View source for Lyme disease

{{For|the pseudo-medical diagnosis from long-term non-specific symptoms|Chronic Lyme disease}}{{Short description|Infectious disease caused by Borrelia bacteria, spread by ticks}}
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{{Use American English|date=May 2025}}
{{Use dmy dates|date=September 2017}}
{{Infobox medical condition (new)
| name = Lyme disease
| synonyms = Lyme borreliosis
| image = Adult deer tick.jpg
| caption = An adult [[Ixodes scapularis|deer tick]] (Most cases of Lyme disease are caused by nymphs.)
| field = [[Infectious disease (medical specialty)|Infectious disease]]
| symptoms = Expanding area of redness at the site of a [[tick]] bite, [[fever]], [[headache]], [[fatigue (medical)|tiredness]]<ref name=CDC2013S/>
| complications = [[Facial nerve paralysis]], [[arthritis]], [[meningitis|meningitis-like symptoms]],<ref name="CDC2024">{{cite web |title=Clinical Care and Treatment of Neurologic Lyme Disease |url=https://www.cdc.gov/lyme/hcp/clinical-care/neurologic-lyme-disease.html#:~:text=Neurological%20complications%20most%20often%20occur,stiff%20neck%2C%20and%20severe%20headache. |website=Lyme Disease |access-date=27 May 2024 |language=en-us |date=20 May 2024}}</ref> Heart rhythm irregularities<ref>{{cite web |title=Lyme disease - Symptoms and causes |url=https://www.mayoclinic.org/diseases-conditions/lyme-disease/symptoms-causes/syc-20374651 |website=Mayo Clinic |access-date=7 June 2022 |language=en |archive-date=9 November 2022 |archive-url=https://web.archive.org/web/20221109165306/https://www.mayoclinic.org/diseases-conditions/lyme-disease/symptoms-causes/syc-20374651 |url-status=live }}</ref>
| onset = A week after a bite<ref name=CDC2013S/>
| duration = 
| causes = ''[[Borrelia]]'' spread by ticks<ref name=NEJM2014/>
| risks = 
| diagnosis = Based on symptoms, tick exposure, blood tests<ref name=CDC2013Diag/>
| differential = 
| prevention = Prevention of tick bites (clothing the limbs, [[DEET]]), [[doxycycline]]<ref name=NEJM2014/>
| treatment = 
| medication = [[Doxycycline]], [[amoxicillin]], [[ceftriaxone]], [[cefuroxime]]<ref name=NEJM2014/>
| prognosis = 
| frequency = ~476k/year in U.S. (a likely overestimate), 200k/year in Europe<ref name="cdc-how-many">{{cite web |title=Lyme Disease Surveillance and Data
|url=https://www.cdc.gov/lyme/data-research/facts-stats/index.html |website=Centers for Disease Control and Prevention |access-date=16 August 2024 |language=en-us |date=15 May 2024}}</ref><ref name="cdc-estimate-2021">{{cite journal | vauthors = Kugeler KJ, Schwartz AM, Delorey MJ, Mead PS, Hinckley AF | title = Estimating the Frequency of Lyme Disease Diagnoses, United States, 2010-2018 | journal = Emerging Infectious Diseases | volume = 27 | issue = 2 | pages = 616–619 | date = February 2021 | pmid = 33496229 | pmc = 7853543 | doi = 10.3201/eid2702.202731 }}</ref><ref name="comparison-2021">{{cite journal | vauthors = Marques AR, Strle F, Wormser GP | title = Comparison of Lyme Disease in the United States and Europe | journal = Emerging Infectious Diseases | volume = 27 | issue = 8 | pages = 2017–2024 | date = August 2021 | pmid = 34286689 | pmc = 8314816 | doi = 10.3201/eid2708.204763 }}</ref>
| deaths = 
}}
<!-- Definition and symptoms -->

'''Lyme disease''', also known as '''Lyme borreliosis''', is a [[tick-borne disease]] caused by species of ''[[Borrelia]]'' bacteria, [[Disease vector|transmitted by]] blood-feeding [[ticks]] in the genus ''[[Ixodes]]''.<ref name="NEJM2014" /><ref name="NYT-20210611" /><ref name="Wolcott Host association of Borrelia">{{cite journal | vauthors = Wolcott KA, Margos G, Fingerle V, Becker NS | title = Host association of Borrelia burgdorferi sensu lato: A review | journal = Ticks and Tick-Borne Diseases | volume = 12 | issue = 5 | article-number = 101766 | date = September 2021 | pmid = 34161868 | doi = 10.1016/j.ttbdis.2021.101766 }}</ref> It is the most common disease spread by ticks in the Northern Hemisphere.<ref>{{cite book|title=Regional Disease Vector Ecology Profile: Central Europe|date=April 2001|publisher=DIANE Publishing|isbn=978-1-4289-1143-7 |page=136|url=https://books.google.com/books?id=Hpr10wAwoE0C&pg=PA136|url-status=live|archive-url=https://web.archive.org/web/20170908151350/https://books.google.com/books?id=Hpr10wAwoE0C&pg=PA136|archive-date=8 September 2017}}</ref><ref name="comparison-2021"/> Infections are most common in the spring and early summer.<ref name=NEJM2014/>  

The most common sign of infection is an expanding red [[rash]], known as [[erythema migrans]] (EM), which appears at the site of the tick bite about a week afterwards.<ref name="CDC2013S">{{cite web |date=11 January 2013 |title=Signs and Symptoms of Lyme Disease |url=https://www.cdc.gov/lyme/signs_symptoms/index.html |archive-url=https://web.archive.org/web/20130116063305/http://www.cdc.gov/lyme/signs_symptoms/index.html |archive-date=16 January 2013 |access-date=2 March 2015 |website=cdc.gov}}</ref> The rash is typically neither itchy nor painful.<ref name="CDC2013S" /> Approximately 70–80% of infected people develop a rash.<ref name="CDC2013S" /> Other early symptoms may include fever, headaches and [[fatigue (medical)|tiredness]].<ref name="CDC2013S" /> If untreated, symptoms may include [[Facial nerve paralysis|loss of the ability to move one or both sides of the face]], [[arthritis|joint pains]], [[Meningitis|severe headaches with neck stiffness]] or [[heart palpitation]]s.<ref name="CDC2013S" /> Months to years later, repeated episodes of joint pain and swelling may occur.<ref name="CDC2013S" /> Occasionally, shooting pains or tingling in the arms and legs may develop.<ref name="CDC2013S" />

Diagnosis is based on a combination of symptoms, history of tick exposure, and possibly testing for specific [[antibodies]] in the blood.<ref name="CDC2013Diag">{{cite web|title=Lyme Disease Diagnosis and Testing|website=cdc.gov|date=10 January 2013|url=https://www.cdc.gov/lyme/diagnosistesting/index.html|access-date=2 March 2015|archive-url=https://web.archive.org/web/20150302013440/http://www.cdc.gov/lyme/diagnosistesting/index.html|archive-date=2 March 2015|url-status=live}}</ref><ref>{{cite web|title=Two-step Laboratory Testing Process |url=https://www.cdc.gov/lyme/diagnosistesting/LabTest/TwoStep/index.html|website=cdc.gov|access-date=2 March 2015|date=15 November 2011|url-status=live|archive-date=12 March 2015|archive-url=https://web.archive.org/web/20150312123313/http://www.cdc.gov/lyme/diagnosistesting/labtest/twostep/index.html}}</ref> If an infection develops, several antibiotics are effective, including [[doxycycline]], [[amoxicillin]] and [[cefuroxime]].<ref name=NEJM2014/> Standard treatment usually lasts for two or three weeks.<ref name=NEJM2014/> People with persistent symptoms after appropriate treatments are said to have [[Lyme_disease#Post-treatment_Lyme_disease_syndrome|Post-Treatment Lyme Disease Syndrome]] (PTLDS).<ref name=":0">{{Cite web |last=CDC |date=2024-06-11 |title=Chronic Symptoms and Lyme Disease |url=https://www.cdc.gov/lyme/signs-symptoms/chronic-symptoms-and-lyme-disease.html |access-date=2024-07-27 |website=Lyme Disease |language=en-us}}</ref>

Prevention includes efforts to prevent tick bites by wearing clothing to cover the arms and legs and using [[DEET]] or [[picaridin]]-based [[insect repellent]]s.<ref name=NEJM2014/><ref name="NYT-20210611">{{cite news |vauthors=Wenner M |title=Let's Do a Tick Check - These pervasive bloodsuckers can give you more than just Lyme disease. Here's how to protect yourself. (Interactive) |url=https://www.nytimes.com/interactive/2021/06/11/well/tick-disease-lyme.html |date=11 June 2021 |work=[[The New York Times]] |access-date=19 June 2021 |archive-date=19 June 2021 |archive-url=https://web.archive.org/web/20210619021727/https://www.nytimes.com/interactive/2021/06/11/well/tick-disease-lyme.html |url-status=live }}</ref> {{As of|2023}}, clinical trials of proposed human [[#Vaccination|vaccines for Lyme disease]] were being carried out, but no vaccine was available. A vaccine, LYMERix, was produced but discontinued in 2002 due to insufficient demand.<ref name="cdc-vaccine" /> There are several vaccines for the prevention of Lyme disease in dogs.

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==Signs and symptoms==

Lyme disease can produce a broad range of symptoms.

{{Gallery
|width=150
|align=right
|File:Erythema migrans - erythematous rash in Lyme disease - PHIL 9875.jpg|20% of Lyme rashes in the United States show a "bull's eye" or "target-like" appearance.<ref name=wright_2012/><ref name=CDC_Lyme_rashes>{{cite web |title=Lyme disease rashes and look-alikes |url=https://www.cdc.gov/lyme/signs_symptoms/rashes.html |website=Lyme Disease |publisher=Centers for Disease Control and Prevention |date=December 21, 2018 |archive-url=https://web.archive.org/web/20190402185303/https://www.cdc.gov/lyme/signs_symptoms/rashes.html |archive-date=April 2, 2019 |url-status=live |access-date=April 18, 2019}}</ref><ref name=lyme_rashes_uk>{{cite web |title=Lyme disease: erythema migrans |url=https://www.nice.org.uk/guidance/ng95/resources/lyme-disease-rash-images-pdf-4792273597 |website=Lyme disease NICE guideline [NG95] |publisher=National Institute for Health and Care Excellence |access-date=May 8, 2019 |archive-url=https://web.archive.org/web/20190509035408/https://www.nice.org.uk/guidance/ng95/resources/lyme-disease-rash-images-pdf-4792273597 |archive-date=May 9, 2019 |url-status=live}}</ref>
|File:Solid_erythema_migrans_rash_on_the_neck_of_a_woman_with_Lyme_disease.jpg|[[Erythema migrans]] ("migrating redness") on a woman's neck.<ref name="boyce">{{cite journal |last1=Boyce |first1=RM |last2=Pretsch |first2=P |last3=Tyrlik |first3=K |last4=Schulz |first4=A |last5=Giandomenico |first5=DA |last6=Barbarin |first6=AM |last7=Williams |first7=C |title=Delayed Diagnosis of Locally Acquired Lyme Disease, Central North Carolina, USA. |journal=Emerging Infectious Diseases |date=March 2024 |volume=30 |issue=3 |pages=564–567 |doi=10.3201/eid3003.231302 |pmid=38407256 |pmc=10902532}}</ref> Rashes from non-Lyme causes may look similar.<ref name=tibbles_2007/><ref name="annular">{{cite journal |last1=Trayes |first1=KP |last2=Savage |first2=K |last3=Studdiford |first3=JS |title=Annular Lesions: Diagnosis and Treatment. |journal=American Family Physician |date=1 September 2018 |volume=98 |issue=5 |pages=283–291 |pmid=30216021 |url=https://www.aafp.org/pubs/afp/issues/2018/0901/p283.html}}</ref>
}}

The [[incubation period]] is usually one to two weeks, but can be much shorter (days) or much longer (months to years).<ref name="Lymedisease"/> Lyme symptoms most often occur from May to September in the Northern Hemisphere because the nymphal stage of the tick is responsible for most cases.<ref name="Lymedisease" />

===Early localized infection===
Approximately 80% of Lyme infections begin with a rash of some sort at the site of a tick bite, often near skin folds such as the [[armpit]], [[groin]], [[Popliteal fossa|back of the knee]], or the [[Torso|trunk]] under clothing straps, or in children's hair, ears, or neck.<ref name=wright_2012/><ref name=NEJM2014/> Most people who get infected do not remember seeing a tick or a bite. The rash appears typically one or two weeks (range 3–32 days) after the bite and expands 2–3&nbsp;cm (around 1 inch) per day up to a diameter of 5–70&nbsp;cm (2 to 28 inches) (median is 16&nbsp;cm; 6 inches).<ref name=wright_2012/><ref name=NEJM2014/><ref name=tibbles_2007>{{cite journal | vauthors = Tibbles CD, Edlow JA | title = Does this patient have erythema migrans? | journal = JAMA | volume = 297 | issue = 23 | pages = 2617–2627 | date = June 2007 | pmid = 17579230 | doi = 10.1001/jama.297.23.2617 }}</ref>

The rash is usually circular or oval, red or bluish, and may have an elevated or darker center.<ref name=NEJM2014/><ref name=CDC_Lyme_rashes/><ref name=lyme_rashes_uk/> This rash is termed an [[erythema migrans]] (EM), which translates as "migrating redness." In approximately 79% of cases in Europe, this rash gradually clears from the center toward the edges, possibly forming a "bull's eye" or "target-like" pattern. This clearing only happens in 19% of cases in endemic areas of the United States.<ref name=tibbles_2007/><ref name=CDC_Lyme_rashes/><ref name=lyme_rashes_uk/> The rash may feel warm, usually is not itchy, is rarely tender or painful, and takes up to four weeks to resolve if untreated.<ref name=NEJM2014/>

The Lyme rash is often accompanied by symptoms of a flu-like illness, including fatigue, headache, body aches, fever, and chills [though usually neither nausea nor upper-respiratory problems]. These symptoms may also appear without a rash or linger after the rash has disappeared. Lyme can progress to later stages without a rash or these symptoms.<ref name=NEJM2014/>

People with high fever for more than two days or whose other symptoms of viral-like illness do not improve despite [[antibiotic]] treatment for Lyme disease, or who have abnormally low levels of [[leukopenia|white]] or [[anemia|red]] cells or [[thrombocytopenia|platelets]] in the blood, should be investigated for possible coinfection with other [[tick-borne diseases]] such as [[ehrlichiosis]] and [[babesiosis]].<ref name="idsa guideline"/>

Not everyone with Lyme disease has all the symptoms. Many of these symptoms can also occur with other diseases.<ref>{{cite web |url=https://www.lecturio.com/concepts/lyme-disease/| title=Lyme Disease|website=The Lecturio Medical Concept Library |access-date= 9 July 2021}}</ref> This can make obtaining a diagnosis particularly challenging, especially with the rise of co-infection.

[[Asymptomatic]] infection exists, but some studies suggest that this occurs in less than 7% of infected individuals in the United States as opposed to about 50-70% of cases in Europe.<ref name="pmid12905137"/> 

===Early disseminated infection===
Within days to weeks after the onset of local infection, the ''Borrelia'' bacteria may spread through the lymphatic system or bloodstream. In 10–20% of untreated cases, EM rashes develop at sites across the body that bear no relation to the original tick bite.<ref name=wright_2012/> Transient [[myalgia|muscle pains]] and [[arthralgia|joint pains]] are also common.<ref name=wright_2012/>

In about 10–15% of untreated people, Lyme causes neurological problems known as [[neuroborreliosis]].<ref name="Halperin2008"/> Early neuroborreliosis typically appears 4–6 weeks (range 1–12 weeks) after the tick bite and involves some combination of lymphocytic meningitis, cranial neuritis, radiculopathy, and/or mononeuritis multiplex.<ref name="idsa guideline"/><ref name=efns_guidelines>{{cite journal | vauthors = Mygland A, Ljøstad U, Fingerle V, Rupprecht T, Schmutzhard E, Steiner I | title = EFNS guidelines on the diagnosis and management of European Lyme neuroborreliosis | journal = European Journal of Neurology | volume = 17 | issue = 1 | pages = 8–16 | date = January 2010 | pmid = 19930447 | doi = 10.1111/j.1468-1331.2009.02862.x | doi-access = free }}</ref> [[Aseptic meningitis|Lymphocytic meningitis]] causes [[Lymphocytic pleocytosis|characteristic changes]] in the [[cerebrospinal fluid]] (CSF) and may be accompanied for several weeks by variable headache and, less commonly, usually mild [[Meningism|meningitis signs]] such as [[Neck stiffness|inability to flex the neck fully]] and [[Photophobia|intolerance to bright lights]] but typically no or only very low fever.<ref name=steere_neuro_findings>{{cite journal | vauthors = Pachner AR, Steere AC | title = Neurological findings of Lyme disease | journal = The Yale Journal of Biology and Medicine | volume = 57 | issue = 4 | pages = 481–483 | date = July 1984 | pmid = 6516450 | pmc = 2590042 }}</ref> After several months neuroborreliosis can also present [[Otorhinolaryngology|otolaryngological symptoms]]. Up to 76.5% of them present as [[tinnitus]], the most common symptom. [[Vertigo]] and dizziness (53.7%) and hearing loss (16.7%) were the next most common symptoms.<ref>{{cite journal | vauthors = Moscatello AL, Worden DL, Nadelman RB, Wormser G, Lucente F | title = Otolaryngologic aspects of Lyme disease | journal = The Laryngoscope | volume = 101 | issue = 6 Pt 1 | pages = 592–595 | date = June 1991 | pmid = 2041438 | doi = 10.1288/00005537-199106000-00004 }}</ref> In children, [[Papilledema|partial loss of vision]] may also occur.<ref name="idsa guideline"/> Cranial [[neuritis]] is an inflammation of [[cranial nerves]]. When due to Lyme, it most typically causes [[facial palsy]], impairing blinking, smiling, and chewing on one or both sides of the face. It may also cause intermittent [[Diplopia|double vision]].<ref name="idsa guideline"/><ref name=steere_neuro_findings/> Lyme [[radiculopathy]] is an inflammation of spinal [[nerve root]]s that often causes [[radiculitis|pain]] and less often [[paresis|weakness]], [[hypoesthesia|numbness]], or [[paresthesia|altered sensation]] in the [[Dermatome (anatomy)|areas of the body served by nerves connected to the affected roots]], e.g. limb(s) or part(s) of trunk. The pain is often described as unlike any other previously felt, excruciating, migrating, worse at night, rarely symmetrical, and often accompanied by extreme sleep disturbance.<ref name=efns_guidelines/><ref name=ogrinc_bannwarth>{{cite journal | vauthors = Ogrinc K, Lusa L, Lotrič-Furlan S, Bogovič P, Stupica D, Cerar T, Ružić-Sabljić E, Strle F | title = Course and Outcome of Early European Lyme Neuroborreliosis (Bannwarth Syndrome): Clinical and Laboratory Findings | journal = Clinical Infectious Diseases | volume = 63 | issue = 3 | pages = 346–353 | date = August 2016 | pmid = 27161773 | doi = 10.1093/cid/ciw299 | doi-access = free }}</ref> [[Peripheral neuropathy#Mononeuritis multiplex|Mononeuritis multiplex]] is an inflammation causing similar symptoms in one or more unrelated peripheral nerves.<ref name="Halperin2008"/><ref name="idsa guideline"/> Rarely, early neuroborreliosis may involve inflammation of the [[encephalitis|brain]] or [[myelitis|spinal cord]], with symptoms such as confusion, [[ataxia|abnormal gait, ocular movements, or speech]], [[paresis|impaired movement]], [[apraxia|impaired motor planning]], or [[Tremor|shaking]].<ref name="idsa guideline"/><ref name=efns_guidelines/>

In North America, facial palsy is the typical early neuroborreliosis presentation, occurring in 5–10% of untreated people, in about 75% of cases accompanied by lymphocytic meningitis.<ref name="idsa guideline"/><ref name=garro_2018/> Lyme radiculopathy is reported half as frequently, but many cases may be unrecognized.<ref name=halperin_2010>{{cite journal | vauthors = Halperin JJ | title = Nervous system Lyme disease | journal = The Journal of the Royal College of Physicians of Edinburgh | volume = 40 | issue = 3 | pages = 248–255 | date = September 2010 | pmid = 21127770 | doi = 10.4997/JRCPE.2010.314 | doi-access = free }}</ref> In European adults, the most common presentation is a combination of lymphocytic meningitis and radiculopathy known as [[Lymphocytic meningoradiculitis|Bannwarth syndrome]], accompanied in 36-89% of cases by facial palsy.<ref name=efns_guidelines/><ref name=ogrinc_bannwarth/> In this syndrome, radicular pain tends to start in the same body region as the initial [[erythema migrans]] rash, if there was one, and precedes possible [[facial palsy]] and other [[Paresis|impaired movement]].<ref name=ogrinc_bannwarth/> In extreme cases, permanent [[paraparesis|impairment of motor or sensory function]] of the lower limbs may occur.<ref name="pmid23319969"/> In European children, the most common manifestations are facial palsy (in 55%), other cranial neuritis, and lymphocytic meningitis (in 27%).<ref name=efns_guidelines/>

{{Anchor|Carditis2021-05-10}}In about 4–10% of untreated cases in the United States and 0.3–4% of untreated cases in Europe, typically between June and December, about one month (range 4 days to 7 months) after the tick bite, the infection may cause heart complications known as Lyme [[carditis]].<ref name=fish_2008>{{cite journal | vauthors = Fish AE, Pride YB, Pinto DS | title = Lyme carditis | journal = Infectious Disease Clinics of North America | volume = 22 | issue = 2 | pages = 275–88, vi | date = June 2008 | pmid = 18452801 | doi = 10.1016/j.idc.2007.12.008 }}</ref><ref name="Stanek2012">{{cite journal | vauthors = Stanek G, Wormser GP, Gray J, Strle F | title = Lyme borreliosis | journal = Lancet | volume = 379 | issue = 9814 | pages = 461–473 | date = February 2012 | pmid = 21903253 | doi = 10.1016/S0140-6736(11)60103-7 }}</ref> Symptoms may include heart [[palpitations]] (in 69% of people), [[dizziness]], [[syncope (medicine)|fainting]], [[shortness of breath]], and [[chest pain]].<ref name=fish_2008/> Other symptoms of Lyme disease may also be present, such as [[Erythema migrans|EM]] rash, [[arthralgia|joint aches]], [[facial palsy]], [[headaches]], or [[radiculitis|radicular pain]].<ref name=fish_2008/> In some people, however, carditis may be the first manifestation of Lyme disease.<ref name=fish_2008/> Lyme carditis in 19–87% of people adversely impacts the heart's electrical conduction system, causing atrioventricular [[Heart block|block]] that often manifests as heart rhythms that alternate within minutes between abnormally slow and abnormally fast.<ref name=fish_2008/><ref name="Stanek2012"/> In 10–15% of people, Lyme causes [[Cardiac muscle|myocardial]] complications such as [[cardiomegaly]], left [[Ventricle (heart)|ventricular]] dysfunction, or congestive heart failure.<ref name=fish_2008/>

Another skin condition, found in Europe but not in North America, is [[borrelial lymphocytoma]], a purplish lump that develops on the ear lobe, nipple, or [[scrotum]].<ref name="pmid18452805"/>

==={{anchor|Bannwarth syndrome}} Late disseminated infection===
[[File:Right knee swelling caused by Lyme arthritis in a 3-year-old girl.jpg|thumb|Lyme arthritis caused this 3-year-old girl's knee to become swollen. Though painless, it made her limp.<ref name="knee-swelling">{{cite journal | vauthors = Guardado KE, Sergent S | title = Pediatric unilateral knee swelling: a case report of a complicated differential diagnosis and often overlooked cause | journal = Journal of Osteopathic Medicine | volume = 122 | issue = 2 | pages = 105–109 | date = January 2022 | pmid = 34989214 | doi = 10.1515/jom-2020-0332 | doi-access = free }}</ref>]]
Lyme arthritis occurs in up to 60% of untreated people, typically starting about six months after infection.<ref name=wright_2012/> It usually affects only one or a few joints, often a knee or possibly the [[hip]], other large joints, or the [[temporomandibular joint]].<ref name="idsa guideline"/><ref name="pmid18452802"/> Usually, large [[joint effusion]] and swelling occur, but only mild or moderate pain.<ref name="idsa guideline"/> Without treatment, swelling and pain typically resolve over time, but periodically return.<ref name="idsa guideline"/> [[Baker's cyst]]s may form and rupture.

In early US studies of Lyme disease, a rare [[peripheral neuropathy]] was described that included numbness, tingling, or burning starting at the feet or hands and, over time, possibly moving up the limbs. In a later analysis that discovered poor documentation of this manifestation, experts wondered if it exists at all in the US or is merely very rare.<ref name="idsa guideline"/><ref name="axonal">{{cite journal | vauthors = Wormser GP, Strle F, Shapiro ED, Dattwyler RJ, Auwaerter PG | title = A critical appraisal of the mild axonal peripheral neuropathy of late neurologic Lyme disease | journal = Diagnostic Microbiology and Infectious Disease | volume = 87 | issue = 2 | pages = 163–167 | date = February 2017 | pmid = 27914746 | pmc = 5924701 | doi = 10.1016/j.diagmicrobio.2016.11.003 }}</ref>

A neurologic syndrome called Lyme encephalopathy is associated with subtle memory and cognitive difficulties, [[insomnia]], [[malaise|a general sense of feeling unwell]], and changes in personality.<ref name=MayoClin2008>{{cite journal | vauthors = Bratton RL, Whiteside JW, Hovan MJ, Engle RL, Edwards FD | title = Diagnosis and treatment of Lyme disease | journal = Mayo Clinic Proceedings | volume = 83 | issue = 5 | pages = 566–571 | date = May 2008 | pmid = 18452688 | doi = 10.4065/83.5.566 | doi-access = free }}</ref> Lyme encephalopathy is controversial in the US and has not been reported in Europe.<ref name="comparison-2021"/> Problems such as depression and [[fibromyalgia]] are as common in people with Lyme disease as in the general population.<ref name=Shadick/><ref name=seltzer_2000/> There is no compelling evidence that Lyme disease causes psychiatric disorders, behavioral disorders (e.g. [[Attention deficit hyperactivity disorder|ADHD]]), or developmental disorders (e.g. [[autism]]).<ref name="guidelines-2020"/>

[[Acrodermatitis chronica atrophicans]] is a chronic skin disorder observed primarily in Europe among the elderly.<ref name="pmid18452805"/> It begins as a reddish-blue patch of discolored skin, often on the backs of the hands or feet. The lesion slowly atrophies over several weeks or months, with the skin becoming first thin and wrinkled and then, if untreated, completely dry and hairless.<ref name=mullegger_2004/> 

==Cause==
{{Main|Lyme disease microbiology}}

[[File:Borrelia burgdorferi-cropped.jpg|thumb|right|''[[Borrelia]]'' bacteria, the causative agents of Lyme disease, magnified]]
Lyme disease is caused by [[spirochete]]s, [[gram-negative bacteria]] from the [[genus]] ''[[Borrelia]]''. Spirochetes are surrounded by [[peptidoglycan]] and [[flagella]].<ref name="Winslow">{{cite journal |vauthors=Winslow C, Coburn J |title=Recent discoveries and advancements in research on the Lyme disease spirochete Borrelia burgdorferi |journal=F1000Res |volume=8 |issue= |date=2019 |page=763 |pmid=31214329 |pmc=6545822 |doi=10.12688/f1000research.18379.1 |doi-access=free |url=}}</ref> The Lyme-related ''Borrelia'' species are collectively known as ''[[Borrelia burgdorferi]] [[sensu lato]]'', and show a great deal of [[genetic diversity]].<ref>{{cite book |veditors= Radolf JD, Samuels DS |year= 2021 |title= Lyme Disease and Relapsing Fever Spirochetes: Genomics, Molecular Biology, Host Interactions, and Disease Pathogenesis |url= https://www.caister.com/lyme |publisher= Caister Academic Press |isbn= 978-1-913652-61-6 |archive-date= 14 May 2021 |access-date= 9 July 2021 |archive-url= https://web.archive.org/web/20210514123712/https://www.caister.com/lyme |url-status= live }}</ref>

''B. burgdorferi sensu lato'' is a species complex made up of 20 accepted and three proposed genospecies. Eight species are known to cause Lyme disease: ''B. mayonii'' (found in North America), ''B. burgdorferi [[sensu stricto]]'' (found in North America and Europe), ''B. afzelii'', ''B. garinii, B. spielmanii,'' and ''B. lusitaniae'' (all found in [[Eurasia]]).{{efn|Attributed to multiple references:<ref name=Cutler2016>{{cite journal | vauthors = Cutler SJ, Ruzic-Sabljic E, Potkonjak A | title = Emerging borreliae - Expanding beyond Lyme borreliosis | journal = Molecular and Cellular Probes | volume = 31 | pages = 22–27 | date = February 2017 | pmid = 27523487 | doi = 10.1016/j.mcp.2016.08.003 | url = http://roar.uel.ac.uk/5199/1/RBG_Emerging%20borreliosis%20for%20submissionmodHPFAug10_corrected%20without%20track%20change%20SJC.pdf | archive-date = 20 July 2018 | access-date = 18 July 2022 | archive-url = https://web.archive.org/web/20180720065950/http://roar.uel.ac.uk/5199/1/RBG_Emerging%20borreliosis%20for%20submissionmodHPFAug10_corrected%20without%20track%20change%20SJC.pdf | url-status = live }}</ref><ref name=Stanek2011/><ref name=Lancet2016/><ref name="Wolcott Host association of Borrelia"/>}} Some studies have also proposed that ''B. valaisiana'' may sometimes infect humans. This species does not appear to be an important cause of disease.<ref name="pmid18454594"/><ref name="pmid18650352"/>

=== Ticks ===
[[File:Deer Tick life cycle.svg|thumb|Deer tick life cycle]]
[[File:Ixodes scapularis.png|thumb|right|''[[Ixodes scapularis]]'', the primary vector of Lyme disease in eastern North America]]
====Tick life cycle====
Three stages occur in the life cycle of a tick: larva, nymph, and adult. During the nymph stage, ticks most frequently transmit Lyme disease and are typically most active in late spring and early summer in regions with a mild climate. During the adult stage, Lyme disease transmission is less common because adult ticks are less likely to bite humans and tend to be larger, so they can be easily seen and removed.<ref>{{Cite web|title=UpToDate|url=https://www.uptodate.com/contents/evaluation-of-a-tick-bite-for-possible-lyme-disease|access-date=2021-07-10|website=www.uptodate.com}}</ref>

====Tick appearance changes when feeding====
Both nymph and female ticks increase in size (engorge) when feeding.<ref>{{Cite journal|url=https://journals.sagepub.com/doi/10.1016/j.wem.2015.05.001?icid=int.sj-full-text.similar-articles.4&|title=Lyme Disease: What the Wilderness Provider Needs to Know|first1=Joseph D.|last1=Forrester|first2=J. Priyanka|last2=Vakkalanka|first3=Christopher P.|last3=Holstege|first4=Paul S.|last4=Mead|date=1 December 2015|journal=Wilderness & Environmental Medicine|volume=26|issue=4|pages=555–564|via=SAGE Journals|doi=10.1016/j.wem.2015.05.001|pmid=26141918 |url-access=subscription}}</ref>

