Lyme Disease

Question 1

What is lyme disease?

Answer 1

• prototype emerging infectious disease
• a multisystemic disorder
• commonly presents as skin lesions (erythema migrans)
• if untreated, can lead to arthritis, carditis and nervous system manifestations
• most common vector-borne disease in North America
• ‘Bullseye’ lesions on affected area
• most were misdiagnosed with rheumatoid arthritis
• many were noted to have a “bulls eye” rash prior to development of symptoms
• rash was associated with a tick bite
• a ‘spirochete’ was isolated from the ticks, and subsequently from skin, blood and cerebral spinal fluid of patients
• Borrelia burgdorferi

Question 2

What is borrelia burgdoferi

Answer 2

• Named after Willie Burgdorfer
• Gram negative spirochete
  thin (~0.5 µm) and long (>10 µm), spiral shaped
• Lyme Borrelia are widely found throughout temperate zones in the Northern hemisphere
• B. burgdorferi is the major cause in North America
  other species can cause Lyme Disease – collectively called B. burgdorferi sensu lato
• B. burgdorferi are spread by the bite of ‘hard’ ticks (Ixodes species) = vector borne disease

Question 3

Reservoir for Borrelia burgdorferi

Answer 3

• B. burgdorferi is transmitted to different mammalian hosts through ticks
• B. burgdorderi is only found in their vertebrate or arthropod hosts
• white footed mice are the major reservoir

Question 4

Ixodes Tick (black legged or deer tick)

Answer 4

• hard bodied ticks
• In North America, B. burgdorferi is transmitted primarily by Ixodes scapularis and Ixodes pacifica
• other species transmit in Europe and Asia

Question 5

Ixodes life cycle

Answer 5

3 stages:
- larva -> nymph -> adult
ticks require blood meals between stages
- no adult to egg transmission – ticks must acquire B. burgdorferi
- mice, squirrels and birds can carry B. burgdorferi
- majority of human infections come from nymphs

Question 6

Lyme disease transmission

Answer 6

• ticks do not fly or jump
• ticks sit on grasses/shrubs and wait for a host to pass by
• bites often occur in ‘hard-to-see’ areas
• dogs and cats can get Lyme disease
• no evidence of direct person to person transmission
• tick inserts a feeding tube with barbs
• secretes a local anesthetic
• transmission is not thought to occur during the first ~24h following a bite
• transmission increases >24h
• nymphs normally transmit the disease
• tick sucks blood slowly for several days
• ticks appear grey when engorged

Question 7

How to remove a tick

Answer 7

• use fine tipped tweezers
• grasp the tick as close to the skin as possible
• steadily pull upwards
• thoroughly wash the area
• keep the tick

do not squish the tick body
do not burn the tick off
do not apply petroleum jelly

Question 8

The pathogen: Borrelia burgdoferi

Answer 8

• following initial infection, B. burgdorferi must cause disseminated and persistent infection to propagate through it’s life cycle
• hematogenous dissemination is a central event in the development of Lyme Borreliosis
• contain periplasmic flagella

Question 9

Compounds in tick saliva are though to inhibit DC function on what levels?

Answer 9

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

Question 10

What is periplasmic flagella

Answer 10

• axial filaments wrap around cells to produce cork-screw shape
• rotation of the axial filament causes the bacteria to move in a corkscrew like manner
• promotes movement through extracellular matrix of host tissues and invasion of vasculature

Question 11

Why does B. burgdorferi contain an unusual outer membrane?

Answer 11

• no LPS
• many surfaces expressed lipoproteins that can act as adhesions
• escape from the vasculature requires adhesion to slow down the bacteria
• repetitive motility required to ivade endothelium

Question 12

Why does B. burgdorferi have an unusual genetic structure?

Answer 12

• ‘linear’ chromosome
• multiple plasmids – some linear and some circular
• plasmids are required for infection but are variable from strain to strain
• limited metabolic capability

Question 13

What happens at the early localized stage

Answer 13

• most common symptom is erythema migrans – ‘Bulls-eye rash’ (~25% of patients do not have a rash)
• occurs ~1-2 weeks after tick bite
• groin, axilla, waist, back, legs, (head and neck in children)
• rash will expand and if untreated can reach >12 inches diameter
• flu-like symptoms including fever, chills, fatigue, body aches

Question 14

What happens at the early disseminated stage (days to weeks)

Answer 14

• occurs in untreated patients
• multiple rashs would indicate dissemination of B. burgdorferi
• pain and swelling of large joints
• heart palpitations – interference with heart electrical signals
• meningitis - severe headaches and neck stiffness
• Bell’s (facial) palsy – loss of muscle tone on one or both sides of the face

Question 15

What happens during the late disseminated stage (months to years)

Answer 15

• can cause serious long-term disability
• response to antibiotics takes longer
• muscle pain
• arthritis
• severe pain and swelling in large joints
• ~5% of patients can develop neurological problems

Question 16

What is post-treatment lyme disease syndrome?

Answer 16

• 10-20% experience symptoms following treatment with antibiotics
• cause is unknown
• lingering symptoms including
• fatigue, muscle and joint pain, cognitive defects, sleep disturbances
• may involve an autoimmune response or possibly persistent infection
• most patients recover after a number of months
• long-term antibiotics are not thought to help

Question 17

Prevention

Answer 17

• avoid wooded areas endemic with Lyme disease
• stay on paths, avoid low lying brush and long grass
• wear long pants (tucked into socks) and long-sleeved shirts
• light coloured clothing
• repellants (containing DEET)
• check for ticks and remove them

Question 18

Diagnosis

Answer 18

• erythema migrans and other ‘typical’ symptoms
• tick bite or reason to suspect tick exposure
• anti-B. burgdorferi antibody tests (no ‘Gold-standard’)
• detect antibodies to a laboratory strain of B. burgdorferi
• false negatives often due to early testing (no antibody response yet) and genetic diversity of B. burgdorferi
• sensitivity is somewhat controversial
• submission of tick for testing (if you have it) to the National Microbiology Laboratory

Question 19

Treatment

Answer 19

• if bitten by a black legged tick, watch for a rash (30 days) and be aware of symptoms
• patients when diagnosed early will recover following antibiotic treatment
• 2 - 4 week course of an antibiotic
• without treatment can lead to joint, heart, nervous system problems
• ~10-20% of patients, typically with a late diagnosis, have post-treatment Lyme disease syndrome

Question 20

What is “Chronic Lyme Disease”?

Answer 20

• very controversial
• some think this is due to chronic infection by B. burgdorferi
• can be diagnosed without evidence of prior Lyme Disease
• persistant symptoms including fatigue, headaches, sleep disturbances, cognitive dysfunction and other neurological problems
• long-term antimicrobial therapy is not helpful – demonstrated by 4 clinical trials

Question 21

Lyme disease vaccine?

Answer 21

• LYMErix – based on an outer membrane protein
• human trial (11,000 adults) showed it to be 75% effective
• ‘should be considered’ for those in high risk areas (not ’recommended’)
• claims (and lawsuits) that the vaccine caused arthritis – no evidence
• pulled from the market in 2002 due to ‘lack of demand’ – only now approved for dogs