Diagnosis of Lyme Disease, Research Paper Example

Abstract

Lyme disease is a highly infectious tick-borne illness that is increasing in the number of cases across the United States.  Spread through tick bites, the causative agent Borrelia burgdorferi is a spiral organism in which causes several cardiac, joint, and neurological problems. The tick bite can rapidly spread to a bright red rash that can be fatal in most cases. The main purpose in conducting this research is to highlight the problems in which have been difficult for accurately identifying, monitoring, and subsequently treating Lyme disease in patients. Previous laboratory studies and Chemistry and Immunology data has shown that in diagnosing Lyme disease there is problem with the initial serological test used. The present serological test does not accurately diagnose the incoming number of patients that have been newly infected with the disease. The objectives that the current study investigates, offers alternatives to the common two-step approach in serological testing. With the increase in cases of Lyme disease, in which has doubled since 1991, research has focused on finding new ways to accurately detect the disease. There have been increasing numbers of alternative tests available that have been found to be more accurate and efficient in diagnosing and monitoring Lyme diseases in patients compared to the original serological test.  The current case study illustrates the alternative tests that are available. The results of the alternative tests suggest a breakthrough in the diagnosis and treatment in patients that suffer from Lyme disease.

Objectives

1. The perceived objectives of this case study is to introduce alternatives to the common two-step approach in serological testing for Lyme Disease due to the increase in cases since 1991.
2. The present serological testing does not accurately diagnose the incoming number of patients that have been newly infected with the disease.
3. The case study will investigate recent case studies and laboratory reports from the Immunology and Chemistry field.
4. The case study will analyze the newly introduced testing alternatives that have been found to be more efficient and more effective in diagnosing, monitoring, and providing options for treatment for patients with Lyme disease.

Introduction

Lyme disease was first identified over 30 years ago, and since its discovery has spread throughout the United States, and other cases around the world. Lyme disease is an infection that is caused by Borrelia burgdoeferi that is largely transmitted by ticks throughout areas of Eurasia and North America. According to information from the public health perspective is it one the major emerging diseases. The causative organism, Borrelia burgdorferi , causes erythema migrans (EM), an expanding red skin lesion. EM has been found to be associated with neurologic and cardiac abnormalities such as skin and neurologic manifestations and arthritis, that can persists for numerous year, and to a small percentage of patients become chronic. Since 1991, in the United States the number of cases for patients with Lyme disease has more than doubled.. (Depietropaolo et al., 2005)

One of the significant problems that have been found with providing clinical care for patients, is that many health officials are not familiar with the disease. This is due to primarily the lack of necessary clinical skills, which can provide infected patients with comprehensive care. The primary purpose of this case study is to present not only the fundamental examination of Lyme disease, but to also provide research which provides health care officials with alternative and efficient means to diagnosing, monitoring, and treating patients with Lyme disease. According to the latest statistical data, “Approximately 30,000 cases of Lyme disease are reported to the US Centers for Disease Control and Prevention each year; in 2012, it was the seventh most common nationally notifiable disease.” (Meyerhoff, Diamond, Steele, Zaidman, et al., 2013)

Lyme disease origin can be traced back to 1959 in Lyme, Connecticut, where it was discovered a few years later by Polly Murray. Polly begin to experience flu-like systems, odd rashes, and headaches, until she was convinced she needed to go to the doctor. While at first the doctors confused the illness for rheumatic fever and gave her penicillin, her systems would soon return. In evaluating her illness, she asked her doctor if it was possible she contracted the disease from a tick bite. While at first doctors denied this was the case, since the only illness associated with that was Rocky Mountain spotted fever, research would soon reveal that her disease stemmed from lxodes dammini.  (Citation)

