Standing in contrast to the CDC/Wormser decidedly un-exciting research report discussed here, is the incredible work by Melanie Wills and team, supported by the G. Magnotta Foundation for Vector-Borne Diseases. 🇨🇦
Read the whole thing. It’s almost as if TruthCures commissioned an analysis.
“Integrating findings that have been generated over decades from many different subspecialties portrays Lyme disease as a complex biological, medical, and socio-political scourge.”
The group addressed many of the issues we raise as barriers to care for those suffering chronic consequences of a tick bite. Here I'll share some notable quotes.
“When considering protracted disease classifications, it is pertinent to note that terminology has not been used consistently in the literature, clinical practice, or socially. Post-treatment (PTLDS) and chronic Lyme (CLD) may also be challenging to delineate due a high degree of variability between patients, and the lack of responsive biological correlates indicative of disease progression and resolution. Based on consensus definitions, however, it is possible to distinguish PTLDS and treatment-refractory Lyme arthritis (TRLA), as the terms describe mutually-exclusive, longstanding manifestations. PTLDS requires the resolution of objective disease presentation, whereas TRLA specifically focuses on objective, relapsing, or non-resolving joint effusion. The genetic predisposition to OspA-stimulated autoimmunity that has been hypothesized to promote development of TRLA was not found to factor in the clinical trajectory of CLD, according to one study that probed this association (Section 3). While TRLA is estimated to occur in only a small percentage of cases , >10% of early LD diagnosed on the American Eastern seaboard progresses despite timely intervention to fulfil operationalized criteria for PTLDS, while another ~30% of patients experience ongoing symptoms or impairment, but fail to meet the definition  (Section 2 and Section 5). Overall then, the postulated heritable autoimmune predisposition of the host accounts for only a minority of LD sequalae, while the rest remain largely uninvestigated."
Translation: Post-Treatment Lyme Disease Syndrome (PTLDS) and Treatment Refractory Lyme Arthritis are NOT the same thing and neither describes those patients who are chronically ill and mostly seronegative.
“Meanwhile, the variability in presentation and lack of consensus criteria around CLD have often excluded this population from high-quality research investigation. Some sources suggest that this umbrella term captures some of the more debilitated patients . Yet, with the exception of case studies and registry-mining initiatives, which are generally downgraded in the hierarchy of medical evidence, biomedical research is largely failing to adequately represent this cohort. The most common explanation for dismissing the CLD population is a lack of objective evidence of prior or ongoing Borrelia infection, and indeed, debates continue about whether chronic “alternatively diagnosed” Lyme is in fact chronic fatigue syndrome (CFS) . But what is CFS? Like CLD, CFS/myalgic encephalomyelitis has thus far defied a unified physicochemical definition, and endured decades of scorn and marginalization in the medical community instead of receiving an adequate infusion of resources to elucidate the underlying pathology. Shuffling ill patients between poorly-defined “syndrome” classifications without addressing fundamental pathophysiological mechanism and improving outcomes is counterproductive. A paradigm shift is required to enable appropriate and relevant evaluation of such patients without a priori assumptions.”
Translation: Since the two-tier testing identifies only the minority of cases which are autoimmune or high-antibody arthritis cases, those with "Chronic Lyme disease" are not represented in any research considered "high quality". Thus, those victims are trapped in a vicious cycle of marginalization and denial of care.
“Overall, the microbiological implications of soluble antigens, ICs, and their involvement in Borrelia pathogenesis are intriguing, but not well understood. Outstanding questions remain around the origins and identities of the shed proteins that become antigenic cargo nucleating the complex, as well as their larger role in driving disease or defining its progression. Cell-free pathogen proteins are thought to arise from borrelial membrane vesicles that have been observed under various conditions , although immune-mediated disruption of the bacterial cell has also been postulated as a source of membrane proteins in host blood . Likewise, the antigenic composition of ICs has not been thoroughly characterized. Sequestration of antibodies in ICs by decoy antigens is speculated to prevent effective opsonization and clearance of the pathogen , but has yet to be demonstrated experimentally. Thus, epitope shedding as a dedicated virulence mechanism is conceivable, and warrants further investigation.”
