Raport z konferencji ILADS pazdziernik 2008

[artur737]

Teraz nie mam czasu wiec tylko wklejam tekst.

The LDA and ILADS conferences 2008- Summary of scientific and medical
presentations with commentary.

Dr. David C Owen BSc MB BCh LLM

The LDA and ILADS conferences were held in the Cathedral Hill Hotel, San
Francisco 17-19 October 2008.

Following a welcome address by Pat Smith, president of the LDA, Steven
Barthold DVM PhD gave the keynote address concerning persistence of B
burgdorferi using a mouse model of infection. That persistence of infection
occurs is proven but the mechanism or mechanisms of persistence are not clear.
It was hypothesised that sequestration of non replicating forms of Borrelia in
collagen occurs and these dormant forms begin replication when conditions are
appropriate for example when the host’s antibody response has subsided. Much
collagen is found in the dermis, the target area of a feeding tick, and
Barthold has demonstrated that transmission of Borrelia to ticks can occur
even after antibiotic treatment of the host.

Mariio Phillipp PhD has been trying to shed light on how cognitive dysfunction
occurs in Lyme Borreliosis. Using monkeys he has demonstrated that in the
laboratory when monkey brains are exposed to Borrelia numerous cytokines are
released which result in neuronal apoptosis in the presence of microglia. The
relevance for chronic Lyme in humans is unclear but if damage is cytokine
mediated then interventions which reduce this may be expected to help.
Phillipp noted that Doxycycline reduces the immune mediator IL 6 in his
experiments and he suggested that this may be relevant to the therapeutic
benefit observed when this agent is used in chronic Lyme patients.

Steven Schutzer MD reported on a technique to identify the microbial
population in ticks. It is becoming clear that ticks harbour a complex array
of microorganisms just as many Lyme disease patients appear to be multiply
infected. The technique referred to as Ibis T5000 uses non specific DNA
primers enabling simultaneous identification of an array of microbes. It is
hoped that the technique will result in enhanced mapping of tick borne
pathogens and there is a possibility that new infective agents will be identified.

Patricia Conrad DVM PhD is a Parasitologist with an interest in Babesiosis.
Conrad reported that Babesia microti is endemic in the mid west USA and in
humans it may be present without causing symptoms or in some cases it may
cause a flu-like illness. Anemia and thrombocytopenia may be a clue to its
presence. The more recently described Babesia ducani (formerly WA1) is
phylogenetically quite distinct from B. Microti but it was stated that this
too may be carried asymptomatically. It was stated that there is currently no
evidence that B. ducani is a Lyme co-infection and Conrad questioned the
validity of some tests used to infer Babesiosis in humans. Conrad suggested
that some cases of Babesia may be falsely reported as Malaria but careful
examination of blood films may lead to the detection of “Maltese Cross” forms
of erythrocytic inclusions typical of Babesia infection. There are few reports
of Babesiosis in Europe and most of these are due to B divergens which
typically appears to cause a fulminant illness. It is clear further work is
needed worldwide to enhance our understanding of the pathology and ecology of
this elusive protozoan.

[artur737]

Diego Cadavid MD is another worker who has been attempting to shed light on
neuroborreliosis. He reported on the results of experiments using Borrelia
turicatae, the relapsing fever spirochete, in mice. Mice deficient in IL 10 and
antibody production were rapidly killed by the spirochtete unlike wild mice
which were relatively unaffected. Mice only deficient in IL 10 production had
higher cerebro-vascular vascular complications despite a low spirochete load and
this lead Cadavid to conclude that IL10 plays a critical role in protecting the
brain and other organs from vascular complications during borrelial infection.
Comment: Lyme disease has been associated many different neurological events
central and peripheral, reversible and irreversible. There is no
“neuroborreliosis syndrome” and the causes of neurologic disturbance in Lyme
disease in humans appear to be multi-factorial and complex.

