Emerging Stratton Protocol 4/2008: a new approach to an old set of problems

Emerging Stratton Protocol 4/2008: a new approach to an old set of problems

Reported by Jim K

A number of dilemmas appear in treating Cpni. As we all know here at Cpnhelp, treating with protein-synthase inhibitors alone induces chlamydial persistence---conversion to the cryptic/persistent form of "aberrant" non-replicating RB's. Infectious EBi's still remain in extracellular fluids and tissues to reinfect once antibiotics are withdrawn. The CAPi which addresses all three phases has been the answer to this multi-phase nature of Cpn, but it has problems of its own. The biggest problem is the tendency to induce strong reactions to treatment which have been attributed to bacterial release of LPSi endotoxini and inflammatory HSP60 endotoxin, and to secondary porphyria. This makes for the additional problem, which is the requirement of a gradual, slow, and long term process of treatment when addressing Cpn infections. There are more potent anti-chlamydials around, but using them kills the Cpn too fast for the body to tolerate resulting in mass apoptosisi of infected cells and subsequent organ failure or neutropeniai.

Existing CAP protocols have been focused on first halting replication, kill a lot of the RBs and force the rest into non-metabolizing and non-replicating cryptic/persistent form, with the notion that this will stop the progression of the disease. The cryptic Cpn can then be dealt with at one's leisure, gradually over time.

But emerging research has been suggesting that Cryptic Cpn is not benign even if it is not replicating. Cryptic Cpn is essentially a stressed form of Cpn, and stress causes it to generate of Heat Shock Protein (HSP60). HSP60 is many times more inflammatory than LPS endotoxin. LPS endotoxin is the one that causes the fever and chills and is released mostly when RB's are killed and lyse, or when EB's are killed. The inflammation of plaques in cardiovascular disease has been associated specifically with Cpn HSP60 and with the persistent (cryptic) form of Cpn. Inflammationi by HSP60 when forcing Cpn into cryptic form may in fact, in Dr. Stratton's current view, be the major cause of so-called die-off reactions. "So-called" because HSP60 is induced not by the bacteria dying off, as the release of LPS is, but rather by the Cpn surviving in a stressed, cryptic form.

Additionally, ongoing disease and tissue damage may be occurring as much from the cryptic form, this is apparently so in heart and lung disease, as it is occurring from replication and sub-optimal cell functioning by infected cells. Autoimmune diseases, for example, also exhibit antibodies to HSP.

Some additional observations have collected together to add to this shift in viewpoint. A medical colleague who has treated Cpn through IV treatments using all the agents for all.

So this new approach is based on inducing existing persistent/cryptic Cpn to convert back to RB form and limit the conversion into persistent/cryptic form by the threat of antibiotic.

Paul Griffith, a non-medical friend researching this whole area, found that supplementing pyruvate might do the trick. Pyruvate may also have other beneficial effects. Basically, this approach uses 6 grams of calcium pyruvate one hour before taking the antibiotics, and an additional 6 grams if needed later for reactions when the antibiotics exert their effect. In theory the first dose of pyruvate encourages the cryptic/persistent form of Cpn to convert back into RB (replicating) form by supplying it with a ready source for generating cellular energy.

In RB form it is:

a) Susceptible to the regular antibiotics and,

b) Can be killed when it is not in "stress" so it is not stimulated into producing and releasing so much the highly inflammatory HSP60.

In essence, you are feeding it until it is comfy and sprawling in its chair at the dining table, and then whacking it upside the head before it can spew its hot sauce at you. I know, a terrible metaphor, but it's the best I could do. You get the point?

In theory this approach should limit turning Cpn into cryptic form by the treatment and make it more directly susceptible to the protein synthase inhibitors (like doxycycline and azithromycin).

In theory, it should also winnow down the cryptic load one has acquired, along with its inflammatory affects, without needing to kill it directly with flagyl. Flagyl would be used to "clean up" persistent/cryptic forms not gotten to by this approach.

Also in theory, the second dose of pyruvate for reactions to the antibiotics should supply the fundamental cellular energy needed to help lower the generation of porphyrins.

Dr. Stratton outlines below the experimental protocol that they have found, in a small subset of cases, to offer less difficult and faster treatment of Cpn. Please remember that this is experimental, and has not been clinically used with a wide array of Cpn related diseases yet, so should not be engaged in without a knowledgeable clinician to monitor treatment.

