Traditional treatment of acute Lyme disease usually consists of a minimum two-week to one-month course of antibiotics. Oral antibiotics do not reliably cure the disease except in the very early phase, before the bacteria have a chance to disseminate throughout the body and cross the blood-brain barrier.
Chronic or late diagnosed Lyme is often treated with IV antibiotics, frequently ceftriaxone, for a minimum of four weeks. As it is thought to inhibit the once a month breeding cycle of borrelia burgdorferi, a longer course is recommended.
With little research conducted specifically on chronic Lyme disease, treatment remains controversial. Currently there are two sets of peer-reviewed published guidelines; one advocates extended courses of antibiotics for chronic Lyme patients, while the other recommends no treatment (see The Lyme controversy--Two standards of care). Double-blind, placebo-controlled trials of long-term antibiotics for chronic Lyme have produced mixed results (see The Lyme controversy--Long-term antibiotic therapy).
Many alternative (or supplemental) therapies have been suggested. Clinical trials of large doses of IV sodium ascorbate (vitamin C) have been shown to kill cancer cells and possibly parasites in the body. Largely due to this, there are many chronic lyme disease sufferers turning to natural therapies.
It should be noted that the most important factor in treating lyme disease is finding a doctor that is familiar with the disease and all of the possible treatments. Some experts, such as Dr. Joseph J. Burrascano recommend both (sometimes long-term) IV treatment and a cocktail of various vitamins.
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The Lyme controversy
Although there is no doubt that Lyme disease exists, there is considerable controversy as to the prevalence of the disease, the proper procedure for diagnosis and treatment, and the likelihood of a chronic, antibiotic-resistant Lyme infection.
On one side are those who believe that Lyme disease is relatively rare, easily diagnosed with available blood tests, and easily treated with two to four weeks of antibiotics. On the other side are those who believe that Lyme disease is under-diagnosed, that available blood tests are unreliable, and that extended antibiotic treatment is often necessary.[91][92][93][94] The majority of public health agencies such as the U.S. Centers for Disease Control maintain the former position, and recommend adherence to the IDSA guidelines. While this narrower position is sometimes described as the "mainstream" view of Lyme disease, physician surveys suggest otherwise. Studies show that physicians practicing in endemic areas in the U.S. are evenly split in their views, with the majority recognizing seronegative Lyme disease, and roughly half prescribing extended courses of antibiotics for chronic Lyme disease.[95][96]
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Two standards of care
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ILADS (The International Lyme and Associated Diseases Society) IDSA (The Infectious Diseases Society of America)
Peer-reviewed, published treatment guidelines ILADS Guidelines (full text)[4] IDSA Guidelines (pdf)[97]
EM rash Present less than 50% of the time. Studies that show otherwise are flawed because they rely on circular logic, as subjects must meet CDC criteria which prioritize the rash over other disease manifestations. Among those who would be excluded from such studies are: 1) seronegative Lyme patients without a rash (even if there is definitive evidence of infection such as a positive PCR), 2) seropositive patients without a rash who present with fever, flu-like symptoms, joint and muscle pain, paresthesias and/or encephalopathy (symptoms not included in the restrictive CDC case definition), and 3) late-stage patients whose diagnosis was delayed because no rash was present. The exclusion of these groups leads to an artificially high estimate of the incidence of EM rash among those infected with Lyme. "The great majority of Lyme patients" present with an EM rash, according to studies of patients with early Lyme disease diagnosed by CDC criteria.
Testing Not reliable, particularly for late cases; used to support a clinical diagnosis (see Testing section for discussion). Nearly always reliable after the first few weeks of infection.
Chronic Lyme disease Persistent Lyme infection exists due to various mechanisms of antibiotic resistance, particularly when diagnosis and treatment are delayed, as numerous studies have demonstrated (see Mechanisms of persistence section). Lengthy treatment regimens are sometimes required. Persistent Lyme infection is extremely rare. If symptoms remain after a standard course of antibiotics (several weeks), the illness becomes "Post-Lyme disease syndrome." Remaining symptoms are often attributed to an unspecified autoimmune process and/or the development of fibromyalgia or chronic fatigue syndrome, psychiatric disorders such as somatization, or simply stress.
