Lyme Disease Patients Research Articles

Evaluation of Prospectively Followed Adult Patients with Erythema Migrans Using the Beck Depression Inventory Second Edition

BackgroundThe Beck Depression Inventory (BDI-II) may be used to evaluate individuals for symptoms of depression. MethodsIn a 1-year prospective study, 52 adult Lyme disease patients with erythema migrans and 104 matched control subjects were clinically assessed and completed the BDI-II at study entry and approximately 6 and 12 months later following antibiotic treatment. ResultsThe mean BDI-II score was significantly higher at the baseline visit among Lyme disease patients compared with controls (P = .002), but no significant differences between the groups were observed at either the 6- or 12-month study visits. Over the course of the study, the mean BDI-II scores decreased an average of approximately 0.22 points per month (P < .0005) for Lyme disease patients, whereas the mean scores changed very little for controls (mean change = −0.02 per month, P = .50). The total number of somatic symptoms, of the 12 symptoms evaluated, strongly and directly correlated with the BDI-II scores at the baseline visit for the Lyme disease patients. ConclusionsThe mean BDI-II scores of patients with early Lyme disease significantly exceeded that of matched controls at study entry, but by 6 months the values did not differ significantly. There was a good-to-excellent direct correlation between the BDI-II score and the total number of symptoms, suggesting that the BDI-II scores were reflecting somatic rather than affective depressive symptoms. When using the BDI-II as an assessment tool of patients with Lyme disease, infection-related somatic symptoms per se need to be considered in the interpretation of the results.

1760. Interferon Gamma Release Assay for Diagnosis of Lyme disease

BackgroundThe sensitivity of current antibody detection assays against Borrelia burgdorferi in the early stage of Lyme disease is very low. In children especially, who commonly have febrile viral illnesses, manifestations of early Lyme disease can be misdiagnosed. We previously demonstrated that IFNγ secretion could be detected in whole blood collected from Lyme disease patients at first clinical presentation following overnight incubation of the blood with peptides derived from B. burgdorferi. In the present study, we further evaluated the utility of IFNγ release for the laboratory diagnosis of Lyme disease in children with varying stages of the illness.MethodsChildren ages 2–18 years with no prior history of Lyme disease and with manifestations of Lyme disease at any stage were enrolled in the study. Sick and healthy controls were enrolled for comparison. We collected history and physical examination data and blood samples at the time of enrollment, at 1 month, and at 6 months. Standard 2-tier testing with ELISA (whole cell sonicate [WCS] and C6) and western blot were run in parallel to the IFNγ release assay for all blood samples. Sensitivity and specificity of the study assay were determined for presentation at all stages of Lyme disease. Clinical data were summarized.ResultsBlood samples from 22 patients with Lyme disease and 7 controls (4 sick, 3 healthy) were obtained at the first visit. The IFNγ release assay detected early and early disseminated Lyme disease with 78% sensitivity compared with 59% sensitivity of 2-tier testing in our study. For patients presenting with a single erythema migrans (EM) lesion, the IFNγ release assay detected Lyme disease with 63% sensitivity compared with 14% sensitivity with 2-tier testing. The IFNγ release assay had only 25% sensitivity for detecting late disease. A single control patient was positive for both the IFNγ release assay and 2-tier serology.ConclusionA novel IFNγ release assay demonstrated significantly increased sensitivity when compared with 2-tier testing in the laboratory diagnosis of Lyme disease in patients presenting with a single EM lesion. Future study is needed to determine its utility in detecting early Lyme disease in patients with nonspecific febrile illness in the absence of erythema migrans.Disclosures R. Dattwyler, Qiagen: Collaborator, Research support. P. Arnaboldi, Qiagen: Collaborator, research materials.

