Unorthodox alternative therapies marketed to treat Lyme disease.

BACKGROUND: Some patients with medically unexplained symptoms or alternative medical diagnoses suspect that they chronically suffer from the tick-borne infection Lyme disease. These patients are commonly targeted by providers of alternative therapies. This study was designed to identify and characterize the range of unorthodox alternative therapies advertised to patients with a diagnosis of Lyme disease. METHODS: Internet searches using the Google search engine were performed to identify the websites of clinics and services that marketed nonantimicrobial therapies for Lyme disease. We subsequently used the PubMed search engine to identify any scientific studies evaluating such treatments for Lyme disease. Websites were included in our review so long as they advertised a commercial, nonantimicrobial product or service that specifically mentioned utility for Lyme disease. Websites with patient testimonials (such as discussion groups) were excluded unless the testimonial appeared as marketing on a commercial site. RESULTS: More than 30 alternative treatments were identified, which fell into several broad categories: these included oxygen and reactive oxygen therapy; energy and radiation-based therapies; nutritional therapy; chelation and heavy metal therapy; and biological and pharmacological therapies ranging from certain medications without recognized therapeutic effects on Borrelia burgdorgeri to stem cell transplantation. Review of the medical literature did not substantiate efficacy or, in most cases, any rationale for the advertised treatments. CONCLUSIONS: Providers of alternative therapies commonly target patients who believe they have Lyme disease. The efficacy of these unconventional treatments for Lyme disease is not supported by scientific evidence, and in many cases they are potentially harmful.

The pain of "chronic Lyme disease": moving the discourse in a different direction.

About 30% of the population of the United States suffers from acute or chronic pain, often of unknown cause. Among this group might be included patients with symptoms claimed to be caused by a poorly defined condition called "chronic Lyme disease" in which chronic pain is a major contributor. Since there is no evidence to indicate that chronic Lyme disease is due to a persistent infection and that extended antibiotic therapy is beneficial and safe, this condition should not be viewed solely as an infectious disease problem. Rather, it should be considered within the context of a broad-based, multidisciplinary approach to determining the cause of chronic pain per se and developing more effective strategies for its treatment as outlined in a recent report on pain issued by the Institute of Medicine.

Experimental bacterial dysbiosis with consequent immune alterations increase intrarectal SIV acquisition susceptibility.

Variations in the composition of the intestinal bacterial microbiome correlate with acquisition of some sexually transmitted pathogens. To experimentally assess the contribution of intestinal dysbiosis to rectal lentiviral acquisition, we induce dysbiosis in rhesus macaques (RMs) with the antibiotic vancomycin prior to repeated low-dose intrarectal challenge with simian immunodeficiency virus (SIV) SIVmac239X. Vancomycin administration reduces T helper 17 (TH17) and TH22 frequencies, increases expression of host bacterial sensors and antibacterial peptides, and increases numbers of transmitted-founder (T/F) variants detected upon SIV acquisition. We observe that SIV acquisition does not correlate with measures of dysbiosis but rather associates with perturbations in the host antimicrobial program. These findings establish a functional association between the intestinal microbiome and susceptibility to lentiviral acquisition across the rectal epithelial barrier.

Temporal genetic variation of the red fox, Vulpes vulpes, across western Europe and the British Isles.

Quaternary climatic fluctuations have had profound effects on the phylogeographic structure of many species. Classically, species were thought to have become isolated in peninsular refugia, but there is limited evidence that large, non-polar species survived outside traditional refugial areas. We examined the phylogeographic structure of the red fox (Vulpes vulpes), a species that shows high ecological adaptability in the western Palaearctic region. We compared mitochondrial DNA sequences (cytochrome b and control region) from 399 modern and 31 ancient individuals from across Europe. Our objective was to test whether red foxes colonised the British Isles from mainland Europe in the late Pleistocene, or whether there is evidence that they persisted in the region through the Last Glacial Maximum. We found red foxes to show a high degree of phylogeographic structuring across Europe and, consistent with palaeontological and ancient DNA evidence, confirmed via phylogenetic indicators that red foxes were persistent in areas outside peninsular refugia during the last ice age. Bayesian analyses and tests of neutrality indicated population expansion. We conclude that there is evidence that red foxes from the British Isles derived from central European populations that became isolated after the closure of the landbridge with Europe.

Butyrate administration is not sufficient to improve immune reconstitution in antiretroviral-treated SIV-infected macaques.

Defective gastrointestinal barrier function and, in turn, microbial translocation have been identified as significant contributors to persistent inflammation in antiretroviral (ARV)-treated people living with HIV. Metabolic supplementation of short-chain fatty acids (SCFAs), generally produced by the commensal microbiome, may improve these outcomes. Butyrate is a SCFA that is essential for the development and maintenance of intestinal immunity and has a known role in supporting epithelial integrity. Herein we assessed whether supplementation with the dietary supplement sodium butyrate would improve immune reconstitution and reduce inflammation in ARV-treated, simian immunodeficiency virus (SIV)-infected rhesus macaques. We demonstrate that butyrate supplementation does not significantly improve immune reconstitution, with no differences observed in systemic CD4+ T-cell frequencies, T-cell functionality or immune activation, microbial translocation, or transcriptional regulation. Our findings demonstrate that oral administration of sodium butyrate is insufficient to reduce persistent inflammation and microbial translocation in ARV-treated, SIV-infected macaques, suggesting that this therapeutic may not reduce co-morbidities and co-mortalities in treated people living with HIV.

