Lyme Disease

Introduction

Disease History, Characteristics, and Transmission

Scope and Distribution

Treatment and Prevention

Impacts and Issues

Primary Source Connection

BIBLIOGRAPHY

Introduction

Lyme disease is a bacterial infection caused by the spirochete (corkscrew-shaped bacterium) Borrelia burgdorferi. It is transmitted to humans through the bites of several kinds of ticks, including deer ticks (Ixodes scapularis) and the western black-legged tick (Ixodes pacificus) in the United States and Ixodes ricinis) in Europe. The untreated disease presents in two or three stages, starting with a localized infection that produces a skin rash and sometimes fever, headache, and other symptoms. The second stage may involve arthritis, neurological symptoms, such as depression and Bell's facial palsy, and meningitis (inflammation of the membranes that enclose the central nervous system). In the third stage, longterm arthritis and neurological symptoms may occur. The disease is treated using antibiotics. Earlier treatment is more effective, as the symptoms of untreated Lyme disease may take years to reverse or be irreversible. There is controversy between Lyme patient advocacy groups and many doctors about the existence of hard-to-detect, chronic Lyme infection and the advisability of treating such infections with antibiotics.

Disease History, Characteristics, and Transmission

History

Lyme disease has probably existed for centuries. Judging by case records, observations of what was probably Lyme disease were recorded in Germany and Scandinavia in the late nineteenth and early twentieth centuries. Examination of museum specimens of deer ticks collected in the United States has detected Lyme disease bacteria dating to the 1940s. In 1975, some mothers in the town of Lyme, Connecticut—for which the disease is named—began noticing arthritis, fatigue, erythema migrans rashes, and other symptoms in about 50 local children. Two of these women, Judith Mensch and Polly Murray, began tracking the cases by recording dates and locations. Several of the children recalled being bitten by a tick just before becoming ill. Murray called rheumatologist Allen Steer, who investigated the cases and concluded that a tick-borne pathogen was to blame for the disease.

Thus, the existence of Lyme disease was recognized and its transmission by ticks was known in 1975. However, the specific pathogen causing the disease was still unknown. In 1981, Dr. Willy Burgdorfer, working at the National Institute of Allergy and Infectious Diseases (NIAID) of the U.S. National Institutes of Health, was studying the transmission of Rocky Mountain spotted fever by ticks. Studying the microorganisms found in black-legged ticks (one of the two U.S. tick varieties that transmits Lyme disease), Burgdorfer noticed a hithertounknown variety of corkscrew-shaped bacterium (spirochetes) in fluids from two ticks. Within a year, this bacterium had been named Borrelia burgdorferi in Burgdorfer's honor.

In 1982, other researchers found Borrelia burgdorferi in deer ticks. By combining cultured B. burgdorferi bacteria with blood samples from people with Lyme disease, it was shown that the patients’ blood contained an antibody specific to B. burgdorferi. This showed that the blood donors had been infected with B. burgdorferi. Finally, in 1983, researchers found B. burgdorferi in blood and tissue samples from patients with Lyme disease, and the proof that the bacterium caused the disease was clinched.

In the years since 1983, there has been persistent controversy over the question of whether Lyme disease can exist in a chronic form that is not detected by standard tests, causing a wide range of neurological and other symptoms that overlap with those of fibromyalgia and chronic fatigue syndrome. There is also expert disagreement over the question of whether treatment of possible chronic Lyme infection with antibiotics is good medical practice.

Characteristics and Transmission

Lyme disease is caused by the spirochete B. burgdorferi, a member of the phylum Spirochaetes. Spirochetes are corkscrewor helix-shaped bacteria. B. burgdorferi are about 0.2–0.5 μm wide, 3–18 μm long, and are built with a double-layered structure, like a long, blunt-ended corkscrew nested within a slightly larger corkscrew of the same shape. In the space between the two layers are flagella. Each flagellum is a long, hairlike filament attached to a rotating base embedded in the outer cell wall. Many types of bacteria have flagella, but normally the flagella protrude into the bacterium's environment and are used for propulsion like tiny outboard propellers. A spirochete uses a different strategy—its internal flagella wrap lengthwise around the inner layer of the bacterium, forcing it into its characteristic corkscrew shape. Furthermore, as the flagella rotate, they cause the whole shape of the bacterium to change as if it were rotating on its axis. Just as an actual corkscrew is driven into a cork by rotating, a spirochete progresses through the medium in which it is embedded. Its corkscrewing mode of locomotion gives it a mobility advantage over other bacteria in more viscous (thicker, stickier) media.

Both syphilis and Lyme disease are caused by spirochetes. There are three common species of B. burgdorferi, namely Borrelia garinii, Borrelia afzellia, and Borrelia burgdorferi sensu stricto (meaning in the strict sense); together, these three are known as Borrelia burgdorferi sensu lato (“in the wide sense”) or simply, for convenience, as Borrelia burgdorferi. Borrelia burgdorferi sensu strictu is the only Lyme strain so far found in the United States as of 2007. Three other, less-common species of Borrelia burgdorferi sensu lato (in the broad sense) have been discovered to cause Lyme disease in Africa, Asia, and Europe.

Lyme disease is a vector-borne disease, meaning that it is transmitted to human beings by an intermediate host (in this case a tick), not directly from other human beings. Although far from the most common infectious disease in the United States, it is the most common vector-borne disease, accounting for over 95% of reported vector-borne illness cases. The vector for Lyme disease is the deer tick, and the transmission of Lyme disease to humans is intimately involved with the life cycle of both the B. burgdorferi spirochete and the tick.

In the spring, tick eggs lying on the ground hatch, producing tick larvae. Each larva attaches to a small mammal, usually a mouse. Ticks attach firmly to the skin and feed on their host by sucking blood. The larval tick ingests B. burgdorferi from its mouse host and becomes infected: this infection does not sicken the tick. In the fall and winter, the larva drops off the mouse and becomes dormant, attaching itself to vegetation. The next spring, it molts and becomes a nymph-stage tick. The nymph attaches to a deer, mouse, or human host— its preferred host is the deer—and bites the host, transmitting Lyme disease. The tick develops to an adult form throughout the summer, living on the host. In this stage it mates. In the fall, it drops off its host and lays eggs in leaf litter on the ground (about 3,000 eggs per laying female), beginning a new two-year cycle. This is the basic ecology of Lyme disease in the northeastern and north-central United States.

WORDS TO KNOW

BABESIOSIS: An infection of the red blood cells caused by Babesia microti, a form of parasite (parasitic sporozoan).

ENDEMIC: Present in a particular area or among a particular group of people.

GRANULOCYTE: Any cell containing granules (small, grain-like objects) is a granulocyte. The term is often used to refer to a type of white blood cell (leukocyte).

HOST: Organism that serves as the habitat for a parasite, or possibly for a symbiont. A host may provide nutrition to the parasite or symbiont, or simply a place in which to live.

MENINGITIS: Meningitis is an inflammation of the meninges—the three layers of protective membranes that line the spinal cord and the brain. Meningitis can occur when there is an infection near the brain or spinal cord, such as a respiratory infection in the sinuses, the mastoids, or the cavities around the ear. Disease organisms can also travel to the meninges through the bloodstream. The first signs may be a severe headache and neck stiffness followed by fever, vomiting, a rash, and, then, convulsions leading to loss of consciousness. Meningitis generally involves two types: non-bacterial meningitis, which is often called aseptic meningitis, and bacterial meningitis, which is referred to as purulent meningitis.

NYMPH: In aquatic insects, the larval stage.

SPIROCHETE: A bacterium shaped like a spiral. Spiralshaped bacteria, which live in contaminated water, sewage, soil, and decaying organic matter, as well as inside humans and animals.

SPOROZOAN: The fifth Phylum of the Protist Kingdom, known as Apicomplexa, comprises several species of obligate intracellular protozoan parasites classified as Sporozoa or Sporozoans, because they form reproductive cells known as spores. Many sporozoans are parasitic and pathogenic species, such as Plasmodium falciparum, P. malariae, P. vivax, Toxoplasma gondii, Pneumocysts carinii, Cryptosporidum parvum and Cryptosporidum muris, The Sporozoa reproduction cycle has both asexual and sexual phases. The asexual phase is termed schizogony (from the Greek, meaning generation through division), in which merozoites (daughter cells) are produced through multiple nuclear fissions. The sexual phase is known as sporogony (i.e., generation of spores) and is followed by gametogony or the production of sexually reproductive cells termed gamonts.

VECTOR: Any agent, living or otherwise, that carries and transmits parasites and diseases. Also, an organism or chemical used to transport a gene into a new host cell.

In northern California and Oregon, a more complex vector ecology exists. A reservoir of B. burgdorferi is maintained in the wild by Ixodes neotomaei ticks (which do not bite humans) and the dusky-footed wood rat. A second type of tick, Ixodes pacificus, which usually feeds on lizards—which does not host B. burgdorferi—occasionally feeds on infected wood rats in its nymphal stage. Those few Ixodes pacificus ticks that feed on infected wood rats and then on humans can cause Lyme disease.

Once in a human host, Borrelia burgdorferi can cause three stages of disease. Stage 1 is the erythema migrans rash, which is centered on the site of the tick bite. There is disagreement over how common this rash is. Some experts say that less than 50% of Lyme disease patients experience it, while others say 80%. Stage 2 affects the nervous system, joints, and heart. Stage 3 is late or chronic infection.

Stage 1 (early Lyme disease). The characteristic Lyme rash is a red, inflamed patch of skin about 2 in (5 cm) or more wide. It sometimes takes on a bull's-eye form with a central clear space. The rash usually develops within 3–30 days (most often 7–14 days) of the detachment of the tick. A single spot is most common, but multiple spots may develop as the bacteria spread widely from the tick bite. Influenzalike symptoms are also common at this stage. Symptoms include joint pain, fatigue, neck pain, headache, and fever. Coughing, vomiting, and diarrhea do not happen, allowing this condition to be told apart from a real flu.

Stage 2 (early disseminated Lyme disease). Within 4–6 weeks, neurological and arthritic symptoms develop. About 15% of untreated patients develop neurological symptoms. Meningitis (inflammation of the meninges, the membranes that enclose the central nervous system) may occur, with headache and neck stiffness, Bell's palsy (partial paralysis of facial muscles), blindness due to pressure on the optic nerve (especially in children), depression, anxiety, memory loss, and more. These neurological symptoms usually go away after some weeks or months; however, the infection may remain, and in up to 5% of untreated patients may become chronic. (These figures are disputed by some physicians, who argue that the chronic rate is higher in both treated and untreated patients.) About 5% of untreated patients also develop cardiac symptoms, including atrioventricular block and inflammation of the heart. Several months into the illness, most untreated patients (about 60%) develop arthritis—joint swelling and pain, especially in large joints such as the knee. These arthritic symptoms may become chronic in some patients. Arthritis may persist in the knees even years after antibiotic therapy. In Stage 2, other common symptoms include diarrhea, shortness of breath, rapid or irregular heartbeat, testicular pain, shaking hands, frequent need to urinate, and poor sense of balance. Exactly how Borrelia burgdorferi causes all these symptoms remains largely unknown.

