Video
microscopy on blood from danish
chronically
ill patients
- with symptoms of chronic / relapsing Borrelia
infection after antibiotic
treatment
Microscopy done by Marie
Kroun (phasecontrast, 1000X optical plus
?x digital)
&
Bela Bozsik (darkfield, 10.000X) on #1 and AP91
Video's
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right click on
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AP91
2008/10/15 (11 Mb, 1 min., by Bozsik) & 02-12-2008 (4
Mb, 1 min., by MK)
(Note This pt. was not fat-fasting for 24
hours
before the darkfield microscopy, some of the small dots are probably
fat micelles reflecting the indirect light) http://lymerick.net/AP91-20081015-DFM.wmvhttp://lymerick.net/AP91-20081202.wmv
...
2008/12-2009/03 AP91 was treated with antibiotics and got
well; the improvement lasted until
201009 clinical relapse, videomicroscopy 2010/10/29 (23 Mb, 2 min., by
MK): http://lymerick.net/AP91-20100929.wmv
Microscopy of same sample buffy-coat blood smear stained with Diff-Quik
and Acridin Orange: http://case.ulmarweb.dk/SD68/SD68-20100907-smear.pdf
This
blood sample is taken AFTER previous Tx. with antibiotics IV
(early 2010) and while pt. is currently on minocycline plus
clarithromycin!
---- NOTE: These above
selected
videos are presented in order to show DOCTORs with a
special interest in diagnosing and
treating chronic spirochetosis / chronic Borreliosis by doing
microscopy themselves, what they need to look out for in the microscope.
MK only does microscopy as research on selected members of http://daninfekt.dk
who - judged from their history, previous test result and not the least
the patients current symptomatology, visualized on symptom scores and
log curves via the Excel symptomdiary (english
& danish version) - displays a recurrent relapse
pattern suggesting the patient could be suffering from a currently
active Borrelia infection! - read more about the diary and
curve drawing here: http://lymerick.net/why-diary.html
Microscopy
procedure / hints:
Bozsik's Dualdur reagent / dobbelt centrifugation method is described
in #1 video from 15-10-2008.
MK
takes 4-5 ml EDTA full blood
- prepare for buffy-coat examination like shown in video:
http://lymerick.net/video/buffy-coat.wmv
- and examine at least 1 wet drop of
buffy-coat fraction in 1000X oil
objective, the QBC-Paralens objective, with external
UV-light source, can be used without the external UV-light for
doing phasecontrast microscopy, thus a quick switch between
phasecontrast and fluorescence microscopy is possible without having to
move the object/viewfield; the microscopic examination is done
systematically, i.e. always begin scanning from one edge of
the cover-glass, scrolling up
or down to the opposite edge of the cover-glass, then stepping
one
viewfield to the side, then scoll back to the opposite edge and so
forth,
continue until the whole blood preparation under the cover-glass have
been examined thoroughly. MK
NEED A BETTER TRINOCULAR MICROSCOPE WITH DARKFIELD, PHASECONTRAST with
SEPARATE VIDEOTUBE, and a much better quality video camera (connect
to computer via USB), that
can magnify the picture from the microscope 100X! - to get up to a
total of 10000X total
magnification, so I can take videos of spirochetes in the good
quality, as dr. Bela Bozsik and dr. Andy Wright can do (in
work on blood microscopy before 2006: http://lymerick.net/videomicroscopy.htm)
Please support the research by donating to
Patientforeningen DanInfekt
(labelled research/forskning), see account number on http://daninfekt.dk
at KONTINGENT subpage.
Please beware
that finding spirochetes and their alternative structures by simple
microscopy, as illustrated in videos above, is not
a "test-result" that
can stand alone
- since all spirochetes look
pretty much alike in
the microscope, and since all spirochetes may undergo the same
(cyclical) developmental changes such as degranulation,
formation of
cysts, blebs etc., as illustrated in this 100 years pictorial "Survival in Adverse
Conditions" and described by DeLamater
1951 and by Hindle 1912 and others, also read Willy Burgdorfer's 1999 Keynote lecture
on the historic observations on (relapsing fever) Borrelia spirochetes;
so when the human eye and/or
camera detect a few moving ("baby")
spirochetes in a blood or spinal fluid samplefrom a human patient, it
is not possible to
say with absolute certainty which spirochete is in action,
though a history of tickbite(s) aquired in the temperate
climate zone followed by EM, point more likely to Borrelia
burgdorferi / Lyme borreliosis, than to another type of spirochete ..
