Publications by authors named "Cécile Beck"

33 Publications

Entry-competent-replication-abortive African horse sickness virus strains elicit robust immunity in ponies against all serotypes.

Vaccine 2021 May 3. Epub 2021 May 3.

Department of Infection Biology, Faculty of Infectious and Tropical Disease, London School of Hygiene and Tropical Medicine, United Kingdom. Electronic address:

African horse sickness virus (AHSV) is an Orbivirus within the Reoviridae family, spread by Culicoides species of midges, which infects equids with high mortality, particularly in horses and has a considerable impact on the equine industry. In order to control the disease, we previously described Entry Competent Replication Abortive (ECRA) virus strains for each of the nine distinct AHSV serotypes and demonstrated their potential as vaccines, first in type I interferon receptor (IFNAR-/-) knockout mice, and then in ponies. In this report we have investigated whether or not a combination ECRA vaccine comprising nine vaccine strains as two different cocktails is as efficient in ponies and the duration of the immunity triggered by ECRA vaccines. In one study, a group of ponies were vaccinated with a cocktail of 4 vaccine strains, followed by a vaccination of the remaining 5 vaccine strains, mimicking the current live attenuated vaccine regimen. In the second study, ponies were vaccinated with a single ECRA-AHSV strain and monitored for 6 months. The first group of ponies developed neutralising antibody responses against all 9 serotypes, indicating that no cross-serotype interference occurred, while the second group developed robust neutralising antibody responses against the single serotype that were sustained at the same level throughout a 6-month study. The results support our previous data and further validate ECRA vaccines as a safe and efficacious replacement of current live vaccines.
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http://dx.doi.org/10.1016/j.vaccine.2021.04.034DOI Listing
May 2021

Serological evidence of West Nile virus infection in human populations and domestic birds in the Northwest of Morocco.

Comp Immunol Microbiol Infect Dis 2021 Apr 5;76:101646. Epub 2021 Apr 5.

Institut Pasteur du Maroc, Service de Parasitologie et des Maladies Vectorielles, Place Louis Pasteur, Casablanca 20360, Morocco. Electronic address:

West Nile virus (WNV) was recently detected in Culex pipiens mosquitoes in Morocco. The aim of this study was to evaluate the seroprevalence of WNV in humans and in domestic birds in two regions of Morocco by the detection of IgG antibodies. Blood samples were obtained from 91 human patients and 92 domestic birds from September to December 2019. All study samples were tested using competitive enzyme-linked immunosorbent assay (cELISA) and WNV neutralization tests (VNT) were performed on positive sera. Of all samples, 4 (4.39 %) humans and 4 (4.34 %) birds were found to be seropositive for flaviviruses by the cELISA test. The VNT revealed that three of the four human samples detected positive by cELISA contained neutralizing antibodies against WNV. Two bird samples were confirmed positive by VNT. These results show a significant seroprevalence of anti-WNV antibodies and therefore suggest the active circulation and exposure of human and bird populations in the northwest of Morocco.
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http://dx.doi.org/10.1016/j.cimid.2021.101646DOI Listing
April 2021

Mapping geographical areas at risk for tick-borne encephalitis (TBE) by analysing bulk tank milk from Swedish dairy cattle herds for the presence of TBE virus-specific antibodies.

Acta Vet Scand 2021 Apr 7;63(1):16. Epub 2021 Apr 7.

Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden.

Background: The vector-borne human viral zoonosis tick-borne encephalitis (TBE) is of growing concern in Sweden. The area where TBE is considered endemic has expanded, with an increasing geographical distribution of Ixodes ricinus as the tick vector and a rising number of reported TBE cases in humans. Efforts to map TBE risk areas have been carried out by sentinel monitoring, mainly based on individual sampling and analysis of wild and domestic animals, as well as ticks, for tick-borne encephalitis virus (TBEV). However, the interpretation of the geographical distribution has been hampered by the patchy and focal nature of TBEV occurrence. This study presents TBEV surveillance data based on antibody analysis of bulk tank milk collected from dairy herds located throughout Sweden before (May) and after (November) the vector season. A commercial TBEV antibody ELISA was modified and evaluated for use in this study.

Results: The initial comparative TBEV antibody analysis revealed a good correlation between milk and serum antibody levels from individually sampled cows. Also, the TBEV-antibody levels for the mean-herd serum showed good comparability with TBEV antibody levels from bulk tank milk, thus indicating good predictability of seroprevalence when analysing bulk tank milk from a herd. Analyses of bulk tank milk samples collected from 616 herds in May and 560 herds in November showed a geographical distribution of TBEV seropositive herds that was largely consistent with reported human TBE cases. A few TBEV-reactive herds were also found outside known locations of human TBE cases.

Conclusion: Serological examination of bulk tank milk from dairy cattle herds may be a useful sentinel surveillance method to identify geographical presence of TBEV. In contrast to individual sampling this method allows a large number of animals to be monitored. TBEV seropositive herds were mainly found in coastal areas of southern Sweden similar to human TBE cases. However, some antibody-reactive herds were found outside known TBE areas at the time of the study.
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http://dx.doi.org/10.1186/s13028-021-00580-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8028798PMC
April 2021

[Which tools for monitoring emerging arboviruses within their mammalian hosts and arthropod vectors ?]

Virologie (Montrouge) 2021 Feb;25(1):12-28

Anses, Inrae, École nationale vétérinaire d'Alfort, UMR Bipar, Laboratoire de Santé animale, Maisons-Alfort, F-94700, France.

