Mycobacterium Tuberculosis
Introduction
Mycobacterium tuberculosis is a species of bacteria that is pathogenic( Herchline, 2012). It is one of the members of the Mycobacterium genus. It was first discovered by Robert Koch in 1882. It is described as being an acid-fast organism because it has a waxy coat composed of mycotic acid. This coat, which does not allow gram, stains to take. Mycobacterium tuberculosis is an aerobic organism that requires high level of oxygen to survive.
Mycobacterium Tuberculosis is an acid-fast bacterium that forms stable complexes with aryl methane dyes. Mycobacterium has peptidoglycan structures, which confers on them the acid-fast properties that they possess. It has a cell wall, which is tough, prevents the passage of nutrients into, and excreted from the cell. This gives it the slow-growing characteristic. The cell envelope contains a polypeptide layer, a peptidoglycan layer and free lipids. Fatty acids such as mycotic acid also give it the glossy appearance. Mycobacterium is found abundantly in soil and water. However, Mycobacterium tuberculosis, which is the pathogenic form, is found in the host (Knechel, 2009). .
Mycobacterium forms a complex with other bacteria in what is called the Mycobacterium tuberculosis complex. This complex consists of six members; including Mycobacterium tuberculosis and africanmun, these two species infect humans. Mycobacterium microti and bovis infects other mammals as well as humans. Mycobacterium tuberculosis is a non-motile bacillus. It is an obligate aerobe. It is a facultative intracellular parasite found in macrophages. Mycobacterium is acid-fast and does not stain with gram staining so it is neither gram positive or gram negative.
Tuberculosis
Tuberculosis is one of the oldest diseases known to affect humans( Herchline, 2012). It is a disease caused by infection with mycobacterium tuberculosis. Tuberculosis is caused by Mycobacterium tuberculosis. Tuberculosis is the most common cause of mortality related to infectious disease worldwide. The disease affects the lungs especially the upper one third in most cases. Other organs may also be involved, including the central nervous system, the lymphatic system, the genitourinary system and the gastrointestinal system. Tuberculosis is curable if properly treated. However, if left untreated, the disease is fatal in 5 years at the most.
Epidemiology
The global prevalence of Mycobacterium tuberculosis infection is 33%, meaning that one in every three individuals has been infected by the bacillus. In 1999, there were an estimated 8.4 million new cases (WHO, 2001). In 2010, there were 8.8 million new cases of Tuberculosis out of which 1.1 million resulted in deaths among HIV-negative people. 0.35 Million people with HIV/AIDS also died of causes associated with tuberculosis (WHO, 2011). This shows that the incidence rate of Tuberculosis has not shown any reduction over the last ten years.
There were 3.2 million incident cases of Tuberculosis and 0.32 million deaths among women in 2010. About 13% of Tuberculosis cases occur among people living with HIV.
There has been a steady decline in the number of patients in the United States reported to have Tuberculosis. This number has been on the decline since the 1940s, coinciding with an improvement in living conditions and the introduction of streptomycin as the drug of choice for treatment of Tuberculosis. As at 2001, the incidence of Tuberculosis stands at 10, 521. This figure is at an all-time low from 126 000.
Internationally, tuberculosis is a major contributor to mortality and morbidity. Socioeconomic factors like poverty and overcrowding have both been implicated in the causation of Tuberculosis infection. More than 60% of Tuberculosis cases occur in individuals between 25 and 64 years. The prevalence of tuberculosis is also high in persons over the age of 65 years (WHO, 2010).
Mycobacterium Tuberculosis does not possess any classical virulence factors like other major pathogen. It is known that mycobacterium possesses some characteristics that allow it to evade the body's immune system. The virulence factors would be discussed together with the Pathophysiology.
Mycobacterium tuberculosis is spread by airborne droplets. The droplets are generated by sneezing, coughing, talking or singing of an individual who has pulmonary tuberculosis. The droplets remain suspended in the atmosphere for a few minutes to hours. The bacterium finds its way down the respiratory tract to the lungs. However, it can also find its way into other organs. The most common manifestation, though, is the pulmonary tuberculosis, which affects the lungs (Knechel, 2009).
Most particles of the bacteria are trapped by the ciliary action of the mucus laden upper respiratory tract that removes particulate matter from the inhaled air. This removes most of the bacteria and serves as the first line of defense against the organism. Those bacteria that are not trapped by the mococilliary system reach the alveoli of the lungs where they are engulfed by macrophages found in the alveoli. The macrophages are part of the host immune system that destroys invading microorganisms and prevent infection. Macrophages are phagocytic cells that do not require prior antigen presentation, or memory. Several macrophage receptors are involved in the uptake of the mycobacterium by the macrophage. The lipoarabinomannan is the principal ligand for the binding. The C3 portion of the complement system is also key to the phagocytosis of mycobacterium. C3 binds to the cell wall and this enhances recognition of the mycobacterium by macrophages. This sequence of actions leads to rapid and successful control of the initial infection. This is called primary infection. A cascade of events are initiated which could either lead to control of the infection and progression to latent tuberculosis or the development of the active disease called primary progressive tuberculosis. The outcome depends on the state of the host immune system. Mycobacterium continues to multiply slowly in the macrophages even after phagocytosis (Knechel, 2009). The doubling rate is between 25 and 32 hours. In an attempt to control the proliferation of the mycobacterium, the macrophages produce certain cytokines and proteolytic enzymes to degrade the bacteria. The cytokines released attract T-lymphocytes to the site. The antigens of mycobacterium are thereafter presented to the T cells. This sequence of events takes place within 2 to 12 weeks during which the mycobacterium continue to proliferate. By the end of the 12th week, the mycobacterium can elicit an immune response, which can be detected by a skin test( Herchline, 2012), (Knechel, 2009).