Long-term antibiotic treatment ILADS advocates long-term antibiotic therapy for symptomatic patients, while acknowledging the lack of published data supporting either long-term or short-term treatment durations. The medical literature provides a compelling rationale for the use of longer regimens for some patients. While more research is needed, treatment should not be withheld from patients in the meantime. (See Evidence section for list of published clinical trials.) The IDSA does not recommend long-term antibiotic therapy for patients with chronic Lyme disease because of a lack of published data supporting its use. (See Evidence section for list of published clinical trials.)
Primary concern regarding misdiagnosis The under-diagnosis of Lyme may lead to untreated chronic, persistent infection resulting in severe disability and possibly even death. The over-diagnosis of Lyme may lead to the unnecessary use of antibiotics resulting in side effects (most commonly nausea), and rarely, complications from intravenous antibiotics. There are also concerns about the cost of antibiotic treatment.
Risk-benefit analysis The potential harm in letting a persistent Lyme infection go untreated far outweighs the potential side-effects of long-term antibiotic use. This therapy is generally safe when administered by skilled clinicians who take appropriate precautions. If it is considered safe enough for acne patients, its use is certainly justified for chronic Lyme patients. Since chronic Lyme infection is presumed not to exist, any potential adverse effects of long-term antibiotic therapy outweigh the (non-existent) benefits.
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The CDC case definition
Confusion about the significance of the U.S. Centers for Disease Control Case Definition for Lyme disease lies at the heart of the controversy over diagnosis. The CDC has explicitly stated that the following definition is meant to be used for surveillance purposes, not diagnostic purposes.[70][71]
CDC Case Definition for Lyme disease
Erythema migrans rash (at least 5 cm in diameter)
- OR -
Positive blood tests (ELISA followed by Western blot) AND one or more of the following manifestations:
Recurrent arthritis
Bell's Palsy or other cranial neuritis, radiculoneuropathy, lymphocytic meningitis, encephalomyelitis, or positive Lyme titer in CSF
2nd or 3rd degree heart block
A number of well-documented symptoms of chronic Lyme disease including encephalopathy[98][99][100] (manifested by memory loss, mood changes and sleep disturbance) are not part of the CDC case definition. Therefore clinicians using the CDC criteria for diagnostic purposes may miss some patients who have the disease.[101] Additionally, reliance on the CDC case definition for clinical purposes would result in the misdiagnosis of those with false-negative test results, a widely reported phenomenon (see Diagnosis).
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Testing
The debate over Lyme disease testing remains a heated one, with concern over both false-positives and false-negatives (see Diagnosis). Tests currently rely on indirect methods of detection (i.e. the body's immune system response), because it is very difficult to culture the bacteria directly from patients. Specific issues with regard to the testing controversy include the following:
Sensitivity of the CDC's testing protocol. Critics argue that the CDC's 2-tiered testing protocol (ELISA test, followed by confirmatory Western blot test if positive or equivocal) misses many patients who are infected. A study from the College of American Pathologists concluded that "these tests will not be useful as screening tests until their sensitivity is improved."[102]
Inadequate lab standardization. Standardization of testing has been found to be inadequate, with a high degree of interlaboratory variability.[72][102][103]
No diagnostic gold standard to determine sensitivity of tests in late disease. Without a diagnostic gold standard to identify those with chronic Lyme disease, circular reasoning becomes a problem in studies that evaluate the sensitivity of serologic tests for this population. Bias is unavoidable if subjects are selected by CDC criteria, since late-stage patients must have tested positive previously in order to qualify for a study. In a study cited by the CDC to defend the tests' validity, the authors acknowledge this risk of selection bias.[104]
False negative test results due to the following, particularly in late and chronic Lyme disease:
Immune system evasion by Borrelia burgdorferi. Intracellular sequestration, antigen variation, immune suppression, the formation of immune complexes, and predominance of cystic forms have all been cited as reasons for seronegativity in late and chronic Lyme disease (see Mechanisms of persistence section).
