Lyme disease

Summary

Lyme disease (MONDO:0019632) is a disease with 3 GWAS associations across 3 studies and 69 clinical trials. Top therapeutic interventions include doxycycline anhydrous, ceftriaxone, and amoxicillin. A subtype of primary bacterial infectious disease — broader associated-gene and molecular evidence is on the parent page (see Disease family below).

At a glance

• Prevalence: >1 / 1000 (Europe) [Orphanet-validated]
• GWAS associations: 3
• Phenotypes (HPO): 24
• Clinical trials: 69

Clinical features

Epidemiology

Prevalence records

6 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Annual incidence	>1 / 1000	177.5	Europe	Validated
Annual incidence	1-5 / 10 000	16.6	France	Validated
Annual incidence	1-5 / 10 000	12.37	Hungary	Validated
Annual incidence	>1 / 1000	100	United States	Validated
Annual incidence	1-5 / 10 000	21.9	Worldwide	Not yet validated
Annual incidence	1-5 / 10 000	36	Sweden	Not yet validated

Signs & symptoms

Clinical features (HPO)

24 HPO clinical features (Orphanet curated; top 24 by frequency):

HPO ID	Term	Frequency
HP:0001287	Meningitis	Frequent (30-79%)
HP:0001369	Arthritis	Frequent (30-79%)
HP:0001386	Joint swelling	Frequent (30-79%)
HP:0006824	Cranial nerve paralysis	Frequent (30-79%)
HP:0000554	Uveitis	Occasional (5-29%)
HP:0000613	Photophobia	Occasional (5-29%)
HP:0000708	Atypical behavior	Occasional (5-29%)
HP:0001324	Muscle weakness	Occasional (5-29%)
HP:0001678	Atrioventricular block	Occasional (5-29%)
HP:0001945	Fever	Occasional (5-29%)
HP:0002017	Nausea and vomiting	Occasional (5-29%)
HP:0002315	Headache	Occasional (5-29%)
HP:0002354	Memory impairment	Occasional (5-29%)
HP:0002383	Infectious encephalitis	Occasional (5-29%)
HP:0002829	Arthralgia	Occasional (5-29%)
HP:0003326	Myalgia	Occasional (5-29%)
HP:0003401	Paresthesia	Occasional (5-29%)
HP:0004334	Dermal atrophy	Occasional (5-29%)
HP:0009830	Peripheral neuropathy	Occasional (5-29%)
HP:0011675	Arrhythmia	Occasional (5-29%)
HP:0012378	Fatigue	Occasional (5-29%)
HP:0100576	Amaurosis fugax	Occasional (5-29%)
HP:0100785	Insomnia	Occasional (5-29%)
HP:0200036	Skin nodule	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Lyme disease
Mondo ID	MONDO:0019632
EFO	EFO:0008510
MeSH	D008193
Orphanet	91546
DOID	DOID:11729
ICD-10-CM	A69.2
ICD-11	1600014919
NCIT	C45161
SNOMED CT	48982009
UMLS	C0024198
MedGen	44213
GARD	0027870
MedDRA	10025169
Is cancer (heuristic)	no

Also known as: Borrelia · Borrelia burgdorferi infection · Borreliella burgdorferi caused disease or disorder · Borreliella burgdorferi disease or disorder · Borreliella burgdorferi infectious disease · Lyme borreliosis · Lyme disease

Data availability: 3 GWAS associations (3 studies).

Disease family

This is a subtype of primary bacterial infectious disease. Genetic, therapeutic, and trial evidence is largely curated at the broader-term level — see the parent page for the associated-gene cohort and molecular evidence.

Classification path: disease › human disease › disease by etiologic mechanism › disease of primarily extrinsic mechanism › infectious disease › bacterial infectious disease › primary bacterial infectious disease › Lyme disease

Related subtypes (36): Buruli ulcer disease, sennetsu fever, salmonellosis, pinta disease, chancroid, gonorrhea, anthrax infection, leprosy, botulism, diphtheria, tetanus, bartonellosis, brucellosis, campylobacteriosis, glanders, granuloma inguinale, legionellosis, leptospirosis, listeriosis, Mycobacterium avium complex disease, ornithosis, rhinoscleroma, staphyloenterotoxemia, syphilis, cholera, ehrlichiosis, melioidosis, tuberculosis, tularemia, plague, Q fever, shigellosis, relapsing fever, spirillary rat-bite fever, streptobacillary rat-bite fever, Borrelia miyamotoi disease

