Lyme Disease

Question 1

Lyme Disease (Lyme Borreliosis)

Answer 1

• prototype emerging infectious disease
• a multisystemic disorder
• commonly presents as skin lesions (erythema migrans)
• most common vector-borne disease in North America

Question 2

What can result if lyme disease is left untreated?

Answer 2

if untreated, can lead to arthritis, carditis and nervous system manifestations

Question 3

How was Lyme Disease first recognized?

Answer 3

• first recognized in 1975 in rural communities surrounding Lyme, Connecticut
• noticed that children had a distinct rash that was associated with a tick bite
• eventually isolated the bacteria rom the ticks, skin, blood and CSF of patients

Question 4

Borrelia burgdorferi

Answer 4

• gram negative spirochete
• thin (0.5 um) and long (10um), spiral shaped
• found throughout temperate zones in the Northern Hemisphere
• major cause
• spread by the bite of “hard ticks” = vector born disease

Question 5

What is the reservoir for B. burgdoferi?

Answer 5

• transmitted to different mammalian hosts through ticks
• only found in vertebrate or arthropod hosts
• white footed mice are the major reservoir

Question 6

Ixodes tick (black legged or deer tick)

Answer 6

• 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 7

Ixodes Life Cycle

Answer 7

3 stages:
larva -> nymph -> adult
- ticks require blood meals between stages
- no adult to egg transmission (ticks must acquire B. burgdorferi)
- larva are not born infected!
- mice, squirrels and birds can carry B. burgdorferi
- majority of human infections come from nymphs

Question 8

Why do majority of human infections from from nymphs?

Answer 8

• because they are very small and difficult to see

Question 9

Lyme Disease Transmission

Answer 9

• 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

Question 10

How do Ticks transmit the disease?

Answer 10

• tick inserts a feeding tube with barbs
• secretes a local anesthetic
• suck blood slowly for several days
• ticks appear grey when engorged

Question 11

Following a bite, when does transmission occur?

Answer 11

After 24 hrs

Question 12

Tick Removal

Answer 12

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

Question 13

Things you should not do during tick removal

Answer 13

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

Question 14

What must occur after initial infection for B. burgdorferi to propagate through its life cycle?

Answer 14

Hematogenous dissemination and persistent infection

Question 15

What functions of DC do the bacteria, B. burgdorferi inhibit?

Answer 15

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

Question 16

Axial Filaments of B. Burgdorferi

Answer 16

• periplasmic flagella
• filaments wrap about the cells to produce a cork-screw shape
• rotation causes the bacteria to move in a cork-skrew manner
• promotes movement through extracellular matrix of host tissues and invasion of vasculature (like a drill)

Question 17

Outermembrane of B. burgdorferi

Answer 17

• no LPS
• many surface expressed lipoproteins that can act as adhesins
• escape from the vasculature requires adhesion to slow down B. burgdorferi
• repetitive motility required to invade endothelium

Question 18

Genetic Structure of B. burgdorferi

Answer 18

• linear chromosome
• multiple plasmids (both linear and circular)
• plasmids are required for infection but are variable from strain to strain
• limited metabolic capability (gets things like amino acids, through the host)

Question 19

Early Localized Stage of Lyme Disease

Answer 19

• 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 20

Early Disseminated Stage (days to weeks)

Answer 20

• 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 21

Late Disseminated Stage (months to years)

Answer 21

• can cause serious long-term disability
• response to antibiotics takes longer
• muscle pain
• arthritis
• severe pain and swelling in large joints
• ~5% of patients develop neurological problems (shooting pains, numbness, tingling in hands and feet, and memory)

Question 22

Post - treatment Lyme Disease Disorder

Answer 22

• 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 23

Prevention of Lyme Disease

Answer 23

• 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 24

Diagnosis of Lyme Disease

Answer 24

• erythema migrans and other ‘typical’ symptoms
• tick bite or reason to suspect tick exposure
• submission of tick for testing (if you have it) to the National Microbiology Laboratory

Question 25

Diagnosis of Lyme Disease

Answer 25

• erythema migrans and other ‘typical’ symptoms
• tick bite or reason to suspect tick exposure
• anti-B. burgorferi antibody tests
• submission of tick for testing (if you have it) to the National Microbiology Laboratory

Question 26

anti-B. burgdorferi antibody tests

Answer 26

• 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

Question 27

Treatment of Lyme Disease

Answer 27

• 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
• lack of 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 28

Chronic Lyme Disease

Answer 28

• 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
• medical community says that this does not exist

Question 29

Lyme Disease Vaccine

Answer 29

• 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 (but in control population, just as many people developed arthritis)
• pulled from the market in 2002 due to ‘lack of demand’ – only now approved for dogs

Question 30

Transversing the BBB (B. burgdorferi)

Answer 30

most likely paracellular transversal