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Philippe Lemey

Publications and source records attributed to Philippe Lemey.

8 recordsLinked to original sources

Unraveling the epidemiological and dispersal dynamics of the 2024-2025 chikungunya virus epidemic on Réunion Island.

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.

Reunion

Nosocomial Outbreak of Lassa Fever in Conakry, Guinea, 2022.

BACKGROUND: Lassa fever is endemic in Guinea, with high seroprevalence in the forest region. However, clinical cases have been only anecdotally reported. In August 2022, a nosocomial outbreak occurred at a private clinic in the capital, Conakry, an area previously considered low risk. METHODS: Suspected cases were confirmed by real-time reverse-transcription polymerase chain reaction within 24 hours. Viremia was monitored during hospitalization, and whole-genome sequencing was performed in-country within 13 days of outbreak detection. Outbreak investigation involved rodent testing in the home village of the suspected primary case. RESULTS: Six cases were laboratory-confirmed, 5 of which were healthcare workers of the clinic. The case fatality rate was 16.7%. Viral RNA remained detectable in blood of survivors for a median of 26 days (interquartile range, 24-41 days) post-disease onset. Epidemiological investigations identified a suspected primary case, who had died of a febrile disease compatible with Lassa fever, had contact with all secondary cases, and had a travel history from Kissidougou area. Three near-complete and 1 partial Lassa virus genomes were recovered from the secondary cases, which phylogenetically clustered with genomes from central Guinea. Consistent with a common transmission source, the 4 genomes were almost identical. Rodent testing revealed a new reservoir area in eastern-central Guinea. CONCLUSIONS: This outbreak highlights the vulnerability of healthcare settings in low-prevalence areas of West Africa to nosocomial Lassa virus transmission due to human mobility. Facilitated by capacity-building programs for viral hemorrhagic fevers, rapid diagnosis, genomic analysis, and ecological assessment enabled an efficient outbreak response and control.

Lassa Fever

Three thousand five hundred years of sheeppox virus evolution inferred from archaeological and codicological genomes.

Sheeppox virus (SPPV) is a major livestock pathogen causing economic hardship through reduced production and death of vulnerable sheep, with written descriptions of sheeppox-like disease recorded since antiquity. We report 21 novel ancient SPPV genomes spanning the Eurasian steppe Bronze Age (∼1700 BCE) to the Early Modern period in Western Europe, including multiple genomes obtained from medieval parchment. We estimate that major capripoxvirus lineages diverged ∼11,500 to 3700 years ago, overlapping known translocations and bio-cultural developments in sheep. Our dataset supports SPPV diverging first within the lineage leading to goatpox virus and lumpy skin disease virus, and that known gene inactivation events within SPPV and goatpox virus occur in our earliest SPPV genomes. These findings reveal that the food security of Eurasian communities has been threatened by sheeppox for more than 3700 years and provide insights into the genomic evolution and potential host adaptation of SPPV.

Animals

Genomic surveillance of a deeply sampled local population reveals age-specific drivers of RSV transmission.

Respiratory syncytial virus (RSV) disproportionately causes severe infections among infants and older adults, yet the key age group responsible for viral spread to other age groups remains poorly defined. While current immunization approaches effectively reduce disease severity among the most vulnerable, identifying the core drivers of infection is essential to effectively disrupt population-level transmission. By generating 910 whole-genome viral sequences of RSV from all age groups (<1 to 65+ years) in Connecticut, we identified that children aged 12-35 months are the primary drivers of viral transmission to other age groups. This group significantly shapes the genetic diversity of circulating strains. Furthermore, we found that RSV is introduced into the community through frequent and independent entries from other US regions throughout the year, rather than through a single explosive seasonal introduction or long-term local persistence. Ultimately, our findings justify prevention strategies that expand beyond reducing disease burden to actively prioritizing the reduction of transmission and infection.

Journal Article

Evolutionary history of Jamestown Canyon virus reveals complex multi-vector ecology.

