Hope for Chronic Bart and Lyme

i saw this on another forum and thought it worth posting here as i know there are alot of members who have either suspected or confirmed lyme and bart -

its pretty long - even though just a summary of some of his reccent trials - but the spoiler is he is showing a significant number of his sickest patients - even those that fail double dapsone therapy - are getting better with several rounds of even higher dose dapsone - pulsed for a few days at a time
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I would like to offer a gift to the Lyme disease community for May, Lyme Awareness month. As many of you know, I have been searching for short, safe and effective treatments for Lyme disease and associated co-infections for over 30 years. Dr Freeman and I worked feverishly over the last 5-6 weeks to submit an article to the journal Microorganisms, for their special issue on Ticks and Tick-borne Infections:
Horowitz, R.I.; Freeman, P.R. Efficacy of Short-Term High Dose Pulsed Dapsone Combination Therapy in the Treatment of Chronic Lyme Disease/Post-Treatment Lyme Disease Syndrome (PTLDS) and Associated Co-infections: A Report of Three Cases and Literature Review. Preprints 2022, 2022040296 (doi: 10.20944/preprints202204.0296.v1).
https://www.preprints.org/manuscript/202204.0296/v1

This treatment regimen, which needs to be replicated in large controlled trials, potentially represents a major advance in the treatment of Lyme and associated TBD's. Treatment using pulsed high dose dapsone combination therapy (HDDCT, 4 day pulses) illustrates that it is not only the length of time on persister drugs like DSF and dapsone, but it is also the DOSE that is critically important. Please take the time to read the three case studies and 25 patients who did this treatment protocol. These were highly resistant tickborne cases who had multiple abnormalities on the 16 point MSIDS map, including chronic babesiosis and Bartonellosis. Many of these chronically ill patients, even if they had some benefit from dapsone combination therapy in the past, had failed to achieve remission with 8 weeks of double dose dapsone combination therapy (DDDCT). We found that 8/25 patients achieved remission for three months or longer with one to three pulses of HDDCT (4 -8 day regimens), including several who were Bartonella FISH positive.

"Treatment results: Twenty-one of 25 patients (84 %) showed improvement of their tick-borne symptoms, and one patient had a temporary worsening of symptoms post therapy, secondary to a severe Herxheimer reaction. Thirty-two percent (8/25) had a resolution of all active Lyme symptoms post treatment for 3 months or longer even if there was evidence of prior active co-infections, including Babesia and Bartonella. Three out of 7 patients (43%) with an EM rash and history of PTLDS remained in remission, and the remainder, 57%, showed a mild-moderate improvement in underlying symptoms above their baseline functioning. Among 11 patients who were Babesia FISH positive, three (27 %) remained in remission, six improved (55%) and two (18%) had no change in sweats, chills, or flushing or dyspnea. Among 19 patients (76%) with a history of Bartonella exposure, 15/19 improved (79%), and four patients (21%) had no change in symptoms. Among 8 patients with proof of active Bartonella infection (PCR positive, FISH positive, and/or elevated VEGF), 3/8 (38%) remained in remission, and 5/8 (62%) improved their underlying symptomatology. Further examination of those patients revealed that among those who were Bartonella FISH positive, two out of four went into remission (50%) and the other two improved their underlying symptomatology by 10% to 20% above baseline functioning. The largest symptom improvement seen among this cohort treated with HDDCT were cognition 17/25 (68%), joint and muscle pain 16/25 (64%), fatigue 15/25 (60%), headache 9/25 (36%), neuropathy 5/25 (20%), insomnia 5/25 (20%), sweats/chills/flushing (20%), palpitations 2/25 (8%), tinnitus 2/25 (8%), dyspnea 1/25 (4%), and visual “snow” 1/25 (4%). "

As many of you know, there is no published 'cure' for chronic Bartonella. In the past, highly resistant Bartonella required either long term treatments with multiple intracellular antibiotics and/or use of medications like Gentamycin to achieve remission. This protocol uses oral, generic medication with excellent penetration into the CNS and was effective using short term, high dose pulses for patients who had failed prior protocols. This obviously needs to be confirmed in large, clinical trials, but having been in the field for over 30 years, I know when I have discovered something with great potential. It will up to clinicians in the field to replicate the study (the details are in the paper). I would suggest that the RCT that be performed, to answer the questions on CLD/PTLDS once and for all, is an 8 week double dose dapsone combination therapy regimen (DDDCT), and in those who fail to achieve remission (appx 50% based on prior published clinical studies) after all MSIDS variables have been addressed, is to have these patients undergo several rounds of high dose pulsed dapsone combination therapy (HDDCT) to evaluate response and remission rates.

