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Adult deer tick.jpg|
Lyme Disease
ICD-10 A692
ICD-9 088.81
DiseasesDB 1531
MedlinePlus 001319
eMedicine med/1346 ped/1331 neuro/521 emerg/588
MeSH {{{MeshNumber}}}

This is a background article. See:Psychological issues in Lyme disease

Lyme disease, or borreliosis, is an emerging infectious disease caused by at least three species of bacteria belonging to the genus Borrelia.[1] Borrelia burgdorferi is the predominant cause of Lyme disease in the United States, whereas Borrelia afzelii and Borrelia garinii are implicated in most European cases.

Lyme disease is the most common tick-borne disease in the Northern Hemisphere. Borrelia is transmitted to humans by the bite of infected ticks belonging to certain species of the genus Ixodes (the hard-bodied 'hard ticks').[2] Early manifestations of infection may include fever, headache, fatigue, depression, and a characteristic skin rash called erythema migrans. Left untreated, late manifestations involving the joints, heart, and nervous system can occur. In most cases, the infection and its symptoms are eliminated with antibiotics, especially if diagnosis and treatment occur early in the course of illness. Late, delayed, or inadequate treatment can lead to late manifestations of Lyme disease which can be disabling and difficult to treat.[3]

Some Lyme disease patients who have completed a course of antibiotic treatment continue to have symptoms such as severe fatigue, sleep disturbance, and cognitive difficulties. Some groups have argued that "chronic" Lyme disease is responsible for a range of medically unexplained symptoms beyond the objectively recognized manifestations of late Lyme disease, and that additional, long-term antibiotic treatment is warranted in such cases.[4] Of four randomized controlled trials of long-term antibiotic courses in patients with ongoing symptoms, two found no benefit[5][6], and two found inconsistent benefits and significant side effects and risks from further antibiotic treatment.[7][8][9] Most expert groups including the Infectious Diseases Society of America and the American Academy of Neurology have found that existing scientific evidence does not support a role for Borrelia nor ongoing antibiotic treatment in such cases.[10][11]


Lyme disease can affect multiple body systems, producing a range of potential symptoms. Not all patients with Lyme disease will have all symptoms, and many of the symptoms are not specific to Lyme disease but can occur in other diseases as well. The incubation period from infection to the onset of symptoms is usually 1–2 weeks, but can be much shorter (days), or much longer (months to years). Symptoms most often occur from May through September because the nymphal stage of the tick is responsible for most cases.[12] Asymptomatic infection exists but is found in less than 7% of infected individuals in the United States.[13] Asymptomatic infection may be much more common among those infected in Europe.[14]

Stage 1 – Early localized infection

File:Bullseye Lyme Disease Rash.jpg

Common bullseye rash pattern associated with Lyme Disease.


Characteristic "bulls-eye"-like rash caused by Lyme disease.

The classic sign of early local infection is a circular, outwardly expanding rash called erythema chronicum migrans (also erythema migrans or EM), which occurs at the site of the tick bite 3 to 32 days after being bitten.[15] The rash is red, and may be warm, but is generally painless. Classically, the innermost portion remains dark red and becomes indurated; the outer edge remains red; and the portion in between clears – giving the appearance of a bullseye. However, the partial clearing is uncommon, and thus a true bullseye occurs in as few as 9% of cases.[16]

Erythema migrans is thought to occur in about 80% of infected patients.[15] Patients can also experience flu-like symptoms such as headache, muscle soreness, fever, and malaise.[17]

Lyme disease can progress to later stages even in patients who do not develop a rash.[18]

Stage 2 – Early disseminated infection

Within days to weeks after the onset of local infection, the borrelia bacteria may begin to spread through the bloodstream. Erythema migrans may develop at sites across the body that bear no relation to the original tick bite.[19] Another skin condition, which is apparently absent in North American patients, is borrelial lymphocytoma, a purplish lump that develops on the ear lobe, nipple, or scrotum.[20] Other discrete symptoms include migrating pain in muscles, joint, and tendons, and heart palpitations and dizziness caused by changes in heartbeat.

Acute neurological problems, which appear in 15% of untreated patients, encompasses a spectrum of disorders.[17] One is facial or Bell's palsy, which is the loss of muscle tone on one or both sides of the face. Another common neurologic manifestation is meningitis, characterized by severe headaches, neck stiffness, and sensitivity to light. Radiculoneuritis causes shooting pains that may interfere with sleep and abnormal skin sensations. Mild encephalitis may lead to memory loss, sleep disturbances, or changes in mood or affect. In addition, simple altered mental status as the sole presenting symptom has been reported in early neuroborreliosis.[21]

Stage 3 – Late persistent infection

After several months, untreated or inadequately treated patients may go on to develop severe and chronic symptoms affecting many organs of the body including the brain, nerves, eyes, joints and heart. Myriad disabling symptoms can occur.

Chronic neurologic symptoms occur in up to 5% of untreated patients.[17] A polyneuropathy manifested primarily as shooting pains, numbness, and tingling in the hands or feet may develop. A neurologic syndrome called Lyme encephalopathy is associated with subtle cognitive problems such as difficulties with concentration and short term memory. Such patients may also experience profound fatigue.[22] Other problems such as depression and fibromyalgia are no more common in people who have been infected with Lyme than in the general population.[23][22] Chronic encephalomyelitis, which may be progressive, may involve cognitive impairment, weakness in the legs, awkward gait, facial palsy, bladder problems, vertigo, and back pain. In rare cases, frank psychosis has been attributed to chronic Lyme disease effects, including mis-diagnoses of schizophrenia and bipolar disorder. Panic attack and anxiety can occur, also delusional behavior, including somatoform delusions, sometimes accompanied by a depersonalization or derealization syndrome similar to what was seen in the past in the prodromal or early stages of general paresis.[24][25]

Lyme arthritis usually affects the knees.[26] In a minority of patients arthritis can occur in other joints, including the ankles, elbows, wrist, hips, and shoulders. Pain is often mild or moderate, usually with swelling at the involved joint. Baker's cysts may form and rupture. In some cases joint erosion occurs.

Acrodermatitis chronica atrophicans (ACA) is a chronic skin disorder observed primarily in Europe.[20] ACA begins as a reddish-blue patch of discolored skin, usually in sun-exposed regions of the upper or lower limbs. The lesion slowly atrophies, and the skin may become so thin that it resembles wrinkled cigarette paper.


Main article: Lyme disease microbiology
File:Borrelia burgdorferi-cropped.jpg

Borrelia bacteria, the causative agent of Lyme disease. Magnified 400 times.

File:Ixodes scapularis.png

Ixodes scapularis, the primary vector of Lyme disease in eastern North America.

Lyme disease is caused by Gram-negative spirochetal bacteria from the genus Borrelia. At least 11 Borrelia species have been described, 3 of which are Lyme related.[27][28] The Borrelia species known to cause Lyme disease are collectively known as Borrelia burgdorferi sensu lato, and have been found to have greater strain diversity than previously estimated.[29]

Three closely-related species of spirochetes are well-established as causing Lyme disease and are probably responsible for the large majority of cases: B. burgdorferi sensu stricto (predominant in North America, but also in Europe), B. afzelii, and B. garinii (both predominant in Eurasia).[27] Some studies have also proposed that B. bissettii and B. valaisiana may sometimes infect humans, but these species do not seem to be important causes of disease.[30][31]


Hard-bodied ticks of the genus Ixodes are the primary vectors of Lyme disease.[1] The majority of infections are caused by ticks in the nymph stage, since adult ticks are more easily detected and removed as a consequence of their relatively large size.[How to reference and link to summary or text] Transmission is relatively rare, with only about 1% of recognized tick bites resulting in Lyme disease: this may be due to the fact that an infected tick has to be attached for at least a day for transmission to occur.[32]

In Europe, the sheep tick, castor bean tick, or European castor bean tick (Ixodes ricinus) is the transmitter.[How to reference and link to summary or text]

In North America, the black-legged tick or deer tick (Ixodes scapularis) has been identified as the key to the disease's spread on the east coast. Only about 20% of people who become infected with Lyme disease by the deer tick can remember having been bitten,[33] making early detection difficult in the absence of a rash. 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. 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 Borrelia burgdorferi,[34] though it may be implicated in a related syndrome called southern tick-associated rash illness, which resembles a mild form of Lyme disease.[35]

On the West Coast, the primary vector is the western black-legged tick (Ixodes pacificus).[36] The tendency of this tick species to feed predominantly on host species that are resistant to Borrelia infection appears to diminish transmission of Lyme disease in the West.[37][38]

While Lyme spirochetes have been found in insects other than ticks,[39] reports of actual infectious transmission appear to be rare.[40] Sexual transmission has been anecdotally reported; Lyme spirochetes have been found in semen[41] and breast milk,[42] however transmission of the spirochete by these routes is not known to occur.[43]

Congenital transmission of Lyme disease can occur from an infected mother to fetus through the placenta during pregnancy, however prompt antibiotic treatment appears to prevent fetal harm.[44]

Tick borne co-infections

Ticks that transmit B. burgorferi to humans can also carry and transmit several other parasites such as Theileria microti and Anaplasma phagocytophilum, which cause the diseases babesiosis and human granulocytic anaplasmosis (HGA), respectively.[32] Among early Lyme disease patients, depending on their location, 2-12% will also have HGA and 2-40% will have babesiosis.[45] Cat scratch fever is another common co-infection, although there is debate among experts on this topic on tick-to-human transmission.[How to reference and link to summary or text]

Co-infections complicate Lyme symptoms, especially diagnosis and treatment. It is possible for a tick to carry and transmit one of the co-infections and not Borrelia, making diagnosis difficult and often elusive. The Centers for Disease Control (CDC)'s emerging infections diseases department did a study in rural New Jersey of 100 ticks and found that 55% of the ticks were infected with at least one of the pathogens.[46]


Lyme disease is diagnosed clinically based on symptoms, objective physical findings (such as erythema migrans, facial palsy, or arthritis), a history of possible exposure to infected ticks, as well as serological tests. When making a diagnosis of Lyme disease, health care providers should consider other diseases that may cause similar illness. Most but not all patients with Lyme disease will develop the characteristic bulls-eye rash, and many may not recall a tick bite. Laboratory testing is not recommended for persons who do not have symptoms of Lyme disease.

