Human Lyme Disease Research Articles

Comparing the Climatic and Landscape Risk Factors for Lyme Disease Cases in the Upper Midwest and Northeast United States.

Lyme disease, recognized as one of the most important vector-borne diseases worldwide, has been increasing in incidence and spatial extend in United States. In the Northeast and Upper Midwest, Lyme disease is transmitted by Ixodes scapularis. Currently, many studies have been conducted to identify factors influencing Lyme disease risk in the Northeast, however, relatively few studies focused on the Upper Midwest. In this study, we explored and compared the climatic and landscape factors that shape the spatial patterns of human Lyme cases in these two regions, using the generalized linear mixed models. Our results showed that climatic variables generally had opposite correlations with Lyme disease risk, while landscape factors usually had similar effects in these two regions. High precipitation and low temperature were correlated with high Lyme disease risk in the Upper Midwest, while with low Lyme disease risk in the Northeast. In both regions, size and fragmentation related factors of residential area showed positive correlations with Lyme disease risk. Deciduous forests and evergreen forests had opposite effects on Lyme disease risk, but the effects were consistent between two regions. In general, this study provides new insight into understanding the differences of risk factors of human Lyme disease risk in these two regions.

A fluorescent plasmonic biochip assay for multiplex screening of diagnostic serum antibody targets in human Lyme disease

Lyme disease (LD) diagnosis using the current two-tier algorithm is constrained by low sensitivity for early-stage infection and ambiguity in determining treatment response. We recently developed a protein microarray biochip that measures diagnostic serum antibody targets using grating-coupled fluorescent plasmonics (GC-FP) technology. This strategy requires microliters of blood serum to enable multiplexed biomarker screening on a compact surface and generates quantitative results that can be further processed for diagnostic scoring. The GC-FP biochip was used to detect serum antibodies in patients with active and convalescent LD, as well as various negative controls. We hypothesized that the quantitative, high-sensitivity attributes of the GC-FP approach permit: 1) screening of antibody targets predictive for LD status, and 2) development a diagnostic algorithm that is more sensitive, specific, and informative than the standard ELISA and Western blot assays. Notably, our findings led to a diagnostic algorithm that may be more sensitive than the current standard for detecting early LD, while maintaining 100% specificity. We further show that analysis of relative antibody levels to predict disease status, such as in acute and convalescent stages of infection, is possible with a highly sensitive and quantitative platform like GC-FP. The results from this study add to the urgent conversation regarding better diagnostic strategies and more effective treatment for patients affected by tick-borne disease.

Ecological Fallacy and Aggregated Data: A Case Study of Fried Chicken Restaurants, Obesity and Lyme Disease.

Interdisciplinary approaches are merited when attempting to understand the complex and idiosyncratic processes driving the spillover of pathogens from wildlife and vector species to human populations. Public health data are often available for zoonotic pathogens but can lead to erroneous conclusions if the data have been spatially or temporally aggregated. As an illustration, we use human Lyme disease incidence data as a case study to examine correlations between mammalian biodiversity, fried chicken restaurants and obesity rates on human disease incidence. We demonstrate that Lyme disease incidence is negatively correlated with mammalian biodiversity, the abundance of fried chicken restaurants and obesity rates. We argue, however, that these correlations are spurious, representing both an 'ecologic fallacy' and Simpson's paradox, and are generated by the use of aggregated data. We argue that correlations based on aggregated data across large spatial scales must be rigorously examined before being invoked as proof of disease ecology theory or as a rationale for public health policy.

Maintenance of Borrelia burgdorferi among vertebrate hosts: a test of dilution effect mechanisms

AbstractA better understanding of the mechanisms through which host diversity can influence reservoir pathogen infection is needed to mitigate disease risk. Efforts may involve computational modeling, especially since it is infeasible to perform large‐scale experimental studies of different host composition scenarios in natural settings. We used individual‐based models to examine how changes in host diversity characterized by differences in host reservoir competency for both Ixodes scapularis and Borrelia burgdorferi can influence the maintenance of the pathogen and subsequent human Lyme disease risk. We simulated 1440 different host communities, with 10 repetitions each, consisting of varying densities of Peromyscus leucopus (white‐footed mouse, 0–50), Tamias striatus (eastern chipmunk, 0–30), Blarina brevicauda (short‐tailed shrew, 0–30), Sciurus carolinensis (eastern gray squirrel, 0–15), and Didelphis virginiana (Virginia opossum, 0–2). We then quantified support for three mechanisms (i.e., vector regulation, encounter reduction, and transmission reduction) through which biodiversity–disease relationships occurred using species richness, Shannon H diversity, and host abundance. For each of the dilution effect mechanisms, host abundance was consistently the best‐supported predictor of disease risk. In our model, a dilution effect occurred via vector regulation and transmission reduction, where increasing both species richness and host abundance reduced both density of nymphs (DON) and density of infected nymphs (DIN). However, if disease risk is measured solely by calculating nymphal infection prevalence (NIP), it may seem that host diversity amplifies disease risk. Understanding the mechanisms through which the wildlife host community influences pathogen transmission cycles in nature will help foster effective control and reduction of disease risk in humans.

