Lyme Disease 

Lyme disease is due to systemic infection with the spirochete Borrelia burgdorferi and the body's immune response to the infection.^[1] The bacteria are inoculated into the skin by a tick bite, from ticks of the genus Ixodes.

The original descriptions of the dermatologic manifestations of Lyme disease date back to 1883 in Europe, when a German physician, Alfred Buchwald, described what is now termed acrodermatitis chronica atrophicans (ACA). Several decades later in 1912, a Swedish dermatologist, Arvid Afzelius, described the rash, then called erythema chronicum migrans (ECM), which currently is referred to simply as erythema migrans (EM).

Clinical Image Atlas: View clinical images on the features, causes, epidemiology, diagnosis, and treatment of Lyme disease.

In the 1920s, Garin and Bujadoux described a patient with meningoencephalitis, painful sensory radiculitis, and erythema migrans following a tick bite, and they postulated the symptoms were due to a spirochetal infection. The neurologic manifestations and the association with Ixodes ticks (also known as deer ticks) were recognized by the mid 1930s and were known as tick-borne meningoencephalitis. In the 1940s, Bannwarth described several cases of chronic lymphocytic meningitis and polyradiculoneuritis, some of which were accompanied by erythematous skin lesions.

In the United States, Lyme disease was not recognized until the early 1970s, when a statistically improbable cluster of pediatric arthritis occurred in the region around Lyme, Connecticut. This outbreak was investigated by Allen Steere, MD, and others from Yale and stimulated intense clinical and epidemiologic research that led to the discovery of the causative agent and its ecology and an expanding geographic range and list of clinical manifestations. The recognition that the patients in the United States had ECM and the initial antibiotic responsiveness of the cutaneous manifestations that had been described in the 1950s in the European literature was confirmed, leading 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 (see the image below), it was recovered from patients with clinical Lyme disease, confirming Borrelia 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 between 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 populations 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.

Go to Pediatric Lyme Disease for complete information on this topic.

Many of the manifestations of this disease are caused by active infection by the spirochete; others may be driven by immunopathogenetic mechanisms. Although any part of the body can be affected, after entering the circulation, the organism shows a distinct tropism for the skin, heart, central nervous system (CNS), joints, and eyes. Spirochetes have also been demonstrated histologically in bone marrow, the spleen, lymph nodes, the liver, testes, and the placenta during early hematogenous dissemination.

The clinical manifestations generally follow 3 stages of disease progression: early localized, early disseminated, and chronic disseminated (see also Clinical Presentation). All are potentially curable with antibiotic therapy. The infection progresses to disseminated disease in approximately 50% of untreated patients.

Stage 1 of disease progression

Once B burgdorferi is injected into the host, patients may clear the infection without developing any manifestations, as demonstrated by patients who are asymptomatic but seropositive.

Stage 2 of disease progression

B burgdorferi spreads throughout the body and produces symptoms by direct invasion (eg, erythema migrans), 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 is also difficult. The inflammatory response to B burgdorferi in the skin is probably the explanation for multiple lesions of erythema migrans, as almost all patients with multiple lesions are seropositive, regardless of duration.^[2]

Antibodies against spirochetal protein membrane epitopes have been shown to cross-react with neural and connective tissues. This molecular mimicry possibly generates an autoimmune inflammatory reaction. The pathophysiology of early versus late manifestations of the disease is similar to that seen with syphilis.

Early studies showed that in roughly 10% of patients with isolated erythema migrans and no systemic symptoms, B burgdorferi or its DNA, can be detected in the bloodstream. In addition, early in the course of disease and while erythema migrans still is present, spirochetal DNA has been detected in cerebrospinal fluid (CSF), indicating early CNS penetration. This can occur even in the absence of neurologic symptoms.

