Post-treatment Lyme Disease Research Articles

Post-treatment Lyme Disease as a Model for Persistent Symptoms in Lyme Disease.

It has long been observed in clinical practice that a subset of patients with Lyme disease report a constellation of symptoms such as fatigue, cognitive difficulties, and musculoskeletal pain, which may last for a significant period of time. These symptoms, which can range from mild to severe, have been reported throughout the literature in both prospective and population-based studies in Lyme disease endemic regions. The etiology of these symptoms is unknown, however several illness-causing mechanisms have been hypothesized, including microbial persistence, host immune dysregulation through inflammatory or secondary autoimmune pathways, or altered neural networks, as in central sensitization. Evaluation and characterization of persistent symptoms in Lyme disease is complicated by potential independent, repeat exposures to B. burgdorferi, as well as the potential for co-morbid diseases with overlapping symptom profiles. Antibody testing for B. burgdorferi is an insensitive measure after treatment, and no other FDA-approved tests currently exist. As such, diagnosis presents a complex challenge for physicians, while the lived experience for patients is one marked by uncertainty and often illness invalidation. Currently, there are no FDA-approved pharmaceutical therapies, and the safety and efficacy of off-label and/or complementary therapies have not been well studied and are not agreed-upon within the medical community. Post-treatment Lyme disease represents a narrow, defined, mechanistically-neutral subset of this larger, more heterogeneous group of patients, and is a useful definition in research settings as an initial subgroup of study. The aim of this paper is to review the current literature on the diagnosis, etiology, risk factors, and treatment of patients with persistent symptoms in the context of Lyme disease. The meaning and relevance of existing patient subgroups will be discussed, as will future research priorities, including the need to develop illness biomarkers, elucidate the biologic mechanisms of disease, and drive improvements in therapeutic options.

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.

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]). 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. 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. 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.

Anti-lysoganglioside and other anti-neuronal autoantibodies in post-treatment Lyme Disease and Erythema Migrans after repeat infection

BackgroundMolecular mimicry targeting neural tissue has been reported after Borrelia burgdorferi(Bb) infection. Herein, we investigate whether antineuronal autoantibodies are increased and whether antibody-mediated signaling of neuronal cells is elevated in a cohort of symptomatic adults with a history of Lyme Disease (LD). MethodsParticipants (n ​= ​179) included 24 with recent Erythema Migrans (EM) without prior LD, 8 with recent EM and prior LD (EM ​+ ​prior LD), 119 with persistent post-treatment LD symptoms (PTLS), and 28 seronegative endemic controls with no prior LD history. Antineuronal immunoglobulin G (IgG) titers were measured by standard ELISA and compared with mean titers of normal age-matched sera against lysoganglioside, tubulin, and dopamine receptors (D1R and D2R). Antibody-mediated signaling of calcium calmodulin dependent protein kinase II (CaMKII) activity in a human neuronal cell line (SK-N-SH) was identified in serum. ResultsEM ​+ ​prior LD cases had higher antibody titers than controls for anti-lysoganglioside GM1 (p ​= ​0.002), anti-tubulin (p ​= ​0.03), and anti-D1R (p ​= ​0.02), as well as higher expression in the functional antibody-mediated CaMKII Assay (p ​= ​0.03). The EM cases with no prior history showed no significant differences on any measures. The PTLS cases demonstrated significantly higher titers (p ​= ​0.01) than controls on anti-lysoganglioside GM1, but not for the other measures. ConclusionThe finding of elevated anti-neuronal autoantibodies in our small sample of those with a prior history of Lyme disease but not in those without prior Lyme disease, if replicated in a larger sample, suggests an immune priming effect of repeated infection; the CaMKII activation suggests that antineuronal antibodies have functional significance. The elevation of anti-lysoganglioside antibodies among those with PTLS is of particular interest given the established role of anti-ganglioside antibodies in peripheral and central neurologic diseases. Future prospective studies can determine whether these autoantibodies emerge after Bb infection and whether their emergence coincides with persistent neurologic or neuropsychiatric symptoms.

There is no magic cure for post treatment Lyme disease syndrome, but many patients do recover with time.