Development and optimization of OspC chimeritope vaccinogens for Lyme disease

Experimental Outer surface protein (Osp) C based subunit chimeritope vaccinogens for Lyme disease (LD) were assessed for immunogenicity, structure, ability to elicit antibody (Ab) responses to divergent OspC proteins, and bactericidal activity. Chimeritopes are chimeric epitope based proteins that consist of linear epitopes derived from multiple proteins or multiple variants of a protein. An inherent advantage to chimeritope vaccinogens is that they can be constructed to trigger broadly protective Ab responses. Three OspC chimeritope proteins were comparatively assessed: Chv1, Chv2 and Chv3. The Chv proteins possess the same set of 18 linear epitopes derived from 9 OspC type proteins but differ in the physical ordering of epitopes or by the presence or absence of linkers. All Chv proteins were immunogenic in mice and rats eliciting high titer Ab. Immunoblot and enzyme linked immunosorbent assays demonstrated that the Chv proteins elicit IgG that recognizes a diverse array of OspC type proteins. The panel included OspC proteins produced by N. American and European strains of the LD spirochetes. Rat anti-Chv antisera uniformly labeled intact, non-permeabilized Borreliella burgdorferi demonstrating that vaccinal Ab can bind to targets that are naturally presented on the spirochete cell surface. Vaccinal Ab also displayed potent complement dependent-Ab mediated killing activity. This study highlights the ability of OspC chimeritopes to serve as vaccinogens that trigger potentially broadly protective Ab responses. In addition to the current use of an OspC chimeritope in a canine LD vaccine, chimeritopes can serve as key components of human LD subunit vaccines.

Zoonotic Babesia: A scoping review of the global evidence.

BackgroundBabesiosis is a parasitic vector-borne disease of increasing public health importance. Since the first human case was reported in 1957, zoonotic species have been reported on nearly every continent. Zoonotic Babesia is vectored by Ixodes ticks and is commonly transmitted in North America by Ixodes scapularis, the tick species responsible for transmitting the pathogens that also cause Lyme disease, Powassan virus, and anaplasmosis in humans. Predicted climate change is expected to impact the spread of vectors, which is likely to affect the distribution of vector-borne diseases including human babesiosis.MethodsA scoping review has been executed to characterize the global evidence on zoonotic babesiosis. Articles were compiled through a comprehensive search of relevant bibliographic databases and targeted government websites. Two reviewers screened titles and abstracts for relevance and characterized full-text articles using a relevance screening and data characterization tool developed a priori.ResultsThis review included 1394 articles relevant to human babesiosis and/or zoonotic Babesia species. The main zoonotic species were B. microti, B. divergens, B. duncani and B. venatorum. Articles described a variety of study designs used to study babesiosis in humans and/or zoonotic Babesia species in vectors, animal hosts, and in vitro cell cultures. Topics of study included: pathogenesis (680 articles), epidemiology (480), parasite characterization (243), diagnostic test accuracy (98), mitigation (94), treatment (65), transmission (54), surveillance (29), economic analysis (7), and societal knowledge (1). No articles reported predictive models investigating the impact of climate change on Babesia species.ConclusionKnowledge gaps in the current evidence include research on the economic burden associated with babesiosis, societal knowledge studies, surveillance of Babesia species in vectors and animal hosts, and predictive models on the impact of climate change. The scoping review results describe the current knowledge and knowledge gaps on zoonotic Babesia which can be used to inform future policy and decision making.

What is the real number of Lyme disease cases in Canada?

