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Lyme disease

*** Shopping-Tip: Lyme disease
see Lyme disease {{DiseaseDisorder infobox | Name = Lyme disease | ICD10 = {{ICD10|A|69|2|a|65}} | ICD9 = {{ICD9|088.81}} | ICDO = | Image = Adult deer tick.jpg | Caption = Nymphal and adult deer ticks can be carriers of Lyme disease. Nymphs are about the size of a poppy seed. | OMIM = | MedlinePlus = 001319 | eMedicineSubj = med | eMedicineTopic = 1346| DiseasesDB = 1531 | }} {{Wikispecies|Borrelia}} '''Lyme disease''' or '''Lyme borreliosis''' is a infectious diseases infectious tick-borne disease, caused by Borrelia burgdorferi, a gram-negative spirochete bacterium. The causitive agent Borrelia burgdorferi, was first identified by Willy Burgdorfer, a tick-born disease expert at Rocky Mountain Labs, Montana. Lyme disease is named after a cluster of cases that occurred in and around Old Lyme and Lyme, Connecticut Lyme, Connecticut in 1975. Before 1975, elements of ''Borrelia'' infection were also known as "tick-borne meningopolyneuritis", Garin-Bujadoux syndrome, Bannwarth syndrome or sheep tick fever. It is transmitted to humans by the bite of infected ticks.

History
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 (wood tick) as its vector, and symptoms that included not only the rash but additional ones that affected e.g. the nervous system. Researchers in the US had been aware of tick infections since the early 1900s. For example, an infection called tick relapsing fever was reported in 1905, and the wood tick, which carries an agent that causes Rocky Mountain spotted fever, was identified soon after. However, the full syndrome now known as Lyme disease, was not identified until a cluster of cases thought to be juvenile rheumatoid arthritis occurred in three towns in southeastern Connecticut, in the United States. Two of these towns, Lyme and Old Lyme, Connecticut 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. ''Borrelia burgdorferi'' has been isolated in skin specimens of white-footed mice in museum specimens as far back as the 1870s in Massachusetts.

