Tuberculosis Prevention - Essay Example

TUBERCULOSIS PREVENTION By Location Tuberculosis For many years, tuberculosis (TB) has remained a health threat. The world health organization has demonstrated concerted efforts towards the eradication of TB from the globe. Evidently, TB exhibit minimal prevalence in some regions, while proving highly prevalent in others. Since the 1930’s a vaccine has existed that targeted to reduce the fatality of the disease. However, evidence based research has served to prove that the vaccine only exhibits limited efficiency. With the advancing technology and increased research in biology, a new realm of possibilities is becoming evident in the globe. Scientists are focusing on exploiting the emerging techniques in a bid to develop a new vaccine. This paper will discuss some fact about TB, the existing vaccine since 1930s and the possibility of developing a new vaccine through the application of biotechnology (Madkour 2004, p. 56). TB has been categorized as one of the serious bacterial infections that pose greater health risks. Initially, the disease targeted the lungs, but research and reported cases in the recent past has revealed the existence of multiple forms of TB. The bacteria can affect the bones, joints, kidneys and other body organs according to reliable medical research. According to the World Health Organization (WHO), Mycobacterium tuberculosis is second only to HIV as the greatest killer worldwide due to a single infectious agent (Madkour 2004, p. 87). The organization estimates that in 2011, 8.7 million people have been diagnosed with TB and 1.8 million have died because of the disease. TB is the leading killer in people living with HIV causing one quarter of all the deaths. The WHO organization has addressed TB in the following ways. First, it has provided global leadership in matters critical to TB. Secondly, it has developed policies and strategies for TB prevention. Lastly, it has facilitated research in effective ways of controlling TB. After primary infection, the disease may be latent especially in immunocompetent individuals or may become progressive, especially in immunocompromised children (Rivas-Santiago & Cervantes-Villagrana 2014, p. 163). In latent tuberculosis, the organism is present, but usually without any signs and symptoms or any radiographic or bacteriologic evidence of tuberculosis infection. However, the annual risk of developing active disease is five to fifteen percent. Lifetime risk increases to approximately fifty percent in HIV co-infected persons. Mycobacterium tuberculosis may also lead to extra pulmonary tuberculosis, which include infection in the following; bones and joints (pots disease), meninges (meningitis), genital tract, abdomen, pericardium, eye (ocular tuberculosis), adrenal gland (Addison’s disease) and on the skin. Causative Agent of Tuberculosis Mycobacterium tuberculosis (TB) is the causative agent of tuberculosis. It is a facultative intracellular bacterium. Other members of the Mycobacterium tuberculosis complex include; Mycobacterium bovis found mainly in cattle and man and Mycobacterium caprae found in goats.This bacteria is non-motile. It also lacks a capsule and does not form spores. It only grows in the presence of oxygen, therefore referred to as a strict aerobe. It is strongly acid fast and is rod shaped. It requires enriched culture media that is egg based media or agar based media or broth. Mycobacterium tuberculosis has high lipid content in its cell wall and has a slow generation time. It is spread from person to person through the air (Allman 2007, p. 89). Symptoms The following are the common symptoms exhibited by TB patients: Persistent cough Weight loss Fever Night sweats Loss of appetite Tiredness and fatigue Treatment Tuberculosis is sensitive to various chemical and physical agents. The treatment of tuberculosis involves first and second line drugs. Treatment mainly involves combination chemotherapy to prevent emergence of resistance and to eradicate the infection within the shortest time possible. The number of drugs should be kept minimal to reduce the incidence of adverse effects (Dixon & Donnelly 2011, p. 76). If monotherapy is given to patients with a large and actively dividing bacillary population, the relatively small number of resistant mutants already present overgrows the drug sensitive bacilli. First line drugs are the most effective and less toxic. They include isoniazid, rifampicin, streptomycin, Pyrazinamide and Ethambutol. Mycobacterium tuberculosis is also sensitive to second line drugs. These are used when there is resistance to first line drugs or in case of failure of clinical response to conventional therapy.These drugs include: amikacin, capreomycin, kanamycin, Ethionamide, levofloxacin, cycloserine, viomycin, linezolid and para-aminosalicylic acid. Amikacin is mainly used to treat streptomycin resistant Mycobacterium tuberculosis. Treatment for Mycobacterium tuberculosis is not an easy process and may take many months