Diagnosis and Treatment of TB Research Paper

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Tuberculosis

Causative agent

Tuberculosis is an infectious disease of animals and humans. The most common causative agent of the disease is a bacterium a mycobacteria known as Mycobacterium tuberculosis. This bacterium was first discovered by Robert Koch in 1882. The physiology of this bacterium is aerobic and hence requires very high oxygen levels. This is primarily a pathogen of the mammalian respiratory system which infects the lungs. The most common methods used to diagnose tuberculosis are acid-fast stain, tuberculin skin test and chest radiations. M. tuberculosis requires oxygen in order for it to grow. Due to the presence of mycolic acid, M.tuberculosis has an waxy coating on its surface which is unusual making the cells impervious to Gram staining It can not retain any bacteriological stain as a result of a high lipid content on its wall therefore acid-fast staining or ziehl-Neelsen staining are used. Despite this M.tuberculosis is still considered to be a Gram-positive bacterium. While mycobacterium does not fit in the Gram-positive category looking at it from an empirical standpoint, they can be classified as acid-fast Gram-positive bacteria because they lack an outer membrane.

M.tuberculosis divides after every 15-20 hours which is relatively slow as compared to other bacteria that have divisions that are divided in minutes. It is a small bacillus hence it is able to withstand weak disinfectants and hence is able to survive for weeks in a dry state. The mycolic acid found in its cell wall makes it resistant and is a key virulence factor. When it is in the lungs the bacteria is taken up by alveolar macrophages but they are not able to digest and get rid of this bacterium. The cell wall of the bacteria prevents any fusion between the phagosome and lysosome that contains various antimycobacterial factors. M.tuberculosis blocs the bridging molecule but this blockage does not prevent fusion of vesicles that are filled with nutrients. Therefore the bacteria multiply unchecked within the macrophage. M.tuberculosis also carries the UreC gene that prevents phagosome acidification. It also produces isotuberculosinol that prevents the phagosome from maturing. The bacterium is also able to evade macrophage-killing through neutralizing the reactive nitrogen intermediaries.

History

Tuberculosis has been a disease known to mankind since ancient times. Earlier the disease was referred to using many names which includes consumption due to the severe loss in weight and how the infection seemed like it consumed a patient, phthisis pulmonaris and white plague since there was an extreme pallor that was seen through the people who were infected. The organism that causes tuberculosis has been in existence for over 15,000-20,000 years. It has been found in relics from ancient India, Egypt and China. Spinal tuberculosis known as Pott's disease has been detected by archeologists among Egyptian mummies. The evidence of tuberculosis of the lymph nodes of the neck referred to as scrofula is found within the middle ages. This was termed as the king's evil and there was a belief that kings of England and France were able to cure scrofula by simply touching the infected people. Tuberculosis reached its peak in the 18th century in Europe having prevalence high as 900 deaths in every 100,000. The poor ventilated and crowded housing, malnutrition, primitive sanitation as well as other risk factors led to this rise. This is around the time the term white plague emerged.

There have been a lot of inaccurate misconceptions about tuberculosis cause and transmission throughout time. People frequently believed that TB was transmitted by direct contact with an infected person's skin or even the sharing of eating utensils. There has also been a lot of stigma associated to TB that has had a significant impact on the willingness of a person to be tested and possibly receive treatment for the disease. However, in recent times there has been a lot of public education on tuberculosis. This public education has equipped people with information on TB and hence there are no longer misconceptions on the disease. People are also coming out to test for the disease and consequently receive appropriate treatment. We can say that there have been a lot of changes when it comes to the knowledge and attitudes towards tuberculosis over time (Mandal, 2014).

Epidemiology

Roughly a third of the word's population has been infected by M.tuberculosis. New infections occur at a rate of one in every second. However, it is not all infections of M.tuberculosis cause the tuberculosis disease and many of the infections are normally asymptomatic. 13.7 million Chronic cases were estimated in 2007 and in 2008 there were 8.8 million new cases reported, 14.5million deaths were recorded and they mostly occurred in developed countries.