Positive test criteria is based on early Lyme disease. The CDC's criteria for a positive Western blot were developed based upon on a study of patients with early Lyme disease.[105] The serologic response of patients with late-stage Lyme disease was not analyzed and incorporated, despite that fact that such cases require a positive Western blot for diagnosis by CDC standards.
Specific markers for late-stage Lyme disease left out. Several highly specific antibody bands for Lyme (31-kDa and 34-kDa, corresponding to outer surface proteins A and B) were not included in the CDC criteria for a positive Western blot because they only appear late in the disease.[106] As a result, the vast majority of laboratories do not report these bands, even if they are positive. This is one reason some clinicians use laboratories that specialize in tick-borne disease, as they usually report all antibody bands.
Tests based on only one strain. Current tests at most laboratories are based on only one strain of Borrelia burgdorferi (the B31 strain is used in the U.S.) despite the fact that there are over three hundred strains worldwide and over one hundred in North America[107] (see #Strains). Several studies have found that this practice can lead to false-negatives[108][109] - another reason some clinicians use tick-borne disease specialty labs, which utilize multiple strains of Borrelia burgdorferi in the preparation of test kits.
Concern about false-positives. Many physicians with a conservative view of Lyme disease believe it is over-diagnosed and over-treated. One of the most widely cited studies concluded that 57% of patients diagnosed with Lyme in an endemic area did not actually have the disease.[110] Critics have responded with the following arguments:[111][112]
45% of those considered "misdiagnosed" in the study received positive results from another laboratory, and negative results from the authors' laboratory. However there was no independent evaluation, and no reason to assume that the authors' laboratory was superior.
The authors failed to consider the phenomenon of seronegative Lyme disease (false-negatives).[34][81][82][83][84]
Rather than consider the possibility of persistent infection, the authors considered treatment failure to be evidence of misdiagnosis, i.e. patients could not possibly have Lyme if they were not cured by a standard course of antibiotics. This was also taken as evidence that all patients with Lyme respond to treatment - another example of circular reasoning.
The authors excluded patients from a diagnosis of Lyme disease if they had psychiatric symptoms, despite the fact that Lyme can cause such symptoms.[101][113][114]
Testing positive after treatment. Because the tests measure antibodies to Borrelia burgdorferi and not the organism itself, it is theoretically possible to test positive even if the organism has been eradicated. All agree that no treatment is required in asymptomatic patients regardless of test results; however, controversy arises when a patient continues to have symptoms after a course of treatment. In this scenario, those who hold a conservative view believe the infection must have been eradicated by the treatment, and the positive test no longer indicates active infection but rather a persisting antibody response, regardless of the clinical picture. Those with a broader view of Lyme believe the evidence and clinical picture in this case most likely point to a persisting infection requiring further antibiotic treatment.
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Long-term antibiotic therapy
There is little concrete evidence either for or against the use of antibiotics for chronic Lyme disease, because only three such double-blind, placebo-controlled clinical trials have been funded to date by the U.S. National Institutes of Health, with conflicting results.
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Evidence from controlled studies
1) Klempner et al (2001).[85] One month of intravenous ceftriaxone followed by two months of low-dose oral doxycycline (or placebo) given to chronic Lyme patients with one or more of the following symptoms: musculoskeletal pain, cognitive impairment, radicular pain, paresthesias or dysesthesias.
No significant benefit found in physical or mental health. However critics maintain that the study contains serious methodological flaws (ILADS Position Paper) including the following:[93][115][116]
The dose of doxycycline used in the study (200 mg daily) is too low to penetrate the central nervous system; failure was to be expected at this dose.
This was not in actuality a "long-term" trial as described, but rather a short-term trial of ceftriaxone, because of the sequential use of two antibiotics with different modes of action (and with the second antibiotic inadequately dosed). Since patients had failed similar treatment previously, it was unlikely that this regimen would produce any benefit.
Cognitive status was measured only subjectively using patient surveys (the SF-36), making it impossible to assess changes in executive functioning often seen in chronic Lyme patients. Objective neuropsychiatric testing results were not reported.