Note that Willy Burgdorfer - the discoverer
of Borrelia
burgdorferi - was honest enough to admit
that he was
wrong way back
in 1951 when he did not - as he writes / said - find evidence
of
"a
negative phase or complex life cycle" ...
"Although
most of the above mentioned opponents of the "granulation theory"
verified the formation and existence of cysts, blebs, spherules
associated with spirochetes, they considered them as degeneration
products." ... "Of particular interest to our discussion is the
presence in freshly engorged Lyme disease ticks of spirochetes
with
outer membrane-associated cysts, blebs or spherules that often contain
numerous granules with surrounding trilaminar membranes (Figs. 11,12). Because the internal
material of these granules is similar in appearance and electron
density to that of typical spirochetes and because these cysts (blebs,
spherules) strongly react
when treated with FITC-labeled conjugates,
the questions concerning a complex life cycle of borreliae have again
been raised and induced investigators to critically examine the nature
and function of these formations -- a research problem
referred to for
the first time almost 100 years ago by Dutton and Todd. Thus, RML
scientists Dave Dorward and Claude Garon using silver staining,
transmission and scanning electron microscopy investigated
the nature of naturally elaborated membrane blebs on the surface of
cultured B burgdorferi or free in the medium, and found both linear and
circular DNA (Fig. 13).
The fact that his material was packaged within the membrane-derived
vesicles suggested that it might play a role in the protection of
genetic markers. In vivo and in vitro exposure of B
burgdorferi
to antibiotics (penicillin G, ceftriaxon) were shown by Preac-Mursic
and associates to produce cytomorphic atypical but motile spirochetes
with numerous membrane-derived vesicles (spheroblast -- L-forms) (Fig.
14).[1]. In
their recent publication, Brorson and Brorson reported on
the "In
vitro Conversion of Borrellia burgdorferi to Cystic Forms in Spinal
Fluid, and on the Transformation to Mobile Spirochetes by Incubation in
BSK-H Medium."[2]
Accordingly, B burgdorferi converted rapidly to cystic forms when
transferred to spinal fluid. No normal spirochetes were
left after 24
hours of incubation at 37° C; all were converted to cysts. When these
cystic forms were transferred to a rich (BSK-H) medium, the cysts were
converted back to normal, mobile spirochetes after incubation for 9 to
17 days.[young cysts]" ...
"Using
silver impregnations and immunochemical staining, cystic material has
been demonstrated in every animal and human tissue infected by B
burgdorferi.
As yet, it is not known whether these forms of Borrelia represent
products of degenerated spirochetes or of surviving organisms capable
of transforming to typical spirochetes once the faborable environmental
conditions are restored. It
is
tempting to speculate, however, that the survival mechanism of
spirochetes is responsible for the diverse pathology of these organisms
as well as for their ability to
survive as cystic forms thereby producing prolonged, chronic and
periodically recurrent disease." ...
Hampp
1948 did electron microscopy studies on spirochetes and
wrote:
"Typical free granules,
the end
products of granule 'shedding', are shown in
figure 18. They are roughly
circular in
outline and sharply bounded. They consist
for the most part of what
appear to
be short sections of spirochetes closely packed together.
The
contents of these granules are probably responsible for the fine
lacelike appearance
and the bright white, highly
refractile bodies
described by Hampp (1946) under the dark-field
microscope. Examples of another type of free granule
repeatedly observed are shown in
figures 19 and 20. These granules consist of tangled masses of
spirochetes or spirochetal
segments. The
significance of granules in the
life history of the spirochetes is unknown but certain investigators
have
suggested that they may be germinative
units (Balfour,
1911; Noguchi, 1911; Noguchi, 1917; Leishman,
1918; Mudd et al.,
1943; Hampp, 1946).
Others are undecided or hesitant in accepting this hypothesis (Fantham,
1916; Akatsu, 1917; Wenyon, 1926; Warthin and Olsen,
1930). Topley and
Wilson (1936) have indicated that
they are probably particles of culture medium adhering to the sides of
the
spirochetes. The electron micrographs demonstrate that this explanation
is
wrong, and that free
granules
are definitely a phase in the development of spirochetes. Although
it is not possible to determine from these micrographs that the
granules are germinative
units their constant rhythmic
occurrence in
living cultures suggests this possibility. Further
support of this hypothesis is provided by the fact
that cultures up to 31
months old, showing only refractile
granules by dark-field examination have invariably given normal growths
on
transfer to fresh medium (Hampp,
1946) ...
