Arthur Kocher

Selon l'hypothèse de l'effet de dilution, les écosystèmes les plus riches en espèces seraient également les moins propices à la circulation des agents infectieux du fait de la présence d'hôtes non compétents constituant des impasses épidémiologiques. Dans cette thèse, nous explorons l'existence de ce phénomène sur le modèle des leishmanioses cutanées zoonotiques en Guyane. Des outils moléculaires basés sur l'utilisation des technologies de séquençage haut-débit ont été développés pour étudier le système épidémiologique. Ces outils ont ensuite été employés pour caractériser le cycle de transmission des leishmanioses dans des sites forestiers sujets à différents niveaux de perturbation d'origine humaine. Nos résultats semblent globalement congruents avec l'hypothèse de l'effet de dilution, et indiquent un risque infectieux plus élevé sur le site le plus perturbé. Toutefois, les différences observées entre les sites ne sont pas significatives et d'avantage de données seraient nécessaires pour tirer des conclusions générales.

Major advances in metagenomic and biomolecular techniques have opened avenues for the recovery and sequencing of rare and highly fragmented DNA molecules from ancient biological samples, including those of pathogens that may persist in the remains of infected hosts long after their death. Initially consisting of relatively rare findings for a few disease-causing agents of historical importance, the field of ancient pathogen genomics is rapidly progressing towards genome-level analyses of larger sample sets encompassing a wider range of bacterial, viral and eukaryotic taxa. These advances have provided important insights into past pathogen distribution and genomic make-up, and the unprecedented opportunity to track their evolution ‘in action’ over large timescales. In this Review, we explore the major contributions of ancient DNA research to the understanding of pathogen evolution and its association with past epidemics, as well as human sociocultural and migration history, including numerous important studies that have been published in recent years. Moreover, we discuss existing limitations and future prospects of ancient pathogen genomics and the relevance of the field to current public health challenges.

The preservation of ancient DNA in archaeological remains enables identification of past disease agents. However, pathogen DNA is typically highly diluted by host and environmental DNA, limiting detection. Here, we present a proof-of-concept study using in-solution hybridization capture to improve detectability of a pre-defined set of 12 pathogens. We validate the method by detecting Yersinia pestis , the plague agent, in six individuals from 17 ^th and 18 ^th century French plague cemeteries with minimal sequencing. Expanding our probe set to target biomarkers of virtually any pathogen of interest offers a powerful tool for tracking the prevalence of infectious diseases in ancient populations.

The origin of the medieval Black Death pandemic (ad 1346–1353) has been a topic of continuous investigation because of the pandemic’s extensive demographic impact and long-lasting consequences^1,2. Until now, the most debated archaeological evidence potentially associated with the pandemic’s initiation derives from cemeteries located near Lake Issyk-Kul of modern-day Kyrgyzstan^1,3–9. These sites are thought to have housed victims of a fourteenth-century epidemic as tombstone inscriptions directly dated to 1338–1339 state ‘pestilence’ as the cause of death for the buried individuals⁹. Here we report ancient DNA data from seven individuals exhumed from two of these cemeteries, Kara-Djigach and Burana. Our synthesis of archaeological, historical and ancient genomic data shows a clear involvement of the plague bacterium Yersinia pestis in this epidemic event. Two reconstructed ancient Y. pestis genomes represent a single strain and are identified as the most recent common ancestor of a major diversification commonly associated with the pandemic’s emergence, here dated to the first half of the fourteenth century. Comparisons with present-day diversity from Y. pestis reservoirs in the extended Tian Shan region support a local emergence of the recovered ancient strain. Through multiple lines of evidence, our data support an early fourteenth-century source of the second plague pandemic in central Eurasia.

Changes in biodiversity may impact infectious disease transmission through multiple mechanisms. We explored the impact of biodiversity changes on the transmission of Amazonian leishmaniases, a group of wild zoonoses transmitted by phlebotomine sand flies (Psychodidae), which represent an important health burden in a region where biodiversity is both rich and threatened. Using molecular analyses of sand fly pools and blood‐fed dipterans, we characterized the disease system in forest sites in French Guiana undergoing different levels of human‐induced disturbance. We show that the prevalence of Leishmania parasites in sand flies correlates positively with the relative abundance of mammal species known as Leishmania reservoirs. In addition, Leishmania reservoirs tend to dominate in less diverse mammal communities, in accordance with the dilution effect hypothesis. This results in a negative relationship between Leishmania prevalence and mammal diversity. On the other hand, higher mammal diversity is associated with higher sand fly density, possibly because more diverse mammal communities harbor higher biomass and more abundant feeding resources for sand flies, although more research is needed to identify the factors that shape sand fly communities. As a consequence of these antagonistic effects, decreased mammal diversity comes with an increase of parasite prevalence in sand flies, but has no detectable impact on the density of infected sand flies. These results represent additional evidence that biodiversity changes may simultaneously dilute and amplify vector‐borne disease transmission through different mechanisms that need to be better understood before drawing generalities on the biodiversity‐disease relationship.

Ancient DNA traces the history of hepatitis B: Hepatitis B virus (HBV) infections represent a worldwide human health concern. To study the history of this pathogen, Kocher et al . identified 137 human remains with detectable levels of virus dating between 400 and 10,000 years ago. Sequencing and analyses of these ancient viruses suggested a common ancestor between 12,000 and 20,000 years ago. There is no evidence indicating that HBV was present in the earliest humans as they spread out of Africa; however, HBV was likely present in human populations before farming. Furthermore, the virus was present in the Americas by about 9000 years ago, representing a lineage sister to the viral strains found in Eurasia that diverged about 20,000 years ago. —LMZ

Surra, caused by Trypanosoma evansi, is a widely distributed animal trypanosomosis; it affects both domestic and wild mammals with high economic impact. Clinical picture is moderate in bovines but severe in equids. Surra is also an important constraint for international animal trade and movements. Despite its impact, surra remains poorly diagnosed because of low sensitivity tests. To improve epidemiological knowledge of the disease and to secure international movement, efficient diagnosis tools are required. Here, we optimized and applied to equids the OIE-recommended indirect ELISA T. evansi that was validated in other species. Based on 96 positive and 1,382 negative horse reference samples from Thailand, a TG-ROC analysis was conducted to define the cutoff value. ELISA’s sensitivity and specificity were estimated at 97.5% and 100%, respectively, qualifying the test to provide a reliable immune status of equids. The test was then applied on 1,961 horse samples from 18 Thai Provinces; the only scarce positives suggested that horses do not constitute a reservoir of T. evansi in Thailand. All samples from racing horses were negative. Conversely, two outbreaks of surra reported to our laboratory, originating from a bovine reservoir, exhibited high morbidity and lethality rates in horses. Finally, posttreatment follow-ups of infected animals allowed us to provide outbreak management guidelines.