Arboviruses are viruses transmitted to humans and/or animals by hematophagous arthropods. They have a significant economic and public health impact. Given the number of arboviruses already identified and their great genetic variability, it is essential to have highly flexible tools for their monitoring. Arbovirus circulation within animal populations can be demonstrated by direct and/or indirect screening of a specific virus within vertebrate hosts and/or arthropod vectors. Viruses have great adaptive capacities that enable them to emerge into new geographic areas and/or cross species barriers. Over the decades, arbovirus monitoring has considerably evolved due to innovations in detection technologies. The objectives of this review are to list and assess (i) the current tools for direct or indirect screening for arboviruses, (ii) the new generation tools that best meet expectations in terms of optimal arbovirus monitoring and (iii) the potentials for improved arbovirus monitoring.
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http://dx.doi.org/10.1684/vir.2021.0880DOI Listing
February 2021

Differential neurovirulence of Usutu virus lineages in mice and neuronal cells.

J Neuroinflammation 2021 Jan 6;18(1):11. Epub 2021 Jan 6.

Pathogenesis and Control of Chronic Infections, Université de Montpellier, INSERM, EFS, Montpellier, France.

Background: Usutu virus (USUV) is an emerging neurotropic arthropod-borne virus recently involved in massive die offs of wild birds predominantly reported in Europe. Although primarily asymptomatic or presenting mild clinical signs, humans infected by USUV can develop neuroinvasive pathologies (including encephalitis and meningoencephalitis). Similar to other flaviviruses, such as West Nile virus, USUV is capable of reaching the central nervous system. However, the neuropathogenesis of USUV is still poorly understood, and the virulence of the specific USUV lineages is currently unknown. One of the major complexities of the study of USUV pathogenesis is the presence of a great diversity of lineages circulating at the same time and in the same location.

Methods: The aim of this work was to determine the neurovirulence of isolates from the six main lineages circulating in Europe using mouse model and several neuronal cell lines (neurons, microglia, pericytes, brain endothelial cells, astrocytes, and in vitro Blood-Brain Barrier model).

Results: Our results indicate that all strains are neurotropic but have different virulence profiles. The Europe 2 strain, previously described as being involved in several clinical cases, induced the shortest survival time and highest mortality in vivo and appeared to be more virulent and persistent in microglial, astrocytes, and brain endothelial cells, while also inducing an atypical cytopathic effect. Moreover, an amino acid substitution (D3425E) was specifically identified in the RNA-dependent RNA polymerase domain of the NS5 protein of this lineage.

Conclusions: Altogether, these data show a broad neurotropism for USUV in the central nervous system with lineage-dependent virulence. Our results will help to better understand the biological and epidemiological diversity of USUV infection.
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http://dx.doi.org/10.1186/s12974-020-02060-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789689PMC
January 2021

Evidence of Exposure to USUV and WNV in Zoo Animals in France.

Pathogens 2020 Nov 30;9(12). Epub 2020 Nov 30.

Pathogenesis and Control of Chronic Infections, University of Montpellier, INSERM, EFS, 34000 Montpellier, France.

West Nile virus (WNV) and Usutu virus (USUV) are zoonotic arboviruses. These flaviviruses are mainly maintained in the environment through an enzootic cycle involving mosquitoes and birds. Horses and humans are incidental, dead-end hosts, but can develop severe neurological disorders. Nevertheless, there is little data regarding the involvement of other mammals in the epidemiology of these arboviruses. In this study, we performed a serosurvey to assess exposure to these viruses in captive birds and mammals in a zoo situated in the south of France, an area described for the circulation of these two viruses. A total of 411 samples comprising of 70 species were collected over 16 years from 2003 to 2019. The samples were first tested by a competitive enzyme-linked immunosorbent assay. The positive sera were then tested using virus-specific microneutralization tests against USUV and WNV. USUV seroprevalence in birds was 10 times higher than that of WNV (14.59% versus 1.46%, respectively). Among birds, greater rhea () and common peafowl () exhibited the highest USUV seroprevalence. Infections occurred mainly between 2016-2018 corresponding to a period of high circulation of these viruses in Europe. In mammalian species, antibodies against WNV were detected in one dama gazelle () whereas serological evidence of USUV infection was observed in several , especially in African wild dogs (). Our study helps to better understand the exposure of captive species to WNV and USUV and to identify potential host species to include in surveillance programs in zoos.
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http://dx.doi.org/10.3390/pathogens9121005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7760666PMC
November 2020

Contrasted Epidemiological Patterns of West Nile Virus Lineages 1 and 2 Infections in France from 2015 to 2019.

Pathogens 2020 Oct 30;9(11). Epub 2020 Oct 30.

UMR 1161 Virology, ANSES, INRAE, ENVA, ANSES Animal Health Laboratory, EURL for Equine Diseases, 94704 Maisons-Alfort, France.

Since 2015, annual West Nile virus (WNV) outbreaks of varying intensities have been reported in France. Recent intensification of enzootic WNV circulation was observed in the South of France with most horse cases detected in 2015 ( = 49), 2018 ( = 13), and 2019 ( = 13). A WNV lineage 1 strain was isolated from a horse suffering from West Nile neuro-invasive disease (WNND) during the 2015 episode in the Camargue area. A breaking point in WNV epidemiology was achieved in 2018, when WNV lineage 2 emerged in Southeastern areas. This virus most probably originated from WNV spread from Northern Italy and caused WNND in humans and the death of diurnal raptors. WNV lineage 2 emergence was associated with the most important human WNV epidemics identified so far in France (n = 26, including seven WNND cases and two infections in blood and organ donors). Two other major findings were the detection of WNV in areas with no or limited history of WNV circulation (Alpes-Maritimes in 2018, Corsica in 2018-2019, and Var in 2019) and distinct spatial distribution of human and horse WNV cases. These new data reinforce the necessity to enhance French WNV surveillance to better anticipate future WNV epidemics and epizootics and to improve the safety of blood and organ donations.
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http://dx.doi.org/10.3390/pathogens9110908DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7692118PMC
October 2020

Serological evidence of West Nile virus infection among birds and horses in some geographical locations of Iran.

