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1-800-228-0872 |
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Lyme Disease |
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Borrelia burgdorferi FA stain. CDC Lyme disease was first recognized in the United States in 1975 by Dr. Allen Steere, following a mysterious outbreak of juvenile rheumatoid arthritis near the community of Lyme, Connecticut. The rural location of the Lyme outbreak and the onset of illness during summer and early fall suggested that the transmission of the disease was by an arthropod vector. In 1982, the etiologic agent of Lyme disease was discovered by Willy Burgdorfer who isolated spirochetes belonging to the genus Borrelia from the mid-guts of Ixodes ticks. He showed that these spirochetes reacted with immune serum from patients that had been diagnosed with Lyme disease. Consequently, the etiologic agent was given the name Borrelia burgdorferi. Since then, reports of Lyme disease have increased dramatically to the point that the disease has become an important public health problem in some areas of the United States. Today Lyme disease is the most prevalent tick-borne illness in the US. Lyme disease has been reported in 47 states and on four different continents. In 1995, over 13,000 new cases were reported in the U.S. (see table below)
Biology of Borrelia burgdorferiBorrelia burgdorferi, like the human pathogen Treponema pallidum, is a spirochete. Spirochetes are a group of phylogenetically-distinct procaryotes that have a unique mode of motility by means of axial filaments (endoflagella). Spirochetes are widespread in viscous environments and they are found in the intestinal tracts of animals and the oral cavity of humans. The spirochetes have a unique cell surface which accompanies their unique type of motility. The endoflagella are contained within the periplasmic space between a rigid peptidoglycan helix and a multi-layer, flexible outer membrane sheath. When the filaments rotate within this space, the spirochetes move in cork-screw fashion. This mode of motility in spirochetes is thought to be an adaptation to viscous environments such as aquatic sediments and the intestinal tracts of animals. For pathogens, this allows the spirochetes to hide their flagella, which are normally antigenic, from the host immune defenses.
Spirochetes are usually much longer than they are wide, and often their width is below the resolving power of the light microscope. For example, Borrelia may have a length of 20-30um but a width of only .2-.3um. Hence, most spirochetes cannot be viewed using conventional light microscopy. Dark-field microscopy must be used to view spirochetes. Dark field microscopy utilizes a special condenser which directs light toward an object at a angle, rather than from the bottom. As a result, particles or cells are seen as light objects against a dark background.
Borrelia burgdorferi. Dark Field Illumination The spirochetes are not classified as either Gram-positive or Gram-negative. When Borrelia burgdorferi is Gram-stained, the cells stain a weak Gram-negative by default, as safranin is the last dye used. Borrelia, like most spirochetes, does have an outer membrane that contains an LPS-like substance, an inner membrane, and a periplasmic space which contains a layer of peptidoglycan. Therefore, it has a Gram-negative bacterial type cell wall, despite its staining characteristics. Unlike Treponema pallidum, Borrelia burgdorferi can be cultivated in vitro. However, the bacterium is fastidious and requires a very complex growth medium. The medium used to grow Borrelia burgdorferi is called Barbour-Stoenner-Kelly (BSK) medium. It contains over thirteen ingredients in a rabbit serum base. Borrelia burgdorferi has an optimal temperature for growth of 32 C, in a microaerobic environment. Even under optimal conditions, the generation time is slow, about 10-12 hours. Recently, the spirochetes causing Lyme disease were divided into several "genospecies", three of which have been firmly established and are well accepted:
The term used to collectively describe all three genospecies is Borrelia burgdorferi sensu lato. The differences in genospecies are revealed by restriction fragment length polymorphism, (RFLP), multi-locus enzyme electrophoresis (MLEE) and ssuRNA sequences. All US isolates fall into genospecies I. Examples of all three genospecies have been found in Europe and Asia, although II and III predominate there. The outer membrane of Borrelia burgdorferi is composed of various unique outer surface proteins (Osp) that have been characterized (Osp A through OspF). They are presumed to play a role in virulence. Osp A and Osp B are by far the most abundant outer surface proteins. The genes encoding these proteins are transcribed from a common promoter, and are located on a 49 kb linear plasmid. The chromosome of Borrelia burgdorferi is also linear and is almost 1100 kb in size. Borrelia burgdorferi invades the blood and tissues of various infected mammals and birds. The natural reservoir for Borrelia burgdorferi is thought to be the white-footed mouse. Ticks transfer the spirochetes to the white-tailed deer, humans, and other warm-blooded animals after a blood meal on an infected animal. In humans, dogs, and many other animals, infection with Borrelia burgdorferi results in the pathology of Lyme Disease. Distribution of Lyme Disease in the United StatesLyme disease has a wide distribution in northern temperate regions of the world. In the United States, the highest incidence occurs in the Northeast, from Massachusetts to Maryland, the North-central states, especially Wisconsin and Minnesota, and on the West Coast, particularly northern California.
