Development of a Vaccine for Lyme Disease - Term Paper Example

Problem to be solved or partially Solved Using the technology Name: Course: College: Tutor: Date: The vaccine against the borne infectious Lyme disease is the problem that this study paper wants to be solved. This is because there is a big risk of being infected by this disease particularly in highly endemic areas and the sooner a vaccine is got the better. (Feder, 2005) Paradigm A multicenter arbitrary trial involving 10,000 subjects in a highly prevalent area in the US was conducted. Subjects received an injection of either recombinant Borrelia burgdorferi outer surface lipoprotein A (OspA) with adjuvant or placebo at enrollment and one and twelve months later. In situations of suspected Lyme disease, culture of skin lesions, serologic testing or polymerase chain reaction testing was done.Following these tests in the first year after two injections 22 subjects in the vaccine group and 43 in the placebo group contacted definite Lyme disease. Vaccine efficacy was 49 percent. In the second year after the third injection 16 vaccine recipients and 66 placebo subjects contacted the Lyme disease. The efficiency of the vaccine was 76%.The effectiveness of the vaccine was thus 100% in the second year compared to a paltry 83% in the first year and 100% in the second. The vaccine injection was associated with mild reactions lasting about three days. These three injections of the vaccine prevented occurrence of Lyme disease was the conclusion from these tests. (Feder, 2005) Introduction Lyme is a vector borne infectious disease caused by the spirochetal B.afzeli and B. garini in Europe and Borrelia, burgdorferi in the US (Meek, 2005). These spirochetals use ticks as vectors to enter their hosts. Their prevalence rates in Europe and the US have been reported to have doubled over the last decade to a record over 100 people being reported to be infected in a population of 100,000 inhabitants in these regions. The reason for this increase in infections is due to the increase in population in areas that are of high risk. Rodents and dears are now working in conjunction as hosts at different times for these ticks. This disease is capable of causing facial muscle paralysis, inflammation of the heart muscle, and disease in the joints, abnormal sensation due to disease peripheral nerves, confusion and meningitis. (Kalish, 2005) Lyme disease is a multi system vector borne zoonosis. It’s mainly caused by a spirochete and the small mammals and birds are just but reservoirs. In North America it’s transmitted by two kinds of black legged ticks of the lixodes genus; the lxodes pacificus and lxodes scapularis. (Tibbles, 2007) The Technology used in Treating Lyme Disease The best currently available means of treating Lyme disease is avoiding being bitten by ticks at all costs. If exposure to i.pacificus and I Scapularis is unavoidable measures that this study recommends to reduce the risk of infection include the use of tick repellants and use of protective clothing. It’s also advisable that one checks their entire bodies for ticks daily and promptly remove attached ticks before their transmission occurs. (Wormser, 2005) For the Prevention of Lyme disease after a recognized tick bite a single dose of doxycycline can be offered to adult patients (200mg) dose as well as to children under the age of 8 years (4mg per kg up to a maximum dose of 200mg) This happens if the tick that attacks the victims is reliably confirmed to be an adult or nymphal i.scapularis .In addition it should have been attached to the body for more than 36 hours. Prophylaxis should be started 72 hours after the removal of the tick (Bacon, 2008) Prophylaxis after I. pacificus bites is not necessary. Because infections rates of B.burgdorferi in these ticks are low in all areas where ticks are endemic. But if the area in question has higher rates of infection then prophylaxis with a single dose of doxicycline would be more effective. The exterior surface membrane protein of B.burgdorferi OspA is amongst a number of antigens found in patients in the severe phase of Lyme borreliosis.In a laboratory test to verify if it really lies outside the membrane OspA open reading frame was expressed in Escherichia coli and thereafter several deletion constructs of the gene were generated and expressed as trpE fusion proteins in E.coli.The resultant constructs were utilized to identify antibody binding sites of mouse monoclonal and rabbit antiserum antibodies that are directed against OspA.All antibodies tested failed to bind to a fusion protein containing the first 61 amino acids of OspA, an indication that the amino terminal domain of OspA is not exposed to the cell surface.(Luft,2005) In order to prescribe prophylaxis so as to prevent Lyme disease medical practitioners in the areas in question should identify I scapularis ticks including their stages of development. They should also be able to identify ticks that are enjoined to blood. Medical practitioners especially in areas with high prevalence rates should be aware of ways of treating Lyme disease and the clinical manifestation. This is because a study conducted in Massuchetes found out that physicians relied on professional journals and educative material to gain more insight about Lyme disease.