Microbiology
The disease is caused by the parasite ''Borrelia'', which has well over three hundred known genomic strains but is usually cultured as ''Borrelia burgdorferi'', ''Borrelia afzelii'' or ''Borrelia garinii''. Different ''Borrelia'' strains are predominant in Europe and North America. The disease has been found to be transmitted to humans by the bite of infected ''Ixodes'' ticks. Not all ticks carry or can transmit this particular disease. ''Borrelia burgdorferi'' resembles other spirochetes in that it is a highly specialized, motile, two-membrane, spiral-shaped bacterium which lives primarily as an extracellular pathogen. One of the most striking features of ''Borrelia burgdorferi'' as compared with other eubacteria is its unusual genome, which includes a linear chromosome approximately one megabase in size and numerous linear and circular plasmids. Genetic exchange, including plasmid transfers, contributes to the pathogenicity of the organism.{{cite journal | author=Qiu WG, Schutzer SE, Bruno JF, Attie O, Xu Y, Dunn JJ, Fraser CM, Casjens SR, Luft BJ | title=Genetic exchange and plasmid transfers in Borrelia burgdorferi sensu stricto revealed by three-way genome comparisons and multilocus sequence typing | journal=Proc Natl Acad Sci U S A | year=2004 | pages=14150-5 | volume=101 | issue=39 | id=PMID 15375210 [http://www.pnas.org/cgi/reprint/101/39/14150.pdf Full PDF]}} Long-term culture of ''Borrelia burgdorferi'' results in a loss of some plasmids and changes in expressed protein profiles. Associated with the loss of plasmids is a loss in the ability of the organism to infect laboratory animals, suggesting that the plasmids encode key genes involved in virulence. ''Borrelia burgdorferi'' may persist in humans and animals for months or years following initial infection, despite a robust humoral immune response. ''Borrelia burgdorferi'' is susceptible to antibiotics in vitro in vitro. However, there are contradictory reports as to the efficacy of antibiotics in vivo in vivo. While prompt treatment leads to full recovery in terms of signs and symptoms in the majority of cases, questions have arisen in regard to complete eradication of the bacterium from the host. Numerous studies have demonstrated persistence of infection despite repeated courses of antibiotic therapy.{{cite journal | author=Nocton JJ, Dressler F, Rutledge BJ, Rys PN, Persing DH, Steere AC | title=Detection of Borrelia burgdorferi DNA by polymerase chain reaction in synovial fluid from patients with Lyme arthritis | journal=N Engl J Med | year=1994 | pages=229-34 | volume=330 | issue=4 | id=PMID 8272083 [http://content.nejm.org/cgi/content/abstract/330/4/229 Full Text]}}{{cite journal | author=Bayer ME, Zhang L, Bayer MH | title=Borrelia burgdorferi DNA in the urine of treated patients with chronic Lyme disease symptoms. A PCR study of 97 cases | journal=Infection | year=1996 | pages=347-53 | volume=24 | issue=5 | id=PMID 8923044}}{{cite journal | author=Preac-Mursic V, Weber K, Pfister HW, Wilske B, Gross B, Baumann A, Prokop J | title=Survival of Borrelia burgdorferi in antibiotically treated patients with Lyme borreliosis | journal=Infection | year=1989 | pages=355-9 | volume=17 | issue=6 | id=PMID 2613324}}{{cite journal | author=Pfister HW, Preac-Mursic V, Wilske B, Schielke E, Sorgel F, Einhaupl KM | title=Randomized comparison of ceftriaxone and cefotaxime in Lyme neuroborreliosis | journal=J Infect Dis | year=1991 | pages=311-8 | volume=163 | issue=2 | id=PMID 1988514}}{{cite journal | author=Oksi J, Marjamaki M, Nikoskelainen J, Viljanen MK | title=Borrelia burgdorferi detected by culture and PCR in clinical relapse of disseminated Lyme borreliosis | journal=Ann Med | year=1999 | pages=225-32 | volume=31 | issue=3 | id=PMID 10442678}}{{cite journal | author=Hudson BJ, Stewart M, Lennox VA, Fukunaga M, Yabuki M, Macorison H, Kitchener-Smith J | title=Culture-positive Lyme borreliosis | journal=Med J Aust | year=1998 | pages=500-2 | volume=168 | issue=10 | id=PMID 9631675}}{{cite journal | author=Lawrence C, Lipton RB, Lowy FD, Coyle PK | title=Seronegative chronic relapsing neuroborreliosis | journal=Eur Neurol | year=1995 | pages=113-7 | volume=35 | issue=2 | id=PMID 7796837}}

Transmission

Transmission by ticks
In Europe, ''Ixodes ricinus'', known commonly as the sheep tick, castor bean tick, or European castor bean tick is the transmitter. On the east coast of North America, ''Ixodes scapularis'' (black-legged tick or deer tick) has been identified as the key to the disease's spread. On the west coast, the tick responsible for spread of the disease is ''Ixodes pacificus'' The number of reported cases of the disease have been increasing, as are endemic regions in the United States. Lyme disease is reported in nearly every state in the U.S., but there are concentrated areas in the northeast, mid-Atlantic states, Wisconsin, Minnesota, and northern California. Lyme disease is endemic to Europe and Asia. The longer the duration of tick attachment, the greater the risk of disease transmission. Even short-term attachment can result in transmission of the disease. Also, improper tick removal can result in early disease transmission so it is very important to remove a tick properly.

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 it's 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, and pull it out. 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).

Lyme Disease and Life Cycle of East Coast Tick
In the fall, large acorn forests attract deer and mice infected with ''B. burgdorferi''. During the following spring, the ticks lay their eggs. The mouse population then "booms." Tick eggs hatch into larvae, which feed on the mice, thus infecting the larvae. The infected larvae molt into "nymphs" (this is the ticks' "juvenile form"). Infected nymphs feed on humans from spring through summer, thus transmitting the bacteria to people. ''Note: on the west coast, Lyme disease is spread by the western black-legged tick, which has a different life cycle.''