Brian Fallon MD gave an overview of the clinical profile of chronic Lyme disease
with an emphasis on biomarkers. He noted that C6 Elisa is one of the best
markers of Borreliosis and has a specificity of close to 100%. As with other
tests sensitivity is lacking and the search for a reliable bio-marker continues.
Fallon’s studies have shown that clinical features (symptoms) are the best
predictors of response to treatment in Lyme disease. Fallon suggested that
chronic Lyme disease should be defined in a way which is aetiologically neutral.
Comment: Fallon wishes to define chronic Lyme disease to incorporate both “Post
Lyme syndrome” and persistent infection. The problem with this approach is that
there are many patients who have never received treatment for Lyme disease
despite clinical features of the condition and this category of patient would be
left with no diagnostic label. This author suggests that chronic Lyme disease
should imply persistent infection even though this fact may remain unproven in
an individual case. Such a label is not inconsistent with a concomitant
pathological process which is independent of infection.

Christopher Contag PhD described a technique of Bio-Luminescence Imaging which
enables localisation of bacteria in the living host. So far the technique has
been used with Listeria in mice and the results have contradicted existing dogma
about the condition such as the belief that the organisms are obligate
intra-cellular parasites. One problem if the technique is used for Borrelia may
be the need for a threshold of 100-1000 organisms for detection but if
sensitivity can be improved the technique appears to have potential to increase
our understanding of the pathogenesis of Borreliosis.

George Chaconas PhD has also been imaging bacterial infection in the living
host. Chaconas pointed out the advantages of studies involving real time
parasite-host interactions over a reductionist scientific approach which will
inevitably lead to caveats. Chaconas has produced remarkable real time 2D and 3D
videos of Borrelia in a laboratory host which include actual penetration of
blood vessels by the organism. We were told that the images are available for
viewing on the World Wide Web.

Armin Alaedinin PhD spoke about Immunologic abnormalities in post Lyme syndrome.
Numerous immunologic changes are known to occur following Borrelia and other
infections and auto-immunity is frequently invoked to explain some symptoms of
Lyme disease when infection is no longer thought to be present. The example of
Guillain Barre syndrome, which has been associated with prior Campylobacter
jejuni infection, was cited as a specific example of a neurologic auto-immune
pathologic process. Borrelia being a complex microbe has the capacity to
stimulate the production of many different antibodies and Alaedinin’s work has
demonstrated that Post Lyme Syndrome patients have increased IL10 levels when
compared to Lyme patients who have symptomatically recovered. The increase was
comparable to those found in some other auto-immune disorders such as SLE. The
hope is that a better understanding of the disturbed immunologic reactions will
lead to targeted immune modulating therapies in the future. In response to a
very good question from the audience Alaedini agreed that it was possible that
raised the raised IL10 levels could be masking symptoms in his control group of
patients and these could in fact have latent infection.

[artur737]

John Keilp PhD has worked closely with Brian Fallon at Columbia University.
Keilp has been addressing the difficult question of whether depression in Lyme
patients is secondary to the illness or independent of it. By comparing two
groups of depressed patients one with a Lyme diagnosis and one without Keilp
concluded that Lyme patients with mild depression have greater impairment of
memory and verbal fluency than is the case in depressed patients who do not have
Lyme disease.

Fabio Tavora MD is a pathologist who presented a case of fatal Lyme carditis.
Evidence for Lyme in the case included EM type rash, positive blots and positive
cardiac PCR. In the case in question it appears an opportunity to treat Lyme
disease at an early stage was missed but whether this would have affected the
outcome is, of course, unknown.
Comment: The case raises the question of how often Lyme might be an underlying
infection in cases of myocarditis which are commonly attributed to viral
infections or hypersensitivity reactions.

Suzanne Vernon PhD gave a talk on Chronic Fatigue Syndrome (CFS) which she has
studied extensively. It was stated that there are many parallels between CFS and
Lyme including the lack of a bio-marker. Vernon noted that CFS is a diverse
group of conditions. She has developed a model of the condition in which
disturbance of the HPA axis is central.
Comment: CFS affects around 4 million Americans and the severity of the illness
is such that many are incapable of work. How many CFS patients have symptoms
attributable to tick borne illness is not known. Even if the proportion is small
the Public Health implications would be significant.

Benjamin J Luft PhD gave the final LDA talk. He spoke about studies which have
investigated gene expression in B. Burgdorferi. He told the audience that under
laboratory conditions around half of the potential 1400 Borrelia proteins are
expressed. Conditions such as pH and temperature can be varied and the effects
on gene expression can be studied.
Comment: It may be rewarding to study the effects on gene expression in Borrelia
under hypoxic conditions since Borrelia appears to favour areas of the host
which are relatively low in oxygen saturation.

