Submitted by Jim K on Tue, 2005-08-23 22:16

Edited from post on http://www.thisisms.com/modules.php?name=Forums&file=viewforum&f=28

I've learnt a lot in the last year through treating a number of patients with MS. As a patient goes through RRMS, he or she tends to accrue progressive deficits; this is often unnoticed at first, but seems to equate with rising bacterial load. It's almost as though there were two parallel components to the disease, an idea which is supported by studies of sequential MRI data. I've recently seen two patients with early RRMS who have had no reactions on starting antibiotics. Both are improving, and have lost many of their accrued deficits. In the case of one patient, the deficits were so slight that the patient noticed them only when they started to go. In later RRMS and in early SP disease the reactions are often more severe; one assumes that this is because the bacterial load has grown. As the disease progresses ever deeper the immune system usually gains the upper hand and destroys the organism. It's a hard-won victory, and there may be immense collateral damage. At this stage there is little or no reaction to antibiotics, and little benefit from treatment. But a trial is worthwhile.

These acute reactions on starting doxycycline/minocycline are probably due to a freezing of bacterial protein synthesis. The organisms are intracellular; one of the host-cell defences against intracellular infections is host-cell suicide; this releases bacterial antigen so that antibodies can be raised against it. In an amazing evolutionary strategy, Chlamydia pneumoniae can prevent host-cell suicide. This, however, requires continuous synthesis of a specific protein. (It is now known that Chlamydia pneumoniae in the CSF of MS patients actively makes this protein; furthermore, persons with MS have antibodies to the same protein.) So the infected host cells are now free to die, releasing their bacteria; these cannot survive in their current state and die also. Their death releases endotoxins, which are a component of the bacterial cell wall. (In an interesting parallel, another chlamydia with a similar strategy is associated with a very rare periocular lymphoma which shrinks when treated with tetracycline.) Unfortunately, a lot of bacteria remain in other cell-lines, and need to be actively killed.

Roxithromycin is a powerful immunomodulator, and partially suppresses the immune system, allowing the toxins to be flushed away rather than evoking an inflammatory response. Both doxycycline and minocycline are immunomodulatory too.

The risk of the emergence of a resistant mutant is, as you say, an unpleasant thought. Workers have tried to do produce resistance in the laboratory with negative results. I suspect the risk of resistance emerging is actually minimal. Resistant mutants usually emerge in rapidly growing cultures treated with minimally inhibitory concentrations of antibiotic; this gives the right evolutionary drive to produce resistance. The organism is in 'tickover' mode in chronic infections like MS and some of the evolutionary pressure is removed. Using two antibiotics which act synergically certainly reduces any risk.

So I should be in no hurry to start metronidazole. Long-term minocycline is likely to be effective, with roxithromycin if this can be obtained, together with full supplementation - I'd allow three months before metronidazole is considered; and it should be started gently. Having witnessed a bad reaction to minocycline it would be beneficial to 'waste' as many organisms as possible before starting the killing phase.

One interesting rider. Serology is usually negative in MS, but this is not always the case. I've just seen a man with early PPMS (18 months), retinal vasculitis and follicular conjunctivitis. He has raised antibodies to Chlamydia pneumoniae, with an MIF of 1:1024 and high Chlamydia pneumoniae-specific IgA. (This is a fairly reliable indicator of persistent infection.) It's early days, but his carer reports good early improvement. His neurologist was very dismissive (rudely so), so I must write to him and tell him the serology results.

MS is multifactorial. A number of genes seems to play a part in the expression of the disease. I have recently seen a patient with a multisystem disorder including retinal vasculitis and Crohn's disease. She had grossly elevated Chlamydia pneumoniae serology. An MRI scan showed typical white-matter hyperintensities which transected the long motor tracts in several places. However, she had no focal neurological signs. Presumably she was fortunate in her genetic make-up.

Work has been done in many different disciplines, in microbiology, immunohistology, cellular biochemistry and neuroimmunology. The science is all there, but not many people have yet joined up the dots.