This is also the first paper to be submitted to the scientific literature where two persister drugs were used simultaneously in a certain percentage of patients. In one patient, who did well with disulfiram (DSF) but failed to achieve remission, one 4 day pulse of HDDCT led to remission for 3 months or longer. This novel regimen potentially offers a brand new treatment approach for those who have failed long term oral and/or IV therapy. We still need however to find effective treatment regimens for babesia, which persisted in several patients (we are doing trials of tafenoquine now, read the paper) and we can't know the full long term results for Borrelia and Bartonella without longer term follow-up and performing this protocol in large numbers of chronically ill patients. That being said, this protocol helped certain very ill patients who were sick for decades.

Lyme community, governmental agencies, researchers: Please make sure we get a RCT performed on this protocol. It has the potential to answer many questions that have plagued the Lyme community for over 40 years. Having now published on over 340 patients who have done dapsone combination therapy, I can say with certainty, these persister drugs, dapsone and DSF, are a major advance for the Lyme and TBD community. And short term oral generic protocols with combination therapy offers potential answers while avoiding issues with antibiotic resistance. We now need to use scientific rigor to explore the use of these protocols, as it is described in the paper, in greater detail. This regimen is not without potential side effects however, and we explained in detail in the paper how we managed them effectively in our patient population. I will be doing my yearly training course for health care providers on Lyme and TBDS and the MSIDS model in early August of this year. For those practitioners who want to learn how to use this model in their chronically ill patients, and sign up for the training course, please contact Heather at: [email protected]

I am very excited to present this scientific investigation to the Lyme community for May, Lyme Awareness month. You have all been searching for durable cures and answers for your chronic illness. I have been doing my best to help you for over 30 years. I hope from the bottom of my heart, that this regimen of HDDCT and addressing MSIDS variables, will be part of the solution you have all been looking for.
Blessings,
Dr Richard Horowitz

Sorry if I sound like a party pooper, but I don’t find this news exciting. Am I remembering correctly that many people who have done this protocol had horrific herxes or were too afraid to even try it? I don’t like his line of thinking either. Sounds like he’s trying to use this protocol to prove a point to a stubborn, unbelieving medical community that chronic Lyme is real. At whose expense? Even for the few - 8 of 25 - who went into remission - what long term repercussions might they suffer from those high dose regimens that may be yet unknown? Just my 2 cents.

Frankly, I wouldn’t feel safe doing that unless it was inpatient treatment in a mold and chemical safe building in a padded room with trained doctors and staff and a facility that had detox modalities and all the varieties of herbs, supplements, and paraphernalia that we might find useful for riding out the horrors.

Thank you sir for posting this.

Unfortunately, Horowitz frequently sounds as if he can't accept this idea of his isn't the solution to Lyme. When will he admit Dapsone isn't appropriate for the majority of patients? When people begin taking ten tablets every day or what? Enough already with the Dapsone. He also sounds self-applauding when he writes that he has a "gift" to give us.

apologies to anyone who felt i was presenting this as a perfect solution.

i think that given what these infections do in our body - where the current state of medical technology is at present - versus the many sophisticated ways these pathogenic organisms have developed to survive inside their hosts long term - it seems to me that its very unlikely someone will suddenly stumble across a curative treatment that kills these multiple concurrent bacteria infections without causing us significant side effects.

even if some such miracle drug were found tomorrow - unless its already FDA approved (which again seems unlikely - given how many large scale drug screening studies have been done already) we are looking at at east 5 years till its available in the clinical setting for lyme patients.

even then - given the very high cost of developing such a drug - and the need for financial return on that investment in all models in use for such endeavours to date - we would be faced with a very high cost to the patient for its use - think in terms of 3yrs payback for investors on $5-$10m cost of development - which would put the cost of such treatment into the thousands of dollars range per course. which is out of reach for many - possibly even the majority of sufferers.

so for the foreseeable future - we patients appear to have a choice - between treating or not treating - and if we decide to treat - that choice amounts to choosing alternative approaches - or a drug treatment that is available and at least moderately effective, whilst also being affordable and accessible to the patient today.

most alternative approaches appear to have much less evidence base behind them than pharma drugs that have been through randomised control trials - so have to be taken on faith - and on the whole seem to work for only a small subset of patients - especially of the more ill patients.

so my assessment of this is that although of course its not ideal - and i do agree Horovitz is a self promotor - its worth remembering he has also done a great deal of good for the lyme community including sharing more information than most prominent LLMDs on how to diagnose and treat lyme disease, and standing on the HHS Tick borne disease working group inside the USA government apparatus which has helped to change awareness and policy at least a little in the right direction and make it harder for patients to be ignored.

