Pathophysiology and Management of Tuberculosis Infection

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Introduction

The origin of acquired immune against infectious diseases was discovered almost two thousand year earlier. In 430 BC Thucydides observed that the great plague in Athens never attacked the one who ailed once; they were either killed or recovered and were never to be tormented twice. By the end of the 18th century, Jenner observed that immunization for small pox could be provided through a vaccination with cowpox virus, which became the basic idea behind all vaccination literature.

Today vaccination is used worldwide to provide immunity against many infectious and fatal diseases. The concept behind this vaccine which has made it so successful is that behind all viral or bacterial diseases, primary protection is though t to be provided by a long-lived biological immune response of the human body through production of antibodies in the body. This was the basis for all vaccines throughout medical history.

Tuberculosis (TB) disease is not infected by ninety percent of the people infected with Mycobacterium tuberculosis. This implies that human beings are inherently immune to TB. The people who do get infected are those who have low-immunity because of their infection with HIV or due to their low socio-economic background that characterize many TB patients. Thus, it is believed that “immune suppression, rather than an inherently inadequate immune system, is the most important determinant of predisposition to disease.” (Hanekom et al, 2007) It is further believed that an immunocompetent person may still be infected by TB, although less frequently, and the virulence nature of the infecting pathogen may transform eh scenario into a confusing one.

Presently TB vaccine research and development has been undergoing an era of renaissance. This, though, is in sharp contrast to the limited development of BCG in the first two decades of the 20th century. This is so because after almost seventy years of development of BCG, it is the only TB vaccine available to medical science. Mostly the researches in the field have been operational which tried to innumerate areas like expanding the delivery program of BCG through Expanded Programme on Immunization, holding field trials in various geographical locations using different BCG strains (Ferguson & Simes, 1949; Aronson et al, 1958; Rosenthal et al, 1961; Vandiviere et al, 1973; Hart & Sutherland, 1977).

A meta-analysis of these studies shows that the effectiveness of the BCG vaccine varies greatly (<0% to >80%) (Colditz et al, 1994; Colditz et al, 1995) and there are various opinions regarding the effectiveness of BCG vaccine today (Rahman et al, 2001; Fine, 2001).

Research has shown that the incidence of TB in Great Britain has increased over the years (Rose et al, 2001; Nursing Times, 2007). According to statistics the reported cases of TB increased by 2 percent in England and Northern Ireland in 2007 (Nursing Times, 2007).

But research has also proven that there has been a dramatic decline in cases of TB in developed countries (Vynnycky & Fine, 1999). Given these two contradictory views, it is safe to assume that the death toll and rate of infection due to Tb has drastically gone down in developed countries like the US and the UK where proper immunization is provided to the mass. But does this indicate that TB can be eradicated completely and there would be no need for TB vaccine? This is an area that requires proper understanding regarding the present researches of TB and search for new vaccines.

In this paper, we will critically analyze the vaccination developed for tuberculosis (TB) and how the process of immunization for the bacteria takes place. Then we will try to ascertain that if TB vaccines are required in the UK with the decreased number of incidents of TB. The main aim of this paper is to facilitate an understanding of how pathogen (e.g. TB) interacts with the host producing metabolic and immunological events. In this paper we will discuss how vaccinations work to immunize human body from fatal and infectious diseases. The vaccinations which are used to prevent TB like BCG and discuss them critically. Further, this paper will try to ascertain if TB vaccination can be or should be removed from UK.

Role of Vaccine

The immune system of all humans has two distinct arms but they are interactive viz. innate and adaptive (Hanekom et al, 2007). ‘Innate’ immunity is the response that the host gives when it has its first encounter with a pathogen. This immunity is capable of providing immunity against a broad variety of microbial challenges in non-specific nature. The different cell types which belong to the innate system comprise of macrophages, which form the front line in defence against TB.