Congenital Lyme disease
Lyme disease can be transmitted from an infected mother to fetus through the placenta during pregnancy, possibly resulting in stillbirth.{{cite journal | author=MacDonald AB | title=Gestational Lyme borreliosis. Implications for the fetus | journal=Rheum Dis Clin North Am | year=1989 | pages=657-77 | volume=15 | issue=4 | id=PMID 2685924}}{{cite journal | author=Schlesinger PA, Duray PH, Burke BA, Steere AC, Stillman MT | title=Maternal-fetal transmission of the Lyme disease spirochete, Borrelia burgdorferi | journal=Ann Intern Med | year=1985 | pages= 67-8 | volume=103 | issue=1 | id=PMID 4003991}} The risk of transmission is minimized if the mother receives prompt antibiotic treatment, though physicians disagree as to the duration of treatment required.

Other modes of transmission
There is also some anecdotal, largely unconfirmed evidence of Sexually-transmitted infection sexual transmission.

Symptoms
Lyme disease has many signs and symptoms, but skin signs, arthritis and/or various neurology neurological symptoms are often present. Like syphilis, the symptoms frequently seem to resolve, yet the disease progresses. Conventional therapy is with antibiotics. People who suspect they have been exposed to Lyme disease should consult a doctor with knowledge of the disease immediately.

Acute (early) symptoms that may occur
*Erythema migrans rash (EM) - Contrary to popular belief, the characteristic "bull's-eye" rash with central clearing is ''not'' the most common form. Rashes that are homogeneously red are seen more frequently.{{cite journal | author=Smith RP, Schoen RT, Rahn DW, Sikand VK, Nowakowski J, Parenti DL, Holman MS, Persing DH, Steere AC | title=Clinical characteristics and treatment outcome of early Lyme disease in patients with microbiologically confirmed erythema migrans | journal=Ann Intern Med | year=2002 | pages=421-8 | volume=136 | issue=6 | id=PMID 11900494 [http://www.annals.org/cgi/reprint/136/6/421.pdf Full PDF]}} {{cite journal | author=Edlow JA | title=Erythema migrans | journal=Med Clin North Am | year=2002 | pages=239-60 | volume=86 | issue=2 | id=PMID 11982300}} Multiple painless EM rashes may occur, indicating disseminated infection. *fever *malaise *fatigue (physical) fatigue *headache *myalgia muscle and arthralgia joint aches in large joints *sore throat *sinus infection *facial paralysis - usually associated with Lyme meningitis or Rocky Mountain spotted fever *palpitations The incubation period from infection to the onset of symptoms is usually 1–2 weeks, but can be much shorter (a couple of days), or even as long as one month.

Chronic (late) symptoms
*meningitis *neuropathy - numbness, tingling, burning, itching, oversensitivity *muscle and joint aches *tremor, twitches *Bell's palsy *vision problems (double vision) *nausea or vomiting *immune suppression *myalgia *fatigue *hallucinations *short-term memory loss *adrenal disorders *severe startle reaction *seizures *sensitivity to light, motion *vestibular symptoms (balance; inner/middle ear) *hyperacusis (severe sensitivity to sound & vibration) *tachycardia (too-rapid heartbeat) *depression (mood) depression *panic attacks *arthritis *cardiac arrythmias The late symptoms of Lyme disease can appear months from infection. Fatality can occur when the spirochete enters brain fluids and causes meningitis, or due to conductivity defects in the heart. Lyme disease is sometimes misdiagnosed as multiple sclerosis, rheumatoid arthritis, fibromyalgia, chronic fatigue syndrome (CFS), or other (mainly autoimmune and neurological) diseases, which leaves the infection untreated and allows it to further penetrate the organism. Many of these conditions may also be misdiagnosed as Lyme disease, e.g. due to false-positive Lyme serology. However it should be noted that chronic fatigue syndrome (CFS) is by definition a diagnosis of exclusion, meaning it would be inaccurate to say that a patient does not have Lyme ''because'' he or she has CFS. The substantial overlap in symptomology between Lyme and CFS makes this a crucial point.{{cite journal | author=Donta ST | title=Late and chronic Lyme disease | journal=Med Clin North Am | year=2002 | pages=341-9, vii | volume=86 | issue=2 | id=PMID 11982305 [http://www.immunesupport.com/library/print.cfm?ID=3579&t=CFIDS_FM Reprinted Full Text]}}

