AUTHOR AND EDITOR INFORMATION

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INTRODUCTION

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Background

Lyme disease is due to infection with a spirochete, Borrelia burgdorferi, and the body's immune response to the infection. In Europe, the rash (then called erythema chronicum migrans or ECM) was first described at the beginning of the 20th century. The neurologic manifestations and the association with Ixodes ticks (also known as deer ticks, see Image 1) were recognized by the mid 1930s and were known as tick-borne meningoencephalitis. In the United States, Lyme disease was not recognized until the early 1970s, when an outbreak of childhood arthritis occurred in the Lyme, CT region. This was investigated by Allen Steere, MD, and others from Yale. The recognition that the patients in the United States had ECM led to the recognition that Lyme arthritis was one manifestation of the same tick-borne condition known in Europe.

After Willy Burgdorfer, MD, discovered a borrelial organism in Ixodes ticks, it was recovered from patients with clinical Lyme disease, confirming it as the causative agent. This led to the development of antibody tests for the disease. Different strains of Borrelia are recognized, which probably explains why the clinical manifestations of Lyme disease are different in the United States and Europe.

Lyme disease has become common in the United States from Maryland to Maine and in Wisconsin and Minnesota, with a smaller focus in northern California. A great deal of fear and concern exists among residents and visitors to these areas. The development of vaccines against Lyme disease and the subsequent advertising of one of the vaccines have led to further apprehension among the population of these areas. The emergence of Lyme disease is probably due to the explosion of deer and tick populations with the reforestation of the northeastern United States and the subsequent contact between ticks and humans as people move into deer habitats. B burgdorferi has been found in tick specimens collected in the 1940s on eastern Long Island.

Pathophysiology

B burgdorferi is a spirochete. It is transmitted from host to host by the Ixodes, or deer tick. The life cycle of the Ixodes tick and B burgdorferi is important, as it relates to the epidemiology of Lyme disease.

The Ixodes tick is born as a larval tick in the summer and feeds only once. Its preferred host is the common field mouse, but other animals apparently suffice. The following spring, it becomes a nymph and again feeds only once, with its preferred host again being the field mouse. In the fall, the nymph becomes an adult and feeds a single time. Its preferred host is the white-tailed deer. Thus, unless the tick feeds on an infected host before feeding on a person, an individual cannot be infected from that tick bite. Even if a tick feeds on an infected animal, it may not pick up the infection. Mice do not appear to develop Lyme disease, but they do carry the bacteria. They may be considered infested rather than infected.

Not all strains of mice continue to carry the bacteria after exposure to B burgdorferi. As mice mature, they may be less able to sustain a B burgdorferi bacteremia. Even when they are exposed to the bacteria, they do not remain carriers for extended periods. Other animals are even poorer hosts for B burgdorferi.

Some studies suggest that uninfected ticks do not become infected unless they feed next to infected ticks that have been feeding on the same animal. This suggests that, although the B burgdorferi may disseminate throughout the body of its victim, not enough bacteria may be present in the distant sites to pass on the infection.

A tick must be attached to a person for 2-3 days to pass on the infection. This is due to the life cycle of B burgdorferi in ticks. In previously infected ticks, only small numbers of bacteria are present until the tick feeds. Once feeding begins, the bacteria then multiply in the gut of the tick. The bacteria then migrate to the salivary glands of the tick after 2-3 days. There, they are injected into the animal by the tick as it ends its feeding. Until this multiplication occurs, ticks are rarely able to pass on the infection.

Humans are infected by ticks in the nymph stage 85% of the time (spring to summer) and the adult stage 15% of the time (fall). Thus, for many reasons, only approximately 1% of all tick bites occurring in an endemic area result in a case of Lyme disease.

Once B burgdorferi is injected into the host, 1 of 3 events occurs, as follows:

In the first event, patients may clear the infection without developing any manifestations, as demonstrated by patients who are asymptomatic but seropositive.

In the second event, B burgdorferi spreads throughout the body and produces symptoms by direct invasion, particularly in the early stages of the disease. Because growing B burgdorferi is difficult, confirming that the organism is actually present in a specific organ that may be involved in Lyme disease also is difficult. The inflammatory response to B burgdorferi in the skin probably is the cause of erythema migrans.

