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Lecture 19 Treponema-Borrelia-ELMS

Lecture 19 Treponema-Borrelia-ELMS - Lecture 19 Treponema...

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Unformatted text preview: Lecture 19 Treponema Last sexually transmitted The Magic Bullet­The birth of Chemotherapy­1909 Paul Ehrlich 1854-1915 -differential staining of cells and bacteria inspired him to look for a compound that would only kill bacteria “Magic Bullet” Started looking for cure of syphilis, screened 605 compounds for 7 years, finally compound 606 was successful (Salvarsan) http://nobelprize.org Classification Classification Family Genera Species Spirochaetaceae Treponema/Leptospira/Borrelia STD limes Treponema pallidum General Characteristics General Characteristics Spirochetes Gram­negative No capsule­ like gnorrheae, not menditidis Thin, helical (o.1x 5 to 20um) Too thin to be observed by light microscopy (including gram/giemsa staining!) Three periplasmic flagella (motile!) Cannot be grown in vitro except on selected cultured cell lines (like Chlamydia) Human only known host Periplasmic Flagella Periplasmic Flagella (e.g.: Borrelia) Periplasmic Flagella Periplasmic Flagella •Flagella rotate and bacteria move in a corkscrew­ like fashion •Might be advantageous to move in viscous environments •Also internal flagella is hidden from host immune response Immunofluorescence staining Immunofluorescence staining 3rd most common STD in USA Human only known host Spread by sexual contact via breaches in the epithelium Transmission occurs primarily during early stages of disease Mother to fetus transmission is possible (bacteria can cross placenta) Epidemiology Epidemiology Epidemiology Epidemiology ~30­40,000 total cases of Syphilis per year in US ­age group 20­40 most affected­ younger adults to middle aged ­increase in cases between 2000­2006 ­300­400 case of congenital (mother)syphilis per year ­Syphilis increases chances of acquiring HIV by 2­5fold Primary Syphilis: (men and women are symptomatic) most infectious Primary chancre on genitals­ both men and women symptomatic­ cancres on the genitals­ highly infectious Clinical Manifestation Clinical Manifestation Painless lesion with high numbers of bacteria (transmission) Heals spontaneously within 2 month but bacteria spread into blood and lymph system Clinical Manifestation Secondary Syphilis Secondary Syphilis Disseminated disease Flu­like syndrome (sore throat, headache, muscle aches, fatigue, slight fever, anorexia) Followed by a disseminated skin rash Rash is highly infectious! Symptoms resolve spontaneously­ nasty cause comes back Patient enters latent phase of disease­ Secondary Syphilis Secondary Syphilis Clinical Manifestation Tertiary Syphilis / Latent Stage: Tertiary Syphilis / Latent Stage: Small portion (10­15%) of latently infected individuals can progress (10­20 years after infection)­ comes back after infection Devastating chronic inflammation Leads to possible destruction of any organ or tissue; common symptoms: loss of coordinated muscle movement, blindness, dementia­ range of very serious complications Clinical Manifestation Congenital Syphilis: Congenital Syphilis: Infection in utero Multi­organ malformation and death of fetus Newborn without symptoms may suffer from teeth and bone malformations, blindness, deafness Diagnosis Diagnosis Serological tests Staining of specimens ELISA of blood for specific antibodies against T. pallidum antigens Problem: Treponemas (not T. pallidum) are part of the normal microflora in the oropharynx , thus potential for crossreactivity of antibodies Diagnosis Diagnosis Dark­field microscopy Immunofluorescence microscopy ­ Direct observation of specimen from chancre ­specimen from chancre is stained with specific antibody (conjugated to fluorophore) Prevention Use of condoms ­problem: sores can be in areas not easily noticed and outside area protected by condom No vaccine Screen mother at first prenatal visit (mother remains infections during latent stage for estimated 4years!) Penicillin! Treat sex partner also Alternative: Tetracycline Treatment Treatment Case study example: 20 yo woman­ rash, feverish and anorexic­ rash over chest and hands­ no vesicles, cervical and lymph nodes palpable Aemophilus ucreyi­ nope Neisseria gonorrhea­ usually not the same rash Treponema pallidum­ YES on trunk rash Chlamydia trachomatis Not enough info Lecture 19 Borrelia Classification Classification Family Genera Species Spirochaetaceae Treponema/Leptospira/Borrelia Borrelia burgdorferi Borrelia garinii Borrelia afzelii Borrelia recurrentis US and Europe Only in Europe and Asia General Characteristics General Characteristics Spirochetes Thin, helical (0.2­0.5x 8 to 30um) 7­20 periplasmic flagella Can be observed with Giemsa stain Can be grown in vitro but very complex media requirements (generation times >18h) Diagnosis usually not by culture Vector­borne disease­ yersinia another one Periplasmic Flagella Periplasmic Flagella Giemsa staining Giemsa staining Overview Epidemiology of Borrelia Overview Epidemiology