Dr Beryl Beynon OBE, MBChB and
Dr Chris Newton PhD
Well-One Clinic, Beverley, East Yorkshire and
Centre for Immuno-Metabolism Microbiome
and
Bio-Energetic Research
Tick bite depositing microbiological ‘cargo’ through epidermis
into dermis- the immuno-competent layer of the skin
Lyme disease: the great imitator (confuse all
concerned in making clinical diagnosis)
• From:
From: Smith et al. (2014) Borrelia burgdorferi: cell biology and clinical manifestations in latent chronic Lyme.
Open Journal of Medical Microbiology. 4: 210-223
Hierarchy of influence on general health
Emotional stress
acute/chronic
Physical stress
Endogenous ‘infection’
gut microbiome
Ageing of
immune syste
Exogenous infection/
environmental factors
Dietary components: minerals/vitamins carbohydrate fats proteins/fibre
Metabolism
Endocrine System
(Pit./Adrenal/Thyroid)
IMMUNE SYSTEM
(genetics make-up e.g. HLA
markers/ etc)
mTORC1
Autophargy
Local inflammation
(FUTILE inflammation)
Systemic inflammation
© Newton CJ 2015
Typical scenario (1) for interaction with
NHS physician
•
Worst case scenario: present at GP with a range of symptoms, one may not
know that one has been bitten, so how does one know how to point GP in
right direction-long haul, much frustration and pain!
•
‘Partial’ solution- EDUCATION- have to make people aware (without wishing
to alarm) that Lyme disease could be responsible
•
Throughout the 1990s, living in a small village just North of Munich always
checked kids for ticks-it was what everyone did)
•
If tick still embedded (but don’t ignore other bites-but what does one do?),
what about chance of infection (number of ticks infected) and time tick
attached (time needed to transfer infection into skin)?
Prevalence of tick infestations in continental
Europe and in UK and transmission time
• Cook MJ. (2015) Lyme borreliosis: a review of data on transmission time
after tick attachment. International Journal of General Medicine. 8: 1-8
• We don’t have a great deal of data yet for UK but Michael has referenced
work from Switzerland, where the proportion of ticks carrying Borrelia
ranges from 9 to 47% depending on region.
• For the UK, I would make a guess (but I have no solid data) that the
incidence of infected ticks carrying Borrelia is considerably less than the
9% reported for some areas of Switzerland
• Transmission time for transfer of organisms after tick attachment from
studies using animal models <16h
Data from UK: Veterinary and Parsitology and Ecology Group Uni.
Bristol -2011 Study
• Smith et al. (2011) Prevalence, distribution and risk associated with tick
infestation of dogs in Great Britain. Medical and Veterinary Entomology
25: 377-384
Examination of 3,534
dogs at random over 9
months. Found 810 dogs
carrying at least 1 tick
Incidence of tick
attachment in June
0.096, so per 10 walks
in June, expect 1 tick
Per year therefore,
around 12 ticks
Same group (Veterinary and Parsitology and Ecology Group Uni.
Bristol) more recent and different study protocol
• Jennett AL et al. (2013) Tick infestation risk for dogs in a peri-urban park.
Parasites and Vectors 6: 358-367
• If a dog was walked once per week in this area of land then should expect
1 tick per year, but a daily walk would reveal on average 7 tick infestations
per year.
• Conclusion from this paper: In peri-urban green spaces, tick-biting risk for
dogs may be high and related to exposure frequency. While tick-biting is of
direct veterinary importance for dogs, dogs also represent useful sentinels
for human tick-exposure.
Calculations on tick-bites per typical summer
day in large peri-urban green space
• In a large woodland/park area with 100 people/dogs (equivalence?)
per day in June
• At rate of 10 ticks per year per dog/person (based on daily walks)
• Then…….. 10/365 x 100= 2.7 people get bitten per day
• This is just ticks, what about other vectors such as mosquito?
Other vectors and means of transmission of Borrelia
and associated microorganisms
• The bottom line is that the overall number of just tick bites throughout the
UK’s major parks and indeed back gardens is not insignificant. (We have
ticks in our garden in Hull evidenced by our dogs)
• More research needed on extent of tick infestation and the means of
vector transmission i.e. can other insect vectors transmit Borrelia and
other microorganisms (web literature -non peer review-suggests they can)
• Not mentioned so far and despite lack of peer review evidence (as far as I
am aware), Borrelia spirochetes may be sexually transmitted and may be
passed through placenta. If so, this would amplify the incidence of
infection quite considerably
But there are these data……..
