A Tour around Tuberculosis

(Date of publication 25 April 2005)

If you had contracted tuberculosis (TB) in the first half of the last century, the most advanced treatment available was rest in a sanatorium and collapsing the lung; not surprisingly, the chances of survival were only around 50%. Cure rates soared in the developed world with the advent of antibiotics, but the latter years of the twentieth century saw a resurgence of the disease, with the emergence of multi-drug resistance and the deadly combination of tuberculosis and AIDS. Incidence rates have since generally declined, but the numbers involved are truly staggering.

More than one third of the world's population is infected with the tuberculosis bacterium; each year 8 million people become ill with TB and 2 million die from it. In the USA, the overall case rate in 2004 was the lowest ever recorded, at 4.9 per 100,000 people, but the significant decline seen over the past few years is slowing. Encouragingly, the number of cases of multi-drug resistant tuberculosis (MDR TB) there declined by 76.5% between 1993 and 2003. A detailed breakdown of the figures, however, reveals marked racial and ethnic disparities; the incidence in Asians was 20 times that in whites, and in blacks was 8 times that in whites.

World-wide, TB rates are stable or falling in five of the six regions of the world, according to the World Health Organisation's 2005 Global Tuberculosis Control report. Prevalence has declined by 20% since 1990. The exception to this trend is Africa, where TB rates have tripled since 1990 and are still rising at 3% to 4% each year. This increase is inextricably bound to the AIDS epidemic raging across the continent, which weakens the immune systems of many people exposed to the tuberculosis bacillus; TB is the biggest killer of AIDS patients. Another cause of concern is the high incidence of MDR TB, especially in Russia. An indication of the seriousness of the situation there is that earlier this month Moscow's City Duma proposed the forcible hospitalisation of TB patients who are unwilling to undergo examination or treatment.

Clear patient-orientated information about tuberculosis can be found on the US National Institute of Allergy and Infectious Diseases site. Most people who are infected harbour the bacterium without symptoms; only about 10% develop active tuberculosis at some time during their lives. The causative agent, Mycobacterium tuberculosis, is spread by droplet infection, but prolonged contact is required to contract the disease. On average, people have a 50% chance of becoming infected if they spend eight hours a day for six months or 24 hours a day for two months working or living with someone with active TB.

The risk of active disease is greatest in the first year after infection, although it may develop many years later. Early symptoms include weight loss, fever, night sweats and loss of appetite. Necrotising (caseating) and non-necrotising (non-caseating) granulomas (or tubercles) develop, surrounded by lymphocytes and macrophages. The great majority of cases involve pulmonary disease, producing a cough, chest pain and bloody sputum. Here is an X-ray of an infected lung, and here a photograph in which the lesions are clearly visible. However, many other organs may also be affected, including the kidney and bone. More detailed information about the pathophysiology of TB can be found on this site.

For an up to date clinical view of tuberculosis, the emedicine site has a good article. Among the important points made are that fewer than 10 bacilli can initiate a pulmonary infection, the incidence in the US is twice as high in men as in women, MDR TB cases have a reported fatality rate of more than 70%, and treatment should begin with at least 4 medications until drug susceptibilities are known, to avoid selecting drug-resistant organisms.

Mycobacterium tuberculosis (see this electron micrograph) is thought to have evolved from a soil bacterium and initially infected cows, making the jump to humans when cattle were domesticated about 10,000 years ago. An aerobic, facultative intracellular parasite which is very slow-growing, doubling its population only every 18 – 24 hours, it is not classified as Gram-positive or Gram-negative because it does not have the characteristics of either. This online Textbook of Bacteriology has a wealth of detail about all aspects of the organism, including its unique cell wall structure, virulence mechanisms, and the progression of active disease.

The encouraging general decline in the prevalence of TB over the past two decades is complemented by some exciting new discoveries. This month a team at Harvard announced that it had found a mouse gene which limits multiplication of M. tuberculosis inside cells. Called Ipr 1 (intracellular pathogen resistance 1), it turns on a regulated cell death pathway and leads to apoptosis, rather than necrosis. Further studies could lead to the development of new diagnostic tests and approaches to prevention. The identification last year of all the genes that the bacterium activates at all stages of infection holds out the promise of a much more targeted and effective vaccine. Finally, a new anti-TB drug with a novel mechanism of action has been announced, which not only clears infection more quickly than current treatments, but has proved effective against all MDR TB strains tested so far. Thus the signs are promising, but the magnitude of the challenge is enormous.

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