Lyme Disease

Question 1

What is Lyme disease ?

Answer 1

a bacterial (vector-born) disease caused by Borrelia species (Borrelia burgdoferi)

Question 2

Basic characteristics (3)

Answer 2

GRAM NEGATIVE BACTERIA
motile
spiral shaped (Spirochete)

Question 3

Transmission (3)

Answer 3

TRANSMITTED by bite of blacklegged tick (DEER TICK)

Tick is infected by Borrelia burgdorferi and RARELY by Borrelia mayonii

TRANSMISSION OCCURS after an infected tick has been attached for AT LEAST 24-36 hours (most transmission occurs after 36-48 hours)

Removing the tick (within 24 hours) after it is ATTACHED greatly reduces the chances of getting Lyme disease.

Question 4

Geographic distribution of Borrelia species

Answer 4

B. burgdorferi
North America, Europe

B. mayonii
Upper Midwestern USA

B. afzelii AND B. garinii,
Europe, Asia

Question 5

Lyme disease vectors

Answer 5

Ixodes scapularis - EASTERN and NORTH central regions of North America

Ixodes pacificus - WESTERN North America (eg, northern California and Oregon)

Ixodes persulcatus - Asia and Eastern Europe

Ixodes ricinus - Europe and Western Asia

Question 6

Life Cycle

Answer 6

Blacklegged ticks have a 2 - 3 YEARS OF LIFE CYCLE

FOUR life stages: EGG, LARVA, NYMPH, and ADULT.

The LARVA and NYMPH each must take a blood meal to develop to another stage of their life (female need blood to produce eggs)

LARVA AND NYMPHAL TICKS might get infected with Borrelia burgdorferi when feeding on an infected wildlife host, usually a RODENT such as mice.

The bacteria are passed along to the next life stage.

Deer are important sources of blood for ticks and are important for tick ‘s survival and movement to new areas but are NOT INFECTED by Borrelia burgdorferi . Other mammals e.g., dogs, and sheep (Europe) can be host for Borrelia

Question 7

Symptoms (MOST COMMON)

Answer 7

Lyme disease —> MULTIPHASE & MULTISYSTEM disease

1) Fever/chills. All tickborne diseases can cause fever.

2) Aches and pains (JOINT PAIN)

3) RASH —> Lyme disease, Southern tick associated rash illness (STAR), Rocky mountain spotted fever (RMSF), ehrlichiosis and tularemia can cause DISTINCTIVE rashes

4) Tick paralysis —> caused by a toxin in the saliva of an attached tick. (PARALYSIS MOVES UP THE BODY) also resembles Guillain-Barré syndrome or botulism. (patients gain movement if removed tick within 24 hours)

Question 8

Clinical manifestations (3)

Answer 8

Early Localized Disease — STAGE 1
The bacteria have not yet spread throughout the body.

Early Disseminated Disease — STAGE 2
The bacteria have begun to spread throughout the body.

Late Disseminated Disease — STAGE 3
The bacteria have spread to distant sites such as the joints and nerves.

Question 9

Types of rashes

Answer 9

Check the slides it’s better

Question 10

Erythema migrans (EM) rash

Answer 10

Occurs in 70 to 80 PERCENT of infected persons

ALSO CALLED BULL’S EYE RASH

• Begins at the site of a tick bite after 3 to 30 days (average is about 7 days)
• Expands gradually over several days reaching up to 12 inches or more (30 cm) across
• May feel warm to the touch but is rarely itchy or painful
• May appear on any area of the body
• Does not always appear as a “classic” erythema migrans rash

Question 11

Stage 2: Early disseminated Lyme disease

Answer 11

• MAY OCCUR weeks to months after the tick bite
• Numbness or pain in the distribution of a nerve
• Paralysis or weakness in the muscles of the face, especially a facial nerve palsy
• Meningitis, characterized by severe headache, stiff neck, fever
• Heart problems, such as skipped heartbeats, which can cause light headedness or fainting.

Question 12

Stage 3: Late disseminated Lyme disease

Answer 12

OCCURS when treatment was either not successful or never started (usually occurring many months after the initial bite).

Usually associated with intermittent or persistent arthritis

Joint inflammation (arthritis), typically in the knees, occurs and may become chronic.

Abnormal nervous system sensation develops because of disease of peripheral nerves (peripheral neuropathy), and confusion.

Heart problems including inflammation of the heart muscle and an irregular beat may occur .

Paralysis or weakness in the muscles of the face, especially a facial nerve palsy.

Meningitis, characterized by severe headache, stiff neck, fever.

Question 13

Cycle after transmission

Answer 13

• B. burgdorferi enters the skin at the site of the tick bite.