And you are right; treating someone close to you for a large-load Chlamydia pneumoniae infection of the brain is an emotional roller-coaster.

Comments

"Roxithromycin is a powerfulimmunomodulator, and partially suppresses the immune system, allowing the toxins to be flushed away rther than evoking an inflamatory response..." Can someone please expand on this? I do seem to have less tendon pain since starting Roxithromycin, and occasional periods throughout the day of increased well being, but am now concerned that it is an immune suppression effect, rather than the roxithromycin eradicating organisms and addressing infection (whether that infection be Borrelia, CPn, or both). Is this the "anti-inflamatory antibiotic effect"?  DX: +Borrelia, +Babesia, +CPn, suspected Bartonella  CAP: Omnicef, Minocycline, Roxithromycin, pulsed Tindamax

DX: Borrelia, Babesia, CP, suspected Bartonella CAP: Omnicef, Minocycline, Tindamax

Thanks Louise, but is Roxy immunosuppressant or not? Does anyone know what D.W. was aluding to in his previous comment?  DX: Borrelia, Babesia, CP, suspected Bartonella CAP: Omnicef, Minocycline, Tindamax

DX: Borrelia, Babesia, CP, suspected Bartonella CAP: Omnicef, Minocycline, Tindamax

Andrea, I believe it is not rather than it is also working toward eradicating organisms.   I see it as a very good thing.  LouiseCFS/ME.CPnPositive.BbPositive.WheldonCAPbegan6/24/07. NowNAC,Doxy, Roxi, TiniPulse#5 day 3 in process. Cholestyramine at Bedtime for Phorphoria & liposacaride Endotoxin Die-Off Experiences.

  • CAP(TiniOnly): 06/07-02/09 for CFS
  • MethylationProtocolSupplements: Started08/08
  • Intermtnt CAP: 02/09-02/10
  • Full MethylProtocol & LDN 02/09
  • Off CAP: 02/10, cont LDN & MethlyProtocol support

Is there any reason for using Roxi over Zith or vice versa? Also, what about Flagyl over Tini?  MP for 3 1/2 yrs. NAC 1200 mg/2x day, Iodoral 12.5 mg, myco+ I (still) want my life back! CFIDS/FMS, Hashimoto's, Psoriasis, PA, IBS, Secondary Addison's When I change what I believe I change what I do

NAC 2.4g, Zith 250mg/MWF, mino 200mg, Tini 5day/1g/5 pulses, ValcyteSupplements, CFIDS/FMS, Hashimoto's, Psoriasis, PA, IBS, Sec Addisons Don't believe everything you think!  

 He means "immunomodulatory," meaning that it helps modulate the body's inflammatory reaction to the bacterial kill. It doesn't suppress the immune system, it suppresses only certain cytokine response (the immediate innate immune response) which can actually help prevent tissue damage from inflammation and necrosis. The acquired immune response is not affected, so no worries.Roxy seems to be more immunomodulatory than Zith, which may be only because it is in your bloodstream longer (twice a day dosing) while zith has some immunomodulatory effect but is rapidly taken up into the cells. Roxy is supposed to have better tissue penetration than Zith, especially in the Central Nervous System. I tried it myself a while back and didn't notice any difference. I recently went back to it and am finding it leaves me more clear headed than zith so I'm sticking with it for now. A lot of MS folks find it helps modulate their reactions to inflammation from bacterial kill and result in less decrement of function. I'm hoping that Dr. Stratton will take a look at it in the Cpn Lab once he begins his research... soon! CAP for Cpn 11/04. Dx: 25yrs CFS & FMS. Protocol: 200mg Doxy, 250mg MWF Azith, Tini 1000mg/day pulses; Vit D1000 units, Iodoral 50mg, T4 & T3

Thanks Jim, that helps set my mind at ease!Andrea   DX: Borrelia, Babesia, CP, suspected Bartonella CAP: Omnicef, Minocycline, Tindamax

DX: Borrelia, Babesia, CP, suspected Bartonella CAP: Omnicef, Minocycline, Tindamax

