LYME DISEASE Flashcards
history of lyme disease
from relative obscurity to become a prototypical emerging infectious disease
- epidemic of oligoarthritis in the mid 1970s, mainly in children, in rural communities near Lyme in connecticut
- an expanding annular skin lesion before the onset of arthritis
- previously associated with the bite of the sheep tick in northern europe
- a bacterial spirochaete was isolate fron: north american deer tick and from skin, blood and cerebrospinal fluid speciments obtained from patients with erytheme migraines
- a new species within the genus Borrelia, names Borrelia burgdoferi
lyme disease in the US
- most prevalent vector-borne human infection in the US and Europe
- 96% of cases from 14 states in US
what time of year is Lyme disease most common
june and July
is lyme disease an issue in england and Wales
- cases have been rising since reporting began in 1986 - now standing at 2.7 cases per 100,000
likely due to: - changes in the distribution of ticks
- improved awareness of the disease among the public and healthcare professionals
- increased testing
celular ultrastructure of B.burgdorferi
2 membranes
- has flagella within the space between the membranes
motile organism
key feature of Lyme disease
is an Arthropod vector
life cycle of tick and transmission of B.burgdorferi
- eggs hatch into spirochete free larvae
- larve affed on first host
- replete larva drops to ground and moults to nymph
- nymph feeds on second host
- replete nymph drops to ground and moults to adult
-two routes: incidental or dead end host / adult feeds on third host - if adult feeds on 3rd host, replete female drops to ground and lays egg
lyme disease infection
- deer tick obtaining blood meal from human
- partially engorged tick with bulls eye’ rash evident
- circular rash or erythema migraines
pathology
- transmitted to humans during feeding - may be attached for some time
acute stage
- systemic infection: headache, backache, chills, fatigue and rash
- treatable with antibiotics
untreated progresses over weeks/ months to chronic stage
- arthritis
- neurological symptoms: palsy, limb weakness, facial ticks
the course of B.burgdorferi infection and Lyme disease in humans
- bacteria multiply, alter gene expression, disseminate in tick
- bacteria are inoculated into the skin
- bacteria spread in the skin: erythema migrans lesion
- blood vessel invasion: continued multiplication, penetration through vasculature, dissemination, entry into tissue matrix and tissue colonisation
- tissue invasion: persistent infection of multiple tissue, including joints, CNS, PNS, skin: arthritis, encephalopathy, peripheral neuropathy, acrodermatitis
borrelia burgdorferi - genomics
- complex with a 1Mbp linear chromosome
- also large number of linear and circular plasmids totalling 600 kb
- very unusually linear replicons terminate with covalently closed hairpins and require a telomere resolvase for replication
- recent evidence that cells are polyploid with multiple copies of chromosome and plasmids along cell length
- reductive evolution due to parasitic lifestyle means borrelia has lost many metabolic activities
- no TCA cycle or oxidative phosphorylation: energy from fermentation of sugars
borrelia the organism - cell surface
- outer membrane lacks LPS
- outer membrane composed of lipids phosphatidylcholine, phosphatidylglycerol and cholesterols
- few proteins with membrane-spanning domains
- key property is presence of many lipoproteins
Proteins that are produced are very different on cell surface to those that are produced on the mammalian environment - Adapted to survive in both
anitgenic diversity of B.burgdorferi VlsE
- VlsE 35 kDa lipoprotein
- present on linear plasmid, located at telomere
- functions to sheild borrelia cell surface proteins from antibody
- mechanism to generate antigenic diversity evading host adaptive immune response
- variation observed in mice/ humans not in ticks
- mutants lacking VslE do not persist and are cleared from mice
