The Journey of Adult Patients with Lyme Disease in the United States: A Qualitative Interview Study and Patient-Reported, Health-Related Quality-of-Life Assessment

Abstract

Introduction

Lyme disease (LD) is the most common tick-borne illness in the USA, with an estimated 476,000 cases diagnosed and treated annually. Common signs, symptoms, and manifestations of LD are well described; however, there is limited qualitative understanding of the signs and symptoms patients experience during their illness and the associated impacts patients endure along the way. Thus, we aimed to explore the patient journey and experience with LD, including patient-reported signs and symptoms and impacts to health-related quality of life (HRQOL). No a priori hypotheses were evaluated.

Methods

In-depth, one-on-one, semi-structured interviews were conducted with US adults aged ≥ 18 years who had physician-diagnosed LD in 2023 to explore their experience with LD diagnosis, management, and treatment. The EQ-5D (a standardised HRQOL measure) was administered, and a patient journey map was developed. Interview transcripts were analysed via inductive and deductive coding, using an experiential, realist approach.

Results

Twenty-five participants with LD were interviewed (female, 13/25, 52%; male, 12/25, 48%), including those classified as having localised (10/25, 40%), disseminated (10/25, 40%), and indeterminate (5/25, 20%) LD. Participants reported various impacts at diagnosis, such as fear and anxiety, difficulty exercising, needing time off work, and spending increased time indoors. Most participants (19/25, 76%) stated that their symptoms resolved after antibiotic therapy; however, nearly a quarter (6/25, 24%) reported persistent symptoms. Most (15/25, 60%) reported continued emotional impacts after treatment, including fear of future LD infection, fear of the outdoors, and LD-related anxiety. As reported, all EQ-5D domains were worst at diagnosis, but most participants returned to their pre-LD score by the time of the interview.

Conclusion

The patient journey with LD is highly varied and individualised, and this study highlights the range of signs, symptoms, physical and emotional impacts that many individuals with LD experience throughout their journey.

Key Summary Points

Why carry out this study?

The patient journey with Lyme disease (LD) is highly varied and complex. There is limited qualitative understanding of the signs and symptoms of LD.

Using in-depth, qualitative interviews and a standardised, patient-reported, health-related quality of life measure (the EQ-5D), this study evaluated the journey of adult patients with LD in the USA.

What was learned from the study?

Participants in this study reported a range of signs, symptoms, and impacts; whilst most participants returned to pre-diagnosis health following LD treatment, participants reported notable impacts to their quality of life before, during, and after LD diagnosis.

Ultimately, understanding the significant and complex burden experienced by patients with LD provides necessary information to support enhanced awareness and prevention measures.

Introduction

Lyme disease (LD), caused by the bacterium Borrelia burgdorferi sensu stricto and transmitted through the bite of an infected black-legged tick (Ixodes scapularis or Ixodes pacificus) in the USA, is the most common tick-borne illness in the USA, with an estimated 476,000 persons diagnosed and treated each year [1, 2]. Most cases occur in the northeastern and midwestern regions of the USA; however, local transmission also occurs in parts of California, Oregon, and Washington [3].

For approximately 70–80% of persons, LD manifests as localised disease with erythema migrans (EM), considered an expanding red skin lesion (sometimes bullseye-like) that is ≥ 5 cm in size, that can be accompanied by non-specific symptoms [4, 5]. In persons who do not develop or identify EM or otherwise go untreated, infection can progress to disseminated disease, including early-stage (e.g. multiple EM, Lyme carditis, Lyme neuroborreliosis) or late-stage (e.g. Lyme arthritis) disseminated disease [4]. Symptoms usually resolve with appropriate antibiotic treatment [6]; however, around 5–10% of persons with LD experience persistent symptoms even after completing antibiotic treatment, including fatigue, body aches, and cognitive impairment [7, 8].

Common signs and symptoms of LD are well described in the literature; however, there is limited qualitative understanding of the signs and symptoms that patients undergo during their illness. Although research exists to describe the quality of life (QOL) impacts on patients with LD, these most often report on more severe LD manifestations involving the musculoskeletal and nervous systems and have been conducted in European countries such as Germany, Norway, and Ukraine [9–13]. In the USA specifically, much of the published research uses quantitative methods and pertains to the negative impact of persistent symptoms such as fatigue, joint pain, muscle aches, and brain fog on QOL [14, 15]. Although important, these studies have generally focused on populations in singular states or on patients with long-term persistent symptoms, and the results may not be generalisable to patients in other states or with acute LD.

To fill these gaps, the objective of this study was to explore the journey and experience of adults with LD in the USA through concept elicitation, including the signs and symptoms and impacts on health-related quality of life (HRQOL). No a priori hypotheses were evaluated.

Methods

Study Design

We conducted in-depth, one-on-one, semi-structured interviews in 2023 and early 2024 with persons who had been diagnosed within the year to explore their experience with LD diagnosis, management, and treatment and the impacts of LD on their life. Additionally, a standardised measure of HRQOL, the EQ-5D, was administered to participants [16], and a patient journey map was developed to summarise how patients transition from initial tick bite (where reported) through symptom onset, diagnosis, and treatment. The methods and results of this qualitative interview study followed US Food and Drug Administration (FDA) Patient-Focused Drug Development guidance [17, 18], the Standards for Reporting Qualitative Research (SRQR) [19], and Good Publication Practice guidelines [20].