Importantly, one study found that if large-volume cultures (9 mL of plasma) were performed in early presenting patients with erythema migrans, 93 (43.7%) of 213 had spirochetemia. Some of these patients had only isolated erythema migrans and no systemic symptoms.^[3]

The organism also can persist in the skin for very long periods. Experimentally, the spirochete can penetrate human fibroblasts and live intracellularly, even when the extracellular medium contains ceftriaxone at concentrations well above bacteriocidal levels. Although intracellular organisms have never been demonstrated in vivo, this may be one mechanism by which the organism eludes host defense mechanisms. Clinically, B burgdorferi has been cultured from skin lesions of patients with acrodermatitis chronica atrophicans 10 years after initial infection.

Stage 3 of disease progression

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 immunologic factors, including the production of proinflammatory cytokines and the formation of immune complexes, and genetic factors, such as human leukocyte antigen (HLA)–DR4 and HLA-DR2.

Patients with HLA haplotype DR4 or DR2 and antibodies to OspA and OspB proteins in their joint fluid may be more susceptible to long-term arthritis than persons without these characteristics. The presence of these genes is related to the development of autoimmunity in the joint, which can lead to persistent inflammation even after the spirochete is apparently eradicated.

Animal studies have suggested a primary role of astrocytes and microglial cells in the pathogenesis of neuroborreliosis. Interleukin 6 (IL-6) production by astrocytes and subsequent oligodendrocyte apoptosis have been proposed as mechanisms of cell injury.^[4]

B burgdorferi infectious cycle

The infectious cycle of B burgdorferi involves colonization, infection of Ixodes ticks, and then transmission to broad a range of mammalian hosts, including humans. Variation in environmental and host conditions promotes different gene expression and changes in the composition of the membrane proteins of the spirochete. This adaptation is a critical step in the pathogenesis and transmission of Lyme disease.

The Ixodes tick progresses through 4 stages of development: egg, larva, nymph, and adult (see the following image for examples of each stage). Only larvae, nymphs, and adult female ticks require blood meals, and only ticks in the nymphal and adult stages can transmit B burgdorferi. The risk of Lyme disease is highest during the time of the year when the nymphal stage is seeking a blood meal.

The Ixodes ticks feed in a seasonal pattern, with larvae feeding once in the late summer, nymphs feeding once in the following spring and summer, and adults feeding once in the fall. Ixodes ticks acquire B burgdorferi by feeding on an infected animal host. The white-footed mouse is the preferred feeding source of nymphs, but other animals apparently suffice, and it is an important reservoir of B burgdorferi in the United States. The white-tailed deer is the preferred host of adults.

Unless the tick feeds on an infected host before feeding on a person, infection cannot result from that tick bite. Even if a tick feeds on an infected animal, the animal may not acquire the infection. Mice do not appear to develop Lyme disease, but they do carry the bacteria. They may be considered infested rather than infected.

Although the prevalence of B burgdorferi infection in adult ticks is twice that of nymph ticks, nymphs are responsible for 90% of human disease transmissions because of the great abundance of nymphs, the increase in human outdoor activity in the summer (peak feeding season of nymphs), and the relative ease with which large adult ticks are detected and removed.

Ticks carry B burgdorferi organisms in their midgut. The bacteria are introduced into the skin by a bite from an infected Ixodes tick, and disease is transmitted to humans as the spirochete is translocated from the gut to the salivary glands and then to the person at the site of the bite. Once in the skin, the spirochete can be overwhelmed and eliminated by host defense mechanisms; B burgdorferi can remain viable and invade the surrounding local tissue, remaining localized at the site of inoculation; or it may undergo hematogenous and lymphatic dissemination within days or weeks of the initial infection.

The primary risk factor for developing cutaneous manifestations of Lyme disease is exposure to Ixodes (deer) ticks (from areas likely to harbor ticks, such as woody, brushy, or grassy outdoor habitats), which transmit B burgdorferi from host to host. The life cycle of the Ixodes tick and B burgdorferi is important, as it relates to the epidemiology of Lyme disease (see B burgdorferi infectious cycle under Pathophysiology).

