infection, inflammation and mitochondrial dysfunction

Discussion in 'Lyme Disease Archives' started by tansy, Jul 24, 2006.

  1. tansy

    tansy New Member

    THE TERRIBLE TRIO

    (Infection, Inflammation and Mitochondrial
    dysfunction)

    Dr Andrew Wright

    This short document is just to briefly
    outline the role of the three processes of
    infection, inflammation and mitochondrial
    dysfunction in patients with CFS/ME.

    When one looks at the total number of symptoms
    of CFS/ME, as described by patients and best
    outlined by the Canadian Consensus Criteria for this illness,
    one finds that the symptoms of this illness
    most closely match the illness called Chronic
    Lyme disease. This is where a patient with
    clinical Lyme disease develops a multi-system
    illness even despite antibiotic therapies.

    One physician who has had a particular interest
    in this is Dr William Harvey, in Texas. He himself
    became ill with CFS/ME and after making a partial
    recovery, he started to work in a CFS/ME clinic
    in Texas. He found that if he repeatedly tested
    his patients, using Western Blot and PCR, he
    invariably found the majority of patients positive
    for Borrelia Burgdorferi sensu lato (that is the
    genus species and not necessarily the same bacteria
    as Borrelia Burgdorferi sensu stricto which is the
    Lyme agent). However, he realised that there were
    not many ticks or vectors in Texas that were known
    to carry this bacteria. He then spent the next two
    years researching everything that was ever written
    about Borrelia, both in medical and veterinary
    literature. He realised, following this very careful
    analysis of the literature that Borrelia has been
    around as a bacterial infection for many years.

    The DNA of Borrelia Burgdorferi can be found in museum
    specimens of ticks collected in the late 1800's. The
    first written description of Lyme disease appeared
    in the 1920's. Further reports occurred early in the
    1970's and 1980's before the causative agent for the
    illness, known as Lyme disease, was elucidated.
    Indeed, it was shown that Borrelia as an infection
    has been linked to not only Lyme disease but many
    other illnesses such as Motor Neurone disease,
    Multiple Sclerosis, Thyroid autoimmune disease and
    Rheumatoid Arthritis in both the past and recent
    literature.

    One of the stumbling blocks is that the standard
    two-tiered assay is not probably applicable in
    chronic illness. Even in acute Lyme disease, a
    two year study recently undertaken by John Hopkins
    University, has shown that using the combination
    of culture, ELISA testing, skin biopsy and PCR
    and blood PCR they could only detect somewhere in
    the region of 55% of patients with clinical Lyme
    disease. In chronic illness, studies have shown
    that the ELISA is variable negative. My own
    experience is that it turns out to be positive
    in around 2% of patients. I myself use a dark-field
    microscope looking for certain diagnostic
    morphological appearances of spirochetes that
    have been validated as being Borrelia Burgdorferi
    sensu lato by Dr Bella Bozsik, a Lyme disease
    clinician and a National Institute of Health
    scientist from Hungary. I have been able to
    identify spirochetes in the vast majority of
    my own patients. The bacteria are extremely
    clever genetically. It seems that the only
    logical explanation for our current confusion
    is one of semantics. Lyme disease is only one
    part of the much bigger human infection with
    Borrelia species, of which we know very little.
    The total human infection burden has been called
    'Epidemic Human Borreliosis'.

    The main difference is that ticks are very
    efficient at transmitting the bacteria, even
    after a single inoculation. Obviously, though
    as we know the majority of CFS/ME patients have
    not been bitten by ticks. There is evidence however
    that Borrelia may be present in populations at a much
    greater prevalence than we conventionally think of.
    A study in 1991 looking at seropositivity in
    asymptomatic adults in Ireland, performed by
    Dr Smith at the Department of Bacteriology in
    Glasgow, showed that using samples from the blood
    transfusion service in Ireland, prevalence figures
    of between 5 and 15% were found in random samples
    tested. This can be explained by the presence of
    ticks, but the figures were surprisingly high.
    An even more interesting study was performed by
    Burkot in 1997 where a large proportion of serum
    sample (57%) were positive by the Dressler
    criteria for IgG positivity, despite the fact
    that in Papua New Guinea all know arthropod and
    other vectors of the Lyme disease spirochete are
    absent. These studies show that the Borrelia
    bacteria are indeed probably present in larger
    numbers than we have anticipated. Because these
    Human Epidemic Borreliosis type patterns have
    not yet been fully researched, it is impossible
    to present a full picture of the possible
    patho-physiological consequences, but I do believe
    the evidence is accumulating as per Dr William
    Harvey's excellent work, that this bacteria may
    be an important aetiological agent in not only
    CFS/ME and also in many other illnesses.

    It seems likely that people pick up smaller
    amounts of infection through multiple means as
    they go through life before becoming unwell.
    For example studies have shown the bacteria to
    be present in mosquitoes and mites. Congenital
    and sexual spread has been documented in the
    medical and vetinary literature. Borrelia has
    been isolated from many body fluids, including
    blood, breast milk and sperm. In the first case,
    i.e. tick vectored illness a brisk antibody
    response is usual, but in the second cases,
    it seems that the infections are completely
    different in their patho-physiological features.
    It is suggested that many exist as 'L-forms'.
    his is a cell wall deficient form inside cells.
    Here they exist quietly and for the majority of
    people carrying the bacteria asymptomatically.
    Similar situations are found in asymptomatic
    carriage of e.g. Meningococcal bacteria and MRSA.
    This is the ideal situation for the bacteria.
    Only stupid microbes make themselves known! This
    results in a brisk immune response and even death
    eventually limiting the spread of the microbe
    according to Evolutional Biology principles.
    Even in acute Lyme disease the symptomatic to
    asymptomatic ratio is thought to be around 1:1.

