New Research Reveals Leprosy Existed in the Americas Long Before European Arrival

[Un article de The Conversation écrit par Nicolas Rascovan – Chercheur à l”Institut Pasteur, Université Paris Cité – Charlotte Avanzi – Assistant Professor, Colorado State University – et Maria Lopopolo – Chercheur à l’Institut Pasteur, Université Paris Cité]

Leper is an ancient chronic disease that manifests itself in lesions of the skin, peripheral nerves, the mucous membrane of the upper respiratory tract as well as the eyes. It is present in more than 120 countries and 200,000 cases are notified each year according to the WHO. People affected by leprosy have physical deformities and are also faced with stigma and discrimination. However, leprosy is curable and treatment at an early stage avoids sequelae.

This disease has long been associated with a single bacteria: Mycobacterium lepraeresponsible for the so -called “classic” form of the disease, described in manuals and predominant on a global scale. In 2008, a second species, Mycobacterium lepromatosiswas identified in Mexico. It causes clinically very similar symptoms, so that it often goes unnoticed – only targeted genetic tests make it possible to distinguish it from Mr. Leprae. Although the development of genetic tools has enabled an intensification of research on this bacteria, confirmed human cases remained mainly located in America, especially in Mexico and the Caribbean region. In 2016, the unexpected discovery of Mr. Lepromatosis In red squirrels in the British islands – an animal reservoir in a non -endemic area – raised the question of the geographic origin of this bacteria.

Despite intensive research in former European DNA data, Mr. Lepromatosis has never been detected on the continent. It is in this context that the hypothesis of an American origin has grown. Our project was born from a fortuitous discovery of this species in the published data of an individual from North America dated 1,300 years before the present. This unexpected signal has led us to extend our research, by retracing its presence passed by ancient DNA analyzes, and by documenting its current diversity through modern cases, to better understand the history and circulation of this largely neglected pathogen.

This study is essential to clarify the mechanisms for the transmission of bacteria responsible for leprosy, in particular taking into account the diversity of possible tanks. By reconstructing the evolutionary history and the geographic distribution of Mr. Lepromatosiswe hope to understand how this bacteria is still transmitted today.

We have analyzed nearly 800 samples, including ancient remains of Aboriginal ancestors (covering several millennia, up to 6,000 years back) and modern clinical cases. Our results confirm that Mr. Lepromatosis was already widespread, from north to south of the American continent, long before colonization, and bring a new perspective to the strains circulating today.

This discovery deeply modifies our understanding of the history of leprosy in America. It shows that the disease has already been present among the indigenous populations for centuries before European contact, and that it has evolved locally on the continent.

An essential aspect of this project was collaboration with Aboriginal communities from Canada and Argentina. These were actively involved in decisions concerning the study of ancient human remains, the restitution of materials, as well as the interpretation of the results. An indigenous representative is among the authors of the article. This approach aims to respect the principles of research ethics and strengthen dialogue between community sciences and knowledge.

A continent level survey

We have led the largest screening ever made for this pathogen, by analyzing both ancient human remains and clinical samples from five countries: Mexico, United States, Brazil, Paraguay and French Guyana. Most positive cases have been identified in Mexico and the United States, which probably reflects both a real presence of the pathogen in these regions, but also a more intensive sampling in these countries.

To find traces of pathogens in ancient human remains, we used a paleogenomic approach, a discipline that makes it possible to extract and analyze DNA preserved in the bones or in the teeth for centuries, even millennia. What we recover is a very complex mixture: DNA of the soil, environmental bacteria, of the deceased, and sometimes – if the individual was sick at the time of his death – of the DNA of the pathogen who infected him. Thanks to high -speed sequencing technologies, we read all these DNA fragments (often very short, between 30 and 100 bases), then we compare them to large databases containing the genomes of all the known pathogens.

In this specific case, we have identified in the old samples of small DNA fragments covering about 80 % of the genome of Mycobacterium lepromatosiswhich allowed us to confirm his presence in a pre -Columbian individual. Then, we focused our efforts on this sample to recover more fragments of the pathogen, until we can reconstruct its complete genome. This allowed us not only to confirm the infection, but also to analyze the genetic evolution of the bacteria through time.

Remarkable, the bacteria was found in the bones of three ancient individuals – a woman from current Canada, dated by radiocarbon at around 1,300 years before the present (AP), and a woman and a current Argentina man, dated about 900 years AD. Although separated by more than 10,000 km, their infections date from a relatively close period (almost 1,000 years ago), and their strains are genetically and evolving. This suggests that the bacteria had spread on the continent in just a few centuries. It is still unknown whether this rapid dispersion is due to human networks (trade, contacts) or animals with high mobility.

Our study also makes it possible to better understand an old mystery: the presence of Mycobacterium lepromatosis in red squirrels in the British islands. In 2016, a study conducted by the D^D Charlotte Avanzi, today co-prime author of our work, had revealed for the first time that these animals had the bacteria, but without being able to explain its origin or how she had reached the British Islands.

Thanks to our new phylogenetic analyzes, we show that these animal strains belong to a lineage derived from a common ancestor which would have emerged about 3,200 years ago – well before the first transatlantic contacts -, but that their local diversification only started in the XIX^e century. This strongly suggests a recent introduction from the Americas, followed by expansion in the population of squirrels. This is the first proof that Mr. Lepromatosishistorically endemic to the Americas, has started to spread on other continents – a dynamic opposite to that of Mr. Lepraearrived in America from Europe and Africa with colonization.

These results raise important implications in public health and call to monitor the intercontinental spread of this pathogen.

An ancient evolutionary history still in progress

Among the most striking discoveries of our study is the identification of a very old lineage of Mycobacterium lepromatosiscalled NHDP-LPM-9, which we found in two people in the United States. This lineage is distinguished from all the other strains known by a significantly higher number of mutations, and our analysis suggests that it would have diverged other lineages, more than 9,000 years ago. By way of comparison, the vast majority of modern strains that we have analyzed – 24 out of 26 – belong to a much more homogeneous group, which we have called “current dominant clade” (Present-day dominant cladeor PDDC), which represents about two thirds of the genetic diversity known today. This clade seems to have extended after European colonization, probably in connection with the deep social, ecological and demographic upheavals of the time.

The current co-circulation of two lineages having diverged there are several millennia suggests that other old lines may still exist, but have gone unnoticed so far. Given its very low apparent frequency in recent human cases, it is likely that Mr. Lepromatosis has evolved in part in one or more tanks, from which it could occasionally infect humans. These results underline the importance of better monitoring this pathogen, still very little known, to understand the mechanisms of infection and transmission.

This research not only upsets our understanding of the origin of leprosy, but contributes to a broader question: what infectious diseases existed in America before 1492? For centuries, Aboriginal researchers and communities have been wondering about the role of diseases in the history of the continent. This study brings a new piece to this complex puzzle.