By-degree Health and Economic Impacts of Lyme Disease, Eastern and Midwestern United States.

Lyme disease (LD) is the most common vector-borne disease in the United States (U.S.). This paper assesses how climate change may influence LD incidence in the eastern and upper Midwestern U.S. and the associated economic burden. We estimated future Ixodes scapularis habitat suitability and LD incidence with a by-degree approach using variables from an ensemble of multiple climate models. We then applied estimates for present-day and projected habitat suitability for I. scapularis, present-day presence of Borrelia burgdorferi, and projected climatological variables to model reported LD incidence at the county level among adults, children, and the total population. Finally, we applied an estimate of healthcare expenses to project economic impacts. We show an overall increase in LD cases with regional variation. We estimate an increase in incidence in New England and the upper Midwestern U.S. and a concurrent decrease in incidence in Virginia and North Carolina. At 3°C of national warming from the 1986-2015 baseline climate, we project approximately 55,000 LD cases, a 38-percent increase from present-day estimates. At 6°C of warming, our most extreme scenario, we project approximately 92,000 LD cases in the region, an increase of 145 percent relative to current levels. Annual LD-related healthcare expenses at 3°C of warming are estimated to be $236 million (2021 dollars), approximately 38 percent greater than present-day. These results may inform decision-makers tasked with addressing climate risks, the public, and healthcare professionals preparing for treatment and prevention of LD.

Clinical and economic outcomes evaluated in Lyme disease: a systematic review.

BACKGROUND: The financial implications of Lyme disease (LD) can vary widely for both the health system and the individual patients experiencing the disease. The aim of this review was to summarize published data on clinical and economic outcomes associated with LD. METHODS: A literature review was conducted to identify all studies of LD that incorporate both clinical outcomes and costs. Included studies were described and categorized based on costs consistent with best practices used in economic evaluation. RESULTS: The most frequent costs identified focused on formal health costs and productivity losses were the most common costs identified outside of the health system. Travel and informal care costs were less frequently reported. Clinical and economic outcomes of LD are primarily studied through economic models or observational analyses and focus on formal health care. CONCLUSIONS: This review provides and overview of existing evidence and recommendations for future economic analyses in LD.

Epidemiology and cost of Lyme disease-related hospitalizations among patients with employer-sponsored health insurance-United States, 2005-2014.

An estimated 300,000 cases of Lyme disease occur in the United States annually. Disseminated Lyme disease may result in carditis, arthritis, facial palsy or meningitis, sometimes requiring hospitalization. We describe the epidemiology and cost of Lyme disease-related hospitalizations. We analysed 2005-2014 data from the Truven Health Analytics MarketScan Commercial Claims and Encounters Databases to identify inpatient records associated with Lyme disease based on International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. We estimated the annual number and median cost of Lyme disease-related hospitalizations in the United States in persons under 65 years of age. Costs were adjusted to reflect 2016 dollars. Of 20,983,165 admission records contained in the inpatient databases during the study period, 2,823 (0.01%) met inclusion criteria for Lyme disease-related hospitalizations. Over half of the identified records contained an ICD-9-CM code for meningitis (n = 614), carditis (n = 429), facial palsy (n = 400) or arthritis (n = 377). Nearly 60% of hospitalized patients were male. The median cost per Lyme disease-related hospitalization was $11,688 (range: $140-$323,613). The manifestation with the highest median cost per stay was carditis ($17,461), followed by meningitis ($15,177), arthritis ($13,012) and facial palsy ($10,491). Median cost was highest among the 15- to 19-year-old age group ($12,991). Admissions occurring in January had the highest median cost ($13,777) for all study years. Based on extrapolation to the U.S. population, we estimate that 2,196 Lyme disease-related hospitalizations in persons under 65 years of age occur annually with an estimated annual cost of $25,826,237. Lyme disease is usually treated in an outpatient setting; however, some patients with Lyme disease require hospitalization, underscoring the need for effective prevention methods to mitigate these serious cases. Information from this analysis can aid economic evaluations of interventions that prevent infection and advances in disease detection.

