Tuberculosis

Erin King

Introduction

• • Tuberculosis is an infectious disease which primarily affects the lungs • Its name is derived from the bacterial source which causes it called

Mycobacterium tuberculosis

¹ http://www.medicinenet.com/tuberculosis/article.htm

• Latent • Active Types of TB

Introduction

TB has the ability to lie dormant in the body asymptomatic and not being able to be spread • Becomes active when the immune system of the infected person is compromised • Once activated, TB can affect the lungs or other parts of the body

Transmission

• A person contracts the disease by inhaling the actual bacteria in the air • When an infected person coughs or sneezes, it is possible for someone else to breathe in the bacteria

Signs and symptoms

• Hacking cough • Chest pains • Sputum or blood • Chills • Fever • Weakness/fatigue • Night sweats

Diagnosis

• TB skin test – Developed in 1907 by Clemens Von Pirquet to identify latent TB in children – Done by injecting tuberculin in the arm and examining the arm 48-72 hours later for a reaction

Treatment

• Since TB is resistant to many drugs over a period of time, a combination of drugs is usually given – Isoniazoid – Rifampin – Ethambutol – Pyrazinamide

History on Development

• Tuberculosis decay has been found in the spines of Egyptians dating back to 3000-2400B.C.

• Was not identified as a disease until 1820’s and was not classified as tuberculosis until 1839 by J.L. Schonlein • Roman physicians suggested bathing in urine, eating wolf livers, and drinking elephant’s blood to cure the disease

History of Development

• Robert Koch, a German physician, found TB was caused by microscopic organisms in 1832He gave an important lecture in which he brought his “lab” to the lecture, so people could see the results for themselves.

• He dissected the tissue from guinea pigs which had previously been inoculated with TB • He performed a stain on the culture and allowed people to look through the microscope to discover his newfound bacteria:

Mycobacterium tuberculosis

History of Early Treatment

• • • Artificial pneumothorax – Discovered by Italian physician Carlo Forlanini in 1882 Chemotherapy – Used in WW2 for TB patients and was a combination of Sulfonamide and penicillin. Radiation – Wilhelm Konrad von Roentgen discovered in 1895 that radiation reduces severity of TB by inactivating the bacteria

Antibiotics

• 1943-Selman Waksman developed the antibiotic streptomycin – First administered to a TB patient in 1944 • Result was the disease stopped progressing and bacteria disappeared • Eventually became new mutants became resistant

Common drug treatments today

• Isoniazoid – Discovered in 1912 and discovered to treat TB in 1951 – Mechanism of Action: unclear but has been proven to prevent TB bacteria from making mycolic acids which are needed in order to form the bacteria’s cell wall.

– Oral/Injected

Isoniazoid

• Chemical name: 4-pyridinecarboxylic acid hydrazide • Molecular formula: C6H7N3O • Organic compound also known as Laniazid or Nydrazid • FW: 137.14

Rifampin

• Introduced in 1967 • Works in combination with other drugs to prevent or stop the growth of TB bacteria by directly inhibiting RNA synthesis • Chemical Formula: C43H58N4O12 • Chemical Name: 3-[(4-methyl-1 piperazinyl)imino-methyl]-nfamycin

Pyrazinamide

• Stops the growth of TB bacteria by inhibiting the fatty acid synthetase I of bacteria • Mechanism is still unclear on how • Used in combination with isoniazid, rifampin, and ethambutol

Ethambutol

• Similar to Isoniazid in the sense that it obstructs the formation of the cell wall of TB bacteria via of preventing bacteria from producing mycolic acids

Latest Discovery

• Biochemical researchers have discovered that minimal amounts of sulfur dioxide can kill TB bacteria – The idea came from a researcher in India who knew about SO2 and its antibiotic effect on wine and wanted to do further testing on TB bacteria – A group of 2,4-dinitrylphenlsulfonamides that can react with thiols to produce sulfur dioxide

Latest Discovery

• The idea was tested by adding cysteine to different groups of 2,4-diphenylsulfonamides in order to determine which ones produced the most SO2.The resulting SO2 was then added to different Mycobacterium colonies. After about a month, researchers examined that the molecules which produced the most SO2 inhibited the concentration growth of bacteria even more than the drug Isoniazid. It reduced growth by 99% at 0.15uM, while Izoniazid accomplishes the same but at a concentration of 0.37uM. Further research must be done.

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References

History of TB. Global Tuberculosis Institute. Accessed 23 Jan 2012. http://www.umdnj.edu.ntbc/tbhistory.htm

Mason, Margie. New TB Strain Resistant to all Drugs. ABC News. 16 Jan 2012. Accessed 25 Jan 2012. http://www.ABCnews.go.cm/health/winestory/india-reports-tb-strain-resistant-drugs Robert Koch and Tuberculosis. Nobel Prize.Org.9 Dec 2003. Accessed 23 Jan 2012. http://www.nobelprize.org/educational/medicine/tuberculosis RX List. Internet Drug Index. 17 Dec 2010. Accessed 23 Jan 2012. http://rxlist.om/rimfampin/isoniazid/ethambutol/pyrazinamide-drug Sanderson, Katharine. Hitting TB with Toxic Gas. Chemical and Engineering News. 9 Dec 2011. Accessed Jan 26 2012. http://www.cen.acs.org/articles/89/web/2011/Hitting-TB-Toxic-Gas Tuberculosis. National Institute of Allergy and Infectious Diseases. National Institute of Health. 13 May 2010. Accessed 24 Jan 2012. http://www.niand.nih.gov/topics/tuberculosis Tuberculosis. Center for Disease Control and Prevention. 5 Jan 2012. Accessed 24 Jan 2012. http://www.cdc.gov/tb Tuberculosis. World Health Organization. Accessed 24 Jan 2012. http://www.who.int/topics/tb/en/2012 Working on New Drugs. Accessed 26 Jan 2012. http://www.newtodrugs.org/pipeline.php

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Image References

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