But in contrast, ‘adaptive’ immunity is pathogen specific. This is why it is also called ‘specific’ immunity. In case of ‘innate’ immunity, once the system identifies the approach of a pathogen, it tries to control its initial spread, and adaptive immunity grows within the system to deal with the specific challenge. This primary tackling of the pathogen by the adaptive design within the system is called the ‘immunological memory’, which implies that the infection is remembered by the system, which enables it to react more rapidly and vigorously when there occurs a case of re-infection with the same pathogen. For example, in case of TB, the T lymphocyte is a key example of an adaptive immune cell.

Is a TB vaccine possible?

TB Vaccine

History of TB in the UK

TB has been around in the European continent since 8000 BC (this can be said due to the presence of skeletal deformities caused due to TB has been identified). The disease reached epidemic proportions in the early 19th century when there was a rapid growth of urban poor population due to industrialization. Historians have estimated that one-third of all the deaths in London during the period were due to TB from 1800 to 1840 (Storey, 2004). Although the disease attacked mostly the underprivileged, but its occurrence among the affluent class could not be negated.

In the early times, TB was known as “the white plague”, was not completely understood by medical science. Theories of the disease, then, were attributed to moral turpitude, to drinking of contaminated water, air and soil or to socio-economic causes particular to the locality. It was not until 1882; Robert Koch identified tubercle bacillus that the realization doomed on medical science that it could be transmitted.

This led to the confinement of the patient in his home, hospitals, or sanatoriums for such patients. Radical surgical methods were tried to remove the affected areas, other than phrenicolysis (dividing the phrenic nerve), plombage (a process of extrapleural insertion of fat, soft paraffin wax, sponge, and Lucite shpheres) and scalenectomy (process by which scalene muscle is divided) were attempted as treatments of TB.

Even though proper modern day treatment was absent in the UK along with chemotherapy, the incidence of the disease declined in the UK, mainly due to public health policy reforms and improved “nutritional status and social and physical environment of the urban poor” (Storey, 2004, p.291) in the early 20th century. Such reforms had its origin from the belief that insanity caused this epidemic proportion disease. In 1913 it was made a law that all TB infections are to be informed to the authorities according to the National Public Health Tuberculosis Act.

The arrival of proper and effective drug therapy helped in declining the onset of TB in the UK. The introduction of radiology to be used to screen, improve surveillance, pasteurize milk, treat the contact individuals, and widespread use do BCG vaccine declined the rate of TB considerably. But in the 1980s there was a relapse of TB in the UK and reasons were more due to rise in social deprivation, HIV co-infection and a failure to control the spread of the disease.

Vaccination

In order to understand how the TB vaccines work it is important to understand the natural history of TB. When a healthy uninfected person is exposed to the source case it may lead to primary infection with Mycobacterium tuberculosis. This infection with M. tuberculosis may lead to primary TB or to a persistent asymptomatic infection, which is difficult to be diagnosed, as it remains silent throughout the person’s life.

But in case of 10 percent of immunocompetent people and 8 percent of HIV-positive individuals that such a latent infection may go undiagnosed which leads to TB. This history of TB provides avenues for three possible ways of vaccination for TB, which are “one that would prevent primary infection and disease following exposure; a second that would prevent reactivation in those already infected; and a third, an immunotherapeutic adjunct to standard TB treatment, which would speed and enhance standard TB treatment in those already ill from TB.” (Ginsberg, 2002, p.483) These different forms of immunizations are discussed in greater detail later.

Types of vaccine for TB

There are four basic types of vaccine for TB. The first comprises of one or more mycobacterial components which are thought to produce protective immunity, and comprises of almost 50 percent of the people who are identified as contracts (Ginsberg, 2002). These individuals who were given this vaccine were tested and were found to be composed of protein subunits, while a few use lipid or carbohydrate subunits. The second form of immunization is an unalloyed DNA vaccine.

