Yrj�n�inen H, Hyt�nen J, Hartiala P, Oksi J, Viljanen MK. Persistence of borrelial DNA in the joints of Borrelia burgdorferi-infected mice after ceftriaxone treatment.
APMIS 2010; 118: 665-73.
We have earlier shown that Borrelia burgdorferi-infected and ceftriaxone-treated mice have viable spirochetes in their body,
since immunosuppressive treatment allows B. burgdorferi to be detected by culture.
However, the niche of the persisting spirochetes remained unknown.
In the present study, we analyzed the tissues of B. burgdorferi-infected and ceftriaxone-treated mice by culture and PCR to reveal the foci of persisting spirochetes.
C3H/HeN mice were infected via intradermal needle injection with B. burgdorferi s.s. N40. The mice were treated as follows: (i) short (5 days) and (ii) long (18 days) course of ceftriaxone at 2 weeks of infection and killed after either 10 or 30 weeks,
or (iii) the mice received ceftriaxone for 5 days at 18 weeks of infection and were killed 21 weeks after the treatment.
All samples of ceftriaxone-treated mice were culture negative, whereas all untreated controls were culture positive.
Importantly, B. burgdorferi DNA was detected in the joints of 30-100% of the treated mice.
In conclusion, these results combined with earlier results suggest that the joint or a tissue adjacent to the joint is the niche of persisting B. burgdorferi in ceftriaxone-treated mice.
-------------------- Suspected Lyme 07 Test neg One band migrating in IgG region unable to identify.Igenex Jan.09IFA titer 1:40 IND IgM neg pos 31 +++ 34 IND 39 IND 41 IND 83-93 + DX:Neuroborreliosis Posts: 5850 | From Kentucky | Registered: Dec 2008
| IP: Logged |
TerryK
Frequent Contributor (5K+ posts)
Member # 8552
posted
Thanks for posting. How is this proof that antibiotics alter test results? Are they saying for a fact that ceftriaxone suppresses the immune system? If so, I don't think that applies to all abx, do you?
Odd that they don't even consider cystic forms as part of the problem with persistent infection.
Terry
Posts: 6286 | From Oregon | Registered: Jan 2006
| IP: Logged |
posted
They are talking about culturing the mice (attempting to grow bacteria from them) not testing them (by detecting antibiodies), those are two different things.
It says after treatment they couldn't culture them to grow borellia bacteria, but they could find borellia DNA in the joints still.
Posts: 526 | From NJ | Registered: May 2007
| IP: Logged |
nenet
Frequent Contributor (1K+ posts)
Member # 13174
posted
quote:Originally posted by TerryK: Thanks for posting. How is this proof that antibiotics alter test results?
I might be wrong, but as I read it, they are saying that the antibiotic-treated mice are testing negative in culture because the Lyme is hiding in the joints.
My guess is they are drawing blood to culture the Lyme, but the antibiotics are killing off the Lyme in the blood, and/or chasing the remaining Lyme to harder-to-reach areas. (I would venture to guess the joints are not the only place it's hiding out though, based on other studies).
This is a different scenario than Western Blot antibody testing, since they are culturing the Lyme (looking for live spirochete) as well as performing PCR of joint tissue (looking for DNA).
Some LLMDs believe that too-recent antibiotic treatment can effect a Western Blot test as well, by causing false negatives in some cases, but that's a different kind of problem.
TerryK
Frequent Contributor (5K+ posts)
Member # 8552
posted
rad and nenet - thanks for trying to help answer my question.
I was asking based on the subject line. "Proof antibiotic may alter testing results."
I'm sure Pinelady had something specific in mind when she posted that subject line because she is a smart lady.
I'm sure she'll be back to explain.
nenet wrote: I might be wrong, but as I read it, they are saying that the antibiotic-treated mice are testing negative in culture because the Lyme is hiding in the joints
That's how I read it as well.
Thanks, Terry
Posts: 6286 | From Oregon | Registered: Jan 2006
| IP: Logged |
Pinelady
Frequent Contributor (5K+ posts)
Member # 18524
posted
All samples of ceftriaxone-treated mice were culture negative,
whereas all untreated controls were culture positive.