ranging between four to six months. Multidrug resistance occurs when Mycobacterium tuberculosis is resistant to at least Rifampin and isoniazid. Extensive drug resistance occurs when the organism is resistant to isoniazid and Rifampin. Resistance to any flouroquinolone and at least one of the three-second line drugs that are administered through injections (amikacin, kanamycin and capreomycin) means that the Mycobacterium tuberculosis has developed multidrug resistance (Allman 2007, p. 89). Mycobacterium tuberculosis is also sensitive to various physical agents. It is easily killed by heat at sixty-five degrees for thirty minutes. It is also sensitive to radiation. The chemicals it is sensitive to include ethylene oxide. Bacille-Calmette-Guérin (BCG) vaccine As highlighted above, TB is a disease with a high level of fatality. Therefore, the focus has been on preventing infection. The development of the BCG vaccine in the 1930s sought to reduce the TB infections. The vaccine comprises of a weakened strain of Mycobacterium bovis, a close relative of Mycobacterium tuberculosis. The basis of developing vaccines is developing substances that have the potential of triggering an immune response, yet one that lacks the capacity to cause infection (Crisp 2013, p. 497). The triggered immune response serves to prevent any infection with the virulent strain responsible for causing TB. In the case of BCG, the weakened strain does not lead to infection, but has the potential to trigger a positive immune response, registering efficiency levels of between 70-80 percent. BCG is administered several times in infants, in areas that register high prevalence rates. BCG has remained the sole vaccine against TB for many years. However, this vaccine has exhibited varied efficiency in different populations. Messenger RNA Vaccine There is evidence suggesting that TB has graduated into a global illness, unlike in the previous years when it was prevalent in poor countries. As highlighted above, the BCG vaccine is not a reliable preventive intervention. Moreover, Mycobacterium tuberculosis have exhibited a salient resistant both first line and second line drugs. These factors have prompted scientists to develop new strategies of vaccine production. Without doubt, the success in genetics in the recent years has presented the globe with a new realm of possibilities. Evidently, scientists have highlighted the possibility of developing DNA vaccines. DNA vaccines have the potential of presenting a higher efficiency because of the salient potential to trigger a specific immune response. In the last decade, oncologists have focused on the possibility of developing genetic therapies against different types of cancer. Such efforts have defined the new pattern adopted by specialists today. One of the successful experiments in the case of cancer was the demonstration of the experimental efficiency of messenger RNA vaccines. Lorenzi et al (2010) followed the model of Messenger RNA vaccines in an experiment to demonstrate the potential of the technique in the development of an effective TB vaccine. The researchers realized that the heat shock protein of the Mycobacterium tuberculosis was one of the critical proteins in the virulence of the bacterium. After successful sequencing of the gene coding for this protein from Mycobacterium leprae, transcription of the gene was achieved using a relevant kit. After obtaining the purified messenger RNA, transfection into autologous dendritic cells occurred. This study adopted the use of dendritic cells because of its reported efficiency compared other vectors. After successful transfection, the dendritic cells can be re-introduced into the patient. In one of the experiments carried out in a bid to demonstrate the efficiency of the messenger RNA vaccines against tuberculosis, Lorenzi et la (2010) used mice. The established evidence that transfected dendritic cells had the capacity to trigger an immune response prompted this experiment. After preparation of the messenger RNA vaccine, it was introduced into mice infected with Mycobacterium tuberculosis using an intranasal route. The choice of this route of administration had its basis of the fact that the lungs were an initial target for the Mycobacterium tuberculosis. Evidently, this route would ensure that the transfected dendritic cells found their way into the lungs. Moreover, the fact that this rout placed no requirement for an injection was an additional benefit, because it offered the assurance that no other immune response was triggered. This research revealed that the messenger RNA, which was of considerable size, could be translated once it found their way into the lungs. According to the findings of this research, antigen presenting cells of the lungs demonstrated the capacity to take up the messenger RNA. Analysis revealed that dendritic cells took up most of the messenger RNA. Within 30 minutes, there was evidence that the process of translation had started. The use of bio-informatics