Because of the difficulty in culturing Borrelia bacteria in the laboratory, diagnosis of Lyme disease is typically based on the clinical exam findings and a history of exposure to endemic Lyme areas.[1] The EM rash, which does not occur in all cases, is considered sufficient to establish a diagnosis of Lyme disease even when serologies are negative.[47][48] Serological testing can be used to support a clinically suspected case but is not diagnostic.[1]

Diagnosis of late-stage Lyme disease is often difficult because of the multi-faceted appearance which can mimic symptoms of many other diseases. For this reason, a reviewer called Lyme the new "great imitator."[49] Lyme disease may be misdiagnosed as multiple sclerosis, rheumatoid arthritis, fibromyalgia, chronic fatigue syndrome (CFS), lupus, or other autoimmune and neurodegenerative diseases.

Laboratory testing

Several forms of laboratory testing for Lyme disease are available, some of which have not been adequately validated. Most recommended tests are blood tests that measure antibodies made in response to the infection. These tests may be falsely negative in patients with early disease, but they are quite reliable for diagnosing later stages of disease.

The serological laboratory tests most widely available and employed are the Western blot and ELISA. A two-tiered protocol is recommended by the CDC: the more sensitive ELISA is performed first, if it is positive or equivocal, the more specific Western blot is run. The reliability of testing in diagnosis remains controversial,[1] however studies show the Western blot IgM has a specificity of 94–96% for patients with clinical symptoms of early Lyme disease.[50][51]

Erroneous test results have been widely reported in both early and late stages of the disease. These errors can be caused by several factors, including antibody cross-reactions from other infections including Epstein-Barr virus and cytomegalovirus,[52] as well as herpes simplex virus.[53]

Polymerase chain reaction (PCR) tests for Lyme disease have also been developed to detect the genetic material (DNA) of the Lyme disease spirochete. PCR tests are susceptible to false-positive results from poor laboratory technique.[54] Even when properly performed, PCR often shows false-negative results with blood and CSF specimens.[55] Hence PCR is not widely performed for diagnosis of Lyme disease. However PCR may have a role in diagnosis of Lyme arthritis because it is highly sensitive in detecting ospA DNA in synovial fluid.[56] With the exception of PCR, there is no currently practical means for detection of the presence of the organism, as serologic studies only test for antibodies of Borrelia. High titers of either immunoglobulin G (IgG) or immunoglobulin M (IgM) antibodies to Borrelia antigens indicate disease, but lower titers can be misleading. The IgM antibodies may remain after the initial infection, and IgG antibodies may remain for years.[57]

Western blot, ELISA and PCR can be performed by either blood test via venipuncture or cerebrospinal fluid (CSF) via lumbar puncture. Though lumbar puncture is more definitive of diagnosis, antigen capture in the CSF is much more elusive; reportedly CSF yields positive results in only 10–30% of patients cultured. The diagnosis of neurologic infection by Borrelia should not be excluded solely on the basis of normal routine CSF or negative CSF antibody analyses.[58]

New techniques for clinical testing of Borrelia infection have been developed, such as LTT-MELISA,[59] which is capable of identifying the active form of Borrelia infection (Lyme disease). Others, such as focus floating microscopy, are under investigation.[60] New research indicates chemokine CXCL13 may also be a possible marker for neuroborreliosis.[61]

Some laboratories offer Lyme disease testing using assays whose accuracy and clinical usefulness have not been adequately established. These tests include urine antigen tests, immunofluorescent staining for cell wall-deficient forms of Borrelia burgdorferi, and lymphocyte transformation tests. In general, CDC does not recommend these tests.


Single photon emission computed tomography (SPECT) imaging has been used to look for cerebral hypoperfusion indicative of Lyme encephalitis in the patient.[62] Although SPECT is not a diagnostic tool itself, it may be a useful method of determining brain function.

In Lyme disease patients, cerebral hypoperfusion of frontal subcortical and cortical structures has been reported.[63] In about 70% of chronic Lyme disease patients with cognitive symptoms, brain SPECT scans typically reveal a pattern of global hypoperfusion in a heterogeneous distribution through the white matter.[64] This pattern is not specific for Lyme disease, since it can also be seen in other central nervous system (CNS) syndromes such as HIV encephalopathy, viral encephalopathy, chronic cocaine use, and vasculitides. However, most of these syndromes can be ruled out easily through standard serologic testing and careful patient history taking.

The presence of global cerebral hypoperfusion deficits on SPECT in the presence of characteristic neuropsychiatric features should dramatically raise suspicion for Lyme encephalopathy among patients who inhabit or have traveled to endemic areas, regardless of patient recall of tick bites.[How to reference and link to summary or text] Late disease can occur many years after initial infection. The average time from symptom onset to diagnosis in these patients is about 4 years. Because seronegative disease can occur, and because CSF testing is often normal, Lyme encephalopathy often becomes a diagnosis of exclusion: once all other possibilities are ruled out, Lyme encephalopathy becomes ruled in. Although the aberrant SPECT patterns are caused by cerebral vasculitis, a vasculitide, brain biopsy is not commonly performed for these cases as opposed to other types of cerebral vasculitis.

Abnormal magnetic resonance imaging (MRI) findings are often seen in both early and late Lyme disease.[How to reference and link to summary or text] MRI scans of patients with neurologic Lyme disease may demonstrate punctuated white matter lesions on T2-weighted images, similar to those seen in demyelinating or inflammatory disorders such as multiple sclerosis, systemic lupus erythematosus (SLE), or cerebrovascular disease.[65] Cerebral atrophy and brainstem neoplasm has been indicated with Lyme infection as well.[66]

Diffuse white matter pathology can disrupt these ubiquitous gray matter connections and could account for deficits in attention, memory, visuospatial ability, complex cognition, and emotional status. White matter disease may have a greater potential for recovery than gray matter disease, perhaps because neuronal loss is less common. Spontaneous remission can occur in multiple sclerosis, and resolution of MRI white matter hyper-intensities, after antibiotic treatment, has been observed in Lyme disease.[67]


Attached ticks should be removed promptly.[68] Protective clothing includes a hat and long-sleeved shirts and long pants that are tucked into socks or boots. Light-colored clothing makes the tick more easily visible before it attaches itself. People should use special care in handling and allowing outdoor pets inside homes because they can bring ticks into the house.

A more effective, community wide method of preventing Lyme disease is to reduce the numbers of primary hosts on which the deer tick depends such as rodents, other small mammals, and deer. Reduction of the deer population may over time help break the reproductive cycle of the deer ticks and their ability to flourish in suburban and rural areas.[69]

An unusual, organic approach to control of ticks and prevention of Lyme disease involves the use of domesticated guineafowl. Guinea Fowl are voracious consumers of insects and have a particular fondness for ticks. localized use of domesticated guineafowl may reduce dependence on chemical pest-control methods.[70]. Many victims of ticks and others with concern often turn to the Guinea Fowl Breeders Association found at Guinea Fowl Breeders Association for advice on this topic.

Management of host animals

Lyme and all other deer-tick-borne diseases can be prevented on a regional level by reducing the deer population that the ticks depend on for reproductive success. This has been demonstrated in the communities of Monhegan, Maine[71] and in Mumford Cove, Connecticut.[72] The black-legged or deer tick (Ixodes scapularis) depends on the white-tailed deer for successful reproduction.

For example, in the US, it is suggested that by reducing the deer population to levels of 8 to 10 per square mile (from the current levels of 60 or more deer per square mile in the areas of the country with the highest Lyme disease rates), the tick numbers can be brought down to levels too low to spread Lyme and other tick-borne diseases.[73] However, such a drastic reduction may be impractical in many areas.


A recombinant vaccine against Lyme disease, based on the outer surface protein A (OspA) of B. burgdorferi, was developed by GlaxoSmithKline. In clinical trials involving more than 10,000 people, the vaccine, called LYMErix, was found to confer protective immunity to Borrelia in 76% of adults and 100% of children with only mild or moderate and transient adverse effects.[74] LYMErix was approved on the basis of these trials by the U.S. Food and Drug Administration (FDA) on December 21, 1998.

