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  1. 1. Lyme Disease April 29, 2003 Madina Agenor Sogole Moin
  2. 2. Disease History <ul><li>In the early 1900s, manifestation first reported in Europe </li></ul><ul><ul><li>associated it with tick bites </li></ul></ul><ul><li>In 1975, outbreak in Lyme, Connecticut </li></ul><ul><ul><li>Believed to be juvenile rheumatoid arthritis </li></ul></ul><ul><li>In 1982, spirochetes were identified in the midgut of the black-legged tick ( Ixodes scapularis ) and named Borrelia burgdorferi . </li></ul><ul><li>In 1984, Borrelia burgdorferi was isolated from the blood of patients with EM and from the rash lesion itself. </li></ul><ul><ul><li>Determined etiologic agent </li></ul></ul><ul><li>Today, it is the most common tick-borne infection in the U.S. </li></ul><ul><ul><li>more than 16,000 infections each year. </li></ul></ul>
  3. 3. Distribution <ul><li>Mostly localized to states in the northeastern, mid-Atlantic, and north-central regions, and to several counties in northwestern California </li></ul>http://www.cdc.gov/ncidod/dvbid/lyme/
  4. 4. <ul><li>In 1996-1999, the states with the highest reported number of Lyme disease cases were: New York, Connecticut, Pennsylvania, New Jersey, Wisconsin, Maryland and Rhode Island </li></ul><ul><li>Also reported in Europe, Asia and Australia </li></ul><ul><li>Where suburban and country residential dwellings encroach on wooded areas </li></ul><ul><li>Most common during late spring and summer </li></ul>
  5. 5. Causative Agent <ul><li>Borrelia burgdorferi sensu stricto </li></ul><ul><li>Spirochete: slender helical </li></ul><ul><li>shaped bacteria </li></ul><ul><li>Gram negative </li></ul><ul><li>Motile </li></ul><ul><li>Extracellular pathogen </li></ul><ul><li>Aerobic or microaerophilic </li></ul>http://www.cdc.gov/ncidod/dvbid/lyme/
  6. 6. <ul><li>.2um to 5um in width and 10 to 25 um in length </li></ul><ul><li>Protoplasmic cylinder </li></ul><ul><li>Cell membrane </li></ul><ul><li>Outer membrane </li></ul><ul><li>7 to 11 flagella </li></ul>
  7. 7. <ul><li>Cell division after 12 to 24 hours of elongation </li></ul><ul><li>Optimal temperature is 33C </li></ul><ul><li>Incubation period of 3 to 32 days after infecting the human host through a tick bite </li></ul><ul><li>Genome: linear chromosome and numerous linear/circular plasmids </li></ul><ul><li>Plasmids encode key genes involved in virulence </li></ul>
  8. 8. <ul><li>B. burgdorferi discovered in 1982 </li></ul><ul><li>Isolated and cultured from the tick Ixodes scapularis </li></ul><ul><li>Midgut contents of the tick removed and cultured on BSKII medium </li></ul><ul><li>Motile spirochetes isolated and observed by dark field microscopy </li></ul><ul><li>Spirochetes identified as B. burgdorferi </li></ul>
  9. 9. <ul><li>U.S.: B. burgdorferi sensu stricto </li></ul><ul><li>Europe: B. burgdorferi sensu stricto, B. garinii , and B. afzelii </li></ul><ul><li>Asia: B. garinii and B. afzelii </li></ul>
  10. 10. Methods of Transmission <ul><li>Vector-borne disease </li></ul><ul><li>Vector is deer or black-legged tick ( Ixodes scapularis ) or by the western black-legged tick ( Ixodes pacificus) on the Pacific Coast. </li></ul><ul><li>Transmits B. burgdorferi while feeding on an uninfected host </li></ul><ul><ul><li>the spirochetes are present in the midgut and migrate during blood feeding to the salivary glands, from which they are transmitted to the host via saliva. </li></ul></ul><ul><li>B. burgdorferi cannot penetrate intact skin </li></ul>
  11. 11. <ul><li>Two-year life cycle of tick </li></ul><ul><ul><li>Larval, nymphal and adult stages </li></ul></ul>http://www.cdc.gov/ncidod/dvbid/lyme <ul><li>Nymphal ticks are size of </li></ul><ul><li>poppy seeds </li></ul>
  12. 12. <ul><li>Reservoir for B. burgdoferi is deer </li></ul><ul><li>or white-footed mouse </li></ul><ul><li>Human contact can occur through pets </li></ul><ul><li>and outdoor activities in wooded areas </li></ul><ul><li>If tick is attached for less than 24 hours, </li></ul><ul><li>risk of acquiring Lyme disease is significantly reduced. </li></ul><ul><li>Once in the host, B. burgdorferi recognizes polysaccharides on the surface of mammalian cells </li></ul>
  13. 13. Symptoms <ul><li>Symptoms of B. burgdorferi </li></ul><ul><li>Stage 1 </li></ul><ul><ul><li>Localized erythema migrans (EM) </li></ul></ul><ul><ul><li>Red macule/papule </li></ul></ul><ul><ul><li>Round lesion that measures 5cm to 15cm.  </li></ul></ul><ul><li>Stage 2 </li></ul><ul><ul><li>Early disseminated infection </li></ul></ul><ul><ul><ul><li>multiple secondary erythema migrans lesions </li></ul></ul></ul><ul><ul><ul><li>systemic non specific symptoms </li></ul></ul></ul>http://www.cdc.gov/ncidod/dvbid/lyme/diagnosis.htm
