A Study of the Technique of Western Blot for Diagnosis of Lyme Disease caused by Borrelia afzelii in China

Objective To study the technique of Western blot for the diagnosis of Lyme disease caused by Borrelia afzelii in China and to establish the standard criteria by operational procedure. Methods FP1, which is the representative strain of B. afzelii in China, was analyzed by SDS-PAGE, electro transfer and irnmunoblotting assays. The molecular weights of the protein bands of FP1 were analyzed by Gel-Pro analysis software. In a study using 451 serum samples （159 patients with Lyme disease and 292 controls）, all observed bands were recorded. The accuracy of the WB as a diagnostic test was established by using the ROC curve and Youden index. Results Criteria for a positive diagnosis of Lyme disease were established as at least one band of P83/100, P58, P39, OspB, OspA, P30, P28, OspC, P17, and P14 in the IgG test and at least one band of P83/100, P58, P39, OspA, P30, P28, OspC, P17, and P41 in the IgM test. For IgG criteria, the sensitivity, specificity and Youden index were 69.8%, 98.3%, and 0.681, respectively; for IgM criteria, the sensitivity, specificity and Youden index were 47%, 94.2%, and 0.412, respectively.

Cochlear and Vestibular Functional Study in Patients with Sudden Deafness and Lyme Disease

Lyme disease (LD) and idiopathic sudden deafness (ISD) are supposed to be different diseases with different aetiologies. In an attempt to confirm this assumption, 10 patients with confirmed LD and 12 patients with ISD were consecutively included into the study. Further to the laboratory and audio logical investigation, a low frequency sound (LFS) stimulation on posturography was performed and evaluated. Patients with ISD had higher pure tone average (PTA) than patients with LD (PTA ISD/LD was 72 decibel (dB)/23 dB). There was no difference of vertigo between LD and ISD patients. Patients with ISD have more body sway velocity during the first stimulation than patients with LD. We conclude that the cochlear organ is more affected in ISD patients than in patients with LD. However, the vestibular organ seems to be affected in both diseases. ISD and LD are two different disease entities with different aetiologies but with common otological clinical signs.

Respiratory modulation of cardiac vagal tone in Lyme disease

AIM: To conduct the first systematic test of the hypothesis that modulation of cardiac vagal tone is impaired in Lyme disease.METHODS: The response of cardiac vagal tone to respiratory modulation was measured in 18 serologically positive Lyme disease patients and in 18 controls.RESULTS: The two groups were matched in respect of age,sex,body mass,mean arterial blood pressure,mean resting heart rate and mean resting cardiac vagal tone. The mean maximum cardiac vagal tone during deep breathing in the Lyme disease patients [11.2(standard error 1.3)] was lower than in the matched controls [16.5(standard error 1.7); P = 0.02].CONCLUSION: Respiratory modulation of cardiac vagal tone is impaired in Lyme disease,which suggests that Lyme disease may directly affect the vagus nerve or the brainstem.

A Preliminary Study of C-reactive Protein in the Diagnosis and Monitoring of Lyme Disease

Concentrations of C-reactive protein (CRP) in the serum of 14 patients suffering from Lyme diseasc were measured. 86% of these patients were found to have abnormally high concentrations of serum CRP (range 14-158 mg/L). The CRP concentration of a 60-yearold patient abated from 29 mg/L to 13 mg/L after treatrnent. Results suggest that serum CRP concentration can provide a valuable and accurate means for the clinical diagnosis and monitoring of Lyme disease

PathoDNA, an Advanced Diagnostic for Lyme Disease &Co-Infections Utilizing Next Generation DNA Sequencing with Greater Sensitivity and Selectivity than ELISA/Western Blot

The controversial subject of chronic Lyme disease has occupied medical discourse for years while contributing to unprecedented patient suffering in the United States and abroad. A general misunderstanding of Lyme disease and overconfidence in the Center for Disease Control’s (CDC) recommended two-step test for Lyme disease has led to misdiagnosis and incorrect treatment over the years. This leads to increasing medical expenses and worse outcomes for patients. The two-step test, an ELISA immunoblot followed by a confirmatory Western blot, yields accuracy rates as low as 29% for acute Lyme disease and 75% for chronic Lyme disease. While these practices have been a staple of microbiology for decades, these accuracy rates are unacceptable for diagnostic tests when better technology is available. PathoDNA, a Next-Generation DNA sequencing test for Lyme disease and other tick-borne pathogens, achieves accuracy rates of 98% for B. burgdorferi and 95% or greater for other common tick-borne pathogens with superior sensitivity and selectivity. PathoDNA is a Clinical Laboratory Improvement and Amendments (CLIA)-validated laboratory test that achieves these results utilizing Next Generational DNA Sequencing and a proprietary bioinformatics database. Thus, it allows for rapid results and specific identification of tick-borne illnesses. In this article, we will compare this promising technology against the existing standards for diagnosing and testing Lyme disease. We believe that PathoDNA can set a new standard for identifying Borrelia and diagnosing Lyme disease along with other tick-borne infections.

