Tuberculosis

From Ganfyd

Tuberculosis is the infectious disease caused by Mycobacterium tuberculosis (or, less commonly, Mycobacterium bovis). It is responsible for 3% of all deaths globally, mainly in the developing world.^[1] Since the early 1980s there has been a resurgence in the West associated with Acquired immunodeficiency syndrome (AIDS). There are several different types of clinical infection.

Revised guidelines on the management and prevention of TB were published by NICE on 22 March 2006.^[2] According to the NICE website:

"The NICE tuberculosis clinical guideline covers:

• "diagnosing and treating active and latent TB in adults and children
• "preventing the spread of TB, for example by offering tests to people at high risk, and by vaccination

"The guideline does not explain TB or its treatments in detail."

These are to be the new "bible", and should replace the BTS guidelines.

Until there is more content at GANFYD, there are some good external links below.

Bovine tuberculosis

See Bovine tuberculosis article.

Historical

Epidemiology

• Influenced by natural resistance patterns in human populations, sanitation, nutrition and other disease such as AIDS.

Aetiology

Mycobacterium tuberculosis, or "MTB".

Clinical

Caseous Necrosis

Symptoms

Caution as it is a systemic disease not just a respiratory disease and presentations can range from meningitis to bowel symptoms. Classically:

• Night sweats
• Chronic cough
• Weight loss
• Malaise

Signs

Classically:

• Fever
• Pallor
• Cachexia
• Lymphadenopathy
• Upper lobe crackles

Investigations

Sputum testing

The initial test for tuberculosis is often sputum testing. Ideally several early morning samples of sputum are sent, as the bacteria may be scanty, and not seen in all samples. Presence of Mycobacteria in sputum indicates that a patient is more likely to be infectious to others - and the likelihood is increased if large quantities of bacteria are seen.

"Sputum smear positive tuberculosis" is the infectious sort and requires contact tracing and action

Mycobacteria are fairly large nonmotile rod-shaped bacteria (bacilli), which can be stained with a pink dye and, once stained, the stain is not easily removed by acids or by alkalis - it is said to be "acid and alkali-fast". Mycobacteria are bacilli, so they are often described, on microscopy, as "acid and alkali fast bacilli" (AAFBs). An image can be seen at the Todar's Online Textbook of Bacteriology.

If sputum cannot be obtained directly, or if AAFBs are not found, sometimes samples are aspirated at bronchoscopy; these may be more likely to detect the bacteria in infected individuals (although if AAFBs cannot be identified in ordinary sputum samples but only in bronchoscopy aspirates, the individual is probably less likely to be infectious to others - at least at that time.)

Blood tests

Various tests based on recognition of mycobacterial DNA are now available. These interferon-gamma release assays have the advantage of being blood tests, and may also be able to distinguish MTB from BCG and some other mycobacteria.

Radiology

While the chest X-ray can be essentially diagnostic in the patient context, the relative rarity of tuberculosis in say elderly smokers of European stock can make the radiological diagnosis, including with CT chest imaging relatively easy to confuse with a tumour.

Tuberculin skin tests

A tuberculin skin test (TST) work by introducing tuberculin, a protein derived from mycobacteria, into the skin. Somebody with prior immunity to mycobacteria will produce a response to test, and a vigorous response may indicate current infection with a mycobacterium, most likely (in the UK) MTB.

In 2005 the UK changed from the Heaf test to the Mantoux test - the main test used internationally - for routine screening. This (like BCG) has to be given as an intradermal injection, which requires skill, and has to be read after 48-72 hours (up to 96 hours may be acceptable) - but certainly less than a week.

Treatment

• Based around monitored triple chemotherapy (see guidelines)

Prevention

• The disease can be prevented by vaccination with BCG vaccine
• Occupational health policies to prevent people with active TB from working with vulnerable people
• Contact tracing of cases plays a major part.
• Public health interventions with institutional care (eg prisons)
• Screening high risk populations

BCG vaccine

Bacillus Calmette-Guérin (often referred to in French as Bacille Calmette-Guérin, as it was developed by two French microbiologists, Albert Calmette and Camille Guérin) a live attenuated bacterial vaccine. Far less effective than other vaccines in routine use in the UK; but nevertheless effective at preventing the more serious presentations of TB (miliary TB; TB meningitis) in children, and in preventing leprosy. All children were routinely offered BCG vaccination as teenagers in the UK, until 2005; however, routine vaccination of all children has not been cost-effective for many years, as transmission between UK residents of UK origin had fallen to an all-time low. Vaccination of individuals in high risk groups continues.^[4]

See the Green Book for further information on the use of BCG in the UK, or Wikipedia for a broader overview.