====Types of ticks, and hosts====

Lyme disease is transmitted to humans by the bites of infected ticks of the genus ''Ixodes''.<ref>{{cite book |vauthors=Johnson RC |chapter=Borrelia |title=Baron's Medical Microbiology |veditors=Baron S |display-editors=etal |edition=4th |publisher=Univ of Texas Medical Branch |year=1996 |chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK8451/ |isbn=978-0-9631172-1-2 |pmid=21413339 |archive-url=https://web.archive.org/web/20090207104450/http://www.ncbi.nlm.nih.gov/books/bv.fcgi |archive-date=7 February 2009 |url-status=live}}</ref> In the United States, ''[[Ixodes scapularis]]'' is the primary vector. In Europe, ''[[Ixodes ricinus]]'' ticks may spread the bacteria more quickly.<ref name=Ste2016>{{cite journal | vauthors = Steere AC, Strle F, Wormser GP, Hu LT, Branda JA, Hovius JW, Li X, Mead PS | title = Lyme borreliosis | journal = Nature Reviews. Disease Primers | volume = 2 | article-number = 16090 | date = December 2016 | pmid = 27976670 | pmc = 5539539 | doi = 10.1038/nrdp.2016.90 }}</ref><ref>{{cite web |url=https://ecdc.europa.eu/sites/portal/files/media/en/healthtopics/emerging_and_vector-borne_diseases/tick_borne_diseases/public_health_measures/Documents/HCP_factsheet_LB_highres.pdf |title=Lyme borreliosis|website=[[ECDC]]|access-date=29 September 2018|url-status=live|archive-url=https://web.archive.org/web/20180929000428/https://ecdc.europa.eu/sites/portal/files/media/en/healthtopics/emerging_and_vector-borne_diseases/tick_borne_diseases/public_health_measures/Documents/HCP_factsheet_LB_highres.pdf |archive-date=29 September 2018}}</ref> In North America, the bacterial species  ''[[Borrelia burgdorferi]] ''and [[Borrelia mayonii|''B. mayonii'']] cause Lyme disease.<ref name="NEJM2014" /><ref name="Lancet2016">{{cite journal | vauthors = Pritt BS, Mead PS, Johnson DK, Neitzel DF, Respicio-Kingry LB, Davis JP, Schiffman E, Sloan LM, Schriefer ME, Replogle AJ, Paskewitz SM, Ray JA, Bjork J, Steward CR, Deedon A, Lee X, Kingry LC, Miller TK, Feist MA, Theel ES, Patel R, Irish CL, Petersen JM | title = Identification of a novel pathogenic Borrelia species causing Lyme borreliosis with unusually high spirochaetaemia: a descriptive study | journal = The Lancet. Infectious Diseases | volume = 16 | issue = 5 | pages = 556–564 | date = May 2016 | pmid = 26856777 | pmc = 4975683 | doi = 10.1016/S1473-3099(15)00464-8 }}</ref> In Europe and Asia,'' [[Borrelia afzelii]], [[Borrelia garinii]], [[Borrelia spielmanii|B. spielmanii]]'' and four other species also cause the disease.<ref name="NEJM2014">{{cite journal | vauthors = Shapiro ED | title = Clinical practice. Lyme disease | journal = The New England Journal of Medicine | volume = 370 | issue = 18 | pages = 1724–1731 | date = May 2014 | pmid = 24785207 | pmc = 4487875 | doi = 10.1056/NEJMcp1314325 | url = http://portal.mah.harvard.edu/templatesnew/departments/MTA/Lyme/uploaded_documents/NEJMcp1314325.pdf | access-date = 5 July 2016 | archive-url = https://web.archive.org/web/20160821071927/http://portal.mah.harvard.edu/templatesnew/departments/MTA/Lyme/uploaded_documents/NEJMcp1314325.pdf | archive-date = 21 August 2016 }}</ref>

While ''[[Borrelia burgdorferi|B. burgdorferi]]'' is most associated with ticks hosted by [[white-tailed deer]] and [[White-footed Mouse|white-footed mice]], ''[[Borrelia afzelii]]'' is most frequently detected in rodent-feeding [[Disease vector|vector]] ticks, and ''[[Borrelia garinii]]'' and ''[[Borrelia valaisiana]]'' appear to be associated with birds. Both rodents and birds are competent reservoir hosts for ''B. burgdorferi sensu stricto''. The resistance of a genospecies of Lyme disease [[Spirochaete|spirochetes]] to the [[bacteriolytic]] activities of the alternative complement pathway of various host species may determine its reservoir host association.<ref name="pmid16820453" />

Budding research has suggested that ''B. burgdorferi sensu lato'' may also be able to form [[enzootic]] cycle among lizard populations;<ref name="pmid17417956" /> this was previously assumed not to be possible in major areas containing populations of lizards, such as California. Except for one study in Europe,<ref name="pmid16820453"/> much of the data implicating lizards is based on DNA detection of the spirochete and has not demonstrated that lizards can infect ticks feeding on them.<ref name="pmid17417956"/><ref name="pmid17626342"/><ref name="pmid17427701"/><ref name="pmid17326941"/> As some experiments suggest lizards are refractory to infection with ''Borrelia'', it appears likely their involvement in the enzootic cycle is more complex and species-specific.<ref name="pmid16995383"/>

[[File:Ixodes-ricinus-life-cycle.jpg|thumb|right|Tick ''[[Ixodes ricinus]]'', developmental stages]]
In Europe, the main vector is ''[[Ixodes ricinus]]'', which is also called the sheep tick or [[Castor oil plant|castor bean]] tick.<ref name=de_1997/> In China, ''[[Ixodes persulcatus]]'' (the taiga tick) is probably the most important vector.<ref name=Sun_2003/> In North America, the black-legged tick or deer tick (''[[Ixodes scapularis]]'') is the main vector on the East Coast.<ref name=pmid15117014/>

The lone star tick (''[[Amblyomma americanum]]''), which is found throughout the Southeastern United States as far west as [[Texas]], is unlikely to transmit the Lyme disease [[spirochete]]s,<ref name=Ledin_2005/> though it may be implicated in a related syndrome called [[southern tick-associated rash illness]], which resembles a mild form of Lyme disease.<ref name=Masters2008/>

On the [[West Coast of the United States]], the main vector is the western black-legged tick (''[[Ixodes pacificus]]'').<ref name="Clark"/> The tendency of this tick species to feed predominantly on host species such as the [[Western Fence Lizard|western fence lizard]] that are resistant to ''Borrelia'' infection appears to diminish transmission of Lyme disease in the West.<ref name="pmid15709249"/><ref name="pmid16995383"/>

===Transmission===

====Mechanism====
Lyme disease is classified as a [[zoonosis]], as it is [[Transmission (medicine)|transmitted]] to humans from a [[natural reservoir]] among small mammals and birds by [[tick]]s that feed on both sets of [[Host (biology)|hosts]].<ref name=pmid18452798/> Hard-bodied ticks of the genus ''Ixodes'' are the [[Vector (epidemiology)|vectors]] of Lyme disease (also the vector for ''[[Babesia]]'').<ref name=Sherris /> Most infections are caused by ticks in the [[Nymph (biology)|nymphal stage]], because they are tiny, and may thus feed undetected for long periods of time.<ref name=pmid18452798/> Nymphal ticks are generally the size of a poppy seed and sometimes with a dark head and a translucent body.<ref name=Rut2005>{{cite web | url = https://ocean.njaes.rutgers.edu/garden/documents/fs443.pdf | title = 2005 Fact Sheet, Prevent Tick Bites: Prevent Lyme Disease | archive-url = https://web.archive.org/web/20130626133450/http://ocean.njaes.rutgers.edu/garden/documents/fs443.pdf | archive-date=26 June 2013 | publisher = Rutgers University, Rutgers Cooperative Research & Extension, New Jersey Agricultural Experiment Station | vauthors = Smith-Fiola D, Hamilton GC | date = March 2005 }}</ref> Or, the nymphal ticks can be darker.<ref>{{cite web | url = https://www.deseret.com/2019/5/31/20674560/people-are-freaking-out-over-the-cdc-s-photo-of-a-muffin-with-ticks-in-it | title = People are freaking out over the CDC's photo of a muffin with ticks in it | archive-url = https://web.archive.org/web/20200125192618/https://www.deseret.com/2019/5/31/20674560/people-are-freaking-out-over-the-cdc-s-photo-of-a-muffin-with-ticks-in-it | archive-date=25 January 2020 | work = Deseret News | location = Utah | vauthors = Scribner H | date = 31 May 2019 | quote = The U.S. CDC published a picture of a poppy seed muffin in which some of the "poppy seeds" were actually ticks }}</ref> The younger larval ticks are very rarely infected.<ref name=pmid15117014/> Although deer are the preferred hosts of adult deer ticks, and tick populations are much lower in the absence of deer, ticks generally do not acquire ''Borrelia'' from deer; instead, they obtain them from infected small mammals such as the [[white-footed mouse]], and occasionally birds.<ref name="Westport">{{cite web |title = Westport Weston Health District |url = http://www.wwhd.org/TLD_CD/deertick.htm |year = 2004 |access-date = 26 September 2013 |archive-url = https://web.archive.org/web/20130929110519/http://www.wwhd.org/TLD_CD/deertick.htm |archive-date = 29 September 2013}}</ref> Areas where Lyme is common are expanding.<ref name=CDC-Lyme-Data/>

Within the tick midgut, the ''Borrelia''{{'}}s [[Lyme disease microbiology#Outer surface proteins|outer surface protein]] A (OspA) binds to the tick receptor for OspA, known as TROSPA. When the tick feeds, the'' Borrelia'' [[Downregulation and upregulation|downregulates]] OspA and [[Downregulation and upregulation|upregulates]] OspC, another surface protein. After the bacteria migrate from the midgut to the salivary glands, OspC binds to Salp15, a tick salivary protein that appears to have immunosuppressive effects that enhance infection.<ref name=hovius_2007/> Successful infection of the mammalian host depends on bacterial expression of OspC.<ref name="pmid15085185"/>

====Duration of attachment====
Reviews have considered whether the length of time of attachment impacts transmission.<ref>{{Cite journal|title=Pathogen transmission in relation to duration of attachment by Ixodes scapularis ticks|first=Lars|last=Eisen|date=6 March 2018|journal=Ticks and Tick-Borne Diseases|volume=9|issue=3|pages=535–542|doi=10.1016/j.ttbdis.2018.01.002|pmid=29398603|pmc=5857464}}</ref><ref>{{Cite journal|title=Lyme borreliosis: a review of data on transmission time after tick attachment|first=Michael J.|last=Cook|date=6 May 2015|journal=International Journal of General Medicine|volume=8|pages=1–8|doi=10.2147/IJGM.S73791|doi-access=free |pmid=25565881|pmc=4278789}}</ref>

====Prevalence====
Tick bites often go unnoticed because of the small size of the tick in its nymphal stage, as well as tick secretions that prevent the host from feeling any itch or pain from the bite. However, transmission is quite rare, with only about 1.2 to 1.4 percent of recognized tick bites resulting in Lyme disease.<ref>{{Cite web|url=https://www.uptodate.com/contents/what-to-do-after-a-tick-bite-to-prevent-lyme-disease-beyond-the-basics|title=Patient education: What to do after a tick bite to prevent Lyme disease (Beyond the Basics)| vauthors = Hu L |date=13 May 2019|website=www.uptodate.com|publisher=UpToDate|url-status=live|archive-url=https://web.archive.org/web/20200101124546/https://www.uptodate.com/contents/what-to-do-after-a-tick-bite-to-prevent-lyme-disease-beyond-the-basics|archive-date=1 January 2020|access-date=30 January 2020}}</ref>

====In pregnancy====
Lyme disease spreading from mother to fetus is possible but extremely rare, and with antibiotic treatment, there is no increased risk of adverse birth outcomes.<ref name="auto">{{Cite web|url=https://www.cdc.gov/lyme/causes/index.html|title=How Lyme Disease Spreads|date=24 September 2024|website=Lyme Disease|access-date=5 May 2025|archive-date=15 June 2024|archive-url=https://web.archive.org/web/20240615000549/https://www.cdc.gov/lyme/causes/index.html|url-status=live}}</ref> NICE guidance is that antibiotics appropriate for pregnancy be used.<ref>{{Cite web|url=https://www.nice.org.uk/guidance/ng95/chapter/recommendations#management-for-women-with-lyme-disease-during-pregnancy-and-their-babies|title=Recommendations &#124; Lyme disease &#124; Guidance &#124; NICE|date=11 April 2018|website=www.nice.org.uk|access-date=5 May 2025|archive-date=11 May 2019|archive-url=https://web.archive.org/web/20190511145123/https://www.nice.org.uk/guidance/ng95/chapter/Recommendations#management-for-women-with-lyme-disease-during-pregnancy-and-their-babies|url-status=live}}</ref> There are no studies on developmental outcomes of children whose mothers had Lyme.<ref name="auto"/>

====Other human transmission====
There is no scientific evidence to support Lyme disease transmission via blood transfusion, sexual contact, or breast milk.<ref name=CDC-FAQ/><ref name="auto"/>

===Tick-borne co-infections===

{{Main|Tick-borne disease}}

Ticks that transmit ''B. burgdorferi'' to humans can also carry and transmit several other microbes, such as ''[[Babesia microti]]'' and ''[[Anaplasma phagocytophilum]]'', which cause the diseases [[babesiosis]] and [[human granulocytic anaplasmosis]] (HGA), respectively.<ref name=pmid17041141/> Among people with early Lyme disease, depending on their location, 2–12% will also have HGA and 2–10% will have babesiosis.<ref name="guidelines-2020">{{cite journal | vauthors = Lantos PM, Rumbaugh J, Bockenstedt LK, Falck-Ytter YT, Aguero-Rosenfeld ME, Auwaerter PG, Baldwin K, Bannuru RR, Belani KK, Bowie WR, Branda JA, Clifford DB, DiMario FJ, Halperin JJ, Krause PJ, Lavergne V, Liang MH, Meissner HC, Nigrovic LE, Nocton JJ, Osani MC, Pruitt AA, Rips J, Rosenfeld LE, Savoy ML, Sood SK, Steere AC, Strle F, Sundel R, Tsao J, Vaysbrot EE, Wormser GP, Zemel LS | title = Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 Guidelines for the Prevention, Diagnosis and Treatment of Lyme Disease | journal = Clinical Infectious Diseases | volume = 72 | issue = 1 | pages = e1–e48 | date = January 2021 | pmid = 33417672 | doi = 10.1093/cid/ciaa1215 | doi-access = free }}</ref> Ticks in certain regions also transmit viruses that cause [[tick-borne encephalitis]] and [[Powassan encephalitis|Powassan virus disease]].<ref name=Lindgren_2001/><ref name="guidelines-2020"/> Co-infections of Lyme disease may not require additional treatment, since they may resolve on their own or—as in the case of HGA—can be treated with the doxycycline prescribed for Lyme.<ref name="idsa guideline"/> Persistent fever or compatible anomalous laboratory findings may be indicative of a co-infection.<ref name="guidelines-2020"/>

==Pathophysiology==
''B. burgdorferi'' can spread throughout the body during the course of the disease, and has been found in the skin, heart, joints, peripheral nervous system, and central nervous system.<ref name="pmid15085185"/><ref name="pmid17509489"/> ''B. burgdorferi'' does not produce toxins.<ref name="ALDF-toxins">{{cite web |title=Does Borrelia burgdorferi produce a neurotoxin ? |url=https://www.aldf.com/does-borrelia-burgdorferi-produce-a-neurotoxin-2/ |website=American Lyme Disease Foundation |access-date=30 July 2022 |archive-date=29 June 2022 |archive-url=https://web.archive.org/web/20220629125942/https://www.aldf.com/does-borrelia-burgdorferi-produce-a-neurotoxin-2/ |url-status=live }}</ref> Therefore, many of the signs and symptoms of Lyme disease are a consequence of the immune response to the spirochete in those tissues.<ref name="pmid14987414" />

''B. burgdorferi'' is injected into the skin by the bite of an infected ''Ixodes'' tick.<ref name="Strand">{{cite journal |vauthors=Strnad M, Rudenko N, Rego RO |title=Pathogenicity and virulence of Borrelia burgdorferi |journal=Virulence |volume=14 |issue=1 |article-number=2265015 |date=December 2023 |pmid=37814488 |pmc=10566445 |doi=10.1080/21505594.2023.2265015 |url=}}</ref> Tick saliva, which accompanies the spirochete into the skin during the feeding process, contains substances that disrupt the immune response at the site of the bite.<ref name="pmid16698304"/> This provides a protective environment where the spirochete can establish infection. The spirochetes multiply and migrate outward within the [[dermis]]. The host inflammatory response to the bacteria in the skin causes the characteristic circular EM lesion.<ref name="pmid15085185"/> [[Neutrophils]], however, which are necessary to eliminate the spirochetes from the skin, fail to appear in necessary numbers in the developing EM lesion because tick saliva inhibits neutrophil function. This allows the bacteria to survive and eventually spread throughout the body.<ref name="pmid17404293"/>

Days to weeks following the tick bite, the spirochetes spread via the bloodstream to joints, heart, nervous system, and distant skin sites, where their presence gives rise to the variety of symptoms of the disseminated disease. The spread of ''B. burgdorferi'' is aided by the attachment of the host protease [[plasmin]] to the surface of the spirochete.<ref name="pmid9215633"/>

If untreated, the bacteria may persist in the body for months or even years, despite the production of ''B. burgdorferi'' antibodies by the immune system.<ref name=pmid11450660/> The spirochetes may avoid the immune response by decreasing expression of surface proteins that are targeted by antibodies, [[antigenic variation]] of the VlsE surface protein, inactivating key immune components such as [[Complement system|complement]], and hiding in the [[extracellular matrix]], which may interfere with the function of immune factors.<ref name="pmid18097481"/><ref name="pmid17600717"/>

===Immunological studies===
Exposure to the ''Borrelia'' bacterium during Lyme disease possibly causes a long-lived and damaging [[inflammatory response]],<ref name=Ercolini/> a form of pathogen-induced [[autoimmune]] disease.<ref name=Singh/> The production of this reaction might be due to a form of [[molecular mimicry]], where ''Borrelia'' avoids being killed by the immune system by resembling normal parts of the body's tissues.<ref name=Oldstone_1998/><ref name=Raveche_2005/>

Chronic symptoms from an autoimmune reaction could explain why certain symptoms persist even after the spirochetes have been eliminated from the body. This hypothesis may explain why chronic arthritis persists after antibiotic therapy, similar to [[rheumatic fever]], but its wider application is controversial.<ref name=Weinstein_2002/><ref name=Bolz_2004/>

==Diagnosis==
Lyme disease is [[Medical diagnosis|diagnosed]] based on symptoms, objective physical findings (such as [[erythema migrans]] (EM) rash, [[facial palsy]], or [[arthritis]]), history of possible exposure to infected [[ticks]], and possibly [[#Laboratory testing|laboratory tests]].<ref name=NEJM2014/><ref name=wright_2012/> People with symptoms of early Lyme disease should have a total body skin examination for EM rashes and be asked whether EM-type rashes had manifested within the last 1–2 months.<ref name="idsa guideline"/> Presence of an EM rash and recent tick exposure (i.e., being outdoors in a likely tick habitat where Lyme is [[endemic (epidemiology)|common]], within 30 days of the appearance of the rash) are sufficient for Lyme diagnosis; no laboratory confirmation is needed or recommended.<ref name=NEJM2014/><ref name=wright_2012/><ref name="Brown"/><ref name="Hofmann"/> Most people who get infected do not remember a tick or a bite, and the EM rash need not look like a bull's eye (most EM rashes in the U.S. do not) or be accompanied by any other symptoms.<ref name=NEJM2014/><ref name="Wormser"/> In the U.S., Lyme is most common in the [[New England]] and [[Mid-Atlantic (United States)|Mid-Atlantic]] states and parts of [[Wisconsin]] and [[Minnesota]], but it is expanding into other areas.<ref name=CDC-Lyme-Data>{{cite web |title=Lyme Disease Data and surveillance |url=https://www.cdc.gov/lyme/datasurveillance/ |website=Lyme Disease |publisher=Centers for Disease Control and Prevention |access-date=12 April 2019 |date=5 February 2019 |archive-url=https://web.archive.org/web/20190413133319/https://www.cdc.gov/lyme/datasurveillance/ |archive-date=13 April 2019 |url-status=live }}</ref> Several bordering areas of Canada also have high Lyme risk.<ref name=canada_lyme_map>{{cite web | title = Lyme Disease risk areas map | url = https://www.canada.ca/en/public-health/services/diseases/lyme-disease/risk-lyme-disease.html#map | website = Risk of Lyme disease to Canadians | publisher = Government of Canada | access-date = 8 May 2019 | date = 27 January 2015 | archive-url = https://web.archive.org/web/20190510195225/https://www.canada.ca/en/public-health/services/diseases/lyme-disease/risk-lyme-disease.html#map | archive-date = 10 May 2019 | url-status = live }}</ref>

In the absence of an EM rash or history of tick exposure, Lyme diagnosis depends on laboratory confirmation.<ref name=Sherris /><ref name=aucott_2008>{{cite journal | vauthors = Aucott J, Morrison C, Munoz B, Rowe PC, Schwarzwalder A, West SK | title = Diagnostic challenges of early Lyme disease: lessons from a community case series | journal = BMC Infectious Diseases | volume = 9 | issue = 79 | article-number = 79 | date = June 2009 | pmid = 19486523 | pmc = 2698836 | doi = 10.1186/1471-2334-9-79 | doi-access = free }}</ref> The bacteria that cause Lyme disease are difficult to observe directly in body tissues and also difficult and too time-consuming to [[Microbiological culture|grow]] in the laboratory.<ref name=NEJM2014/><ref name="Sherris" /> The most widely used tests look instead for presence of [[antibodies]] against those bacteria in the blood.<ref name="cdc-diagnosis"/> A positive antibody test result does not by itself prove active infection, but can confirm an infection that is suspected because of symptoms, objective findings, and history of tick exposure in a person.<ref name=Sherris /> Because as many as 5–20% of the normal population have antibodies against Lyme, people without a history and symptoms suggestive of Lyme disease should not be tested for Lyme antibodies: a positive result would likely be false, possibly causing unnecessary treatment.<ref name="idsa guideline"/><ref name=efns_guidelines/>

In some cases, when history, signs, and symptoms are strongly suggestive of early disseminated Lyme disease, [[empiric treatment]] may be started and reevaluated as laboratory test results become available.<ref name=garro_2018/><ref name=lyme_guidelines_uk>{{cite web | title = Lyme disease | url = https://www.nice.org.uk/guidance/ng95/chapter/recommendations | website = NICE guideline [NG95] | date = 11 April 2018 | publisher = National Institute for Health and Care Excellence | access-date = 24 May 2019 | archive-url = https://web.archive.org/web/20190511145123/https://www.nice.org.uk/guidance/ng95/chapter/Recommendations | archive-date = 11 May 2019 | url-status = live }}</ref>

===Laboratory testing===
Tests for antibodies in the blood by [[ELISA]] and [[Western blot]] are the most widely used methods for Lyme diagnosis. A two-tiered protocol is recommended by the [[Centers for Disease Control and Prevention]] (CDC): the [[Sensitivity and specificity|sensitive]] ELISA test is performed first, and if it is positive or equivocal, then the more [[Sensitivity and specificity|specific]] Western blot is run.<ref name=Wilske_2005/> The [[immune system]] takes some time to produce antibodies in quantity. After Lyme infection onset, antibodies of types [[Immunoglobulin M|IgM]] and [[Immunoglobulin G|IgG]] usually can first be detected respectively at 2–4 weeks and 4–6 weeks, and peak at 6–8 weeks.<ref name=Depietropaolo-2005>{{cite journal | vauthors = DePietropaolo DL, Powers JH, Gill JM, Foy AJ | title = Diagnosis of lyme disease | journal = American Family Physician | volume = 72 | issue = 2 | pages = 297–304 | date = July 2005 | pmid = 16050454 | doi = 10.1093/cid/cir464 | doi-access = free }}</ref> When an EM rash first appears, detectable antibodies may not be present. Therefore, it is recommended that testing not be performed and diagnosis be based on the presence of the EM rash.<ref name="idsa guideline"/> Up to 30 days after suspected Lyme infection onset, infection can be confirmed by detection of IgM or IgG antibodies; after that, it is recommended that only IgG antibodies be considered.<ref name=Depietropaolo-2005/> A positive IgM and negative IgG test result after the first month of infection is generally indicative of a false-positive result.<ref name="ALDF-serologic-tests">{{cite web |title=Are serological tests of any value in the diagnosis of Lyme disease? |url=https://www.aldf.com/are-serological-tests-of-any-value-in-the-diagnosis-of-lyme-disease-2/ |website=American Lyme Disease Foundation |access-date=2 December 2019 |ref=ALDF-serologic-tests |archive-url=https://web.archive.org/web/20191219210825/https://www.aldf.com/are-serological-tests-of-any-value-in-the-diagnosis-of-lyme-disease-2/ |archive-date=19 December 2019 |url-status=live }}</ref> The number of IgM antibodies usually collapses 4–6 months after infection, while IgG antibodies can remain detectable for years.<ref name=Depietropaolo-2005/>

Other tests may be used in neuroborreliosis cases. In Europe, neuroborreliosis is usually caused by [[Borrelia garinii]] and almost always involves [[lymphocytic pleocytosis]], i.e., the densities of [[lymphocytes]] (infection-fighting cells) and protein in the [[cerebrospinal fluid]] (CSF) typically rise to characteristically abnormal levels, while glucose level remains normal.<ref name=steere_neuro_findings/><ref name="idsa guideline"/><ref name=ogrinc_bannwarth/> Additionally, the immune system produces antibodies against Lyme inside the intrathecal space, which contains the CSF.<ref name="idsa guideline"/><ref name=ogrinc_bannwarth/> Demonstration by [[lumbar puncture]] and CSF analysis of pleocytosis and intrathecal antibody production are required for definite diagnosis of neuroborreliosis in Europe (except in cases of peripheral neuropathy associated with [[acrodermatitis chronica atrophicans]], which usually is caused by [[Borrelia afzelii]] and confirmed by blood antibody tests).<ref name=efns_guidelines/> In North America, neuroborreliosis is caused by [[Borrelia burgdorferi]] and may not be accompanied by the same CSF signs; they confirm a diagnosis of central nervous system (CNS) neuroborreliosis if positive, but do not exclude it if negative.<ref name=Coyle_1995/> American guidelines consider CSF analysis optional when symptoms appear to be confined to the peripheral nervous system (PNS), e.g., facial palsy without overt meningitis symptoms.<ref name="idsa guideline"/><ref name="pmid17522387"/> Unlike blood and intrathecal antibody tests, CSF pleocytosis tests revert to normal after infection ends and therefore can be used as objective markers of treatment success and inform decisions on whether to retreat.<ref name=ogrinc_bannwarth/> In infection involving the PNS, [[electromyography]] and [[nerve conduction studies]] can be used to monitor objectively the response to treatment.<ref name=steere_neuro_findings/>

In Lyme carditis, [[Electrocardiography|electrocardiograms]] are used to evidence heart conduction abnormalities, while [[echocardiography]] may show [[Cardiac muscle|myocardial]] dysfunction.<ref name=fish_2008/> [[Biopsy]] and confirmation of Borrelia cells in myocardial tissue may be used in specific cases, but are usually not done because of the risk of the procedure.<ref name=fish_2008/>

[[Polymerase chain reaction]] (PCR) tests for Lyme disease have also been developed to detect the genetic material ([[DNA]]) of the Lyme disease spirochete. Culture or PCR are the current means for detecting the presence of the organism, as [[Serology|serologic]] studies only test for [[antibodies]] of ''Borrelia''. PCR has the advantage of being much faster than culture. However, PCR tests are susceptible to [[Type I and type II errors|false positive]] results, e.g., by detection of debris of dead Borrelia cells or specimen contamination.<ref name="pmid11438915"/><ref name=efns_guidelines/> Even when properly performed, PCR often shows false-negative results because few Borrelia cells can be found in blood and [[cerebrospinal fluid]] (CSF) during infection.<ref name="pmid16020686"/><ref name=efns_guidelines/> Hence, PCR tests are recommended only in special cases, e.g., diagnosis of Lyme arthritis, because it is a highly sensitive way of detecting ''ospA'' DNA in synovial fluid.<ref name="pmid8272083"/> Although the sensitivity of PCR in CSF is low, its use may be considered when intrathecal antibody production test results are suspected of being falsely negative, e.g., in very early (< 6 weeks) neuroborreliosis or in [[Immunosuppression|immunosuppressed]] people.<ref name=efns_guidelines/>

Several other forms of laboratory testing for Lyme disease are available, some of which have not been adequately validated. [[Lyme disease microbiology|OspA antigens]], shed by live ''Borrelia'' bacteria into urine, are a promising technique being studied.<ref>{{cite journal | vauthors = Hyde FW, Johnson RC, White TJ, Shelburne CE | title = Detection of antigens in urine of mice and humans infected with Borrelia burgdorferi, etiologic agent of Lyme disease | journal = Journal of Clinical Microbiology | volume = 27 | issue = 1 | pages = 58–61 | date = January 1989 | pmid = 2913036 | pmc = 267232 | doi = 10.1128/JCM.27.1.58-61.1989 }}</ref> The use of nanotrap particles for their detection is being examined. The OspA protein has been linked to active symptoms of Lyme.<ref>{{cite journal | vauthors = Shafagati N, Patanarut A, Luchini A, Lundberg L, Bailey C, Petricoin E, Liotta L, Narayanan A, Lepene B, Kehn-Hall K | title = The use of Nanotrap particles for biodefense and emerging infectious disease diagnostics | journal = Pathogens and Disease | volume = 71 | issue = 2 | pages = 164–176 | date = July 2014 | pmid = 24449537 | pmc = 7108521 | doi = 10.1111/2049-632X.12136 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Shafagati N, Patanarut A, Luchini A, Lundberg L, Bailey C, Petricoin E, Liotta L, Narayanan A, Lepene B, Kehn-Hall K | title = The use of Nanotrap particles for biodefense and emerging infectious disease diagnostics | journal = Pathogens and Disease | volume = 71 | issue = 2 | pages = 164–176 | date = July 2014 | pmid = 24449537 | pmc = 7108521 | doi = 10.1111/2049-632x.12136 | doi-access = free }}</ref> High [[titer]]s of either immunoglobulin G (IgG) or immunoglobulin M (IgM) antibodies to ''Borrelia'' antigens indicate disease, but lower titers can be misleading, because the IgM antibodies may remain after the initial infection, and IgG antibodies may remain for years.<ref name=Burdash_1991/>

The CDC does not recommend urine antigen tests, PCR tests on urine, immunofluorescent staining for cell-wall-deficient forms of ''B. burgdorferi'', and lymphocyte transformation tests.<ref name="pmid16020686"/>

===Imaging===
[[Neuroimaging]] is controversial in whether it provides specific patterns unique to [[neuroborreliosis]], but may aid in [[differential diagnosis]] and in understanding the pathophysiology of the disease.<ref name="Hildenbrand2009"/> Though controversial, some evidence shows certain neuroimaging tests can provide data that are helpful in the diagnosis of a person. [[Magnetic resonance imaging]] (MRI) and [[single-photon emission computed tomography]] (SPECT) are two tests that can identify abnormalities in the brain of a person affected with this disease. Neuroimaging findings in an MRI include lesions in the periventricular white matter, as well as enlarged ventricles and cortical atrophy. The findings are considered somewhat unexceptional because the lesions have been found to be reversible following antibiotic treatment. Images produced using SPECT show numerous areas where an insufficient amount of blood is being delivered to the cortex and subcortical white matter. However, SPECT images are known to be nonspecific because they show a heterogeneous pattern in the imaging. The abnormalities seen in the SPECT images are very similar to those seen in people with cerebral vasculitis and [[Creutzfeldt–Jakob disease]], which makes them questionable.<ref>{{cite journal | vauthors = Westervelt HJ, McCaffrey RJ | title = Neuropsychological functioning in chronic Lyme disease | journal = Neuropsychology Review | volume = 12 | issue = 3 | pages = 153–177 | date = September 2002 | pmid = 12428915 | doi = 10.1023/A:1020381913563 }}</ref>

===Differential diagnosis===
Community clinics have been reported to misdiagnose 23–28% of [[erythema migrans]] (EM) rashes and 83% of other objective manifestations of early Lyme disease.<ref name=aucott_2008/> EM rashes are often misdiagnosed as [[spider bites]], [[cellulitis]], or [[shingles]].<ref name=aucott_2008/> Many misdiagnoses are credited to the widespread misconception that EM rashes should look like a bull's eye.<ref name=NEJM2014/> Actually, the key distinguishing features of the EM rash are the speed and extent to which it expands, respectively up to 2–3&nbsp;cm (around 1 inch) per day and a diameter of at least 5&nbsp;cm (2 inches), and in 50% of cases more than 16&nbsp;cm (6 inches). The rash expands away from its center, which may or may not look different or be separated by a ring-like clearing from the rest of the rash.<ref name=wright_2012/><ref name=tibbles_2007/> Compared to EM rashes, [[spider bites]] are more common in the limbs, tend to be more painful and itchy or become swollen, and some may cause [[necrosis]] (sinking dark blue patch of dead skin).<ref name=wright_2012/><ref name=NEJM2014/> [[Cellulitis]] most commonly develops around a wound or ulcer, is rarely circular, and is more likely to become swollen and tender.<ref name=wright_2012/><ref name=NEJM2014/> EM rashes often appear at sites that are unusual for cellulitis, such as the armpit, groin, abdomen, or back of the knee.<ref name=wright_2012/> Like Lyme, [[shingles]] often begins with headache, fever, and fatigue, which are followed by pain or numbness. However, unlike Lyme, in shingles, these symptoms are usually followed by the appearance of rashes composed of multiple small blisters along with a nerve's [[Dermatome (anatomy)|dermatome]], and shingles can also be confirmed by quick laboratory tests.<ref name=Dwo2007>{{cite journal | vauthors = Dworkin RH, Johnson RW, Breuer J, Gnann JW, Levin MJ, Backonja M, Betts RF, Gershon AA, Haanpaa ML, McKendrick MW, Nurmikko TJ, Oaklander AL, Oxman MN, Pavan-Langston D, Petersen KL, Rowbotham MC, Schmader KE, Stacey BR, Tyring SK, van Wijck AJ, Wallace MS, Wassilew SW, Whitley RJ | title = Recommendations for the management of herpes zoster | journal = Clinical Infectious Diseases | volume = 44 | issue = Suppl 1 | pages = S1-26 | date = January 2007 | pmid = 17143845 | doi = 10.1086/510206 | doi-access = free }}</ref>