And the third, is based on “love, accentuated mycobacteria, including recombinant BCGs (rBCGs) expressing immunodominant antigens and/or cytokines, attenuated strains of M. tuberculosis, and nonpathogenic mycobacteria (e.g. M. vaccae, M. smegmatis, M. microti, and M. habana)” (Ginsberg, 2002, p.484). And the fourth vaccine was made based upon live, attenuated, nonmycobacterial vectors, such as Salmonella or vaccinia virus.” (Ginsberg, 2002, p.484)

The vaccine that is currently used against TB is called bacille Calmette-Guérin (BCG), was developed by the French scientists Calmette and Guérin in the early 20th century. BCG has been effectively used around the globe for over 80 years and has been provided to more people than any other vaccine. It has minimal side effects and is used to prevent miliary and meningeal TB in children and infants to a certain degree. But BCG fails to prevent any immunization from the most prevalent from of the disease i.e. pulmonary TB in adults. Actually, the efficacy of BCG in adults ranges from 0 to 80 percent depending on the geographic location and other socio-economic conditions (Fine, 1995).

Though a meta-analysis of the vaccination, data available shows that it has a theoretical effectiveness of 50 percent; it is prevalent knowledge that only 5 percent of the vaccine-preventable deaths caused by TB could have been prevented by BCG. Hence, it can be concluded that BCG is not a satisfactory vaccination to prevent TB. But there are still arguments regarding the need of a new vaccine to prevent TB (Kaufmann, 2000).

Kauffman even question the necessity of a vaccine when chemotherapy can completely cure TB. But the reason a preventive measure is required is due to the nature of the drugs which need to be taken for a long period of time (usually 6 months or more) and a combination of three specific drugs have to be taken to develop drug resistance. Studies have shown that compliance to the drug regime is very high and a patient suffering to chronic TB cannot be properly treated using this strategy (Kaufmann, 2000). Moreover, such therapy is expensive and cannot be accessed by the mass. Hence, there is a need to develop an effective but less costly medical prevention or treatment to fight TB.

The feasibility of TB vaccination usually receives support from the fact that less than 10 percent of the candidates infected by M. tuberculosis develop acute TB. The main cause of TB, as is believed, is due to the weakening of the immune system, which keeps the bacteria under check till the time its active. This fact is re-established due to the infection of TB to HIV positive individuals. But experiments with mice after been treated with chemotherapy show that the mice are not immune to M. tuberculosis, which shows that there is a need for vaccine against TB. Thus, the immune system fails to control the pathogen in the long run, and it gets weakened due to exogenous interventions, thus allowing reactivation of the bacteria. This explains the triggering of acute TB in BCG expressed candidates.

Even though there are a number of vaccinations available, why BCG is the most commonly used vaccine? First, even though there are a number of available vaccinations against TB, all these strains of BCG work effectively in combating TB. This is a sure prevention due to the “low dose, aerosol challenge models in mice and guinea pigs, currently considered the standard for such experiments, most closely mimic primary TB disease in a naive host” (Ginsberg, 2002, p.484). BCG helps in prevention of children and infants who are “immunologically naïve hosts” from getting infected.

Second reason behind this is that only a few animal vaccines models have provided protection as well as BCG. A few of them have provided better protection than control BCGs, which is measured by the “number of colony forming units in lung, liver, and spleen, and clinical features such as weight change and survival” (Ginsberg, 2002, p.484). Now testing of these candidates are being done for safety and immunogenicity testing in humans.

Improvement of BCG

Research is being conducted to improve BCG. Strategies being followed by a small number of researchers involve testing the effectiveness of BCG at lower doses and in a prime-boost protocol. This strategy follows the data from the deer infection model which indicates that double vaccinations delivered as a prime, followed by a booster dose are more effective than single vaccines to protect against infection and disease (Griffin et al, 1999; Griffin et al, 2001). Hoft et al. have investigated the human system’s response to BCG when delivered in various methods, to see if BCG may become more effective if the delivery method is altered (Hoft et al, 2000; Hoft & Worku, 2000). For instance, oral delivery, which was the initial method used provide better mucosal immunity then the present method of intradermal route.

Further researches are being conducted to improve using the prime-boost strategy that combines BCG (either as a boost/prime vaccine) along with a new candidate vaccine. It is expected that the two vaccines will act additively and maybe even synergistically to improve the effectiveness of BCG (Feng et al, 2001; McShane et al, 2001; Brooks et al, 2001). If BCG vaccine could be improved or be used with another vaccine then the administrative problem of commissioning a completely new vaccine could be eliminated. This would make the acceptability and usability easier and will provide better immunity.