Diagnosis
The most reliable method of diagnosing Lyme disease is a clinical exam by an experienced practitioner. The EM rash, which does not occur in all cases, is considered sufficient to make a diagnosis of Lyme disease and prompt treatment without further testing. In fact because of the undisputed high rate of false negatives during the early stage of the disease (often before a sufficient antibody response has been established), it is recommended that tests ''not'' be performed when a patient has an EM rash.{{cite journal | author=Hofmann H | title=Lyme borreliosis--problems of serological diagnosis | journal=Infection | year=1996 | pages=470-2 | volume=24 | issue=6 | id=PMID 9007597}} The serology serological laboratory tests available are the Western blot and ELISA. In the two-tiered protocol recommended by the U.S. Centers for Disease Control, the ELISA is performed first, and if it is positive or equivocal, a Western blot is then performed to support the diagnosis. The reliability of testing in diagnosis remains #Testing controversial. False-positive results for the Western blot IgM are described with varicella-zoster virus,{{cite journal | author=Feder HM Jr, Gerber MA, Luger SW, Ryan RW | title=False positive serologic tests for Lyme disease after varicella infection | journal=N Engl J Med | year=1991 | pages=1886-7 | volume=325 | issue=26 | id=PMID 1961232}}{{cite journal | author=Woelfle J, Wilske B, Haverkamp F, Bialek R | title=False-positive serological tests for Lyme disease in facial palsy and varicella zoster meningo-encephalitis | journal=Eur J Pediatr | year=1998 | pages=953-4 | volume=157 | issue=11 | id=PMID 9835449}} Epstein-Barr virus,{{cite journal | author=Goossens HA, Nohlmans MK, van den Bogaard AE | title=Epstein-Barr virus and cytomegalovirus infections cause false-positive results in IgM two-test protocol for early Lyme borreliosis | journal=Infection | year=1999 | pages=231 | volume=27 | issue=3 | id=PMID 10378140}}{{cite journal | author=Berardi VP, Weeks KE, Steere AC | title=Serodiagnosis of early Lyme disease: analysis of IgM and IgG antibody responses by using an antibody-capture enzyme immunoassay | journal=J Infect Dis | year=1988 | pages=754-60 | volume=158 | issue=4 | id=PMID 3049839}} cytomegalovirus. and herpes simplex type virus 2.{{cite journal | author=Strasfeld L, Romanzi L, Seder RH, Berardi VP | title=False-positive serological test results for Lyme disease in a patient with acute herpes simplex virus type 2 infection | journal=Clin Infect Dis | year=2005 | pages=1826-7 | volume=41 | issue=12 | id=PMID 16288417}} However studies show the Western blot IgM has a specificity of 94-96% for patients with symptoms suggestive of Lyme disease.{{cite journal | author=Engstrom SM, Shoop E, Johnson RC | title=Immunoblot interpretation criteria for serodiagnosis of early Lyme disease | journal=J Clin Microbiol | year=1995 | pages=419-27 | volume=33 | issue=2 | id=PMID 7714202 [http://jcm.asm.org/cgi/reprint/33/2/419.pdf Full PDF]}}{{cite journal | author=Sivak SL, Aguero-Rosenfeld ME, Nowakowski J, Nadelman RB, Wormser GP | title=Accuracy of IgM immunoblotting to confirm the clinical diagnosis of early Lyme disease | journal=Arch Intern Med | year=1996 | pages= 2105-9 | volume=156 | issue=18 | id=PMID 8862103}} False-negative test results have been widely reported in both early and late disease.{{cite journal | author=Coyle PK, Schutzer SE, Deng Z, Krupp LB, Belman AL, Benach JL, Luft BJ | title=Detection of Borrelia burgdorferi-specific antigen in antibody-negative cerebrospinal fluid in neurologic Lyme disease | journal=Neurology | year=1995 | pages=2010-5 | volume=45 | issue=11 | id=PMID 7501150}}{{cite journal | author=Paul A | title=[Arthritis, headache, facial paralysis. Despite negative laboratory tests Borrelia can still be the cause] | journal=MMW Mortschr Med | year=2001 | pages=17 | volume=143 | issue=6 | id=PMID 11247357}}{{cite journal | author=Pikelj F, Strle F, Mozina M | title=Seronegative Lyme disease and transitory atrioventricular block | journal=Ann Intern Med | year=1989 | pages=90 | volume=111 | issue=1 | id=PMID 11247357}}{{cite journal | author=Oksi J, Uksila J, Marjamaki M, Nikoskelainen J, Viljanen MK | title=Antibodies against whole sonicated Borrelia burgdorferi spirochetes, 41-kilodalton flagellin, and P39 protein in patients with PCR- or culture-proven late Lyme borreliosis | journal=J Clin Microbiol | year=1995 | pages=2260-4 | volume=33 | issue=9 | id=PMID 7494012 [http://jcm.asm.org/cgi/reprint/33/9/2260.pdf Full PDF]}} Polymerase chain reaction (PCR) tests for Lyme disease may also be available to the patient. A PCR test attempts to detect the genetic material (DNA) of the Lyme disease spirochete, whereas the Western blot and ELISA tests look for antibodies to the organism. PCR tests are rarely susceptible to false-positive results but can often show false-negative results.

