Lyme Disease

April 29, 2003

Madina AgenorSogole Moin

Disease History• In the early 1900s, manifestation first reported in Europe

– associated it with tick bites• In 1975, outbreak in Lyme, Connecticut

– Believed to be juvenile rheumatoid arthritis• In 1982, spirochetes were identified in the midgut of the

black-legged tick (Ixodes scapularis) and named Borrelia burgdorferi.

• In 1984, Borrelia burgdorferi was isolated from the blood of patients with EM and from the rash lesion itself.– Determined etiologic agent

• Today, it is the most common tick-borne infection in the U.S.– more than 16,000 infections each year.

Distribution

• Mostly localized to states in the northeastern, mid-Atlantic, and north-central regions, and to several counties in northwestern California

http://www.cdc.gov/ncidod/dvbid/lyme/

• 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

• Also reported in Europe, Asia and Australia• Where suburban and country residential

dwellings encroach on wooded areas • Most common during late spring and summer

Causative Agent

• Borrelia burgdorferi sensu stricto• Spirochete: slender helical

shaped bacteria• Gram negative• Motile • Extracellular pathogen• Aerobic or microaerophilic

http://www.cdc.gov/ncidod/dvbid/lyme/

• .2um to 5um in width and 10 to 25 um in length

• Protoplasmic cylinder

• Cell membrane

• Outer membrane

• 7 to 11 flagella

• Cell division after 12 to 24 hours of elongation• Optimal temperature is 33C• Incubation period of 3 to 32 days after

infecting the human host through a tick bite• Genome: linear chromosome and numerous

linear/circular plasmids• Plasmids encode key genes involved in

virulence

• B. burgdorferi discovered in 1982 • Isolated and cultured from the tick Ixodes

scapularis • Midgut contents of the tick removed and

cultured on BSKII medium• Motile spirochetes isolated and observed by

dark field microscopy• Spirochetes identified as B. burgdorferi

• U.S.: B. burgdorferi sensu stricto

• Europe: B. burgdorferi sensu stricto, B. garinii, and B. afzelii

• Asia: B. garinii and B. afzelii

Methods of Transmission

• Vector-borne disease• Vector is deer or black-legged tick (Ixodes scapularis)

or by the western black-legged tick (Ixodes pacificus) on the Pacific Coast.

• Transmits B. burgdorferi while feeding on an uninfected host– 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.

• B. burgdorferi cannot penetrate intact skin

• Two-year life cycle of tick– Larval, nymphal and

adult stages

http://www.cdc.gov/ncidod/dvbid/lyme

• Nymphal ticks are size of poppy seeds

• Reservoir for B. burgdoferi is deer

or white-footed mouse

• Human contact can occur through pets

and outdoor activities in wooded areas

• If tick is attached for less than 24 hours,

risk of acquiring Lyme disease is significantly reduced.

• Once in the host, B. burgdorferi recognizes polysaccharides on the surface of mammalian cells

Symptoms

• Symptoms of B. burgdorferi • Stage 1

– Localized erythema migrans (EM)– Red macule/papule– Round lesion that measures 5cm to 15cm. 

• Stage 2– Early disseminated infection

• multiple secondary erythema migrans lesions• systemic non specific symptoms

http://www.cdc.gov/ncidod/dvbid/lyme/diagnosis.htm

– Persistent or late infection• Symptoms of neurologic disease• Symptoms of musculoskeletal disease• Symptoms of cardiac disease• Chronic inflammatory eye disease

• Stage 3– 6 months after primary skin lesion

• Swelling and pain in large weight-bearing joints, especially in the knee.

• Chronic arthritis

– Years after infection, if left untreated:• Late neurological syndrome

• Post-Lyme disease syndrome– Persistent disease after antibiotic treatment– Controversial

• Some infected individuals show asymptomatic infection

• Some only manifest nonspecific symptoms

Diagnosis

• Serologic data by IFA, ELISA and immmunoblotting techniques.– Detect presence of IgM or IgG antibodies in patient’s

serum against Borrelia burgdorferi

– Tests are insensitive the first several weeks of infection

– Western blot is more accurate and is used 6-12 weeks after infection to confirm results

• Direct Isolation– Biopsies of the skin lesions may yield the organism in 50%

or more of cases

Cure• Antibiotic therapy• Doxycycline and amoxicillin are used for two to four

weeks in early cases• Doxycycline is also effective against human

granulocytic ehrlichiosis • Cefuroxime axetil or erythromycin can be used for

patients who are allergic to penicillin or who cannot take tetracyclines.

• More developed cases, may require treatment with intravenous ceftriaxone or penicillin for 4 weeks or more

Prevention

• Avoid tick habitats• Wear appropriate barrier clothing that follow personal

protection procedures• Apply insect repellent containing DEET to skin• Apply permethrin to clothes• Perform regular body checks for ticks• Remove ticks promptly with tweezers and clean area

with antiseptic• Education of the general public

• Lyme disease vaccine: LYMErix– Recommended to 15-70 year olds living in endemic

areas– Recommended to those who are at risk due to

occupation– Only suggested to those who have a seasonal

problem of infection greater than 1%– No longer commercially available since February

25, 2002

Control

• Habitat modification for ticks-Clear trees and brush

•  Chemical control of tick populations-Apply pesticides to residential properties

• Habitat modification for deer and rodents-Keep rodents and deer away from houses and gardens

• Host management-Deer feeding stations equipped with pesticide

applicators-Baited devices to kill ticks on rodents

Works Cited• 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.

• Benenson, Abram. Ed. Control of Communicable Diseases Manual. Washington, DC: American Public Health Association, 1995.

• 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.

• Durham, Jerry D. and Felissa R. Lashley. Emerging Infectious Diseases: Trends and Issues. New York: Springer Publishing Co., 2002.

• 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.

• Perry, Jerome, James Staley, Stephen Lory. Microbial Life. Sunderland, MA: Sinauer Associates, Publishers, 2002.

• CDC Lyme Disease Home Page. http://www.cdc.gov/ncidod/dvbid/lyme/• Zeus Scientific, Inc. “IFA Assays – Bacterial Diseases”. http://

www.zeusscientific.com/ifabact.html. 23 April 2003.