|Pathogen/||Life Cycle/||Clinical Disease/||Prevention/||Detection/||Epidemiology|
Lyme disease is caused by infection with the bacteria Borrelia burgdorferi. It was not until the 1970s that the association of these bacteria with what came to be known as Lyme disease was discovered. Borrelia belong to a category of bacteria known as spirochetes, so named because of their corkscrew-like appearance. Borrelia burgdorferi survive in the guts of certain ticks in the genus Ixodes, and enter host organisms in the saliva of the feeding ticks. In the eastern U. S. white-footed mice, Peromyscus leucopus, are the principal reservoir hosts for B. burgdorferi , and it is from feeding on infected mice that ticks become infected. In susceptible animals these bacteria can reside in many types of tissue (e. g., muscle, nervous).
Persons become infected with Borrelia burgdorferi when they are bitten by an infected tick. In the eastern and central U. S. the blacklegged tick, often referred to as the deer tick, Ixodes scapularis, is the species responsible for transmitting B. burgdorferi to humans and other vertebrate hosts. In the Pacific coast states the western blacklegged tick, I. pacificus, fills the same role as I. scapularis as vector of B. burgdorferi. Both I. scapularis and I. pacificus are similar in appearance and biology. The blacklegged tick has 3 active life stages (larva, nymph and adult) that feed on a wide variety of vertebrate hosts, including birds and lizards, but most adults feed on white-tailed deer. Having found a host, larvae and nymphs feed 3-5 days, and adult females about 1 week then drop off the host. Although the life cycle of I. scapularis is about 2 years, each tick spends only about 2 weeks feeding on hosts.
I. scapularis feeds once during each of its 3 active life stages: larva, nymph, and adult
Ixodes scapularis and I. pacificus have 3 feeding stages: larva, nymph and adult. In the eastern U. S., the six-legged larvae (later stages have 8 legs) hatch from eggs in the late spring/ early summer, and seek hosts through mid-summer. After feeding on a suitable host, such as a white-footed mouse, for 3-5 days, the larvae drop off the host, enter the leaf litter on the forest floor and molt into the nymphal stage. These unfed nymphs remain inactive in the leaf litter through the fall, winter and early spring. Around May the nymphs start seeking hosts. In the Mid-Atlantic states the greatest numbers of nymphs seek hosts in late May and June. In diminishing numbers, nymphs seek hosts until early fall. Nymphs feed on hosts for 3-5 days, drop off into the leaf litter, and molt into adults which begin seeking hosts in the fall. Adult I. scapularis will seek hosts through the winter if temperatures are not too cold (below about 70C, 450F). Characteristically there is a spring peak of adult activity as temperatures rise. Although larvae and nymphs can feed on small, medium and large mammals as well as birds and reptiles, adult I. scapularis feed on large to medium-sized mammals, predominantly on white-tailed deer. Mated females feed about 1 week before dropping off the host. Fed females remain in the leaf litter where they can lay as many as 2,000 - 3,000 eggs. Acquiring a suitable host is critical to tick survival and reproduction. Ticks use various chemical cues produced by hosts that aid ticks in making physical contact with the hosts. Research conducted at PBESL has shown that ticks detect substances rubbed onto vegetation and the substrate by passing hosts influence where ticks wait in ambush for hosts. The life cycle of I. scapularis lasts about 2 years in the northeastern U. S.
It takes about 2 years for I. scapularis to complete its life cycle
(Pictures courtesy of the CDC)
Clinical disease in humans:
Lyme disease is a multisystem illness involving the skin, nervous system, heart, and joints. Initially, symptoms resemble the onset of influenza, including severe headache, fatigue, joint and muscle pain, fever and possibly swollen lymph glands. About 60% of Lyme disease patients present with a characteristic "bull's eye" rash, or erythema migrans (EM) which appears at the site of the tick bite usually within 3 days to 1 month after the bite of an infected tick. Later stage symptoms may occur weeks after a tick bite and are more severe, including neurological complications such as facial palsy, irritability, and poor motor coordination. Further, cardiac problems including irregular heart beat and varying degrees of heart blockage causing dizziness may eventually occur. Third stage Lyme disease can occur months or years after the initial infection and may involve chronic arthritis or chronic neurological effects. Lyme disease is rarely, if ever fatal. Prompt treatment with antibiotics during early stages of the disease affords complete recovery. However, later stages are more difficult to treat. For this reason, it is important for patients to receive prompt diagnosis.
