Evaluation and 1-year follow-up of patients presenting at a Lyme borreliosis expertise centre: a prospective cohort study with validated questionnaires.

OBJECTIVES: To describe the course of symptoms reported by patients with symptoms attributed to Lyme borreliosis (LB) without being subsequently diagnosed with LB. METHODS: We performed a prospective cohort study with patients presenting at the outpatient clinic of two clinical LB centres. The primary outcome was the prevalence of persistent symptoms, which were defined as clinically relevant fatigue (CIS, subscale fatigue), pain (SF-36, subscale bodily pain), and cognitive impairment (CFQ) for ≥ 6 months and onset < 6 months over the first year of follow-up. Outcomes were compared with a longitudinal cohort of confirmed LB patients and a general population cohort. Prevalences were standardised to the distribution of pre-defined confounders in the confirmed LB cohort. RESULTS: Participants (n = 123) reported mostly fatigue, arthralgia, myalgia, and paraesthesia as symptoms. The primary outcome could be determined for 74.8% (92/123) of participants. The standardised prevalence of persistent symptoms in our participants was 58.6%, which was higher than in patients with confirmed LB at baseline (27.2%, p < 0.0001) and the population cohort (21.2%, p < 0.0001). Participants reported overall improvement of fatigue (p < 0.0001) and pain (p < 0.0001) but not for cognitive impairment (p = 0.062) during the follow-up, though symptom severity at the end of follow-up remained greater compared to confirmed LB patients (various comparisons p < 0.05). CONCLUSION: Patients with symptoms attributed to LB who present at clinical LB centres without physician-confirmed LB more often report persistent symptoms and report more severe symptoms compared to confirmed LB patients and a population cohort.

Metabolic Response in Patients With Post-treatment Lyme Disease Symptoms/Syndrome.

BACKGROUND: Post-treatment Lyme disease symptoms/syndrome (PTLDS) occurs in approximately 10% of patients with Lyme disease following antibiotic treatment. Biomarkers or specific clinical symptoms to identify patients with PTLDS do not currently exist and the PTLDS classification is based on the report of persistent, subjective symptoms for ≥6 months following antibiotic treatment for Lyme disease. METHODS: Untargeted liquid chromatography-mass spectrometry metabolomics was used to determine longitudinal metabolic responses and biosignatures in PTLDS and clinically cured non-PTLDS Lyme patients. Evaluation of biosignatures included (1) defining altered classes of metabolites, (2) elastic net regularization to define metabolites that most strongly defined PTLDS and non-PTLDS patients at different time points, (3) changes in the longitudinal abundance of metabolites, and (4) linear discriminant analysis to evaluate robustness in a second patient cohort. RESULTS: This study determined that observable metabolic differences exist between PTLDS and non-PTLDS patients at multiple time points. The metabolites with differential abundance included those from glycerophospholipid, bile acid, and acylcarnitine metabolism. Distinct longitudinal patterns of metabolite abundance indicated a greater metabolic variability in PTLDS versus non-PTLDS patients. Small numbers of metabolites (6 to 40) could be used to define PTLDS versus non-PTLDS patients at defined time points, and the findings were validated in a second cohort of PTLDS and non-PTLDS patients. CONCLUSIONS: These data provide evidence that an objective metabolite-based measurement can distinguish patients with PTLDS and help understand the underlying biochemistry of PTLDS.

Prospective Evaluation of the Frequency and Severity of Symptoms in Lyme Disease Patients With Erythema Migrans Compared With Matched Controls at Baseline, 6 Months, and 12 Months.