[[Facial palsy]] caused by Lyme disease (LDFP) is often misdiagnosed as [[Bell's palsy]].<ref name=garro_2018/> Although Bell's palsy is the most common type of one-sided facial palsy (about 70% of cases), LDFP can account for about 25% of cases of facial palsy in areas where Lyme disease is common.<ref name=garro_2018/> Compared to LDFP, Bell's palsy much less frequently affects both sides of the face.<ref name=garro_2018/> Even though LDFP and Bell's palsy have similar symptoms and evolve similarly if untreated, corticosteroid treatment is beneficial for Bell's Palsy, while being detrimental for LDFP.<ref name=garro_2018/> Recent history of exposure to a likely tick habitat during warmer months, EM rash, viral-like symptoms such as headache and fever, and/or palsy in both sides of the face should be evaluated for the likelihood of LDFP; if it is more than minimal, [[empiric therapy]] with antibiotics should be initiated, without corticosteroids, and reevaluated upon completion of laboratory tests for Lyme disease.<ref name=garro_2018/>

Unlike [[viral meningitis]], Lyme lymphocytic meningitis tends not to cause fever, last longer, or recur.<ref name=steere_neuro_findings/><ref name="idsa guideline"/> Lymphocytic meningitis is also characterized by possibly co-occurring with EM rash, [[facial palsy]], or [[Papilledema|partial vision obstruction]] and having much lower percentage of polymorphonuclear leukocytes in [[Cerebrospinal fluid|CSF]].<ref name="idsa guideline"/>

Lyme radiculopathy affecting the limbs is often misdiagnosed as a [[radiculopathy]] caused by nerve root compression, such as [[sciatica]].<ref name=aucott_2008/><ref name=halperin_chronic>{{cite journal | vauthors = Halperin JJ | title = Chronic Lyme disease: misconceptions and challenges for patient management | journal = Infection and Drug Resistance | volume = 8 | pages = 119–128 | date = May 2015 | pmid = 26028977 | pmc = 4440423 | doi = 10.2147/IDR.S66739 | doi-access = free }}</ref> Although most cases of radiculopathy are compressive and resolve with conservative treatment (e.g., rest) within 4–6 weeks, guidelines for managing radiculopathy recommend first evaluating risks of other possible causes that, although less frequent, require immediate diagnosis and treatment, including infections such as Lyme and shingles.<ref name=tarulli_radiculopathy>{{cite journal | vauthors = Tarulli AW, Raynor EM | title = Lumbosacral radiculopathy | journal = Neurologic Clinics | volume = 25 | issue = 2 | pages = 387–405 | date = May 2007 | pmid = 17445735 | doi = 10.1016/j.ncl.2007.01.008 }}</ref> A history of outdoor activities in likely tick habitats in the last 3 months possibly followed by a rash or viral-like symptoms, and current headache, other symptoms of lymphocytic meningitis, or facial palsy would lead to suspicion of Lyme disease and recommendation of [[Serology|serological]] and [[lumbar puncture]] tests for confirmation.<ref name=tarulli_radiculopathy/>

Lyme radiculopathy affecting the trunk can be misdiagnosed as myriad other conditions, such as [[diverticulitis]] and [[acute coronary syndrome]].<ref name=halperin_2010/><ref name=aucott_2008/> Diagnosis of late-stage Lyme disease is often complicated by a multifaceted appearance and nonspecific symptoms, prompting one reviewer to call Lyme the new "great imitator".<ref name=Pachner_1989/> As all people with later-stage infection will have a positive antibody test, simple blood tests can exclude Lyme disease as a possible cause of a person's symptoms.<ref name="Branda 541–7">{{cite journal | vauthors = Branda JA, Linskey K, Kim YA, Steere AC, Ferraro MJ | title = Two-tiered antibody testing for Lyme disease with use of 2 enzyme immunoassays, a whole-cell sonicate enzyme immunoassay followed by a VlsE C6 peptide enzyme immunoassay | journal = Clinical Infectious Diseases | volume = 53 | issue = 6 | pages = 541–547 | date = September 2011 | pmid = 21865190 | doi = 10.1093/cid/cir464 | doi-access = free }}</ref>

==Treatment==
<!-- regimens -->
[[Antibiotics]] are the primary treatment.<ref name=NEJM2014/><ref name=wright_2012/> The specific approach to their use is dependent on the individual affected and the stage of the disease.<ref name=wright_2012/> For most people with early localized infection, oral administration of [[doxycycline]] is widely recommended as the first choice, as it is effective against not only ''Borrelia'' bacteria but also a variety of other illnesses carried by ticks.<ref name=wright_2012/> People taking doxycycline should avoid sun exposure because of [[Photosensitivity|higher risk of sunburns]].<ref name="idsa guideline"/> Doxycycline is contraindicated in children younger than eight years of age and women who are pregnant or breastfeeding;<ref name=wright_2012/> alternatives to doxycycline are [[amoxicillin]], [[cefuroxime axetil]], and [[azithromycin]].<ref name=wright_2012/> Azithromycin is recommended only in case of intolerance to the other antibiotics.<ref name="idsa guideline"/> The standard treatment for [[cellulitis]], [[cephalexin]], is not useful for Lyme disease.<ref name="idsa guideline"/> When it is unclear if a rash is caused by Lyme or cellulitis, the [[Infectious Diseases Society of America|IDSA]] recommends treatment with [[cefuroxime]] or [[amoxicillin/clavulanic acid]], as these are effective against both infections.<ref name="idsa guideline"/> Individuals with early disseminated or late Lyme infection may have symptomatic cardiac disease, Lyme arthritis, or neurologic symptoms like [[facial palsy]], [[radiculopathy]], [[meningitis]], or [[peripheral neuropathy]].<ref name=wright_2012/> Intravenous administration of [[ceftriaxone]] is recommended as the first choice in these cases;<ref name=wright_2012/> [[cefotaxime]] and doxycycline are available as alternatives.<ref name=wright_2012/>

<!-- duration/time effects -->
Treatment regimens for Lyme disease range from 7–14 days in early localized disease, to 14–21 days in early disseminated disease, to 14–28 days in late disseminated disease.<ref name="guidelines-2020"/> [[Neuroborreliosis|Neurologic complications of Lyme disease]] may be treated with [[doxycycline]] as it can be taken by mouth and has a lower cost, although in North America evidence of efficacy is only indirect.<ref name="pmid17522387"/> In case of failure, guidelines recommend retreatment with injectable [[ceftriaxone]].<ref name="pmid17522387"/> Several months after treatment for Lyme arthritis, if joint swelling persists or returns, a second round of antibiotics may be considered; intravenous antibiotics are preferred for retreatment in case of poor response to oral antibiotics.<ref name=wright_2012/><ref name="idsa guideline"/> Outside of that, a prolonged antibiotic regimen lasting more than 28 days is not recommended, as no evidence shows it to be effective.<ref name=wright_2012/><ref>{{cite journal | vauthors = Berende A, ter Hofstede HJ, Vos FJ, van Middendorp H, Vogelaar ML, Tromp M, van den Hoogen FH, Donders AR, Evers AW, Kullberg BJ | title = Randomized Trial of Longer-Term Therapy for Symptoms Attributed to Lyme Disease | journal = The New England Journal of Medicine | volume = 374 | issue = 13 | pages = 1209–1220 | date = March 2016 | pmid = 27028911 | doi = 10.1056/NEJMoa1505425 | doi-access = free }}</ref> IgM and IgG antibody levels may be elevated for years even after successful treatment with antibiotics.<ref name=wright_2012/> As antibody levels are not indicative of treatment success, testing for them is not recommended.<ref name=wright_2012/>

Facial palsy may resolve without treatment; however, antibiotic treatment is recommended to stop other Lyme complications.<ref name="idsa guideline"/> Corticosteroids are not recommended when facial palsy is caused by Lyme disease.<ref name=garro_2018>{{cite journal | vauthors = Garro A, Nigrovic LE | title = Managing Peripheral Facial Palsy | journal = Annals of Emergency Medicine | volume = 71 | issue = 5 | pages = 618–624 | date = May 2018 | pmid = 29110887 | doi = 10.1016/j.annemergmed.2017.08.039 | doi-access = free }}</ref> In those with facial palsy, frequent use of artificial tears while awake is recommended, along with ointment and a patch or taping the eye closed when sleeping.<ref name="garro_2018"/><ref name=OTC-Drops>{{cite web | vauthors = Stephenson M |title=OTC Drops: Telling the Tears Apart |url=https://www.reviewofophthalmology.com/article/otc-drops-telling-the-tears-apart |website=Review of Ophtalmology |publisher=Jobson Medical Information LLC |date=4 October 2012 |access-date=16 April 2019 |archive-url=https://web.archive.org/web/20190417202911/https://www.reviewofophthalmology.com/article/otc-drops-telling-the-tears-apart |archive-date=17 April 2019 |url-status=live }}</ref>

About a third of people with Lyme carditis need a temporary [[Artificial cardiac pacemaker|pacemaker]] until their heart conduction abnormality resolves, and 21% need to be hospitalized.<ref name=fish_2008/> Lyme carditis should not be treated with corticosteroids.<ref name=fish_2008/>

People with Lyme arthritis should limit their level of physical activity to avoid damaging affected joints, and in case of limping, should use crutches.<ref name=arvikar_2015/> Pain associated with Lyme disease may be treated with [[nonsteroidal anti-inflammatory drug]]s (NSAIDs).<ref name="idsa guideline"/> Corticosteroid [[joint injection]]s are not recommended for Lyme arthritis that is being treated with antibiotics.<ref name="idsa guideline"/><ref name=arvikar_2015/> People with Lyme arthritis treated with intravenous antibiotics or two months of oral antibiotics who continue to have [[synovitis|joint swelling]] two months after treatment and have negative [[Polymerase chain reaction|PCR]] test for ''[[Borrelia]]'' [[DNA]] in the [[synovial fluid]] are said to have post-antibiotic Lyme arthritis; this is more common after infection by certain Borrelia strains in people with certain genetic and immunologic characteristics.<ref name="idsa guideline"/><ref name="guidelines-2020"/><ref name=arvikar_2015>{{cite journal | vauthors = Arvikar SL, Steere AC | title = Diagnosis and treatment of Lyme arthritis | journal = Infectious Disease Clinics of North America | volume = 29 | issue = 2 | pages = 269–280 | date = June 2015 | pmid = 25999223 | pmc = 4443866 | doi = 10.1016/j.idc.2015.02.004 }}</ref> Post-antibiotic Lyme arthritis may be symptomatically treated with NSAIDs, [[disease-modifying antirheumatic drugs]] (DMARDs), arthroscopic [[synovectomy]], or physical therapy.<ref name="guidelines-2020"/><ref name=arvikar_2015/>

People receiving treatment should be advised that reinfection is possible and [[#Prevention|how to prevent it]].<ref name=lyme_guidelines_uk/>

==Prognosis==
Lyme disease's typical first sign, the [[erythema migrans]] (EM) rash, resolves within several weeks even without treatment.<ref name=NEJM2014/> However, in untreated people, the infection often disseminates to the nervous system, heart or joints, possibly causing permanent damage to body tissues.<ref name="idsa guideline"/>

People who receive recommended antibiotic treatment within several days of the appearance of an initial EM rash have the best prospects.<ref name=aucott_2008/> Recovery may not be total or immediate. The percentage of people achieving full recovery in the United States increases from about 64–71% at the end of treatment for EM rash to about 84–90% after 30 months; higher percentages are reported in Europe.<ref name=wormser_2003>{{cite journal | vauthors = Wormser GP, Ramanathan R, Nowakowski J, McKenna D, Holmgren D, Visintainer P, Dornbush R, Singh B, Nadelman RB | title = Duration of antibiotic therapy for early Lyme disease. A randomized, double-blind, placebo-controlled trial | journal = Annals of Internal Medicine | volume = 138 | issue = 9 | pages = 697–704 | date = May 2003 | pmid = 12729423 | doi = 10.7326/0003-4819-138-9-200305060-00005 }}</ref><ref name=stupica_2012>{{cite journal | vauthors = Stupica D, Lusa L, Ruzić-Sabljić E, Cerar T, Strle F | title = Treatment of erythema migrans with doxycycline for 10 days versus 15 days | journal = Clinical Infectious Diseases | volume = 55 | issue = 3 | pages = 343–350 | date = August 2012 | pmid = 22523260 | doi = 10.1093/cid/cis402 | doi-access = free }}</ref> Treatment failure, i.e. persistence of original or appearance of new signs of the disease, occurs only in a few people.<ref name=wormser_2003/> Remaining people are considered cured but continue to experience subjective symptoms, e.g., [[arthralgia|joint]] or [[myalgia|muscle pains]] or [[fatigue]].<ref name=dattwyler_1997/> These symptoms are usually mild and nondisabling.<ref name=dattwyler_1997>{{cite journal | vauthors = Dattwyler RJ, Luft BJ, Kunkel MJ, Finkel MF, Wormser GP, Rush TJ, Grunwaldt E, Agger WA, Franklin M, Oswald D, Cockey L, Maladorno D | title = Ceftriaxone compared with doxycycline for the treatment of acute disseminated Lyme disease | journal = The New England Journal of Medicine | volume = 337 | issue = 5 | pages = 289–294 | date = July 1997 | pmid = 9233865 | doi = 10.1056/NEJM199707313370501 | doi-access = free }}</ref>

People treated only after nervous system manifestations of the disease may end up with objective neurological deficits, in addition to subjective symptoms.<ref name="idsa guideline"/> In Europe, an average of 32–33 months after initial Lyme symptoms in people treated mostly with doxycycline 200&nbsp;mg for 14–21 days, the percentage of people with lingering symptoms was much higher among those diagnosed with [[neuroborreliosis]] (50%) than among those with only an EM rash (16%).<ref name=vrethem_2002>{{cite journal | vauthors = Vrethem M, Hellblom L, Widlund M, Ahl M, Danielsson O, Ernerudh J, Forsberg P | title = Chronic symptoms are common in patients with neuroborreliosis -- a questionnaire follow-up study | journal = Acta Neurologica Scandinavica | volume = 106 | issue = 4 | pages = 205–208 | date = October 2002 | pmid = 12225315 | doi = 10.1034/j.1600-0404.2002.01358.x | doi-access = free }}</ref> In another European study, 5 years after treatment for neuroborreliosis lingering symptoms were less common among children (15%) than adults (30%), and in the latter were less common among those treated within 30 days of the first symptom (16%) than among those treated later (39%); among those with lingering symptoms, 54% had daily activities restricted and 19% were on sick leave or incapacitated.<ref name=berglund_2002>{{cite journal | vauthors = Berglund J, Stjernberg L, Ornstein K, Tykesson-Joelsson K, Walter H | title = 5-y Follow-up study of patients with neuroborreliosis | journal = Scandinavian Journal of Infectious Diseases | volume = 34 | issue = 6 | pages = 421–425 | date = 2002 | pmid = 12160168 | doi = 10.1080/00365540110080421 }}</ref>

Some data suggest that about 90% of Lyme [[Facial palsy|facial palsies]] treated with antibiotics recover fully a median of 24 days after appearing and most of the rest recover with only mild abnormality.<ref name=clark_1985>{{cite journal | vauthors = Clark JR, Carlson RD, Sasaki CT, Pachner AR, Steere AC | title = Facial paralysis in Lyme disease | journal = The Laryngoscope | volume = 95 | issue = 11 | pages = 1341–1345 | date = November 1985 | pmid = 4058212 | doi = 10.1288/00005537-198511000-00009 }}</ref><ref name=dovetall_1999>{{cite journal | vauthors = Dotevall L, Hagberg L | title = Successful oral doxycycline treatment of Lyme disease-associated facial palsy and meningitis | journal = Clinical Infectious Diseases | volume = 28 | issue = 3 | pages = 569–574 | date = March 1999 | pmid = 10194080 | doi = 10.1086/515145 | doi-access = free }}</ref> However, in Europe 41% of people treated for facial palsy had other lingering symptoms at followup up to 6 months later, including 28% with [[hypoesthesia|numbness]] or [[paresthesia|altered sensation]] and 14% with [[fatigue]] or [[Attentional control|concentration]] problems.<ref name=dovetall_1999/> Palsies in both sides of the face are associated with worse and longer time to recovery.<ref name=clark_1985/><ref name=dovetall_1999/> Historical data suggests that untreated people with facial palsies recover at nearly the same rate, but 88% subsequently have Lyme arthritis.<ref name=clark_1985/><ref name=kalish_2001>{{cite journal | vauthors = Kalish RA, Kaplan RF, Taylor E, Jones-Woodward L, Workman K, Steere AC | title = Evaluation of study patients with Lyme disease, 10-20-year follow-up | journal = The Journal of Infectious Diseases | volume = 183 | issue = 3 | pages = 453–460 | date = February 2001 | pmid = 11133377 | doi = 10.1086/318082 | doi-access = free }}</ref> Other research shows that [[synkinesis]] (involuntary movement of a facial muscle when another one is voluntarily moved) can become evident only 6–12 months after facial palsy appears to be resolved, as damaged nerves regrow and sometimes connect to incorrect muscles.<ref name=jowett_2017>{{cite journal | vauthors = Jowett N, Gaudin RA, Banks CA, Hadlock TA | title = Steroid use in Lyme disease-associated facial palsy is associated with worse long-term outcomes | journal = The Laryngoscope | volume = 127 | issue = 6 | pages = 1451–1458 | date = June 2017 | pmid = 27598389 | doi = 10.1002/lary.26273 }}</ref> Synkinesis is associated with [[corticosteroid]] use.<ref name=jowett_2017/> In longer-term follow-up, 16–23% of Lyme facial palsies do not fully recover.<ref name=jowett_2017/>

In Europe, about a quarter of people with [[Bannwarth syndrome]] (Lyme [[radiculopathy]] and [[Aseptic meningitis|lymphocytic meningitis]]) treated with [[intravenous]] [[ceftriaxone]] for 14 days an average of 30 days after first symptoms had to be retreated 3–6 months later because of unsatisfactory clinical response or continued [[Lymphocytic pleocytosis|objective markers of infection]] in [[cerebrospinal fluid]]; after 12 months, 64% recovered fully, 31% had nondisabling mild or infrequent symptoms that did not require regular use of analgesics, and 5% had symptoms that were disabling or required substantial use of analgesics.<ref name=ogrinc_bannwarth/> The most common lingering nondisabling symptoms were headache, [[fatigue]], [[paresthesia|altered sensation]], [[arthralgia|joint pains]], [[memory]] disturbances, [[malaise]], [[Radiculitis|radicular pain]], [[sleep]] disturbances, [[myalgia|muscle pains]], and [[Attentional control|concentration]] disturbances. Lingering disabling symptoms included [[facial palsy]] and other [[paresis|impaired movement]].<ref name=ogrinc_bannwarth/>

Recovery from late neuroborreliosis tends to take longer and be less complete than from early neuroborreliosis, probably because of irreversible neurologic damage.<ref name="idsa guideline"/>

About half the people with Lyme carditis progress to complete [[heart block]], but it usually resolves in a week.<ref name=fish_2008/> Other Lyme heart conduction abnormalities resolve typically within 6 weeks.<ref name=fish_2008/> About 94% of people have full recovery, but 5% need a permanent [[Artificial cardiac pacemaker|pacemaker]] and 1% end up with persistent heart block (the actual percentage may be higher because of unrecognized cases).<ref name=fish_2008/> Lyme [[Cardiac muscle|myocardial]] complications usually are mild and self-limiting.<ref name=fish_2008/> However, in some cases Lyme carditis can be fatal.<ref name=fish_2008/>

Recommended antibiotic treatments are effective in about 90% of Lyme arthritis cases, although it can take several months for inflammation to resolve and a second round of antibiotics is often necessary.<ref name="idsa guideline"/> Antibiotic-refractory Lyme arthritis also eventually resolves, typically within 9–14 months (range 4 months – 4 years); [[DMARD]]s or [[synovectomy]] can accelerate recovery.<ref name=arvikar_2015/>

Reinfection is not uncommon. In a U.S. study, 6–11% of people treated for an EM rash had another EM rash within 30 months.<ref name=wormser_2003/> The second rash typically is due to infection by a different [[Borrelia]] strain.<ref name=nadelman_2012>{{cite journal | vauthors = Nadelman RB, Hanincová K, Mukherjee P, Liveris D, Nowakowski J, McKenna D, Brisson D, Cooper D, Bittker S, Madison G, Holmgren D, Schwartz I, Wormser GP | title = Differentiation of reinfection from relapse in recurrent Lyme disease | journal = The New England Journal of Medicine | volume = 367 | issue = 20 | pages = 1883–1890 | date = November 2012 | pmid = 23150958 | pmc = 3526003 | doi = 10.1056/NEJMoa1114362 }}</ref>

=== Post-treatment Lyme disease syndrome ===

====Symptoms and prevalence====
Chronic symptoms like pain, fatigue, or cognitive impairment are experienced by 5–20% of people who contract Lyme disease, even after completing treatment. This is called Post-treatment Lyme disease syndrome, or PTLDS.<ref name=":0" /><ref name=":1">{{cite journal | vauthors = Bai NA, Richardson CS | title = Posttreatment Lyme disease syndrome and myalgic encephalomyelitis/chronic fatigue syndrome: A systematic review and comparison of pathogenesis | journal = Chronic Diseases and Translational Medicine | volume = 9 | issue = 3 | pages = 183–190 | date = September 2023 | pmid = 37711861 | pmc = 10497844 | doi = 10.1002/cdt3.74 }}</ref>

====Causes====
The cause is unknown.<ref name="auto2">{{Cite journal|title=What Makes It Tick: Exploring the Mechanisms of Post-treatment Lyme Disease Syndrome|first1=Kate E.|last1=Wester|first2=Bianca C.|last2=Nwokeabia|first3=Rehana|last3=Hassan|first4=Taylor|last4=Dunphy|first5=Michael|last5=Osondu|first6=Carson|last6=Wonders|first7=Misbahuddin|last7=Khaja|date=5 July 2024|journal=Cureus|volume=16|issue=7|article-number=e64987|doi=10.7759/cureus.64987|doi-access=free |pmid=39161484|pmc=11332314}}</ref> Hypotheses include;
*that a persistent, difficult-to-detect infection remains. However, human and animal trials have not provided compelling evidence to support this hypothesis.<ref name="marques-2022">{{cite journal |last1=Marques |first1=Adriana |title=Persistent Symptoms After Treatment of Lyme Disease |journal=Infectious Disease Clinics of North America |date=September 2022 |volume=36 |issue=3 |pages=621–638 |doi=10.1016/j.idc.2022.04.004 |pmid=36116839 |pmc=9494579}}</ref> 
*that the infection triggered autoimmunity. Autoimmune responses are known to occur following other infections, including ''Campylobacter'' ([[Guillain–Barré syndrome]]), ''Chlamydia'' (reactive arthritis), and strep throat (rheumatic heart disease). 
*that debris from a previous infection could remain.<ref name="marques-2022"/> 
*that symptoms are unrelated to a Lyme infection.<ref name="CDC_2016">{{cite web |date=3 November 2016 |title=Post-Treatment Lyme Disease Syndrome |url=https://www.cdc.gov/lyme/postLDS/index.html |archive-url=https://web.archive.org/web/20170617203133/https://www.cdc.gov/lyme/postlds/index.html |archive-date=17 June 2017 |publisher=CDC}}{{PD-notice}}</ref><ref name="Post-treatment Lyme, Rebman">{{cite journal |last1=Rebman |first1=Alison W. |last2=Aucott |first2=John N. |title=Post-treatment Lyme Disease as a Model for Persistent Symptoms in Lyme Disease |journal=Frontiers in Medicine |date=2020 |volume=7 |article-number=57 |doi=10.3389/fmed.2020.00057 |doi-access=free |pmid=32161761 |pmc=7052487 }}</ref> In studies of people who presented to clinics with concerns about Lyme disease, 47 to 80% had no evidence of Lyme infection while 15 to 55% (median 34%) were able to obtain other diagnoses.<ref name="marques-2022"/>

====Risk factors====
Risk factors for PTLDS include delayed diagnosis and treatment, incomplete or short-course treatment, and higher severity of initial disease.<ref name="auto2"/>

====Treatment and management====
There is no proven treatment for Post-treatment Lyme disease syndrome. While short-term antibiotics are effective in early Lyme disease, prolonged antibiotics are not. They have been shown to be ineffective in placebo-controlled trials and carry the risk of serious, sometimes deadly complications. Generally, treatment is symptomatic and is similar to the management of [[fibromyalgia]] or [[Myalgic encephalomyelitis/chronic fatigue syndrome|ME/CFS]]. A 2023 review found that PTLDS and ME/CFS had similar pathogenesis despite different infectious origins.<ref>{{Cite journal|title=Posttreatment Lyme disease syndrome and myalgic encephalomyelitis/chronic fatigue syndrome: A systematic review and comparison of pathogenesis|first1=Natalie A.|last1=Bai|first2=Christie S.|last2=Richardson|date=5 September 2023|journal=Chronic Diseases and Translational Medicine|volume=9|issue=3|pages=183–190|doi=10.1002/cdt3.74|pmid=37711861|pmc=10497844}}</ref>

====Prognosis====
Patients typically improve over time without additional antibiotics, but this may take several months.<ref>{{Cite web|url=https://www.cdc.gov/lyme/signs-symptoms/chronic-symptoms-and-lyme-disease.html|title=Chronic Symptoms and Lyme Disease|date=31 January 2025|website=Lyme Disease}}</ref> There is a lack of long-term data, with few studies of symptoms more than 12 months from initial infection.

==Epidemiology and prevalence==
[[File:Geographical distribution of reported Lyme Disease cases.png|thumb|upright=1.35|Countries with reported Lyme disease cases]]

===Overview===
Lyme disease [[Endemic (epidemiology)|occurs regularly]] in [[Northern Hemisphere]] temperate regions.<ref name=Higgins_2004/> 

Lyme disease effects are comparable among males and females. A wide range of age groups is affected, though the number of cases is highest among 10- to 19-year-olds.

An estimated 476,000 people a year are diagnosed and treated for the disease in the United States. This number is probably an overestimate due to overdiagnosis and overtreatment.<ref name="cdc-how-many"/><ref name="cdc-estimate-2021"/> This number has grown over time.<ref>{{Cite web|url=https://www.epa.gov/climate-indicators/climate-change-indicators-lyme-disease|title=Climate Change Indicators: Lyme Disease|first=OAR|last=US EPA|date=1 July 2016|website=www.epa.gov|access-date=5 May 2025|archive-date=1 May 2025|archive-url=https://web.archive.org/web/20250501192750/https://www.epa.gov/climate-indicators/climate-change-indicators-lyme-disease|url-status=live}}</ref> Over 200,000 people a year are diagnosed and treated in Europe.<ref name="comparison-2021" /><ref name=NEJM2014/><ref name=Berg2014>{{cite book| vauthors = Berger S |title=Lyme disease: Global Status 2014 Edition|date=2014|publisher=GIDEON Informatics Inc|isbn=978-1-4988-0343-4|page=7|url=https://books.google.com/books?id=DuKCBQAAQBAJ&pg=PA7|url-status=live|archive-url=https://web.archive.org/web/20170908151350/https://books.google.com/books?id=DuKCBQAAQBAJ&pg=PA7|archive-date=8 September 2017}}</ref> 

===Climate change===
{{Further|Weather and climate effects on Lyme disease exposure}}
Climate change is seen as potentially supportive for ticks.<ref>{{Cite web|url=https://www.bbc.co.uk/news/articles/c74llex44d3o|title=Lyme disease increase risk in Scotland due to climate change|date=6 August 2024|website=BBC News|access-date=5 May 2025|archive-date=14 February 2025|archive-url=https://web.archive.org/web/20250214223332/https://www.bbc.co.uk/news/articles/c74llex44d3o|url-status=live}}</ref><ref>{{Cite journal|title=Impact of prior and projected climate change on US Lyme disease incidence|first1=Lisa I.|last1=Couper|first2=Andrew J.|last2=MacDonald|first3=Erin A.|last3=Mordecai|date=5 February 2021|journal=Global Change Biology|volume=27|issue=4|pages=738–754|doi=10.1111/gcb.15435|pmid=33150704|pmc=7855786|bibcode=2021GCBio..27..738C }}</ref> There is a suggestion that tick populations and Lyme disease occurrence are increasing and spreading into new areas, owing in part to the warming temperatures of [[climate change]].<ref>{{Cite web|url=https://www.ft.com/content/482e3eb0-cc26-4ef7-a53f-828a86303a34|title=Lyme disease bites as ticks gain ground in US|first=Andrew|last=Jack|work=Financial Times |date=29 April 2024}}</ref> However, tick-borne disease systems are complex, and determining whether changes are due to climate change or other drivers can be difficult.<ref name="Chrobak"/><ref name="Gilbert">{{cite journal | vauthors = Gilbert L | title = The Impacts of Climate Change on Ticks and Tick-Borne Disease Risk | journal = Annual Review of Entomology | volume = 66 | issue = 1 | pages = 373–388 | date = January 2021 | pmid = 33417823 | doi = 10.1146/annurev-ento-052720-094533 | doi-access = free }}</ref>

===North America===
Many studies in North America have examined ecological and environmental correlates of the number of people affected by Lyme disease. A 2005 study using climate suitability modelling of ''I. scapularis'' projected that [[Effects of climate change on human health|climate change would cause]] an overall 213% increase in suitable vector habitat by 2080, with northward expansions in Canada, increased suitability in the central U.S., and decreased suitable habitat and vector retraction in the southern U.S.<ref name=Brownstein_etal_2005>{{cite journal | vauthors = Brownstein JS, Holford TR, Fish D | title = Effect of Climate Change on Lyme Disease Risk in North America | journal = EcoHealth | volume = 2 | issue = 1 | pages = 38–46 | date = March 2005 | pmid = 19008966 | pmc = 2582486 | doi = 10.1007/s10393-004-0139-x }}</ref> A 2008 review of published studies concluded that the presence of forests or forested areas was the only variable that consistently elevated the risk of Lyme disease whereas other environmental variables showed little or no concordance between studies.<ref name=Killilea_etal_2008>{{cite journal | vauthors = Killilea ME, Swei A, Lane RS, Briggs CJ, Ostfeld RS | title = Spatial dynamics of lyme disease: a review | journal = EcoHealth | volume = 5 | issue = 2 | pages = 167–195 | date = June 2008 | pmid = 18787920 | doi = 10.1007/s10393-008-0171-3 }}</ref> The authors argued that the factors influencing tick density and human risk between sites are still poorly understood, and that future studies should be conducted over longer periods, become more standardized across regions, and incorporate existing knowledge of regional Lyme [[disease ecology]].<ref name=Killilea_etal_2008/>

==== United States ====
[[File:Lyme Disease Risk Map.gif|thumb|upright=1.35|[[Centers for Disease Control and Prevention|CDC]] map showing the risk of Lyme disease in the United States, particularly its concentration in the [[Northeast Megalopolis]] and western [[Wisconsin]] (2004)]]

Lyme disease is the most common tick-borne disease in North America and Europe, and one of the fastest-growing infectious diseases in the United States. Of cases reported to the United States CDC, the ratio of Lyme disease infection is 7.9 cases for every 100,000 persons. In the ten states where Lyme disease is most common, the average was 31.6 cases for every 100,000 persons for the year 2005.<ref name=cdc_stats_2012/><ref name=mmwr_2007/><ref name=Bacon_2008/>

Although Lyme disease has been reported in all states due to travel-associated infections, about 99% of all reported cases are confined to just five geographic areas (New England, Mid-Atlantic, East-North Central, South Atlantic, and West North-Central).<ref name=CDC-FAQ/><ref name=cdc_stats2/><ref name="nytimes.com"/> CDC implemented national surveillance of Lyme disease cases in 1991. Since then, reporting criteria have been modified multiple times.<ref name="cdc-surveillance">{{cite web |title=National Notifiable Diseases Surveillance System (NNDSS) - Lyme Disease |url=https://ndc.services.cdc.gov/conditions/lyme-disease/ |website=Centers for Disease Control and Prevention |access-date=11 January 2023 |date=7 September 2021 |archive-date=11 January 2023 |archive-url=https://web.archive.org/web/20230111234149/https://ndc.services.cdc.gov/conditions/lyme-disease/ |url-status=live }}</ref> The 2022 surveillance case definition classifies cases as confirmed, probable, and suspect.<ref name="cdc-surveillance-2022">{{cite web |title=Lyme Disease (Borrelia burgdorferi) 2022 Case Definition  |url=https://ndc.services.cdc.gov/case-definitions/lyme-disease-2022/ |website=Centers for Disease Control and Prevention |access-date=11 January 2023 |date=12 August 2022}}</ref> The number of reported cases of the disease has been increasing, as are endemic regions in North America.