Transmission of Lyme DiseaseLyme disease is is spread by the bite of ticks of the genus Ixodes that areinfected with Borrelia burgdorferi. Ixodes, commonly known as the deer tick, normally feeds on the white-footed mouse, the white-tailed deer, and certain other mammals. It is responsible for transmitting the spirochetes to humans in the northeastern and north-central United States. On the Pacific Coast, the bacteria are transmitted to humans by the western black-legged tick, and in the southeastern states by the black-legged tick. Ixodes ticks are much smaller than common dog and cattle ticks. In their larval and nymphal stages, they are no bigger than a pinhead. Adult ticks are slightly larger. The tick nymphs, which are most likely to feed on a person and are rarely noticed because of their small size (less than 2 mm), are usually involved in the transmission of the disease.
Ixodes ticks. CDC Spirochete prevalence in adult Ixodes ticks has been shown to be approximately 35% (for example, in the Baraboo Hills, northwest of Madison, Wisconsin), but varies greatly among geographic locations (e.g. California = 2%, New York =50%). For Lyme disease to exist in an area, at least three closely interrelated elements must be present in nature: the Lyme disease bacteria, ticks that can transmit them, and mammals (such as mice and deer) to provide food for the ticks in their various life stages. The tick life cycle consists of three distinctive stages: larvae, nymphs, and adults. A blood meal is required for ticks to molt from the larvae stage to the nymph stage and from the nymph stage to the adult stage. The tick larvae and nymphs typically become infected with Lyme disease bacteria when they feed on infected small animals, particularly the white-footed mouse. The bacteria remain in the tick as it changes from larva to nymph or from nymph to adult. Infected nymphs and adult ticks then bite and transmit Lyme disease bacteria to other small rodents, other animals, and humans, all in the course of their normal feeding behavior. Adult ticks preferentially feed on the white-tailed deer, which thereby becomes an important reservoir in regions of infestation. The tick life cycle takes two years to complete.
Lyme disease occurs in domestic animals, as well. In dogs, the disease usually presents as arthritis. Domestic animals can carry infected ticks into areas where humans live, but whether pet owners are more likely than others to get Lyme disease is not known. Symptoms of Lyme diseaseThe symptoms of Lyme disease in humans occur in three stages. Stage one (early infection). The early stage of Lyme disease is often characterized by a distinctive, expanding red rash that usually develops at the site of the tick bite. This rash, known as erythema migrans, is seen in 60-80% of infected individuals (it is important to remember that the converse is true: no rash is ever observed in 20-40 % of the cases!). Spirochetes can be isolated from the leading edge of the rash. Erythema migrans is a red circular patch that appears usually 3 days to 1 monthfollowing the bite of the tick. The patch then expands, often to a large size and develops a characteristic "bull's eye"appearance. However, not all rashes that occur at the site of a tick bite are due to Lyme disease. An allergic reaction to tick saliva often occurs at the site of a tick bite. This rash can be confused with the rash of Lyme disease. Allergic reactions to tick saliva usually occur within hours to a few days after the tick bite, usually do not expand, and disappear within a few days. Erythema migrans persists longer, but usually subsides within 3-4 weeks.
