In a groundbreaking study, researchers have unraveled the intricate 5,500-year history of malaria by analyzing ancient DNA, shedding light on how trade, war, and colonization contributed to the global dissemination of this deadly disease.

Imagine studying biology in the early 2000s; two topics that would surely excite any university would be advancements in cancer treatments and malaria eradication. I distinctly remember my microbiology professor entering the classroom, beaming with pride...

One of my PhD students led a project that will help us advance in Malaria prevention!

Years later, I still take pride in my alma mater. However, that semester taught me a crucial lesson: despite significant progress, our understanding of malaria remains limited, and each fact we uncover brings us closer to a world where this disease no longer claims lives.

Malaria, a severe illness caused by parasites transmitted through the bites of infected female Anopheles mosquitoes, has plagued humanity throughout history. Yet, its origins and spread have largely been shrouded in mystery. What are its roots, and how did it evolve into a global threat?

Recent findings published in Nature by an international team led by the Max Planck Institute for Evolutionary Anthropology in Germany offer insights into this puzzle. Prepare for a narrative filled with twists and compelling evidence!

By reconstructing the ancient genomes of Plasmodium falciparum and Plasmodium vivax, the researchers traced the evolutionary journey and global spread of malaria over the last 5,500 years.

To appreciate the significance of this timeline, consider that human civilization was just starting to emerge around 3500 BCE. Here are some historical highlights from that era:

• In Mesopotamia, the Sumerians were establishing some of the earliest cities, such as Uruk, while developing cuneiform writing and advanced agricultural practices.
• Early communities along the Nile in Egypt were laying the groundwork for one of history's greatest civilizations.
• The Indus Valley was witnessing the rise of small farming communities that would later evolve into the sophisticated Harappan Civilization.
• Neolithic cultures like the Yangshao were flourishing in China, renowned for their painted pottery and early agricultural practices.
• Europe was constructing megalithic structures, the predecessors to monumental sites like Stonehenge.
• The Great Pyramid of Giza, a symbol of ancient achievement, would not emerge for another millennium.

As you can see, when civilization flourishes, so too do diseases.

Returning to the study, this pioneering research highlights how trade, warfare, and human movement have shaped the spread of malaria, one of the deadliest diseases globally.

Malaria, a vector-borne disease caused by Plasmodium protozoa transmitted via bites from infected Anopheles mosquitoes, continues to be a significant cause of morbidity and mortality worldwide. The World Health Organization estimates around 250 million infections and over 600,000 deaths annually.

The impact of malaria extends to human evolution. Genetic traits, such as those leading to sickle cell disease, persist in populations due to the partial resistance they confer against malaria.

“Malaria’s legacy is embedded in our genomes; genetic variants responsible for serious blood disorders, like sickle cell disease, are thought to persist as they offer partial resistance to malaria infections,” states lead author Dr. Megan Michel from the Max Planck-Harvard Research Center for the Archaeoscience of the Ancient Mediterranean.

Despite its significant modern-day impact, tracing the origins and historical spread of P. falciparum and P. vivax has proven challenging. Why? Malaria infections leave no clear markers on human remains, and historical references are often scarce and vague, complicating interdisciplinary research efforts.

However, recent advances in ancient DNA analysis have opened new avenues for studying these elusive pathogens. Interestingly, while Jurassic Park popularized ancient DNA science, we are still far from recovering dinosaur DNA from amber.

By examining ancient DNA preserved in human dental remains, researchers can reveal traces of malaria parasites present at the time of death, providing a unique perspective into the past.

To investigate the history of malaria, the research team analyzed genome-wide data from 36 malaria-infected individuals over 5,500 years across five continents. Their findings offer an unparalleled opportunity to reconstruct the global spread of malaria and its historical ramifications.

One particularly intriguing discovery involved P. falciparum found at a high-altitude archaeological site in Chokhopani, Nepal, dating back to around 800 BCE. This site, located at 2,800 meters above sea level, lies beyond the typical habitat for both the malaria parasite and the Anopheles mosquito. How did that DNA arrive there?

“The environment around Chokhopani is cold and arid,” explains co-author Dr. Christina Warinner, an associate professor of anthropology at Harvard University. “Neither the malaria parasite nor the mosquitoes capable of transmitting it can survive at this altitude. This raised an essential question: how did the Chokhopani individual contract the malaria infection that may have led to his demise?”

The plot thickens. Genetic analysis revealed that the infected individual was a local male with adaptations for high-altitude living. Archaeological evidence suggests these Himalayan populations were engaged in long-distance trade. Copper artifacts found in Chokhopani’s burial sites indicate connections with northern India, where malaria is endemic.

What did the researchers conclude? They hypothesize that the man likely contracted malaria while traveling to a lower-altitude area before returning to Chokhopani. This indeed makes us detectives of history!

The study also unveils significant insights regarding malaria's spread in Europe and the Americas.

In Europe, the researchers investigated remains from St. Rombout’s cemetery in Mechelen, Belgium, near the first permanent military hospital in early modern Europe. They discovered local cases of P. vivax among the general populace prior to the hospital’s establishment, and cases of the more virulent P. falciparum among non-local male individuals during the hospital's operational period. These men were likely soldiers from Mediterranean regions enlisted in the Hapsburg Army of Flanders.

“Large-scale troop movements significantly contributed to the spread of malaria during this time, akin to modern cases of so-called airport malaria in temperate Europe,” explains Dr. Alexander Herbig, group leader of computational pathogenomics at the MPI-EVA.

In the Americas, genomic analysis of a malaria-infected individual from Laguna de los Cóndores in Peru suggests that P. vivax was introduced by European colonizers shortly after contact. This strain exhibited genetic links to contemporary Peruvian P. vivax populations, indicating a long-term establishment and continued transmission. Malaria, once introduced, has remained prevalent in the region.

“Amplified by warfare, enslavement, and population displacement, infectious diseases, including malaria, wreaked havoc on Indigenous populations of the Americas during the colonial era,” states co-author Dr. Evelyn Guevara, a postdoctoral researcher at the University of Helsinki and the MPI-EVA.

What are the implications of this study for contemporary populations and their health?

The research underscores the role of human mobility, trade, and colonization in the historical spread of malaria. Without these factors, malaria might have remained localized, highlighting our knowledge and technological progress. It also draws parallels between ancient and modern malaria transmission, as globalization and environmental changes present new challenges for malaria control today. Climate change, unfortunately, rears its head again.

“For the first time, we can investigate the ancient diversity of parasites from regions like Europe, where malaria has now been eradicated,” says senior author Dr. Johannes Krause, director of archaeogenetics at the Max Planck Institute for Evolutionary Anthropology. “We aspire to study ancient diseases like malaria to gain a better understanding of these organisms that continue to shape our world.”

This research paves the way for a deeper understanding of malaria's historical and ongoing effects, providing valuable insights that could shape future public health strategies. Ultimately, looking into the past could yield answers for addressing future challenges. In the fight against malaria, every piece of information might save lives down the line.

Published in Fossils et al. Follow to learn more about Paleontology.