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Article ; Online: The genetic diversity of Nipah virus across spatial scales.

Cortes-Azuero, Oscar / Lefrancq, Noémie / Nikolay, Birgit / McKee, Clifton / Cappelle, Julien / Hul, Vibol / Ou, Tey Putita / Hoem, Thavry / Lemey, Philippe / Rahman, Mohammed Ziaur / Islam, Ausraful / Gurley, Emily S / Duong, Veasna / Salje, Henrik

The Journal of infectious diseases

2024

Abstract: Background: Nipah virus (NiV), a highly lethal virus in humans, circulates in Pteropus bats throughout South and Southeast Asia. Difficulty in obtaining viral genomes from bats means we have a poor understanding of NiV diversity.: Methods: We develop ...

Abstract	Background: Nipah virus (NiV), a highly lethal virus in humans, circulates in Pteropus bats throughout South and Southeast Asia. Difficulty in obtaining viral genomes from bats means we have a poor understanding of NiV diversity. Methods: We develop phylogenetic approaches applied to the most comprehensive collection of genomes to date (N=257, 175 from bats, 73 from humans) from six countries over 22 years (1999-2020). We divide the four major NiV sublineages into 15 genetic clusters. Using Approximate Bayesian Computation fit to a spatial signature of viral diversity, we estimate the presence and the average size of genetic clusters per area. Results: We find that, within any bat roost, there are an average of 2.4 co-circulating genetic clusters, rising to 5.5 clusters at areas of 1500-2000km2. We estimate that each genetic cluster occupies an average area of 1.3million km2 (95%CI: 0.6-2.3 million), with 14 clusters in an area of 100,000km2 (95%CI: 6-24). In the few sites in Bangladesh and Cambodia where genomic surveillance has been concentrated, we estimate that most clusters have been identified, but only ∼15% of overall NiV diversity has been uncovered. Conclusion: Our findings are consistent with entrenched co-circulation of distinct lineages, even within roosts, coupled with slow migration over larger spatial scales.
Language	English
Publishing date	2024-04-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jiae221
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Article: Geographic migration and vaccine-induced fitness changes of

Belman, Sophie / Lefrancq, Noémie / Nzenze, Susan / Downs, Sarah / du Plessis, Mignon / Lo, Stephanie / McGee, Lesley / Madhi, Shabir A / von Gottberg, Anne / Bentley, Stephen D / Salje, Henrik

bioRxiv : the preprint server for biology

2023

Abstract: Streptococcus ... ...

Abstract	Streptococcus pneumoniae
Language	English
Publishing date	2023-01-18
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.01.18.524577
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Article: The genetic diversity of Nipah virus across spatial scales.

Azuero, Oscar Cortés / Lefrancq, Noémie / Nikolay, Birgit / McKee, Clifton / Cappelle, Julien / Hul, Vibol / Ou, Tey Putita / Hoem, Thavry / Lemey, Philippe / Rahman, Mohammed Ziaur / Islam, Ausraful / Gurley, Emily S / Duong, Veasna / Salje, Henrik

medRxiv : the preprint server for health sciences

2023

Abstract: Nipah virus (NiV), a highly lethal virus in humans, circulates silently ... ...

Abstract	Nipah virus (NiV), a highly lethal virus in humans, circulates silently in
Language	English
Publishing date	2023-10-04
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.07.14.23292668
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Article ; Online: Antigenic distance between primary and secondary dengue infections correlates with disease risk.

Wang, Lin / Huang, Angkana T / Katzelnick, Leah C / Lefrancq, Noémie / Escoto, Ana Coello / Duret, Loréna / Chowdhury, Nayeem / Jarman, Richard / Conte, Matthew A / Berry, Irina Maljkovic / Fernandez, Stefan / Klungthong, Chonticha / Thaisomboonsuk, Butsaya / Suntarattiwong, Piyarat / Vandepitte, Warunee / Whitehead, Stephen S / Cauchemez, Simon / Cummings, Derek A T / Salje, Henrik

Science translational medicine

2024 Volume 16, Issue 744, Page(s) eadk3259

Abstract: Many pathogens continuously change their protein structure in response to immune-driven selection, resulting in weakened protection even in previously exposed individuals. In addition, for some pathogens, such as dengue virus, poorly targeted immunity is ...

