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Lyme disease and related tick-borne infections

Highlights

Lyme Disease Rates Double in Past 15 Years

The annual number of people newly infected with Lyme disease has doubled from around 10,000 cases per year in the early 1990s to about 20,000 cases per year now. Improved diagnosis and reporting probably contribute to this increase. In the United States, Massachusetts, New Jersey, and Pennsylvania have reported the highest number of Lyme disease cases in recent years. People ages of 5 - 14 years and 45- 54 years are at highest risk for contracting Lyme disease.

New Guidelines for Treatment of Neurological Lyme Disease

Most cases of Lyme disease can be prevented or cured with prompt antibiotic treatment following a deer tick bite. However, neurological complications can later develop in some patients. In 2007, the American Academy of Neurology released new guidelines for the treatment of nervous system Lyme disease. The guidelines recommend that patients with severe disease receive a 2 - 4 week course of intravenous antibiotics (penicillin, ceftriaxone, or cefotaxime). Patients with milder neurological cases may do well with a 2 - 4 week course of oral doxycycline. No guidelines currently recommend long-term antibiotic treatment for any stage or complication of Lyme disease.

Introduction

Lyme disease is the most commonly reported vector-borne disease in the United States. Vector-borne infections are transmitted by insects.

Borrelia Burgdorferi

The Lyme disease infection in the U.S. is caused by a spirochete called Borrelia (B.) burgdorferi. A spirochete is a bacteria-like organism with a cylinder-like shape surrounded by an outer membrane.

Lyme researchers have the completion of DNA encoding of B. burgdorferi. Researchers learned that certain proteins coat its outer surface. These proteins, collectively called Osp, are responsible for attaching the spirochete to cells in humans and other mammals.

Ixodes Ticks

The vector that carries B. burgdorferi in the U.S. Northeast and North Central states is the Ixodes scapularis tick. The Ixodes scapularis tick goes through three stages over the course of about two years:

• It is born from eggs as a larva.
• It develops into the nymph stage.
• It develops into the adult stage.

The Cycle of Infection

Cycle of Infection in the Northeast and North Central U.S. For Lyme disease to exist in these regions, three factors must come into close contact:

• The Borrelia (B.) burgdorferi spirochete
• The spirochete's host, the Ixodes scapularis tick
• The mammal for the tick to bite

The following describes the most common cycle in the Northeast and North Central U.S. by which the Lyme disease infection eventually reaches a person:

• The cycle of infection is related to the tick's life cycle, which requires 2 years to complete. The tick typically first picks up the spirochete during its larva stage, when it needs a blood meal to mature further.
• The tick's initial meal is typically blood from the white-footed mouse, which is commonly infected with Borrelia burgdorferi. After it dines on the infected blood, the tick then becomes a carrier of this spirochete.
• Borrelia burgdorferi lodges in the tick throughout one of both of its following life stages, nymph and adult. It is during these stages that the infection is passed on to other animals, including humans. Nymph ticks emerge around mid-June and can be about the size of poppy seeds. They are very difficult to spot and are estimated to be responsible for 90% of all Lyme disease cases. Adult ticks can be as large as a raisin after feeding, and easy to spot, but they usually prefer their dinner on the white-tailed deer.
• The infected nymph or adult tick crawls (it does not fly or jump) onto another animal, which can be mice or larger animals, such as deer, birds, or humans. If the tick bites these animals, it may then infect them with the B. Burgdorferi spirochete. (It should be noted that infected humans cannot pass the spirochete on to other humans by any means, including infected blood or urine or sexual contact.)
• A tick can feed for several days while being imbedded in the skin, after which it falls off. The tick's bite is painless, however, so only about half of people with Lyme disease recall being bitten.

Cycle of Infection in the Northwest. In the Northwest, the infecting insect is the Western blacklegged tick, Ixodes Pacificus. Here, the frequency of Lyme disease is much lower than in the other two regions because the animal carrier of the infection is the dusky-footed wood rat. This animal is bitten and infected by the Ixodes neotomae tick, which does not bite humans. The actual tick that spreads B. burgdorferi to people is Ixodes pacificus, which must feed first on an already infected wood rat.

Other Infections Carried by the Ixodes Tick

The two other important infections carried by the Ixodes scapularis tick are human granulocytic anaplasmosis (HGA) and babesiosis. Although they are both borne by the same tick as Lyme disease, all three of these infections are entirely different diseases.

Risk for Coinfection. Because Lyme disease, HGA, and babesiosis can all be carried by the same tick, there is some risk for co-infection with two or more of these organisms. The risk, however, is not wholly known. Studies have reported that 2 - 25% of ticks in several high-tick locations carry both HGA and Lyme. In one study of patients located in high-risk areas in New England, 39% had more than one of these infections transmitted by the Ixodes tick. There is no evidence that co-infection with one or more of these infections causes a more severe condition than either infection separately.

Symptoms

Symptoms of Lyme disease are diverse and often occur in early and late phases. They vary widely from person to person. Any one symptom may fail to appear, and symptoms may overlap in various combinations. Death from Lyme disease is very rare and occurs only in a few cases in which the heart is severely affected.

Typical Course

• Stage 1. In the majority of cases, the first sign of early Lyme disease is the appearance of a bull's-eye skin rash. It usually develops about 1 - 2 weeks after the bite, although it may appear as soon as 3 days, and as late as 1 month. In some cases, it is never detected. Flu-like symptoms (joint aches, fever, and general fatigue) commonly develop.
• Stage 2. Untreated, the infection spreads through the bloodstream and lymph nodes within days to weeks, involving the joints, nervous system, and possibly the heart. Multiple rashes may erupt in other places. If the infection affects the nervous system in stage 2, it most often causes weakness or paralysis in the nerves of the face (Bell's palsy) or in nerves of the spine.
• Stage 3. If the disease remains untreated, a persistent infection can occur after a few weeks or months, leading to prolonged bouts of arthritis and neurologic problems, such as concentration problems or personality changes. Fatigue is a prominent feature of both early and late stages.

