Each March 'World TB Day' draws attention to tuberculosis (TB). On 22 March 2006, NICE and the National Collaborating Centre for Chronic Conditions launched a clinical guideline to help the NHS identify, prevent and treat people with tuberculosis in England and Wales.1
NICE guidelines are based on the best available evidence, and the Department of Health asks NHS organizations to work towards implementation with the Healthcare Commission monitoring compliance.2
This is the first clinical guideline from NICE that makes major recommendations on both the prevention as well as the treatment of a condition.3
These guidelines were commissioned by NICE as a successor to previous TB guidance that had been published in many different documents by both the British Thoracic Society, and the Department of Health.4,5
Why is this guideline important?
With improvements in living conditions and anti-tuberculous treatment, cases of TB in England and Wales declined from the 1950s to 5086 notifications in 1987, and it was considered by many to be a disappearing disease.6 However, recent years have seen sustained re-emergence of TB as an important communicable disease, with 7086 cases noted in 2004,6 and the emergence of drug-resistant disease. Tuberculosis is responsible for around 350 deaths per year in England and Wales.6
There are marked geographical differences in the incidence of tuberculosis in England and Wales. Most new cases occur in major cities, but the incidence continues to decline in other areas.6 It remains predominantly a disease of poverty, with specific groups of the population at increased risk, reflecting a combination of factors including migration from high-incidence countries, homelessness and HIV co-infection.7
The NICE guideline sets the gold standard for prevention, control, diagnosis and treatment of TB. It also identifies priorities for tackling TB, such as screening for individuals at increased risk, vaccination, and ways of encouraging adherence to treatment. Almost all cases of TB are preventable, and most people with TB can be cured if the correct drugs are given and taken for the correct length of time.7 Making sure that people with active TB are diagnosed and treated promptly is one of the most important ways to control the disease. This guideline aims to help healthcare professionals identify and treat active disease, to control latent infection, and to prevent further transmission.
How good is the evidence?
The classification of recommendations and the levels of evidence for intervention studies are adapted from SIGN,8 and are summarized in Figure 1.
This NICE guideline includes nearly 200 recommendations.1 However, because TB has not been the subject of recent robust research activity, there is a paucity of research evidence and about three-quarters of the recommendations made are good practice points (GPP). After reviewing the evidence, the guideline development group (GDG) made recommendations for important research areas to improve NICE guidance and patient care in the future. I have emphasized the recommendations that are most relevant in primary care below.
Figure 1: Hierarchy of evidence and recommendation classification
Reproduced by kind recommendation of the National Institute of Health and Clinical Excellence
How is tuberculosis spread?
Tuberculosis is a complex disease that can be difficult to diagnose.7 However, early diagnosis and treatment of infectious TB is the most important aspect of TB control. Individual clinicians will not see many cases of TB and so the guideline describes the nature of TB infection and disease.
It is spread by one person inhaling Mycobacterium tuberculosis (M. Tb) in droplets that have been coughed or sneezed out by someone with infectious TB of the lungs, particularly those with bacteria that can be seen on simple microscope examination of the sputum (i.e. smear positive). Other forms of TB, including latent TB, are rarely infectious.7
The risk of becoming infected is greatest in those with prolonged, close household exposure to a person with infectious TB.7
Once inhaled, the bacteria grow slowly in the lungs over several weeks. In over 80% of people the immune system kills the bacteria, but a small number develop latent TB where the bacteria are not killed and lie dormant.
People with latent TB are neither ill, nor infectious. If the immune system fails to maintain its defence, active TB disease can develop within the lung, or in any part of the body that the infection has spread to (e.g. the lymphatic or blood system). About half of the cases of active TB develop within a few years of the original infection; the remainder occur from reactivation of the latent infection many years later.7
Who is at risk?
Anyone can catch TB but the people at particular risk are those who have been exposed to M. Tb, and those who are less able to fight latent infection. These groups of people include:
- close contacts of infectious cases
- those who have lived in, travel to, or receive visitors from places where TB is still very common
- those people who live in ethnic minority communities that originate from places where TB is very common
- those with immune systems weakened by HIV infection or other medical problems
- the very young and the elderly, as their immune systems are less robust
- those with chronic poor health and nutrition because of lifestyle problems, such as homelessness, drug abuse or alcoholism
- those living in poor or crowded housing conditions, including those living in hostels.7
GPs can play an important role in identifying 'new entrants' who should be screened for tuberculosis when they register with a new practice, having moved into the area.1
New entrants are people who have recently arrived from a country with a high annual incidence of tuberculosis (i.e. any country with >40 cases per 100,000 of the population).7
Assessment, which can be incorporated into larger health screening programmes for new entrants, should include a chest X-ray and clinical assessment for those with an abnormal X-ray [Grade D(GPP)].