Stage 3 (chronic or late Lyme disease). According to some physicians, 30–50% of treated and untreated Lyme patients develop a disorder with several symptoms that is hard to distinguish from fibromyalgia and chronic fatigue syndrome. Symptoms include fatigue, joint paint (arthralgia), muscle pain (myalgia), and other dysfunctions of the nervous system. It should be noted that the existence of a third-stage, chronic or late form, of Lyme disease has been controversial. Some researchers have maintained that Lyme disease is reliably eradicated by treatment with antibiotics and that cases of apparent chronic infection are actually psychiatric (mental) disorders. This controversy persists partly because laboratory tests for the presence of B. burgdorferi are unreliable, with many false negatives (tests showing no infection when there is infection).

One reason why Lyme disease may produce such varied symptoms is that the ticks that transmit it are also host to numerous other pathogens, and can serve as vectors for such disorders as babesiosis (infection of the red blood cells caused by the parasitic sporozoan Babesia microti) and human granulocytic ehrlichiosis (an infection of white blood cells caused a species of bacteria in the Ehrlichia genus). When more than one pathogen infects a person at a time, the result is called co-infection. Some researchers state that the majority of Lyme disease victims are probably co-infected with other organisms.

Even untreated, Lyme disease is rarely fatal.

Scope and Distribution

Lyme disease is a larger problem in the United States than elsewhere in the world, with about 15,000 new cases reported each year. However, most experts agree that the disease is greatly underreported and that the true number of new cases is probably more on the order of 100,000 per year. As of 2006, about 150,000 cases had been reported in the U.S. since 1976, the year after Lyme disease was officially recognized as a new disease.

There are 12 U.S. states in which Lyme disease is most commonly found: Connecticut, Delaware, Maine, Maryland, Massachusetts, Minnesota, New Jersey, New Hampshire, New York, Pennsylvania, Rhode Island, and Wisconsin. Lyme disease is endemic (normally occurs), with incidences as high as 3%, in parts of these states. About 70% of persons who contract Lyme disease catch it from a tick picked up in their own backyard; most of the remaining 30% acquire ticks while hiking or walking in woods or fields away from home.

Treatment and Prevention

Lyme disease is treated primarily with antibiotics. Which antibiotics are used depends on disease stage, symptoms, and allergic reactions. If Lyme disease is diagnosed early—as often happens when a person visiting his physician displays a characteristic rash and or flulike symptoms and reports a tick bite—treatment is a 14to 21-day course of oral (swallowed) antibiotics, most often doxycycline, clarithomycin, or amoxicillan. Treatment success at this stage is about 95% (although some researchers state that a much higher percentage of patients than 5% go on to develop a chronic form of the disease).

For Stage 2 (early disseminated) Lyme disease, the same agents are used but in large doses. In this case they are given intravenously (by needle, into a vein) rather than in pill form. If the heart is inflamed, penicillin G also may be used. Supportive medicines may be given for specific symptoms, such as pain relievers for arthritis symptoms and antidepressants for neurological symptoms, such as depression and anxiety.

Lyme disease is prevented by avoiding infected ticks. Particularly in spring, areas that are known to be infested with ticks should be avoided. Light-colored clothing makes it easier to spot ticks and remove them before they bite. Wearing long-sleeved shirts, tucking pants into socks, and applying insect repellents containing DEET (n,n,diethyl-m-toluamide) or treated with permethrin can decrease the chances of a tick bite. Promptly removing a tick that has attached is important, because B. burgdorferi usually does not infect the host until 36 hours after tick attachment. Ticks should be removed by gripping them right next to the skin with tweezers and pulling: the body of the tick should never be squeezed or irritated by heat or chemicals while the tick is attached, as this will drive its stomach contents into the skin and increase the chances of infection.

Many of the ticks acquired by people engaged in outdoor activity in the northeast United States, where 90% of all Lyme disease cases have been reported, are dog ticks (Dermacentor variabilis), which cannot transmit Lyme disease. The Lyme-transmitting deer tick Ixodes scapularis is notably smaller than a dog tick. Even if one is bitten by a tick, it is not necessary to seek treatment for Lyme disease unless flulike symptoms or the characteristic erythema migrans rash appear.

As of early 2007, no vaccine for Lyme disease was available.

IN CONTEXT: PERSONAL RESPONSIBILITY AND PROTECTION

The Division of Vector Borne Infectious Diseases at Centers for Disease Control and Prevention (CDC) states that to reduce risks of contracting Lyme Disease that you should:

• Avoid areas with a lot of ticks. Ticks prefer wooded and bushy areas with high grass.
• Take extra precautions when ticks that transmit Lyme disease are most active.
• If you do enter a tick area, walk in the center of the trail to avoid contact with overgrown grass, brush, and leaf litter.
• Keep ticks off your skin. Properly use insect repellent with 20% 30% DEET on adult skin and clothing to prevent tick bite. Effective repellents are found in drug, grocery and discount stores. Permethrin is another type of repellent. It can be purchased at outdoor equipment stores that carry camping or hunting gear. Permethrin kills ticks on contact! One application to pants, socks, and shoes typically stays effective through several washings. Permethrin should not be applied directly to skin. For details on permethrin visit the National Pesticide Information Center.
• Wear long pants, long sleeves, and long socks to keep ticks off your skin. Light-colored clothing will help you spot ticks more easily. Tucking pant legs into socks or boots and tucking shirts into pants help keep ticks on the outside of clothing. If you'll be outside for an extended period of time, tape the area where your pants and socks meet to prevent ticks from crawling under your clothes.
• Check your skin and clothes for ticks every day!
• If a tick is attached to your skin for less than 24 hours, your chance of getting Lyme disease is extremely small. But just to be safe, monitor your health closely after a tick bite and be alert for any signs and symptoms of tick-borne illness.

SOURCE: Division of Vector Borne Infectious Diseases at Centers for Disease Control and Prevention (CDC), Division of Vector Borne Infectious Diseases

Impacts and Issues

Lyme disease has become the most common vectorborne inflammatory disease in the United States thanks to changing human activities. In the nineteenth century, the central and northeastern United States were largely deforested and deer populations were eliminated or greatly reduced by hunting and habitat loss over large areas. After food production shifted elsewhere, these regions have largely reforested, and deer populations, along with the ticks that infest them, have rebounded. At the same time, greater numbers of human beings have been brought into contact with ticks by living in suburban developments and enjoying outdoor recreations such as hiking.

A 79 percent-effective vaccine for Lyme disease, LYMErix, was placed on the market in 1999. It was withdrawn in 2002, however, because of low sales. Low demand was caused by a combination of the vaccine's high cost ($50 per inoculation), its inconvenience (three shots were needed over a year), and fears that the vaccine might trigger permanent arthritis or neurological problems. Debate among experts over whether LYMErix was sufficiently safe remains fierce to this day. As of 2007, a European company was developing a vaccine that is intended to work for a wider range of B. burgdorferi species and to avoid the possible health dangers of the LYMErix vaccine.

Lyme disease is a notoriously contentious subject, dividing patient advocacy groups from many physicians. This is partially due to the fact that Lyme disease has no definitive, predictable course. Some infected persons show no symptoms; others show symptoms, are debilitated for a time, and are successfully treated; still others are left with permanent disabilities from the disease. Disagreements, often angry, persist on whether longterm Lyme infection exists, what its symptoms and proper treatment are (if any), and whether Lyme disease is diagnosed too much or too little. As Lyme disease is argued to be drastically under-reported—both Lyme disease patient groups and the CDC claim that the number of cases meeting CDC diagnostic criteria is about 10 times greater than the number actually counted in official figures—the total economic and personal impact of the disease is hard to estimate.

Finally, patient advocacy groups argue that Lyme disease research is greatly underfunded compared to that for other diseases such as West Nile virus, although there were eight times more reported Lyme disease cases than West Nile virus cases in 2005. This is with only the reported number, but since the CDC states that there may be 10 times more cases of Lyme disease each year that meet CDC diagnostic standards than are reported, the underfunding situation is much worse than it seems from official numbers. Advocates for greater attention to Lyme disease introduced Federal Lyme Bill HR 741, the Lyme & Tick-Borne Disease Prevention, Education & Research Act of 2007, which would allot $100 million over a five-year period for research, prevention, and other measures to combat Lyme disease. As of March, 2007, the House of Representatives had not voted on the bill.

PETS CAN CONTRACT LYME DISEASE, TOO

The tiny deer ticks that harbor Lyme disease bacteria can also transmit the disease to many pets, including dogs, horses, and occasionally, cats. Although a vaccine against Lyme exists for dogs, reducing the opportunity for ticks to bite an animal remains the front line of defense against Lyme disease in pets. Veterinarians recommend that pet owners:

• Walk dogs and ride horses on cleared trails.
• Use an approved anti-tick and flea product specific to dogs, cats, and horses.
• Groom horses daily, checking for ticks, especially near the head, throat area, belly, and under the tail.
• Remove brush and woodpiles from horse pastures.
• Mow lawns and pastures, keeping grass short.
• Examine dogs and cats regularly for ticks, especially pets that spend time both indoors and outdoors.
• Watch for symptoms of Lyme disease in pets, including fever, limping, loss of appetite, and fatigue in dogs and cats, and weight loss, swollen joints, muscle tenderness, and intermittent lameness in horses.

Primary Source Connection

Travel advisories are maintained by most developed countries in an effort to provide citizens with information about health and safety hazards while traveling abroad. In the United States, the Centers for Disease Control and Prevention (CDC) maintains a Traveler's Health website at <http://www.cdc.gov/travel/> that features vaccination recommendations and other health information for specific countries and destinations. In the newspaper article below, the author discusses recommendations, including Lyme disease prevention, made by foreign governments for its citizens traveling to the United States. It should be again noted that the LYMErix vaccine mentioned in the article is no longer available.

Travel Advisories: Wait 'Til You Hear What They Say about Us

You've checked the travel advisories, gotten a few vaccinations and stocked up on Imodium and antimalarials.

Now, you're off on that exotic vacation.

But what about travelers heading here, to the good old U.S.A.?

They get travel advisories, too. The advisories aim to keep U.S.-bound tourists, students and workers safe from our health hazards.

Most international health and travel organizations agree that travelers risk little in the United States by drinking the tap water or eating food bought from street vendors.

But they warn about West Nile encephalitis, an illness that is passed on to humans by infected mosquitoes, who in turn, are infected by birds. West Nile virus can cause flu-like symptoms and is especially worrisome for adults over 50, who are at a greater risk for developing serious complications.

“Use insect repellent accordingly” and “stay in during dusk and dawn hours,” Great Britain's travel Web site advises.

Visitors from Japan, where U.S. beef is banned, worry about bovine spongiform encephalopathy, better-known as “mad cow disease.” One Washington-state cow was found to have the brain-wasting disease in 2003.

“They are very afraid of mad cow disease in Japan,” said Chigusa Suzuki, a Japanese editor and translator living in New York City. “But once they get to the United States, the fear disappears and they go to a steakhouse. They want the American experience and that includes having a steak.”