Jamestown Canyon virus (JCV) is a historically understudied mosquito-borne virus of increasing concern in North America. We generated 658 whole-genome JCV sequences from northeast United States, including 84% (500/597) of all JCV-positive mosquitoes detected in Connecticut from 1997 to 2022. Then, we applied phylodynamic methods to demonstrate how mosquito phenology structures the maintenance and evolution of JCV. Our phylogenetic analyses estimate that JCV was introduced in the Northeast by at least the early 1700s, and the primary introductions of lineages A and B into Connecticut occurred during the mid-1800s to mid-1900s. Further, we estimate that JCV evolves at a rate of &#x223c;3 &#xd7; 10-5 substitutions per site per year (s/s/y), making it one of the slowest-evolving known RNA viruses, because the virus spends &#x223c;10 months per year in evolutionary stasis while overwintering in mosquito eggs. To investigate ecological drivers of JCV spread in Connecticut, we paired discrete trait and continuous phylogeographic reconstructions with mosquito surveillance data. We estimate that JCV has a low diffusion rate of &#x223c;30-60 km2/year, which is more similar to slow-moving tick-borne viruses than to other mosquito-borne viruses. We found that univoltine Aedes mosquitoes were likely to maintain the virus across years through overwintering in eggs, accounting for its slow evolution and dispersal, while multivoltine mosquitoes contributed to periodic bursts of spatial diffusion and amplification within seasons. We demonstrate the utility of dense sequencing and phylodynamics to disentangle complex transmission cycles, offering a framework for rapidly advancing our evolutionary and ecological knowledge of understudied viruses.

Animals

Parallel algorithms for phylogenetic inference under a structured coalescent approximation.

While advances in molecular epidemiology and computational modeling have enhanced our capacity to track pathogen evolution, the accurate reconstruction of spatiotemporal transmission dynamics remains essential for developing epidemic preparedness frameworks and implementing outbreak response measures. Structured coalescent models offer a phylogeographic framework by restricting lineage coalescence events to geographically proximate host populations. Although the Bayesian structured coalescent approximation (BASTA) provides a tractable approach, contemporary phylogeographic analyses involving dozens of geographic localities and hundreds to thousands of viral genomes substantially exceed the computational capacity of existing implementations. The BASTA likelihood scales cubically with deme count and quadratically with sequence count due to matrix exponentiation and pairwise coalescent probability calculations. Here, we introduce a comprehensive algorithmic restructuring of the structured coalescent likelihood that eliminates redundancies, optimizes memory access, and exposes parallelization opportunities. Our approach reorganizes computations along three dimensions: (i) independent calculation of deme-transition probability matrices across time intervals; (ii) simultaneous evaluation of partial likelihood vectors within temporal slices; and (iii) concurrent aggregation of coalescent probabilities. Algorithmic restructuring cuts average coalescent likelihood computation by 7-8 fold, and parallelization further boosts performance to 10-26 fold, enabling joint phylogeographic analyses of dengue virus across 10 South American countries and H5N1 avian influenza across 20 Eurasian regions to finish in a fraction of prior time. This computational efficiency also enables comparison between backward-in-time structured coalescent approximations and forward-in-time phylogeographic methods, revealing that the former provides appropriately conservative posterior estimates, particularly at intermediate phylogenetic depths. We integrate our implementation into the popular BEAST X and BEAGLE software packages, with an accompanying interface in BEAUti X to easily set up the analyses, providing researchers with an accessible and scalable tool for real-time phylogeographic surveillance of rapidly evolving pathogens.

Journal Article

Genomic epidemiology of clade Ia monkeypox viruses circulating in the Central African Republic in 2022-24: a retrospective cross-sectional study.