Following approval of the vaccine, its entry in clinical practice was slower than expected for a variety of reasons including its cost, which was often not reimbursed by insurance companies.[75] Subsequently, hundreds of vaccine recipients reported that they had developed autoimmune side effects. Supported by some patient advocacy groups, a number of class-action lawsuits were filed against GlaxoSmithKline alleging that the vaccine had caused these health problems. These claims were investigated by the FDA and the U.S. Centers for Disease Control (CDC), who found no connection between the vaccine and the autoimmune complaints.[76]

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[77] in the setting of negative media coverage and fears of vaccine side effects.[78][76] The fate of LYMErix was described in the medical literature as a "cautionary tale";[78] an editorial in 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,"[79] while the original developer of the OspA vaccine at the Max Planck Institute told Nature: "This just shows how irrational the world can be... There was no scientific justification for the first OspA vaccine [LYMErix] being pulled."[76]

New vaccines are being researched using outer surface protein C (OspC) and glycolipoprotein as methods of immunization.[80][81]

Tick removal

Many old wives' tales exist about the proper and effective method to remove a tick, however it is generally agreed that the most effective method is to pull it straight out with tweezers.[82] Data have demonstrated that prompt removal of an infected tick, within approximately 36 hours, reduces the risk of transmission to nearly zero; however the small size of the tick, especially in the nymph stage, may make detection difficult.[68]


Antibiotics are the primary treatment for Lyme disease; the most appropriate antibiotic treatment depends upon the patient and the stage of the disease.[1] The antibiotics of choice are doxycycline (in adults), amoxicillin (in children), and ceftriaxone. Alternative choices are cefuroxime and cefotaxime.[1] Macrolide antibiotics have limited efficacy when used alone.

Results of a recent double blind, randomized, placebo-controlled multicenter clinical study, done in Finland, indicated that oral adjunct antibiotics were not justified in the treatment of patients with disseminated Lyme borreliosis who initially received intravenous antibiotics for three weeks. The researchers noted the clinical outcome of said patients should not be evaluated at the completion of intravenous antibiotic treatment but rather 6–12 months afterwards. In patients with chronic post-treatment symptoms, persistent positive levels of antibodies did not seem to provide any useful information for further care of the patient.[83]

In later stages, the bacteria disseminate throughout the body and may cross the blood-brain barrier, making the infection more difficult to treat. Late diagnosed Lyme is treated with oral or IV antibiotics, frequently ceftriaxone for a minimum of four weeks. Minocycline is also indicated for neuroborreliosis for its ability to cross the blood-brain barrier.[84]

Post-Lyme disease symptoms and "chronic Lyme disease"

A very small minority[85] of Lyme disease patients who have completed a course of antibiotic treatment, in the early stages of infection, continue to have symptoms such as severe fatigue, sleep disturbance, and cognitive difficulties.[3] While it is undisputed that these patients can have severe symptoms, the cause of these symptoms and treatment of such patients is disputed. Some doctors attributed these symptoms to persistent infection with Borrelia, or with coinfections of other tick-borne infections such as Ehrlichia and Babesia.[86] Additionally, "chronic" Lyme disease has been cited by a doctor with the International Lyme And Associated Diseases Society (ILADS) as responsible for a range of medically unexplained symptoms beyond the objectively recognized manifestations of late Lyme disease, with or without any evidence of past or present infection.[4] ILADS campaigns for insurance companies to pay for expensive, long-term antibiotic treatment in such cases.[87]

Four randomized controlled trials have been performed in patients who have persisting complaints and a history of Borrelia infection. Some of them had evidence of an ongoing Borrelia infection and almost all of them were previously treated with antibiotics. Of these four studies,

  • two studies showed no benefit from 30 days of IV antibiotics and 60 days of oral antibiotics.[5][6] The president of the "chronic" Lyme interest group ILADS questioned the generalizability of the results because the studied patients had been ill an average of 4.7 years and had an average of 3 previous courses of antibiotics.[88]
  • one study showed an improvement only in fatigue after 28 days of IV antibiotics, an effect that was significant only in a group of patients that never had antibiotics previously.[9] The results may have been compromised by unblinding, and a large placebo effect was seen.[87] These trials also confirmed the significant side effects and risks that are known to accompany long-term antibiotic therapy.
  • one study reported an improvement in fatigue in a subset of patients and a transient improvement in cognition after 10 weeks of IV antibiotics[7][8], but again these patients had been ill for many years and had taken many antibiotic courses. Also, this study performed ad hoc statistical analysis[89] and its results were questionably significant.[85]

Most medical authorities, including the Infectious Diseases Society of America and the American Academy of Neurology, have concluded that there is no convincing evidence that Borrelia is implicated in the various syndromes of "chronic Lyme disease", and recommend against long-term antibiotic treatment as ineffective and possibly harmful.[90][91][10] It is well established that there are significant side effects and risks of prolonged antibiotic therapy, and at least one death has been reported from complications of a 27-month course of intravenous antibiotics for an unsubstantiated diagnosis of "chronic Lyme disease".[92]

Antibiotic-resistant therapies

Antibiotic treatment is the central pillar in the management of Lyme disease. In the late stages of borreliosis, symptoms may persist despite extensive and repeated antibiotic treatment.[93][94] Lyme arthritis which is antibiotic resistant may be treated with hydroxychloroquine or methotrexate.[95] Corticosteroid injections into the affected joint are not recommended for any stage of Lyme arthritis.[96]

Antibiotic refractory patients with neuropathic pain responded well to gabapentin monotherapy with residual pain after intravenous ceftriaxone treatment in a pilot study.[97] The immunomodulating, neuroprotective and anti-inflammatory potential of minocycline may be helpful in late/chronic Lyme disease with neurological or other inflammatory manifestations. Minocycline is used in other neurodegenerative and inflammatory disorders such as multiple sclerosis, Parkinson's disease, Huntington's disease, rheumatoid arthritis (RA) and ALS.[98]

Alternative therapies

A number of other alternative therapies have been suggested, though clinical trials have not been conducted. For example, the use of hyperbaric oxygen therapy (which is used conventionally to treat a number of other conditions), as an adjunct to antibiotics for Lyme has been discussed.[99] Though there are no published data from clinical trials to support its use, preliminary results using a mouse model suggest its effectiveness against B. burgdorferi both in vitro and in vivo.[100] Anecdotal clinical research has suggested that antifungal azole medications such as diflucan could be used in the treatment of Lyme, but the use of these drugs has yet to be tested in a controlled study.[101]

Alternative medicine approaches include bee venom because it contains the peptide melittin, which has been shown to exert inhibitory effects on Lyme bacteria in vitro;[102] no clinical trials of this treatment have been carried out, however.


For early cases, prompt treatment is usually curative.[103] However, the severity and treatment of Lyme disease may be complicated due to late diagnosis, failure of antibiotic treatment, and simultaneous infection with other tick-borne diseases (co-infections) including ehrlichiosis, babesiosis, and bartonella, and immune suppression in the patient.

A meta-analysis published in 2005 found that some patients with Lyme disease have fatigue, joint or muscle pain, and neurocognitive symptoms persisting for years despite antibiotic treatment.[3] Patients with late stage Lyme disease have been shown to experience a level of physical disability equivalent to that seen in congestive heart failure.[104] In rare cases, Lyme disease can be fatal.[105]


Urbanization and other anthropogenic factors can be implicated in the spread of Lyme disease to humans. In many areas, expansion of suburban neighborhoods has led to the gradual deforestation of surrounding wooded areas and increasing border contact between humans and tick-dense areas. Human expansion has also resulted in a gradual reduction of the predators that normally 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, the likelihood of transmission to Lyme residents has greatly increased.[106][107] Researchers are also investigating possible links between global warming and the spread of vector-borne diseases including Lyme disease.[108]

The deer tick (Ixodes scapularis, the primary vector in the northeastern U.S.) has a two-year life cycle, first progressing from larva to nymph, and then from nymph to adult. The tick feeds only once at each stage. In the fall, large acorn forests attract deer as well as mice, chipmunks and other small rodents infected with B. burgdorferi. During the following spring, the ticks lay their eggs. The rodent population then "booms". Tick eggs hatch into larvae, which feed on the rodents; thus the larvae acquire infection from the rodents. At this stage, tick infestation may be controlled using acaricides (miticides).

Adult ticks may also transmit disease to humans. After feeding, female adult ticks lay their eggs on the ground, and the cycle is complete. On the West Coast of the United States, Lyme disease is spread by the western black-legged tick (Ixodes pacificus), which has a different life cycle.

The risk of acquiring Lyme disease does not depend on the existence of a local deer population, as is commonly assumed. New research suggests that eliminating deer from smaller areas (less than 2.5 ha or 6 acres) may in fact lead to an increase in tick density and the rise of "tick-borne disease hotspots".[109]


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.[110]

Although Lyme disease has been reported in 49 of 50 states in the U.S, 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).[111] New 2008 CDC Lyme case definition guidelines are used to determine confirmed CDC surveillance cases.[112] Effective January 2008, the CDC gives equal weight to laboratory evidence from 1) a positive culture for B. burgdorferi; 2) two-tier testing (ELISA screening and Western Blot confirming); or 3) single-tier IgG (old infection) Western Blot. Previously, the CDC only included laboratory evidence based on (1) and (2) in their surveillance case definition. The case definition now includes the use of Western Blot without prior ELISA screen.

The number of reported cases of the disease have been increasing, as are endemic regions in North America. For example, it had previously been thought that B. burgdorferi sensu lato was hindered in its ability to be maintained in an enzootic cycle in California because it was assumed the large lizard population would dilute the prevalence of B. burgdorferi in local tick populations, but this has since been brought into question as some evidence has suggested that lizards can become infected.[113] Except for one study in Europe,[114] much of the data implicating lizards is based on DNA detection of the spirochete and has not demonstrated that lizards are able to infect ticks feeding upon them.[115][116][117][118] 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.[38]

While B. burgdorferi is most associated with ticks hosted by white-tailed deer and white-footed mice, Borrelia afzelii is most frequently detected in rodent-feeding vector ticks, 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 spirochetes to the bacteriolytic activities of the alternative complement pathway of various host species may determine its reservoir host association.