New Vaccines

There are various new vaccines which have been introduced as substitutes of BCG. The first new candidate vaccine to enter the first phase of trials for safety and immunogenicity was an immunodominant protective antigen called Ag85A. This was made from M. tuberculosis which is expressed in individuals in the same process as vaccinia virus (MVA-Ag85A) (McShane et al, 2001). McShane and Hill have tested MVA-Ag85A in a few tuberculin skin test-positive candidates.

They expect that in order to investigate the “safety, immunogenicity, and efficacy of a BCG prime/MVA-Ag85A boost strategy” in both case of skin test positive and negative individuals will provide the desired result. They further intend to test, in similar fashion o f a prime-boost strategy, a poxvirus called FP9 while expressing Ag85A in candidates.

There are other tests which are being conducted in the UK to provide a substitute of BCG or to provide BCG along with a new vaccine following the prime-boost strategy. These have been mentioned by Ginsberg:

Other candidates being readied for human testing in the next 6 months–2 years include: a recombinant BCG over expressing Ag85B (M. Horwitz, personal communication, 2002), in a collaborative effort with the Sequella Global TB Foundation

and the United States National Institute of Allergy and Infectious Disease; a subunit vaccine composed of M. tuberculosis-derived immunodominant fusion proteins, Ag72f+/-Ag85 (S. Reed, personal communication, 2002); a multi-epitope subunit vaccine/adjuvant combination developed by InterCell Corporation; and, potentially, attenuated mutants of M. tuberculosis being developed at Albert Einstein College of Medicine, New York, USA, and the Howard Hughes Medical Institute, New York, USA, by William Jacobs Jr (W.R. Jacobs Jr, personal communication, 2002). These attenuated strains of M. tuberculosis lack the ability to make key amino acids or vitamins and cannot survive in the host for long. The hope is this will render them safe for use, even in immunocompromised individuals.” (Ginsberg, 2002, p.485)

Jacobs et al. have made new M. tuberculosis which is said to be the inventive attenuating transmutation of M. bovis, following the same process of RD1 deletion that helped in the making of BCG (Behr et al, 1999). This process of RD1 deletion in M. tuberculosis will be helpful to test the working hypothesis that by deletion of RD1, the strain will be attenuated, but will remain in the human system for a long enough time to make the system immune and self-protective response, which would be stronger than the protection provided by BCG. This experimentation is being furthered by exploring M. tuberculosis virulence by comparing the genomes of virulent mycobacteria, and also various strains of BCG to each other and the virulent mycobacteria.

An environmental bacterium called M. vaccae is also being tested on humans. This experimentation includes a heat-inactivated investigation as a preventive vaccine in a form of 5 doses expressed in HIV-positive individuals (Waddell et al, 2000).

An alternative to BCG vaccine is required, as it has been found through research that the effectiveness of BCG vaccine differs greatly in different population. The underlying hypothesis to this effect is due to the interaction of the vaccine and microbacteria which is commonly found in the environment. But no precise mechanism as to how this affects the vaccine is yet to be found. This study was conducted on mice who were priory given BCG. The study revealed that BCG enabled only a transient immune response with low frequency of microbacterium cells and no immunity against TB (Brandt et al, 2002). The test also showed that the TB subunit vaccines had no effect after exposure to environmental microbacterium and hence provided a better protection against TB (Brandt et al, 2002).

DNA vaccines are presently being tested experimentally as an alternative to BCG (20). DNA vaccines are expected to have higher responsiveness due to their ability to induce persistent, cell emanated immune responses to antibodies isolated from various viruses, bacteria, and parasitic pathogens. In animals, DNA vaccines have been used to provide protective immunization against HIV, influenza, bovine herpesvirus, rabies, leishmaniasis, malaria, herpes simplex virus, and tuberculosis (Chattergoon et al, 1997; Donnelly et al, 1997; Huygen, 1998). So it has been tested to see its effectiveness as prevention against TB in humans.

