In decades-old slides, blood and hints of malaria's path

In 1925, the Spanish government hired a doctor named Ildefonso Canicio to head up a malaria research centre in the Ebro Delta, where the disease was endemic. Ildefonso worked with patients from the surrounding rice fields for several decades, until he contracted malaria himself. He died of unrelated causes in 1961, the year malaria was eradicated from Spain.

Among the belongings he left behind were blood samples used to diagnose three patients in the 1940s. Now those samples, each just one or two drops of blood smeared onto a microscope slide, may have solved a long-running mystery: how some strains of the malaria parasite arrived in Europe and in the Americas.

Malaria has not been endemic in Europe for more than half a century, but the continent once was a hot zone. The European strains are now extinct, however, so it has been difficult for scientists to figure out exactly how the disease evolved and spread across the globe.

In a study published in Proceedings of the National Academy of Sciences, researchers report that they retrieved DNA from malaria parasites in Ildefonso’s old blood samples: Plasmodium vivax, found today in Asia, the Middle East, South and Central America, and parts of Africa; and its more virulent cousin, Plasmodium falciparum, which accounts for 90% of malaria deaths.

Looking backAn extinct version of P. vivax in the samples was closely related to strains seen today in Central and South America, the researchers found. A strain of P. falciparum was identical to one currently found only in India. Together with historic data, the findings suggest that some strains of malaria closely followed the migrations of people: from India to Europe around the fourth and fifth centuries BC, and then from Europe to the Americas after Christopher Columbus’ arrival.

“Malaria closely related to the human type was already present in the New World some 15 to 20 million years ago,” George Poinar, a biologist who studies the origins of malaria and has traced the parasites back to dinosaurs, wrote in an email. The new research, he said, fills in some of the map of malaria’s travels with humans. Ildefonso’s son-in-law offered the samples to Raul Escosa and Carles Aranda, two researchers working on mosquito control who were searching for records of the doctor’s work. The researchers asked Carles Lalueza-Fox, a paleogeneticist at the Institute of Evolutionary Biology in Barcelona, Spain, if he’d be interested in extracting genetic information about malaria parasites from the blood.

In the leftoversCarles Lalueza-Fox studies ancient humans and extinct hominid species, not extinct pathogens. But his family has some history with malaria. “It happened that my father — during the Spanish Civil War — contracted malaria while crossing the Ebro region in 1938,” he said. 

Carles Lalueza-Fox knew that most of the small amount of DNA on each microscope slide would be human. He relied on a method normally used to pull ancient human DNA from bones and teeth, only this time he reversed it: he looked for DNA in the leftovers — and found the parasites.

With just a few drops of dried blood, Carles Lalueza-Fox was able to reconstruct the genomes of the European parasites — the full genome of P. falciparum and nearly 70% of the genome of P. vivax. And with that, he said he had more than enough information to make the historical and geographical connections. Carles Lalueza-Fox is now searching for more old European samples to gather enough data to reconstruct the whole genome of P. vivax from decades ago, before its more recent evolutionary changes.

By doing this, he and other scientists may be able to identify the mutations that allowed the parasite to develop resistance over the years to a growing number of drugs. By looking at even older samples, they may discover how the disease originated in the first place.