The CDC emphasizes that, while surveillance data have limitations, they are useful due to "uniformity, simplicity, and timeliness." While cases are under-reported in high-incidence areas, over-reporting is likely in low-incidence areas. Additionally, surveillance cases are reported by the county of residence and not where an infection was necessarily contracted.<ref name="cdc-surveillance-faq">{{cite web |title=Lyme disease surveillance and available data |url=https://www.cdc.gov/lyme/stats/survfaq.html |website=Centers for Disease Control and Prevention |access-date=11 January 2023 |language=en-us |date=15 November 2022}}</ref><ref name=CDC-FAQ/>

Several similar but distinct conditions may exist, caused by various species or subspecies of ''Borrelia'' in North America. A regionally restricted condition that may be related to ''Borrelia'' infection is [[southern tick-associated rash illness]] (STARI), also known as Masters disease. ''[[Amblyomma americanum]]'', known commonly as the lone-star tick, is recognized as the primary vector for STARI. In some parts of the geographical distribution of STARI, Lyme disease is quite rare (e.g., Arkansas), so people in these regions experiencing Lyme-like symptoms—especially if they follow a bite from a lone-star tick—should consider STARI as a possibility. It is generally a milder condition than Lyme and typically responds well to antibiotic treatment.<ref>{{Cite web|url=https://www.cdc.gov/stari/disease/index.html|title=STARI or Lyme?|date=19 November 2018|website=Centers for Disease Control and Prevention|url-status=live|archive-url=https://web.archive.org/web/20191112160112/https://www.cdc.gov/stari/disease/index.html|archive-date=12 November 2019}}</ref>

In recent years,{{when|date=November 2025}} five to ten cases a year of a disease similar to Lyme have been occurring in Montana. It occurs primarily in pockets along the [[Yellowstone River]] in central Montana. Symptons have bee a red bull's-eye rash around a tick bite, followed by weeks of fatigue and a fever.<ref name="nytimes.com"/>

==== Canada ====
The range of ticks capable of carrying Lyme disease has expanded from a limited area of Ontario to include areas of southern Quebec, Manitoba, northern Ontario, southern New Brunswick, southwest Nova Scotia and limited parts of Saskatchewan and Alberta, as well as British Columbia. Cases have been reported as far east as the island of Newfoundland.<ref name=canada_lyme_map/><ref name=min_ag_2012/><ref name=fact_sheet_2012/><ref name=Ogden_2009/> A model-based prediction by Leighton ''et al.'' (2012) suggests that the range of the ''I. scapularis'' tick will expand into Canada by 46&nbsp;km/year over the next decade, with warming climatic temperatures as the main driver of increased speed of spread.<ref name=Leighton_2012/>

===Europe===
In Europe, Lyme disease is caused by infection with one or more pathogenic European genospecies of the spirochaete ''B. burgdorferi sensu lato'', mainly transmitted by the tick ''[[Ixodes ricinus]]''.<ref name="pmid21794218"/> Cases of ''B. burgdorferi sensu lato''-infected ticks are found predominantly in central Europe, particularly in [[Slovenia]] and Austria, but have been isolated in almost every country on the continent.<ref name="pmid16819127"/> The number of cases in southern Europe, such as Italy and Portugal, is much lower.<ref name="pmid17130658"/> Diagnosed cases in some Western countries, such as Iceland, are rising.<ref>{{cite journal | vauthors = Vandekerckhove O, De Buck E, Van Wijngaerden E | title = Lyme disease in Western Europe: an emerging problem? A systematic review | journal = Acta Clinica Belgica | volume = 76 | issue = 3 | pages = 244–252 | date = June 2021 | pmid = 31739768 | doi = 10.1080/17843286.2019.1694293 }}</ref> Lyme disease is rare in Iceland. On average, around 6 to 7 cases are diagnosed every year, primarily localised infections presenting as erythema migrans. None of the cases had a definitive Icelandic origin and the yearly number of cases has not been increasing.<ref>{{cite journal | vauthors = Vigfusson HB, Hardarson HS, Ludviksson BR, Gudlaugsson O | title = [Lyme disease in Iceland - Epidemiology from 2011 to 2015] | journal = Laeknabladid | volume = 105 | issue = 2 | pages = 63–70 | date = February 2019 | pmid = 30713153 | doi = 10.17992/lbl.2019.02.215 | doi-access = free }}</ref>

==== United Kingdom ====
In the United Kingdom the number of laboratory-confirmed cases of Lyme disease has been rising steadily since voluntary reporting was introduced in 1986<ref name=hpaEpidemiology/> when 68 cases were recorded in the UK and Ireland combined.<ref name=Muhlemann_1987/> In the UK there were 23 confirmed cases in 1988 and 19 in 1990,<ref name=hansard1991/> but 973 in 2009<ref name=hpaEpidemiology /> and 953 in 2010.<ref name=hpa5-15/> Provisional figures for the first 3 quarters of 2011 show a 26% increase on the same period in 2010.<ref name=disease_action_2011/>

It is thought, however, that the actual number of cases is significantly higher than suggested by the above figures, with England's [[Health Protection Agency]] estimating that there are between 2,000 and 3,000 cases in England and Wales per year<ref name=hpa5-15 /> (with an average of around 15% of the infections acquired overseas<ref name=hpaEpidemiology />), while Dr Darrel Ho-Yen, Director of the Scottish Toxoplasma Reference Laboratory and National Lyme Disease Testing Service, believes that the number of confirmed cases should be multiplied by 10 "to take account of wrongly diagnosed cases, tests giving false results, sufferers who weren't tested, people who are infected but not showing symptoms, failures to notify and infected individuals who don't consult a doctor."<ref name=cassidy_2011/><ref name=danger_2009/>

Lyme disease is a [[notifiable disease]] in Scotland.<ref name=scotland_2012/><ref name=hansard_1997/> Mandatory reporting, limited to laboratory test results only, is required in the UK under the provisions of the Health Protection (Notification) Regulations 2010.<ref name=hpaEpidemiology />

Although there is a greater number of cases of Lyme disease in the [[New Forest]], [[Salisbury Plain]], [[Exmoor]], the [[South Downs]], parts of [[Wiltshire]] and [[Berkshire]], [[Thetford Forest]]<ref name=hpa_2013/> and the West coast and islands of Scotland,<ref name=defra_2009/> infected ticks are widespread and can even be found in the parks of London.<ref name=hansard1991 /><ref name=tick_bite/> A 1989 report found that 25% of forestry workers in the New Forest were [[seropositive]], as were between 2% and 4–5% of the general local population of the area.<ref name="pmid8037992"/><ref name="pmid2563850"/>

Tests on pet dogs carried out throughout the country in 2009 indicated that around 2.5% of ticks in the UK may be infected, considerably higher than previously thought.<ref name=Smith_2012/><ref name=bbc_dogs_2012/> It is speculated that [[global warming]] may lead to an increase in tick activity in the future, as well as an increase in the amount of time that people spend in public parks, thus increasing the risk of infection.<ref name=londong_2008/> However, no published research has proven this to be so.

===South America===
In Brazil, Lyme disease is not considered endemic.<ref name="BYS-2024"/> A Lyme-like disease known as [[Baggio–Yoshinari syndrome]] has been described, attributed to microorganisms that do not belong to the ''B. burgdorferi sensu lato'' complex and transmitted by ticks of the ''[[Amblyomma]]'' and ''[[Rhipicephalus]]'' genera.<ref name=Mantovani_2007/> The first reported case of BYS in Brazil was made in 1992 in [[Cotia]], São Paulo.<ref name=Yoshinari_1993/> A 2024 analysis concluded that evidence to connect BYS to ''Borrelia'' bacteria was lacking.<ref name="BYS-2024">{{cite journal |last1=Labruna |first1=Marcelo B. |last2=Faccini-Martínez |first2=Álvaro A. |last3=Muñoz-Leal |first3=Sebastián |last4=Szabó |first4=Matias P. J. |last5=Angerami |first5=Rodrigo N. |title=Lyme borreliosis in Brazil: a critical review on the Baggio–Yoshinari syndrome (Brazilian Lyme-like disease) |journal=Clinical Microbiology Reviews |date=4 November 2024 |volume=37 |issue=4 |pages=e0009724 |doi=10.1128/cmr.00097-24|pmid=39494872 |pmc=11629638 }}</ref>

====Mexico====
A 2007 study suggests ''Borrelia burgdorferi'' infections are endemic to Mexico, with four cases reported between 1999 and 2000.<ref name="cdc_dispatch_oct_2007" />

===Africa===
In northern Africa, ''B. burgdorferi sensu lato'' has been identified in [[Morocco]], [[Algeria]], [[Egypt]] and [[Tunisia]].<ref name=Bouattour_2004/><ref name=Dsouli_2006/><ref name=Helmy_2000/>

Lyme disease in sub-Saharan Africa is presently unknown, but evidence indicates it may occur in humans in this region. The abundance of hosts and tick vectors would favor the establishment of Lyme infection in Africa.<ref name=Fivaz_1989/> In East Africa, two cases of Lyme disease have been reported in [[Kenya]].<ref name=Jowi_2005/> According The Federation of Infectious Diseases Societies of Southern Africa, Lyme disease is not known to be endemic in either South Africa or Mozambique.<ref>{{Cite web | title = Case of the Month | date = December 2015 | url = https://www.fidssa.co.za/news-events/case-2015-dec-issue-12 | access-date = 2023-11-02 | work = Federation of Infectious Diseases Societies of Southern Africa (FIDSSA) | language = en | archive-date = 2 November 2023 | archive-url = https://web.archive.org/web/20231102193248/https://www.fidssa.co.za/news-events/case-2015-dec-issue-12 | url-status = live }}</ref>

===Asia===
''B. burgdorferi sensu lato''-infested ticks are being found more frequently in Japan, as well as in northwest China, [[Nepal]], [[Thailand]] and far eastern Russia.<ref name=Li_1998/><ref name="pmid15623946"/> ''Borrelia'' has also been isolated in [[Mongolia]].<ref name=Walder_2006/>

===Australia===
Lyme disease is not considered endemic to Australia.<ref name="pmid30746341">{{cite journal | vauthors = Dehhaghi M, Kazemi Shariat Panahi H, Holmes EC, Hudson BJ, Schloeffel R, Guillemin GJ | title = Human Tick-Borne Diseases in Australia | journal = Frontiers in Cellular and Infection Microbiology | volume = 9 | issue =  | article-number = 3 | year = 2019 | pmid = 30746341 | pmc = 6360175 | doi = 10.3389/fcimb.2019.00003 | doi-access = free }}</ref> While there have been reports of people acquiring Lyme disease in Australia, and even evidence of closely related ''Borrelia'' species in ticks,<ref name="pmid35502617">{{cite journal | vauthors = Gofton AW, Blasdell KR, Taylor C, Banks PB, Michie M, Roy-Dufresne E, Poldy J, Wang J, Dunn M, Tachedjian M, Smith I | title = Metatranscriptomic profiling reveals diverse tick-borne bacteria, protozoans and viruses in ticks and wildlife from Australia | journal = Transboundary and Emerging Diseases | volume = 69 | issue = 5 | pages = e2389–e2407 | date = September 2022 | pmid = 35502617 | pmc = 9790515 | doi = 10.1111/tbed.14581 }}</ref> the evidence linking these cases to local transmission is limited. Ongoing research on resolving potential ''Borrelia'' species to Debilitating Symptom Complexes Attributed to Ticks (DSCATT) in Australia is ongoing.<ref name="pmid36365042">{{cite journal | vauthors = Barbosa AD, Long M, Lee W, Austen JM, Cunneen M, Ratchford A, Burns B, Kumarasinghe P, Ben-Othman R, Kollmann TR, Stewart CR, Beaman M, Parry R, Hall R, Tabor A, O'Donovan J, Faddy HM, Collins M, Cheng AC, Stenos J, Graves S, Oskam CL, Ryan UM, Irwin PJ | title = The Troublesome Ticks Research Protocol: Developing a Comprehensive, Multidiscipline Research Plan for Investigating Human Tick-Associated Disease in Australia | journal = Pathogens | volume = 11 | issue = 11 | page = 1290 | date = November 2022 | pmid = 36365042 | pmc = 9694322 | doi = 10.3390/pathogens11111290 | doi-access = free }}</ref>

==Prevention==
Tick bites can be prevented by avoiding or reducing time in likely tick habitats and taking precautions while in and when getting out of one.<ref name=CDC_Lyme_prev_on_people>{{cite web | title=Preventing tick bites on people | url=https://www.cdc.gov/lyme/prev/on_people.html | website=Lyme Disease | publisher=Centers for Disease Control and Prevention | access-date=21 May 2019 | date=8 March 2019 | archive-url=https://web.archive.org/web/20190615054936/https://www.cdc.gov/lyme/prev/on_people.html | archive-date=15 June 2019 | url-status=live }}</ref><ref name="NYT-20210611" />

Most Lyme human infections are caused by [[Ixodes]] nymph bites between April and September.<ref name=wright_2012/><ref name=CDC_Lyme_prev_on_people/> Ticks prefer moist, shaded locations in [[woodland]]s, shrubs, tall grasses and [[leaf litter]] or wood piles.<ref name=wright_2012/><ref name=CVBD_tick_preventative>{{cite web | title=About ticks – preventative measures | url=https://www.cvbd.org/en/tick-borne-diseases/about-ticks/preventative-measures/ | website=Tick-borne diseases | publisher=Companion Vector-Borne Diseases | access-date=21 May 2019 | archive-url=https://web.archive.org/web/20190607052340/http://www.cvbd.org/en/tick-borne-diseases/about-ticks/preventative-measures/ | archive-date=7 June 2019 | url-status=live }}</ref> Tick densities tend to be highest in woodlands, followed by unmaintained [[ecotone|edges between woods and lawns]] (about half as high), ornamental plants and perennial [[groundcover]] (about a quarter), and lawns (about 30 times less).<ref name=eisen_2016>{{cite journal | vauthors = Eisen L, Eisen RJ | title = Critical Evaluation of the Linkage Between Tick-Based Risk Measures and the Occurrence of Lyme Disease Cases | journal = Journal of Medical Entomology | volume = 53 | issue = 5 | pages = 1050–1062 | date = September 2016 | pmid = 27330093 | pmc = 5777907 | doi = 10.1093/jme/tjw092 }}</ref> Ixodes [[larva]]e and nymphs tend to be abundant also where mice nest, such as [[Dry stone|stone walls]] and wood logs.<ref name=eisen_2016/> Ixodes larvae and nymphs typically wait for potential [[Host (biology)|hosts]] ("quest") on leaves or grasses close to the ground with forelegs outstretched; when a host brushes against its limbs, the tick rapidly clings and climbs on the host looking for a skin location to bite.<ref name=CVBDhost>{{cite web |url=http://www.cvbd.org/en/tick-borne-diseases/about-ticks/tick-feeding/host-seeking/ |title=Host seeking |work=CVBD: Companion Vector-Borne Diseases |access-date=8 December 2016 |archive-url=https://web.archive.org/web/20161016105430/http://www.cvbd.org/en/tick-borne-diseases/about-ticks/tick-feeding/host-seeking/ |archive-date=16 October 2016 |url-status=live }}</ref> In Northeastern United States, 69% of tick bites are estimated to happen in residences, 11% in schools or camps, 9% in parks or recreational areas, 4% at work, 3% while hunting, and 4% in other areas.<ref name=eisen_2016/> Activities associated with tick bites around residences include yard work, brush clearing, gardening, playing in the yard, and letting dogs or cats that roam outside in woody or grassy areas into the house.<ref name=eisen_2016/><ref name=CDC_Lyme_prev_on_people/> In parks, tick bites often happen while hiking or camping.<ref name=eisen_2016/> Walking on a mown lawn or center of a trail without touching adjacent vegetation is less risky than crawling or sitting on a log or stone wall.<ref name=eisen_2016/><ref name=EPA_tick_prevention/> Pets should not be allowed to roam freely in likely tick habitats.<ref name=CVBD_tick_preventative/>

As a precaution, [[Centers for Disease Control and Prevention|CDC]] recommends soaking or spraying clothes, shoes, and camping gear such as tents, backpacks and sleeping bags with 0.5% [[permethrin]] solution and hanging them to dry before use.<ref name=CDC_Lyme_prev_on_people/><ref name=CDC_travelers_protection>{{cite web | title=Protection against Mosquitoes, Ticks, & Other Arthropods | url=https://wwwnc.cdc.gov/travel/yellowbook/2018/the-pre-travel-consultation/protection-against-mosquitoes-ticks-other-arthropods | website=Travelers' Health | publisher=Centers for Disease Control and Prevention | access-date=21 May 2019 | archive-url=https://web.archive.org/web/20190509191123/https://wwwnc.cdc.gov/travel/yellowbook/2018/the-pre-travel-consultation/protection-against-mosquitoes-ticks-other-arthropods | archive-date=9 May 2019 | url-status=live }}</ref> Permethrin is odorless and safe for humans but highly toxic to ticks.<ref name=miller_2011/> After crawling on permethrin-treated fabric for as few as 10–20 seconds, tick nymphs become irritated and fall off or die.<ref name=miller_2011/><ref name=eisen_2017>{{cite journal | vauthors = Eisen L, Rose D, Prose R, Breuner NE, Dolan MC, Thompson K, Connally N | title = Bioassays to evaluate non-contact spatial repellency, contact irritancy, and acute toxicity of permethrin-treated clothing against nymphal Ixodes scapularis ticks | journal = Ticks and Tick-Borne Diseases | volume = 8 | issue = 6 | pages = 837–849 | date = October 2017 | pmid = 28754599 | pmc = 5665650 | doi = 10.1016/j.ttbdis.2017.06.010 }}</ref> Permethrin-treated closed-toed shoes and socks reduce by 74 times the number of bites from nymphs that make first contact with a shoe of a person also wearing treated shorts (because nymphs usually quest near the ground, this is a typical contact scenario).<ref name=miller_2011>{{cite journal | vauthors = Miller NJ, Rainone EE, Dyer MC, González ML, Mather TN | title = Tick bite protection with permethrin-treated summer-weight clothing | journal = Journal of Medical Entomology | volume = 48 | issue = 2 | pages = 327–333 | date = March 2011 | pmid = 21485369 | doi = 10.1603/me10158 | doi-access = free }}</ref> Better protection can be achieved by tucking permethrin-treated trousers (pants) into treated socks and a treated long-sleeve shirt into the trousers so as to minimize gaps through which a tick might reach the wearer's skin.<ref name=EPA_tick_prevention>{{cite web | title=Tips to prevent tick bytes | url=https://www.epa.gov/insect-repellents/tips-prevent-tick-bites | website=Insect repellents | publisher=Environmental Protection Agency | access-date=21 May 2019 | date=15 July 2013 | archive-url=https://web.archive.org/web/20190415170027/https://www.epa.gov/insect-repellents/tips-prevent-tick-bites | archive-date=15 April 2019 | url-status=live }}</ref> Light-colored clothing may make it easier to see ticks and remove them before they bite.<ref name = EPA_tick_prevention/> Military and outdoor workers' uniforms treated with permethrin have been found to reduce the number of bite cases by 80–95%.<ref name=eisen_2017/> Permethrin protection lasts several weeks of wear and washings in customer-treated items and up to 70 washings for factory-treated items.<ref name=CDC_travelers_protection/> Permethrin should not be used on human skin, underwear or cats.<ref name=CDC_travelers_protection/><ref name=dymond_2008>{{cite journal | vauthors = Dymond NL, Swift IM | title = Permethrin toxicity in cats: a retrospective study of 20 cases | journal = Australian Veterinary Journal | volume = 86 | issue = 6 | pages = 219–223 | date = June 2008 | pmid = 18498556 | doi = 10.1111/j.1751-0813.2008.00298.x }}</ref>

The [[United States Environmental Protection Agency|EPA]] recommends several tick [[Insect repellent|repellents]] for use on exposed skin, including [[DEET]], [[picaridin]], [[IR3535]] (a derivative of amino acid beta-alanine), [[Eucalyptus oil|oil of lemon eucalyptus]] (OLE, a natural compound) and OLE's active ingredient [[P-Menthane-3,8-diol|para-menthane-diol (PMD)]].<ref name=CDC_Lyme_prev_on_people/><ref name = EPA_insect_repellents>{{cite web | title=Repellents: protection against mosquitoes, ticks and other arthropods | url=https://www.epa.gov/insect-repellents | website=Insect repellents | publisher=Environmental Protection Agency | access-date=21 May 2019 | date=9 July 2013 | archive-url=https://web.archive.org/web/20190520074421/https://www.epa.gov/insect-repellents | archive-date=20 May 2019 | url-status=live }}</ref><ref name=nguyen_2018/> Unlike permethrin, repellents repel but do not kill ticks, protect for only several hours after application, and may be washed off by sweat or water.<ref name=CDC_travelers_protection/> The most popular repellent is DEET in the U.S. and picaridin in Europe.<ref name=nguyen_2018>{{cite journal | vauthors = Nguyen QD, Vu MN, Hebert AA | title = Insect repellents: An updated review for the clinician | journal = Journal of the American Academy of Dermatology | volume = 88 | issue = 1 | pages = 123–130 | date = January 2023 | pmid = 30395919 | doi = 10.1016/j.jaad.2018.10.053 }}</ref> Unlike DEET, picaridin is odorless and is less likely to irritate the skin or harm fabric or plastics.<ref name=nguyen_2018/> Repellents with higher concentration may last longer but are not more effective; against ticks, 20% picaridin may work for 8 hours vs. 55–98.11% DEET for 5–6 hours or 30–40% OLE for 6 hours.<ref name=CDC_travelers_protection/><ref name=EPA_insect_repellents/> Repellents should not be used under clothes, on eyes, mouth, wounds or cuts, or on babies younger than 2 months (3 years for OLE or PMD).<ref name=CDC_travelers_protection/><ref name=CDC_Lyme_prev_on_people/> If [[sunscreen]] is used, repellent should be applied on top of it.<ref name=CDC_travelers_protection/> Repellents should not be sprayed directly on a face, but should instead be sprayed on a hand and then rubbed on the face.<ref name = CDC_travelers_protection/>

After coming indoors, clothes, gear and pets should be checked for ticks.<ref name = CDC_Lyme_prev_on_people/> Clothes can be put into a hot dryer for 10 minutes to kill ticks (just washing or a warm dryer is not enough).<ref name=CDC_Lyme_prev_on_people/> Showering as soon as possible, looking for ticks over the entire body, and removing them reduces the risk of infection.<ref name = CDC_Lyme_prev_on_people/> Unfed tick nymphs are the size of a poppy seed, but a day or two after biting and attaching themselves to a person, they look like a small [[blood blister]].<ref name=CT_tick-management>{{cite web | vauthors = Stafford KC | title=Tick management handbook (rev. ed.) | date=2007 | volume=1010 | url=https://portal.ct.gov/-/media/CAES/DOCUMENTS/Publications/Bulletins/b1010pdf.pdf?la=en | website=Bulletins | publisher=Connecticut Agricultural Experiment Station | access-date=21 May 2019 | archive-url=https://web.archive.org/web/20190403234108/https://portal.ct.gov/-/media/CAES/DOCUMENTS/Publications/Bulletins/b1010pdf.pdf?la=en | archive-date=3 April 2019 | url-status=live }}</ref> The following areas should be checked especially carefully: armpits, between legs, back of knee, bellybutton, trunk, and in children ears, neck and hair.<ref name=CDC_Lyme_prev_on_people/>

===Tick removal===
[[File:Tickremoval.svg|thumb|Removal of a tick using tweezers]]
Attached ticks should be removed promptly. The risk of infection increases with the time of attachment. In North America, the risk of Lyme disease is small if the tick is removed within 36 hours.<ref name="piesman2002"/> [[Centers for Disease Control and Prevention|CDC]] recommends inserting a fine-tipped tweezer between the skin and the tick, grasping very firmly, and pulling the closed tweezer straight away from the skin without twisting, jerking, squeezing or crushing the tick.<ref name=CDC_tick_removal>{{cite web | title=Tick removal and testing | url=https://www.cdc.gov/lyme/removal/ | website=Lyme Disease | publisher=Centers for Disease Control and Prevention | access-date=21 May 2019 | date=22 April 2019 | archive-url=https://web.archive.org/web/20171123052303/https://www.cdc.gov/lyme/removal/ | archive-date=23 November 2017 | url-status=live }}</ref> After tick removal, any tick parts remaining in the skin should be removed with a clean tweezer, if possible.<ref name=CDC_tick_removal/> The wound and hands should then be cleaned with alcohol or soap and water.<ref name=CDC_tick_removal/> The tick may be disposed of by placing it in a container with alcohol, a sealed bag, tape, or flushing it down the toilet.<ref name=CDC_tick_removal/> The bitten person should write down where and when the bite happened so that this information can be provided to a doctor if the person gets a rash or flu-like symptoms in the following several weeks.<ref name=CDC_tick_removal/> CDC recommends not using fingers, nail polish, [[petroleum jelly]] or heat on the tick to try to remove it.<ref name=CDC_tick_removal/>

In Australia, where the [[Ixodes holocyclus|Australian paralysis tick]] is prevalent, the [[Australasian Society of Clinical Immunology and Allergy]] recommends not using tweezers to remove ticks, because if the person is allergic, [[anaphylaxis]] could result.<ref name=australia_tick_freeze>{{cite web|title=Tick Allergy|url=http://www.allergy.org.au/patients/insect-allergy-bites-and-stings/tick-allergy|access-date=30 April 2015|date=2014|url-status=live|archive-url=https://web.archive.org/web/20150514060441/http://www.allergy.org.au/patients/insect-allergy-bites-and-stings/tick-allergy|archive-date=14 May 2015}}</ref> Instead, a product should be sprayed on the tick to cause it to freeze and then drop off.<ref name=australia_tick_freeze/> Another method consists in using about 20&nbsp;cm (8 inches) of [[dental floss]] or fishing line for slowly tying an overhand knot between the skin and the tick and then pulling it away from the skin.<ref>{{cite journal | vauthors = Röggla G | title = Death of unknown origin in alpine medicine | journal = Wilderness & Environmental Medicine | volume = 13 | issue = 2 | page = 181 | year = 2002 | pmid = 12092975 | doi = 10.1580/1080-6032(2002)013[0181:ltte]2.0.co;2 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Ghirga G, Ghirga P | title = Effective tick removal with a fishing line knot | journal = Wilderness & Environmental Medicine | volume = 21 | issue = 3 | pages = 270–271 | date = September 2010 | pmid = 20832708 | doi = 10.1016/j.wem.2010.04.005 | doi-access = free }}</ref>

===Preventive antibiotics===
<!-- prophylaxis if found early -->
The risk of infectious transmission increases with the duration of tick attachment.<ref name=wright_2012/> It requires between 36 and 48 hours of attachment for the bacteria that cause Lyme to travel from within the tick into its saliva.<ref name=wright_2012/> If a deer tick that is sufficiently likely to be carrying ''Borrelia'' is found attached to a person and removed, and if the tick has been attached for 36 hours or is engorged, a single dose of doxycycline administered within the 72 hours after removal may reduce the risk of Lyme disease. It is not generally recommended for all people bitten, as development of infection is rare: about 50 bitten people would have to be treated this way to prevent one case of erythema migrans (i.e., the typical rash found in about 70–80% of people infected).<ref name=NEJM2014/><ref name=wright_2012/>

===Garden landscaping===
Several landscaping practices may reduce the risk of tick bites in residential yards.<ref name=CT_tick-management/><ref name=CDC_Lyme_prev_in_yard>{{cite web | title=Preventing tick bites in the yard | url=https://www.cdc.gov/lyme/prev/in_the_yard.html | website=Lyme Disease | publisher=Centers for Disease Control and Prevention | access-date=21 May 2019 | date=8 March 2019 | archive-url=https://web.archive.org/web/20190615054940/https://www.cdc.gov/lyme/prev/in_the_yard.html | archive-date=15 June 2019 | url-status=live }}</ref> These include keeping lawns mown, removing [[leaf litter]] and weeds and avoiding the use of ground cover.<ref name=CT_tick-management/> A 3-ft-wide rock or woodchip barrier is recommended to separate lawns from wood piles, [[woodland]]s, [[Dry stone|stone walls]] and shrubs.<ref name = CDC_Lyme_prev_in_yard/> Without vegetation on the barrier, ticks will tend not to cross it; [[acaricides]] may also be sprayed on it to kill ticks.<ref name=CDC_Lyme_prev_in_yard/> A sun-exposed tick-safe zone at least 9&nbsp;ft from the barrier should concentrate human activity on the yard, including any patios, playgrounds and gardening.<ref name=CDC_Lyme_prev_in_yard/> Materials such as wood decking, concrete, bricks, gravel or woodchips used on the ground under patios and playgrounds would discourage ticks there.<ref name=CT_tick-management/> An 8-ft-high fence may be added to keep deer away from the tick-safe zone.<ref name=CDC_Lyme_prev_in_yard/><ref name=CT_tick-management/>

===Occupational exposure===
Outdoor workers are at risk of Lyme disease if they work at sites with infected ticks. This includes construction, landscaping, forestry, brush clearing, land surveying, farming, railroad work, oil field work, utility line work, park or wildlife management.<ref>{{Cite web|title = CDC – Lyme Disease – NIOSH Workplace Safety and Health Topic|url = https://www.cdc.gov/niosh/topics/lyme/|website = www.cdc.gov|access-date = 3 November 2015|url-status=live |archive-url = https://web.archive.org/web/20151113075310/http://www.cdc.gov/niosh/topics/lyme/|archive-date = 13 November 2015|date = 3 August 2017}}</ref><ref>{{cite web |title=Risks: Lyme Disease {{!}} NIOSH {{!}} CDC |url=https://www.cdc.gov/niosh/topics/lyme/risks.html |website=www.cdc.gov |access-date=26 April 2019 |language=en-us |date=14 November 2018 |archive-url=https://web.archive.org/web/20190426005009/https://www.cdc.gov/niosh/topics/lyme/risks.html |archive-date=26 April 2019 |url-status=live }}</ref> U.S. workers in the northeastern and north-central states are at highest risk of exposure to infected ticks. Ticks may also transmit other tick-borne diseases to workers in these and other regions of the country. Worksites with woods, bushes, high grass or [[leaf litter]] are likely to have more ticks. Outdoor workers should be most careful to protect themselves in the late spring and summer when young ticks are most active.<ref name=cdclyme>{{cite web | publisher = The Centers for Disease Control and Prevention | url = https://www.cdc.gov/niosh/topics/lyme/ | date = 12 October 2016 | access-date = 22 June 2017 | title = Lyme disease | url-status=live | archive-url = https://web.archive.org/web/20170617203154/https://www.cdc.gov/niosh/topics/lyme/ | archive-date = 17 June 2017}}{{CDC}}</ref>