Travelers to the United States also are warned about Lyme disease, which is passed on by ticks.

Many international travel Web sites recommend being watchful for tick bites or even considering a three-dose vaccine of LYMErix if tourists plan on spending a lot of time in U.S. forests.

The U.S. Centers for Disease Control, which advises U.S. travelers heading to foreign lands, reassures people coming here: “There are, of course, health risks, but in general, the precautions required are minimal,” its Web site says.

But often, health dangers that are of little concern to people actually living in the United States seem most pressing for visitors from afar. For instance, while you might not worry about contracting rabies, the illness can be spotted on nearly every international health advisory Web site.

The United Kingdom's Department of Health Web site warns travelers to the United States to be especially wary of rabies and to “avoid being bitten by any animal.”

That's good advice for any traveler, of course.

Maureen McKinney

MCKINNEY, MAUREEN. “TRAVEL ADVISORIES: WAIT 'TIL YOU HEAR WHAT THEY SAY ABOUT US.” DAILY HERALD (ARLINGTON HEIGHTS, IL) MARCH 21, 2005.

See AlsoArthropod-borne Disease; Climate Change and Infectious Disease; Emerging Infectious Diseases; Mosquito-borne Disease; Rocky Mountain Spotted Fever; Vector-borne Disease; Zoonoses.

BIBLIOGRAPHY

Books

Edlow, Jonathan A. Bull's Eye: Unraveling the Medical Mystery of Lyme Disease. New Haven, CT: Yale University Press, 2004.

Vanderhoof-Forschner, Karen. Everything You Need to Know About Lyme Disease and Other Tick-Borne Disorders. 2nd ed. New York: Wiley, 2003.

Periodicals

Donta, Sam. “Late and Chronic Lyme Disease: Symptom Overlap with Chronic Fatigue Syndrome and Fibromyalgia.” Medical Clinics of North America 86 (2002): 341–349.

Hayes, Edward B., and Joseph Piesman. “How Can We Prevent Lyme Disease?” New England Journal of Medicine 348 (2003): 2424–2429.

Ramamoorthi, Nandhini, et al. “The Lyme Disease Agent Exploits a Tick Protein to Infect the Mammalian Host.” Nature 436 (July 28, 2005): 573–577.

Steere, Allen C. “Lyme Disease.” New England Journal of Medicine 345 (2001): 115–123.

Wormser, Gary P. “Early Lyme Disease.” New England Journal of Medicine 354 (2006): 2794–2800.

Web Sites

American Lyme Disease Foundation. “Home Page.” September 22, 2006. <http://www.aldf.com/> (accessed February 7, 2007).

Lyme Disease

Definition

Lyme disease is an infection transmitted by the bite of ticks carrying the spiral-shaped bacterium Borrelia burgdorferi. The disease was named for Lyme, Connecticut, the town where it was first diagnosed in 1975 after a puzzling outbreak of arthritis. The organism was named for its discoverer, Willy Burgdorfer. The effects of this disease can be long-term and disabling unless it is recognized and treated properly with antibiotics.

Description

Lyme disease, which is also called Lyme borreliosis, is a vector-borne disease. This term means that it is delivered from one host to another. It is also classified as a zoonosis, which means that it is a disease of animals that can be transmitted to humans under natural conditions. In this case, a tick bearing the Borrelia burgdorferi organism literally inserts it into a host's bloodstream when it bites the host to feed on its blood. It is important to note that neither Borrelia burgdorferi nor Lyme disease can be transmitted directly from one person to another, or from pets to humans.

Controversy clouds the true incidence of Lyme disease because no test is definitively diagnostic for the disease, and many of its symptoms mimic those of so many other diseases. Cases of Lyme disease have been reported in 49 of the 50 states; however, 92% of the 17,730 cases reported to the Centers for Disease Control and Prevention (CDC) in 2000 were from only nine states (Connecticut, Rhode Island, New York, Pennsylvania, Delaware, New Jersey, Maryland, Massachusetts, and Wisconsin). The disease is also found in Scandinavia, continental Europe, the countries of the former Soviet Union, Japan, and China; in addition, it is possible that it has spread to Australia.

In the United States, Lyme disease accounts for more than 90% of all reported vector-borne illnesses. It is a significant public health problem and continues to be diagnosed in increasing numbers. The Centers for Disease Control and Prevention (CDC) attributes this increase to the growing size of the deer herd and the geographical spread of infected ticks rather than to improved diagnosis. In addition, some epidemiologists believe that the actual incidence of Lyme disease in the United States may be 5-10 times greater than that reported by the CDC. The reasons for this difference include the narrowness of the CDC's case definition as well as frequent misdiagnoses of the disease.

The risk for acquiring Lyme disease varies, depending on what stage in its life cycle a tick has reached. A tick passes through three stages of development—larva, nymph, and adult—each of which is dependent on a live host for food. In the United States, Borrelia burgdorferi is borne by ticks of several species in the genus Ixodes, which usually feed on the white-footed mouse and deer (and are often called deer ticks). In the summer, the larval ticks hatch from eggs laid in the ground and feed by attaching themselves to small animals and birds. At this stage they are not a problem for humans. It is the next stage—the nymph—that causes most cases of Lyme disease. Nymphs are very active from spring through early summer, at the height of outdoor activity for most people. Because they are still quite small (less than 2 mm), they are difficult to spot, giving them ample opportunity to transmit Borrelia burgdorferi while feeding. Although far more adult ticks than nymphs carry Borrelia burgdorferi, the adult ticks are much larger, more easily noticed, and more likely to be removed before the 24 hours or more of continuous feeding needed to transmit Borrelia burgdorferi.

Causes and symptoms

Lyme disease is caused by Borrelia burgdorferi. Once Borrelia burgdorferi gains entry to the body through a tick bite, it can move through the bloodstream quickly. Only 12 hours after entering the bloodstream, Borrelia burgdorferi can be found in cerebrospinal fluid (which means it can affect the nervous system). Treating Lyme disease early and thoroughly is important because Lyme disease can hide for long periods within the body in a clinically latent state. That ability explains why symptoms can recur in cycles and can flare up after months or years, even over decades. It is important to note, however, that not many people who are exposed to Borrelia burgdorferi develops the disease.

Lyme disease is usually described in terms of length of infection (time since the person was bitten by a tick infected with Lyme disease) and whether Borrelia burgdorferi is localized or disseminated (spread through the body by fluids and cells carrying Borrelia burgdorferi ). Furthermore, when and how symptoms of Lyme disease appear can vary widely from patient to patient. People who experience recurrent bouts of symptoms over time are said to have chronic Lyme disease.

Early localized Lyme disease

The most recognizable indicator of Lyme disease is a rash around the site of the tick bite. Often, the tick exposure has not been recognized. The eruption might be warm or itch. The rash—erythema migrans (EM)-generally develops within 3-30 days and usually begins as a round, red patch that expands outward. About 75% of patients with Lyme disease develop EM. Clearing may take place from the center out, leaving a bull's-eye effect; in some cases, the center gets redder instead of clearing. The rash may look like a bruise on people with dark skin. Of those who develop Lyme disease, about 50% notice flu-like symptoms, including fatigue, headache, chills and fever, muscle and joint pain, and lymph node swelling. However, a rash at the site can also be an allergic reaction to the tick saliva rather than an indicator of Lyme disease, particularly if the rash appears in less than three days and disappears only days later.

Late disseminated disease and chronic Lyme disease

Weeks, months, or even years after an untreated tick bite, symptoms can appear in several forms, including:

• Fatigue, forgetfulness, confusion, mood swings, irritability, numbness.
• Neurologic problems, such as pain (unexplained and not triggered by an injury), Bell's palsy (facial paralysis, usually one-sided but may be on both sides), and a mimicking of the inflammation of brain membranes known as meningitis; (fever, severe headache).
• Arthritis (short episodes of pain and swelling in joints) and other musculoskeletal complaints. Arthritis eventually develops in about 60% of patients with untreated Lyme disease.

Less common effects of Lyme disease are heart abnormalities (such as irregular rhythm or cardiac block) and eye abnormalities (such as swelling of the cornea, tissue, or eye muscles and nerves).

Diagnosis

A clear diagnosis of Lyme disease can be difficult, and relies on information the patient provides and the doctor's clinical judgment, particularly through elimination of other possible causes of the symptoms. Lyme disease may mimic other conditions, including chronic fatigue syndrome (CFS), multiple sclerosis (MS), and other diseases with many symptoms involving multiple body systems. Differential diagnosis (distinguishing kyme disease from other diseases) is based on clinical evaluation with laboratory tests used for clarification when necessary. A two-test approach is common to confirm the results. Because of the potential for misleading results (false-positive and false-negative), laboratory tests alone cannot establish the diagnosis.

In February 1999 the Food and Drug Administration (FDA) approved a new blood test for Lyme disease called PreVue. The test, which searches for antigens (substances that stimulate the production of antibodies) produced by Borrelia burgdorferi, gives results within one hour in the doctor's office. A positive result from the PreVue test is confirmed by a second blood test known as the Western blot, which must be done in a laboratory.

Doctors generally know which disease-causing organisms are common in their geographic area. The most helpful piece of information is whether a tick bite or rash was noticed and whether it happened locally or while traveling. Doctors may not consider Lyme disease if it is rare locally, but will take it into account if a patient mentions vacationing in an area where the disease is commonly found.

Treatment

The treatment for Lyme disease is antibiotic therapy; however, overprescribing of antibiotics can lead to serious problems, so the decision to treat must be made with care. Disease organisms can develop resistance to families of medications over time, rendering the drugs useless. Furthermore, testing and treatments can be expensive. If a patient has strong indications of Lyme disease (symptoms and medical history), the doctor will probably begin treatment on the presumption of this disease. The American College of Physicians recommends treatment for a patient with a rash resembling EM or who has arthritis, a history of an EM-type rash, and a previous tick bite.

The benefits of treating early must be weighed against the risks of over treatment. The longer a patient is ill with Lyme disease before treatment, the longer the course of therapy must be, and the more aggressive the treatment. The development of opportunistic organisms may produce other symptoms. For example, after long-term antibiotic therapy, patients can become more susceptible to yeast infections. Treatment may also be associated with adverse drug reactions.

For most patients, oral antibiotics (doxycycline or amoxicillin) are prescribed for 21 days. When symptoms indicate nervous system involvement or a severe episode of Lyme disease, intravenous antibiotic (ceftriaxone) may be given for 14-30 days. Some physicians consider intravenous ceftriaxone the best therapy for any late manifestation of disease, but treatments for late Lyme disease are still controversial as of 2003. Corticosteroids (oral) may be prescribed if eye abnormalities occur, but they should not be used without first consulting an eye doctor.

The doctor may have to adjust the treatment regimen or change medications based on the patient's response. Treatment can be difficult because Borrelia burgdorferi comes in several strains (some may react to different antibiotics than others) and may even have the ability to switch forms during the course of infection. Also, Borrelia burgdorferi can shut itself up in cell niches, allowing it to hide from antibiotics. Finally, antibiotics can kill Borrelia burgdorferi only while it is active rather than dormant.