BACKGROUND: Erythema migrans is the most common clinical manifestation of Lyme disease. Despite antibiotic therapy, typically at least 10% of adult patients with erythema migrans experience persistence of at least 1 subjective symptom for ≥6 months (posttreatment Lyme disease symptoms [PTLDS]). METHODS: This study was designed to determine whether the frequency and severity (based on a visual analogue scale) of 12 particular symptoms in patients with erythema migrans (n = 52) differed from matched control subjects (n = 104) followed prospectively for 12 months. RESULTS: At baseline, patients with Lyme disease were more likely than controls to have at least 1 symptom (P = .006). Among symptomatic subjects, Lyme disease patients had a higher mean number of symptoms (P < .001) and a higher mean total symptom severity score (P < .001). At both 6 and 12 months, however, there were no significant differences for these variables and no significant differences in the frequency or severity of any of the 12 individual symptoms assessed. However, 10 patients were clinically assessed as having possible PTLDS. CONCLUSIONS: Patients with erythema migrans were more likely than matched control subjects to be symptomatic at baseline with a greater symptom severity score, but this was not found at ≥6 months. Use of symptom survey data alone, however, was less likely to identify patients with possible PTLDS compared with individual clinical assessments. Because it is very challenging to be certain that the presence of long-term symptoms in a particular patient is correctly attributable to having had Lyme disease, an objective biomarker would be highly desirable.

Combining Double-Dose and High-Dose Pulsed Dapsone Combination Therapy for Chronic Lyme Disease/Post-Treatment Lyme Disease Syndrome and Co-Infections, Including Bartonella: A Report of 3 Cases and a Literature Review.

Three patients with relapsing and remitting borreliosis, babesiosis, and bartonellosis, despite extended anti-infective therapy, were prescribed double-dose dapsone combination therapy (DDDCT) for 8 weeks, followed by one or several two-week courses of pulsed high-dose dapsone combination therapy (HDDCT). We discuss these patients' cases to illustrate three important variables required for long-term remission. First, diagnosing and treating active co-infections, including Babesia and Bartonella were important. Babesia required rotations of multiple anti-malarial drug combinations and herbal therapies, and Bartonella required one or several 6-day HDDCT pulses to achieve clinical remission. Second, all prior oral, intramuscular (IM), and/or intravenous (IV) antibiotics used for chronic Lyme disease (CLD)/post-treatment Lyme disease syndrome (PTLDS), irrespective of the length of administration, were inferior in efficacy to short-term pulsed biofilm/persister drug combination therapy i.e., dapsone, rifampin, methylene blue, and pyrazinamide, which improved resistant fatigue, pain, headaches, insomnia, and neuropsychiatric symptoms. Lastly, addressing multiple factors on the 16-point multiple systemic infectious disease syndrome (MSIDS) model was important in achieving remission. In conclusion, DDDCT with one or several 6-7-day pulses of HDDCT, while addressing abnormalities on the 16-point MSIDS map, could represent a novel effective clinical and anti-infective strategy in CLD/PTLDS and associated co-infections including Bartonella.

Neuropsychiatric Symptoms and Tick-Borne Diseases.

In North America, Lyme disease (LD) is primarily caused by the spirochetal bacterium Borrelia burgdorferi, transmitted to humans by Ixodes species tick bites, at an estimated rate of 476,000 patients diagnosed per year. Acute LD often manifests with flu-like symptoms and an expanding rash known as erythema migrans (EM) and less often with neurologic, neuropsychiatric, arthritic, or cardiac features. Most acute cases of Lyme disease are effectively treated with antibiotics, but 10-20% of individuals may experience recurrent or persistent symptoms. This chapter focuses on the neuropsychiatric aspects of Lyme disease, as these are less widely recognized by physicians and often overlooked. Broader education about the potential complexity, severity, and diverse manifestations of tick-borne diseases is needed.

Lyme disease and the pursuit of a clinical cure.