After having had effective antibiotic treatment for Lyme disease, some people continue to have problems that can last a long time. I caught Lyme disease in 1998, had a delay in diagnosis and in getting effective treatment, and so was ill for several years. I could still do many normal everyday things despite feelings of extreme fatigue which led me to spending most of each day lying down. I read a lot in those years and noticed in the literature the various descriptions of the fatigue following Lyme disease as profound, notable, unusual, debilitating, and extreme. That fit with what I experienced, and so it was clear to me that I was not the only one with the problem. It was a real shock when, after suffering for a few months, a colleague told me that it may last another three years or more. Later I asked a specialist if I could expect to get completely better, and he said that he knew patients who, after three years, had completely forgotten their fatigue, so I then thought I just had to hang on for a couple more years. There were several times in those years when I looked back and thought that the fatigue that I had felt at the same time in the previous year had been worse. That was encouraging because I realized I was slowly improving. I had been told that if I was getting better, however slowly, this was a sign that I did not need any more antibiotics, and so I did not worry that I needed any specific treatment.

The General Symptom Questionnaire-30 (GSQ-30): A Brief Measure of Multi-System Symptom Burden in Lyme Disease.

Introduction: The multi-system symptoms accompanying acute and post-treatment Lyme disease syndrome pose a challenge for time-limited assessment. The General Symptom Questionnaire (GSQ-30) was developed to fill the need for a brief patient-reported measure of multi-system symptom burden. In this study we assess the psychometric properties and sensitivity to change of the GSQ-30.Materials and Methods: 342 adult participants comprised 4 diagnostic groups: Lyme disease (post-treatment Lyme disease syndrome, n = 124; erythema migrans, n = 94); depression, n = 36; traumatic brain injury, n = 51; healthy, n = 37. Participants were recruited from clinical research facilities in Massachusetts, Maryland, and New York. Validation measures for the GSQ-30 included the Patient Health Questionnaire-4 for depression and anxiety, visual analog scales for fatigue and pain, the Sheehan Disability Scale for functional impairment, and one global health question. To assess sensitivity to change, 53 patients with erythema migrans completed the GSQ-30 before treatment and 6 months after 3 weeks of treatment with doxycycline.Results: The GSQ-30 demonstrated excellent internal consistency (Cronbach α = 0.95). The factor structure reflects four core domains: pain/fatigue, neuropsychiatric, neurologic, and viral-like symptoms. Symptom burden was significantly associated with depression (rs = 0.60), anxiety (rs = 0.55), pain (rs = 0.75), fatigue (rs = 0.77), functional impairment (rs = 0.79), and general health (rs = −0.58). The GSQ-30 detected significant change in symptom burden before and after antibiotic therapy; this change correlated with change in functional impairment. The GSQ-30 total score significantly differed for erythema migrans vs. three other groups (post-treatment Lyme disease syndrome, depression, healthy controls). The GSQ-30 total scores for traumatic brain injury and depression were not significantly different from post-treatment Lyme disease syndrome.Conclusions and Relevance: The GSQ-30 is a valid and reliable instrument to assess symptom burden among patients with acute and post-treatment Lyme disease syndrome and is sensitive in the detection of change after treatment among patients with erythema migrans. The GSQ-30 should prove useful in clinical and research settings to assess multi-system symptom burden and to monitor change over time. The GSQ-30 may also prove useful in future precision medicine studies as a clinical measure to correlate with disease-relevant biomarkers.

Antabuse for Lyme Disease: The Way Forward

Despite leadership by dedicated lay organization and patient-based advocacy groups, the way forward for prospective candidates for disulfiram treatment has been difficult. This article provides the background, overview of disulfiram, in particular its intended use in post-treatment Lyme disease syndrome after a standard of care course of antibiotics fails to alleviate symptoms of tick borne disease. A series of recommendations are offered to guide patients and clinicians.

Disulfiram (Antabuse) Neurotoxicity: Implications of Painful Small Fiber Sensory Polyneuropathy for Lyme Disease and Addiction

This article describes the prototypical clinical presentation, electrodiagnostic and neuropathological findings and treatment of a patient with painful peripheral neuropathy due to disulfiram toxicity. Although a review of the literature fails to reveal cases of painful peripheral neuropathy due to disulfiram toxicity, there has been heightened publicity of its risk in the treatment of persistent symptoms of Lyme disease following a standard of care course of antibiotics known as post-treatment Lyme disease syndrome. This article reviews the etiopathogenesis and diagnosis of predominant small fiber neuropathy resulting from disulfiram neurotoxicity, and offers recommendations for its use in Lyme disease and alcoholism.