(Magri,2005) People who may have removed ticks from their bodies should be monitored for signs and symptoms of tick borne diseases for a period of a month. Particularly for any signs of the development of an expanding skin liaison at the point of the tick bite. If one feels sick within a month after the removal of an attached tick they should sick immediate medication to avoid any tick borne infections. HGA and babesiosis should be included in the differential diagnosis of patients after an ixodes tick bite particularly in areas where the infections are prevalent. Any past recipients of a Lyme vaccine or history of an earlier Lyme disease shouldn’t alter these recommendations. (Bacon, 2008) Erythema migrans is an earlier lyme disease and patients who have had it are recommended to use.Doxicycline, (100mg twice in a day), amoxicillin (500mg three times in a day) or cefuroxine axetil (500mg twice in a day) for 14 days. 10 to 21 days for doxycycline and 14 to 21 days for amoxicillin are recommended for adult patients with early symptoms of Lyme disease. Its symptoms include a spreading lesion, that begins as a macule or papule and after some days turns into a red expanding macule that has to be clinically diagnosed since some lab tests are usually negative and only distinguish the symptoms from normal insect bites once the swelling becomes big.(Coyle,2005)All microbial agents are effective in treating erythema migrans and their symptoms. Doxycycline will treat HGA but won’t treat babesiosis it’s also somehow contraindicated during pregnancy and in children under the age of eight years. Children are adviced to use antibiotics such as; amoxilin (50 mg per kg per day in three doses) where each dose should be a maximum of 500mg.Cefuroxime axetil (30mg per day per kg in two doses) If the children are below eight years then give them doxycycline (4mg per kg per day in two doses) Every dose should have a maximum of 100mg. Macrolide antibiotics are less effective and thus shouldn’t be recommended for first lyme disease. When used they should be given to patients who are intolerant of amoxicillin, cerufoxine axetil, doxicycline.Adults that have these shortcomings should be given macrolide antibiotics that have the following descriptions;azithromycin 500mg orally per day for 7 to 10 days and Clarithromycin,500mg orally 2 times a day for two to three weeks. First generation cephalexin are ineffective in the treatment of Lyme disease and shouldn’t be used.(Nowakowski,2005) If erythema migrans can’t be distinguished from community acquired bacterial cellulites the best way out is to treat with cefuroxime axetil or amoxicillin clavulanic acid incase of adults. As much as cetriaxone is effective it’s not superior to oral agents and may cause serious adverse effects. Thus it’s not recommended for treatment of persons with early Lyme disease in the absence of advanced atrioventricular heart block or neurological involvement. (Wormser, 2005) Manifestations of early neurological Lyme disease include Lyme meningitis. The use of cetriaxone (2g once in a day intravenously for two weeks in a period of one month) In early Lyme disease is recommended for adult patients with acute neurologic disease manifested through radiculopathy or meningitis.Parenteral therapy with cefotaxime (2g intravenously for every 8 hours) or penicillin (18 to 24 million u per day) should be administered to patients with normal renal function. For patients that are intolerant to lactum antibiotics evidence shows that doxycycline (200 to 400mg per day in two divided doses) is enough. Since doxycycline is efficiently absorbed orally intravenous administration will rarely be needed. For kids ceftriaxone (50to 75kg per day per) is recommended. A substitute would be cefotaxime 150-200mg per kg per day. This is divided into three to four intravenous doses in a day. With a maximum of 6g per day. Or penicillin G (200,000 to 400,000 units per kg per day) maximum 16 to 24 million units per day. These are divided into doses that are given after every four hours for patients that have good renal functions. (Bacon, 2008) Patients with atrioventricular heart block or myopericarditis associated with early lyme disease can be treated with oral or potential antibiotic therapy two weeks within a period of three weeks.Hospitalisation and continuous monitoring are advisable for patients with symptoms. (Wormser, 2005) Comparison of the Fronted Technology with others that have been used before The first clinical randomized trial compared erythromycin, tetracycline and penicillin at dosages of 250mg 4 times per day for 10 days in 112 adult patients. Signs and symptoms after treatment included; minor ones such as; headache,fatigue,supraventricular tachycardia,arthralygias,brief arthritis of two weeks and isolated facial palcy.The major ones include;meningitis,meningoencephalitis,recurrent attacks of arthritis,carditis.15% of patients had a transient intensification of symptoms during the 24 hours of therapy. The mild reactions were only documented at the start of treatment. There is no evidence that they can last for a day or that they can recur. They have no diagnostic value and have