... 31 months ~
2½ years! - muchlonger than the duration of the usually for spirochetal
infection recommended antibiotic treatments!
The
latter question mentioned by Burgdorfer, if cysts can convert
back to
spirochetes also in vivo, have later been answered by Gruntar
et al. - APMIS 2001. PMID: 11478686 - who
injected variably aged cystic form of Borrelia garinii intraperitoneally
in mice, and found it could result in Borrelia infection,
judged both
by seroconversion of the mice and
by finding spirochetes in the heart and bladder
tissues of the with
Borrelia cysts experimentally inoculated mice, when they were
sacrified
and dissected at end of the study!
In
order to be able to put a family name / substrain name to the
spirochete seen in the microscope, we'll need to do specific
and
unfortunately expensive supplementary ANTIGEN TESTING,
depending
on which spirochete we suspect it can be, judged from patients
history
and previous test results, and depending on what is availble
on the
marked to buy for supplementary testing, at present it is possible to
buy FITC-labelled affinity purified Borrelia burgdorferi antibodies
from KPL and ready to use solution of BSK-H medium.
While it can be
quite difficult and time consuming to get positive result with
specific direct immune stain or PCR test when there are only a few
spirochetes
present in the material (usually less than 5 spirochetes found per
buffy-coat drop) i.e. at about the detection limit for
PCR? - it should be possible to increase chance of these methods give
positiv result, if we
can first get a positive culture of spirochetes, so
there will be much more spirochete material to do PCR or
specific immune stain
on, thus less waste of time and expensive materials on "nothing found"
and the chance of getting a positive culture should increase when
one can
first find spirochetes by a simple microscopy screening like
above, that cost some hours but not much money. So far
I've already got some positive cultures, already in the first
few tries; preliminary investigations for a
future DanInfekt Borrelia culture project, where we will
attempt to culture in BSK-H as explained by Barbour and others in my
selected: http://lymerick.net/Borrelia-culture.html;
it is probably quite important to avoid oxygen mixing (Borrelia are
microaerophilic) and to keep the
optimal temperature for increasing chance of growth of Borrelia: http://lymerick.net/Borrelia-growth-optimum.html
... in case of positive culture, we can split a serum
sample taken from same prick / at same time as
microscopy as the blood for culture and do WB (like
Mikrogen Borrelia recomBlot) abroad and DAKO/OXOID
Borrelia
flagella IgM and IgG antibody analysis on serum, for a direct
comparison, a similar study to what
Oksi et al. did in JCM 1995, se ref. below.
Many doctors continue to claim there is not sufficent proof of
persistent infection in "chronic Borreliosis / chronic Lyme disease" -
this can only be because the people who claim that has not read the
literature on by direct detection method proven persistent Borrelia
infection - to help find the articles and cases I long ago (first put
on Internet 2003) made a reference list Persistent
borreliosis / relapsing Borreliosis verified by direct detection
methods culture, microscopy, PCR:http://lymerick.net/persistent-borreliosis.htm MK noticed that some
Bowen test project participants developed neuroborreliosis /
later
relapsed and suffered from chronic/relapsing Lyme borreliosis
(verified by microscopy with DFA i.e. Direct Fluorescent
Antibody
stain for Borrelia burgdorferi)
- despite they had
had what is normally considered to be "appropiate" early antibiotic
therapy
for erythema migrans - and moreover confirmed
relapses / pregression of disease were seen,
both after
penicillin and after doxycycline in officially recommended doses!
Below focus is set on some publications on European culture or
PCR
verified LATE (>
3 month duration) cases /
or relapses
-
and DAKO
(OXOID) serology result!
-
which is of special interest
to MK
/ danish patients, because the DAKO test was developed in Statens Serum
Institut (SSI), Copenhagen, Denmark - by Hansen, Lebech and DAKO
- and is still the ONLY test for
Borrelia in use in Denmark, however since 2006 under name OXOID
- read more about it in: http://lymerick.net/2006-OXOID-DAKO.html
Unfortunately danish microbiologist still refuse to to
microscopy
(enhanced with acridin orange or specific direct immune stain for
Borrelia), culture nor will they do PCR for Borrelia, nor a WB
- despite new
recombinant multi-antigenic, rather cheap WBs are now
available, where only
the
diagnostic relevant bands are selected, i.e. the result is easy to
read,
creates less confusion, since most selected bands on the test strip are
Borrelia specific!
