Lec 15. Lyme Disease
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What was the initial presentation of the Lyme disease epidemic, and who was mostly affected?
Was the epidemic of polyarthritis
mostly in children
What were most Lyme disease patients initially misdiagnosed with?
A: Rheumatoid arthritis.
Q: What skin finding did many Lyme disease patients have before symptoms developed?
A “bulls-eye” rash.
What was the bulls-eye rash in Lyme disease associated with?
A: A tick bite.
What is the spirochete? What is its relation with ticks? What is the specific spirochete that causes lyme disease?
Type of bacteria that was found in ticks associated with bulls eye rashes
Borrelia burgdorferi
Where was spirochete found in patients with lyme disease?
Skin
Blood
Cerebral spinal fluid
What is the Gram stain result Borrelia burgdorferi?
Gram negative spirochete.
What is shape of Lyme burgdorferi
thin, long, spiral shaped
Where are Lyme Borrelia widely found?
A: Throughout temperate zones in the Northern hemisphere.
Q: What is the major cause of Lyme disease in North America?
A: B. burgdorferi.
Q: Can species other than B. burgdorferi cause Lyme disease? What are they collectively called?
A: Yes. They are collectively called B. burgdorferi sensu lato.
Q: How is B. burgdorferi spread?
A: By the bite of “hard” ticks (Ixodes species).
Q: Why is Lyme disease called a vector borne disease?
A: Because B. burgdorferi is spread by the bite of hard ticks, which act as the vector.
How is B. burgdorferi transmitted to different mammalian hosts?
A: Through ticks.
Q: Where is B. burgdorferi only found?
A: In their vertebrate or arthropod hosts.
Q: What is the major reservoir for B. burgdorferi?
A: White footed mice.
Q: How does an unfed tick larva acquire B. burgdorferi?
A: By feeding on an infected host (mouse) for 3-5 days (acquisition).
Q: What happens to the fed larva after acquiring B. burgdorferi?
A: It moults into an unfed nymph, taking 1 month to 1 year.
Q: How is B. burgdorferi transmitted by the nymph?
A: The unfed nymph feeds on a mouse for 3-5 days, becoming a fed nymph (transmission).
Q: In the B. burgdorferi life cycle, what are the two stages of the tick feeding process?
A: Acquisition (larva feeds on an infected mouse) and transmission (nymph feeds and passes the bacteria on).
Q: What are the common names of the Ixodes tick?
A: Black legged tick or deer tick.
Q: What type of body do Ixodes ticks have?
A: Hard bodied.
Q: Which Ixodes species primarily transmit B. burgdorferi in North America?
A: I. scapularis and I. pacifica
What method does Lyme disease use to transmit disease?
Ticks sit on grass/shrubs and wait for host to pass by
Bites often occur in hard to see areas
T or F- Dogs and Cats can get lyme disease
T
T or F - There is no evidence of direct person to person transmission of lyme disease
T
What are the 3 stages of Ixodes life cycle
Larva
Nymph
Adult
Q: What do Ixodes ticks require between life cycle stages?
Blood meals
Q: Is B. burgdorferi transmitted from adult Ixodes ticks to their eggs?
No adult to egg transmission
ticks must aquire B.burg throughout lifetime
Q: Which animals can carry B. burgdorferi in the Ixodes life cycle?
A: Mice, squirrels, and birds.
Q: Which Ixodes stage causes the majority of human B. burgdorferi infections?
A: Nymphs.
Q: When is the risk of human B. burgdorferi infection greatest in the Ixodes life cycle?
A: Late spring and summer.
What does the tick insert into the host to transmit Lyme disease?
A: A feeding tube with barbs.
Q: What does the tick secrete while feeding in Lyme disease transmission?
A: A local anesthetic.
Q: How does the likelihood of Lyme disease transmission change after 24 hours of tick attachment?
A: Transmission increases after >24 hours.
Q: How does the tick feed during Lyme disease transmission?
A: It sucks blood slowly for several days.
Q: What color do ticks appear when engorged with blood in Lyme disease transmission?
grey when engorged
How to remove tick? Do’s and Don’ts
fine tipped tweezer
grasp tick close to skin
slowly pull up
wash area
dont squish body
dont burn tick
dont apply petroleum jelly
What must B. burgdorferi do after initial infection to propagate through its life cycle in Lyme disease?
A: Cause disseminated and persistent infection.
Q: What is a central event in the development of Lyme borreliosis?
A: Hematogenous dissemination (spread through the blood).
Q: What happens to B. burgdorferi inside the tick before Lyme disease transmission?
A: The bacteria multiply, alter gene expression, and disseminate in the tick.
Q: How does B. burgdorferi enter the host in Lyme disease?
A: The bacteria are inoculated into the skin by the tick.
Q: What skin lesion forms as B. burgdorferi spreads in the skin in Lyme disease?
A: Erythema migrans lesion (the bulls-eye rash).
Q: How does B. burgdorferi leave the skin to spread through the body in Lyme disease?
A: By invading blood vessels (blood vessel invasion).
Q: What does B. burgdorferi do once in the blood vessels in Lyme disease?
It continues multiplying, penetrates, and colonizes tissue of PNS, CNS, skin, joints (tissue invasion).