Lyme disease, caused by the spirochete Borrelia burgdorferi, is the most common vector-borne illness in the United States. Many aspects of the disease are still topics of controversy within the scientific and medical communities. One particular point of debate is the etiology behind antibiotic treatment failure of a significant portion (10-30%) of Lyme disease patients. The condition in which patients with Lyme disease continue to experience a variety of symptoms months to years after the recommended antibiotic treatment is most recently referred to in the literature as post treatment Lyme disease syndrome (PTLDS) or just simply post treatment Lyme disease (PTLD). The most commonly proposed mechanisms behind treatment failure include host autoimmune responses, long-term sequelae from the initial Borrelia infection, and persistence of the spirochete. The aims of this review will focus on the in vitro, in vivo, and clinical evidence that either validates or challenges these mechanisms, particularly with regard to the role of the immune response in disease and resolution of the infection. Next generation treatments and research into identifying biomarkers to predict treatment responses and outcomes for Lyme disease patients are also discussed. It is essential that definitions and guidelines for Lyme disease evolve with the research to translate diagnostic and therapeutic advances to patient care.

Classical Borrelia Serology Does Not Aid in the Diagnosis of Persistent Symptoms Attributed to Lyme Borreliosis: A Retrospective Cohort Study.

OBJECTIVE: The diagnosis of Lyme borreliosis is based on two-tier testing using an ELISA and Western blot. About 5-10% of patients report persistent symptoms of unknown etiology after treatment, resulting in substantial difficulties in further diagnostic workup. This paper presents a study aimed at determining whether serology can differentiate between patients with persistent symptoms attributed to Lyme and other patients with Lyme borreliosis. METHODS: A retrospective cohort study included 162 samples from four subgroups: patients with persistent symptoms of Lyme (PSL), early Lyme borreliosis with erythema migrans (EM), patients tested in a general practitioner setting (GP), and healthy controls (HC). ELISA, Western blots, and multiplex assays from different manufacturers were used to determine inter-test variations in PSL and to compare reactivity against Borrelia-specific antigens among the groups. RESULTS: In comparing the IgG and IgM reactivity by Western blot, IgG was more often positive in the PSL group than in the GP group. The individual antigen reactivity was similar between the PSL and EM or GP groups. Inter-test agreement among the manufacturers was variable, and agreement was higher for IgG testing compared to IgM. CONCLUSIONS: Serological testing is unable to define the subgroup of patients with persistent symptoms attributed to Lyme borreliosis. Additionally, the current two-tier testing protocol shows a large variance among different manufacturers in these patients.

Systematic comparisons between Lyme disease and post-treatment Lyme disease syndrome in the U.S. with administrative claims data.

BACKGROUND: Post-treatment Lyme disease syndrome (PTLDS) is used to describe Lyme disease patients who have the infection cleared by antibiotic but then experienced persisting symptoms of pain, fatigue, or cognitive impairment. Currently, little is known about the cause or epidemiology of PTLDS. METHODS: We conducted a data-driven study with a large nationwide administrative dataset, which consists of more than 98 billion billing and 1.4 billion prescription records between 2008 and 2016, to identify unique aspects of PTLDS that could have diagnostic and etiologic values. We defined PTLDS based on its symptomatology and compared the demographic, longitudinal changes of comorbidity, and antibiotic prescriptions between patients who have Lyme with absence of prolonged symptoms (APS) and PTLDS. FINDINGS: The age and temporal distributions were similar between Lyme APS and PTLDS. The PTLDS-to-Lyme APS case ratio was 3.42%. The co-occurrence of 3 out of 19 chronic conditions were significantly higher in PTLDS versus Lyme APS-odds ratio and 95% CI for anemia, hyperlipidemia, and osteoarthrosis were 1.46 (1.11-1.92), 1.39 (1.15-1.68), and 1.62 (1.23-2.12) respectively. We did not find significant differences between PTLDS and Lyme APS for the number of types of antibiotics prescribed (incidence rate ratio = 1.009, p = 0.90) and for the prescription of each of the five antibiotics (FDR adjusted p values 0.72-0.95). INTERPRETATION: PTLDS cases have more codes corresponding to anemia, hyperlipidemia, and osteoarthrosis compared to Lyme APS. Our finding of hyperlipidemia is consistent with a dysregulation of fat metabolism reported by other researchers, and further investigation should be conducted to understand the potential biological relationship between the two. FUNDING: Steven & Alexandra Cohen Foundation, Global Lyme Alliance, and the Pazala Foundation; National Institutes of Health R01ES032470.