Conclusion
The culture of viable B. burgdorferi
in genital secretions suggests that
Lyme disease could be transmitted
by intimate contact from person
to person.
Middelveen MJ Journal of Investigative
Medicine • Volume 62, Number 1, January 2014
So, returning to the GP scenario: typical scenario (2)
• Better case scenario? So one has convinced GP to do get blood taken and
do test, but the result is negative
• What are the alternatives to NHS testing for second opinion?
1) Live blood microscopy-Dark Field/Phase Contrast Microscopy (Peter Kemp/Alan
MacDonald/Michael Cook/ Laane and Mysterud
2) Labs in States and labs in Continental Europe. Western blot testing, Line blot
testing, LTT testing, PCR testing/FISH
• But results of labs outside UK are not generally accepted by NHS, so still
no antibiotics
Treatment with antibiotics despite
NHS-lab test negative result
• Is there a rational to provide antibiotics even in a (NHS) lab test negative
scenario given that the clinical picture screams Lyme (despite similarity of
symptoms for many other conditions). In my opinion and as an informed
scientist, I would say YES, particularly if person has provided evidence of
testing (with positive result) from other labs
• Lets not be too arrogant and except the fact that other European labs are
as good as NHS labs! Let us not hide behind national accreditation
systems-ours are better than yours!
• Without a truly definitive testing paradigm, one could argue that many
other conditions with similar symptoms to Lyme disease might involve an
infective agent and possibly a Lyme-related bacteria, parasite or
mycoplasma
Is there any testing that could be truly definitive?
• The most optimal testing scenario would be to use the very best antibody
testing strategy (which in my opinion would be to use a line blot
methodology), not to bother with an ELISA for pre-screening and combine
this with an LTT test and DNA methodology -both PCR and/or FISHmicroscopy
• Screening could therefore be done with Line blot serology test and well
validated very high sensitivity nested PCR as for example Lee et al. 2014
Returning to the GP scenario for last time:
typical scenario (3)
• Best-case scenario so far: GP is persuaded, test is made and is positiveget antibiotics but….. may not be for long enough or may be less effective
due to time elapsed from bite to treatment- the greater the interval the
greater the chance that the bugs will have escaped from skin to find sites
throughout the body-nervous system, muscle, joints, biofilms, etc
•
A biofilm is any group of microorganisms in which cells stick to each other on a surface.
These adherent cells are frequently embedded within a self-produced matrix of extracellular
polymeric substance (EPS)- Wiki definition
• New antibiotics-will come back to this
Dr Alan MacDonald’s work on Parkinson’s/ Alzheimer’s and
association with Borrelia and microscopic observations on
various forms of Borrelia with FISH methodology
• Results of Research Study on human peripheral blood with
Fluorescence In Situ DNA Hybridization(FISH method) and Borrelia
burgdorferi family Specific DNA Probes BBO 0147 and BBO 0740
Images and Experimental Methodology and DNA probes design,
manufacturer, quality control, and external multicenter Validation of
DNA probe unique specificity for binding to Borrelia burgdorferi
group (Sensu lato) DNA completed by Alan B. MacDonald MD. FCAP
All images Copyright All intellectual content Copyright year 2013 by
Alan B. MacDonald, MD
Dr Alan MacDonald’s Fluorescent in-situ hybridization
(FISH)
Dr Alan MacDonald’s FISH-work
Dr Alan MacDonald’s Fluorescent in-situ hybridization
(FISH)
Post GP/Consultant/Specialist
• If individuals with suspected Lyme disease can get treatment with
appropriate antibiotics (and this leaves a very large number of individuals
who cannot get treatment) what do we do if the antibiotics fail?
• Try others- what about new antibiotics?