BACKGROUND: The spread of monkeypox virus (Orthopoxvirus monkeypox) clade Ib from the Democratic Republic of the Congo to neighbouring countries has raised global concerns, leading to WHO declaring mpox a public health emergency on Aug 14, 2024. We applied genomic epidemiology to investigate the causes of recurrent mpox outbreaks in the Central African Republic. We aimed to determine whether frequent zoonotic spillovers or increased human-to-human transmissions are driving mpox epidemiology. METHODS: We performed a retrospective cross-sectional study of monkeypox virus genomic sequences among PCR-confirmed mpox cases detected in the Central African Republic between Feb 17, 2022, and Sept 17, 2024. We used hybridisation capture coupled to high throughput sequencing to analyse 46 samples from mpox outbreaks that occurred in eight of the 20 prefectures (14 of 35 health districts). Near-complete genomes were used for phylogenomic analyses. FINDINGS: Between Jan 10, 2022, and Sept 15, 2024, 89 mpox cases were confirmed, including 53 cases in the first 9 months of 2024. We generated 41 near-complete genomes from this period, including 33 from 2024. All new and already published monkeypox virus genomes from the Central African Republic belonged to clade Ia. These genomes spanned the phylogenetic diversity of clade Ia viruses, and most likely represented several dozen independent transmission events to humans. The monkeypox virus phylogenetic diversity was geographically structured within the country. Plausibly linked cases often showed indistinguishable genomes. Conversely, we detected identical genomes in cases that epidemiological information would suggest were independent outbreaks. Finally, we found that three distinct viruses caused cases in the capital city of Bangui in July, 2024, with all three detected on the same day (July 24, 2024). We did not detect substantial enrichment of APOBEC3 editing, suggesting limited human-to-human transmission. INTERPRETATION: The data indicate that mpox epidemiology in the Central African Republic is primarily driven by short-lived outbreaks resulting from many independent zoonotic spillover events, particularly in rural areas. Although evidence remains limited, in Bangui additional factors such as movement of people and importation of bushmeat from other regions might be introducing the virus into urban settings. Similar spillover patterns have been observed in the Democratic Republic of the Congo. The poorly understood nature of monkeypox virus reservoirs in both countries is a regional concern, as frequent spillovers increase the risk of outbreaks leading to sustained human transmission. Beyond strengthening surveillance and developing countermeasures, it is important to better understand the reservoirs and focus on reducing transmission opportunities to prevent further outbreaks. FUNDING: Pasteur Institute of Bangui, Africa CDC, AFROSCREEN, WHO, the Helmholtz Institute for One Health, and the Deutsche Forschungsgemeinschaft.

Humans

Grains, trade and war in the multimodal transmission of Rice yellow mottle virus: An historical and phylogeographical retrospective.

Rice yellow mottle virus (RYMV) is a major pathogen of rice in Africa. RYMV has a narrow host range limited to rice and a few related poaceae species. We explore the links between the spread of RYMV in East Africa and rice history since the second half of the 19th century. The phylogeography of RYMV in East Africa was reconstructed from coat protein gene sequences (ORF4) of 335 isolates sampled over two million square kilometers between 1966 and 2020. Dispersal patterns obtained from ORF2a and ORF2b, and full-length sequences converged to the same scenario. The following imprints of rice cultivation on RYMV epidemiology were unveiled. RYMV emerged in the middle of the 19th century in the Eastern Arc Mountains where slash-and-burn rice cultivation was practiced. Several spillovers from wild hosts to cultivated rice occurred. RYMV was then rapidly introduced into the nearby large rice growing Kilombero valley and Morogoro region. Harvested seeds are contaminated by debris of virus infected plants that subsist after threshing and winnowing. Long-distance dispersal of RYMV is consistent (i) with rice introduction along the caravan routes from the Indian Ocean Coast to Lake Victoria in the second half of the 19th century, (ii) seed movement from East Africa to West Africa at the end of the 19th century, from Lake Victoria to the north of Ethiopia in the second half of the 20th century and to Madagascar at the end of the 20th century, (iii) and, unexpectedly, with rice transport at the end of the First World War as a troop staple food from the Kilombero valley towards the South of Lake Malawi. Overall, RYMV dispersal was associated to a broad range of human activities, some unsuspected. Consequently, RYMV has a wide dispersal capacity. Its dispersal metrics estimated from phylogeographic reconstructions are similar to those of highly mobile zoonotic viruses.

Oryza