668. Clinical Spectrum of Powassan Virus Infection in Patients Presenting with Suspected Acute Tick-Borne Illness From a Lyme-Endemic Focus in the Midwest

BackgroundPowassan virus (POWV) is the North American member of the tick-borne encephalitis complex of viruses. The potential for concurrent transmission with other tick-borne pathogens, particularly the Lyme disease agent Borrelia burgdorferi, is under studied. To better understand the clinical spectrum of POWV infection patient health records were reviewed and laboratory studies performed to evaluate the frequency of tick-borne pathogen exposure in patients presenting with suspected acute tick-borne illness (TBI) from a Lyme-endemic focus in the Midwest.MethodsOne hundred and thirty-five samples selected from patients seen at Gundersen Health System presenting during 2016 with Lyme-like symptoms were tested for Anaplasmosis, Babesiosis, Lyme disease and POWV. PCR testing was performed for Anaplasma and Babesia. Serologic testing for B. burgdorferi was performed using two-tier serologic testing. POWV infection was confirmed by POWV-EIA/IFA (Coppe Laboratories). IRB approval was obtained.ResultsAnaplasma infection was seen in 44/88 (50%), Babesia infection in 5/67 (7.5%), Lyme disease in 45/135 (33.3%) and POWV infection in 16/132 (12.1%) patients. Co-infections were seen in 21/135 (15.5%) patients. Patients with Babesia more often presented with anemia, myalgia and decreased appetite. Patients with Anaplasma presented with fever, chills/sweats, nausea/vomiting, rash, elevated liver function tests, thrombocytopenia, leukopenia, and remembered the tick exposure. Lyme disease patients complained of fatigue, rash, chills/sweats, headache and remembered the tick exposure. Co-infection with both Lyme and Powassan virus was seen in 10/45 (23%) of patients. Patients with Lyme, Powassan virus or co-infection had no other significant difference in symptoms.ConclusionPOWV infection is more prevalent in the Midwest than previously appreciated. Clinical data suggest that symptoms of POWV infection may be indistinguishable from those of Lyme disease, requiring laboratory testing for proper TBD diagnosis and avoidance of unnecessary antibiotic use. The high rate of POWV co-occurrence with Lyme disease may have relevance for patient outcomes and warrants further investigation. Disclosures S. Kehl, Coppe Laboratories: Consultant, Consulting fee. A. Thomm, Coppe Laboratory: Employee, Salary. P. Pratt, Coppe Laboratory: Employee, Salary. K. Knox, Coppe Laboratory: Owner, Equity as compensation.

Identification of Essential Oils with Strong Activity against Stationary Phase Borrelia burgdorferi.

Lyme disease is the most common vector borne-disease in the United States (US). While the majority of the Lyme disease patients can be cured with 2–4 weeks antibiotic treatment, about 10–20% of patients continue to suffer from persisting symptoms. While the cause of this condition is unclear, persistent infection was proposed as one possibility. It has recently been shown that B. burgdorferi develops dormant persisters in stationary phase cultures that are not killed by the current Lyme antibiotics, and there is interest in identifying novel drug candidates that more effectively kill such forms. We previously identified some highly active essential oils with excellent activity against biofilm and stationary phase B. burgdorferi. Here, we screened another 35 essential oils and found 10 essential oils (Allium sativum L. bulbs, Pimenta officinalis Lindl. berries, Cuminum cyminum L. seeds, Cymbopogon martini var. motia Bruno grass, Commiphora myrrha (T. Nees) Engl. resin, Hedychium spicatum Buch.-Ham. ex Sm. flowers, Amyris balsamifera L. wood, Thymus vulgaris L. leaves, Litsea cubeba (Lour.) Pers. fruits, Eucalyptus citriodora Hook. leaves) and the active component of cinnamon bark cinnamaldehyde (CA) at a low concentration of 0.1% have strong activity against stationary phase B. burgdorferi. At a lower concentration of 0.05%, essential oils of Allium sativum L. bulbs, Pimenta officinalis Lindl. berries, Cymbopogon martini var. motia Bruno grass and CA still exhibited strong activity against the stationary phase B. burgdorferi. CA also showed strong activity against replicating B. burgdorferi, with a MIC of 0.02% (or 0.2 μg/mL). In subculture studies, the top five essential oil hits Allium sativum L. bulbs, Pimenta officinalis Lindl. berries, Commiphora myrrha (T. Nees) Engl. resin, Hedychium spicatum Buch.-Ham. ex Sm. flowers, and Litsea cubeba (Lour.) Pers. fruits completely eradicated all B. burgdorferi stationary phase cells at 0.1%, while Cymbopogon martini var. motia Bruno grass, Eucalyptus citriodora Hook. leaves, Amyris balsamifera L. wood, Cuminum cyminum L. seeds, and Thymus vulgaris L. leaves failed to do so as shown by visible spirochetal growth after 21-day subculture. At concentration of 0.05%, only Allium sativum L. bulbs essential oil and CA sterilized the B. burgdorferi stationary phase culture, as shown by no regrowth during subculture, while Pimenta officinalis Lindl. berries, Commiphora myrrha (T. Nees) Engl. resin, Hedychium spicatum Buch.-Ham. ex Sm. flowers and Litsea cubeba (Lour.) Pers. fruits essential oils all had visible growth during subculture. Future studies are needed to determine if these highly active essential oils could eradicate persistent B. burgdorferi infection in vivo.