of Borrelia infections caused by B. recurrentis caused by B.burgdorferi in US Body Louse Body Louse Soft tick Soft tick Hard tick Hard tick Clinical Manifestation Clinical Manifestation Epidemic Relapsing Fever / Louse­borne relapsing fever Caused by B. recurrentis, spread from person­ to­person via human body louse Human only known reservoir Requires crowded and unsanitary conditions Currently only in few underdeveloped countries Clinical Manifestation Endemic Relapsing Fever/ tick­borne disease Endemic Relapsing Fever/ tick­borne disease Zoonotic disease (rodents,ticks) Many Borrelia species may cause disease Mainly found in western USA Bite of soft­shelled ticks Clinical Manifestation Relapsing Fever One week after infection (bite), abrupt onset of shaking chills, fever, muscles aches and headache (=bacteremic phase= febrile period) Symptoms resolve after 3­7 days (clearance of bacteria) And return after about one week (afebrile period) Subsequent febrile periods are less severe Evasion of immune response via Evasion of immune response via antigenic variation Relapsing Fever -Ab recognize surface lipoproteins , variable major proteins (VMPs) -high-frequency variation of VMPs due to programmed rearrangements of vmp genes (phase variation!!) Diagnosis/Treatment/Prevention Relapsing Fever High numbers of bacteria during febrile period allow detection in blood samples via Giemsa staining Tetracycline and Erythromycin No vaccine Avoid exposure to ticks Diagnosis Diagnosis Fluorescence Dark­field Giemsa staining Clinical Manifestation Clinical Manifestation History of Lyme Disease 1977 in Lyme (Connecticut) unusual cluster of rheumatoid arthritis in children 1982, W. Burgdorfer discovers spirochetes in midgut of Ixodes ticks Demonstrated the spirochetes react with serum from patients Clinical Manifestation Clinical Manifestation Early infection (Stage I) Erythema migrans seen in 60­80% of people (20­40% no rash!) Spirochetes can be isolated from edges of rash Rash expands over time (bull’s eye) up to 50cm in diameter Rash persists 3­4 weeks Clinical Manifestation Stage II (Dissemination) Spread of bacteria via bloodstream Fatigue, chills and fever Headache Muscle and joint pains Swollen lymph nodes (lymphadenopathy) May appear weeks, months or years after tick bite Very variable Meningitis: headache, stiff neck fever) Bell’s palsy (paralysis of facial muscles) Arthritis: brief bouts of pain and swelling (knees) Disturbance in memory, mood or sleep pattern Sensation of numbness in hands or feet Clinical Manifestation Stage III (Persistence) Bell’s Palsy Bell’s Palsy Causes: •Tumor •Lyme disease •Viral infection Clinical Manifestation Clinical Manifestation Stage I Stage III Erythema Migrans Swelling and discoloration of skin; more common in Europe; associated with arthritis Epidemiology Epidemiology Lyme disease Since initial discovery cases have increased Most prevalent vector­borne illness in USA Most cases (95%) concentrated in 12 states Seasonal incidences correspond to feeding pattern of ticks and are higher in late spring/early summer Epidemiology Epidemiology Epidemiology Epidemiology Some high case loads, back down in some states Maryland is a high risk From CLIN INFECT DIS 43(9):1089-1134. © 2006 by the Infectious Diseases Society of America. All rights reserved. For permission to reuse, contact [email protected] Figure 1.  From left to right, an Ixodes scapularis larva, nymph, adult male tick, and adult female tick. The picture is a generous gift from Dr. Richard Falco (Fordham University). From CLIN INFECT DIS 43(9):1089-1134. © 2006 by the Infectious Diseases Society of America. All rights reserved. For permission to reuse, contact [email protected] Figure 2.  Ixodes scapularis ticks demonstrating changes in blood engorgement after various durations of attachment. A, Nymphal stage (reprinted from [1], with permission from Elsevier). B, Adult stage. The pictures are a generous gift from Dr. Richard Falco (Fordham University). Transmission Transmission Blood meal needed for transformation from Larva­ Nymph and Nymph to Adult Diagnosis Diagnosis Difficult because symptoms variable and resemble other disease (e.g. viral infections) Diagnosis often based on patient’s history of possible exposure Serology useful in patients in Stage I and II but potential of cross reactivity Microscopy not useful PCR amplification Treatment Treatment Doxycycline (2­3 weeks, twice daily) Successful even in Stage III patients Symptoms may recur but usually resolved with 2nd treatment Prevention Reduce risk of exposure to ticks: ­cover legs and arms, use insect repellent (DEET), on cloth use permethrin which kills ticks on contact ­walk in center of trail to avoid overhanging grass and brushes ­avoid tick­infested areas, especially in May, June and July Check for ticks daily (removal within 36h prevents infection) Tick control in highly endemic areas Prevention Vaccine available…. but not anymore introduced in 1998, withdrawn from market in 2002 due to poor sales ...
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