ONE CAUSE OF ALZHEIMER'S DISEASE AND OTHER NEUROLOGICAL DISEASES - ALS, MOTOR NEURONE, MULTIPLE SCLEROSIS, PARKINSON'S

Dr Alan MacDonald has been posting some excellent and informative posts on Lymenet Europe of late


Many patients with Chronic lyme Disease will remember Dr MacDonald from scenes in Under our skin As you can see in the above video Borrelia has not just been found in patients with Alzheimer's but also patients with other Neurological Diseases - ALS, Motor Neurone, Multiple Sclerosis and Parkinson's.


According to Under Our Skin news clip Dr MacDonald became ill with an Alzheimer's like illness and had to retire. He says on the Lymenet forum that he is doing well providing he is on medication, clearly reading his posts there is not a lot wrong with his cognitive abilities and I was delighted to read the following.


'My research was interrupted by several years when I was ill. I have now returned to limited Alzheimer's disease Research as an Affiliated Researcher at the Harvard University McLean Brain Bank.'


Taken from the comment below:-


I am glad that you asked:
Dr Judith Miklossy has always worked independently commencing her studies on Neuroborreliosis and Alzheimer's Disease in 1993 with her initial publication in Neuroreport.
She is presentlythe President of a Foundation which is devoted to Alzheimer's research and connections
to neuroborreliosis. She operates her own website, which contains her credentials and her biblography.


I have always worrked independently commencing my Studies of Alzheimer's disease and connections
between Neuroborreliosis and Alzheimer's disease in 1986 with my publication in the Journal of the American Medical Association "Borrelia inthe Brains of patiens dying with Dementia", followed by the 1987
article "Concurrent Neocortical Borreliosis and Alzheimer's Disease" published in Human Pathology,
and then"Concurrent Neocortical borreliosis and Alzheimer's Disease - Description of a spirochetal cyst form", in 1988 in the Annalsof the New York Academy of Sciences.


Although Dr Miklossy and I have a close friendship, we beleive that maintaining independent
research Laboratories ( In New York and in Switzerland) is the ideal pathway to establish 
a bibliographic base of independently produced papers to support th concept of an infectious
pathway to future development of some ( but not all) cases of Alzheimer's Disease.


I have never been a reviewer nor referee for the peer review of any of Judith's papers.
Judith has never been a reviewer or referee for the peer review of any of my papers.


My Last published works were reviewed and accepted for presentation at the Alzheimer's Disease
and Related Disorders International conference in 2006 Madrid Spain. My research was interrupted by
several years when I was ill. I have now returned to limited Alzheimer's disease Research as an Affiliated
Researcher at the Harvard University McLean Brain Bank.


What commonalities have been gleaned by two independent investigators working on the Chronic
Neuroborreliosis /Alzheimer's disease connection:
1. Identification of Borrelia burgdorferi spirochetes in Autopsy Alzheimer's brain tissue by
Silver staining ( Miklossy+ MacDonald+)
2. Culture of Autopsy Alzheimer's Brain tissue to yield growth of Borrelia burgdorferi spirochetes
(Miklossy + MacDonald +)
3. Idenification of argyrophilic plaques in Autopsy General Paresis brain tissue 
which are exactly the same size, density and distribution as argyrophilic plaques in
Alzheimer's disease autopsy tissue ( Miklossy + MacDonald +)
4. Identification of bacterial peptidoglycan staining in Alzheimer's plaques
(Miklossy + MacDonald -not studied)
5. Indentification of Intracellular borrelia burgdorferi spirochetes within diseases neurons
inautopsy Alzheimer's Brain tissue ( Miklosssy + macDonald+)
6. Identification of the role of the granular form of borrelia burgdorferi as a contributor to
the classical finding of "granuolo-vacuolar" degeneration of Neurons in Alzheimer's disease
(Miklossy +( immunohistochemistry) MacDonald + (In Situ DNA hybridization))
7. The use of highly specific molecular beacons to pick up evidence of Borrelia burgdorferi DNA
sequences in Alzheimer's disease Plaques ( MacDoanld +)
8. The use of PCR performed on total Alzheimer's frozen brain tissue from the Harvard Brain Bank
to amplify borrelia specific DNA sequences from Orf BB0147 and to confirm the DNA structure
by DNA sequence analysis of PCR amplified products. (MacDonald +)


We seek to analyze Cerebrospinal fluid from Alzheimer's Disease patients for the following:
a. Borrelia burgdorferi Specific DNA
b. Whole proteome analysis using Dr Steven Schutzer's MASS spectroscopy analysis
protocol which was published in PlosONE. Dr Schutzer's program is able to
reliably distinguish CSF specimens from Chronic Lyme Disease patients
and to separate such patients from those with Chronic Fatique (notlyme),
Based on State of the art Proteome analysis via Mass Spectrographic Analysis.
Respectfully,
Alan B.MacDonald MD
PS: Ifyou have a moment,please read Dr Hideyo Noguchi and J E.Moore's paper in the Journal of Experimental Medicine from their lab at the Rockefeller Research Institute in New York City
(Link: http://jem.rupress.org/content/17/2/232.full.pdf+html ) and you will read about the "politics of Paresis" which prompted heated debates between Noguchi and Professor Max Nonne.


Lymenet Europe forum here


Dr Alan Macdonald was the first person to find Borrelia spirochetes in the brains of patients who had diesd from Alzheimer's I have posted before about him and his work here 





Dr MacDonald is the first person I have heard of diagnosed with an Alzheimer's type illness retired from work who has sufficiently recovered to return to work, albeit limited and for that work - to be research into Alzheimer's Disease this most important research area.

IDSA GUIDELINE AUTHOR ON FAILURE OF LYME DISEASE TESTS

Alan Barbour's patent tells the tale

This one statement is powerful, contradicting the stance that Barbour and the IDSA Lyme Disease Guideline supporters have made for years.

Alan Barbour in one paragraph summarizes strain variation, immune system evasion, persistent infection, failure of Lyme tests and the uniqueness of Borrelia amongst other pathogens.

"This mechanism of genetic switching appears to be different from any other antigenic variation mechanism described in bacteria or protozoa and has important implications in Lyme disease. By combining different regions of the silent vls cassettes, it is possible for many different vlsE serotypes to coexist the same patient. It may be impossible for the host to mount a protective response against any one of these clonal populations, because of the small number of each type. Even mounting a response against one serotype would not protect against rapidly evolving, new serotypes."

Read an excellent report on this patent by Camp Other Blog, helpful for those who are not able to understand the technicalities, at the link here

To access the full patent click here

Another extract:-

[0006] These organisms are closely related and cause similar manifestations with multiple stages: an expanding rash at the site of the tick bite (erythema migrans), fever, lymphadenopathy, fatigue, and malaise; effects of disseminated infection, including carditis, meningoradiculitis, and polyarthritis; and chronic manifestations including arthritis and neurologic disorders. Lyme disease is often difficult to diagnose because of shared manifestations with other disorders, and it can also be refractory to treatment during late stages of the disease."

My Chronic symptoms of Arthritis, Muscle Weakness, Fatigue and peripheral neuropathies turned out to be Lyme Disease and on long term antibiotics have all resolved, how many more patients with similar symptoms as a result of a tick bite could be helped on just simple antibiotics?

I posted earlier on Barbour here

PROBLEMS WITH TESTING

'Therefore using only ELISA as a screening test or for diagnosing Lyme borreliosis seems debatable.'

Well that is an understatement, but a step in the right direction, if only our Health Authorities would listen.


Arch Immunol Ther Exp (Warsz). 2011 Jan 22. [Epub ahead of print]

Serodiagnosis of Borreliosis: Indirect Immunofluorescence Assay, Enzyme-Linked Immunosorbent Assay and Immunoblotting.