Under-Detection of Lyme Disease in Canada.

Lyme disease arises from infection with pathogenic Borrelia species. In Canada, current case definition for confirmed Lyme disease requires serological confirmation by both a positive first tier ELISA and confirmatory second tier immunoblot (western blot). For surveillance and research initiatives, this requirement is intentionally conservative to exclude false positive results. Consequently, this approach is prone to false negative results that lead to underestimation of the number of people with Lyme disease. The province of New Brunswick (NB), Canada, can be used to quantify under-detection of the disease as three independent data sets are available to generate an estimate of the true human disease prevalence and incidence. First, detailed human disease incidence is available for the US states and counties bordering Canada, which can be compared with Canadian disease incidence. Second, published national serology results and well-described sensitivity and specificity values for these tests are available and deductive reasoning can be used to query for discrepancies. Third, high-density tick and canine surveillance data are available for the province, which can be used to predict expected human Lyme prevalence. Comparison of cross-border disease incidence suggests a minimum of 10.2 to 28-fold under-detection of Lyme disease (3.6% to 9.8% cases detected). Analysis of serological testing predicts the surveillance criteria generate 10.4-fold under-diagnosis (9.6% cases detected) in New Brunswick for 2014 due to serology alone. Calculation of expected human Lyme disease cases based on tick and canine infections in New Brunswick indicates a minimum of 12.1 to 58.2-fold underestimation (1.7% to 8.3% cases detected). All of these considerations apply generally across the country and strongly suggest that public health information is significantly under-detecting and under-reporting human Lyme cases across Canada. Causes of the discrepancies between reported cases and predicted actual cases may include undetected genetic diversity of Borrelia in Canada leading to failed serological detection of infection, failure to consider and initiate serological testing of patients, and failure to report clinically diagnosed acute cases. As these surveillance criteria are used to inform clinical and public health decisions, this under-detection will impact diagnosis and treatment of Canadian Lyme disease patients.

Clinical evaluation of Morgellons disease in a cohort of North American patients.

Morgellons disease (MD) is a dermatological condition characterized by aberrant production of keratin and collagen fibers in skin. Although infection with Borrelia burgdorferi, the causative agent of Lyme disease (LD), has been associated with MD, relatively few studies have hitherto provided epidemiological evidence regarding this association. A cohort of 1000 seropositive North American LD patients was evaluated for the presence of MD. Patients were diagnosed with MD based on detection of microscopic fibers in skin lesions or under unbroken skin. Demographic and clinical features of MD patients were analyzed, and laboratory testing for tickborne coinfections and other infectious agents, was performed. Subjective and objective features of MD were analyzed using statistical methods. Of 1000 seropositive LD patients, 60 (6%) were diagnosed with MD. Of these 60 patients, 75% were female and 78% presented in the late disseminated stage of MD. All 60 patients (100%) were seropositive for B. burgdorferi infection. Tickborne coinfections in these patients included Babesia spp (62%), Bartonella and Rickettsia (25% each), Ehrlichia (15%) and Anaplasma (10%). Helicobacter pylori was detected in 12% of MD patients. In all, 77% of MD patients had one or more coinfections. This study confirms recent findings that MD occurs in a limited subset of LD patients. The clinical and genetic determinants of MD in LD patients require further study.

Aggressiveness, violence, homicidality, homicide, and Lyme disease.