In the third event, B burgdorferi induces an immune response that may lead to symptoms in various organs, with little evidence of bacterial invasion. Studies of Lyme arthritis have shown that the arthritis is associated with certain immunological factors, including the production of proinflammatory cytokines and the formation of immune complexes, and also genetic factors, such as human leukocyte antigen (HLA)–DR4 and HLA-DR2.

The manifestations of Lyme disease are related to the particular strain of Borrelia involved. In the United States, isolates from the East Coast are known as B burgdorferi sensu stricto. In Europe, B burgdorferi garinii is associated with neurologic disease while B burgdorferi afzelii is associated with a dermatologic manifestation known as acrodermatitis chronica atrophicans.

Frequency

United States

At best, data are approximations, for the following reasons:

• Separating false-positive antibody tests from asymptomatic infection is impossible. Approximately 5-10% of patients in endemic areas are positive without a history of symptoms.
• Although it is a reportable disease, not all cases are reported or discovered through laboratory records because early disease should be treated without antibody testing.
• In 1999, state health departments reported 13,306 cases. This was 3500 cases fewer than in 1998. Approximately 90.5% of cases were reported from the states between Maryland and Maine, 2.8% from Wisconsin and Minnesota, and 1.1% from California and Oregon. Wisconsin had an 82% drop in reported cases between 1998 and 1999.
• In 1997, Connecticut had the highest reported rate in the United States at 69.9 cases per 100,000 persons, with a 16.6-fold difference among the 8 counties in Connecticut. Maryland had only 9.6 cases per 100,000 persons but a 180-fold difference in rates by county. In both states, the lowest rates were reported from the most urban areas.
• Actual rates may be 5 times higher than state health department rates.

International

European rates may be similar. A rate of 69 cases per 100,000 persons was reported in southern Sweden, with peaks at ages 5-9 years and 60-69 years.

Race

• The disease is reported primarily in whites. In the United States in 1998, whites represented 76% of reported cases, followed by other ethnic groups at 21%.

Sex

• Reports from Europe indicate that among children, the rate is slightly higher in boys than in girls, but, in the older age peak, more women were reported than men.

Age

• Incidence by age has 2 peaks. A peak occurs at 5-9 years and another at 50-54 years. Incidence is lowest in individuals aged 20-24 years.

CLINICAL

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History

The manifestations of Lyme disease have been divided into 3 stages: localized, disseminated, and persistent. The first 2 stages are part of the early infection, while persistent disease is considered late infection. Unlike syphilis, stage 3 disease may occur within 1 year of infection, not many years later. Certain manifestations of Lyme disease are more common in the United States, while others are more common in Europe.

The primary symptoms of stage 1 are erythema migrans and some associated symptoms. The primary symptoms of stage 2 are intermittent arthritis, cranial nerve palsies and radicular symptoms, atrioventricular (AV) nodal block, and severe malaise and fatigue. The primary symptoms of stage 3 are prolonged arthritis; chronic encephalitis, myelitis, and parapareses; and symptoms consistent with fibromyalgia.

The natural history of Lyme disease is as follows:

• Tick bite
• • The Ixodes tick is small, and the bite often is innocuous enough that 30% of patients in the United States do not remember being bitten.
  • In Europe, 64% do not remember being bitten.
• Erythema migrans
• • Erythema migrans (see Image 2) is an erythematous lesion that increases in size (hence the name) over several days. It may be asymptomatic or it may itch or burn. It often occurs at or near the site of the tick bite, which may be an area not normally visualized by individuals, such as the axilla, groin, or popliteal areas. The rash may not be observed until it is already full size.
  • Untreated, the rash persists for 2-3 weeks. Eighty percent of patients have only one episode of erythema migrans, while 20% may have recurrent episodes. Multiple lesions may occur in 40% of patients and are not the result of multiple tick bites.
  • Approximately one third of all patients with erythema migrans develop no further manifestations of Lyme disease, while two thirds of patients develop further symptoms. These may be associated with lymphadenopathy and symptoms such as fever and myalgias, which may be described by the patient as flulike in nature.
• Intermittent inflammatory arthritis
• • This often begins as a migratory polyarticular process involving bursae, tendons, and joints, which evolves over 1-2 days into a monoarticular process involving the knee, ankle, and wrist in decreasing frequency. When asked about their symptoms after they have resolved, patients are less likely to remember those symptoms that occurred prior to the monoarthritis. Polyarticular episodes also may occur.
  • In two thirds of patients, the first episode occurs within 6 months of the erythema migrans lesion. Untreated, the episodes last approximately a week. Two thirds of patients have 3 recurrences approximately 2.5 months apart. The recurrences are more likely to involve more than one joint than the initial event. With time, these episodes become less frequent and severe and involve fewer joints. Even without treatment, the recurrent episodes usually resolve over a 10-year period.
  • Some patients may present with intermittent joint pain without inflammatory findings. This is more common in Europe, where arthritis was not recognized as a manifestation of Lyme disease until the early reports from the United States.
• Cranial nerve palsies
• • This is the most common neurologic manifestation in the United States and is probably the most common in Europe, particularly in children. More than half of children with neurologic symptoms have a facial palsy. It may be bilateral.
  • The palsy lasts less than 2 months and may begin to resolve even in the first several days.
• Meningoradiculoneuritis (Bannwarth syndrome)
• • This occurs much more frequently in Europe than in the United States.
  • It is characterized by severe radicular pain (due to neuritis), with a prominent nocturnal component. The meningitis may be relatively mild.
• Carditis
• • This usually presents with fever and syncope due to AV block.
  • The level of AV block varies and fluctuates so that the symptoms may be intermittent. The block rarely lasts longer than a week; a temporary pacemaker rarely is required.
• Malaise and fatigue
• • These are the most common findings after the skin lesion in early disease.
  • They affect as many as 80% of patients in the United States but less than 35% in Europe.
• Meningitis
• • This may occur along with other neurologic manifestations or by itself.
  • Severity ranges from mild to severe and usually presents as headache, photophobia, and/or a stiff neck. The severity of the meningitis is less than that observed in patients with more typical bacterial meningitis.
• Chronic arthritis
• • Approximately 10% of patients with intermittent arthritis develop a chronic arthritis that typically involves the knee.
  • While it may last several years, it rarely develops into a destructive arthritis.
• Chronic neuropathy
• • Chronic paresthesias and, less frequently, radicular pain without sensory or motor deficits may occur.
  • This usually is not associated with other chronic neurologic symptoms.
• Chronic meningoencephalitis
• • This appears to be more common in Europe than in the United States.
  • Abnormalities in mood, memory, and sleep may develop.
  • Symptoms may vary from mild to severe. More severe symptoms of ataxia, spastic paresis, and cognitive dysfunction may develop, possibly more often in patients who have had CNS involvement. Children who have had Lyme disease seem to be at low risk for the development of such findings.
• Fibromyalgia and chronic fatigue
• • Symptoms consistent with fibromyalgia/chronic fatigue syndrome develop in patients who have had clear-cut Lyme disease, even after adequate treatment.
  • A biological relationship does not seem to exist between these symptoms and Lyme disease, and it does not appear to be due to active infection.
• Other manifestations
• • A bluish-red nodular lymphocytic infiltrate known as a lymphocytoma, typically appearing on the earlobe or nipple, occurs in Europe but not the United States. It usually is found as part of stage 2 disease.
  • Atrophic areas can develop over the extensor surfaces of the extremities during late disease and are known as acrodermatitis chronica atrophicans. This has not been reported in the United States.

Physical

• Erythema migrans is an erythematous lesion. The entire lesion may be uniform in color or central clearing may be present (one third of US cases and two thirds of European cases). More proximal to the clearing may be additional erythema leading to a so-called "bull's eye" appearance. The center may be scaly or discolored. Single lesions average 16 cm in diameter.
• Lyme arthritis presents with the usual findings of an acute arthritis. These include warmth, erythema, and swelling and pain upon motion of the joints, but usually not as severe as in a septic joint. Effusions may be large and generally recur following aspiration, as is often seen in spondyloarthropathies.
• Lyme meningitis does not present with the usual signs of bacterial meningitis (boardlike rigidity, Kernig and Brudzinski signs).
• Chronic radicular paresthesias usually are not associated with motor or sensory deficits, and the physical examination results are normal.

