Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Version 1 : Received: 27 April 2022 / Approved: 29 April 2022 / Online: 29 April 2022 (10:12:41 CEST)

A peer-reviewed article of this Preprint also exists.

Journal reference: Antibiotics 2022
DOI: 10.3390/antibiotics11070912


Lyme disease and associated co-infections are increasing worldwide and approximately 20% of individuals develop chronic Lyme disease (CLD)/Post-Treatment Lyme Disease Syndrome (PTLDS) despite early antibiotics. A 7–8-week protocol of double dose dapsone combination therapy (DDDCT) for CLD/PTLDS results in symptom remission in approximately 50% of patients for one year or longer, with published culture studies indicating higher doses of dapsone demonstrate efficacy against resistant biofilm forms of Borrelia burgdorferi. The purpose of this study was therefore to evaluate higher doses of dapsone in the treatment of resistant CLD/PTLDS and associated co-infections. Twenty-five patients with a history of Lyme and associated co-infections, most of whom had ongoing symptoms despite several courses of DDDCT, took one or more courses of high dose pulsed dapsone combination therapy (200 mg dapsone X 3-4 days and/or 200 mg BID x 4 days), depending on persistent symptoms. The majority of patients noticed sustained improvement in 8 major Lyme symptoms, including fatigue, pain, headaches, neuropathy, insomnia, cognition, and sweating, where dapsone dosage, not just treatment length, positively affected outcomes. High dose pulsed dapsone combination therapy may represent a novel therapeutic approach for the treatment of resistant CLD/PTLDS, and should be confirmed in randomized, controlled clinical trials.


dapsone; disulfiram; chronic Lyme disease; Post-Treatment Lyme Disease Syndrome; babesia; bartonella; persisters; biofilms.



Comments (2)

Comment 1
Received: 29 April 2022
Commenter: Christine Small
The commenter has declared there is no conflict of interests.
Comment: I see no mention of disulfiram in the article.
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Comment 2
Received: 6 May 2022
Commenter: Benjamin Dangerfield
The commenter has declared there is no conflict of interests.
Comment: This is promising work in terms of showing significant efficacy in the toughest to treat patient groups.

a couple of points that I think could add to the papers impact

1, dapsone is known to be a hard drug to tolerate due to strong side effects in this patient population - it also has a long list of potentially serious adverse events associated with its use. eg toxic dermatologic reactions and psychosis. But I see very little mention of the patient experience of these side effects - which surely is an important consideration to cover for patients and clinicians and any future researchers. Did your patent population experience any of the severe adverse events listed for this drug? What should the patient and clinician expect in terms of severity of Herxhiemer like reactions? if variable - how many patients had to stop or pause treatment due to the severity - how was this managed? etc - such data points would seem to be appropriate to document in the paper.

2, overall the paper is rather text dense - long paragraphs of text describing percentages typically have greater impact on the intended audience when displayed in graphical format

for instance - would it not be possible to show that double dose dapsone therapy achieved remission in ~50% of the original patient population - and pulsed high dose dapsone therapy achieved remission in a further 30+% of those that failed double dapsone.
so now overall you can demonstrate visually, perhaps via a bar chart, an approach that gets 65+% of the toughest cases into remission - and most of the reminder have useful improvements - which is I think the central message.
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