BackgroundNo study has previously analyzed aggressiveness, homicide, and Lyme disease (LD).Materials and methodsRetrospective LD chart reviews analyzed aggressiveness, compared 50 homicidal with 50 non-homicidal patients, and analyzed homicides.ResultsMost aggression with LD was impulsive, sometimes provoked by intrusive symptoms, sensory stimulation or frustration and was invariably bizarre and senseless. About 9.6% of LD patients were homicidal with the average diagnosis delay of 9 years. Postinfection findings associated with homicidality that separated from the non-homicidal group within the 95% confidence interval included suicidality, sudden abrupt mood swings, explosive anger, paranoia, anhedonia, hypervigilance, exaggerated startle, disinhibition, nightmares, depersonalization, intrusive aggressive images, dissociative episodes, derealization, intrusive sexual images, marital/family problems, legal problems, substance abuse, depression, panic disorder, memory impairments, neuropathy, cranial nerve symptoms, and decreased libido. Seven LD homicides included predatory aggression, poor impulse control, and psychosis. Some patients have selective hyperacusis to mouth sounds, which I propose may be the result of brain dysfunction causing a disinhibition of a primitive fear of oral predation.ConclusionLD and the immune, biochemical, neurotransmitter, and the neural circuit reactions to it can cause impairments associated with violence. Many LD patients have no aggressiveness tendencies or only mild degrees of low frustration tolerance and irritability and pose no danger; however, a lesser number experience explosive anger, a lesser number experience homicidal thoughts and impulses, and much lesser number commit homicides. Since such large numbers are affected by LD, this small percent can be highly significant. Much of the violence associated with LD can be avoided with better prevention, diagnosis, and treatment of LD.

A Child with Unilateral Visual Impairment Caused by Neuroborreliosis

AbstractThis case report describes a 7-year-old male patient with painless unilateral visual impairment due to optic neuropathy confirmed by visual evoked potentials (VEP), which was found to be attributed to neuroborreliosis. The diagnosis was confirmed by applying both European (European Federation of Neurological Societies [EFNS]) and American (Centers for Disease Control and Prevention [CDC]) criteria. Following intravenous treatment with broad-spectrum antibiotics, his vision gradually improved. This case report adds to the scarce evidence for an association between optic neuropathies and neuroborreliosis. It illustrates that, although uncommon, the clinician should be aware of the possibility of Lyme disease in patients with unilateral visual impairment due to optic neuropathy. Recognition is especially important because visual acuity can return to normal after adequate treatment. We reviewed the differences in criteria by the European EFNS guidelines and the American CDC criteria for making the diagnosis.

Single-photon emission tomography imaging in patients with Lyme disease treated with human embryonic stem cells.

Aim The purpose of this study was to evaluate the longitudinal changes in brain perfusion in patients with Lyme disease treated with human embryonic stem cells. Material and methods The study included 59 (age range 41.68 ± 16.37 years) patients with Lyme disease whose single-photon emission tomography imaging was performed before and after the human embryonic stem cell therapy. Technetium-hexa methyl propylene aminoxime single-photon emission tomography imaging was used to assess the hypoperfused lesions/regions in the brain prior to the therapy, as well as the improvement in perfusion after human embryonic stem cell treatment. Results After receiving human embryonic stem cell therapy, single-photon emission tomography imaging reflects a significant (>60%) improvement in 43 patients along with moderate (30-60%) and mild (<30%) improvement in 12 and four patients, respectively. The cerebral perfusion flow improved and the degree of hypoperfusion in the other regions significantly decreased after the human embryonic stem cell therapy. Interpretation of single-photon emission tomography imaging of brain images (before and after therapy) clearly presented the changes in color at various brain regions which represent the improvements in patients. Conclusion Single-photon emission tomography imaging could be used as a potential diagnostic tool to assess the response of Lyme disease patients to human embryonic stem cell therapy.