Wojciechowska-Koszko I, Mączyńska I, Szych Z, Giedrys-Kalemba S.
Department of Microbiology and Immunology, Pomeranian Medical University, Powstańców Wielkopolskich 72, 70-111, Szczecin, Poland, IwonaKoszko@interia.pl.
Abstract
Lyme disease is an infectious, multi-system, tick-borne disease caused by genospecies of Borrelia burgdorferi bacteria sensu lato, characterized by remarkable heterogeneity. In this situation choosing an optimal antigen array for diagnostic tests seems problematic. The serological tests for borrelia routinely done in laboratories often produce ambiguous results, which makes a proper diagnosis rather complicated and thus delays the implementation of an appropriate treatment regimen. Thirty-seven outpatients and eight inpatients with suspected borreliosis diagnosis hospitalized at the Clinics of the Pomeranian Medical University (Szczecin, Poland), participated in the study. In order to detect the antibodies against Borrelia sensu lato three kinds of serological tests were used: indirect immunofluorescence assay (IIFA), enzyme-linked immunosorbent assay (ELISA), and immunoblot. The IIFA and immunoblot tests conducted on 45 patients (100%) produced positive results for both the IgM and IgG antibody types. In the case of ELISA, positive or borderline results were observed in only 24 patients (53.3%). The immunoblot test for IgM most frequently detected antibodies against the outer surface protein C (OspC) antigen (p25), and, in the case of IgG, against the recombinant variable surface antigen (VlsE). The IIFA screening test used for diagnosing Lyme borreliosis produced the highest percentage of positive results, which were then confirmed by immunoblot, but not by ELISA. Therefore using only ELISA as a screening test or for diagnosing Lyme borreliosis seems debatable.
PMID: 21258869 [PubMed - as supplied by publisher]


http://www.ncbi.nlm.nih.gov/pubmed/21258869

In fact there has been a considerable body of research over many years showing the problems over testing for Lyme Disease and not just the Elisa but also the Western Blot.

See Steven Phillips presentation to the IDSA review panel 25 studies on seronegativity and persistent infection. here

Interestingly Steven Phillips highlights on 18 occasions were the authors of the discredited IDSA Lyme Disease guidelines were involved in those studies but failed to include in their guidelines. When asked why by the Chairwoman at the end on the hearing Steere replies that he has changed his opinion. Yes OPINION is what is driving the IDSA guidelines for Lyme disease.

The recent Institute of Medicine workshop on the state of the science for Lyme Disease and other Tick borne diseases leaves the listener in no doubt that testing is just not reliable in any of these illnesses and that for some long courses of treatment are needed to deal with some chronic tick borne diseases.

The Video casts are still available to watch here

One of the most significant presentations was that of Ben Luft who recently Sequenced the Genome for Borrelia here he points out the difficulties over testing because of the various different strains of Borrelia but he also emphasises that it is a relapsing illness. You can read a phonetic translation of his presentation here

How many thousands of patients have had negative test results for Lyme Disease and been told by their doctors they don't have Lyme Disease, when in reality they do but the poor testing has missed the result.

Interestingly Doctors are not warned about the possible seronegative results even though here in the UK the makers of those test kits Trinity Biotech say-

'Negative results (either first or second-tier) should not be used to exclude Lyme disease.'

How many patients with Fibromyalgia, ME/CFS, Arthrits, Muscle weakness, Polymyalgia Rheumatica, Neurological illnesses like Multiple Sclerosis, Motor Neurons, Parkinson's and many more health problems are properly assessed for Lyme Disease or other tick borne diseases?

THE DOCTOR OF LAST RESORT

The Doctor of last resort - no truer words were written about those pioneering doctors who treat patients with Chronic Lyme Disease and other tick borne illnesses.

Through CALDA blog here I was able to read all three of these excellent articles in The Roanoke Times.

Lost in the Woods Navigating the Chronic Lyme Debate by Beth Macy

In search of hope, facts here
Salvos launched in Lyme debate here and
The Doctor of last resort here
plus the excellent video here

One day I look forward to seeing similar articles run in our UK Media, the dearth of good investigative journalism on chronic Lyme isn't for lack of trying or lack of patient experiences.

Until then how many patients with symptoms of arthritis, neurological problems, chronic fatigue, fibromyalgia and many more health problems will ever realise that like me their symptoms were related to that tiny tick that bit them years before.

More importantly how many doctors will consider as a differential diagnosis.

22000+ PEER REVIEWED ARTICLES ABOUT TICK-BORNE DISEASE

'more than 22,000 peer-reviewed articles about tick-borne diseases'

Sure looks soooo simple and soooo easy to cure doesn't it.

Are all those researchers so stupid that they need to do 22000 research articles on something so simple or maybe perhaps the science on this emerging disease/s is not yet written.

Why then do IDSA believe they have a cure all on just a few weeks antibiotics?

Once again an excellent article from
Raphael B. Stricker1 and Lorraine Johnson

The Lyme disease chronicles, continued Chronic Lyme disease: in defense of the patient enterprise

please click here to read

Those with illness such as arthritis, ME/CFS, Multiple Sclerosis, Fibromyalgia, Polymyalgia Rheumatica, Neurological illness following a tick bite will find the above article very enlightening.

OVER RELIANCE ON TEST RESULTS! WE NEED CLINICAL DIAGNOSIS

A recent Freedom of Information request to the Health Protection Agency on the number of samples tested for Lyme Disease resulted in the following:-

In 2009/10, there were 14,093 samples submitted and the number of positives that year was 867.

That is 6%.

The above if analysed closely is rather shocking.

The figures relate to samples tested in England and Wales because Scotland having a separate HPA keep separate figures. An earlier post about the figures is here

These above samples relate to the second of a two tier testing protocol.

So in general all these 14,093 samples from patients will have been sent by their doctors because they are suspected of having Lyme Disease.

In essence doctors consider Lyme Disease to be so rare in the UK because that is what they are taught at Med school.

The experience of many patients is that doctors are reluctant to consider Lyme Disease even when patients present with a Bulls Eye rash, the Hall Mark of Lyme Disease.

If in fact a doctor considers the possibility of Lyme Disease the initial test is the Elisa, which by many doctors experienced in treating Lyme Disease is considered next to worthless because of it's false negatives and false positives.

However if a patient gets a positive Elisa then eventually, if they are lucky and their sample does not get lost( which seems to happen not infrequently) their samples are forwarded to the Lyme reference unit at Southampton for the final test the Western blot, of which the above figures relate to.

The HPA constantly say that the Western Blot is the best available test but what they fail to say is that there is a considerable body of research which shows the problems over the Western blots which can in fact miss up to 50% of cases ( Steven Phillips presentation to IDSA review panel is a useful reference for this where he presents 25 studies on seronegativity and persistent infection here and here as well as other presentations from ILADS website here ).

Even the makers of the test kits Trinity Biotech say

"B. burgdorferi strains exhibit considerable antigenic variation. Patients often develop early antibodies to the flagellar antigen which can be cross reactive. Patients in the early stage of disease and a portion of patients with late manifestations may not have detectable antibodies. Early antimicrobial treatment, after appearance of EM may lead to diminished antibody concentrations. Serologic tests have been shown to have low sensitivity and specificity and, therefore, cannot be relied upon for establishing a diagnosis of Lyme disease (6,7,8). The Second National Conference on Serological Diagnosis of Lyme disease (1994) recommended the use of a two-tier test system for Lyme serology in which positive and equivocal samples from a sensitive first-tier test must be further tested by a more specific method such as Western blot (second tier). Positive results in the second tier test provide supportive evidence of exposure to B. burgdorferi which could support a clinical diagnosis of Lyme disease but should not be used as a criterion for diagnosis (9). "

This information is not being relaid back to our doctors.