B. burgdorferi DNA was detected in the joints of 30-100% of the treated mice.
In conclusion, these results combined with earlier results suggest that the joint or a tissue adjacent to the joint is the niche of persisting B. burgdorferi in ceftriaxone-treated mice. ------------- Yes the antibiotic caused them to be culture neg. and unable to be seen.
Or they scramble to the juicy parts for a hide out.
Or the antibiotics simply cannot get to them. -------------
While the DNA was still in the joints. Meaning it is still there.
The mice were treated as follows: (i) short (5 days) and
(ii) long (18 days) course of ceftriaxone at
2 weeks of infection and killed after
either 10 or 30 weeks,
or (iii) the mice received ceftriaxone for 5 days
at 18 weeks of infection and were killed 21
weeks after the treatment.
Meaning if they get it----4 weeks of treatment may not get it....
-------------------- Suspected Lyme 07 Test neg One band migrating in IgG region unable to identify.Igenex Jan.09IFA titer 1:40 IND IgM neg pos 31 +++ 34 IND 39 IND 41 IND 83-93 + DX:Neuroborreliosis Posts: 5850 | From Kentucky | Registered: Dec 2008
| IP: Logged |
Pinelady
Frequent Contributor (5K+ posts)
Member # 18524
And TerryK thanks---but I am just learning and fighting like everyone else...I wish I could do more---If I was smarter I could, we just do what we can...
-------------------- Suspected Lyme 07 Test neg One band migrating in IgG region unable to identify.Igenex Jan.09IFA titer 1:40 IND IgM neg pos 31 +++ 34 IND 39 IND 41 IND 83-93 + DX:Neuroborreliosis Posts: 5850 | From Kentucky | Registered: Dec 2008
| IP: Logged |
Bugg
Frequent Contributor (1K+ posts)
Member # 8095
posted
I know we don't know exactly how this translates to humans treated with ceftriaxone...But, does anyone else see that this could mean that our current abx and administration methods may not reach into the tissues around the joints?
Maybe they could develop a method whereby joints could be injected directly....
Posts: 1155 | From Southeast | Registered: Oct 2005
| IP: Logged |
Pinelady
Frequent Contributor (5K+ posts)
Member # 18524
posted
Your right Bugg. There are lots of things they haven't tried!
The ones that want to-- need money.
The ones that don't want to have loads!!!!
So you see where we are...
-------------------- Suspected Lyme 07 Test neg One band migrating in IgG region unable to identify.Igenex Jan.09IFA titer 1:40 IND IgM neg pos 31 +++ 34 IND 39 IND 41 IND 83-93 + DX:Neuroborreliosis Posts: 5850 | From Kentucky | Registered: Dec 2008
| IP: Logged |
Marnie
Frequent Contributor (5K+ posts)
Member # 773
posted
"We now present results of the first studies on interactions between B. burgdorferi and mammalian laminin,
a major component of vertebrate ***basement membranes*** and
Extracellular perhaps until phagocytized or attempt at that (not happening in macrophages).
Basement membranes are very close to blood vessels...making Bb a "vascular disease" or fitting in the "H16" category.
Our defense cells need help.
Posts: 9424 | From Sunshine State | Registered: Mar 2001
| IP: Logged |
Pinelady
Frequent Contributor (5K+ posts)
Member # 18524
posted
Your right Marnie. You know I thought most of our problem was in the cellular systems.
But I now believe it is a leaky vascular system also.
Whats that stuff they give thoroughbreds to prevent leaky lungs when racing?
-------------------- Suspected Lyme 07 Test neg One band migrating in IgG region unable to identify.Igenex Jan.09IFA titer 1:40 IND IgM neg pos 31 +++ 34 IND 39 IND 41 IND 83-93 + DX:Neuroborreliosis Posts: 5850 | From Kentucky | Registered: Dec 2008
| IP: Logged |
TerryK
Frequent Contributor (5K+ posts)
Member # 8552
posted
Back to the subject line, my thought is how do we know that borrelia deep tissue infection produces antibodies in the first place? Blood supply is limited in deep tissues which is why we have trouble getting antibiotic penetration there. I guess I just assumed that deep tissue infection would be much less likely to produce antibodies but of course that may not be the case. I also assume that cysts don't produce antibodies but who knows?