Vet Med Sci 2021 01 28;7(1):204-209. Epub 2020 Aug 28.

Department of virology, Arboviruses and Insect Vectors, Institut Pasteur, Paris, France.

Recent expansion of arboviruses such as West Nile (WNV), Usutu (USUV), and tick-borne encephalitis (TBEV) over their natural range of distribution needs strengthening their surveillance. As common viral vertebrate hosts, birds and horses deserve special attention with routine serological surveillance. Here, we estimated the seroprevalence of WNV, USUV and TBEV in 160 migrating/resident birds and 60 horses sampled in Mazandaran, Golestan, North Khorasan, Kordestan provinces and Golestan province of Iran respectively. ELISA results showed that of 220 collected samples, 32 samples (14.54%), including 22 birds and 10 horses, were positive. Microsphere immunoassay results showed that 16.7% (10/60) of horse blood samples collected in Golestan province were seropositive against WNV (7; 11.7%), Flavivirus (2; 3.3%) and seropositive for USUV or WNV (1; 1.7%). Furthermore, micro virus neutralization tests revealed that four of seven ELISA-positive bird blood samples were seropositive against WNV: two Egyptian vultures, and one long-legged buzzard collected in Golestan province as well as a golden eagle collected in North Khorasan province. No evidence of seropositivity with TBEV was observed in collected samples. We showed that WNV, responsible for neuroinvasive infection in vertebrates, is circulating among birds and horses in Iran, recommending a sustained surveillance of viral infections in animals, and anticipating future infections in humans.
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http://dx.doi.org/10.1002/vms3.342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840194PMC
January 2021

Study of Usutu virus neuropathogenicity in mice and human cellular models.

PLoS Negl Trop Dis 2020 04 23;14(4):e0008223. Epub 2020 Apr 23.

Pathogenesis and Control of Chronic Infections, University of Montpellier, INSERM, EFS, Montpellier, France.

Usutu virus (USUV), an African mosquito-borne flavivirus closely related to West Nile virus, was first isolated in South Africa in 1959. USUV emerged in Europe two decades ago, causing notably massive mortality in Eurasian blackbirds. USUV is attracting increasing attention due to its potential for emergence and its rapid spread in Europe in recent years. Although mainly asymptomatic or responsible for mild clinical signs, USUV was recently described as being associated with neurological disorders in humans such as encephalitis and meningoencephalitis, highlighting the potential health threat posed by the virus. Despite this, USUV pathogenesis remains largely unexplored. The aim of this study was to evaluate USUV neuropathogenicity using in vivo and in vitro approaches. Our results indicate that USUV efficiently replicates in the murine central nervous system. Replication in the spinal cord and brain is associated with recruitment of inflammatory cells and the release of inflammatory molecules as well as induction of antiviral-responses without major modulation of blood-brain barrier integrity. Endothelial cells integrity is also maintained in a human model of the blood-brain barrier despite USUV replication and release of pro-inflammatory cytokines. Furthermore, USUV-inoculated mice developed major ocular defects associated with inflammation. Moreover, USUV efficiently replicates in human retinal pigment epithelium. Our results will help to better characterize the physiopathology related to USUV infection in order to anticipate the potential threat of USUV emergence.
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http://dx.doi.org/10.1371/journal.pntd.0008223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7179837PMC
April 2020

Serological Evidence of West Nile and Usutu Viruses Circulation in Domestic and Wild Birds in Wetlands of Mali and Madagascar in 2008.

Int J Environ Res Public Health 2020 03 18;17(6). Epub 2020 Mar 18.

UMR 1161 Virology, ANSES, INRA, ENVA, ANSES Animal Health Laboratory, EURL for Equine Diseases, 94704 Maisons-Alfort, France.

The geographical distribution and impact on animal and human health of both West Nile and Usutu viruses, two flaviviruses of the Japanese encephalitis complex, have been increasing during the past two decades. Both viruses circulate in Europe and Africa within a natural cycle between wild birds and mosquitoes, mainly from the genus. We retrospectively analyzed sera from domestic and wild birds sampled in 2008 in two wetlands, namely the Inner Niger Delta, Mali, and the Lake Alaotra area, Madagascar. Sera were first tested using a commercial ID Screen West Nile Competition Multi-species ELISA kit. Then, positive sera and sera with insufficient volume for testing with ELISA were tested with a Microneutralization Test. In Mali, the observed seroprevalence in domestic birds was 28.5% [24.5; 32.8] , 3.1 % [1.8; 5.2] , 6.2% [3.4; 10.2] and 9.8 % [7.3; 12.8] , for West Nile virus (WNV), Usutu virus (USUV), undetermined flavivirus, and WNV/USUV respectively. Regarding domestic birds of Madagascar, the observed seroprevalence was 4.4 % [2.1; 7.9] for WNV, 0.9% [0.1; 3.1] for USUV, 1.3% [0.5; 2.8] for undetermined flavivirus, and null for WNV/USUV. Among the 150 wild birds sampled in Madagascar, two fulvous whistling-ducks () were positive for WNV and two for an undetermined flavivirus. One white-faced whistling-duck () and one Hottentot teal () were tested positive for USUV. African and European wetlands are linked by wild bird migrations. This first detection of USUV-as well as the confirmed circulation of WNV in domestic birds of two wetlands of Mali and Madagascar-emphasizes the need to improve the surveillance, knowledge of epidemiological patterns, and phylogenetic characteristics of flavivirus in Africa, particularly in areas prone to sustained, intense flavivirus transmission such as wetlands.
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http://dx.doi.org/10.3390/ijerph17061998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7142923PMC
March 2020

Evidence of circulation of West Nile virus in Culex pipiens mosquitoes and horses in Morocco.