Skin Rash

Evidence suggests that up to 90% of patients with Lyme disease exhibit a rash a few days to a month after a tick bite. The rash, known as erythema migrans, usually first appears on the thigh, buttock, or trunk in older children and adults, and on the head or neck in young children.

The bull's eye rash, which is commonly believed to be the classic sign of Lyme disease, may take the following course:

• It can first appear as a pimple-like spot, which expands over the next few days into a purplish circle. The circle may reach up to 6 inches in diameter with a deeper red rim. In some cases the ring is incomplete, forming an arc rather than a full circle.
• The center of the rash often clears or may turn bluish. Or secondary concentric rings may develop within the original ring, creating the bull's-eye pattern. Over the next several weeks, the circular rash may grow to as large as 20 inches across.
• Patients often describe the sensation of the rash as burning rather than itching.

It is important to note that in one study, only 9% of patients diagnosed with Lyme disease exhibited this classic pattern. Nearly 60% had a rash that was more general in appearance and 32% had a circular dense red rash.

In most patients, any rash fades completely after 3 - 4 weeks, although secondary rashes may appear during the later stages of disease.

Flu-like Symptoms

A flu-like condition is the most common sign of Lyme infection, and it can occur with or without a rash. Symptoms can last from 5 - 21 days and may include:

• Fatigue
• Chills and fever (100 - 103 F)
• Headache (usually most prominent at the back of the head)
• Joint aches (usually in the large joints)
• Stiff neck
• Backache
• Swollen glands (in the area around the tick bite or elsewhere)
• Less often, nausea, vomiting, and sore throat occur

Some experts recommend that children in high-risk areas be tested for Lyme in the summer months if they have the most common Lyme symptoms (fever, headache, joint aches) -- even if they have no tell-tale rash. Severe and sustained flu symptoms without the rash in such patients may indicate the presence of human granulocytic anaplasmosis (HGA) or babesiosis -- the other infections carried by the Ixodes tick.

Arthritis

Joint pain can arise at any time after the appearance of a skin rash. In the absence of a rash, arthritic symptoms may be the first indication of Lyme disease. Or, as suggested by some studies, it can develop months after the disease has been diagnosed. Arthritic symptoms may occur as follows:

• Aches, stiffness, and swelling, sometimes massive, of large joints, such as the knee, elbow, or shoulder. One or both knees are affected most often. The ankle, wrist, jaw, and finger joints are involved less often.
• Typically, no more than three joints are affected during the course of the disease. If several joints are involved, they tend to be asymmetrically distributed.
• Joint pain flare-ups are often accompanied by muscle pain.
• Arthritis symptoms usually last for a few days or weeks and are interspersed with longer periods during which the joints feel fine.
• The severity and frequency of attacks peak within 1 - 2 years then decrease and usually resolve, even without treatment.

Neurologic Symptoms

About 15% of untreated patients develop neurologic symptoms. They can occur in all stages of the disease and can affect any part of the nervous system.

Common Early Neurologic Symptoms. Most often, neurologic symptoms first appear while the initial skin rash is still present or within 6 weeks after its disappearance. Sometimes they are the first symptoms that the patient experiences. The most common neurologic symptoms may be headaches, sleep problems, and mood disturbance. Memory problems can also occur. Neurologic symptoms typically improve or resolve within a few weeks or months, even in untreated patients.

Bell's Palsy. In 5 - 10% of untreated Lyme patients, the facial nerve is affected, which results in Bell's palsy. This is a sudden weakness and drooping of the facial muscles and eyelid on one side of the face. Nerves around the facial area may also cause numbness, dizziness, double vision, and hearing changes. Another common neurologic problem is pain in the lower spine. It resembles low back pain from arthritis (although in the case of Lyme disease the skin near the spine may have abnormal sensations). Of note, Lyme disease has been observed in more than half the children who develop Bell's palsy.

Symptoms of Meningitis. In about 10 - 15% of patients, the infection takes place in the membranes that surround the brain and spinal cord (called meningitis). This can cause:

• Episodes of headache not relieved by over-the-counter medication
• Mild stiff neck
• Sensitivity to light

Symptoms of Lyme Encephalopathy. In some cases of untreated disease, the infection causes a condition called Lyme encephalopathy or neuroborreliosis. This causes the following symptoms:

• Unexplained mood changes
• Depression
• Trouble concentration and remembering
• Irritability
• Feelings of "pins and needles" or numbness in the arms or legs

Other Neurologic Symptoms.

• If the infection affects the white brain matter, symptoms resemble multiple sclerosis.
• If the infection occurs in the nerves affecting the skin, some patients experience pricking, tingling, or creeping feelings.
• Children have a higher risk than adults for neurologic effects on the eye. (This is still rare, however.)

Heart Symptoms

The infection may affect electrical conduction to the heart and cause symptoms suggesting heart rhythm disturbances:

• Palpitations
• Shortness of breath
• Chest pain
• Dizziness
• Fainting can occur if the infection affects the heart

These symptoms almost never produce serious problems in people without other types of heart disease.

Eye Symptoms

Symptoms in the eyes have been reported at every stage. Conjunctivitis ("pink eye") may be a symptom in the early stages. In late, untreated Lyme disease, neurologic problems can affect the eye, causing pain and sensitivity to light.

Risk Factors

Since 1991, when Lyme disease became a reportable disease, annual cases have doubled. (This increase is probably both due to increased infection rates as well as better diagnosis.) In general, about 21,000 cases of Lyme disease are now reported in the U.S. each year.

General Risk Factors

Anyone exposed to ticks is at risk for Lyme disease and other tick-borne diseases. Pets are also at risk. Naturally, anyone who is regularly outside in areas where tick rates are high has a greater than average risk for becoming infected.

Age. The highest reported incidence of Lyme disease occurs among children 5 - 14 years old and adults 45 - 54 years old.

Sex. Men and women are equally at risk.

