Syphilis stands as the only major human disease for which strong evidence supports transmission from the Americas to Europe after 1492, and even that case was debated for centuries. The exchange of pathogens between hemispheres was staggeringly lopsided: smallpox, measles, influenza, and typhus devastated Indigenous populations in the Americas, while comparatively little traveled the other way. Recent ancient-DNA research has sharpened the picture considerably, confirming some long-held suspicions about syphilis while overturning assumptions about other diseases like tuberculosis and malaria.
Syphilis and the Strongest Case for a New World Origin
When Columbus’s crew returned to Spain in 1493, a devastating new sexually transmitted disease began tearing through Europe. The first well-documented outbreak struck Naples in 1495 during a French military campaign, and within a few years syphilis had spread across the continent. The timing was suspicious enough that scholars proposed what became known as the “Columbian hypothesis”: the idea that Columbus’s sailors carried the bacterium Treponema pallidum back from the Caribbean.
For centuries, this remained a plausible but unproven theory. A 2024 study in Nature provided what researchers called the strongest molecular support yet. By analyzing ancient genomes from pre-Columbian human remains across the Americas, the team confirmed that deeply derived lineages of all three known T. pallidum subspecies existed in the Americas before 1492, with the most recent common ancestor of all T. pallidum dating to roughly 9,000 years ago.1Nature. Ancient genomes reveal a deep history of Treponema pallidum in the Americas A separate study recovered a 5,500-year-old T. pallidum genome from Colombia’s Sabana de Bogotá, placing the pathogen in the Americas millennia before European contact and before the subspecies causing syphilis, yaws, and bejel had even diverged from one another.2PubMed. A 5500-year-old Treponema pallidum genome from Sabana de Bogotá, Colombia
These genomic findings paint a picture of a pathogen with deep American roots that diversified into its modern forms over thousands of years, consistent with one of those forms crossing the Atlantic with returning European sailors.
Why the Debate Lasted So Long
The Columbian hypothesis had a persistent rival: the idea that syphilis had always been present in Europe but was simply misidentified or confused with leprosy until the late fifteenth century. Over the decades, researchers published more than fifty reports claiming to show treponemal bone lesions in Old World skeletons that predated Columbus. A systematic review of all 54 published cases, however, found that not a single one had both a certain diagnosis of treponemal disease and a securely established pre-Columbian date.3PubMed. The origin and antiquity of syphilis revisited: an appraisal of Old World pre-Columbian evidence for treponemal infection Many relied on nonspecific bone changes that could result from other infections, and many lacked adequate dating methods or photographic documentation.
A handful of cases remain contested. One skeleton from medieval Norwich, England, showed widespread bilateral periostitis of the leg bones, and its burial context was securely dated before 1492. The researchers argued the lesions were consistent with treponemal disease, and differential diagnosis pointed toward syphilis.4International Journal of Osteoarchaeology. Pre‐Columbian treponematosis in medieval Britain Cases like this one keep the debate from being entirely closed, but the weight of the genomic evidence has shifted the consensus heavily toward an American origin. It is worth noting that treponemal diseases include not just venereal syphilis but also yaws, bejel, and pinta, all caused by bacteria so similar they cannot be distinguished under a microscope or by standard blood tests.5PubMed Central. Pinta: Latin America’s Forgotten Disease? Some isolated Old World cases may represent yaws or bejel rather than syphilis, which would be consistent with treponemal bacteria existing on multiple continents while venereal syphilis specifically evolved in the Americas.
The Blame Game and What It Reveals
Syphilis spread so rapidly across Europe that every nation blamed its neighbors. The French called it the “Neapolitan disease.” Italians called it the “French disease.” Russians called it the “Polish disease.” Poles called it the “German disease.” The pattern went on and on. This habit of naming a feared infection after a foreign enemy tells us something about how the disease was experienced: it appeared suddenly, moved fast, and seemed to arrive from elsewhere. The word “syphilis” itself came from a 1530 poem by the Italian physician Girolamo Fracastoro, whose fictional shepherd character Syphilus was cursed with the illness. The literary origin stuck, eventually replacing the nationalistic labels.
This cascade of finger-pointing also reflects a genuine epidemiological mystery at the time. People could see that the disease was new in Europe, which is itself evidence for the Columbian hypothesis. If syphilis had been circulating in Europe for centuries under different names, as the pre-Columbian camp argued, it would be hard to explain why so many contemporaries recorded it as something they had never seen before.
