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Lyme borreliosis in Belgium: a cost-of-illness analysis

BMC Public Health volume 22, Article number: 2194 (2022) Cite this article

Abstract

Background

Lyme borreliosis (LB) is the most common tick-borne disease in Europe and North America, yet its economic burden remains largely unknown. This study aimed to estimate the economic cost associated with the different clinical manifestations of LB in Belgium.

Methods

An incidence approach and societal perspective were used to estimate the total cost-of-illness for LB in Belgium. Costs were calculated for patients with erythema migrans (EM) or disseminated/late LB, including patients who developed post-treatment Lyme disease syndrome (PTLDS). Direct medical, direct non-medical (transportation & paid help) and indirect non-medical costs (productivity losses) were included in the analysis. Ambulatory cost data were collected through a prospective cohort study from June 2016 to March 2020, in which patients with LB were followed up 6 to 12 months after diagnosis. Hospitalization costs were retrieved from the Minimal Clinical Data registry, a mandatory registry for all Belgian hospitals, linked to the Minimal Financial Data registry. Costs were expressed in 2019 euros.

Results

The total annual cost associated with clinical manifestations of LB in Belgium was estimated at €5.59 million (95% UI 3.82–7.98). Of these, €3.44 million (95% UI 2.05–5.48) or 62% was related to disseminated/late LB diagnoses and €2.15 million (95% UI 1.30–3.26) to EM. In general, direct medical costs and productivity losses accounted for 49.8% and 46.4% of the total costs, respectively, while direct non-medical costs accounted for only 3.8%. The estimated mean costs were €193 per EM patient and €5,148 per disseminated/late LB patient. While patients with PTLDS seemed to have somewhat higher costs compared to patients without PTLDS, the number of patients was too small to have representative estimates.

Conclusions

We estimate the total annual direct medical costs, direct non-medical and indirect non-medical costs associated with LB to exceed €5.5 million per year, almost evenly distributed between EM (40%) and disseminated/late LB (60%). EM costs 26 times less per patient but occurs also 16 times more frequently than disseminated/late LB. The cost burden remains limited by comparison to other infectious diseases due to the relative lower incidence.

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Introduction

Lyme borreliosis (LB) is the most common tick-borne disease in Europe. An erythema migrans (EM), a red expanding rash at the site of the tick bite, is one of the first and often the only symptom present. If left untreated the infection can disseminate causing more severe disease such as Lyme neuroborreliosis (LNB), Lyme arthritis (LA), Lyme carditis or acrodermatitis chronica atrophicans (ACA) [1, 2]. Even after appropriate antibiotic treatment, persisting non-specific symptoms such as fatigue, widespread musculoskeletal pain or cognitive difficulties have been reported by a subset of patients. When these symptoms persist for 6 months or more and are of such severity that they impact daily activities, this is often referred to as post-treatment Lyme disease syndrome (PTLDS) [3]. In Belgium, the annual incidence of LB has been estimated at 103 per 100,000 inhabitants (95% UI 87–120) for the period 2015–2017 [4]. A study on the prioritization of communicable diseases for future surveillance, performed in 2018, categorized it in its “high priority” diseases group [5]. Yet, the exact burden remains unknown. Cost-of-illness studies are an important part of the assessment of the impact of a disease on the healthcare system and society. They provide essential information for cost-effectiveness and budget-impact analyses, which in turn can be used for policy making on budget allocation and on prioritizing interventions that prevent or control disease burden. Studies assessing the economic burden of LB are limited, both in North-America and Europe [6, 7]. To the best of our knowledge, no such studies have been published yet for Belgium. The aim of this cost-of-illness study was to assess the economic burden of LB in Belgium, taking into account different clinical manifestations and PTLDS.

Methods

The total cost of LB was estimated through an incidence-based costing approach for patients with (i) an EM (including multiple EM) or (ii) disseminated/late LB, including patients who later developed PTLDS. A societal perspective, which considers costs for the national healthcare insurer, the patients and their employers, was taken. Direct medical costs (ambulatory [aka outpatient] and hospital [aka inpatient] care), direct non-medical costs (transportation) and indirect non-medical costs (productivity losses due to sick leave) were included using different data sources. Mean costs were extrapolated to the population level using LB incidence estimates [4] and the number of hospitalizations over multiple years to account for yearly fluctuations.

Direct medical costs

Ambulatory care

The current study is part of a larger project in which a prospective cohort study, “HUMTICK”, was set up to collect data on LB in Belgium. The methodology of this study has been described elsewhere [8]. Briefly, between June 2016 and December 2019, adult patients with an EM or disseminated/late LB (LNB, LA, Lyme carditis or ACA) were included in the study through a network of general practitioners and eight Belgian hospitals, respectively. The cohorts were followed up and patients who developed PTLDS were identified based on the case definition proposed by the Infectious Disease Society of America (IDSA) [3]. The results of the PTLDS analysis are published elsewhere [9]. A total of 108 EM patients and 15 disseminated/late LB patients, prospectively recruited for the PTLDS baseline analysis, were included in the current cost analysis. Six EM and three disseminated/late LB patients fulfilled the complete PTLDS definition. Three EM patients and two disseminated/late LB patients had a missing value for PTLDS, and the information for these cases was imputed [9]. Since for each of these patients, either all imputations or the majority of the imputations led to the conclusion of “no PTLDS”, these five patients were assigned to the “no PTLDS” groups for the purpose of our analysis.

Data on volumes of resource use, more specifically consultations, medication, but also travel expenses, non-medical paid help, informal care and productivity losses (see further) were collected through patient questionnaires. All patients were asked to fill in a questionnaire at diagnosis, and then at 1 and 3 months post-diagnosis and at 6 months post-treatment. If included in the first years of the study, longer follow-up was possible with a questionnaire at 12 and possibly 24 months post-treatment. A cost diary was provided for patients’ personal use. In the current analysis, costs occurring until six months after treatment were included for EM patients and disseminated/late LB patients and costs occurring until 12 months for patients with PTLDS. In the end, the number of patients with data at 24 months was too limited to include this time point for the cost calculations in the sections below.