Pinelady wrote: But I now believe it is a leaky vascular system also.
I know that leaky capilaries have a lot to do with the orthostatic hypotension that some of us get or at least that is the case for me according to the doctor who diagnosed mine.
From the second study you posted: Collectively, these data suggest that insufficient basal adenosine level and/or pathogen-induced disordered lymphoid purine homeostasis may serve as important prerequisite for promotion of inflammatory responses and further host's commitment to persistence of bacterial infection and arthritis development
I don't know if this is related without really digging but from what I read below (written by Rich Van Konynenburg, Ph.D.), combined with the info from the study you posted, it's possible that there is a relationship that could mean that treatment of the methylation cycle could normalize adenosine and thus allow borrelia to be less treatment resistant in some individuals. That is if this is the reason they are treatment resistant.
written by Rich Van Konynenburg, Ph.D. Adenosine is a product of the reaction that converts SAH to homocysteine. In some PWCs it is high, in some it is low, and in some it is in the reference range. I don't yet understand what controls the adenosine level, and I suspect there is more than one factor involved. In most PWCs who started with abnormal values, the adenosine level appears to be moving into the reference range with methylation cycle treatment, but more data are needed.
Posts: 6286 | From Oregon | Registered: Jan 2006
| IP: Logged |
Marnie
Frequent Contributor (5K+ posts)
Member # 773
posted
Horses: I'm really sticking my neck out here:
The bactericidal effect of Fab-CB2 is not dependent on the induction of spirochetal proteases but is dependent on the presence of Ca2+ and Mg2+.
Supplementation of Ca2(+)- and Mg2(+)-free medium with these cations restored the bactericidal effects of Fab-CB2.
The mechanism by which a Fab fragment of an antibody destroys a bacterium directly may represent a novel form of antibody-organism interaction.
PMID: 9125579
Duh...Mg levels DIVE at the outset of lyme (time of the rash). Antibodies take DAYS to be made. And it takes Mg and Ca to MAKE antibodies. Basic knowledge.
The trick/goal is to get ATP levels back up in the infected and weakened defense cells. This will drive Mg back into the cell where it (ahead of all other electrolytes) binds to ATP as Mg-ATP.
-------------------- Suspected Lyme 07 Test neg One band migrating in IgG region unable to identify.Igenex Jan.09IFA titer 1:40 IND IgM neg pos 31 +++ 34 IND 39 IND 41 IND 83-93 + DX:Neuroborreliosis Posts: 5850 | From Kentucky | Registered: Dec 2008
| IP: Logged |
TerryK
Frequent Contributor (5K+ posts)
Member # 8552
posted
Marnie wrote: The trick/goal is to get ATP levels back up in the infected and weakened defense cells. This will drive Mg back into the cell where it (ahead of all other electrolytes) binds to ATP as Mg-ATP.
I've been taking an herbal product that downregulates ATP in abnormal cells. It's called Paw Paw. Hopefully the cell dies and the infection inside the cell dies. It's used for malaria and cancer. Lots of research on it but I've read that a lot of it is not allowed to be published on the internet.
I thought this would make me more fatigued but it had the opposite effect. I feel it has made a difference with my hard to treat babesia infection but I have no proof of that.
-------------------- Suspected Lyme 07 Test neg One band migrating in IgG region unable to identify.Igenex Jan.09IFA titer 1:40 IND IgM neg pos 31 +++ 34 IND 39 IND 41 IND 83-93 + DX:Neuroborreliosis Posts: 5850 | From Kentucky | Registered: Dec 2008
| IP: Logged |
The Lyme Disease Network is a non-profit organization funded by individual donations. If you would like to support the Network and the LymeNet system of Web services, please send your donations to:
The
Lyme Disease Network of New Jersey 907 Pebble Creek Court,
Pennington,
NJ08534USA http://www.lymenet.org/