Willy Burdorfer PhD gave the first ILADS talk. He enthralled the audience by
relating the story of his discovery of the Lyme disease spirochete. Although
many scientific discoveries have an element of fortuity it was clear that
Burgdorfer’s discovery was the result of many years of dedication and hard work
in the study of the biology of ticks. In early work Burgdorfer had focussed on
Relapsing fever the infectious agent of which could be readily identified in the
arthropod’s haemolymph. Much later in his career Burgdorfer found a Nematode
worm in one of the American ticks he was studying. This was unusual and led him
to investigate specific tissues of the tick. In the mid gut he found spirochetes
and, as the saying goes, the rest is history.

Stephen Phillips MD considered in detail available published evidence pertaining
to chronic Lyme disease. He presented numerous citations which establish
sero-negative Lyme disease and persistence of Borrelia infection as facts.

Robert C Bransfield MD is a psychiatrist who specialises in Lyme disease.
Patients with Lyme disease are invariably polysymptomatic and complaints such as
sleep disturbance and neuropathic pain may be severe enough to warrant
symptomatic treatment. Bransfield noted that sleep disturbances occur in many
chronic inflammatory disorders and he suggested a number of therapeutic
approaches which may help the distressing symptoms of a patient with Lyme disease.

Judith G Llevanthal PhD has been analysing data from physicians who have been
treating Lyme disease. In common with findings in adults it was reported that in
children neurocognitive symptoms were among those most commonly reported by
patients with Lyme disease.

Deborah A Metzger PhD MD specialises in Chronic Pelvic Pain (CPP) which is an
intractable and incapacitating symptom for some women. CPP is known to be
associated with various inflammatory conditions and infections and Metzger
considers that Lyme disease is a very important association. Her experience in
treating this difficult group of patients with various types of therapy was
discussed.

[artur737]

Richard Horowitz MD gave a talk on his holistic approach to patients with Lyme
disease. Horowitz emphasised the need to consider many other factors in Lyme
patients in addition to infection. These include consideration of the need for
heavy metal detoxification and correction of minor endocrine disturbances. In
addition Horowitz reminded us that psychological factors may be an impediment to
improvement in some cases. Horowitz noted that the symptoms of chronic Lyme
disease are similar to those reported in other conditions and there was a need
for continuous vigilance to ensure coexisting conditions are not missed.
Comment: There is clearly a need for studies to address the efficacy of many of
the therapeutic interventions in Lyme disease. One problem in doing this is
patient selection since Lyme disease patients are a diverse group and in many
cases the diagnosis of Lyme disease cannot be made with certainty. In the
absence of such data patients are the arbiters. Judged by the numbers of
patients Horowitz has treated his approach is a successful one.

Ann F Corson MD gave a talk on her experience in using German Biological
medicine in the treatment of tick borne disease. These treatments are often
combined by Corson with allopathic antibiotics to treat her Lyme disease
patients. The methods are strongly linked to the traditional Chinese medicine
theory Shan Han Lun.
Comment: It is clear that for many patients antibiotics are not a complete
answer to their symptoms and alternative approaches should be welcomed. Medicine
is not science and physicians cannot wait for all treatments to be thoroughly
proven before offering them to patients.

Garth L Nicolson PhD gave a talk on the relationship between neurodegenerative
disorders and tick borne pathogens. Nicolson has intensively studied veterans of
the Gulf War many of whom developed medical problems commonly known as “Gulf War
Syndrome”. Veterans additionally had a much higher than average incidence of
ALS. Nicolson considers that tick borne pathogens (especially Mycoplasma and
Borrelia) were an important cause of the disease burden in the veterans.
Additional factors such as multiple vaccination and toxic exposure were also
likely to have played an important role due to immunosuppression. Nicolson has
noted that children of Gulf War Veterans have a higher than average incidence of
Autism Spectrum disorders and it was suggested that this may be due to
Mycoplasma transmission.
Comment: Lyme disease patients often report Lyme like illness in family members.
While common exposure to ticks is one possible explanation an alternative
explanation of non tick associated transmission of co-infections is an
interesting hypothesis.

