Molecular characterization of dengue virus serotype 1 infections in French travelers from Africa between 2013 and 2019

Laboratory-confirmed dengue virus (DENV) infections in Africa are rarely reported. In this study, we report 18 DENV serotype 1 (DENV-1) infections, diagnosed by the French National Reference Center for Arboviruses, in patients who had histories of recent travel in Africa. Our analyses revealed two cases, one from Niger in 2018 and one from the Republic of the Congo in 2016, where dengue fever had not been previously reported, and one case from Mauritania in 2015, where DENV-1 had not been previously reported. These cases support the reported spread of DENV outside its well-established tropical and subtropical environment toward the arid deserts of the Sahel. Phylogenetic analyses suggest that a single monophyletic DENV-1 lineage is currently in circulation in West Africa, having spread from East Africa after its original importation from Asia. Our study provides an improved understanding of DENV dynamics in Africa and underlines the importance of surveillance of travel-acquired infections

Challenges of viral infection diagnostics in conflicts zones : fevers of unknown origin and arboviral infections in French forces deployed in Africa

Les opérations militaires françaises récentes en Afrique Sub-Saharienne ont engendré le déploiement d'un important dispositif humain. En soutien médical, le Service de Santé des Armées est confronté à des difficultés pour la prise en charge des fièvres en zone de conflit. Le principal défi est le diagnostic de fièvres inexpliquées en zones reculées. Le constat est double : le risque infectieux réel reste méconnu et les contraintes logistiques rendent les outils de diagnostic conventionnels inaccessibles. Le premier objectif de cette thèse est d'explorer l'amélioration des outils de diagnostic viral pour les échantillons récoltés sur le théâtre africain. Pour cela, nous avons évalué l'échantillonnage de sang total sur papier buvard comme moyen de diagnostic différencié et exploré l'utilisation du séquençage de nouvelle génération sur ce type d'échantillon. Nous avons également développé une approche non-spécifique d’isolement viral in vitro. Cette nouvelle approche est testée dans le cadre d'une étude en cours sur des échantillons sanguins de fièvres inexpliquées provenant d'Afrique Sub-Saharienne. Le second objectif consistait dans l’amélioration des connaissances sur les arbovirus endémiques en Afrique. Transmis par des moustiques et pathogène chez l'homme, ils représentent un risque conséquent pour les forces armées. La diversité virale et leur circulation reste sous-étudiées, alors que plusieurs épidémies explosives d’arboviroses d'origine africaine ont émergé. Grâce aux échantillons et aux données issus de voyageurs et de la Communauté de la Défense, cet axe de recherche a débouché à la description d’émergences du virus de la dengue et chikungunya sur le continent.Recent French military operations in Sub-Saharan Africa has resulted in an important deployment of forces on the African theatre. Responsible for medical support, the French Military Medical Service is confronted with difficulties to provide health care to fever cases in forward conflict zones. The main challenge is diagnosis of unexplained fevers in isolated places. First assessment revealed that the real infectious risk is unknown and logistical constraints in the field render conventional diagnostics inaccessible. In this context, the first purpose of this thesis was to explore improvement of viral infection diagnostic tools for samples collected in the African theatre. To do so, we evaluated the sampling of dried blood spots as a mean of differentiated diagnosis and explore next generation sequencing on those samples. In parallel, we developed an unbiased approach to in vitro viral isolation from sera and plasma. This new approach was tested on a cohort of unexplained fevers from Sub-Saharan Africa. The second purpose of this thesis was to improve knowledge of endemic African arboviruses. Indeed, pathogenic to humans and vector-borne, they represent a real risk for the deployed armed forces. The diversity of such viruses and their circulation remain under-study, yet several explosive outbreaks due to arboviruses originated from Africa during the last twenty years. Thanks to the use of samples and data from travellers and from the Defence community, this research axis led up to the description of dengue and chikungunya virus emergences on the continent

Variability of Zika Virus Incubation Period in Humans

International audienceZika virus (ZIKV) has recently emerged in numerous tropical countries worldwide. In this study, we estimated ZIKV incubation period distribution using time-to-event models adapted to interval-censored data based on declared date of travels from 123 symptomatic travelers returning from areas with active ZIKV transmission. The median time and 95th percentile of ZIKV incubation period was estimated to 6.8 days (95% confidence interval [CI], 5.8-7.7 days) and 15.4 days (95% CI, 12.7-19.7 days), respectively. Determining the incubation period for ZIKV is beneficial to improve protection guidelines

Emergence of Indian lineage of ECSA chikungunya virus in Djibouti, 2019

The chikungunya virus (CHIKV) originated from Africa and has spread worldwide. Since 2017, multiple chikungunya outbreaks have been reported in the Horn of Africa, without molecular characterization. In November 2019, an autochthonous acute chikungunya infection was diagnosed in a French patient living in Djibouti, marking the re-emergence of the virus in the country. The strain was isolated and fully sequenced. Phylogenetic analysis revealed that the Djiboutian strain belongs to the Indian lineage of the Eastern/Central/South African (ECSA) genotype. Two mutations highly increasing the virus’s fitness in Aedes aegypti, the sole vector present in Djibouti city, were identified

Emergence of dengue virus serotype 2 in Mauritania and molecular characterization of its circulation in West Africa