Optic Neuritis in Acute Neuroborreliosis (Lyme Disease) in the U.S.-Mexican Border: Case Report

Objective: We describe a patient diagnosed with acute neuroborreliosis presenting with anterior optic neuritis (papillitis) in a non-endemic region. Case Presentation: A 43-year-old previously healthy right handed man admitted due to an insidious onset of severe headache and spells of ascending paresthesias from his right foot into his right arm and face followed by speech arrest and clumsiness of his right hand. His neurologic exam was significant for somnolence, nuchal rigidity and Kernig and Brudzinski signs were present. MRI of the brain with gadolinium showed diffuse hyperintense signal involving the supra and infratentorial cortical sulci, with associated faint diffuse leptomeningeal enhancement, consistent most likely with diffuse leptomeningoencephalitis. EEG: normal. CSF VDRL was negative. Dilated fundus exam revealed mild optic nerve edema more significant to the left than to the right eye, confirmed and measured by spectral domain OCT (Optical Coherence Tomography). There was an evidence of posterior uveitis with an early vitreous hemorrhage superficial to the left optic nerve. Lyme disease serum antibody (IgM) Immunoblotting was positive in 2 bands confirming the diagnosis of neuroborreliosis. Conclusion: Optic nerve involvement in Lyme disease is an uncommon complication that should be confirmed by specific diagnostic criteria to establish its causal relation.

Lyme Disease Presenting as Ankylosing Spondylitis: A Case Report

Lyme disease is a rapidly growing tick-borne infection in many parts of the United States. Due to the complexity of the various symptom presentations associated with Lyme disease, Borrelia burgdorferi, the bacteria that causes Lyme disease, is thought of as a disease-mimicking infection. The present case report summarizes the case of an adult female patient who was initially diagnosed with ankylosing spondylitis. After becoming refractory to autoimmune-based treatment interventions, she presented to an integrative medicine clinic where she was diagnosed with Lyme disease. Symptoms resolved after following and completing an anti-microbial based protocol, symptoms resolved. Her symptoms remained resolved at follow-up.

Posttreatment Lyme disease syndrome and myalgic encephalomyelitis/chronic fatigue syndrome:A systematic review and comparison of pathogenesis

Lyme disease is the most common vector-borne illness in the United States and has been causing significant morbidity since its discovery in 1977.It is well-documented that about 10%of patients properly treated with antibiotics never fully recover,but instead go on to develop a chronic illness dubbed,posttreatment Lyme disease syndrome(PTLDS)characterized by severe fatigue,cognitive slowing,chronic pain,and sleep difficulties.This review includes 18 studies that detail the symptoms of patients with PTLDS and uses qualitative analysis to compare them to myalgic encephalitis/chronic fatigue syndrome(ME/CFS),a strikingly similar syndrome.In the majority of the PTLDS studies,at least four of the six major symptoms of ME/CFS were also noted,including substantial impairment in activity level and fatigue for more than 6 months,post-exertional malaise,and unrefreshing sleep.In one of the included PTLDS articles,26 of the 29 ME/CFS symptoms were noted.This study adds to the expanding literature on the post-active phase of infection syndromes,which suggests that chronic illnesses such as PTLDS and ME/CFS have similar pathogenesis despite different infectious origins.

The conflict on posttreatment Lyme disease syndrome: a clinical mini review

Is Borrelia burgdorferi responsible for the persistence of symptoms after the standard successful course of antibiotics in Lyme disease patients?This highly controversial issue,concerning the underlying mechanism of posttreatment Lyme disease syndrome(PTLDS),still seems to be a matter of intense conflict of opinion.PTLDS is the manifestation of nonspecific symptoms including fatigue,musculoskeletal pain,dysesthesias,and neurocognitive deterioration after the standard antimicrobial therapy administered to patients suffering from Lyme disease.In this article,we review the conflicting views and published highlights of recent human studies regarding PTLDS.