Analyzing the cost-effectiveness of Lyme disease risk reduction approaches.

Lyme disease (LD) is endemic in many regions of the Northeastern United States. Given the elusive nature of the disease, a systematic approach to identify efficient interventions would be useful for policymakers in addressing LD. We used Markov modeling to investigate the efficiency of interventions. These interventions range from awareness-based to behavioral-based strategies. Targeting animal reservoirs of LD using fungal spray or bait boxes did not prove to be an effective intervention. Results of awareness-based interventions, including distribution of signage, fliers, and presentations, implementable in different geographical scales, suggest that policymakers should focus on these interventions, as they are both cost-effective and have the highest impact on lowering LD risk. Populations may lose focus of LD warnings over time, thus quick succession of these interventions is vital. Our modeling results identify the awareness-based intervention as the most cost-effective strategy to lower the number of LD cases. These results can aid in the establishment of effective LD risk reduction policy at various scales of implementation.

Increasing Burden of Lyme Carditis in United States Children's Hospitals.

We sought to characterize the shifting epidemiology and resource utilization of Lyme disease and associated carditis in US children's hospitals. We hypothesized that the Lyme carditis burden has increased and that hospitalizations for Lyme carditis are costlier than those for Lyme disease without carditis. The PHIS database was queried for Lyme disease encounters between January 1, 2007 and December 31, 2013. Additional diagnostic codes consistent with carditis identified Lyme carditis cases. Demographic, clinical, and resource utilization data were analyzed. All costs were adjusted to 2014 US dollars. Lyme disease was identified in 3620 encounters with 189 (5%) associated with carditis. Lyme disease (360 cases in 2007 vs. 672 in 2013, p = 0.01) and Lyme carditis (17 cases in 2007 vs. 40 in 2013, p = 0.03) both significantly increased in frequency. This is primarily accounted for by their increase within the Midwest region. Carditis frequency among cases of Lyme disease was stable (p = 0.15). Encounters for Lyme carditis are dramatically costlier than those for Lyme disease without carditis [median $9104 (3741-19,003) vs. 922 (238-4987), p < 0.001] The increase in Lyme carditis cases in US children's hospitals is associated with an increased Lyme disease incidence, suggesting that there has not been a change in its virulence or cardiac tropism. The increasing number of serious cardiac events and costs associated with Lyme disease emphasize the need for prevention and early detection of disease and control of its spread.

Combining primary care surveillance and a meta-analysis to estimate the incidence of the clinical manifestations of Lyme borreliosis in Belgium, 2015-2017.

Lyme borreliosis (LB) is an important tick-borne disease which can cause a broad range of symptoms mainly affecting the skin, the nervous system and the joints. This study aims to estimate the incidence of the different clinical manifestations of LB in Belgium. The incidence of erythema migrans (EM) was estimated through the network of sentinel general practices at 97.6/100,000 inhabitants (uncertainty interval [UI] 82.0-113.0) for the period 2015-2017. This result was used to estimate the incidence of other LB manifestations based on their proportional distribution (ratios) to EM reported in the neighboring countries of Belgium. To estimate these ratios, we performed a systematic review of studies published between February 1, 2008 and January 31, 2018 and pooled the results using a random effects meta-analysis. Six studies were retained in the systematic review, and the meta-analysis estimated the occurrence ratios for Lyme neuroborreliosis/EM, Lyme arthritis/EM and other manifestations/EM at 0.024 (95% confidence interval [CI] 0.016-0.037), 0.022 (95% CI 0.020-0.024) and 0.014 (95% CI 0.012-0.016) respectively. Applying these ratios to the EM incidence in Belgium resulted in an incidence estimation of 2.4/100,000 inhabitants (95% UI 1.5-3.7) for Lyme neuroborreliosis, 2.1/100,000 (95% UI 1.7-2.6) for Lyme arthritis and 1.4/100,000 (95% UI 1.1-1.7) for other less frequent manifestations. Some of these LB manifestations, other than EM, are more severe, hence these estimates are essential to assess the health burden and economic cost of LB which would be highly relevant for patients, healthcare providers and policymakers. As both over- and underestimation of different clinical LB manifestations remain possible due to characteristics of the primary surveillance systems and the disease itself, future studies to validate these estimates would be of great value.