Translation: It's the blebs.
“Even though the adaptive defense against Bb is already suboptimal, it appears to be further subverted by the formation of immune complexes (ICs) that sequester antibodies . Early observations of weak humoral response prompted speculation that sub-threshold immunoglobulin titer could result from the formation of antibody-antigen aggregates that are not recovered or accounted for during routine serological analysis . Subsequent studies of ICs in human Lyme patients revealed several anti-Borrelia antibodies along with pathogen-derived proteins, of which OspA is the only antigen that has been definitively identified within the complexes [186,187]. Experiments in animal models support the hypothesis that OspA-specific antibodies can be generated early in the course of infection, but are enriched in complexes and may be undetectable without appropriate IC processing . Indeed, recovery of Borrelia-specific ICs from human patients, who were otherwise seronegative by conventional assessment of free antibody, has been documented . These findings, coupled with the observation that ICs diminish upon treatment, became the basis for a proposed modification to the serological diagnostic test that ostensibly increased sensitivity and improved the capacity to distinguish active infection from past exposure [189,190]. The concept was met with criticism, however , and did not appear to gain widespread traction.”
Translation: Some antibodies cannot be characterized on antibody-based diagnostic tests because they are attached to the antigen they are attacking.
“More recent work in mouse models has further probed the relationship between the lymphatic microenvironment of Borrelia processing, and the resulting adaptive immune response. As reviewed by Tracey and Baumgarth , a more complete picture has thus since emerged, portraying a vigorous but misguided host defense that confers some protection without fully eliminating spirochetes from murine tissues. The response appears to be mediated by borrelial invasion of the lymph node cortex, where the pathogen triggers lymphadenopathy and loss of functional lymph node architecture , essentially reducing T and B cell synchronicity [182,183]. Germinal centres (GC), which contribute to a mature and sustained immune response through the generation of robust antibody-secreting cells and memory cells, rely on T and B cell coordination . Upon experimental infection with Borrelia, murine GCs were found to be delayed, abnormal, and short-lived, predicting the weak long-term humoral responses that have been documented in mice and human Lyme patients after antibiotic treatment [183,184]. Moreover, the immunosuppression observed in mice was not limited to the spirochetal infection, as an influenza vaccine co-administered with Borrelia also failed to induce a protective response . Although the usual caveats apply about extrapolating murine data, this work provides a plausible mechanism of immune suppression that may be relevant to the human manifestations of the disease.”
Translation: Mouse studies do not necessarily repeat in humans, but if this one does, it would suggest profound immune suppression.
“Lymphocytes and lymphatic infrastructure are likewise targets of Borrelia survival tactics, although the mechanisms of evasion have been somewhat elusive. Early accounts identified Borrelia and their extracts as potent lymphocyte mitogens, eliciting both specific and non-specific B cell proliferation and antibody production [172,173,174,175,176]. It was also recognized that the adaptive response was often insufficient to eliminate the pathogen from patients , and that polyclonal B cell activation and high levels of interleukin-6 (IL-6) observed in mice and in isolated human cells could be driving elements of the pathology . Paradoxically, application of Borrelia cell extracts to cultured lymphocytes in the presence of other mitogens was found to yield a pronounced inhibitory effect on cell proliferation , which was also noted in animal models of live infection . A similar response was observed by exposing cultured human lymphocytes to a canine Lyme disease vaccine composed of recombinant, non-adjuvanted, lipidated OspA. The inhibition elicited by OspA alone was more profound than that of the whole cell sonicate, suggesting that OspA may be a key component of the lymphocyte cell cycle block . Another in vitro co-culture study reported Bb invasion and lysis of human B and T cells .”
Translation: Lyme causes immunosuppression, and so did the OspA "vaccine", LYMErix, all by itself, with no spirochetes in sight. Read about OspA here.
We are thankful for this excellent literature review and hopeful that it will lead to further investigation into the true mechanisms of disease, rather than ad nauseam studies of Antibiotics and How to Kill Spirochetes.