Lyme Disease and Post-treatment Lyme Disease Syndrome: Current and Developing Treatment Options.

Lyme disease and its treatment implications have become an ever-increasing area of concern within the United States related to the markedly increased prevalence of infection within the last two decades. The presentation, pathophysiology, and epidemiology of Lyme disease have been well studied, and thus treatments for this disease are widely available. While the treatment of its early and late stages is relatively simple with 10-14 day and four-week courses of doxycycline, respectively, the main problem rests in the understanding of the etiology and pathology of post-treatment Lyme disease syndrome (PTLDS). With the time of symptoms onsetting approximately six months after treatment and potentially lasting indefinitely, this syndrome's effect on patients' quality of life could be devastating. Searching on PubMed, Google Scholar, MEDLINE, and ScienceDirect using keywords including Lyme disease, PTLDS, doxycycline, erythema migrans, azlocillin, and treatment, the authors have tried to make clear the different aspects. The authors have reviewed and discussed clinical studies of Lyme disease and its treatments/potential therapeutics as well as PTLDS and its sparse treatments/potential therapeutics.

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.

Twenty-five patients with relapsing and remitting Borreliosis, Babesiosis, and bartonellosis despite extended anti-infective therapy were prescribed double-dose dapsone combination therapy (DDDCT), followed by one or several courses of High Dose Dapsone Combination Therapy (HDDCT). A retrospective chart review of these 25 patients undergoing DDDCT therapy and HDDCT demonstrated that 100% improved their tick-borne symptoms, and patients completing 6-7 day pulses of HDDCT had superior levels of improvement versus 4-day pulses if Bartonella was present. At the completion of treatment, 7/23 (30.5%) who completed 8 weeks of DDDCT followed by a 5-7 day pulse of HDDCT remained in remission for 3-9 months, and 3/23 patients (13%) who recently finished treatment were 1 ½ months in full remission. In conclusion, DDDCT followed by 6-7 day pulses of HDDCT could represent a novel, effective anti-infective strategy in chronic Lyme disease/Post Treatment Lyme Disease Syndrome (PTLDS) and associated co-infections, including Bartonella, especially in individuals who have failed standard antibiotic protocols.

The Role of the Infectious Disease Consultation in Lyme Disease.

A consultation regarding Lyme disease can be challenging for the infectious disease physician when the referral question centers on the use of prolonged or empirical antibiotic treatment of Lyme disease and associated tick-borne infections. Patients who have been infected with Borrelia burgdorferi, and many who have been misdiagnosed, are confronted with a seemingly endless array of misinformation that is not in keeping with the current understanding of the clinical spectrum of Lyme disease and its response to evidence-based treatment. Preparing for these conversations with a good grasp of the public beliefs regarding Lyme disease and its treatment can be beneficial.

Real time micro-organisms PCR in 104 patients with polymorphic signs and symptoms that may be related to a tick bite.

INTRODUCTION: Ticks are frequently polyinfected and can thus transmit numerous microorganisms. A large number of bacteria, parasites and viruses are transmitted by tick bites and could cause different signs and symptoms in patients. The main goal of this study was to search for these numerous microorganisms in patients presenting with persistent polymorphic syndrome possibly due to a tick bite (SPPT). PATIENTS AND METHODS: The following microorganisms were searched for in saliva, urine, venous and capillary blood by using real time PCR: Borrelia burgdorferi sensu lato, Borrelia miyamotoi, Borrelia hermsii, Bartonella spp., Bartonella quintana, Bartonella henselae, Ehrlichia spp., Anaplasma spp., Rickettsia spp., Coxiella burnetii, Brucella spp., Francisella tularensis, Mycoplasma spp., Chlamydia spp., Babesia spp., Theileria spp. RESULTS: 104 patients were included. 48% of the patients were poly-infected, and 25% harboured at least three different microorganisms. Borrelia spp. were not the most frequent bacteria observed, observed far behind Mycoplasma spp., Rickettsia spp. and Ehrlichia spp. which were the most frequent microorganisms observed. Piroplasms were found in a significant number of patients. The most sensitive matrix was saliva, followed by urine, capillary blood and venous blood. CONCLUSION: Our prospective study has shown that patients with SPPT, a syndrome close to fibromyalgia, could harbour several tick borne microorganisms.