The complete genome of B burgdorferi, which has several distinct genetic groupings, was described in 1998; there is also evidence that additional strains or closely related Borrelia species also exist. The generic species is B burgdorferi (eg, sensu lato). Within this species exists several well-characterized groupings that account for the different clinical manifestations seen in North America and Europe. Three groups are well established, including B burgdorferi sensu stricto, B garinii, and B afzelii. Many other strains exist, but most are not pathogenic to humans. This is an area of active and constantly evolving research. Note the following:

• B burgdorferisensu stricto is a broad category of closely related but genetically distinct genospecies that constitutes all North American isolates and is found in Europe as well. These subspecies are associated with different clinical presentations, probably due to genomic variation. Infection with this organism has a particular predilection to affect joints. In European erythema migrans, B afzelii can be isolated from about 80% of lesions and B garinii from 15%.^[5]
• B garinii, found exclusively in Europe, has some neurotropism and is the isolate that accounts for most cases of the neurologic syndrome lymphocytic meningoradiculitis (Bannwarth syndrome) and a white matter encephalitis, which is rare in North America. However, this organism can cause all the various cutaneous manifestations (see Clinical Presentation).
• Although B afzelii, found mainly in Europe, is the most common organism causing acrodermatitis chronica atrophicans, all 3 species groups have been isolated from these patients.

In the northeastern and upper midwestern United States, Ixodes scapularis (sometimes termed Ixodes dammini) is the vector. In the northwestern United States, Ixodes pacificus is the vector. In other parts of the world, other Ixodes ticks serve this function. Other tick species (eg, Amblyomma americanum) and insects can carry B burgdorferi, but the vast majority of cases are believed to be caused by bites by Ixodes ticks. Note that in the southern and midcentral United States, a Lyme-like disease has been reported for which the vector appears to be A americanum.

B burgdorferi has not been isolated from the southern patients, although a closely related spirochete is suspected to be involved. Although some cases from the southern United States are documented with this new spirochete, called Borrelia lonestari, no organism can be isolated in the vast majority of cases of erythema migrans in this geographic area.^{[6, 7]}

Lyme disease is endemic in North America, Europe, and Asia, and the distribution of the vectors directly affects the incidence of the disease. Ixodes scapularis is the principal vector found in the Northeast and Central United States and Canada, whereas Ixodes pacificus is more common on the Pacific coast. Ixodes ricinus is the principal vector in Europe. The vector in Asia is the taiga tick, Ixodes persulcatus.

The US Centers for Disease Control and Prevention (CDC) tracks cases of Lyme disease by using strict surveillance criteria (not designed for diagnosis of individual cases). The incidence has been increasing over time; this is not simply a result of increased recognition, because in states that perform active surveillance, true incidence and geographic range have increased. The likely causes of this increase are expansion of deer herds and the expanded range of the vector.

Estimated incidence and frequency

Lyme disease is the fastest growing vector-borne disease in the United States, with infection occurring most often between May and November, with a peak incidence in June and July. From 1992-2006, approximately a quarter million cases of Lyme disease were reported to the CDC; 70% of cases were of erythema migrans, although it is possible that cases of erythema migrans were less commonly reported than those patients with later manifestations. Over that period, the incidence roughly doubled.

Although year-to-year variation is significant, approximately 20,000 cases are reported annually in the United States. More than 27,000 cases were reported during 2007, yielding a national average of 9.1 cases per 100,000 persons. Most of the states in the United States have reported Lyme disease; however, more than 95% of cases come from 12 states (Connecticut, Delaware, Maine, Maryland, Massachusetts, Minnesota, New Hampshire, New Jersey, New York, Pennsylvania, Rhode Island, and Wisconsin). Within these states, incidence can be quite variable from county to county and even neighborhood to neighborhood.^[8] In the states where Lyme disease is most common, the average is 34.7 cases per 100,000 persons.^[9]

More cases of Lyme disease are probably being reported now because of enhanced physician awareness and sophisticated laboratory surveillance. In addition, urban expansion into formerly wooded habitats has increased the incidence of Lyme disease as more people than before are living near tick-infested fauna.