In an individual with a functional cell-mediated immunity, granulomas are formed around the Mycobacterium tuberculosis in an attempt to wall off the infection. The granulomas are nodular lesions formed by activated T-lymphocytes and macrophages, together with the bacteria. There is eventual destruction of the macrophages and produces necrosis at the center of the lesion. The lesion is described as caseating necrosis, because of the cheese-like appearance it has. This necrotic environment is low in pH, oxygen and nutrients and this tends to limit the progression of the infection. The infection thereafter enters the latency phase. The lesions would eventually undergo fibrosis and calcification in individuals with an immunocompetent host. However, in immunocompromised individuals, the granuloma is initially formed but it is unable to wall off the infection and the necrosis is the liquefactive type. The necrotic tissue tracks down and eventually finds its way into adjourning structures, including bronchus and nearby blood vessels, infecting them. This leads to rapid spread of the infection to other parts of the lungs, and potentially through the blood stream to other parts of the body. The necrotic tissue that finds its way to the bronchus may be coughed up as droplet and re-infect other individuals.
Clinical Manifestation
Patients that are more likely to have tuberculosis are those with an ongoing HIV infection, patients with a history of prior Tuberculosis treatment, individuals exposed to Tuberculosis, Homelessness, incarceration or shelter dwelling( Herchline, 2012).
Features suggestive of Pulmonary Tuberculosis include Cough productive of sputum, weight loss/anorexia, fever, night sweats, hemoptysis and chest pain. For extrapulmonary tuberculosis, features are vague and non-specific( Herchline, 2012).
Culture and Diagnosis
The Gold standard for the diagnosis of Tuberculosis is through Zehl-Neelsen staining of a sputum sample of the affected individual (Todar, 2012). A smear of the sputum is fixed on the slide and this is stained with hot carbofuschin, which is a pink dye, it is decolorized with acid alcohol. The smear is thereafter counterstained with methylene blue (Todar, 2012). The slide is viewed under the microscope and the acid-fast bacilli appear pink. The test is specific but sensitivity is low, an excess of 10000 organisms per ml of sputum sample must be present before this test is positive (Todar, 2012).
Culture can be done with Lowenstein-Jensen or Middlebrook 7H10 media. It takes about 4-5 weeks to grow because Mycobacterium has a slow doubling time. Radiometric broth culture (BACTEC) grows it in 2 weeks.
Treatment and Prevention
The WHO recommends that Directly Observed Therapy (DOT) be used in treating any individual with Tuberculosis( Herchline, 2012). The antituberculous drugs include Isoniazid, Rifampicin, Ethambutol and Pyrazinamide. These drugs are initially used to treat the tuberculosis for about two months after which the regimen is changed to three drugs, discontinuing Ethambutol. Periodic sputum smears are carried out in order to determine the effectiveness of the treatment regimen and monitor progress of treatment.
Prevention of Tuberculosis includes the proper treatment of all individuals who are infected with tuberculosis so that drug resistant strains do not develop. In addition, proper ventilation of buildings and avoiding overcrowding are also essential in preventing tuberculosis. Good nutrition would also go a long way in nourishing the body and developing a competent immune system that can combat diseases when they arise. Regular testing especially for individuals that are susceptible to tuberculosis would also prevent its occurrence. Vaccination is important, especially in children.
Vaccination
BCG (Bacille Calmette Guerin) is the vaccine used to prevent tuberculosis. It contains a strain of mycobacterium bovis that is live attenuated. BCG is not part of the routine childhood vaccination schedule. It is only given to children who are at a high risk of contacting Tuberculosis (CDC, 2012).
References
CDC (2012). Tuberculosis (TB). Centers for Disease Control and Prevention,. Retrieved on 13th May 2012 from
Kenneth, Todar (2012). Mycobacterium Tuberculosis and Tuberculosis. Online Textbook of Bacteriology. Retrieved on 12th May, 2012 from
Thomas, Herchline (2012). Tuberculosis. Medscape Reference: Drugs, Disease and Procedures. Retrieved on 12th May, 2012 from
World Health Organization (2001). Global Tuberculosis Control. WHO Report 2001. Geneva, Switzerland, WHO/CDS/TB/2001.287
World Health Organization (2011). Global Tuberculosis Control. WHO Report 2011. Geneva, Switzerland, WHO/HTM/TB/2011.16
World Health Organization (2010). Global tuberculosis control 2010. World Health Organization. Available at http://www.who.int/tb/publications/global_report/en/index.html. Accessed Jan 21, 2011.
Nancy, Knechel (2009). Tuberculosis: Pathophysiology, Clinical features and Diagnosis. Crit Care Nurse April 2009 vol. 29 no. 2 34-43. DOI 10.4037/ccn2009968. Retrieved on 12th May 2012 from
Iademarco M & Castro, K (2003). Epidemiology of Tuberculosis. Semin Respir INfect Vol 18(4):224-40. Retrieved on 13th May, 2012 from
WHO (2012). BCG - the current vaccine for tuberculosis. Initiative for Vaccine Research (IVR). Retrieved on 13th May 2012 from