DIFFERENTIALS

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Other Problems to be Considered

Arthritis of inflammatory bowel disease
AV nodal block
Encephalitis
Radiculopathy
Reiter syndrome

WORKUP

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Lab Studies

• Culturing organisms is the usual way of confirming infection with bacterial organisms. Although culturing B burgdorferi from skin biopsy specimens is possible, this is not practical in the usual clinical settings. While a recent article from an endemic area reported positive culture results in 43.7% of patients, this required culturing specifically for Lyme disease. In addition, all but 2 of the 213 patients met US Centers for Disease Control and Prevention (CDC) criteria for Lyme disease and warranted treatment, regardless of culture results. Culturing the organism from joint fluid rarely is effective. Polymerase chain reaction (PCR) testing of biologic specimens is not clinically useful because of the uncertainty about the relationship between a positive test result and live organisms in biologic fluids.
• The most widely used tests for Lyme disease are antibody detection tests. Unfortunately, no national standards have been set for the best antigen for the test, and the performance of clinical laboratories has been spotty, with numerous false-positive and false-negative results.
• The current recommendation from the CDC is for a 2-step testing process.
• • The first step, in patients with symptoms consistent with Lyme disease, is to order an antibody titer. This can be either a total Lyme titer or separate immunoglobulin G (IgG) and immunoglobulin M (IgM) titers.
  • The second step is to confirm positive titers with a Western blot. For IgM blots, if any 2 of the following 3 bands are positive, the test is positive: 23 kd, 39 kd, and 41 kd. For IgG blots, any 5 of the following bands are considered a positive test result: 18, 21, 28, 30, 39, 41, 45, 58, 66, and 93 kDa.
  • In the absence of treatment, patients continue to produce IgM antibodies long after the initial infection because they are presumably exposed to new borrelial antigens. Thus, patients may have both IgM and IgG antibodies at the same time.
  • While some authors recommend other bands and bypassing antibody titers, no other testing recommendations are available from other national organizations.
  • In patients who have not been in endemic areas, the false-positive and false-negative rates of these tests make it unlikely that the predictive values of the results will be helpful.
• Antibody testing in patients with erythema migrans is not indicated because the rash may develop before the antibodies.
• In the United States, patients with extracutaneous involvement in the absence of treatment almost universally have positive titers and Western blots. In Europe, negative serum titers have been reported in patients with neurologic Lyme disease that was confirmed by intrathecal antibody production.
• Synovial fluid usually is inflammatory, with cell counts ranging from 500-98,000/µL reported. In adult patients, the fluid also should be examined for crystals to rule out gout and pseudogout.
• Spinal fluid should be obtained in patients with neurologic symptoms whose diagnosis is not obvious (eg, patients without erythema migrans).
• • Unlike most bacterial infections in the spinal fluid, Lyme disease produces a pleocytosis characterized by mononuclear cells.
  • Spinal fluid levels of IgM and IgG antibodies to B burgdorferi should be measured, and an index of cerebrospinal fluid (CSF) to serum antibody (immunoglobulin-to-albumin ratio) should be calculated. This is particularly true in patients who have no other signs of Lyme disease.
  • IgG and IgM antibodies may persist in CSF long after adequate treatment and in the absence of evidence of active neurologic disease.
• All of the currently available and recommended tests are antibody tests, which can only ascertain that a patient has been exposed to B burgdorferi but cannot determine if a patient is currently infected. In the presence of typical clinical manifestations and laboratory results suggestive of current activity (elevated synovial and spinal fluid cell counts), they can be used to confirm the clinical diagnosis.

Other Tests

• ECGs show fluctuating levels of AV block in patients with syncopal or near-syncopal symptoms secondary to Lyme carditis. In patients with possible exposure but without symptoms of myocardial ischemia, such changes should prompt further investigation for Lyme disease.

TREATMENT

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Medical Care

Treatment primarily is through the use of outpatient antibiotics. Patients with carditis may need hospitalization to prevent syncope during episodes of AV block. For these patients, prompt institution of appropriate antibiotics usually is the only treatment needed.

The Infectious Diseases Society of America recently released clinical practice guidelines for the assessment, treatment, and prevention of Lyme disease. The treatment guidelines are consistent with the recommendations presented in this article.

In 2003, Wormser et al suggested that patients who present can be treated with only 10 days of doxycycline. Patients with other manifestations who are treated with oral formulations should be treated for 30 days because, with these manifestations, accurately pinpointing the date of infection is not always possible. This regimen also may be effective for neurologic disease.