The economic burden of Lyme disease and the cost-effectiveness of Lyme disease interventions: A scoping review.

INTRODUCTION: While Lyme disease (LD) is mostly treatable, misdiagnosed or untreated LD can result in debilitating sequelae and excessive healthcare usage. The objective of this review was to characterize the body of literature on the economic burden of Lyme disease (LD) and the cost-effectiveness of LD interventions, such as antibiotic treatment and vaccination. METHODS: We followed Joanna Briggs Institute scoping review methodologies. We systematically searched terms related to LD, economic evaluations, costs, and cost-effectiveness in Medline, Embase, PsycInfo, Cochrane Library, and the grey literature up to November 2017. We included primary economic evaluations conducted in North America and Europe, reporting LD-related costs or cost-effectiveness of human interventions. Two reviewers screened articles and charted data independently. Costs were standardized to 2017 United States dollars (USD). RESULTS: We screened 923 articles, and included 10 cost-effectiveness analyses (CEA) and 11 cost analyses (CA). Three CEAs concluded LD vaccination was likely cost-effective only in endemic areas (probability of infection ≥1%). However, LD vaccination is not currently available as an intervention in the US or Europe. Six studies assessed economic burden from a societal perspective and estimated significant annual national economic impact of: 735,550 USD for Scotland (0.14 USD per capita, population = 5.40M), 142,562 USD in Sweden (0.014 USD per capita, 9.96M), 40.88M USD in Germany (0.51 USD per capita, 80.59M), 23.12M USD in the Netherlands (1.36 USD per capita, 17.08M), and up to 786M USD in the US (2.41 USD per capita, 326.63M). CONCLUSIONS: Lyme disease imposes an economic burden that could be considered significant in the US and other developed countries to justify further research efforts in disease control and management. Societal costs for Lyme disease can be equally impactful as healthcare costs, but are not fully understood. Economic literature from countries with historically high incidence rates or increasing rates of Lyme disease are limited, and can be useful for future justification of resource allocation.

Estimating direct healthcare costs attributable to laboratory-confirmed Lyme disease in Ontario, Canada: A population-based matched cohort study using health administrative data.

The objective of this study was to determine healthcare costs attributable to laboratory-confirmed Lyme disease (LD) from the healthcare payer perspective in Ontario, Canada. A cost-of-illness study was conducted for incident LD subjects from 1 January 2006 through 31 December 2013 ascertained from provincial laboratory and reportable disease databases, linked to health administrative data. All LD subjects included were laboratory-confirmed, according to provincial case definitions. Incident LD subjects were propensity-score matched to uninfected subjects on age, sex, comorbidities and urban/rural status. We used phase-of-care methods to calculate attributable costs for two phases of illness: initial care (≤30 days following "index date") and continuing care (>30 days after index date to the end of the follow-up period). A total of 663 incident, confirmed LD subjects were identified from 2006 through 2013. Mean age was 44.2 ± 20.1 years; 339 (51.1%) were female; and 31 (4.7%) were hospitalized ≤30 days after index date. Six hundred fifty-eight (99.2%) LD subjects were matched to uninfected subjects; mean follow-up time was 3.3 years. Mean attributable costs per case during the initial care phase and continuing care were $277 (95% CI: $197, $357) and -$5 (-$27, $17), respectively. Attributable costs per LD subject aged 5-14 years were $440 ($132, $747), greater than the costs observed for other age strata. Expected 1-year attributable costs were $832, given continuing care costs were negligible. Limitations to our study include estimating costs using a cohort of only laboratory-confirmed LD cases, introducing selection bias for diagnosed and treated patients who may have a lower risk of developing sequelae. In conclusion, the initial care phase of LD is associated with increased healthcare costs, but without significant costs attributable to LD infection after 30 days. Estimates of costs attributable to LD are important for healthcare resource prioritization and the evaluation of novel interventions.

Recognizing and treating Lyme disease.