Tuberculosis Was Already on Both Sides, but the Strains Tell a Strange Story
Tuberculosis is sometimes mentioned as a disease that moved between hemispheres during the Columbian exchange, but the reality is more surprising. TB was already present in the pre-Columbian Americas, and its arrival there had nothing to do with humans walking across the Bering land bridge. A landmark 2014 study recovered three 1,000-year-old mycobacterial genomes from Peruvian skeletons and found that the strains did not resemble known human-adapted forms of TB. Instead, they were most closely related to strains found in seals and sea lions, suggesting that marine mammals carried the disease across the ocean and transmitted it to coastal human populations.6PubMed Central. Pre-Columbian mycobacterial genomes reveal seals as a source of New World human tuberculosis
A follow-up study complicated this picture further. Researchers recovered additional ancient seal-lineage TB genomes from individuals buried at inland sites in Peru and Colombia, places where direct contact with seals would have been unlikely. This pointed to secondary human-to-human transmission after the initial animal-to-human jump, meaning the disease had already established itself in inland communities before any European ship arrived.7Nature Communications. Geographically dispersed zoonotic tuberculosis in pre-contact South American human populations
The TB strains that went on to devastate the Americas after contact, however, were European human-adapted lineages. Those were far more virulent in the specific context of Indigenous populations who had no prior exposure. So rather than TB traveling from the New World to the Old, the catastrophic tuberculosis epidemics in the Americas were another instance of Old World pathogens moving west.
Yellow Fever and Malaria Went the Wrong Way
Two of the most feared tropical diseases in the Americas, yellow fever and malaria, are sometimes assumed to be indigenous to the New World. Both assumptions are wrong.
Yellow fever virus originated in Africa. Molecular clock analyses of the virus’s genetic diversity estimated that the West African and South American strains diverged roughly 470 years ago, a timeframe that aligns squarely with the transatlantic slave trade. The genetic diversity of South American yellow fever strains arose within the last three to four centuries, providing strong evidence that the virus was introduced to the Americas from Africa during first contact between the continents.8PLOS Pathogens. Out of Africa: A Molecular Perspective on the Introduction of Yellow Fever Virus into the Americas The mosquito vector Aedes aegypti, which spreads yellow fever in urban settings, also originated in Africa and likely crossed the Atlantic in the water barrels of slave ships.
Malaria tells a similar story. Genomic analysis of a historic European strain of Plasmodium vivax, the parasite responsible for the more common form of malaria, showed it was genetically closest to strains currently circulating in Central and South America. Historical records confirm vivax malaria in Europe as far back as classical Greece. The most straightforward explanation is that European colonists introduced P. vivax to the Americas, not the other way around, with the estimated divergence falling in the fifteenth century.9Molecular Biology and Evolution. Plasmodium vivax Malaria Viewed through the Lens of an Eradicated European Strain Additional genomic modeling supports this European origin while also suggesting some contribution from West African P. vivax populations, consistent with the slave trade introducing a second wave of the parasite.10PLOS Pathogens. Genomic exploration of the journey of Plasmodium vivax in Latin America
Both diseases became so entrenched in the tropical Americas that their African and European origins were obscured for generations. Understanding the actual direction of transmission matters for more than historical accuracy: it shapes how researchers model disease reservoirs and predict where future outbreaks might emerge.
Chagas Disease and the Modern Slow Export
Chagas disease, caused by the parasite Trypanosoma cruzi and spread by blood-sucking triatomine bugs, is unambiguously American in origin. It was not part of the original Columbian exchange because its insect vectors don’t survive Atlantic crossings, and the disease requires prolonged contact with infected bugs or contaminated food. For centuries it remained confined to Latin America.
That has been changing. Migration of T. cruzi-infected people from Latin America to non-endemic countries in Europe, North America, and the western Pacific has created a modern, slow-motion export of Chagas disease.11PubMed Central. The history of Chagas disease In Europe, Spain has been particularly affected because of large-scale Latin American immigration. Chagas can be transmitted through blood transfusions, organ transplants, and from mother to child during pregnancy, which means it can persist in non-endemic countries even without the insect vector. European blood banks have had to develop screening protocols in response. This makes Chagas an example of a New World disease reaching Europe, but through a mechanism entirely unlike the fast-moving epidemic exchange of the 1490s.
Mayaro Virus and Emerging Threats
A less familiar arbovirus called Mayaro virus, endemic to the tropical Americas, has been generating concern because its incidence is increasing.12PubMed Central. A cluster of Mayaro virus infections in a film team returning from Suriname, February 2024 The virus causes fever, joint pain, and rash that can be confused with dengue or chikungunya. Imported cases have appeared in Europe among travelers returning from South America, including a cluster of infections in a film crew returning from Suriname in 2024.
So far, Mayaro has not established local transmission in Europe. But the presence of potentially competent mosquito vectors in southern Europe, combined with increasing global travel, puts it on the watchlist. Much remains unknown about Mayaro’s ecology: the apparent restriction of certain viral genotypes to specific regions of Brazil may reflect genuine biological constraints on dispersal or may simply be a gap in surveillance.13Emerging Infectious Diseases. Evolutionary and Ecological Characterization of Mayaro Virus Strains Isolated during an Outbreak, Venezuela, 2010 Either way, Mayaro represents a category of New World pathogen that could become a European concern if the right ecological conditions align.