"Roxithromycin is a powerful immunomodulator, and partially suppresses the immune system, allowing the toxins to be flushed away rather than evoking an inflammatory response" This is an incredibly important observation IMHO which has potentially massive repurcussions in how we treat this disease. I've been meaning to post for a while about my experiences re: tini and flagyl. I believe that tini is a powerful immunomodulator, much in the same vein as Roxi. Together they pack a powerful immunomodulatory punch. I get little or no reaction from them. Also I very much get the impression that toxins are being "flushed away"  by tini as DW so eloquently puts it, rather than causing an immune reaction.  Flagyl on the other hand knocks me sideways. Lots and lots of inflammation. I call flagyl the "scorched earth" approach. It works, but you can get a lot of collateral damage. Many of us tend to associate progress with herxing, which for Cpn generally means inflammation type reactions. No pain, no gain right? It seems not necessarily so, which can only be good news. CFS. Started CAP 03-07. Currently: Roxi 600mg + INH 600mg + Tini 1000mg. 10 Pulses done. Sauna every other day. D 7200IU

Hunter: Don't think - experiment

Garcia, Do you feel you're noticing improvement without having to deal with the "scorched earth" approach? This is very important to me as I decide which abx to use. (hdwhit seemed to be having less reaction too from Roxi in the latest pulse HERE) I already have close to a yr's worth of Z so will need to take that for now when I begin but am fearing the dreaded Flagyl and if there's a softer way bring it on... I want good results as we all do, but with the least amount of pain and suffering. I get enough of that from daily living! Embarassed MP for 3 1/2 yrs. NAC 1200 mg/2x day, Iodoral 12.5 mg, myco+ I (still) want my life back! CFIDS/FMS, Hashimoto's, Psoriasis, PA, IBS, Secondary Addison's When I change what I believe I change what I do

NAC 2.4g, Zith 250mg/MWF, mino 200mg, Tini 5day/1g/5 pulses, ValcyteSupplements, CFIDS/FMS, Hashimoto's, Psoriasis, PA, IBS, Sec Addisons Don't believe everything you think!  

Reenie, If you are dreading Flagyl you could start with Tinidazole.  It is easier on the empty stomach.  LouiseCFS/ME.CPnPositive.BbPositive.WheldonCAPbegan6/24/07. NowNAC,Doxy, Roxi, Full Tini Pulse#5 day 4 in process. Cholestyramine at BedtimeforPhorphoria&liposacarideEndotoxinDie-OffExperiences.

  • CAP(TiniOnly): 06/07-02/09 for CFS
  • MethylationProtocolSupplements: Started08/08
  • Intermtnt CAP: 02/09-02/10
  • Full MethylProtocol & LDN 02/09
  • Off CAP: 02/10, cont LDN & MethlyProtocol support

Reenie I don't want to put anyone off using flagyl. The great thing about flagyl is that you can feel it working. Psychologically thats very reassuring.I'm sicker than most people here so I really have to minimize reactions. My body just can't cope with much in the way of inflammation.  Both drugs have their ups and downs. My personal opinion is that both should be tried. What Louise said is an excellent recommendation - start off on tini. Then if at some stage you feel up to it give flagyl a try. CFS. Started CAP 03-07. Currently: Roxi 600mg + INH 600mg + Tini 1000mg. 10 Pulses done. Sauna every other day. D 7200IU

Hunter: Don't think - experiment

Louise and Garcia, Yes, I am dreading Flagyl and welcome the idea of starting pulses with Tini if it will make like more bearable.  I think that'll be the plan for starters anyway, when I get to that point.  Wink  MP for 3 1/2 yrs. NAC 1200 mg/2x day, Iodoral 12.5 mg, myco+ I (still) want my life back! CFIDS/FMS, Hashimoto's, Psoriasis, PA, IBS, Secondary Addison's When I change what I believe I change what I do

NAC 2.4g, Zith 250mg/MWF, mino 200mg, Tini 5day/1g/5 pulses, ValcyteSupplements, CFIDS/FMS, Hashimoto's, Psoriasis, PA, IBS, Sec Addisons Don't believe everything you think!  

