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How effective is tuberculosis (TB) treatment in less economically developed countries?

Tuberculosis (TB) is an infectious disease that is caused by several bacteria called ‘Tubercle bacillus’.The bacterium were discovered and named as a cause of TB in 1882 by the German Biologist Robert Koch.Tubercle bacillus is a small and extremely dangerous bacterium; it has a long life span and can survive for months in dryness and resist mild disinfectants (Stefan, 2000).

TB is a contagious disease which spreads in similar way to common cold and flu viruses; the bacteria are transferred from host to host in small droplets.

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There are numerous types of TB, of which Pulmonary TB is one. It can be transferred when an infected person sneezes, coughs or spits and an uninfected person comes into contact with the droplets, for example in saliva (Stefan, 2000).

Symptoms

The symptoms of this disease are severe coughing including bloody mucus, chest pains, shortness in breathe, fever, weight loss and sweating. The secondary infection affects the immune system, bones and gut. The most common scenario when infected with TB is when a person contacts it following another disease or infection which has weakened the immune system. For example when a person has the human immunodeficiency virus (HIV) their immune system is weakened; people with HIV therefore show an increased rate of TB infections. Only when you show symptoms of TB can you infect others (Ottenhoff and Kaufmann, 2012).

Organ infected by tuberculosis

TB is an extremely harmful disease cause by microorganisms called ‘Tubercle bacillus’. It harms many organs in the human body. It mainly affects the lung (as shown in figure 1) and that is called ‘pulmonary tuberculosis’ the initial symptom last up to 6/7 months. During this long time period the immune system fights of the disease and bacterium. After that period and the immune system resisting the disease some particles of the bacteria escapes into the bloodstream, this is then carried around the body. Usually the immune system cannot stop the bacteria and leads to being untreated. If left untreated for a long period of time then the environment in the body is perfect for the bacteria to multiple, this is extremely dangerous as the tissues of the organ for example; the tissue of the lung may become infected. When the lung is infected it results in destruction in the respiratory system. It is important this is not left unattended as it will cause permanent scarring to the tissues of organs.

Diagnosis

The main method of diagnosing TB is a harmless skin test. This is performed by injecting a small amount of fluid under the skin around the forearm; this is a special fluid containing a protein copied from the microorganism Tubercle bacillus. After a few days the area where the fluid was injected is visually scanned. To determine whether you have the infection the scientist will measure the diameter and hardness of skin where the injection was placed. If the area if hard and the skin appears to be raised it will mean you have a bacterial protein present in your body. The redness in the area injection is not taken in to account. With this test it is possible to get false positive, for example a negative test does not mean you do not have TB. If the test is positive a chest x-ray will be taken to assess whether the TB infection is active (see figure 1).

Areas affected by tuberculosis

TB was a main cause of death in the late 19th century and early 20th century. TB still occurs in humans worldwide but more concentrated in many developing countries and kills 4 out of 10 people who are infected.

Figure 2 shows that over 15 years (1990 to 2005) the estimated TB incidence rate global has not changed much, with incidence in Europe slowly increasing whilst staying below the global average. In Africa however the estimated incidence has remained above the global average. Figure 2 also demonstrates that having human immunodeficiency virus (HIV) is a risk factor for being infected with TB. HIV is a condition which affects a person immune system, and so makes suffers more vulnerable disease. Therefore attempting to reduce the prevalence of HIV could also reduce the rate of TB in Africa population. This is a social problem as HIV is spread by contact with bodily fluid from a HIV suffer, therefor social education programs about safe conduct with HIV suffers could help reduce both disease and HIV. However the data (fig 2) only shows up to 2005. More recent data would be needed to see how the rates have changed from 2005-present.

suffers more vulnerable disease.

There is also a correllation between TB and economic condition. Hihgest incidences are seen in africa, where the gross domestic product (GDP) is low. The world health organisation (WHO) predicted that 8 million people per annum contract TB, 95% of these cases are found in developing countries. It is estimated that 3 million perople die from TB every year, which means the 4 put of 10 people infected from developing countries die each year.

Immigration (process of relocation permanently to a foreign country or area) is increasing which leads to countries that usually have relatively low incidence of TB reporting an increase in the number if case per annum.

TB is often referred to as a disease of poverty because it is common in developing countries. TB is transmitted in those conditions with areas that are overcrowded, have poor ventilation and a lack of nutrients in their diet. Living in an overcrowded area increases the risk of contracting TB as the airborne droplets are able spread faster; an example of this would be an overcrowded area such as a prison. Groups who have the largest chances of catching the disease are those who have close contact with infected persons over a long period of time and live in a poorly ventilated room.