In Europe, cases of B. burgdorferi sensu lato infected ticks are found predominantly in Norway, Netherlands, Germany, France, Italy, Slovenia and Poland, but have been isolated in almost every country on the continent.[119]

B. burgdorferi sensu lato infested ticks are being found more frequently in Japan, as well as in Northwest China and far eastern Russia.[120][121] Borrelia has been isolated in Mongolia as well.[122]

In South America tick-borne disease recognition and occurrence is rising. Ticks carrying B. burgdorferi sensu lato, as well as canine and human tick-borne disease, have been reported widely in Brazil, but the subspecies of Borrelia has not yet been defined.[123] The first reported case of Lyme disease in Brazil was made in 1993 in Sao Paulo.[124] B. burgdorferi sensu stricto antigens in patients have been identified in Colombia and Bolivia.

In Northern Africa B. burgdorferi sensu lato has been identified in Morocco, Algeria, Egypt and Tunisia.[125][126][127]

Lyme disease in sub-Saharan is presently unknown, but evidence indicates that Lyme disease may occur in humans in this region. The abundance of hosts and tick vectors would favor the establishment of Lyme infection in Africa.[128] In East Africa, two cases of Lyme disease have been reported in Kenya.[129]

In Australia there is no definitive evidence for the existence of B. burgdorferi or for any other tick-borne spirochete that may be responsible for a local syndrome being reported as Lyme disease.[130] Cases of neuroborreliosis have been documented in Australia but are often ascribed to travel to other continents. The existence of Lyme disease in Australia is controversial.

Northern hemisphere temperate regions are most endemic for Lyme disease.[131][132]

Controversy and politics

While there is general agreement on the optimal treatment of early Lyme disease, considerable controversy has attached to the existence, prevalence, diagnostic criteria, and treatment of "chronic" Lyme disease.[133] The popularity of "chronic Lyme disease" as a concept despite a lack of supporting medical evidence led to a 2008 New England Journal of Medicine article calling it "the latest in a series of syndromes that have been postulated in an attempt to attribute medically unexplained symptoms to particular infections."[10] Most medical authorities, including the Infectious Diseases Society of America (IDSA), the American Academy of Neurology, and the Centers for Disease Control, do not recommend long-term antibiotic treatment for "chronic" Lyme disease, since trials have shown little or no benefit and considerable risk from long-term antibiotics, especially when given intravenously.

Groups of patients, patient advocates, and physicians who support the concept of chronic Lyme disease have organized to lobby for recognition of the disease, as well as insurance coverage of long-term antibiotic therapy, which most insurers deny as it is at odds with guidelines released by major medical organizations.[134] As part of this controversy, Connecticut Attorney General Richard Blumenthal, whose decade-long ties to chronic Lyme advocacy groups[134] had prompted the rebuke of medical experts,[135] opened an antitrust investigation against the IDSA, accusing the IDSA panel of undisclosed conflicts of interest and of unduly dismissing alternative therapies. This investigation was closed on May 1, 2008 without charges after the IDSA agreed to a review of its guidelines by a panel of independent scientists and physicians.[136] Blumenthal's corresponding press release argued that the agreement vindicated his investigation and again alleged conflicts of interest.[137] A journalist writing in Nature Medicine[133] later wrote that some IDSA members may not have disclosed potential conflicts of interest. The IDSA's press release focused on the fact that the medical validity of the IDSA guidelines was not challenged.[138] Paul G. Auwaerter, director of infectious disease at Johns Hopkins School of Medicine, cited this political controversy as an example of the "poisonous atmosphere" surrounding Lyme disease research which has led younger researchers to avoid the field.[136]

In 2001, the New York Times Magazine reported that Allen Steere, chief of immunology and rheumatology at New England Medical Center and a leading expert on Lyme disease, had been harassed, stalked, and threatened by patients and patient advocacy groups angry at his refusal to substantiate their diagnoses of "chronic" Lyme disease and endorse long-term antibiotic therapy.[139] Because of death threats, security guards were assigned to Steere.[76]

A significant amount of inaccurate information on Lyme disease exists on the Internet. A 2004 study found that 9 of 19 websites surveyed contained major inaccuracies. Sites found to be good sources of accurate information in this study included those of the American College of Physicians, the Centers for Disease Control, the Food and Drug Administration, and Johns Hopkins University ([140]


Borrelia burgdorferi has the ability to disseminate to numerous organs during the course of disease. The spirochete has been found in many tissues, including the skin, heart, joint, peripheral nervous system, and central nervous system.[141][142] Many of the signs and symptoms of Lyme disease are a consequence of the inflammatory response to the presence of the spirochete in those tissues. [17]

B. burgdorferi is injected into the skin by the bite of an infected Ixodes tick. 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. [143] 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 is associated with the appearance of the characteristic EM lesion.[141] However neutrophils, which are necessary to eliminate the spirochetes from the skin, fail to appear in the developing EM lesion thereby permitting the bacteria to survive and eventually spread throughout the body.[144]

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 clinical manifestations of disseminated disease. The spread of B. burgdorferi is aided by the attachment of the host protease plasmin to the surface of the spirochete.[145] The bacteria may persist in the body for months or even years, despite the production of anti-B. burgdorferi antibodies by the immune system.[32] 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, and hiding in the extracellular matrix, which may interfere with the function of immune factors.[146][147]

In the brain B. burgdorferi may induce astrocytes to undergo astrogliosis (proliferation followed by apoptosis), which may contribute to neurodysfunction.[148] The spirochetes may also induce host cells to secrete products toxic to nerve cells, including quinolinic acid and the cytokines IL-6 and TNF-alpha, which can produce fatigue and malaise.[149][150][151] Both microglia and astrocytes secrete IL-6 and TNF-alpha in the presence of the spirochete.[148][152] IL-6 is also significantly indicated in cognitive impairment.[153]

A developing hypothesis is that the chronic secretion of stress hormones as a result of Borrelia infection may reduce the effect of neurotransmitters, or other receptors in the brain by cell-mediated pro-inflammatory pathways, thereby leading to the dysregulation of neurohormones, specifically glucocorticoids and catecholamines, the major stress hormones.[154][155] This process is mediated via the hypothalamic-pituitary-adrenal axis. Additionally tryptophan, a precursor to serotonin appears to be reduced within the central nervous system (CNS) in a number of infectious diseases that affect the brain, including Lyme.[156] Researchers are investigating if this neurohormone secretion is the cause of neuropsychiatric disorders developing in some patients with borreliosis.[157]

Antidepressants acting on serotonin, norepinephrine and dopamine receptors have been shown to be immunomodulatory and anti-inflammatory against pro-inflammatory cytokine processes, specifically on the regulation of IFN-gamma and IL-10, as well as TNF-alpha and IL-6 through a psycho-neuroimmunological process.[158] Antidepressants have also been shown to suppress Th1 upregulation.[159]

Immunological studies

Research has found that chronic Lyme patients have higher amounts of Borrelia-specific forkhead box P3 (FoxP3) than healthy controls, indicating that regulatory T cells might also play a role, by immunosuppression, in the development of chronic Lyme disease. FoxP3 are a specific marker of regulatory T cells.[160] The signaling pathway P38 mitogen-activated protein kinases (p38 MAP kinase) has also been identified as promoting expression of pro-inflammatory cytokines from Borrelia.[161]

These immunological studies suggest that cell-mediated immune disruption in the Lyme patient amplifies the inflammatory process, often rendering it chronic and self-perpetuating, regardless of whether the Borrelia bacterium is still present in the host. This would be a form of pathogen-induced autoimmune disease.[162] It is therefore possible that chronic symptoms could come from an autoimmune reaction, even after the spirochetes have been eliminated from the body. This hypothesis may explain chronic arthritis that persists after antibiotic therapy, but the wider application of this hypothesis is controversial.[163][164]


The early European studies of what is now known as Lyme disease described its skin manifestations. The first study dates to 1883 in Wrocław, Poland (then known as Breslau, Germany) where physician Alfred Buchwald described a man who had suffered for 16 years with a degenerative skin disorder now known as acrodermatitis chronica atrophicans. 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.[165] The skin condition now known as borrelial lymphocytoma was first described in 1911.[166]

Neurological problems following tick bites were recognized starting in 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 Hellerstrom was the first to propose that EM and neurological symptoms following a tick bite were related.[167] 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 that many skin conditions were caused by spirochetes. In 1948, he used a special stain to microscopically observe what he believed were spirochetes in various types of skin lesions, including EM.[168] Although his conclusions were later shown to be erroneous, interest in the study of spirochetes was sparked. In 1949, Nils Thyresson, who also worked at the Karolinska Institute, was the first to treat ACA with penicillin.[169] 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.[170][171]

In 1970 a dermatologist in Wisconsin named Rudolph Scrimenti recognized an EM lesion in a patient after recalling a paper by Hellerstrom 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 patient with penicillin.[172]

The full syndrome now known as Lyme disease was not recognized until a cluster of cases originally thought to be juvenile rheumatoid arthritis was identified in three towns in southeastern Connecticut in 1975, including the towns [[Lyme, Lyme and Old Lyme],which gave the disease its popular name.[173] This was investigated by physicians David Snydman and Allen Steere of the Epidemic Intelligence Service, and by others from Yale University. The recognition that the patients 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.[174]

Before 1976, elements of B. burgdorferi sensu lato infection were called or known as tickborne meningopolyneuritis, Garin-Bujadoux syndrome, Bannworth syndrome, Afzelius syndrome, Montauk Knee or sheep tick fever. Since 1976 the disease is most often referred to as Lyme disease,[175][176] Lyme borreliosis or simply borreliosis.

