The three sickly beings in this 19th-century drawing represent diphtheria, scrofula (a form of tuberculosis) and cholera. The woman symbolizes the city of London.
Conquistadors and missionaries didn't just bring colonialism and Western religion to other parts of the world. They likely brought tuberculosis, too.
That's a key finding of an international study published this week in Science Advances, which looks at how the most common strain of TB developed — and how resistance to antibiotics, a serious issue in fighting tuberculosis, has spread as well.
Tuberculosis is one of the world's most serious health issues. It is the deadliest infectious disease, claiming 1.6 million lives a year, and one of the top 10 causes of death worldwide.
In recent years, scientists have offered two prominent narratives to explain the evolutionary history of this bacterial infection. The first is that tuberculosis emerged about 70,000 years ago and spread out of Africa when early humans left the continent. The second theory suggests the disease evolved in Africa more recently, roughly 4,000 to 6,000 years ago.
"You have two different stories that are often mingled together," says Vegard Eldholm, a senior researcher at the Norwegian Institute of Public Health and an author of the new study. In an effort to add some clarity to understanding the disease's past, Eldholm and his colleagues decided to focus on only one of TB's seven lineages. They chose to study "lineage 4," the most widely dispersed type of TB internationally, investigating both how the lineage originally evolved and how antibiotic-resistant forms of the lineage have spread.
According to the study, one of the most common types of tuberculosis seems to have reached Africa, the Americas and southeast Asia at the same time European colonizers arrived, suggesting Europeans carried the disease across the globe.
This does not negate the African origin narratives but could, says Vegard, indicate that TB traveled from Africa to Europe, where lineage 4 originated. And then lineage 4 traveled back to Africa.
The disease's resistance to antibiotics, by contrast, seems to have evolved at a much more local level. This finding adds new detail to health experts' understanding of tuberculosis.
"It means we may be able to control tuberculosis resistance at the local level," says David Dowdy, an epidemiologist at the Johns Hopkins Bloomberg School of Public Health, who was not involved in the study.
The study relied on 1,669 DNA samples of lineage 4 previously collected in Africa, Europe, North America, South America and Vietnam. In addition to surveying recent DNA, the researchers analyzed older samples of TB, including DNA collected from three 18th-century Hungarian mummies. By analyzing the extent of genetic variations across TB strains, the scientists could estimate how closely related the lineage 4 strains were to one another, a means of determining when the lineage arrived on different continents and how old different strains of the disease are.
The scientists found the spread of lineage 4 corresponded with a well-known historical phenomenon: European colonialism. "We can say with confidence the lineage evolved in Europe or close to Europe," Eldholm says. DNA analysis also suggests the lineage originated relatively recently: about 1,000 years ago.
The earliest introduction the scientists found seems to have occurred during the 13th century to Vietnam. Although the scientists cannot offer a specific colonial event for this introduction, the subsequent spread of TB within Vietnam seems contemporaneous with known colonial events. Lineage 4 became well established within the region around the late 16th century. This timing corresponds with French missionary expeditions to the country in the 1600s, and subsequent European military occupation seems to have enabled local spread within the country.
By the 15th century, the DNA samples show that the lineage had spread to Africa, reaching new countries in tandem with Europeans up to the 19th century. The earliest introductions to South America occurred between 1466 and 1593 and to North America between 1566 and 1658.
This pattern should not be interpreted to suggest that all TB originated in Europe, Dowdy of Johns Hopkins stresses. He notes that this study focused on only one lineage and excluded some areas with high levels of TB, such as India and China.
While the lineage as a whole has spread across continents, antibiotic resistance seems to be a local affair. Antibiotics were developed in the mid-20th century. Since then, some strains of TB have evolved to become resistant to antibiotic treatment. Eldholm and his colleagues investigated whether resistant lineage 4 strains have spread around the world. In contrast with their study of lineage 4 broadly, the scientists found no antibiotic-resistant strains in their study that had crossed national borders. In other words, if a resistant strain developed in the Netherlands, it is unlikely to have reached Portugal or Brazil.
"We saw antibiotic resistance has developed all over the world multiple times," Eldholm says. "That wasn't surprising. But the fact that we didn't find any [resistant] strains jumping from one country to another — that was a really big surprise." The regional boundaries of resistance may be explained by the relative newness of antibiotics. Antibiotic-resistant TB strains may have not had enough time to spread around the world.
In continuing to understand how TB moves internationally, Eldholm plans to conduct a similar study on tuberculosis lineage 2. Although it's not as common as lineage 4 globally, he says it's very common in the former Soviet Union, and "the rates of antibiotic resistance are insane."
Dire possibilities aside, there may be tidbits of good news in studying TB's epidemiology. Although modern health officials can't undo the colonial spread of lineage 4, they may be able to combat local resistance to antibiotics.
In the 1990s, Dowdy notes, the U.S. saw a surge of antibiotic-resistant TB; one report by the Centers for Disease Control and Prevention shows there were more than 400 cases diagnosed in the U.S. in 1993, contrasted to roughly 100 as of 2013. Multiple initiatives at the national level — such as separating infected people in hospitals and prisons from healthy individuals — significantly curbed the spread.
"I think what our study suggests is that antibiotic resistance can be fought successfully at the level of individual countries," says Eldholm, although he acknowledges international coordination is useful. "There's no excuse for countries not to do everything they can to fight TB. Because if they do everything they can, they might be able to fix this problem."
Natalie Jacewicz is a writer in New York. Follower her at @NatalieJacewicz.