Early Disseminated Lyme Disease Masquerading as Mononucleosis: A Case Report

BackgroundDisseminated Lyme disease can be difficult to diagnose, as it begins with nonspecific signs and symptoms, which, if not treated correctly, can lead to atrioventricular conduction blocks and meningitis. In addition, the diagnosis can be further complicated by potentially false-positive test results. Case ReportWe report a case of early-disseminated Lyme disease presenting with Borrelia meningitis and concomitant Lyme carditis, which was misdiagnosed as mononucleosis. A young, previously healthy patient had been hiking in the woods of upstate New York and 4 weeks later developed fever, night sweats, and myalgias. He was diagnosed with mononucleosis via a positive rapid heterophile agglutination antibody test to the Epstein-Barr virus at a walk-in clinic and was started on medications, but then subsequently developed left hip pain, a facial droop, and a very long first-degree atrioventricular conduction block. He went to the Emergency Department, where he had testing that confirmed disseminated Lyme disease. Why Should an Emergency Physician Be Aware of This?This case highlights the difficulty in early diagnosis of disseminated Lyme disease and how a potentially false-positive laboratory test can lead to the complications of Borrelia meningitis and Lyme carditis in untreated young healthy patients. Emergency physicians need to consider Lyme disease in patients with nonspecific signs and symptoms, especially if they have been outdoors for prolonged periods of time in Lyme-endemic areas.

Borrelia infection and risk of celiac disease

BackgroundEnvironmental factors, including infectious agents, are speculated to play a role in the rising prevalence and the geographic distribution of celiac disease, an autoimmune disorder. In the USA and Sweden where the regional variation in the frequency of celiac disease has been studied, a similarity with the geographic distribution of Lyme disease, an emerging multisystemic infection caused by Borrelia burgdorferi spirochetes, has been found, thus raising the possibility of a link. We aimed to determine if infection with Borrelia contributes to an increased risk of celiac disease.MethodsBiopsy reports from all of Sweden’s pathology departments were used to identify 15,769 individuals with celiac disease. Through linkage to the nationwide Patient Register, we compared the rate of earlier occurrence of Lyme disease in the patients with celiac disease to that in 78,331 matched controls. To further assess the temporal relationship between Borrelia infection and celiac disease, we also examined the risk of subsequent Lyme disease in patients with a diagnosis of celiac disease.ResultsTwenty-five individuals (0.16%) with celiac disease had a prior diagnosis of Lyme disease, whereas 79 (0.5%) had a subsequent diagnosis of Lyme disease. A modest association between Lyme disease and celiac disease was seen both before (odds ratio, 1.61; 95% confidence interval (CI), 1.06–2.47) and after the diagnosis of celiac disease (hazard ratio, 1.82; 95% CI, 1.40–2.35), with the risk of disease being highest in the first year of follow-up.ConclusionsOnly a minor fraction of the celiac disease patient population had a prior diagnosis of Lyme disease. The similar association between Lyme disease and celiac disease both before and after the diagnosis of celiac disease is strongly suggestive of surveillance bias as a likely contributor. Taken together, the data indicate that Borrelia infection is not a substantive risk factor in the development of celiac disease.

Diagnosis of Lyme-associated uveitis: value of serological testing in a tertiary centre

AimsTo determine the frequency and clinical presentation of Lyme disease in patients with uveitis and to assess the value of Borrelia burgdorferi serological testing.MethodsRetrospective study on all patients with uveitis...

Lyme disease in the Dutch policy context: patient consultation in government research agenda setting

Prevalence of Lyme disease (LD) is increasing in the Netherlands. The Dutch Association for Lyme Disease Patients (NVLP) presented a petition to the Dutch Parliament for more LD research and political attention. The Parliament requested advice from the Health Council of the Netherlands, which among others initiated a stakeholder consultation process to identify experiences and research needs. This article presents patients’ consultation results, including their research agenda, and compares it to the advisory report. Patients ascribed high research priority to improved diagnostic tools, new treatment options, and improving fundamental knowledge. Including patients’ research needs in the advisory report reflected patients’ perspectives in agenda setting to be valued by political and patient institutions. Some issues were not included, leading to criticism by the NVLP. This study suggests that organising a multi-stakeholder dialogue, particularly focusing on further exploring differences in opinion and creating mutual understanding, might have a beneficial effect on stakeholder satisfaction.

