the true course of lyme disease in the uk
TRANSCRIPT
The true course of Lyme Disease in the UK
Matthew Dryden
Hampshire Hospitals Foundation Trust
& Rare and Imported Pathogens
Department, PHE
The controversy – Lyme disease means different things to different people
• Occurs focally and is transmitted by infected ticks
• Presents with objective clinical findings
• Requires a laboratory test to confirm diagnosis
• Responds to antibiotic treatment for 14-28 days
• Is insidious and ubiquitous
• Presents with non-specific symptoms alone
• Diagnosis based on clinical judgement
• Requires antibiotics for months or years
• ‘Lyme literate doctors’
Interest in uncertainties?
Clinicians Patients
1. Lyme disease
2. Chronic arthropod borne
neuropathy
Borrelia burgdorferi
J Clin Microbiol. 1998 March; 36(3): 768–776
Anatomy of a professional
OspC cell
attachment
protein
P 17/
Decorin
binding
protein
VlsE
protein
Flagellin strands
between membranes
rotate to propel
organism
Inner
membrane
Outer
membrane
P83 surface
protein
Borrelia
membrane
protein A
p66
porin
In the tick
Organism expresses OspA to bind
to tick tissue
As blood rushes in when tick feeds,
OspA is replaced by Osp C to suit life
in mammals and spirochaete swims
upwards reaching new host in 12-17
hours
Early infection
As organism starts to
proliferate IgM and then
IgG to OspC appear.
They are short-lived
Many people
develop p17
IgM/G
IgM/G to
BmpA appear
in 30% of
cases
IgM/G to
p83
occasionally
appear
If infection limits
early or is treated
antibodies may not
have time to develop
Organism
can be
found in
skin biopsy
VlsE
antibodies
appear a
little later
Rash may be absent
in up to 30% of cases
Disseminated infection
Neuroborreliosis
Pcr occasionally
positive
IgM in CSF
Arthritis
PCR Negative
Acrodermatitis
chronicum atrophans
Pcr may be positive
Antibody pattern
All antibodies may
appear
OspC antibodies
decline early
IgM slowly disappears
leaving variable
patterns of IgG
responses
Pattern may correlate
to species in some
cases
VlsE dominates
Mycocarditis
is rare
Making the VlsE protein
Conserved region
creates conserved
protein
A 6-mer peptide
C6 is part of this
region
Variable region
creates
variable parts
of protein
Linear
protein
LP28
Evading the immune system
VlsE constantly
changes so organism
keeps ahead of immune
system. At least 15
variants exist
Conserved regions
stay constant and C6
peptide stimulates
antibodies across all
variants
As VlsE changes many
people are anti-VlsE
negative when tested on a
single protein
Pattern of antibodies
to VlsE epitopes is
linked to persistence
of symptoms
Lyme service at RIPL Started 1 June 2012
Fully automated testing
Allows paperless data transfer
Based on C6 ELISA as screen
Immunetics® IgM/IgG combination
Virastripe printed blots
Read by densitometer
Lyme C6 assay
DS2 ELISAbot
Q-pulse automated
Levy-Jennings QC
Blots
Why use a printed blot? Defined bands
Machine readable
No background
Only the bands you want
Reporting the result
Borrelia IgG Lineblot (virastripe)
IgG to Borrelia P83 antigen Negative
IgG to Borrelia P58 antigen Negative
IgG to Borrelia P43 antigen Negative
IgG to Borrelia P39 antigen Negative IgG to Borrelia P30 antigen Negative
IgG to Borrelia OspC antigen POSITIVE
IgG to Borrelia p21 antigen Negative
IgG to Borrelia Osp17 antigen Negative
IgG to Borrelia DBPA antigen POSITIVE IgG to Borrelia P14 antigen Negative
IgG to Borrelia VlsE antigen POSITIVE
Borrelia IgG Lineblot interpretation POSITIVE
B.BURGDORFERI IgG/IgM (C6 EIA) POSITIVE
Borrelia IgM Lineblot (virastripe)
IgM to Borrelia P41 antigen POSITIVE
IgM to Borrelia P39 antigen Negative
IgM to Borrelia OspC antigen POSITIVE
IgM to Borrelia Osp17 antigen Negative IgM to Borrelia VlsE antigen Negative
Borrelia IgM Lineblot interpretation POSITIVE Composite report
for early acute
Lyme Disease
Lyme Borreliosis rate in Winchester –
total 508 Total number of cases of Lyme Disease between 1992 - 2012
Diagnosed at RHCH Winchester
0
5
10
15
20
25
30
35
40
45
50
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
2010
2011
2012
Year
No
. c
as
es
Lyme Borreliosis rate in Winchester
National rate: 1.7 http://www.hpa.org.uk/Topics/InfectiousDiseases/InfectionsAZ/LymeDisease/ last accessed June 2013
Lyme Disease Annual Rate per 100,000 population
0
2
4
6
8
10
12
14
16
18
20
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
2010
2011
2012
National rate: 1.7 http://www.hpa.org.uk/Topics/InfectiousDiseases/InfectionsAZ/LymeDisease/ last accessed June 2013
Rates in Europe
Rates of Lyme disease in some
European countries are much higher.
with an estimated
206 per 100 000 population in Slovenia
(based on laboratory reports)
135 per 100 000 population in Austria
(based on physician surveys).