Erythema migrans. CDC Stage two (dissemination stage): occurs days to weeks following infection. At this stage the spirochetes spread hematogenously to additional body tissues. One or more of the following symptoms and signs may be noted:
Stage three (persistent infection). Some symptoms and signs of Lyme disease may not appear until weeks, months, or years after a tick bite. Stage three typically involves intermittent episodes of joint pain. Common clinical manifestations at this stage may include meningitis, Bell's palsy, cardiac involvement, and migratory pain to joints, tendons, muscle and bone: Arthritis is most likely to appear as brief bouts of pain and swelling, usually in one or more large joints, especially the knees. Nervous system abnormalities can include numbness, pain, Bell's palsy (paralysis of the facial muscles, usually on one side), and meningitis (fever, stiff neck, and severe headache). Less frequently, irregularities of the heart rhythm occur. In a minority of individuals (11%) the development of chronic Lyme arthritis may lead to erosion of cartilage and/or bone. Other clinical manifestations associated with stage three Lyme disease include neurologic complications such as disturbances in memory, mood, or sleep patterns, and sensations of numbness and tingling in the hands or feet. Lyme disease mimicks other diseases and pathologies and is highly variable in its presentation. In some persons the rash never forms; in some, the first and only sign of Lyme disease is arthritis, and in others, nervous system problems are the only evidence of Lyme disease. Diagnosis of Lyme diseaseLyme disease is often difficult to diagnose because its symptoms and signs mimic those of so many other diseases. The fever, muscle aches, and fatigue of Lyme disease can easily be mistaken for viral infections, such as influenza or infectious mononucleosis. Joint pain can be mistaken for other types of arthritis, such as rheumatoid arthritis, and neurologic signs can mimic those caused by other conditions, such as multiple sclerosis. At the same time, other types of arthritis or neurologic diseases can be misdiagnosed as Lyme disease.Diagnosis of Lyme disease should include:History of possible exposure to ticks, especially in areas where Lyme disease is known to occur. Symptoms and signs.Seodiagnosis to detect anti-borrelia antibodies (This test is not useful until in later stages of illness).The most commonly used methods to diagnose Lyme disease are indirect immunofluorescent assays (IFAs) and enzyme-linked immunosorbent assays (ELISAs). Western blotting has also been used by some laboratories. However, IFAs, ELISAs and Western blotting have all been shown to lack a high degree of both sensitivity and specificity. Also,n one of these tests can effectively diagnose early cases of Lyme disease since the depend upon the development of an immune response. Furthermore, these tests are associated with a high degree of cross-reactivity, since sera from patients with Rocky Mountain spotted fever, relapsing fever, mononucleosis, syphilis, and rheumatoid arthritis often test positive for Lyme disease. Recently, a new serodiagnostic test for Lyme disease has been developed, known as the Gundersen lyme Test (GLT). GLT uses flow cytometry to detect borreliacidal antibodies in the sera of infected individuals. The test is no more sensitive than conventional tests at diagnosing early Lyme Disease, but GLT eliminates nearly all cross-reactivity and has a sensitivity near 100%. Treatment of Lyme diseaseSeveral antibiotics are effective in the treatment of Lyme disease. The present drug of choice is doxycycline, a semisynthetic derivative of tetracycline. Even patients who are treated in later stages of the disease respond well to antibiotics. In a few patients who are treated for Lyme disease, symptoms of persisting infection may continue or recur, making additional antibiotic treatment necessary. Varying degrees of permanent damage to joints or the nervous system can develop in patients with late chronic Lyme disease. Typically these are patients in whom Lyme disease was unrecognized in the early stages or for whom the initial treatment was unsuccessful. PreventionRemoving leaves and clearing brush and tall grass around houses and at the edges of gardens may reduce the numbers of ticks that transmit Lyme disease. A relationship has been observed between the abundance of deer and the abundance of deer ticks in some parts United States. Reducing and managing deer populations in geographic areas where Lyme disease occurs may reduce tick abundance.CDC recommends the following for personal protection from tick bites and Lyme disease: Avoid tick-infested areas, especially in May, June, and July.Wear light-colored clothing so that ticks can be spotted more easily. Tuck pant legs into socks or boots and shirt into pants or tape the area where pants and socks meet so that ticks cannot crawl under clothing.Spray insect repellent containing DEET on clothes and on exposed skin other than the face, or treat clothes (especially pants, socks, and shoes) with permethrin, which kills ticks on contact.
A whole cell vaccine for the prevention of Lyme disease in dogs is commercially available. However, its efficacy has been questioned. Also, concern about the safety of whole-cell vaccines in humans has been raised. Human vaccine trials using a monovalent, recombinant OspA vaccine are currently in progress. Preliminary results indicate that it stimulates protective immunity in experimental animals to Borrelia burgdorferi sensu stricto, but may not provide complete protection against Borrelia burgdorferi sensu lato. |
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