The number of LB serological tests performed for EM patients at diagnosis or during the first 2 months after diagnosis, although not required, was estimated from data of the network of sentinel general practices (SGP) which follows up the incidence of EM in Belgium [4]. When ELISA and/or immunoblot were performed, it was assumed to include both IgM and IgG testing. For disseminated/late LB, the specialists enlisting patients in the cohort study provided this information. For hospitalized patients in the cohort study, costs occurring during these hospitalizations, e.g., part of treatment, laboratory testing, were removed as these are calculated based on separate data (see further). Intravenous treatment was considered to be provided during (day) hospitalization only.

Unit prices in euro (€) for the reference year 2019 were used. For serological tests and consultations with reimbursed care providers (general practitioner (GP), specialist, physiotherapist, psychologist), unit prices were obtained from the National Institute of Health and Disability Insurance [10, 11] (Additional file 1, Table S1 and S2). For alternative therapists (osteopath, homeopath, chiropractor) prices are not fixed in Belgium. Based on reports of the Belgian Health Care Knowledge Centre (KCE) [12, 13] and the website of the Belgian professional association of osteopathy [14], an amount of €50 per consult was attributed (Additional file 1, Table S1). Prices of medication were retrieved from the Belgian Centre for Pharmacotherapeutic Information [15]. For antibiotics, and in line with the Belgian guidelines for economic evaluations [16], the cheapest brand was counted as pharmacists in Belgium are obliged to substitute (Additional file 1, Table S3). For food supplements, not described by the BCPI, prices were obtained from the website of the brand itself or – if not available – online pharmacies. If no brand was given for a product, a random value based on a uniform distribution between the minimum and maximum price of brands available online was drawn. In general, the smallest package size containing the number of tablets used by the patient was counted. If the number of tablets was not specified, the smallest box on the market was counted.

Hospitalizations

Data on the costs of hospitalizations for LB were retrieved from the Minimal Clinical Data registry (MCD) linked to the Minimal Financial Data registry (MFD) for the year 2016. The MCD is a registry mandatory for all Belgian hospitals containing information such as the primary and secondary diagnosis, the length of stay and patient demographics, on both classical hospitalizations (at least one overnight) and day hospitalizations. Diagnosis coding in the MCD registry is, since 2015, based on the International Statistical Classification of Diseases—10th revision—Clinical Modification (ICD-10-CM). Hospitalizations were identified based on the primary diagnosis being LB, corresponding to the ICD-10-CM LB codes listed in Table 1.

Table 1 ICD-10-CM codes Lyme Borreliosis, 2016, Belgium
Full size table

For the classical hospitalizations, hospital specific 100% day prices for the year 2019 were multiplied by the number of inpatient days. Other hospital costs available in the MFD registry for 2016 were converted to the reference year 2019 by applying an inflation of 5.16% (Health index 2016–2019) [17]. The cost of drugs administered during overnight hospitalizations consists of three components: a lump sum per admission, a lump sum by day (€0.62) and a cost per drug administered. For day hospitalizations (hospital stay without night), there is no lump sum for medication. Day costs, medication and radiopharmaceuticals, include both reimbursed and non-reimbursed costs. In contrast, costs for laboratory diagnostics, medical acts or implants include reimbursed costs only since information on non-reimbursed costs is not available in the MFD. Costs counted included both LB specific (e.g. antibiotics, LB serology) and non-LB specific costs. Supplements for a single room, costs for food, ambulance, etc. could not be counted as this information was not available in the MCD-MFD data. Such supplements tend to be highly variable between hospitals and depends also on the socioeconomic background of patients [18, 19].

Direct non-medical costs

For travel expenses related to both ambulatory care and hospitalizations, volumes reported by the patients in the prospective cohort study were used. The number of kilometers travelled by private transport were multiplied with the Belgian kilometric allowance 2019 (€0.3653). If public transport was used, the ticket price was counted. Paid non-medical help (household cleaning, childcare, yard maintenance) was valued using expenditures reported by the patients. Informal care from friends or family was measured but not attributed a monetary value, following Belgian guidelines for economic evaluations [16].

Indirect non-medical costs

The costs of productivity losses (work absenteeism) were estimated using the human capital approach (i.e., without friction period), i.e., the number of hours of sick leave were multiplied with the gross national average hourly labor cost being €40.5 in 2019 [20]. Hours of ambulatory productivity loss (not related to hospitalization) were estimated based on the prospective cohort study responses. In accordance with the Belgian Labour Act, one week of sick leave was counted as 38 h productivity losses for fulltime work and 19 h for part-time work. Hours of productivity losses due to hospitalization was calculated based on the mean length of hospital stay for cases < 65 years old in the MCD-MFD data, an employment rate of 65.3% for the Belgian population aged 15–65 years (of which 72% fulltime, 13% 4/5th, 10% halftime and 4.9% other part-time work counted as halftime) [21, 22] and, following KCE guidelines, assuming 18.8 working days per month with 7.6 working hours per day [16]. For day hospitalization, half a day productivity loss was counted (estimation based on the duration of IV treatment administration). For children it was assumed that one parent takes sick leave.

Number of LB cases in Belgium

To extrapolate to the population level, the estimated average ambulatory costs by group were multiplied with (i) the total number of EM cases and (ii) the total number of disseminated/late LB cases in Belgium, based on the average annual incidence reported by Geebelen et al. (2019) for the period 2015─2017 [4]. In these, the disseminated/late LB group included LNB, LA, Lyme carditis and ACA but also borrelial lymphocytoma and ocular manifestations (not included in the prospective cohort study). A total population size of 11,462,024 was applied (Belgium, mid-year 2019) [23]. The PTLDS patients and their costs were included in the cost estimation as part of the group from which they emanated (group (i) or (ii)). For the hospitalizations, the annual mean number of hospital admissions for the period 2016–2018 was used. As there are no specific codes for EM in the ICD-10-CM coding system, and as EM is not expected to cause hospitalization when occurring on its own, the hospitalization costs were assigned to the more severe manifestation group (ii) disseminated/late LB.