From Dr. Charles Strattoni, 4/24/08

My thoughts on the current Stratton Protocol is that this is a work in

progress, but given what we know now, it would be the following:

NACi 600 mg one a day to test "Chlamydial Load."

If no reaction, go to 1,200 mg twice a day.

If a severe reaction ("Flu-Like" reaction), use low dose prednisone (5 mg per day) for the first few weeks of therapy.

The next step would be two weeks of a macrolide (clarithromycin preferred because of higher levels obtained, roxithromycin, or azithromycin) with 6 grams of pyruvate given 1 hour prior to the antibiotic dose. In addition, 400 mg of Ibuprofen should be taken twice a day along with 1,200 mg of NAC twice a day. For those with severe reaction, low dose prednisone 5 mg per day. For those who get a severe reaction with the pyruvate/macrolide, 3-4 days of low dose prednisone could be tried. Also, using additional pyruvate (3-6 grams) for reaction should be tried.

For those that have a major side effect on the pyruvate/macrolide alone, I'd continue to treat with the macrolide alone until the side effects are manageable. For those that don't, I'd add doxycycline 100 mg twice a day with 6 grams of pyruvate 1 hour before. Continue the NAC and Ibuprofen.

After two weeks of doxycycline if all went well, I'd add metronidazolei 500mg twice a day with 6 grams of pyruvate before that. If a reaction is seen.

To the metronidazole, I'd then pulse it until the reactions were manageable.

If minimal reactions, I'd continue therapy for at least 1 year and then recheck titers. If titers were low, I'd add rifampin or rifabutin (preferably), using the rifamycin with pyruvate taken 1 hour before the rifamycin. If no reactions to this, I'd consider the therapy to be complete.

I would continue to monitor titers every several years. If the titers increased, I'd retreat with 6 months of clarithromycin or roxithromycin plus rifabutin plus pyruvate and ibuprofen. I'd continue the NAC for life.

For people on the existing CAP who are being switched:

For those on the current Doxycycline, Azithromycin, Metronidazole, and NAC protocol, my thoughts are that they should first switch from Azithromycin 250 MWF to Clarithromycin 500 mg twice a day (or Roxithromycin) and then add pyruvate

Dr. Stratton adds that Levaquin may be used instead of Clarithromycin for a short period (one month) as it has excellent activity for a short period of time. Clarithromycin = higher levels. Levoquin Both when combined with pyruvate theoretically will provide better killing.

Severe neutropenia among healthy volunteers given rifabutin in clinical trials

Glen Apseloff, MD, Clinical Pharmacology & Therapeutics, December 2003

This is probably why those "big" studies of 6 months of azithromycin showed no lowering of risk of heart disease---it's not caused by the replicating form of Cpn and the idiots never asked a microbiologist about what might kill cryptic Cpn!

Heat shock protein 60 from Chlamydia pneumoniae elicits an unusual set of inflammatory responses via Toll-like receptor 2 and 4 in vivo.

Da Costa CU, Wantia N, Kirschning CJ, Busch DH, Rodriguez N, Wagner H, Miethke T.

Institute of Medical Microbiology, Immunology and Hygiene, Technical University of Munich, Munich, Germany. Eur J Immunol. 2004 Oct;34(10):2874

Effects of Repeated Chlamydia pneumoniae Inoculations on Aortic Lipid Accumulation and Inflammatory Response in C57BL/6J Mice†

Liisa Tormakangas, et al

INFECTION AND IMMUNITY, Oct. 2005, p. 6458-6466 Vol. 73, No. 10

Worsened MRI Findings During the Early Period of Treatment with Penicillin in a Patient with General Paresis.

Zhang SQ, Wan B, Ma XL, Zheng HM.

J Neuroimaging. 2007 Nov 6

Role of Heat Shock Proteins in Protection from and Pathogenesis of Infectious Diseasesi<

Ulrich Zugel and Stefan H.E. Kaufmann

Microbiology Reviews, Jan. 1999, p. 19-39 Vol. 12, No. 1

Ethyl pyruvate: a novel anti-inflammatory agent

M. P. Fink

2007 Blackwell Publishing Ltd Journal of Internal Medicine 261; 349-362