Post-treatment Lyme disease symptoms score: Developing a new tool for research.

Some patients have residual non-specific symptoms after therapy for Lyme disease, referred to as post-treatment Lyme disease symptoms or syndrome, depending on whether there is functional impairment. A standardized test battery was used to characterize a diverse group of Lyme disease patients with and without residual symptoms. There was a strong correlation between sleep disturbance and certain other symptoms such as fatigue, pain, anxiety, and cognitive complaints. Results were subjected to a Logistic Regression model using the Neuro-QoL Fatigue t-score together with Short Form-36 Physical Functioning scale and Mental Health component scores; and to a Decision Tree model using only the QoL Fatigue t-score. The Logistic Regression model had an accuracy of 97% and Decision Tree model had an accuracy of 93%, when compared with clinical categorization. The Logistic Regression and Decision Tree models were then applied to a separate cohort. Both models performed with high sensitivity (90%), but moderate specificity (62%). The overall accuracy was 74%. Agreement between 2 time points, separated by a mean of 4 months, was 89% using the Decision Tree model and 87% with the Logistic Regression model. These models are simple and can help to quantitate the level of symptom severity in post-treatment Lyme disease symptoms. More research is needed to increase the specificity of the models, exploring additional approaches that could potentially strengthen an operational definition for post-treatment Lyme disease symptoms. Evaluation of how sleep disturbance, fatigue, pain and cognitive complains interrelate can potentially lead to new interventions that will improve the overall health of these patients.

Characterization of 5′-methylthioadenosine/S-adenosylhomocysteine nucleosidases from Borrelia burgdorferi: Antibiotic targets for Lyme disease

BackgroundBorrelia burgdorferi causes Lyme disease, the most common tick-borne illness in the United States. The Center for Disease Control and Prevention estimates that the occurrence of Lyme disease in the U.S. has now reached approximately 300,000 cases annually. Early stage Borrelia burgdorferi infections are generally treatable with oral antibiotics, but late stage disease is more difficult to treat and more likely to lead to post-treatment Lyme disease syndrome. MethodsHere we examine three unique 5′-methylthioadenosine/S-adenosylhomocysteine (MTA/SAH) nucleosidases (MTNs or MTANs, EC 3.2.2.9) responsible for salvage of adenine and methionine in B. burgdorferi and explore their potential as antibiotic targets to treat Lyme disease. Recombinant Borrelia MTNs were expressed and purified from E. coli. The enzymes were extensively characterized for activity, specificity, and inhibition using a UV spectrophotometric assay. In vitro antibiotic activities of MTN inhibitors were assessed using a bioluminescent BacTiter-Glo™ assay. ResultsThe three Borrelia MTNs showed unique activities against the native substrates MTA, SAH, and 5′-deoxyadenosine. Analysis of substrate analogs revealed that specific activity rapidly dropped as the length of the 5′-alkylthio substitution increased. Non-hydrolysable nucleoside transition state analogs demonstrated sub-nanomolar enzyme inhibition constants. Lastly, two late stage transition state analogs exerted in vitro IC50 values of 0.3–0.4 μg/mL against cultured B. burgdorferi cells. ConclusionB. burgdorferi is unusual in that it expresses three distinct MTNs (cytoplasmic, membrane bound, and secreted) that are effectively inactivated by nucleoside analogs. General significanceThe Borrelia MTNs appear to be promising targets for developing new antibiotics to treat Lyme disease.

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.

Lyme neuroborreliosis.