Ethical Approval

All study materials received Institutional Review Board (IRB) approval from Western Copernicus Group, an independent review board (approval number 1360766, initial approval date 25 September 2023). Before the interview, participants signed an informed consent form indicating their agreement to participate and for study results to be published. An honorarium was provided after the interview to compensate participants for the time spent participating in the study. This study complied with relevant laws and institutional guidelines and was conducted in accordance with the Declaration of Helsinki. Participant’s privacy rights were observed.

Participants

In alignment with the study objective, participants were recruited across the USA via a specialist recruitment agency. Most patients were identified through clinician referral; other mechanisms included pre-existing research databases, patient advocacy groups, and website/social media advertisements.

Persons with clinical verification of their LD diagnosis that included antibiotic treatment on or after January 1, 2023, were eligible for inclusion. To ascertain an LD diagnosis, eligible individuals were asked to provide written confirmation of their clinical LD diagnosis and other clinical eligibility criteria, including the antibiotic treatment used for LD, through a clinician-completed case report form (CRF). The CRF could also provide details on laboratory testing done to confirm the LD diagnosis. If a CRF was not available, participants were required to provide other written confirmation of a clinically verified LD diagnosis and related antibiotic treatment (e.g. a screenshot or copy of medical record, letter from physician); these documents were required to clearly state that the participant had been given a diagnosis of LD by a physician and had received antibiotic treatment. Participants without a CRF also answered questions on a recruitment screener relating to their treatment history and comorbidities. Only participants with clearly indicated manifestations noted by the healthcare provider or site (clinician office) were considered established localized (i.e. EM) or disseminated (i.e. Lyme carditis, Lyme neuroborreliosis, Lyme arthritis) cases as documented. This study did not distinguish between participants with early- versus late-stage disseminated disease. If documentation was unclear, no assumptions were made, and cases were considered “indeterminate.” Additional study inclusion criteria were the following: at least 18 years of age, English speaking, living in the USA at time of recruitment, and willing and able to sign informed consent and participate in a 60-min telephone or virtual interview. Persons with a history of chronic fatigue syndrome, fibromyalgia, Parkinson’s disease, lupus, or multiple sclerosis were excluded from the study, as these diseases can have signs and symptoms that overlap with LD.

All participants completed a demographic form, including questions on race/ethnicity, sex, and residential geography that were used to inform soft quotas for race/ethnicity, sex, disease manifestation, and residential geography.

Discussion Guide and Interviews

A semi-structured interview guide was developed for the study, which included probes informed by a prior targeted literature review (TLR) to identify published literature on the patient journey of LD. Interviews were conducted virtually or by telephone. Participants were asked to describe the signs, symptoms, and impacts they experienced related to LD at each point in their patient journey (e.g. before diagnosis, at diagnosis, after treatment, at time of interview). Additionally, participants were asked to describe how their symptoms impacted aspects of daily life, including social, mental, and emotional well-being. The interview concluded with administration of the EQ-5D, a generic patient-reported outcome measure developed by the EuroQol Group that assesses health status across five dimensions: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression [16, 21]. Scores for the five dimensions of the EQ-5D were scaled from 0 to 1, where 0 is the value of a health state equivalent to dead and 1 is the value of full health. Scores for the EQ-5D VAS (Visual Analogue Scale) were scaled from 0 to 100, with 0 representing the worst and 100 the best imaginable health. During the interview, participants were asked to provide a score for each of the EQ-5D domains based on how they felt on the day of the interview, in line with the directions for digital interviewer administration of the EQ-5D provided by EuroQol. Scores were not captured longitudinally. After providing an answer based on how they currently felt, participants were asked if any of their answers to the domains would be different before contracting LD, or at the point of their LD diagnosis. As a result of the nature of qualitative research (e.g. time constraints in the interview), not all participants were asked every question in the interview.

Data Analysis

Analysis of de-identified interview transcripts followed a pre-specified qualitative analysis plan and was facilitated using Atlas.ti software (Version 9), an established tool that supported traditional qualitative analysis of transcripts and breakdown of data into subgroups [22]. Transcripts were analysed based on semantic, qualitative, directed content analysis techniques, using a combination of inductive and deductive coding. Inductive and deductive coding was used where open (patient journey) and direct (EQ-5D) questions were asked, respectively. The analyses used an experiential, realist approach, focusing on participants’ individual perspectives and experiences of their self-reported LD journey up to the point of interview [23]. Coding was developed by two qualified research analysts at Clarivate, where the project lead oversaw the complete process. First, overarching analytic insights were identified, and descriptive codes were assigned to quotes within the transcripts. The initial fit of the codes to the data was revisited throughout the coding process, and revisions were made (where applicable) to ensure coding was consistent across multiple coders. Codes were then organised to identify, define, and refine concepts and domains relevant to the research question and objectives. During code organisation, the domains and concept names within each code were reviewed to ensure they were an accurate reflection of the participant description of their experience and to ensure they were distinct experiences; codes were broken into domains (e.g. symptom or impact), and then symptom domains were further split into groups on the basis of bodily location (e.g. skin symptoms versus muscle or joint symptoms).

