Wheldon Cpn protocal comments

[Guest guest]

I had these comments from Wheldon stored on my

computor. They are from an MS treatment forum, I don't

have the url right now. Thought they would contribute

to the general discussion about inflammation and

host/infection interactions, as well as to those of us

dealing with Cpn.

Jim

From the MS forum:

2004

Posts: 162

Location: England

PostPosted: Fri Sep 10, 2004 1:23 pm Post subject:

Reply with quote

Hello again, Byron,

This is the reply given to me by my husband, ,

aka Dr. Wheldon FRCPath! While he was working

hard on this, I was working hard on repairing a

damaged canvas, so now we must both go for some

dinner.

Quote:

A response to Byron's post.

Your points are acutely observed and well thought out.

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.

[Guest guest]

Jim:

Thanks very much for posting this.

Barb

> I had these comments from Wheldon stored on my

> computor. They are from an MS treatment forum, I don't

> have the url right now. Thought they would contribute

> to the general discussion about inflammation and

> host/infection interactions, as well as to those of us

> dealing with Cpn.

> Jim

> From the MS forum:

> 2004

> Posts: 162

> Location: England

>

> PostPosted: Fri Sep 10, 2004 1:23 pm Post subject:

> Reply with quote

> Hello again, Byron,

> This is the reply given to me by my husband, ,

> aka Dr. Wheldon FRCPath! While he was working

> hard on this, I was working hard on repairing a

> damaged canvas, so now we must both go for some

> dinner.

>

> Quote:

> A response to Byron's post.

>

> Your points are acutely observed and well thought out.

> 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.