not been shown to be predictive of outcome. Erythrema migrans and its associated symptoms resolved more rapidly in penicillin or tetracycline treated patients compared to those who were given erythromycin. Apart from that treatment with penicillin or tetracycline was associated with very little major manifestations as compared to erythromycin. Minor signs and symptoms after treatment occurred in 45% of patients. Extending therapy for 20 days had no effect on the frequency of post treatment symptoms. The results of this trial supported the findings of a previous open therapy of penicillin on early Lyme disease. (Bacon, 2008) From these findings it was concluded that Erythema migraines was responsive to penicillin and tetracycline, erythromycimn was less effective and optimal therapy had not been defined. Subsequent small studies found that doxycycline and amoxicillin plus probenecid; the tetracycline and lactam preparations usually prescribed in current medical practice for patients with erythema migrans were effective therapies. Two of the largest studies of the treatment of erythema migrans in adults compared cefuroxime axetil with doxycycline. The first was a multicenter study in which 123 patients with erythema migrans were randomized to receive cefuroxime axetil (500mg twice per day for 20 days) or doxycycline (100mg three times a day for 20 days). This study demonstrated comparable efficacy with satisfactory outcomes in 90% of patients observed for one year after treatment. Although 10% of subjects were considered to have experienced treatment failure on the basis of prevalent symptoms most of them didn’t have any objective clinical finding. (Wormser, 2005) Similar results were found in 232 patients of erythema migrant who were also to receive 20 days of either cefuroxime or docycline. In a separate randomsized trial of 43 children with erythema migrans, two different dosage regimens of cefuroxime axetil (20mg per kg in a day or 30mg per kg in a day) were found to have efficacy compared to amoxilin. (52mg per kg per day) (Bacon, 2008) A multicenter, double blind, randomized, prospective trial compared azithromycin (500mg once per day for a week) with amoxicillin (500mg thrice a day for 20 days) for treatment of patients with erythema migrans. Amoxicillin was found to be more effective than erythromycin for complete resolution of the acute manifestation of erythema migrans and for prevention of relapse in a 6 months period. Of 217 subjects only 4% those treated with amoxicillin experienced relapse compared to 16% of those treated with azithromycin. (Luft, 2005) Only one study has particularly addressed the treatment of acute disseminated nonneurologic Lyme disease which was defined by the presence of either multiple erythema migrans lesions or an objective non neurologic extra cuteneous manifestation. Patients with objective CNS involvement were excluded. This rospective, randomized multicenter trial of 140 patients demonstrated that oral doxycycline (100mg twice in a day for 21 days) and intravenous ceftriaxone (2g per day for 2 weeks) were equally effective none of the patients in this study developed a significant late complication. (Wormser, 2005) In most of the controlled trials patients’ assigned treatment with either doxycycline or amoxicillin received three weeks of therapy. However comparable success rates have been reported in studies in which shorter treatment courses with these antibiotics were used. Duration of antibiotic therapy for erythema migrans was addressed in a prospective, randomized, double blind, clinical trial of 180 patients. Patients were put into three treatment groups; doxycycline (100mg twice a day per mouth for 10 days) and doxycycline; (100mg twice a day per mouth for 20 days) the rate of complete resolution of signs and symptoms was similar for all three treatment groups in both on study and intention to treat analysis. (Bacon, 2008) Despite the potential for B.burgdorferi to disseminate to the CNS in some patients with erythema migrans the addition of a single dose of ceftriaxone to a 10 day course of doxycycline did not improve outcome. The single ceftriaxone dose was associated with a four fold increase in the frequency of diarrhea. Although none of the studies enrolled pregnant subjects with Lyme disease there is no data to suggest that they should be treated differently from other Lyme disease patients except that doxycycline therapy should be avoided. Strengths and Weaknesses of This Technology and their solutions Strengths Weaknesses Solutions Studies show that antibiotics can cure B.burgdorferi in infected animals even those that are highly immunocompromised Many of these studies did not follow currently recommended standards for serologic testing When laboratory testing is done it should be performed in well qualified laboratories that use recommended methods of validation (Cairns,2007) Studies show no evidence of persistence historical findings of an active inflammatory process consistent with B.burgdorferi infections when antibiotic treated animals are immunosuppresed. Several methodological issues may have had a negative impact on the validity of the findings in this study Persistence of a chronic condition after 28 hours