Concept saturation was assessed by sequentially reviewing sets of five interviews until all interviews were reviewed. If no new concepts arose in the fifth set, then this was considered conceptual saturation [24]. Descriptive statistics (e.g. mean and standard deviation, median and range, frequency, and percentage means) were used for demographics and to compare EQ-5D scores among participants, including by LD manifestation. Differences were not assessed statistically. Artificial intelligence was not used during the analysis process.

Patient Journey Map

A patient journey map was developed to illustrate the patient journey with LD. The map included concepts derived from the directed content analysis and prior TLR. Published literature specifically documenting the patient experience with LD, including signs, symptoms, or impacts, were identified from searches in Embase^®, Medline^®, and PsycINFO^® within Ovid^®. Hand-searching of FDA and European Medicines Agency (EMA) websites, conference proceedings, and the reference lists of studies identified from database searches were also reviewed for additional relevant literature. A total of 21 articles were selected for full data extraction (11 qualitative and 10 quantitative studies) and used to develop the patient journey map along with results from participant interviews.

Results

Participant Characteristics

The study included 25 persons with a diagnosis of LD in the year before the interview. Most participants (20/25, 80%) had a clinician-completed CRF as their proof of LD diagnosis. Sample demographics are included in Table 1. The average age of participants was 46.6 years old; about half were female (female, 13/25, 52%; male, 12/25, 48%). About half of participants reported their race as White, and nearly one-quarter identified as Hispanic or Latino. Participants came from eight states; about 44% were from California, followed by Florida, New Jersey, and New York. About half of the participants had a bachelor’s degree and one-third reported a household income of more than $175,000 per year.

Table 1.

Demographic characteristics of participants in Lyme disease patient journey qualitative interviews

Characteristic
Sex, n (%)
Female	13 (52%)
Male	12 (48%)
Age, years
Mean (SD)	46.6 (11.1)
Median (range)	48.0 (29.0–64.0)
Race, n (%)
White	13 (52%)
Black or African American	4 (16%)
Native Hawaiian or Other Pacific Islander	3 (12%)
Prefer not to say	5 (20%)
Ethnicity, n (%)
Not Hispanic or Latino	14 (56%)
Hispanic or Latino	6 (24%)
Prefer not to say	5 (20%)
Urbanicity of residence, n (%)
Large city	5 (20%)
Small city	6 (24%)
Suburb near a large city	6 (24%)
Town	3 (12%)
Rural area	5 (20%)
State of residence, n (%)
California	11 (44%)
Florida	4 (16%)
New Jersey	3 (12%)
New York	3 (12%)
Georgia	1 (4%)
Arizona	1 (4%)
Ohio	1 (4%)
Massachusetts	1 (4%)
Employment status, n (%)
Employed for wages or salary	10 (40%)
Self-employed	6 (24%)
Homemaker	4 (16%)
Retired	2 (8%)
Unemployed	2 (8%)
Unable to work	1 (4%)
Highest level of education, n (%)
High school diploma/GED equivalent	4 (16%)
Some college	7 (28%)
Bachelor’s degree	14 (56%)
Household income, n (%)
Less than $25,000	1 (4%)
$25,000 to $75,000	2 (8%)
$75,000 to $125,000	2 (8%)
$125,000 to $175,000	2 (8%)
More than $175,000	8 (32%)
Prefer not to say	10 (40%)

GED general educational development, SD standard deviation

The median time from LD diagnosis to interview was 126 days. Ten of the participants had disease classified as localised (40%), 10 as disseminated (40%), and the manifestation was indeterminate for the remaining 5 (20%) (Table 2). Most participants (20/25, 80%) documented having an LD enzyme-linked immunosorbent assay (ELISA) test, an assay that is part of the recommended two-tiered testing algorithm. Reported comorbidities included asthma, psoriasis, irritable bowel disease, and ulcerative colitis.

Table 2.

Clinical characteristics of 25 participants in Lyme disease patient journey qualitative interviews

Characteristic	N = 25
Days between LD diagnosis and interview, median (range)	126 (26–337)
LD manifestation, n (%)
Localised	10 (40%)
Disseminateda	10 (40%)
Carditis	6 (60%)
Neuroborreliosis	3 (30%)
Arthritis	1 (10%)
Indeterminate	5 (20%)
LD diagnostic test received, n (%)b
ELISA	20 (80%)
Western blot	6 (24%)
PCR	1 (4%)
Unknown	5 (20%)
Comorbidities reported, n (%)c
Asthma	1 (4%)
Psoriasis	1 (4%)
Irritable bowel syndrome	1 (4%)
Ulcerative colitis	1 (4%)

CRF case report form, ELISA enzyme-linked immunosorbent assay, LD Lyme disease, PCR polymerase chain reaction

^aDenominator for calculation of disseminated manifestations is total disseminated cases

^bNot mutually exclusive; 7/25 (28%) reported more than one diagnostic test. Clinical parameters were not collected or reported

^cFour participants (4/25, 16%) had comorbidities listed in their CRF, one of these participants (1/4, 25%) had 2 comorbidities listed (asthma and ulcerative colitis), whilst the other participants (3/4, 75%) had 1 comorbidity each

Pre-diagnosis Experience

Most participants (20/25, 80%) reported participating in an outdoor activity, including hiking, camping, visiting a lake, or visiting a park. For example, as one participant, a 46-year-old man with disseminated LD, reported,

“It began last summer…I’m not sure exactly when the tick got me, but I’m pretty sure it’s when we were up in the mountains and doing hiking and all that sort of thing.”

