 years old immunocompromised man with late stages of syphilis was presented to the STD clinic and neurosyphilis was suspected. Which of the following tests is expected to be Positive in the examination to confirm the diagnosis? A-Specific IgGantibody. B-Fluorescent Treponemal Antibody (FTA ABS). C-Microhemagglutination test for Treponema pallidum (MHA TP). D-Rapid Plasma Reagin (RPR). E-Venereal Disease Research Laboratory (VDRL). Answer: E 7