To review the recent evidence clarifying the symptomatology and diagnosis of nervous system Lyme disease. Two-tier testing combining pairs of ELISAs, using C6 or VlsE assays to replace second tier Western blots, may eliminate confusion about test interpretation. Cerebrospinal fluid (CSF) can be informative in diagnosing central nervous system (CNS) Lyme disease, not peripheral nervous system (PNS) disorders. CSF CXCL13 may provide useful adjunctive information in CNS infection; its specificity remains to be defined. Lyme encephalopathy is not indicative of CNS infection. Post treatment Lyme disease symptoms do not occur in patients who have had definite CNS Lyme infection. Whether post treatment Lyme disease symptom (PTLDS) is an actual entity, or reflects anchoring bias when commonly occurring symptoms arise in patients previously treated for Lyme disease, remains to be determined. Regardless, these symptoms do not reflect CNS infection and do not respond to additional antimicrobial therapy. Serologic testing is robust in individuals with a priori likelihood of infection of greater than 2-6 weeks duration. Western blots provide useful confirmation of screening ELISAs, but may be replaced by second ELISAs. CSF testing, including CXCL13, may be informative in CNS Lyme, not PNS, and is generally normal in Lyme encephalopathy. PTLDS does not occur following CNS infection, and may not be a distinct entity.

Genetic variation in the ABCB1 gene associated with post treatment lyme disease syndrome status

Post Treatment Lyme Disease Syndrome (PTLDS) poses a difficult to understand health issue. This multi-centered, randomized control trial studied the possible correlation between ABCB1 (MDR1) gene variants and the incidence of PTLDS in affected patients. Genomic DNA was isolated and analyzed for four ABCB1 gene SNPs (rs1128503, rs1045642, rs2235067, and rs4148740). Significant findings include the association of rs1128503 TC variant with PTLDS status. Additionally, the rs1128503+ rs1045642+ rs2235067 SNP combination increased rs1128503 genotype TC significance to 3.83 times the rs1128503 genotype CC. The TT variant of rs4148740 in conjunction with rs1128503 reduced the odds ratio and appeared to convey a PTLDS protective status to the rs1128503 TC variant.

Estimation of cumulative number of post-treatment Lyme disease cases in the US, 2016 and 2020

BackgroundLyme disease (LD) is an infectious multi-system illness caused by the bacterial genus Borrelia and spread by bites of infected ticks. Although most patients are successfully treated by timely antibiotic therapy, it is broadly accepted that a sizeable number of patients experience treatment failure and continue to suffer long-term, debilitating symptoms, including pain, fatigue, cognitive dysfunction and other symptoms. This is known as post-treatment LD (PTLD), for which diagnosis is not standardized and treatment remains controversial. The prevalence and societal burden of PTLD is unknown.MethodsIn an effort to help characterize the LD landscape, we estimated the number of PTLD cases in the US in 2016 and 2020 using Monte-Carlo simulation techniques, publically-available demographic datasets, uncertainty in the inputs and realistic assumptions about incidence and treatment failure rates.ResultsDepending on the input assumptions, PTLD prevalence estimates for 2016 ranged from 69,011 persons (95% CI 51,796 to 89,312) to 1,523,869 (CI 1,268,634 to 1,809,416). Prevalence in 2020 is predicted to be higher than 2016, and may be as high as 1,944,189 (CI 1,619,988 to 2,304,147) cases.ConclusionsThe cumulative prevalence of PLTD in the United States is estimated to be high and continues to increase. These findings will be of interest to epidemiologists and health economists studying disease burden in the US and elsewhere, and justify funding to study PTLD diagnosis and treatment.

Prevalence and determinants of persistent symptoms after treatment for Lyme borreliosis: study protocol for an observational, prospective cohort study (LymeProspect)

BackgroundAfter antibiotic treatment of Lyme borreliosis, a subset of patients report persistent symptoms, also referred to as post-treatment Lyme disease syndrome. The reported prevalence of persistent symptoms varies considerably, and its pathophysiology is under debate. The LymeProspect study has been designed to investigate the prevalence, severity, and a wide range of hypotheses on the etiology of persistent symptoms among patients treated for Lyme borreliosis in the Netherlands.MethodsLymeProspect is a prospective, observational cohort study among adults with proven or probable Lyme borreliosis, either erythema migrans or disseminated manifestations, included at the start of antibiotic treatment. During one year of follow-up, participants are subjected to questionnaires every three months and blood is collected repeatedly during the first three months. The primary outcome is the prevalence of persistent symptoms after treatment, assessed by questionnaires online focusing on fatigue (CIS, subscale fatigue severity), pain (SF-36, subscale pain) and neurocognitive dysfunction (CFQ). Potential microbiological, immunological, genetic, epidemiological and cognitive-behavioral determinants for persistent symptoms are secondary outcome measures. Control cohorts include patients with long-lasting symptoms and unconfirmed Lyme disease, population controls, and subjects having reported a tick bite not followed by Lyme borreliosis.DiscussionThis article describes the background and design of the LymeProspect study protocol. This study is characterized by a prospective, explorative and multifaceted design. The results of this study will provide insights into the prevalence and determinants of persistent symptoms after treatment for Lyme borreliosis, and may provide a rationale for preventive and treatment recommendations.Trial registrationNTR4998 (Netherlands Trial Register). Date of registration: 13 February 2015.