Lyme disease is the most commonly reported vector-borne disease in the United States. After initial antibiotic treatment for patients with Lyme disease, ongoing symptoms that may persist have considerable long-term impact on healthcare costs. Posttreatment Lyme disease syndrome is characterized by a host of chronic symptoms that can leave patients physically and mentally disabled.

Cost-effectiveness of longer-term versus shorter-term provision of antibiotics in patients with persistent symptoms attributed to Lyme disease.

BACKGROUND: The treatment of persistent symptoms attributed to Lyme disease remains controversial. Recently, the PLEASE study did not demonstrate any additional clinical benefit of longer-term versus shorter-term antibiotic treatment. However, the economic impact of the antibiotic strategies has not been investigated. METHODS: This prospective economic evaluation, adhering a societal perspective, was performed alongside the PLEASE study, a multicenter, placebo-controlled, double-blind 1:1:1 randomized clinical trial in which all patients received open-label intravenous ceftriaxone for two weeks before the 12-week randomized blinded oral antibiotic regimen (doxycycline, clarithromycin plus hydroxychloroquine, or placebo). Between 2010 and 2013, patients (n = 271) with borreliosis-attributed persistent symptoms were enrolled and followed for one year. Main outcomes were costs, quality-adjusted life years, and incremental net monetary benefit of longer-term versus shorter-term antibiotic therapy. RESULTS: Mean quality-adjusted life years (95% CI) were not significantly different (p = 0.96): 0.82 (0.77-0.88) for ceftriaxone/doxycycline (n = 82), 0.81 (0.76-0.88) for ceftriaxone/clarithromycin-hydroxychloroquine (n = 93), and 0.81 (0.76-0.86) for ceftriaxone/placebo (n = 96). Total societal costs per patient (95% CI) were not significantly different either (p = 0.35): €11,995 (€8,823-€15,670) for ceftriaxone/doxycycline, €12,202 (€9,572-€15,253) for ceftriaxone/clarithromycin-hydroxychloroquine, and €15,249 (€11,294-€19,781) for ceftriaxone/placebo. Incremental net monetary benefit (95% CI) for ceftriaxone/doxycycline compared to ceftriaxone/placebo varied from €3,317 (-€2,199-€8,998) to €4,285 (-€6,085-€14,524) over the willingness-to-pay range, and that of ceftriaxone/clarithromycin-hydroxychloroquine compared to ceftriaxone/placebo from €3,098 (-€888-€7,172) to €3,710 (-€4,254-€11,651). For every willingness-to-pay threshold, the incremental net monetary benefits did not significantly differ from zero. CONCLUSION: The longer-term treatments were similar with regard to costs, effectiveness and cost-effectiveness compared to shorter-term treatment in patients with borreliosis-attributed persistent symptoms after one year of follow-up. Given the results of this study, and taking into account the external costs associated with antibiotic resistance, the shorter-term treatment is the antibiotic regimen of first choice.

Control of Lyme borreliosis and other Ixodes ricinus-borne diseases.

Lyme borreliosis (LB) and other Ixodes ricinus-borne diseases (TBDs) are diseases that emerge from interactions of humans and domestic animals with infected ticks in nature. Nature, environmental and health policies at (inter)national and local levels affect the risk, disease burden and costs of TBDs. Knowledge on ticks, their pathogens and the diseases they cause have been increasing, and resulted in the discovery of a diversity of control options, which often are not highly effective on their own. Control strategies involving concerted actions from human and animal health sectors as well as from nature managers have not been formulated, let alone implemented. Control of TBDs asks for a "health in all policies" approach, both at the (inter)national level, but also at local levels. For example, wildlife protection and creating urban green spaces are important for animal and human well-being, but may increase the risk of TBDs. In contrast, culling or fencing out deer decreases the risk for TBDs under specific conditions, but may have adverse effects on biodiversity or may be societally unacceptable. Therefore, in the end, nature and health workers together must carry out tailor-made control options for the control of TBDs for humans and animals, with minimal effects on the environment. In that regard, multidisciplinary approaches in environmental, but also medical settings are needed. To facilitate this, communication and collaboration between experts from different fields, which may include patient representatives, should be promoted.

