Lyme Disease - Part 1

I'm going to do a Lyme Series from various sources.


Since Newport has done a lot of research on Lyme, I'd be interested on his input and what he's found in regard to the below. Are any of treatments better than antibiotic therapy? Thanks.


http://chronicneurotoxins.com/learnmore/latestAbstracts.cfm


Use of Pioglitazone to prevent intensification of persistent symptoms following Cholestyramine treatment of patients with Post-Lyme Syndrome.

Ritchie Shoemaker, Dennis House
Center for Research on Biotoxin-Associated Illness (a not-for-profit Corporation)
500 Market Street, Suite 102, Pocomoke City, MD 21851

Introduction
Since the first description of Lyme disease there have been subsets of patients identified with persistent symptoms, refractory to antibiotics. A recent prospective study of 51 Post-Lyme Syndrome (PLS) patients demonstrating a mid-spatial frequency deficit in visual contrast sensitivity (VCS) showed significant reduction of symptoms with use of a cholestyramine (CSM) treatment protocol. The symptoms and VCS deficits in the PLS patients were similar to those demonstrated by patients with other chronic, neurotoxin-mediated illnesses reported previously. Early in the course of CSM treatment, 33% of the 51 PLS patients experienced a significant intensification of symptoms, a phenomenon not seen with different biotoxin exposures. Pretreatment in 12 subsequent PLS patients with pioglitazone, a PPAR agonist, was shown to prevent the intensification associated with CSM use and to reduce plasma levels of a pro-inflammatory cytokine, TNF alpha. A multisite, prospective clinical trial on pioglitazone and CSM use in PLS patients was conducted to confirm benefit of CSM therapy in PLS and determine if pretreatment with pioglitazone could prevent intensification.

Methods
All patients referred to the study had long-standing symptoms following a known tick bite or exposure to areas where others had tick bites, and a clinical and/or laboratory diagnosis of Lyme Disease. Diagnostic parameters used by referring physicians included a history of erythema chronicum migrans (ECM) rash, ELISA assay, Borrelia burgdorferi Western blot, LUAT assay, PCR, CSF antibodies to B. burgdorferi and culture. Patients with a clinical diagnosis of PLS but without a positive serologic test were included at the discretion of the attending physician. 241 patients were included in the study at one of two centers, Pocomoke, MD or Chico, CA. All patients had past antibiotic treatment, but retained symptoms refractory to antibiotics. All patients were pretreated with pioglitazone (pio), 45mg daily for 10 days. On day 6 of pio, CSM treatment was initiated. An orally administered checklist monitored symptoms, and sequential VCS testing was performed. CSM was continued until the treatment endpoints of maximum symptom abatement and maximum improvement in VCS scores were noted. No antibiotics or other therapeutic interventions were administered during the study.

Results
No patients had adverse effects from pio, including hypoglycemia or abnormal liver function tests. Only 5 of 241 (2%) patients experienced significant symptom intensification, not severe enough to stop treatment. 83.8% of patients had at least 50% reduction of symptoms following use of the CSM protocol, with complete resolution of symptoms in 23%. 3.4% of patients had no improvement. VCS deficits prior to treatment and resolution with treatment were better correlated with symptom abatement than other diagnostic markers. Conclusion. The results support the hypotheses that: 1) PLS may be a chronic, neurotoxin-mediated illness; 2) antibiotic treatment should be followed by adjuvant treatment with the pio and CSM protocol; 3) VCS is an effective diagnostic tool that can indicate neurotoxicity in PLS patients and; 4) TNF may participate in the intensification reaction. These results must be confirmed in a prospective double-blinded, placebo-controlled clinical trial, with frequent monitoring of TNF levels measured appropriately by validated laboratory protocols.

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Use of atovaquone (Mepron) in patients coinfected with Borrelia burgdorferi and Babesia microti with symptoms refractory to antibiotics and cholestyramine.

