(B) Lecture 17: Lyme Disease

Question 1

Lyme Disease

Answer 1

• first recognized in Conneticut
• epidemic of ‘polyarthritis’ mainly in kids
• most were misdiagnose w/ rheumatoid arthritis
• BULLS EYE RASH
• spirochete isolated from ticks

Question 2

Borrelia burgdorferi characteristics

Answer 2

• gram NEGATIVE
• long spirochete
• mostly found in temperate zones
• main cause in North America
• VECTOR borne disease = spread by bite of ‘hard’ ticks

Question 3

B. burgdorferi sensu lato

Answer 3

Whole group of species

Question 4

Reservoir for B. burgdorferi

Answer 4

Tick is required for transmission

• WHITE FOOTED MICE are the major reservoir
• uninfected/unfed larva eat to get bloodmeal and become fed

Question 5

Ixodes Tick

Answer 5

black legged or deer tick

• hard bodied ticks
• B. burgdorferi is mainly transmitted by Ixodes scapularis (East coast) and Ixodes Pacifica (West coast)

Question 6

Lyme Disease transmission

Answer 6

• ticks do not fly or jump
• ticks wait in grasses/shrubs and wait for host to pass by
• bites in ‘hard-to-see’ areas - groin, armpits, hairline, neck
• no evidence of person-to-person transmission`

Question 7

Ixodes life cycle

Answer 7

3 stages: large –> nymph –> adult

• no adult to egg transmision
• mice, squirrels and birds can carry B. burgorferi
• MAJORITY of human infections are from NYMPHS (so small = hard to see)

Question 8

How does a tick infect?

Answer 8

• tick inserts feeding tube w/ BARBS = secretes anaesthetic
• transmission doesn’t occur in first 24h after a bite
• ticks appear grey when engorge

Question 9

Tick removal

Answer 9

• use sharp, fine-tipped tweezers
• grasp as close to skin as possible
• keep tick + send in for Lyme testing

Question 10

B. burgdorferi infection

Answer 10

After initial infection, B. burgdorferi causes disseminated and persistent infection to spread through its life cycle

Hematogenous dissemination is important for development of Lyme disease

Question 11

B. burgdorferi virulence factors

Answer 11

• compound in tick saliva
• periplasmic flagella
• unusual outer membrane
• genetic structure

Question 12

Tick saliva

B. burgdorferi

Answer 12

Compounds in saliva inhibit DC function (immune function)

• decreased phagocytosis
• decreased maturation
• decreased inflammatory mediators
• decreased antigen presentation

Question 13

Periplasmic flagella

B. burgdorferi

Answer 13

Periplasmic flagella: btwn cytoplasmic membrane + outer membrane

• contain axial filaments that wrap around cells
• rotation of axial filament causes the bacteria to move in corkscrew-like manner

important for invading + escaping vessels

Question 14

Outer membrane of B. burgdorferi

Answer 14

Unusual outer membrane

• no LPS
• many surface expressed lipoproteins that can act as ADHESINS
• escape from vasculature needs adhesion to slow down B. burgdorferi

Question 15

Genetic structure of B. burgdorferi

Answer 15

Unusual genetic structure

• LINEAR chromosome = weird
• multiple plasmids
• plasmids are needed for infection and are variable from strain to strain
• limited metabolic capacity

Question 16

Early Localized Stage of Lyme Disease

Answer 16

• ERYTHEMA MIGRANS = BULLS-EYE RASH is most common symptom
• 1-2 weeks after tick bite
• groin, axilla, waist, back, legs
• flu-like symptoms: fever, chills, fatigue, body aches

Question 17

Early Disseminated Stage of Lyme Disease

Answer 17

• days to weeks
• in untreated patients
• pain + swelling of LARGE JOINTS
• heart palpitations
• meningitis - severe headaches + neck stiffness
• BELL’S FACIAL PALSY - loss of muscle tone on one or both sides of face

Question 18

How does B. burgdorferi traverse the BBB?

Answer 18

Paracellular traversal using flagella
- squeezing btwn tight junctions

Question 19

How does meningitis pathogen traverse the BBB?

Answer 19

Transcellular traversal
- invades inside endothelial cell

Question 20

Late Disseminated Stage of Lyme Disease

Answer 20

• months to years
• can cause long-term disability
• muscle pain, arthritis, severe pain and swelling in large joints
• 5% of patients get neurological problems

Question 21

Post-treatment Lyme disease syndrome

Answer 21

• 10-20% experience symptoms after antibiotics
• cause is unknown
• may involve AUTOIMMUNE disease
• long-term antibiotics are not thought to help

Question 22

Lyme Disease in Canada

Answer 22

Ticks continue to expand due to
- migratory birds
- warmer climate

Question 23

Prevention of Lyme Disease

Answer 23

• avoid wooded areas endemic w/ Lyme disease
• stay on paths, avoid low lying brush and long grass
• wear long pants tucked into socks
• repellants w/ DEET
• light coloured clothing (more likely to see)

Question 24

Diagnosis of Lyme Disease

Answer 24

• erythema migrans and other symptoms
• tick bite or reason to suspect tick exposure

anti-B. burgdorferi antibody tests (no ‘Gold-standard’
- detect antibodies to a lab strain of B. burgdorferi
- false negatives often due to early testing and genetic diversity

Question 25

Treatment of Lyme Disease

Answer 25

• if bitten by black legged tick, watch for a rash
• early diagnosis = recovery after antibiotic treatment
• 2-4 weeks of antibiotic (usually protein synthesis inhibitor)
• w/o treatment –> joint , heart + nervous system problems

Question 26

Chronic Lyme Disease

Answer 26

• very controversial
• can get diagnosis w/o proof of ever having Lyme disease
• persistent symptoms like fatigue, headaches, sleep disturbances, cognitive dysfunction, neurological problems

Question 27

Manhattan Project to combat Chronic Lyme Disease

Answer 27

• most common in children and women
• case definition may have been too narrow - many symptoms in chronic Lyme disease are not properly recognized
• commercial tests probably not sensitive enough for B. burgdorferi
• treatment may be too restrictive + short

Question 28

Lyme Disease Vaccine

Answer 28

• LYMErix is not recommended but can be considered for those in high risk
• claims that it caused arthritis
• pulled from market and won’t come back