Acta Trop 2020 May 20;205:105414. Epub 2020 Feb 20.

Institut Pasteur du Maroc, Service de Parasitologie et des Maladies Vectorielles, Place Louis Pasteur, Casablanca 20360, Morocco. Electronic address:

West Nile virus (WNV) is one of the most widely distributed mosquito-borne viruses in the world. In North Africa, it causes human cases of meningoencephalitis with fatalities in Algeria and in Tunisia, whereas only horses were affected in Morocco. The aims of this study were to detect WNV in mosquitoes and to determine seroprevalence of WNV in Moroccan horses by the detection of IgG antibodies. A total of 1455 mosquitoes belonging to four different species were grouped by collection site, date, and sex with 10 specimens per pool and tested for 38 arboviruses using a high-throughput chip based on the BioMark Dynamic array system. Out of 146 mosquito pools tested, one pool was positive for WNV. This positive pool was confirmed by real time RT-PCR. The serosurvey showed that 33.7% (31/92) of horses were positive for competitive enzyme-linked immunosorbent assay (cELISA) test. The flavivirus-sphere microsphere immnoassay (MIA) test, targeting three flaviviruses (WNV, Usutu virus (USUV) and Tick borne encephalitic virus (TBEV)) showed that 23 sera out of 31 were positive for WNV, two for USUV, two for USUV or WNV, and four for an undetermined flavivirus. Virus neutralization tests with USUV and WNV showed that 28 of 31 sera were positive for WNV and all sera were negative for USUV. This study reports, for the first time, the detection of WNV from Culex pipiens mosquitoes in Morocco and its circulation among horses. This highlights that the detection of arboviruses in mosquitoes could serve as an early warning signal of a viral activity to prevent future outbreaks in animals and humans.
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http://dx.doi.org/10.1016/j.actatropica.2020.105414DOI Listing
May 2020

First serological evidence of West Nile virus infection in wild birds in Northern Algeria.

Comp Immunol Microbiol Infect Dis 2020 Apr 7;69:101415. Epub 2020 Jan 7.

UMR1161 Virologie, INRAE, Ecole Nationale Vétérinaire d'Alfort, ANSES, Université Paris-Est, Maisons-Alfort, Paris, France.

While the epidemiology of Flaviviruses has been extensively studied in most of the Mediterranean basin, little is known about the current situation in Algeria. In order to detect the circulation of West Nile (WNV) and Usutu viruses (USUV) in Kabylia, 165 sera were collected from two wild birds species, namely the long distance migrant Turdus philomelos (song thrush) (n = 92) and the resident Passer domesticus (house sparrow) (n = 73). A total of 154 sera were first analyzed by commercial competition ELISA. WNV and USUV micro-neutralization tests were performed on all c-ELISA positive sera and all samples with poor volume. Overall, 7.8 % (CI95 %: 3.5-11.9) were positive by c-ELISA. Positive results were detected in 12.5 % (CI95 %:5.6-19.4) of song thrushes and 1.5 % (CI95 %: 0.0-4.5) for sparrow. Micro-neutralization tests revealed an overall seroprevalence of 6.7 % for WNV (CI95 %: 2.9-10.3), Neutralizing antibodies were found in 8.7 % (CI95 %: 3.0-14.4) for song thrushes and in 4.1 % (CI95 %: 0.0-8.7) of sparrows. The current study demonstrates significant seroprevalence of WNV antibodies in wild birds in Algeria.
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http://dx.doi.org/10.1016/j.cimid.2020.101415DOI Listing
April 2020

Viral Equine Encephalitis, a Growing Threat to the Horse Population in Europe?

Viruses 2019 12 24;12(1). Epub 2019 Dec 24.

RESPE (Réseau d'épidémio-surveillance en pathologie équine), 14280 Saint-Contest, France.

Neurological disorders represent an important sanitary and economic threat for the equine industry worldwide. Among nervous diseases, viral encephalitis is of growing concern, due to the emergence of arboviruses and to the high contagiosity of herpesvirus-infected horses. The nature, severity and duration of the clinical signs could be different depending on the etiological agent and its virulence. However, definite diagnosis generally requires the implementation of combinations of direct and/or indirect screening assays in specialized laboratories. The equine practitioner, involved in a mission of prevention and surveillance, plays an important role in the clinical diagnosis of viral encephalitis. The general management of the horse is essentially supportive, focused on controlling pain and inflammation within the central nervous system, preventing injuries and providing supportive care. Despite its high medical relevance and economic impact in the equine industry, vaccines are not always available and there is no specific antiviral therapy. In this review, the major virological, clinical and epidemiological features of the main neuropathogenic viruses inducing encephalitis in equids in Europe, including rabies virus (), Equid herpesviruses (), Borna disease virus () and West Nile virus (), as well as exotic viruses, will be presented.
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http://dx.doi.org/10.3390/v12010023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7019608PMC
December 2019

Exposure of Wild Ungulates to the Usutu and Tick-Borne Encephalitis Viruses in France in 2009-2014: Evidence of Undetected Flavivirus Circulation a Decade Ago.

Viruses 2019 12 19;12(1). Epub 2019 Dec 19.

UMR (Unité mixte de recherche) Virologie, INRAE, Ecole Nationale Vétérinaire d'Alfort, ANSES, Université Paris-Est, 94700 Maisons-Alfort, France.