This central fact was only discovered as many children around her area begin to show the same symptoms. This prompted doctors to search out probable causes, which narrowed down the agent to deer ticks that carried Borrelia burgdorferi. This agent can cause infection through the spread of the disease through tissues throughout the host. The complications from the spread of this disease can range from mild to deadly. Lyme disease systems can vary from one individual to the next, and over time can have a range of dramatic results. Even though there is a pattern that is classic for the disease, it is not the same for each patient contracting Lyme disease. For medical professionals this causes much frustration and prolonged pain for patients, in trying to identify the source of the illness.  There are three stages in which Lyme disease progresses in patients. One of the most common symptoms displayed by patients in the first stage is a particular rash. In about 60 percent of patients, this can be seen for those that have Lyme disease. EMC is the name giving to the distinctive rash in which is correlated to be described as migrating, chronic, red rash.  After the initial tick bite, between two and thirty days a rash will appear at the site. When not treated initially, sometimes in up to three weeks it will disappear on its own. In some patients, approximately 60-80% of individuals, that do not show the system of a rash, and for those that do, they might also have symptoms such as flu-like illness,. Many of the symptoms that some patients will exhibit in the first stage includes vomiting, nausea, sore throat, loss of appetite, stiff neck, aching muscles, chills, fever, and headache.    Soon after, in a manner of months since the initial tick bite, the individual will begin to experience the second stage. In the second stage, the disease will affect the neurological systems in the body, and will create joint and cardiac manifestations. When patients still go untreated throughout the first two stages, this can be caused for a serious problem. In the third stage, is characterized by various neurologic problems and chronic arthritis. While some patients will not experience all of these symptoms, with few not experiencing any at all, it is increasingly being hard for doctors to diagnose.  (Citation)  Table 1, illustrates the stages and symptoms that persist in patients with Lyme Disease.

The problem in diagnosing Lyme disease represents the purpose of the current case study. In diagnosing Lyme disease, it is primarily based on serological tests, epidemiological background, and clinical manifestations. According to studies, in treating Lyme disease patients there is a growing divide in what many physicians are telling and treating patients, as the accepted medical opinion is that the disease never lasts more than 30 days.

“Sharpening the dispute is the treatment frequently prescribed for chronic Lyme disease: a lot of antibiotics for a long time. Many of these treatments can go on for years, completely contrary to one of the Ten Commandments of today’s medical correctness: preserve the effectiveness of all antibiotics by using each of them sparingly.” (Marash, 2015)

Taking a two-step approach in serodiagnosis tests,utilizes the sensitive first test and is followed by the confirmatory immunoblotting of serum samples with positive first or equivocal results.  As seen in Figure 1, the positive result from a Serology test incorporates a Western Blot test using immunogloblulins IgM and IgG less than four weeks from the onset of the symptoms and IgG only, if more than four weeks from the onset of the symptoms.  (Depietropaolo et al., 2005)   In addition, in analyzing information from the Chemistry and Immunology laboratories, there has been an decrease in specificity with serological tests used in diagnosing Lyme disease, as it has a low sensitivity to in early diagnosis.  As seen in Figure 2, if a patient undergoes the serological testing at a late stage in the disease, there is an 81 percent specificity compared to the two-step approach (including the Western Blot), which has a 99-100 percent specificity.  In addition, there is a decrease in sensitivity to the test due to the lack of antibody response in patients treated with antibiotics.  (Depietropaolo et al., 2005)

The purpose of this research project is to examine other alternatives to testing for Lyme disease such as LIPS (luciferase immunoprecipitation systems), and others, that can be used to profile the antibody responses of the causative organism. This will be analyzed using conducted research from medical databasesand case studies on the misdiagnosis caused by serological testing.

Overview/Methodology

The problem that has been pointed out by several doctors and researchers is that in terms of medical care for Lyme disease, diagnosis is the greatest problem. According to Meyerhoff et al. (2013), “Because only approximately 25-30% of United States patients with early Lyme disease recall the tick bite, the clinician must direct the history toward the possibility of a tick bite.” (Meyerhoff et al., 2013) The physician will likely not run diagnostic test unless they have a high-level index of suspicion of the illness, such as awareness of all of the symptoms and the factors they are looking for. Many of the diagnostic tests for Lyme disease produce false negative results, and only about half of all confirmed tests are correctly identified. Therefore, when the disease is not properly and promptly identified and treated, the patient may not be aware they are carrying the disease. Lyme disease symptoms can disappear over a matter of months, and in a month or years’ time, reappear.