So what of those 14093 less 867 = 13226 patients?

Are they still struggling with symptoms which have now become chronic?

Have they like me and many others been dismissed as having Fibromyalgia, ME/CFS, an imaginary all in your head diagnosis, or worse some neurological or Psychiatric disorder and treated on palliative drugs when perhaps antimicrobial therapy would have been more appropriate?

What of the many more patients who failed the initial Elisa and never got to have a Western blot?

What of the many patients who never suspected their illness could be the result of a tickbite or whose doctors never suspected Lyme Disease?

What of the many other tick borne illnesses that are rarely ever tested for here in the UK?

Will our UK 'expert' open her mind and start to redress the problems after listening to the presentations at the recent Institute of Medicine-

A Workshop on the Critical Needs and Gaps in Understanding Prevention, Amelioration, and Resolution of Lyme and Other Tick-borne Diseases: the Short-Term and Long-Term Outcomes here

her presentation and links to the conference can be found here

or will doctors remain ill informed and patients remain without adequate care?

Until better tests can be found patients need better clinical diagnosis.

335 EMERGING INFECTIOUS DISEASES SINCE 1940-60% ZOONOTIC

A Systems Approach in Understanding Tick-Borne Diseases: People, Animals, and the Ecosystem
Richard Ostfeld, Ph.D. Disease Ecologist
Cary Institute of Ecosystem Studies

'We live in an age of emerging infectious diseases. A recent study by Jones et al demonstrates that no fewer than 335 new infectious diseases of humans have emerged since 1940.

Of those Infectious Diseases about 60% of them are Zoonotic, meaning that the pathogen replicates within and is transmitted from non humans vertebrate species to humans.

Of these Zoonotic diseases about 72% are from wildlife with the remainder coming from domestic animals of various kinds.

Fully 30% of the newly emerging diseases are vector borne including most of the Tick borne diseases we will be talking about today and tomorrow and throughout the 20th Centuray and into the 21st Century the rate of emergence of new Infectious Diseases of humans has increased.'

The above were the opening remarks by Richard Ostfeld at A Workshop on the Critical Needs and Gaps in Understanding Prevention, Amelioration, and Resolution of Lyme and Other Tick-borne Diseases: the Short-Term and Long-Term

To view and listen to the whole presentation click here

*****************************************************************************
Much of the controversy over diagnosis and treatment of Lyme Disease comes back to the old problem of definition of Lyme Disease and it is interesting to see how the ILADS conferences (London and USA) moved away from that narrow definition of Lyme Disease, (Dr Bransfield's presentation of the Decade of the Microbe) as they are finding many of their patients are multiply infected with different organisms.

Dr Richard Horowitz interviewed for a TV program here refers to MCIDS - Multiple Chronic Infectious Diseases Syndrome found through CALDA website here

********************************************************************

I was lucky that my Chronic symptoms of Arthritis and muscle weakness which developed following tick bites and Bulls eye rashes responded so well to long term antibiotics although it took 4 years for my GP to realise the connection to the tick bites.

I never tested fully positive on any of the two tests given but listening to the Institute of Medicine Workshop it seems that many of the tick borne illnesses have problems over testing and many of the available tests are not given to patients like myself who are chronically ill.

Through Eurolyme I am in touch with patients who have Neurolgical symptoms, some diagnosed with Multiple Sclerosis, Parkinson's and Motor Neurons who are responding well to long term antibiotics.

So whilst science is still evolving over these complex emerging diseases it is best to keep an open mind and see what works well for us as individuals.

CHRONIC FATIGUE, ARTHRALGIAS, MYALGIAS, DYSESTHESIA, DEPRESSION

This recent research article is a start in the right direction looking at Chronic Lyme Disease, so far most research concentrates on the early acute form only.

The recent Institute of Medicine workshop highlighted that more studies need to be done in this later chronic state of illness with or without positive serology.

Abstract can be found on Pub med here

The diagnostic spectrum in patients with suspected chronic Lyme neuroborreliosis - the experience from one year of a university hospital's Lyme neuroborreliosis outpatients clinic.

Most common symptoms in all categories were arthralgia, myalgia, dysaesthesia, depressive mood and chronic fatigue. Conclusion:  Patients with persistent symptoms with elevated serum antibodies against BB but without signs of cerebrospinal fluid inflammation require further diagnostic examinations to exclude ongoing infection and to avoid co-infections and other treatable conditions (e.g. autoimmune diseases). One patient with acute LNB, who was treated with ceftriaxone for 3 weeks suffered from LNB with new headaches and persistent symptoms 6 months later. These data should encourage further studies with new experimental parameters.

details also found on Prohealth here

I found the above interesting because it highlights that Borrelia infection may not be ruled out by lack of Cerebrospinal fluid inflamation, something that many Neurologists tend to do with people with Neurological illness or Multiple Sclerosis.

Also the study talks about 122 patients in one year with suspected Chronic Lyme Neuroborreliosis that in itself is interesting because 114 of these people had tested positive for Lyme Disease and all had received antibiotic treatment.

To have such a number suffering with Arthralgias, myalgias, Dysesthesia, Depression and Chronic Fatigue after the standard treatment has to raise some serious questions beyond what this study was aiming at.

Because current guidelines adopted from the IDSA guidelines suggest that these remaining symptoms are rare, all in your head or the aches and pains of daily life it would seem they are not so rare after all.

One has to wonder with the poor state of reliable testing for Lyme Disease how many more people with the above symptoms could infact be suffering from an undiagnosed case of Lyme Disease and may benefit from antibiotic treatment following such as the ILADS guidelines .

UK ADVICE ON LYME DISEASE

PATIENT UK article on Lyme Disease link here

Lyme Disease

This disease was formally described following the investigation of a collection of patients with rashes and swollen joints occurring in Lyme, Connecticut in 1975, and acquired the name 'Lyme disease' (Lyme arthritis) in 1977.1 The various rashes, however, had been recognised many years previously, as had their association with neurological problems.

Lyme disease is caused by a tick-borne spirochaete, Borrelia burgdorferi2 and others. The infectious spirochetes are transmitted to humans through the bite of certain Ixodes spp. ticks.

The disease is caused by the infection and the body's immune response to infection. Different strains of Borrelia spp. cause different clinical manifestations of Lyme disease and this explains differences between the disease in Europe and the disease in the USA.

Although there is a rising incidence this is likely to be due to better detection and surveillance.3 It is still a rare disease.

Pathophysiology
The spirochete responsible is transmitted from host to host by Ixodes spp. or deer ticks. Understanding the life cycle of these organisms gives better understanding of the epidemiology, other clinical aspects and prevention of Lyme disease.
The Ixodes tick:

Is made up of different species, found in different areas of the world. For example:
Ixodes persulcatus and Ixodes ricinus (European ticks), Ixodes scapularis, Ixodes pacificus.
Emerges in a larval form in the summer and feeds just once on a host animal (often a mouse).
In the spring the larva becomes a nymph and feeds, again only once, from a similar animal host. Humans can be victims in the nymph stage (85% of tick bites in humans occur at this time in spring and early summer).
In the autumn the adult tick finally emerges to feed on deer, again just once. Humans can be hosts at this stage (15% of tick bites in humans are at this stage and occur in the autumn).
The spirochete responsible:

Is transmitted by the tick. The tick must have fed on a host significantly infected with spirochete to pass on the infection to man.