BackgroundLyme disease is emerging in Canada due to expansion of the range of the tick vector Ixodes scapularis from the United States. National surveillance for human Lyme disease cases began in Canada in 2009. Reported numbers of cases increased from 144 cases in 2009 to 2025 in 2017. It has been claimed that few (< 10%) Lyme disease cases are reported associated with i) supposed under-diagnosis resulting from perceived inadequacies of serological testing for Lyme disease, ii) expectation that incidence in Canadian provinces and neighbouring US states should be similar, and iii) analysis of serological responses of dogs to the agent of Lyme disease, Borrelia burgdorferi.We argue that performance of serological testing for Lyme disease is well studied, and variations in test performance at different disease stages are accounted for in clinical diagnosis of Lyme disease, and in surveillance case definitions. Extensive surveillance for tick vectors has taken place in Canada providing a clear picture of the emergence of risk in the Canadian environment. This surveillance shows that the geographic scope of I. scapularis populations and Lyme disease risk is limited but increasing in Canada. The reported incidence of Lyme disease in Canada is consistent with this pattern of environmental risk, and the differences in Lyme disease incidence between US states and neighbouring Canadian provinces are consistent with geographic differences in environmental risk. Data on serological responses in dogs from Canada and the US are consistent with known differences in environmental risk, and in numbers of reported Lyme disease cases, between the US and Canada.ConclusionThe high level of consistency in data from human case and tick surveillance, and data on serological responses in dogs, suggests that a high degree of under-reporting in Canada is unlikely. We speculate that approximately one third of cases are reported in regions of emergence of Lyme disease, although prospective studies are needed to fully quantify under-reporting. In the meantime, surveillance continues to identify and track the ongoing emergence of Lyme disease, and the risk to the public, in Canada.

Quantifying the relationship between human Lyme disease and Borrelia burgdorferi exposure in domestic dogs.

Lyme disease (LD) is the most common vector-borne disease in the United States. Early confirmatory diagnosis remains a challenge, while the disease can be debilitating if left untreated. Further, the decision to test is complicated by under-reporting, low positive predictive values of testing in non-endemic areas and travel, which together exacerbate the difficulty in identification of newly endemic areas or areas of emerging concern. Spatio-temporal analyses at the national scale are critical to establishing a baseline human LD risk assessment tool that would allow for the detection of changes in these areas. A well-established surrogate for human LD incidence is canine LD seroprevalence, making it a strong candidate covariate for use in such analyses. In this paper, Bayesian statistical methods were used to fit a spatio-temporal spline regression model to estimate the relationship between human LD incidence and canine seroprevalence, treating the latter as an explanatory covariate. A strong non-linear monotonically increasing association was found. That is, this analysis suggests that mean incidence in humans increases with canine seroprevalence until the seroprevalence in dogs reaches approximately 30%. This finding reinforces the use of canines as sentinels for human LD risk, especially with respect to identifying geographic areas of concern for potential human exposure.

Genome-wide screen identifies novel genes required for Borrelia burgdorferi survival in its Ixodes tick vector.

Borrelia burgdorferi, the causative agent of Lyme disease in humans, is maintained in a complex biphasic life cycle, which alternates between tick and vertebrate hosts. To successfully survive and complete its enzootic cycle, B. burgdorferi adapts to diverse hosts by regulating genes required for survival in specific environments. Here we describe the first ever use of transposon insertion sequencing (Tn-seq) to identify genes required for B. burgdorferi survival in its tick host. We found that insertions into 46 genes resulted in a complete loss of recovery of mutants from larval Ixodes ticks. Insertions in an additional 56 genes resulted in a >90% decrease in fitness. The screen identified both previously known and new genes important for larval tick survival. Almost half of the genes required for survival in the tick encode proteins of unknown function, while a significant portion (over 20%) encode membrane-associated proteins or lipoproteins. We validated the results of the screen for five Tn mutants by performing individual competition assays using mutant and complemented strains. To better understand the role of one of these genes in tick survival, we conducted mechanistic studies of bb0017, a gene previously shown to be required for resistance against oxidative stress. In this study we show that BB0017 affects the regulation of key borrelial virulence determinants. The application of Tn-seq to in vivo screening of B. burgdorferi in its natural vector is a powerful tool that can be used to address many different aspects of the host pathogen interaction.

Antigen Engineering Approaches for Lyme Disease Vaccines.

Increasing rates of Lyme disease necessitate preventive measures such as immunization to mitigate the risk of contracting the disease. At present, there is no human Lyme disease vaccine available on the market. Since the withdrawal of the first and only licensed Lyme disease vaccine based on lipidated recombinant OspA, vaccine and antigen research has aimed to overcome its risks and shortcomings. Replacement of the putative cross-reactive T-cell epitope in OspA via mutation or chimerism addresses the potential risk of autoimmunity. Multivalent approaches in Lyme disease vaccines have been pursued to address sequence heterogeneity of Lyme borreliae antigens and to induce a repertoire of functional antibodies necessary for efficient heterologous protection. This Review summarizes recent antigen engineering strategies that have paved the way for the development of next generation vaccines against Lyme disease, some of which have reached clinical testing. Bioconjugation methods that incorporate antigens to self-assembling nanoparticles for immune response potentiation are also discussed.