They state
they find these methods too laborious, too time consuming, too
expensive
for the lab to run them - however these labs do NOT take into
consideration,
what
it costs the patient not to get diagnosed and remain ill for years /
lifetime from Borrelia infection, not take into
consideration what
it can cost the danish health
system - since these patients go to many specialist, who must
each
evaluate the chronic multi-organ-system symptomatic patients for a lot
of diseases that all come out negative/normal, because that is diseases
that this patient have, nor was it very likely,
judged by
the
history pointing to Borrelia infection
- but doctors rather tend to do "defensive medicine", i.e. do all the
ROUTINE
tests they traditionally do on most of their patient to "outrule
disease within our field of medical speciality", and when they
have done that, the doctors feel they've done alle what they
can /
must do, despite they have not helped the patient to get
well -
none of them can't (or won't do) the test which the
tickbitten
patient really need most of all, multiple tests for tickborne
infection, for immune dysfunction etc.!
- and they not comsider either how much it costs the
danish social system, when the long-term ill
patients
are way too sick to work, but can't get a diagnosis / prognosis and
must go on transfer income paid over our taxes ...
... 3
serology tests evaluated on 41 late (> 3 mdr.) culture or
PCR verified Borrelia cases
- amongst them DAKO
/ OXOID
flagella ELISA came
out false serum antibody negative in 24/41
(58%) cases with symptoms of Borreliosis for at least 3 months duration!
SSI failed to repeat a similar study in Denmark on danish
patients with
late culture confirmed Borreliosis and moreover IGNORE DISCUSSING /
REFERENCING THIS IMPORTANT STUDY IN THEIR "guidelines"
- in
DanInfekt we intend to try to examine OXOID serology in culture
verified chronic Borreliosis cases, and compare OXOID result with WB
....
... in spinal
fluid culture verified Borreliosis, 23
w/Borrelia garinii, 10 w/Borrelia afzelii
- in the Borrelia afzelii neuroborreliosis group 9/10
tested negative
on DAKO/OXOID
neuroborreliosis kit, hereof had only two been sick for shorter than 6
months
- i.e. 7/10
(70%) had
been sick for at least 6 months and up to seven years, with wrong or no
(?) diagnosis, and those CSF ELISA Borrelia
index. neg. would not have gotten the correct
borreliosis diagnosis, if serology had been the only
test for Borrelia done (like would be the case in DK, where
microbiologist, SSI will NOT do culture nor PCR test for
Borrelia on
chronic (seroneg.) patients!
... IgG and
IgM titres to the Lyme spirochete were determined by ELISA
using standard conditions as recommended by the supplier (Test-Line
Ltd, CR).
In ELISA with sonicated antigens, a positive value was
defined as 0.73
for IgG and 0.850 for IgM. In the
IgM capture ELISA(The 98th percentile of absorbance
values for the controls was used as the cut-off level. Dako Diagnostika GmbH),
a positive value was 0.380.
Compared IgG
serology measures and which treatment failed first (from table 3 and
1), for IgM look at full text:
Patient’snumber
First
treatment before
1st detection of Borrelia antigen
(from table 1)
IgG
ELISA
1st/2nd detection
IgG
WB
1
neg. /
neg.
pos.
2
ROX / 4
neg. /
neg.
pos.
3
DOX/ 7
neg.
/neg.
pos.
4
pos.
/pos.
pos.
5
DOX / 10
neg.
/neg.
neg.
6
DOX / 12
neg.
/pos.
pos.
7
pos. /neg.
pos.
8
pos. /neg.
pos.
9
neg.
/neg.
pos.
10
neg.
/neg.
pos.
11
DOX / 16
neg.
/neg.
pos.
12
neg.
/neg.
pos.
13
DOX / 9
pos.
/pos.
pos.
14
pos.
/pos.
pos.
15
neg.
/neg.
pos.
16
neg.
/neg.
neg.
17
DOX / 12
neg.
/neg.
pos.
18
neg.
/neg.
pos.
Regarding
CUT-OFF values confusion - just for
comparison: Dako Glostrup
cut-off values, also used 98 percentile as cut-off level, but cut-off
level has changed over time, and apparently without scientific
justification,
since it seems no
new validation study is searchable PubMed in between
the following article publication dates nor at a later date?!
Ann
Neurol.
1991 Aug;30(2):197-205.
Cut-off for IgM: 0,300 henh.
IgG: 0,160 (sent in for publ juli 25.
1990).
J
Clin
Microbiol. 1992 Jul;30(7):1646-53 (PDF).