Modeling Lyme disease transmission

Lyme disease,a typical tick-borne disease,imposes increasing global public health challenges.A growing body of theoretical models have been proposed to better understand various factors determining the disease risk,which not only enrich our understanding on the ecological cycle of disease transmission but also promote new theoretical developments on model formulation,analysis and simulation.In this paper,we provide a review about the models and results we have obtained recently on modeling and analyzing Lyme disease transmission,with the purpose to highlight various aspects in the ecological cycle of disease transmission to be incorporated,including the growth of ticks with different stages in the life cycle,the seasonality,host diversity,spatial disease pattern due to host short distance movement and bird migration,co-infection with other tick-borne pathogens,and climate change impact.

Modeling transmission dynamics of lyme disease: Multiple vectors, seasonality, and vector mobility

Lyme disease is the most prevalent tick-borne disease in the United States,which humans acquire from an infected tick of the genus Ixodes(primarily Ixodes scapularis).While previous studies have provided useful insights into various aspects of Lyme disease,the tick's host preference in the presence of multiple hosts has not been considered in the existing models.In this study,we develop a transmission dynamics model that includes the interactions between the primary vectors involved:blacklegged ticks(I.scapularis),white-footed mice(Peromyscus leucopus),and white-tailed deer(Odocoileus virginianus).Our model shows that the presence of multiple vectors may have a significant impact on the dynamics and spread of Lyme disease.Based on our model,we also calculate the basic reproduction number,R 0,a threshold value that predicts whether a disease exists or dies out.Subsequent extensions of the model consider seasonality of the tick's feeding period and mobility of deer between counties.Our results suggest that a longer tick peak feeding period results in a higher infection prevalence.Moreover,while the deer mobility may not be a primary factor for short-term emergence of Lyme disease epidemics,in the long-run it can significantly contribute to local infectiousness in neighboring counties,which eventually reach the endemic steady state.

Dissociating Delusional Disorders and Infections from Dermatologic and Neurologic Effects of Morgellons Disease

Morgellons disease (MD) is a multi-system disorder characterized by multicolor filaments extruding out of the skin along with an array of dermatologic and neuropsychiatric symptoms. It was previously termed Delusional parasitosis. However, published scientific data found the association of MD symptoms with the systemic manifestations of Lyme disease, caused by Borrelia spirochete. In a retrospective study of 122 MD patients, skin specimens were examined and 96% of them showed Borrelia spirochete in their histology sample. Hence, this association suggests that spirochete infection could be a possible cause of chronic illness in MD patients, and this rejected the physician’s perception that MD lesions might be self-inflicted. A cohort study reported tick-borne co-infections among MD patients, which could also be an etiological factor for dermopathy in MD patients. Some literature also discussed neuropsychiatric manifestations like cognitive impairment, dementia anxiety, depression, paranoia, and sensory hallucinations in Lyme disease and associated tick-borne infection. The objectives of this review are to identify the differences in the past and current perception regarding the pathogenesis of MD and determine the associations of spirochetal and tick-borne diseases with MD and psychiatric illnesses. More than 50 new research articles and case reports were reviewed and only 31 articles were shortlisted and used as references. This review has a detailed discussion on Morgellons disease and its association with Spirochete infection.

Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma of the Colon in a Patient with <i>Borrelia burgdorferi</i>Infection (Lyme Arthritis)

Mucosa-associated lymphoid tissue (MALT) lymphoma generally occurs in the context of chronic inflammation or autoimmune disorders. The most common infections linked to MALT lymphomas include Helicobacter pylori (Hp)-associated gastritis, Chlamydophila psittacii and hepatitis C infection. Although Borrelia burgdorferi infection has been linked to primary cutaneous B-cell lymphoma (PCBCL), there is no known link between Borrelia burgdorferi infection and MALT lymphomas in the US. We report a patient who developed mucosa-associated lymphoid tissue (MALT) lymphoma of the colon in the context of untreated Lyme arthritis, and no other autoimmune disorders or infections known to be associated with MALT lymphoma. We recommend that Lyme disease due to Borrelia burgdorferi be considered as a possible underlying infection potentially contributing to the emergence of extranodal lymphoma.