Analysis of the antigenic determinants of the OspC protein of the Lyme disease spirochetes: Evidence that the C10 motif is not immunodominant or required to elicit bactericidal antibody responses

As Ixodes ticks spread to new regions, the incidence of Lyme disease (LD) in companion animals and humans will increase. Preventive strategies for LD in canines center on vaccination and tick control (acaricides). Both subunit and bacterin based LD veterinary vaccines are available. Outer surface protein C (OspC), a potent immunogen and dominant early antigen, has been demonstrated to elicit protective antibody (Ab) responses. However, a single OspC protein elicits a relatively narrow range of protection. There are conflicting reports as to whether the immunodominant epitopes of OspC reside within variable or conserved domains. A detailed understanding of the antigenic determinants of OspC is essential for understanding immune responses to this essential virulence factor and vaccinogen. Here, we investigate the contribution of the conserved C-terminal C10 motif in OspC triggered Ab responses. Using a panel of diverse recombinant full length OspC proteins and their corresponding C10 deletion variants (OspCΔC10), we demonstrate that the C10 motif does not significantly contribute to immunization or infection induced Ab responses in rabbits, rats, canines, horses and non-human primates. Furthermore, the C10 motif is not required to trigger potent bactericidal Ab responses. This study provides insight into the antigenic structure of OspC. The results enhance our understanding of immune responses that develop during infection or upon vaccination and have implications for interpretation of LD diagnostic assays that employ OspC.

Detection of municipalities at-risk of Lyme disease using passive surveillance of Ixodes scapularis as an early signal: A province-specific indicator in Canada.

Lyme disease, the most commonly reported vector-borne disease in North America, is caused by the spirochete Borrelia burgdorferi sensu stricto, which is transmitted by Ixodes scapularis in eastern Canada and Ixodes pacificus in western Canada. Recently, the northward range expansion of I. scapularis ticks, in south-eastern Canada, has resulted in a dramatic increase in the incidence of human Lyme disease. Detecting emerging areas of Lyme disease risk allows public health to target disease prevention efforts. We analysed passive tick surveillance data from Ontario and Manitoba to i) assess the relationship between the total numbers of I. scapularis submissions in passive surveillance from humans, and the number of human Lyme disease cases, and ii) develop province-specific acarological indicators of risk that can be used to generate surveillance-based risk maps. We also assessed associations between numbers of nymphal I. scapularis tick submissions only and Lyme disease case incidence. Using General Estimating Equation regression, the relationship between I. scapularis submissions (total numbers and numbers of nymphs only) in each census sub-division (CSD) and the number of reported Lyme disease cases was positively correlated and highly significant in the two provinces (P ≤ 0.001). The numbers of I. scapularis submissions over five years discriminated CSDs with ≥ 3 Lyme disease cases from those with < 3 cases with high accuracy when using total numbers of tick submission (Receiver Operating Characteristics area under the curve [AUC] = 0.89) and moderate accuracy (AUC = 0.78) when using nymphal tick submissions only. In Ontario the optimal cut-off point was a total 12 tick submissions from a CSD over five years (Sensitivity = 0.82, Specificity = 0.84), while in Manitoba the cut-off point was five ticks (Sensitivity = 0.71, Specificity = 0.79) suggesting regional variability of the risk of acquiring Lyme disease from an I. scapularis bite. The performances of the acarological indicators developed in this study for Ontario and Manitoba support the ability of passive tick surveillance to provide an early signal of the existence Lyme disease risk areas in regions where ticks and the pathogens they transmit are expanding their range.

Lyme Disease Emergence after Invasion of the Blacklegged Tick, Ixodes scapularis, Ontario, Canada, 2010-2016.

Analysis of surveillance data for 2010–2016 in eastern Ontario, Canada, demonstrates the rapid northward spread of Ixodes scapularis ticks and Borrelia burgdorferi, followed by increasing human Lyme disease incidence. Most spread occurred during 2011–2013. Continued monitoring is essential to identify emerging risk areas in this region.

Social-behavioral/ecological risk assessment for Lyme disease in southern Québec, Canada.