Evaluation of selected variables to determine if any had predictive value for, or correlated with, residual symptoms at approximately 12 months after diagnosis and treatment of early Lyme disease.

Subjective symptoms may persist after antibiotic treatment of patients with erythema migrans. Selected baseline variables were evaluated to determine if any correlated with symptom persistence to 12 months (PTLDS). Tingling or an abnormal skin sensation were reported by 5 (71.4%) of the 7 PTLDS cases at the baseline visit versus 4 (13.3%) of the 30 initially symptomatic subjects without PTLDS (P= 0.005). The frequency of having a total score of ≥17, when the Beck Depression Inventory score was added to the number of pain sites that the subject reported at the baseline visit, also showed a significant difference: 71.4% versus 10%, P= 0.002. All but 1 of the 7 subjects with possible PTLDS had either a total score of at least 17 on these 2 measures combined or had a score of ≥2 on the stress event questionnaire used. Clinical investigations should be conducted to validate these findings with other patient cohorts.

Predicting Lyme Disease From Patients' Peripheral Blood Mononuclear Cells Profiled With RNA-Sequencing.

Although widely prevalent, Lyme disease is still under-diagnosed and misunderstood. Here we followed 73 acute Lyme disease patients and uninfected controls over a period of a year. At each visit, RNA-sequencing was applied to profile patients' peripheral blood mononuclear cells in addition to extensive clinical phenotyping. Based on the projection of the RNA-seq data into lower dimensions, we observe that the cases are separated from controls, and almost all cases never return to cluster with the controls over time. Enrichment analysis of the differentially expressed genes between clusters identifies up-regulation of immune response genes. This observation is also supported by deconvolution analysis to identify the changes in cell type composition due to Lyme disease infection. Importantly, we developed several machine learning classifiers that attempt to perform various Lyme disease classifications. We show that Lyme patients can be distinguished from the controls as well as from COVID-19 patients, but classification was not successful in distinguishing those patients with early Lyme disease cases that would advance to develop post-treatment persistent symptoms.

Induced Native Phage Therapy for the Treatment of Lyme Disease and Relapsing Fever: A Retrospective Review of First 14 Months in One Clinic.