International audienceThe number of sporadic and epidemic dengue fever cases have reportedly been increasing in recent years in some West African countries, such as Senegal and Mali. The first epidemic of laboratory-confirmed dengue occurred in Nouakchott, the capital city of Mauritania situated in the Saharan desert, in 2014. On-site diagnosis of dengue fever was established using a rapid diagnostic test for dengue. In parallel, the presence of Aedes aegypti mosquitoes in the city was confirmed. The initial diagnosis was confirmed by RT-PCR, which showed that all samples from the 2014 dengue epidemic in Nouakchott were dengue virus serotype 2 (DENV-2). The whole genome or envelope protein gene of these strains, together with other DENV-2 strains obtained from travelers returning from West African countries to France between 2016 and 2019 (including two Mauritanian strains in 2017 and 2018), were sequenced. Phylogenetic analysis suggested a recent emergence of an epidemic strain from the cosmopolitan genotype belonging to West African cosmopolitan lineage II, which is genetically distinct from African sylvatic genotype. The origin of this DENV-2 lineage is still unknown, but our data seem to suggest a recent and rapid dispersion of the epidemic strain throughout the region. More complete genome sequences of West African DENV-2 are required for a better understanding of the dynamics of its circulation. Arboviral surveillance and outbreak forecasting are urgently needed in West Africa

Long-Term Infectivity of Chikungunya Virus Stored in the Dark at 4°C

International audienceWe call into question the established dogma that viruses with envelopes and RNA genomes have limited stability by demonstrating the staggering long-term viability, ∼2 years, of chikungunya virus when stored in liquid environments at +4°C in the dark. We contend that our understanding of the infectivity of a variety of enveloped viruses requires a new approach to identify under standardized conditions the primary determinants of their viability

Publisher Correction: Heterogeneous SARS-CoV-2 humoral response after COVID-19 vaccination and/or infection in the general population

International audienceNo abstract availabl

Eight Months of Serological Follow-Up of Anti-SARS-CoV-2 Antibodies in France: A Study among an Adult Population

International audienceBackground: Uncertainties remain regarding the nature and durability of the humoral immune response to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Aim: This study investigated immunoglobulin G response and neutralizing activity to evaluate the mean antibody concentrations and response duration induced by each vaccination regimen in a French adult population. Methods: A study including blood sampling and questionnaires was carried out from November 2020 to July 2021 with three separate follow-up phases. Spike proteins and neutralizing antibodies were quantified using ELISA and a virus-neutralization test. Results: Overall, 295 participants were included. Seroprevalences were 11.5% (n = 34), 10.5% (n = 31), and 68.1% (n = 201) in phases 1, 2, and 3, respectively. Importantly, 5.8% (n = 17) of participants lost their natural antibodies. Antibody response of participants with only a prior infection was 88.2 BAU/mL, significantly lower than those vaccinated, which was 1909.3 BAU/mL (p = 0.04). Moreover, the antibody response of vaccinated participants with a prior infection was higher (3593.8 BAU/mL) than those vaccinated without prior infection (3402.9 BAU/mL) (p = 0.78). Vaccinated participants with or without prior infection had a higher seroneutralization rate (91.0%) than those unvaccinated with prior infection (65.0%). Conclusion: These results demonstrated that single infection does not confer effective protection against SARS-CoV-2

Heterogeneous SARS-CoV-2 humoral response after COVID-19 vaccination and/or infection in the general population

International audienceAssessment of the intensity, dynamics and determinants of the antibody response after SARS-CoV-2 infection or vaccination in the general population is critical to guide vaccination policies. This study characterized the anti-spike IgG titers in 13,971 participants included in a French multicohort population-based serological survey on COVID-19 between April and October 2020 and followed-up with serological testing between May and October 2021. Eight follow-up profiles were defined depending on SARS-CoV-2 infection (0, 1 or 2) and COVID-19 vaccination (0, 1, 2 or 3). The anti-spike titer was lower in adults with no vaccination even in case of infection or reinfection, while it was higher in adults with infection followed by vaccination. The anti-spike titer was negatively correlated with age in vaccinated but uninfected adults, whereas it was positively correlated with age in unvaccinated but infected adults. In adults with 2 vaccine injections and no infection, the vaccine protocol, age, gender, and time since the last vaccine injection were independently associated with the anti-spike titer. The decrease in anti-spike titer was much more rapid in vaccinated than in infected subjects. These results highlight the strong heterogeneity of the antibody response against SARS-CoV-2 in the general population depending on previous infection and vaccination

A Cross-Sectional Study of Exposure Factors Associated with Seropositivity for SARS-CoV-2 Antibodies during the Second Epidemic Wave among a Sample of the University of Corsica (France)

This study aimed to estimate the seroprevalence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection within the staff and student populations of the University of Corsica (France) during the second wave of the epidemic. Methods: A cross-sectional survey was conducted from 23 November 2020 to 31 January 2021. The participants underwent blood sampling using a fingerstick procedure and completed an anonymized questionnaire. Sera were tested for the presence of anti-SARS-CoV-2 IgG (ELISA-S) and, if positive, with an in-house virus neutralization test (VNT). Results: A total of 418 persons were included in the study. The overall seroprevalence was 12.8% (95% confidence interval (CI), 9.8\textendash 16.6%). A total of 15 (31%) of the 49 individuals who had a positive ELISA-S also had a positive VNT. Seropositivity was associated with living at the city campus during the week and on weekends (OR = 3.74 [1.40\textendash 12.00]), using public transportation/carpooling (OR = 2.00 [1.01\textendash 4.02]), and being in contact with a person who tested positive for SARS-CoV-2 (OR = 2.32 [1.20\textendash 4.40]). The main symptoms associated with seropositivity were ``having had an acute respiratory infection'' (OR = 3.05 [1.43\textendash 6.43]) and ``experiencing loss of smell'' (OR = 16.4 [5.87\textendash 50.7]). Conclusion: These results could be useful for SARS-CoV-2 prevention and control on university campuses