The health agencies, such as Center for Disease Control and Prevention (CDC), Food Drug Administation (FDA),  and the Canadian Public Health Laboraty Networt, all advocate for the two-step process metioned above, in which antibodies are measure in blood when Lyme disease is suspected in the patient.  However, the two-step blood test currently available and economical for individuals suspected of Lyme infection does not identify the spirochete, Borrelia burgdorferi that causes the ailment. Two different tests are utilized as a part of examination research centers. Numerous doctors are sticking their trusts on another test for Lyme disease now a work in progress. The currently available blood test that is used include the ELISA (enzyme-linked immunosorbent assay) and ELFA (enzyme-linked fluorescent immunoassay).  These tests measures for an immunse response to the bacteria that cause Lyme disease.  The tests are sensitive and when used accordingly, most people will test positive if they have Lyme disease.  (CDC, 2015)      In studying this problem, the methodology used will be to examine lab reports, as well as current and past research on the case study.  The studies are analyzedfrom several databases that  works with chemistry and immunology laboratories, as well as research based on new serological testing in the field of diseases. New testing is being developed in hopes of seeking out the spirochete antigens in the urine or the blood. The utilization of serologic testing and its esteem in the conclusion of Lyme sickness stay mistaking and questionable for doctors, particularly low risk patients. The way to diagnosing Lyme malady fluctuates relying upon the likelihood of infection (taking into account endemicity and clinical discoveries) and the phase at which the sickness may be. These patients do not oblige serologic testing, despite the fact that it might be considered by inclination. Patients who hint at no goal Lyme ailment have a low likelihood of the sickness, and serologic testing in this gathering ought to be maintained at a base in view of the high danger of false-positive results.

At the point when unexplained non-particular systemic side effects. For example, myalgia, weakness, and paresthesia have held on for quite a while in an individual from an endemic zone, serologic testing ought to be conducted with the complete two-stage methodology portrayed previously. The response to the host antibody to B. nurgdorferi agent in spite of the fact that IgM normally decreases to low levels following four to six months of ailment. Despite successful treatment, IgG remains at low levels regardless. Therefore, doctors ought to assess the essentialness of a serologic result in the setting of the understanding’s epidemiologic history. According to Depietropaoloa, Powers, and Gill (2005), “When serologic testing is indicated, physicians should use the two-step approach recommended by the CDC’s Association of State and Territorial Public Health Laboratory Directors (ASTPHLD), in which a positive or indeterminate serology is followed by a more specific Western blot test.” (Depietropaoloa et al., 2005) Patient samples are usually drawn at round the early stages are only tested for IgG, due to the higher risk of false-positives. While in the late stages, it is the opposite. An overwhelming majority of testing is done in the late stages of Lyme disease in order to ensure a more accurate result.

Serologic testing may give important data in patients who have endemic introduction and clinical discoveries that recommend later-stage spread Lyme infection. Additionally stage three patients’ with delayed established manifestations that may propose the early phases of Lyme sickness without erythema migrans. (Depietropaoloa et al., 2005). This declines the quantity of false-positive results, as well as the precision of the combined two-step test, and individual tests. At the point when requesting research facility tests for Lyme ailment, doctors should also report the quantity of time from the onset of illness.

Looking at the medical data, patients, particularly grown-ups, who receivelate treatment or introductory treatment with amoxicillin or doxycycline, and other antibiotics, may create endless musculoskeletal side effects and challenges with memory, fixation, and exhaustion. These manifestations can be weakening and hard to annihilate. A few patients create ceaseless joint pain that is determined by immunopathogenic components and not dynamic contamination. This is more common in patients with HLA-DR types. The joint inflammation is impervious to anti-toxin treatment however regularly reacts to symptomatic treatment and shows possible determination. (Meyerhoff et al. 2014)

Cardiovascular association in Lyme disease is seldom endless. Notwithstanding, patients with third-degree heart piece regularly oblige a permanent pacemaker insertion, or a brief insertion on rare occasions. Lyme illness seems to infrequently be deadly. In those cases in which the disease is fatal, they usually have some accompanying illnesses along with the tick-borne illness such as B microti and Ehrilichia. “A US Centers of Disease Control and Prevention (CDC) study of death records from 1999-2003 found that only one of 114 total records listing Lyme disease as an underlying or multiple cause of death was consistent with clinical manifestations of Lyme disease.” . (Meyerhoff et al. 2013 ).Consequent discoveries from CDC studies propose that inborn disease with B burgdorferi is unrealistic and not straightforwardly in charge of antagonistic fetal results.

Pathogenesis/Results

For about 2 to 5 percent of healthy individuals in the low endemicity region, they produce a false positive result. Without Lyme disease, the most well known purpose behind a positive serology test is the vicinity of an alternate spirochetal contamination, for example, relapsing fever, periodontal infection, spirochete, or syphilis. Patients with infectious mononucleosis or rheumatoid diseases likewise may have false-positive responses, particularly IgM.