Utilidad de los estudios serológicos en los centros de Atención Primaria para el diagnóstico precoz de la enfermedad de Lyme

ObjectiveThe main aim of this study was to determine the usefulness of an early diagnosis of Lyme disease (LD) in Primary Health Care Centres (PHCC) using the ELISA test as serological screening technique. MethodsA retrospective study (2006-2013) was performed in order to determine the anti-Borrelia seropositivity in 2,842 people at risk of having LD. The possible relationship between the environment and the area of residence with anti-Borrelia seropositivity was also studied according to the origin of the specimens (PHCC/Hospital). ResultsOverall, 15.2% of samples were positive to Borrelia spp. Seropositivity was significantly higher in samples sent by PHCC doctors than those sent by Hospital doctors. Seropositivity was significantly higher in rural than in urban populations and in those who live in mountainous or flat areas. The percentage of seropositivity has increased over the years. ConclusionsThe role of the PHCC doctor is essential for achieving an early diagnosis of Lyme disease, as a higher percentage of seropositives was detected in samples submitted from PHCC. Furthermore, most early localised LD patients were diagnosed in PHCC, avoiding the appearance of sequelae. Therefore, detection of Borrelia specific antibodies using an ELISA assay is a useful screening test for patients at risk of LD.

Borrelia burgdorferi-specific IgA in Lyme Disease

The laboratory diagnosis of Lyme disease is currently dependent on the detection of IgM and IgG antibodies against Borrelia burgdorferi, the causative agent of the disease. The significance of serum IgA against B. burgdorferi remains unclear. The production of intrathecal IgA has been noted in patients with the late Lyme disease manifestation, neuroborreliosis, but production of antigen-specific IgA during early disease has not been evaluated. In the current study, we assessed serum IgA binding to the B. burgdorferi peptide antigens, C6, the target of the FDA-cleared C6 EIA, and FlaB(211-223)-modVlsE(275-291), a peptide containing a Borrelia flagellin epitope linked to a modified VlsE sequence, in patients with early and late Lyme disease. Specific IgA was detected in 59 of 152 serum samples (38.8%) from early Lyme disease patients. Approximately 50% of early Lyme disease patients who were seropositive for peptide-specific IgM and/or IgG were also seropositive for peptide-specific IgA. In a subpopulation of patients, high peptide-specific IgA could be correlated with disseminated disease, defined as multiple erythema migrans lesions, and neurological disease complications. These results suggest that there may be an association between elevated levels of antigen-specific IgA and particular disease manifestations in some patients with early Lyme disease.

Standardized Symptom Measurement of Individuals with Early Lyme Disease Over Time.

Understanding the Lyme disease (LD) literature is challenging given the lack of consistent methodology and standardized measurement of symptoms and the impact on functioning. This prospective study incorporates well-validated measures to capture the symptom picture of individuals with early LD from time of diagnosis through 6-months post-treatment. One hundred seven patients with confirmed early LD and 26 healthy controls were evaluated using standardized instruments for pain, fatigue, depressive symptoms, functional impact, and cognitive functioning. Prior to antibiotic treatment, patients experience notable symptoms of fatigue and pain statistically higher than controls. After treatment, there are no group differences, suggesting that symptoms resolve and that there are no residual cognitive impairments at the level of group analysis. However, using subgroup analyses, some individuals experience persistent symptoms that lead to functional decline and these individuals can be identified immediately post-completion of standard antibiotic treatment using well-validated symptom measures. Overall, the findings suggest that ideally-treated early LD patients recover well and experience symptom resolution over time, though a small subgroup continue to suffer with symptoms that lead to functional decline. The authors discuss use of standardized instruments for identification of individuals who warrant further clinical follow-up.

Ceftriaxone Pulse Dosing Fails to Eradicate Biofilm-Like Microcolony B. burgdorferi Persisters Which Are Sterilized by Daptomycin/ Doxycycline/Cefuroxime without Pulse Dosing.

