Marc Artois

Crossing the Interspecies Barrier: Opening the Door to Zoonotic Pathogens

This research was funded by EU FP7 grant ANTIGONE (#278976). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

USE OF RECOMBINANT VACCINIA-RABIES GLYCOPROTEIN VIRUS FOR ORAL VACCINATION OF WILDLIFE AGAINST RABIES: INNOCUITY TO SEVERAL NON-TARGET BAIT CONSUMING SPECIES

The pathogenicity of a vaccinia recombinant virus expressing the rabies glycoprotein (VVTGgRAB) was tested in several wild animal species which could compete with the natural rabies host, the red fox (Vulpes vulpes) in consuming vaccine baits in Europe. The following species were included in this study, wild boar (Sus scrofa), Eurasian badger (Meles meles), wood mouse (Apodemus sylvaticus), yellow-necked mouse (Apodemus flavicollis), bank vole (Clethrionomys glareolus), common vole (Microtus arvalis), field vole (Microtus agrestis), water vole (Arvicola terrestris), common buzzard (Buteo buteo), kestrel (Falco tinnunculus), carrion crow (Corvus corone), magpie (Pica pica) and jay (Garrulus glandarius). During the observation period, the 107 animals given the VVTGgRAB vaccine orally did not show any clinical signs. Daily monitoring for 28 days and postmortem examination did not result in the detection of pox lesions in the oral mucosa or the skin in mammals or the unfeathered portions of birds. VVTGgRAB seems to multiply in the mammalian species tested, since rabies seroconversion was observed in all of them. Birds failed to develop demonstrable rabies virus-neutralizing antibody. A seroconversion against vaccinia virus was observed in two of four wild boars. Serological results obtained in badgers and wild boars also demonstrates the absence of direct or indirect horizontal transmission oi the recombinant virus. The potential of the recombinant virus for the immunization of badgers against rabies also was investigated. Only 50% of the badgers orally administered with 1 × 1083 TCID50 of this vaccine were protected against rabies.

Potential pathogenicity for rodents of vaccines intended for oral vaccination against rabies: a comparison.

Different oral vaccines intended to control fox rabies were administered to 271 wild rodents. Vaccines were administered orally or by the mucosal route to four different European species belonging to the genera Apodemus, Arvicola, Clethrionomys and Microtus. These rodents are likely to consume baits and to have contact with the vaccine. Two genetically engineered vaccines were tested: SAG1 (an avirulent mutant of the rabies virus) and V-RG (vaccinia recombinant virus expressing the rabies glycoprotein gene). Both were found to be completely innocuous when administered orally or by the mucosal route. The residual pathogenicity of conventional modified live vaccines derived from the SAD strain was confirmed.

The status of tularemia in Europe in a one-health context: a review

The bacterium Francisella tularensis causes the vector-borne zoonotic disease tularemia, and may infect a wide range of hosts including invertebrates, mammals and birds. Transmission to humans occurs through contact with infected animals or contaminated environments, or through arthropod vectors. Tularemia has a broad geographical distribution, and there is evidence which suggests local emergence or re-emergence of this disease in Europe. This review was developed to provide an update on the geographical distribution of F. tularensis in humans, wildlife, domestic animals and vector species, to identify potential public health hazards, and to characterize the epidemiology of tularemia in Europe. Information was collated on cases in humans, domestic animals and wildlife, and on reports of detection of the bacterium in arthropod vectors, from 38 European countries for the period 1992-2012. Multiple international databases on human and animal health were consulted, as well as published reports in the literature. Tularemia is a disease of complex epidemiology that is challenging to understand and therefore to control. Many aspects of this disease remain poorly understood. Better understanding is needed of the epidemiological role of animal hosts, potential vectors, mechanisms of maintenance in the different ecosystems, and routes of transmission of the disease.

BLOOD PARASITES OF SOME BIRDS FROM THE LORRAINE REGION, FRANCE

A total of 1650 birds of 56 species representing 21 families (primarily Passeriformes), was examined for blood parasites in the Lorraine region of France. Only 120 (7.3%) birds were infected, with members of the Paridae, Sylviidae and Turdidae the most frequently parasitized. Haemoproteids were the most commonly encountered parasites followed by the leucocytozoids. Other avian hematozoon genera were uncommon. Prevalence of parasitism was closely similar each year over a three-year period. Immature birds were first noted to be infected with Leucocytozoon in mid-June, suggesting transmission in late May to early June. Haemoproteids were first noted in immature birds in early July, suggesting transmission in mid-June. A review of the literature indicates that the prevalence of parasitism by avian blood parasites has decreased in western Europe since the turn of the century and is currently much lower than the prevalence encountered in Scandinavia, central Russia and eastern North America.

Antibody response to rabbit viral hemorrhagic disease virus in red foxes (Vulpes vulpes) consuming livers of infected rabbits (Oryctolagus cuniculus).

Six red foxes (Vulpes vulpes) were given oral doses of homogenized liver from rabbits (Oryctolagus cuniculus) that died from rabbit viral hemorrhagic disease (RVHD) and four control foxes were given liver from uninfected rabbits. Antibodies to RVHD virus were monitored over 6 months. There was a pronounced antibody response 7 days after exposure which persisted to 14 days and then diminished. Low titers still were evident in three foxes at the end of the experiment. Based on these results, fox serum may be useful as an index of the prevalence of RVHD in sympatric rabbit populations.