The overall failure rate of standard therapeutic options for late/chronic/persistent borreliosis emphasizes the need for novel therapeutic strategies. In this report, we are presenting a novel therapeutic option based on a new technology, Induced Native Phage Therapy (INPT; PhagenCorp, LLC, Sarasota, FL), and its ability to facilitate the elimination of infection more rapidly, efficiently, and with less harm to the patient than conventional treatments. Borrelia species in the environment are themselves always infected by their own type of Borrelia bacteriophages. Both the Borrelia spirochete and the Borrelia bacteriophages are transmitted into humans via the bite of a vector, such as ticks. The Borrelia bacteriophages (phages) are called native phages in that they coexist naturally within the human body, and only infect the specific bacteria host population. Native phages persist in humans only as long as there are host bacteria of the correct type to continue replicating more phages. The purposeful manipulation of native phages to kill their host bacteria is the basis of INPT. INPT is a patent-pending technology that uses a proprietary adjunctive assay called Biospectral Emission Sequencing to identify and isolate the specific complex electromagnetic signatures necessary to induce the native phages to epigenetically revert from their normal quiescent, lysogenic activity to virulent, lytic activity, thereby killing their host bacteria. The strategic subtle, low-frequency/low-energy signatures are imprinted into a proprietary oral formula, Inducen-LD, which serves as a carrier to introduce the signals therapeutically into the body. As a proof-of-concept method validation, a total of 26 patients with post-treatment (antibiotic) Lyme disease syndrome, who initially were found upon Phelix Borrelia-phage testing (R.E.D. Laboratories, Belgium) to have one or more Borrelia species, were submitted to INPT treatment. A total of 20 patients (77%) were found to be negative after two weeks of the total program of care. Six patients who remained positive after the initial therapy received an extended INPT treatment and were retested. Four were subsequently found to be negative for one or more of their previously diagnosed Borrelia strains. Thus a total of 24 out of 26 (92%) patients were successfully treated with INPT. Mild to substantial clinical improvements were reported by all participants without noticeable adverse reactions to the INPT treatments. We have demonstrated a possible mechanism in which native bacteriophages can be induced to epigenetically switch from lysogenic to lytic actions, thereby eliminating the targeted bacteria efficiently, with little to no harm to tissues or the microbiome.

Prevalence of persistent symptoms after treatment for lyme borreliosis: A prospective observational cohort study.

BACKGROUND: Concerns about long-lasting symptoms attributed to Lyme borreliosis (LB) are widespread in the Western world, while such symptoms are highly prevalent in the general population. METHODS: In the largest prospective study to date, adults with physician-confirmed LB were included at the start of antibiotic treatment. Primary outcomes, prevalence of persistent symptoms and symptom severity, were assessed using three-monthly standardised questionnaires during one year. Persistent symptoms were defined as impaired scores for fatigue (CIS, subscale fatigue), cognitive impairment (CFQ) or pain (SF-36, subscale bodily pain) ≥6 months, with onset <6 months. Outcomes were compared with a longitudinal general population and a tick-bite cohort without LB as a reference. FINDINGS: Of 1135 LB patients (94•8% erythema migrans, 5•2% disseminated LB), 1084 fulfilled primary analysis criteria, as well as 1942 population and 1887 tick-bite controls. Overall prevalence of persistent symptoms in LB patients was 27•2% (95%CI, 24•7%-29•7%); 6•0% and 3•9% higher than in population (21•2%, 95%CI, 19•3%-23•1%; p < 0•0001) and tick-bite (23•3%, 95%CI 21•3%-25•3%; p = 0•016) cohorts, respectively. At 12 months, fatigue, cognitive impairment, and pain were significantly more severe in erythema migrans patients than in reference cohorts, while in disseminated LB patients, only pain was more severe. INTERPRETATION: In treated LB patients, persistent symptoms were significantly more prevalent and symptoms were more severe than in individuals without LB, although the background prevalence was substantial. This suggests an association, either direct or indirect, between persistent symptoms and LB in a relatively small subset of patients. FUNDING: ZonMw; Dutch Ministry of Health, Welfare and Sport.

Evaluation of Disulfiram Drug Combinations and Identification of Other More Effective Combinations against Stationary Phase Borrelia burgdorferi.

Lyme disease, caused by Borrelia burgdorferi, is the most common vector-borne disease in USA, and 10-20% of patients will develop persistent symptoms despite treatment ("post-treatment Lyme disease syndrome"). B. burgdorferi persisters, which are not killed by the current antibiotics for Lyme disease, are considered one possible cause. Disulfiram has shown to be active against B. burgdorferi, but its activity against persistent forms is not well characterized. We assessed disulfiram as single drug and in combinations against stationary-phase B. burgdorferi culture enriched with persisters. Disulfiram was not very effective in the drug exposure experiment (survival rate (SR) 46.3%) or in combinations. Clarithromycin (SR 41.1%) and nitroxoline (SR 37.5%) were equally effective when compared to the current Lyme antibiotic cefuroxime (SR 36.8%) and more active than disulfiram. Cefuroxime + clarithromycin (SR 25.9%) and cefuroxime + nitroxoline (SR 27.5%) were significantly more active than cefuroxime + disulfiram (SR 41.7%). When replacing disulfiram with clarithromycin or nitroxoline in three-drug combinations, bacterial viability decreased significantly and subculture studies showed that combinations with these two drugs (cefuroxime + clarithromycin/nitroxoline + furazolidone/nitazoxanide) inhibited the regrowth, while disulfiram combinations did not (cefuroxime + disulfiram + furazolidone/nitazoxanide). Thus, clarithromycin and nitroxoline should be further assessed to determine their role as potential treatment alternatives in the future.