Prognosis
Prompt treatment is usually curative. The severity and treatment of Lyme disease can be complicated due to late diagnosis, failure of antibiotic treatment, simultaneous infection with other tick-borne diseases including ehrlichiosis, babesiosis, and bartonella, and immune suppression in the patient. The disease is rarely fatal in and of itself.

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 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. Safety/Efficacy concerns re: Lyme vaccine: LYMErix [http://www.lymeinfo.net/vaccine2.html Controversy] 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 100mg twice a day for three days.Antibiotic Prophylaxis After Tick Bite For Prevention Of Lyme Disease [http://www.geocities.com/HotSprings/Oasis/6455/prophylaxis-biblio.html An Annotated Bibliography] Patients should be advised to report any Erythema Migrains 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.

Treatment
Traditional treatment of acute Lyme disease usually consists of a minimum two-week to one-month course of antibiotics. 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. If the blood/brain barrier has been crossed and the spirochetes have reached the brain, oral antibiotics are not curative; however studies suggest that long-term oral therapy may still be helpful.{{cite journal | author=Donta ST | title=Macrolide therapy of chronic Lyme Disease | journal=Med Sci Monit | year=2003 | pages=PI136-42 | volume=9 | issue=11 | id=PMID 14586290}}{{cite journal | author=Donta ST | title=Tetracycline therapy for chronic Lyme disease | journal=Clin Infect Dis | year=1997 | pages=Suppl 1:S52-6 | volume=25 | id=PMID 9233665}} 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, such as those outlined at [http://www.lymephotos.com/ Lyme Photos]. 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.

The Lyme controversy
Though 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 medical practitioners 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 medical practitioners, patients and advocates who believe that Lyme disease is under-diagnosed, that available blood tests are unreliable, and that extended antibiotic treatment is often necessary.{{cite journal | author=Stricker RB, Lautin A, Burrascano JJ | title=Lyme Disease: The Quest for Magic Bullets | journal=Chemotherapy | year=2006 | pages=53-59| volume=52 | issue=2 | id=PMID 16498239}}{{cite journal | author=Phillips SE, Harris NS, Horowitz R, Johnson L, Stricker RB | title=Lyme disease: scratching the surface | journal=Lancet | year=2005 | pages=1771 | volume=366 | issue=9499 | id=PMID 16298211 [http://www.canlyme.com/lyme_scratching_the_surface_05.html Reprinted Full Text]}}{{cite web | author=Phillips S, Bransfield R, Sherr V, Brand S, Smith H, Dickson K, and Stricker R | year=2003 | title=Evaluation of antibiotic treatment in patients with persistent symptoms of Lyme disease: an ILADS position paper | format=PDF | work=International Lyme and Associated Diseases Society | url=http://www.ilads.org/files/position2.pdf | accessdate=2006-03-15}}{{cite journal | author=Harvey WT, Salvato P | title='Lyme disease': ancient engine of an unrecognized borreliosis pandemic? | journal=Med Hypotheses | year=2003 | pages=742-59 | volume=60 | issue=5 | id=PMID 12710914 [http://www.ilads.org/files/harvey.pdf Full PDF]}}