Data analysis

All analyses were conducted in R version 3.6.3 [24]. For different cost categories within the ambulatory data and hospital data, uncertainty was estimated performing a non-parametric bootstrap procedure with 10,000 replications to calculate 10,000 bootstrapped means (distributions). The bootstrapped means of ambulatory costs for (i) EM patients and (ii) disseminated/late LB patients, more specifically the bootstrapped means of the total direct medical costs, the direct non-medical (travel expenses, paid non-medical help) and the indirect non-medical costs (productivity losses), were multiplied with the number of cases in Belgium on which uncertainty was propagated using 10,000 Monte Carlo simulations following a uniform distribution defined by the mean minimum and mean maximum incidence estimate for the period 2015─2017 [4]. Bootstrapped means of direct medical and indirect non-medical costs related to (day-)hospitalizations were multiplied with the mean number of stays for the period 2016─2018. The results for the different cost categories (distributions) were further summed by patient group to calculate total costs for Belgium capturing the uncertainty on the input parameters in the final outputs. All results were summarized by the mean and 95% uncertainty interval (UI) defined as the 2.5th and 97.5th percentile of the bootstrap or uncertainty distribution. Additional file 2 provides an overview of the estimated median costs by patient, calculated by performing a non-parametric bootstrap procedure with 10,000 replications to calculate 10,000 bootstrapped medians, summarized by the mean and uncertainty interval of the bootstrap distribution, as described above. Unless specified differently earlier (e.g. medication), missing values were imputed with the median of the observed values in the same group at the same time point or multiple time points combined if n observations < 5. When patients reported a range instead of an exact value, the mean of the range was used.

Results

Direct medical costs

Ambulatory care

The mean ambulatory direct medical cost was estimated at €124 (95% UI 90.3–165)) for EM patients (i) and €516 (95% UI 350–731) for disseminated/late LB patients (ii), including patients who developed PTLDS in both groups (Table 2). Estimates for patients without or with PTLDS separately are shown in Table 2. Ambulatory direct medical costs were highest for patients with disseminated/late LB at a mean of €524 (95% UI 327–787) and €478 (95% UI 262–723) for those without and with PTLDS, respectively. Within the EM group, the mean ambulatory direct medical cost was almost twice as high for patients with PTLDS (€214, 95% UI 87.7–382) compared to without PTLDS (€118, 95% UI 85.7–162). The latter was mainly due to a difference in Over-The-Counter (OTC) medication (mean difference €65.2) followed by consultations (mean difference €30.1).

Table 2 Estimated mean ambulatory cost per patient, expressed in 2019 euros, for the different manifestation groups of Lyme borreliosis in the prospective cohort study (HUMTICK), 2016─2020, Belgium. Mean and 95% uncertainty intervals of the bootstrap distribution of the mean
Full size table

Hospitalizations

In 2016, there were 286 classical hospital admissions (for at least one night) for 269 patients in total, with LB as a primary diagnosis. The mean duration of a hospital stay equaled 5.6 days (95% UI 4.8–6.5 days) corresponding to a mean direct medical cost of €4,159 per hospital admission (Table 3). Within the direct medical cost for overnight hospitalizations, hospital day price was the most important cost at a mean of €3,036 (73%), followed by the medical acts (20%), medication (4%) and laboratory tests (2%). LB serology was performed during 79% of stays and at least one antibiotic treatment, possibly for LB, was given during 67% of stays. Pain killers were given during 41% of stays.

Table 3 Estimated mean costs per classical hospitalization and day hospitalization, 2016 euros converted to 2019 euros, Belgium. Mean and 95% uncertainty intervals of the bootstrap distribution of the mean
Full size table

MCD-MFD data were available for 613 out of 684 days for day hospitalizations with LB as a primary diagnosis in 2016. As these concerned 68 unique patients, they each had on average 9 day hospitalisations. The mean direct medical cost for one day hospitalization equaled €50.5. The majority of patients (n = 57/68) received intravenous antibiotic treatment and medication caused 53% of costs.

Direct non-medical costs

The estimated mean travel expenses related to ambulatory care or hospitalization equaled €5.0 (95% UI 1.0–11.5) in EM patients and €190 (95% UI 92–297) in disseminated/late LB patients. Within the EM group, mean costs were higher in patients with PTLDS (€16.2, 95% UI 0.9–42.1) compared to no PTLDS (€4.4, 95% UI 0.6–10.7). For disseminated/late LB, costs were lower for patients with PTLDS (€97.2, 95% UI 0–219) than no PTLDS (€213, 95% UI 94.4–341), but the number of patients in the disseminated/late LB group and PTLDS groups were low.

Only 6/108 (5.6%) EM patients reported the use of informal care of family or friends compared to 8/15 (53.3%) of disseminated/late LB patients. The mean number of hours of help received was highest for EM patients with PTLDS (18.8, 95% UI 0.33–48.50), followed by disseminated/late LB without PTLDS (12.7, 95% UI 4.7–21.7), disseminated/late LB with PTLDS (2.01, 95% UI 0.0–6.0) and EM patients without PTLDS (1.21, 95% UI 0.0–3.4). Paid non-medical help was only reported by one patient with disseminated/late LB without PTLDS, declaring a cost of €600 (gardener), leading to a mean cost of €40.8 (95% UI 0.0–120) for all disseminated/late LB patients (n = 15).

Indirect non-medical costs

The estimated mean costs for productivity losses, not related to hospitalization, by patient group are shown in Table 2. The cost was highest for disseminated/late LB patients with PTLDS, at a mean of €3,341 (95% UI 0–5,604) corresponding to 10.9 working days, followed by disseminated/late LB without PTLDS (€2432; 95% UI 286–5724; 7.9 days), EM with PTLDS (€71; 95% UI 0–213; 1.75 h) and EM without PTLDS (€62.7; 95% UI 6–145; 1.55 h). The mean cost for productivity losses related to hospitalizations (group ii) was estimated at €399 (95% UI 348–452) per overnight hospital admission and €29.8 per day hospitalization (Table 3).