Abstract	Many pathogens continuously change their protein structure in response to immune-driven selection, resulting in weakened protection even in previously exposed individuals. In addition, for some pathogens, such as dengue virus, poorly targeted immunity is associated with increased risk of severe disease through a mechanism known as antibody-dependent enhancement. However, it remains unclear whether the antigenic distances between an individual's first infection and subsequent exposures dictate disease risk, explaining the observed large-scale differences in dengue hospitalizations across years. Here, we develop a framework that combines detailed antigenic and genetic characterization of viruses with details on hospitalized cases from 21 years of dengue surveillance in Bangkok, Thailand, to identify the role of the antigenic profile of circulating viruses in determining disease risk. We found that the risk of hospitalization depended on both the specific order of infecting serotypes and the antigenic distance between an individual's primary and secondary infections, with risk maximized at intermediate antigenic distances. These findings suggest that immune imprinting helps determine dengue disease risk and provide a pathway to monitor the changing risk profile of populations and to quantifying risk profiles of candidate vaccines.
MeSH term(s)	Humans ; Dengue/immunology ; Dengue/epidemiology ; Dengue/virology ; Dengue Virus/immunology ; Antigens, Viral/immunology ; Thailand/epidemiology ; Risk Factors ; Hospitalization
Chemical Substances	Antigens, Viral
Language	English
Publishing date	2024-04-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2518854-9
ISSN	1946-6242 ; 1946-6234
ISSN (online)	1946-6242
ISSN	1946-6234
DOI	10.1126/scitranslmed.adk3259
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Article: Antigenic diversity and dengue disease risk.

Wang, Lin / Huang, Angkana T / Katzelnick, Leah C / Lefrancq, Noémie / Escoto, Ana Coello / Duret, Loréna / Chowdhury, Nayeem / Jarman, Richard / Conte, Matthew A / Berry, Irina Maljkovic / Fernandez, Stefan / Klungthong, Chonticha / Thaisomboonsuk, Butsaya / Suntarattiwong, Piyarat / Vandepitte, Warunee / Whitehead, Stephen / Cauchemez, Simon / Cummings, Derek A T / Salje, Henrik

Research square

2023

Abstract: Many pathogens continuously change their protein structure in response to immune-driven selection, resulting in weakened protection. In addition, for some pathogens such as dengue virus, poorly targeted immunity is associated with increased risk of ... ...

Abstract	Many pathogens continuously change their protein structure in response to immune-driven selection, resulting in weakened protection. In addition, for some pathogens such as dengue virus, poorly targeted immunity is associated with increased risk of severe disease, through a mechanism known as antibody-dependent enhancement. However, it remains a mystery whether the antigenic distance between an individual's first infection and subsequent exposures dictate disease risk, explaining the observed large-scale differences in dengue hospitalisations across years. Here we develop an inferential framework that combines detailed antigenic and genetic characterisation of viruses, and hospitalised cases from 21 years of surveillance in Bangkok, Thailand to identify the role of the antigenic profile of circulating viruses in determining disease risk. We find that the risk of hospitalisation depends on both the specific order of infecting serotypes and the antigenic distance between an individual's primary and secondary infections, with risk maximised at intermediate antigenic distances. These findings suggest immune imprinting helps determine dengue disease risk, and provides a pathway to monitor the changing risk profile of populations and to quantifying risk profiles of candidate vaccines.
Language	English
Publishing date	2023-08-02
Publishing country	United States
Document type	Preprint
DOI	10.21203/rs.3.rs-3214507/v1
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Article ; Online: Evolution of outcomes for patients hospitalised during the first 9 months of the SARS-CoV-2 pandemic in France: A retrospective national surveillance data analysis.