Another new vaccine tested as TB vaccine is DNA vaccines encoding native ESAT-6, MPT-64, KatG, or HBHA mycrobacterial proteins or similar protein fused in the tissue plasminogen activator (TPA) signal sequences were tested for their capacity to combat “elicit, humoral, cell-mediated, and protective immune responses in vaccinated mice” (Li et al, 1999, p.4780). All the eight induced plasmids produced specific humoral responses, the constructs of TPA fusions created a higher antibody in vaccinated individuals.

Even though the DNA vaccines induced in vaccinated individuals created a substantial gamma interferon response in spleen, the antigen-specific response of the lung was 2 to 10 times lower than the spleen’s response during the time of infection. But the research showed that “DNA vaccines encoding the ESAT-6, MPT-64, and KatG antigens fused to TPA signal sequences evoked significant protective responses in mice aerogenically challenged with low doses of Mycobacterium tuberculosis Erdman 17 to 21 days after the final immunization.” (Li et al, 1999, p.4780) The research further indicates that the response of BCG to M. tuberculosis has greater than that of the DNA vaccines tested; the authors believe further research in the area could produce alternative results.

T cells are central to the protection of the system against TB; further development of vaccines should be focused on T-lymphocyte populations. All the vaccines which are in use today work through antibodies rather than T-cells. Moreover, most of the vaccines do not prevent infection, but try to prevent the disease but they allow the entering and settling of the pathogen in the host but simply prevent its harmful effects initially.

Further, vaccines are given in an early date when infection did not occur, which shows that vaccinations by nature are preventive rather than therapeutic. This is effective for other disease, but TB, when these tissues need to be considered. Since a large group o people who are living with the infection, a post-infection vaccine strategy must be developed. Moreover, due to the increasing concern of co-infection of HIV and MDR-TB, therapeutic vaccines need special attention.

DNA vaccination has been developed as an alternative as has been done by many researchers, who have tried a successful therapy of TB on mice by treating them with DNA construct encoding HSP60 (Lowrie & al., 1999) and ESAT-6, MPT-64, and KatG (Li et al, 1999). Thus, a vaccine which could prevent the infection with M. tuberculosis would be ideal to prevent TB as because at the time of infection the host usually encounters small number of bacterium. Thus, a theoretical experiment to prevent infection of TB exists.

In another strain, if an antibody successfully prevented and eliminated the eliminate M. tuberculosis in the alveolar stage before they reach macrophages, would provide a solution to the problem. But this possibility is yet to be conceptualized.

Vaccine induced immunity is a more likely prospect. This vaccine induced immunity will attack the pathogen once it establishes itself in the macrophages, which is exclusively done by T lymphocytes.

Table 1 show that current vaccines available. The subunit approach relies on the axiom that a few antigens are enough to trigger a protective immune response of the system. Recent research in the area of M. tuberculosis genome and due to the availability of increased information regarding gene introduced from transcriptome and proteome analyses, the availability of protective antigens is a lot (Cole & al., 1998; Jungblut & al., 1999; Behr et al, 1999). The DNA technique showed 129 types of M. tuberculosis –which are specific open reading frames unavailable in the BCG vaccine strains (Behr et al, 1999). Evidently, the M. tuberculosis genes absent in BCG are the causes for the virulence factors, but also decrease the protective antigens. This development has triggered the interest for the hunt for M. tuberculosis genes which are of interest for the development of a vaccine, as destroyers or as protective antigens.

Table 1: TB vaccine candidates.