The CDC case definition
In the United States, confusion over the application of the Centers for Disease Control and Prevention CDC's case definition for Lyme disease lies at the heart of the controversy. The Centers for Disease Control and Prevention CDC has explicitly stated that the definition is meant for ''Clinical surveillance surveillance'' purposes only, and is "not intended to be used in clinical diagnosis."{{cite web | title=Lyme Disease (Borrelia burgdorferi): 1996 Case Definition | work=CDC Case Definitions for Infectious Conditions under Public Health Surveillance | url=http://www.cdc.gov/epo/dphsi/casedef/lyme_disease_current.htm | accessdate=2006-03-15}}{{cite web | title=CDC Testimony before the Connecticut Department of Health and Attorney General's Office | work=CDC's Lyme Prevention and Control Activities | url=http://www.hhs.gov/asl/testify/t040129.html | accessdate=2006-03-15}} ;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{{cite journal | author=Fallon BA, Keilp J, Prohovnik I, Heertum RV, Mann JJ | title=Regional cerebral blood flow and cognitive deficits in chronic lyme disease | journal=J Neuropsychiatry Clin Neurosci | year=2003 | pages=326-32 | volume=15 | issue=3 | id=PMID 12928508 [http://neuro.psychiatryonline.org/cgi/reprint/15/3/326.pdf Full PDF]}} 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.{{cite journal | author=Fallon BA, Kochevar JM, Gaito A, Nields JA | title=The underdiagnosis of neuropsychiatric Lyme disease in children and adults | journal=Psychiatr Clin North Am | year=1998 | pages=693-703, viii | volume=21 | issue=3 | id=PMID 9774805}} Additionally, this practice may result in the misdiagnosis of those with false-negative test results, a widely reported phenomenon documented #Diagnosis above.

