A disease as old as humanity itself: How TB took over the world

New analysis shows the resilient and adaptable disease is as old as humanity itself

Perhaps no other disease has had such a dramatic influence on art, music and literature. Now science has shown that tuberculosis is as old as humanity itself.

Studies have revealed that the tuberculosis bacterium originated many tens of thousands of years ago when the first anatomically modern humans had yet to start their global migration from their African homeland.

The horror of “consumption”, as TB was once called, suffuses modern history – no doubt a reflection the number of novelists and artists it struck down. But the origins of this debilitating lung infection go back much further in time, long before Neolithic people about 12,000 years ago first started to domesticate livestock and build the urban centres where TB could spread easily from one person to another.

A detailed genetic analysis of more than 250 contemporary strains of TB bacteria from around the world has revealed that the infectious agent originated with the emergence of Homo sapiens in Africa more than 70,000 years ago.

By studying the diverse genetic variation of Mycobacterium tuberculosis, the researchers were able to show TB must have spread around the world with the first modern humans to emerge from Africa. This early origin of TB also shows the lung infection did not, as previously thought, spread to humans from their domesticated animals – as farming came much later.

“We have found that TB was infecting humans before they left Africa around 70,000 year ago. This implies the bacteria have been able to survive in small hunter-gatherer populations,” said Iñaki Comas of the Centre for Public Health Research in Valencia, the lead author of one of the study published in the journal Nature Genetics.

“At the same time we show that its evolution parallels that of humans and benefits from human demographic explosions,” Dr Comas said. As the human population increased, both during the Neolithic age with the invention of agriculture and later on as a result of the Industrial Revolution, then so also did TB, she said.

Sebastian Gagneux of the Swiss Tropical and Public Health Institute in Basel said: “The evolutionary path of humans and the TB bacteria shows striking similarities. We see that the diversity of tuberculosis bacteria has increased markedly when human populations expanded.”

Parallel research by three other teams of scientists has also revealed the nature of the genetic mutations causing the tuberculosis bacterium to become resistant to antibiotic drugs, which have largely relegated TB to a disease of the poor and underprivileged in the developing world.

The discovery of the genetic mechanisms conferring antibiotic resistance on the TB bacteria should enable researchers to devise better strategies for blocking the emergence of the drug-resistant strains of TB that are now spreading from one country to another.

“Our study makes a new association of 39 genes and genetic regions with drug resistance in the TB bacterium. These genes were not previously recognised as associated with drug resistance, and they range from genes of known to those of unknown function,” said Maha Farhat of Harvard University, a lead author of one of the studies in Nature Genetics.

“Identifying the new mutations will allow us to design better diagnostics for drug-resistant tuberculosis. In addition, these findings may help to design new drugs to target drug-resistant tuberculosis,” Dr Farhat said.

About one death in five in the Western world between the 17th and 19th centuries was caused by tuberculosis, which has thrived in overcrowded living conditions. Even today some 8.7 million people a year worldwide succumb to the disease, of which about 1.4 million will die.

Tuberculosis is second only to HIV and Aids as the greatest killer worldwide due to a single infectious agent, and more than 95 per cent of TB deaths occur in low and middle-income countries, according to the World Health Organisation.

TB strains that are resistant to more than one antibiotic have now emerged in virtually all countries surveyed by the WHO.

“TB over the years begins to acquire resistance to every drug soon after it is introduced,” said David Alland of Rutgers University in New Jersey. “We need to break this cycle by finding new ways to prevent resistance from occurring in the first place. Our study shows that we may be able to target resistance at its earliest stages, and potentially prevent resistance by altering drug doses or treatment intervals.”

The 'Great White Plague' through the ages

The long tentacles of tuberculosis have touched the lungs of many hundreds of millions of people throughout history. It was a disease of ancient times, and some scholars have suggested that King Tutankhamun may have suffered from the lung condition.

There were many cases between the 16th and 19th centuries, when the “great white plague”, as it was known, accounted for about 20 per cent of premature deaths. It aggravated the early demise of many artistic luminaries, such as the Romantic poet John Keats, the composer Frédéric Chopin and the novelists Emily Brontë and Robert Louis Stevenson.

Little was known about how to treat the condition prior to the discovery of bacteria in the 19th century and antibiotics in the 20th century. The Czech novelist Franz Kafka was one of many who tried to alleviate the symptoms by breathing the fresh air and drinking the pure waters of the many sanatoriums that sprang up around Europe in the 19th century to treat TB.

The true hero of tuberculosis science was Robert Koch, the German physician, who showed in research in 1882 that the causative agent for the lung infection was a bacterium called Mycobacterium tuberculosis. The rules linking a disease with its causative agent are still known as “Koch’s postulates”.

The TB bacterium can invade the macrophage cells of the lungs, which are designed to eradicate invaders. Antibiotics can kill the infection but the treatment needs to be taken over many weeks without stopping.

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