===Host animals===
Ticks can feed upon the blood of a wide array of possible host species, including [[lizards]], [[birds]], [[mice]], [[cats]], [[dogs]], [[deer]], [[cattle]] and [[humans]]. The extent to which a tick can feed, reproduce, and spread will depend on the type and availability of its hosts. Whether it will spread disease is also affected by its available hosts. Some species, such as lizards, are referred to as "dilution hosts" because they don't tend to support Lyme disease pathogens and decrease the likelihood that the disease will be passed on by ticks feeding on them. [[White-tailed deer]] are both a food source and a "reproductive host", where ticks tend to mate.<ref>{{Cite journal |last1=Levi |first1=Taal |last2=Kilpatrick |first2=A. Marm |last3=Mangel |first3=Marc |last4=Wilmers |first4=Christopher C. |date=2012-07-03 |title=Deer, predators, and the emergence of Lyme disease |journal=Proceedings of the National Academy of Sciences |volume=109 |issue=27 |pages=10942–10947 |doi=10.1073/pnas.1204536109 |doi-access=free |pmc=3390851 |pmid=22711825|bibcode=2012PNAS..10910942L }}</ref> The [[white-footed mouse]]  is a [[reservoir host]] in which the pathogen for Lyme disease can survive. The availability of hosts can have significant impacts on the transmission of Lyme disease. A greater diversity of hosts, or of those that don't support the pathogen, tends to decrease the likelihood that the disease will be transmitted.<ref name="Chrobak">{{cite journal |vauthors=Chrobak U |title=Lyme and other tick-borne diseases are on the rise. But why? |journal=Knowable Magazine |date=3 February 2022 |doi=10.1146/knowable-020222-1 |doi-access=free |url=https://knowablemagazine.org/article/health-disease/2022/lyme-other-tickborne-diseases-rise |access-date=4 March 2022 |archive-date=26 February 2022 |archive-url=https://web.archive.org/web/20220226082534/https://knowablemagazine.org/article/health-disease/2022/lyme-other-tickborne-diseases-rise |url-status=live }}</ref>

In the United States, one approach to reducing the incidence of Lyme and other deer tick-borne diseases has been to greatly reduce the deer population on which the adult ticks depend for feeding and reproduction. Lyme disease cases fell following deer eradication on an island, [[Monhegan, Maine]],<ref name="Rand"/> and following deer control in Mumford Cove, Connecticut.<ref name=managing_deer_2007/>  Advocates have suggested reducing the deer population to levels of 8 to 10 deer per square mile, compared to levels of 60 or more deer per square mile in the areas of the country with the highest Lyme disease rates.<ref name=kirby_2004/> While these studies have found these effects, other studies have found opposite effects. A study done in Massachusetts removed deer and did not see a significant decrease in tick abundance afterwards.<ref>{{Cite journal |last1=Wilson |first1=Mark L |last2=Levine |first2=Jay F. |last3=Spielman |first3=Andrew |date=1984 |title=Effect of deer reduction on abundance of the deer tick (Ixodes dammini). |journal=Yale Journal of Biology and Medicine |volume=57 |issue=4 |pages=697–705 |pmid=6516462 |pmc=2589992 }}</ref> Another study done in New Jersey removed deer and also did not see a reduction in the number of questing ticks and determined that deer culling is an unlikely way to control tick populations effectively.<ref>{{Cite journal |last1=Jordan |first1=Robert A. |last2=Schulze |first2=Terry L. |last3=Jahn |first3=Margaret B. |date=2007-09-01 |title=Effects of Reduced Deer Density on the Abundance of''Ixodes scapularis''(Acari: Ixodidae) and Lyme Disease Incidence in a Northern New Jersey Endemic Area |journal=Journal of Medical Entomology |volume=44 |issue=5 |pages=752–757 |doi=10.1093/jmedent/44.5.752 |pmid=17915504 |doi-access=free }}</ref> One study summarized the results of multiple studies all looking at deer reduction controlling tick populations and determined that deer control can't be used as a standalone reduction for Lyme disease. It also claims that most studies examining this are not representative of areas with high human Lyme disease risk.<ref>{{Cite journal |last1=Kugeler |first1=K. J. |last2=Jordan |first2=R. A. |last3=Schulze |first3=T. L. |last4=Griffith |first4=K. S. |last5=Mead |first5=P. S. |date=2016 |title=Will Culling White-Tailed Deer Prevent Lyme Disease? |journal=Zoonoses and Public Health |language=en |volume=63 |issue=5 |pages=337–345 |doi=10.1111/zph.12245 |pmc=4912954 |pmid=26684932 }}</ref> There is varying information on whether or not the removal of deer is actually a way to control the Lyme disease epidemic. Removal of smaller mammals that are fed on by juveniles who are more actively acquiring and spreading the pathogen would decrease Lyme disease risk the most.<ref>{{Cite journal |last1=Van Buskirk |first1=Josh |last2=Ostfeld |first2=Richard S. |date=1995 |title=Controlling Lyme Disease by Modifying the Density and Species Composition of Tick Hosts |url=https://esajournals.onlinelibrary.wiley.com/doi/10.2307/2269360 |journal=Ecological Applications |volume=5 |issue=4 |pages=1133–1140 |doi=10.2307/2269360 |jstor=2269360 |bibcode=1995EcoAp...5.1133V |url-access=subscription }}</ref>

Others have noted that while deer are reproductive hosts, they are not ''Borrelia burgdorferi'' reservoirs. This is because it was found that white-tailed deer blood actually kills the ''Borrelia burgdorferi'' bacteria.<ref>{{Cite journal |last1=Pearson |first1=Patrick |last2=Rich |first2=Connor |last3=Feehan |first3=Martin J.R. |last4=Ditchkoff |first4=Stephen S. |last5=Rich |first5=Stephen M. |date=May 2023 |title=White-Tailed Deer Serum Kills the Lyme Disease Spirochete, Borrelia burgdorferi |journal=Vector-Borne and Zoonotic Diseases |volume=23 |issue=5 |pages=303–305 |doi=10.1089/vbz.2022.0095 |pmc=10178931 |pmid=36944114}}</ref> Researchers have suggested that smaller, less obviously visible Lyme reservoirs, like [[white-footed mice]] and [[Eastern chipmunks]], may more strongly impact Lyme disease occurrence. Ecosystem studies in New York state suggest that white-footed mice thrive when forests are broken into smaller, isolated chunks of woodland with fewer rodent predators. With more rodents harboring the disease, the odds increase that a tick will feed on a disease-harboring rodent and that someone will pick up a disease-carrying tick in their garden or while walking in the woods. Data indicates that the smaller the wooded area, the more ticks it will contain and the likely they are to carry Lyme disease, supporting the idea that  [[deforestation]] and habitat fragmentation affect ticks, hosts and disease transmission.<ref name="Chrobak"/>

Tick-borne diseases are estimated to affect ~80 % of [[cattle]] worldwide.<ref name="Rochlin">{{cite journal | vauthors = Rochlin I, Toledo A | title = Emerging tick-borne pathogens of public health importance: a mini-review | journal = Journal of Medical Microbiology | volume = 69 | issue = 6 | pages = 781–791 | date = June 2020 | pmid = 32478654 | pmc = 7451033 | doi = 10.1099/jmm.0.001206 }}</ref> They also affect cats, dogs, and other pets. Routine veterinary control of [[ticks of domestic animals]] through the use of [[acaricide]]s has been suggested as a way to reduce exposure of humans to ticks. However, chemical control with acaricides is now criticized on several grounds.  Ticks appear to develop resistance to acaricides; acaricides are costly; and there are concerns over their toxicity and the potential for chemical residues to affect food and the environment.<ref name="Rajput">{{cite journal | vauthors = Rajput ZI, Hu SH, Chen WJ, Arijo AG, Xiao CW | title = Importance of ticks and their chemical and immunological control in livestock | journal = Journal of Zhejiang University. Science. B | volume = 7 | issue = 11 | pages = 912–921 | date = November 2006 | pmid = 17048307 | pmc = 1635821 | doi = 10.1631/jzus.2006.B0912 }}</ref>

In Europe, known reservoirs of ''Borrelia burgdorferi'' were 9 small mammals, 7 medium-sized mammals and 16 species of birds (including passerines, sea-birds and pheasants).<ref name=gern1998/> These animals seem to transmit spirochetes to ticks and thus participate in the natural circulation of B. burgdorferi in Europe. The [[Mus musculus|house mouse]] is also suspected as well as other species of small rodents, particularly in Eastern Europe and Russia.<ref name=gern1998>{{cite journal | vauthors = Gern L, Estrada-Peña A, Frandsen F, Gray JS, Jaenson TG, Jongejan F, Kahl O, Korenberg E, Mehl R, Nuttall PA | title = European reservoir hosts of Borrelia burgdorferi sensu lato | journal = Zentralblatt für Bakteriologie | volume = 287 | issue = 3 | pages = 196–204 | date = March 1998 | pmid = 9580423 | doi = 10.1016/S0934-8840(98)80121-7 }}</ref> "The reservoir species that contain the most pathogens are the European roe deer ''[[Capreolus capreolus]]'';<ref name="Wodecka2013" /> "''it does not appear to serve as a major reservoir of B. burgdorferi''" thought Jaenson & al. (1992)<ref>{{cite journal | vauthors = Jaenson TG, Tälleklint L | title = Incompetence of roe deer as reservoirs of the Lyme borreliosis spirochete | journal = Journal of Medical Entomology | volume = 29 | issue = 5 | pages = 813–817 | date = September 1992 | pmid = 1404260 | doi = 10.1093/jmedent/29.5.813 }}</ref> (incompetent host for ''B. burgdorferi'' and TBE virus) but it is important for feeding the ticks,<ref>{{cite journal | vauthors = Tälleklint L, Jaenson TG | title = Transmission of Borrelia burgdorferi s.l. from mammal reservoirs to the primary vector of Lyme borreliosis, Ixodes ricinus (Acari: Ixodidae), in Sweden | journal = Journal of Medical Entomology | volume = 31 | issue = 6 | pages = 880–886 | date = November 1994 | pmid = 7815401 | doi = 10.1093/jmedent/31.6.880 }}</ref> as [[red deer]] and wild [[boars]] (''[[Sus scrofa]]''),<ref name="Wodecka2013">{{cite journal | vauthors = Wodecka B, Rymaszewska A, Skotarczak B | title = Host and pathogen DNA identification in blood meals of nymphal Ixodes ricinus ticks from forest parks and rural forests of Poland | journal = Experimental and Applied Acarology | volume = 62 | issue = 4 | pages = 543–555 | date = April 2014 | pmid = 24352572 | pmc = 3933768 | doi = 10.1007/s10493-013-9763-x }}</ref> in which one ''Rickettsia'' and three ''Borrelia'' species were identified",<ref name="Wodecka2013"/> with high risks of coinfection in roe deer.<ref>{{cite journal | vauthors = Overzier E, Pfister K, Herb I, Mahling M, Böck G, Silaghi C | title = Detection of tick-borne pathogens in roe deer (Capreolus capreolus), in questing ticks (Ixodes ricinus), and in ticks infesting roe deer in southern Germany | journal = Ticks and Tick-Borne Diseases | volume = 4 | issue = 4 | pages = 320–328 | date = June 2013 | pmid = 23571115 | doi = 10.1016/j.ttbdis.2013.01.004 }}{{Dead link|date=March 2022 |bot=InternetArchiveBot |fix-attempted=yes }}</ref> Nevertheless, in the 2000s, in roe deer in Europe "''two species of Rickettsia and two species of Borrelia were identified''".<ref name="Wodecka2013"/>

==Vaccination==
{{As of|2023}}, no human vaccines for Lyme disease were available.<ref name="cdc-vaccine">{{Cite web |date=2022-08-11 |title=Lyme disease vaccine|url=https://www.cdc.gov/lyme/about/lyme-disease-vaccine.html?CDC_AAref_Val=https://www.cdc.gov/lyme/prev/vaccine.html |access-date=2024-11-13 |publisher=[[Centers for Disease Control and Prevention]]}}</ref> The only human vaccine to advance to market was LYMErix, which was available from 1998, but discontinued in 2002.<ref name="O'Bier2021">{{cite journal | vauthors = O'Bier NS, Hatke AL, Camire AC, Marconi RT | title = Human and Veterinary Vaccines for Lyme Disease | journal = Current Issues in Molecular Biology | volume = 42 | issue =  | pages = 191–222 | date = 2021 | pmid = 33289681 | pmc = 7946718 | doi = 10.21775/cimb.042.191 }}</ref> The vaccine candidate VLA15 was scheduled to start a phase 3 trial in the third quarter of 2022, with other research ongoing. Multiple vaccines are available for the prevention of Lyme disease in dogs.

===LYMErix===
The vaccine LYMErix was available from 1998 to 2002. The [[Recombinant DNA#Applications of recombinant DNA technology|recombinant vaccine]] against Lyme disease, based on the outer surface protein A (OspA) of ''B. burgdorferi'' with aluminum hydroxide as adjuvant, was developed by [[GlaxoSmithKline#SmithKline Beecham|SmithKline Beecham]]. In [[clinical trial]]s involving more than 10,000 people, the vaccine was found to confer protective immunity to Lyme disease in 76% of adults after three doses with only mild or moderate and transient [[adverse effect]]s.<ref name=Poland_2001/><ref name=Poland2011/> On 21 December 1998, the [[Food and Drug Administration]] (FDA) approved LYMErix based on these trials for persons of ages 15 through 70.<ref name="Poland2011">{{cite journal | vauthors = Poland GA | title = Vaccines against Lyme disease: What happened and what lessons can we learn? | journal = Clinical Infectious Diseases | volume = 52 | issue = Suppl 3 | pages = s253–s258 | date = February 2011 | pmid = 21217172 | doi = 10.1093/cid/ciq116 | doi-access = free }}</ref><ref name="O'Bier2021"/>

Following approval of the [[vaccine]], its entry into clinical practice was slow for a variety of reasons, including its cost, which was often not reimbursed by insurance companies.<ref name=rowe_199/> Subsequently, hundreds of vaccine recipients reported they had developed [[autoimmunity|autoimmune]] and other side effects. Supported by some advocacy groups, a number of [[class-action lawsuit]]s were filed against [[GlaxoSmithKline]], alleging the vaccine had caused these health problems. These claims were investigated by the FDA and the Centers for Disease Control, which found no connection between the vaccine and the autoimmune complaints.<ref name="uphill"/>

Despite the lack of evidence that the complaints were caused by the vaccine, sales plummeted and LYMErix was withdrawn from the U.S. market by GlaxoSmithKline in February 2002,<ref name=vaccine_2008/> in the setting of negative media coverage and fears of vaccine side effects.<ref name="uphill"/><ref name="cautionary"/> The fate of LYMErix was described in the medical literature as a "cautionary tale";<ref name="cautionary"/> an editorial in ''[[Nature (journal)|Nature]]'' cited the withdrawal of LYMErix as an instance in which "unfounded public fears place pressures on vaccine developers that go beyond reasonable safety considerations."<ref name="safe"/> The original developer of the OspA vaccine at the [[Max Planck Institute]] told ''Nature'': "This just shows how irrational the world can be&nbsp;... There was no scientific justification for the first OspA vaccine LYMErix being pulled."<ref name="uphill"/><ref>{{cite journal | vauthors = Aronowitz RA | title = The rise and fall of the lyme disease vaccines: a cautionary tale for risk interventions in American medicine and public health | journal = The Milbank Quarterly | volume = 90 | issue = 2 | pages = 250–277 | date = June 2012 | pmid = 22709388 | pmc = 3460208 | doi = 10.1111/j.1468-0009.2012.00663.x }}</ref>

===VLA15===
The hexavalent (OspA) protein subunit-based vaccine candidate VLA15 was developed by [[Valneva]]. It was granted [[Fast track (FDA)|fast track designation]] by the U.S. [[Food and Drug Administration]] in July 2017.<ref>{{cite web|title=Anti-vaxxers stopped the last Lyme disease vaccine. The FDA has just fast-tracked a new one|url=http://www.newsweek.com/lyme-disease-vaccine-valneva-fda-approva-641796|website=Newsweek|access-date=25 December 2017|date=25 July 2017|archive-url=https://web.archive.org/web/20171225092005/http://www.newsweek.com/lyme-disease-vaccine-valneva-fda-approva-641796|archive-date=25 December 2017|url-status=live}}</ref><ref>{{cite web |url=https://www.concordmonitor.com/lyme-disease-vaccine-trials-18056240 |title=A Lyme vaccine for humans is getting closer, says French biotech firm |work=Concord Monitor | vauthors = Brooks D |date=6 August 2018 |access-date=20 July 2021 }}</ref> In April 2020 [[Pfizer]] paid $130 million for the rights to the vaccine, and the companies are developing it together, performing multiple phase 2 trials.<ref name="fiercebt-022022">{{Cite web | vauthors =  Taylor NP |date=2022-02-04 |title=Pfizer's $130M Lyme disease vaccine advances to phase 3 after 3rd shot shown to increase antibodies |url=https://www.fiercebiotech.com/biotech/pfizer-s-130m-lyme-disease-vaccine-advances-to-phase-3-after-booster-shown-to-increase |access-date=2022-06-05 |website=Fierce Biotech}}</ref>

A phase 3 trial of VLA15 was scheduled for late 2022, recruiting volunteers at test sites located across the northeastern United States and in Europe.<ref>{{cite news |vauthors=Neergaard L, Lum S |title=Major test of first possible Lyme vaccine in 20 years begins |url=https://apnews.com/article/science-health-ticks-73fab8e29f3e2243c2db5bc33b3265e1 |work=Associated Press |date=8 August 2022 |access-date=11 August 2022 |archive-date=11 August 2022 |archive-url=https://web.archive.org/web/20220811235530/https://apnews.com/article/science-health-ticks-73fab8e29f3e2243c2db5bc33b3265e1 |url-status=live }}</ref><ref name=ClinicalTrial>{{cite journal |url=https://clinicaltrials.gov/ct2/show/NCT05477524 |title=An Efficacy, Safety, Tolerability, Immunogenicity, and Lot-Consistency Clinical Trial of a 6-Valent OspA-Based Lyme Disease Vaccine (VLA15) (VALOR) |author=<!--not stated--> |date=28 July 2022 |website=[[ClinicalTrials.gov]] |publisher=National Institute of Health |access-date=11 August 2022}}</ref> Participants were scheduled to receive an initial three-dose series of vaccines over the course of five to nine months, followed by a booster dose after twelve months, with both the initial series and the booster dose scheduled to be complete before the year's peak Lyme disease season.<ref name=ClinicalTrial />

===Other research===
An [[mRNA vaccine]] designed to cause a strong, fast immune response to tick saliva allowed the immune system to detect and remove the ticks from test animals before they were able to transmit the infectious bacteria.<ref>{{cite web | vauthors = Klein A | url = https://www.newscientist.com/article/2297648-mrna-vaccine-against-tick-bites-could-help-prevent-lyme-disease/ | title = An mRNA vaccine that causes a red, itchy skin rash in response to bites by ticks may allow them to be removed before they transmit Lyme disease-causing bacteria | work = [[New Scientist]] | date = 17 November 2021 | access-date = 19 November 2021 | archive-date = 19 November 2021 | archive-url = https://web.archive.org/web/20211119150714/https://www.newscientist.com/article/2297648-mrna-vaccine-against-tick-bites-could-help-prevent-lyme-disease/ | url-status = live }}</ref> The vaccine contains mRNAs for the body to build 19 proteins in tick saliva which, by enabling quick development of [[erythema]] (itchy redness) at the bite site, protects guinea pigs against Lyme disease. It also protects the test animals if the tick is not removed, if only one tick, but not three, remains attached.<ref>{{cite news | vauthors = Hathaway B |title=Novel Lyme vaccine shows promise |url=https://medicalxpress.com/news/2021-11-lyme-vaccine.html |access-date=13 December 2021 |work=[[Yale University]] |language=en |quote=Compared to non-immunized guinea pigs, vaccinated animals exposed to infected ticks quickly developed redness at the tick bite site. None of the immunized animals developed Lyme disease if the ticks were removed when redness developed. In contrast, about half of the control group became infected with B. burgdorferi after tick removal. When a single infected tick was attached to immunized guinea pigs and not removed, none of the vaccinated animals were infected, compared to 60 percent of the control animals. However, protection waned in immunized guinea pigs if three ticks remained attached to the animal. Ticks in immunized animals were unable to feed aggressively and dislodged more quickly than those on guinea pigs in the control group.}}</ref><ref>{{cite journal | vauthors = Sajid A, Matias J, Arora G, Kurokawa C, DePonte K, Tang X, Lynn G, Wu MJ, Pal U, Strank NO, Pardi N, Narasimhan S, Weissman D, Fikrig E | title = mRNA vaccination induces tick resistance and prevents transmission of the Lyme disease agent | journal = Science Translational Medicine | volume = 13 | issue = 620 | article-number = eabj9827 | date = November 2021 | pmid = 34788080 | doi = 10.1126/scitranslmed.abj9827 }}</ref>

Sanofi, in cooperation with the Choumet Group and the [[Norbert Pardi|Pardi]] lab, also developed and evaluated new mRNA vaccine candidates targeting the bacterium's outer surface protein A (OspA), delivered via [[lipid nanoparticles]]. In mouse models, the mRNA-OspA vaccine elicited robust immune responses and offered complete protection against infection—outperforming traditional protein-based vaccines. The findings suggest that mRNA-OspA vaccines hold promise for preventing Lyme disease in humans.<ref>{{cite journal |last1=Tahir |first1=Djamel |last2=Geolier |first2=Virginie |last3=Bruant |first3=Hugo |last4=Le Flèche-Matéos |first4=Anne |last5=Mallet |first5=Adeline |last6=Varloud |first6=Marie |last7=Civat |first7=Céline |last8=Girerd-Chambaz |first8=Yves |last9=Montano |first9=Sandrine |last10=Pion |first10=Corinne |last11=Ferquel |first11=Elisabeth |last12=Pavot |first12=Vincent |last13=Choumet |first13=Valérie |title=A Lyme disease mRNA vaccine targeting Borrelia burgdorferi OspA induces strong immune responses and prevents transmission in mice |journal=Molecular Therapy Nucleic Acids |date=June 2025 |volume=36 |issue=2 |article-number=102514 |doi=10.1016/j.omtn.2025.102514 |pmid=40226328 |pmc=11986965 }}</ref><ref>{{cite journal |last1=Pine M |first1=Arora G, Hart TM, Bettini E, Gaudette BT, Muramatsu H, Tombacz I, Kambayashi T, Tam YK, Brisson D, Allman D, Locci M, Weissman D, Fikrig E, Pardi N. |title=Development of an mRNA-lipid nanoparticle vaccine against Lyme disease |journal=Molecular Therapy |date=6 September 2023 |volume=31 |issue=9 |pages=2702–2714 |doi=10.1016/j.ymthe.2023.07.022 |pmid=37533256 |pmc=10492027 }}</ref>

===Canine vaccines===
[[Vaccination of dogs|Canine vaccines]] have been formulated and approved for the prevention of Lyme disease in dogs. Currently, three Lyme disease vaccines are available. LymeVax, formulated by Fort Dodge Laboratories, contains intact dead spirochetes, which expose the host to the organism. Galaxy Lyme, Intervet-[[Schering-Plough]]'s vaccine, targets [[Virulence-related outer membrane protein family|proteins OspC and OspA]]. The OspC antibodies kill any of the bacteria that the OspA antibodies did not kill. Canine Recombinant Lyme, formulated by [[Merial]], generates antibodies against the OspA protein, so a tick feeding on a vaccinated dog draws in blood full of anti-OspA antibodies, which kill the spirochetes in the tick's gut before they are transmitted to the dog.<ref name="Brooks, DVM"/>

== Etymology ==
Lyme disease was diagnosed as a separate condition for the first time in 1975 in [[Lyme, Connecticut]].<ref>{{cite book| vauthors = Murray P |title=The Widening Circle: A Lyme Disease Pioneer Tells Her Story|date=1006|publisher=St. Martin's Press|location=New York|isbn=978-0-312-14068-7}}</ref>

==History==

===Early evidence===
The earliest known evidence of Lyme disease was found in [[Oetzi]], a 5300 year old mummy in the [[Eastern Alps]] near the Italian border.<ref>{{Cite journal |last=Wynne Parry |date=2012-02-28 |title=Iceman Mummy May Hold Earliest Evidence of Lyme Disease |url=https://www.livescience.com/18704-oldest-case-lyme-disease-spotted-iceman-mummy.html |journal=Live Science |language=en}}</ref>
The evolutionary history of ''Borrelia burgdorferi'' genetics has been examined by scientists. One study has found that before the [[reforestation]] that accompanied post-colonial farm abandonment in [[New England]] and the wholesale migration into the [[Midwest]] that occurred during the early 19th century, Lyme disease had been present for thousands of years in America and had spread along with its tick hosts from the Northeast to the Midwest.<ref name=Hoen_2009/>

John Josselyn, who visited New England in 1638 and again from 1663 to 1670, wrote, "There be infinite numbers of ticks hanging upon the bushes in summertime that will cleave to man's garments and creep into his breeches, eating themselves in a short time into the very flesh of a man. I have seen the stockings of those that have gone through the woods covered with them."<ref name=Josselyn_1670/>

This is also confirmed by the writings of [[Peter Kalm]], a Swedish botanist who was sent to America by [[Carl Linnaeus|Linnaeus]], and who found the forests of New York "abound" with ticks when he visited in 1749. When Kalm's journey was retraced 100 years later, the forests were gone and the Lyme bacterium had probably become isolated to a few pockets along the northeast coast, Wisconsin, and Minnesota.<ref name=Drymon_2008/>

Perhaps the first detailed description of what is now known as Lyme disease appeared in the writings of [[John Walker (natural historian)|John Walker]] after a visit to the island of [[Jura, Scotland|Jura]] (Deer Island) off the west coast of Scotland in 1764.<ref name=summerton_1995/> He gives a good description both of the symptoms of Lyme disease (with "exquisite pain [in] the interior parts of the limbs") and of the tick vector itself, which he describes as a "worm" with a body which is "of a reddish color and of a compressed shape with a row of feet on each side" that "penetrates the skin". Many people from this area of Great Britain emigrated to North America between 1717 and the end of the 18th century.<ref>{{Cite web |title=US Voyage New World |url=https://www.ulsterscotsagency.com/fs/doc/new_range_of_ulster-scots_booklets/US_Voyage_New_World_BK7_AW_3.pdf |access-date=May 1, 2024 |website=www.ulsterscotsagency.com}}</ref>

The examination of preserved museum specimens has found ''Borrelia'' DNA in an infected ''[[Ixodes ricinus]]'' tick from Germany dating back to 1884, and an infected mouse from Cape Cod that died in 1894.<ref name=Drymon_2008/> The 2010 autopsy of [[Ötzi the Iceman]], a 5,300-year-old [[mummy]], revealed the presence of ~60% of the DNA sequence of ''Borrelia burgdorferi''.<ref name="ngautopsy"/><ref name="iceman-primary">{{cite journal |last1=Keller |first1=Andreas |last2=Graefen |first2=Angela |last3=Ball |first3=Markus |last4=Matzas |first4=Mark |last5=Boisguerin |first5=Valesca |last6=Maixner |first6=Frank |last7=Leidinger |first7=Petra |last8=Backes |first8=Christina |last9=Khairat |first9=Rabab |last10=Forster |first10=Michael |last11=Stade |first11=Björn |last12=Franke |first12=Andre |last13=Mayer |first13=Jens |last14=Spangler |first14=Jessica |last15=McLaughlin |first15=Stephen |last16=Shah |first16=Minita |last17=Lee |first17=Clarence |last18=Harkins |first18=Timothy T. |last19=Sartori |first19=Alexander |last20=Moreno-Estrada |first20=Andres |last21=Henn |first21=Brenna |last22=Sikora |first22=Martin |last23=Semino |first23=Ornella |last24=Chiaroni |first24=Jacques |last25=Rootsi |first25=Siiri |last26=Myres |first26=Natalie M. |last27=Cabrera |first27=Vicente M. |last28=Underhill |first28=Peter A. |last29=Bustamante |first29=Carlos D. |last30=Vigl |first30=Eduard Egarter |last31=Samadelli |first31=Marco |last32=Cipollini |first32=Giovanna |last33=Haas |first33=Jan |last34=Katus |first34=Hugo |last35=O'Connor |first35=Brian D. |last36=Carlson |first36=Marc R.J. |last37=Meder |first37=Benjamin |last38=Blin |first38=Nikolaus |last39=Meese |first39=Eckart |last40=Pusch |first40=Carsten M. |last41=Zink |first41=Albert |title=New insights into the Tyrolean Iceman's origin and phenotype as inferred by whole-genome sequencing |journal=Nature Communications |date=28 February 2012 |volume=3 |issue=1 |doi=10.1038/ncomms1701| doi-access = free|display-authors=1 |article-number=698 |pmid=22426219 |bibcode=2012NatCo...3..698K }}</ref>

The early European studies of what is now known as Lyme disease described its skin manifestations. The first study dates to 1883 in [[Breslau]], Germany (now [[Wrocław]], Poland), where physician Alfred Buchwald described a man who for 16 years had had a degenerative [[skin disorder]] now known as [[acrodermatitis chronica atrophicans]].<ref name="Afzelius1910"/>

At a 1909 research conference, Swedish dermatologist [[Arvid Afzelius]] presented a study about an expanding, ring-like lesion he had observed in an older woman following the bite of a sheep tick. He named the lesion ''erythema migrans''.<ref name="Afzelius1910" /> The skin condition now known as [[borrelial lymphocytoma]] was first described in 1911.<ref name=burckhardt_1911/>

===1950-1970===
Neurological problems following tick bites have been recognized since the 1920s. French physicians Garin and Bujadoux described a farmer with a painful sensory [[radiculitis]] accompanied by mild [[meningitis]] following a tick bite. A large, ring-shaped rash was also noted, although the doctors did not relate it to the meningoradiculitis. In 1930, the Swedish dermatologist Sven Hellerström was the first to propose that EM and neurological symptoms following a tick bite were related.<ref name=hellerstrom_1930/> In the 1940s, German neurologist [[Alfred Bannwarth]] described several cases of chronic lymphocytic meningitis and polyradiculoneuritis, some of which were accompanied by erythematous skin lesions.