Genetics & variants

GWAS landscape

3 GWAS associations across 3 studies. Top hits map to 2 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs2232950	8e-86	SCGB1D2	T	1.21
rs17616434	6e-11	TLR1	T	0.92
rs9276610	7e-10	HLA-DQB2 - HLA-DOB	C	0.92

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90296666	Strausz S	2024	25,355	592,376	SCGB1D2 inhibits growth of Borrelia burgdorferi and affects susceptibility to Lyme disease.
GCST90481467	Verma A	2024	1,148	448,302	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90624363	Vrijmoeth HD	2024	506	0	Genome-wide analyses in Lyme borreliosis: identification of a genetic variant associated with disease susceptibility and its immunological implications.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	1
Tier 2: splice/UTR	0
Tier 3: regulatory	0
Tier 4: intronic/intergenic	2

MAF distribution

Bucket	Variants
common (>=0.05)	3
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	0

Functional consequences

Consequence	Count
intergenic_variant	2
missense_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs2232950	11	62243391	C>A,T	0.05	missense_variant	SCGB1D2	8e-86	Tier 1: coding
rs17616434	4	38811255	T>C	0.05	intergenic_variant	TLR1	6e-11	Tier 4: intronic/intergenic
rs9276610	6	32774318	A>C,G,T	0.05	intergenic_variant	HLA-DQB2 - HLA-DOB	7e-10	Tier 4: intronic/intergenic

Genes & proteins

No associated-gene cohort resolved for this disease. Atlas builds the molecular and therapeutic sections — associated genes, protein families, druggability, pathways, interactions, and drug associations — by aggregating over a disease’s associated genes (resolved via GWAS / GenCC / ClinVar / CIViC), and none resolved here. This is expected for antibody-mediated, autoimmune, or otherwise non-gene-defined conditions; the curated evidence for this disease is its clinical features, GWAS susceptibility, and clinical trials (above).

Function

No pathway enrichment — requires an associated-gene cohort.

Therapeutics

Drugs indicated for this disease

0 approved, 3 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Ceftriaxone	Phase 3 (in late-stage trials)
Permethrin	Phase 3 (in late-stage trials)
Sodium Chloride	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Tetracycline.