Smith R, Takkinen J. Lyme borreliosis: Europe-wide coordinated surveillance and
action needed? Euro Surveill 2006; 11:pii=2977
Tick bite 508 patients - Hampshire
Presenting symptoms 508 patients
Neurological presentation
Lyme myelitis
Clinic and screen + Lyme
Encourage urgent referral
Monitor evolution of serology
Biopsy lesions
Culture
PCR
Monitor clinical progress on treatment
Collate data on Lyme – acute and
chronic
Proposed case definitions for Lyme Disease and Chronic Arthropod-borne Neuropathy (CAN)
Lyme Disease CAN
History of tick or insect bite
initiating illness
Ususally Usually
B. burgdorferi serology by
ELISA and immunoblot
Positive Negative
Routine haematology and
biochemistry investigations
Normal Normal
Inflammatory markers Rarely raised Normal
Early presentation <1month
after bite
Rash + occasional non-specific
symptoms
Does not usually present early
Later presentation Specific neurology + occasional
non-specific symptoms
Non-specific symptoms, Fatigue,
myalgia, cognitive impairment,
arthralgia, general paraesthesiae,
neurology not specific
Clinical examination Rash or specific neurological
deficit: CN palsy, radiculopathy,
peripheral neuropathy, meningo-
encephalitis, myelitis; (arthritis in
N.America)
Normal
Complete response to defined
short antibiotic course
Yes. Recurrence or relapse
extremely unusual
No. Recurrence or relapse
common.
Persistent symptoms • Tissue damage
• Cf. healing scars, poliomyelitis
• On-going immune reaction against self antigens • Cf. Goodpasture’s syndrome, Guillain-Barre syndrome, Rheumatoid arthritis
• Untreated disease
• Re-infection
• Another illness
Research is needed to define each of these
Chronic Lyme or CAN
What Lyme Looks Like: Photos Of Some Of My 2 Years Of Lyme Treatment This is what 2 years of Lyme treatment looks like for most with chronic lyme disease. This
photo is only some of my meds, injections and a small portion of IV stuff.
Other Chronic/Persisting Infections
• Viral
– HIV, VZV, HSV, EBV, CMV
• Bacterial
– Mycobacteria, Coxiella, Treponema pallidum
• Fungal
– Histoplasmosis, Coccidiomycosis
• Protozoal
– Malaria, Toxoplasma
BUT, they all leave a pathological signal
Infection clinic in September
2013
Clinical Diagnosis Number
Lyme 11
CAN 12
Pyoderma 2
Dermatophyte infection 1
Typhoid 1
Tick typhus 1
Q fever - Coxiella 1
Sarcocystis 1
Cutaneous larva migrans 1
TOTAL 32
Two patients’ stories - CAN
42 yr old woman ?bitten by tick 2008
Travel Cyprus
Unwell since 2010
Fatigue
Lack of concentration
Myalgia
Post exertional fatigue
Shooting limb pains
Borrelia tests negative
Convinced of Lyme diagnosis
Positive IgG serology for West Nile Virus
15 yr old boy Febrile illness with LN in
2011
Complete energy loss, lack of concentration, unable to return to school
No specific neurology
Diagnosed as Lyme at private clinic based on non-validated blood test
Extensive antibiotics and alternative treatments and nutritional supplements
Positive persistant OpsC IgM band on Borrelia blot
EBV PCR + in 2013
Infection panel for Lyme-like
disease
Borrelia burgdorferi
Bartonella spp.
Coxiella spp.
Brucella sp.
Babesia spp.
Anaplasma / Ehrlichia spp.
Rickettsia
TBE/WNV
EBV / CMV PCR
Lyme clinic
Diagnosis. The clinic offers the latest validated diagnostic
technology for Borrelia burgdorferi infection – ELISA, immunoblot and
polymerase chain reaction techniques.
Clinical assessment Consultation and investigations for
general health including laboratory tests for generalised inflammation,
autoimmune disease, other infections.
Research diagnostics – Partnership with the Rare & Imported
Pathogens Department, PHE Porton and Southampton University School of
Medicine . Investigate novel pathogens and unusual strains of known pathogens,
follow the immunological response to Borrelia burgdorferi, and the immunological
changes in chronic disease, collate clinical data.
Treatment and management. Appropriate treatment
and management consistent with clinical presentation and investigations.
LDA. Patient support and advocacy with Lyme Disease Action to promote the
understanding, diagnosis and management of tick-borne infection.
http://www.lymediseaseaction.org.uk/
