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

Abstract

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 seven- to eight-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. A total of 25 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 × 3–4 days and/or 200 mg BID × 4 days), depending on persistent symptoms. The majority of patients noticed sustained improvement in eight major Lyme symptoms, including fatigue, pain, headaches, neuropathy, insomnia, cognition, and sweating, where dapsone dosage, not just the 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.

Superior Efficacy of Combination Antibiotic Therapy versus Monotherapy in a Mouse Model of Lyme Disease

“…The combinations of dapsone with rifampicin, clofazimine or both are already the therapies of choice to treat multidrug-resistant M.tuberculosis and leprosy have ample evidence for safety and tolerability in that population(46- 49). Furthermore, clinical studies have demonstrated efficacy of dapsone combination therapy in Lyme disease patients with chronic symptoms/PTLD(50)(51)(52). The results of this study and welldocumented use in humans make this combination attractive for further investigation.The presence of Bb DNA in tissues and xenodiagnostic tick midguts in the absence of Bb RNA occurred in mice in most combination therapy groups.…”

Comparison of the Efficacy of Longer versus Shorter Pulsed High Dose Dapsone Combination Therapy in the Treatment of Chronic Lyme Disease/Post Treatment Lyme Disease Syndrome with Bartonellosis and Associated Coinfections

“…In five separate clinical studies involving more than 365 patients, dapsone combination therapy led to statistically verified improvement in relieving eight major Lyme symptoms in our patients, including sweats/chills, fatigue, joint, muscle, and/or nerve pain, headaches, insomnia, and cognition [ 50 , 51 , 102 , 103 , 104 ]. In a 6th clinical case study involving chronic LD and Behçet’s disease (a severe multisystemic autoimmune illness), a patient who had been ill for 20 years reported significant symptom improvement when pyrazinamide (PZA) was added to dapsone combination therapy (DDSCT) despite a history of failing multiple disease-modifying antirheumatic drugs (DMARDS) [ 105 ].…”

“…Among 14 antibiotics and 25 antibiotic combinations for activity against stationary phase B. henselae in culture, methylene blue and rifampin were the most active agents against the biofilm B. henselae after 6 days of drug exposure, whereas both rifampin and methylene blue and azithromycin and methylene blue completely eradicated the biofilm form of B. henselae in culture after treatment for 6 days [ 101 ]. To date, only two studies have examined using rifampin, azithromycin, and methylene blue along with tetracycline, rifampin, and dapsone in the treatment of chronic Lyme, Babesia , and chronic bartonellosis, with variable results [ 102 , 103 ].…”

“…Among 11 patients with a history of Bartonella exposure and no evidence of active infection (biopsy negative, PCR negative, FISH negative), 5 (45%) remained in remission, and 6 (55%) improved their underlying symptomatology [ 102 ]. When higher-dose pulse dapsone therapy (200 mg PO BID) was used for 4 days in those who failed to go into remission after 8 weeks of DDDCT, the majority of patients noticed sustained improvement in eight major Lyme symptoms [ 103 ]. A total of 32% (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 .…”

“…Of 19 patients (76%) with a history of Bartonella exposure, 15/19 improved (79%), and among 8 patients with proof of active Bartonella infection, i.e., PCR positive, FISH positive, and/or elevated vascular endothelial growth factor (VEGF), 3/8 (38%) remained in remission, with two out of four who were Bartonella FISH positive going into remission (50%). The conclusion of the study was that the higher dapsone dosage, not just the treatment length, positively affected outcomes [ 103 ].…”