KATHMANDU, JUNE 17

A team of geneticists and archaeologists has identified the earliest known case of P. falciparum malaria at the high Himalayan site of Chokhopani located along the Kali Gandaki River Valley in the Mustang District of Nepal.

According to Mark Aldenderfer, Distinguished Professor Emeritus at the University of California, Merced, an archeological study conducted by a team of international scientists has identified tantalizing clues about early malaria in Nepal and the role that long-distance trade have played in its spread.

"Our team unexpectedly identified the earliest known case of P. falciparum malaria at Chokhopani (ca. 800 BCE) in Upper Mustang," Aldenderfer told THT. Along with Mustang, the scientists identified 36 cases of malaria, from a man who died 5600 years ago in Germany to soldiers buried in Belgium in the early 1700s. "The comprehensive results suggest ancient people spread malaria around the world long before air travel and automobiles," Aldenderfer shared.

At 2800 meters above sea level, the Upper Mustang site lies far outside the habitat range for both the malaria parasite and the Anopheles mosquito. "The region surrounding Chokhopani is cold and quite dry," said co-author Christina Warinner, Associate Professor of Anthropology at Harvard University, who was also part of the study team, said.

For the past 12 years, an international team of scientists, led by Aldenderfer and Warinner, has applied cutting-edge techniques in the Upper Mustang, with the goal of understanding the lives of the first people to settle the High Himalayas more than 3,400 years ago and to reconstruct the trade routes they controlled for nearly three millennia.

"Neither the parasite nor the mosquitoes capable of transmitting malaria can survive at this altitude. For us this raised a key question: how did the Chokhopani individual acquire the malaria infection that may have ultimately led to his death?" Warinner wondered.

Human genetic analysis revealed that the infected individual was a local male with genetic adaptations for life at high altitude. However, archaeological evidence at Chokhopani and other nearby sites suggests that these Himalayan populations were actively engaged in long-distance trade.

"We think of these regions today as remote and inaccessible, but in fact the Kali Gandaki River Valley served as a kind of trans-Himalayan highway connecting people on the Tibetan Plateau with the Indian

Sub-continent," Aldenderfer, whose excavations in the region have revealed its long-distance trade connections, added.

According to Mark, located some 4000 meters above sea level, in the Kali Gandaki river valley of the Upper Mustang region, lies the sky cave of Samdzong. Archeological excavations conducted, between 2010 and 2012, revealed several tombs, among which the tomb 5, which contained human remains and cultural artifacts associated with food and beverage production.

"Copper artifacts recovered from Chokhopani's burial chambers prove that the ancient inhabitants of

Mustang were part of larger exchange networks that included northern India, and you don't have to travel very far to reach the low-lying, poorly drained regions of the Nepalese and Indian Terai where malaria is endemic today," the scientists shared.

According to them, the team believes that the man likely traveled to a lower-altitude malaria- endemic region, possibly for trade or other purposes, before returning or being brought back to Chokhopani, where he was later buried. The intimate details revealed by ancient DNA give clues to the myriad ways that infectious diseases like malaria spread in the past, giving rise to our current disease landscape.

"To explore malaria's enigmatic history, an international team of researchers representing 80 institutions and 21 countries reconstructed ancient Plasmodium genome-wide data from 36 malaria-infected individuals spanning 5,500 years of human history on five continents. These ancient malaria cases provide an unprecedented opportunity to reconstruct the worldwide spread of malaria and its historical impact at global, regional, and even individual scales."