Daniel J Cameron MD (current ILADS President) spoke about strategies to prevent
chronic Lyme disease. He noted that the number of cases of Lyme disease reported
to the CDC continues to rise. Furthermore the CDC acknowledges that reported
cases may represent less than 10% of the true incidence. Additionally other tick
borne illnesses are not considered in the figures. Cameron believes that it is
only through consideration of neglected facts about Lyme disease that public
bodies such as the CDC could develop more effective prevention strategies.

Dr. David C Owen

Cardiff, Wales, UK October 2008-10-20

[artur737]

Przelomu nie bylo jak widac. Mowiono troche o zespole poboreliozowym.
Tytulem wyjasnienia - bylo tak, poniewaz byl to pierwszy otwarty zjazd w ktorym
uczestniczyli takze lekarze IDSA. Aby nie przezyli szoku starano sie zachowac
rownowage miedzy pogladami IDSA/ILADS.

W zjezdzie uczestniczyla chyba rekordowa liczba uczestnikow bo okolo 300.
Z tego prawie wszyscy lekarze + pojedyncze sztuki cywilow, pielegniarek i
naukowcow.

[stachenka]

> Aby nie przezyli szoku starano sie zachowac
> rownowage miedzy pogladami IDSA/ILADS.

Naprawdę taki był powód?

[artur737]

Naprawde!

[artur737]

Tak strategia, nie wiem na ile okaze sie dobra, ale chodzilo o to by zwabic
pojedynczych idsowcow i ich przekabacic. Zjazd sie zaczal o dylemacie, ze niby
nie wiadomo czy infekcja czy stan po boreliozie. To byla koncepcja Dr Fallona.
W miare trwania zjazdu coraz bardziej odchodzono od koncepcji stanu po
boreliozie w kierunku czynnej boreliozy by blisko konca dac najbardziej
konserwatywnych ILADSowcow na wokande. Jak ktorys z idsowcow nie wytrzymywal to
mogl wczesniej wyjsc.


Osobiscie nie mam do tej strategii glebokiego przekonania, ale pozyjemy, zobaczymy.
Ten zjazd byl rodzajem okraglego stolu (tak jak kiedys Jaruzelski z
Solidarnoscia) i moga sie zaczac od tego jakies zmiany.

[stachenka]

A więc to jednak nie z troski o słabe serduszka ułomków z IDSA.

[franiolek1]

Wlasnie bardzo dobrze robia, wedlug mnie.
Walka otwarta na noze od lat niewiele osiagneli.
Wedlug mnie tylko lisia metoda moze cos zdzialac.

Zaczynam tlumaczyc

[artur737]

Laczona LDA/ILADS konferencja 2008 - Podsumowanie naukowej i medycznej
prezentacji z komentarzem.
Dr. David C Owen BSc MB BCh LLM

Obie konferencje LDA ILADS odbyły się w Hotelu Cathedral Hill w San Francisco
17-19 pazdziernika 2008.

Konferencje otworzyla Pat Smith, prezydent LDA. Zaraz potem glos zabral Steven
Barthold lekarz weterynarii, ktory mowil o uporczywosci zakazenia Bb na mysim
modelu choroby.
Uporczywosc zakazenia wg niego nie podlega watpliwosci, ale jej mechanizmy nie
sa jeszcze w pelni zrozumiane. Hipoteza glosi, ze nastepuje osiedlenie sie formy
nierozmnazajacej sie w kolagenie. Te formy przetrwalnikowe zaczynaja sie jednak
rozmnazac kiedy dojdzie do wytworzenia korzystnych warunkow, zwlaszcza wtedy
kiedy mechanizmy obronne gospodarza ulegna oslabieniu.
Duzo kolagenu znajduje sie w skorze czyli w rejonie atakowanym przez kleszcza.
Dr Barthold wykazal, ze przejscie zakazenia Bb ze skory zwierzecia zakazonego Bb
do kleszcza moze sie zdarzyc nawet po leczeniu abx.

Dr. Mariio Phillipp staral się rzucić troche światła na temat zaburzeń
poznawczych występujacych w boreliozie z Lyme. W badaniach na malpach wykazal,
ze jezeli ich mozg zostal zakazony Bb to nastepuje wydzielenie roznorakich
cytokinaz co prowadzi do smierci neuronow otoczonych komorkami glejowymi.
Znaczenie tego dla chronicznej choryby z Lyme u ludzi jest niejasne, ale jeśli
uszkodzenia rzeczywiscie następuja za pośrednictwem cytokin to moga pojawic sie
sposoby na ich redukcje co moze okazac sie pomocne w klinice. Phillipp zauważyl,
że doksycyklina zmniejsza ilosc immuno mediatora IL 6 co moze tlumaczyc
korzystny efekt doksycykliny obserwowany u pacjentow leczonych na Bb.