Once it infects, the tick has to go through a particular cycle of multiplication and dissemination to salivary glands within the tick before it can be passed on to the animal victim. Hence a tick must be attached for 2-3 days to a person before infection can be passed on.

Once the spirochete infects the host there may be one of several consequences:

The infection is cleared by host defences. This means the person will have had no clinical manifestations, be asymptomatic but seropositive.
The organism spreads by direct invasion. This is believed to be a feature in early disease. For example, erythema migrans is thought to result from the inflammatory response to direct invasion of the organism in the skin.
The organism excites an immune response in the host which causes a variety of clinical manifestations around the body. In such cases there is no evidence of direct bacterial invasion. Host factors (immunological and genetic) are associated with development of disease in this form. For example, HLA- DR4 and HLA- DR2 are associated with such disease. The manifestations of Lyme disease are also related to the particular Borrelia spp. strain involved. Particular strains are found in different countries. For example:
B. burgdorferi garnii, found in Europe, is associated with neurological disease.
B. burgdorferi afzelii from Europe is associated with acrodermatitis chronica atrophicans.
B. burgdorferi sensu stricto is found on the East Coast of the USA.
B. burgdorferi predominates in the USA4 with an associated pattern of musculoskeletal complications.
B. valaisiana has a relatively high prevalence in British ticks, and does not appear to be associated with manifestations of disseminated borreliosis, which may explain the low incidence of Lyme borreliosis in the UK.
Lyme disease is now becoming global and mixed infections are becoming recognised.

Epidemiology
In the UK, areas where infection is acquired include:
Exmoor
The New Forest
The South Downs
Parts of Wiltshire and Berkshire
Thetford Forest
The Lake District
The Yorkshire moors
The Scottish Highlands

About 20% of confirmed cases are reported to have been acquired abroad:3
The USA
France
Germany
Austria
Scandinavia
Eastern Europe

Laboratory-confirmed reports of Lyme borreliosis have risen steadily since reporting began in 1986. Several factors have contributed to the observed increase, including increased awareness of the disease, access to diagnostic facilities, more sensitive diagnostic methods, the enhanced surveillance scheme (introduced in 1996) and, since 2000, more complete reporting of cases.3 Other possible factors producing a real increase include changes in the geographical ranges of I. ricinus both in the UK and Europe (successive mild winters), more recreational travel to high endemic areas and the increasing popularity of activity holidays (walking, trekking and mountain biking).3

Over 3,000 reports of Lyme borreliosis have been received since 1986, almost 2,800 of which have been reported since the introduction of enhanced surveillance in 1997.3

Mean annual incidence rates for laboratory-confirmed cases have risen from 0.06 per 100,000 total population for the period 1986 to 1992, to 0.64 cases per 100,000 total population in 2002, to 1.1 cases per 100,000 total population in 2005.3 The highest rates in the USA are 69.9 cases per 100,000 persons in Connecticut.

Lyme disease occurs in temperate regions of North America, Europe, and Asia.

In some countries of Europe, the incidence of Lyme disease has been estimated to be over 100 per 100,000 people a year.

Lyme disease infection has occurred in northern forested regions of Russia, in China, and in Japan.

It has not been found in tropical areas or in the southern hemisphere.

Risk of infection is greater if the tick is attached for more than 24 hours.

There is a rise in reported cases in autumn, but the peak occurs in spring and summer.

It is not possible to separate false-positive antibody tests from asymptomatic infection. In endemic areas as many as 10% of the population may have positive serology without any history of symptoms.

Cases of Lyme disease are lowest in urban areas in the eastern states of the USA.
In the USA there are peaks in incidence in the 5-9 year age group and the 50-54 year age group.

Presentation
It should be remembered that some infected people will have no symptoms. In Europe as many as 64% of patients with Lyme disease do not remember being bitten by the often innocuous tick. The presentation depends on the stage of disease at the time of presentation. For example:

Early Lyme Disease (Stage 1 or localised disease):
The characteristic manifestation is erythema migrans:
A circular rash at the site of the infectious tick attachment that radiates from the bite, within 2-40 days.
It expands over a period of days to weeks in 80-90% of people with Lyme disease.
It may be the only manifestation of disease in one third of patients.
In most patients there is only one episode of erythema migrans but, in about 20%, there are recurrent episodes.
About 40% of patients have multiple lesions (not the result of multiple bites).
Pyrexia, arthritis, musculoskeletal symptoms and local lymphadenopathy may occur in about two thirds of patients but one third of patients will develop no further symptoms.

Disseminated Lyme disease (or stage 2 disease ). This disseminated stage is still considered to be early infection and occurs weeks to months later, with:
Flu-like illness, oligoarthralgia (60%). Typically, with myalgia, multiple erythema migrans and sometimes systemic upset. Malaise and fatigue are very marked (particularly in the USA where 80% of patients are affected - about double that recorded in Europe).
Intermittent inflammatory arthritis:
This is more common in the USA.
In Europe joint pains are less often associated with inflammation.
Untreated episodes last about a week.
Most patients have at least 2 or 3 episodes and, even untreated, these resolve over a a few years.
Central nervous system disorders (15%):
These include facial (and other cranial nerve) palsies. These are the most common neurological manifestations in Europe and the USA.
Meningism and meningitis may occur alone or with other neurological manifestations. It is usually at the mild end of the spectrum but can be more severe.
Mild encephalitis producing malaise and fatigue.
Peripheral mononeuritis
Lymphocytic meningoradiculitis (or Bannwarth's syndrome which is more common in Europe than the USA).
Cardiovascular problems (10%):
This usually presents with syncopal episodes associated with fever.
Manifestations include transient atrioventricular block, myocarditis, or chronic dilated cardiomyopathy.
Occasionally hepatitis, orchitis, uveitis and panophthalmitis.
Lymphocytomas:
These are bluish-red nodular lesions infiltrated with lymphocytes.
They typically appear on the earlobe or nipple.
They occur in Europe but not the USA.
Late manifestations of Lyme disease (or stage 3 disease):
Untreated or inadequately treated Lyme disease can cause late disseminated manifestations weeks to months after infection. These late manifestations typically include prolonged arthritis, polyneuropathy, encephalopathy and symptoms consistent with fibromyalgia.

Chronic lyme arthritis - a chronic erosive arthropathy typically involving the knees.
Acrodermatitis chronica atrophicans . This is a bluish discolouration (normally on the lower leg over extensor surfaces) signifying epidermal atrophy, usually with mild sensory neuropathy and myalgia. It is generally seen in Europe not the USA.

Chronic neurological syndromes . Generally these appear to be more common in Europe. These include chronic neuropathies (usually with paraesthesia and occasionally with pain but not with motor deficit). They may even present as chronic fatigue syndromes, spastic paraparesis or depression.

Differential diagnosis

Chronic Lyme disease can be indistinguishable from fibromyalgia and chronic fatigue syndrome and in the assessment of these illnesses B. burgdorferi infection should be considered.

Noninfectious:
Urticaria
Gout
Psoriatic arthritis
Thyroid disease
Degenerative arthritis
Metabolic disorders (vitamin B12 deficiency, diabetes)
Heavy metal toxicity
Vasculitis
Systemic lupus erythematosus
Psychiatric disorders
Localised infections:
Gonococcal arthritis
Meningitis

Infections which can mimic certain aspects of the typical multisystem illness seen in chronic Lyme disease include:
Viral infections, for example:
Parvovirus B19
West Nile virus infection
Bacterial infections, for example:
Relapsing fever
Syphilis
Leptospirosis
Mycoplasma
Infective endocarditis
Investigations5

When to test and when to refer?
It is useful to have clear guidance on when to test and when to refer.