However, at best, frequency data for Lyme disease in the United States are approximations, for the following reasons:

• Epidemiologic data suggest that the actual incidence of Lyme disease could be as much as 10 times higher than the CDC data indicate. The latter is probably a result of a restrictive case definition from the CDC, inevitable misdiagnosis, and the fact that physicians tend to underreport reportable diseases of all kinds.
• Separating false-positive antibody tests from asymptomatic infection is impossible. Approximately 5-10% of patients in endemic areas have positive antibody results without a history of symptoms.
• Although Lyme disease is a reportable disease, not all cases are reported or discovered through laboratory records, because early disease should be treated without antibody testing.
• Health department reporting of Lyme disease among states is highly variable, as well as reporting among counties within the states. Actual rates of Lyme disease may be 5 times higher than state health department rates.

Rates of Lyme disease in Europe may be similar to those in the United States. 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.

Global distribution

Lyme disease exists throughout much of the world including Canada, Scandinavia, Central Europe, Southern Europe, and Western Europe, the former Soviet Union, Japan, and China. Occasionally, cases are reported in more tropical locales, and Lyme disease may exist in Australia. In addition, different strains of the organism exist in Europe that account for differences in clinical manifestations and have implications for diagnostic testing and vaccine strategies. Even in Europe, borrelial lymphocytoma, a form of B-cell pseudolymphoma, occurs only in approximately 1% patients with Lyme disease, and acrodermatitis chronica atrophicans occurs in 10%; however, borrelial lymphocytoma has not been described in North America, and only a handful of cases of acrodermatitis chronica atrophicans have been reported in this region.

In one publication, the estimated incidence of Lyme disease was as high as 206 cases per 100,000 population in Slovenia and 135 cases per 100,000 population in Austria. Increases in prevalence have been also observed in Poland, Germany, Bulgaria, Norway, and Finland.

Racial, sex, and age distribution

Lyme disease is reported primarily in white individuals, although it occurs in individuals of all races. No genetic explanation is known for this, and it is likely the frequency stems from social or environmental factors (ie, whites have a higher exposure rate to ticks than do other races) and possibly to the fact that erythema migrans is more difficult to diagnose in dark-skinned individuals.

No strong preponderance of Lyme disease is noted in either sex, and there is a bimodal age peak in incidence. Reports from Europe indicate that, among children, the rate of Lyme disease is slightly higher in boys than in girls aged 5-19 years,^[9] but, in the older age peak (>30 y), the disease is more common in women than in men. The incidence of Lyme disease is lowest in individuals aged 20-24 years. Roughly 25% of cases occur in children younger than 14 years (see the image below). In general, this pattern is related to increased levels of outdoor activity and environmental exposure in patients in these age groups rather than any intrinsic difference in susceptibility.

Age has some effect on the location of borrelial lymphocytoma, as children tend to develop lesions on the ears (see the first image below), whereas adults develop lesions on the nipples. Acrodermatitis tends to occur more commonly in older patients (see the second image below).

Go to Pediatric Lyme Disease for complete information on this topic.

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 are often negative at that stage), (3) the lack of uniform treatment regimens, and (4) the absence of long-term follow-up in most patients.

Morbidity from this disease is usually neurologic and rheumatic. Patients with neurologic disease who are not diagnosed and treated promptly can suffer from neurologic and cognitive dysfunction that can be difficult to treat. Some patients may have fixed neurologic deficits that are unresponsive to antibiotics. Cranial nerve palsies usually resolve without treatment, and patients with cardiac disease rarely exhibit chronic morbidity from their heart involvement. Similarly, some genetically predisposed individuals with arthritis may have ongoing joint inflammation that is not responsive to further antibiotic therapy. Note that neurologic symptoms may take 6 months to reach maximum improvement.

The prognosis for treated patients with erythema migrans is excellent. Careful follow-up monitoring is very important in patients with Lyme disease in the later stages to ensure that patients have responded to treatment and do not develop extracutaneous symptoms and signs. A study of the long-term symptoms and effect on activities of daily living revealed no significant difference between patients previously treated for Lyme disease and age-matched control subjects 15-135 months after diagnosis.

Children who are appropriately treated seem to have a good prognosis for complete recovery.