Lefrancq, Noémie / Paireau, Juliette / Hozé, Nathanaël / Courtejoie, Noémie / Yazdanpanah, Yazdan / Bouadma, Lila / Boëlle, Pierre-Yves / Chereau, Fanny / Salje, Henrik / Cauchemez, Simon

The Lancet regional health. Europe

2021 Volume 5, Page(s) 100087

Abstract: Background: As SARS-CoV-2 continues to spread, a thorough characterisation of healthcare needs and patient outcomes, and how they have changed over time, is essential to inform planning.: Methods: We developed a probabilistic framework to analyse ... ...

Abstract	Background: As SARS-CoV-2 continues to spread, a thorough characterisation of healthcare needs and patient outcomes, and how they have changed over time, is essential to inform planning. Methods: We developed a probabilistic framework to analyse detailed patient trajectories from 198,846 hospitalisations in France during the first nine months of the pandemic. Our model accounts for the varying age- and sex- distribution of patients, and explore changes in outcome probabilities as well as length of stay. Findings: We found that there were marked changes in the age and sex of hospitalisations over the study period. In particular, the proportion of hospitalised individuals that were >80y varied between 27% and 48% over the course of the epidemic, and was lowest during the inter-peak period. The probability of hospitalised patients entering ICU dropped from 0·25 (0·24-0·26) to 0·13 (0·12-0·14) over the four first months as case numbers fell, before rising to 0·19 (0·19-0·20) during the second wave. The probability of death followed a similar trajectory, falling from 0·25 (0·24-0·26) to 0·10 (0·09-0·11) after the first wave before increasing again during the second wave to 0·19 (0·18-0·19). Overall, we find both the probability of death and the probability of entering ICU were significantly correlated with COVID-19 ICU occupancy. Interpretation: There are large scale trends in patients outcomes by age, sex and over time. These need to be considered in ongoing healthcare planning efforts. Funding: INCEPTION.
Language	English
Publishing date	2021-03-21
Publishing country	England
Document type	Journal Article
ISSN	2666-7762
ISSN (online)	2666-7762
DOI	10.1016/j.lanepe.2021.100087
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Article ; Online: Evaluating the impact of curfews and other measures on SARS-CoV-2 transmission in French Guiana.

Andronico, Alessio / Tran Kiem, Cécile / Paireau, Juliette / Succo, Tiphanie / Bosetti, Paolo / Lefrancq, Noémie / Nacher, Mathieu / Djossou, Félix / Sanna, Alice / Flamand, Claude / Salje, Henrik / Rousseau, Cyril / Cauchemez, Simon

Nature communications

2021 Volume 12, Issue 1, Page(s) 1634

Abstract: While general lockdowns have proven effective to control SARS-CoV-2 epidemics, they come with enormous costs for society. It is therefore essential to identify control strategies with lower social and economic impact. Here, we report and evaluate the ... ...

Abstract	While general lockdowns have proven effective to control SARS-CoV-2 epidemics, they come with enormous costs for society. It is therefore essential to identify control strategies with lower social and economic impact. Here, we report and evaluate the control strategy implemented during a large SARS-CoV-2 epidemic in June-July 2020 in French Guiana that relied on curfews, targeted lockdowns, and other measures. We find that the combination of these interventions coincided with a reduction in the basic reproduction number of SARS-CoV-2 from 1.7 to 1.1, which was sufficient to avoid hospital saturation. We estimate that thanks to the young demographics, the risk of hospitalisation following infection was 0.3 times that of metropolitan France and that about 20% of the population was infected by July. Our model projections are consistent with a recent seroprevalence study. The study showcases how mathematical modelling can be used to support healthcare planning in a context of high uncertainty.
MeSH term(s)	Adolescent ; Adult ; Aged ; Aged, 80 and over ; Basic Reproduction Number/prevention & control ; Basic Reproduction Number/statistics & numerical data ; COVID-19/epidemiology ; COVID-19/prevention & control ; COVID-19/transmission ; Child ; Child, Preschool ; Female ; French Guiana/epidemiology ; Hospitalization/statistics & numerical data ; Hospitalization/trends ; Humans ; Infant ; Infant, Newborn ; Male ; Middle Aged ; Models, Statistical ; Pandemics/prevention & control ; Pandemics/statistics & numerical data ; Quarantine/methods ; Quarantine/statistics & numerical data ; Quarantine/trends ; SARS-CoV-2 ; Young Adult
Language	English
Publishing date	2021-03-12
Publishing country	England
Document type	Evaluation Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-021-21944-4
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Article ; Online: SARS-CoV-2 transmission across age groups in France and implications for control.