Treatment recommendations are as follows (see Medication for doses):

• Tick bite
• • Until recently, no therapy was indicated for tick bites, even in endemic areas. However, a 2001 article in the New England Journal of Medicine suggested that treatment with a single dose of 200 mg of doxycycline within 72 hours of removing a tick can prevent the development of Lyme disease.
  • This still should be limited to patients who have had possible tick exposure in endemic areas.
• Skin manifestations: Institute an oral regimen for 30 days.
• Arthritis
• • Institute an oral regimen for 30 days.
  • Re-treat for 30 days with oral regimen or intravenous (IV) ceftriaxone for 14-30 days if the first oral course is unsuccessful.
• Neuroborreliosis
• • Facial palsies: Institute an oral regimen for 30 days. Although facial palsies may resolve without treatment, antibiotic therapy may prevent further sequelae.
  • Paresthesias/radiculopathy: Institute IV therapy for 14 days. Oral doxycycline for 30 days may be as good as IV ceftriaxone for neuroborreliosis.
  • Encephalitis/encephalopathy: Institute IV therapy for 28 days.
• Fibromyalgia: The treatment of fibromyalgia and fibromyalgialike symptoms following Lyme disease has not been shown in any controlled trials to be responsive to antibiotic therapy. The latest trial, published in the New England Journal of Medicine, failed to show a benefit of treatment with 2 g of IV ceftriaxone daily for 30 days followed by oral doxycycline at 200 mg/d for 60 days.

Surgical Care

• Patients with chronic arthritis that does not respond to IV antibiotics may need a synovectomy to eradicate the inflammatory arthritis in the involved joint.
• Rarely, patients with carditis require a temporary pacemaker.

Consultations

• Consultation with a rheumatologist and neurologist may be indicated to ensure that other diseases are not the cause of unusual presenting symptoms in a patient with a positive Lyme titer.
• Consultation with a rheumatologist may be helpful in the evaluation and treatment of patients who present with fibromyalgia occurring after treated Lyme disease.

Activity

• Activity restrictions are not indicated for patients who are feeling well.

MEDICATION

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The goals of pharmacotherapy with antibiotics are to reduce morbidity and to prevent complications.

Drug Category: Antibiotics

Antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

FOLLOW-UP

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Further Outpatient Care

• Patients whose conditions do not respond to therapy with improvement in symptoms may need retreatment. Patients who continue to improve but plateau in their improvement also may need retreatment.
• Given the cost and convenience, a 30-day course of oral therapy may be indicated before repeating IV therapy.
• Repeat serologic testing is not indicated because IgM titers may persist with treatment, and changes in IgG titers do not reflect the efficacy of treatment.

Deterrence/Prevention

• Avoidance of ticks and areas associated with ticks
• • Back yard patios, decks, and grassy areas that are mowed regularly are unlikely to have ticks present. This may be because of the lack of cover for mice from owls and other raptors that prey on mice. The ticks also need moisture, which these areas do not provide.
  • The areas around ornamental plantings and gardens are more hospitable for mice and ticks. The highest concentration of ticks is found in wooded areas.
  • Individuals should try to prevent ticks from getting onto skin and crawling to preferred areas.
  • Long hair should be worn under a hat.
  • Wearing long-sleeved shirts and tucking long pants into socks are recommended.
• Inspection
• • Because the above recommendations are not always practical, particularly for children and during the summer, and because ticks do not appear to transmit Lyme disease until they have been attached for several days, close inspection for ticks should be performed each time one has been outdoors.
  • The groin, axilla, and hairline should be inspected particularly well.
• Animals
• • Because pets can get Lyme disease and can carry ticks, making sure they are wearing tick collars seems prudent. Applying the suggestions concerning skin inspection also may be prudent after playing with outdoor pets.
  • If ticks are found, they should be removed promptly. In animal studies, a preferred method of removing ticks is not clearly evident. Removal by holding on to the body of the tick does not increase the transmission rate.
• Repellants
• • The use of tick repellants may be appropriate for adults.
  • In children, increased absorption and resultant toxicity is a concern.
• Vaccination
• • The Lyme disease vaccine is no longer available because not enough patients were being vaccinated to justify keeping it on the market. As a result, the prevention methods mentioned above are even more important.