Of those that commented (24/25, 96%), most participants (18/24, 75%) reported that they did not know they had been bitten by a tick or did not see a tick, although one participant reported having had tick bites in the past. Three participants reported that their healthcare provider noticed their tick bite or rash and one that their partner noticed it. Of the participants who discussed awareness of LD, most (10/14, 71%) said they did not have prior knowledge of LD before they were diagnosed. Three of 14 participants (21%) said that their friends or family had suspected their symptoms could be LD and suggested that they see a healthcare provider. Eight of 25 participants (24%) described conducting their own research (e.g. online searches) into possible causes once they began experiencing symptoms. Most participants (11/14, 79%) did not suspect they had LD before seeing their healthcare provider. As one participant, a 50-year-old woman with LD with indeterminate manifestations, said,

“No, I absolutely didn’t think Lyme disease was even a possibility…it wasn’t something that was on my radar.”

Participants reported a variety of signs and symptoms that led them to seek a diagnosis for their illness (Table 3). Saturation of signs and symptoms was not achieved, as new concepts continued to arise by the 25th interview.

Table 3.

Signs and symptoms reported by 25 participants in Lyme disease qualitative interview study

Sign or symptom	Localised (n = 10)	Disseminated (n = 10)	Indeterminate (n = 5)	Total sample (N = 25)
General rash	9 (90%)	10 (100%)	3 (60%)	22 (88%)
Bullseye rash	8 (80%)	8 (80%)	1 (20%)	17 (68%)
Fatigue	4 (40%)	9 (90%)	5 (100%)	18 (72%)
Body aches	3 (30%)	5 (50%)	4 (80%)	12 (48%)
Headache	2 (20%)	5 (50%)	1 (20%)	8 (32%)
Flu-like symptoms (fever/chills)	1 (10%)	2 (20%)	2 (40%)	5 (20%)
Brain fog	1 (10%)	1 (10%)	3 (60%)	5 (20%)
Sensitivity to light/noise	1 (10%)	0 (0%)	1 (20%)	2 (8%)
Poor concentration	0 (0%)	4 (40%)	2 (40%)	6 (24%)
Heart racing	0 (0%)	3 (30%)	0 (0%)	3 (12%)
Joint stiffness/tightness	0 (0%)	2 (20%)	3 (60%)	5 (20%)
Shortness of breath	0 (0%)	2 (20%)	1 (20%)	3 (12%)
Chest pressure	0 (0%)	2 (20%)	0 (0%)	2 (8%)
Poor memory	0 (0%)	1 (10%)	2 (40%)	3 (12%)
Weakness	0 (0%)	1 (10%)	2 (40%)	3 (12%)
Back pain	0 (0%)	1 (10%)	0 (0%)	1 (4%)
Skin tightness	0 (0%)	0 (0%)	2 (40%)	2 (8%)
Nausea	0 (0%)	0 (0%)	2 (40%)	2 (8%)
Decreased appetite	0 (0%)	0 (0%)	2 (40%)	2 (8%)
Vision issues	0 (0%)	0 (0%)	2 (40%)	2 (8%)
Stomach issues	0 (0%)	0 (0%)	1 (20%)	1 (4%)
Runny nose	0 (0%)	0 (0%)	1 (20%)	1 (4%)
Erectile dysfunction	0 (0%)	0 (0%)	1 (20%)	1 (4%)

Participants reported a range of impacts across multiple domains before their LD diagnosis (Table 4), most commonly anxiety, fear, poor sleep quality, and difficulty exercising. As one participant, a 42-year-old woman with localised disease, reported,

“…when the rash was observed, and then, once that was detected, I, err, suffered with some—a lot of anxiety and I wasn’t sleeping and I was really, err, traumatised, to be honest with you.”

Table 4.

Impacts of Lyme disease reported by 25 participants in qualitative interview study