Tran Kiem, Cécile / Bosetti, Paolo / Paireau, Juliette / Crépey, Pascal / Salje, Henrik / Lefrancq, Noémie / Fontanet, Arnaud / Benamouzig, Daniel / Boëlle, Pierre-Yves / Desenclos, Jean-Claude / Opatowski, Lulla / Cauchemez, Simon

Nature communications

2021 Volume 12, Issue 1, Page(s) 6895

Abstract: The shielding of older individuals has been proposed to limit COVID-19 hospitalizations while relaxing general social distancing in the absence of vaccines. Evaluating such approaches requires a deep understanding of transmission dynamics across ages. ... ...

Abstract	The shielding of older individuals has been proposed to limit COVID-19 hospitalizations while relaxing general social distancing in the absence of vaccines. Evaluating such approaches requires a deep understanding of transmission dynamics across ages. Here, we use detailed age-specific case and hospitalization data to model the rebound in the French epidemic in summer 2020, characterize age-specific transmission dynamics and critically evaluate different age-targeted intervention measures in the absence of vaccines. We find that while the rebound started in young adults, it reached individuals aged ≥80 y.o. after 4 weeks, despite substantial contact reductions, indicating substantial transmission flows across ages. We derive the contribution of each age group to transmission. While shielding older individuals reduces mortality, it is insufficient to allow major relaxations of social distancing. When the epidemic remains manageable (R close to 1), targeting those most contributing to transmission is better than shielding at-risk individuals. Pandemic control requires an effort from all age groups.
MeSH term(s)	Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; COVID-19/epidemiology ; COVID-19/prevention & control ; COVID-19/transmission ; COVID-19 Vaccines ; Child ; Child, Preschool ; Computer Simulation ; Female ; France/epidemiology ; Hospitalization/statistics & numerical data ; Humans ; Infant ; Infant, Newborn ; Male ; Middle Aged ; Pandemics/prevention & control ; Physical Distancing ; SARS-CoV-2 ; Young Adult
Chemical Substances	COVID-19 Vaccines
Language	English
Publishing date	2021-11-25
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-021-27163-1
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Article ; Online: Emergence and global spread of

Moura, Alexandra / Lefrancq, Noémie / Wirth, Thierry / Leclercq, Alexandre / Borges, Vítor / Gilpin, Brent / Dallman, Timothy J / Frey, Joachim / Franz, Eelco / Nielsen, Eva M / Thomas, Juno / Pightling, Arthur / Howden, Benjamin P / Tarr, Cheryl L / Gerner-Smidt, Peter / Cauchemez, Simon / Salje, Henrik / Brisse, Sylvain / Lecuit, Marc

Science advances

2021 Volume 7, Issue 49, Page(s) eabj9805

Abstract: The bacterial foodborne ... ...

Abstract	The bacterial foodborne pathogen
Language	English
Publishing date	2021-12-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	2810933-8
ISSN	2375-2548 ; 2375-2548
ISSN (online)	2375-2548
ISSN	2375-2548
DOI	10.1126/sciadv.abj9805
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Article ; Online: Ongoing diphtheria outbreak in Yemen: a cross-sectional and genomic epidemiology study.

Badell, Edgar / Alharazi, Abdulilah / Criscuolo, Alexis / Almoayed, Khaled Abdullah Ali / Lefrancq, Noémie / Bouchez, Valerie / Guglielmini, Julien / Hennart, Melanie / Carmi-Leroy, Annick / Zidane, Nora / Pascal-Perrigault, Marine / Lebreton, Manon / Martini, Helena / Salje, Henrik / Toubiana, Julie / Dureab, Fekri / Dhabaan, Ghulam / Brisse, Sylvain

The Lancet. Microbe

2021 Volume 2, Issue 8, Page(s) e386–e396

Abstract: Background: An outbreak of diphtheria, declared in Yemen in October, 2017, is ongoing. We did a cross-sectional study to investigate the epidemiological, clinical, and microbiological features of the outbreak.: Methods: Probable cases of diphtheria ... ...