The Risk for Lyme Disease after a Tick Bite

In general, the risk for developing Lyme disease after a tick bite is only between 1 - 3%. The risk varies depending on different factors:

• The longer the tick has fed, the greater the risk. In fact, in one study, no individuals developed Lyme disease after being bitten by a nymph tick for fewer than 72 hours. The risk was 25% in people on whom the tick had been feeding for longer than 72 hours.
• Nymph ticks carry a greater risk than adult ticks, probably because they are often too small to be detected (about the size of a pinhead). In addition, only nymph ticks that are at least partially swollen when removed pose any significant risk. (This suggests that they have feeding for a prolonged period.)

Geographic Locations

Locations in the U.S. Lyme disease has been reported in nearly all U.S. states. However, most Lyme disease cases are concentrated in the northeastern, mid-Atlantic, and north central states. Although Lyme disease was named for a town in Connecticut where the first American cases of the disease were described, in recent years Massachusetts, New Jersey, and Pennsylvania have reported the greatest number of cases.

Worldwide Locations. Pockets of Lyme disease exist around the world. The disease is common in Europe, particularly in forested areas of middle Europe and Scandinavia. The Borrelia family is also responsible for tick infections in Europe, but different subspecies (B. garinii and B. afzelii) may be more common there and cause slightly different symptoms. The infection has also been reported in Russia, China, and Japan.

High-Risk Landscapes

Deer ticks thrive in grassy areas that have low sunlight and high humidity. Woodlands and fields are prime habitats, but these ticks can also be found in the long grasses adjacent to beaches. The ticks are not confined to rural settings. In suburban areas, they can live in overgrown lawns, groundcover plants, and leaf litter.

Time of Year

The exact time of year for risk depends on a geographic regions seasons and how they affect the ticks breeding cycle. In general, the highest risk for Lyme disease onset is from June through August, and the lowest risk is from December through March.

Complications

Prompt treatment with antibiotics is very effective in curing Lyme disease in nearly all infected people, including children. One study showed that the long-term outcome of patients with Lyme disease who are treated with antibiotic therapy is excellent. However, even if Lyme disease has been successfully treated, it may be possible to become reinfected with Lyme disease again at a later date. The risk appears to occur only in patients who had been treated for the rash. In those who also developed arthritic symptoms, the antibody response appears to persist and prevent reinfection.

Complications of Late-Stage Lyme Disease

People at highest risk for persistent symptoms are those who go the longest before treatment. Fortunately, public vigilance has significantly reduced the rates of late-stage Lyme disease. Antibiotics given at late stages will relieve symptoms in most people, although about 5% may continue to have problems. Also at risk for persistent symptoms are those who show evidence of having severe infections. Retreatment at later stages has been shown to be effective in about three quarters of these patients.

Left untreated, Lyme disease can spread (disseminate). The infection may affect almost any part of the body and cause the following complications:

• Severe arthritis
• Persistent fatigue
• Mood disturbances and loss of concentration
• Neuropathy (numbness, tingling, or other odds sensations in the hands, arms, feet or legs)
• Life-threatening disorders affecting the heart, lungs, or nervous system can occur, but are very rare.

Arthritis. Without treatment, 60% of patients develop intermittent joint inflammation, especially in the knees. Lyme arthritis usually responds to a 28-day course of oral antibiotics (doxycycline, amoxicillin, or cefuroxime). A small number of patients may require intravenous antibiotics.

If the arthritis persists or joint swelling recurs after several months, patients may be treated by another 4-week course of oral antibiotics or 2 - 4 weeks of intravenous antibiotics (ceftriaxone). If symptoms still persist, nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroid injections, or disease-modifying antirheumatic drugs may be recommended by a rheumatologist. In severe cases, patients may require surgery (synovectomy) to reduce joint inflammation.

Persistent Neurological Disorders. In general neurological problems persist in 5% of patients, although some studies have reported much higher rates of up to 50%. Persistent symptoms usually include headache, attention and memory problems, and depression. Patients may also experience neurologic pain, numbness, or abnormalities in the face. Neurologic symptoms generally resolve and improve within a year.

Heart Problems. About 5% of untreated patients experience acute heart events from electrical conduction problems caused by the infection. Heart symptoms can appear within a few days to several months after the onset of disease. They include:

• Arrhythmias (irregular heartbeats)
• Pericarditis (inflammation of the lining of the heart), which occurs in about 5% of patients

Lyme-related heart problems almost always resolve without serious consequences within a week. About 30% of patients may need a temporary pacemaker, however. In very rare cases, these heart rhythm abnormalities have been fatal. There is some debate about whether there are any long-term consequences to the heart, such as the development of heart failure in some patients. One study of patients who had Lyme-related heart effects reported no greater long-term risk for heart problems than in people without a history of Lyme disease.

Miscellaneous Complications. Other complications reported include:

• Problems in the eye, including swelling that can cause pain and sensitivity to light
• Hepatitis (inflammation in the liver)
• Respiratory difficulties

Infections in the Pregnant Patient. The occurrence of any infection during pregnancy is of special concern. While the current research indicates that complications during pregnancy due to Lyme disease are very rare, pregnant women should still adhere scrupulously to preventive measures.

• Some studies indicate that Borrelia burgdorferi may be transmitted to the fetus during pregnancy, with the risk highest during the first trimester. If this occurs, however, it is likely to be very rare and not an issue of great concern. There is no evidence of any severe effects in the offspring of infected pregnant women.
• There are no reports of human infant Lyme disease infection from breast-feeding. Studies on animals, however, have reported transmission of the organism to infant mice through breast milk, but these findings do not appear to be applicable to people.

Post-Lyme Disease Syndrome

Lyme disease is a curable condition. Nearly all patients (95%) improve after a short course of antibiotics. In very rare cases, patients continue to complain of persistent non-specific symptoms, such as fatigue, muscle aches, cognitive problems, and headache lasting years after completing antibiotic treatment for the initial infection.