Flaviviruses have become increasingly important pathogens in Europe over the past few decades. A better understanding of the spatiotemporal distribution of flaviviruses in France is needed to better define risk areas and to gain knowledge of the dynamics of virus transmission cycles. Serum samples from 1014 wild boar and 758 roe deer from 16 departments (administrative units) in France collected from 2009 to 2014 were screened for flavivirus antibodies using a competitive ELISA (cELISA) technique. Serum samples found to be positive or doubtful by cELISA were then tested for antibodies directed against West Nile virus (WNV), Usutu virus (USUV), Bagaza virus (BAGV), and tick-borne encephalitis/Louping ill viruses (TBEV/LIV) by microsphere immunoassays (except BAGV) and micro-neutralization tests. USUV antibodies were detected only in southeastern and southwestern areas. TBEV/LIV antibodies were detected in serum samples from eastern, southwestern and northern departments. The results indicate continuous circulation of USUV in southern France from 2009 to 2014, which was unnoticed by the French monitoring system for bird mortality. The findings also confirm wider distribution of TBEV in the eastern part of the country than of human clinical cases. However, further studies are needed to determine the tick-borne flavivirus responsible for the seroconversion in southwestern and northern France.
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http://dx.doi.org/10.3390/v12010010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7019733PMC
December 2019

Infestation of small seabirds by Ornithodoros maritimus ticks: Effects on chick body condition, reproduction and associated infectious agents.

Ticks Tick Borne Dis 2020 01 25;11(1):101281. Epub 2019 Aug 25.

CEFE CNRS Université Montpellier, Campus CNRS, Montpellier, France.

Ticks can negatively affect their host by direct effects as blood feeding causing anaemia or discomfort, or by pathogen transmission. Consequently, ticks can have an important role in the population dynamics of their hosts. However, specific studies on the demographic effects of tick infestation on seabirds are still scarce. Seabird ticks have also the potential to be responsible for the circulation of little known tick-borne agents, which could have implications for non-seabird species. Here, we report the results of investigations on potential associations between soft tick Ornithodoros maritimus load and reproductive parameters of storm petrels Hydrobates pelagicus breeding in a large colony in a cave of Espartar Island, in the Balearic archipelago. We also investigated by molecular analyses the potential viral and bacterial pathogens associated with O. maritimus ticks present at the colony. Lower nestling survival was recorded in the most infested area, deep in the cave, compared to the area near the entrance. The parasite load was negatively associated with the body condition of the nestlings. One pool of ticks tested positive for West Nile virus and 4 pools tested positive for a Borrelia species which was determined by targeted nested PCR to have a 99% sequence identity with B. turicatae, a relapsing fever Borrelia. Overall, these results show that further investigations are needed to better understand the ecology and epidemiology of the interactions between ticks, pathogens and Procellariiform species.
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http://dx.doi.org/10.1016/j.ttbdis.2019.101281DOI Listing
January 2020

Evaluation of the Antiviral Activity of Sephin1 Treatment and Its Consequences on eIF2α Phosphorylation in Response to Viral Infections.

Front Immunol 2019 12;10:134. Epub 2019 Feb 12.

Université de Toulouse, ENVT, INRA, UMR 1225, Toulouse, France.

The guanabenz derivative Sephin1 has recently been proposed to increase the levels of translation initiation factor 2 (eIF2α) phosphorylation by inhibiting dephosphorylation by the protein phosphatase 1-GADD34 (PPP1R15A) complex. As phosphorylation of eIF2α by protein kinase R (PKR) is a prominent cellular antiviral pathway, we evaluated the consequences of Sephin1 treatment on virus replication. Our results provide evidence that Sephin1 downregulates replication of human respiratory syncytial virus, measles virus, human adenovirus 5 virus, human enterovirus D68, human cytomegalovirus, and rabbit myxoma virus. However, Sephin1 proved to be inactive against influenza virus, as well as against Japanese encephalitis virus. Sephin1 increased the levels of phosphorylated eIF2α in cells exposed to a PKR agonist. By contrast, in virus-infected cells, the levels of phosphorylated eIF2α did not always correlate with the inhibition of virus replication by Sephin1. This work identifies Sephin1 as an antiviral molecule in cell culture against RNA, as well as DNA viruses belonging to phylogenetically distant families.
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http://dx.doi.org/10.3389/fimmu.2019.00134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6379315PMC
January 2020

Utility of examining fallen stock data to monitor health-related events in equids: Application to an outbreak of West Nile Virus in France in 2015.

Transbound Emerg Dis 2019 May 6;66(3):1417-1419. Epub 2019 Mar 6.

Dozulé Laboratory for Equine Diseases, ANSES, Goustranville, France.

Few studies about the use of quantitative equine mortality data for monitoring purposes are available. Our study evaluated the utility of monitoring emerging equine diseases using mortality data collected by rendering plants. We used approaches involving modelling of historical mortality fluctuations and detection algorithm methods to analyse changes in equine mortality in connection with the West Nile Virus (WNV) outbreak that occurred between July and September 2015 along the Mediterranean coast of France. Two weeks after the first equine WNV case was detected by clinical surveillance, detection algorithms identified excess mortality. The temporal distribution of this excess mortality suggested that it was related to the WNV outbreak, which may helped to assess the impact of the WNV epizootic on equine mortality. The results suggest that real-time follow-up of mortality could be a useful tool for equine health surveillance.
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http://dx.doi.org/10.1111/tbed.13150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6850354PMC
May 2019

Serological evidence of infection with dengue and Zika viruses in horses on French Pacific Islands.

PLoS Negl Trop Dis 2019 02 7;13(2):e0007162. Epub 2019 Feb 7.

UMR 1161 Virology, ANSES, INRA, ENVA, ANSES Animal Health Laboratory, EURL for equine diseases, Maisons-Alfort, France.