Abstract	Background: An outbreak of diphtheria, declared in Yemen in October, 2017, is ongoing. We did a cross-sectional study to investigate the epidemiological, clinical, and microbiological features of the outbreak. Methods: Probable cases of diphtheria that were defined clinically and recorded through a weekly electronic diseases early warning system (from 2017, week 22, to 2020, week 17) were used to identify trends of the outbreak (we divided the epidemic into three time periods: May 29, 2017, to June 10, 2018; June 11, 2018, to June 3, 2019; and June 4, 2019, to April 26, 2020). We used the line list of diphtheria reports for governorate-level descriptions. Vaccination coverage was estimated using the 2017 and 2018 annual reports by the national Expanded Programme on Immunization. To confirm cases biologically, Corynebacterium diphtheriae was isolated and identified from throat swabs using standard microbiological culture and identification procedures. We assessed differences in the temporal and geographical distributions of cases, including between different age groups. For in-depth microbiological analysis, tox gene and species-specific rpoB real-time PCR, Illumina genomic sequencing, antimicrobial susceptibility analysis (disk diffusion, E-test), and the Elek diphtheria toxin production test were done on confirmed cases. We used genomic data for phylogenetic analyses and to estimate the nucleotide substitution rate. Findings: The Yemen diphtheria outbreak affected almost all governorates (provinces), with 5701 probable cases and 330 deaths recorded up to April 26, 2020. We collected clinical data for 888 probable cases with throat swab samples referred for biological confirmation, and genomic data for 42 positive cases, corresponding to 43 isolates (two isolates from one culture were included due to distinct colony morphologies). The median age of patients was 12 years (range 0·2-80). The proportion of cases in children aged 0-4 years was reduced during the second time period, after a vaccination campaign, compared with the first period (19% [95% CI 18-21] in the first period vs 14% [12-15] in the second period, p<0·0001). Among 43 tested isolates, 39 (91%) produced the diphtheria toxin and two had low level (0·25 mg/L) antimicrobial resistance to penicillin. We identified six C diphtheriae phylogenetic sublineages, four of which are genetically related to isolates from Saudi Arabia, Eritrea, and Somalia. Inter-sublineage genomic variations in genes associated with antimicrobial resistance, iron acquisition, and adhesion were observed. The predominant sublineage (30 [70%] of 43 isolates) was resistant to trimethoprim and was associated with unique genomic features, more frequent neck swelling (p=0·0029) and a younger age of patients (p=0·060) compared with the other sublineages. Its evolutionary rate was estimated at 1·67 × 10 Interpretation: In the Yemen outbreak, C diphtheriae shows high phylogenetic, genomic, and phenotypic variation. Laboratory capacity and real-time microbiological monitoring of diphtheria outbreaks need to be scaled up to inform case management and transmission control of diphtheria. Catch-up vaccination might have provided some protection to the targeted population (children aged 0-4 years). Funding: National Centre of the Public Health Laboratories (Yemen), Institut Pasteur, and the French Government Investissement d'Avenir Programme. Translation: For the Arabic translation of the abstract see Supplementary Materials section.
MeSH term(s)	Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anti-Infective Agents ; Child ; Child, Preschool ; Corynebacterium ; Corynebacterium diphtheriae/genetics ; Cross-Sectional Studies ; Diphtheria/epidemiology ; Diphtheria Toxin/genetics ; Disease Outbreaks ; Genomics ; Humans ; Infant ; Middle Aged ; Phylogeny ; Yemen/epidemiology ; Young Adult
Chemical Substances	Anti-Infective Agents ; Diphtheria Toxin
Language	English
Publishing date	2021-05-26
Publishing country	England
Document type	Journal Article
ISSN	2666-5247
ISSN (online)	2666-5247
DOI	10.1016/S2666-5247(21)00094-X
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