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Site author Richard Steane
The BioTopics website gives access to interactive resource material, developed to support the learning and teaching of Biology at a variety of levels.


TB prevention and control

The prevention of tuberculosis involves the detection of infected individuals and appropriate treatment so that they do not spread the disease.

On the other hand, general protection of the population, or at least the most susceptible members, by means of mass vaccination seems advisable - along the same lines as mass immunisation against Smallpox, Measles, Mumps and Rubella.

Diagnosis of infected individuals

Although it is fairly obvious (from their symptoms) when someone has active tuberculosis, the protection of the general population requires the identification of latent TB sufferers, so that they can be treated and monitored.

Skin testing

Screening tests for antibodies to TB were routinely run in schools before vaccination programmes were carried out.

Tuberculin is a purified protein extracted from Mycobacterium (tuberculosis?) which acts as an antigen, and if a person has been either active or latenr TB infection, their immune system will have produced antibodies to tuberculin. An exposure to tuberculin thus produces an allergy-like reaction.

heaf test mantoux test This generally involves a skin test. There are two main techniques: the Heaf or Mantoux tests. A liquid containing tuberculin is introduced using a needle (or set of them!) under the skin of the arm. 2-3 days later the inoculation site is checked to see if there is a reaction to the test. The result to the test is counted as positive if a raised bump is visible. This signifies latent TB infection, although it is often explained as showing that the patient has been exposed to TB infection in some way.

Further testing, such as a chest X-ray, may be necessary to determine if active TB disease is present.

X-ray screening

X-ray van From the 1950s there was a programme of mass X-ray testing in the UK and America ; X-ray machines routinely visited cities and towns throughout the British Isles and adults were persuaded to present themselves for testing; usually no appointments were necessary. This was phased out in the 1970's, presumably due to reductions in the incidence of TB, or because likely candidates did not present themselves for testing.
Ancient X-ray equipment More modern X-ray equipment

X-ray testing is not particularly effective for the identification of latent tuberculosis, but very useful to identify active TB and to monitor the progress of control measures.

chest x-ray showing a lesion in right upper lobe of lungsignificant improvement one month later


Sputum examination

Sputum is the dense mucus-like secretion coughed up from the lungs, although it can be extracted by a vacuum method using a tube. A sample is sent to a specialist laboratory for further processing.

Smear test

TBbacteria.jpg Sputum may be examined under the microscope, after being spread on a slide, stained with special stain then treated with heat and acid. If Mycobacterium shows up as acid fast bacilli (rod-shaped bacteria, still staining darkly), this is a very direct diagnosis of active TB.

Culture test

Sputum may also be spread on the surface of a special microbiological medium (an agar plate) and incubated under special conditions. Bacteria will grow into colonies which are visible to the naked eye, but this takes some time - a matter of weeks.
Colonies of Mycobacterium tuberculosis on Lowenstein-Jensen medium. CDC
This technique can also be used to identify other lung infections such as pneumonia, and to find out what antibiotics the bacteria are sensitive to, which makes prescribing antibiotics more effective.

Vaccination

BCG

Albert Calmette Camille Guérin BCG is short for "Bacille Calmette-Guérin". Mycobacterium is a rod shaped bacterium, and this shape is described as a bacillus. Albert Calmette and Camille Guérin worked at the Pasteur Institute at Lille and Paris from 1908 to 1919.

By subculturing various virulent strains of Mycobacterium tuberculosis and Mycobacterium bovis on different culture media, they developed a strain that was less virulent. This attenuated strain - which could not cause an infection, but which stimulated the body's immune system to produce antibodies - was used as the basis for vaccine production.

This vaccine was used in the UK from 1953 to 2005 for immunisation of children, and it is still used on a limited scale if required. e.g. as a protective measure in the case of exposure to active TB. It has not been widely used in some countries, especially the USA, because of uncertainties about its efficacy, and because its use confuses interpretation of skin tuberculin tests.

Other vaccines are currently being developed but none are at present reasdy for large-scale use.

Control (drug therapy) using antibiotics

Tuberculosis can usually be controlled using drugs called antibiotics to kill the infecting bacteria. It is not susceptible to antibiotics like penicillin. From 1945 the antibiotic streptomycin was used against TB; initially it was very successful and quickly replaced the sanatoria which provided treatment based on fresh air and isolation! However streptomycin has several unwelcome side-effects.

isoniazid bottlerifampicin capsules Nowadays, isoniazid is the main antibiotic of choice because (when activated by bacterial catalase) it prevents the formation of the waxy component of cell walls in Mycobacterium tuberculosis which are its main defence. Another antibiotic often used is rifampicin which prevents bacteria from producing proteins.

For treatment of latent TB, isoniazid is used on its own. However this treatment must be continued for 6-9 months.

Active TB is usually treated with a mixture of antibiotics, switching part way through the treatment to a completely different antibiotic.