In 1980 Steere, et al, began to test antibiotic regimens in adult patients with Lyme disease.[177] In 1982 a novel spirochete was cultured from the mid-gut of Ixodes ticks in Shelter Island, New York, and subsequently from patients with Lyme disease. The infecting agent was then identified by Jorge Benach at the State University of New York at Stony Brook, and soon after isolated by Willy Burgdorfer, a researcher at the National Institutes of Health, who specialized in the study of arthropod-borne bacteria such as Borrelia and Rickettsia. The spirochete was named Borrelia burgdorferi in his honor. Burgdorfer was the partner in the successful effort to culture the spirochete, along with Alan Barbour.

After identification 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.[178][179] 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.[180]


  1. 1.0 1.1 1.2 1.3 1.4 1.5 1.6 Ryan KJ, Ray CG (editors) (2004). Sherris Medical Microbiology, 4th ed., 434–437, McGraw Hill.
  2. Johnson RC (1996). "Borrelia" Baron's Medical Microbiology (Baron S et al, eds.), 4th ed., Univ of Texas Medical Branch.
  3. 3.0 3.1 3.2 Cairns V, Godwin J (2005). Post-Lyme borreliosis syndrome: a meta-analysis of reported symptoms. Int J Epidemiol 34 (6): 1340–1345.
  4. 4.0 4.1 Stricker RB (July 2007). Counterpoint: long-term antibiotic therapy improves persistent symptoms associated with Lyme disease. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 45 (2): 149–57.
  5. 5.0 5.1 Klempner MS, Hu LT, Evans J, et al (July 2001). Two controlled trials of antibiotic treatment in patients with persistent symptoms and a history of Lyme disease. N. Engl. J. Med. 345 (2): 85–92.
  6. 6.0 6.1 Kaplan RF, Trevino RP, Johnson GM, et al (June 2003). Cognitive function in post-treatment Lyme disease: do additional antibiotics help?. Neurology 60 (12): 1916–22.
  7. 7.0 7.1 Fallon BA, Keilp JG, Corbera KM, Petkova E, Britton CB, Dwyer E, Slavov I, Cheng J, Dobkin J, Nelson DR, Sackeim HA (March 2008). ["" A randomized, placebo-controlled trial of repeated IV antibiotic therapy for Lyme encephalopathy]. Neurology 70 (13): 992–1003.
  8. 8.0 8.1
  9. 9.0 9.1 Krupp LB, Hyman LG, Grimson R, et al (June 2003). Study and treatment of post Lyme disease (STOP-LD): a randomized double masked clinical trial. Neurology 60 (12): 1923–30.
  10. 10.0 10.1 10.2 Feder HM, Johnson BJ, O'Connell S, et al (October 2007). A critical appraisal of "chronic Lyme disease". N. Engl. J. Med. 357 (14): 1422–30.
  11. Frequently Asked Questions about Lyme Disease, from the Infectious Diseases Society of America. Released October 2006; accessed June 24, 2008.
  12. Edlow JA. Lyme disease. eMedicine. URL accessed on 2007-08-21.
  13. Steere AC, Sikand VK, Schoen RT, Nowakowski J (2003). Asymptomatic infection with Borrelia burgdorferi. Clin. Infect. Dis. 37 (4): 528–532.
  14. Fahrer H, Sauvain MJ, Zhioua E, Van Hoecke C, Gern LE (1998). Longterm survey (7 years) in a population at risk for Lyme borreliosis: what happens to the seropositive individuals?. Eur. J. Epidemiol. 14 (2): 117–123.
  15. 15.0 15.1 Fauci, Anthony S. (2008). Harrison's Principles of Internal Medicine: Editors, Anthony S. Fauci ... [Et Al.], Chapter 166, McGraw-Hill Medical Publishing.
  16. Smith RP, Schoen RT, Rahn DW, Sikand VK, Nowakowski J, Parenti DL, Holman MS, Persing DH, Steere AC (March 2002). Clinical characteristics and treatment outcome of early Lyme disease in patients with microbiologically confirmed erythema migrans. Ann. Intern. Med. 136 (6): 421–428.
  17. 17.0 17.1 17.2 17.3 Auwaerter PG, Aucott J, Dumler JS (January 2004). Lyme borreliosis (Lyme disease): molecular and cellular pathobiology and prospects for prevention, diagnosis and treatment. Expert Rev Mol Med 6 (2): 1–22.
  18. Steere AC, Dhar A, Hernandez J, et al (January 2003). Systemic symptoms without erythema migrans as the presenting picture of early Lyme disease. Am. J. Med. 114 (1): 58–62.
  19. Dandache P, Nadelman RB (June 2008). Erythema migrans. Infect. Dis. Clin. North Am. 22 (2): 235–60, vi.
  20. 20.0 20.1 Stanek G, Strle F (June 2008). Lyme disease: European perspective. Infect. Dis. Clin. North Am. 22 (2): 327–39, vii.
  21. Chabria SB, Lawrason J (2007). Altered mental status, an unusual manifestation of early disseminated Lyme disease: A case report. Journal of Medical Case Reports 1 (1): 62.
  22. 22.0 22.1 Shadick NA, Phillips CB, Sangha O, et al (December 1999). Musculoskeletal and neurologic outcomes in patients with previously treated Lyme disease. Ann. Intern. Med. 131 (12): 919–26.
  23. Seltzer EG, Gerber MA, Cartter ML, Freudigman K, Shapiro ED (February 2000). Long-term outcomes of persons with Lyme disease. JAMA 283 (5): 609–16.
  24. Fallon BA, Nields JA (1994). Lyme disease: a neuropsychiatric illness. The American journal of psychiatry 151 (11): 1571–1583.
  25. Hess A, Buchmann J, Zettl UK, et al (1999). Borrelia burgdorferi central nervous system infection presenting as an organic schizophrenia-like disorder. Biol. Psychiatry 45 (6): 795.)
  26. Puius YA, Kalish RA (June 2008). Lyme arthritis: pathogenesis, clinical presentation, and management. Infect. Dis. Clin. North Am. 22 (2): 289–300, vi–vii.
  27. 27.0 27.1 Wang G, van Dam AP, Schwartz I, Dankert J (October 1999). Molecular typing of Borrelia burgdorferi sensu lato: taxonomic, epidemiological, and clinical implications. Clin. Microbiol. Rev. 12 (4): 633–53.
  28. Derdáková M, Lencáková D (2005). Association of genetic variability within the Borrelia burgdorferi sensu lato with the ecology, epidemiology of Lyme borreliosis in Europe. Ann Agric Environ Med 12 (2): 165–72.
  29. Bunikis J, Garpmo U, Tsao J, Berglund J, Fish D, Barbour AG (2004). Sequence typing reveals extensive strain diversity of the Lyme borreliosis agents Borrelia burgdorferi in North America and Borrelia afzelii in Europe. Microbiology 150 (Pt 6): 1741–1755.
  30. Schneider BS, Schriefer ME, Dietrich G, Dolan MC, Morshed MG, Zeidner NS (October 2008). Borrelia bissettii isolates induce pathology in a murine model of disease. Vector Borne Zoonotic Dis. 8 (5): 623–33.
  31. Rudenko N, Golovchenko M, Mokrácek A, et al (October 2008). Detection of Borrelia bissettii in cardiac valve tissue of a patient with endocarditis and aortic valve stenosis in the Czech Republic. J. Clin. Microbiol. 46 (10): 3540–3.
  32. 32.0 32.1 32.2 Steere AC (July 2001). Lyme disease. N. Engl. J. Med. 345 (2): 115–25.
  33. Wormser G, Masters E, Nowakowski J, et al (2005). Prospective clinical evaluation of patients from missouri and New York with erythema migrans-like skin lesions. Clin Infect Dis 41 (7): 958–965.
  34. Ledin KE, et al (2005). Borreliacidal activity of saliva of the tick Amblyomma americanum. Med Vet Entomol 19 (1): 90–95.
  35. Masters EJ, Grigery CN, Masters RW (June 2008). STARI, or Masters disease: Lone Star tick-vectored Lyme-like illness. Infect. Dis. Clin. North Am. 22 (2): 361–76, viii.
  36. Clark K (2004). Borrelia species in host-seeking ticks and small mammals in northern Florida. J Clin Microbiol 42 (11): 5076–5086.
  37. Eisen L, Eisen RJ, Lane RS (2004). The roles of birds, lizards, and rodents as hosts for the western black-legged tick Ixodes pacificus. J. Vector Ecol. 29 (2): 295–308.
  38. 38.0 38.1 Lane RS, Mun J, Eisen L, Eisen RJ (2006). Refractoriness of the western fence lizard (Sceloporus occidentalis) to the Lyme disease group spirochete Borrelia bissettii. J. Parasitol. 92 (4): 691–696.
  39. Magnarelli L, Anderson J (1988). Ticks and biting insects infected with the etiologic agent of Lyme disease, Borrelia burgdorferi. J Clin Microbiol 26 (8): 1482–1486.
  40. Luger S (1990). Lyme disease transmitted by a biting fly. N Engl J Med 322 (24): 1752.