"Repurposing" Disulfiram in the Treatment of Lyme Disease and Babesiosis: Retrospective Review of First 3 Years' Experience in One Medical Practice.

A total of 71 patients with Lyme disease were identified for analysis in whom treatment with disulfiram was initiated between 15 March 2017 and 15 March 2020. Four patients were lost to follow-up, leaving 67 evaluable patients. Our retrospective review found patients to fall into a "high-dose" group (≥4 mg/kg/day) and a "low-dose" group (<4 mg/kg/day). In total, 62 of 67 (92.5%) patients treated with disulfiram were able to endorse a net benefit of the treatment with regard to their symptoms. Moreover, 12 of 33 (36.4%) patients who completed one or two courses of "high-dose" therapy enjoyed an "enduring remission", defined as remaining clinically well for ≥6 months without further anti-infective treatment. The most common adverse reactions from disulfiram treatment in the high-dose group were fatigue (66.7%), psychiatric symptoms (48.5%), peripheral neuropathy (27.3%), and mild to moderate elevation of liver enzymes (15.2%). We observed that although patients on high dose experienced a higher risk for adverse reactions than those on a low dose, high-dose patients were significantly more likely to achieve enduring remission.

Efficacy of Double-Dose 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 Retrospective Chart Review.

Three patients with multi-year histories of relapsing and remitting Lyme disease and associated co-infections despite extended antibiotic therapy were each given double-dose dapsone combination therapy (DDD CT) for a total of 7-8 weeks. At the completion of therapy, all three patients' major Lyme symptoms remained in remission for a period of 25-30 months. A retrospective chart review of 37 additional patients undergoing DDD CT therapy (40 patients in total) was also performed, which demonstrated tick-borne symptom improvements in 98% of patients, with 45% remaining in remission for 1 year or longer. In conclusion, double-dose dapsone therapy could represent a novel and effective anti-infective strategy in chronic Lyme disease/ post-treatment Lyme disease syndrome (PTLDS), especially in those individuals who have failed regular dose dapsone combination therapy (DDS CT) or standard antibiotic protocols. A randomized, blinded, placebo-controlled trial is warranted to evaluate the efficacy of DDD CT in those individuals with chronic Lyme disease/PTLDS.

Complement Evasion in Borrelia spirochetes: Mechanisms and Opportunities for Intervention.

Lyme disease (LD) is an increasingly prevalent, climate change-accelerated, vector-borne infectious disease with significant morbidity and cost in a proportion of patients who experience ongoing symptoms after antibiotic treatment, a condition known as post-treatment Lyme disease syndrome (PTLDS). Spirochetal bacteria of Borrelia species are the causative agents of LD. These obligate parasites have evolved sophisticated immune evasion mechanisms, including the ability to defeat the innate immune system's complement cascade. Research on complement function and Borrelia evasion mechanisms, focusing on human disease, is reviewed, highlighting opportunities to build on existing knowledge. Implications for the development of new antibiotic therapies having the potential to prevent or cure PTLDS are discussed. It is noted that a therapy enabling the complement system to effectively counter Borrelia might have lower cost and fewer side-effects and risks than broad-spectrum antibiotic use and could avert the need to develop and administer a vaccine.