Alternative treatment

Supportive therapies may minimize symptoms of LD or improve the immune response. These include vitamin and nutritional supplements, mostly for chronic fatigue and increased susceptibility to infection. For example, yogurt and Lactobacillus acidophilus preparations help fight yeast infections, which are common in people on long-term antibiotic therapy. In addition, botanical medicine and homeopathy can be considered to help bring the body's systems back to a state of health and well being. A Western herb, spilanthes (Spilanthes spp.), may be effective in treating diseases like LD that are caused by spirochetes (spiral-shaped bacteria).

Prognosis

If aggressive antibiotic therapy is given early, and the patient cooperates fully and sticks to the medication schedule, recovery should be complete. Only a small percentage of Lyme disease patients fail to respond or relapse (have recurring episodes). Most long-term effects of the disease result when diagnosis and treatment is delayed or missed. Co-infection with other infectious organisms spread by ticks in the same areas as Borrelia burgdorferi (babesiosis and ehrlichiosis, for instance) may be responsible for treatment failures or more severe symptoms. Most fatalities reported with Lyme disease involved patients coinfected with babesiosis.

Prevention

Update on vaccination

A vaccine for Lyme disease known as LYMErix was available from 1998 to 2002, when it was removed from the United States market. The decision was influenced by reports that LYMErix may be responsible for neurologic complications in vaccinated patients. Researchers from Cornell-New York Hospital presented a paper at the annual meeting of the American Neurological Association in October 2002 that identified nine patients with neuropathies linked to vaccination with LYMErix. In April 2003, the National Institute of Allergy and Infectious Diseases (NIAID) awarded a federal grant to researchers at Yale University School of Medicine to develop a new vaccine against Lyme disease. As of late 2003, the best prevention strategy is through minimizing risk of exposure to ticks and using personal protection precautions.

Minimizing risk of exposure

Precautions to avoid contact with ticks include moving leaves and brush away from living quarters. Most important are personal protection techniques when outdoors, such as:

• Spraying tick repellent on clothing and exposed skin.
• Wearing light-colored clothing to maximize ability to see ticks.
• Tucking pant legs into socks or boot top.
• Checking children and pets frequently for ticks.

In highly tick-populated areas, each individual should be inspected at the end of the day to look for ticks.

Minimizing risk of disease

The two most important factors are removing the tick quickly and carefully, and seeking a doctor's evaluation at the first sign of symptoms of Lyme disease. When in an area that may be tick-populated:

• Check for ticks, particularly in the area of the groin, underarm, behind ears, and on the scalp.
• Stay calm and grasp the tick as near to the skin as possible, using a tweezer.
• To minimize the risk of squeezing more bacteria into the bite, pull straight back steadily and slowly.
• Do not try to remove the tick by using petroleum jelly, alcohol, or a lit match.
• Place the tick in a closed container (for species identification later, should symptoms develop) or dispose of it by flushing.
• See a physician for any sort of rash or patchy discoloration that appears three to 30 days after a tick bite.

KEY TERMS

Babesiosis— A disease caused by protozoa of the genus Babesia characterized by a malaria-like fever, anemia, vomiting, muscle pain, and enlargement of the spleen. Babesiosis, like Lyme disease, is carried by a tick.

Bell's palsy— Facial paralysis or weakness with a sudden onset, caused by swelling or inflammation of the seventh cranial nerve, which controls the facial muscles. Disseminated Lyme disease sometimes causes Bell's palsy.

Blood-brain barrier— A blockade of cells separating the circulating blood from elements of the central nervous system (CNS); it acts as a filter, preventing many substances from entering the central nervous system.

Cerebrospinal fluid— Clear fluid found around the brain and spinal cord and in the ventricles of the brain.

Disseminated— Scattered or distributed throughout the body. Lyme disease that has progressed beyond the stage of localized EM is said to be disseminated.

Erythema migrans (EM)— A red skin rash that is one of the first signs of Lyme disease in about 75% of patients.

Lyme borreliosis— Another name for Lyme disease.

Spirochete— A spiral-shaped bacterium. The bacteria that cause Lyme disease and syphilis, for example, are spirochetes.

Vector— An animal carrier that transfers an infectious organism from one host to another. The vector that transmits Lyme disease from wildlife to humans is the deer tick or black-legged tick.

Zoonosis (plural, zoonoses)— Any disease of animals that can be transmitted to humans under natural conditions. Lyme disease and babesiosis are examples of zoonoses.

Resources

BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors. "Bacterial Diseases Caused by Spirochetes: Lyme Disease (Lyme Borreliosis)." In The Merck Manual of Diagnosis and Therapy. Whitehouse Station, NJ: Merck Research Laboratories, 2004.

PERIODICALS

Edlow, Jonathan A., MD. "Tick-Borne Diseases, Lyme." eMedicine December 13, 2002. 〈http://www.emedicine.com/emerg/topic588.htm〉.

Krupp, L. B., L. G. Hyman, R. Grimson, et al. "Study and Treatment of Post Lyme Disease (STOP-LD): A Randomized Double Masked Clinical Trial." Neurology 60 (June 24, 2003): 1923-1930.

Nachman, S. A., and L. Pontrelli. "Central Nervous System Lyme Disease." Seminars in Pediatric Infectious Diseases 14 (April 2003): 123-130.

Pavia, C. S. "Current and Novel Therapies for Lyme Disease." Expert Opinion on Investigational Drugs 12 (June 2003): 1003-1016.

Susman, Ed. "ANA: Neurological Impairment Seen in Patients Given LYMErix Lyme Disease Vaccine." Doctor's Guide October 16, 2002. 〈http://www.plsgroup.com/dg/220652.htm〉.

Wormser, G. P., R. Ramanathan, J. Nowakowski, et al. "Duration of Antibiotic Therapy for Early Lyme Disease. A Randomized, Double-Blind, Placebo-Controlled Trial." Annals of Internal Medicine 138 (May 6, 2003): 697-704.

ORGANIZATIONS

Centers for Disease Control and Prevention. 1600 Clifton Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404) 639-3311. 〈http://www.cdc.gov〉.

Lyme Disease Foundation. One Financial Plaza, Hartford, CT, 06103. (800) 886-LYME. 〈http://www.lyme.org〉.

Lyme Disease Network of NJ, Inc. 43 Winton Road, East Brunswick, NJ 08816. 〈http://www.lymenet.org〉.

National Institute of Allergy and Infectious Diseases (NIAID). 31 Center Drive, Room 7A50 MSC 2520, Bethesda, MD, 20892. (301) 496-5717. 〈http://www.niaid.nih.gov〉.

OTHER

Centers for Disease Control and Prevention, Division of Vector-Borne Infectious Diseases. CDC Lyme Disease Home Page. 〈http://www.cdc.gov/ncidod/dvbid/lyme/〉.

National Institute of Neurological Disorders and Stroke (NINDS) Fact Sheet. Bell's Palsy. Bethesda, MD: NINDS, 2003.

NINDS Information Page. Neurological Complications of Lyme Disease. Bethesda, MD: NINDS, 2003.

Lyme disease

Definition

Lyme disease, which is also known as Lyme borreliosis, is an infection transmitted by the bite of ticks carrying the spiral-shaped bacterium (spirochete) Borrelia burgdorferi (Bb). The disease was named for Old Lyme, Connecticut, the town where it was first diagnosed in 1975, after a puzzling outbreak of arthritis. The spiral-shaped bacterium was named for its discoverer, Willy Burgdorfer. The effects of this disease can be long-term and disabling, unless it is recognized and treated properly with antibiotics.

Description

Lyme disease is a vector-borne disease, which means it is delivered from one host to another. It is also classified as a zoonosis, which means that it is a disease of animals that can be transmitted to humans under natural conditions. In this case, a tick bearing the Bb organism literally inserts it into a host's bloodstream when it bites the host to feed on its blood. It is important, however, to note that neither Bb nor Lyme disease can be transmitted directly from one person to another.

In the United States, Lyme disease accounts for more than 90% of all reported vector-borne illnesses. It is a significant public health problem and continues to be diagnosed in increasing numbers. The Centers for Disease Control and Prevention (CDC) attributes this increase to the growing size of the deer herd and the geographical spread of infected ticks rather than to improved diagnosis. In addition, some epidemiologists believe that the actual incidence of Lyme disease in the United States may be 5–10 times greater than that reported by the CDC. The reasons for this difference include the narrowness of the CDC's case definition as well as frequent misdiagnoses of the disease.

Controversy clouds the true incidence of Lyme disease because no test is definitively diagnostic for the disease, and many of its symptoms mimic those of so many other diseases. Cases of Lyme disease have been reported in 49 of the 50 states; however, 92% of the 17,730 cases reported to the CDC in 2000 were from only nine states (Connecticut, Rhode Island, New York, Pennsylvania,

Delaware, New Jersey, Maryland, Massachusetts, and Wisconsin). The disease is also found in Scandinavia, continental Europe, the countries of the former Soviet Union, Japan, and China; in addition, it is possible that it has spread to Australia.

The risk for acquiring Lyme disease varies, depending on what stage in its life cycle a tick has reached. A tick passes through three stages of development—larva, nymph, and adult—each of which is dependent on a live host for food. In the United States, Bb is borne by ticks of several species in the genus Ixodes, which usually feed on the white-footed mouse and deer (and are often called deer ticks). In the summer, the larval ticks hatch from eggs laid in the ground and feed by attaching themselves to small animals and birds. At this stage they are not a problem for humans. It is the next stage—the nymph—that causes most cases of Lyme disease. Nymphs are very active from spring through early summer, at the height of outdoor activity for most people. Because they are still quite small (less than 2 mm in length), they are difficult to spot, giving them ample opportunity to transmit Bb while feeding. Although far more adult ticks than nymphs carry Bb, the adult ticks are much larger, more easily noticed, and more likely to be removed before the 24 hours or more of continuous feeding needed to transmit Bb.

Causes & symptoms

Lyme disease is a collection of effects caused by Bb. Once Bb gains entry to the body through a tick bite, it can move through the bloodstream quickly. Only 12 hours after entering the bloodstream, Bb can be found in cerebrospinal fluid (which means it can affect the nervous system). Treating Lyme disease early and thoroughly is important because Bb can hide for long periods within the body in a clinically latent state. That ability explains why symptoms can recur in cycles and can flare up after months or years, even over decades. It is important to note, however, that not everyone exposed to Bb develops the disease.

Lyme disease is usually described in terms of length of infection (time since the person was bitten by a tick infected with Bb) and whether Bb is localized or disseminated (spread through the body by fluids and cells carrying Bb). Furthermore, when and how symptoms of Lyme

disease appear can vary widely from patient to patient. People who experience recurrent bouts of symptoms over time are said to have chronic Lyme disease.