Social-behavioral/ecological risk assessment for Lyme disease in southern Québec, Canada.

Seroprevalence of Lyme disease in Eastern Slovakia.

Lyme disease (LD) is chronic, multi-system zoonosis transmitted by ticks, and LD aetiological agents are spirochetes of the Borrelia burgdorferi sensu lato complex. The aim of the cross-sectional study was to analyze the LD incidence on the basis of the presence of specific antibodies in the serum of patients in Eastern Slovakia, and to compare the results of serological ELISA and immunoblot assays. Venous blood with questionnaires was obtained by field sampling of respondents from Eastern Slovakia. Overall, we examined 537 human sera by the ELISA and for confirmation we tested all positive IgG antibodies against the Borrelia immunoblot assay. Our results confirmed the high serum prevalence of anti-Borrelia antibodies (17.9% for IgG), while the immunoblot seropositive test was confirmed in 69.8% of responders from ELISA IgG positive sera. Positive antibodies of the IgM class were found in 7.6% of the population under study. Most commonly found were antibodies against VlsE (80.2%), p41 (66.7%), p18 (56.3%), p100 (41.7%), p58 (31.3%), and p39 (30.2%). It should be noted that detection of antibodies against B. burgdorferi s.l. is only an indirect evidence of the presence of this bacterium in the development of clinical signs of LD in humans. Laboratory LD tests should be performed in accordance with valid standards, positive and uncertain results must be confirmed by the Western Blot/Immunoblot assay.

Interventions to prevent Lyme disease in humans: A systematic review.

Lyme disease (LD) is an infection transferred to humans through bites from infected ticks. Surveillance indicates that the number of LD cases is increasing in the UK, therefore, improved knowledge about reducing transmission from ticks to humans is needed. Eighteen electronic databases were searched and additional web-based searching was conducted, to locate empirical research, published from 2002 onwards. Sixteen studies that evaluated five types of prevention intervention were included: personal protection (n = 4), domestic strategies (landscape modification and chemical pest control) (n = 3), education (n = 6), vaccination (n = 3), and deer-reduction programmes (n = 2). In general the quality of evidence was low. Results suggest that personal protection strategies, including the use of tick repellents and wearing of protective clothes, can prevent tick bites and reduce the incidence of LD among adults. Educational interventions were generally successful for improving adults' knowledge, behavioural beliefs (e.g., self-efficacy for performing tick checks) and preventative behaviour, but for children, the findings were mixed. For adults and children, knowledge changes did not typically translate into a lower incidence of LD. Whilst evidence on vaccination against LD is promising, too few studies were available to reach robust conclusions. There was no evidence of effectiveness for deer culling, and the evidence was inconclusive for applying acaricide (tick poison) to deer's ears and heads. Low-quality evidence suggests that personal protective strategies, that limit exposure to ticks, should continue to be recommended, as should education to encourage the adoption of personal protective strategies; further investigation of education interventions for children, vaccination and deer programmes is needed.

A systematic review on the impact of gestational Lyme disease in humans on the fetus and newborn.

Lyme disease (LD), caused by bacteria of the Borrelia burgdorferi sensu lato species complex, is the most common vector-borne disease in North America and Europe. A systematic review (SR) was conducted to summarize the global literature on adverse birth outcomes associated with gestational LD in humans. The SR followed an a priori protocol of pretested screening, risk of bias, and data extraction forms. Data were summarized descriptively and random effects meta-analysis (MA) was used where appropriate. The SR identified 45 relevant studies, 29 describing 59 cases reported as gestational LD in the United States, Europe, and Asia (1969–2017). Adverse birth outcomes included spontaneous miscarriage or fetal death (n = 12), newborn death (n = 8), and newborns with an abnormal outcome (e.g. hyperbilirubinemia, respiratory distress and syndactyly) at birth (n = 16). Only one report provided a full case description (clinical manifestations in the mother, negative outcome for the child, and laboratory detection of B. burgdorferi in the child) that provides some evidence for vertical transmission of B. burgdorferi that has negative consequences for the fetus. The results of 17 epidemiological studies are included in this SR. Prevalence of adverse birth outcomes in an exposed population (defined by the authors as: gestational LD, history of LD, tick bites or residence in an endemic area) was compared to that in an unexposed population in eight studies and no difference was reported. A meta-analysis of nine studies showed significantly fewer adverse birth outcomes in women reported to have been treated for gestational LD (11%, 95%CI 7–16) compared to those who were not treated during pregnancy (50%, 95%CI 30–70) providing indirect evidence of an association between gestational LD and adverse birth outcomes. Other risk factors investigated; trimester of exposure, length of LD during pregnancy, acute vs. disseminated LD at diagnosis, and symptomatic LD vs. seropositive women with no LD symptoms during pregnancy were not significantly associated with adverse birth outcomes. This SR summarizes evidence from case studies that provide some limited evidence for transplacental transmission of B. burgdorferi. There was inconsistent evidence for adverse birth outcomes of gestational LD in the epidemiological research, and uncommon adverse outcomes for the fetus may occur as a consequence of gestational LD. The global evidence does not fully characterize the potential impact of gestational LD, and future research that addresses the knowledge gaps may change the findings in this SR. Given the current evidence; prompt diagnosis and treatment of LD during pregnancy is recommended.