New Caledonia and French Polynesia are areas in which arboviruses circulate extensively. A large serological survey among horses from New Caledonia and French Polynesia was carried out to investigate the seroprevalence of flaviviruses in the horse population. Here, 293 equine sera samples were screened for flaviviruses using a competitive enzyme-linked immunosorbent assay (cELISA). The positive sera were then confirmed using a flavivirus-specific microsphere immunoassay (MIA) and seroneutralization tests. This serosurvey showed that 16.6% (27/163) and 30.8% (40/130) of horses were positive for cELISA tests in New Caledonia and French Polynesia, respectively, but the MIA technique, targeting only flaviviruses causing neuro-invasive infections in humans and horses (i.e. West Nile virus [WNV], Japanese encephalitis virus [JEV] and tick-borne encephalitis virus [TBEV]), showed negative results for more than 85% (57/67) of the cELISA-positive animals. Seroneutralization tests with the main flaviviruses circulating in the South Pacific revealed that 6.1% (10/163; confidence interval [95% CI] 3.0%-11.0%) of sera in New Caledonia and 7.7% (10/130; 95% CI 3.8%-13.7%) in French Polynesia were positive for dengue virus serotype 1 (DENV1) and 4.3% (7/163; 95% CI 1.7%-8.6%) in New Caledonia and 15.4% (20/130, 95% CI 9.7%-22.8%) in French Polynesia were found positive for Zika virus (ZIKV). Seroprevalence of the JEV and WNV flaviviruses on the 293 samples from both island groups were comparatively much lower (less than 2%). This seroprevalence study in the horse population shows that horses can be infected with dengue and Zika viruses and that these infections lead to seroconversions in horses. The consequences of these infections in horses and their role in ZIKV and DENV epidemiological cycles are two issues that deserve further investigation.
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http://dx.doi.org/10.1371/journal.pntd.0007162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6382171PMC
February 2019

Emerging Mosquito-Borne Threats and the Response from European and Eastern Mediterranean Countries.

Int J Environ Res Public Health 2018 12 7;15(12). Epub 2018 Dec 7.

UMR BIPAR, Animal Health Laboratory, ANSES, INRA, Ecole Nationale Vétérinaire d'Alfort, Université Paris-Est, 94700 Maisons-Alfort, France.

Mosquito-borne viruses are the cause of some of the greatest burdens to human health worldwide, particularly in tropical regions where both human populations and mosquito numbers are abundant. Due to a combination of anthropogenic change, including the effects on global climate and wildlife migration there is strong evidence that temperate regions are undergoing repeated introduction of mosquito-borne viruses and the re-emergence of viruses that previously were not detected by surveillance. In Europe, the repeated introductions of West Nile and Usutu viruses have been associated with bird migration from Africa, whereas the autochthonous transmission of chikungunya and dengue viruses has been driven by a combination of invasive mosquitoes and rapid transcontinental travel by infected humans. In addition to an increasing number of humans at risk, livestock and wildlife, are also at risk of infection and disease. This in turn can affect international trade and species diversity, respectively. Addressing these challenges requires a range of responses both at national and international level. Increasing the understanding of mosquito-borne transmission of viruses and the development of rapid detection methods and appropriate therapeutics (vaccines / antivirals) all form part of this response. The aim of this review is to consider the range of mosquito-borne viruses that threaten public health in Europe and the eastern Mediterranean, and the national response of a number of countries facing different levels of threat.
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http://dx.doi.org/10.3390/ijerph15122775DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6313739PMC
December 2018

[Epidemiological surveillance of Usutu virus in avifauna].

Virologie (Montrouge) 2018 10;22(5):261-263

UMR 1161 Virologie, Anses, INRA, ENVA, LNR West Nile, Laboratoire de santé animale de Maisons-Alfort, 94704 Maisons-Alfort, France.

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http://dx.doi.org/10.1684/vir.2018.0751DOI Listing
October 2018

[Usutu virus: the phantom menace].

Med Sci (Paris) 2018 Aug-Sep;34(8-9):709-716. Epub 2018 Sep 19.

Pathogenesis and control of chronic infections, Université de Montpellier, Inserm, EFS, 60, rue de Navacelle, 34000 Montpellier, France.

Usutu virus, an arbovirus discovered in Africa in 1959, has spread over a large part of Europe over the last twenty years causing significant bird mortality as reported in France since 2015. The zoonotic risk, associated with this succession of avian epizootics in Europe, deserves to be taken into account even if human cases remain rare to date. Human infections are most often asymptomatic or present a benign clinical expression. However, neurological complications such as encephalitis or meningoencephalitis have been described. In addition, the recent description of an atypical case of facial paralysis in France suggests that the clinical spectrum of infections caused by Usutu virus is not fully characterized. Finally, the recent history of other arboviral outbreaks invites the scientific community to be extremely vigilant.
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http://dx.doi.org/10.1051/medsci/20183408018DOI Listing
January 2019

Assessment of reproducibility of a VP7 Blocking ELISA diagnostic test for African horse sickness.

Transbound Emerg Dis 2019 Jan 2;66(1):83-90. Epub 2018 Aug 2.

The Pirbright Institute, Pirbright, UK.

The laboratory diagnosis of African horse sickness (AHS) is important for: (a) demonstrating freedom from infection in a population, animals or products for trade (b) assessing the efficiency of eradication policies; (c) laboratory confirmation of clinical diagnosis; (d) estimating the prevalence of AHS infection; and (e) assessing postvaccination immune status of individual animals or populations. Although serological techniques play a secondary role in the confirmation of clinical cases, their use is very important for all the other purposes due to their high throughput, ease of use and good cost-benefit ratio. The main objective of this study was to support the validation of AHS VP7 Blocking ELISA up to the Stage 3 of the World Animal Health Organization (OIE) assay validation pathway. To achieve this, a collaborative ring trial, which included all OIE Reference Laboratories and other AHS-specialist diagnostic centres, was conducted in order to assess the diagnostic performance characteristics of the VP7 Blocking ELISA. In this trial, a panel of sera of different epidemiological origin and infection status was used. Through this comprehensive evaluation we can conclude that the VP7 Blocking ELISA satisfies the OIE requirements of reproducibility. The VP7 Blocking ELISA, in its commercial version is ready to enter Stage 4 of the validation pathway (Programme Implementation). Specifically, this will require testing the diagnostic performance of the assay using contemporary serum samples collected during control campaigns in endemic countries.
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http://dx.doi.org/10.1111/tbed.12968DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6378617PMC
January 2019

Seroprevalence of horses to Coxiella burnetii in an Q fever endemic area.