Carl Lennhoff, who worked at the [[Karolinska Institute]] in Sweden, believed spirochetes caused many skin conditions. In 1948, he published on his use of a special stain to microscopically observe what he believed were spirochetes in various types of skin lesions, including EM.<ref name=lenhoff_1948/> Starting in 1946, facilities in Sweden experimented with treating EM rashes with substances known to kill spirochetes.<ref name="hollstrom-1951">{{cite journal |last1=Hollström |first1=Einar |title=Successful treatment of erythema migrans Afzelius |journal=Acta Dermato-venereologica |date=1951 |volume=31 |issue=2 |pages=235–43 |doi=10.2340/0001555531235243 |doi-broken-date=1 July 2025 |pmid=14829185 |url=https://www.medicaljournals.se/acta/content/abstract/10.2340/0001555531235243 }}</ref> {{ill|Einar Hollström|sv}} reported that "penicillin was found to be the most effective."<ref name="hollstrom-1958">{{cite journal |last1=Hollström |first1=Einar |title=Penicillin Treatment of erythema chronicum migrans afzelius |journal=Acta Dermato-Venereologica |date=1958 |volume=38 |issue=5 |pages=285–289 |url=https://medicaljournalssweden.se/actadv/article/view/2707 }}</ref> In 1949, Nils Thyresson, who also worked at the Karolinska Institute, was the first to treat ACA with penicillin.<ref name="pmid18140373"/> In the 1950s, the relationship among tick bite, lymphocytoma, EM and Bannwarth's syndrome was recognized throughout Europe, leading to the widespread use of [[penicillin]] for treatment in Europe.<ref name=Bianchi_1950/><ref name=Paschoud_1954/>

In 1970, a dermatologist in [[Wisconsin]] named Rudolph Scrimenti recognized an EM lesion in a person after recalling a paper by Hellerström that had been reprinted in an American science journal in 1950. This was the first documented case of EM in the United States. Based on the European literature, he treated the person with penicillin.<ref name=Scrimenti_1970/>

===From 1970===

Before 1976, the elements of ''B. burgdorferi sensu lato'' infection were called or known as tick-borne meningopolyneuritis, Garin-Bujadoux syndrome, Bannwarth syndrome, Afzelius's disease,<ref name="Bolognia"/> [[Montauk, New York|Montauk Knee]] or sheep tick fever. Since 1976, the disease has been most often referred to as Lyme disease,<ref name="Hazard Leland Mathewson Lyme Arthritis"/><ref name=Steere_1977/> Lyme borreliosis, or simply borreliosis.<ref>{{Cite web|url=https://www.ecdc.europa.eu/en/borreliosis/facts/factsheet|title=Factsheet about Borreliosis|website=European Centre for Disease Prevention and Control|date=17 June 2017 |language=en|access-date=30 January 2020|archive-url=https://web.archive.org/web/20190927011644/https://ecdc.europa.eu/en/borreliosis/facts/factsheet|archive-date=27 September 2019|url-status=live}}</ref><ref>{{Cite web|url=https://www.who.int/ith/diseases/lyme/en/|title=WHO {{!}} Lyme Borreliosis (Lyme disease)|website=WHO|access-date=30 January 2020|archive-url=https://web.archive.org/web/20191129114243/https://www.who.int/ith/diseases/lyme/en/|archive-date=29 November 2019}}</ref>

The full [[syndrome]] now known as Lyme disease was not recognized until a cluster of cases originally thought to be [[juvenile rheumatoid arthritis]]<ref name=Car2007>{{cite book| vauthors = Williams C |title=Infectious disease epidemiology: theory and practice|date=2007|publisher=Jones and Bartlett Publishers|location=Sudbury, Mass.|isbn=978-0-7637-2879-3|page=447|edition=2nd|url=https://books.google.com/books?id=o_j-G4zJ4cQC&pg=PA447|url-status=live|archive-url=https://web.archive.org/web/20170908151350/https://books.google.com/books?id=o_j-G4zJ4cQC&pg=PA447|archive-date=8 September 2017}}</ref> was identified in three towns in southeastern [[Connecticut]] in 1975, including the towns [[Lyme, Connecticut|Lyme]] and [[Old Lyme]], which gave the disease its popular name.<ref name=Borchers2015>{{cite journal | vauthors = Borchers AT, Keen CL, Huntley AC, Gershwin ME | title = Lyme disease: a rigorous review of diagnostic criteria and treatment | journal = Journal of Autoimmunity | volume = 57 | pages = 82–115 | date = February 2015 | pmid = 25451629 | doi = 10.1016/j.jaut.2014.09.004 }}</ref> This was investigated by physicians David Snydman and [[Allen Steere]] of the [[Epidemic Intelligence Service]], and by others from [[Yale University]], including [[Stephen Malawista]], who is credited as a co-discover of the disease.<ref name=hcourant>{{cite news| vauthors = Weir W |title=Lyme Disease Pioneer Stephen Malawista Dies|url=https://www.courant.com/2013/09/19/lyme-disease-pioneer-stephen-malawista-dies/|work=[[Hartford Courant]]|date=19 September 2013|access-date=14 October 2013|url-status=live|archive-url=https://web.archive.org/web/20131014173239/http://articles.courant.com/2013-09-19/health/hc-malawista-lyme-0920-20130919_1_lyme-disease-rheumatology-department-disease-control|archive-date=14 October 2013}}</ref> The recognition that the people in the United States had EM led to the recognition that "Lyme arthritis" was one manifestation of the same tick-borne condition known in Europe.<ref name=Sternbach/>

Ecological factors contributed to the emergence of Lyme disease in the 20th century of northeastern United States. These factors include large-scale reforestation, the increase of white-tailed deer populations, and suburban development into formerly rural woodlands.<ref>{{Cite journal |last1=Levi |first1=T |last2=Kilpatrick |first2=A.M. |last3=Mangel |first3=M |last4=Wilmers |first4=C.C. |title=Deer, predators, and the emergence of Lyme disease |journal=Proceedings of the National Academy of Sciences of the United States of America |year=2012 |volume=109 |issue=27 |pages=10942–10947 |doi=10.1073/pnas.1204536109 |doi-access=free |pmc=3390851 |pmid=22711825 |bibcode=2012PNAS..10910942L }}</ref>

In 1980, Steere, ''et al.'', began to test [[antibiotics|antibiotic]] regimens in adults with Lyme disease.<ref name=Steere_1983/> In the same year, New York State Health Dept. epidemiologist [[Jorge Benach]] provided [[Willy Burgdorfer]], a researcher at the [[Rocky Mountain Biological Laboratory]], with collections of ''I. dammini'' [''scapularis''] from Shelter Island, New York, a known Lyme-endemic area as part of an ongoing investigation of [[Rocky Mountain spotted fever]]. In examining the ticks for rickettsiae, Burgdorfer noticed "poorly stained, rather long, irregularly coiled spirochetes." Further examination revealed spirochetes in 60% of the ticks. Burgdorfer credited his familiarity with the European literature for his realization that the spirochetes might be the "long-sought cause of ECM and Lyme disease." Benach supplied him with more ticks from Shelter Island and [[Blood serum|sera]] from people diagnosed with Lyme disease. University of Texas Health Science Center researcher Alan Barbour "offered his expertise to culture and immunochemically characterize the organism." Burgdorfer subsequently confirmed his discovery by isolating spirochetes identical to those found in ticks from people with Lyme disease.<ref name=Burgdorfer_1984/> In June 1982, he published his findings in [[Science (journal)|Science]], and the spirochete was named ''Borrelia burgdorferi'' in his honor.<ref name=Burgdorfer_1982/><ref name=Tele2014>{{cite news|url=https://www.telegraph.co.uk/news/obituaries/11265730/Willy-Burgdorfer-obituary.html|title=Willy Burgdorfer – obituary|work=Daily Telegraph|date=1 December 2014|access-date=1 December 2014|url-status=live|archive-url=https://web.archive.org/web/20141201213904/http://www.telegraph.co.uk/news/obituaries/11265730/Willy-Burgdorfer-obituary.html|archive-date=1 December 2014}}</ref> 

After the identification of ''B. burgdorferi'' as the causative agent of Lyme disease, antibiotics were selected for testing, guided by ''in vitro'' antibiotic sensitivities, including [[tetracycline antibiotics]], [[amoxicillin]], [[cefuroxime axetil]], intravenous and intramuscular penicillin and intravenous [[ceftriaxone]].<ref name=Luft_1988/><ref name=Dattwyler_1990/> The mechanism of tick transmission was also the subject of much discussion. ''B. burgdorferi'' spirochetes were identified in tick saliva in 1987, confirming the hypothesis that transmission occurred via tick salivary glands.<ref name=Ribeiro_1987/>

==Society, culture, and controversy==
===Landscape changes and urbanization===

Urbanization and other [[Human impact on the environment|anthropogenic]] factors can be implicated in the spread of Lyme disease to humans. In many areas, the expansion of suburban neighborhoods has led to the gradual deforestation of surrounding wooded areas and increased border contact between humans and tick-dense areas. Human expansion has also resulted in a reduction of predators that hunt deer as well as mice, chipmunks and other small rodents—the primary reservoirs for Lyme disease. As a consequence of increased human contact with host and [[Vector (epidemiology)|vector]], the likelihood of transmission of the disease has greatly increased.<ref name="The ecology of infectious disease"/><ref name="Patz"/> Researchers are investigating possible links between [[global warming]] and the spread of vector-borne diseases, including Lyme disease.<ref name="Khasnis"/>

===The dilution effect===

Given these habitat-host dynamics, in 2003, some researchers began to postulate whether the so-called dilution effect could mitigate the spread of Lyme disease.<ref name="The ecology of infectious disease"/> The dilution effect is a hypothesis that predicts that an increase in host biodiversity will result in a decrease in the number of vectors infected with ''B. burgdorferi''.<ref name="The ecology of infectious disease"/> Scientific research has shown that nymphal infection prevalence (NIP) decreases as the number of host species increases, supporting the dilution effect.<ref name="The ecology of infectious disease"/> That said, there is no direct relationship between decreased NIP and decreased epidemiological risk, as this has yet to be proven.<ref name="The ecology of infectious disease"/> Additionally, as of 2018, the dilution effect is only supported in the Northeastern United States, and has been disproved in other parts of the world that also experience high Lyme disease incidence rates <ref>{{cite journal | vauthors = Ruyts SC, Landuyt D, Ampoorter E, Heylen D, Ehrmann S, Coipan EC, Matthysen E, Sprong H, Verheyen K | title = Low probability of a dilution effect for Lyme borreliosis in Belgian forests | journal = Ticks and Tick-Borne Diseases | volume = 9 | issue = 5 | pages = 1143–1152 | date = July 2018 | pmid = 29716838 | doi = 10.1016/j.ttbdis.2018.04.016 }}</ref>

===Chronic Lyme disease===
{{main|Chronic Lyme disease}}

The term "chronic Lyme disease" is controversial and not recognized in the medical literature,<ref name="nejm-feder"/> and most medical authorities advise against long-term antibiotic treatment for Lyme disease.<ref name="idsa guideline"/><ref name="pmid17522387"/><ref name="nih-cld"/> Studies have shown that most people diagnosed with "chronic Lyme disease" either have no objective evidence of previous or current infection with ''[[Borrelia burgdorferi|B. burgdorferi]]'' or are people who should be classified as having post-treatment Lyme disease syndrome (PTLDS), which is defined as continuing or relapsing [[non-specific symptoms]] (such as fatigue, musculoskeletal pain, and cognitive complaints) in a person previously treated for Lyme disease.<ref name="Marques"/>

The 2008 documentary ''[[Under Our Skin]]'' promoted controversial and unrecognized theories about "chronic Lyme disease".<ref name="under-our-skin-sbm">{{cite web | vauthors = MacBeth B |title=A Review of Under Our Skin, A Cult Classic |url=https://sciencebasedmedicine.org/a-review-of-under-our-skin-a-cult-classic/ |website=Science-Based Medicine |access-date=10 September 2021 |date=8 April 2019}}</ref>

===Conspiracy theories about origins ===

Prolific but unfounded [[Conspiracy theory|conspiracy theories]] have alleged that Lyme disease was a biological weapon that originated in the [[Plum Island Animal Disease Center|Plum Island laboratory]], which is near Old Lyme, Connecticut.<ref name="Telford-wapo">{{cite news|last1=Telford|first1=Sam|date=11 August 2019|title=No, Lyme disease is not an escaped military bioweapon, despite what conspiracy theorists say|language=en|newspaper=Washington Post|url=https://www.washingtonpost.com/health/no-lyme-diease-is-not-an-escaped-military-bioweapon-despite-what-conspiracy-theorists-say/2019/08/09/5bbd85fa-afe4-11e9-8e77-03b30bc29f64_story.html|access-date=10 August 2020}}</ref> A 2004 book entitled ''Lab 257: The Disturbing Story of the Government's Secret Plum Island Germ Laboratory'' fueled the conspiracy theories.<ref name="cnn">{{cite web|last=Dunn|first=Adam|title=The mysterious lab off New York's shore|url=http://www.cnn.com/2004/SHOWBIZ/books/04/02/lab.257/index.html|date=2009-04-02|archive-url= https://web.archive.org/web/20240915215926/https://www.cnn.com/2004/SHOWBIZ/books/04/02/lab.257/index.html|archive-date=2024-09-15|website=CNN.com|access-date=2009-01-10|url-status=live}}</ref><ref name="kirby">{{cite journal|last=Kirby|first=Reid|title=Book Reviews|journal=Army Chemical Review|url=http://www.wood.army.mil/chmdsd/pdfs/Jan-June%202005/BookReviews.pdf|archive-url=https://web.archive.org/web/20090309171459/http://www.wood.army.mil/chmdsd/pdfs/Jan-June%202005/BookReviews.pdf|archive-date=2009-03-09|issue=January–June 2005|page=51|access-date=2009-01-10}}</ref> Archived specimens show that Lyme disease was endemic well before the establishment of Plum Island laboratory.<ref name="Telford-wapo" /> Additionally, Lyme disease was never a topic of research at Plum Island, according to the US Department of Homeland Security and Department of Agriculture.<ref name="plum-island-web-site">{{cite web|date=6 July 2009|title=Plum Island Animal Disease Center|url=https://www.dhs.gov/science-and-technology/plum-island-animal-disease-center|access-date=10 August 2020|website=Department of Homeland Security|language=en}}</ref><ref name="cnn" />

In 2024 and 2025, conspiracy theories about the origins of Lyme disease were further spread due to attention from [[Robert F. Kennedy Jr]].<ref name="afp-rfk">{{cite news |last1=Galgano |first1=Daniel Patrick |title=RFK Jr Senate hearing resurrects Lyme disease bioweapon conspiracy theory |url=https://factcheck.afp.com/doc.afp.com.36X42X4 |access-date=24 February 2025 |work=AFP |date=5 February 2025 |archive-date=24 February 2025 |archive-url=https://web.archive.org/web/20250224160349/https://factcheck.afp.com/doc.afp.com.36X42X4 |url-status=live }}</ref>

==Other animals==
=== Dogs ===
Prevention of Lyme disease is an important step in keeping dogs safe in endemic areas. Prevention education and a number of preventive measures are available. First, for dog owners who live near or visit tick-infested areas, routine vaccinations of their dogs are an important step.<ref name=pmid20207198/>

Another crucial preventive measure is the use of persistent acaricides, such as topical repellents or pesticides that contain triazapentadienes ([[Amitraz]]), phenylpyrazoles ([[Fipronil]]), or permethrin ([[pyrethroids]]).<ref name=pmid20933139/> These acaricides target primarily the adult stages of Lyme-carrying ticks and reduce the number of reproductively active ticks in the environment.<ref name=pmid20207198/> Formulations of these ingredients are available in a variety of topical forms, including spot-ons, sprays, powders, impregnated collars, solutions, and shampoos.<ref name=pmid20933139/>

Examining a dog for ticks after visiting a tick-infested area is an important precautionary measure to prevent Lyme disease. Key spots to examine include the head, neck, and ears.<ref name=hahn/>

In dogs, a serious long-term prognosis may result in glomerular disease,<ref name=merck_2012/> a category of kidney damage that may cause [[chronic kidney disease]].<ref name="Brooks, DVM"/> Dogs may also experience chronic joint disease if the disease is left untreated. However, the majority of cases of Lyme disease in dogs result in complete recovery with, and sometimes without, treatment with antibiotics.<ref name=staubinger/>{{Verify source|date=July 2013}} In rare cases, Lyme disease can be fatal to both humans and dogs.<ref name="fatal-cases"/>

=== Cats ===
Unlike dogs, it is unusual for a cat to be infected with Lyme disease. However, cats are nevertheless capable of being infected with ''[[Borrelia burgdorferi|B. burgdorferi]] ,'' following a bite from an infected tick. Cats infected with Lyme Disease may show symptoms including, but not limited to, lameness, fatigue, or loss of appetite.<ref name="Merck Veterinary Manual">{{Cite web |last=Straubinger |first=Reinhard |year=2018 |title=Lyme Disease (Lyme Borreliosis) in Cats - Cat Owners |url=https://www.merckvetmanual.com/cat-owners/disorders-affecting-multiple-body-systems-of-cats/lyme-disease-lyme-borreliosis-in-cats |url-status=live |archive-url=https://web.archive.org/web/20210420102458/https://www.merckvetmanual.com/cat-owners/disorders-affecting-multiple-body-systems-of-cats/lyme-disease-lyme-borreliosis-in-cats |archive-date=2021-04-20 |access-date=2023-10-26 |website=Merck Veterinary Manual |language=en-US}}</ref> In two cases, the infected cats experienced cardiac irregularities similar to symptoms of Lyme in both dogs and humans.<ref name="Tørnqvist-Johnsen_2020">{{cite journal | vauthors = Tørnqvist-Johnsen C, Dickson SA, Rolph K, Palermo V, Hodgkiss-Geere H, Gilmore P, Gunn-Moore DA | title = First report of Lyme borreliosis leading to cardiac bradydysrhythmia in two cats | journal = JFMS Open Reports | volume = 6 | issue = 1 | article-number = 2055116919898292 | date = 2020 | pmid = 31949917 | pmc = 6950542 | doi = 10.1177/2055116919898292 }}</ref> However, cats who are infected with Lyme disease are likely to be [[asymptomatic]], and show no noticeable signs of the disease.<ref name="Tørnqvist-Johnsen_2020" /><ref name="Merck Veterinary Manual" /> Cats with Lyme are often treated with antibiotics, much like other animals. In some cases, additional treatment or therapy may be required.<ref name="Merck Veterinary Manual" />

=== Horses ===
Lyme disease in horses is challenging to diagnose due to variable symptoms. Common acute symptoms include weight loss, fever, [[Lameness (equine)|lameness]], [[ataxia]], and other muscle and joint-related issues.<ref name=":02">{{Cite journal |last1=Parker |first1=J. L. |last2=White |first2=K. K. |date=1992 |title=Lyme borreliosis in cattle and horses: a review of the literature |journal=The Cornell Veterinarian |volume=82 |issue=3 |pages=253–274 |pmid=1643876 }}</ref><ref name=":12">{{Cite journal |last1=Johnstone |first1=L. K. |last2=Engiles |first2=J. B. |last3=Aceto |first3=H. |last4=Buechner-Maxwell |first4=V. |last5=Divers |first5=T. |last6=Gardner |first6=R. |last7=Levine |first7=R. |last8=Scherrer |first8=N. |last9=Tewari |first9=D. |last10=Tomlinson |first10=J. |last11=Johnson |first11=A. L. |date=2016 |title=Retrospective Evaluation of Horses Diagnosed with Neuroborreliosis on Postmortem Examination: 16 Cases (2004-2015) |journal=Journal of Veterinary Internal Medicine |volume=30 |issue=4 |pages=1305–1312 |doi=10.1111/jvim.14369 |pmc=5094551 |pmid=27327172 }}</ref><ref>{{Cite journal |last=Van der Kolk |first=J. H. |date=2016 |title=Lyme borreliosis in the horse: A mini-review |journal=Journal of Experimental Biology and Agricultural Sciences |volume=4 |issue=Spl-4-EHIDZ |pages=S196–S202 |doi=10.18006/2016.4(Spl-4-EHIDZ).S196.S202 |doi-access=free }}</ref> Additional symptoms include muscle tenderness, swollen joints, [[arthritis]], and neck stiffness.<ref name=":2">{{Cite journal |last1=Burgess |first1=E. C. |last2=Gillette |first2=D. |last3=Pickett |first3=J. |date=1986 |title=Arthritis and panuveitis as manifestations of Borrelia burgdorferi infection in a Wisconsin pony |journal=Journal of the American Veterinary Medical Association |volume=189 |issue=10 |pages=1340–1342 |doi=10.2460/javma.1986.189.10.1340 |pmid=3793582 }}</ref><ref name=":3">{{Cite journal |last1=Browning |first1=A. |last2=Carter |first2=S. D. |last3=Barnes |first3=A. |last4=May |first4=C. |last5=Bennett |first5=D. |date=1993 |title=Lameness associated with Borrelia burgdorferi infection in the horse |journal=The Veterinary Record |volume=132 |issue=24 |pages=610–611 |doi=10.1136/vr.132.24.610 |doi-broken-date=12 July 2025 |pmid=8337810 }}</ref><ref>{{Cite journal |last1=Gall |first1=Y |last2=Pfister |first2=K |date=2006 |title=Survey on the subject of equine Lyme borreliosis |journal=International Journal of Medical Microbiology |volume=296 |issue=1 |pages=274–279 |doi=10.1016/j.ijmm.2006.01.004 |pmid=16524771 }}</ref> Chronic symptoms of the disease typically include neurological manifestations, such as [[meningitis]], cranial neuritis, [[radiculoneuritis]], and [[encephalitis]].{{efn|Attributed to multiple references:<ref>{{Cite journal |last1=Burgess |first1=E. C. |last2=Mattison |first2=M. |date=1987 |title=Encephalitis associated with Borrelia burgdorferi infection in a horse |journal=Journal of the American Veterinary Medical Association |volume=191 |issue=11 |pages=1457–1458 |doi=10.2460/javma.1987.191.11.1457 |pmid=3692996 }}</ref><ref name=":02" /><ref name=":4">{{Cite journal |last1=Hahn |first1=C. N. |last2=Mayhew |first2=I. G. |last3=Whitwell |first3=K. E. |last4=Smith |first4=K. C. |last5=Carey |first5=D. |last6=Carter |first6=S. D. |last7=Read |first7=R. A. |date=1996 |title=A possible case of Lyme borreliosis in a horse in the UK |journal=Equine Veterinary Journal |volume=28 |issue=1 |pages=84–88 |doi=10.1111/j.2042-3306.1996.tb01595.x |pmid=8565961 }}</ref><ref>{{Cite journal |last1=James |first1=F. M. |last2=Engiles |first2=J. B. |last3=Beech |first3=J. |date=2010 |title=Meningitis, cranial neuritis, and radiculoneuritis associated with Borrelia burgdorferi infection in a horse |journal=Journal of the American Veterinary Medical Association |volume=237 |issue=10 |pages=1180–1185 |doi=10.2460/javma.237.10.1180 |pmid=21073390 }}</ref>}} Furthermore, some horses do not slow clinical signs of Lyme disease.<ref name=":5">{{Cite journal |last1=Divers |first1=T. J. |last2=Gardner |first2=R. B. |last3=Madigan |first3=J. E. |last4=Witonsky |first4=S. G. |last5=Bertone |first5=J. J. |last6=Swinebroad |first6=E. L. |last7=Schutzer |first7=S. E. |last8=Johnson |first8=A. L. |date=2018 |title=Borrelia burgdorferi Infection and Lyme Disease in North American Horses: A Consensus Statement |journal=Journal of Veterinary Internal Medicine |volume=32 |issue=2 |pages=617–632 |doi=10.1111/jvim.15042 |pmc=5866975 |pmid=29469222 }}</ref>

There are three main testing strategies used to diagnose horses with Lyme disease. They include clinical evaluation, [[serological testing]], and [[polymerase chain reaction]] (PCR) testing.<ref>{{Cite journal |last1=Cohen |first1=N. D. |last2=Heck |first2=F. C. |last3=Heim |first3=B. |last4=Flad |first4=D. M. |last5=Bosler |first5=E. M. |last6=Cohen |first6=D. |date=1992 |title=Seroprevalence of antibodies to Borrelia burgdorferi in a population of horses in central Texas |journal=Journal of the American Veterinary Medical Association |volume=201 |issue=7 |pages=1030–1034 |doi=10.2460/javma.1992.201.07.1030 |pmid=1429127 }}</ref><ref>{{Cite journal |last1=Metcalf |first1=K. B. |last2=Lilley |first2=C. S. |last3=Revenaugh |first3=M. S. |last4=Glaser |first4=A. L. |last5=Metcalf |first5=E. S. |date=2008 |title=The prevalence of antibodies against Borrelia burgdorferi found in horses residing in the northwestern United States |journal=Journal of Equine Veterinary Science |volume=28 |issue=10 |pages=587–589 |doi=10.1016/j.jevs.2008.08.010 }}</ref><ref name=":12" /> Detection of [[Antibody|specific antibodies]] against ''B. burgdorferi'' alone is not sufficient for a diagnosis of [[Equinae|equine]] Lyme disease, and unspecific testing for antibodies is not recommended.<ref>{{cite journal |vauthors=Gehlen H, Inerle K, Bartel A, Stöckle SD, Ulrich S, Briese B, Straubinger RK |date=June 2023 |title=Seroprevalence of ''Borrelia burgdorferi'' sensu lato and ''Anaplasma phagocytophilum'' Infections in German Horses |journal=Animals |volume=13 |issue=12 |page=1984 |doi=10.3390/ani13121984 |pmc=10295046 |pmid=37370494 |doi-access=free}}</ref>

Typical treatment involves antibiotics such as [[oxytetracycline]], [[doxycycline]], [[ceftriaxone]], or [[minocycline]].<ref>{{Cite journal |last1=Bryant |first1=J. E. |last2=Brown |first2=M. P. |last3=Gronwall |first3=R. R. |last4=Merritt |first4=K. A. |date=2000 |title=Study of intragastric administration of doxycycline: pharmacokinetics including body fluid, endometrial and minimum inhibitory concentrations |journal=Equine Veterinary Journal |volume=32 |issue=3 |pages=233–238 |doi=10.2746/042516400776563608 |pmid=10836479 }}</ref><ref name=":6">{{Cite journal |last1=Chang |first1=Y. F. |last2=Ku |first2=Y. W. |last3=Chang |first3=C. F. |last4=Chang |first4=C. D. |last5=McDonough |first5=S. P. |last6=Divers |first6=T. |last7=Pough |first7=M. |last8=Torres |first8=A. |date=2005 |title=Antibiotic treatment of experimentally Borrelia burgdorferi-infected ponies |journal=Veterinary Microbiology |volume=107 |issue=3 |pages=285–294 |doi=10.1016/j.vetmic.2005.02.006 |pmid=15863289 }}</ref><ref name=":5" /> In some cases, a combination of antibiotics may be administered. Doxycycline and minocycline are taken orally, while oxytetracycline and ceftriaxone are usually administered intravenously.<ref name=":6" /><ref>{{Cite journal |last1=Schnabel |first1=L. V. |last2=Papich |first2=M. G. |last3=Divers |first3=T. J. |last4=Altier |first4=C. |last5=Aprea |first5=M. S. |last6=McCarrel |first6=T. M. |last7=Fortier |first7=L. A. |date=2012 |title=Pharmacokinetics and distribution of minocycline in mature horses after oral administration of multiple doses and comparison with minimum inhibitory concentrations |journal=Equine Veterinary Journal |volume=44 |issue=4 |pages=453–458 |doi=10.1111/j.2042-3306.2011.00459.x |pmid=21950341 }}</ref><ref name=":5" /> The duration and dosage of treatment vary widely among cases. In most cases, the infected horse is [[euthanized]].{{efn|Attributed to multiple references:<ref name=":2" /><ref name=":3" /><ref name=":4" /><ref>{{Cite journal |last1=Sears |first1=K. P. |last2=Divers |first2=T. J. |last3=Neff |first3=R. T. |last4=Miller |first4=W. H. |last5=McDonough |first5=S. P. |date=2012 |title=A case of Borrelia-associated cutaneous pseudolymphoma in a horse |journal=Veterinary Dermatology |volume=23 |issue=2 |pages=153–156 |doi=10.1111/j.1365-3164.2011.01013.x |pmid=22029872 }}</ref>}} Death of horses as a result of ''Borrelia burgdorferi'' infection remains unknown.<ref>{{Cite journal |last1=Divers |first1=T. J. |last2=Grice |first2=A. L. |last3=Mohammed |first3=H. O. |last4=Glaser |first4=A. L. |last5=Wagner |first5=B. |date=2012 |title=Changes in Borrelia burgdorferi ELISA antibody over time in both antibiotic treated and untreated horses |journal=Acta Veterinaria Hungarica |volume=60 |issue=4 |pages=421–429|doi=10.1556/avet.2012.036 |pmid=23160024 }}</ref>

Currently, there is no approved Lyme disease vaccine for horses.<ref name=":7">{{Cite journal |last1=Guarino |first1=C. |last2=Asbie |first2=S. |last3=Rohde |first3=J. |last4=Glaser |first4=A. |last5=Wagner |first5=B. |date=2017 |title=Vaccination of horses with Lyme vaccines for dogs induces short-lasting antibody responses |journal=Vaccine |volume=35 |issue=33 |pages=4140–4147 |doi=10.1016/j.vaccine.2017.06.052 |doi-access=free |pmid=28668566 }}</ref> However, a study demonstrated that ponies could be protected using an aluminum adjuvanted recombinant [[Outer surface protein|outer-surface protein]] A (rOspA) vaccine.<ref>{{Cite journal |last1=Chang |first1=Y. F. |last2=Novosol |first2=V. |last3=McDonough |first3=S. P. |last4=Chang |first4=C. F. |last5=Jacobson |first5=R. H. |last6=Divers |first6=T. |last7=Quimby |first7=F. W. |last8=Shin |first8=S. |last9=Lein |first9=D. H. |date=1999 |title=Vaccination against Lyme Disease with recombinant Borrelia burgdorferi outer-surface protein A (rOspA) in horses |journal=Vaccine |volume=18 |issue=5 |pages=540–548 |doi=10.1016/S0264-410X(99)00187-5 |pmid=10519945 |doi-access=free }}</ref> While horses have been administered a Lyme disease vaccine designed for dogs, it elicits only a short-lasting antibody response.<ref name=":7" /> Another study supports the use of commercial Lyme disease vaccines, showing that they do elicit an antibody response, which can be significantly enhanced when horses receive an additional booster vaccine.<ref>{{Cite journal |last1=Knödlseder |first1=J. M. |last2=Fell |first2=S. F. |last3=Straubinger |first3=R. K. |date=2019 |title=A study with a commercial vaccine against Lyme borreliosis in horses using two different vaccination schedules: Characterization of the humoral immune response |journal=Vaccine |volume=37 |issue=49 |pages=7207–7212 |doi=10.1016/j.vaccine.2019.09.087 |pmid=31635975 }}</ref>

== References ==
=== Notes ===
{{Notelist}}

=== Citations ===
{{Reflist|refs=
<ref name="Afzelius1910">{{cite journal |doi=10.1007/BF01832773 |title=Verhandlungen der dermatologischen Gesellschaft zu Stockholm |year=1910 | vauthors = Marcus K |journal=Archiv für Dermatologie und Syphilis |volume=101 |issue=2–3 |pages=403–06 }}</ref>

<ref name=burckhardt_1911>{{cite journal | vauthors = Burckhardt JL | title = Zur Frage der Follikel- und Keimzentrenbildung in der Haut | journal = Frankf. Z. Pathol. | language = de | year = 1911 | volume = 6 | pages = 352–59}}</ref>

<ref name=Bianchi_1950>{{cite journal | vauthors = Bianchi GE | title = [Penicillin therapy of lymphocytoma] | language = de | journal = Dermatologica | volume = 100 | issue = 4–6 | pages = 270–273 | year = 1950 | pmid = 15421023 | doi = 10.1159/000257185 | trans-title = Penicillin therapy of lymphocytoma }}</ref>

<ref name="Bolognia">{{cite book | vauthors = Bolognia JL, Jorizzo JL, Rapini RP |title=Dermatology |publisher=Mosby |location=St. Louis |year=2007 |isbn=978-1-4160-2999-1 | edition = 2nd }}{{page needed|date=March 2013}}</ref>

<ref name=Burgdorfer_1984>{{cite journal | vauthors = Burgdorfer W | title = Discovery of the Lyme disease spirochete and its relation to tick vectors | journal = The Yale Journal of Biology and Medicine | volume = 57 | issue = 4 | pages = 515–520 | year = 1984 | pmid = 6516454 | pmc = 2590008 }}</ref>

<ref name=Burgdorfer_1982>{{cite journal | vauthors = Burgdorfer W, Barbour AG, Hayes SF, Benach JL, Grunwaldt E, Davis JP | title = Lyme disease-a tick-borne spirochetosis? | journal = Science | volume = 216 | issue = 4552 | pages = 1317–1319 | date = June 1982 | pmid = 7043737 | doi = 10.1126/science.7043737 | bibcode = 1982Sci...216.1317B | url = https://www.escholarship.org/uc/item/9vj3t37b }}</ref>

<ref name=CDC-FAQ>{{cite web |title=CDC Lyme disease FAQ |url=https://www.cdc.gov/lyme/faq/index.html |website=Centers for Disease Control and Prevention |access-date=11 January 2023 |language=en-us |date=8 January 2021 |archive-date=26 March 2013 |archive-url=https://web.archive.org/web/20130326120941/http://www.cdc.gov/lyme/faq/index.html |url-status=live }}</ref>

<ref name=Bolz_2004>{{cite journal | vauthors = Bolz DD, Weis JJ | title = Molecular mimicry to Borrelia burgdorferi: pathway to autoimmunity? | journal = Autoimmunity | volume = 37 | issue = 5 | pages = 387–392 | date = August 2004 | pmid = 15621562 | doi = 10.1080/08916930410001713098 }}</ref>

<ref name="Brown">{{cite journal | vauthors = Brown SL, Hansen SL, Langone JJ | title = Role of serology in the diagnosis of Lyme disease | journal = JAMA | volume = 282 | issue = 1 | pages = 62–66 | date = July 1999 | pmid = 10404913 | doi = 10.1001/jama.282.1.62 }}</ref>

<ref name="cdc-diagnosis">{{cite web | publisher = [[Centers for Disease Control and Prevention]] (CDC) | url = https://www.cdc.gov/ncidod/dvbid/lyme/ld_humandisease_diagnosis.htm | title = Lyme disease diagnosis | date = 7 October 2008 | access-date = 6 July 2009 | url-status=live | archive-url = https://web.archive.org/web/20090828074557/http://www.cdc.gov/ncidod/dvbid/LYME/ld_humandisease_diagnosis.htm | archive-date = 28 August 2009}}</ref>

<ref name=Burdash_1991>{{cite journal | vauthors = Burdash N, Fernandes J | title = Lyme borreliosis: detecting the great imitator | journal = The Journal of the American Osteopathic Association | volume = 91 | issue = 6 | pages = 573–4, 577–8 | date = June 1991 | pmid = 1874654 | doi = 10.1515/jom-1991-910610 | doi-access = free }}</ref>

