Dr Richard Godfrey answers questions from GP Dr Rubin Minhas
Dr Richard Godfrey answers questions from GP Dr Rubin Minhas
Even though there has been a slow decrease in prevalence in much of the world, TB is increasing sharply among poor and socially deprived people in certain countries such as the South Asia subcontinent and the Western Pacific, including China
In many European countries, including Britain, poor and socially deprived groups are found in cities where there are many immigrants in relatively well demarcated districts. Some London boroughs have shown a rise in new case incidence over the past 10 years from 14 to over 80 per 100,000, and nearly the whole of this rise has occurred in people born outside the UK. Many have come from South Asia, but other immigrant groups are also at risk. In global terms, the most vulnerable are those infected with HIV. TB in many of the former Soviet Union countries is particularly worrying, and a threat to the whole global population, because up to 40 per cent of new cases are resistant to first-line TB drugs.
The golden rule is always to think about TB, because it is not exclusively confined to the vulnerable groups. Many doctors will be surprised at some point in their career to hear that a colleague or other professional person has developed TB. However, the groups most at risk are:
- Recent immigrants from high burden countries (not only those from South Asia)
- Socially dislocated people (eg vagrants and alcoholics)
- Substance misusers
- HIV-infected people
- People with diabetes
- People with medical causes of weakened immunity: severe renal disease, leukaemia, Hodgkin's disease, cancer (especially head and neck), immunosuppressive treatment (arthritis, post-transplant), Crohn's disease, steroid treatment, malnutrition, low body weight.
Extra-pulmonary TB is seen more frequently now in the UK. About 80 per cent of all cases of extra-pulmonary TB notifications are of South Asian origin. Extra-pulmonary TB can be very difficult to diagnose, and there should be a high index of suspicion in any patient complaining of nonspecific malaise, weight loss and fever. Remember that almost every organ of the body can be affected. It can only be fully diagnosed by microbiological detection of TB bacilli from affected tissues (microscopy and culture). However the pathological appearance of active disease on microscopic histological examination is characteristic, and is accepted as proof of extra-pulmonary disease if the clinical picture fits, even though no actual TB bacilli are found. Diagnosis of extra-pulmonary disease always requires tissue or tissue fluid to be obtained by biopsy or aspiration of affected organs. In patients who have not had BCG vaccination, a positive Mantoux test increases suspicion, but never provides a full certain diagnosis.
If the clinical presentation even remotely suggests TB, the important investigations are a chest X-ray and three sputum samples for direct microscopy and culture (at least one sample should be freshly coughed up in the early morning when there is the greatest chance of finding TB mycobacteria which have collected in the bronchi overnight). These two investigations will pick up patients with sputum-positive active pulmonary TB, but they will not reliably exclude other forms. GPs might also organise for patients to keep a temperature chart, to validate a patient's history of recurrent fever. Tuberculin testing will generally be organised through the local TB service. The current round of NICE consultations has resulted in a recommendation that the Heaf test should be withdrawn in favour of universal use of the Mantoux test in the UK.
Beyond these investigations, GPs will need the help of the local hospital respiratory department. A blood test to detect TB is likely to be introduced in the NHS within the next few years.
Tuberculin is a protein derived from killed mycobacteria (Purified Protein Derivative, PPD). It is used in the Heaf test and the Mantoux test to discover whether a person has been, or is currently exposed to Mycobacterium tuberculosis. As the question implies, there are considerable problems in interpreting the results.·The strongest reactions (Heaf grade 4, Mantoux >10mm induration) are seen in people with active TB, but these strong responses may be attenuated by concomitant illness, notably HIV infection, but also any severe infection or other illness.
Because tuberculin is a relatively crude preparation, there is cross-reaction with other mycobacteria, including BCG (Bacillus Calmette Guèrin). Therefore anybody who has had BCG vaccination (usually in their early teens in the UK) may have a positive tuberculin test long into adult life.
The tuberculin reaction takes several weeks to become fully established after acquiring mycobacterial infection naturally or being vaccinated with BCG.
Cross-reactions also occur to the atypical mycobacteria, which can occasionally cause disease in humans as well as their animal hosts (the commonest in the UK are m. avium intracellulare, m. xenopi, and m. kansasii).
The response to tuberculin varies naturally from person to person, even when their degree of exposure has been identical. Some people never develop a positive tuberculin reaction after BCG vaccination.
The tuberculin response fades gradually after exposure, but at widely different rates. People with immunosuppression from drugs (including steroids), the elderly, HIV-positive people, patients with sarcoidosis in fact any ill person may have reduced or absent tuberculin response.
Last, there are the practical difficulties: Mantoux testing requires a good intradermal injection technique, and patients must return at 48 hours for the result to be read.
Probably the best approach to the tuberculin test is to regard it as useful additional evidence of active TB when it is unequivocally strongly positive, but it must never be taken by itself as evidence of active TB, latent TB, or absence of TB. The gold standard must always be diagnosis through bacteriological or histological confirmation.
Standard internationally recommended TB treatment consists of two months intensive phase treatment (rifampicin, isoniazid, pyrazinamide, ethambutol) followed by four months continuation phase (rifampicin, isoniazid). The drugs are nowadays nearly always given in combined preparations for convenience (see BNF). Cure is officially defined by the WHO as negative sputum (direct microscopy and culture) during the last month of treatment and on at least one occasion previously during treatment. A patient is no longer infectious once the sputum converts to negative (usually about four to six weeks after starting treatment). In fact patients probably become non-infectious much earlier, because the mycobacteria that are coughed up have already lost virulence under treatment after just a few days.
Yes, absolutely. It is most important to realise that treatment can usually be given entirely on an outpatient basis. The only restriction should be to avoid close contact with vulnerable people during the first few weeks of treatment there is no official standard policy but it makes sense that people such as school teachers and nursery helpers should stay away from work for four to six weeks while treatment takes effect.Richard Godfrey is health adviser to Merlin, a specialist charity providing health care and medical relief to people caught up in natural disasters, conflict, disease and health system collapse. Dr Godfrey is a former consultant in respiratory medicine and is now visiting professor at Moi University, KenyaCompeting interests None declared
The most important investigations are a CXR and three sputum samples at least one freshly coughed up in the early morning· Have a high index of suspicion for extra-pulmonary TB in any patient complaining of non-specific malaise, weight loss and fever. Standard treatment is two months' intensive medication (rifampicin, isoniazid, pyrazinamide, ethambutol) followed by four months' continuation phase (rifampicin, isoniazid). Combination preparations are convenient· A patient is no longer infectious once sputum converts to negative (usually 4-6 weeks after treatment)
What I will do now
Dr Rubin Minhas responds to the answers to his questions· Our practice is in an inner-city area with significant deprivation. As our list has many patients with drug problems, some with HIV and many others who are recent immigrants, Dr Godfrey's advice has considerable resonance with me although the high prevalence of deprivation is reason enough.
- I will give TB a high ranking in my differential diagnosis of respiratory diseases but also with the presentation of non-specific illness.
- I will request three early morning sputum samples and a chest X-ray from patients who present with any appropriate history or who do not respond to treatment for an alternative working diagnosis.
Dr Minhas is a GP in Medway, Kent