Detection of Borrelia americana in the Avian Coastal Tick, Ixodes auritulus (Acari: Ixodidae), Collected from a Bird Captured in Canada

We document the first record of Borrelia americana in Canada. This Borrelia was detected in an avian coast tick, Ixodes auritulus (Acari: Ixodidae), collected from a Varied Thrush, Ixoreus naevius, along coastal British Columbia. Using real-time PCR and DNA sequencing of the flagellin gene, we determined that the borrelial amplicon from the I. auritulus nymph was 99% homologous with B. americana type strain SCW-41. Because patients infected with B. americana can be seronegative for Lyme disease, medical professionals should be willing to pursue molecular analyses and consider treatment for patients with Lyme disease-like symptoms.

Estimates for Lyme borreliosis infections based on models using sentinel canine and human seroprevalence data

Two models were developed to estimate Lyme borreliosis(LB)cases.One was based on the seroprevalence of Borrelia infections in human samples.This model used corrections for false negative and false positive results from published test sensitivity and specificity measures.A second model based on Borrelia infections in sentinel dogs was used to quantify the prevalence of Lyme disease Borrelia infections in humans;the reference baseline for this model was human and canine infections in Germany.A comparison of the two models is shown and differences discussed.The relationships between incidence,prevalence and total infection burden for LB were derived from published data and these were used in both models to calculate annual incidence,prevalence and total LB infections.The modelling was conservative and based on medical insurance records coded for erythema migrans.Linear model growth rates were used in place of the commonly adopted exponential growth.The mean of the two models was used to create estimates for various countries and continents.Examples from the analyses for LB estimated for 2018 include:incidence e USA 473,000/year,Germany 471,000/year,France 434,000/year and UK 132,000/year;prevalence e USA 2.4 million,Germany 2.4 million,France 2.2 million and UK 667,000;total infections e USA 10.1 million,Germany 10.0 million,France 9.3 million and UK 2.8 million.Estimates for the world for 2018 are:incidence 12.3 million/year;prevalence 62.1 million;and total infection burden 262.0 million.These figures are far higher than officially published data and reflect not only the underestimation of diagnosed cases,which is acknowledged by health agencies,but also undiagnosed and misdiagnosed cases.

Nitroxoline Drug Combinations Are More Active Than Lyme Antibiotic Combination and Can Eradicate Stationary-Phase Borrelia burgdorferi

Lyme disease(LD),caused by Borrelia burgdorferi,is themost common vector-borne disease in the United States and Europe.Despite the standard 2–4 weeks'antibiotic treatment,approximately 10%–20%of patients will develop posttreatment LD syndrome,a condition that is poorly understood.One of the probable causes is thought to be the presence of B.burgdorferi persister forms that are not effectively killed by the current LD antibiotics.In this study,we evaluated nitroxoline,an antibiotic used to treat urinary tract infections,for its activity against a stationary-phase culture enriched with persister forms of B.burgdorferi.Nitroxoline was found to be more active than doxycycline and equally active as cefuroxime(standard LD antibiotics)against B.burgdorferi.Importantly,the nitroxoline two-drug combinations nitroxoline+cefuroxime and nitroxoline+clarithromycin,as well as the nitroxoline three-drug combination nitroxoline+cefuroxime+clarithromycin,were as effective as the persister drug daptomycin-based positive control three-drug combination cefuroxime+doxycycline+daptomycin,completely eradicating stationary-phase B.burgdorferi in the drug-exposure experiments and preventing regrowth in the subculture study.Future studies should evaluate these promising drug combinations in a persistent LD mouse model.

Female ticks (Ixodes scapularis) infected with Borrelia burgdorferi have increased overwintering survival, with implications for tick population growth

The tick, Ixodes scapularis, vectors pathogens such as Borrelia burgdorferi, the bacterium that causes Lyme disease. Over the last few decades I. scapularis has expanded its range, introducing a novel health threat into these areas. Warming temperatures appear to be one cause of its range expansion to the north. However, other factors are also involved. We show that unfed adult female ticks infected with B. burgdorferi have greater overwintering survival than uninfected female ticks. Locally collected adult female ticks were placed in individual microcosms and allowed to overwinter in both forest and dune grass environments. In the spring we collected the ticks and tested both dead and living ticks for B. burgdorferi DNA. Infected ticks had greater overwintering survival compared with uninfected ticks every winter for three consecutive winters in both forest and dune grass environments. We discuss the most plausible explanations for this result. The increased winter survival of adult female ticks could enhance tick population growth. Our results suggest that, in addition to climate change, B. burgdorferi infection itself may be promoting the northern range expansion of I. scapularis. Our study highlights how pathogens could work synergistically with climate change to promote host range expansion.