What cells are thought to be inhibited by compounds in tick saliva during B. burgdorferi infection in Lyme disease?
dendritic cells
Which four dendritic cell functions are decreased by tick saliva compounds in Lyme disease?
Phagocytosis
maturation
inflammatory mediators
antigen presentation
What type of flagella does B. burgdorferi (the cause of Lyme disease) contain?
Periplasmic flagella called axial filaments.
Q: How do axial filaments produce the cork-screw shape of B. burgdorferi?
They wrap around the cells instead of sticking out like flagella usually do
Q: What causes B. burgdorferi to move in a corkscrew like manner?
Rotation of axial filament allows bac. to move
Q: What does the corkscrew movement of B. burgdorferi promote in Lyme disease?
A: Movement through the extracellular matrix of host tissues and invasion of the vasculature.
What is unusual about the outer membrane of B. burgdorferi (the cause of Lyme disease)?
A: It contains no LPS.
Q: What is expressed on the surface of B. burgdorferi, and what can they act as? What is the purpose?
Many surface expressed lipoproteins that can act as adhesins.
Required for it to escape the blood vessels and invade the endothelium.
Q: What is required for B. burgdorferi to invade the endothelium in Lyme disease?
A: Repetitive motility and adhesion to leave and stick to epithelial cell
Q: Why is the genetic structure of B. burgdorferi (Lyme disease) considered unusual?
has linear chromosome (rather than the typical circular bacterial chromosome)
has multiple plasmids, some linear and some circular.
Q: Why are plasmids important in B. burgdorferi infection (Lyme disease)?
A: They are required for infection, but they vary from strain to strain.
Q: What is the time frame of the early localized stage of Lyme disease?
A: 3-30 days.
Q: What is the most common symptom of early localized Lyme disease?
A: Erythema migrans = a painless “bulls-eye rash.”
Q: Where on the body does the Lyme disease rash commonly appear?
A: Groin, axilla, waist, back, and legs (head and neck in children).
Q: What happens to the Lyme disease rash if left untreated?
expands
Q: What flu-like symptoms can occur in early localized Lyme disease?
A: Fever, chills, fatigue, and body aches.
Q: In which patients does early disseminated Lyme disease occur?
untreated patients
Q: What joint symptoms occur in early disseminated Lyme disease?
A: Pain and swelling of large joints.
Q: What heart symptom occurs in early disseminated Lyme disease, and what causes it?
A: Heart palpitations, caused by interference with the heart’s electrical signals.
Q: What are the symptoms of meningitis in early disseminated Lyme disease?
A: Severe headaches and neck stiffness.
Q: What is Bell’s (facial) palsy in early disseminated Lyme disease?
A: Loss of muscle tone on one or both sides of the face.
How does lyme disease traverse the BBB
uses paracellular traversal transmission
screwdrives between epithealeal cells
Q: What long-term outcome can late disseminated Lyme disease cause?
A: Serious long-term disability.
Q: How does late disseminated Lyme disease respond to antibiotics?
takes longer to respond to antibiotics
Q: What muscle symptom occurs in late disseminated Lyme disease?
Muscle pain
Q: What neurological problems may patients with late disseminated Lyme disease develop?
Shooting pains
numbness
tingling in hands and feet
memory
Q: What may post-treatment Lyme disease syndrome involve?
autoimmune response or persistent infection
Are long-term antibiotics thought to help in post-treatment Lyme disease syndrome?
No
Q: What two factors are causing the Lyme disease tick habitat in Canada to expand?
Migratory birds
Warmer climate
How to prevent lyme disease
avoid wooded areas
wear long, light coloured pants + long sleeve shirt
repellents
check for ticks and remove them
Q: What exposure history supports a Lyme disease diagnosis?
A: A tick bite or reason to suspect tick exposure.
Q: What do the antibody tests for Lyme disease detect?
A: Antibodies to strains of B. burgdorferi.
Q: What causes false negatives in Lyme disease antibody tests?
A: Early testing (no antibody response yet) and the genetic diversity of B. burgdorferi.
What is the outcome for Lyme disease patients diagnosed early and treated with antibiotics?
will recover
Q: How long is the antibiotic course for Lyme disease?
2 weeks
Q: How is “chronic Lyme disease” regarded?
A: It is very controversial.
Q: What do some people think causes “chronic Lyme disease”?
A: Chronic infection by B. burgdorferi.
Q: Can “chronic Lyme disease” be diagnosed without evidence of prior Lyme disease?
Yes
Q: Is long-term antimicrobial therapy helpful for “chronic Lyme disease”?
A: No, this was demonstrated by 4 clinical trials.
What is the article about the Manhatten Prohject about?
The authors argue Lyme disease is more common than we thought.
They say it’s often missed because the case definition is too narrow, the tests aren’t sensitive enough, and treatment may be too limited.
Q: What was the first Lyme disease vaccine, and what was it based on?
A: LYMErix, based on an outer membrane protein.
Q: How effective was the LYMErix Lyme disease vaccine in the human trial?
75% effective
Q: What claims were made against the Lyme disease vaccine, and was there evidence?
A: Claims (and lawsuits) that it caused arthritis, but there was no evidence of this.
Q: Why was the Lyme disease vaccine pulled from the market in 2002?
Lack of demand
Q: Is a Lyme disease vaccine approved for any animals?
Yes, for dogs. Effective and safe