Drug-resistant TB

20 pounds a month in a country like the Democratic Republic of Congo pays to test 80 people for deadly tuberculosis (TB) every month. MSF
Within a large population of any living organisms, there will be some individuals that due to a mutation have a different feature which might (or might not) possibly give its owner an advantage under certain circumstances.
The same is true of bacteria, although they reproduce asexually. They exist in very large numbers and individual mutant bacteria will exist with features such as a different cell wall structure or a different metabolism (way of working at a chemical level), either due to a modified version of a gene, or an extra gene. When these are challenged by being exposed to antibiotic taken by the patient they survive and reproduce, passing on the gene responsible to their offspring - a clone of themselves. As a result the other (antibiotic-sensitive) bacteria die and are replaced by the offspring of the mutant form which make an antibiotic-resistant strain .

This situation has unfortunately developed with TB on a worldwide scale. Strains which are resistant to one antibiotic can also develop resistance to other antibiotics. Multiple drug resistant - MDR - strains are produced as a result, and these are very difficult, if not impossible, to treat with antibiotics. There are several categories of antibiotics, depending on their agreed role in treatment: first line, second line, third line. Isoniazid and rifampicin are first line drugs. Extensively (or extremely) drug-resistant tuberculosis (XDR-TB) is not treatable using first and second line drugs.


The phenomenon of extensively drug resistant strains has a number of ethical consequences. In some instances, many of which have attracted media attention, sufferers have been forcibly excluded from exposure to the general public; compulsory quarantine is not far removed from imprisonment!

TB treatment regimes

The treatment of TB is essentially quite different from that of other diseases: Many sufferers in the developing world will be of limited financial resources, and possibly illiterate. Any mistake is likely to increase the chances of (multiple) drug resistance developing. For this reason, the policy of DOTS (Directly Observed Treatment, Short-course) has been developed by the World Health Organisation.

This depends on the sufferer being expected to be seen to take their medication under the supervision of another qualified individual, who can check the drug requirements and carry out the appropriate administration, as well as the necessary backup arrangements. The main points of this programme are as follows:

TB control before the antibiotics era

Crossley sanatoriumbed-rest and fresh air in a sanatorium
From the 1850s onwards, people who could afford it were sent to sanatoria where they were subject to bed rest and lots of fresh air. This was only partially effective, but it did have the side-effect of putting infected people into isolation. deformity that results from removal of ribs for lung compression in a surgery called thoracoplasty (1944).

A more direct therapy fairly popular in the early 1900s involved surgically collapsing the lung either by injecting air into the chest cavity, or by more direct intervention including cutting ribs.



Some questions

Move the mouse pointer near to the > prompt for possible answers

Why do you think that treatment of TB using antibiotics takes such a long time to have an effect?
>The TB bacteria are hidden inside white blood cells, surrounded by others in tubercles
>TB bacteria have waxy cell walls
>TB bacteria naturally grow slowly so they are not as susceptible as faster-growing species

Why are different antibiotics used?
>Each antibiotic has a different mode of action

Why do you think they switch to a different antibiotic treatment part way through treating active TB?
>To prevent the development of multiple resistant strains.

What is the basis for the differences between normal antibiotic-sensitive bacteria and mutant antibiotic-resistant bacteria?
>Different DNA: different base combinations or an extra section of DNA

Why is it true to say that antibiotic-resistant bacteria are a clone?
>They are produced as a result of asexual reproduction
>They are genetically identical

What are likely to be the main differences between first line drugs and second, or third line drugs?
>cost
>efficacy (how well they work)
>side-effects

Why are the authorities so concerned about people with TB travelling on aeroplanes (or airplanes)?
>Close proximity with others in the aircraft (air is recirculated), and long transit times, mean greater exposure risk to all travellers.
> Also a plane-load of travellers can spread the disease widely when they disembark.

What process is the development of antibiotic-resistant strains of bacteria an example of?
(Clue: Charles Darwin probably wasn't thinking of this when he wrote about it!)
>evolution - by (natural?) selection

Web references

Clicking on each link below will bring it up as a new page

Heaf test

Mantoux test

More accurate TB test unveiled Some old BBC news

Tuberculosis overview from emedicinehealth.com Quite a good description with good images

CANADA's ROLE in FIGHTING TUBERCULOSIS A very comprehensive treatment of the topic

Bacillus Calmette-Guérin From Wikipedia, the free encyclopedia

Frequently Asked Questions about BCG

Tuberculosis From Wikipedia, the free encyclopedia

Isoniazid From Wikipedia, the free encyclopedia

Tuberculosis_treatment From Wikipedia, the free encyclopedia

Brief History of Tuberculosis

Multidrug-Resistant Tuberculosis Fact Sheet

TB with resistance to second-line drugs increasing, a 'serious and emerging public health threat' warn doctors

Multi-Drug Resistant Tuberculosis

XDR-TB Extensively drug-resistant tuberculosis

'Virtually untreatable' TB found

Drug-resistant TB 'threatens EU'

Man With Drug-Resistant TB Remains Locked Up

Air Traveler With Drug-Resistant TB Quarantined

US in TB flight infection warning

The five elements of DOTS

Crossley sanatorium A PHOTOGRAPHIC DOCUMENTARY

The Pinewood Sanatorium, Wokingham

malady of the month archives



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