Tuberculosis

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40 Tuberculosis

Clinical aspects

Infection with tubercle bacilli occurs in the vast majority of cases by the respiratory route. The lung lesions caused by infection commonly heal, leaving no residual changes except occasional pulmonary or tracheobronchial lymph node calcification (Heymann, 2004). About 5% of those initially infected will develop active primary disease (Hawker et al., 2005). This can include pulmonary disease, through local progression in the lungs, or by lymphatic or haematogenous spread of bacilli, to pulmonary, meningeal or other extrapulmonary involvement, or lead to disseminated disease (miliary TB). In the other 95%, the primary lesion heals without intervention but in at least one-half of patients, the bacilli survive in a latent form, which may then reactivate later in life. Infants, adolescents and immunosuppressed people are more susceptible to the more serious forms of TB such as miliary or meningeal TB.

Pulmonary (respiratory) TB is more common in the UK than extrapulmonary (non-respiratory) TB. Sites of extrapulmonary disease include the pleura, lymph nodes, pericardium, kidneys, meninges, bones and joints, larynx, skin, intestines, peritoneum and eyes. In the UK, the lymph nodes are the most common site for extrapulmonary disease. In 2008, 55% of cases were pulmonary and 21% involved the extrathoracic lymph nodes.

Pulmonary TB may arise from exogenous reinfection or endogenous reactivation of a latent focus remaining from the initial infection. If untreated, about 65% of patients will die within 5 years, the majority of these within 2 years. Completion of chemotherapy using drugs to which the tubercle bacilli are sensitive almost always results in a cure, even with HIV infection.

Epidemiology

Epidemiology is a measure of the occurrence of a disease in different populations. It helps to identify population groups at increased risk of TB. The key measures for TB are the number of new cases in a specified period of time, usually 1 year, and the incidence rates, that is, new cases per 100,000 of the population. Incidence rates are a good comparative measure of differences in the occurrence of TB between countries or different sub-groups in the population, as they take into account the size of those groups. TB surveillance, which involves monitoring its occurrence and epidemiology, is an essential component of TB control programmes, because it helps to evaluate their effectiveness in reducing disease rates.

Global

Globally, it is estimated that TB causes about 2 million deaths worldwide each year. One-third of the world’s population is infected with the tubercle bacillus. It is becoming the leading cause of death among HIV-positive people. Over 4 million cases of TB disease are notified annually although the estimated number of new cases is put at 9 million. The majority of cases occur in poor countries in the southern hemisphere (WHO, 2009).

The numbers of cases estimated to have occurred in 2008, globally and by WHO region, is presented in Table 40.1. Most cases of TB are in South East Asia, although the highest rates are in Africa.

Table 40.1 Estimated epidemiological burden of tuberculosis incidence globally and by WHO region (Source: WHO, 2010)

WHO region Numbers (000s), 2008 (lower and upper bounds) Rates per 100,000 population, 2008 (lower and upper bounds)
Africa 2800 (2700–3000) 350 (330–370)
Americas 280 (260–300) 31 (29–33)
Eastern Mediterranean 650 (580–740) 110 (99–130)
Europe 430 (400–460) 48 (45–51)
South-East Asia 3200 (2800–3700) 180 (160–210)
Western Pacific 1900 (1700–2200) 110 (95–130)
Global 9400 (8900–9900) 140 (130–150)

In 2008, it was estimated that 440,000 people had MDR-TB worldwide, and one-third of these died. The brunt of the MDR-TB epidemic is borne by Asia, with almost 50% of cases worldwide estimated to occur in China and India. However, in some areas of the world, up to one in four people have drug-resistant TB. For example, 28% of all people newly diagnosed with TB in one region of North-Western Russia had the multidrug-resistant form of the disease (WHO, 2010).

UK

In the UK, since the late 1980s, there have been changes in the epidemiology of TB. Following a decrease in notifications over several decades, from the late 1980s cases of TB started to increase again.

A total of 8655 cases were reported in 2008 (Health Protection Agency, 2009). The overall rate across all population groups was 14.1 per 100,000 population. Of all cases, 39% occurred in the London region, where the rate was 44.3 per 100,000 population. Nineteen primary care organisations in England had a rate of 40 per 100,000 or over, all of which were in major urban areas. Rates of TB in England outside London varied from 5.7 per 100,000 in South-West England to 18.7 per 100,000 in the West Midlands. Incidence rates per 100,000 population were 8.7 in Scotland, 5.8 in Wales and 3.3 in Northern Ireland. The majority of cases (72%) were in the population born outside the UK and in those aged 16–44 years (61%). The TB rate was higher in those born abroad than among those born in the UK (86 compared with 4.4 per 100,000). This reflected higher rates of TB in people from high-incidence countries, mainly South Asia. The risk of TB is highest in the 5 years after arrival in the UK. TB can also occur as a travel-related disease in UK residents from high-incidence countries, who return to visit their country of birth and are exposed to TB. The numbers of cases by region in England, Wales and Northern Ireland, in 2008, is shown in Table 40.2.

Table 40.2 Tuberculosis case reports and rates by UK region/country 2008 (adapted from Health Protection Agency, 2009)

UK region/country Number of cases Rate per 100,000 population
London 3376 44.3
West Midlands 1012 18.7
North West 745 10.8
Yorkshire and the Humber 647 12.4
East Midlands 517 11.7
South East 719 8.6
East of England 478 8.3
South West 297 5.7
North East 179 7.0
England 7970 15.5
Scotland 452 8.7
Wales 174 5.8
Northern Ireland 59 3.3

Diagnosis

Symptoms

The symptoms and signs of TB include:

Investigations

Investigations are essential to confirm clinically suspected TB and should be arranged even if the diagnosis is strongly suspected on clinical grounds. Microbiological tests are crucial, especially for pulmonary disease, as they facilitate both the clinical and public health management of TB and ensure the appropriate implementation of infection control procedures for cases managed in healthcare settings.

Microbiological

Microbiological investigations are undertaken to assess the infectious state of the patient, and distinguish between infection with mycobacteria causing TB and other mycobacteria. They also determine the drug-susceptibility patterns of the infecting organisms, to ensure that the drugs prescribed will be effective in treating the individual patient. Investigations comprise microscopy, culture, drug-susceptibility testing and strain typing.

Direct microscopy of sputum is the simplest and quickest method of detecting the infectious patient, by looking for acid-fast bacilli. A minimum of three sputum samples, one of which should be early morning, should be collected from patients with suspected respiratory TB.

Direct microscopy is not as useful in non-pulmonary disease, any specimens taken should be sent for culture.

If conventional culture methods are used, such as the Lowenstein–Jensen medium, growth may take up to 6 weeks. Modern liquid cultures can produce results more quickly. Polymerase chain reaction (PCR)-based tests can also detect M. tuberculosis complex in clinical specimens.

A rapid test is available for assessing rifampicin resistance in individuals thought to have drug-resistant TB. A positive result indicates the need to assess susceptibility to other first-line anti-TB drugs. Drug-susceptibility testing still needs to be done on isolates grown on culture media.

DNA fingerprinting, or strain typing, is useful in the public health management of TB. In 2010, a new method, mycobacterial interspersed repetitive unit/variable number of tandem repeats (MIRU/VNTR) 24-loci strain typing, became available in the UK. Strain typing will help in establishing links between cases not previously identified, disproving links between apparent clusters of cases, and also in detecting cross-contamination in laboratories.