suggests that the diagnosis was incorrect or the patient is co infected Although patients reported cognitive difficulties the study population had normal baseline neuropsychological test scores The reports are unclear as to whether the patients had objective evidence of significant cognitive impairment Doxycycline is recommended as the treatment of choice for patients suspected to have symptoms of HGA. Several controlled treatment trials of patients with post Lyme disease symptoms have been published. Clinical manifestations of HGA are none specific and may include fever, chills and headache suggesting that Lyme disease may be more complex and doesn’t include B.burgdorferi alone(Sigal,2005) All symptomatic patients suspected to have HGA should be treated with antimicrobial therapy because of the risk of complications Conclusions Conclusions that can be drawn from these trials are that; there is convincing biological evidence for the existence of symptomatic chronic B.burgdorferi infections amongst patients after the receipt of recommended antibiotic treatment for Lyme disease. (Steere, 2005) Doxycycline, amoxicillin and cefuroxime are effective for the treatment of early Lyme disease. This is because most patients respond promptly and completely. Some individuals have persistent subjective complaints despite receiving therapy that appears curative. (Klempner, 2005) Less than 10% of individuals don’t respond to antibiotic therapy as evidenced by the presence of objective clinical manifestations and rarely is treatment required. Patients who are ill at the time of diagnosis take long to respond to therapy. For there is strong evidence that some patients have symptoms that persist for years after being infected by Lyme borreliosis regardless of being treated. (Shadick, 2005) Inadequately recognized CNS at the time of institution of antibiotic therapy may be the explanation of antibiotic failures in some circumstances. All antibiotics in early Lyme disease are associated with a low frequency of serious adverse effects. Drug induced rushes occur with both amoxillin and cefuroxime axetil. Doxycycline may cause photosensitivity which is a concern because early Lyme disease occurs mostly during the summer month. Thus individuals undergoing this therapy are advised to avoid direct exposure to the sun. In addition doxycycline is constricted in pregnant women and in children below the age of eight years. Despite of all these findings the bottom line is Lyme disease is preventable and treatable. (Magri, 2005) References: Bacon R.M. (2008) Surveillance for lime disease United States; MMWR Surveillance Summaries Retrieved from; www.cdc.gov/mmwr/pdf/ss/ss5710.pdf on 14th June 2011 Cairns V, (2007) Post-Lyme borreliosis syndrome: An-analysis of marked symptoms on 18th June 2011 Retrieved from; www.ilads.org/lyme_disease/.../14%20Green%20-%20Post-Lyme%20Syndrome%20Challenge.pdf on 18th June 2011 Coyle BS, (2005): Lyme disease; its health impact on the Maryland Public. Retrieved from; www.iom.edu/~/.../Disease/.../10-Disease-Surveillance-and-Case-Definitions.pdf on 18th June 2011 Feder Jr, (2005): Erythema migrans; Its Misdiagnosis Retrieved from; www.sepeap.org/archivos/pdf/10092.pdf on 18th June 2011 Kalish RA, (2005): Evaluation of study patients with Lyme disease; 10–20-year follow-up. Retrieved from; www.fchp.org/providers/medical-management/~/.../LymeDisease.pdf.ashx on 18th June 2011 Klempner MS (2005) Controlled trials of antibiotic treatment in patients with post-treatment chronic Lyme disease. Retrieved from; www.cardiologyjournal.org/inpress/122010Kanjwal.pdf on 18th June 2011 Luft BJ, (2005) Amoxicillin compared with Azithromycin in treating Erythema Migrans. Retrieved from; www.ilads.org/lyme_disease/written.../9%20Maloney-Early%20Lyme.pdf on 18th June 2011 Magri JM, (2005): Lyme disease knowledge and beliefs; New Hampshire primary care physicians practices. Retrieved from; www.jsi.com/.../Lymes_Disease.../MA_Lyme_Disease_Needs_Assessment_Final_Report.pdf on 18th June 2011 Meek, (2005): Connecticut physicians; Lyme disease underreporting Retrieved from; ideha.dhmh.maryland.gov/phase/ppt/2007/MargaretDoll.pdf on 18th June 2011 Nowakowski J, (2005): The failure of cephalexin to treat Lyme disease. Retrieved from; archfami.ama-assn.org/cgi/content/full/9/6/563 on 18th June 2011 Shadick NA, (2005): Musculoskeletal and neurologic outcomes in patients with previously treated Lyme disease. Retrieved from; Lyme%20borreliosis%20syndrome%2C%20a%20meta... on 18th June 2011 Sigal LH (2005): Early Lyme disease without erythema migrans; toward a more complete appreciation of the clinical spectrum of Borrelia burgdorferi infection. Retrieved from; www.ncbi.nlm.nih.gov › Journal List › BMC Infect Dis › v.9; 2009 on 18th June 2011 Steere AC, (2005): The picture of early Lyme disease through Systemic symptoms without erythema migrans. Retrieved from; www.idsociety.org/WorkArea/linkit.aspx?LinkIdentifier= on 18th June 2011 Tibbles CD, (2007): How to detect Erythema migrans in patients Retrieved from; www.lymediseaseaction.org.uk/conf2008/owen.pdf on 18th June 2011 Wormser, G.P. (2005)”Prevention of Lyme Borreliosis Retrieved from; www.biomedcentral.com/content/pdf/ar2853.pdf on 14th June 2011 Read More