Prognosis

• Making definitive statements regarding the outcome of Lyme disease is difficult because of (1) the inability to separate false-positive titers from asymptomatic infection, (2) the necessity of depending on clinical acumen in diagnosing erythema migrans (because titers often are negative at that stage), (3) the lack of uniform treatment regimens, and (4) the absence of long-term follow-up of most patients.
• • Lyme disease appears to rarely be a fatal disease, with only several fatal cases reported.
  • Cranial nerve palsies usually resolve without treatment.
  • Carditis does not seem to be associated with long-term cardiac sequelae.
  • Even without treatment, the recurrent episodes of Lyme arthritis resolve over a 10-year period.
• Children who are appropriately treated seem to have a good prognosis for complete recovery.
• In adults, the long-term outcome is not clear.
• • Several studies have suggested that chronic musculoskeletal symptoms and difficulties with memory, concentration, and fatigue may be more common in adults. This may be associated with an extended time to treatment (years vs months) and initial treatment with antibiotics other than doxycycline or amoxicillin.
  • A recently published large-scale outcome study suggested that patients with confirmed Lyme disease did, in fact, have increasing symptoms following diagnosis, but not at a greater rate than age-matched controls. Other reports exist of chronic symptoms in patients with a diagnosis of Lyme disease who did not meet the case definition, thus raising the question of whether these patients actually had Lyme disease.

Patient Education

• For excellent patient education resources, visit eMedicine's Bites and Stings Center, Arthritis Center, and Muscle Disorders Center. Also, see eMedicine's patient education articles Lyme Disease, Ticks, Chronic Fatigue Syndrome, and Chronic Pain.

MISCELLANEOUS

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Special Concerns

• Pregnancy
• • Pregnant women who develop Lyme disease should be treated, but not with doxycycline or another tetracycline.
  • No evidence indicates an increase in congenital heart or neurologic disease in endemic areas. This suggests that if a pregnant woman is bitten by a tick, antibiotic treatment is not indicated.

MULTIMEDIA

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Media file 1:  Normal and engorged Ixodes ticks.
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Media type:  Photo

Media file 2:  Erythema migrans, the characteristic rash of early Lyme disease.
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Media type:  Photo

REFERENCES

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• Adams WV, Rose CD, Eppes SC, Klein JD. Cognitive effects of Lyme disease in children: a 4 year followup study. J Rheumatol. May 1999;26(5):1190-4. [Medline].
• Karlsson M, Hammers-Berggren S, Lindquist L, et al. Comparison of intravenous penicillin G and oral doxycycline for treatment of Lyme neuroborreliosis. Neurology. Jul 1994;44(7):1203-7. [Medline].
• Klempner MS, Hu LT, Evans J, et al. Two controlled trials of antibiotic treatment in patients with persistent symptoms and a history of Lyme disease. N Engl J Med. Jul 12 2001;345(2):85-92. [Medline].
• Logigian EL, Kaplan RF, Steere AC. Successful treatment of Lyme encephalopathy with intravenous ceftriaxone. J Infect Dis. Aug 1999;180(2):377-83. [Medline].
• Meyerhoff J. Lyme disease. Am J Med. Oct 1983;75:663-70. [Medline].
• Nadelman RB, Wormser GP. Lyme borreliosis. Lancet. Aug 15 1998;352:557-65. [Medline].
• Nadelman RB, Nowakowski J, Fish D, et al. Prophylaxis with single-dose doxycycline for the prevention of Lyme disease after an Ixodes scapularis tick bite. N Engl J Med. Jul 12 2001;345(2):79-84. [Medline].
• Seltzer EG, Gerber MA, Cartter ML, et al. Long-term outcomes of persons with Lyme disease. JAMA. Feb 2 2000;283(5):609-16. [Medline].
• Steere AC. Lyme disease. N Engl J Med. Aug 31 1989;321:586-96. [Medline].
• Wormser GP, McKenna D, Carlin J, et al. Brief communication: hematogenous dissemination in early Lyme disease. Ann Intern Med. May 3 2005;142(9):751-5. [Medline]. [Full Text].
• Wormser GP, Ramanathan R, Nowakowski J, et al. Duration of antibiotic therapy for early Lyme disease. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. May 6 2003;138(9):697-704. [Medline].
• Wormser GP, Dattwyler RJ, Shapiro ED, et al. The clinical assessment, treatment, and prevention of lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. Nov 1 2006;43(9):1089-134. [Full Text].

Article Last Updated: Jan 4, 2007