Cut-off for IgM:
0,500
henh. IgG: 0,160
(received Jan 1992)
[IgM cut-off increased with factor 1,6]
Neurology.
1993
Jan;43(1):169-75.
Cut-off for IgM: 0,500
henh. IgG:
0,240(received Apr. 6, 1992) [IgG cut-off
increased with factor 1,5]
Increased cut-off value
means the antibody level need to be ~1,5 times higher in order for the
patient get a positive Borrelia antibody test
result!
SICK
PEOPLE NEED A TEST THAT IS SENSITIVE ENOUGH (LOWER CUT-OFF) TO DETECT
THEIR REACTION TO BORRELIA INFECTION, SO THEY CAN GET DIAGNOSED AND GET
ANTIBIOTIC TREATMENT!
Note
that Honegr
et al. - when looking at IgG - found a discrepant
/ unexpected discrepant second
negative ELISA IgG
results, when compared
to WB! - a pos. WB but neg. 2nd ELISA IgG
is marked with bold in table: 12/18 (2/3, 66%) were IgG
ELISA neg. but were WB-IgG-positive, and since they all
had positive detection of Borreliae by either PCR or IEM, it
is the WB result that was the TRUE POSITIVE RESULT! - and the neg. IgG
ELISA was false negative result!
NOTE
that pt. #7 and #8 both developed negative IgG ELISA result,
despite they had positive IgG at first test, and despite positive WB!
-
like other cases on the persistent borreliosis reference list with by
direct method detected persistent borrelia infection post treatment, at
time of clinical and confirmed relapse! NOTE that 6
/18 (1/3,
33%) relapsed despite they were treated before
the first detection of Borrelia by IEM or PCR
with doxycycline
...and one had
roxithromycin, a drug earlier known to fail (1992, PMID: 1357894)
- maybe this pt. was treated with roxithromycin before
publication since pts. were enrolled / detected between
1991-2000?
IMO 1/3
VERIFIABLE RELAPSES IS WAY TOO HIGH
FIRST TREATMENT FAILURE RATE!
- so lets look at some probable reasons, why so many patients relapse
after doxycycline ...
Borrelia
has been detected by PCR very early - within the first 2 weeks
after the tickbite - in the central nervous system
(CNS),
i.e. before and without later development of an erythema migrans:
http://lymerick.net/Bb-EarlySpread.htm Therefore
it does not really make good common sense to treat erythema migrans
with drugs
like peroral penicillin, that can not penetrate over membranes into the
CNS
- nor does it make sense to give a low dose / shorter duration
treatment for an EM, than what is recommended for treatment of
neuroborreliosis!
Thus
the Bulls-Eye rash, Erythema (chronicum) migrans (EM / ECM), is a
side-manifestation, that may sometimes occur, but it is not
a prerequisite, that EM must occur before Borrelia can spread
into
the CNS and cause neuroborreliosis! - around half of patients later
diagnosed with neuroborreliosis never saw an EM rash!
Problem
is that treatment with a sub-inhibitory / sub-lethal dose / drug
concentration will not kill all Borrelia, but will select the most
resistant of the bugs, which later are those that cause the relapse,
and will need either another drug or a higher dose for the
bugs to
be sensitive and be killed!
Therefore a second antibiotic treatment
with same drug and dose often does not show as much clinical effect as
the first treatment, unless using other drugs with very good
penetration to CNS, and/or if a much higher dose is used!
Lack of a
good response to retreatment is often evaluated as if the
chronic / relapsing symptoms can not be caused by an ongoing
Borrelia
infection; however, when searching for the
microbes by direct
method like microscopy we can actually find the spirochetes again and
again - as illustrated in videos from different patients above
- especially in patients that has turned seronegative
after
the first treatment, since many or all the antibodies they
form,
during a relapse with so many bacteria in the blood stream that they
can be detected by simple microscopy, are quickly used up by binding in
immune complexes to all the
circulating Borrelia antigens, which
precipitate in vessels, cause vascular damage and vasculitis with
chronic inflammatory cells, the micropathological Hallmark of
Borreliosis (and syphilis)! - elicit complement cascade,
proinflammatory cytokine response, like increased TNF-alfa ... it is the
immune
reaction that cause the symptoms ...
Serology
can detect early infection only several weeks after aquiring
the
infection, when serial serology tests confirm a positive
seroconversion, and in late infection can detect past exposure
to
Borrelia antigens or alike when positive
- but since IgG
serology can stay high for years in patients with previous Lyme
borreliosis (who do not have circulating antigen to bind the
antibodies) who became asymptomatic on given antibiotic treatment,
serology really has no use whatsoever in the diagnosis of chronically
ill patients of longer than 3-6 months disease duration!