Vet Microbiol 2018 Feb 13;215:49-56. Epub 2017 Nov 13.

University of Lyon, VetAgroSup, Marcy L'Etoile, France; EPIA, UMR 0346, Epidemiologie des maladies animales et zoonotiques, INRA, VetAgroSup, 63122 Saint-Genès Champanelle, France. Electronic address:

Coxiella burnetii can infect many animal species, but its circulation dynamics in and through horses is still unclear. This study evaluated horse exposure in an area known to be endemic for ruminants and humans. We assessed antibody prevalence in horse serum by ELISA, and screened by qPCR horse blood, ticks found on horses and dust from stables. Horse seroprevalence was 4% (n = 335, 37 stables) in 2015 and 12% (n = 294, 39 stables) in 2016. Of 199 horses sampled both years, 13 seroconverted, eight remained seropositive, and one seroreverted. Seropositive horses were located close to reported human cases, yet none displayed Q fever-compatible syndromes. Coxiella DNA was detected in almost 40% of collected ticks (n = 59/148 in 2015; n = 103/305 in 2016), occasionally in dust (n = 3/46 in 2015; n = 1/14 in 2016) but never in horse blood. Further studies should be implemented to evaluate if horses may be relevant indicators of zoonotic risk in urban and suburban endemic areas.
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http://dx.doi.org/10.1016/j.vetmic.2017.11.012DOI Listing
February 2018

Improved reliability of serological tools for the diagnosis of West Nile fever in horses within Europe.

PLoS Negl Trop Dis 2017 Sep 15;11(9):e0005936. Epub 2017 Sep 15.

University Paris Est, UMR 1161 Virology, ANSES, INRA, Ecole Nationale Vétérinaire d'Alfort, ANSES Animal Health Laboratory, EURL on Equine Diseases, Maisons-Alfort, France.

West Nile Fever is a zoonotic disease caused by a mosquito-borne flavivirus, WNV. By its clinical sensitivity to the disease, the horse is a useful sentinel of infection. Because of the virus' low-level, short-term viraemia in horses, the primary tools used to diagnose WNV are serological tests. Inter-laboratory proficiency tests (ILPTs) were held in 2010 and 2013 to evaluate WNV serological diagnostic tools suited for the European network of National Reference Laboratories (NRLs) for equine diseases. These ILPTs were designed to evaluate the laboratories' and methods' performances in detecting WNV infection in horses through serology. The detection of WNV immunoglobulin G (IgG) antibodies by ELISA is widely used in Europe, with 17 NRLs in 2010 and 20 NRLs in 2013 using IgG WNV assays. Thanks to the development of new commercial IgM capture kits, WNV IgM capture ELISAs were rapidly implemented in NRLs between 2010 (4 NRLs) and 2013 (13 NRLs). The use of kits allowed the quick standardisation of WNV IgG and IgM detection assays in NRLs with more than 95% (20/21) and 100% (13/13) of satisfactory results respectively in 2013. Conversely, virus neutralisation tests (VNTs) were implemented in 33% (7/21) of NRLs in 2013 and their low sensitivity was evidenced in 29% (2/7) of NRLs during this ILPT. A comparison of serological diagnostic methods highlighted the higher sensitivity of IgG ELISAs compared to WNV VNTs. They also revealed that the low specificity of IgG ELISA kits meant that it could detect animals infected with other flaviviruses. In contrast VNT and IgM ELISA assays were highly specific and did not detect antibodies against related flaviviruses. These results argue in favour of the need for and development of new, specific serological diagnostic assays that could be easily transferred to partner laboratories.
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http://dx.doi.org/10.1371/journal.pntd.0005936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5617233PMC
September 2017

Detection of West Nile Virus and other common equine viruses in three locations from the Leeward Islands, West Indies.

Acta Trop 2017 Oct 22;174:24-28. Epub 2017 Jun 22.

Department of Veterinary Science, Gluck Equine Research Center, University of Kentucky, Lexington, KY, USA.

Equines in the West Indies are used for recreational purposes, tourism industry, racing and agriculture or can be found in feral populations. Little is known in the Caribbean basin about the prevalence of some major equine infectious diseases, some with zoonotic potential, listed as reportable by the OIE. Our objective was to study the prevalence of antibodies for West Nile Virus (WNV), Equine Herpes Virus-1 and 4 (EHV-1 and EHV-4), Equine Influenza (EI), Equine Viral Arteritis (EVA) and Equine Infectious Anemia Virus (EIAV) using a retrospective serological convenience study. We used 180 equine serum samples, 140 from horses and 40 from donkeys in St. Kitts, Nevis, and Sint Eustatius, collected between 2006 and 2015 that were tested with ELISA kits and virus neutralization (for WNV and EVA). Combining ELISA with virus neutralization testing, 25 (13.8%) equine sera were WNV positive (a mixture of indigenous and imported equines) and 3 sera (1.6%) showed doubtful results. For EHV-1, 41 equines (23.7%), mean age 6.7 years, were seropositive. For EHV-4, 138 equines were found seropositive (82.8%), mean age 6.3 years. For EI, 49 equines (27.2%), mean age 7.5 years, were seropositive on ELISA, some previously vaccinated horses. No antibodies against EAV were found on virus neutralization testing, although one animal (0.6%), was EAV positive on ELISA. All samples were EIAV negative. The seroprevalence for EHV-1 and EHV-4 is similar to other parts of the world. For the first time in the study location serologic evidence of antibodies against WNV and EI is reported. This was found in both indigenous and imported animals, highlighting the need for developing proper surveillance plans based on complementary methods of virus detection. Further studies will be needed to define the prevalence, rates of transmission, characterize local virus strains, and study their impact on these populations.
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http://dx.doi.org/10.1016/j.actatropica.2017.06.023DOI Listing
October 2017

Protective efficacy of multivalent replication-abortive vaccine strains in horses against African horse sickness virus challenge.