Symptoms of tuberculosis
Typical symptoms of pulmonary TB include:
- chronic cough
- weight loss
- intermittent fever
- night sweats
- coughing blood.
A diagnosis of tuberculosis should also be considered in anyone with intermittent fever, weight loss and other unexplained symptoms.7
Investigations in primary care
If active pulmonary TB is suspected, a posterior–anterior chest X-ray should be taken, and X-ray appearances suggestive of TB should lead to further diagnostic investigation (Grade C). If there are clinical signs and symptoms consistent with a diagnosis of TB, the patient should be referred to a physician with training in, and experience of, the specialized care of people with TB (Grade C).7Treatment should be started without waiting for culture results [Grade D(GPP)].1
How is latent tuberculosis diagnosed?
Recently, tuberculin skin testing using the Heaf test has been replaced with Mantoux testing.7 However, evidence is emerging on the new interferon-gamma tests. These blood tests appear to offer greater specificity and sensitivity.
Based on available evidence, the recommendation is that Mantoux testing should be performed, and those with positive results (or in whom Mantoux testing may be less reliable) should then be considered for interferon-gamma immunological testing, if available (Grade D).1 With appropriate training, these tests can be undertaken in primary care, allowing TB teams to concentrate their expertise where it will be most effective.
Tuberculosis requires prolonged treatment. Standard treatment for drug-sensitive TB is for 6 months (i.e. 6 months of isoniazid and rifampicin, supplemented in the first 2 months with pyrazinamide and ethambutol) (Grade A/B). Fixed-dose combination tablets should be used (Grade C). Some forms of TB require longer courses of treatment.
In certain groups of patients, including children, young people, and those with HIV infection who have no evidence of disease, latent TB may be treated with isoniazid for 6 months or rifampicin and isoniazid for 3 months (Grade A).1
For years, all secondary school children have been given Bacille-Calmette-Guè1,7 In developing this guidance, the cost-effectiveness of BCG vaccination was examined in various models.7
Primary care clinicians have an important role in ensuring that neonatal BCG vaccination is discussed with the parents or legal guardian of any baby at increased risk of TB (born in, or having a parent or grandparent born in a country with a high incidence of TB).1
In areas of the country with a high incidence of TB, neonatal BCG may be offered to all neonates soon after birth [Grade D(GPP)].1 Neonatal BCG may be given in a primary care setting. Opportunistic vaccination of high-risk children should continue to be undertaken together with vaccination of specific groups without evidence of latent TB who remain at higher risk of infection.1
The scope of the guideline is unusually wide, which necessitated the work to be divided between two separate GDGs: one covering diagnosis and management, the other concentrating on prevention and control.
The GDGs attempted to produce practical recommendations, even though in some areas it was unusually difficult to find good evidence. Great efforts were made to link the advice contained in the guideline to that available from other sources, in particular, the advice from the Joint Committee on Vaccination and Immunisation.9
This guideline is a major weapon in our fight against TB. It should help ensure the NHS improves the way it prevents, screens, identifies and treats TB for all those affected. It will enable every patient to be treated with the best available treatment regimen. With the introduction of more effective screening programmes, and better monitoring and adherence to treatment, we can make a real difference to the prevalence of TB, and help slow down or even halt the spread of this disease.
However, implementation of the guideline will present a significant challenge to the NHS, as there is now a greater emphasis on screening and prevention in primary care.
- National Institute for Health and Care Excellence. Tuberculosis. Clinical diagnosis and management of tuberculosis and measures for its prevention and control. Clinical Guideline 33. London: NICE, 2006.
- Joint Tuberculosis Committee of the British Thoracic Society. Control and prevention of tuberculosis in the United Kingdom: code of practice 2000. Thorax 2000; 55 (11): 887–901.
- Department of Health. The Interdepartmental Working Group on Tuberculosis: The prevention and control of tuberculosis in the United Kingdom. London: DH, 1998.
- Royal College of Physicians. Tuberculosis. Clinical diagnosis and management of tuberculosis and measures for its prevention and control. London: RCP, 2006.
- Scottish Intercollegiate Guidelines Network. SIGN 50:A guideline developers' handbook. Edinburgh: SIGN, 2001, updated 2004.