The cost of Lyme borreliosis.

Background: Lyme borreliosis (LB) is the most frequently reported tick-borne infection in Europe and North America. The aim of this study was to estimate the cost-of-illness of LB in the Netherlands. We used available incidence estimates from 2010 for tick bite consultations and three symptomatic LB outcomes: erythema migrans (EM), disseminated LB and Lyme-related persisting symptoms. The cost was estimated using these incidences and the average cost per patient as derived from a patient questionnaire. We estimated the cost from a societal perspective, including healthcare cost, patient cost and production loss, using the friction cost method and a 4% annual discount rate. Tick bites and LB in 2010 led to a societal cost of €19.3 million (95% CI 15.6-23.4; 16.6 million population) for the Netherlands. Healthcare cost and production loss each constituted 48% of the total cost (€9.3 and €9.2 million/year), and patient cost 4% (€0.8 million/year). Of the total cost, 37% was related to disseminated LB, followed by 27% for persisting symptoms, 22% for tick bites and 14% for EM. Per outcome, for an individual case the mean cost of disseminated LB and Lyme-related persisting symptoms was both around €5700; for EM and GP consultations for tick bites this was €122 and €53. As an alternative to the friction cost method, the human capital method resulted in a total cost of €23.5 million/year. LB leads to a substantial societal cost. Further research should therefore focus on additional preventive interventions.

Vaccines for tick-borne diseases and cost-effectiveness of vaccination: a public health challenge to reduce the diseases' burden.

Tick-borne encephalitis (TBE) and Lyme borreliosis (LB) are tick-borne diseases (TBDs), and both present an increasing burden worldwide. Vaccination as public health intervention could be the most effective way to reduce this burden. TBE vaccines are available, but vaccines against LB are still in the phase of development. At the European level, TBE vaccines are likely under-administered to effectively prevent the disease. Cost-effectiveness of vaccination is a helpful tool in the decision making process to include novel vaccines in the national vaccination program or to extend current programs, and its role is only increasing. Cost-effectiveness studies on TBE vaccines have been performed in Slovenia, Sweden, Finland and Estonia so far. Cost-effectiveness studies with the novel vaccines against LB are expected to be performed in the near future.

Health care costs, utilization and patterns of care following Lyme disease.

BACKGROUND: Lyme disease is the most frequently reported vector borne infection in the United States. The Centers for Disease Control have estimated that approximately 10% to 20% of individuals may experience Post-Treatment Lyme Disease Syndrome - a set of symptoms including fatigue, musculoskeletal pain, and neurocognitive complaints that persist after initial antibiotic treatment of Lyme disease. Little is known about the impact of Lyme disease or post-treatment Lyme disease symptoms (PTLDS) on health care costs and utilization in the United States. OBJECTIVES: 1) to examine the impact of Lyme disease on health care costs and utilization, 2) to understand the relationship between Lyme disease and the probability of developing PTLDS, 3) to understand how PTLDS may impact health care costs and utilization. METHODS: This study utilizes retrospective data on medical claims and member enrollment for persons aged 0-64 years who were enrolled in commercial health insurance plans in the United States between 2006-2010. 52,795 individuals treated for Lyme disease were compared to 263,975 matched controls with no evidence of Lyme disease exposure. RESULTS: Lyme disease is associated with $2,968 higher total health care costs (95% CI: 2,807-3,128, p<.001) and 87% more outpatient visits (95% CI: 86%-89%, p<.001) over a 12-month period, and is associated with 4.77 times greater odds of having any PTLDS-related diagnosis, as compared to controls (95% CI: 4.67-4.87, p<.001). Among those with Lyme disease, having one or more PTLDS-related diagnosis is associated with $3,798 higher total health care costs (95% CI: 3,542-4,055, p<.001) and 66% more outpatient visits (95% CI: 64%-69%, p<.001) over a 12-month period, relative to those with no PTLDS-related diagnoses. CONCLUSIONS: Lyme disease is associated with increased costs above what would be expected for an easy to treat infection. The presence of PTLDS-related diagnoses after treatment is associated with significant health care costs and utilization.