This syndrome, which resembles chronic fatigue syndrome (CFS) or fibromyalgia, is referred to as post-Lyme disease syndrome. In the past, it has been called chronic Lyme disease. However, based on many reviews of scientific literature, experts strongly believe that Lyme disease does not have a chronic state. According to the 2006 guidelines from the Infectious Diseases Association of America, post-Lyme disease syndrome is the preferred name for this condition.

Patients are considered to have this syndrome if they still have symptoms 6 months after treatment. Most importantly, there must be definitive evidence that the patient was originally infected by the B. burgdorferi spirochete. If there is no documented evidence of infection, it could be that the patient never had Lyme disease, or may be experiencing a new or different type of illness. If the patient did have Lyme disease, symptoms should eventually resolve without additional antibiotic treatments.

Experts strongly advise against prolonged antibiotic treatment. There is no evidence that long-term antibiotics help treat post-Lyme disease syndrome symptoms. In addition, long-term antibiotic treatment carries its own serious risks, such as the development of antibiotic-resistant superbugs.

Diseases with Similar Symptoms

Many other illnesses can mimick various features of Lyme disease. Depending on the symptoms, a doctor may be able to perform the evaluations necessary to rule out other conditions.

Ruling Out Other Tick-Borne or Spirochete Infections

Other infections can produce fever, headache, muscle aches, fatigue, and some of the neurologic or cardiac features of early Lyme disease. Some are transmitted by the same tick as Lyme disease.

Co-Infections Transmitted by the Ixodes Tick. Babesiosis and human granulocytic anaplasmosis (HGA) are transmitted by the same tick that carries Lyme disease. People may be co-infected with one or more of these infections, all of which can cause flu-like symptoms. If these symptoms persist and there is no rash, it is less likely that Lyme disease is present. Still, diagnosing a co-infection is difficult.

Other Spirochete Infections. Leptospirosis is a spirochete infection spread through animals or contaminated water that most often affects young people during the summer or fall.

Other Tick-Borne Infections. A number of other tick-borne diseases may resemble Lyme disease, although they are more common in parts of the U.S. where Lyme disease is less prevalent.

• Tick-borne relapsing fever (TBRF), a flu-like illness that occurs in mountainous areas of the West during the summer, may be misdiagnosed as Lyme disease. The antibiotic doxycycline may be prescribed to patients who have been bitten by ticks suspected of carrying TBRF, to help prevent development of the disease.
• Rocky Mountain spotted fever, which is also transmitted by ticks, is most prevalent in the south central and southeastern parts of the United States, but occurs throughout North and South America. The most characteristic symptom is a spotty rash that appears 5 - 10 days after infection. The disease is caused by ticks that carry the bacterial organism Rickettsia rickettsii, and is considered the most severe tick-borne illness in the United States. Unlike Lyme disease, which is rarely fatal, Rocky Mountain spotted fever causes death in 10% of all cases. Recent outbreaks of Rocky Mountain spotted fever have been linked to increases in wild dog populations.
• A tick-borne infection called by human monocyte ehrlichiosis (HME), carried by the Lone Star tick, strongly resembles Lyme disease, including a similar rash. It is not caused by the Lyme spirochete, however, and has been identified in patients who live in the southern United States.

Researchers speculate that ticks may be responsible for other diseases not previously thought to be carried by these vectors. For example, the Bartonella family of bacteria causes cat-scratch fever (which is transmitted from cat to cat by fleas) and trench fever (historically transmitted by lice).

Allergic Reaction to the Tick. If a rash, even ring-shaped, appears hours rather than days after a tick bite, it is most likely an allergic reaction to the tick, not a symptom of Lyme disease.

Other Insect Bites. Not every rash seen in regions where Lyme disease is common is caused by a tick. The bites of many insects and spiders can cause a skin reaction.

Autoimmune Diseases

A number of autoimmune diseases have chronic and low-level symptoms that may be confused with Lyme disease.

• Systemic lupus erythematosus (SLE) produces a rash (usually on the face), flu-like symptoms, and arthritis, but they usually develop very slowly over time.
• Rheumatoid arthritis or Reiter syndrome causes pain, swelling, or stiffness of the joints that may be confused with post-Lyme disease syndrome.
• Scleroderma has a limited form of the disease called morphea, which produces hard patches of skin. Some studies have even reported an association between B. burgdorferi and some cases of morphea. However, the evidence is weak and if it exists it is possibly limited to a specific variant in Europe and Asia. There is no association between severe scleroderma and Lyme disease.
• In children, juvenile rheumatoid arthritis or rheumatic fever, which follows strep throat, should be considered.

Diseases Resembling Post-Lyme Disease Syndrome

A number of conditions cause chronic fatigue and joint and muscle aches that resemble descriptions of post-Lyme disease syndrome:

• Mononucleosis -- this viral infection is common in adolescents
• Chronic fatigue syndrome (CFS)
• Fibromyalgia
• Depression (may include persistent fatigue and vague aches and pains)

Meningitis

The early neurologic symptoms of Lyme disease (headache, stiff neck, and fatigue) can easily be mistaken for viral meningitis. Children with viral meningitis are more likely to have a higher fever. Patients with Lyme disease often have other symptoms, such as the bull's-eye rash.

Diagnosis

Proper diagnosis of Lyme disease is important. A diagnosis of Lyme disease is straightforward if the patient meets the following criteria:

• Lives in an area of tick-infestation
• Has the tell-tale bulls-eye rash
• Has other symptoms (headache, joint aches, malaise, flu-like symptoms)

If the patient meets all the criteria, except the rash, the doctor may undertake the enzyme-linked immunosorbent assay (ELISA) or the Western Blot test.

Culture

In some cases, if the patient seeks a diagnosis within the first 2 - 3 weeks, the doctor may take a sample of the skin or of the blood. If Lyme spirochete is present, it may be identified in the laboratory in a culture medium (a substance in which the organism can thrive and reproduce). This is necessary only if a doctor suspects Lyme but the diagnosis is not clear.