Impact	Before diagnosis	At diagnosis	During treatment	After treatment/time of interview
Emotional	21 (84%)	20 (80%)	8 (32%)	15 (60%)
Anxiety	15 (60%)	11 (44%)	4 (16%)	6 (24%)
Fear	12 (48%)	13 (52%)	5 (20%)	7 (28%)
Fear of future Lyme disease	–	–	–	9 (36%)
Fear of outdoor risk	–	–	–	6 (24%)
Fear of treatment not working	–	–	2 (8%)	–
Worry	4 (16%)	2 (8%)	0 (0%)	0 (0%)
Depression	3 (12%)	0 (0%)	0 (0%)	2 (8%)
Confusion	3 (12%)	1 (4%)	0 (0%)	0 (0%)
Annoyance	2 (8%)	1 (4%)	0 (0%)	0 (0%)
Relief	0 (0%)	4 (16%)	0 (0%)	0 (0%)
Upset	0 (0%)	2 (8%)	1 (4%)	2 (8%)
Stress	0 (0%)	3 (12%)	0 (0%)	0 (0%)
Sleep	9 (36%)	1 (4%)	2 (8%)	6 (24%)
Poor sleep quality	6 (24%)	0 (0%)	1 (4%)	6 (24%)
Increased sleep	5 (20%)	1 (4%)	1 (4%)	0 (0%)
Activities of daily living	7 (28%)	7 (28%)	2 (8%)	4 (16%)
Difficulties doing errands or chores	4 (16%)	0 (0%)	0 (0%)	1 (4%)
Increased time indoors	3 (12%)	7 (28%)	2 (8%)	4 (16%)
Difficulty with physical labour	2 (8%)	1 (4%)	0 (0%)	0 (0%)
Work	7 (28%)	9 (36%)	0 (0%)	0 (0%)
Time off	3 (12%)	7 (28%)	2 (8%)	0 (0%)
Reduced productivity	0 (0%)	3 (12%)	1 (4%)	0 (0%)
Physical	7 (28%)	9 (36%)	3 (12%)	4 (16%)
Difficulty exercising	5 (20%)	8 (32%)	2 (8%)	4 (16%)
Resting more	4 (16%)	0 (0%)	2 (8%)	0 (0%)
Social	4 (16%)	8 (32%)	3 (12%)	8 (32%)
Reduced social activity	3 (12%)	5 (20%)	2 (8%)	3 (12%)
Changes in hobbies	0 (0%)	5 (20%)	1 (4%)	0 (0%)
Reduced outdoor activities	0 (0%)	5 (20%)	0 (0%)	6 (24%)
Behavioural
Motivated to contact healthcare provider quickly in future	–	–	–	12 (48%)
Extra precautions to avoid tick bites	–	–	–	6 (24%)

Diagnosis and Treatment Experience

Fifteen of 25 participants (60%) saw more than one type of provider during their LD diagnosis and treatment experience; participants frequently reported being referred to an infectious disease doctor after their initial healthcare provider visit. Most participants (16/25, 64%) reported seeing a primary care or general practitioner, followed by seeing an infectious disease doctor (15/25, 60%) and going to an emergency room (ER) or urgent care (12/25, 48%). Visiting an ER or urgent care was most common among participants with disseminated disease (8/10, 80%) than with localised (3/10, 30%) and indeterminate (1/5, 20%) disease.

Participants generally described their experience obtaining a healthcare provider appointment to be straightforward with nearly half (11/25, 44%) reporting a positive experience with the healthcare provider who diagnosed them. Over half of the participants (13/25, 52%) noted that their LD diagnosis was made within 2 weeks of their initial provider visits. Five of 25 participants (20%) reported negative experiences with their healthcare provider, including 3 of 5 (60%) who noted that their healthcare provider did not understand their symptom presentation very well. One 48-year-old woman with disseminated LD said,

“I honestly, um, think maybe they thought…I was overreacting or that I was just sick, normally sick…but I guess that’s not the case. I don’t even really know if they thought it was anything beforehand other than just possibly having a really bad flu.”

All participants took antibiotics, an inclusion criterion for the study. The most frequently reported antibiotics prescribed for LD were amoxicillin (11/25, 44%), doxycycline (7/25, 36%), and cefuroxime (5/25, 20%). Six of 24 participants (24%) reported taking two antibiotics, either concurrently or sequentially. Eight of 24 participants (32%) reported management of their symptoms through other means (e.g. diet, stretching, increasing water intake), and 3 of 24 (12%) reported that they used alternative medicine or therapy (e.g. acupuncture) to treat their LD symptoms. In general, participants felt the treatment would cure LD and were optimistic about their treatment. As a 35-year-old man with localised disease said,

“As soon as I knew that it was an antibiotic…I knew I was positive and up for it. Usually, anti-antibiotics, they’re pretty effective…they go to work really—fairly quickly.”

Participants reported a range of impacts at the time of their LD diagnosis, including fear, anxiety, difficulty exercising, needing time off work, and spending increased time indoors (Table 4). Participant quotes illustrate the range of impacts. For example, one 57-year-old man with disseminated disease described his fear,

“Yeah, once I got diagnosed, I was fatigued…just, a lack of energy…it scared me, you know.”

Participants also noted impacts on their social lives. For example, a 35-year-old man with localised disease described his experience,

“…as soon as my circle of friends heard of the phrase ‘disease’ they just said…‘Stay home.’ They think that, that it was, err, something that…they can contract or something.”

Several participants described a feeling of relief associated with their LD diagnosis. For example, as one 45-year-old man with disseminated LD disease said,

“…this might sound strange, but I was, kind of, happy and relieved…I knew it was something that I could, err, take care of, It wasn’t, err, too late, something that I could…have some, kind of, control over it and maybe, err, get rid of. So, if anything, I probably was more grateful, happy, kind of, feeling than anything. I mean, it actually was a bit—it was relieving when we discovered this in that short relative time.”

Post-diagnosis to Current Experience

Most participants (19/25, 76%) stated that their LD-related symptoms resolved after taking antibiotics. Six of 25 participants (24%; 2 with localised disease, 1 with disseminated disease, 3 with indeterminate manifestations) reported at least one unresolved symptom following treatment, including fatigue, brain fog, flu-like symptoms, skin tightness, body aches, joint stiffness or tightness, and weakness. As described by one of the participants who reported ongoing symptoms, a 48-year-old woman with disseminated LD,

“On a regular day, I feel like I am still, um, a bit fatigued and I do experience the brain fog and those are my main two things right now. Um, yeah, mainly the fatigue and brain fog.”