    If the immune system does recognise the presence
    of the bacteria due to other factors such as
    further exposure, prolonged stress, trauma or
    co-infections, all altering immune responses,
    then bacteria have a secondary survival strategy.
    This is to drive inflammation. Dr Trevor Marshall
    has elucidated the mechanism of this inflammation
    recently. It involves the coupling of the human
    hormone, produced by the kidneys, Angiotensin II,
    to receptors on diseased macrophages and Angiotensin
    II `like' receptors on Borrelia and other bacterial
    membranes. This drives the conversion on the
    inactive seco-steroid 25 (OH)2D, stored in the
    liver, by the kidneys to be active 1, 25, (OH)D.
    This eventually leads to a TH I cytokine response
    and inflammation. During this the immune system
    is simply unable to deal with the intracellular i
    nfections and persistent illness results. Vitamin D
    is in fact not a vitamin in the accepted sense of
    the word, but a seco-steroid molecule, acts as a
    hormone or chemical messenger, having influence
    on over 60 genes concerned with hormone regulation,
    immunity and cell-death. All these are known to
    be affected in CFS/ME.

    Following on from this you then also see
    mitochondrial dysfunction in the vast majority
    of patients. Clinically this is manifested as a
    lack of energy in many systems of the body. This
    may be cognitive or brain functioning problems
    and / or physical problems such as myalgia,
    postural orthostatic tachycardia syndrome,
    irritable guts and the severe post exertional
    malaise that people exhibit. Fortunately, there
    is now a test to measure this.

    Dr. John McClaren-Howard at Biolab in London has
    developed an ADP/ATP assay, which will measure
    the efficiency of ADP/ATP conversion. It will
    look for blockages in the pathway leading to
    the release of sustainable unusable energy and
    also if there are any blockages in protein such
    as Translocator proteins, which have an impact
    on mitochondrial ATP production. Most importantly
    it does enable some therapeutic interventions
    to overcome this.

    As regards other evidence for the role of chronic
    infections causing illness, recent work from the
    Vascular Biology Unit at Dundee has shown that
    CFS/ME patients have a marked degree of
    inflammation and oxidative stress, compared to the
    other groups. This is using high sensitive
    C-reactive proteins, plasma Isoprostanes and
    other oxidised products as a measure of the
    inflammation and oxidative stress that occurs
    in chronic infection. This was compared to
    controls and other fatigued groups i.e.
    organophosphate poisoned persons and Gulf
    War Syndrome sufferers, showing the pathogenesis
    of these Fatigue disorders is almost certainly
    different.

    Following on from this work Professor John Gow
    at the University of Glasgow, has shown that the
    gene expression profile in carefully selected
    CFS/ME patients is identical to that seen in
    Lyme disease.

    Obviously this is a very important finding with
    regards to the suggestion that CFS/ME is similar
    but not the same to Chronic Lyme.

    To summarise-

    CFS/ME and Chronic Lyme have virtually the same
    symptoms.

    CFS/ME is a 'Pro-Inflammatory' and 'Pro-Oxidant
    disorder' typical of chronic infection.

    Transmission is by different routes and vectors,
    with a different response to this by both the
    bacteria and the immune system.

    High prevalence of the genospecies has been
    found in studies, not always related to tick
    exposure.

    The gene expression profile is identical.

    Other work that I have been involved in suggests
    that other bacteria's such as coagulese negative
    staphylococcus and gram negative endotoxin
    producing bacteria may be important. Other workers
    have noted high levels of other bacteria's such
    as Chlamydia pneumonia, Mycoplasma and Rickettsia.
    What characterises all of these bacteria is their
    intracellular habitat and their ability to produce
    inflammation. Dr. Marshall has shown that many do
    carry an Angiotensin II like receptor on their
    membranes, by the use of the molecular modelling
    techniques. Hopefully as scientific and medical
    interest in this novel and as yet under-researched
    field we will find many more answers to the many
    questions about chronic illness which, so far,
    defy explanation.

    A full and exhaustive list of references is available
    on request, including microscopic pictures and proof
    of the nature of them as Borrelia burgdorferi sensu
    lato from Dr Bozsik.

    Dr. Andrew Wright
    April 2006
    [This Message was Edited on 07/24/2006]
  2. ajp

    ajp New Member

    Hi,

    Thanks so much for posting it. It was very interesting and informative. I hope you can post it also on the fibro/CFS board.

    I know have chronic advanced Lyme disease and my LLMD thinks it started almost twenty years ago, when I has misdiagnosed with CFS. It is now harder to treat and according to my LLMD, my never completely be gone. I wish I had known about Lyme disease back then.

    Thanks again for posting this.

    Mindy
  3. tansy

    tansy New Member

    for many of us it's part of the soup, not the one cause of all our symptoms.

    My Dr has not promised a cure due to the length and severity of my illness, but he did say there was every chance of improving. It's been a difficult journey but the improvements made are visable.

    This has been posted on the CFS and FM board as well.

    TC, Tansy