The authors’ statement that not a single one of 1800 patients screened were PCR positive for Lyme[117] is puzzling in light of numerous studies documenting persisting infection in patients who remain symptomatic after treatment.[28][29][30][31][32][35][56][118][119] Either selection bias resulted in a study population that was not representative of chronic Lyme patients (and thus the study is not generalizable), or the accuracy of the authors’ PCR methods is in doubt. In either scenario, the authors' conclusion that chronic Lyme patients do not suffer from persistent infection is invalid.
2) Krupp et al (2003).[120] Four weeks of intravenous ceftriaxone or placebo given to chronic Lyme patients with "persistent severe fatigue".
Significant improvement in fatigue. The treatment effect remained even after adjusting for age, pain, history of psychiatric disorder and depressive symptoms.
No improvement in cognitive symptoms. However the only symptom criteria for entrance into the study was severe fatigue. The authors acknowledge that the patients’ cognitive deficits at baseline were mild, which may explain the lack of treatment effect on cognition.
3) Fallon et al (not yet published).[121][122] Results presented on October 22, 2004 at the Columbia University/Lyme Disease Association Conference in Rye, NY (Press release). Ten weeks of intravenous ceftriaxone or placebo given to chronic Lyme patients with ongoing memory impairment.
Significant improvement in both physical and cognitive symptoms. Physical improvement was maintained at 12 weeks followup. Patients relapsed on cognitive measures at followup, suggesting longer regimens may be required.
Improvements in cognitive functioning correlated with changes in blood flow to the brain as measured by SPECT scans.
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Evidence from uncontrolled studies
While the results of placebo-controlled studies are mixed, several uncontrolled studies suggest that longer durations of antibiotic treatment may be beneficial for chronic Lyme disease.[32][123][124][125][126][127]
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Implications for treatment
The widely publicized results of the Klempner study have led some to proclaim that long-term antibiotics are unhelpful for patients with chronic Lyme disease, warning patients and clinicians that the evidence does not support their use. Others see this as an abuse of the concept of evidence-based medicine. They argue that treatment failure in one questionably designed clinical trial does not justify such warnings in light of other evidence, and that withholding antibiotic treatment is unethical in the face of patient suffering. Since the optimal choice of antibiotic(s) and treatment duration is unknown and may vary by strain, many believe additional research on chronic Lyme disease is needed before strict treatment recommendations can be issued.
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Prevention
The best prevention involves avoiding areas in which ticks are found and can reduce the probability of contracting Lyme disease. Other good prevention practices include wearing clothing that covers the entire body when in a wooded area; using mosquito/tick repellent; after exposure to wooded areas, check all parts of the body (including hair) for ticks.
A method of protecting your whole property - Damminix - is also cited. It consists of biodegradable cardboard tubes stuffed with permethrin-treated cotton and works in the following way: Mice collect the cotton for lining their nests. The pesticide on the cotton kills any immature ticks that are feeding on the mice. It is important to put the tubes where mice will find them, such as in dense, dark brush or at the base of a log; mice are unlikely to gather the cotton from an open lawn. Best results are obtained with regular applications early in the spring and again in late summer. The more neighbors who also use Damminix, the better. Damminix appears to help control tick populations, particularly in the year following initial use. Note that it is not effective on the West Coast. [128]
A vaccine against a North American strain of the spirochetal bacteria was available between 1998 and 2002. When taking it off the market, the manufacturer cited poor sales, though some people believe that the actual reason was that the vaccine was not safe or effective at all.[129]
The advice of the UK's Hospital for Tropical Diseases is that significant exposure (an attached mite for more than twelve hours) should be managed, as in America & Germany, with Doxycycline 100 mg twice a day for three days.[130] Patients should be advised to report any Erythema migrans over the subsequent two to six weeks. If there should be suspicion of disease, then a course of Doxycycline should be immediately given for ten days; without awaiting serology tests which only yield positive results after an interval of one to two months.