Lyme Disease Patient Trajectories Learned from Electronic Medical Data for Stratification of Disease Risk and Therapeutic Response

Lyme disease (LD) is the most common tick-borne illness in the United States. Although appropriate antibiotic treatment is effective for most cases, up to 20% of patients develop post-treatment Lyme disease syndrome (PTLDS). There is an urgent need to improve clinical management of LD using precise understanding of disease and patient stratification. We applied machine-learning to electronic medical records to better characterize the heterogeneity of LD and developed predictive models for identifying medications that are associated with risks of subsequent comorbidities. For broad disease categories, we identified 3, 16, and 17 comorbidities within 2, 5, and 10 years of diagnosis, respectively. At a higher resolution of ICD-9 codes, we identified known associations with LD including chronic pain and cognitive disorders, as well as particular comorbidities on a timescale that matched PTLDS symptomology. We identified 7, 30, and 35 medications associated with risks of these comorbidities within 2, 5, and 10 years, respectively. For instance, the first-line antibiotic doxycycline exhibited a consistently protective association for typical symptoms of LD, including backache. Our approach and findings may suggest new hypotheses for more personalized treatments regimens for LD patients.

Association of small fiber neuropathy and post treatment Lyme disease syndrome.

ObjectivesTo examine whether post-treatment Lyme disease syndrome (PTLDS) defined by fatigue, cognitive complaints and widespread pain following the treatment of Lyme disease is associated with small fiber neuropathy (SFN) manifesting as autonomic and sensory dysfunction.MethodsThis single center, retrospective study evaluated subjects with PTLDS. Skin biopsies for assessment of epidermal nerve fiber density (ENFD), sweat gland nerve fiber density (SGNFD) and functional autonomic testing (deep breathing, Valsalva maneuver and tilt test) were performed to assess SFN, severity of dysautonomia and cerebral blood flow abnormalities. Heart rate, end tidal CO2, blood pressure, and cerebral blood flow velocity (CBFv) from middle cerebral artery using transcranial Doppler were monitored.Results10 participants, 5/5 women/men, age 51.3 ± 14.7 years, BMI 27.6 ± 7.3 were analyzed. All participants were positive for Lyme infection by CDC criteria. At least one skin biopsy was abnormal in all ten participants. Abnormal ENFD was found in 9 participants, abnormal SGNFD in 5 participants, and both abnormal ENFD and SGNFD were detected in 4 participants. Parasympathetic failure was found in 7 participants and mild or moderate sympathetic adrenergic failure in all participants. Abnormal total CBFv score was found in all ten participants. Low orthostatic CBFv was found in 7 participants, three additional participants had abnormally reduced supine CBFv.ConclusionsSFN appears to be associated with PTLDS and may be responsible for certain sensory symptoms. In addition, dysautonomia related to SFN and abnormal CBFv also seem to be linked to PTLDS. Reduced orthostatic CBFv can be associated with cerebral hypoperfusion and may lead to cognitive dysfunction. Autonomic failure detected in PTLDS is mild to moderate. SFN evaluation may be useful in PTLDS.

Imaging glial activation in patients with post-treatment Lyme disease symptoms: a pilot study using [11C]DPA-713 PET

The pathophysiology of post-treatment Lyme disease syndrome (PTLDS) may be linked to overactive immunity including aberrant activity of the brain’s resident immune cells, microglia. Here we used [11C]DPA-713 and positron emission tomography to quantify the 18 kDa translocator protein, a marker of activated microglia or reactive astrocytes, in the brains of patients with post-treatment Lyme disease symptoms of any duration compared to healthy controls. Genotyping for the TSPO rs6971 polymorphism was completed, and individuals with the rare, low affinity binding genotype were excluded. Data from eight brain regions demonstrated higher [11C]DPA-713 binding in 12 patients relative to 19 controls. [11C]DPA-713 PET is a promising tool to study cerebral glial activation in PTLDS and its link to cognitive symptoms.