Total LB cost in Belgium

Table 4 shows the mean number of LB cases, the mean number of hospitalizations and the total cost estimates for the different clinical manifestations of LB for the whole of Belgium per year. The total annual cost, including ambulatory care, hospital care, travel expenses, non-medical help and productivity losses, equaled €5.59 million (95% UI 3.82–7.98). Of these, €3.44 million (95% UI 2.05–5.48) or 62% was related to disseminated/late LB diagnoses and €2.15 million (95% UI 1.30–3.26) or 38.4% to EM. In general, direct medical costs and productivity losses accounted for 49.8% and 46.4% of the total costs, respectively. Direct non-medical costs accounted for 3.8%. The proportion of costs for productivity losses was higher in disseminated/late LB patients (54.6%) than in EM patients (33.2%). Out of the direct medical costs in all patients, 38.0% was related to hospitalizations or day hospitalizations, whereas within the disseminated/late LB patient group this was 75.1%. The majority of direct medical costs were reimbursed, namely 75.5%, yet not all non-reimbursed costs for hospitalizations could be counted and the proportion reimbursed depends on the patient’s insurance. A division between costs reimbursed by the health insurance system and non-reimbursed costs for the patients themselves is provided in Additional file 3 (Table S7).

Table 4 Incidence number of cases and total costs for Lyme borreliosis in Belgium. Total costs and 95% uncertainty interval
Full size table

Per patient, the total cost, including ambulatory care, hospital care, travel expenses and productivity losses, corresponded to a mean of €193 for EM patients and €5,148 for disseminated/late LB patients. Regarding the latter, €1,778 per patient was related to hospitalizations (direct medical costs and productivity losses due to classical hospitalization or day hospitalization).

Discussion

In order to estimate the economic burden of LB in Belgium, the current study used different data sources (a prospective cohort study and national hospital registries) which allowed the inclusion of direct medical costs, direct non-medical costs and indirect non-medical costs associated with this multisystem infectious disease. Based on an incidence approach, societal perspective and 2019 euros, the total annual cost associated with LB in Belgium was estimated at €5.59 million with a 95% UI between €3.82 and €7.98 million. Direct medical costs and productivity losses accounted for the majority of the costs, 49.8% and 46.4% of the total, respectively. Despite the much lower incidence of disseminated/late LB manifestations compared to EM, the former accounted for more than half of the total national LB costs per year (62%), because of its high mean cost of €5,148 (95% UI 3,091–7,911) per patient compared to a mean of €193 (95% UI 121–284) per EM patient. While the mean ambulatory direct medical cost was almost twice as high for patients with PTLDS after EM compared to EM patients without PTLDS, patients with PTLDS after disseminated/late LB incurred only higher productivity losses relative to patients without PTLDS after disseminated/late LB but no higher direct medical costs. The latter is unexpected, yet, these results need to be interpreted with caution as the sample sizes for the groups with PTLDS in the prospective cohort study were very small, causing uncertainty to be high. Although the majority of direct medical costs were reimbursed (75.5%), patients still pay €43.9 (EM) or €286 (Disseminated/late) of direct medical costs themselves. In addition, all direct non-medical costs are payed by the patient (i.e. travel expenses: €5 (EM) or €190 (Disseminated/late) and paid help: €50.9 (Disseminated/late)), making the cost to the patient still quite high. Furthermore, depending on the employment status and duration of sick leave there can be loss in salary.

Comparison of the current results with LB cost studies performed elsewhere is challenging as there is heterogeneity in the methods used, the patient populations studied and the cost data collected, as well as in the healthcare systems in place in the countries concerned. In Europe, some older cost studies have been performed for LB in Scotland (1999) [25], for LNB patients in Sweden (2000–2005) [26] and for hospitalized patients in Germany (2008–2011) [27]. Similar to our study, van den Wijngaard et al. (2017) estimated LB costs for the Netherlands, including direct medical and indirect non-medical costs [28]. For EM, a mean ambulatory cost of €136 was estimated (amount adjusted to 2019 price level [29, 30]), which is lower than our mean estimate of €193 in EM patients (including 5.9% patients with PTLDS [31]). Note that in contrast to the Dutch study, our study included OTC medication, laboratory testing and travel expenses with a cost of €40. The mean total cost for disseminated LB in the Dutch study, including ambulatory and hospital costs as well as costs for productivity losses, was estimated at €6,327 (inflated [29]), which is higher compared to the mean of €5,148 in our study (including 20.9% patients with PTLDS). The total costs for patients with persisting symptoms in the Netherlands were estimated as a separate category, which represented a substantial amount of €6,361 per patient (inflated [29]), on top of the costs for EM or disseminated LB. Out of these, €1,362 concerned ambulatory direct medical costs, which is much higher than the additional ambulatory direct medical costs found for PTLDS patients in our study (Table 2), yet sample size for the latter was very small. Also, patients with persisting symptoms were defined differently than our PTLDS patients and were included based on a GP diagnosis, so it may be that these were more seriously ill patients; the duration of persisting symptoms in that study was longer (4.6 years). Furthermore, some cost studies have also been performed in the US, but comparisons with non-US estimates are problematic due to fundamental differences in pricing and healthcare organization, as well as differences in clinical manifestations, with a higher proportional occurrence of more costly LA cases in the US [32,33,34,35]. Further research on the costs of patients with PTLDS seems warranted.

Comparison of our study results with the cost-of-illness of infectious diseases other than Lyme borreliosis in Belgium is also not straightforward as both costs and incidence data must be taken into account. For several infectious diseases, the average cost per case is lower (e.g., influenza [36, 37], rotavirus [38]) or similar (e.g., herpes zoster [39]) than the cost of LB, but due to the higher incidence of these infections in Belgium, their total national cost is much higher than that of LB. For example, for influenza, mean ambulatory direct costs have been estimated at €51–64 per case and hospitalization cost at €2,599, which, with an estimated 400 000 cases [36, 37], leads to a national cost of more than €30 million (2011–2012, indirect costs not included). Also for human papilloma virus (HPV), where mean costs per case and incidences differ largely by outcome (e.g., cervical cancer vs. anogenital warts), overall national costs are higher than LB [40]. Some other infections, have a lower direct cost due to a low incidence (e.g. hepatitis A [41]) or due to a low cost per case (e.g. Varicella [39]).