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Proper Removal of Ticks
There are many urban legends about the proper and effective method to remove a tick. One legend states that something hot (cigarette; burnt match) should be applied to the back of the tick, which causes the tick to remove its head from the victim. It further states that ticks "screw" their heads into their victims; therefore, one must "unscrew" the head. These legends are incorrect and dangerous. Proper removal of a tick: use a pair of tweezers, grab the head of the tick near the mouth, and pull it out. The area should then be disinfected with rubbing alcohol or hydrogen peroxide. If the head is not completely removed, local infection of the person/animal bitten may result, and a doctor should be consulted (or a veterinarian if the tick was removed from a pet).
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Ecology
Urbanization and other anthropomorphic behaviors can be implicated in the spread of the Lyme disease into the human population. In many areas, expansion of suburban neighborhoods has led to the gradual deforestation of surrounding wooded areas and increasing "border" contact between humans and tick-dense areas. Human expansion has also resulted in a gradual reduction of the predators that normally hunt deer as well as mice, chipmunks and other small rodents--the primary reservoirs for Lyme disease. As a consequence of increased human contact with host and vector, the likelihood of transmission to Lyme residents has greatly increased and precipitated the emerging cases (McMichael 2004).[citation needed]
The deer tick (Ixodes scapularis, the primary vector in the northeastern U.S.) has a two-year life cycle, first progressing from larva to nymph, and then from nymph to adult. The tick feeds only once at each stage. In the fall, large acorn forests attract deer as well as mice, chipmunks and other small rodents infected with B. burgdorferi. During the following spring, the ticks lay their eggs. The rodent population then "booms." Tick eggs hatch into larvae, which feed on the rodents; thus the larvae acquire infection from the rodents. (Note: At this stage, it is proposed that tick infestation may be controlled using acaricides (miticide). A commercial method is to provide nesting material soaked in permethrin (Damminix).) The infected larvae molt into nymphs. These infected nymphs transmit the majority of Lyme infection to humans, feeding on humans and small animals from spring through summer. The nymphs then molt into adults, which feed on larger animals such as deer in the fall and early spring. Adult ticks may also transmit disease to humans. After feeding, female adult ticks lay their eggs on the ground, and the cycle is complete. Note: on the west coast, Lyme disease is spread by the western black-legged tick (Ixodes pacificus), which has a different life cycle.
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Epidemiology
The number of reported cases of the disease have been increasing, as are endemic regions in North America. Lyme disease is reported in nearly every state in the U.S., but there are concentrated areas in the north-east, mid-Atlantic states, Wisconsin, Minnesota, and northern California. Lyme disease is also endemic to Europe and Asia.
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History
Lyme disease is named after a cluster of cases that occurred in and around Old Lyme and Lyme, Connecticut in 1975. Before 1975, elements of Borrelia infection were also known as Tickborne meningopolyneuritis, Garin-Bujadoux syndrome, Bannwarth syndrome or sheep tick fever.
The disease was first documented as a skin rash in Europe in 1883. Over the years, researchers there identified additional features of the disease, including an unidentified pathogen, its response to penicillin, the role of the Ixodes tick (black legged tick) as its vector, and other symptoms including those affecting the central nervous system.
In the U.S., Borrelia burgdorferi has been isolated in the skin of white-footed mice in museum specimens that date back to the 1870s in Massachusetts, but researchers were unaware of the organism's existence until the 1970s. Interest in tick-borne infections in the U.S. began with the first report of tick-borne relapsing fever in 1905, and the discovery of the wood tick's role as a vector of Rocky Mountain spotted fever the following year. However, the full syndrome now known as Lyme disease was not recognized until a cluster of cases originally thought to be juvenile rheumatoid arthritis was identified in three towns in southeastern Connecticut in 1977. Two of these towns, Lyme and Old Lyme, gave the disease its popular name.
In 1982 a novel spirochete was isolated and cultured from the midgut of Ixodes ticks, and subsequently from patients with Lyme disease. The infecting agent was first identified by Jorge Benach, and soon after isolated by Willy Burgdorfer, a scientist at the National Institutes of Health, who specialized in the study of spirochete microorganisms. The spirochete was named Borrelia burgdorferi in his honor. Burgdorfer was the partner in the successful effort to culture the spirochete, along with Alan Barbour.
2006-07-02 08:03:58
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answer #1
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answered by Linda 7
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