<ref name="Clark">{{cite journal | vauthors = Clark K | title = Borrelia species in host-seeking ticks and small mammals in northern Florida | journal = Journal of Clinical Microbiology | volume = 42 | issue = 11 | pages = 5076–5086 | date = November 2004 | pmid = 15528699 | pmc = 525154 | doi = 10.1128/JCM.42.11.5076-5086.2004 }}</ref>

<ref name=Bacon_2008>{{cite journal | vauthors = Bacon RM, Kugeler KJ, Mead PS | title = Surveillance for Lyme disease--United States, 1992-2006 | journal = Morbidity and Mortality Weekly Report. Surveillance Summaries | volume = 57 | issue = 10 | pages = 1–9 | date = October 2008 | pmid = 18830214 | url = https://www.cdc.gov/mmwr/preview/mmwrhtml/ss5710a1.htm | url-status = live | archive-url = https://web.archive.org/web/20121110131222/http://www.cdc.gov/mmwr/preview/mmwrhtml/ss5710a1.htm | archive-date = 10 November 2012 }}</ref>

<ref name=Coyle_1995>{{cite journal | vauthors = Coyle PK, Schutzer SE, Deng Z, Krupp LB, Belman AL, Benach JL, Luft BJ | title = Detection of Borrelia burgdorferi-specific antigen in antibody-negative cerebrospinal fluid in neurologic Lyme disease | journal = Neurology | volume = 45 | issue = 11 | pages = 2010–2015 | date = November 1995 | pmid = 7501150 | doi = 10.1212/WNL.45.11.2010 }}</ref>

<ref name=bbc_dogs_2012>{{Cite news |url=https://www.bbc.co.uk/news/health-16706942 |title=Lyme disease risk from dogs 'higher than thought' |journal=BBC News |date=24 January 2012 |url-status=live |archive-url=https://web.archive.org/web/20120131034350/http://www.bbc.co.uk/news/health-16706942 |archive-date=31 January 2012 | vauthors = Roberts M }}</ref>

<ref name=Dattwyler_1990>{{cite journal | vauthors = Dattwyler RJ, Volkman DJ, Conaty SM, Platkin SP, Luft BJ | title = Amoxycillin plus probenecid versus doxycycline for treatment of erythema migrans borreliosis | journal = Lancet | volume = 336 | issue = 8728 | pages = 1404–1406 | date = December 1990 | pmid = 1978873 | doi = 10.1016/0140-6736(90)93103-V }}</ref>

<ref name=de_1997>{{cite journal | vauthors = de Mik EL, van Pelt W, Docters-van Leeuwen BD, van der Veen A, Schellekens JF, Borgdorff MW | title = The geographical distribution of tick bites and erythema migrans in general practice in The Netherlands | journal = International Journal of Epidemiology | volume = 26 | issue = 2 | pages = 451–457 | date = April 1997 | pmid = 9169184 | doi = 10.1093/ije/26.2.451 | doi-access = free }}</ref>

<ref name="cautionary">{{cite journal | vauthors = Nigrovic LE, Thompson KM | title = The Lyme vaccine: a cautionary tale | journal = Epidemiology and Infection | volume = 135 | issue = 1 | pages = 1–8 | date = January 2007 | pmid = 16893489 | pmc = 2870557 | doi = 10.1017/S0950268806007096 }}</ref>

<ref name=Bouattour_2004>{{cite journal | vauthors = Bouattour A, Ghorbel A, Chabchoub A, Postic D | title = Situation de la borreliose de Lyme au Maghreb | trans-title = Lyme borreliosis situation in North Africa | language = fr | journal = Archives de l'Institut Pasteur de Tunis | volume = 81 | issue = 1–4 | pages = 13–20 | year = 2004 | id = {{INIST|17501974}} | pmid = 16929760 | url = https://applications.emro.who.int/imemrf/Arch_Inst_Pasteur_Tunis/Arch_Inst_Pasteur_Tunis_2004_81_1_4_13_20.pdf }}</ref>

<ref name=Drymon_2008>{{cite book | author = Drymon M. M. |year=2008 |title=Disguised as the devil: how Lyme disease created witches and changed history |chapter=Affliction | chapter-url=https://books.google.com/books?id=w-x8LwQ2ZeYC&pg=PA51 |pages=51–52 |publisher=Wythe Avenue Press |isbn=978-0-615-20061-3}}</ref>

<ref name="Brooks, DVM">{{cite web| vauthors = Brooks WC |title=Lyme Disease|url=http://www.VeterinaryPartner.com/Content.plx?P=A&S=0&C=0&A=1588&EVetID=3001782|publisher=Veterinary Information Network|access-date=10 February 2012|archive-url=https://web.archive.org/web/20150404175140/http://www.veterinarypartner.com/Content.plx?P=A&S=0&C=0&A=1588&EVetID=3001782|archive-date=4 April 2015|url-status=live}}</ref>

<ref name=disease_action_2011>{{cite web |url=http://www.lymediseaseaction.org.uk/latest-news/concern-about-rise-in-lyme-disease-cases/ |title=Concern about rise in Lyme disease cases |publisher=Lyme Disease Action |date=15 December 2011 |access-date=15 December 2012 |url-status=live |archive-url=https://web.archive.org/web/20130619044643/http://www.lymediseaseaction.org.uk/latest-news/concern-about-rise-in-lyme-disease-cases/ |archive-date=19 June 2013 }}</ref>

<ref name=cassidy_2011>{{cite news |url=http://www.pressandjournal.co.uk/Article.aspx/2177018 |work=Press and Journal |title=Tayside revealed as a Lyme disease hotspot as cases soar | vauthors = Cassidy F |date=14 March 2011 |url-status=live |archive-url=https://web.archive.org/web/20160311055843/http://pressandjournal.co.uk/article.aspx/2177018 |archive-date=11 March 2016 }}</ref>

<ref name=danger_2009>{{cite web |url=http://www.rcn.org.uk/development/communities/specialisms/travel_health/news_stories/lyme_disease_a_clear_and_present_danger |title=Lyme disease: A clear and present danger |publisher=RCN |date=28 April 2009 |access-date=15 December 2012 |url-status=live |archive-url=https://web.archive.org/web/20130329024552/http://www.rcn.org.uk/development/communities/specialisms/travel_health/news_stories/lyme_disease_a_clear_and_present_danger |archive-date=29 March 2013 }}</ref>

<ref name=cdc_stats_2012>{{cite web | url = https://www.cdc.gov/lyme/stats/chartstables/reportedcases_statelocality.html | author = CDC | title = Reported Lyme disease cases by state, 2000-2010 | date = 4 January 2012 | access-date = 29 April 2012 | publisher = [[Centers for Disease Control and Prevention]] (CDC) | url-status=live | archive-url = https://web.archive.org/web/20120504101019/http://www.cdc.gov/lyme/stats/chartstables/reportedcases_statelocality.html | archive-date = 4 May 2012}}</ref>

<ref name=cdc_stats2>{{cite web | url = https://www.cdc.gov/lyme/stats/index.html | title = Lyme Disease Data | archive-url = https://web.archive.org/web/20120430203213/http://www.cdc.gov/lyme/stats/index.html | archive-date=30 April 2012 | publisher = [[Centers for Disease Control and Prevention]] (CDC) }}</ref>

<ref name=Ercolini>{{cite journal | vauthors = Ercolini AM, Miller SD | title = The role of infections in autoimmune disease | journal = Clinical and Experimental Immunology | volume = 155 | issue = 1 | pages = 1–15 | date = January 2009 | pmid = 19076824 | pmc = 2665673 | doi = 10.1111/j.1365-2249.2008.03834.x }}</ref>

<ref name="Halperin2008">{{cite journal | vauthors = Halperin JJ | title = Nervous system Lyme disease | journal = Infectious Disease Clinics of North America | volume = 22 | issue = 2 | pages = 261–74, vi | date = June 2008 | pmid = 18452800 | doi = 10.1016/j.idc.2007.12.009 }}</ref>

<ref name=hellerstrom_1930>{{cite journal | vauthors = Hellerström S | title = ''Erythema chronicum migrans Afzelii'' | journal = Acta Derm. Venerol. | language = de | year = 1930 | volume = 11 | pages = 315–21}}</ref>

<ref name=defra_2009>{{cite web |url=http://www.defra.gov.uk/publications/files/pb13571-zoonoses2009-110125.pdf |title=Zoonoses report UK 2009 |publisher=[[Department for Environment, Food and Rural Affairs|DEFRA]] |date=24 January 2011 |url-status=live |archive-url=https://web.archive.org/web/20121103141930/http://www.defra.gov.uk/publications/files/pb13571-zoonoses2009-110125.pdf |archive-date=3 November 2012 }}</ref>

<ref name=Hoen_2009>{{cite journal | vauthors = Hoen AG, Margos G, Bent SJ, Diuk-Wasser MA, Barbour A, Kurtenbach K, Fish D | title = Phylogeography of Borrelia burgdorferi in the eastern United States reflects multiple independent Lyme disease emergence events | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 106 | issue = 35 | pages = 15013–15018 | date = September 2009 | pmid = 19706476 | pmc = 2727481 | doi = 10.1073/pnas.0903810106 | doi-access = free | bibcode = 2009PNAS..10615013H | jstor = 40484546 }}<br />Lay summary: {{cite web | title = Lyme Bacterium, Once Nearly Eradicated In U.S., Rebounded With Forests | url = http://news.yale.edu/2009/08/10/lyme-bacterium-once-nearly-eradicated-us-rebounded-forests | date = 10 August 2009 | website = YaleNews }}</ref>

<ref name=hovius_2007>{{cite journal | vauthors = Hovius JW, van Dam AP, Fikrig E | title = Tick-host-pathogen interactions in Lyme borreliosis | journal = Trends in Parasitology | volume = 23 | issue = 9 | pages = 434–438 | date = September 2007 | pmid = 17656156 | doi = 10.1016/j.pt.2007.07.001 }}</ref>

<ref name=Dsouli_2006>{{cite journal |last1=Dsouli |first1=Najla |last2=Younsi-kabachii |first2=Hend |last3=Postic |first3=Danièle |last4=Nouira |first4=Said |last5=Gern |first5=Lise |last6=Bouattour |first6=Ali |title=Reservoir Role of Lizard Psammodromus algirus in Transmission Cycle of Borrelia burgdorferi Sensu Lato (Spirochaetaceae) in Tunisia |journal=Journal of Medical Entomology |date=July 2006 |volume=43 |issue=4 |pages=737–742 |doi=10.1093/jmedent/43.4.737 |pmid=16892633 }}</ref>

<ref name="Hofmann">{{cite journal | vauthors = Hofmann H | title = Lyme borreliosis--problems of serological diagnosis | journal = Infection | volume = 24 | issue = 6 | pages = 470–472 | year = 1996 | pmid = 9007597 | doi = 10.1007/BF01713052 }}</ref>

<ref name="Hildenbrand2009">{{cite journal | vauthors = Hildenbrand P, Craven DE, Jones R, Nemeskal P | title = Lyme neuroborreliosis: manifestations of a rapidly emerging zoonosis | journal = AJNR. American Journal of Neuroradiology | volume = 30 | issue = 6 | pages = 1079–1087 | date = June 2009 | pmid = 19346313 | pmc = 7051319 | doi = 10.3174/ajnr.A1579 | doi-access = free }}</ref>

<ref name="idsa guideline">{{cite journal | vauthors = Wormser GP, Dattwyler RJ, Shapiro ED, Halperin JJ, Steere AC, Klempner MS, Krause PJ, Bakken JS, Strle F, Stanek G, Bockenstedt L, Fish D, Dumler JS, Nadelman RB | title = The clinical assessment, treatment, and prevention of lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America | journal = Clinical Infectious Diseases | volume = 43 | issue = 9 | pages = 1089–1134 | date = November 2006 | pmid = 17029130 | doi = 10.1086/508667 | first12 = D | doi-access = free }}</ref>

<ref name="fatal-cases">Fatal cases of Lyme disease reported in the medical literature include:
* {{cite journal | vauthors = Kirsch M, Ruben FL, Steere AC, Duray PH, Norden CW, Winkelstein A | title = Fatal adult respiratory distress syndrome in a patient with Lyme disease | journal = JAMA | volume = 259 | issue = 18 | pages = 2737–2739 | date = May 1988 | pmid = 3357244 | doi = 10.1001/jama.1988.03720180063034 }}
* {{cite journal | vauthors = Oksi J, Kalimo H, Marttila RJ, Marjamäki M, Sonninen P, Nikoskelainen J, Viljanen MK | title = Inflammatory brain changes in Lyme borreliosis. A report on three patients and review of literature | journal = Brain | volume = 119 | issue = Pt 6 | pages = 2143–2154 | date = December 1996 | pmid = 9010017 | doi = 10.1093/brain/119.6.2143 | doi-access = free }}
* {{cite journal | vauthors = Waniek C, Prohovnik I, Kaufman MA, Dwork AJ | title = Rapidly progressive frontal-type dementia associated with Lyme disease | journal = The Journal of Neuropsychiatry and Clinical Neurosciences | volume = 7 | issue = 3 | pages = 345–347 | year = 1995 | pmid = 7580195 | doi = 10.1176/jnp.7.3.345 }}
* {{cite journal | vauthors = Cary NR, Fox B, Wright DJ, Cutler SJ, Shapiro LM, Grace AA | title = Fatal Lyme carditis and endodermal heterotopia of the atrioventricular node | journal = Postgraduate Medical Journal | volume = 66 | issue = 772 | pages = 134–136 | date = February 1990 | pmid = 2349186 | pmc = 2429516 | doi = 10.1136/pgmj.66.772.134 }}</ref>

<ref name=Fivaz_1989>{{cite journal | vauthors = Fivaz BH, Petney TN | title = Lyme disease--a new disease in southern Africa? | journal = Journal of the South African Veterinary Association | volume = 60 | issue = 3 | pages = 155–158 | date = September 1989 | pmid = 2699499 }}</ref>
<ref name=fact_sheet_2012>{{cite web |url=http://www.phac-aspc.gc.ca/id-mi/lyme-fs-eng.php |title=Lyme Disease Fact Sheet |publisher=Phac-aspc.gc.ca |date=4 July 2012 |access-date=15 December 2012 |url-status=live |archive-url=https://web.archive.org/web/20121227120507/http://www.phac-aspc.gc.ca/id-mi/lyme-fs-eng.php |archive-date=27 December 2012 }}</ref>

<ref name=Josselyn_1670>{{cite book | vauthors = Josselyn J |year=1670 |title=An Account of Two Voyages to New-England Made during the Years 1638, 1663 |url=http://www.americanjourneys.org/aj-107/ |url-status=live |archive-url=https://web.archive.org/web/20130625005205/http://www.americanjourneys.org/aj-107/ |archive-date=25 June 2013 }}page 92</ref>

<ref name=kirby_2004>{{cite book | vauthors = Stafford KC | title = Tick Management Handbook | url = http://www.ct.gov/caes/lib/caes/documents/special_features/TickHandbook.pdf | year = 2004 | publisher = Connecticut Agricultural Experiment Station and Connecticut Department of Public Health | page = 46 | access-date = 21 August 2007 | archive-url = https://web.archive.org/web/20071025220415/http://www.ct.gov/caes/lib/caes/documents/special_features/TickHandbook.pdf | archive-date = 25 October 2007}}</ref>

<ref name=Ledin_2005>{{cite journal | vauthors = Ledin KE, Zeidner NS, Ribeiro JM, Biggerstaff BJ, Dolan MC, Dietrich G, Vredevoe L, Piesman J | title = Borreliacidal activity of saliva of the tick Amblyomma americanum | journal = Medical and Veterinary Entomology | volume = 19 | issue = 1 | pages = 90–95 | date = March 2005 | pmid = 15752182 | doi = 10.1111/j.0269-283X.2005.00546.x }}</ref>

<ref name=hahn>{{cite web| vauthors = Hahn J |title=Ticks and Their Control|url=http://www.extension.umn.edu/distribution/horticulture/DD1013.html|publisher=Regents of the University of Minnesota|archive-url=https://web.archive.org/web/20120225120056/http://www.extension.umn.edu/distribution/horticulture/DD1013.html|archive-date=25 February 2012|access-date=19 February 2012}}</ref>

<ref name=lenhoff_1948>{{cite journal | vauthors = Lennhoff C | title = Spirochaetes in aetiologically obscure diseases | journal = Acta Dermato-Venereologica | volume = 28 | issue = 3 | pages = 295–324 | year = 1948 | pmid = 18891989 }}</ref>

<ref name=hansard1991>{{cite web | url = https://api.parliament.uk/historic-hansard/lords/1991/nov/11/lyme-disease | title = Lyme Disease | archive-url = https://web.archive.org/web/20130615185628/http://hansard.millbanksystems.com/lords/1991/nov/11/lyme-disease | archive-date=15 June 2013 | work = [[Hansard|Parliamentary Debates (Hansard)]] | url-status = live | date = 11 November 1991 }}</ref>

<ref name=Lindgren_2001>{{cite journal | vauthors = Lindgren E, Gustafson R | title = Tick-borne encephalitis in Sweden and climate change | journal = Lancet | volume = 358 | issue = 9275 | pages = 16–18 | date = July 2001 | pmid = 11454371 | doi = 10.1016/S0140-6736(00)05250-8 }}</ref>

<ref name=hansard_1997>{{cite web | url = https://api.parliament.uk/historic-hansard/written-answers/1997/feb/03/lyme-disease#S6CV0289P0_19970203_CWA_15 | title = Lyme Disease | archive-url = https://web.archive.org/web/20130615175146/http://hansard.millbanksystems.com/written_answers/1997/feb/03/lyme-disease | archive-date=15 June 2013 | work = [[Hansard|Parliamentary Debates (Hansard)]] | url-status = live | date = 3 February 1997 }}</ref>

<ref name=Luft_1988>{{cite journal | vauthors = Luft BJ, Volkman DJ, Halperin JJ, Dattwyler RJ | title = New chemotherapeutic approaches in the treatment of Lyme borreliosis | journal = Annals of the New York Academy of Sciences | volume = 539 | issue = 1 | pages = 352–361 | year = 1988 | pmid = 3056203 | doi = 10.1111/j.1749-6632.1988.tb31869.x | bibcode = 1988NYASA.539..352L }}</ref>

<ref name=Helmy_2000>{{cite journal | vauthors = Helmy N | title = Seasonal abundance of Ornithodoros (O.) savignyi and prevalence of infection with Borrelia spirochetes in Egypt | journal = Journal of the Egyptian Society of Parasitology | volume = 30 | issue = 2 | pages = 607–619 | date = August 2000 | pmid = 10946521 }}</ref>
<ref name="Lymedisease">{{EMedicine|article|330178|Lyme disease}}</ref>

<ref name=Higgins_2004>{{cite journal | vauthors = Higgins R | title = Emerging or re-emerging bacterial zoonotic diseases: bartonellosis, leptospirosis, Lyme borreliosis, plague | journal = Revue Scientifique et Technique | volume = 23 | issue = 2 | pages = 569–581 | date = August 2004 | pmid = 15702720 | doi = 10.20506/rst.23.2.1503 | doi-access = free }}</ref>

<ref name=hpaEpidemiology>{{cite web |url=http://www.hpa.org.uk/Topics/InfectiousDiseases/InfectionsAZ/LymeDisease/EpidemiologicalData/lymLymeepidemiology/ |title=Epidemiology of Lyme borreliosis in the UK |publisher=HPA |access-date=15 December 2012 |url-status=live |archive-url=https://web.archive.org/web/20130610054850/http://www.hpa.org.uk/Topics/InfectiousDiseases/InfectionsAZ/LymeDisease/EpidemiologicalData/lymLymeepidemiology/ |archive-date=10 June 2013 }}</ref>

<ref name=hpa5-15>{{cite press release|title=Tick Lyme disease off your holiday list |publisher=Health Protection Agency |date=14 April 2011 |url=http://www.hpa.org.uk/web/HPAweb&HPAwebStandard/HPAweb_C/1296685255812 |access-date=29 March 2013 |archive-url=https://web.archive.org/web/20110428004436/http://www.hpa.org.uk/web/HPAweb%26HPAwebStandard/HPAweb_C/1296685255812 |archive-date=28 April 2011 }}</ref>

<ref name=hpa_2013>{{cite web |url=https://www.gov.uk/government/publications/lyme-borreliosis-epidemiology/lyme-borreliosis-epidemiology-and-surveillance |title=Lyme borreliosis epidemiology and surveillance: May 2013 |publisher=HPA |access-date=24 November 2015 |url-status=live |archive-url=https://web.archive.org/web/20151125115822/https://www.gov.uk/government/publications/lyme-borreliosis-epidemiology/lyme-borreliosis-epidemiology-and-surveillance |archive-date=25 November 2015 }}</ref>

<ref name="Hazard Leland Mathewson Lyme Arthritis">{{cite journal |last1=Hazard |first1=Gerald W. |last2=Leland |first2=Katherine |last3=Mathewson |first3=Herbert O. |title=Erythema Chronicum Migrans and 'Lyme Arthritis' |journal=JAMA |date=22 November 1976 |volume=236 |issue=21 |page=2392 |doi=10.1001/jama.1976.03270220014012 }}</ref>

<ref name=Masters2008>{{cite journal | vauthors = Masters EJ, Grigery CN, Masters RW | title = STARI, or Masters disease: Lone Star tick-vectored Lyme-like illness | journal = Infectious Disease Clinics of North America | volume = 22 | issue = 2 | pages = 361–76, viii | date = June 2008 | pmid = 18452807 | doi = 10.1016/j.idc.2007.12.010 }}</ref>

<ref name=managing_deer_2007>{{cite book |title=Managing Urban Deer in Connecticut |chapter=Figure 2: Changes in deer density and cases of Lyme disease in Mumford Cove, Connecticut, 1996–2004 (CT DEP data) |page=4 |publisher=Connecticut Department of Environmental Protection – Wildlife Division |edition=2nd |date=June 2007 |chapter-url=http://www.ct.gov/deep/lib/deep/wildlife/pdf_files/game/urbandeer07.pdf |url-status=live |archive-url=https://web.archive.org/web/20130602194618/http://www.ct.gov/deep/lib/deep/wildlife/pdf_files/game/urbandeer07.pdf |archive-date=2 June 2013 }}</ref>

<ref name=mullegger_2004>{{cite journal | vauthors = Mullegger RR | title = Dermatological manifestations of Lyme borreliosis | journal = European Journal of Dermatology | volume = 14 | issue = 5 | pages = 296–309 | year = 2004 | pmid = 15358567 }}</ref>

<ref name=Jowi_2005>{{cite journal | vauthors = Jowi JO, Gathua SN | title = Lyme disease: report of two cases | journal = East African Medical Journal | volume = 82 | issue = 5 | pages = 267–269 | date = May 2005 | pmid = 16119758 | doi = 10.4314/eamj.v82i5.9318 }}</ref>

<ref name=merck_2012>{{cite web|title=Glomerular Disease|url=http://www.merckvetmanual.com/pharmacology/systemic-pharmacotherapeutics-of-the-urinary-system/glomerular-disease|publisher=The Merck Veterinary Manual.|access-date=19 May 2017|url-status=live|archive-url=https://web.archive.org/web/20170626001610/http://www.merckvetmanual.com/pharmacology/systemic-pharmacotherapeutics-of-the-urinary-system/glomerular-disease|archive-date=26 June 2017}}</ref>

<ref name="Khasnis">{{cite journal | vauthors = Khasnis AA, Nettleman MD | title = Global warming and infectious disease | journal = Archives of Medical Research | volume = 36 | issue = 6 | pages = 689–696 | year = 2005 | pmid = 16216650 | doi = 10.1016/j.arcmed.2005.03.041 }}</ref>

<ref name=Li_1998>{{cite journal | vauthors = Li M, Masuzawa T, Takada N, Ishiguro F, Fujita H, Iwaki A, Wang H, Wang J, Kawabata M, Yanagihara Y | title = Lyme disease Borrelia species in northeastern China resemble those isolated from far eastern Russia and Japan | journal = Applied and Environmental Microbiology | volume = 64 | issue = 7 | pages = 2705–2709 | date = July 1998 | pmid = 9647853 | pmc = 106449 | doi = 10.1128/AEM.64.7.2705-2709.1998 | bibcode = 1998ApEnM..64.2705L }}</ref>

<ref name=Muhlemann_1987>{{cite journal | vauthors = Muhlemann MF, Wright DJ | title = Emerging pattern of Lyme disease in the United Kingdom and Irish Republic | journal = Lancet | volume = 1 | issue = 8527 | pages = 260–262 | date = January 1987 | pmid = 2880076 | doi = 10.1016/S0140-6736(87)90074-2 }}</ref>

<ref name=londong_2008>{{cite web|url=http://legacy.london.gov.uk/mayor/publications/2008/docs/climate-change-adapt-strat.pdf|title= The London climate change adaptation strategy - Draft report|publisher=[[Greater London Authority]]|date= August 2008|archive-url=https://web.archive.org/web/20120817222243/http://legacy.london.gov.uk/mayor/publications/2008/docs/climate-change-adapt-strat.pdf|archive-date=17 August 2012}}</ref>

<ref name=min_ag_2012>{{cite web |author=BC Ministry of Agriculture |url=http://www.agf.gov.bc.ca/cropprot/ticksbc.htm |title=Ticks and Humans in British Columbia |publisher=Agf.gov.bc.ca |access-date=15 December 2012 |archive-url=https://web.archive.org/web/20130103031719/http://www.agf.gov.bc.ca/cropprot/ticksbc.htm |archive-date=3 January 2013 }}</ref>

<ref name=Leighton_2012>{{cite journal | vauthors = Leighton PA, Koffi JK, Pelcat Y, Lindsay LR, Ogden NH |doi=10.1111/j.1365-2664.2012.02112.x |title=Predicting the speed of tick invasion: An empirical model of range expansion for the Lyme disease vector Ixodes scapularis in Canada |year=2012 |journal=Journal of Applied Ecology |volume=49 |issue=2 |pages=457–64|bibcode=2012JApEc..49..457L |doi-access=free }}</ref>

<ref name=mmwr_2007>{{cite journal | title = Lyme disease--United States, 2003-2005 | journal = MMWR. Morbidity and Mortality Weekly Report | volume = 56 | issue = 23 | pages = 573–576 | date = June 2007 | pmid = 17568368 | url = https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5623a1.htm | url-status = live | archive-url = https://web.archive.org/web/20121119113810/http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5623a1.htm | archive-date = 19 November 2012 | author1 = Centers for Disease Control and Prevention (CDC) }}</ref>

<ref name=Mantovani_2007>{{cite journal | vauthors = Mantovani E, Costa IP, Gauditano G, Bonoldi VL, Higuchi ML, Yoshinari NH | title = Description of Lyme disease-like syndrome in Brazil. Is it a new tick borne disease or Lyme disease variation? | journal = Brazilian Journal of Medical and Biological Research = Revista Brasileira de Pesquisas Medicas e Biologicas | volume = 40 | issue = 4 | pages = 443–456 | date = April 2007 | pmid = 17401487 | doi = 10.1590/S0100-879X2006005000082 | doi-access = free }}</ref>

<ref name="The ecology of infectious disease">{{cite journal | vauthors = LoGiudice K, Ostfeld RS, Schmidt KA, Keesing F | title = The ecology of infectious disease: effects of host diversity and community composition on Lyme disease risk | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 100 | issue = 2 | pages = 567–571 | date = January 2003 | pmid = 12525705 | pmc = 141036 | doi = 10.1073/pnas.0233733100 | doi-access = free | bibcode = 2003PNAS..100..567L }}</ref>

<ref name="Marques">{{cite journal | vauthors = Marques A | title = Chronic Lyme disease: a review | journal = Infectious Disease Clinics of North America | volume = 22 | issue = 2 | pages = 341–60, vii–viii | date = June 2008 | pmid = 18452806 | pmc = 2430045 | doi = 10.1016/j.idc.2007.12.011 }}</ref>

<ref name="ngautopsy">{{cite magazine | vauthors = Hall SS | url = http://ngm.nationalgeographic.com/2011/11/iceman-autopsy/hall-text | title = Iceman Autopsy | date = November 2011 | access-date = 17 October 2011 | magazine = [[National Geographic Magazine|National Geographic]] | archive-url = https://web.archive.org/web/20111019172457/http://ngm.nationalgeographic.com/2011/11/iceman-autopsy/hall-text | archive-date = 19 October 2011}}</ref>

<ref name=Paschoud_1954>{{cite journal | vauthors = Paschoud JM | title = [Lymphocytoma after tick bite] | language = de | journal = Dermatologica | volume = 108 | issue = 4–6 | pages = 435–437 | year = 1954 | pmid = 13190934 | trans-title = Lymphocytoma after tick bite }}</ref>

<ref name=Oldstone_1998>{{cite journal | vauthors = [[Michael Oldstone|Oldstone MB]] | title = Molecular mimicry and immune-mediated diseases | journal = FASEB Journal | volume = 12 | issue = 13 | pages = 1255–1265 | date = October 1998 | pmid = 9761770 | pmc = 7164021 | doi = 10.1096/fasebj.12.13.1255 | doi-access = free }}</ref>

<ref name=Pachner_1989>{{cite journal | vauthors = Pachner AR | title = Neurologic manifestations of Lyme disease, the new "great imitator" | journal = Reviews of Infectious Diseases | volume = 11 | issue = Suppl 6 | pages = S1482–S1486 | year = 1989 | pmid = 2682960 | doi = 10.1093/clinids/11.Supplement_6.S1482 }}</ref>

<ref name="piesman2002">{{cite journal | vauthors = Piesman J, Dolan MC | title = Protection against lyme disease spirochete transmission provided by prompt removal of nymphal Ixodes scapularis (Acari: Ixodidae) | journal = Journal of Medical Entomology | volume = 39 | issue = 3 | pages = 509–512 | date = May 2002 | pmid = 12061448 | doi = 10.1603/0022-2585-39.3.509 | doi-access = free }}</ref>

<ref name=Ogden_2009>{{cite journal | vauthors = Ogden NH, Lindsay LR, Morshed M, Sockett PN, Artsob H | title = The emergence of Lyme disease in Canada | journal = CMAJ | volume = 180 | issue = 12 | pages = 1221–1224 | date = June 2009 | pmid = 19506281 | pmc = 2691438 | doi = 10.1503/cmaj.080148 }}</ref>

<ref name="nytimes.com">{{cite news | url=https://www.nytimes.com/2003/05/20/health/montana-lab-tries-to-identify-tick-borne-disease.html | title=Montana Lab Tries to Identify Tick-Borne Disease | date=20 May 2003 | vauthors = Robbins J | newspaper=The New York Times | url-status=live | archive-url=https://web.archive.org/web/20170903080910/http://www.nytimes.com/2003/05/20/health/montana-lab-tries-to-identify-tick-borne-disease.html | archive-date=3 September 2017}}</ref>

<ref name="Patz">{{cite journal | vauthors = Patz JA, Daszak P, Tabor GM, Aguirre AA, Pearl M, Epstein J, Wolfe ND, Kilpatrick AM, Foufopoulos J, Molyneux D, Bradley DJ | title = Unhealthy landscapes: Policy recommendations on land use change and infectious disease emergence | journal = Environmental Health Perspectives | volume = 112 | issue = 10 | pages = 1092–1098 | date = July 2004 | pmid = 15238283 | pmc = 1247383 | doi = 10.1289/ehp.6877 | bibcode = 2004EnvHP.112.1092P }}</ref>

<ref name="nejm-feder">{{cite journal |last1=Feder |first1=Henry M. |last2=Johnson |first2=Barbara J.B. |last3=O'Connell |first3=Susan |last4=Shapiro |first4=Eugene D. |last5=Steere |first5=Allen C. |last6=Wormser |first6=Gary P. |title=A Critical Appraisal of 'Chronic Lyme Disease' |journal=New England Journal of Medicine |date=4 October 2007 |volume=357 |issue=14 |pages=1422–1430 |doi=10.1056/NEJMra072023 |pmid=17914043 }}</ref>

<ref name="nih-cld">{{cite web | publisher = [[National Institute of Allergy and Infectious Diseases]] | title = "Chronic Lyme Disease" Fact Sheet | date = 17 April 2009 | url = https://www.niaid.nih.gov/topics/lymedisease/understanding/pages/chronic.aspx | archive-date = 15 December 2012 | archive-url = https://archive.today/20121215073909/http://www.niaid.nih.gov/topics/lymedisease/understanding/pages/chronic.aspx}}</ref>

<ref name="pmid12905137">{{cite journal | vauthors = Steere AC, Sikand VK, Schoen RT, Nowakowski J | title = Asymptomatic infection with Borrelia burgdorferi | journal = Clinical Infectious Diseases | volume = 37 | issue = 4 | pages = 528–532 | date = August 2003 | pmid = 12905137 | doi = 10.1086/376914 | doi-access = free }} (primary source)</ref>