A
negative serology test can not not outrule Borrelia infection; pt. may
be immune depressed or have so much circulating antigen that all
antibodies are bound in the patient so nothing is measured by the test!
A positive serology can not prove the patient have a currently active
infection! BUT THE PATIENTS SYMPTOM
DIARY WILL SHOW RELAPSE PATTERN CONSISTENT WITH RECURRENT
BORRELIA ACTIVITY
- and such patients should be investigatede thoroughly, not be
dismissed as if they are malingering hypochondriacs!
CHRONICALLY
ILL PATIENTS WITH RECURRING SYMPTOMS OF BORRELIOSIS AFTER PREVIOUSLY
FAILED ANTIBIOTIC TREATMENT NEED ACCESS TO DIRECT BORRELIA DETECTION
METHODS LIKE MIKROSCOPY (w/specific immune stain if possible, but
Bb-antibodies are expensive to buy); CULTURE (cheap comparable to
serology), PCR (expensive 2-300€)!
Treatment with (low dose) doxycyclin for
Borrelia infection fails very often(like
in #45, #23, #1, #50 and RM81 above!)
... the only patient above who did
not relapse after doxycycline was AP91, who was a child and therefore
got penicillin, not doxycycline, for her first EMs! - still she
relapsed despite penicillin in the usually recommended EM dose, not
only for the 10 days that is usually recommended here in
Denmark,
but for 6 weeks, as suggested by Burrascano!
- see the latest version of his guidelines at http://www.ilads.org/lyme_disease/treatment_guidelines.html
More of 50 project
participants relapsed despite early recommended treatment for their EM
!!!
- probably because
the usually recommended dosis of doxycycline 100 mg x 2 does NOT REACH
A CONCENTRATION OVER THE MINIMUM INHIBITORY CONCENTRATION (MIC) IN CNS
and other "remote areas"?!
- since doxycycline distribute well in
fatty tissues, especially fat
people 100-150 kg will have 2-3 times larger
distribution
volume of the drug, hence will reach a lower tissue concentration on
the same dose
that give sufficient concentration in the small 50 (-70) kg
person: http://kroun.ulmarweb.dk/doxycyclin-dosis.htm
(some text is in danish, but references and abstract is in english, use
Google translate!)
The actually
achieved steady state
concentration of doxycyclin was measured in
spinal fluid by Dotevall
&
Hagberg 1989
(PDF)
-
and they even used a lower MIC of only 0.6-0.7 micrograms/ml,
where others state that MIC for doxycycline for Borrelia is 1 or even 2
micrograms/ml!
Excerpt:
A
dose of 100 mg of doxycycline (Vibramycin; Pfizer Inc.) was taken
orally b.i.d. for 10 days by 10 patients, while 200 mg was taken orally
b.i.d. for 10 days by 12 patients. On days 5 through 8 of treatment,
CSF was collected 2 to 3 h after the last drug administration. In one
patient, an intraspinal catheter was inserted for treatment of severe
chronic pains, and repeated CSF samples were taken through the catheter
during the doxycycline treatment. On the day of lumbar puncture, the
patients were questioned regarding adverse reactions to the drug. No
other antibiotics were given simultaneously. ...
Please note that NONE
of the patients on doxycycline 100 mg x 2 and even some of the
patients on 200 mg x 2, did NOT reach a concentration in
spinal fluid (CSF) over 1 microgram/ml
- which many state is the MINIMUM
INHIBITORY CONCENTRATION for doxycycline for Borrelia!
Honegr.
does not tell us dosis and duration of the given treatments,
however, if the
patients - all got the usually recommended DOXYCYCLINE dosis of 100 mg
x 2
daily
- IT CAN NOT REALLY COME AS A BIG SURPRISE TO ANYONE,
THAT SO MANY OF HONEGRs PATIENTS ON DOXYCYCLINE BEFORE THE FIRST
BORRELIA ANTIGEN DETECTION LATER DEVELOPED BY DIRECT DETECTION METHOD
PROVEN PERSISTING BORRELIA INFECTION HAD PROGRESSED TO
NEUROBORRELIOSES!