the positives as i see them are

1, the drug has been shown to be effective in even some of the toughest cases who have failed many previous antibiotic protocols - including disulfiram ie the most hopeless cases who have very few options left to them

2, the effectiveness appears to increase with dose ( not something that happens with all conventional antibiotics)

3, the drug shows effectiveness for both bartonella and lyme concurrently

4, the dose does not need to be continuous to be effective - so getting away from regimes of years of antibiotics for lyme and especially bartonella - instead a few rounds of a few days appears to cure a decent proportion of the toughest cases ( that's actually pretty amazing - when you consider what else they have tried )

5, this opens a pathway to prove, via larger randomised controlled trials, that Post Treatment Lyme Disease Syndrome is the fictitious diagnosis we all know it to be - and that could be the final impetus to change health policy and insurance rules in the USA - and eventually around the world as, whether they admit it or not, most countries policy makers look to the USA CDC as a basis for their own policy making.

6, the drug is inexpensive - approx $30 per 1000x 100mg tablets - and available worldwide

so whilst its not perfect - and i also would be concerned about the adverse effects - we do not live in a perfect world - and so i think we have to take what positives we can where we can find them.

just my two cents

Post Edited (Garzie) : 5/3/2022 4:35:30 AM (GMT-6)

What are the most common side effects of this drug? Didn't Girlie use it?

its an old drug and a strong one at that

the common side effects are given here

https://www.rxlist.com/dapsone-side-effects-drug-center.htm#overview

in lyme patients the two clinically significant side effects that people like Horowitz try to manage are
1, anaemia driven by the folate blocking action of dapsone - high dose folate supplements are normally used to try to avoid this
2, methemoglobinemia - which is i think where the patients haemoglobin is oxidised more than it should be and the ability of the blood to carry oxygen is diminished causing breathlessness, dizziness, fatigue etc 50 to 100mg of methylene blue is usually used to prevent / counter this.

but by all accounts it tends to make people feel generally very rough

interestingly, if you read the prescribing guides for MD's for dapsone in its most typical use case - for leprosy - 100mg is typically given for 1-2 years without either of the above being mentioned and seems tolerable by most people - so it may well be that people with Lyme and Co just have a much harder time tolerating it

i noticed the pre-print page has a comments section for people to post any notes to the authors they think might be helpful -

i think this is a good feature as it encourages direct contact between interested parties and the authors/ researchers - we are after all stakeholders - so i have added something there

that is interesting Jason ....

if the 70 fold decrease in dapsone is true - makes me wonder if the rifampin is working mostly on bart in the liver where we know bart exists in chronic infection and could well be a reservoir - and where the drugs will be taken first for first pass detoxification - even if they do not make it into general circulation so well - and then dapsone - even in lower concentrations is still good in the CNS for instance.

well hunted Rainy

i was just thinking along similar lines -

ie if it takes a while for rifampicin to exert its dapsone plasma concentration lowering effects - then dapsone could reach good concentrations in the first few days - and since Horowitz seems to have demonstrated its doing its work in those first few days - that would fit

that paper says dapsone concentrations fell from day two to day 15 of combined rifampicin/dapsone - so presumably for a day or so concentrations were good/high

looking at the data tables in that study - they found only a 2-3 fold decrease in dapsone after 15 days
- rather than 70fold - and the levels in plasma were after 15 days still way higher than MIC for leprosy bacteria - not sure about the Dapsone MIC for Borrelia.....

Interesting Garzie!
We could probably narrow down the µM's for the biofilm forms from the tables here:

https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7523330/

Garzie said...
no wonder we are stuck with long courses and stubborn symptoms!

Yes, honestly, if we don't address biofilms we're basically throwing money and time down the drain. If you think about the odds of someone having chronic lyme without having any biofilms... I doubt that's even possible after it becomes chronic.

FeelingLymey said...
Thank you sir for posting this.

Unfortunately, Horowitz frequently sounds as if he can't accept this idea of his isn't the solution to Lyme. When will he admit Dapsone isn't appropriate for the majority of patients?

Probably when he gets from Dapsone -> Double Dapsone -> Quadruple Dapson -> Quintuple Dapsone and somebody dies. Wouldn't be surprised if some of his patients didn't end up with kidney or liver failure. He's at step three already so not far away we are.

In general it seems like he went the following route:
1. if a drug doesn't eradicate pathogens, increase the dose two fold
2. if a two fold increase didn't eradicate pathogens but patient still alive, increase the dose two fold
3. repeat step 2 until either of them is still alive