Posts Tagged ‘Tuberculosis’
In 1943, Selman A Waksman found the antibiotic effective against Mycobacterium tuberculosis. Streptomycin purified from streptomyces grieseus was administered to human in 1944.
Drug resistance in TB occurred as a result of tubercle bacillus mutations. Soon the resistant mutants appeared, prooving the antibiotic therapy unsuccessful. Therefore combination of drugs were used to solve the problem of antibiotic resisitance.
Multidrug reisistant tuberculosis– MDR TB is TB that is resisitant to atleast two of the best anti TB drugs, isoniazed and rifamycin which are called first line drugs.
Extensively drug resistant TB is defined as TB which is resistant to isoniazed and rifamycin plus resisitant to any fluoroquinolone and atleast one of three injectable second line drugs(amikacin, kanamycin or capreomycin.
MDR-TB varies from patients to patients.
Antibiotics such as para-aminosalicyclic acid and streptomycin have been in use for more than 50 years.
Patients are required to take upto 15 pills a day, plus daily injections, for atleast six months.
Medical treatment is lengthy and protection through vaccination is today, as before is insufficient.
Every year nearly two million people die from the disease. The bacterium that cause TB are spread in airborne droplets when people with disease cough or sneeze.
TB is considered lung disease however it can attack other parts of body such as kidneys or the brain.
TB is highly contagious and is spread through air.
Mycobacterium tuberculosis is resisitant to disinfectants, desiccation and are difficult to stain with water based stain such as Gram.
Infection with tubercle bacillus is characterised by the formation of tubercles, hard nodules in the lungs when Mycobacterium tubercle enters the lungs the macrophages engulf the pathogen but are unable to digest the bacteria due to it’s waxy mycolic acid cell wall.
Mycobacteria begin to multiply within the macrophages, eventually killing the macrophages that protect the host.
The cycle continues as the bacteria released from dead macrophages are then engulfed by other macrophages.
The infected macrophages result in inflammatory response(heat, swelling, dilated capillaries)
The cells at the centre of the tubercle may eventually die, producing either an area of necrosis or an actual cavity.
Mycobacterium tuberculosis can be differentiated from most other mycobacteria by the production of niacin.
Mycobacterium tuberculosis is a Gram positive aerobic mycobacterium that divides every 16-20 hours. This is extremely slow as compared to other bacteria which tend to have division times measured in minutes(for example Ecoli can divide roughly every 20 minute.)
Mycobacterium tuberculosis are grown on lowenstein jensen media. Middlebrook media are used for faster culture.
Bacteria can takes weeks to grow on culture media.
The Polymerase chain reaction is the rapid method which provides results within hours from specimen of the patients.
TB refers only to disease caused by Mycobacterium tuberculosis.
Similar disease ocassionally result from M.bovis,M africanum, M.microti.
TB of tonsils, lymph node, abdominal organs, bones and joints was once commonly caused by ingestion of milk infected with M. bovis but such infection is largely eradicated in developed countries by slaughtering cows that test positive.
Cell wall of Mycobacterium tuberculosis contains peptidoglycan and complex lipids. 60% of the cell wall is lipid. The lipid fraction consisit of mycolic acid, cord factor and wax D.
Mycolic acid are hydrophobic molecules that affect permeability properties at cell surface.
Mycolic acid prevent attack of the Mycobacteria by cationic proteins, lysozyme and oxygen radicals in phagocytic granule.
Cord factor is toxic to mammalian cells.
Lipids cause resistance to many antibiotics and killing by acidic and alkaline compounds and resistance to lethal oxidation and survival inside the macrophages.
Mycolic acid give rigid cell shape to the bacteria.
The type of mycolic acid can be used to distinguish different Mycobacteria.
Mycolic acid isolated from Mycobacteria are called eumycolic acids which have elevated 60-90 carbon atoms.
Mycolic acids are complex hydroxylated branched chain fatty acids with elevated carbon numbers.
They may also contain diverse functional groups such as methoxy, keto, epoxy ester group and cyclopropane ring.
Mycolic acids containing a methoxy group with double bond or cyclopropane ring are known as methoxymycolic acids.
Mycolic acids containing an a methyl-branched ketone are known as ketomycolic acids and those containing an a-methyl-branch epoxide as epoxymycolic acids.
Tuberculosis is an infection caused by the Koch bacillus, also known as Mycobacterium tuberculosis, it primarily affects the lungs and it is contagious. Besides the lungs, TB can also affect lymph nodes, intestinal tract, kidneys, bones, and brain.
