Raphaëlle Klitting

Réunion Island experienced a massive chikungunya virus epidemic in 2024–2025, with >54,000 confirmed cases. This is the second major chikungunya epidemic on the island, following the first one that peaked 20 years ago. It has been asserted that this new outbreak finds its origin in a single introduction event into the island, offering an opportunity to exploit viral genomic data to understand the epidemiological and dispersal dynamics of the introduced transmission chain. We sequenced >3,000 viral genomes collected during the epidemic. Harnessing this genomic dataset, we used several phylogeographic and phylodynamic approaches to unravel the paths taken by the transmission chain and the external factors that might have impacted its dispersal and epidemiological dynamics on the island. Our analyses highlight a dispersal pattern in line with a gravity-model dynamic with viral transition events being more frequent from and toward more populated areas. Our analyses reveal that the transmission chain was overall spatially intermixed, with frequent exchanges among residential areas. In addition, we show that the temporal dynamic and intensity of the epidemic were associated with climatic variables, namely temperature and precipitation. Our results also show that in theory, the population immunity—resulting from this epidemic and the previous one (2005–2006)—could be sufficient to explain on its own the decrease in the transmission rate that led to the end of the epidemic. While a short-term resurgence cannot be excluded, the risk of a large-scale circulation of the virus in the human population appears therefore relatively limited in the upcoming seasons.

Environmental changes are reshaping the distribution and seasonal dynamics of vector-borne diseases, with important implications for public health. Tick-borne encephalitis virus (TBEV) and West Nile virus (WNV) cause growing concern in Europe, with rising case numbers and ever-expanding circulation areas. The transmission risk of TBEV and WNV follows characteristic seasonal patterns, driven largely by weather-dependent activity of their arthropod vectors. The relative roles of climate and land-use change on the seasonal dynamics and spread of these diseases and their vectors remain, however, poorly quantified. Here, we assess the spread and phenology of TBEV and WNV in response to historical and future climate and land-use changes across Europe. We developed spatiotemporal species distribution models (SDMs) for the viruses and their primary vector species, generating monthly environmental suitability predictions from the 1970s to 2050s. Virus models incorporated vector suitability as a nested predictor to capture the dependence of virus occurrence on vector presence. To disentangle drivers of observed changes, we applied counterfactual historical simulations, attributing shifts in seasonal transmission risk to climate or land-use changes. Historical attribution results show that land-use changes mainly affected absolute vector suitability, whereas climatic changes drove shifts in seasonal transmission risk. Transmission risk is projected to rise continent-wide for both TBEV and WNV over the coming decades. Further, TBEV is projected to undergo pronounced phenological shifts, with a dominant spring peak and a delayed autumn peak extending into October. Prolonged seasonal transmission windows are projected to create hotspots that both intensify and expand across large regions. Taken together, our findings underscore the need for coordinated transnational efforts to manage the projected health burden of TBEV and WNV across Europe, and support upstream prevention by providing climate-informed guidance on intervention timing and spatial prioritisation.

In 2024-2025, Réunion Island experienced a large outbreak driven by East-Central-South African (ECSA)-2 lineage of chikungunya virus (CHIKV), leading to the implementation of a vaccination campaign using live-attenuated IXCHIQ (VLA1553). Currently, distinguishing vaccine-derived viremia from wild-type infection relies on genomic sequencing, which is resource-intensive and not routinely available in many diagnostic laboratories. To address this gap, we developed a duplex real-time RT-qPCR assay specifically designed to differentiate VLA1553 from wild-type ECSA strains circulating in La Réunion. The assay targets the non-structural protein 3 hypervariable region, including the 61-amino-acid deletion characteristic of the VLA1553 backbone. Analytical performance was assessed using a panel of CHIKV isolates representing different lineages and a VLA1553-like strain generated using an Infectious Subgenomic Amplicon system. Clinical performance was evaluated using samples from recently vaccinated individuals and patients infected with ECSA-2 strains, and compared with two RT-qPCR assays routinely used by the French National Reference Centers for arboviruses. The duplex assay proved to be specific, detecting wild-type ECSA strains exclusively in the FAM channel and the vaccine strain exclusively in the HEX channel, with no cross-reactivity. It demonstrated high sensitivity, with LOD95 values of 0.9 and 1.1 copies/µL for the vaccine-specific and wild-type-specific targets, respectively. All clinical samples were correctly classified, including one vaccinated individual simultaneously infected with a circulating wild-type strain, as confirmed by sequencing. This duplex assay provides a rapid and reliable method to distinguish vaccine-derived from naturally-acquired CHIKV viremia, supporting more accurate clinical and epidemiological investigations in settings where vaccination and viral circulation overlap.