Immune Testing

If the infection is not obvious from the patient's history and physical symptoms, but Lyme disease is suspected, the doctor may run tests for evidence of specific factors that suggest infection with B. burgdorferi. Such factors include:

• Proteins referred to as Osps. These proteins (referred to as Osp A through F) coat the outer surface of the B. burgdorferi spirochete and then attach to human cells after infection.
• Antibodies that attack these Osps. Antibodies are the weapons of the immune system that are launched when foreign invaders (called antigens) are detected. In the case of Lyme disease, these antigens are the Osps.

Specific Tests.

The U.S. Centers for Disease Control (CDC) recommends a two-step process for Lyme disease blood tests:

• ELISA and Other Initial Tests. The first tests used are either enzyme-linked immunosorbent assay (ELISA) or an indirect fluorescent antibody (IFA) test. ELISA is the immune test used most often for Lyme disease. (The IFA test is less accurate but may be used when ELISA isn't available.) ELISA measures antibodies that are directed against the B. burgdorferi spirochete. A newer variant is a rapid test (PreVue) that can provide results within an hour. Positive results from any of these tests still require confirmation with a Western blot test. Negative results do not require further testing.
• Western Blot. If any of these tests is positive or uncertain, they are followed by the Western immunoblot (WB). This test is more accurate and is very helpful in confirming the diagnosis. The Western blot creates a visual graph showing bands of different colors or shading that experts use to interpret the immune response.

The CDC recommends only these tests. In 2005, the CDC warned against tests -- such as urine antigen, immunofluroescent staining, and lymphocyte transformation -- that do not have enough scientific evidence to support their use.

Accuracy of the Tests. These tests are very expensive, and none are completely accurate in either identifying Lyme or ruling it out. They should never be used to make a primary diagnosis of Lyme disease in patients who do not have obvious symptoms of the disease.

Both false positive and false negative results are common with these tests.

False positive results occur when the test suggests the presence of the disease, but the person does not actually have an active infection. This may occur in different ways:

• The antibodies to the infectious organism triggering the antibodies are not the Lyme spirochetes. Other organisms that can trigger such antibodies include syphilis and relapsing fever. Dental infections may trigger a false positive response.
• The patient may have been infected with Lyme disease previously and harbor antibodies to the disease.

False negative results miss the actual presence of the disease. These results are also common. (If the results are negative but Lyme disease is highly suspected, the doctor will probably prescribe antibiotics anyway.) False negative results occur for a number of reasons:

• The test is taken too early in the course of Lyme disease. In such cases, the antibodies that fight the spirochete might not have reached a level that is high enough to be detected. (Only about 20 - 30% of patients can be identified using immune system tests in the first 2 - 4 weeks. By the fourth week, up to 80% of patients will have detectable antibodies.)
• The patient has taken certain medications, such as steroids or certain anti-cancer drugs, which reduce the immune system's ability to produce antibodies, including those in response to Lyme disease.
• There are too many infection-fighting antibodies attached to the bacteria. In this case, there are not enough loose antibodies in the blood sample to trigger a response.
• The laboratory itself has set its sensitivity point too high. Some laboratories establish a standard of very high antibody levels before the test results will trigger a finding of Lyme disease. (They do this to avoid too many false-positive responses.) In so doing, however, their tests may miss the disease in patients with lower antibody levels. A related diagnostic problem concerns the possibility of missing persistent Lyme disease after antibiotic treatments, when antibody levels would be low.

All of this means that a negative blood test does not rule out a diagnosis of Lyme disease, particularly if symptoms strongly suggest its presence. Conversely, a weakly positive blood test does not prove that Lyme disease is causing the symptoms. A second blood test, taken several weeks later, may help.

Polymerase Chain Reaction (PCR) Test

The polymerase chain reaction (PCR) test detects the DNA of the bacteria that causes Lyme disease. However, it requires technical expertise and expensive equipment, and can be performed only in a few laboratories in the country. The test also has a high risk of false-positive results. Research indicates that blood or urine samples do not provide accurate results, but skin biopsies may be useful in some cases. At this point, the PCR test is reserved for certain patients with specific diagnostic problems. For most patients, standard antibody tests are preferred.

Tests for Neurologic Involvement

Analysis of Spinal Fluid. In patients who have neurologic symptoms, a lumbar puncture (a spinal tap) may be used to test for the bacteria in spinal fluid and may be useful for an early diagnosis of Lyme disease.

Treatment

Antibiotics are the drugs of choice for all phases of Lyme disease. In nearly all cases they can cure Lyme, even in later stages.

Preventive Antibiotics after a Tick Bite

According to the 2006 guidelines from the Infectious Diseases Society of America (IDSA), people bitten by deer ticks should not routinely receive antibiotics to prevent the disease.

A single dose of the antibiotic doxycycline may be given in situations that meet all of the following conditions:

• The tick is still attached to the patient and is positively identified as an adult or nymphal I. scapularis (the tick that carries the Lyme disease B. burgdorferi spirochete).
• Doxycycline treatment can be started within 72 hours of the tick bite.
• There is proof that at least 20% of ticks in that geographic area are infected with B. burgdorferi.
• It is safe for the patient to receive doxycycline (this drug should not be given to pregnant women or children younger than 8 years of age).

In general, the risk of developing Lyme disease after being bitten by a tick is only 1 - 3%. However, patients who have removed attached ticks from themselves should inform their doctors. Patients who have been bitten by a tick should be monitored for up to 30 days to make sure they do not develop symptoms of Lyme disease, especially the tell-tale bulls-eye rash. If you do develop a skin lesion or flu-like illness during this time, be sure to tell your doctor.

Treating Early Stage Lyme Disease

The early stages of Lyme disease usually involve classic bulls-eye rash (erythema migrans) and flu-like symptoms of chills and fever, fatigue, muscle pain, and headache. In rare cases, patients develop an abnormal heartbeat (Lyme carditis).