WHO
WAS RESPONSIBLE FOR THE CHOICE? - AND WHY WAS A
DOXYCYCLIN
DOSIS OF DOXYCYCLINE 100 mg x 2 chosen to be the recommended
dose
for treatment of EM and for (early) neuroborreliosis
- when
Dotevall & Hagberg already in 1989 had showed by their
experiment
that 100 mg x 2 may not result in a concentration above 1
mg/ml in
ANY patient!?
-
who are NOWADAYS TO BE MADE RESPONSIBLE for continuing to
maintain
the obviously bad advice of recommending too low doxycyclin dosis for
EM and neuroborreliosis?
WE ALSO NEED TO CLEAR
ANOTHER LONG TIME AGO DISPROVEN MISUNDERSTANDING! THERE IS
OFTEN NOT (as often stated in the media) ANY SAFE 24 HOUR PERIOD / A
DELAYED TRANSMISSION OF BORRELIA, and TBE can be
transmitted within ONE HOUR after tickbite started: http://lymerick.net/Transmission-Bb-rate-time.htm
...
25 of 35
(71%) of patients who
remembered the duration of the infecting tickbite got a
culture confirmed erythema migrans, despite less than 24 hour tick
attachment time! 9 of 35 (26%) even
got infected with Borrelia via a tickbite of less than 6 hours
duration!
Around 1/3
of Ixodes ricinus ticks have been found to have a systemic
Borrelia
infection and may thus have Borrelia in their saliva glands all the
time, and can thus transmit Borrelia immediately when they
begin
spitting; systemically infected female adult
ticks may also have
Borrelia in their
eggs, thus can transmit Borrelia to their larvae transovarially /
vertically, i.e. tick larvae
can be infective despite they have not yet had a blood meal!
Experts who continue to inform
people incorrectly / out-of -date, who does not give
a balanced review of all published literature so far on subject
tickborne infection to the public
- should be held economically personally
responsible for their actions
- by those patients who do not remove the tick within 24 hours due to
misinformation, get infected and thereafter must
suffer the consequences, by developing debilitating disease
-
because they got bad/wrong information from the official
sources,
or who was denied testing and treatment by ignorant doctors!
MY
ADVICE IS THEREFORE RATIONAL / LOGIC:
FIRST OF ALL WE NEED TO AVOID TICK INFECTION by informing
people that SOME
TICKS CAN TRANSMIT BORRELIA IMMEDIATELY WHEN THEY BEGIN SPITTING IN THE
WOUND DIRECTLY INTO THE CAPILLARY THE TICK SUCK BLOOD FROM
- i.e.
tickborne infections are probably spread hematogenously right
from start of the tickbite!
- see the nice tick bite pictures and animation at LDA-UK
website: http://www.lymediseaseaction.org.uk/image/tick_animation.htm
...
Animation: http://www.lymediseaseaction.org.uk/images/kullancs/kullancs01.avi
THEREFORE
IN CASE OF TICK EXPOSURE / RISK OF TICKBITE, DO TICK CHECK VERY
OFTEN AND PULL OFF THOSE TICKS IMMIDIATELY with
fine branched tweezers or a special TICK REMOVAL EQUIPMENT / SAFECARD
- after photographing the tick in situ with date on the picture as
documentation for the bite!
- after marking the bite site, so you can look out for
development of a growing red rash / erythema migrans. Only
this way can all tickborne infections and disease from these agents be
totally prevented, the person will not need tests, nor treatment, will
not have sick days etc.!
IN CASE OF A
TICK BITE MEASURE C3A & C4A COMPLEMENT SPLIT
PRODUCTS ...
-
since the split products from complement activation may
increase
within 96 hours after a tickbite in
patients that developed signs of Borrelia infection /
seroconversion ...
Borrelia serology will NOT become positive
so early in Borrelia
infection, unless the patient got reinfected with Borrelia and had
memory immune cells that can raise a very quick serology response! The Complement system is the first
line and innate unspecific immune defense reaction raised in
infection, but
note increased split products does not tell for sure which
infection / inflammatory proces activated the complement
cascade! HOWEVER
IT MAKES GOOD SENSE TO ME TO TREAT PATIENTS WITH RECENT TICKBITE AND
INCREASED COMPLEMENT SPLIT PRODUCTS WITH ANTIBIOTICS, BECAUSE EARLY
BORRELIA INFECTION CAN BE CURED BY SUFFICIENT ANTIBIOTIC
TREATMENT!
- while chronic borrelia infection > 3 months
and of many years duration is very hard to cure, meaning the
patient can improve very much while staying on antibiotic treatment and
may even become asymptomatic, but relapses are common after
stopping the treatment! - because dormant cysts can not be hit, since
the microbial metabolic processes with which antibiotics interfere are
not active during dormancy!