It is important to note that, in the current study, only costs for patients with clinical LB manifestations, either EM or laboratory confirmed disseminated/late LB, were included [31]. As such, costs for consultations for a tick bite without LB development were not counted even though they might take place due to worries about LB. Based on data from the SGP network (2015─2017), the annual number of GP consultations for tick bites can be estimated at 19,422 (95% UI 16,384–22,523), which corresponds to an estimated cost of €510,806 (95% UI 430,901–592,368) (productivity losses not counted). For the same reason, only laboratory tests performed in patients with clinical LB manifestations were included, however, many more LB serological tests are performed each year in Belgium. In the period 2015─2017, in ambulatory care only, an annual mean of 220,270 IgG EIA tests and 11,405 IgG Immunoblots were performed on blood, indicating a low positivity rate (5.18%) for the EIA (first-tier test) as immunoblot is recommended to only be performed when EIA is positive or equivocal. This indicates a potential over-use of these tests without benefits for patient management. Note that these serological tests are not advised for EM diagnosis, as in this early disease stage sensitivity is too low. In addition, tests do not differentiate between active and past infection and are not useful to follow-up antibiotic treatment success [42]. A high economic burden of several million euros related to these tests can be expected; the mean annual cost for all LB serological tests (IgG, IgM, EIA, Immunoblot, on blood, on CSF) in 2015─2017 equaled €1,092,801 and in addition a forfeit by analysis by patient (not by test) of €19.84─€30.5, depending on the number of tests performed, applies. More research into these costs and the reasons why these high numbers of tests are carried out is therefore of great importance. Also, no costs for prophylaxis treatment were included in the current study.

Since there are yearly fluctuations in the number of LB cases, this study used mean incidence estimates for a period of three years. Nevertheless, this incidence estimate was probably not representative for the number of LB cases in 2019, as 2019 was a year with an exceptionally low number of tick bites, probably due to extreme dry and warm periods during the summer [43]. It is therefore expected that the total costs for the year 2019 would be lower than the current cost estimates based on the LB incidence 2015─2017, but the latter are expected to be more representative for an average year.

As is the case for many healthcare cost data, most costs were skewed with a few patients incurring much higher costs than the majority of patients, causing estimated mean costs to be higher than median costs (Additional file 2). For example, for ambulatory productivity loss the median cost equaled €0 in EM patients and €656 for disseminated/late LB patients compared to a mean of €63.9 and €2,624, respectively. Yet, as is appropriate for cost-of-illness and cost-effectiveness analysis, we focused on mean costs, and extrapolated these to the population level to produce our overall cost burden estimates [44].

There are some limitations to the current study. First, for the ambulatory cost calculation, no children were included, hence the same costs are assumed as for adults. Second, as data are based on the incidence estimates 2015─2017 published by Geebelen et al. (2019), limitations mentioned there also apply to the current estimates [4]. As a possible underestimation of the proportion of disseminated/late LB manifestations was suspected, national costs for this group in the current study, can also be underestimated. Third, the sample size of the disseminated/late LB group and the group of patients with PTLDS in the prospective cohort study, used for ambulatory cost calculation, was small and uncertainty in the results high. Further research into their costs is needed. Fourth, hospitalizations for LB were selected based on ICD-10-coding of LB, which mainly serves for financing and was not necessarily developed for surveillance purposes. Quality of the coding could not be checked. Since there is no specific ICD-10-CM code for EM or PTLDS, all hospital costs were allocated to the disseminated/late LB group. Although no hospital costs are expected due to the mild nature of the symptoms of EM, they may be present in exceptional cases. Fifth, while a societal perspective was taken, it was not possible to include all costs that might have occurred; no ambulatory laboratory testing other than LB serology, no medical acts for emergency visits and not all non-reimbursed costs and supplements for hospitalizations could be included. On the other hand, for hospitalizations, costs for all types of medication, laboratory testing or medical acts were included, comprising also costs for comorbidities not related to LB (e.g. blood pressure medication). Finally, for EM or disseminated/late LB patients, no costs exceeding 6 months post diagnosis were included, which could result in an underestimation of the true cost of LB in Belgium. Nevertheless, after a longer period it becomes more difficult (also for the patient) to relate specific costs to the disease.

In conclusion, we provide for the first time, a comprehensive assessment of the costs related to LB in Belgium. As EM and disseminated/late LB are estimated to cause about 40% and 60% of the total national costs, respectively, both measures to prevent EM, such as prevention of tick bites and fast removal of ticks and prevention of dissemination of disease, such as informing GPs and the public on EM to improve fast treatment, are essential. Ideally, a vaccine will be developed that prevents tick bites, hence prevents LB (all manifestations), but also prevents transmission of other tick-borne pathogens. The current cost estimation can serve as an input in future cost-effectiveness analyses of such vaccines or other pharmaceutical and non-pharmaceutical interventions. While patients with PTLDS seem to have somewhat higher costs compared to patients without PTLDS this needs further research.

Availability of data and materials

The datasets generated and analyzed during the current study are not publicly available as restrictions apply to the availability of these data. Part of the data can be made available from the corresponding author on reasonable request if compliant with the approvals received for the data collection.

Abbreviations

EM:

Erythema migrans

LNB:

Lyme neuroborreliosis

LA:

Lyme arthritis

ACA:

Acrodermatitis chronica atrophicans

PTLDS:

Post-treatment Lyme disease syndrome

IDSA:

Infectious Disease Society of America

SGP:

Sentinel general practices

GP:

General practitioner

KCE:

Belgian Health Care Knowledge Centre

MCD:

Minimal Clinical Data registry

MFD:

Minimal Financial Data registry

ICD-10-CM:

International Statistical Classification of Diseases—10th revision—Clinical Modification

UI:

Uncertainty interval

OTC:

Over-The-Counter

References

  1. Stanek G, Wormser GP, Gray J, Strle F. Lyme borreliosis. The Lancet. 2012;379:461–73.

    Article  Google Scholar 

  2. Steere AC, Strle F, Wormser GP, Hu LT, Branda JA, Hovius JWR, et al. Lyme borreliosis. Nat Rev Dis Primer. 2016;2:1–19.