Vaccine Candidate Potential Advantage Potential Disadvantage
Subunit Vaccine
  • Naked DNA
Protective antigens, low side effects limited number of T-cell clones, mainly
CD4+, low immunogenicity, short-lived
  • Recombinant carrier expressing antigen
Protective antigens limited number of T-cell clones, mainly
CD8+, persistence, safety issues
Whole Bacterial Vaccine: CD4+ and/or CD8+ T cells, protective antigens limited number of T-cell clones, safety issues
  • M. tuberculosis deletion mutant
CD4+ CD8+ T cells, unconventional T cells Safety issues
  • rBCG expressing cytolysin
CD4+ CD8+ T cells, unconventional T cells Devoid of TB-specific antigens, safety issues
  • rBCG expressing cytokine
Improved immunogenicity, unconventional T cells mainly CD4+ T cells, absence of TB-specific antigens, safety issues
  • rBCG over-expressing antigen
Protective antigens, unconventional T cells mainly CD4+ T cells, safety issues
Combination Vaccine:
  • rBCG co-expressing immunomodulator + antigen
Enhanced immunogenicity, protective antigens Safety issues
  • rM. tuberculosis deletion mutant expressing immunomodulator
Enhanced immunogenicity Safety issues
  • Prime-boost
Enhanced immunogenicity Safety issues

Even though there is a plethora of literature regarding genomics and proteomics, there are no clear parameters that define protective antigens. The question that arises is if there are M. tuberculosis-specific antigens that are missing in BCG? Are they antigens which are unseen or cell-bound? Or do they possess certain unique functions? Maybe they are most profusely expressed proteins? The present research do not provide any clear understanding of all these questions or any plan of action which leaves the researchers to screen every single antigen as a possible candidate for vaccine. This is most likely best attained with naked DNA constructs, because they are easy to make and have a proven history of vaccine efficiency.

Protective antigens has been identified to belong to the antigen 85 family and hsp60 (Huygen & al., 1996; Tascon et al, 1996) and both have shown that this could protect mouse more this way than by BCG. Researchers who have been working for Malaria vaccine have identified that protective antigens with a vaccinomics approach which is a term for immunization free of the biological features of the candidate’s antigens (Hoffman et al, 1998).

On identifying the protective antigens, synthetic polypeptides uniting promiscuous defensive epitopes from numerous antigens can easily be done. The success of a protein vaccine will depends on the identification of a protective antigen and potent adjuvant which develops its immunogenicity. Even though naked DNA vaccines have substantial immunogenicity, additional developments are required in the area. Recombinant carriers comprise of attenuated salmonella and vaccination virus. The advantage of the former is that that it can be given orally and thus rouses a mucosal immune response, while the latter is a potent stimulator of CD8+ T cells. Both are equally feasible mainly in other systems.

The bacterial vaccine approach is based on the assumption that numerous antigens – proteinaceous and non-proteinaceous – naturally act together to provide maximum protection (Table 1). Additionally, entire bacterial vaccines yield from integral adjuvanticity. The methods to establish deletion of mutants in M. tuberculosis has been developed and the evidence of standard has been recognized i.e. if a single gene is deleted it can cause adequate attenuation (Berthet & al., 1998).

Assuming M. tuberculosis damages the immune reaction and thus stimulates inadequate protection, which is targeted for deletion, would comprise of classical virulence factors and immunosuppressive components. These consist of inhibitors of macrophage activation since the preeminent T cell fails when macrophages is not fully activated. Similarly, efforts have been made to develop the immunogenicity of BCG by two ways:

  • by developing the CD8+ T cell stimulating capacity,
  • by providing it with Th1 cell-evoking cytokines.

Another method is through engineering BCG to over-express discrete antigens, mainly due to its lack of the encoding gene and since it creates the antigen in inadequate amount.

The third method, i.e. the combination-vaccine strategy intends to unite both the approaches. According to this theory, both BCG and M. tuberculosis may be improved by merging both the options. On the other hand, as discussed earlier, prime-boost strategies, have already established their effectiveness in the investigational malaria model, are being used to make TB vaccination (Sedegah & al., 1998).

All the approaches discussed above are presently at the stage of animal experimentation or have just passed Phase I. but none have attained the efficiency of BCG. Thus, it is difficult to find a way to set a benchmark for a vaccine for TB. Here the question arises if a vaccine that provides protection equal to BCG, should it be considered inadequate? Or there should be a vaccine that can provide immunization in both pre- and post-infection stages?