<ref name="pmid14987414">{{cite journal | vauthors = Auwaerter PG, Aucott J, Dumler JS | title = Lyme borreliosis (Lyme disease): molecular and cellular pathobiology and prospects for prevention, diagnosis and treatment | journal = Expert Reviews in Molecular Medicine | volume = 6 | issue = 2 | pages = 1–22 | date = January 2004 | pmid = 14987414 | doi = 10.1017/S1462399404007276 }}</ref>

<ref name=pmid15117014>{{cite journal | vauthors = Lo Re V, Occi JL, MacGregor RR | title = Identifying the vector of Lyme disease | journal = American Family Physician | volume = 69 | issue = 8 | pages = 1935–1937 | date = April 2004 | pmid = 15117014 | url = http://www.aafp.org/link_out?pmid=15117014 | archive-date = 22 September 2021 | access-date = 30 March 2013 | archive-url = https://web.archive.org/web/20210922025012/https://www.aafp.org/afp/2004/0415/p1935.html | url-status = live }}</ref>

<ref name="pmid15085185">{{cite journal | vauthors = Steere AC, Coburn J, Glickstein L | title = The emergence of Lyme disease | journal = The Journal of Clinical Investigation | volume = 113 | issue = 8 | pages = 1093–1101 | date = April 2004 | pmid = 15085185 | pmc = 385417 | doi = 10.1172/JCI21681 }}</ref>

<ref name=pmid11450660>{{cite journal | vauthors = Steere AC | title = Lyme disease | journal = The New England Journal of Medicine | volume = 345 | issue = 2 | pages = 115–125 | date = July 2001 | pmid = 11450660 | doi = 10.1056/NEJM200107123450207 }}</ref>

<ref name="pmid15709249">{{cite journal | vauthors = Eisen L, Eisen RJ, Lane RS | title = The roles of birds, lizards, and rodents as hosts for the western black-legged tick Ixodes pacificus | journal = Journal of Vector Ecology | volume = 29 | issue = 2 | pages = 295–308 | date = December 2004 | pmid = 15709249 }}</ref>

<ref name="pmid16995383">{{cite journal | vauthors = Lane RS, Mun J, Eisen L, Eisen RJ | title = Refractoriness of the western fence lizard (Sceloporus occidentalis) to the Lyme disease group spirochete Borrelia bissettii | journal = The Journal of Parasitology | volume = 92 | issue = 4 | pages = 691–696 | date = August 2006 | pmid = 16995383 | doi = 10.1645/GE-738R1.1 }}</ref>

<ref name=pmid17041141>{{cite journal | vauthors = Swanson SJ, Neitzel D, Reed KD, Belongia EA | title = Coinfections acquired from ixodes ticks | journal = Clinical Microbiology Reviews | volume = 19 | issue = 4 | pages = 708–727 | date = October 2006 | pmid = 17041141 | pmc = 1592693 | doi = 10.1128/CMR.00011-06 }}</ref>

<ref name="pmid17509489">{{cite journal | vauthors = Pachner AR, Steiner I | title = Lyme neuroborreliosis: infection, immunity, and inflammation | journal = The Lancet. Neurology | volume = 6 | issue = 6 | pages = 544–552 | date = June 2007 | pmid = 17509489 | doi = 10.1016/S1474-4422(07)70128-X }}</ref>

<ref name="pmid16698304">{{cite journal | vauthors = Fikrig E, Narasimhan S | title = Borrelia burgdorferi--traveling incognito? | journal = Microbes and Infection | volume = 8 | issue = 5 | pages = 1390–1399 | date = April 2006 | pmid = 16698304 | doi = 10.1016/j.micinf.2005.12.022 | doi-access = free }}</ref>

<ref name="pmid17404293">{{cite journal | vauthors = Xu Q, Seemanapalli SV, Reif KE, Brown CR, Liang FT | title = Increasing the recruitment of neutrophils to the site of infection dramatically attenuates Borrelia burgdorferi infectivity | journal = Journal of Immunology | volume = 178 | issue = 8 | pages = 5109–5115 | date = April 2007 | pmid = 17404293 | doi = 10.4049/jimmunol.178.8.5109 | doi-access = free }}</ref>

<ref name="pmid17600717">{{cite journal | vauthors = Cabello FC, Godfrey HP, Newman SA | title = Hidden in plain sight: Borrelia burgdorferi and the extracellular matrix | journal = Trends in Microbiology | volume = 15 | issue = 8 | pages = 350–354 | date = August 2007 | pmid = 17600717 | doi = 10.1016/j.tim.2007.06.003 }}</ref>

<ref name="pmid18140373">{{cite journal | vauthors = Thyresson N | title = The penicillin treatment of acrodermatitis atrophicans chronica (Herxheimer) | journal = Acta Dermato-Venereologica | volume = 29 | issue = 6 | pages = 572–621 | year = 1949 | pmid = 18140373 }}</ref>

<ref name="pmid11438915">{{cite journal | vauthors = Molloy PJ, Persing DH, Berardi VP | title = False-positive results of PCR testing for Lyme disease | journal = Clinical Infectious Diseases | volume = 33 | issue = 3 | pages = 412–413 | date = August 2001 | pmid = 11438915 | doi = 10.1086/321911 | doi-access = free }}</ref>

<ref name="pmid18452805">{{cite journal | vauthors = Stanek G, Strle F | title = Lyme disease: European perspective | journal = Infectious Disease Clinics of North America | volume = 22 | issue = 2 | pages = 327–39, vii | date = June 2008 | pmid = 18452805 | doi = 10.1016/j.idc.2008.01.001 }}</ref>

<ref name="pmid18452802">{{cite journal | vauthors = Puius YA, Kalish RA | title = Lyme arthritis: pathogenesis, clinical presentation, and management | journal = Infectious Disease Clinics of North America | volume = 22 | issue = 2 | pages = 289–300, vi–vii | date = June 2008 | pmid = 18452802 | doi = 10.1016/j.idc.2007.12.014 }}</ref>

<ref name="pmid18454594">{{cite journal | vauthors = Schneider BS, Schriefer ME, Dietrich G, Dolan MC, Morshed MG, Zeidner NS | title = Borrelia bissettii isolates induce pathology in a murine model of disease | journal = Vector Borne and Zoonotic Diseases | volume = 8 | issue = 5 | pages = 623–633 | date = October 2008 | pmid = 18454594 | doi = 10.1089/vbz.2007.0251 }}</ref>

<ref name="pmid16020686">{{cite journal | vauthors = Aguero-Rosenfeld ME, Wang G, Schwartz I, Wormser GP | title = Diagnosis of lyme borreliosis | journal = Clinical Microbiology Reviews | volume = 18 | issue = 3 | pages = 484–509 | date = July 2005 | pmid = 16020686 | pmc = 1195970 | doi = 10.1128/CMR.18.3.484-509.2005 }}</ref>

<ref name="pmid23319969">{{cite journal | vauthors = Biesiada G, Czepiel J, Leśniak MR, Garlicki A, Mach T | title = Lyme disease: review | journal = Archives of Medical Science | volume = 8 | issue = 6 | pages = 978–982 | date = December 2012 | pmid = 23319969 | pmc = 3542482 | doi = 10.5114/aoms.2012.30948 }}</ref>

<ref name="pmid15623946">{{cite journal | vauthors = Masuzawa T | title = Terrestrial distribution of the Lyme borreliosis agent Borrelia burgdorferi sensu lato in East Asia | journal = Japanese Journal of Infectious Diseases | volume = 57 | issue = 6 | pages = 229–235 | date = December 2004 | doi = 10.7883/yoken.JJID.2004.229 | pmid = 15623946 }}</ref>

<ref name="pmid18650352">{{cite journal | vauthors = Rudenko N, Golovchenko M, Mokrácek A, Piskunová N, Ruzek D, Mallatová N, Grubhoffer L | title = Detection of Borrelia bissettii in cardiac valve tissue of a patient with endocarditis and aortic valve stenosis in the Czech Republic | journal = Journal of Clinical Microbiology | volume = 46 | issue = 10 | pages = 3540–3543 | date = October 2008 | pmid = 18650352 | pmc = 2566110 | doi = 10.1128/JCM.01032-08 }}</ref>

<ref name=pmid18452798>{{cite journal | vauthors = Tilly K, Rosa PA, Stewart PE | title = Biology of infection with Borrelia burgdorferi | journal = Infectious Disease Clinics of North America | volume = 22 | issue = 2 | pages = 217–34, v | date = June 2008 | pmid = 18452798 | pmc = 2440571 | doi = 10.1016/j.idc.2007.12.013 }}</ref>

<ref name="pmid16819127">{{cite journal | vauthors = Smith R, Takkinen J | title = Lyme borreliosis: Europe-wide coordinated surveillance and action needed? | journal = Euro Surveillance | volume = 11 | issue = 6 | pages = E060622.1 | date = June 2006 | pmid = 16819127 | doi = 10.2807/esw.11.25.02977-en | doi-access = free }}</ref>

<ref name="pmid17130658">{{cite journal | vauthors = Lopes de Carvalho I, Núncio MS | title = Laboratory diagnosis of Lyme borreliosis at the Portuguese National Institute of Health (1990-2004) | journal = Euro Surveillance | volume = 11 | issue = 10 | pages = 257–260 | year = 2006 | pmid = 17130658 | url = http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=650 | url-status = live | archive-url = https://web.archive.org/web/20120617082119/http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=650 | archive-date = 17 June 2012 }}</ref>

<ref name="pmid9215633">{{cite journal | vauthors = Coleman JL, Gebbia JA, Piesman J, Degen JL, Bugge TH, Benach JL | title = Plasminogen is required for efficient dissemination of B. burgdorferi in ticks and for enhancement of spirochetemia in mice | journal = Cell | volume = 89 | issue = 7 | pages = 1111–1119 | date = June 1997 | pmid = 9215633 | doi = 10.1016/S0092-8674(00)80298-6 | doi-access = free }}</ref>

<ref name="pmid16820453">{{cite journal | vauthors = Richter D, Matuschka FR | title = Perpetuation of the Lyme disease spirochete Borrelia lusitaniae by lizards | journal = Applied and Environmental Microbiology | volume = 72 | issue = 7 | pages = 4627–4632 | date = July 2006 | pmid = 16820453 | pmc = 1489336 | doi = 10.1128/AEM.00285-06 | bibcode = 2006ApEnM..72.4627R }}</ref>

<ref name=Ribeiro_1987>{{cite journal | vauthors = Ribeiro JM, Mather TN, Piesman J, Spielman A | title = Dissemination and salivary delivery of Lyme disease spirochetes in vector ticks (Acari: Ixodidae) | journal = Journal of Medical Entomology | volume = 24 | issue = 2 | pages = 201–205 | date = March 1987 | pmid = 3585913 | doi = 10.1093/jmedent/24.2.201 }}</ref>

<ref name="pmid17417956">{{cite journal | vauthors = Swanson KI, Norris DE | title = Detection of Borrelia burgdorferi DNA in lizards from Southern Maryland | journal = Vector Borne and Zoonotic Diseases | volume = 7 | issue = 1 | pages = 42–49 | year = 2007 | pmid = 17417956 | pmc = 4128253 | doi = 10.1089/vbz.2006.0548 }}</ref>

<ref name="pmid18097481">{{cite journal | vauthors = Rupprecht TA, Koedel U, Fingerle V, Pfister HW | title = The pathogenesis of lyme neuroborreliosis: from infection to inflammation | journal = Molecular Medicine | volume = 14 | issue = 3–4 | pages = 205–212 | year = 2008 | pmid = 18097481 | pmc = 2148032 | doi = 10.2119/2007-00091.Rupprecht }}</ref>

<ref name="pmid17326941">{{cite journal | vauthors = Majláthová V, Majláth I, Derdáková M, Víchová B, Pet'ko B | title = Borrelia lusitaniae and green lizards (Lacerta viridis), Karst Region, Slovakia | journal = Emerging Infectious Diseases | volume = 12 | issue = 12 | pages = 1895–1901 | date = December 2006 | pmid = 17326941 | pmc = 3291370 | doi = 10.3201/eid1212.060784 }}</ref>

<ref name="pmid17427701">{{cite journal |last1=Amore |first1=Giuseppina |last2=Tomassone |first2=Laura |last3=Grego |first3=Elena |last4=Ragagli |first4=Charlotte |last5=Bertolotti |first5=Luigi |last6=Nebbia |first6=Patrizia |last7=Rosati |first7=Sergio |last8=Mannelli |first8=Alessandro |title=Borrelia lusitaniae in Immature Ixodes ricinus (Acari: Ixodidae) Feeding on Common Wall Lizards in Tuscany, Central Italy |journal=Journal of Medical Entomology |date=March 2007 |volume=44 |issue=2 |pages=303–307 |doi=10.1093/jmedent/44.2.303 |pmid=17427701 |doi-access=free }}</ref>

<ref name="pmid17522387">{{cite journal | vauthors = Halperin JJ, Shapiro ED, Logigian E, Belman AL, Dotevall L, Wormser GP, Krupp L, Gronseth G, Bever CT | title = Practice parameter: treatment of nervous system Lyme disease (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology | journal = Neurology | volume = 69 | issue = 1 | pages = 91–102 | date = July 2007 | pmid = 17522387 | doi = 10.1212/01.wnl.0000265517.66976.28 | doi-access = free }}</ref>

<ref name=Scrimenti_1970>{{cite journal | vauthors = Scrimenti RJ | title = Erythema chronicum migrans | journal = Archives of Dermatology | volume = 102 | issue = 1 | pages = 104–105 | date = July 1970 | pmid = 5497158 | doi = 10.1001/archderm.102.1.104 }}</ref>

<ref name="pmid17626342">{{cite journal | vauthors = Giery ST, Ostfeld RS | title = The role of lizards in the ecology of Lyme disease in two endemic zones of the northeastern United States | journal = The Journal of Parasitology | volume = 93 | issue = 3 | pages = 511–517 | date = June 2007 | pmid = 17626342 | doi = 10.1645/GE-1053R1.1 }}</ref>

<ref name=Sherris>{{cite book | veditors = Ryan KJ, Ray CG | title = Sherris Medical Microbiology | url = https://archive.org/details/sherrismedicalmi00ryan | url-access = limited | edition = 4th | pages = [https://archive.org/details/sherrismedicalmi00ryan/page/n451 434]–37 | publisher = McGraw Hill | year = 2004 | isbn = 978-0-8385-8529-0}}</ref>

<ref name=Shadick>{{cite journal | vauthors = Shadick NA, Phillips CB, Sangha O, Logigian EL, Kaplan RF, Wright EA, Fossel AH, Fossel K, Berardi V, Lew RA, Liang MH | title = Musculoskeletal and neurologic outcomes in patients with previously treated Lyme disease | journal = Annals of Internal Medicine | volume = 131 | issue = 12 | pages = 919–926 | date = December 1999 | pmid = 10610642 | doi = 10.7326/0003-4819-131-12-199912210-00003 }}</ref>

<ref name=Raveche_2005>{{cite journal | vauthors = Raveche ES, Schutzer SE, Fernandes H, Bateman H, McCarthy BA, Nickell SP, Cunningham MW | title = Evidence of Borrelia autoimmunity-induced component of Lyme carditis and arthritis | journal = Journal of Clinical Microbiology | volume = 43 | issue = 2 | pages = 850–856 | date = February 2005 | pmid = 15695691 | pmc = 548028 | doi = 10.1128/JCM.43.2.850-856.2005 }}</ref>

<ref name=seltzer_2000>{{cite journal | vauthors = Seltzer EG, Gerber MA, Cartter ML, Freudigman K, Shapiro ED | title = Long-term outcomes of persons with Lyme disease | journal = JAMA | volume = 283 | issue = 5 | pages = 609–616 | date = February 2000 | pmid = 10665700 | doi = 10.1001/jama.283.5.609 | doi-access = free }}</ref>

<ref name="pmid8272083">{{cite journal | vauthors = Nocton JJ, Dressler F, Rutledge BJ, Rys PN, Persing DH, Steere AC | title = Detection of Borrelia burgdorferi DNA by polymerase chain reaction in synovial fluid from patients with Lyme arthritis | journal = The New England Journal of Medicine | volume = 330 | issue = 4 | pages = 229–234 | date = January 1994 | pmid = 8272083 | doi = 10.1056/NEJM199401273300401 | doi-access = free }}</ref>

<ref name=Stanek2011>{{cite journal | vauthors = Stanek G, Reiter M | title = The expanding Lyme Borrelia complex--clinical significance of genomic species? | journal = Clinical Microbiology and Infection | volume = 17 | issue = 4 | pages = 487–493 | date = April 2011 | pmid = 21414082 | doi = 10.1111/j.1469-0691.2011.03492.x | doi-access = free }}</ref>

<ref name=pmid20207198>{{cite journal | vauthors = Little SE, Heise SR, Blagburn BL, Callister SM, Mead PS | title = Lyme borreliosis in dogs and humans in the USA | journal = Trends in Parasitology | volume = 26 | issue = 4 | pages = 213–218 | date = April 2010 | pmid = 20207198 | doi = 10.1016/j.pt.2010.01.006 }}</ref>

<ref name=pmid20933139>{{cite journal | vauthors = Krupka I, Straubinger RK | title = Lyme borreliosis in dogs and cats: background, diagnosis, treatment and prevention of infections with Borrelia burgdorferi sensu stricto | journal = The Veterinary Clinics of North America. Small Animal Practice | volume = 40 | issue = 6 | pages = 1103–1119 | date = November 2010 | pmid = 20933139 | doi = 10.1016/j.cvsm.2010.07.011 }}</ref>

<ref name=Steere_1977>{{cite journal | vauthors = Steere AC, Malawista SE, Snydman DR, Shope RE, Andiman WA, Ross MR, Steele FM | title = Lyme arthritis: an epidemic of oligoarticular arthritis in children and adults in three Connecticut communities | journal = Arthritis and Rheumatism | volume = 20 | issue = 1 | pages = 7–17 | year = 1977 | pmid = 836338 | doi = 10.1002/art.1780200102 }}</ref>

<ref name="pmid21794218">{{cite journal | vauthors = Rizzoli A, Hauffe H, Carpi G, Vourc'h IG, Neteler M, Rosa R | title = Lyme borreliosis in Europe | journal = Euro Surveillance | volume = 16 | issue = 27 | date = July 2011 | pmid = 21794218 | url = http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19906 | url-status = live | archive-url = https://web.archive.org/web/20110709084836/http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19906 | archive-date = 9 July 2011 }}</ref>

<ref name=Steere_1983>{{cite journal | vauthors = Steere AC, Hutchinson GJ, Rahn DW, Sigal LH, Craft JE, DeSanna ET, Malawista SE | title = Treatment of the early manifestations of Lyme disease | journal = Annals of Internal Medicine | volume = 99 | issue = 1 | pages = 22–26 | date = July 1983 | pmid = 6407378 | doi = 10.7326/0003-4819-99-1-22 }}</ref>

<ref name="pmid2563850">{{cite journal | vauthors = Guy EC, Bateman DE, Martyn CN, Heckels JE, Lawton NF | title = Lyme disease: prevalence and clinical importance of Borrelia burgdorferi specific IgG in forestry workers | journal = Lancet | volume = 1 | issue = 8636 | pages = 484–486 | date = March 1989 | pmid = 2563850 | doi = 10.1016/S0140-6736(89)91377-9 }}</ref>

<ref name="pmid8037992">{{cite journal | vauthors = Haywood GA, O'Connell S, Gray HH | title = Lyme carditis: a United Kingdom perspective | journal = British Heart Journal | volume = 70 | issue = 1 | pages = 15–16 | date = July 1993 | pmid = 8037992 | pmc = 1025222 | doi = 10.1136/hrt.70.1.15 }}</ref>

<ref name=Sternbach>{{cite journal | vauthors = Sternbach G, Dibble CL | title = Willy Burgdorfer: Lyme disease | journal = The Journal of Emergency Medicine | volume = 14 | issue = 5 | pages = 631–634 | year = 1996 | pmid = 8933327 | doi = 10.1016/S0736-4679(96)00143-6 | doi-access = free }}</ref>

<ref name="Rand">{{cite journal | vauthors = Rand PW, Lubelczyk C, Holman MS, Lacombe EH, Smith RP | title = Abundance of Ixodes scapularis (Acari: Ixodidae) after the complete removal of deer from an isolated offshore island, endemic for Lyme Disease | journal = Journal of Medical Entomology | volume = 41 | issue = 4 | pages = 779–784 | date = July 2004 | pmid = 15311475 | doi = 10.1603/0022-2585-41.4.779 }}</ref>

<ref name=summerton_1995>{{cite journal |doi=10.1136/bmj.311.7018.1478 |title=Lyme disease in the eighteenth century |year=1995 | vauthors = Summerton N |journal=BMJ |volume=311 |issue=7018 |page=1478 }}</ref>

<ref name=Poland_2001>{{cite journal | vauthors = Poland GA, Jacobson RM | title = The prevention of Lyme disease with vaccine | journal = Vaccine | volume = 19 | issue = 17–19 | pages = 2303–2308 | date = March 2001 | pmid = 11257352 | doi = 10.1016/S0264-410X(00)00520-X }}</ref>

<ref name=Sun_2003>{{cite journal | vauthors = Sun Y, Xu R | title = Ability of Ixodes persulcatus, Haemaphysalis concinna and Dermacentor silvarum ticks to acquire and transstadially transmit Borrelia garinii | journal = Experimental and Applied Acarology | volume = 31 | issue = 1–2 | pages = 151–160 | year = 2003 | pmid = 14756409 | doi = 10.1023/B:APPA.0000005119.30172.43 }}</ref>

<ref name=rowe_199>{{cite news | url = https://www.nytimes.com/1999/06/13/nyregion/lukewarm-response-to-new-lyme-vaccine.html | title = Lukewarm Response To New Lyme Vaccine | vauthors = Rowe C | work = [[The New York Times]] | date = 13 June 1999 | access-date = 11 July 2008 | url-status=live | archive-url = https://web.archive.org/web/20120210123556/http://www.nytimes.com/1999/06/13/nyregion/lukewarm-response-to-new-lyme-vaccine.html | archive-date = 10 February 2012}}</ref>

<ref name=Singh>{{cite journal | vauthors = Singh SK, Girschick HJ | title = Lyme borreliosis: from infection to autoimmunity | journal = Clinical Microbiology and Infection | volume = 10 | issue = 7 | pages = 598–614 | date = July 2004 | pmid = 15214872 | doi = 10.1111/j.1469-0691.2004.00895.x | doi-access = free }}</ref>

<ref name="safe">{{cite journal | vauthors =  | title = When a vaccine is safe | journal = Nature | volume = 439 | issue = 7076 | page = 509 | date = February 2006 | pmid = 16452935 | doi = 10.1038/439509a | doi-access = free | bibcode = 2006Natur.439Q.509. }}</ref>

<ref name=scotland_2012>{{cite web|url=http://www.scotland.gov.uk/Topics/Health/NHS-Scotland/publicact/Implementation/Timetable3333/Part2Guidance/Q/EditMode/on/ForceUpdate/on |title=Guidance on Part 2 – Notifiable Diseases, Notifiable Organisms and Health Risk States |publisher=Scotland.gov.uk |date=10 September 2012 |access-date=15 December 2012}}</ref>

<ref name=Weinstein_2002>{{cite journal | vauthors = Weinstein A, Britchkov M | title = Lyme arthritis and post-Lyme disease syndrome | journal = Current Opinion in Rheumatology | volume = 14 | issue = 4 | pages = 383–387 | date = July 2002 | pmid = 12118171 | doi = 10.1097/00002281-200207000-00008 }}</ref>

<ref name="Wormser">{{cite journal | vauthors = Wormser GP, Masters E, Nowakowski J, McKenna D, Holmgren D, Ma K, Ihde L, Cavaliere LF, Nadelman RB | title = Prospective clinical evaluation of patients from Missouri and New York with erythema migrans-like skin lesions | journal = Clinical Infectious Diseases | volume = 41 | issue = 7 | pages = 958–965 | date = October 2005 | pmid = 16142659 | doi = 10.1086/432935 | doi-access = free }}</ref>

<ref name=Wilske_2005>{{cite journal | vauthors = Wilske B | title = Epidemiology and diagnosis of Lyme borreliosis | journal = Annals of Medicine | volume = 37 | issue = 8 | pages = 568–579 | year = 2005 | pmid = 16338759 | doi = 10.1080/07853890500431934 | doi-access = free }}</ref>

<ref name=Smith_2012>{{cite journal | vauthors = Smith FD, Ballantyne R, Morgan ER, Wall R | title = Estimating Lyme disease risk using pet dogs as sentinels | journal = Comparative Immunology, Microbiology and Infectious Diseases | volume = 35 | issue = 2 | pages = 163–167 | date = March 2012 | pmid = 22257866 | doi = 10.1016/j.cimid.2011.12.009 }}<br />Lay summary: {{cite press release | url = http://www.bris.ac.uk/news/2012/8176.html | date = 25 January 2012 | title = Survey of pet dogs indicates Lyme disease risk much greater than previous estimates suggest | publisher = University of Bristol }}</ref>

<ref name=staubinger>{{cite web| vauthors = Staubinger R |title=Lyme Disease|url=http://siriusdog.com/lyme-disease-spirochete-ticks-dog.htm|publisher=Sirius Dog.|access-date=10 February 2012|url-status=live|archive-url=https://web.archive.org/web/20120623204423/http://siriusdog.com/lyme-disease-spirochete-ticks-dog.htm|archive-date=23 June 2012|date=31 May 2000}}</ref>{{Unreliable source?|date=July 2013}}

<ref name="uphill">{{cite journal | vauthors = Abbott A | title = Lyme disease: uphill struggle | journal = Nature | volume = 439 | issue = 7076 | pages = 524–525 | date = February 2006 | pmid = 16452949 | doi = 10.1038/439524a | doi-access = free }}</ref>

<ref name=vaccine_2008>{{cite news | url = https://www.nytimes.com/2002/02/28/business/sole-lyme-vaccine-is-pulled-off-market.html | title = Sole Lyme Vaccine Is Pulled Off Market | work = [[The New York Times]] | date = 28 February 2002 | access-date = 11 July 2008 | url-status=live | archive-url = https://web.archive.org/web/20100830044423/http://www.nytimes.com/2002/02/28/business/sole-lyme-vaccine-is-pulled-off-market.html | archive-date = 30 August 2010}}</ref>

<ref name=wright_2012>{{cite journal | vauthors = Wright WF, Riedel DJ, Talwani R, Gilliam BL | title = Diagnosis and management of Lyme disease | journal = American Family Physician | volume = 85 | issue = 11 | pages = 1086–1093 | date = June 2012 | pmid = 22962880 | url = http://www.aafp.org/afp/2012/0601/p1086.html | url-status = live | archive-url = https://web.archive.org/web/20130927081243/http://www.aafp.org/afp/2012/0601/p1086.html | archive-date = 27 September 2013 }}</ref>

<ref name=Walder_2006>{{cite journal | vauthors = Walder G, Lkhamsuren E, Shagdar A, Bataa J, Batmunkh T, Orth D, Heinz FX, Danichova GA, Khasnatinov MA, Würzner R, Dierich MP | title = Serological evidence for tick-borne encephalitis, borreliosis, and human granulocytic anaplasmosis in Mongolia | journal = International Journal of Medical Microbiology | volume = 296 | issue = Suppl 40 | pages = 69–75 | date = May 2006 | pmid = 16524782 | doi = 10.1016/j.ijmm.2006.01.031 }}</ref>

<ref name=tick_bite>{{cite web | url = http://www.tickbitepreventionweek.org/overview.html | title = Overview Tick Bite Prevention Week | archive-url = https://web.archive.org/web/20120410220509/http://www.tickbitepreventionweek.org/overview.html | archive-date=10 April 2012 }}</ref>

<ref name="cdc_dispatch_oct_2007">{{cite journal | vauthors = Gordillo-Pérez G, Torres J, Solórzano-Santos F, de Martino S, Lipsker D, Velázquez E, Ramon G, Onofre M, Jaulhac B | title = Borrelia burgdorferi infection and cutaneous Lyme disease, Mexico | journal = Emerging Infectious Diseases | volume = 13 | issue = 10 | pages = 1556–1558 | date = October 2007 | pmid = 18258006 | pmc = 2851501 | doi = 10.3201/eid1310.060630 }}</ref>

<ref name=Yoshinari_1993>{{cite journal | vauthors = Yoshinari NH, Oyafuso LK, Monteiro FG, de Barros PJ, da Cruz FC, Ferreira LG, Bonasser F, Baggio D, Cossermelli W | title = [Lyme disease. Report of a case observed in Brazil] | language = pt | journal = Revista do Hospital das Clinicas | volume = 48 | issue = 4 | pages = 170–174 | year = 1993 | pmid = 8284588 | trans-title = Lyme disease. Report of a case observed in Brazil }}</ref>
}}

{{CDC|article=Post-Treatment Lyme Disease Syndrome|url=https://www.cdc.gov/lyme/postLDS/index.html}}

== Further reading ==
<!-- Currently in ascending chronological order; an observation, not a personal preference. -->
{{refbegin}}
* {{cite book | vauthors = Ostfeld R |year= 2012 |title= Lyme Disease: The Ecology of a Complex System |publisher= [[Oxford University Press]] |location= New York |isbn= 978-0-19-992847-7}}
* {{cite book | vauthors = Barbour AG |title=Lyme disease: why it's spreading, how it makes you sick, and what to do about it |date=2015 |location=Baltimore | publisher = Johns Hopkins University Press |isbn=978-1-4214-1721-9}}
* {{cite book | veditors = Halperin JJ |title=Lyme disease: an evidence-based approach |date=2018 |publisher=CABI |location=Wallingford, Oxfordshire, UK |isbn=978-1-78639-207-7 |edition=2nd}}
* {{cite book | veditors = Radolf JD, Samuels DS |title=Lyme disease and relapsing fever spirochetes: genomics, molecular biology, host interactions and disease pathogenesis |date=2021 |publisher=Caister |location=Poole, UK |isbn=978-1-913652-61-6 |url=https://www.caister.com/lyme}}
* {{cite web | vauthors = Oaklander M |date=June 17, 2021 |title=We Used to Have a Lyme Disease Vaccine. Are We Ready to Bring One Back? |url=https://time.com/6073576/lyme-disease-vaccine/ |magazine=[[Time (magazine)|Time]]}}
{{refend}}

== External links ==
{{sisterlinks|d=Q201989|c=Category:Lyme disease|n=no|q=no|b=no|v=no|voy=no|m=no|mw=no|s=no|wikt=no|species=Borrelia}}
* [https://www.cdc.gov/lyme/ CDC - Lyme Disease]
* [https://www.aphl.org/aboutAPHL/publications/Documents/ID-2021-Lyme-Disease-Serologic-Testing-Reporting.pdf Association for Public Health Laboratories guide] – Suggested Reporting Language, Interpretation and Guidance Regarding Lyme Disease Serologic Test Results
* [https://www.niaid.nih.gov/diseases-conditions/lyme-disease NIH – Lyme Disease]
* [https://www.nice.org.uk/guidance/ng95/chapter/Recommendations NICE Guidelines – Lyme Disease]
* [https://vbdhub.org UK's ''One Health Vector-Borne Diseases Hub'']

{{Medical condition classification and resources
 | DiseasesDB = 1531
 | ICD10 = {{ICD10|A|69|2|a|65}}
 | ICD9 = {{ICD9|088.81}}
 | MedlinePlus = 001319
 | eMedicine_mult = {{eMedicine2|article|330178|330178}}<br />{{eMedicine2|article|965922|965922}}<br />{{eMedicine2|article|786767|786767}}
 | MeshID = D008193
 | Scholia = Q201989
|ICD10CM={{ICD10CM|A69.2}}|ICD11={{ICD11|1C1G}}}}
{{Tick-borne diseases}}
{{Gram-negative non-proteobacterial diseases}}
{{Bacterial cutaneous infections}}
{{Vaccines}}
{{Authority control}}

{{DEFAULTSORT:Lyme Disease}}
[[Category:Lyme disease| ]]
[[Category:Bacterial diseases]]
[[Category:Bacterium-related cutaneous conditions]]
[[Category:Medical controversies]]
[[Category:Neurodegenerative disorders]]
[[Category:Wikipedia medicine articles ready to translate]]
[[Category:Wikipedia emergency medicine articles ready to translate]]
[[Category:Tick-borne diseases]]