  41. Bach G (2001). "Recovery of Lyme spirochetes by PCR in semen samples of previously diagnosed Lyme disease patients.". 14th International Scientific Conference on Lyme Disease. 
  42. Schmidt B, Aberer E, Stockenhuber C, et al (1995). Detection of Borrelia burgdorferi DNA by polymerase chain reaction in the urine and breast milk of patients with Lyme borreliosis. Diagn Microbiol Infect Dis 21 (3): 121–128.
  43. Steere AC. Lyme Disease: Questions and Answers. (PDF) Massachusetts General Hospital / Harvard Medical School. URL accessed on 2007-03-22.
  44. Walsh CA, Mayer EW, Baxi LV (2007). Lyme disease in pregnancy: case report and review of the literature. Obstetrical & gynecological survey 62 (1): 41–50.
  45. Wormser GP (June 2006). Clinical practice. Early Lyme disease. N. Engl. J. Med. 354 (26): 2794–801.
  46. Varde S, Beckley J, Schwartz I (1998). Prevalence of tick-borne pathogens in Ixodes scapularis in a rural New Jersey County. Emerging Infect. Dis. 4 (1): 97–9.
  47. Brown SL, Hansen SL, Langone JJ (1999). Role of serology in the diagnosis of Lyme disease. JAMA 282 (1): 62–66.
  48. Hofmann H (1996). Lyme borreliosis—problems of serological diagnosis. Infection 24 (6): 470–472.
  49. Pachner AR (1989). Neurologic manifestations of Lyme disease, the new "great imitator". Rev. Infect. Dis. 11 Suppl 6: S1482–1486.
  50. Engstrom SM, Shoop E, Johnson RC (1995). Immunoblot interpretation criteria for serodiagnosis of early Lyme disease. J Clin Microbiol 33 (2): 419–427.
  51. Sivak SL, Aguero-Rosenfeld ME, Nowakowski J, Nadelman RB, Wormser GP (1996). Accuracy of IgM immunoblotting to confirm the clinical diagnosis of early Lyme disease. Arch Intern Med 156 (18): 2105–2109.
  52. Goossens HA, Nohlmans MK, van den Bogaard AE (1999). Epstein-Barr virus and cytomegalovirus infections cause false-positive results in IgM two-test protocol for early Lyme borreliosis. Infection 27 (3): 231.
  53. Strasfeld L, Romanzi L, Seder RH, Berardi VP (2005). False-positive serological test results for Lyme disease in a patient with acute herpes simplex virus type 2 infection. Clin Infect Dis 41 (12): 1826–1827.
  54. Molloy PJ, Persing DH, Berardi VP (2001). False-positive results of PCR testing for Lyme disease. Clin. Infect. Dis. 33 (3): 412–413.
  55. Aguero-Rosenfeld ME, Wang G, Schwartz I, Wormser GP (2005). Diagnosis of Lyme borreliosis. Clin. Microbiol. Rev. 18 (3): 484–509.
  56. Nocton JJ, Dressler F, Rutledge BJ, Rys PN, Persing DH, Steere AC (1994). Detection of Borrelia burgdorferi DNA by polymerase chain reaction in synovial fluid from patients with Lyme arthritis. N. Engl. J. Med. 330 (4): 229–234.
  57. Burdash N, Fernandes J (1991). Lyme borreliosis: detecting the great imitator. The Journal of the American Osteopathic Association 91 (6): 573–574, 577–578.
  58. Coyle PK, Schutzer SE, Deng Z, et al (1995). Detection of Borrelia burgdorferi-specific antigen in antibody-negative cerebrospinal fluid in neurologic Lyme disease. Neurology 45 (11): 2010–2015.
  59. Valentine-Thon E, Ilsemann K, Sandkamp M (2007). A novel lymphocyte transformation test (LTT-MELISA) for Lyme borreliosis. Diagn. Microbiol. Infect. Dis. 57 (1): 27–34.
  60. Eisendle K, Grabner T, Zelger B (2007). Focus floating microscopy: "gold standard" for cutaneous borreliosis?. Am. J. Clin. Pathol. 127 (2): 213–222.
  61. Cadavid D (2006). The mammalian host response to borrelia infection. Wien. Klin. Wochenschr. 118 (21–22): 653–658.
  62. Sumiya H, Kobayashi K, Mizukoshi C, et al (1997). Brain perfusion SPECT in Lyme neuroborreliosis. J. Nucl. Med. 38 (7): 1120–1122.
  63. Logigian EL, Johnson KA, Kijewski MF, et al (1997). Reversible cerebral hypoperfusion in Lyme encephalopathy. Neurology 49 (6): 1661–1670.
  64. Fallon BA, Das S, Plutchok JJ, Tager F, Liegner K, Van Heertum R (1997). Functional brain imaging and neuropsychological testing in Lyme disease. Clin. Infect. Dis. 25 Suppl 1: S57–63.
  65. Fallon, BA (2000). "Review of Lyme Neuroborreliosis" in 3th International Scientific Conference on Lyme Disease and other Tick-borne Disorders. {{{booktitle}}}. 
  66. Kalina P, Decker A, Kornel E, Halperin JJ (2005). Lyme disease of the brainstem. Neuroradiology 47 (12): 903–907.
  67. Fallon BA, Keilp J, Prohovnik I, Heertum RV, Mann JJ (2003). Regional cerebral blood flow and cognitive deficits in chronic Lyme disease. The Journal of neuropsychiatry and clinical neurosciences 15 (3): 326–332.
  68. 68.0 68.1 Piesman J, Dolan MC (2002). Protection against Lyme disease spirochete transmission provided by prompt removal of nymphal Ixodes scapularis (Acari: Ixodidae). J Med Entomol 39 (3): 509–512.
  70. Duffy, DC, Downer R, Brinkley C (June 1992). The effectiveness of Helmeted Guineafowl in the control of the deer tick, the vector of Lyme disease. The Wilson Bulletin 104 (2): 342-45.
  71. Rand PW, Lubelczyk C, Holman MS, Lacombe EH, Smith RP (2004). Abundance of Ixodes scapularis (Acari: Ixodidae) after the complete removal of deer from an isolated offshore island, endemic for Lyme Disease. J. Med. Entomol. 41 (4): 779–784.
  72. Managing Urban Deer in Connecticut, Figure 2, p.4.. (PDF) 2nd edition. Connecticut Department of Environmental Protection - Wildlife Division. URL accessed on 2008-05-02.
  73. Stafford KC (2004). Tick Management Handbook. (PDF) Connecticut Agricultural Experiment Station and Connecticut Department of Public Health. URL accessed on 2007-08-21.
  74. Poland GA, Jacobson RM (March 2001). The prevention of Lyme disease with vaccine. Vaccine 19 (17-19): 2303–8.
  75. Lukewarm Response To New Lyme Vaccine, by Claudia Rowe. Published in the New York Times on June 13, 1999; accessed July 11, 2008.
  76. 76.0 76.1 76.2 76.3 Abbott A (February 2006). Lyme disease: uphill struggle. Nature 439 (7076): 524–5.
  77. Sole Lyme Vaccine Is Pulled Off Market, published in the New York Times on February 28, 2002; accessed July 11, 2008.
  78. 78.0 78.1 Nigrovic LE, Thompson KM (January 2007). The Lyme vaccine: a cautionary tale. Epidemiol. Infect. 135 (1): 1–8.
  79. (February 2006) When a vaccine is safe. Nature 439 (7076): 509.
  80. Earnhart CG, Marconi RT (2007). An octavalent Lyme disease vaccine induces antibodies that recognize all incorporated OspC type-specific sequences. Hum Vaccin 3 (6): 281–9.
  81. Pozsgay V, Kubler-Kielb J (2007). Synthesis of an experimental glycolipoprotein vaccine against Lyme disease. Carbohydr. Res. 342 (3–4): 621–626.
  82. Zeller JL, Burke AE, Glass RM (2007). JAMA patient page. Lyme disease. JAMA 297 (23): 2664.
  83. Oksi J, Nikoskelainen J, Hiekkanen H, et al (2007). Duration of antibiotic treatment in disseminated Lyme borreliosis: a double-blind, randomized, placebo-controlled, multicenter clinical study. Eur. J. Clin. Microbiol. Infect. Dis. 26 (8): 571–581.
  84. Elewa HF, Hilali H, Hess DC, Machado LS, Fagan SC (April 2006). Minocycline for short-term neuroprotection. Pharmacotherapy 26 (4): 515–21.
  85. 85.0 85.1 Halperin JJ (2008). Prolonged Lyme disease treatment: Enough is enough. Neurology 70 (13): 986-7. Cite error: Invalid <ref> tag; name "halperin" defined multiple times with different content
  86. Cameron D, Gaito A, Harris N, et al (2004 url=""). Evidence-based guidelines for the management of Lyme disease. Expert Rev Anti Infect Ther 2 (1 Suppl): S1–13.
  87. 87.0 87.1 Baker PJ (2008). Perspectives on “Chronic Lyme Disease”. American Journal of Medicine 121 (7): 562-4.
  89. Marques A et al Neurology, 2008.
  90. Wormser GP, Dattwyler RJ, Shapiro ED, et al (November 2006). The clinical assessment, treatment, and prevention of lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin. Infect. Dis. 43 (9): 1089–134.