• Pay attention to gut microbiome? Gut dysbiosis is one of the effects of
long-term antibiotic treatment and a change in gut bacteria or lack of
certain species in particular may play a role in chronic inflammation that
accompanies chronic Lyme symptoms and long-term antibiotics
Gut Microbiome
• Dysbiosis –microbial imbalance in body. Most common in gut and has
been associated with inflammatory bowel syndrome (that is very often
confused with gluten intolerance and Celiac disease when not checked
for), chronic fatigue syndrome, obesity, cancer etc
• Long term (non-specific) antibiotics may fail perhaps not (just) from an
inability to reduce the bacterial load of the spirochete, but because they
provoke ‘leaky gut syndrome’
• Antibiotics destroy beneficial bacteria and promote the growth of fungi
• Leaky gut- gaps between gut epithelial cells open allowing the passage of
components of gut contents (including bacteria and parts of) through gut
epithelial wall-can induce systemic inflammatory response (will occur
where any damage to gut epitelium is present-ulcers / Celiac disease)
Gut Microbiome and other pro-inflammatory factors
• What about microbiome of individuals who contract Lyme disease?
• Are some individuals more susceptible to Borrelia and associated
microorganisms due to underlying (pre-existing but clinically below
threshold for symptoms) inflammatory conditions?
• How does the stress axis impinge on the disease. Chronic long terms stress
would be expected to deregulate the inflammatory arm of the immune
system (Th1/Th17)?
• Stress systems and inflammation reduce the function of the protein to
which stress hormones bind (glucocorticoid receptor)
• What about MTHR (methylenetetrahydrofolate reductase) pathways and
methylation cycles?
New antibiotics?
• Use new antibiotics, but none have begun their development
in the last 25 years (statement out of date by several day!)
• Longitude Prize?
• But we need NEW ANTIBIOTICS, and in particular, those that
show specificity for Borrelia
New antibiotic identified: Teixobactin
January 2015, a collaboration of four
institutes in the US and Germany
together with two pharmaceutical
companies, reported that they had
isolated and characterized a new
antibiotic, killing "without detectable
resistance- Wiki entry
Development of new antibiotics directed to
Borrelia burgdorferi sensu lato-possible targets (1)
• Borrelia synthesize very few macromolecules and have to steal them from
us
• Cannot make purines
Development of new antibiotics directed to
Borrelia burgdorferi sensu lato-possible targets (2)
•
There are no genes for the synthesis of fatty acids in Borrelia!
•
The cell membrane of Borrelia is composed of phosphatidylglycerol (PG)
phosphatidyly choline (PC) sterol galactoside and monofalatosyl diacylglycerol
(MGalDAG)
There is higher proportion of polyunsaturated fatty acids (PUSFAs) in Borrelia
membrane than in the membranes of many other bacteria, possibly as they
scavenge PUSFAs- Most likely the reason for neuroborreliosis symptoms and MSlike symptoms, Motor Neurone Disease?
Fatty acid decoys?
Borrelia differ from other bacteria (and spirochetes) in that they only contain PG
and PC and unlike other bacteria that use a methylation pathway to synthesise PC,
Borrelia directly combine choline with (CDP)-diacylglycerol using the enzyme
phosphatidylcholine synthase to make PC
•
•
•
No tame pharmaceutical company-what to do when
antibiotics fail?
• Pulsed Magnetic Field Therapy (PMFT)
• Established work with Dr Beryl Beynon at Well One Clinic using a modified
Doug Coil System (often called a Rife machine, but strictly not what Royal
Rife was doing)
• Built system based on:
1) Variable frequency audio oscillator
2) High output audio amplifier (1000W RMS)
3) Large magnetic field coil
Audio frequencies used over range 200Hz to 5KHz but typically between 200 Hz and 1000Hz
How might PMFT work?
•
Gene coding for Heat Shock Protein 70 (Hsp70) has an Electromagnetic Radiation
Response Element (ERE)
•
Heat shock proteins act a molecular chaperones to protect other proteins and also
signal that a stressing agent/modality is present
•
Possibly activate the immune system by acting as PAMPs/DAMPs
•
But response at specific frequencies suggests strong ‘coupling’ and narrow ‘Q’
(frequency range over which effect observed-narrow bandwidth-like tuning of
AM/FM radio to specific station)
Does PMFT target “Bugs” or does it target immune
system?
• Jarisch- Herxheimer (Herx) reaction often apparent after PMFT
• Asymptomatic ‘condition’ seems to correspond to lack of PMFT- effect (no
Herx) at frequencies specific for Borrelia
• My view is that there are specific effects on the ‘Bugs’ as well as effect on
immune system via a Hsp-like mechanism (2012 paper below and
activation of TLR4). Hsps give immune system a ‘prod’.