Why has universal BCG vaccination been stopped?

People do find this puzzling, especially when they hear that TB rates are rising. The reasons are as follows:^{[5] [6]}

• TB rates in the "indigenous" population are at an all time low, and still falling.
• TB rates are increasing - but that's because of immigration, with people coming to the UK from high-prevalence countries.
• People are considered to be at high(er) risk if they have a parent or grandparent from a high prevalence country; these people, if under the age of 16, should be offered BCG vaccination as early as possible in their life. They are offered the vaccine because they are at increased risk; and they are at increased risk because they are more likely to have infected relatives come to stay (or already living with them), or to make prolonged visits to countries with high prevalence rates.
• There is very little spread from higher-risk to lower risk groups in the UK.
• GPs and their staff can - and in some cases do - give BCG; but usually this is done through contracting a service from a particular GP practice, for a wider area. This is because giving an intra-dermal injection is slightly unusual and getting it sub-cutaneous may form an abscess.

BCG vaccine probably doesn't contribute much to herd immunity in the normal way. It's quite good at preventing the more serious forms of TB (TB meningitis and miliary TB) in infants and small children, but not terribly good at preventing pulmonary TB (the only form that's likely to be infectious); and in any case, the R value for TB is low: it's not very infectious, requiring close, prolonged contact. It's also a disease where host factors are very important: well-nourished, otherwise healthy people are much less likely to become ill than others.

People ("indigenous or otherwise") who are significantly exposed will also be followed up, although this will usually involve testing for infection, and in a few cases prophylactic treatment with antimicrobials, rather than BCG.

If BCG was a better vaccine, it might be worth offering universal vaccination against TB; but it's not a very good vaccine, and would never be introduced now, given the adverse reactions it causes.

The Bill and Melinda Gates foundation are working hard to develop a good modern TB vaccine - if they succeed, then perhaps the policy should be changed; in the mean time, the current compromise is probably extremely sensible.

Following up contacts

Contacts will be traced and treated as appropriate. The process starts with a risk assessment of the case: contact tracing is not necessary for non-infectious cases, unless it is to try to identify the source of the disease in the case. Where the case is thought to have been infectious, efforts will be made to trace and follow-up close contacts who meet criteria that suggests that they are at risk of TB. Follow-up may involve: checking for a history of BCG vaccination; skin (Mantoux) testing, chest X-ray, and/or interferon gamma testing.^[7]

If cases are identified amongst very close contacts, a wider set of contacts will be screened, and so on: this is known as the "stone in the pond" (or "ripples in the pond") principle.

Notification

Tuberculosis should be notified on suspicion, and regardless of whether the diagnosis is made in a living case, post-mortem, in order to ensure that necessary control measures (such as contact-tracing) can be undertaken.

ICD code

A15-A19

External links

• Tuberculosis homepage at WHO website
• WHO Global Database - get WHO data on TB prevalence, by country, from this website.
• "TB Alert - the UK's National Tuberculosis Charity"
• TB Essentials - CME module from DNUK (members only)
• Wiki Tuberculosis page
• HPA Tuberculosis index
• National Knowledge Service - TB Pilot ("The National Knowledge Service TB Pilot is a collaborative project, co-ordinated by the HPA working with the NHS and various voluntary organizations. This Project aims to ensure that sources of information and knowledge on tuberculosis are brought together for healthcare professionals and patients. This will enable both professionals and patients to base their decisions on best current knowledge. The National Knowledge Service is part of the NHS National Programme for IT.")
• 2010 Annual Evidence Update: On The Move Against TB - Homepage from NHS Evidence - infections (formerly a Specialist Library of the National Library for Health)
• Revised guidelines on the management and prevention of TB (published by NICE on 22 March 2006).
• Immunisation "Green Book"
• British Thoracic Society (BTS) guidelines relating to TB (See also British Thoracic Society).
• NHS Tuberculosis resources and information website
• CMO letter about the changes to the BCG vaccination programme, and from use of the Heaf test to the use of the Mantoux test, July 2005
• US guidelines and fact sheets about TB from Centers of Disease Control and Prevention (CDC)]

References