Some participants reported continued emotional impacts, including fear of future LD infection, fear of the outdoors, and anxiety (Table 4). As one 63-year-old woman with localised disease said,

“I do worry about the possibility of it happening again, I love to be outside…I’m not the only one that’s gone through this…There’s an awful lot of ticks out there, but I’m not going to let paranoia set in.”

Some participants also reported spending more time indoors or participating in fewer outdoor activities for fear of getting LD again. Nearly half of participants (12/25, 48%) reported that they would be motivated to contact a healthcare provider quickly if they suspected an LD infection in the future, and several (6/25, 24%) reported taking extra precautions to avoid potential tick bites/tick exposure. For example, a 29-year-old man who had localised LD described his heightened vigilance,

“I mean, I love outdoors, err, but I have to be very careful. You know, it’s, like, I’ll never wear shorts ever again…make sure that I’m protected…to look at my body after, you know, I take my clothes off to see if there’s anything, you know, just take extra precautions. I mean, I tell everyone, I say, ‘Listen, you know, you’ve got to give up the outdoors.’”

A 61-year-old woman who had disseminated LD described her aversion to spending time outdoors,

“…when I go out, for example, and my, err, family tells me, ‘Let’s go to the park,’ err, but there are some nice parks around our home, and they’re green…I said, ‘No, no, I’m more comfortable at my home,’ because I’m afraid in the green area or the grass, or something, there are some mosquitoes or some-something like that, and then, um, err, something happens for me…So, I get nervous, unfortunately…I think it’s better not to go to the—a green area, hmmm, even it’s close to my home…I used to go, but, um, not anymore at this time…I’d rather be at home and…you know, I feel more safe.”

EQ-5D

The average index score for respondents recalling before LD diagnosis was 0.93 (range 0.56–1). This decreased to 0.51 (range − 0.31 to 0.94) recalling at the time of diagnosis and increased to 0.88 (range 0.58–1) at the time of the interview. All domains of the EQ-5D (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) were reported to be worse at diagnosis compared with at the time of interview and before LD diagnosis (Table 5). Scores related to the domains of anxiety/depression, pain/discomfort, and usual activities were reported to be most impacted by LD. Participants with disseminated LD and LD with an indeterminate manifestation reported the largest decrease in scores from pre-LD diagnosis to at the time of diagnosis. Similarly, EQ-5D VAS scores showed that participants with disseminated and indeterminate manifestations had the largest change in score between pre-LD and at diagnosis. Most participants reported that they had returned to their pre-LD score by the time of the interview.

Table 5.

Mean EQ-5D-5L domain scores and visual analogue scale responses as reported at time of interview for each of 3 time periods

Domain and disease manifestation	Pre-diagnosis	At diagnosis	At interview
Mobility
Localised	1	1.2	1.1
Disseminated	1	2.2	1
Indeterminate	1.2	2.6	1.4
All	1.04	1.88	1.12
Self-care
Localised	1	1.3	1
Disseminated	1	1.6	1
Indeterminate	1.2	2.6	1
All	1.04	1.68	1
Usual activities
Localised	1	1.6	1
Disseminated	1.1	2.4	1.2
Indeterminate	1.2	3.6	2
All	1.08	2.32	1.28
Pain/discomfort
Localised	1.2	1.9	1.3
Disseminated	1.2	2.9	1.4
Indeterminate	1.8	3.4	2.6
All	1.32	2.6	1.6
Anxiety/depression
Localised	1.5	3	1.5
Disseminated	1.3	2.6	1.7
Indeterminate	2.6	4.2	3.4
All	1.64	3.08	1.96
Visual Analogue Scale
Localised	88.1	66.5	87.7
Disseminated	89.7	52.9	84.4
Indeterminate	86.0	41.8	73.8
All	88.3	56.1	83.6

Domain response options: Mobility: (1) I have no problems walking, (2) I have slight problems walking, (3) I have moderate problems walking, (4) I have severe problems walking, (5) I am unable to walk; Self-care: (1) I have no problems washing or dressing myself, (2) I have slight problems washing or dressing myself, (3) I have moderate problems washing or dressing myself, (4) I have severe problems washing or dressing myself, (5) I am unable to wash or dress myself; Usual activities: (1) I have no problems doing my usual activities, (2) I have slight problems doing my usual activities, (3) I have moderate problems doing my usual activities, (4) I have severe problems doing my usual activities, (5) I am unable to do my usual activities; Pain or discomfort: (1) I have no pain or discomfort, (2) I have slight pain or discomfort, (3) I have moderate pain or discomfort, (4) I have severe pain or discomfort, (5) I have extreme pain or discomfort; Anxiety/depression: (1) I am not anxious or depressed, (2) I am slightly anxious or depressed, (3) I am moderately anxious or depressed, (4) I am severely anxious or depressed, (5) I am extremely anxious or depressed. Scores on the visual analogue scale ranged from 0 to 100

Patient Journey Map

The patient journey map is shown in Fig. 1 and highlights multiple junctures that were important to achieve diagnosis and treatment, including the recognition of a tick bite and decision to seek medical care as well as obtain an accurate diagnosis.

