Mycobacterium tuberculosis is the ‘mother of all pathogensâ€, able to create all its essential nutrients, eat its own cell wall without dying, and hide within the cells sent to kill it for decades.
Under various names, including the ‘white plague†and consumption, TB has been around for thousands of years, with Egyptian mummies showing traces of it.
A third of humankind is estimated to be infected by the bacillus, which is thought to kill two million people a year, with a new TB infection occurring every second.
Yet humanity confronts this talented adversary with inadequate diagnostic tests a century old, a poor vaccination developed 70 years ago, and drugs at least 35 years old.
Mycobacterium tuberculosis (Mtb) was identified by Robert Koch in 1881. It and its many relatives — including one causing leprosy — are thought to be descended from soil bacteria. One theory is that it made the transition via domesticated cattle.
The most common form of TB is pulmonary, but it can occur elsewhere, including the spine and the brain. Active TB eats through body tissues; patients become pale and cough up blood in a drawn-out death, usually from suffocation.
Hendrik Koornhof of the National Institute of Communicable Diseases says Mtb’s success lies partly in its ability to hijack the body’s biochemical defences. On entering the body it is met by macrophages, white blood cells that destroy intruding pathogens. But Mtb survives in the immune cells that should kill it.
It also appears to subvert the chemical message system, sending signals that dampen, rather than ratchet up, defence responses.
In 1998 the battle of science against TB took a leap forward with the deciphering of the 4 000 chemical letters making up Mtb’s genetic code. But scientists estimate they understand the use of only 40% of the genes. Some of its proteins are only known to exist in Mtb, and may help it avoid attack by the immune system.
Mtb also has ways of dealing with antibiotics. Its slow life cycle means it can take days to replicate, so that drugs that interfere in its reproduction must be present in sufficiently high levels for extended periods to be effective. Hence the six-month course of treatment.
Fat is beautiful to Mtb, described as a ‘wax blob†by Valerie Mizrahi of Wits university’s Molecular Mycobacteriology Research Unit. It has five times more genes for biosynthesising lipids (fats) than other bacterias. It can also synthesise all the essential amino acids, enzymes and vitamins it needs and switch its diet from fats to simple sugars if necessary. It is even believed to be able to digest its own cell wall and live.
Armed with a specialised secretion system to moderate its environment, Mtb has a highly water-resistant cell wall containing enzymes to disable toxins such as antibiotics, and appears to have an efflux system to eject them.
Under stress, the bacillus can ‘go to sleepâ€, stop metabolising and avoid taking in antibiotics. In this state it can vegetate for decades without dividing or needing to create spores for survival, as other pathogens do. When the immune system fails, it stirs back to life.
Thirty percent of people exposed to Mtb, usually through coughed droplets of sputum, become infected, but most, if not all, harbour the bacillus in a latent form.
Genetics appears to play a role in susceptibility to TB, and one mutation alone may multiply sevenfold the chances of infection. The link between immune system and pathogen is so intimate that some TB strains appear adapted to attack particular ethnic groups. Six ‘race-specific†strains have been identified.
The biggest driver of active TB in today’s world is the immune-destroying HIV epidemic, which helps explain why Africa carries a quarter of the global TB burden, despite having 11% of the human population.
HIV and TB are so closely linked that they have been dubbed the ‘ugly sistersâ€, and TB is the biggest killer of HIV-positive South Africans. For people with HIV, the risk of active TB infection is 10% a year, compared with 10% over a lifetime in HIV-negative people. Attempts to protect the HIV-positive from active TB by giving them prophylactic anti-TB drugs have been relatively unsuccessful, with doctors fearing the speedier development of drug resistance.
Chemotherapy emerged in the 1940s, and today antibiotic cocktails can kill active infections in six to nine months — if patients take the drugs and they are of good quality.
Incomplete treatment, inadequate diagnosis and failed public health services are driving multi-drug resistant (MDR) TB, which the World Health Organisation estimates 4% of humans carry.
Extensively Drug Resistant (XDR) TB results from failure to treat MDR properly and is effectively immune to all locally available drugs. WHO identified it as a global health emergency 13 years ago.
Douglas Wilson, head of medicine at Edendale Hospital, said that at his facility, 11% of TB patients tested with bacterial cultures had MDR TB — an ominous indicator that some will develop XDR. ‘MDR-TB will be HIV’s long-term gift,†he added.
The only widely used vaccine is the Bacille Calmette Guerin (BCG), which is useless against adult forms of TB but apparently protects children, especially from the cerebral form.
Diagnostic tests are generally slow, inaccurate and expensive, which is particularly problematic because people with advanced HIV and TB often register negative for TB on sputum tests, as their depleted immune systems fail to register the bacillus.
Money is being pumped into TB research, and more medicines, tests and vaccines are in the research pipeline. But it will take years for these to reach those in developing countries most at risk.
Science alone cannot succeed because public health failures bring rapid resistance to new drugs. MTb has been helped on its destructive course by the short-sightedness of its hosts.