    Article  Google Scholar 

  3. Wormser GP, Dattwyler RJ, Shapiro ED, Halperin JJ, Steere AC, Klempner MS, et al. The clinical assessment, treatment, and prevention of lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis Off Publ Infect Dis Soc Am. 2006;43:1089–134.

    Article  Google Scholar 

  4. Geebelen L, Van Cauteren D, Devleesschauwer B, Moreels S, Tersago K, Van Oyen H, et al. Combining primary care surveillance and a meta-analysis to estimate the incidence of the clinical manifestations of Lyme borreliosis in Belgium, 2015–2017. Ticks Tick-Borne Dis. 2019;10:598–605.

    Article  PubMed  Google Scholar 

  5. Klamer S, Van Goethem N, Muyldermans G, Vernelen K, Welby S, Asikainen T, et al. Prioritisation for future surveillance, prevention and control of 98 communicable diseases in Belgium: a 2018 multi-criteria decision analysis study. BMC Public Health. 2021;21:192.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Greig J, Young I, Harding S, Mascarenhas M, Waddell L. A scoping review of Lyme disease research relevant to public health. Can Commun Dis Rep. 2018;44:243–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Mac S, da Silva SR, Sander B. The economic burden of Lyme disease and the cost-effectiveness of Lyme disease interventions: A scoping review. PLoS One. 2019;14(1):e0210280. https://doi.org/10.1371/journal.pone.0210280.

  8. Geebelen L, Lernout T, Kabamba-Mukadi B, Saegeman V, Sprong H, Van Gucht S, et al. The HUMTICK study: protocol for a prospective cohort study on post-treatment Lyme disease syndrome and the disease and cost burden of Lyme borreliosis in Belgium. Arch Public Health. 2017;75:42.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Geebelen L, Lernout T, Devleesschauwer B, Kabamba-Mukadi B, Saegeman V, Belkhir L, et al. Non-specific symptoms and post-treatment Lyme disease syndrome in patients with Lyme borreliosis: a prospective cohort study in Belgium (2016–2020). BMC Infect Dis. 2022;22(1):756. https://doi.org/10.1186/s12879-022-07686-8.

  10. Institut National d’Assurance Maladie-Invalidité (I.N.A.M.I). Tarifs ; médecins - consultations et visites ; 01–01–2019 ; A. 2019. https://www.riziv.fgov.be/SiteCollectionDocuments/tarif_medecins_partie01_20190101.pdf. Accessed 22 Dec 2021.

  11. Institut National d’Assurance Maladie-Invalidité (I.N.A.M.I). Tarifs ; médecins - biologie clinique ; 01–01–2019. 2019. https://www.riziv.fgov.be/SiteCollectionDocuments/tarif_medecins_partie05_20190101.pdf. Accessed 22 Dec 2021.

  12. De Gendt T, Desomer A, Goosens M, Hanquet G, Léonard C, Mertens R, et al. Stand van zaken van de homeopathie in België. Brussel: Federaal Kenniscentrum voor de Gezondheidszorg (KCE): Health Services Research (HSR); 2011.

    Google Scholar 

  13. De Gendt T, Desomer A, Goossens M, Hanquet G, Léonard C, Mélard F, et al. Stand van zaken voor de osteopathie en de chiropraxie in België. Brussel: Federaal Kenniscentrum voor de Gezondheidszorg (KCE): Health Services Research (HSR); 2010.

    Google Scholar 

  14. www.osteopathie.be. Kosten en vergoeding. 2019. https://osteopathie.be/nl/osteopathie-ik-ben-patient/kosten-vergoeding-osteopathische-zorg/. Accessed 25 Nov 2019.

  15. Belgian Centre for Pharmacotherapeutic Information. Répertoire commenté des médicaments. 2019. http://www.cbip.be/fr/start. Accessed 30 Dec 2019.

  16. Cleemput I, Neyt M, Van de Sande S, Thiry N. Belgian guidelines for economic evaluations and budget impact analyses: second edition. Health Technology Assessment (HTA). Brussels: Belgian Health Care Knowledge Centre(KCE). 2012. KCE Report 183C. D/2012/10.273/54. https://kce.fgov.be/sites/default/files/atoms/files/KCE_183_economic_evaluations_second_edition_Report_update.pdf. Accessed 22 Dec 2021.

  17. Statistics Belgium (STATBEL). Consumer price index according to the COICOP nomenclature base year, per year and month. https://bestat.statbel.fgov.be/bestat/crosstable.xhtml?view=208b69bd-05c5-4947-b7f9-2d2300f517b8. Accessed 27 Feb 2021.

  18. Lecluyse A, Van de Voorde C, De Graeve D, Schokkaert E, Van Ourti T. Hospital supplements in Belgium: Price variation and regulation. Health Policy. 2009;92:276–87.

    Article  PubMed  Google Scholar 

  19. Bouckaert N, Maertens de Noordhout C, Van de Voorde C. Health System Performance Assessment: how equitable is the Belgian health system?. Health Services Research (HSR) Brussels: Belgian Health Care Knowledge Centre (KCE). 2020. KCE Reports 334. D/2020/10.273/30. 2020. https://kce.fgov.be/sites/default/files/atoms/files/KCE_334_Equity_Belgian_health_system_Report.pdf.

  20. Eurostat. Labour cost levels by NACE Rev. 2 activity. https://ec.europa.eu/eurostat/databrowser/view/lc_lci_lev/default/table?lang=en. Accessed 11 Jun 2021.