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Tuberculosis is the second most causes of death behind HIV. Tuberculosis distribution is not uniform around the world, about 80% of the population in countries in Africa and Asia test positive while only 5-10% of the population in the U.S. test positive to tuberculosis. In 2012, Swaziland was the country with an estimated high incidence rate with 1200 cases in every 100, 000 people.

India had the largest total incidence with an estimated 2 million cases. In developed countries tuberculosis is not common and is an urban disease. TB incidence varies with age and in Africa it primarily affects young adults and adolescents. However in countries where TB has a low incidence it is commonly a disease for the old people. Tuberculosis is seasonal and its peak is mostly in spring/summer. When a person with tuberculosis coughs, sneezes, or spit they release infectious aerosol droplets. Each of these droplets is capable of transmitting the disease since an infectious dose of TB is very small. Those with a prolonged and frequent close contact with people with TB are at high risk of becoming infected an estimated 22% infection rate (Mathema, Kurepina, Bifani, & Kreiswirth,2006).

Pathology

About 90% of people infected with M.tuberculosis have asymptomatic latent infections with about 10% lifetime chance that this latent infection will move to active tuberculosis disease. The primary site of infection of TB in the lungs is known as Ghon focus. The hematogenous transmission spreads infection to distant sites like kidneys, peripheral lymph's, the bones and even the brain. The disease can affect all parts of the body but for reasons unknown it rarely affects the heart, thyroid, pancreas and skeletal muscles. Tb bacteria enters the blood stream from an area where there is damaged tissues and can spread all over the body and set up many infections which appear as tiny, white tubercles within the tissues. The general signs and symptoms of tuberculosis include chills, fever, loos of appetite, night sweats, and fatigue and weight loss (Knechel, 2009).

Response and Treatment

Once infectious droplets are inhaled they settle down through airways. Mucus catches the foreign substance and the cilia on the surface constantly beat the mucus and the particles. This is the initial physical defense which prevents infection in a person exposed to tuberculosis. These bacteria in the droplets then bypass the mucociliary system and reach the alveoli where they are engulfed by alveolar macrophages. This is the next line of host defense and part of the innate immune system providing an opportunity for the body to destroy this invading mycobacterium hence prevent infection. The subsequent phagocytosis by these macrophages initiate a chain of events which lead to either successful control of infection, then latent tuberculosis or progression to active disease which is called the primary progression of tuberculosis. After infection by the macrophages the M. tuberculosis continues to slowly multiply with a cell division in every 25to 35 hours. Regardless of whether this infection progresses or is controlled the initial development involves proteolytic enzymes and cytokines production by macrophages to degrade the bacteria. For a person that has an intact cell-mediated immunity, the next defensive step is formation of granulomas around the bacteria (Knechel, 2009).

The initial empiric treatment of TB requires that a patient is started on a 4-drug regime: isoniazid, rifampin, pyrazinamide and streptomycin or ethambutol. Patients with TB receiving pyrazimide need to go through baseline and periodic serum uric acid assessment and those that are receiving long-term ethambutol therapy need to go through baseline and periodic visual acuity and red-green color perception testing. After 2 months therapy, pyrazinide can be stopped isoniazid and rifampins are then continued on a daily basis for four months. Directly observed therapy is a recommendation for all patients. Patients should go through sputum analysis for M.tuberculosis on a weekly basis. The antibiotics used in the multi-drug therapy prevent progression of TB by killing M.tuberculosis. Isoniazid and rifampin can be taken alone in order to prevent latent TB infection from turning to active tuberculosis.

Tuberculosis can be prevented through TB vaccination known as Bacillus Calmette-Guerin (BCG). This is used for protecting children rather than interrupting transmission in adults. TB drug treatment can also be used as a means of preventing TB known as chemoprophylaxis. This can reduce the risk of a first episode of active TB occurring in a person exposed to infection or….....

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