Carrión’s Disease and Diseases That Stayed Put
Not every disease native to the Americas made the jump to Europe. Carrión’s disease, caused by the bacterium Bartonella bacilliformis, has been present in the Andean highlands for at least 2,000 years. Skin lesions matching the disease appear on pre-Inca ceramics, and Bartonella-like bacteria have been found in the skin of mummified remains dating back over a millennium.14PLOS Neglected Tropical Diseases. Oroya Fever and Verruga Peruana: Bartonelloses Unique to South America The disease causes two distinct phases: a severe anemia and angiogenic skin lesions. Spanish conquistadors described these lesions in the sixteenth century.
Despite centuries of contact, Carrión’s disease never spread to Europe. The reason is ecological: it depends on a specific sandfly vector, Lutzomyia verrucarum, which thrives only in the arid, high-altitude valleys of the Andes between roughly 600 and 3,200 meters. Humans are the only known reservoir, so without the right vector habitat, the chain of transmission breaks. This illustrates an important point about disease exchange. A pathogen can only cross oceans if its mode of transmission allows it. Syphilis spreads through sexual contact, which needs no insect intermediary. Carrión’s disease is locked to its sandfly, and so it stayed in the Andes.
The Potato Blight and a Different Kind of Pathogen Exchange
Human diseases were not the only pathogens to cross the Atlantic. Phytophthora infestans, the water mold that causes potato late blight, almost certainly originated in the Americas and was carried to Europe on infected plant material. Genetic analysis of the pathogen has traced a plausible migration route: from central Mexico to South America several centuries ago, then from South America to the United States around 1841–1842, and from there to Europe in 1843–1844.15Plant Pathology. The origin of Phytophthora infestans populations present in Europe in the 1840s: a critical review of historical and scientific evidence
Genomic analysis of preserved historic specimens confirmed that the same genetic lineage, called FAM-1, was responsible for both the earliest American outbreaks and the devastating European epidemics of the 1840s, including the Irish Potato Famine.16PLOS ONE. Historic Late Blight Outbreaks Caused by Symmetrical Dominant Lineage of Phytophthora infestans (Mont.) de Bary The famine killed roughly a million people in Ireland and forced another million to emigrate, reshaping the demographics of both Ireland and the United States. While not a human disease in the traditional sense, the potato blight may have caused more European deaths than any human pathogen arriving from the Americas.
Tobacco as a Slow-Motion Health Catastrophe
If you stretch the definition of “disease” to include substances that cause disease, tobacco is by far the most consequential thing the Americas sent to Europe. Indigenous peoples had used tobacco ceremonially and medicinally for thousands of years. European physicians initially embraced it as a botanical medicine, prescribing it for a staggering range of ailments. Over time, skepticism about tobacco as a cure-all evolved into the contemporary understanding that chronic use is devastating to health. Medical opinion eventually arrived at the position that cigarette smoking is the single most important preventable cause of illness, disability, and death.17Journal of Herbal Medicine. The rise and fall of tobacco as a botanical medicine
The transformation took centuries. Tobacco was not recognized as a carcinogen until the mid-twentieth century, and the full scope of its cardiovascular and respiratory damage took even longer to establish. By the time the evidence became overwhelming, tobacco use was deeply embedded in European and global cultures. The death toll from tobacco-related disease over the past five centuries dwarfs the toll from syphilis or any other pathogen that traveled the same route.
How Ancient DNA Reshaped the Whole Conversation
The ability to recover and sequence DNA from centuries-old remains has transformed the study of historical disease exchange. For most of the twentieth century, researchers trying to determine the origins of syphilis, TB, or other infections were limited to interpreting bone lesions, which can look similar across multiple diseases, and parsing incomplete historical records. Ancient DNA changed the game by allowing direct identification of specific pathogen lineages, their divergence dates, and their geographic origins.18PubMed Central. Ancient pathogens provide a window into health and well-being
This is why the syphilis question has progressed so dramatically in recent years. The 2024 Nature study and the Colombian 5,500-year-old genome would have been impossible even two decades ago. Similarly, the discovery that pre-Columbian TB in Peru came from seal-adapted strains, not human-adapted ones, could only be made through genomic comparison. The field is still young. As more ancient remains are sampled from both hemispheres, the picture of which pathogens crossed the Atlantic and when will continue to sharpen. One important lesson from the work so far: many assumptions about disease origins that seemed reasonable based on timing and geography turned out to be wrong once molecular evidence was available. The direction of pathogen flow was not always the direction people assumed.