Fig. 1.

Lyme disease patient journey map derived from literature and interviews. HCP healthcare provider, LD Lyme disease. The map displays the LD journey from pre-diagnosis through symptom onset, initial healthcare visit, diagnosis and treatment, and subsequent impacts. The arrows signify the paths that patients can take during their LD journey

Discussion

The patient journey with LD is highly varied and individualised, with a range of signs, symptoms, and impacts. Although most participants in this study reported a return to their pre-LD health after treatment, participants reported notable impacts to their QOL before, during, and after their LD diagnosis. By describing experiences across the journey, this study provides an important picture of the substantial and complex burden that many individuals with LD experience.

Patient journey maps are useful tools to help understand how patients experience a disease and interact with the healthcare system [25]. The patient journey map for LD developed from this study highlights multiple junctures that were especially important to achieve diagnosis and treatment. First was the recognition of a tick bite or the decision to seek medical care. Most participants never found an attached tick and did not know that they had been bitten by one. In studies of confirmed LD cases, just over half reported recalling a tick bite [26, 27]. Additionally, most participants in this study did not initially consider LD when they experienced early signs and symptoms of disease, and just under half reported that they had no prior knowledge of LD, findings that are in line with prior research. For example, in a survey of adults in states with a high incidence of LD, only 44% knew some or a lot about LD and 31% believed LD to be common or very common in their community [28]. Lack of recognition of tick bites decreases the likelihood of using post-exposure interventions, as antibiotic prophylaxis must occur within 72 h of a bite, or can potentially delay diagnosis of LD cases when non-specific symptoms arise [6]. Thus, further education may be needed to enhance public awareness of LD, including prevention efforts, and ensure patients are seeking medical attention when needed.

Another important juncture was obtaining an accurate diagnosis, which is dependent on physician knowledge about LD to avoid further delays. More than half of the participants in this study reported seeing more than one type of provider to obtain an LD diagnosis and treatment. A study of physicians in California, where many of the participants in this study resided, found that most physicians had a general awareness about LD but only about half correctly answered questions about disease testing protocols [29]. Although diagnosis based on compatible clinical signs and symptoms accompanied by exposure in a high-incidence area is relatively straightforward, the predictive value positivity of laboratory testing decreases for patients in low-incidence areas [30]. Thus, the experiences of patients diagnosed in high-incidence states may differ from those diagnosed in low-incidence states. While most participants in this study were from low-incidence states (18/25, 72%), only two participants in this study reported initial misdiagnosis by healthcare providers, suggesting that inexperience with LD was not a common issue that would have resulted in a prolonged patient journey. Still, further education to improve knowledge about LD is needed for physicians, particularly in areas with low LD incidence [30–32].

Participants reported both emotional and physical impacts of LD. Emotional impacts, particularly anxiety, were reported by most participants throughout the LD journey. Anxiety has been previously documented as associated with LD [15, 33]; however, this study is unique in describing the sources of emotional impacts and anxiety across the patient journey, and in patients with both localised and disseminated LD. This began with uncertainty in the early stages of disease and, even once diagnosis was achieved, participants feared symptom worsening and worried about their treatment not working. Participants also spoke about lingering emotional impacts even after symptoms had resolved, mostly in relation to fear of the future and re-infection, particularly avoidance of outdoor activities. Other notable impacts were physical, including difficulty exercising and low energy levels. For some, this resulted in time off work or being less productive while at work. Participants also avoided unnecessary social interactions and events, either to rest following poor sleep or due to fear of stigma. Although LD is not transmitted from person to person, some participants feared that their friends and colleagues would assume the symptoms were contagious. Understanding both the emotional and physical impacts of LD may improve patient-centred prevention efforts, care, and outcomes.

The results of the EQ-5D complement the qualitative findings by providing an additional quantitative measure of the impacts of LD. Notably, the findings from the EQ-5D illustrate that LD impacted nearly all participants in some way, regardless of disease manifestation; only two participants felt that there was no difference in their general health between their pre-LD health and their health at the time of diagnosis. Based on respondent recall, the average EQ-5D index score before LD diagnosis (0.93) was higher than the US population norm (0.85) [34], suggesting that, overall, this group of patients was healthier than the US average. Although the average index score recalled for the time of LD diagnosis (0.51) decreased considerably, the score at the time of interview (0.88) had returned to nearly pre-diagnosis levels, suggesting treatment was largely effective in resolving participants’ symptoms and impacts of LD. Another study similarly found that even in patients with severe manifestations, most reported a return to physical and mental health scores at or above the national average after treatment [35]. Notably, the EQ-5D has not often been used in LD research. Our results indicate that it can sensitively detect changes in health status from pre-diagnosis, at diagnosis, to post-treatment, as participants were able to delineate in the interview by recalling these three time periods.

Strengths of this study included the use of a case definition that required proof of clinical diagnosis and antibiotic treatment for LD. By enrolling patients within a year of their diagnosis, we attempted to minimise recall bias. Additionally, the use of qualitative methods allowed for robust elicitation of the patient experience and to capture nuances of signs/symptoms and impacts that cannot be adequately elucidated by quantitative studies.