In adults, the long-term outcome is usually good. Although several studies have suggested that subjective chronic musculoskeletal symptoms and difficulties with memory, concentration, and fatigue may be more common in adults and that these may be associated with an extended time to treatment (years vs months) and initial treatment with antibiotics other than doxycycline or amoxicillin, several studies suggest that these patients did not, in fact, have symptoms at a greater rate than age-matched controls.^{[10, 11]}

Post-Lyme disease syndrome

Approximately 80% of untreated or inadequately treated patients develop some manifestation of disseminated disease. Such episodes are typically subacute and transient, but infrequent cases of chronic, severe, and disabling disease have been described. However, although 15-55% of patients with Lyme disease report chronic or intermittent symptoms persisting for months to years after adequate antimicrobial treatment, data do not support postulations of a poorly defined post-Lyme disease syndrome. Reports of chronic symptoms in patients with a reported diagnosis of Lyme disease may include patients who did not meet the case definition for Lyme disease, thus raising the question of whether these patients actually had Lyme disease.^[10]

Common symptoms that patients and their caregivers often attribute to previous Lyme disease include cognitive disturbances, fatigue, joint or muscle pain, headaches, hearing loss, vertigo, mood disturbances, paresthesias, and difficulty sleeping. No evidence suggests that prolonged antibiotic therapy is effective for these symptoms.

Proposed criteria for post-Lyme disease syndromes include the presence of fatigue, musculoskeletal pain, and/or cognitive difficulties within 6 months of the diagnosis of Lyme disease and a persistence of symptoms for at least 6 months after completion of generally accepted antibiotic therapy. The presence of co-infections (babesiosis, human granulocytic anaplasmosis) and objective evidence of associated conditions or underlying disorders that may explain the patient's symptoms exclude the existence of a post-Lyme disease syndrome.

Lyme disease appears to rarely be a fatal disease, with only several fatal cases reported. Many of these fatalities have been in patients co-infected with other tick-borne pathogens such as Ehrlichia species and B microti, and in Europe, tick-borne encephalitis.

A CDC study of death records from 1999-2003 found that only one record of 114 total records listing Lyme disease as an underlying or multiple cause of death was consistent with clinical manifestations of Lyme disease.^[12] .

Basic strategies for preventing Lyme disease include environmental and personal strategies. Environmental strategies are beyond the scope of this article and are not discussed. Personal strategies fall into 2 categories including personal habit modification (eg, avoiding ticks/tick habitats, inspecting clothing and pets, using repellents) and prophylaxis.

Provide patients with instructional material about additional manifestations of Lyme disease. Patients who have erythema migrans can get erythema migrans again; one episode does not necessarily confer immunity.

Avoidance

Educate patients regarding ticks and tick avoidance. Instruct patients regarding other tick-borne diseases and how to take appropriate precautions.

Backyard 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. Staying to centers of trails and applying DEET (N,N- diethyl-m-toluamide) to the skin or permethrin to clothing help avoid contact with ticks.

Individuals should try to prevent ticks from getting onto skin and crawling to preferred areas. In addition, wearing light-colored clothing and long-sleeved shirts and tucking long pants into socks and long hair under a hat when outdoors is 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, daily close inspection for ticks should be performed each time one has been outdoors.

Wearing clothing with white colors improves the odds of seeing ticks on clothing before the ticks attach. Removing ticks before they have been attached for 24 hours is another important way to diminish the risk of contracting Lyme disease. The groin, axilla, and hairline should be inspected particularly well.

Several studies have shown that the likelihood of infection is related to the duration of tick attachment.^[13] Infection is much less likely, but not impossible, with tick attachment durations of less than 24 hours. Proper tick removal technique is important too, that is, grasping the tick with fine tweezers close to the skin and pulling gradually outwards.

The degree of engorgement of the tick (see the following image) can be used as an indicator for tick attachment duration. For patients with unattached ticks or with ticks that are not engorged, no prophylactic therapy is recommended. Some authors recommend treating patients using oral antibiotics for 10 days if an Ixodes tick's bite is engorged (in an endemic area) or if the patient is pregnant

Animals

Because pets can develop Lyme disease and can carry ticks, making sure they are wearing tick collars seems prudent. Applying the suggestions concerning skin inspection may also 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. The American Academy of Pediatrics issued a recommendation that children not be exposed to products containing more than 10% DEET because of several case reports of neurotoxicity occurring in children exposed to high concentrations.^[14] To prevent accidental exposure to the mucous membranes, DEET repellent should not be applied to children's hands.