Although the majority of Lyme disease patients can be cured, at least 10–20% of the patients continue to suffer from persisting symptoms such as fatigue, muscular and joint pain, and neurologic impairment after standard 2–4 week antibiotic treatment. While the causes for this post-treatment Lyme disease symptoms are unclear, one possibility is due to Borrelia burgdorferi persisters that are not effectively killed by current antibiotics such as doxycycline or amoxicillin used to treat Lyme disease. A previous study showed that four rounds of ceftriaxone pulse dosing treatment eradicated B. burgdorferi persisters in vitro using a relatively young late log phase culture (5 day old). In this study, we investigated if ceftriaxone pulse dosing could also eradicate B. burgdorferi persisters in older stationary phase cultures (10 day old) enriched with more resistant microcolony form of persisters. We found that ceftriaxone pulse dosing could only eradicate planktonic log phase B. burgdorferi spirochetal forms and round body forms but not more resistant aggregated biofilm-like microcolony persisters enriched in stationary phase cultures. Moreover, we found that not all drugs are suitable for pulse dosing, with bactericidal drugs ceftriaxone and cefuroxime being more appropriate for pulse dosing than bacteriostatic drug doxycycline and persister drug daptomycin. We also showed that drug combination pulse dosing treatment was more effective than single drug pulse dosing. Importantly, we demonstrate that pulse dosing treatment impaired the activity of the persister drug daptomycin and its drug combination against B. burgdorferi persisters and that the most effective way to kill the more resistant biofilm-like microcolonies is the daptomycin/doxycycline/ceftriaxone triple drug combination without pulse dosing. Our findings indicate pulse dosing may not always work as a general principle but rather depends on the specific drugs used, with cidal drugs being more appropriate for pulse dosing than static or persister drugs, and that drug combination approach with persister drugs is more effective at killing the more resistant microcolony form of persisters than pulse dosing. These observations may have implications for more effective treatment of Lyme disease. Future studies are required to validate these findings in animal models of B. burgdorferi persistence.

Functional and Genomic Architecture of Borrelia burgdorferi-Induced Cytokine Responses in Humans.

Despite the importance of immune variation for the symptoms and outcome of Lyme disease, the factors influencing cytokine production during infection with the causal pathogen Borrelia burgdorferi remain poorly understood. Borrelia infection-induced monocyte- and Tcell-derived cytokines were profiled in peripheral blood from two healthy human cohorts ofWestern Europeans from the Human Functional Genomics Project. Both non-genetic and genetic host factors were found to influence Borrelia-induced cytokine responses. Age strongly impaired IL-22 responses, and genetic studies identified several independent QTLs that impact Borrelia-induced cytokine production. Genetic, transcriptomic, and functional validation studies revealed an important role for HIF-1α-mediated glycolysis in the cytokine response to Borrelia. HIF-1α pathway activation and increase in glycolysis-derived lactate was confirmed in Lyme disease patients. In conclusion, functional genomics approaches reveal the architecture of cytokine production induced by Borrelia infection of human primary leukocytes and suggest a connection between cellular glucose metabolism and Borrelia-induced cytokine production.

Evidence of High Rate of Powassan Virus Co-infection in Lyme Disease Patients

Evidence of High Rate of Powassan Virus Co-infection in Lyme Disease Patients

Multiple independent transmission cycles of a tick-borne pathogen within a local host community.

Many pathogens are maintained by multiple host species and involve multiple strains with potentially different phenotypic characteristics. Disentangling transmission patterns in such systems is often challenging, yet investigating how different host species contribute to transmission is crucial to properly assess and manage disease risk. We aim to reveal transmission cycles of bacteria within the Borrelia burgdorferi species complex, which include Lyme disease agents. We characterized Borrelia genotypes found in 488 infected Ixodes ricinus nymphs collected in the Sénart Forest located near Paris (France). These genotypes were compared to those observed in three sympatric species of small mammals and network analyses reveal four independent transmission cycles. Statistical modelling shows that two cycles involving chipmunks, an introduced species, and non-sampled host species such as birds, are responsible for the majority of tick infections. In contrast, the cycle involving native bank voles only accounts for a small proportion of infected ticks. Genotypes associated with the two primary transmission cycles were isolated from Lyme disease patients, confirming the epidemiological threat posed by these strains. Our work demonstrates that combining high-throughput sequence typing with networks tools and statistical modeling is a promising approach for characterizing transmission cycles of multi-host pathogens in complex ecological settings.