With Lymerix, the first vaccine against the disease, it had a higher rate of false-positive results, which caused it to be taken off the market. A combination of B. burgdorferi and OspA.  OspA was present antigens, used in the vitro cultivated spirochetes whole cell kits. Subsequently, in any of the standard whole-cell enzyme-linked immunosorbent assay kits,  patient getting the immunization doubtlessly will display a positive result To reduce this issue, doctors ought to consider requesting just a Western smear test and slighting the OspA band when figuring out if the test is certain or pessimistic in inoculated persons.

Tests that are taken too early are most commonly the results of false-positive testing. Since the counteracting agent reaction grows gradually, tests taken inside the initial two weeks of contamination have low sensitivities (under 50 percent). For serologic tests, antibiotics influence the results. When given right on time over the span of contamination and have been demonstrated to prematurely end seroconversion, regardless of the possibility that deficient treatment is given. It is uncommon in the later stages of Lyme disease for true seronegativity. For the results of Western blot tests. The most common factors are over diagnosis. The misidentification of ascribing nonspecific symptoms, rashes, such as erythema migrans, and others associated with Lyme disease. Doctors must remember that results from Western blot tests, should go by the CDC ASTPHLD guidelines, to classify results as positive or negative, and should not be intermediate.

Underdiagnoses may happen if doctors apply the CDC observation criteria too entirely. A late study demonstrated that patients with delayed nonspecific manifestations, with no advanced manifestations or erythema migrans rash for nearly 20 % of Lyme infection cases in endemic zones amid the mid-year months.  It is useful to patients in this stage to receive antibiotic therapy to counteracting movement to late-stages, where it is less favorable to have a positive response to treatment. Serologic testings that is inaccurate for Lyme disease speaks to a wasteful utilization of human services assets. According to research, “may add to both underdiagnosis (eg, negative serologic discoveries in patients with erythema migrans) and over-judgment (eg, patients with nonspecific sacred manifestations) of Lyme disease.” (Ramsey, Belongia, Chyou, Davis, 2004). False-positive tests can bring about superfluous anti-microbial treatment, which thus may add to the increase of antimicrobial resistance, and the adverse events. An additional problem that is gathered from the research results is that delayed treatment is often associated with false-negative tests, which build the danger of spirochete dissemination.

In the research of Ramsey et al,. (2004), over one-half of the asymptomatic patients had inappropriate tests. (Ramsey et al., 2004) Contrasted and family doctors and internists, doctors in crisis or pressing consideration were fundamentally more prone to request wrong tests. The explanation behind this finding is vague, yet we theorize that doctors in these environments may utilize testing as an equivocating measure, postponing last treatment choices until the patient can catch up with their primary doctor. A suspected or know tick bite was likewise emphatically connected with improper testing, proposing a requirement for more clinician instruction on the danger of Lyme infection after a tick bite. The same study showed that in the endemic region, when Lyme disease was treated with a single dose of doxycycline, it reduced the risk, but regardless or treatment decision, serologic testing had no benefit. (Ramsey et al, 2004) Intercessions ought to be centered around instructing health professionals about signs for Lyme disease testing, especially that the unlucky deficiency of manifestations regardless of known or suspected late tick bite hinders the requirement for testing

Discussion

Two-tiered serology tests are high specificity and sensitivity which make for goodperformance characteristics after the initial infection of B. burgdorferi. Laboratories have quality assurance programs, and good-quality control are able to have consistent results for Lyme disease testing. However, there are still limitations to be being addressed about two-tiered testing. In searching for newer testing methods, they try to compensate in its weakness of weak neuroborreliosis, and acute EM insensitivity. Additional problems include the technically demanding and complex two-step procedure, which is very costly. It is hard to standardize traditional blots, as judgment is often used in reading the results for weaker bands. Accompanying complexities includes the need to understand the onset of the disease, requesting the appropriate IgM tests, and the drawback of continually drawing blood samples from the patient. This is often the case when another test needs to be administered. Actively in the research community, they are addressing the limitation, and additional approaches to be taken in identifying and diagnosing Lyme disease early in patients. The new approaches are either potential alternatives to two-tiered testing, or improvements to one of the steps in the two-step process.