Early localized Lyme disease

The most recognizable indicator of Lyme disease is a rash around the site of the tick bite. Often, the tick exposure has not been recognized. The area of rash eruption might be warm or itch. The rash—erythema migrans (EM)—generally develops within 3–30 days and usually begins as a round, red patch that expands. Clearing may take place from the center out, leaving a bull's-eye effect; in some cases, the center gets redder instead of clearing. The rash may look like a bruise on individuals with dark skin. Of those who develop Lyme disease, about 50% notice the rash; about 50% notice flu-like symptoms, including fatigue, headache, chills and fever , muscle and joint pain, and lymph node swelling. However, a rash at the site can also be an allergic reaction to the tick saliva rather than an indicator of Lyme disease, particularly if the rash appears in less than 3 days and disappears only days later.

Late disseminated disease and chronic Lyme disease

Weeks, months, or even years after an untreated tick bite, symptoms can appear in several forms, including:

• fatigue, forgetfulness, confusion, mood swings, irritability, numbness
• neurologic problems, such as pain (unexplained and not triggered by an injury), Bell's palsy (facial paralysis, usually one-sided but may be on both sides), and a mimicking of the inflammation of brain membranes known as meningitis ; (fever, severe headache, stiff neck)
• arthritis (short episodes of pain and swelling in joints) and other musculoskeletal complaints
• Less common effects of Lyme disease are heart abnormalities (such as irregular rhythm or cardiac block) and eye abnormalities (such as swelling of the cornea, tissue, or eye muscles and nerves).

Diagnosis

A clear diagnosis of Lyme disease can be difficult, and relies on information the patient provides and the doctor's clinical judgment, particularly through elimination of other possible causes of the symptoms. Lyme disease may mimic other conditions, including chronic fatigue syndrome (CFS), multiple sclerosis (MS), and other diseases with many symptoms involving multiple body systems. Differential diagnosis (distinguishing Lyme disease from other diseases) is based on clinical evaluation with laboratory tests used for clarification, when necessary. A two-test approach is common to confirm the results. Because of the potential for misleading results (false-positive and false-negative), laboratory tests alone cannot establish the diagnosis.

Doctors generally know which disease-causing organisms are common in their geographic area. The most helpful piece of information is whether a tick bite or rash was noticed and whether it happened locally or while traveling. Doctors may not consider Lyme disease if it is rare locally, but will take it into account if a patient mentions vacationing in an area where the disease is commonly found.

Treatment

While antibiotics are essential in treating Lyme disease, many alternative therapies may minimize symptoms, improve the immune response, and help treat late disseminated or chronic disease. General nutritional guidelines include drinking plenty of fluids and eating cooked whole grains and fresh vegetables. The intake of sugar, fat, refined carbohydrates, and dairy products should be reduced. Alternative therapies used in treating Lyme disease include:

• Chinese medicine. Formulae used to treat systemic bacterial infections include Wu Wei Xiao Du Yin (Five-Ingredient Decoction to Eliminate Toxin), Yin Hua Jie Du Tang (Honeysuckle Decoction to Relieve Toxicity), and Huang Lian Jie Du Tang (Coptis Decoction to Relieve Toxicity). Inflammation at the site of infection may be treated externally with Yu Lu San (Jade Dew Extract) or Jin Huang San (Golden Yellow Powder). Specific Chinese herbs and treatments can be used for specific symptoms. For examples, for systemic bacterial infection, one may use honeysuckle flower, forsythia, isatidis, scutellaria, and phellodendron. Acupuncture and ear acupuncture treatments are also utilized.
• Herbals. Botanical remedies include echinacea (Echinacea species) to clear infection and boost the immune system, goldenseal (Hydrastis canadensis ) to clear infection and boost the immune system, garlic to clear bacterial infection, and spilanthes (Spilanthes species) for spirochete infections.
• Hydrotherapy . The joint pain associated with Lyme disease can be treated with hydrotherapy. Dull, penetrating pain may be relieved by applying a warm compress to the affected area. Sharp, intense pain may be relieved by applying an ice pack to the affected area.
• Imagery. The patient may treat Lyme disease by visualizing Bb as looking like ticks swimming in the bloodstream being killed by the flame of a candle.
• Probiotics . Probiotics refers to treatment with beneficial microbes either by ingestion or through a suppository. Probiotics can restore a healthy balance of bacteria to the body in cases where long-term antibiotic use has caused diarrhea or yeast infection. Yogurt or Lactobacillus acidophilus preparations may be ingested.
• Supplements. Use calcium and magnesium for aches, chlorophyll to aide healing, vitamin C for bacterial infection and inflammation, bioflavonoids for joint inflammation and to boost the immune system, digestive enzyme for digestive problems, vitamin B complex to boost overall health, bromelain for inflammation, and zinc to boost the immune system and promote healing.

Allopathic treatment

For most patients, oral antibiotics (doxycycline or amoxicillin) are prescribed for 21 days. The doctor may have to adjust the treatment regimen or change medications based on the patient's response. Antibiotics can kill Bb only while it is active, rather than while it is dormant. When symptoms indicate nervous system involvement or a severe episode of Lyme disease, intravenous antibiotic (ceftriaxone) may be given for 14–30 days. Some physicians consider intravenous ceftriaxone the best therapy for any late manifestation of disease, but treatments for late Lyme disease are still controversial as of 2003.

Expected results

If aggressive antibiotic therapy is given early, and the patient cooperates fully and sticks to the medication schedule, recovery should be complete. Only a small percentage of Lyme disease patients fail to respond or relapse (have recurring episodes). Most long-term effects of the disease result when diagnosis and treatment is delayed or missed. Co-infection with other infectious organisms spread by ticks in the same areas as Bb (babesiosis and ehrlichiosis, for instance) may be responsible for treatment failures or more severe symptoms. In certain cases, Lyme disease has been responsible for deaths, but that is rare. Most fatalities reported with Lyme disease involved patients coinfected with babesiosis.

Prevention

Update on vaccination

A vaccine for Lyme disease known as LYMErix was available from 1998 to 2002, when it was removed from the United States market. The decision was influenced by reports that LYMErix may be responsible for neurologic complications in vaccinated patients. Researchers from Cornell-New York Hospital presented a paper at the annual meeting of the American Neurological Association in October 2002 that identified nine patients with neuropathies linked to vaccination with LYMErix. In April 2003, the National Institute of Allergy and Infectious Diseases (NIAID) awarded a federal grant to researchers at Yale University School of Medicine to develop a new vaccine against Lyme disease. As of late 2003, the best prevention strategy is through minimizing risk of exposure to ticks and using personal protection precautions.

Minimizing risk of exposure

Precautions to avoid contact with ticks include moving leaves and brush away from living quarters. In highly tick-populated areas, each individual should be inspected at the end of the day to look for ticks. Most important are personal protection techniques when outdoors, such as:

• Avoid walking through woods, shrubbery, or tall grasses.
• Use repellents containing DEET.
• Wear light-colored clothing to maximize ability to see ticks.
• Tuck pant legs into socks or boot top.
• Check children and pets frequently for ticks.

Minimizing risk of disease transmission

The two most important factors are removing the tick quickly and carefully, and seeking a doctor's evaluation at the first sign of Lyme disease. When in an area that may be tick-populated:

• Although ticks are quite small, check for them, particularly in the area of the groin, underarm, behind ears, and on the scalp.
• Stay calm and grasp the tick as near to the skin as possible, using tweezers.
• To minimize the risk of squeezing more bacteria into the site of the bite, pull straight back steadily and slowly.
• Do not use petroleum jelly, alcohol, or a lit match to remove the tick.
• Place the tick in a closed container (for species identification later, should symptoms develop) or dispose of it by flushing it in a toilet.
• See a physician for any sort of rash or patchy discoloration that appears 3–30 days after a tick bite.

Resources

BOOKS

"Bacterial Diseases Caused by Spirochetes: Lyme Disease (Lyme Borreliosis)." Section 13, Chapter 157 in The Merck Manual of Diagnosis and Therapy, edited by Mark H. Beers, MD, and Robert Berkow, MD. Whitehouse Station, NJ: Merck Research Laboratories, 2002.

Jerigan, David A. Surviving Lyme Disease Using Alternative Medicine. Somerleyton Press, 1999.

Territo, J., and D.V. Lang. Coping With Lyme Disease: A Practical Guide to Dealing With Diagnosis and Treatment. New York: Henry Holt, 1997.

Ying, Zhou Zhong and Jin Hui De. "Acute Infection." In Clinical Manual of Chinese Herbal Medicine and Acupuncture. New York: Churchill Livingston, 1997.

PERIODICALS

Edlow, Jonathan A., MD. "Tick-Borne Diseases, Lyme." eMedicine, 13 December 2002. <http://www.emedicine.com/emerg/topic588.htm>.

Krupp, L. B., L. G. Hyman, R. Grimson, et al. "Study and Treatment of Post Lyme Disease (STOP-LD): A Randomized Double Masked Clinical Trial." Neurology 60 (June 24, 2003): 1923–1930.

Nachman, S. A., and L. Pontrelli. "Central Nervous System Lyme Disease." Seminars in Pediatric Infectious Diseases 14 (April 2003): 123–130.

Pavia, C. S. "Current and Novel Therapies for Lyme Disease." Expert Opinion on Investigational Drugs 12 (June 2003): 1003–1016.

Susman, Ed. "ANA: Neurological Impairment Seen in Patients Given LYMErix Lyme Disease Vaccine." Doctor's Guide, October 16, 2002. <http://www.plsgroup.com/dg/220652.htm>.

Wormser, G. P., R. Ramanathan, J. Nowakowski, et al. "Duration of Antibiotic Therapy for Early Lyme Disease. A Randomized, Double-Blind, Placebo-Controlled Trial." Annals of Internal Medicine 138 (May 6, 2003): 697–704.

ORGANIZATIONS

Centers for Disease Control and Prevention. 1600 Clifton Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404) 639-3311. <http://www.cdc.gov>.

Lyme Disease Foundation. One Financial Plaza, Hartford, CT, 06103. (800) 886-LYME. <http://www.lyme.org>.

Lyme Disease Network of NJ, Inc. 43 Winton Road, East Brunswick, NJ 08816. http://www.lymenet.org.

National Institute of Allergy and Infectious Diseases (NIAID). 31 Center Drive, Room 7A50 MSC 2520, Bethesda, MD, 20892. (301) 496-5717. <http://www.niaid.nih.gov>.

OTHER

Centers for Disease Control and Prevention, Division of Vector-Borne Infectious Diseases. CDC Lyme Disease Home Page. <http://www.cdc.gov/ncidod/dvbid/lyme/>.

National Institute of Neurological Disorders and Stroke (NINDS) Fact Sheet. Bell's Palsy. Bethesda, MD: NINDS, 2003.

NINDS Information Page. Neurological Complications of Lyme Disease. Bethesda, MD: NINDS, 2003.

Belinda Rowland

Rebecca J. Frey, PhD

Lyme disease

Definition

Lyme disease is an inflammatory disease transmitted through the bite of a deer tick carrying the spiral-shaped bacterium Borrelia burgdorferi. Symptoms can include skin rash, joint inflammation, fever , headache , fatigue, and muscle pain . Lyme disease is also called Lyme borreliosis.