Ritchie Shoemaker, Dennis House
Center for Research on Biotoxin-Associated Illness (a not-for-profit Corporation)
500 Market Street, Suite 102, Pocomoke City, MD 20851

Background
A recent two-site study of 341 patients with Lyme Disease and symptoms refractory to antibiotics (Post-Lyme Syndrome, PLS) showed benefit from a treatment protocol using pioglitazone to lower proinflammatory cytokine levels and cholestyramine (CSM) to bind and eliminate toxins. Statistical analyses showed a significant reduction in the number of symptoms and a significant improvement in visual contrast sensitivity (VCS) scores following treatment. These improvements paralleled those seen in patients with symptoms following exposure to other biotoxin-forming organisms, including dinoflagellate and fungal species. In the PLS studies, however, about 8% of patients did not respond to the toxin-binding protocol. Serologic measures indicated that these patients were disproportionately coinfected with Borrelia burgdorferi and Babesia microti. The coinfected patients had received 3 weeks of atovaquone, targeting b. microti, in combination with azithromycin, targeting b. burgdorferi, without binding therapy prior to the PLS study because recent studies reported success with this protocol. It was hypothesized that: 1) b. burgdorferi had been eliminated by azithromycin; and 2) 3 weeks of atovaquone therapy was insufficient to eliminate b. microti during coinfection with b. burgdorferi. The current study was designed to investigate the efficacy of atovaquone therapy on b. microti. infection during a 3 week period and, if indicated, during an additional 6 week period.

Methods
Twenty-five patients with serologic evidence of exposure to b. microti and b. burgdorferi and chronic symptoms despite 3 weeks of atovaquone and azithromycin therapy followed by toxin-binding therapy were enrolled in an FDA and IRB approved double-blinded, placebo-controlled, crossover clinical trial. Patients were randomly assigned either atovaquone or placebo for 3 weeks in combination with CSM, and then crossed over to the other arm of the trial for 3 weeks. Treatment with atovaquone and CSM, provided on an open label basis, for 6 additional weeks followed. Symptoms and VCS scores were recorded at initiation and at the end of weeks 3, 6, 9 and 12.

Results
Twenty-one patients completed the trial, four dropped out; one for non-study related reasons, two because of CSM intolerance and one patient because of no improvement at 9 weeks. No patients showed notable symptom resolution or vision recovery at the end of week 6. After an additional 6 weeks of therapy, five patients had complete resolution of their longstanding symptoms and 16 had notable reduction in the number and/or severity of symptoms. The cohort showed a statistically significant reduction in symptom number and increase in VCS between initial and week 12 assessments. There were no adverse effects noted other than mild worsening of symptoms experienced by patients during the first few weeks of atovaquone therapy. Patients noticed clinical improvement near the end of the second 3-week course of atovaquone, and noted continued improvement during the third 3-week course of atovaquone and CSM therapy.

Discussion
The study results suggest that prolonged atovaquone therapy is required to eliminate b. microti. None of the patients had shown improvement after 3 weeks of atovaquone in combination with azithromycin therapy, after 3 weeks of binding therapy or after 3 weeks of atovaquone plus binding therapy. Six to 9 continuous weeks of azithromycin therapy are likely required for improvement in most cases. Studies of coinfected patients are needed to confirm and extend these results, particularly due to coinfection rates exceeding 10% in endemic areas. Additional issues to address include: 1) whether b. microti, like b. burgdorferi, also releases a toxin; 2) whether upregulation of anti-inflammatory cytokines triggered by b. burgdorferi toxins interfere with atovaquone's lethal mode of action on b. microti; 3) the role of pro-inflammatory cytokines in symptom induction and the course of coinfection; 4) possible extravascular sequestration of viable Babesia organisms; and 5) the role of the extrachromosomal 35 kb plastid DNA, homologous to DNA of Euglena, in maintaining viable Babesia organisms.

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