MICROIMM Lec 24: Lyme Disease

What is Lyme Borreliosis?

Lyme disease

Where and when was Lyme disease found?

1975 in Lyme, Connecticut

Lyme disease was first believed to be an epidemic of _____ mostly in children

Polyarthritis

A ____ was isolated from the ticks, and subsequently from skin, blood, and cerebral spinal fluid of patients

spirochete

What is the bacteria responsible for Lyme disease?

Borrelia burgdorferi

Who is the bacteria named after?

Willie Burgdorfer

Is B. burgdorferi G+ or G-? What shape?

G- spirochete

Describe the shape and structure of the bacteria

Thin (~0.5 microm) and long (>10 micro m), spiral shaped

Which hemisphere/region is Lyme Borrelia widely found throughout?

Found throughout temperate zones in the Northern Hemisphere

What is B. burgdorferi sensu lato?

Group of species that can collectively cause Lyme disease

What is the Ixodes species?

Hard-bodied tick species that are responsible for spreading B. burgdorferi

Lyme disease is a ____-borne disease

Vector

Define vector-borne disease

human illnesses caused by parasites, viruses and bacteria that are transmitted by vectors (intermediate)

What is the major reservoir species for B. burgdorferi?

White footed mice

B. burgdorferi is transmitted to different mammalian hosts through _____

ticks

After a blood meal, what does the fed larva transform into?

Unfed nymph --> fed nymph --> adults

Where does B. burgdorferi exclusively exist?

Only found in their vertebrate or arthropod hosts; never free floating in the environment

In North America, what two species is B. burgdorferi primarily transmitted by?

Ixodes scapularis, Ixodes pacifica

Which coastline is Ixodes scapularis (tick species) found?

East coast

Which coastline is Ixodes pacifica (tick species) found?

West coast

What are other names for the Ixodes tick?

Black legged or deer tick

How do ticks transmit onto hosts?

Wait for a host to pass by; latches on and crawls into crevices

Why can't deers get Lyme disease?

deer have specific immune system proteins that fight pathogens and induce inflammatory responses

Name the 3 major life stages of Ixodes tick

Larva --> nymph --> adult

At what stage does the tick acquire B. Burgdorferi?

Larva

What do ticks require between stages in order to grow?

Blood meals

Are ticks born infected/sterile?

Sterile; must acquire infection from host

Name some other animals that can carry B. burgdorferi

Mice, squirrels, birds

Which stage of the Ixodes life cycle do the majority of human infections come from?

Nymphs

What season is risk of human infection greatest?

Late spring and summer (nymph stage)

What structure is found on the feeding tube of the ticks?

Barbs; allows it to latch

When does the transmission of disease occur following a bite

After 24 hours

What unique property does the saliva from ticks possess?

anesthetic properties so that the animal or person can't feel that the tick has attached itself

What is a erythema migrans lesion?

Red expanding rash caused by bacteria spread in skin

Is B. burgdorferi localized to the bite location?

No, delocalized: can disseminate throughout blood vessels

What other tissues/areas can the bacteria infect in the body, travelling from the blood vessel?

Joints, CNS, PNS, skin; tissue invasion

Define hematogenous dissemination

originating from the blood

What is the relationship between B. burgdorferi and the tick?

Mutualism

Compounds in tick saliva are thought to inhibit function of _____ cells on multiple levels

dendritic cells

Name some DC functions that tick saliva helps to decrease

- Phagocytosis

- Maturation

- Inflammatory mediators

- Antigen presentation

What is periplasmic flagella?

Internal flagellum enclosed in the space between the cell wall and the cytoplasmic membrane

What is axial filaments?

Another name for periplasmic flagella

What is the function of axial filaments?

Motility: rotation of the axial filament causes the bacteria to move in a corkscrew like manner

How do the axial filaments produce a cork-screw shape?

They wrap around the bacterial cells

The axial filaments promote movement through _____ of host tissues and invasion of ______

extracellular amtrix, vasculature/CNS

Does B. burgdorferi contains LPS?

No

What compound do B. burgdorferi have that allow it to attach to cells?

Many surface expressed lipoproteins that can act as adhesins

Escape from the vasculature requires _____ to slow down B. burgdorferi

adhesion

What is the function of repetitive motility?

Required for the bacteria to invade endothelium

Does the B. burgdorferi in the blood vessel drag itself along/against blood flow direction?

Against

Does B. burgdorferi cause meningitis?

Yes

What is the shape of the B. burgdorferi bacterial chromosome?