TREAT EARLY
LYME BORRELIOSIS / ERYTHEMA MIGRANS AS YOU WOULD TREAT EARLY
NEUROBORRELIOSIS!
-
then eventual few Borrelia that might have reached CNS / CSF already
may be killed also and those killed effectively, will not grow into
many under a sublethal antibiotic concentration, that select the most
resistant bacteria!
Undertreatment is worse than no antibiotic
treatment, because treatment removes antigens from the blood stream
(less immune stimulation) without clearing all the most "remote areas"
for bacteria, i.e. undertreatment will both switch off the maturation
of the immune response and will select the most antibiotic
resistant microbes from the surviving population
especially in "remote areas", from which new growth may
arise under favourable growth conditions, if the patients
immune
system is not able to suppress growth, without help from
antibiotics!
DURATION OF
TREATMENT MUST BE OPENENDED, the goal is to cure the patient! Be aware that Borrelia grows very slowly
and may have very long dormant periods where they can not be hit by
antibiotics, until they enter growth phase again, perhaps at long intervals
(often as monthly relapses) ...
IN CASE THE
PATIENT RELAPSE AFTER ANTIBIOTIC TREATMENT AND DISPLAYS RECURRENT
RELAPSE PATTERN IN SYMPTOM DIARY - USE THE SYMPTOMDIARY TO
DECIDE WHEN IS THE BEST TIME TO DO DIRECT DETECTION METHODS
FOR BORRELIA, FIRST
OF ALL USE THE MICROSCOPE
...
it is both fast and cheap, if you do it yourself ... you have a
probable diagnosis when you see the first spirochete swimming!
- and
if the blood looks perfectly normal in a microscopy done during a
symptomatic period, you should rather seek for another diagnostic
explanation for the patients symptoms, than an active Borrelia
infection! - and in that case you do not need to waste more
energy, time and money on doing the more
difficult / more expensive test methods for Borrelia!
Note
in the old days detecting spirochetes by microscopy in a syphilic
person combined with the clinical picture was enough for a tentative
diagnosis of syphilis and was enough justification for the doctor to
treat the patient with antibiotics! - why is that not so today also for
Borrelia, when we can detect spirochetes in the blood?
FOLLOW THE PATIENT DURING
TREATMENT WITH SYMPTOM DIARY AND REPEATED MICROSCOPIES!
- at least always re-examine the blood before intention to pause
antibiotic treatment!
Don't pause the treatment if the blood look abnormal during ACTIVE
PHASE (day one of a new relapse)!
If
no relapses are visible for 6 weeks in the diary and the blood also
looks very clean, pause antibiotic treatment under surveillance!
-
i.e. THE PATIENT SHOULD CONTINUE THE SYMPTOM DIARY for at least 3
months after stopping treatment; because an early relapse will show as
re-beginning flare cyclicity (usually weekly) and the symptom score
will gradually increase along as more and more spirochetes are born,
make toxins, are being killed, produce waste products, elicit
cytokines etc. ...
- then re-examine the blood and re-treat if finding spirochetes
again and related structures!
For advice on treatment read Burrascano's guidelines at ILADS,
he's got experience since mid 1980ies from more than 10000 Borrelia
patients, and he published guidelines for 20 years, and he know this
infection better than most ... because he's had borrelia
infection himself, like myself!
Finally, getting Borrelia
infected yourself and having to find out how to diagnose and treat the
tickborne infection(s), because you get rejected by illiterate and
ignorant doctors
- is the very best teacher!
YOU are
very wellcome to get some of my blood infused (#1), if you - after
seeing the videomicroscopies and read this - continue to
maintain your stance that Borrelia is very easy to cure, since
-
if you are right - you have nothing to fear by doing this experiment!
Doctors did successful transfer experiments,
including on themselves,
of the skin changes since known to be caused by Lyme Borrelia
species - erythema migrans (EM), lymphadenomatosis benigna cutis
(LABC),
acrodermatitis chronic atrophicans (ACA) - after penicillin treatment
had proven very helpful since 1946; for selected historic "milestone"
references, see my Borrelia history lecture: Hull
2001; Kassel 2006.
IF YOU WON'T ACCEPT MY BLOOD OFFER, BECAUSE YOU FIND THE SPIROCHETES IN
MY BLOOD DISGUSTING, think again!
... read, learn, look in the microscope, revise your stance
and treatment policy!