  21. STATBEL, Belgium in figures. Annual labour marked indicators with regard to activity, sex, age group (population aged 15 to 64) and region of residence. 2020. https://statbel.fgov.be/en/themes/work-training/labour-market/employment-and-unemployment#figures. Accessed 19 Feb 2021.

  22. STATBEL, Belgium in figures. Part-time employment among employees, according to part-time working arrangements and gender (2017–2019). 2017. https://statbel.fgov.be/en/themes/work-training/labour-market/part-time-employment#figures. Accessed 19 Feb 2021.

  23. Structure of the Population | Statbel. https://statbel.fgov.be/en/themes/population/structure-population#panel-13. Accessed 10 Jun 2021.

  24. R Core Team (2018). R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. https://www.R-project.org/. Accessed 24 Feb 2020.

  25. Joss AW, Davidson MM, Ho-Yen DO, Ludbrook A. Lyme disease–what is the cost for Scotland? Public Health. 2003;117:264–73.

    Article  CAS  PubMed  Google Scholar 

  26. Henningsson AJ, Malmvall BE, Ernerudh J, Matussek A, Forsberg P. Neuroborreliosis–an epidemiological, clinical and healthcare cost study from an endemic area in the south-east of Sweden. Clin Microbiol Infect. 2010;16:1245–51.

    Article  CAS  PubMed  Google Scholar 

  27. Lohr B, Muller I, Mai M, Norris DE, Schoffski O, Hunfeld KP. Epidemiology and cost of hospital care for Lyme borreliosis in Germany: lessons from a health care utilization database analysis. Ticks Tick Borne Dis. 2015;6:56–62.

    Article  CAS  PubMed  Google Scholar 

  28. van den Wijngaard C, Hofhuis A, Wong A, Harms MG, de Wit GA, Lugnér AK, et al. The cost of Lyme borreliosis. Eur J Public Health. 2017;27:538–47.

    Article  PubMed  Google Scholar 

  29. StatLine. Consumentenprijzen; prijsindex 2015=100. 2021. https://opendata.cbs.nl/statline/#/CBS/nl/dataset/83131NED/table?fromstatweb. Accessed 7 Sep 2021.

  30. Conversion rates - Purchasing power parities (PPP) - OECD Data. theOECD. http://data.oecd.org/conversion/purchasing-power-parities-ppp.htm. Accessed 5 Jul 2021.

  31. Geebelen L, Lernout T, Devleesschauwer B, Kabamba-Mukadi B, Saegeman V, Belkhir L, et al. Non-specific symptoms and post-treatment Lyme disease syndrome in patients with Lyme borreliosis: a prospective cohort study in Belgium (2016–2020). In review.

  32. Maes E, Lecomte P, Ray N. A cost-of-illness study of lyme disease in the United States. Clin Ther. 1998;20:993–1008.

    Article  CAS  PubMed  Google Scholar 

  33. Zhang X, Meltzer MI, Pena CA, Hopkins AB, Wroth L, Fix AD. Economic impact of Lyme disease. Emerg Infect Dis. 2006;12:653–60.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Coipan EC, Jahfari S, Fonville M, Oei GA, Spanjaard L, Takumi K, et al. Imbalanced presence of Borrelia burgdorferi s.l. multilocus sequence types in clinical manifestations of Lyme borreliosis. Infect Genet Evol. 2016;42:66–76.

    Article  CAS  PubMed  Google Scholar 

  35. Anderson GF, Hussey P, Petrosyan V. It’s Still The Prices, Stupid: Why The US Spends So Much On Health Care, And A Tribute To Uwe Reinhardt. Health Aff (Millwood). 2019;38:87–95.

    Article  PubMed  Google Scholar 

  36. Beutels P, Vandendijck Y, Willem L, Goeyvaerts N, Blommaert A, van Kerckhove K, et al. Vaccinatie tegen seizoensinfluenza: prioritair de kinderen of andere doelgroepen? Deel II: kosten-effectiviteitsanalyse – Synthese. Health Technology Assessment (HTA). Brussel: Federaal Kenniscentrum voor de Gezondheidszorg (KCE). 2013. KCE Reports 204As. D/2013/10.273/40. https://kce.fgov.be/sites/default/files/atoms/files/KCE_204As_Seizoensinfluenza_vaccinatie_deelII.pdf. Accessed 22 Dec 2021.

  37. Beutels P, Vandendijck Y, Willem L, Goeyvaerts N, Blommaert A, van Kerckhove K, et al. Seasonal influenza vaccination: prioritizing children or other target groups? Part II: cost-effectiveness analysis. Health Technology Assessment (HTA) Brussels: Belgian Health Care Knowledge Centre (KCE). 2013. KCE Reports 204. D/2013/10.273/43. 2013. https://kce.fgov.be/sites/default/files/atoms/files/KCE_204_Seasonal_influenza_vaccination_partII.pdf. Accessed 22 Dec 2021.

  38. Bilcke J, Van Damme P, De Smet F, Hanquet G, Van Ranst M, Beutels P. The health and economic burden of rotavirus disease in Belgium. Eur J Pediatr. 2008;167:1409–19.

    Article  PubMed  Google Scholar 

  39. Bilcke J, Ogunjimi B, Marais C, de SF Callens C, Callaert C, et al. The health and economic burden of chickenpox and herpes zoster in Belgium. Epidemiol Infect. 2012;140:2096–109.

    Article  CAS  PubMed  Google Scholar 

  40. Annemans L, Rémy V, Lamure E, Spaepen E, Lamotte M, Muchada J-P, et al. Economic burden associated with the management of cervical cancer, cervical dysplasia and genital warts in Belgium. J Med Econ. 2008;11:135–50.

    Article  PubMed  Google Scholar 

  41. Luyten J, Van de Sande S, de Schrijver K, Van Damme P, Beutels P. Cost-effectiveness of hepatitis A vaccination for adults in Belgium. Vaccine. 2012;30:6070–80.

    Article  PubMed  Google Scholar 

  42. Kullberg BJ, Vrijmoeth HD, van de Schoor F, Hovius JW. Lyme borreliosis: diagnosis and management. BMJ. 2020;369:m1041. https://doi.org/10.1136/bmj.m1041.