Dr. Steven Schutzer opisal technikę uzywana w celu identyfikacji drobnoustrojów
w populacji kleszczy. Jest jasne, że kleszcze stanowia pozywke dla calej grupy
mikroorganizmow , podobnie wielu pacjentow z choroba odkleszczowa ma w sobie
wiele odkleszczowych patogenow. T. Technika ta określana jako Ibis T5000 uzywa
niespecyficznych primerow DNA co pozwala na jednoczesna identyfikacje calego
panelu zakazen. Oczekuje się, że technika doprowadzi do wymapowania wszystkich
odkleszczowych patogenow z mozliwoscia odkrycia nowych, nieznanych jeszcze nauce
i medycynie.

[artur737]

Dr Nauk Weterynaryjnych Patricia Conrad jest parazytologiem szczegolnie
zainteresowanym babesją. Conrad wykazala, ze Babesia microti ma charakter
endemiczny w środkowym zachodzie USA i u ludzi może być obecna bez powodowania
objawów lub w niektórych przypadkach może powodować objawy grypopodobne.
Niedokrwistość i małopłytkowość może być wskazówką na jej obecności. Niedawno
opisana Babesia ducani (dawniej WA1) filogenetycznie jest całkiem odmienna od B.
microti ale stwierdzono, że zakazenia rowniez mogą być asymptomaticzne.
Obecnie nie ma dowodów na to, że B. jest ducani jest koinfekcja choroby z Lyme
i Conrad zakwestionowała ważność niektórych testów używanych w diagnostyce
babeszjozy u ludzi.
Conrad zasugerowała, że w niektórych przypadkach Babesia może być fałszywie
zdiagnozowana jako malaria, ale staranne badanie krwi może wykazac tzw "krzyż
maltański" wewnatrz erytrocytow w przypadku obecnosci Babesji i to pomaga
roznicowac z malarią.
Istnieje tylko kilka doniesien o babeszjozie w Europie. Większość z nich to B
divergens która zazwyczaj wydaje się powodować przebieg piorunujący. Oczywiste
jest, ze potrzebne są dalsze prace na całym świecie, aby zwiększyć naszą wiedzę
o ekologii i patologii tego trudnego pierwotniaka.
Diego Cadavid, lekarz, to inny badacz, który starał się rzucić troche światła na
neuroborrelioze. Przedstawil wyniki eksperymentów z wykorzystaniem Borrelia
turicatae, z nawracającą gorączką kretkową u myszy. Myszy z niedoborem IL 10 i
bez produkcji przeciwciał szybko zostały zabite przez kretki - w odróżnieniu od
dzikich myszy, które były stosunkowo odporne.
Myszy z niedoborem tylko w produkcji IL 10 miały wiecej mózgowo-naczyniowych
powikłań, pomimo wzglednie niskiego obciążenia kretkami co doprowadzilo Dr
Cadavid do wniosku, że IL10 odgrywa kluczową rolę w ochronie mózgu i innych
organów przed komplikacjami naczyniowymi podczas infekcji Borrelia.
Komentarz: Borelioza jest związana z wieloma różnynymi neurologicznymi
procesami, zarowno tymi centralnymi lub obwodowymi, odwracalnymi i
nieodwracalnymi. Nie ma " zespółu neuroborreliozy ", natomiast przyczyny
zaburzeń neurologicznych w Boreliozie u ludzi wydaja się wynikac z wielu
czynników i sa skomplikowane.