Clinical spectrum of Lyme disease.

Lyme disease (borreliosis) is one of the most common vector-borne diseases worldwide. Its incidence and geographic expansion has been steadily increasing in the last decades. Lyme disease is caused by Borrelia burgdorferi sensu lato, a heterogeneous group of which three genospecies have been systematically associated to Lyme disease: B. burgdorferi sensu stricto Borrelia afzelii and Borrelia garinii. Geographical distribution and clinical manifestations vary according to the species involved. Lyme disease clinical manifestations may be divided into three stages. Early localized stage is characterized by erythema migrans in the tick bite site. Early disseminated stage may present multiple erythema migrans lesions, borrelial lymphocytoma, lyme neuroborreliosis, carditis, or arthritis. The late disseminated stage manifests with acordermatitis chronica atrophicans, lyme arthritis, and neurological symptoms. Diagnosis is challenging due to the varied clinical manifestations it may present and usually involves a two-step serological approach. In the current review, we present a thorough revision of the clinical manifestations Lyme disease may present. Additionally, history, microbiology, diagnosis, post-treatment Lyme disease syndrome, treatment, and prognosis are discussed.

Neurocognition in Post-Treatment Lyme Disease and Major Depressive Disorder

Neurocognitive dysfunction in patients with residual or emergent symptoms after treatment for Lyme Disease is often attributed to comorbid depression. In this study, patients with Post-Treatment Lyme Disease Syndrome (PTLDS) were compared to patients with Major Depressive Disorder (MDD), as well as healthy comparison subjects (HC), on neurocognitive measures administered through the same laboratory, to determine if patterns of performance were similar. Two analyses were conducted. First, performance on the Wechsler Adult Intelligence Scale (WAIS-III) and on subtests from the Wechsler Memory Scale (WMS-III) was compared among the groups. Second, comparable subgroups of PTLDS and MDD patients with at least one low WMS-III score were compared on an additional set of measures assessing motor function, psychomotor performance, attention, memory, working memory, and language fluency, to determine if the overall profile of performance was similar in the two subgroups. In the first analysis, PTLDS patients performed more poorly than both MDD and HC on tasks assessing verbal abilities, working memory, and paragraph learning. Processing speed in the two patient groups, however, was equally reduced. In the second analysis, MDD patients with low WMS-III exhibited concomitantly greater difficulties in psychomotor speed and attention, while low-WMS-III PTLDS patients exhibited greater difficulties in language fluency. MDD and PTLDS can be confused neuropsychologically because both exhibit similar levels of psychomotor slowing. However, problems on memory-related tasks, though mild, are more pronounced in PTLDS. PTLDS patients with poorer memory also exhibit poorer language fluency, and less deficit in processing speed and attention compared to MDD.

RETRACTED ARTICLE: Evaluating polymicrobial immune responses in patients suffering from tick-borne diseases

There is insufficient evidence to support screening of various tick-borne diseases (TBD) related microbes alongside Borrelia in patients suffering from TBD. To evaluate the involvement of multiple microbial immune responses in patients experiencing TBD we utilized enzyme-linked immunosorbent assay. Four hundred and thirty-two human serum samples organized into seven categories followed Centers for Disease Control and Prevention two-tier Lyme disease (LD) diagnosis guidelines and Infectious Disease Society of America guidelines for post-treatment Lyme disease syndrome. All patient categories were tested for their immunoglobulin M (IgM) and G (IgG) responses against 20 microbes associated with TBD. Our findings recognize that microbial infections in patients suffering from TBDs do not follow the one microbe, one disease Germ Theory as 65% of the TBD patients produce immune responses to various microbes. We have established a causal association between TBD patients and TBD associated co-infections and essential opportunistic microbes following Bradford Hill’s criteria. This study indicated an 85% probability that a randomly selected TBD patient will respond to Borrelia and other related TBD microbes rather than to Borrelia alone. A paradigm shift is required in current healthcare policies to diagnose TBD so that patients can get tested and treated even for opportunistic infections.