Vaccine 2017 07 29;35(33):4262-4269. Epub 2017 Jun 29.

Department of Pathogen Molecular Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, United Kingdom. Electronic address:

African horse sickness virus (AHSV) is an orbivirus, a member of the Reoviridae family. Nine different serotypes have been described so far. AHSV is vectored by Culicoides spp. to equids, causing high mortality, particularly in horses, with considerable economic impacts. For development of a safe attenuated vaccine, we previously established an efficient reverse genetics (RG) system to generate Entry Competent Replication-Abortive (ECRA) virus strains, for all nine serotypes and demonstrated the vaccine potential of these strains in type I interferon receptor (IFNAR)-knockout mice. Here, we evaluated the protective efficacies of these ECRA viruses in AHSV natural hosts. One monoserotype (ECRA.A4) vaccine and one multivalent cocktail (ECRA.A1/4/6/8) vaccine were tested in ponies and subsequently challenged with a virulent AHSV4. In contrast to control animals, all vaccinated ponies were protected and did not develop severe clinical symptoms of AHS. Furthermore, the multivalent cocktail vaccinated ponies produced neutralizing antibodies against all serotypes present in the cocktail, and a foal born during the trial was healthy and had no viremia. These results validate the suitability of these ECRA strains as a new generation of vaccines for AHSV.
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http://dx.doi.org/10.1016/j.vaccine.2017.06.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5518735PMC
July 2017

Circulation of Zoonotic Arboviruses in Equine Populations of Mallorca Island (Spain).

Vector Borne Zoonotic Dis 2017 05 27;17(5):340-346. Epub 2017 Mar 27.

5 Departament de Biologia Evolutiva, Ecologia i Ciències Ambientals, Facultat de Biologia, IRBIO, Universitat de Barcelona , Barcelona, Spain .

The presence of major arbovirus vector species, climate change that promotes the expansion and increase of their populations, and potential animal reservoirs mean that vector-borne diseases represent a significant health risk for Mallorca's inhabitants. Microbiological monitoring of circulating arboviruses, particularly flaviviruses causing encephalitis, was initiated using domestic horses from localities near wetlands as "sentinel" hosts. A total of 291 blood samples were taken from 172 horses between 2011 and 2012, using paired samples to highlight seroconversion events. A multiplex immunoassay and confirmatory reference serological assays were used to screen sera for immunoglobulin G antibodies against West Nile (WNV), Usutu (USUV), and tick-borne encephalitis (TBEV) viruses. The seroprevalence was 6.4% (confidence interval [95% CI] 3.2%-11.0%) for WNV, 1.2% (95% CI 0.1%-4.1%) for USUV, and 0.6% (95% CI 0.0%-3.2%) for TBEV. In addition, eight horses (4.6%; 95% CI 2.0%-8.9%) were found positive for unidentified flaviviruses. Seroconversion events were detected for WNV and USUV, reflecting recent arboviral infections. These results highlight the active transmission of zoonotic arboviruses in Mallorca wetlands.
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http://dx.doi.org/10.1089/vbz.2016.2042DOI Listing
May 2017

A High-Performance Multiplex Immunoassay for Serodiagnosis of Flavivirus-Associated Neurological Diseases in Horses.

Biomed Res Int 2015 17;2015:678084. Epub 2015 Sep 17.

UMR 1161 of Virology, ANSES, INRA, ENVA, ANSES Animal Health Laboratory, EU-RL on Equine Diseases, UPE, 94701 Maisons-Alfort, France.

West Nile virus (WNV), Japanese encephalitis virus (JEV), and tick-borne encephalitis virus (TBEV) are flaviviruses responsible for severe neuroinvasive infections in humans and horses. The confirmation of flavivirus infections is mostly based on rapid serological tests such as enzyme-linked immunosorbent assays (ELISAs). These tests suffer from poor specificity, mainly due to antigenic cross-reactivity among flavivirus members. Robust diagnosis therefore needs to be validated through virus neutralisation tests (VNTs) which are time-consuming and require BSL3 facilities. The flavivirus envelope (E) glycoprotein ectodomain is composed of three domains (D) named DI, DII, and DIII, with EDIII containing virus-specific epitopes. In order to improve the serological differentiation of flavivirus infections, the recombinant soluble ectodomain of WNV E (WNV.sE) and EDIIIs (rEDIIIs) of WNV, JEV, and TBEV were synthesised using the Drosophila S2 expression system. Purified antigens were covalently bonded to fluorescent beads. The microspheres coupled to WNV.sE or rEDIIIs were assayed with about 300 equine immune sera from natural and experimental flavivirus infections and 172 nonimmune equine sera as negative controls. rEDIII-coupled microspheres captured specific antibodies against WNV, TBEV, or JEV in positive horse sera. This innovative multiplex immunoassay is a powerful alternative to ELISAs and VNTs for veterinary diagnosis of flavivirus-related diseases.
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http://dx.doi.org/10.1155/2015/678084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4589573PMC
June 2016