In all cases of suspected Lyme disease seek further advice on when and how to investigate from one or more sources. The following sources of advice are suggested:5
A microbiologist
An infectious diseases consultant
The Lyme Borreliosis Unit

In patients with erythema migrans:
Testing is not usually necessary with a history of tick bite (or possible exposure).
This characteristic rash with a history of tick bite or exposure is enough to make a diagnosis.
In primary care, testing should be considered:
With erythema migrans but with no tick bite (or tick exposure) and no other features of Lyme disease.
When there is isolated unilateral facial palsy (as with Bell's palsy) and Lyme disease needs excluding because of a history of tick bite (or tick exposure).
In patients with other neurological symptoms, joint or cardiac symptoms:
Test in primary care only after specialist advice.
Usually such patients require hospital admission or urgent specialist assessment.

What test?
There is currently no definitive test. Lyme disease is a clinical diagnosis and tests should be used to support clinical judgement. The most useful tests are antibody detection tests. The only national guidelines for testing come from the US Centers for Disease Control and Prevention (CDC).6 They recommend a 2-step testing process:

Lyme disease symptoms (other than erythema migrans) - take a blood sample for antibodies to B. burgdorferi. But note:
If negative and the sample is within 2 weeks of symptoms, repeat the test after 2 weeks.5
The enzyme immunoassay has a high false positive rate (low specificity) and can be positive with other conditions (for example, glandular fever, syphilis, rheumatoid arthritis and some autoimmune conditions).5
If positive or borderline by antibody testing using enzyme immunoassay, then retest using immunoblot or Western blotting to confirm the positive result.
Antibody testing in patients with erythema migrans is unhelpful because the rash develops before the antibodies.

Serology:
Serology may help in cases of endemic exposure where there are clinical features suggestive of disseminated disease.3
Serology - enzyme-linked immunosorbent assay (ELISA) - remains negative for several weeks in the initial phase, but is usually positive in serum and CSF in the disseminated stage. False positives may occur with other spirochaete infections.
Polymerase chain reaction (PCR) may identify very small numbers of spirochaetes in samples, and may influence decisions about whether to treat asymptomatic individuals with positive serology. Usually, however, PCR techniques are not helpful because of the uncertain correlation between positive results and the presence of live organisms in biological fluids.

Management
Discuss management with microbiologist and/or hospital specialists. The early use of antibiotics can prevent persistent, recurrent, and refractory Lyme disease. Antibiotics shorten clinical course and progression. The duration of therapy should be guided by clinical response, rather than by an arbitrary treatment course but guidance is offered.5 Generally speaking, long courses of antibiotics may be required (2-4 weeks or longer).

Management at a glance:
Tick bite- remove tick and consider a single-dose oral antibiotic in high-risk cases (not recommended routinely in UK-acquired tick bites)3
Skin manifestations - (erythema migrans) oral regimen 14-21 days
Arthritis - oral regimen for 30 days, repeated IV if the oral course is unsuccessful
Neuroborreliosis - oral regimen 30 days for all except encephalitis and encephalopathy
Encephalitis/encephalopathy - IV regimen for 28 days
Fibromyalgia - no evidence of benefit from trials with oral or IV treatment



Jarisch-Herxheimer reaction may occur soon after treatment is initiated.
Oral drug therapies for erythema migrans alone can be started in primary care. These are appropriate when:
There is no evidence of neurological, cardiac, or joint involvement.
Patients are not pregnant or breast-feeding.
Doxycycline (and tetracycline), amoxicillin, azithromycin, cefuroxime, and clarithromycin have similar favourable results in studies. For many Lyme disease patients, there is no clear advantage of parenteral therapy.
The following antibiotic regimens have been suggested:5
Adults:
First choice is doxycycline (100 mg twice-daily for 14 days) or amoxicillin (500 mg three times daily for 14 days).7. Some recommend 3 weeks course.6
If both doxycycline and amoxicillin are contra-indicated, use cefuroxime (500 mg twice-daily for 14 days) unless there is a history of anaphylaxis with a penicillin.
When a bacterial cellulitis cannot be excluded use 14 days of either co-amoxiclav alone (500/125 mg three times daily) or cefuroxime axetil alone (500 mg twice-daily) or amoxicillin (500 mg three times daily) with flucloxacillin (500 mg four times daily for 7 to14 days).

Children:
12 years of age or older, give 14 days of either amoxicillin (50 mg/kg per day in three divided doses) or doxycycline (100 mg twice-daily).
Less than 12 years of age, give 14 days of amoxicillin (50 mg/kg per day in three divided doses).
If both doxycycline and amoxicillin are contra-indicated give 14 days of cefuroxime axetil (30 mg/kg/day in two divided doses) unless there is a history of anaphylaxis with a penicillin.
When erythema migrans is indistinguishable from bacterial cellulitis, give 14 days of either co-amoxiclav, cefuroxime axetil or amoxicillin with flucloxacillin in age-appropriate doses.
Intravenous antibiotics are used in severe cases (for example, encephalitis, meningitis, optic neuritis, joint effusions, and heart block); or where there is failure of oral medications - in patients with persistent, recurrent, or refractory Lyme disease. Ceftriaxone, cefotaxime, and penicillin are commonly used intravenous antibiotics. The precise regime will depend on the individual situation but high doses of antibiotics, combination of antibiotics, sequential regimes and prolonged duration (one month or longer) are advocated.
Surgical synovectomy should be reserved for knee pain failing antibiotic treatment. Intra-articular steroid injection may be useful for persistent knee pain but runs the risk of masking persistent infection.
Treatment of Lyme arthritis - cefotaxime, ceftriaxone, doxycycline and amoxicillin plus probenecid are all effective.
Treatment of late neurological Lyme disease - Cefotaxime has been shown to improve neuropathy in patients with late Lyme disease. Intravenous ceftriaxone has been shown to be effective in Lyme encephalopathy.8 Other studies have shown no benefit of antibiotic for late neurological Lyme disease.
A temporary pacemaker may be required where there are carditis and conduction defects.
Prophylactic treatment of tick bite
Prophylactic antibiotics after Ixodes scapularis tick bites in Lyme disease endemic areas in North America have been shown to reduce the risk of developing clinical Lyme disease.9 This article in the New England Journal of Medicine suggests that a single dose of 200 mg of doxycycline within 72 hours of tick removal can prevent Lyme disease developing. The risk in the UK is such that use of prophylactic antibiotics is not recommended. It might be considered in very exceptional circumstances - for example, when a person travelling from an endemic area discovers a tick which has been attached for more than 48 hours.

Prognosis
Lyme disease is rarely fatal.
However, untreated Lyme disease can result in arthritis (50% of untreated people), meningitis or neuropathies (15% of untreated people), carditis (5-10% of untreated people with erythema migrans) and, rarely, encephalopathy. Over 90% of facial palsies due to Lyme disease resolve spontaneously, and most cases of Lyme carditis resolve without sequelae.10
The natural disease course of European borreliosis is not well defined and the effect of antibiotic treatment is unclear.11 There are no UK studies on the outcome of treatment.
Long-term sequelae also include poor concentration and fatigue.10
Recovery is often incomplete if the disease presents late.

Prevention
Measures to reduce infection in areas associated with ticks:

Wear long hair under a hat.
Keep to the middle of paths and avoid unnecessary brushes with foliage where ticks loiter waiting for the next passing mammal.
Avoid wooded areas where possible. Mowed grass areas are less likely to have ticks in them.
Keep legs and arms covered (wear trousers inside socks).
Use insect repellent for humans.
Use tick collars for pets (they can get Lyme disease) and inspect for (and remove) any ticks.
Inspect skin regularly during the day in at-risk areas (especially the groin, axillae and hairline). Remember ticks are unlikely to transmit Lyme disease until attached for several days.