Use a tick repellent containing DEET or permethrin when exposure to an endemic environment is imminent. DEET is available in 5-100% concentrations as sprays, creams, gels, lotions, solutions, towelettes, and other formulations. In most circumstances, products containing 10-35% DEET are sufficient to provide adequate protection from ticks.

The degree of protection is proportionally related to the concentration of DEET. That is, products with a high DEET concentration provide a long duration of protection. Extended-release liposphere microdispersion DEET preparations (6.5% and 10%) may decrease exposure to high concentrations of DEET while maintaining a relatively long (2-4 h) duration of activity.

Other proposed guidelines to reduce DEET exposure include using a minimal amount of product to cover the exposed skin and clothes; avoiding contact with mucous membranes, open cuts, or irritated skin; and washing treated areas with soap and water as soon as the person goes indoors.^[14]

Prophylaxis

For patients with unattached ticks or with ticks that are not engorged, no prophylactic therapy is recommended. Some authors recommend treating patients using oral antibiotics for 10 days if an Ixodes tick's bite is engorged (in an endemic area) or if the patient is pregnant

An article published in 2001 suggested that a single dose of 200 mg of doxycycline may be used for tick bite prophylaxis.^[15] The investigators also corroborated that the degree of engorgement was an important variable in transmission of disease and that female nymphal ticks accounted for all cases of Lyme disease.^[15]

Prophylactic antibiotic therapy (single 200-mg dose of doxycycline) is only recommended for adults and children older than 8 years if all of the following circumstances exist:

• The attached tick can be recognized as I scapularis (adult or nympha), and it is estimated to have been attached for more than 36 hours. Prophylaxis generally is not necessary after I pacificus bites unless the rate of infection in the area is documented at greater than 20%.
• Prophylaxis can be started within 72 hours of the time the tick was removed.
• Ecologic information indicates that the local rate of infection of these ticks with B burgdorferi is greater than 20%.
• Doxycycline is not contraindicated.

Prophylactic antibiotics are not recommended in pregnant women.^[16]

Vaccination

In December 1998, the FDA approved a vaccine (LYMErix Lyme disease vaccine [recombinant OspA]) directed against the outer surface protein A of B burgdorferi after trials indicated efficacy. In 2002, this vaccine was pulled off the market by the manufacturer and is no longer available due to poor demand.^[17] Vaccinated individuals have positive results with enzyme-linked immunosorbent assays (ELISAs) for Lyme disease antibodies, but they can be distinguished from those with active infection using a Western blot test.

Previously vaccinated patients are not protected against Lyme disease, because the vaccine was not long lasting. In addition, current treatment recommendations are not altered in those with previous vaccination. As a result, the prevention methods mentioned above are even more important.

Because of the expanding endemic range and the difficulties and controversies with regard to diagnosis and treatment of Lyme disease, some authors have called for the redevelopment of a safe and effective vaccine. The incidence of this disease continues to increase despite effective proven preventative strategies. However, past perceptions about the safety of the vaccine may have implications for the development of a future vaccine.^[18]

Demicheli et al reported on the development of a vaccine for tick-borne encephalitis in which adverse effects after vaccination reportedly were common, but they were not deemed serious or life threatening.^[19] The researchers concluded that no relationship could be established between clinical protection and seroconversion, despite the highly immunogenic nature of the vaccine.

Additional information can be obtained from the American Lyme Disease Foundation, Inc. Mail: PO Box 466 Somers, Lyme, CT 06371. E-mail: questions@aldf.com.

For patient education information, see the Bites and Stings Center, Arthritis Center, and Muscle Disorders Center, as well as Lyme Disease, Ticks, Chronic Fatigue Syndrome (CFS), and Chronic Pain.