It is often argued that a subunit vaccine which is as effective as BCG and provides higher degree of safety as compared to particularly in immune-compromised hosts, which provides the possibility to indentify a vaccinated and an infected candidate. Contrarily, a bacterial vaccine has to be much better than BCG if it is to be used further. In practicality, any vaccine has to prove its efficiency greater than BCG, to be accepted as a human vaccination.

Are they required in UK?

The BCG vaccine in the UK was initially provided to all children in schools within the age group of 10-14 years. But in 2005 the Department of Health made changes in its previous policy due to the fact that children in schools are not affected by TB. But the vaccination program was shifted to infants aged 0 to 12 months in areas which have high incidents of TB or whose parents or grandparents belonged to areas where there was high degree of TB. Research has shown that there is very low infection left in the country and the risk of the infection has lowered considerably (Batty, 6 July 2005; Department of Health, 2005).

So the authorities have decided that the universal vaccination programme should be stopped and the focus must shift to the areas, such as London, where the incidence of the infection is still high. Regarding this it can be said that areas which were once prone to TB infections should not be avoided too as these areas were primarily vaccinated with BCG. Research in the area shows that BCG is only helpful in preventing the infection from spreading but it does not terminate it neither does it prevent contamination of a non-infected person. So it may be possible that the infection may spread through the primary contact. So there remains chances of the infection to spread from individual to the other, if not assume the size of an acute disease in an individual. Thus, it is important to vaccinate the areas where the TB was earlier prevalent.

Another argument that must be posed in this respect is that even though it unanimous knowledge that BCG does not provide complete immunity against TB, it does not provide complete immunity. Experts are of the view that it provides immunity only to three-quarter of the people vaccinated with BCG. Thus, even the effectiveness of the vaccine is under scrutiny.

Due to the decreased trend of TB in the UK, this has gone down from 50000 cases in 1950s to 7000 per annum in the 21st century (Scottish Government, 6 July 2005). The concentration of the disease is more in urban areas and large cities. Thus, there seems to be no need to vaccinate infants in non-TB areas. But complete withdrawal of the TB vaccination program is not an option. This is because it will trigger the need to immediately develop a vaccine which will eradicate TB completely.

So as long as a new vaccine is not developed which will be able to eradicate the infection from the candidate systems, removing the vaccination program in the UK cannot be an option. This is because even though BCG is not a complete solution for TB, it does provide some benefit in terms of prevention of spreading of the disease in a system. Thus, removing of the vaccination program is a possibility only if there is a vaccine that proves to be successful in eradicating TB from the roots.

Conclusion

TB has been a scary name to all till the early 20th century. But with the development of BCG in the 1950s there was expected to be a solution that prevents the spreading the disease and reducing fatality caused by it. This provided a clear demarcation for the use of the vaccination which was safe and reduced the incidence considerably. But with the increased incidence of HIV infections in the 1980s, the incidence of TB increased. This was so because BCG vaccinated systems helped to grow immunity against M. Tuberculosis but as the immune system grew weaker due to HIV, the infection which was still present in the system starts to spread. This increases the cases of death due to TB.

So there arose a need to develop another vaccine which could provide immunity against TB and also do away with the infection. This triggered the numerous researches which were conducted in the area to develop a vaccine which could provide better immunity to candidates than BCG. But till date such vaccination has not been developed. Some of these researches tried to make a vaccination which could be expressed in combination with BCG increasing its efficacy while others have tried to travel through a different road altogether. This latter strategy is to make a DNA vaccine which could be effectively eradicate M. Tuberculosis.

But all these researches have not passed phase I of vaccination research where the vaccines have just been tested on animals like rats or guinea pigs. Clearly there is a need for a new vaccine to be developed which could eradicate the disease.

The public health policy in the UK has changed in the UK due to the decreased incidence of TB in the country. But there are still cases of TB found in select areas. The policy presently followed is to immunize small children within the age group of 0 to 12 months with BCG vaccine. This would help them not to get infected with the bacterium.

Clearly neither the policy stance of the UK government as well as the medical research scenario provides the signal that TB could be completely eradicated from the UK in the near future. This vaccination can be done away only if there is developed a vaccination which completely kills the bacteria.

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