Description

Lyme disease is an inflammatory, systemic disease, meaning that it affects multiple body systems. Although clinical signs of Lyme disease have been reported for more than 100 years, the disease was not recognized as a distinct illness until 1975, when a cluster of unusual arthritis cases in Lyme, Connecticut, led physicians to discover that town residents living near heavily wooded areas were most affected by arthritis and other symptoms. Tick bites were then linked to the cause of the arthritis cases. Borrelia burgdorferi, the spiral-shaped bacterium called a spirochete, that causes Lyme disease, was not discovered until 1981 by Willy Burgdorfer.

Although Lyme disease is easily treated, it is not easily diagnosed, since symptoms are often attributed to other conditions. If not treated early and properly with antibiotics , Lyme disease can have long-term and disabling effects. In its early stages, Lyme disease affects the skin and produces flu-like symptoms; the disease spreads to the joints and nervous system in its later stages.

Transmission

Lyme disease is a vector-borne disease, meaning that it is transmitted from one host to another by a carrier—called a vector—that transmits but does not become infected with the disease. In the United States, the deer tick in the genus Ixodes is the vector for Borrelia burgdorferi and Lyme disease transmission. Lyme disease is transmitted when a tick carrying the Borrelia burgdorferi bacterium bites a human to feed on blood. The bacterium is transferred from the intestines of the tick through the mouthparts and into the bloodstream while the tick is feeding. Ticks are most likely to transmit Borrelia burgdorferi after remaining attached and feeding for two or more days. In most areas, ticks are most active from April to October, but in milder climates, ticks may bite year-round.

During their two-year life cycle and three life stages (larva, nymph, and adult), deer ticks feed on a number of mammals that may carry the Borrelia burgdorferi bacterium in their blood, but the white-footed mouse is the most common source of infection. In the summer, the larval ticks hatch from eggs laid in the ground and feed by attaching themselves to small animals and birds. At this stage, they are not a problem for humans. It is the next stage—the nymph—that causes most cases of Lyme disease. Nymphs are very active from spring through early summer, at the height of outdoor activity for most people. Because they are still quite small (less than 2 mm), they are difficult to spot, giving them ample opportunity to transmit Borrelia burgdorferi while feeding. Although far more adult ticks than nymphs carry Borrelia burgdorferi, the adult ticks are much larger, more easily noticed, and more likely to be removed before they have fed long enough to transmit Borrelia burgdorferi. Neither Borrelia burgdorferi nor Lyme disease can be transmitted directly from one person to another or from pets to humans.

Demographics

Lyme disease is the most common vector-borne disease in the United States. In 2002 alone, 23,763 cases were reported to the Centers for Disease Control and Prevention (CDC), a 40-percent increase over the number reported in 2001. According to the CDC, the actual number of Lyme cases may exceed 200,000 due to underreporting and limitations in disease surveillance methods. CDC statistics indicate that the largest proportion of Lyme disease cases occurs in children aged five to 14 years, and more than 50 percent of Lyme disease cases involve children under age 12. Although cases of Lyme disease have been reported in 49 of the 50 states, more than 95 percent of reported cases occur in just twelve states: Connecticut, Rhode Island, New York, Pennsylvania, Delaware, New Jersey, Maryland, Maine, New Hampshire, Minnesota, Massachusetts, and Wisconsin. In the United States, the Great Lakes region and the Pacific Northwest also have a higher incidence of Lyme disease. The disease is also found in Scandinavia, continental Europe, the countries of the former Soviet Union, Japan, China, and Australia.

Causes and symptoms

Lyme disease is caused by the Borrelia burgdorferi bacterium. Once Borrelia burgdorferi gains entry to the body through a tick bite, it can move through the bloodstream quickly. Only 12 hours after entering the bloodstream, Borrelia burgdorferi can be found in cerebrospinal fluid (which means it can affect the nervous system). Treating Lyme disease early and thoroughly is important because Lyme disease can hide for long periods within the body in a clinically latent state. That ability explains why symptoms can recur in cycles and can flare up after months, years, or decades.

Lyme disease is usually described in terms of length of infection (time since the person was bitten by a tick infected with Lyme disease) and whether Borrelia burgdorferi is localized or disseminated (spread through the body by fluids and cells carrying Borrelia burgdorferi ). Furthermore, when and how symptoms of Lyme disease appear can vary widely from patient to patient. People who experience recurrent bouts of symptoms over time are said to have chronic Lyme disease.

Early localized Lyme disease

The most recognizable indicator of Lyme disease is a rash around the site of the tick bite. Often, the tick exposure has not been recognized. The eruption might be warm or itch. The rash—erythema migrans (EM)—generally develops within three to 30 days and usually begins as a round, red patch that expands outward from the tick bite. About 80 percent of patients with Lyme disease develop EM. Clearing may take place from the center out, leaving a bull's-eye effect; in some cases, the center gets redder instead of clearing. On children with dark skin, the rash may look like a bruise. Of those who develop Lyme disease, about 50 percent notice flu-like symptoms, including fatigue, headache, chills and fever, muscle and joint pain, and lymph node swelling. Many children with Lyme disease can develop neurologic symptoms within a few weeks following a tick bite. Neurologic symptoms in children with early Lyme disease include dizziness , stiff neck, unilateral or bilateral facial palsy, inflammation of brain membranes (a form of meningitis ), knee and/or wrist arthralgia, tingling/numbness, sleep disturbance, and difficulties with memory, concentration, and learning.

Late disseminated disease and chronic Lyme disease

Weeks, months, or even years after an untreated tick bite, symptoms can appear in several forms, including the following:

• fatigue, forgetfulness, confusion, mood swings, irritability, numbness
• neurologic problems, such as pain (unexplained and not triggered by an injury), Bell's palsy (facial paralysis, usually one-sided but possibly on both sides), a mimicking of the inflammation of brain membranes known as meningitis fever, and severe headache
• arthritis (short episodes of pain and swelling in joints) and other musculoskeletal complaints (Arthritis eventually develops in about 60 percent of patients with untreated Lyme disease.)

In adults, less common effects of Lyme disease are heart abnormalities (such as irregular rhythm or cardiac block) and eye abnormalities (such as swelling of the cornea, tissue, or eye muscles and nerves). However, children with Lyme disease frequently complain of chest pain and have papilledema (swelling of the optic nerve). In addition, children with late-stage Lyme disease are more likely than adults to have fever and joint swelling and pain.

When to call the doctor

A child should see a doctor if an attached tick is found that is engorged with blood (usually indicating attachment for more than six hours). Parents should remove the tick gently with tweezers. Medical laboratories can test the tick for Borrelia burgdorferi if the tick is alive; parents should place the tick in a tightly sealed plastic bag or small bottle with a moistened cotton ball and take it to the doctor. Most doctors will not prescribe antibiotics immediately following a tick bite but will ask parents to monitor their child for symptoms of early Lyme disease.

Less than 50 percent of children realize that they have been bitten by a tick. And, according to pediatricians specializing in Lyme disease, many children already have chronic Lyme disease when they are first diagnosed because children have difficulties effectively verbalizing their symptoms and their symptoms may be misdiagnosed. Any child that develops a round, bull'seye skin rash, joint pain, flu-like symptoms, and/or neurologic symptoms as described above should see a doctor. Because many children do not develop a rash or the rash may not be readily visible (e.g., on the scalp under hair), children living in or visiting areas with a high incidence of Lyme disease and those participating in frequent outdoor activities during active tick months who develop joint pain and neurologic symptoms should see a doctor.

Diagnosis

In children, symptoms of Lyme disease can mimic those of other common childhood conditions, and children may not realize they have been bitten by a tick; therefore, diagnosis of Lyme disease in children can be difficult. Therefore, diagnosis of Lyme disease relies on information the patient and parents provide and the doctor's clinical judgment, particularly through elimination of other possible causes of the symptoms. Differential diagnosis (distinguishing Lyme disease from other diseases) is based on clinical evaluation with laboratory tests used for clarification when necessary. A two-test approach is common to confirm the results. Because of the potential for misleading results (false-positive and false-negative), laboratory tests alone cannot establish the diagnosis.

In February 1999 the Food and Drug Administration (FDA) approved a new blood test for Lyme disease called PreVue. The test, which searches for antigens (substances that stimulate the production of antibodies) produced by Borrelia burgdorferi, gives results within one hour in the doctor's office. A positive result from the PreVue test is confirmed by a second blood test known as the Western blot, which must be done in a laboratory.

Doctors generally know which disease-causing organisms are common in their geographic area. The most helpful piece of information is whether a tick bite or rash was noticed and whether it happened locally or while traveling. Doctors may not consider Lyme disease if it is rare locally but will take it into account if a patient mentions vacationing in an area where the disease is commonly found.

Treatment

The treatment for Lyme disease is antibiotic therapy. If a child has strong indications of Lyme disease (symptoms and medical history), the doctor will probably begin treatment on the presumption of this disease. The American College of Physicians recommends treatment for a patient with a rash resembling EM or who has arthritis, a history of an EM-type rash, and a previous tick bite.

The benefits of early treatment must be weighed against the risks of overtreatment. The longer a patient is ill with Lyme disease before treatment, the longer the course of therapy must be, and the more aggressive the treatment. The development of opportunistic organisms may produce other symptoms. For example, after long-term antibiotic therapy, patients can become more susceptible to yeast infections. Treatment may also be associated with adverse drug reactions.

For most children, oral antibiotics (amoxicillin) are prescribed for 21 days. When symptoms indicate nervous system involvement or a severe episode of Lyme disease, an intravenous antibiotic (ceftriaxone, cefotaxime, ampicillin) may be given for four to six weeks or longer. Some physicians consider intravenous ceftriaxone the best therapy for any late manifestation of disease, but treatments for late Lyme disease are still controversial as of 2004. Corticosteroids (oral) may be prescribed if eye abnormalities occur, but they should not be used without first consulting an eye doctor. Nonsteroidal anti-inflammatory medications (ibuprofen) may be prescribed for joint pain and inflammation.

The doctor may have to adjust the treatment regimen or change medications based on the patient's response. Treatment can be difficult because Borrelia burgdorferi comes in several strains (some may react to different antibiotics than others) and may even have the ability to switch forms during the course of infection. Also, Borrelia burgdorferi can shut itself up in cell niches, allowing it to hide from antibiotics. Finally, antibiotics can kill Borrelia burgdorferi only while it is active rather than dormant.

Alternative treatment

Supportive therapies may minimize symptoms of Lyme disease or improve the immune response. These include vitamin and nutritional supplements, mostly for chronic fatigue and increased susceptibility to infection. For example, yogurt and Lactobacillus acidophilus preparations help fight yeast infections, which are common in patients on long-term antibiotic therapy. In addition, botanical medicine and homeopathy can be considered to help bring the body's systems back to a state of health and well-being. A Western herb, spilanthes (Spilanthes spp.), may be effective in treating diseases such as Lyme disease that are caused by spirochetes (spiral-shaped bacteria). Therapy using a low-current electrical field or magnetic pulses is also as of 2004 under research to treat bacterial infections. It is important to note that no alternative treatments have been proven to cure Lyme disease.

