Tuberculosis

Owhe Elo-Oghene Osewe

Tuberculosis

• This disease is caused by a microbe called mycobacterium tuberculosis. This bacterium is known to attacks the lungs, nevertheless it can also attack any part of the body such as the spine, brain and the kidney (WHO, 2013). Tuberculosis (is an air borne disease meaning it is spread through the air from one person to another and it is susceptible to people living in crowded conditions (CDC, 2012)

Background information

• One third of the world’s populations are infected with TB. In 2011, nearly 9 million people around the world became sick with TB disease. There were around 1.4 million related death worldwide (CDC, 2012).

• A total of 10,528 TB cases at an alarming rate of 3.4 cases per 100,000 persons) were reported in the united states while in Africa, home to 11% of the world population carried 29%of the global burden of tuberculosis cases and 34% of the TB related deaths. (Chaisson et al, 2009).

Innovation

• If we take care of our body very well and keep our immune system up. Even If we are infected by the mycobacterium we would not be vulnerable to the disease. Especially people who are susceptible to the disease.

• People who work in the hospital and have constant interaction with TB patients.

• People who live in overcrowded areas.

Keep immunity up

Hypothesis

• People with strong immune system are less susceptible to tuberculosis.

Tuberculosis

• Mycobacterium tuberculosis is a high G + C, non-endospore-forming, Gram-positive rod with cell walls containing an abundance of mycolic acid,

• which is a waxy lipid composed of chains of 60–90 carbon atoms.

• This lipid is directly responsible for unique characteristics of this pathogen.

Mechanism of action

• Mycolic acids, a homologous series of C60-C90 long-chain alpha-alkyl-&beta-hydroxy fatty acids, which represent essential components of the mycobacterial cell wall.

• They are important for mycobacterial growth, survival, and pathogenicity.

• They are found as esters of an arabinogalactan as well as free lipids in the form of trehalose di mycolate (TDM).

• There are three distinct structural classes of mycolic acids namely alpha- (more than 70 percent), methoxy- and keto-mycolic acids (10-15 percent) are found in this bacillus.

• The alpha-mycolic acid is a cis,cis-dicyclopropyl fatty acid.

• Both methoxy- and keto-mycolic acids have either cis- or trans-cyclopropane rings. Cyclopropane rings in mycolic acids protect the bacillus from oxidative stress

• They are found as esters of an arabinogalactan as well as free lipids in the form of trehalose di mycolate (TDM).

• Arabinogalactan-mycolate is covalently linked to the cell wall peptidoglycan via a phosphodiester bond located on the inner leaflet of the outer membrane.

• Both arabinogalactan-mycolate and TDM provide a protective thick cell wall and protect the tubercle bacillus from antibiotics and host's immune system.

• TDM also inhibits phago-lysosome fusion and is

often considered to be an indicator of virulent strains.

Inhaled respiratory Droplet

Alveoli

Respiratory bronchiole

Bronchiole

Macrophage

Blood vessels

Mycobacterium

Alveolus

Beginning Of Tubercle

Tubercle Caseous necrosis

Collagen fibres

tubercle

2

RupturedTubercle

Blood vessels

Alveolus

Mycobacterium

Bronchiole

• Macrophages are white blood cells within tissues, produced by the division of monocytes

• Macrophages are the 'big eaters' of the immune system. These cells reside in every tissue of the body, albeit in different guises they engulf apoptotic cells and pathogens.  

• Macrophages in the alveoli of the lungs phagocytize the pathogens but are unable to digest them in part because the bacterium inhibits fusion of lysosomes to the endocytic vesicle.

• Instead, the bacteria replicate freely within macrophages, gradually killing them.

• Bacteria released from dead macrophages are phagocytized by other macrophages, beginning the cycle anew.

• This stage of infection, which lasts for a few weeks, is typically asymptomatic or associated with a mild fever

• Infected macrophages present antigen to T lymphocytes, that play a central role in cell-mediated immunity

• which produce lymphokines that attract and activate more macrophages and trigger inflammation.

• Tightly appressed macrophages surround the site of infection, forming a tubercle over a two- to three-month period

• Other cells of the body deposit collagen fibers, enclosing infected macrophages and lung cells within the tubercle.

• Infected cells in the center of the tubercle die, releasing

• M. tuberculosis and producing caseous13 necrosis—the death of tissue that takes on a cheese-like consistency due to the presence of protein and fat released from dying cells.

• In most patients, the immune system reaches a deadlock with the bacterium at this point: the immune system is able to prevent further spread of the pathogen and stop the progression

• of the disease, but it is not able to rid the body of all mycobacteria.

• M. tuberculosis may remain dormant for decades• within macrophages and in the centers of tubercles. If

the immune• system breaks the stalemate by killing all the

mycobacteria,• the body deposits calcium around the tubercles, which

are• then called Ghon complexes.• In approximately 95% of cases, development of

cell-mediated immunity controls the infection after Ghon complexes.

• CD4 T Cells - They are called helper cells because one of their main roles is to send signals to other types of immune cells, including CD8 killer cells. CD4 cells send the signal and CD8 cells destroy and kill the infection or virus.

• In the diagnosis of tuberculosis certain test most be conducted some more sensitive than others, the most common test are the culture, acid fast bacilli, chest x-ray, geneXpert and the skin test.

Treatment

• Tuberculosis can be treated by administering rifampin, isoniazid and one of a number of other drugs such as ethambutol or streptomycin to the infected person suffering from TB disease

Rifampicin

Isoniazid

Ethambutol

Streptomycin

Economic and social impacts of the disease

• Social impact• 95% of the 8 million new cases of TB, and 98% of

deaths from TB, worldwide are in developing countries

• In these regions, disease and death from TB occur mostly in the economically active segment of the population

• TB kills more women annually than all the causes of maternal mortality combined.

Economic impact• TB and poverty closely linked-  Malnutrition,

overcrowding, poor air circulation and sanitation-factors associated with poverty-increase both the probability of becoming infected and the probability of developing clinical disease

• Self-medication encourages the emergence of drug-resistant TB strains

• The global burden of TB amounts to approximately $12 billion annually