  14. 14. <ul><ul><li>Persistent or late infection </li></ul></ul><ul><ul><ul><li>Symptoms of neurologic disease </li></ul></ul></ul><ul><ul><ul><li>Symptoms of musculoskeletal disease </li></ul></ul></ul><ul><ul><ul><li>Symptoms of cardiac disease </li></ul></ul></ul><ul><ul><ul><li>Chronic inflammatory eye disease </li></ul></ul></ul><ul><li>Stage 3 </li></ul><ul><ul><li>6 months after primary skin lesion </li></ul></ul><ul><ul><ul><li>Swelling and pain in large weight-bearing joints, especially in the knee. </li></ul></ul></ul><ul><ul><ul><li>Chronic arthritis </li></ul></ul></ul><ul><ul><li>Years after infection, if left untreated : </li></ul></ul><ul><ul><ul><li>Late neurological syndrome </li></ul></ul></ul>
  15. 15. <ul><li>Post-Lyme disease syndrome </li></ul><ul><ul><li>Persistent disease after antibiotic treatment </li></ul></ul><ul><ul><li>Controversial </li></ul></ul><ul><li>Some infected individuals show asymptomatic infection </li></ul><ul><li>Some only manifest nonspecific symptoms </li></ul>
  16. 16. Diagnosis <ul><li>Serologic data by IFA, ELISA and immmunoblotting techniques. </li></ul><ul><ul><li>Detect presence of IgM or IgG antibodies in patient’s serum against Borrelia burgdorferi </li></ul></ul><ul><ul><li>Tests are insensitive the first several weeks of infection </li></ul></ul><ul><ul><li>Western blot is more accurate and is used 6-12 weeks after infection to confirm results </li></ul></ul><ul><li>Direct Isolation </li></ul><ul><ul><li>Biopsies of the skin lesions may yield the organism in 50% or more of cases </li></ul></ul>
  17. 17. Cure <ul><li>Antibiotic therapy </li></ul><ul><li>Doxycycline and amoxicillin are used for two to four weeks in early cases </li></ul><ul><li>Doxycycline is also effective against human granulocytic ehrlichiosis </li></ul><ul><li>Cefuroxime axetil or erythromycin can be used for patients who are allergic to penicillin or who cannot take tetracyclines. </li></ul><ul><li>More developed cases, may require treatment with intravenous ceftriaxone or penicillin for 4 weeks or more </li></ul>
  18. 18. Prevention <ul><li>Avoid tick habitats </li></ul><ul><li>Wear appropriate barrier clothing that follow personal protection procedures </li></ul><ul><li>Apply insect repellent containing DEET to skin </li></ul><ul><li>Apply permethrin to clothes </li></ul><ul><li>Perform regular body checks for ticks </li></ul><ul><li>Remove ticks promptly with tweezers and clean area with antiseptic </li></ul><ul><li>Education of the general public </li></ul>
  19. 19. <ul><li>Lyme disease vaccine: LYMErix </li></ul><ul><ul><li>Recommended to 15-70 year olds living in endemic areas </li></ul></ul><ul><ul><li>Recommended to those who are at risk due to occupation </li></ul></ul><ul><ul><li>Only suggested to those who have a seasonal problem of infection greater than 1% </li></ul></ul><ul><ul><li>No longer commercially available since February 25, 2002 </li></ul></ul>
  20. 20. Control <ul><li>Habitat modification for ticks </li></ul><ul><li>-Clear trees and brush </li></ul><ul><li>  Chemical control of tick populations </li></ul><ul><li>-Apply pesticides to residential properties </li></ul><ul><li>Habitat modification for deer and rodents </li></ul><ul><li>-Keep rodents and deer away from houses and gardens </li></ul><ul><li>Host management </li></ul><ul><li>-Deer feeding stations equipped with pesticide applicators </li></ul><ul><li>-Baited devices to kill ticks on rodents </li></ul>
  21. 21. Works Cited <ul><li>Bacon, R.M., B.J. Biggerstaff, M.E. Schriefer ME, R.D. Gilmore Jr, M.T. Philipp, A.C. Steere, G.P. Wormser, A.R. Marques, B.J. Johnson. “Serodiagnosis of Lyme Disease by Kinetic Enzyme-Linked Immunosorbent Assay Using Recombinant VlsE1 or Peptide Antigens of Borrelia burgdorferi Compared with 2-Tiered Testing Using Whole-Cell Lysates.” Journal of Infectious Diseases . 2003 Apr 15;187(8):1187-99. </li></ul><ul><li>Benenson, Abram. Ed. Control of Communicable Diseases Manual . Washington, DC: American Public Health Association, 1995. </li></ul><ul><li>Crippa, M., O. Rais and L. Gern. “Investigations on the mode and dynamics of transmission and infectivity of Borrelia burgdorferi sensu stricto and Borrelia afzelii in Ixodes ricinus ticks.” Vector Borne Zoonotic Diseases . 2002 Spring;2(1):3-9. </li></ul><ul><li>Durham, Jerry D. and Felissa R. Lashley. Emerging Infectious Diseases: Trends and Issues . New York: Springer Publishing Co., 2002. </li></ul><ul><li>Parveen, N., M. Caimano, J.D. Radolf, J.M. Leong. “Adaptation of the Lyme disease spirochaete to the mammalian host environment results in enhanced glycosaminoglycan and host cell binding.” Molecular. Microbiology. 2003 Mar;47(5):1433-44. </li></ul><ul><li>Perry, Jerome, James Staley, Stephen Lory. Microbial Life . Sunderland, MA: Sinauer Associates, Publishers, 2002. </li></ul><ul><li>CDC Lyme Disease Home Page. http://www.cdc.gov/ncidod/dvbid/lyme/ </li></ul><ul><li>Zeus Scientific, Inc. “IFA Assays – Bacterial Diseases”. http:// www.zeusscientific.com/ifabact.html . 23 April 2003. </li></ul>

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