If bitten by a tick:

Remove the tick:
Clean the surrounding skin with disinfectant to prevent bacterial infection.
Gently remove by grasping close to mouth parts with forceps (tweezers).12 The safest, quickest and most reliable method of removal is by using forceps applied to the tick as close to the skin as possible and removed with steady traction (and not twisting).13
Fragments of the mouthparts may be left in the skin, but these are small and rarely cause any problems, especially if the skin is disinfected before and after the procedure.
Note: cigarettes and glowing match heads or suffocating the tick with various agents (for example, petroleum jelly or solvents) are not recommended.13
If tweezers are not available, to avoid delay, find a cotton thread and tie a single loop of cotton around the tick's mouthparts, as close to the skin as possible and pull gently upwards and outwards.
Routine prophylaxis after tick bites is not currently recommended in the UK.3 However, in endemic areas, prophylaxis should be considered if there is a high risk of infection.9

Note: if the tick-bite area does not heal promptly or becomes painful, antibiotics may be necessary to treat other bacteria. Check for a spreading red patch, especially one that appears between 3 and 30 days after removal of the tick. However, remember that the risk of developing Lyme borreliosis from a tick bite is small, even in heavily infested areas and most doctors prefer not to treat patients with antibiotics unless they develop symptoms.13




A vaccine was licensed for use in the USA but later removed from the market.



--------------------------------------------------------------------------------
Document references
Steere AC, Malawista SE, Snydman DR, et al; Lyme arthritis: an epidemic of oligoarticular arthritis in children and adults in three connecticut communities. Arthritis Rheum. 1977 Jan-Feb;20(1):7-17. [abstract]
Burgdorfer W, Barbour AG, Hayes SF, et al; Lyme disease-a tick-borne spirochetosis? Science. 1982 Jun 18;216(4552):1317-9. [abstract]
Lyme borreliosis/Lyme disease, Health Protection Agency
No authors listed; Lyme disease--United States, 2001-2002. MMWR Morb Mortal Wkly Rep. 2004 May 7;53(17):365-9. [abstract]
Lyme disease, Clinical Knowledge Summaries (January 2010)
Wormser GP, Dattwyler RJ, Shapiro ED, et al; The clinical assessment, treatment, and prevention of lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2006 Nov 1;43(9):1089-134. Epub 2006 Oct 2.; (reviewed 22/4/2010 by IDSA - no changes made to guidelines) [abstract]
British National Formulary; 59th Edition (March 2010) British Medical Association and Royal Pharmaceutical Society of Great Britain, London (link to current BNF)
Logigian EL, Kaplan RF, Steere AC; Successful treatment of Lyme encephalopathy with intravenous ceftriaxone. J Infect Dis. 1999 Aug;180(2):377-83. [abstract]
Nadelman RB, Nowakowski J, Fish D, et al; Prophylaxis with single-dose doxycycline for the prevention of Lyme disease after an Ixodes scapularis tick bite. N Engl J Med. 2001 Jul 12;345(2):79-84. [abstract]
Seltzer EG, Gerber MA, Cartter ML, et al; Long-term outcomes of persons with Lyme disease. JAMA. 2000 Feb 2;283(5):609-16. [abstract]
Dinser R, Jendro MC, Schnarr S, et al; Antibiotic treatment of Lyme borreliosis: what is the evidence? Ann Rheum Dis. 2005 Apr;64(4):519-23. [abstract]
Correct Method of Tick Removal, Borreliosis and Associated Diseases Awareness UK Website.
EUCALB - European Union Concerted Action on Lyme Borreliosis; A pan-European information site supported by an advisory board comprising an expert group of physicians and biologists from across Europe.
Acknowledgements EMIS is grateful to Dr Richard Draper for writing this article and to Dr Colin Tidy for earlier versions. The final copy has passed scrutiny by the independent Mentor GP reviewing team. ©EMIS 2010.
Document ID: 7004
Document Version: 8
Document Reference: bgp442
Last Updated: 30 Jun 2010
Planned Review: 29 Jun 2013

THE CONSEQUENCES OF IGNORANCE

The first video is just a handful of the many thousands of patients suffering with Lyme Disease throughout the World.

For every patient that knows they are suffering with Lyme Disease there will be many more who are unaware that their symptoms or Arthritis, Muscle weakness, peripheral Neuropathies, gastric problems, psychosis, heart block could be connected to an undiagnosed case of Lyme Disease.

They will have been diagnosed with a variety of illnesses Fibromyalgia, ME/CFS, Arthritis, Poly Myalgia Rheumatica, Parkinson's, Multiple Sclerosis, Motor Neuron's, Alzheimer's, Psychosis, Chronn's disease and the list is endless.

Even if their doctors test for Lyme Disease they will say that a negative test means you don't have Lyme when infact even the makers of those test kits say that a negative test can not rule out Lyme Disease.

The second Video made based on the experiences of a ME/CFS patient is in reality something that most of us with Lyme Disease experience to.

Infact about 30% of us actually get diagnosed with ME/CFS before we finally find a doctor that diagnosis Lyme Disease.

This video should be watched by the doctors and therapists who see us so that they can consider what foolish things they say to patients.

RESEARCH GAPS IN TICKBORNE DISEASES

Congressional Record
111th Congress (2009-2010)

ISSUES REGARDING LYME DISEASE -- (Extensions of Remarks - September 29, 2010)
http://thomas.loc.gov/cgi-bin/query/z?r111:E29SE0-0367:

[Page: E1872] GPO's PDF
---SPEECH OF
HON. CHRISTOPHER H. SMITH
OF NEW JERSEY
IN THE HOUSE OF REPRESENTATIVES
WEDNESDAY, SEPTEMBER 29, 2010

Mr. SMITH of New Jersey. Madam Speaker, as chair of the congressional Lyme Disease Caucus and a person who has been closely involved in Lyme disease issues for over twenty years, I want to bring to your attention extremely troubling issues regarding Lyme disease.

Lyme disease is the most common of all vector-borne infections in the U.S., with approximately 290,000 new cases in 2008. With the increase in Lyme cases, problems due to poor diagnostics and ineffective treatments for Lyme disease have become almost overwhelming--affecting larger numbers of people over longer periods of time.

Many patients are angry because progress in addressing Lyme disease has been impeded by entrenched bias and a lack of accountability in the science of tick borne diseases. It is critical that we identify biases and impediments that are constraining the science on Lyme and to open up the dialogue to honest and transparent debate. The scientists who have long been marginalized, the treating physicians who have felt intimidated and threatened, and most importantly the sick patients and their families need our help.

My main purpose here today is to introduce for inclusion in the Congressional Record the following statement ``The Patient Perspectives on the Research Gaps in Tick Borne Diseases,'' written by three of the Nation's largest Lyme disease advocacy organizations, who represent tens of thousands of patients. I believe that this statement provides important perspectives that need to be heard and taken to heart.

PATIENT PERSPECTIVES ON THE RESEARCH GAPS IN TICK BORNE DISEASES

(Submitted by Time for Lyme, the national Lyme Disease Association, and the California Lyme Disease Association on behalf of our patients across the United States)

In December 2009, Labor HHS 2010 appropriations language, signed into law by President Obama, encouraged the National Institutes of Health (NIH) to ``sponsor a scientific conference on Lyme and tick-borne diseases ..... the conference should represent the broad spectrum of scientific views ..... and should provide a forum for public participation and input from individuals with Lyme disease.'' The language also requires NIH to identify research gaps to understand the ``mechanisms of persistent infection.'' The passage of this language represents a significant opportunity to summarize and solidify the issues that prevent scientific progress for a disease recognized here for 35 years, if, and only if, this process occurs without bias. Progress can be accomplished if the stewards commit to the elimination of predisposition by key decision makers.