"At this stage there is little or no reaction to antibiotics, and little benefit from treatment.  But a trial is worthwhile".  I was totally surprised (schocked) when I read this.  I thought that D.W.'s wife, Sara, had SPMS.  Am I reading this statement wrong?Cry  I hope so!!

Mary AnnSPMS. Dx 1991. EDSS 6.0, 6.5, 6.9; Weldon CAP. started 3/08.  All supps, NAC, Doxy, Azrith, 13 flagy pulses, 5th tini pulse 11/13/09, 19 total pulses, no improvements, worsening condition 

That was confusing, but I think what he was saying that in late SPMS, your immune system usually has found a way to beat the CPn itself, but in doing so has caused far more damage. By that point, CPn has self-limited and abx treatment may no longer help, but in doing so caused a great deal of damage.I had to scratch my head when I read that, too.Tennessee, USA - Bb positive w/neuro involvement, suspected CPnDoxy/Samento for Bb 2005-2007Started CAP 4/19/08 - NAC 2400mg, Doxy 200mg, Zithro 250mg M/W/F

Tennessee, USA - Bb positive w/neuro involvement, suspected CPnDoxy/Samento for Bb 2005-2007Started CAP 4/19/08 - NAC 2400mg, Pyruvate 6g, Doxy 200mg, Zithro 250mg M/W/F, Metro pulses @ 3x500mg

I read it the same way. That there comes an advanced stage where the abx can no longer do much to fix things as the damage is too severe but it's worth giving it a go.Berkshire, UK. Diagnosed RRMS Feb 4th 2008.NAC 600mg Feb 9th. Increased to 2400mg Feb 19th plus all supplements. No GP/Neuro support. Self medicating with assistance from David Wheldon. Started Doxy 100mg 20th April 200

Berkshire, UK. Diagnosed RRMS Feb 4th 2008.NAC 2400mg. All supps. Doxy 200mg. Zith 250mg. Metro 400mg.No GP/Neuro support. Self medicating with help from David Wheldon. Started CAP 20th April

However, isn't it true that following through with the CAP will stop further progression, even though present damage may not be reversed?  That in itself is pretty positive.   Mary AnnSPMS. Weldon CAP; 3/10/08  NAC 2400, Doxy & Azith.

Mary AnnSPMS. Dx 1991. EDSS 6.0, 6.5, 6.9; Weldon CAP. started 3/08.  All supps, NAC, Doxy, Azrith, 13 flagy pulses, 5th tini pulse 11/13/09, 19 total pulses, no improvements, worsening condition 

Most everyone here was only hoping to stop progression, but recoveries abound. The body may not be able to rebuild every little thing, but once the immune system is allowed to do its job properly again, and once new neural pathways are created and reinforced, a lot can come back.

The difference between what we do and what we are capable of doing would suffice to solve most of the world’s problems.  Mohandas Gandhi

The difference between what we do and what we are capable of doing would suffice to solve most of the world’s problems. Mohandas Gandhi

I think the point he was making was that in some advanced cases the immune system has already put down the CPn on it's own. CAP may not be able to help because there are no bugs left to kill. He didn't elaborate on why he thinks that may be true, but that may be related to personal observation. As a point of support, in the Vanderbilt study of 8 patients, all 4 of the CAP patients were cleared of CPn by CAP, but one of the placebo spontaneous cleared without abx help. If the immune system finally gets with the program and clears the infection, no further treatment is possible. The problem he alluded to, however, is that in the process of clearing the infection, the immune system causes extreme damage to the body.Tennessee, USA - Bb positive w/neuro involvement, suspected CPnDoxy/Samento for Bb 2005-2007Started CAP 4/19/08 - NAC 2400mg, Doxy 200mg, Zithro 250mg M/W/F

Tennessee, USA - Bb positive w/neuro involvement, suspected CPnDoxy/Samento for Bb 2005-2007Started CAP 4/19/08 - NAC 2400mg, Pyruvate 6g, Doxy 200mg, Zithro 250mg M/W/F, Metro pulses @ 3x500mg