All of these conditions are treated with 10 - 28 days of antibiotics. The exact number of days depends on the drug used, and the patients response to it. Antibiotics for treating Lyme disease generally include:

• Doxycycline. This antibiotic is effective against both Lyme disease and human granulocytic anaplasmosis (HGA) and so is the standard antibiotic for any patient over 8 years old (except pregnant women). Doxycycline cannot be used routinely in children under 8 years old. It is a form of tetracycline and as such discolors teeth and inhibits bone growth. It can also cause birth defects, so it should not be used during pregnancy.
• Either amoxicillin (one of the penicillins) or cefuroxime (Ceftin) -- a drug known as a cephalosporin -- are the alternative treatments for young children and some adults. Amoxicillin is the first choice and also probably the best antibiotic for pregnant women. Unfortunately, many people are allergic to penicillin. In addition, strains of bacteria are emerging that are resistant to penicillins.
• Intravenous ceftriaxone -- another cephalosporin -- may be warranted if there are signs of infection in the central nervous system (the brain or spinal region) or heart problems.
• Other types of antibiotics, such as macrolides, are not recommended for first-line therapy.

Side Effects of Antibiotics. The most common side effects of nearly all antibiotics are gastrointestinal problems, including cramps, nausea, vomiting, and diarrhea. Allergic reactions can also occur with all antibiotics, but are most common with medications derived from penicillin or sulfa. These reactions can range from mild skin rashes to rare but severe, even life-threatening, anaphylactic shock. Some drugs, including certain over-the-counter medications, interact with antibiotics. Patients should report to their doctors all medications they are taking.

Treating Late Stage Lyme Disease

Most cases of Lyme disease involve a rash and flu-like symptoms that resolve within 1 month of antibiotic treatment. However, some patients go on to develop late-stage Lyme disease, which includes Lyme arthritis and neurologic Lyme disease.

Slightly more than half of patients infected with B. burgdorferi develop Lyme arthritis. About 10 - 20 % of patients develop neurologic Lyme disease. A very small percentage of patients may develop acrodermatitis chronica atrophicans, a serious type of skin inflammation. These conditions are treated for up to 28 days with antibiotic therapy. If arthritis symptoms persist for several months, a second 2 - 4 week course of antibiotics may be recommended. Oral antibiotics (doxycycline, amoxicillin, or cefuroxime) are used for Lyme arthritis and acrodermatitis chronica atrophicans. (In rare cases, patients with arthritis may need intravenous antibiotics.)

A 2 - 4 week course of intravenous penicillin, ceftriaxone, or cefotaxime is used for treating severe cases of neurological Lyme disease. For milder cases, 2 - 4 weeks of oral doxycycline is an effective option.

Treating Post-Lyme Disease Syndrome

In about 5% of cases, symptoms persist after treatment, a condition referred to as post-Lyme disease syndrome. The treatment of post-Lyme disease syndrome is a controversial issue. Most experts do not recommend continuing antibiotic therapy beyond 30 days. Scientific studies do not show any evidence that the benefits of long-term antibiotic treatment outweigh its risks. Long-term antibiotic treatment can lead to a serious and difficult-to-treat infection called Clostridiumdifficile, and can also cause the patient to become resistant to all types of antibiotics.

Experimental and alternative remedies are also not recommended. However, some patients may benefit from learning pain control and cognitive behavioral techniques to help them cope with and manage their symptoms.

Alternative Remedies

Some people use vitamin B complex, omega-3 and omega-6 fatty acids (found in primrose oil and fish oils), and magnesium supplements (magnesium L-lactate dihydrate) to help relieve symptoms. No evidence suggests that they are beneficial. Any such therapies should be discussed with a doctor. Newsletters and Internet sites have cropped up in recent years advertising untested treatments to patients with symptoms of Lyme disease who are frustrated with traditional medical channels. Some remedies are dangerous, and most are ineffective.

In 2006, the Food and Drug Administration (FDA) warned people not to use an alternative medicine product called bismacine (also known as chromacine). This injectable product contains high amounts of bismuth, a heavy metal that can be poisonous. People who have taken bismacine have experienced heart and kidney failure, and one death has been reported. Although some people claim that bismacine can help treat Lyme disease, it is not approved for the treatment of any illness or condition.

Herbs and Supplements

Generally, manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been a number of reported cases of serious and even lethal side effects from herbal products. Always check with your doctor before using any herbal remedies or dietary supplements.

Prevention

Everyone should avoid specific tick-infested areas, including tall grass, woods, and bushes where ticks tend to congregate. If this is not possible, people should take additional preventive measures. The U.S. Centers for Disease Control (CDC) also recommends:

• Use of tick repellant.
• Routine tick checks -- removal of infected ticks within 48 hours of attachment substantially reduces the likelihood of transmission.
• Prompt antibiotic prevention for tick bites -- although this method is controversial, the CDC concludes that it is probably beneficial.
• Removing brush and leaves -- such landscaping measures can reduce transmission rates by 50 - 90%.
• Applying pesticides to yards once or twice per year, which can decrease the number of ticks by 68 - 100%

Protecting Property from Tick Infestation

Mowing the grass regularly, clearing away leaves, and placing wood chips as a barrier around a lawn can help greatly reduce the tick population.

Permethrin for the Lawn. Insecticides can reduce tick infestation by 90%. Insecticides should be applied in late spring or early fall in a strip a few feet wide along the perimeter of the lawn where small animals are likely to enter or live.

The most commonly used insecticides are pyrethrins, which are compounds derived from the Chrysanthemum family. They are available as natural products or in synthetic forms (permethrin). They are poisons that affect the nerve system of insects. They are safe, particularly the natural products, for humans and pets. All pyrethrins are highly toxic for certain fish and slightly toxic for birds, such as mallard ducks. Some people do experience an allergic reaction to them. As with all insecticides, there is some concern about the possible consequences of long-term exposure, but to date there is no evidence of any harm.

Damminix, available in hardware stores, consists of cardboard tubes stuffed with permethrin-treated cotton. The tubes are placed where mice can find them (dense, dark brush) and collect the cotton for lining their nests. The pesticide on the cotton kills any immature ticks that are feeding on the mice. Best results are obtained with regular applications early in the spring and again in late summer. As many neighbors as possible should use it to be effective.