  91. Halperin JJ, Shapiro ED, Logigian E, Belman AL, Dotevall L, Wormser GP, Krupp L, Gronseth G, Bever CT (2007). Practice parameter: treatment of nervous system Lyme disease (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 69 (1): 91–102.
  92. Patel R, Grogg KL, Edwards WD, Wright AJ, Schwenk NM (October 2000). Death from inappropriate therapy for Lyme disease. Clin. Infect. Dis. 31 (4): 1107–9.
  93. Oksi J, Marjamäki M, Nikoskelainen J, Viljanen MK (1999). Borrelia burgdorferi detected by culture and PCR in clinical relapse of disseminated Lyme borreliosis. Ann. Med. 31 (3): 225–232.
  94. Hartiala P, Hytönen J, Pelkonen J, et al (2007). Transcriptional response of human dendritic cells to Borrelia garinii—defective CD38 and CCR7 expression detected. J. Leukoc. Biol. 82 (1): 33–43.
  95. Massarotti EM (2002). Lyme arthritis. Med. Clin. North Am. 86 (2): 297–309.
  96. Steere AC, Angelis SM (October 2006). Therapy for Lyme arthritis: strategies for the treatment of antibiotic-refractory arthritis. Arthritis Rheum. 54 (10): 3079–86.
  97. Weissenbacher S, Ring J, Hofmann H (2005). Gabapentin for the symptomatic treatment of chronic neuropathic pain in patients with late-stage lyme borreliosis: a pilot study. Dermatology (Basel) 211 (2): 123–127.
  98. Blum D, Chtarto A, Tenenbaum L, Brotchi J, Levivier M (2004). Clinical potential of minocycline for neurodegenerative disorders. Neurobiol. Dis. 17 (3): 359–366.
  99. Taylor R, Simpson I (2005). Review of treatment options for Lyme borreliosis. J Chemother 17 Suppl 2: 3–16.
  100. Pavia C (2003). Current and novel therapies for Lyme disease. Expert Opin Investig Drugs 12 (6): 1003–1016.
  101. Schardt FW (2004). Clinical effects of fluconazole in patients with neuroborreliosis. Eur. J. Med. Res. 9 (7): 334–336.
  102. Lubke LL, Garon CF (1997). The antimicrobial agent melittin exhibits powerful in vitro inhibitory effects on the Lyme disease spirochete. Clin. Infect. Dis. 25 Suppl 1: S48–51.
  103. Krause PJ, Foley DT, Burke GS, Christianson D, Closter L, Spielman A (2006). Reinfection and relapse in early Lyme disease. Am. J. Trop. Med. Hyg. 75 (6): 1090–1094.
  104. Klempner MS, Hu LT, Evans J, et al (2001). Two controlled trials of antibiotic treatment in patients with persistent symptoms and a history of Lyme disease. N Engl J Med 345 (2): 85–92.
  105. Fatal cases of Lyme disease reported in the medical literature include:
    • Kirsch M, Ruben FL, Steere AC, Duray PH, Norden CW, Winkelstein A (1988). Fatal adult respiratory distress syndrome in a patient with Lyme disease. JAMA 259 (18): 2737–2739.
    • Oksi J, Kalimo H, Marttila RJ, et al (1996). Inflammatory brain changes in Lyme borreliosis. A report on three patients and review of literature. Brain 119 (Pt 6): 2143–2154.
    • Waniek C, Prohovnik I, Kaufman MA, Dwork AJ (1995). Rapidly progressive frontal-type dementia associated with Lyme disease. J Neuropsychiatry Clin Neurosci 7 (3): 345–347.
    • Cary NR, Fox B, Wright DJ, Cutler SJ, Shapiro LM, Grace AA (1990). Fatal Lyme carditis and endodermal heterotopia of the atrioventricular node. Postgrad Med J 66 (772): 134–136.
  106. LoGiudice K, Ostfeld R, Schmidt K, Keesing F (2003). The ecology of infectious disease: effects of host diversity and community composition on Lyme disease risk. Proc Natl Acad Sci U S A 100 (2): 567–571.
  107. Patz J, Daszak P, Tabor G, et al (2004). Unhealthy landscapes: Policy recommendations on land use change and infectious disease emergence. Environ Health Perspect 112 (10): 1092–1098.
  108. Khasnis AA, Nettleman MD (2005). Global warming and infectious disease. Arch. Med. Res. 36 (6): 689–696.
  109. Perkins SE, Cattadori IM, Tagliapietra V, Rizzoli AP, Hudson PJ (2006). Localized deer absence leads to tick amplification. Ecology 87 (8): 1981–1986.
  110. CDC. Reported Cases of Lyme Disease by Year, United States, 1991–2005. URL accessed on 2007-08-20.
  113. Swanson KI, Norris DE (2007). Detection of Borrelia burgdorferi DNA in lizards from Southern Maryland. Vector Borne Zoonotic Dis. 7 (1): 42–49.
  114. Richter D, Matuschka FR (July 2006). Perpetuation of the Lyme disease spirochete Borrelia lusitaniae by lizards. Appl. Environ. Microbiol. 72 (7): 4627–4632.
  115. Giery ST, Ostfeld RS (June 2007). The role of lizards in the ecology of Lyme disease in two endemic zones of the northeastern United States. J. Parasitol. 93 (3): 511–517.
  116. Amore G, Tomassone L, Grego E, et al (March 2007). Borrelia lusitaniae in immature Ixodes ricinus (Acari: Ixodidae) feeding on common wall lizards in Tuscany, central Italy. J. Med. Entomol. 44 (2): 303–307.
  117. Swanson KI, Norris DE (2007). Detection of Borrelia burgdorferi DNA in lizards from Southern Maryland. Vector Borne Zoonotic Dis. 7 (1): 42–49.
  118. Majláthová V, Majláth I, Derdáková M, Víchová B, Pet'ko B (December 2006). Borrelia lusitaniae and green lizards (Lacerta viridis), Karst Region, Slovakia. Emerging Infect. Dis. 12 (12): 1895–1901.
  120. Li M, Masuzawa T, Takada N, et al (1998). Lyme disease Borrelia species in northeastern China resemble those isolated from far eastern Russia and Japan. Appl. Environ. Microbiol. 64 (7): 2705–2709.
  121. Masuzawa T (2004). Terrestrial distribution of the Lyme borreliosis agent Borrelia burgdorferi sensu lato in East Asia. Jpn. J. Infect. Dis. 57 (6): 229–235.
  122. Walder G, Lkhamsuren E, Shagdar A, et al (2006). Serological evidence for tick-borne encephalitis, borreliosis, and human granulocytic anaplasmosis in Mongolia. Int. J. Med. Microbiol. 296 Suppl 40: 69–75.
  123. Mantovani E, Costa IP, Gauditano G, Bonoldi VL, Higuchi ML, Yoshinari NH (2007). Description of Lyme disease-like syndrome in Brazil. Is it a new tick borne disease or Lyme disease variation?. Braz. J. Med. Biol. Res. 40 (4): 443–456.
  124. Yoshinari NH, Oyafuso LK, Monteiro FG, et al (1993). Lyme disease. Report of a case observed in Brazil. Revista do Hospital das Clínicas 48 (4): 170–174.
  125. Bouattour A, Ghorbel A, Chabchoub A, Postic D (2004). Lyme borreliosis situation in North Africa. Archives de l'Institut Pasteur de Tunis 81 (1–4): 13–20.
  126. Dsouli N, Younsi-Kabachii H, Postic D, et al (2006). Reservoir role of lizard Psammodromus algirus in transmission cycle of Borrelia burgdorferi sensu lato (Spirochaetaceae) in Tunisia. J. Med. Entomol. 43 (4): 737–742.
  127. Helmy N (2000). Seasonal abundance of Ornithodoros (O.) savignyi and prevalence of infection with Borrelia spirochetes in Egypt. Journal of the Egyptian Society of Parasitology 30 (2): 607–619.
  128. Fivaz BH, Petney TN (1989). Lyme disease—a new disease in southern Africa?. Journal of the South African Veterinary Association 60 (3): 155–158.
  129. Jowi JO, Gathua SN (2005). Lyme disease: report of two cases. East African medical journal 82 (5): 267–269.
  130. Piesman J, Stone BF (1991). Vector competence of the Australian paralysis tick, Ixodes holocyclus, for the Lyme disease spirochete Borrelia burgdorferi. Int. J. Parasitol. 21 (1): 109–111.
  131. Grubhoffer L, Golovchenko M, Vancová M, Zacharovová-Slavícková K, Rudenko N, Oliver JH (2005). Lyme borreliosis: insights into tick-/host-borrelia relations. Folia Parasitol. 52 (4): 279–294.
  132. Higgins R (2004). Emerging or re-emerging bacterial zoonotic diseases: bartonellosis, leptospirosis, Lyme borreliosis, plague. Rev. - Off. Int. Epizoot. 23 (2): 569–581.
  133. 133.0 133.1 Ballantyne C (November 2008). The chronic debate over Lyme disease. Nat. Med. 14 (11): 1135–9.
  134. 134.0 134.1 includeonly>Whelan, David. "Lyme Inc", Forbes, 2007-03-12. Retrieved on 2008-06-24.
  135. includeonly>William Hathaway and Hilary Waldman. "Lyme Disease Experts: Butt Out, Blumenthal", The Hartford Courant, 2007-03-27. Retrieved on 2008-10-18.
  136. 136.0 136.1 Landers, Susan J. Lyme treatment accord ends antitrust probe. American Medical News. URL accessed on 2008-06-24.