Truth be told, on the premise of a late sub-atomic indicative study, the affectability of this testing methodology may be as low as 7.5%.  Late studies have uncovered that “post–Lyme sickness side effects” may speak to disappointment of short-course anti-microbial treatment and relentless disease. Due to the Lyme spirochete, and this perpetual ailment may react to a more extended length of time of anti-infection treatment is reliable with the poor consequences of past studies. In outline, the affectability information displayed by research reflect both the need for better tests for diagnosing this serious infection.

Treatment and Prognosis

Dependent on the clinical manifestation that the patient may exhibit, there are several different steps taken to diagnose a patient with Lyme disease. This includes therapy intervention with doxycycline, amoxicillin, cefuroxime, which are oral therapies. These are usually taken up to three times a day in up to 500 mg. While for a more advanced stage, intravenous therapy is conducted. This includes ceftriaxone, cefotaxime, or penicillin. These are taken usually once a day, but the dosage may vary. There are several other methods that are dependent also on accompany symptoms or diseases that patient might exhibit. Those that symptoms do not improve must undergo retreatment, and have long-term monitoring. The prognosis of Lyme disease patients is largely great when they are dealt with right on time with proper anti-microbial regimens. On the other hand, intermittent contamination is conceivable if a tick carrying the agent again infects the patient.  These diseases are as a rule because of an alternate strain of the neighborhood Borrelia. Patients, particularly grown-ups, who get late treatment or starting treatment with anti-infection agents other than amoxicillin or doxycycline, may create perpetual musculoskeletal manifestations and challenges with memory, focus, and weariness. These indications can be weakening and hard to kill. A few patients create endless joint inflammation that is determined by immunopathogenesis instruments and not dynamic disease. The joint pain is impervious to anti-microbial treatment yet regularly reacts to symptomatic treatment and displays consequent resolution. While Lyme disease is rarely fatal, there have been some cases in Europe and the United States, but is largely infrequent.

Conclusion

The amount of false-positive tests for patients that have Lyme disease is a major problem. One of the significant problems that have been found with providing clinical care for patients is that many health officials are not familiar with the disease. This is due to the complexity primarily of the lack of necessary clinical skills, which can provide infected patients with comprehensive care.

The problem not only points to lack of education for health care professionals, but also the two-tiered approach taken in testing the disease. Lyme disease is an increasing problem, which is linked with increased costs to the healthcare system, and to the patient. There have been many proposals and alternative tests that are used in diagnosing, treating patients, as it more compassionate management, and cost effective treatment is introduced in increasing patient outcomes, and decreasing costs.  It is important for the research community to continue to work towards improving the serologic tests, while also finding alternatives that are cost-efficient, and more accurate in helping to catch the disease early in patients.

Works Cited

Adrion, Emily R., Aucott, John, Lemke, Klaus W., Weiner, Jonathan P. “Health Care Costs, Utilization and Patterns of Care following Lyme Disease.” PLOS One. 4 Feb 2015. Web. 18 March 2015. http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0116767

CDC.  (2015).  Understanding the EIA Test.  Retrieved from: http://www.cdc.gov/lyme/diagnosistesting/labtest/twostep/eia/index.html

Depiertropaolo, Daniel, Powers, John, Gill, James. “Diagnosis of Lyme Disease”. Am Fam Physician. 2005. Web. 10 Feb. 2015.  http://www.aafp.org/afp/2005/0715/p297.html

Johnson, Barbara J.B. “Laboratory Diagnostic Testing for Borrelia burgdorferi Infection.” CAB International. Lyme Disease: An Evidence-Based Approach. 2012. Web. 10 Feb. 2015 http://www.cdc.gov/lyme/resources/Halperin_2012_Chap4_JohnsonB.pdf

Marash, Dave. “Lyme Disease Controversy.” ABC News. 5 July 2015. Web. 17 March 2015. http://abcnews.go.com/Nightline/story?id=128770

Meyerhoff, John, Diamond, Herbert, et. al. “Lyme Disease.” Medscape. 2014. Web. 10 Feb. 2015.  http://emedicine.medscape.com/article/330178-overview#aw2aab6b2b5

Ramsey, A. H., Belongia, E. A., Chyou, P.-H., & Davis, J. P. “Appropriateness of Lyme Disease Serologic Testing.” Annals of Family Medicine, 2(4), 341–344. doi:10.1370/afm.117. 2004. Print.

Stricker, Raphael, Johnson, Lorraine. “Serologic Tests for Lyme Disease: More Smoke and Mirrors” Clin Infect Dis. 47 (8): 1111-1112. doi: 10.1086/592121. 2008. Print.