techniques served to ascertain that translation had taken place (Lorenzi et al 2010, p. 6). Translation yielded the heat shock protein that exhibited the potential to trigger an immune response. The heat shock protein produced after successful translation serves as an effective molecule that found its way into the class 1 pathway of immune responses. Successful presentation of the protein ascertained that the protein eventually triggered the activation of both CD4+ and CD8+ T cells. This response occurred after about 8-12 hours. Another response involved interleukin 10 and TNF alpha cytokines. Notably, the production of IFN- gamma and TNF- alpha were impressive, as these have been described as highly important and specific for protection from TB. The mice used in this study had received a challenge from Mycobacterium tuberculosis. After the intranasal dose, the mice exhibited protection from infection (Rivas-Santiago & Cervantes-Villagrana 2014, p. 165). Implications from the above experiment As highlighted above, messenger RNA vaccines have defined some of the recent trials in a bid to develop vaccines and drugs for some of the diseases that have registered a high mortality in the recent past. Tuberculosis has been placed in the category of fatal diseases, because of the emergence of highly resistant forms and the limited efficiency of the BCG vaccine. The experiment carried out by Lorenzi et al (2010) reveals that the use of the Hsp 65 messenger RNA vaccine as modelled in mice can be a reliable vaccine for TB in the future. Evidently, the successful sequencing of the gene and the availability of an effective transcription tool presents is promising. Moreover, the fact that 10µg of the messenger RNA sufficed to trigger the relevant immune response that ensured that the mice exhibited protection from tuberculosis suggests that the same dosage would be appropriate in a human messenger RNA vaccine. The experiment also confirmed the intranasal route as effective for the administration of a messenger RNA vaccine as dendritic cells captured the RNA within a short time, and successful translation occurred thereafter. Lorenzi et al (2010) demonstrated that the development of a messenger RNA vaccine against TB for human beings was a possibility. The venture would be worthwhile as the experiment exhibited the potential of the messenger RNA vaccine to trigger a specific immune response as evidenced by the production of gamma IFN and TNF-alpha, which are critical for effective protection against tuberculosis (Abebe 2012, p. 215). Setbacks of this method and Conclusion With this technique presenting positive future prospects, it is evident that a messenger RNA vaccine is likely to be in use in the next few years. However, that will happen after successful addressing of certain salient challenges (Billeskov 2013, p. 5). One of such challenges is the cost involved in the production. Evidently, a high cost of production would translate into high prices of the vaccine. That would only place companies at an advantage, while proving inaccessible for many people. Although the experiment suggests that, the dosage used in mice can prove effective in humans, there is a need for further research to ascertain the efficacy of the dosage. Notably, dendritic cells exhibit diverse phenotypic characteristics, and this may pose a challenge in the choice of the ones to be used. A controversy still surrounds the stage at which the transfer of the cells should occur. Despite these challenges, messenger RNA vaccines seem to have a future in preventing the fatal TB infection. Bibliography Abebe, FF 2012, Is interferon-gamma the right marker for bacille Calmette-Guérin-induced immune protection? The missing link in our understanding of tuberculosis immunology, Clinical & Experimental Immunology, 169, 3, pp. 213-219, Consumer Health Complete - EBSCOhost, EBSCOhost, viewed 28 February 2014. Allman, T 2007, Tuberculosis, Detroit, MI: Lucent Books/Thomson Gale Billeskov, R, Elvang, T, Andersen, P, & Dietrich, J 2012, The HyVac4 Subunit Vaccine Efficiently Boosts BCG-Primed Anti-Mycobacterial Protective Immunity, Plos ONE, 7, 6, pp. 1-10, Academic Search Complete, EBSCOhost, viewed 28 February 2014. Crisp, D 2013, The role of the BCG vaccine in preventing tuberculosis in the UK, Practice Nursing, 24, 10, pp. 496-499, CINAHL Complete, EBSCOhost, viewed 28 February 2014. Dixon, A, & Donnelly, E 2011, DNA Vaccines : Types, Advantages, And Limitations, New York: Nova Biomedical Books, eBook Collection (EBSCOhost), EBSCOhost, viewed 28 February 2014. Lorenzi et al 2010, ‘Intranasal vaccination with messenger RNA as a new approach in gene therapy: Use against tuberculosis’, BMC Biotechnology, 10, p. 77. Madkour, M 2004, Tuberculosis, Berlin: Springe Rivas-Santiago, B, & Cervantes-Villagrana, A 2014, Novel approaches to tuberculosis prevention: DNA vaccines, Scandinavian Journal Of Infectious Diseases, 46, 3, pp. 161-168, Academic Search Complete, EBSCOhost, viewed 28 February 2014. Read More