Other Pesticides. Other tick-killing spray pesticides that have been used include those containing diazinon, chlorpyrifos, and carbaryl. Animal studies have reported severe toxic effects associated with these chemicals. Some of these chemicals are being phased out for home use. Parents should balance the effects of a very negligible risk for a highly treatable infection versus excessive use of possibly harmful chemicals.

Eliminating Risk from Deer

Fencing. Deer fencing, a wire fence about 3 - 4 yards high, or electrified fencing can be helpful, but it is costly to put up and maintain.

Ivermectin. Corn that is laced with the anti-parasite medication ivermectin (Ivomec and others) and then eaten by deer helps prevent ticks from feeding on them. Ivermectin is present in a number of products used by veterinarians to control parasites, such as heartworm. It has potential toxic effects in collie or collie mixed breeds, however.

Protective Clothing in the Woods

Hiking and camping in the Northeastern woods carries a significant risk for tick bites and Lyme disease (3% in one study). Anyone out in the woods during tick season should wear protective clothing, including:

• Light-colored clothing -- makes it easier to spot ticks
• Long-sleeved shirts and long pants with cuffs tucked into shoes or socks
• High boots, preferably rubber boots
• Tick-collars for small dogs -- can be worn around a person's ankles over socks or pants

Simply washing clothes will not kill ticks. After venturing outdoors, people should run their clothes through a dryer at high temperature for a half hour. Spraying clothes with solutions containing permethrin (Permanone, Duranon, Permakill) affords additional protection. Keep in mind that these sprays should not be applied to the skin. Clothes should not be retreated with permethrin for 48 hours unless they are washed.

Insect Repellent

DEET. Most insect repellents contain the chemical DEET (N,N-diethyl-meta-toluamide), which remains the gold standard of currently available mosquito and tick repellents. DEET has been used for more than 40 years and is safe for most children when used as directed. Comparison studies suggest that DEET preparations are the most effective insect repellents now available.

Concentrations range from 4% to almost 100%. The concentration determines the duration of protection. Experts recommend that most adults and children over 12 years old use preparations containing a DEET concentration of 20 - 35% (such as Ultrathon), which provides complete protection for an average of 5 hours. (Higher DEET concentrations may be necessary for adults who are in high-risk regions for prolonged periods.)

DEET products should never be used on infants younger than 2 months. According to the Environmental Protection Agency, DEET products can safely be used on all children age 2 months and older. The EPA recommends that parents check insect repellant product labels for age restrictions.

If there is no age restriction listed, the product is safe for any age. The American Academy of Pediatrics recommends that children use concentrations of 10% or less; 30% DEET is the maximum concentration that should be used for children. In deciding what concentration is most appropriate, parents should consider the amount of time that children will be spending outside, and the risk of mosquito bites and mosquito-borne disease.

When applying DEET, take the following precautions:

• Do not use on the face, and apply only enough to cover exposed skin on other areas.
• Do not over apply and do not use under clothing.
• Do not apply over any cuts, wounds, or irritated skin.
• Parents or an adult should apply repellent to a child and not let the child apply it. They should first put DEET on their own hands and then apply it to the child. They should avoid putting DEET not only near the child's eyes and mouth but also on the hands (since children frequently touch their faces).
• Wash any treated skin after going back inside.
• If using a spray, apply DEET outdoors -- never indoors. Spray repellents should not be applied inside or directly on anyone's face.

Other Insect Repellent Products. In 2005, the CDC added two new mosquito repellents to its list of recommended products:

• Picaridin. Picaridin, also known as KBR 3023 or Bayrepel, is an ingredient that has been used for many years in repellents sold in Europe, Latin America, and Asia. A product containing 7% picaridin is now available in the United States. Picaridin can safely be applied to young children and is also safe for women who are pregnant or breastfeeding. According to the CDC, insect repellents containing DEET or picaridin work better than other products.
• Oil of lemon eucalyptus. In scientific tests, oil of lemon eucalyptus, also known as PMD, worked as well as low concentrations of DEET. However, oil of lemon eucalyptus is not recommended for children under the age of 3 years.

Self-Inspection and Tick Removal

Self-Inspection. The tick is unlikely to transmit the infection within 3 days of the bite, but prompt removal is still important. The following tips are important for self-inspection:

• Ticks responsible for Lyme disease are very small and may resemble freckles or scabs.
• People spending time in tick-infested locations should inspect themselves several times a day, including at bedtime.
• Check nonexposed areas, such as the back of the knee, as well as exposed areas. Someone else should check the scalp, back of the neck, and other difficult to reach areas.
• Check clothing as well as skin. A tick on can be hidden in folds or creases.

Tick Removal. If an attached tick is discovered, there is no reason to panic. Do not put a hot match to the tick or try to smother it with petroleum jelly, nail polish, or other noxious substances. This only prolongs exposure time and may cause the tick to eject the Lyme organism into the body.

The safest and most effective way to remove an attached tick is:

• Grasp the tick's mouth area with clean tweezers as close to the skin as possible. (Take care not to handle it with bare fingers as this can also spread infection.)
• Next, pull upward with a steady even pressure. Do not twist, crush, or squeeze the body area of the tick, because this region contains the infectious organism. In fact, do not be alarmed if some of the mouth parts remain in the skin. They are not infectious.
• Put the tick in a jar or container of alcohol, which will kill it. Some people lay a piece of adhesive tape to the top of the tick and fold it over, without touching the insect. Then they simply throw it away. Tape is also effective for trapping a tick that has not yet attached to the skin.
• Once the tick is removed, wash the bite area with soap and water or with an antiseptic to destroy any contaminating microorganisms. Wash hands as well.

Vaccines

The LYMErix Vaccine. The LYMErix vaccine, previously approved, was taken off the market because of poor sales and because of problems encountered with its use. A primary limitation was that the vaccine was effective only in about 75% of cases, and the effects were not long lasting. There were also reports of arthritic and neurologic symptoms in a few vaccinated people. There is no definitive evidence, however, that the vaccine was responsible for these symptoms.