It is not clear why the NIH elected to subcontract this issue to the Institute of Medicine (IOM), given that the existing NIH conference structure contains the best process to address the appropriations language requirements. According to the NIH Consensus Development Program, which explains the two relevant types of conferences offered by NIH, ``when the available evidence is weak or contradictory, or when a common practice is not supported by high-quality evidence, the State-of-the-Science label is chosen.'' This conference format would appropriately address the research gaps that exist for Lyme and tick-borne diseases as it provides a ``snapshot in time'' of the state of knowledge on the conference rather than a policy statement of the NIH or the Federal Government.

In Lyme disease, there are two distinct disease paradigms, each providing science to support its claims. One paradigm views the disease as ``hard to catch and easy to cure'' and denies the existence of chronic Lyme disease--persistent infection with Borrelia burgdorferi, the spirochete that causes the disease. Under this paradigm, the state of the science for patients with chronic Lyme disease is closed. Any treatment is considered too risky because practitioners are unable to determine the cause or extent of patient symptoms, or they view the symptoms

[Page: E1873] GPO's PDFas insignificant and write off the patients' complaints as psychiatric in nature. This leaves seriously ill patients without any viable therapeutic avenues. It also shuts the door on future research necessary to get patients to a state of wellness.

The alternative paradigm says that the science is too unsettled to be definitive and there can be one or more causes of persistent symptoms after initial treatment in an individual who has been infected with the agent of Lyme disease. These causes include the possibility of persistent infection, or a post-infectious process, or a combination of both, with the Lyme bacterium itself driving the autoimmune process. This paradigm allows doctors the ability to exercise their clinical judgment and provide therapies that are helping their patients.

Patients with Lyme disease need a research agenda that reflects outcomes that matter to patients, namely effective diagnostic tools and effective treatments that restore them to health. The reason there are two disease paradigms in Lyme disease is because central pieces of the puzzle are missing or are inadequate. The first area of concern involves testing.

There are no reliable biomarkers of the disease.\1\ Current diagnostic tests commonly used do not detect the spirochete that causes Lyme disease, rather, they detect only whether the patient has developed antibodies to the pathogen. Antibody production, if it registers on the tests at all, takes weeks to appear, thus rendering the current tests ineffective in the earlier and more easily addressed stage. Additionally, the Lyme antibody has been shown to form a ``complex'' with the bacterium itself--and tests cannot detect ``complex'' antibodies. Once triggered, antibody reactions may remain long after an infection has been treated, also clouding the diagnostic and treatment picture.

The two-tier testing system endorsed by the Centers for Disease Control and Prevention (CDC) is very specific for Lyme disease (99%), so it gives few false positives. But the tests have a uniformly low sensitivity (56%)--missing 88 of every 200 patients with Lyme disease. By comparison, AIDS tests have a sensitivity of 99.5%--missing only one of every 200 infected patients.\2\ Sensitive AIDS tests were developed less than 10 years into the disease, while archaic Lyme tests remain unreliable 35 years later. There is a critical need for research exploring newer technologies such as polymerase chain reaction (PCR), which is used with many other diseases, and cutting-edge proteomics. Strain variations and co-infections with other organisms, often transmitted by the same tick bite, obscure the diagnostic picture further.

A vast number of strains of Borrelia burgdorferi have been identified. Variation in strain may cause differing symptoms or severity of symptoms as well as determine the appropriate antibiotics and duration of treatment needed to clear the infection.\3\ Different strains may also express different proteins. Preliminary research shows that proteins need to be examined to find the ones most often expressed, then using microarray technology, doctors may be able to diagnose patients using a chip which contains the proteins.

Research is needed concerning the role of mutation on persistence. Some research indicates that bacteria can exchange genetic material, probably contributing to its ability to invade different systems in the body--some may have a proclivity for the heart muscle, others for the brain, and some for muscles and joints. By exchanging genetic material, bacteria may be able to form a symbiotic relationship to avoid detection by the immune response or to further invade the body.

To date, every NIH-funded treatment research study has been designed using the inaccurate diagnostic test results as part of the entry criteria. The entry criterion in these studies excluded the vast majority of Lyme patients and created sample sizes too small (less than 220 patients to date) to detect clinically important treatment effects or generalize to the clinical population. Moreover, Lyme has not attracted industry funding for treatment approaches, which places the disease at a considerable research disadvantage. To detect clinically relevant treatment effects requires much larger treatment trials with sample populations that reflect those seen in clinical practice.\4\

One thing that past research has demonstrated is that patients with Lyme are a heterogeneous population. Hence, the course of illness and responsiveness to treatment may vary depending on the duration of onset of the disease to its diagnosis and treatment, the presence of co-infections, comorbid factors, other genetic characteristics of the patients, and the virulence of the strain(s) with which the patient is infected. Research sample populations must reflect those seen in clinical practice to yield clinically relevant results.

As advised by the Appropriations language, research on the pathophysiology of Lyme disease is necessary. Research projects need to be designed which determine the course of the disease from inception, and which utilize treatments that effectively interfere with the mechanisms that allow the infection to persist. Little to no government sponsored science has been dedicated to the effects on persistence of the different forms of the Lyme bacterium (cyst vs. flagellar), the role, if any, of biofilms, sequestration of the organism from the immune system, the exchange and mutation of genetic material of the spirochete, and the role that components of the bacterial genome may play in protecting it from eradication by the immune system or antibiotics. Understanding the pathology of the organism can greatly enhance targeted diagnostics and treatment modalities.

Patients also need studies that explore a range of treatment options. The ideal antibiotics, route of administration, and duration of treatment for any stage of Lyme disease are not established. No single antibiotic or combination of antibiotics appears to be capable of completely eradicating the infection in all patients, and treatment failures or relapses are reported with all current regimens, although they are less common with early aggressive treatment.\5\ Treatment failure rates suggest the need to re-examine the effectiveness of the currently recommended monotherapy as a treatment approach. Studies need to explore combination treatments and longer term treatment regimens, which have been critical to the successful treatment of AIDS and tuberculosis.

Patients need the type of outcomes research advocated by the IOM to examine how well treatments are working in actual clinical practice.\6\ While not all patients with chronic Lyme disease have returned to a state of wellness, many have, and we need to find out how and why. This information can then be applied to other patients and used to establish a research agenda for treatment that has a likelihood of success, rather than abandoning patients based on limited treatment trials.

The IOM process does not allow these research ideas to be heard in an unbiased and transparent fashion with balanced divergent viewpoints. While the NIH process precludes bias on the part of panel members, the IOM does not. Four of the six members of the IOM panel that have been selected belong to IDSA, a medical society that has a known bias against chronic Lyme disease diagnosis and treatment. Rather than providing curative treatments that restore health, the IDSA would provide costly and long term palliative treatments, presumably for life. While the NIH requires participation by major stakeholders (including patients and treating physicians), the IOM does not.

The summary of the IOM proceedings will reflect this pervasive lack of objectivity, undermining its integrity and credibility. Additionally, much IOM deliberation is done behind closed doors and an anonymous panel will be permitted to comment on the written record. Because of such flaws in the IOM proceedings, the three largest patient interest groups who were offered a brief opportunity to speak (TFL) at the IOM October 2010 meeting and an opportunity to provide a commissioned paper--CALDA, the LDA and TFL--pulled out of the conference in protest.