Prognosis

If aggressive antibiotic therapy is given early and the patient cooperates fully and sticks to the medication schedule, recovery should be complete. Only a small percentage of Lyme disease patients fail to respond or relapse (have recurring episodes). Most long-term effects of the disease result when diagnosis and treatment is delayed or missed. Co-infection with other infectious organisms spread by ticks in the same areas as Borrelia burgdorferi (babesiosis and ehrlichiosis, for instance) may be responsible for treatment failures or more severe symptoms. Most fatalities reported with Lyme disease involved patients coinfected with babesiosis.

Prevention

Lyme disease can be prevented by taking the following measures to reduce exposure to tick bites:

• Avoid areas likely to be infested with ticks, especially during spring and summer, when tick nymphs are most likely to feed. Areas most likely to be infested with ticks include moist and shady areas, wooded and brushy areas, overgrown grassy areas, and areas with a high rodent and deer population.
• When outdoors, wear light-colored clothing, long-sleeved shirts, and long pants tucked into socks or boots.
• Use insect repellents according to safety guidelines for children.
• Perform a full-body "tick check" after outdoor activities and use tweezers to gently remove and dispose of ticks.
• Do not try to remove the tick by using petroleum jelly, alcohol, or a lit match.
• Place the tick in a closed container (for species identification later, should symptoms develop) or dispose of it by flushing or by placing the tick between scotch tape.
• Check pets frequently for ticks, since ticks can migrate to children from pets.

Update on vaccination

A vaccine for Lyme disease known as LYMErix was available from 1998 to 2002, when it was removed from the United States market. The decision was influenced by reports that LYMErix may be responsible for neurologic complications in vaccinated patients. As of late 2004, the best prevention strategy was minimizing risk of exposure to ticks and using personal protection precautions.

KEY TERMS

Babesiosis —A infection transmitted by the bite of a tick and characterized by fever, headache, nausea, and muscle pain.

Bell's palsy —Facial paralysis or weakness with a sudden onset, caused by swelling or inflammation of the seventh cranial nerve, which controls the facial muscles. Disseminated Lyme disease sometimes causes Bell's palsy.

Blood-brain barrier —An arrangement of cells within the blood vessels of the brain that prevents the passage of toxic substances, including infectious agents, from the blood and into the brain. It also makes it difficult for certain medications to pass into brain tissue.

Cerebrospinal fluid —The clear, normally colorless fluid that fills the brain cavities (ventricles), the subarachnoid space around the brain, and the spinal cord and acts as a shock absorber.

Disseminated —Spread to other tissues.

Erythema migrans —A red skin rash that is one of the first signs of Lyme disease in about 75% of patients.

Lyme borreliosis —Another name for Lyme disease.

Spirochete —A type of bacterium with a long, slender, coiled shape. Syphilis and Lyme disease are caused by spirochetes.

Vector —A carrier organism (such as a fly or mosquito) which serves to deliver a virus (or other agent of infection) to a host. Also refers to a retrovirus that had been modified and is used to introduce specific genes into the genome of an organism.

Parental concerns

Because most children do not realize they have been in tick-infested areas or been bitten by a tick and because deer ticks can be the size of a poppy seed or smaller, parents should be diligent about checking children for ticks, especially if the family lives in or visits an area with a high incidence of Lyme disease or an area near tick habitats. Also, because Lyme disease is difficult to diagnose in children, parents who suspect Lyme disease in their children should inform their doctor about the possibility of the disease and be proactive in requesting further medical evaluation and treatment.

Resources

BOOKS

"Bacterial Diseases Caused by Spirochetes: Lyme Disease (Lyme Borreliosis)." Section 13, Chapter 157 in The Merck Manual of Diagnosis and Therapy. Edited by Mark H. Beers and Robert Berkow. Whitehouse Station, NJ: Merck Research Laboratories, 2002.

Stewart, Gail B. Lyme Disease. Indianapolis, IN: Lucent Books, 2003.

PERIODICALS

Bryant, K. A., and Marshall G. S. "Clinical Manifestations of Tick-Borne Infections in Children." Clinical and Diagnostic Laboratory Immunology 7 (July 2000): 523–27.

Krupp, et al. "Study and Treatment of Post Lyme Disease (STOP-LD): A Randomized Double Masked Clinical Trial." Neurology 60 (June 24, 2003): 1923–30.

Nachman, S. A., and L. Pontrelli. "Central Nervous System Lyme Disease." Seminars in Pediatric Infectious Diseases 14 (April 2003): 123–30.

Pavia, C. S. "Current and Novel Therapies for Lyme Disease." Expert Opinion on Investigational Drugs 12 (June 2003): 1003–16.

Wormser, G. P., et al. "Duration of Antibiotic Therapy for Early Lyme Disease: A Randomized, Double-Blind, Placebo-Controlled Trial." Annals of Internal Medicine 138 (May 6, 2003): 697–704.

ORGANIZATIONS

Centers for Disease Control and Prevention. 1600 Clifton Rd., NE, Atlanta, GA 30333. Web site: <www.cdc.gov>.

Lyme Disease Foundation. One Financial Plaza, Hartford, CT 06103. Web site: <www.lyme.org>.

Lyme Disease Network of New Jersey Inc. 43 Winton Road, East Brunswick, NJ 08816. Web site: <www.lymenet.org>.

National Institute of Allergy and Infectious Diseases (NIAID). 31 Center Drive, Room 7A50 MSC 2520, Bethesda, MD 20892. Web site: <www.niaid.nih.gov>.

WEB SITES

"CDC Lyme Disease Home Page." Centers for Disease Control and Prevention, Division of Vector-Borne Infectious Diseases. Available online at <www.cdc.gov/ncidod/dvbid/lyme> (accessed November 21, 2004).

"Children's Corner." Lyme Disease Foundation. Available online at <www.lyme.org/children.html>(accessed November 21, 2004).

Edlow, Jonathan A. "Tick-Borne Diseases, Lyme." eMedicine, December 13, 2002. Available online at <www.emedicine.com/emerg/topic588.htm> (accessed November 21, 2004).

"Neurological Manifestations of Lyme Disease in Children." LymeNet. Available online at <http://library.lymenet.org> (accessed November 21, 2004).

Jennifer E. Sisk, MA

Lyme disease

Definition

Lyme disease, which is also known as Lyme borreliosis, is an infection transmitted by the bite of deer ticks carrying the spirochete (spiral-shaped bacterium) Borrelia burgdorferi. The disease was named for Lyme, Connecticut, the town where it was first diagnosed in 1975 after a puzzling outbreak of juvenile arthritis. The organism that causes the disease was identified in 1982 and named for its discoverer, Willy Burgdorfer.

Description

Lyme disease is classified as a zoonosis, which means that it is a disease of animals that can be transmitted to humans under natural conditions; it cannot be transmitted person-to-person. B. burgdorferi is carried by infected deer ticks (more precisely known as black-legged ticks) and passed to humans or household pets when they are bitten by the ticks. In the United States, the white-footed mouse is the usual host of immature (nymphal and larval) ticks, while deer are the most common hosts of the adult ticks. In Europe, sheep are the usual hosts of adult infected ticks. Adult black-legged ticks are hard to detect because of their small size; an adult male tick, for example, is about 0.039 in (1 mm) long. An adult female is slightly larger, about 0.051 in (1.3 mm) long.

Ticks feed on their hosts by piercing the skin and slowly sucking blood through the broken tissue. The spiro-chete enters the host as the tick fills itself with blood. After the spirochete has been introduced into the person's skin, it may be destroyed by the body's defense mechanisms. If it is not eliminated, it may either remain in the skin or spread throughout the body through the lymphatic system or the bloodstream. B. burgdorferi can spread to the heart, joints, or central nervous system once it has gained access to the person's circulation. Studies show that B. burgdorferi can penetrate the central nervous system relatively early in the course of the infection without causing any neurologic symptoms. It can also remain in the person's skin for years without causing symptoms.

Lyme disease is a systemic illness, which means that it affects all parts of the body. The most commonly affected areas and organs, however, are the skin, nervous system, heart, joints, and eye. The symptoms of Lyme disease typically emerge in three stages.

It is possible for a person to contract Lyme disease more than once; having the disease does not lead to immunity.

Demographics

The risk of getting Lyme disease depends more on geographical location and the amount of time spent outdoors in tick-infested areas than on age, sex, or race per se, although about 25% of cases in the United States are reported in children younger than 14. Cases of Lyme disease have been reported in 49 of the 50 states; however, 92% of the 17,730 cases reported to the Centers for Disease Control and Prevention (CDC) in 2000 were from only nine states (Connecticut, Rhode Island, New York, Pennsylvania, Delaware, New Jersey, Maryland, Massachusetts, and Wisconsin). The disease is also found in Scandinavia, continental Europe, the countries of the former Soviet Union, Japan, and China; in addition, it is possible that it has spread to Australia.

Lyme disease is seasonal in occurrence. In the United States, humans are most likely to be infected from May through August, when the ticks are most active and people are spending more time outdoors.

The number of cases reported in the United States continues to increase each year; the CDC attributes this increase to the growing size of the deer herd and the geographical spread of infected ticks rather than to improved diagnosis. In addition, some epidemiologists believe that the actual incidence of Lyme disease in the United States may be five to ten times greater than that reported by the CDC. The reasons for this difference include the narrowness of the CDC's case definition as well as frequent misdiagnoses of the disease.

Causes and symptoms

Lyme disease itself is caused by a bacterium known as Borrelia burgdorferi, which enters the skin through the bite of an infected tick belonging to the genus Ixodes. In Europe, the disease is caused by related species known as B. afzinii and B. garinii.

Currently, scientists do not completely understand exactly how B. burgdorferi produces the variety of symptoms that characterize Lyme disease. Some symptoms are

directly caused by the spirochete, but others may result from the body's immune response to the organism.

The symptoms of Lyme disease are typically divided into three stages: early localized, early disseminated, and late. Neurologic complications are most common in disseminated and late-stage Lyme disease.

EARLY LOCALIZED DISEASE Early symptoms of Lyme disease include low-grade fever and erythema migrans, or EM, a red spot or patch on the skin that is found in about 75% of patients with Lyme disease. The initial spot is usually found on the arms, legs, armpits, or trunk within 3–32 days after the tick bite. Erythema migrans often has a ring-like or "bull's-eye" appearance, with the bite itself in the center of the affected area, surrounded by a ring of reddened and inflamed skin. The ring grows outward around the central lesion, sometimes growing as large as 27 in (70 cm) in diameter. Secondary EM lesions appear in about 20% of patients. The rash does not usually itch or burn, and typically fades in a few weeks even if untreated.

Other symptoms of early-stage Lyme disease include flu-like muscular aches and pains, headache , a stiff neck, and fatigue . Nausea and vomiting or sore throat occur in some patients, but are less common symptoms.

EARLY DISSEMINATED DISEASE Early disseminated Lyme disease is characterized by ongoing fatigue; arthritis-like pains in the joints; a headache that comes and goes; inflammation of the tendons and their protective sheaths (synovitis); and red or itchy eyes (conjunctivitis). It is common for the aches and pains in muscles and joints to move from one part of the person's body to another. About 8% of people with Lyme disease develop cardiac complications, which may include heart block and inflammation of the walls of the heart (myocarditis).