• After 3 to 32 days, the organisms migrate locally in the skin around the bite, spread via the lymphatics to cause regional adenopathy or disseminate in blood to organs or other skin sites.

• Initially, an inflammatory reaction (erythema migrans) occurs before significant antibody response to infection (serologic conversion).

It is invasive and persistent but NOT TOXIGENIC.

Tissue pathology appears to be primarily due to host inflammatory reactions

Question 14

Attachment to host membranes

Answer 14

B. burgdorferi possesses:

P66 (outer membrane protein of B. burgdorferi) —> functions as porin protein and, ß3-intergin binding protein that binds to host integrins, proteoglycans and glycoproteins

BBK32 (Fibronectin binding protein of B. burgdorferi) and decorin binding protein facilitates dissemination of the bacteria on entry into the bloodstream, promotes serum resistance.

B. burgdorferi binds plasmin, a serine protease, capable of digesting many extracellular matrix components to disseminate from the site of inoculation.

Question 15

Pathogenesis

Answer 15

Evasion of antibody-mediated killing
• By using borrelial surface proteins, including outer surface protein C (OspC), and flagellin, developed very early in infection.
• Antibodies against OspC can kill the spirochete.

Evasion of complement-mediated killing
• By using outer surface protein E (OspE)- related proteins (Erps), and complement regulator-acquiring surface proteins (CRASPs) that bind complement factor H, and complement factor H-like protein 1 of the mammalian host.

Question 16

Evasion of host’s immune response

Answer 16

• Starts the moment B. Burgdorferi enters the bloodstream via the bite of a tick. The tick saliva contains the salivary protein, Salp15.

• Salp15 suppresses the host immune response via the deactivation of T-cells

• Suppression of the immune response allows the tick to feed for a few days on the host’s blood in order to get the nutrients it needs to survive.

• An active host’s immune system at the site of attachment would prevent the attachment of the tick

• Suppression of the local immune response gives the B. Burgdorferi time to invade the host’s tissues and multiply without being detected.

Question 17

Diagnosis

Answer 17

!!! Laboratory diagnosis is not recommended when a patient already develops the characteristic bull’s eye rash.

The diagnosis is typically based upon physical findings :

• Bull’s eye rash in a patient who lives in an endemic area),
• Facial palsy or arthritis
• History of possible exposure to ticks.
• Other symptoms that are characteristic of Lyme disease

PCR for B. burgdorferi DNA
• in CSF or synovial fluid specimens.

•CSF PCR has low sensitivity. Thus, a negative PCR result does not exclude either neurologic Lyme disease or Lyme arthritis (after treatment)

Culture (useful for epidemiology)
B. burgdorferi has been isolated from skin biopsy specimens, blood, and CSF.
Two commonly used media are the modified Kelly-Pettenkofer and Barbour-Stoenner-Kelly II medium.

Question 18

Serological testing

Answer 18

NOT USEFUL DURING STAGE 1 OF INFECTION

Current recommendations include a TWO TIERED TEST

Detects antibodies with enzyme immunoassay (EIA) or immunofluorescence assay, followed by a western immunoblot assay

Two-tier testing is interpreted using established criteria where:
• POSITIVE IgM is sufficient only during the first month symptom onset
• POSITIVE IgG is sufficient in later months of illness

Question 19

Treatment

Answer 19

Doxycycline or Amoxicillin, or Cefuroxime or Ceftriaxone

• Doses and duration depends on stage of infection and age of patients and patient’s allergy profile

• Doxycycline is NOT RECOMMENDED in pregnant or breastfeeding women.

Question 20

Post exposure prophylaxis

Answer 20

A single dose of doxycycline can lower the risk of Lyme disease when:

1) The tick bite occurred in a state where Lyme disease incidence is high or in an area where >20% of ticks are infected with Borrelia burgdorferi.

2) The attached tick is ADULT or NYMPHAL blacklegged tick

3) The estimated time of attachment is ≥36 hours based on the degree of tick engorgement with blood or likely time of exposure to the tick

4) Prophylaxis can be started within 72 hours of tick removal.

5) The patient has no contraindication to doxycycline.

Question 21

Risk Factors

Answer 21

OUTSIDE ACTIVITIES — gardening, hunting, or hiking, in an area where Lyme disease occurs.

Walking in HIGH GRASSES in areas where Lyme- infected nymph ticks live.

Seasonal Risk — > SUMMER
but Infection is possible throughout the year

Question 22

Management of Lyme disease

Answer 22

1) Tick removal
2) Lyme disease prophylaxis
3) Symptom watch
4) Antibiotic therapy
5) Tick bite prevention counselling