Epidemiology and cost of hospital care for Lyme borreliosis in Germany: lessons from a health care utilization database analysis.

To date, relatively little is known about the economic and medical impact of Lyme borreliosis (LB) on European health care systems, especially for the inpatient sector. This retrospective analysis is based on data provided for the years 2007-2011 by a German statutory health insurance company (DAK-Gesundheit) covering approximately 6 million insured. Total cost was calculated for a 1-year period both from the third-party payers and from the societal perspective, respectively. In our cohort the incident diagnosis of LB was coded for 2163 inpatient cases during the years 2008-2011. The median inpatient time was 9 days resulting in a median direct medical cost per hospital stay of 3917€ for adolescents and 2843€ for adults. Based on extrapolation of our findings to the German population, we would expect an average hospital admission of 5200 adults and 2300 adolescents (<18 years) for LB treatment incurring direct medical costs of more than 23 million Euro annually. The annual indirect costs due to loss of productivity would add up to more than 7 million Euro as assessed by the human capital method. Cases tended to accumulate between June and September with remarkable changes in disease manifestations in the course of the year documented in the coded secondary diagnoses. Also specific differences in the disease pattern of adolescents and adults became obvious. Age-specific incidence showed male predominance and a bimodal distribution. Incidence was highest in children aged between 3 and 17 (highest mean incidence of 29 cases/100,000 inhabitants in 6-9 year olds) with a second peak in 60-79 year old individuals. During the study period the nationwide inpatient incidence was 9/100,000 with marked regional variability. In summary, our study is one of the first European investigations on hospital care for LB inpatients and identifies LB as a possibly underestimated socioeconomic factor for health care in Germany.

Management of suspected Lyme borreliosis: experience from an outpatient parenteral antibiotic therapy service.

OBJECTIVES: Lyme borreliosis (LB) is the most common human tick-borne infection in Europe and the USA. In this study we set out to analyse the outcome of patients treated for Lyme disease via outpatient parenteral antibiotic therapy (OPAT) and the appropriateness of this treatment using current guidelines. METHODS: This was a retrospective review of all patients with suspected LB managed via OPAT in Glasgow in 2000-11. RESULTS: Of 72 patients treated for suspected LB, 35 patients (49%) were treated in accordance with guidelines and 36 (50%) were treated with no specific guidelines. A definite improvement was seen in 20 patients (28%). Adverse reactions were documented in 29 (40%) patients with neutropenia, and mild liver function derangement was most commonly observed. CONCLUSION: These results show the complexity of translating well-substantiated regimens from clinical trials to actual clinical practice. OPAT was an effective way of administering parenteral therapy for Lyme disease but should not be undertaken lightly due to the rate of adverse events and low rates of success in certain patient groups seen in this study. In view of this, stricter criteria for inclusion to OPAT in line with published guidance should be applied to minimize patient harm and optimize success.

Evaluating frequency, diagnostic quality, and cost of Lyme borreliosis testing in Germany: a retrospective model analysis.

BACKGROUND: Data on the economic impact of Lyme borreliosis (LB) on European health care systems is scarce. This project focused on the epidemiology and costs for laboratory testing in LB patients in Germany. MATERIALS AND METHODS: We performed a sentinel analysis of epidemiological and medicoeconomic data for 2007 and 2008. Data was provided by a German statutory health insurance (DAK) company covering approx. 6.04 million members. In addition, the quality of diagnostic testing for LB in Germany was studied. RESULTS: In 2007 and 2008, the incident diagnosis LB was coded on average for 15,742 out of 6.04 million insured members (0.26%). 20,986 EIAs and 12,558 immunoblots were ordered annually for these patients. For all insured members in the outpatient sector, a total of 174,820 EIAs and 52,280 immunoblots were reimbursed annually to health care providers (cost: 2,600,850€). For Germany, the overall expected cost is estimated at 51,215,105€. However, proficiency testing data questioned test quality and standardization of diagnostic assays used. CONCLUSION: Findings from this study suggest ongoing issues related to care for LB and may help to improve future LB disease management.