  137. State of Connecticut Attorney General's Office (2008-05-01). Attorney General's Investigation Reveals Flawed Lyme Disease Guideline Process, IDSA Agrees To Reassess Guidelines, Install Independent Arbiter. Press release. Retrieved on 2008-06-24.
  138. Infectious Diseases Society of America (2008-05-01). Agreement Ends Lyme Disease Investigation By Connecticut Attorney General: Medical Validity of IDSA Guidelines Not Challenged. Press release. Retrieved on 2008-06-24.
  139. includeonly>Grann, David. "Stalking Dr. Steere Over Lyme Disease", New York Times Magazine, 2001-06-17. Retrieved on 2008-06-25.
  140. Cooper JD, Feder HM (December 2004). Inaccurate information about lyme disease on the internet. Pediatr. Infect. Dis. J. 23 (12): 1105–8.
  141. 141.0 141.1 Steere AC, Coburn J, Glickstein L (April 2004). The emergence of Lyme disease. J. Clin. Invest. 113 (8): 1093–101.
  142. Pachner AR, Steiner I (June 2007). Lyme neuroborreliosis: infection, immunity, and inflammation. Lancet Neurol 6 (6): 544–52.
  143. Fikrig E, Narasimhan S (April 2006). Borrelia burgdorferi--traveling incognito?. Microbes Infect. 8 (5): 1390–9.
  144. Xu Q, Seemanapalli SV, Reif KE, Brown CR, Liang FT (April 2007). Increasing the recruitment of neutrophils to the site of infection dramatically attenuates Borrelia burgdorferi infectivity. J. Immunol. 178 (8): 5109–15.
  145. Coleman JL, Gebbia JA, Piesman J, Degen JL, Bugge TH, Benach JL (June 1997). Plasminogen is required for efficient dissemination of B. burgdorferi in ticks and for enhancement of spirochetemia in mice. Cell 89 (7): 1111–9.
  146. Rupprecht TA, Koedel U, Fingerle V, Pfister HW (2008). The pathogenesis of Lyme neuroborreliosis: from infection to inflammation. Mol. Med. 14 (3-4): 205–12.
  147. Cabello FC, Godfrey HP, Newman SA (August 2007). Hidden in plain sight: Borrelia burgdorferi and the extracellular matrix. Trends Microbiol. 15 (8): 350–4.
  148. 148.0 148.1 Ramesh G, Alvarez AL, Roberts ED, et al (September 2003). Pathogenesis of Lyme neuroborreliosis: Borrelia burgdorferi lipoproteins induce both proliferation and apoptosis in rhesus monkey astrocytes. Eur. J. Immunol. 33 (9): 2539–50.
  149. Halperin JJ, Heyes MP (January 1992). Neuroactive kynurenines in Lyme borreliosis. Neurology 42 (1): 43–50.
  150. Treatment of Lyme Disease. Columbia University. URL accessed on 2007-08-23.
  151. Papanicolaou DA, Wilder RL, Manolagas SC, Chrousos GP (1998). The pathophysiologic roles of interleukin-6 in human disease. Ann. Intern. Med. 128 (2): 127–137.
  152. Rasley A, Anguita J, Marriott I (2002). Borrelia burgdorferi induces inflammatory mediator production by murine microglia. J. Neuroimmunol. 130 (1–2): 22–31.
  153. Wright CB, Sacco RL, Rundek TR, et al (2006). Interleukin-6 is associated with cognitive function: the Northern Manhattan Study. Journal of Stroke and Cerebrovascular Diseases 15 (1): 34–38.
  154. Elenkov IJ, Iezzoni DG, Daly A, Harris AG, Chrousos GP (2005). Cytokine dysregulation, inflammation and well-being. Neuroimmunomodulation 12 (5): 255–269.
  155. Calcagni E, Elenkov I (2006). Stress system activity, innate and T helper cytokines, and susceptibility to immune-related diseases. Ann. N. Y. Acad. Sci. 1069: 62–76.
  156. Gasse T, Murr C, Meyersbach P, et al (1994). Neopterin production and tryptophan degradation in acute Lyme neuroborreliosis versus late Lyme encephalopathy. European journal of clinical chemistry and clinical biochemistry : journal of the Forum of European Clinical Chemistry Societies 32 (9): 685–689.
  157. Zajkowska J, Grygorczuk S, Kondrusik M, Pancewicz S, Hermanowska-Szpakowicz T (2006). New aspects of pathogenesis of Lyme borreliosis. Przegla̧d epidemiologiczny 60 Suppl 1: 167–170.
  158. Kubera M, Lin AH, Kenis G, Bosmans E, van Bockstaele D, Maes M (2001). Anti-Inflammatory effects of antidepressants through suppression of the interferon-gamma/interleukin-10 production ratio. Journal of clinical psychopharmacology 21 (2): 199–206.
  159. Diamond M, Kelly JP, Connor TJ (2006). Antidepressants suppress production of the Th1 cytokine interferon-gamma, independent of monoamine transporter blockade. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology 16 (7): 481–490.
  160. Jarefors S, Janefjord CK, Forsberg P, Jenmalm MC, Ekerfelt C (2007). Decreased up-regulation of the interleukin-12Rbeta2-chain and interferon-gamma secretion and increased number of forkhead box P3-expressing cells in patients with a history of chronic Lyme borreliosis compared with asymptomatic Borrelia-exposed individuals. Clin. Exp. Immunol. 147 (1): 18–27.
  161. Ramesh G, Philipp MT (2005). Pathogenesis of Lyme neuroborreliosis: mitogen-activated protein kinases Erk1, Erk2, and p38 in the response of astrocytes to Borrelia burgdorferi lipoproteins. Neurosci. Lett. 384 (1–2): 112–116.
  162. Singh SK, Girschick HJ (2006). Toll-like receptors in Borrelia burgdorferi-induced inflammation. Clin. Microbiol. Infect. 12 (8): 705–717.
  163. Weinstein A, Britchkov M (July 2002). Lyme arthritis and post-Lyme disease syndrome. Curr Opin Rheumatol 14 (4): 383–7.
  164. Bolz DD, Weis JJ (August 2004). Molecular mimicry to Borrelia burgdorferi: pathway to autoimmunity?. Autoimmunity 37 (5): 387–92.
  165. Afzelius A (1910). Verhandlungen der Dermatologischen Gesellshaft zu Stockholm. Archives of Dermatology and Syphilis 101: 100–102.
  166. Burckhardt JL (1911). Zur Frage der Follikel- und Keimzentrenbildung in der Haut. Frankfurter Zeitschrift fur Pathologie 6: 352–359.
  167. Hellerstrom S (1930). Erythema chronicum migrans Afzelii. Archiv Dermatologie and Venereologie (Stockholm) 11: 315–321.
  168. Lenhoff C (1948). Spirochetes in aetiologically obscure diseases. Acta Dermato-Venreol 28: 295–324.
  169. Thyresson N (1949). The penicillin treatment of acrodermatitis atrophicans chronica (Herxheimer). Acta Derm. Venereol. 29 (6): 572–621.
  170. Bianchi GE (1950). Penicillin therapy of lymphocytoma. Dermatologica 100 (4–6): 270–273.
  171. Paschoud JM (1954). Lymphocytoma after tick bite. Dermatologica 108 (4–6): 435–437.
  172. Scrimenti RJ (1970). Erythema chronicum migrans. Archives of dermatology 102 (1): 104–105.
  173. Steere AC (2006). Lyme borreliosis in 2005, 30 years after initial observations in Lyme, Connecticut. Wien. Klin. Wochenschr. 118 (21–22): 625–633.
  174. Sternbach G, Dibble C (1996). Willy Burgdorfer: Lyme disease. J Emerg Med 14 (5): 631–634.
  175. Mast WE, Burrows WM (1976). Erythema chronicum migrans and "Lyme arthritis". JAMA 236 (21): 2392.
  176. Steere AC, Malawista SE, Snydman DR, et al (1977). Lyme arthritis: an epidemic of oligoarticular arthritis in children and adults in three connecticut communities. Arthritis Rheum. 20 (1): 7–17.
  177. Steere AC, Hutchinson GJ, Rahn DW, et al (1983). Treatment of the early manifestations of Lyme disease. Ann. Intern. Med. 99 (1): 22–26.
  178. Luft BJ, Volkman DJ, Halperin JJ, Dattwyler RJ (1988). New chemotherapeutic approaches in the treatment of Lyme borreliosis. Ann. N. Y. Acad. Sci. 539: 352–361.
  179. Dattwyler RJ, Volkman DJ, Conaty SM, Platkin SP, Luft BJ (1990). Amoxycillin plus probenecid versus doxycycline for treatment of erythema migrans borreliosis. Lancet 336 (8728): 1404–1406.
  180. Ribeiro JM, Mather TN, Piesman J, Spielman A (1987). Dissemination and salivary delivery of Lyme disease spirochetes in vector ticks (Acari: Ixodidae). J. Med. Entomol. 24 (2): 201–205.


  • Jonathan A. Edlow MD, Bull's Eye: Unraveling the Medical Mystery of Lyme Disease, Yale University Press, 2003

Documentary Film

  • Under Our Skin: The Untold Story of Lyme Disease (2008)

External links


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