  43. Tersago K, Leroy M, Lernout T. TiquesNet 2019: Surveillance des morsures de tiques en Belgique. Sciensano. 2020. https://tekennet.sciensano.be/reports/Final_Surveillance%20des%20morsures%20de%20tiques_TiquesNet%202019.pdf. Accessed 22 Dec 2021.

  44. WHO guide for standardization of economic evaluations of immunization programmes. 2nd ed. Geneva: World Health Organization; 2019. Licence: CC BY-NC-SA 3.0 IGO. https://apps.who.int/iris/bitstream/handle/10665/329389/WHO-IVB-19.10-eng.pdf. Accessed 9 Nov 2022.

  45. PREVOYANCE SOCIALE.SANTE PUBLIQUE ET ENVIRONNEMENT. 29 AVRIL 1996. - Loi portant des dispositions sociales. 1996. http://www.ejustice.just.fgov.be/cgi_loi/change_lg.pl?language=fr&la=F&table_name=loi&cn=1996042932. Accessed 15 Nov 2021.

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Acknowledgements

We are very grateful to all the GPs participating in the GP network of the HUMTICK study for the inclusion of patients with an EM and to the medical specialists who included patients with disseminated/late LB: Benoït Kabamba-Mukadi (UCL), Leïla Belkhir (UCL), Veroniek Saegeman (UZL), Paul de Munter (UZL), Bénédicte Dubois (UZL), Rene Westhovens (UZL), Jean-Baptiste Giot (CHUL), Philippe Léonard (CHUL), Riet Vangheluwe (ZOL), Grégoire Wieërs (CSPO), Jean-Christophe Marot (CSPO), Frédéric Evrard (CSPO), Bénédicte Delaere (CHU-UCL Namur, Site Godinne), Séverine Noirhomme (CHRSM), Els Binnemans (ReumaClinic) and Johan Vanhoof (ReumaClinic). In addition we sincerely thank all patients who participated to the study. We thank our colleagues involved in the data collection by the SGP network. Finally, we thank all people involved in the data collection in the MCD-MFD registries.

Funding

The study has been funded by Sciensano, the Belgian institute for health.

Author information

Authors and Affiliations

  1. Scientific Directorate of Epidemiology and Public Health, Sciensano, Brussels, Belgium

    Laurence Geebelen, Brecht Devleesschauwer, Tinne Lernout, Katrien Tersago & Herman Van Oyen

  2. Institute of Health and Society (IRSS), Université Catholique de Louvain, Woluwe-Saint-Lambert, Belgium

    Laurence Geebelen & Niko Speybroeck

  3. Department of Translational Physiology, Infectiology and Public Health, Ghent University, Merelbeke, Belgium

    Brecht Devleesschauwer

  4. Flemish Agency for Care and Health, Brussels, Belgium

    Katrien Tersago

  5. Technical Cell (CT-TC), National Institute for Health and Disability Insurance (INAMI-RIZIV), Brussels, Belgium

    Yves Parmentier

  6. Department of Public Health and Primary Care, Ghent University, Ghent, Belgium

    Herman Van Oyen

  7. Centre for Health Economics Research & Modelling Infectious Diseases (CHERMID), Vaccine & Infectious Disease Institute, Faculty of Medicine & Health Sciences, University of Antwerp, Wilrijk, Belgium

    Philippe Beutels

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Contributions

LG, KT and TL designed the study together with NS, PB and HVO. KT and TL coordinated the execution of the project by LG. LG performed the data analysis with contributions from BDV, KT, NS and PB. YP provided the MCD-MFD data. LG drafted the manuscript which was further reviewed by all other authors. All authors read and approved the final version.

Corresponding author

Correspondence to Laurence Geebelen.

Ethics declarations

Ethics approval and consent to participate

The study was performed in accordance with the Declaration of Helsinki. For the prospective cohort study, informed consent was obtained from all study participants, ethical approval was obtained from the “Comité d’Ethique Hospitalo-Facultaire Saint-Luc UCL” (ref.: 2016/13AVR/166) which served as the principal ethical committee for the study and from the ethical committee of each participating hospital (UZ Leuven, Ziekenhuis Oost-Limburg, CHU UCL Namur—site Godinne, CHU de Liège, Clinique Saint-Pierre Ottignies, CHR Namur) and the study was approved by the Commission to Protect the Personal Privacy (Beraadslaging Nr. 16/038, reference: SCSZG/16/144). For the Minimal Clinical Data registry and the Minimal Financial Data registry, all data were linked and pseudonymised by the Technical Cel (NIHDI/Federal Public Service Health) established under articles 155 and 156 of the law of 29 April 1996 on social provisions [45].

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The authors declare that they have no competing interests in relation to this work.

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Supplementary Information

Additional file 1:

Unit prices ambulatory care (2019). Table S1. Consultations. Table S2. Laboratory tests ambulatory care. Table S3. Antibiotic therapy. Table S4. Other ambulatory costs.

Additional file 2:

Estimated median costs per patient. Table S5. Estimated median ambulatory cost per patient, expressed in 2019 euros, for the different manifestation groups of Lyme borreliosis in the prospective cohort study (HUMTICK), 2016─2020, Belgium. Mean and 95% uncertainty intervals of the bootstrap distribution of the median. Table S6. Estimated median costs per classical hospitalization and day hospitalization, 2016 euros converted to 2019 euros, Belgium. Mean and 95% uncertainty intervals of the bootstrap distribution of the median.

Additional file 3:

Incidence number of cases and total costs for LB in Belgium for the healthcare insurance system or patient. Table S7. Incidence number of cases and total costs for LB in Belgium for the healthcare insurance system or patient. Total costs and 95% uncertainty interval.

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Geebelen, L., Devleesschauwer, B., Lernout, T. et al. Lyme borreliosis in Belgium: a cost-of-illness analysis. BMC Public Health 22, 2194 (2022). https://doi.org/10.1186/s12889-022-14380-6

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