Other Vaccines. Deer ticks lay their eggs on mice and other small rodents. These eggs develop into larvae that feed on these small animals. When the larvae develop into nymphs, they seek a larger host like a deer or human. Scientists are exploring the idea of vaccinating mice and other rodents against B. burgdorferi. Inserting an oral vaccine into these animals food supply helps reduce the number of nymph ticks and may be a more effective preventive strategy than vaccinating humans. Recent studies suggest that vaccination of mice produces 89 - 100% protection from B. burgdorferi infection.

Protecting Pets

Since dogs, cats and even horses can get Lyme disease, inspect pets for ticks regularly. Symptoms in animals include lameness and lethargy. Dogs are much more likely to get Lyme disease than cats, but both are susceptible. In dogs, symptoms occur 2 - 5 months after a tick bite and include fever, lameness, and lack of appetite. In rare cases, Lyme disease can cause kidney damage in dogs if it is left untreated.

Preventive Products. Products containing permethrin (Bio Spot, EXspot), amitraz (Preventic), or fipronyl (Frontline) can be used safely on dogs. Not all of these products are safe in cats. Only permethrin is also effective against fleas. Some veterinarians suggest that the combination of BioSpot and Preventic is very effective. [Another product-- selamectin (Revolution) --is sold for flea and tick control, but it appears to have very limited effect against ticks.]

Pet Vaccines. Lyme disease vaccines are available for dogs, but they do not offer total protection. Veterinarians vary in their use of the vaccines.

Treatment. As with people, antibiotics almost always cure the infection in animals.

Human Granulocytic Anaplasmosis (HGA)

In addition to Lyme disease, I. scapularis deer ticks can carry other types of infections that cause disease in humans. Human granulocytic anaplasmosis (HGA) is another illness spread by the deer tick. (HGA was formerly called human granulocytic ehrlichiosis. Another type of ehrlichiosis, human monocytic ehrlichiosis, is carried by a different type of tick.)

Typical HGA symptoms appear very suddenly within 4 - 14 days of being bitten by an infected tick. Symptoms include headache, fever, chills, headache, and muscle pains. Vomiting, diarrhea, and loss of appetite are also common. Blood tests may indicate a low blood platelet count, low white blood cell count, and increased liver enzyme levels.

HGA is caused by a species of bacteria called Anaplasma phagocytophilum. A blood test can identify the presence of this bacterium.

All patients who show signs of symptoms should be treated with doxycycline to reduce the risk of complications. Another type of antibiotic, rifampin, is an alternative option for pregnant women, children younger than 8 years of age, or patients who are allergic to doxycycline. Treatment is not recommended for people who do not exhibit symptoms, even if they test positive for antibodies to A. phagocytophilum.

Babesiosis

The tick that carries Lyme disease and human granulocytic anaplasmosis (HGA) can also carry babesiosis. Babesiosis is caused by a parasite called protozoa. It has been detected in about 10% of Lyme disease patients, and has been reported in Massachusetts, New York, Connecticut, Rhode Island, New Jersey, Minnesota, Wisconsin, Georgia, California, and Washington.

When babesiosis is acquired from ticks, the infection occurs only in the summer. However, unlike in Lyme disease, blood transfusions have also been known to transmit babesiosis, so it can also occur other times of the year. The disease is still very rare, but people in tick-infested areas should be aware of it.

Symptoms of Babesiosis

Symptoms of babesiosis occur 1 - 4 weeks after a tick bite and are similar to those of malaria. Most cases are very mild and nearly unrecognizable. More severe symptom may resemble those in malaria and include:

• Headache
• Fever and chills, with night sweats
• Nausea and vomiting
• Muscle aches
• Anemia

Complications of Babesiosis

In healthy people, babesiosis generally causes only mild and temporary problems, but research indicates that the infection might persist in some people and may be spreading faster than previously reported. In rare cases, it can be severe and even life-threatening, particularly in elderly people or those with chronic health problems or compromised immune systems. In such cases, the infection can cause altered mental states, anemia and other blood abnormalities, very low blood pressure, respiratory distress, and kidney insufficiency. Coinfection with Lyme disease may also increase its severity. Unfortunately, it is very difficult to diagnose.

Treatment of Babesiosis

Babesiosis is caused by a protozoon parasite, not a bacteria, so antibiotics alone wont cure the disease. Treatment involves a two-drug combination of an anti-malaria medication and an antibiotic. The standard drug combinations are atovaquone (Mepron) plus azithromycin (Zithromax, Zmax) or clindamycin plus quinine. About 25% of patients cannot tolerate quinine. Adverse effects associated with quinine include hearing loss, tinnitus, stomach upset, diarrhea, and dizziness.

Resources

• www3.niaid.nih.gov -- National Institute of Allergy and Infectious Disease
• www.cdc.gov/ncidod/dvbid/lyme -- Centers for Disease Control
• www.idsociety.org -- Infectious Diseases Society of America
• www.aldf.com -- American Lyme Disease Foundation
• www.rheumatology.org -- American College of Rheumatology
• www.arthritis.org -- The Arthritis Foundation

References

Centers for Disease Control and Prevention. Lyme disease -- United States, 2003-2005. MMWR Morb Mortal Wkly Rep. 2007 Jun 15;56(23):573-6.

Feder HM Jr, Johnson BJ, O'Connell S, Shapiro ED, Steere AC, Wormser GP; Ad Hoc International Lyme Disease Group. A critical appraisal of "chronic Lyme disease." N Engl J Med. 2007 Oct 4;357(14):1422-30.

Halperin JJ, Shapiro ED, Logigian E, Belman AL, Dotevall L, Wormser GP, et al. 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. 2007 Jul 3;69(1):91-102. Epub 2007 May 23.

Wormser GP, Dattwyler RJ, Shapiro ED, Halperin JJ, Steere AC, Klempner MS, 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. 2006 Nov 1;43(9):1089-134.

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