Lyme disease in cattle:
Antibodies to Borrelia burgdorferi have been demonstrated in cattle in Europe, Australia, the UK and the US. Spirochetes have been detected from the blood and urine of cows in Wisconsin. At the present time, there is no set pattern of symptoms, diagnosis or treatment of the disease in cattle. Typically in the acute stage of the disease, dairy cattle may develop fever, stiffness and swollen joints, lameness, and their milk production decreases. Chronic weight loss, laminitis, and abortion have also been reported. A rash may occur at the site of the tick bite in some cases, but may be difficult to see, if it occurs at all. Unfortunately, the clinical signs of Lyme disease are very similar to other diseases common in cattle and the symptoms vary greatly among cows. Cross-reactivity to other organisms similar to B. burgdorferi may lead to false positive results in serological tests currently in use. As in humans, an accurate diagnosis must include a history of potential exposure to the vector tick (Ixodes scapularis), appropriate clinical signs, elevated antibody titers to specific borrelial antigens, and a positive response to antibiotic treatment. Our lab is engaged in a project that is focused on evaluating the susceptibility of cattle to Lyme disease in this area. This project involves tick surveys in areas surrounding dairies and beef operations and employs the use of specifically designed DNA primers to detect the agent of Lyme disease in ticks and animal samples by PCR.
Tick bite prevention can include personal protection and reduction of tick populations.
Most cases of Lyme disease are the result of persons being bitten by nymphal I. scapularis. The vast majority of host-seeking nymphs and larvae of I. scapularis are found in leaf litter in and adjacent to woods. Nymphs are also frequently found on and about stone fences and fallen logs. Therefore, it is best to limit one's contact with leaf litter, and do not sit on stone fences and fallen logs.
Wear light colored clothing so that it is easy to see ticks on it.
Tuck pants legs into socks.
Carefully tape junctures of shoes, socks and pants legs with wide masking tape Entirely cover shoe laces with tape, because some species of ticks will enter shoes through eyelets and around tongue of shoe. Some larvae and occasionally nymphs can penetrate through the weave of some socks.
Use repellents. Permethrin-based repellents should be used only on clothing. Deet-based repellents can be used on skin. PBESL in conjunction with the Chemicals Affecting Insect Behavior Laboratory, BARC and Walter Reed Army Institute of Research, Silver Spring, MD are evaluating the efficacy of tick repellents that can be used on human skin.
Be careful about long hair that contacts shirt or coat collars. Ticks can crawl from collar to hair undetected.
Examine yourself and children for ticks repeatedly after spending time in tick infested areas. You cannot depend on showering to remove ticks, especially attached ticks.
Place clothing worn in tick infested areas in a closed plastic bag until washing it. Ticks can survive machine washing with cool water.
Unlike mosquitoes, the process by which ixodid ticks feed is slow, lasting a few days. In the case of Lyme disease, 24-36 hours of attachment are needed before transmission of B. burgdorferi starts. Other disease causing agents can be transmitted more quickly.
Attached ticks should be removed as soon as possible.
Tick removal. Attached ticks are best removed using forceps (tweezers) with slender points. The tick should be grasped with the forceps as close to the person's skin as possible. Grasping the tick farther from its mouthparts increases the chance of squeezing its gut contents into the person. Pull the tick from the skin slowly and firmly. Wash the bite area and apply a topical antibiotic to it.
Because the early symptoms of many tick-borne illnesses are like those experienced with other ailments, such as the flu, it is prudent to see a physician, if you notice headache, fever, muscle pains, or other symptoms after having had a tick bite. Lyme disease and other tick-borne illnesses caused by bacteria are generally respond to antibiotics, when treatments are started early. It is important that your physician knows about your tick bite.
Tucking pants into socks and wrapping tape from shoe to pants helps keep ticks from legs and feet.
Habitat Management. Ixodes scapularis survive best under humid conditions. They are more apt to occur in woods and along the edges of woods than open expanses, such as closely mowed sunny lawns. Removing leaf litter and keeping lawns mowed limits the ticks' opportunities for finding humid refuges.
Application of acaricides (insecticides) can reduce or prevent infestations of I. scapularis on one's land, if done annually, properly and at the correct time in the spring. In suburban sites, most host-seeking ticks occur in or near wooded areas, so chemical treatments are best directed there.
Host self-treatment measures kill ticks on host animals.
In one commercially available measure, cotton balls are impregnated with permethrin and stuffed in a cardboard tube. Mice remove the cotton balls and use them as nesting material. In the process the mouse's fur becomes treated with the acaricide which kills ticks.
Another device is a bait box in which mice contact an acaricide when they enter or exit.