Clinical trials & evidence

Clinical trials

Clinical trials: 69.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	45
PHASE3	10
PHASE2	6
PHASE1/PHASE2	3
PHASE4	2
PHASE1	2
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01207739	PHASE4	COMPLETED	Persistent Lyme Empiric Antibiotic Study Europe
NCT01368341	PHASE4	COMPLETED	Comparing 3 Antibiotic Regimes for Erythema Migrans in General Practice
NCT07226882	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Learn About Different Dosing Schedules of a Lyme Disease Vaccine in Healthy Adults
NCT07500506	PHASE3	RECRUITING	A Study to Learn About the Safety, Tolerability, and Immunogenicity of a Fifth Dose of 6-Valent OspA-Based Lyme Disease Vaccine
NCT00000432	PHASE3	COMPLETED	Lyme Disease Prevention Program
NCT00000937	PHASE3	COMPLETED	Study and Treatment of Post Lyme Disease (STOP-LD)
NCT00000938	PHASE3	COMPLETED	A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial of the Safety and Efficacy of Ceftriaxone and Doxycycline in the Treatment of Patients With Seronegative Chronic Lyme Disease
NCT00001101	PHASE3	COMPLETED	A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial of the Safety and Efficacy of Ceftriaxone and Doxycycline in the Treatment of Patients With Seropositive Chronic Lyme Disease
NCT00958139	PHASE3	TERMINATED	Passive Prophylaxis of Lyme Disease Using Permethrin Treated Clothes
NCT04038346	PHASE3	TERMINATED	Symptomatic Management of Lyme Arthritis
NCT05477524	PHASE3	COMPLETED	An Efficacy, Safety, Tolerability, Immunogenicity, and Lot-Consistency Clinical Trial of a 6-Valent OspA-Based Lyme Disease Vaccine (VLA15)
NCT05634811	PHASE3	COMPLETED	Safety Study of a Vaccine to Help Protect Against Lyme Disease in Healthy Children
NCT05036707	PHASE1/PHASE2	RECRUITING	Human Immune Response to Ixodes Scapularis Tick Bites
NCT07561294	PHASE2	RECRUITING	A Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of mRNA-1982 to Prevent Lyme Disease in Healthy Participants (18 to 70 Years of Age)
NCT07562087	PHASE2	RECRUITING	A Study to Evaluate Safety and Efficacy of TP-05 in Healthy Participants With Tick Exposure
NCT00037479	PHASE2	COMPLETED	Brain Imaging and Retreatment Study of Persistent Lyme Disease
NCT01243008	PHASE1/PHASE2	COMPLETED	Safety, Skin and Plasma Concentration of Azithromycin Dermal Formulation
NCT03769194	PHASE2	COMPLETED	Immunogenicity and Safety Study of a Vaccine Against Lyme Borreliosis, in Healthy Adults Aged 18 to 65 Years. Randomized, Controlled, Observer-blind Phase 2 Study.
NCT03970733	PHASE2	COMPLETED	Alternative Schedule Study For VLA15, a Vaccine Candidate Against Lyme Borreliosis
NCT04801420	PHASE2	COMPLETED	Phase 2 Study Of VLA15, A Vaccine Candidate Against Lyme Borreliosis, In A Healthy Pediatric And Adult Study Population
NCT05975099	PHASE1/PHASE2	COMPLETED	A Study to Evaluate the Safety and Immunogenicity of mRNA-1975 and mRNA-1982 Against Lyme Disease in Participants 18 Through 70 Years of Age
NCT04863287	PHASE1	COMPLETED	First Clinical Study of the Safety and Blood Levels of a Human Monoclonal Antibody (2217LS) Against Lyme Disease Bacteria in Healthy People
NCT05305105	PHASE1	COMPLETED	Effects of Psilocybin in Post-Treatment Lyme Disease
NCT01143558	EARLY_PHASE1	COMPLETED	Searching for Persistence of Infection in Lyme Disease
NCT00001539	Not specified	RECRUITING	A Comprehensive Clinical, Microbiological and Immunological Assessment of Patients With Suspected Post Treatment Lyme Disease Syndrome and Selected Control Populations
NCT00028080	Not specified	RECRUITING	Evaluation, Treatment, and Follow-up of Patients With Lyme Disease
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT03418441	Not specified	RECRUITING	Central Nervous System Infections in Denmark
NCT04402086	Not specified	RECRUITING	Rheumatology Patient Registry and Biorepository
NCT04806620	Not specified	RECRUITING	Unhide® Project: A Digital Health Platform to Collect Lifestyle Data for Brain Inflammation Research
NCT05641116	Not specified	RECRUITING	Effectiveness of an Intervention Combining Adapted Physical Activity and Therapeutic Education in Patients With Chronic Symptoms Attributed to Lyme Borreliosis.
NCT06026969	Not specified	RECRUITING	Pregnancy and Early Neurodevelopmental Outcomes Following In Utero Lyme Disease Exposure
NCT06045416	Not specified	RECRUITING	Borrelia B-cell Diagnostics
NCT06397794	Not specified	RECRUITING	Navigating Pregnancy and Parenthood With Lyme Disease
NCT06492668	Not specified	RECRUITING	Risk of Exposure and Prevention of Ticks and Tick-borne Diseases Among Foresters in Alsace
NCT06542289	Not specified	NOT_YET_RECRUITING	Safety and Effectiveness of the BlinkER System in Participants With Facial Nerve Palsy
NCT06583395	Not specified	ENROLLING_BY_INVITATION	Quest to Analyze One Thousand Humans Meditating
NCT06835075	Not specified	ACTIVE_NOT_RECRUITING	Clinicaly Manifested Reinfections with Borrelia Burgdorferi Sensu Lato
NCT06859619	Not specified	NOT_YET_RECRUITING	Serological Measurement of Montpellier Professionals’ Contacts with Infectious Agents Responsible for Animal-borne Diseases
NCT00576082	Not specified	UNKNOWN	Borrelia Species in Cutaneous Lyme Borreliosis

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
DOXYCYCLINE ANHYDROUS	4	13
CEFTRIAXONE	4	3
AMOXICILLIN	4	1
CLARITHROMYCIN	4	1
HYDROXYCHLOROQUINE	4	1
NAPROXEN	4	1
PENICILLIN V	4	1
PERMETHRIN	4	1
CHEMBL1618254	0	1