[artur737]

Brian Fallon, ktory jest lekarzem opisal kliniczny profil chronicznej choroby z
Lyme z naciskiem na biomarkery. Zwrócił uwagę, że C6 Elisa jest jednym z
najlepszych markerów na borelioze i ma specyficznosc zbliżona do 100% (przypis
Artura: w testach wazna jest tez czulosc, a ten ten test nie mial tej az tak
dobrej, ale wydaje sie, ze tym testem mozna wykluczyc borelioze, czyli w koncu
bedzie mozna powiedziec po zrobieniu tego testu „zrobilem/lam wszystkie badania
i wykluczylem/lam borelioze) . Wobec tych problemow z brakiem czulosci nalezy
wiec szukać dalej bardziej wiarygodnych bio-markerow. Badania Fallona wykazały,
że objawy kliniczne są najlepszymi wskaźnikami odpowiedzi na leczenie w
chorobie z Lyme. Fallon sugeruje, ze chroniczna chorobe z Lyme nalezy
definiowac w sposob etiologicznie neutralnyKomentarz: Fallon chce określić
chroniczna Borelioze poprzez polaczenie obu terminow : " syndrom poboreliozowy"
i „przewlekłe zakażenie”. Problem w tego rodzaju podejsciem jest taki, że
stworzy cala grupe pacjentow bez diagnozy – ci, ktorzy nigdy nie otrzymali
leczenia i sa chorzy przewlekle i objawowi. Moze wiec lepiej okreslic ten stan
jako uporczywa, chroniczna infekcje, choc w przypadku niektorych chorych dowodu
na to nie ma. Taka klasyfikacja nie jest w sprzecznosci z jednoczesnym procesem
patologicznym, który jest niezależny od zakażenia. (przypis Artura: alez to
wszystko wymęczone!)
Dr Christopher Contag opisal technikę Luminescencji Bio-Imaging (przypis Artura:
luminescencyjne obrazowanie biologiczne? – moja proba prztlumaczenia terminu),
które umożliwia lokalizację bakterii przebywajacych w żywym organizmie.
Jak dotad ta technika została wykorzystana tylko w badaniach nad Listeria u
myszy i od razu uzyskane wyniki zatrzesly panujacymi w nauce dogmatami na temat
pasozytow wewnatrz komorkowych. Niestety istnieje techniczny problem w
boreliozie: formy Bb sa mniejsze i czulosc metody musi byc znacznie poprawiona
(100-1000 razy) zanim znajdzie ona zastosowanie w chorobie z Lyme. Ale jest tu
potencjał do nowych odkryc.

[artur737]

Dr. George Chaconas także mowił o obrazowaniu w zakażeniach bakteryjnych życia
gospodarza.
Dr Chaconas zwrocil uwage na techniki real-time ukazujace interakcje
pasozyt-gospodarz i ich wyzszosc (tych technik) nad tradycyjnym naukowym
podejsciem kiedy to mozna miec rozne zastrzezenia do uzyskanych wnioskow.
Chaconas opracował zadziwiające 2D i 3D wymiarowe filmy z Borrelia zyjaca w
zwierzeciu laboratoryjnym . Mozna bylo zobaczyc penetracje naczyń krwionośnych
przez Bb. Powiedziano, że filmy są dostępne do oglądania w sieci World Wide Web.
Dr. Armin Alaedinin mówił o nieprawidłowościach immunologicznych w zespole
poboreliozowym. Autor mowil, ze istnieja liczne utrzymujace sie zmiany
immunologiczne, ktore wystepuja juz po przypuszczalnym wybiciu bakterii.
Zacytowal zespół Guillain-Barre, ktory jest obecnie kojarzony z wcześniejszego
zakażeniem Campylobacter jejuni jako przyklad ilustrujacy jego hipoteze.
Borrelia jest skomplikowana bakteria, ktora ma zdolność do stymulowania
produkcji wielu różnych przeciwciał i Alaedinin w swojej pracy wykazał, że w
zespole poboreliozowym bardzo wzrósł IL10. Czegos takiego nie obserwowano u
pacjentow, ktorzy wyzdrowieli klinicznie. Wzrost ten był porównywalny do tych
obserwowanych w innych auto-immunologicznych chorobach takich jak SLE. Wyrazil
nadzieje, że lepsze zrozumienie zakłóconych reakcje immunologiczne doprowadzi do
ukierunkowanej terapii modulacji immunologicznej w przyszłości.
Przycisniety do muru przez pytania od publicznosci Alaedini jednak zgodzil sie
jednak, ze podwyzszony IL10 mogl maskowac objawy infekcji w grupie kontrolnej i
w zwiazku z tym mozliwosc przewleklej infekcji absolutnie nie moze byc
wykluczona poprzez takie podejscie.