Tuberculosis is known to exist even before the year 2000BC, and writings from Egypt and Babylon mention it. Until the discovery of the antibiotic treatment and of the BCG vaccine, TB made a lot of victims during a global epidemic.
There are some germs belonging to the Mycobacterium family, referred to as atypical tuberculosis. Generally these organisms live among other germs in the body and do not cause any harm, but sometimes they can lead to an infection or even to the typical tuberculosis.
Healthy persons receive the infection if living or working in the same place with the infected person. By coughing, shouting or sneezing, the infected person spreads the germs into the air, and others inhale them. Shaking hands or touching clothes does not infect others.
Another form of tuberculosis is transmitted by drinking unpasteurized milk. The responsible bacterium for this form of TB infection is called Mycobacterium bovis. Years before, this bacterium was a major cause of TB in children, but now since most milk is pasteurized (a heating process that kills the bacteria) it does not cause TB any more.
When a person gets infected with TB, the germ enters the lungs and causes a local infection. The lymph nodes are connected to the lymphatic system and could get enlarged. Using the lymphatic system the infection could spread in all the body and affect all the organs. Sometimes the immune system stops the infection by creating a scar tissue all around the infected area, and so the infection becomes inactive. If at some time the immune system becomes weakened due to another infection or to cancer the TB germs could pass by the scar tissue and spread the infection in the body.
In preventing the infection with TB some countries vaccinate their children with the BCG vaccine.This is a vaccine prepared of a weakened Tb germ, and it is considered to be the most effective vaccine in preventing childhood cases of TB.
In treating TB, doctors use a combination of antibiotics because using only one drug could lead to the bacterial resistance to this drug. The drugs used nowadays are: isoniazid, rifampin, pyrazinamide, and ethambutol, in different combinations.
Generally if the treatment is followed all the way, a person can heal without problems, and reintegrate within the society in about 6 to 9 months.
Although antibiotics had been discovered a few years before, sulfonamide and penicillin proved no effect on the bacteria causing Tuberculosis. After years of research In California about soil fungus, in 1039 Waksman isolated the fungus Actynomices that was able to inhibit the development of Mycobacterium Tuberculosis. But the chemo was to dangerous toxic and could not be used in treating Tuberculosis.
In 1943streptomycin was found inside Streptomyces griseus and it was proven to totally inhibit the bacterial strains. In 1944 it was administered to a Tuberculosis patient that immediately improved. Although streptomycin causes side effects like damages to the inner ear, it was for a few years the best medication against Mycobacterium.
The medical treatment of Tuberculosis was put in danger after the assumption that bacteria rapidly gains resistance even to the newer discovered antibiotics. But the issue was quickly solved by using combinations of antibiotics in the treatment.
After streptomycin other major anti Tuberculosis chemo were introduced. P-aminosalicilic acid, Isoniazid, Pyrazinamide, Ethambutol, Rifampicin and Cycloserin showed benefic results in the cure of Tuberculosis. Newer Aminiglicosides such as Viomycin and Kanamycin as well as the quinolones Ciprofloxacin and Ofloxacin are only prescribed in cases of resistant strains. Latest treatment methods like the Macrolides or the combination of Beta-lactamase and Beta-lactams have not been yet enough studied.
The two most important characteristics of the antituberculous ant biotherapy are:
1. The antibacterial activity best resulted in Streptomycin, Isoniazid and Rifampicin.
2. The inhibition of the development of resistance with best results in Rifampicin, Ethambutol and Izoniazid.
After a month of treatment with the four basic antibiotics, the patient should be fever free, feel much improved and show decreased number of bacteria in the sputum. The weight of the patient must increase and the lesions visible on the X-rays should minimize. As the medication persists the bacterial organism in the sputum will become more and more difficult to be cultivated on synthetic cultures inside the laboratories.
If no signs of improvement appear on the radiography after 3 months, the medication and the patient’s compliance must be again verified. Most relapses after treatment appear in the first 6 months after the patient has stopped taking chemo. Also the capacity of developing resistance must be taken into consideration. The National Tuberculosis Center must carefully monitories rebel cases of Tuberculosis.
In case of a reoccurrence at the same patient, doctors must find another schedule of therapy as the bacteria has already developed resistance to the antibiotics used before. A possibility is adding other few antibiotics to the initial medication. If bacteria is resistant to all kind of standard chemical products, other drugs, more toxic however will be put in the schedule: Ethionamide, Cycloserine, Viomycin, Kanamycin, Pyrazinamide or Capreomycin.