Figure 3 shows clearly that the continent of Africa has the highest number of TB cases in its population. There is a link between poverty and TB. This is because the population there is living in a poor lifestyle or HIV is very common. As discussed above, HIV makes a person vulnerable to TB because it weakens the immune system. Another reason for this economic link could be that hard manual workers, with lower economic status, often live on a diet with fewer nutrients, which also weakens the immune system, leaving a person more vulnerable to TB.

Because this is a disease of poverty’ there are economic implications; the countries affected have no money to invest in finding treatment and research. The burden then falls on more economically developed countries. However because of the benefits being gained from this; pharmaceuticals companies invest little money into TB research. The reliability of fig 3 on the estimated of the cases varies depending on the sources. Economically developing countries have easy access to medical data, e.g. NHS in UK. However data on less economically developed countries is less reliable due to less health services.

1.2 Different types of antibiotics

Isoniazoid is the drug most commonly used to treat TB, and is the most effective. Isoniazoid is bactericidal (capable of killing bacteria and viruses), non-toxic, easy to access and inexpensive. The usual dosage is 3 to 5mg/kg body mass produced in a peak concentration. The drug is effective because it travels throughout the entire body, including the cavities. The drug concentration is alike to the concentration found in the serum.

Rifampin is also a bactericidal for TB. Like Isoniazoid it is non-toxic and is easy to access. It is effective as it is absorbed quickly from the stomach lining and intestines. After a few hours the serum concentration increases; when digested it absorbs into the tissues and cells. It can have very bad side affects even though the drug is a protein bound. The most common side effect is damage to the stomach lining. Other side effects include skin irritation, yellow urine, nausea and joint pain. These side effects are quite rare.

TABLE!!!!!

Development in treatment for TB

The technology and knowledge about TB is increasing. There are number of new drugs tested, including amikacin, quinolones, rifamycin derivatives, clofazimine, and beta-lactams. They have all been tested separately but have not been tested in a multidrug regimen for treating TB. The recent increase in the occurrence of multi drug resistant TB creates an increase in the need to consider multi drug regimen as a treatment option. While all these medication have been tested none of them have been evaluated as a well designed drug. Appropriate dosage and intervals for the use of these drugs for TB has not yet be established. However WHO reported that only 1 anti-TB drug has actually come on the market in the last 28 years. This is said to be because pharmaceutical companies have lost interest in TB research because there is little or no profit associated with it (Blanc and Nun, 2000). However the source is from 2000; not up to date. New drugs for TB could have be reported after the time period 2000.

Vaccination

There is only one vaccination for TB available and it is called bacillus calmette Guerin (BCG) (see figure 4). Scientist began testing between 1921 and 1924 on animal models which raised ethical concerns as many deemed testing on animals wrong, therefore BCG was considered a controversial drug. Throughout testing of the BCG vaccine promising results were found, and it was therefore distributed worldwide as an effective treatment for TB. Today BCG is regarded as the most widely used vaccine, and is being provided to less economically developed countries as a quick way of curing TB; this excludes people with HIV. The use of BCG vaccination faces some problems as it uses a live form of TB, the BCG is therefore not suitable for use in patients with HIV as they already have a compromised immune system, so exposing them to a live virus increases their chances of becoming infected with TB.

Many vaccinations against TB are being developed. The most popular vaccine is the subunit vaccine. This vaccine is a protein obtained from the disease TB. Using a mixture of these proteins has shown good results. As it is a cellular vaccine and does not pose a risk of causing the disease.

A DNA bases vaccine has been tested and has also showed promising results. The vaccine uses DNA as a system to deliver TB antigens. The DNA based vaccine does not have any problem with where the disease first originates and induces long lasting immunity. Several trails with DNA vaccination have shown protection against TB. It does this by releasing more concentrated ‘lymphocytes’ blood cells and are more effective towards the infected cells.

Within the next few years, these vaccines should be available and safe for testing on human specimens. When a clinical trial is set up it is always in a lab, firstly on animals. This data is deemed reliable as it is done in a lab, but requires further human testing before data is valid for human treatment.

Conclusion

“We cannot win the battle against HIV/AIDs if we do not also fight TB. TB is too often a death sentence for people with HIV/AIDs” – Nelson Mandela XV international AIDs conference, Bangkok,July 2004

There is a link between developing countries and the prevalence of TB. Ways to prevent this could be to provide new-borns with a vaccine against TB; however that could bring the risk of the new-born being infected with the active disease if their immune system is weak.

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