Testing
The debate over testing remains a heated one, with concern over both false-positive false-positives and false-negative false-negatives (see #Diagnosis above). Tests currently rely on indirect methods of detection (i.e. the body's immune system response), because it is very difficult to culture the Lyme bacteria directly from patients. Specific issues with regard to the testing controversy include the following: * ''Sensitivity (tests) 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) misses many patients with the disease, leading to false negative false negatives. A study from the College of American Pathologists concluded that "these tests will not be useful as screening tests until their sensitivity (tests) sensitivity is improved."{{cite journal | author=Bakken LL, Callister SM, Wand PJ, Schell RF | title=Interlaboratory comparison of test results for detection of Lyme disease by 516 participants in the Wisconsin State Laboratory of Hygiene/College of American Pathologists Proficiency Testing Program | journal=J Clin Microbiol | year=1997 | pages=537-43 | volume=35 | issue=3 | id=PMID 9041384 [http://jcm.asm.org/cgi/reprint/35/3/537.pdf Full PDF]}} * ''Inadequate lab standardization.'' Standardization of testing has been found to be inadequate, with a high degree of interlaboratory variability.{{cite journal | author=Bakken LL, Case KL, Callister SM, Bourdeau NJ, Schell RF | title=Performance of 45 laboratories participating in a proficiency testing program for Lyme disease serology | journal=JAMA | year=1992 | pages=891-5 | volume=268 | issue=7 | id=PMID 1640618}}{{cite journal | author=Brown SL, Hansen SL, Langone JJ | title=Role of serology in the diagnosis of Lyme disease | journal=JAMA | year=1999 | pages=62-6 | volume=282 | issue=1 | id=PMID 10404913}} * ''No gold standard (test) gold standard for evaluation of tests.'' Without a diagnostic gold standard to identify those with late-stage or chronic Lyme, circular reasoning becomes a problem in studies that evaluate the Sensitivity (tests) sensitivity of serology serologic tests for this population. Selection 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 one of few studies that included late-stage patients with neurological symptoms (a study cited by the CDC to defend the validity of the tests), the authors acknowledge this risk of selection bias.{{cite journal | author=Bacon RM, Biggerstaff BJ, Schriefer ME, Gilmore RD Jr, Philipp MT, Steere AC, Wormser GP, Marques AR, Johnson BJ | title=Serodiagnosis of Lyme disease by kinetic enzyme-linked immunosorbent assay using recombinant VlsE1 or peptide antigens of Borrelia burgdorferi compared with 2-tiered testing using whole-cell lysates | journal=J Infect Dis | year=2003 | pages=1187-99 | volume=187 | issue=8 | id=PMID 12695997}} * ''Positive test criteria is based on early Lyme.'' The CDC's criteria for a positive Western blot were developed based upon on a study of patients with ''early'' Lyme disease.{{cite journal | author=Dressler F, Whalen JA, Reinhardt BN, Steere AC | title=Western blotting in the serodiagnosis of Lyme disease | journal=J Infect Dis | year=1993 | pages=392-400 | volume=167 | issue=2 | id=PMID 8380611}} The Serology serologic response of patients with late-stage 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 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.{{cite journal | author=Ma B, Christen B, Leung D, Vigo-Pelfrey C | title=Serodiagnosis of Lyme borreliosis by western immunoblot: reactivity of various significant antibodies against Borrelia burgdorferi | journal=J Clin Microbiol | year=1992 | pages=370-6 | volume=30 | issue=2 | id=PMID 1537905 [http://www.pubmedcentral.gov/picrender.fcgi?artid=265062&blobtype=pdf Full PDF]}} 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 (biology) strain of ''Borrelia burgdorferi'' (the B31 strain is used in the U.S.) despite the fact that there are over three hundred strain (biology) strains worldwide and over one hundred in North America.{{cite web | title=List of 321 Borrelia burgdorferi (Bb) strains from NIH/NLM/NCBI database as of 22 June 2001 | work=Art Doherty's Lots of Links on Lyme disease | url=http://www.geocities.com/HotSprings/Oasis/6455/bb-strains.txt | accessdate=2006-03-18}} Several studies have found that this practice can lead to false-negative false-negatives.