From a research perspective, strongly held paradigms can create a closed loop, and experiments may be designed, implemented and interpreted to support a particular viewpoint.\7\ The antidote to bias is to balance scientific perspectives and to ensure that all scientific viewpoints are being heard and explored. Given the extraordinary stream of federal funding granted to researchers who support the closed paradigm which was created and is supported by the Infectious Diseases Society of America (IDSA) and their vested interest in maintaining the status quo, it is not reasonable to expect this group of researchers to serve as neutral arbiters of scientific debates over competing scientific paradigms. For example, Lyme related panels dominated by IDSA have time and time again excluded opposing viewpoints from participating or controlled the review process to ensure outcomes that reinforce the IDSA paradigm. If past is prologue, it is obvious what the future holds for panels dominated by one group.

Worse, the small treatment trials that have been conducted have been given an undue amount of weight by IDSA researchers and in its guidelines and used to apply a degree of certainty on the science that far exceeds the limitations of the small sample sizes of the studies. Further, they claim that the state of the science is sufficient to determine with certainty that chronic Lyme disease does not exist, is not treatable with antibiotics, and that no further research on this topic is needed. Sample size affects the strength of the conclusions that may be drawn from them: ``Providing definitive answers in the face of low event rates and small-to-moderate treatment effects necessitates sample sizes in the thousands or tens of thousands. ..... Funding for such mega-trials is very limited, and is often restricted to industry sources.'' \8\

For that reason, the Connecticut Attorney General antitrust investigation into the development process of IDSA Lyme guidelines found exclusionary practices and suppression of divergent viewpoints on the part of IDSA panels that crafted IDSA 2000 and the 2006 Lyme disease guidelines. Although IDSA settled the investigation with the Attorney General by agreeing to review its guidelines with a panel without conflicts of interest, the control of the process was in the hands of IDSA, which again selected a panel consisting almost exclusively of IDSA members and excluding treating physicians who held divergent viewpoints.

It was patients who pressed for the language in the Appropriations bill that called for a review of the state of the science of Lyme disease. However, patients need that process to occur in a transparent manner, without bias, and with the participation of all stakeholders. Albert Einstein defined insanity as ``doing the same thing over and over again and expecting different results.''

[Page: E1874] GPO's PDFThis process is a perfect example of that insanity.
Patients want research which will restore their health. Their voice and the voice of the clinicians must be given the necessary weight to legitimize the research agenda and the research process. Truth in science can be achieved through open debate in an independent process free from bias and conflicts of interest. The scientific process fails when one side of a debate controls the arena and sets the rules to ensure that its viewpoint prevails.

Lorraine Johnson, JD, MBA, Chief Executive Officer, California Lyme Disease Association.

Patricia V. Smith, President, Lyme Disease Association, Inc.

Diane Blanchard/Deb Siciliano, Co-Presidents, Time for Lyme, Inc. ENDNOTES

\1\ Steiner I. Treating post Lyme disease: trying to solve one equation with too many unknowns. Neurology 2003; 60:1888-9.

\2\ Stricker RB, Johnson L. Lyme wars: let's tackle the testing. BMJ 2007; 335:1008.

\3\ Weintraub P. What we don't know about Lyme. Experience Life Magazine June 2009.

\4\ Guyatt GH, Mills EJ, Elbourne D. In the era of systematic reviews, does the size of an individual trial still matter. PLoS Med, 2008; 5:e4.

\5\ Hunfeld KP, Ruzic-Sabljic E, Norris DE, Kraiczy P, Strle F. In vitro susceptibility testing of Borrelia burgdorferi sensu lato isolates cultured from patients with erythema migrans before and after antimicrobial chemotherapy. Antimicrobial agents and chemotherapy 2005; 49:1294-301.

\6\ Institute of Medicine (Committee on Quality of Health Care in America). Crossing the Quality Chasm: A New Health System for the 21st Century. Washington, DC: National Academies Press, 2001.

\7\ Ernst E, Canter PH. Investigator bias and false positive findings in medical research. Trends Pharmacol. Sci. 24(5), 219-221 (2003).

\8\ Guyatt GH, Mills EJ, Elbourne D. In the era of systematic reviews, does the size of an individual trial still matter. PLoS Med, 2008; 5:e4.

***************************************************

For detailed information leading to the above Speech see CALDA blog at Lyme Policy Wonk

TIPPING POINT IN THE SCIENCE SURROUNDING LYME DISEASE?

Evolution and Distribution of the ospC Gene, a Transferable Serotype Determinant of Borrelia burgdorferi

Alan G. Barbour and Bridgit Travinsky

http://mbio.asm.org/content/1/4/e00153-10

The full article is available through the above link and something I felt was highly important was

'Nevertheless, we doubt that the observed antigenic diversity of OspC is merely epiphenomenal to functional differences between proteins. The range of pairwise sequence distances among family of surface proteins of the relapsing fever agent ospC alleles nearly matches that of the highly polymorphic Borrelia hermsii immunity (4). Possibly, both immune and niche selective forces are in play, but their relative contributions remain to be determined.'

I was alerted to this through the comments from

Microbe World

Lyme Disease Bacterium Collaborates with Accomplices to Evade Immune System

submitted by Merry Buckley on September 29, 2010

http://www.microbeworld.org/index.php?option=com_jlibrary&view=article&id=4903

Warning: the bacterium behind Lyme disease is collaborating with its accomplices to construct a gene that can defeat your immune defenses.

Although this work supports much that Ben Luft has been studying for some years and has been found by other researchers over the last 20 years, the significance as I see it is that Barbour an IDSA doctor has long since supported the IDSA Guideline Authors stance and this very clearly is a move towards what ILADS doctors have been saying for years.

Are we at last at that long awaited tipping point in the science surrounding this emerging disease?

I previously posted the Tom Grier lectures, links in my side bar an extract from lecture number 4 below shows that Pachner had already published on similar findings.

PACHNER MOUSE BRAIN MODEL

1) Normal uninfected mice are inoculated with Borrelia burgdorferi in the tail vein.

2) One month later, blood is isolated from the tail of the same mouse, and the bacteria are isolated for tests.

3) The bacteria are also isolated from the brain of the same mouse, and kept completely separate for testing.

4) The antibodies from the mouse’s blood recognize and attack the bacteria that were isolated from the blood of the mouse.

5) The same antibodies fail completely to recognize the bacteria that were isolated from the same mouse’s brain; it is as if these bacteria were completely invisible to the mouse’s immune system.

What has happened to the bacteria in the mouse brain?

Once the bacteria were isolated within the brain, it was then cut off from the peripheral immune system.

This allowed the bacteria to change with each new bacterial division, and without the mouse’s immune system recognizing the changes; it is just like a criminal getting a face-lift and wearing a disguise.

The immune system kept up with the bacteria trapped in the blood, but could not make antibodies to the Lyme bacteria trapped within the brain.

The antibodies that were being produced no longer recognized the bacteria because it was still looking for the original strain, and what were now in the mouse’s brain were several generations away from the strain that Dr. Andrew Pachner started with.

Basically in crude terms, the Lyme bacteria that became isolated within the brain, mutated.

The Lyme spirochete we started with that was originally injected into the tail, is no longer the same isolate that Dr. Andrew Pachner found in the brain of the same mouse.

You now begin to see how current Lyme tests that are created using a laboratory strain of bacteria; a strain not even found in nature, can hardly be expected to keep up with the over 200,000 possible variations that Borrelia are capable of producing.

These findings give reasons for:-

the problems with seronegativity,

the problems in finding effective vaccines

the reasons why the immune system and antibiotics combined have difficulty eradicating the infection especially the longer it is allowed to get established.

Public awareness and Doctor awareness is an immediate concern to prevent others un-necessarily being infected and allowed to progress into a chronic health problem for which there is no known definitive treatment cure.