Atténuation des flavivirus viscérotropes: Avec plus de 20% de morts annuels dus aux maladies infectieuses, celles-ci restent un sujet majeur de santé publique. Des maladies d’origine virale (ré)émergent suite aux changements environnementaux, climatiques et sociétaux : le virus Ebola, la Dengue ou, plus récemment, le virus Zika. Dans ce contexte, il est donc aujourd’hui crucial de développer des vaccins efficaces et sûrs contre les infections virales émergentes. Ce projet de thèse vise à mettre en place une nouvelle stratégie de production de vaccins vivants atténués ciblant les virus à ARN en travaillant sur le virus de la fièvre jaune (genre Flavivirus). Après une analyse génomique qui a permis d’approfondir une technique de modification des virus appelée « ré-encodage », des mutants de la fièvre jaune ont été produits puis caractérisés in vitro et in vivo. En parallèle, un modèle rongeur de la fièvre jaune a été développé et a permis de tester in vivo à la fois l’innocuité et l’efficacité vaccinale des virus ré-encodés.

In 2025, chikungunya virus (CHIKV) re-emerged in Cuba after nine years without reported local transmission, with over 51 000 cases. We identified ten infected travellers returning to France from Cuba. Phylogenetic analysis showed that these viral genomes belong to the ECSA-2 genotype and cluster with recent Latin American sequences. These findings highlight the value of traveller-based genomic surveillance and underscore the risk of CHIKV expansion to other regions.

Background: Yellow fever (YF) is a viral hemorrhagic fever transmitted by Aedes aegypti mosquitoes. Symptoms range from mild fever to severe complications such as jaundice and haemorrhages, which can be fatal. Martinique, a French island in the Caribbean, has remained YF-free since 1908. However, the reintroduction of A. aegypti in the 1970s, the limited scope of mandatory vaccination—currently required only for international travellers to endemic areas—and increased connectivity to YF-endemic regions heighten its vulnerability. To inform local preparedness activities, we assessed the risk of YF emergence, defined as introduction and establishment, by looking at vector competence of local native species of A. aegypti in Martinique. Methods: We developed a framework to evaluate YF emergence risk, integrating multiple contributing factors and taking Martinique as a case study. We used reported cases from 2015 to 2022 to estimate the predicted force of infection in endemic countries and map genotype presence in source countries. In addition, we analyzed flight traffic patterns from 2019 to 2022 and computed genotype-specific transmission efficiency by local mosquito populations. Results: Before 2020, Brazil represented the greatest YF introduction risk due to high passenger volumes. However, the moderate transmissibility of the South America II YF virus strain in Martinique’s mosquito populations partially mitigated this risk. The COVID-19 pandemic disrupted global travel, temporarily shifting the risk landscape towards African countries such as Ivory Coast and Cameroon, where the West African strain exhibits higher transmissibility. However, this risk remained limited by the low number of travellers from these regions. Conclusions: There are growing concerns about the risk of YF introduction and emergence in non-endemic territories like Martinique. Climate change, mosquito adaptability (e.g. egg resistance to desiccation, winter diapause) and intensified global travel drive this risk. This integrative risk assessment framework supports YF emergence prevention and could be applied to other at-risk territories.

This study confirms the continued circulation of Toscana virus (TOSV) lineage B in France, with nine laboratory-confirmed autochthonous neuroinvasive cases identified between 2022 and 2024. All patients presented with central nervous system symptoms, predominantly during summer months, and most were confirmed by RT-qPCR (quantitative reverse transcription polymerase chain reaction) on cerebrospinal fluid. Phylogenetic analysis revealed close similarity to previously circulating French strains, supporting long-term local transmission. One case in eastern France raises concern for possible geographic expansion. These findings underscore the need for sustained surveillance and preventive measures in endemic regions, particularly for travellers and clinicians encountering summer-onset neurological syndromes.

Chikungunya virus re-emerged on Réunion Island in August 2024, 18 years after a first major outbreak. Analysis of 173 genomes from the current epidemic reveals a monophyletic clade with mutations linked to adaptation to Aedes albopictus mosquitoes, including E1-A226V. Bayesian inference suggests only brief cryptic circulation before detection. The same lineage was also detected on Mayotte Island in March 2025. Continued spread and confirmed travel-related cases in mainland France and globally highlight the risk of wider regional and international dissemination.