Developed at the USDA, ARS, Knipling-Bushland U. S. Livestock Insects Research Laboratory, Kerrville, TX, '4-poster' deer self-treatment device targets adult I. scapularis and other ticks that feed on deer. When the deer feed on corn bait they rub against paint rollers impregnated with insecticide. Because most adult I. scapularis feed on deer, '4-posters' can have large effect on a tick population over the range of the herd of deer visiting the device. The efficacy of the '4-poster' against I. scapularis is being evaluated in a nearly completed by 5-year, 5-state study, the USDA Northeast Area-Wide Tick Control Project, with 3 study sites in MD maintained by PBESL.
The major diagnostic marker for Lyme disease is the typical "bull's eye rash", or erythema migrans (EM) at the site of the original tick bite. EM occurs in about 60% of patients and when present this rash is particularly useful in clinical diagnosis, especially when accompanied by flu-like symptoms such as fatigue, headache, mild stiff neck, joint and muscle aches, and fever. Importantly, when and if the EM rash does occur, usually the tick has detached. In many cases, patients do not remember being bitten. In those patients where the EM rash was either missed or not present, the first observable signs of Lyme disease may be third-stage nonspecific central nervous system (CNS) manifestations that can be confused with conditions such as multiple sclerosis, brain tumors, and psychiatric derangements.
Isolation of B. burgdorferi in culture is the best diagnostic evidence of Lyme disease, but impractical. The spirochete has been isolated and successfully cultured from blood, spinal fluid and synovial fluid of patients with Lyme disease.
Direct observation of the spirochete can be done with dark field microscopy, or with a variety of tissue stains, such as aniline dyes or silverstains. However, the number of spirochetes in peripheral circulation or captured in routine patient samples is low. Therefore the success rate of using these direct methods of detection is extremely low.
A variety of serologic tests are currently in use for the detection of Lyme disease, such as the enzyme-linked immunosorbant assay (ELISA), indirect fluorescent antibody test (IFA), and the Western immunoblot (WB). These methods are indirect tests that detect the host or patient's response to the pathogen. The Centers for Disease Control and Prevention (CDC) currently recommends a two-step test. The initial test is one of the more sensitive tests, either ELISA or IFA, followed by the more specific WB especially when results are positive or equivocal. Positive results for the IFA are titers greater than or equal to 1:62 and positive results for the ELISA are greater than or equal to 1:160. There are a number of difficulties in the use of serologic methods for diagnosis of Lyme disease. False positives can occur due to cross-reactivity to antibodies of a number of other spirochetes, (Treponema, and Leptospira), also found in humans which bear a close similarity to B. burgdorferi, or in patients who test positive for rheumatoid factor and Epstein Barr virus. Antibody titers to B. burgdorferi may not be detectable for the first week to two weeks post exposure (IgM), or may otherwise be affected by antibiotic treatment. Antibodies (IgG) to B. burgdorferi often persist for months or years following successfully treated or untreated infection. Because of this, seroactivity alone cannot be used as a marker of active disease but may indicate possible exposure at some time.
A number of researchers have developed a variety of genomic primers to amplify B. burgdorferi DNA by the polymerase chain reaction (PCR) from ticks as well as patient samples. The PCR assay has been shown to be sensitive, rapid, repeatable, and accurate, and should greatly facilitate the diagnosis of Lyme disease, especially because the spirochete involved can be difficult or impossible to grow in culture. As with the other methods of detection, PCR has its drawbacks. The sample to be tested must contain at least one recoverable organism for the assay, and the PCR assay has yet to be standardized from lab to lab for routine diagnosis of Lyme disease.
It has been shown that prompt treatment with antibiotics during early stages of Lyme disease affords complete recovery, but later stages are more difficult to cure. For this reason, it is important for patients to receive prompt and accurate diagnosis. As mentioned previously, the diagnosis of Lyme disease is often not straight forward. Both false positives and false negatives are common in standard serologic testing, generally due to the lack of sensitivity and specificity inherent in these types of tests.
When Lyme disease is suspected, physicians should take into account the patient's history of possible exposure to ticks in endemic areas, as well as clinical signs and response to antibiotic treatment.
According to the Centers for Disease Control (CDC), Lyme disease is now the most common vector-borne infection in humans in the United States. More than 16,000 cases of Lyme disease were reported to the CDC in 1999. Ninety-two percent of these were from the New England states. Some years the numbers are not as high, but according to the CDC Lyme disease is under-reported. Since its discovery in 1975, cases have been reported from Canada, Europe, Australia, Asia, and the USSR. Lyme disease has been reported in domestic animals, including dogs, horses, and more recently, cattle.
(Picture courtesy of the U.S. Army)
Persons at risk for getting Lyme disease are those who live, work, or visit parks in endemic areas and frequent sites where infected ticks are common, such as wooded areas inhabited by white-tailed deer.