Chronic Lyme disease: in defense of the scientific enterprise.

There is no better example of a relentless attack on evidence-based biomedical research and the integrity of outstanding scientists than that associated with the treatment of a poorly defined condition called "chronic Lyme disease." Here, a scientifically naive general population, the lay press, and legislators, who in most instances are unable to evaluate and judge scientific evidence properly, have been misled by patient advocate groups to believe that extended antibiotic therapy is the best and only solution to this condition. This has resulted in the unprecedented intrusion of government and the legal systems into the practice of medicine and scientific research. Because there is no clinical evidence that this condition is due to a persistent infection, advocating extended antibiotic therapy is not justified and has been shown to be harmful and of no benefit.

Luminal microvesicles uniquely influence translocating bacteria after SIV infection.

Microbial translocation contributes to persistent inflammation in both treated and untreated HIV infection. Although translocation is due in part to a disintegration of the intestinal epithelial barrier, there is a bias towards the translocation of Proteobacteria. We hypothesized that intestinal epithelial microvesicle cargo differs after HIV infection and contributes to biased translocation. We isolated gastrointestinal luminal microvesicles before and after progressive simian immunodeficiency virus (SIV) infection in rhesus macaques and measured miRNA and antimicrobial peptide content. We demonstrate that these microvesicles display decreased miR-28-5p, -484, -584-3p, and -584-5p, and let-7b-3p, as well as increased beta-defensin 1 after SIV infection. We further observed dose-dependent growth sensitivity of commensal Lactobacillus salivarius upon co-culture with isolated microvesicles. Infection-associated microvesicle differences were not mirrored in non-progressively SIV-infected sooty mangabeys. Our findings describe novel alterations of antimicrobial control after progressive SIV infection that influence the growth of translocating bacterial taxa. These studies may lead to the development of novel therapeutics for treating chronic HIV infection, microbial translocation, and inflammation.

A Review of Antibiotic-Tolerant Persisters and Their Relevance to Posttreatment Lyme Disease Symptoms.

Several well-controlled clinical trials have shown that prolonged antibiotic therapy has no benefit in relieving posttreatment Lyme disease symptoms. However, some insist that such symptoms are due to a persistent Borrelia burgdorferi infection requiring prolonged antibiotic therapy to resolve. This unproven view is bolstered by the results of in vitro experiments where small numbers of viable B. burgdorferi can be detected after treatment with antibiotics. The results described in the present work suggest that the presence of persisters can best be explained by classic biochemical kinetics and that there are alternative explanations for this phenomenon that appears to have no clinical significance.

Is It Possible to Make a Correct Diagnosis of Lyme Disease on Symptoms Alone? Review of Key Issues and Public Health Implications.

There is much confusion and misinformation about the diagnosis of Lyme disease, as well as its treatment. This review explains why one cannot make a correct diagnosis of Lyme disease based on symptoms alone. It also provides evidence to support the validity of two-tier testing for the laboratory diagnosis of Lyme disease. The public health consequences of failing to consider these issues are discussed.

BDPA-Doped Polystyrene Beads as Polarization Agents for DNP-NMR.

The aromatic free radical BDPA (α,γ-bisdiphenylene-ß-phenylallyl), which has been widely used as a polarizing agent for Dynamic Nuclear Polarization (DNP) of hydrophobic analytes, has been incorporated into nanometer-scale polystyrene latex beads. We have shown that the resulting BDPA-doped beads can be used to hyperpolarize (13)C and (7)Li nuclei in aqueous environments, without the need for a glassing cosolvent. DNP enhancement factors of between 20 and 100 were achieved with overall BDPA concentrations of 2 mM or less. These Highly-Effective Polymer/Radical Beads (HYPR-beads) have potential use as an inexpensive polarizing agent for water-soluble analytes, and also have applications as model nanoparticles in DNP studies.

Treatment trials for post-Lyme disease symptoms revisited.

The authors of 4 National Institutes of Health-sponsored antibiotic treatment trials of patients with persistent unexplained symptoms despite previous antibiotic treatment of Lyme disease determined that retreatment provides little if any benefit and carries significant risk. Two groups recently provided an independent reassessment of these trials and concluded that prolonged courses of antibiotics are likely to be helpful. We have carefully considered the points raised by these groups, along with our own critical review of the treatment trials. On the basis of this analysis, the conclusion that there is a meaningful clinical benefit to be gained from retreatment of such patients with parenteral antibiotic therapy cannot be justified.

Critical analysis of treatment trials of rhesus macaques infected with Borrelia burgdorferi reveals important flaws in experimental design.

A critical analysis of two treatment trials of Chinese rhesus macaques infected with Borrelia burgdorferi indicates that insufficient attention was placed on documenting the blood levels, pharmacokinetics, and pharmacodynamic parameters of the antibiotics used in this host. Consequently, it is impossible to conclude that the findings have validity in judging the efficacy of doxycycline or ceftriaxone for the treatment of Borrelia burgdorferi in this animal model.