Tuberculosis. Primary and post-primary infection and pulmonary tuberculosis. The most common causative agent, Mycobacterium Tuberculosis, was discovered in 1882 by the German microbiologist Robert Koch.1 It is a slow growing Gram positive rod with a very

A post-primary infection may occur months or years after primary infection.  During this infection, large concentrations of mycobacterial antigens within tubercules lead to continual T-cell activation and therefore migration of an increasing number of macrophages.  The increased concentration of lytic enzymes causes the necrotic caseous legions to liquefy.  This is an ideal medium for the bacteria previously contained within macrophages in the tubercule to grow extracellularly.  These legions grow to a point where they rupture, releasing bacteria into the lungs.  New legions form and the process repeats itself, slowly destroying the lung tissue.  Eventually a legion will rupture a blood vessel infecting the circulatory system.  From here the bacterium can infect the plural cavity, bone, urino-genital system, meningis, peritoneum or the skin.2

Tuberculosis meningitis

The meninges are the system of  that envelop the .  They provide protection to the CNS and contain blood vessels that supply it.  A M. Tuberculosis infection of the meninges causes Tuberculosis meningitis.  Tuberculosis bacilli will enter the meninges through the blood meaning that patients must have a focus of infection somewhere else.  From here they will form necrotic legions in the same way that they do in the lungs.  The legions rupture into the subarachnoid layer causing an infection of the cerebrospinal fluid and an inflammation of the lining of the brain.  This results in damage to blood vessels, nerves and the brain tissue itself.  Onset of this disease is usually very slow beginning with malaise, apathy and anorexia but within a few weeks proceeds to neck stiffness, photophobia and loss of consciousness.  Occasionally however onset may be very rapid and can often be mistaken for a sub-arachnoid haemorrhage.  About 70-80% of people survive TB meningitis.3 However many are left with symptoms such as:

• Memory loss, difficulty retaining information, lack of concentration
• Clumsiness or co-ordination problems
• Residual headaches
• Deafness, hearing problems, dizziness, loss of balance
• Learning difficulties
• Epilepsy, seizures
• Weakness, paralysis or spasms of part of body (cerebral palsy)
• Speech problems
• Loss of or changes in sight4

Miliary tuberculosis

Miliary tuberculosis is a form of  that is characterized by a wide dissemination into the human body and by the tiny size of the lesions. It is named because of a distinctive pattern seen on a chest  of many tiny spots distributed throughout the lungs which look like millet seeds.  Miliary TB is a very serious condition and nearly always fatal if untreated.  About 25% of patients with this form of TB also develop tuberculosis meningitis.5

Renal tuberculosis

If a bacteria from the lungs gain access to the vascular system then organisms may be spread throughout the body. However, the bacilli have strict growth requirements and generally tend to grow in a small number of sites.  One of these is the kidney. In the kidney, the site of preference is the medulla. Calcified lesions form leading to local tissue destruction.  If left untreated renal TB will lead to renal failure.6

 Spread, Treatment and the difficulty of eradication

Mycobacterium tuberculosis is a very contagious disease.  When an infected individual coughs they release many bacilli into the air which can be inhaled.  This means that the disease is a big problem in highly populated areas.  It is also a large problem in areas where AIDS is common.  Because TB is such a contagious disease there are strict rules set down by the United States Occupational Safety and Health Administration for the protection of health care workers responsible for the care of infectious TB patients.  Patients must be hospitalized in negative pressure rooms and carers are to be provided with a personally fitted face mask with high energy particulate air filters.  These filters will not allow potentially contaminated dust or sputum particles to be inhaled.1 

M. tuberculosis is very difficult to treat effectively.  Firstly it has a high level of lipid in its capsule.  This makes it very impermeable to nutrients, which is why it is slow growing, but also to antibiotics.  Another factor increasing its antibiotic resistance is its intracellular location within macrophages.  These cells are also often surrounded by a layer of caseous tissue making contact with the bacteria very difficult.  These factors mean long term treatment with antibiotics is necessary.  This presents a problem, long term therapy makes the emergence of resistant strains far more likely then short treatments.  The cost of long term treatment is also much higher meaning treatment in developing countries where incidence of TB is very high is difficult.3

There are a number of anti-tuberculosis drugs available.  Most of these are kept restricted to the treatment of tuberculosis to prevent resistance to the drug developing in other organisms which could then be transferred to the TB causing bacteria.  These drugs are also often toxic so they are usually inappropriate for general use.3

The BCG vaccine (Calmette and Guerin’s attenuated tubercle bacillus) has been used for over 70 years to protect people from tuberculosis.  In the UK the vaccine is given to children entering secondary school but in high risk countries it is given at birth.  Although it has been used for so long its level of effectiveness is still in debate.  Trials in the UK and in the USA show that it gives clear protection.  Also trials in South American and African countries show efficiencies of over 70%.  However in two trials in southern India and southern parts of America it was shown to have little or no protective effect and actually seemed to increase incidences of the disease.  One difficulty with obtaining accurate results from trials is the shifting background level of infection that rely on factors other than the BCG vaccine.  Also the strain of the vaccine has not been standardised and it is possible that different strains are having varying success.  Another theory put forward is that genetic differences between populations cause differences in the way that the vaccine works.3

With the worlds increasing population it is becoming ever easier for this very contagious disease to spread from person to person.  The difficulties in curing individuals combined with patients not completing their courses of antibiotics and new strains emerging that are resistant to current drugs mean that tuberculosis is a very difficult disease to eradicate in this country.  The problem is far worse in developing countries where hospitals cannot afford long courses of expensive drugs.  Furthermore the AIDS pandemic is making it even easier for the tuberculosis to infect populations.

Bibliography

1. Biology of Microorganisms.  8th Edition.  Brock.  Madgrim, Martinko, Parker.
2. Immunology.  4th Edition.  Kuby.  R.A.Goldsby, T.J.Kindt, B.A.Osborne.
3. Medical Microbiology.  Mims, Playfair, Roitt, Wakelin, Williams
4. The Meningitis Research Foundation website,
5. Wikipedia,
6. Tuberculosis and the Kidney. J.B. Eastwood, C.M. Corbishley, J.M.Grange (obtained from http://jasn.asnjournals.org)