There were some limitations. Our sample size (N = 25) was limited, despite being in line with other qualitative studies on LD [32, 36] and recommendations for qualitative research [37, 38]. We did not limit enrolment to persons from states with a high incidence of LD and did not attempt to determine where a participant’s exposure occurred. Also, although we had similar proportions of female (n = 13) and male (n = 12) participants, data were not disaggregated by sex. Although we attempted to enrol individuals with a range of clinical manifestations, persons with a diagnosis of Lyme carditis were overenrolled compared with the prevalence of this manifestation among LD cases overall [39]. Thus, it remains possible that the results of this study are not generalisable to all persons with LD, including those in other regions or countries. An additional limitation was that data saturation related to signs and symptoms was not reached during the first 25 interviews. This could be because of the broad approach to elicitation as well as the wide range of signs/symptoms LD can manifest given its multisystem impacts. Thus, future studies would benefit from larger sample sizes. Despite inclusion criteria requiring a written confirmation of diagnosis of LD, results of LD diagnostic testing were not collected and should not be implied, as this level of clinical information was outside the scope of this study. Similarly, we did not validate diagnoses or manifestations with chart review or require laboratory testing, and it remains possible that some cases were misclassified. Finally, because all participants were interviewed within a year of their diagnosis, we were unable to assess the longer-term impacts that some individuals might have experienced.

Conclusion

LD is a major public health challenge in much of the USA, and the geographic distribution and incidence of LD has expanded markedly over the past 2 decades. Through in-depth qualitative interviews and patient-reported HRQOL data, we highlight the complex nature of LD, including the various signs, symptoms, and physical and emotional impacts that patients experience. Enhanced understanding of the patient journey with LD provides necessary information to support enhanced awareness and prevention measures for all persons at risk.

Author Contributions

Conceptualization: L. Hannah Gould, Amanda R. Mercadante, Chris Marshall, Stephanie Fairhurst, Greg Davis, Danielle Burns, Alexander Davidson, Stephanie A. Duench, Holly Yu. Methodology: L. Hannah Gould, Amanda R. Mercadante, Chris Marshall, Stephanie Fairhurst, Greg Davis, Danielle Burns, Alexander Davidson, Stephanie A. Duench, Holly Yu. Software: Chris Marshall, Stephanie Fairhurst, Greg Davis, and Danielle Burns. Validation: Amanda R. Mercadante, Chris Marshall, Stephanie Fairhurst, Greg Davis, and Danielle Burns. Formal analysis: Amanda R. Mercadante, Chris Marshall, Stephanie Fairhurst, Greg Davis, and Danielle Burns. Investigation: Chris Marshall, Stephanie Fairhurst, Greg Davis, and Danielle Burns. Resources: L. Hannah Gould, Amanda R. Mercadante, Chris Marshall, Stephanie Fairhurst, Greg Davis, Danielle Burns, Alexander Davidson, Stephanie A. Duench, and Holly Yu. Data curation: Chris Marshall, Stephanie Fairhurst, Greg Davis, and Danielle Burns. Writing – original draft: L. Hannah Gould and Amanda R. Mercadante. Writing – review and editing: L. Hannah Gould, Amanda R. Mercadante, Chris Marshall, Stephanie Fairhurst, Greg Davis, Danielle Burns, Alexander Davidson, Stephanie A. Duench, and Holly Yu. Visualization: L. Hannah Gould, Amanda R. Mercadante, Chris Marshall, Stephanie Fairhurst, Greg Davis, Danielle Burns, Alexander Davidson, Stephanie A. Duench, and Holly Yu. Supervision: Amanda R. Mercadante, Chris Marshall, and Holly Yu. Project administration: Amanda R. Mercadante, Chris Marshall, Stephanie Fairhurst, and Holly Yu. Funding acquisition: Holly Yu.

Funding

This analysis was supported and jointly funded by Valneva (Saint-Herblain, France) and Pfizer Inc. (New York City, New York, United States) as part of their co-development of an LD vaccine. Valneva and Pfizer Inc. provided funding for publication support and the journal’s rapid service and open access fees.

Data Availability

The datasets generated during and/or analysed during the current study are not publicly available, as study data are primarily in the form of transcripts and cannot be made available to protect participant privacy in accordance with the principles of the Belmont Report.

Declarations

Conflict of Interest

L. Hannah Gould, Alexander Davidson, Stephanie A. Duench, and Holly Yu are employees of Pfizer Inc. and may hold stock or stock options. Amanda R. Mercadante was a Pfizer employee at the time of this study and is now unaffiliated. Chris Marshall, Stephanie Fairhurst, Greg Davis, and Danielle Burns are employees and stockholders of Clarivate Analytics. Clarivate Analytics provides consultancy to various pharmaceutical and biotechnology companies, including Pfizer who was the sponsor of this research.

Ethical Approval

All study materials received IRB approval from Western Copernicus Group, an independent review board (approval number 1360766, initial approval date 25 September 2023). Before the interview, participants signed an informed consent form indicating their agreement to participate and for study results to be published. An honorarium was provided after the interview to compensate participants for the time spent participating in the study. This study complied with relevant laws and institutional guidelines and was conducted in accordance with the Declaration of Helsinki. Participant’s privacy rights were observed.