Risk factors associated with the carriage of Ixodes scapularis relative to other tick species in a population of pet dogs from southeastern Ontario, Canada

In eastern North America, the blacklegged tick, Ixodes scapularis, is the vector for Borrelia burgdorferi sensu stricto and Anaplasma phagocytophilum, the causal agents for human and canine Lyme disease and anaplasmosis, respectively. The extensive range expansion of I. scapularis in Ontario is a growing veterinary and public health concern. However, there is limited information on the risk factors associated with I. scapularis carriage on dogs. Within an emerging area for Lyme disease risk in southeastern Ontario, we identified the tick species carried by dogs; determined the prevalence of B. burgdorferi and A. phagocytophilum in I. scapularis; and examined associations between pet demographics, travel history, and geographical location and the odds of: a dog carrying I. scapularis relative to other tick species (i.e., case-case design), and a removed I. scapularis being infected with B. burgdorferi. Seven species of ticks were collected from 543 companion dogs at 20 participating veterinary hospitals from April to December 2015. Ixodes scapularis were detected on 85.6% of parasitized dogs, and 7.5% of these dogs were carrying at least one B. burgdorferi-positive tick. Based on a multivariable logistic regression model, the odds of I. scapularis infestation relative to other tick species was significantly higher in fall and spring compared to summer, with closer proximity to Lake Ontario, in female compared to male dogs, in dogs weighing over 30 kg compared to lighter dogs, and in dogs that had not visited a farm in the 7 days prior to tick removal. Based on univariable exact logistic regression models, the odds of B. burgdorferi-positive I. scapularis carriage relative to B. burgdorferi-negative I. scapularis were significantly higher for dogs that traveled in the 14 days prior to tick removal, for those dogs under 1 year of age, and for those weighing less than 10 kg. This case-case study provides information for veterinarians and public health practitioners to help protect dogs and their owners from Lyme disease in southeastern Ontario.

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.

A scoping review of Lyme disease research relevant to public health.

Lyme disease (LD) is an emerging infectious disease in Canada associated with expansion of the geographic range of the tick vector Ixodes scapularis in eastern and central Canada. A scoping review of published research was prioritized to identify and characterize the scientific evidence concerning key aspects of LD to support public health efforts. Prior to initiation of this review, an expert advisory group was surveyed to solicit insight on priority topics and scope. A pre-tested search strategy implemented in eight databases (updated September 2016) captured relevant research. Pre-tested screening and data characterization forms were completed by two independent reviewers and descriptive analysis was conducted to identify topic areas with solid evidence and knowledge gaps. Of 19,353 records screened, 2,258 relevant articles were included in the review under the following six public health focus areas: a) surveillance/monitoring in North America (n=809); b) evaluation of diagnostic tests (n=736); c) risk factors (n=545); d) public health interventions (n=205); e) public knowledge, attitudes and/or perceptions in North America (n=202); and f) the economic burden of LD or cost-benefit of interventions (n=32). The majority of research investigated Borrelia burgdorferi (n=1,664), humans (n=1,154) and Ixodes scapularis (n=459). Sufficient research was identified for potential systematic reviews in four topic areas: a) accuracy of diagnostic tests; b) risk factors for human illness; c) efficacy of LD intervention strategies; and d) prevalence and/or incidence of LD in humans or B. burgdorferi sensu stricto in vertebrate reservoirs or ticks in North America. Future primary research could focus on closing knowledge gaps, such as the role of less studied vertebrate reservoirs in the transmission cycle. Results of this scoping review can be used to quickly identify and summarize relevant research pertaining to specific questions about LD or B. burgdorferi sensu lato in humans, vertebrate hosts or vectors, providing evidence-informed information within timelines that are conducive for public health decision-making.