Linear

What is the size (in Mb) of the chromosome?

0.91 Mb (very small)

What are the shapes of its plasmids?

Multiple plasmids - some linear, some circular

Do plasmids remain constant or variable from strain to strain?

Variable

What is the defining characteristic of the early (localized) stage?

Erythema migrans: painless bulls-eye rash

The bulls-eye rash occurs ___ weeks after tick bite

1-2 weeks

Where can the bulls-eye rash be found on the body?

groin, axilla (armpit), waist, back, legs, head and neck in children

What is the max diameter the rash can expand to?

> 12 inches

What are some other symptoms from the early (localized) stage?

Flu-like symptoms, including fever, chills, fatigue, body aches

What stage succeeds the early localized stage in untreated patients?

early disseminated stage

Describe the symptoms of the early disseminated stage

- Multiple rashes

- pain and swelling of large joints

- Heart palpitations

- Severe headaches and neck stiffness

Bell's palsy

What do the presence of multiple rashes on the body indicate about the disease progression?

Indicates dissemination of B. burgdorferi

What do heart palpitations indicate about the disease progression?

Bacteria has made its way into the heart: interferes with the electronic signals in the heart

What do the presence of headaches and neck stiffness indicate about the disease progression?

Meningitis

What is Bell's (facial) palsy?

Loss of muscle tone on one or both sides of the face; occurs when the bacteria affects the nerves

What method of traversal does B. burgdorferi use?

Paracellular traversal

What stage succeeds the early disseminated stage?

Late disseminated stage

At this stage, response to antibiotics takes longer/shorter

longer

What are the symptoms of late disseminated stage?

- Muscle pain

- Arthritis

- Severe pain and swelling in large joints

What are some neurological problems that may develop in 5% of patients?

- Shooting pains

- Numbness

- Tingling in hands and feet

- Memory

What is post-treatment Lyme disease syndrome?

Experience symptoms even following treatment with antibiotics

What % of individuals will experience post-treatment Lyme disease syndrome?

10-20%

What is the cause of post-treatment Lyme disease syndrome?

Cause is unknown, but hypothesized to be an autoimmune disorder

Name some lingering symptoms

- Fatigue

- Muscle and joint pain

- Cognitive defects

- Sleep disturbances

What ingredient in repellants is encouraged for tick removal?

DEET

What does the anti-B. burgdorferi antibody test detect?

Detect antibodies to a laboratory strain of B. burgdorferi

Where can you submit your tick for testing?

National Microbiology Laboratory

What is chronic Lyme disease?

Vague term that encompasses a broad range of persistent symptoms such as chronic fatigue, insomnia, pain, headaches, poor concentration, and depression. But no lab confirmation

Does long-term antimicrobial therapy help chronic lyme disease?

No (demonstrated by 4 clinical trials)

What is LYMErix?

Old vaccine for Lyme disease

What component of the B. burgdorferi is used in LYMErix?

Based on an outer membrane protein

Human trial (11,000 adults) showed LYMErix to be __% effective

75%

Claims and lawsuits that the vaccine caused _____

arthritis

LYMErix is pulled from the market and is now only approved for _____

dogs

Lyme disease is __ times more common than HIV/AIDS

6

Lyme disease may be complicated by infection with other tick-borne agents, such as...

- Babesia

- Anaplasma

- Ehrlichia

- Rickettsia

- Bartonella

What are the 3 methods in the reports that examined number of Lyme disease cases?

1. Examining lab test results for Lyme disease in 2008

2. Examining self-reported cases of Lyme disease in 2009, 2011, 2012

3. Analyzing private insurance claims relating to Lyme disease 2001-2010

Children aged ___ years had the highest rate of Lyme disease diagnosis

5-9 yrs

Between women and men, which is diagnosed with Lyme disease more often in the outpatient settting?

Women

What is the % sensitivity of commercial lab testing for Lyme disease

Sensitivity of only 46% in patients who have been infected for more than 4-6 weeks (poor results)

What is the % sensitivity of commercial lab testing for HIV/AIDS

>99.5%

According to the CDC/IDSA, what is the treatment for Lyme disease?

Monotherapy + questionably effective short courses of antibiotics (very restrictive treatment)

According to the CDC/IDSA, what is the treatment for HIV/AIDS?

Long-term combination antimicrobial therapy is the norm

What is a "gold standard" culture/testing?

a diagnostic test or benchmark that is considered the best available for testing or treating a disease or condition