{{cite journal | author=Kaiser R | title=False-negative serology in patients with neuroborreliosis and the value of employing of different borrelial strains in serological assays | journal=J Med Microbiol | year=2000 | pages=911-5 | volume=49 | issue=10 | id=PMID 11023188 [http://jmm.sgmjournals.org/cgi/reprint/49/10/911.pdf Full PDF]}}{{cite journal | author=Hauser U, Wilske B | title=Enzyme-linked immunosorbent assays with recombinant internal flagellin fragments derived from different species of Borrelia burgdorferi sensu lato for the serodiagnosis of Lyme neuroborreliosis | journal=Med Microbiol Immunol (Berl) | year=1997 | pages=145-51 | volume=186 | issue=2-3 | id=PMID 9403843}} - another reason some clinicians use tick-borne disease specialty labs, which use multiple strains of ''Borrelia burgdorferi'' in the preparation of test kits. * ''Testing positive after treatment.'' Because the tests measure antibodies to ''Borrelia burgdorferi'' and not the organism itself, it is possible to test positive even after 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 who take a broader view of Lyme believe the evidence and clinical picture most likely point to a #Microbiology persisting infection requiring further antibiotic treatment. * ''Concern about false-positive false-positives.'' Many physicians with a conservative view of Lyme 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.{{cite journal | author=Steere AC, Taylor E, McHugh GL, Logigian EL | title=The overdiagnosis of Lyme disease | journal=JAMA | year=1993 | pages=1812-6 | volume=269 | issue=14 | id=PMID 8459513}} Critics have responded with the following arguments:{{cite journal | author=Burrascano JJ | title=The overdiagnosis of Lyme disease [Comment] | journal=JAMA| year=1993| pages=2682 | volume=270 | issue=22 | id=PMID 8192761}}{{cite web | author=Brenner C, Gabriel MC, O'Donnell JS | year=1993 | title=Response to "The overdiagnosis of Lyme disease" | work=The LymeNet Newsletter 1(10) | url=http://www2.lymenet.org/domino/nl.nsf/bce7787f4c707f10852565e3007b8c95/d417ac1dd5a672a2852565e200094f8d?OpenDocument | accessdate=2006-03-16}} ** 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-negative false-negatives).{{cite journal | author=Coyle PK, Schutzer SE, Deng Z, Krupp LB, Belman AL, Benach JL, Luft BJ | title=Detection of Borrelia burgdorferi-specific antigen in antibody-negative cerebrospinal fluid in neurologic Lyme disease | journal=Neurology | year=1995 | pages=2010-5 | volume=45 | issue=11 | id=PMID 7501150}}{{cite journal | author=Paul A | title=[Arthritis, headache, facial paralysis. Despite negative laboratory tests Borrelia can still be the cause] | journal=MMW Mortschr Med | year=2001 | pages=17 | volume=143 | issue=6 | id=PMID 11247357}}{{cite journal | author=Pikelj F, Strle F, Mozina M | title=Seronegative Lyme disease and transitory atrioventricular block | journal=Ann Intern Med | year=1989 | pages=90 | volume=111 | issue=1 | id=PMID 2735630}}{{cite journal | author=Oksi J, Uksila J, Marjamaki M, Nikoskelainen J, Viljanen MK | title=Antibodies against whole sonicated Borrelia burgdorferi spirochetes, 41-kilodalton flagellin, and P39 protein in patients with PCR- or culture-proven late Lyme borreliosis | journal=J Clin Microbiol | year=1995 | pages=2260-4 | volume=33 | issue=9 | id=PMID 7494012 [http://jcm.asm.org/cgi/reprint/33/9/2260.pdf Full PDF]}} ** Rather than consider the possibility of #Microbiology 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 Lyme diagnosis if they had psychiatric symptoms, despite the fact that Lyme may ''cause'' such symptoms.{{cite journal | author=Fallon BA, Nields JA, Burrascano JJ, Liegner K, DelBene D, Liebowitz MR | title=The neuropsychiatric manifestations of Lyme borreliosis | journal=Psychiatr Q | year=1992 | pages=95-117 | volume=63 | issue=1 | id=PMID 1438607}}{{cite journal | author=Sherr VT | title=Panic attacks may reveal previously unsuspected chronic disseminated lyme disease | journal=J Psychiatr Pract | year=2000| pages=352-6 | volume=6 | issue=6 | id=PMID 15990495}}

References

External links

- American Lyme Disease Foundation
- Lyme Disease Association
- Time for Lyme
- The Lyme Disease Foundation
- International Lyme and Associated Diseases Society
- Lyme Disease Medical Literature Summaries
- Lyme Disease Network
- Information on Lyme Disease
- Lyme Disease Articles and Information
- Lyme Disease Action
- Links to pictures of Lyme disease (Hardin MD/Univ of Iowa)
- Lyme Photos - A possible alternative treatment to Lyme disease
- The Lyme Disease Controversy - Columbia University Category:Infectious diseases Category:Zoonoses Category:Bacterial diseases cs:Lymeská borelióza da:Borreliose de:Lyme-Borreliose es:Enfermedad de Lyme fr:Borréliose ja:ライム病 nl:Lyme-ziekte pl:Borelioza pt:Doença de Lyme fi:Borrelioosi sv:Borrelia wa:Må d' Lyme zh:莱姆病

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