Neurologic symptoms in early disseminated Lyme disease affect about 15% of people, usually within a few weeks to months after the onset of EM. The following may be the first symptoms in people who did not develop EM, however:

• Bell's palsy . This refers to weakness or paralysis of the facial muscles caused by inflammation or swelling of the seventh cranial nerve. People with facial palsy caused by Lyme disease may be affected on both sides of the face. This symptom may be important in diagnosis, as Bell's palsy caused by other disorders typically affects only one side of the face.
• Radiculoneuropathy. This is the medical term for disease affecting nerves and nerve roots. In Lyme disease, neuropathy often takes the form of abnormal sensations (paresthesias) in the hands or feet.
• Meningoencephalitis. This refers to inflammation of the brain tissue and the protective membranes that cover it (the meninges ). This complication of Lyme disease often causes sleep disturbances, memory problems, difficulty concentrating, mood swings, headache, ataxia (loss of muscular coordination), paresis (mild paralysis), and disturbances in the person's deep tendon reflexes. To test these reflexes, or involuntary responses of certain muscles to a stimulus, the physician gently taps with a small hammer below the person's kneecap, behind the elbow, over the Achilles tendon at the back of the heel, and over the biceps and triceps muscles in the upper arm. The deep tendon reflexes are often weakened or asymmetrical in people with meningoencephalitis related to Lyme disease.

LATE DISEASE The most common symptom of late disseminated Lyme disease is swelling and pain in a few large weight-bearing joints, most often the knee. The affected joints are typically much more swollen than painful, but the arthritis may be accompanied by low-grade fever and fatigue. Lyme-related arthritis develops within weeks to months after the initial eruption of erythema migrans. About 10% of people diagnosed with Lyme disease develop chronic arthritis of the knee.

A late-stage complication of Lyme disease that affects the skin is acrodermatitis chronica atrophicans, a disorder in which the skin on the person's lower legs or hands becomes inflamed and paper-thin. This disorder is seen more frequently in Europe than in the United States.

People with late-stage Lyme disease may develop a neurologic disorder characterized by personality changes and problems with thinking or memory that persist in spite of antibiotic treatment. This syndrome has been called persistent Lyme disease, or PLD. One study of 33 patients diagnosed with PLD found that the most common symptoms were headache (36.4% of patients); memory problems (27.3%); insomnia (33.3%); problems with gait and coordination (36.4%); and impaired deep tendon reflexes (9%). Children with PLD have difficulty getting along with classmates in school as well as making academic progress, and are at increased risk of developing long-term psychiatric disturbances.

Diagnosis

Early diagnosis and prompt treatment are critical to preventing the neurologic complications of Lyme disease.

Patient history and symptoms

The diagnosis of Lyme disease is complicated by the fact that about 25% of patients do not develop the characteristic rash. It is important for the doctor to determine the likelihood of Lyme disease by taking a careful history of exposure to ticks, as only about 25% of patients recall being bitten. In addition to the history, the doctor will examine the patient for the following symptoms:

• Erythema migrans. When present, EM has a characteristic "bull's-eye" pattern. In addition, the bite location is often significant; tick bites are more frequently found in such body folds as the armpits or on areas on the trunk near elastic bands in bra straps or underwear.
• Fever. The fever that accompanies early Lyme disease is usually low; a high fever indicates either concurrent infection with babesiosis or a different diagnosis altogether.
• Absence of digestive or respiratory symptoms.
• Presence of fatigue, headache, and muscle or joint pains.

Laboratory tests

Blood testing is not considered necessary if the patient has EM, a history of exposure to ticks, and other indications of a high likelihood of Lyme disease. Moreover, it is difficult to culture B. burgdorferi from human tissues and body fluids. Timing is another important factor in interpreting blood tests for Lyme disease; patients in the early stages of the disease may continue to test negative for several weeks after being infected. Blood testing is, however, recommended for patients with Bell's palsy or myocarditis. The CDC advises doctors to perform a two-step blood test: a screening ELISA test, followed by a Western blot test for confirmation.

Polymerase chain reaction (PCR) testing may not be available in all hospitals, but can be used to detect the DNA of B. burgdorferi in fluid drawn from the joints of untreated patients with late-stage symptoms.

Imaging studies

Imaging studies are rarely used to diagnose Lyme disease with the exception of late-stage arthritis. X rays of patients with Lyme-related arthritis usually show considerable swelling of soft tissue; erosion of bone or cartilage also appears in a small minority of these patients.

Treatment team

Patients are usually treated initially by an emergency physician (if they have gone to an emergency room to have the tick removed) or by a primary care physician (PCP).

The PCP may consult a neurologist , dermatologist, or infectious disease specialist to confirm the diagnosis or advise about medications, particularly in cases of chronic or late-stage disease.

Treatment

Initial treatment

Immediate removal of an attached tick is the first step in treatment for people who know they have been bitten. Because black-legged ticks are slow feeders, it takes about 36 hours for B. burgdorferi to make its way into the body; infection is unlikely if the tick is removed within 24 hours of attachment. People who find ticks on themselves should not use a hot match, petroleum jelly, nail polish, or similar items to remove the tick. They should use fine-tipped tweezers, grasp the tick as close to the skin as possible, and pull the tick away from the skin with a steady motion. The area should then be cleansed with an antiseptic.

If the person has been bitten in an area with a high percentage of infected ticks, the doctor will usually prescribe a prophylactic (disease-preventing) course of antibiotics. The usual dosage is 10 days of oral amoxicillin, doxycycline, or cefuroxime, although a study published in 2001 reported that a single 200-mg dose of doxycycline is also effective.

Aspirin or NSAIDs may be given to relieve fever, aching muscles, and other flu-like symptoms of early Lyme disease.

Treatment of disseminated disease and neurologic complications

Patients who have developed heart block as a complication of disseminated Lyme disease may require a temporary pacemaker. Those with swollen knee joints may need to have excess fluid removed by aspiration, a procedure in which the doctor withdraws the fluid through a fine needle.

Patients with Bell's palsy may be given oral antibiotics for 21–30 days. Patients who have neurologic symptoms together with Lyme-related arthritis are usually treated with intravenous ceftriaxone.

Recovery and rehabilitation

Most patients with neurologic complications of Lyme disease recover completely following treatment with antibiotics. Those who do not respond are usually given an additional course of antibiotics. As of 2003, however, treatment recommendations for central nervous system (CNS) complications of Lyme disease are still evolving, and there is ongoing disagreement among specialists regarding the effectiveness of various treatments for PLD.

Clinical trials

As of October 2003, the National Institute of Neurological Disorders and Stroke (NINDS) is recruiting patients for a 24-week treatment study of persistent Lyme disease (PLD). The investigators will be using brain imaging (MRI and PET scans) to study the effects of intra-venous antibiotic treatment on the neurologic symptoms of PLD. Two other trials are recruiting patients with Lyme disease in order to study the immune system's response to the disorder and to evaluate various treatment regimens.

Prognosis

Patients who are treated early with antibiotics and take their medications on schedule should recover completely from Lyme disease. Most long-term effects of the infection result from misdiagnosis or delayed treatment. Co-infection with such other tick-borne diseases as babesiosis and ehrlichiosis may lead to treatment failures or more severe symptoms. The few fatalities reported with Lyme disease occurred in patients who had also contracted babesiosis.

Neurologic symptoms of early disseminated Lyme disease may last for several months but usually resolve completely. Late neurologic complications of Lyme disease, however, may not respond to antibiotic therapy, particularly if diagnosis and treatment were delayed.

Special concerns

A vaccine for Lyme disease known as LYMErix was available from 1998 to 2002, when it was removed from the United States market. The decision was influenced by reports that LYMErix may be responsible for neurologic complications in vaccinated patients. Researchers from Cornell-New York Hospital presented a paper at the annual meeting of the American Neurological Association in October 2002 that identified nine patients with neuropathies linked to vaccination with LYMErix. In April 2003, the National Institute of Allergy and Infectious Diseases (NIAID) awarded a federal grant to researchers at Yale University School of Medicine to develop a new vaccine against Lyme disease.

Resources

BOOKS

"Bacterial Diseases Caused by Spirochetes: Lyme Disease (Lyme Borreliosis)." Section 13, Chapter 157 in The Merck Manual of Diagnosis and Therapy, edited by Mark H. Beers, MD, and Robert Berkow, MD. Whitehouse Station, NJ: Merck Research Laboratories, 2002.

PERIODICALS

Adams, H. B., G. A. Blasko, and L. A. DiDomenico. "An Unusual Case of Bilaterally Symmetrical Neuropathic Osteoarthropathy of the Midfoot as a Result of Lyme Disease-Induced Peripheral Neuropathy: A Case Report." Foot and Ankle International 23 (February 2002): 155–157.

Coyle, P. K. "Lyme Disease." Current Neurology and Neuroscience Reports 2 (November 2002): 479–487.

Edlow, Jonathan A., MD. "Tick-Borne Diseases, Lyme." eMedicine, 13 December, 2002 (February 20, 2004). <http://www.emedicine.com/emerg/topic588.htm>.

Gustaw, K., K. Beltowska, and M. M. Studzinska. "Neurological and Psychological Symptoms after the Severe Acute Neuroborreliosis." Annals of Agricultural and Environmental Medicine 8 (2001): 91–94.

Tager, F. A., B. A. Fallon, J. Keilp, et al. "A Controlled Study of Cognitive Deficits in Children with Chronic Lyme Disease." Journal of Neuropsychiatry and Clinical Neurosciences 13 (Fall 2001): 500–507.

OTHER

National Institute of Neurological Disorders and Stroke (NINDS) Fact Sheet. Bell's Palsy. Bethesda, MD: NINDS, 2003.

NINDS Information Page. Neurological Complications of Lyme Disease. Bethesda, MD: NINDS, 2003.

WEBSITES

Centers for Disease Control and Prevention, Division of Vector-Borne Infectious Diseases. CDC Lyme Disease Home Page. (February 20, 2004.) <http://www.cdc.gov/ncidod/dvbid/lyme/>.

ORGANIZATIONS

Centers for Disease Control and Prevention (CDC). 1600 Clifton Road, NE, Atlanta, GA 30333. (800) 311-3435. inquiry@cdc.gov. <http://www.cdc.gov>.

Lyme Disease Foundation. One Financial Plaza, Hartford, CT 06103. (860) 525-2000 or (860) 525-TICK or (800) 886-LYME. lymefnd@aol.com. <http://www.lyme.org>.

National Institute of Allergy and Infectious Diseases (NIAID). 31 Center Drive, Room 7A50 MSC 2520, Bethesda, MD 20892. (301) 496-5717. <http://www.niaid.nih.gov>.

NIH Neurological Institute. P. O. Box 5801, Bethesda, MD 20824. (301) 496-5751 or (800) 352-9424. <http://www.ninds.nih.gov>.

Rebecca J. Frey, PhD