Wildlife Disease Surveillance and Monitoring

Emerging diseases of human or veterinary importance are a major challenge to human society. As previously discussed, infectious diseases of wild mammal populations can have significant economic impact, may threaten human and livestock health (Artois et al. 2001), and can affect the welfare and conservation of game (Gortazar et al. 2006) and species of high conservation value (Cleaveland et al. 2002). Wild mammals are also implicated as sources of emerging diseases (Daszak et al. 2000a; Cleaveland 2003; Cunningham 2005). Comprehensive epidemiological investigations and disease surveillance of wild mammal populations will enhance our capaCity to detect and control infectious diseases that may emerge in the future in human and domestic animal populations. Given that the majority of diseases that have emerged in the last couple of decades had a wildlife origin (see Chapter 1), surveillance for wildlife diseases may be seen as an essential tool for the protection of human health. For these reasons, the development of effective programmes for the surveillance of disease in wildlife populations is becoming increasingly important. Epidemiological investigations in wildlife are similar in many respects in terms of their objectives, concepts and methodology to those undertaken for domestic animal health surveillance and monitoring. However, there are also substantial differences, owing to the zoological, behavioural and ecological characteristics of wildlife populations. Consequently, definitions, methods and procedures must often be adapted to suit the unique conditions of wildlife disease surveillance.

Use of wild bird surveillance, human case data and GIS spatial analysis for predicting spatial distributions of West Nile virus in Greece.

West Nile Virus (WNV) is the causative agent of a vector-borne, zoonotic disease with a worldwide distribution. Recent expansion and introduction of WNV into new areas, including southern Europe, has been associated with severe disease in humans and equids, and has increased concerns regarding the need to prevent and control future WNV outbreaks. Since 2010, 524 confirmed human cases of the disease have been reported in Greece with greater than 10% mortality. Infected mosquitoes, wild birds, equids, and chickens have been detected and associated with human disease. The aim of our study was to establish a monitoring system with wild birds and reported human cases data using Geographical Information System (GIS). Potential distribution of WNV was modelled by combining wild bird serological surveillance data with environmental factors (e.g. elevation, slope, land use, vegetation density, temperature, precipitation indices, and population density). Local factors including areas of low altitude and proximity to water were important predictors of appearance of both human and wild bird cases (Odds Ratio = 1,001 95%CI = 0,723–1,386). Using GIS analysis, the identified risk factors were applied across Greece identifying the northern part of Greece (Macedonia, Thrace) western Greece and a number of Greek islands as being at highest risk of future outbreaks. The results of the analysis were evaluated and confirmed using the 161 reported human cases of the 2012 outbreak predicting correctly (Odds = 130/31 = 4,194 95%CI = 2,841–6,189) and more areas were identified for potential dispersion in the following years. Our approach verified that WNV risk can be modelled in a fast cost-effective way indicating high risk areas where prevention measures should be implemented in order to reduce the disease incidence.

PCR detection and analyzis of potentially zoonotic Hepatitis E virus in French rats

BackgroundHepatitis E virus has been detected in a wide range of animals. While Genotypes 1-2 of this virus infect only humans, 3-4 can spread from animals to humans and cause sporadic cases of human disease. Pig, and possibly also rats, may act as a reservoir for virus. From a public health perspective it is important to clarify the role of rats for infection of humans. Rats often live close to humans and are therefore of special interest to public health. Rats live of waste and inside the sewage system and may become infected. Reports of hepatitis E virus in rats have been published but not from France. The possibility that rats in an urban area in France were Hepatitis E virus infected, with which type and relationship to other strains was investigated. This study provides information important to public health and better understanding the occurrence of hepatitis E virus in the environment.Eighty one rats (Rattus Norvegicus) were captured, euthanized, sampled (liver and faeces) and analyzed by real-time RT-PCR’s, one specific for Hepatitis E virus in rats and one specific for genotype 1-4 that that is known to infect humans. Positive samples were analyzed by a nested broad spectrum RT-PCR, sequenced and compared with sequences in Genbank.FindingsTwelve liver and 11 faeces samples out of 81 liver and 81 faeces samples from 81 captured rats were positive in the PCR specific for Hepatitis E virus in rats and none in the PCR specific for genotype 1-4. Comparison by nucleotide BLAST showed a maximum of 87% similarity to Hepatitis E virus previously detected in rats and significantly less to genotype 1-4.ConclusionsThis is the first study demonstrating that rats in France carries hepatitis E virus and provide information regarding its relation to other virus strains previously detected in rats and other host animals world-wide. Genotype 1-4 was not detected.

Detection and genetic characterization of Seoul virus from commensal brown rats in France.

BackgroundHantaviruses are single-stranded RNA viruses, which are transmitted to humans primarily via inhalation of aerosolised virus in contaminated rodent urine and faeces. Whilst infected reservoir hosts are asymptomatic, human infections can lead to two clinical manifestations, haemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS), with varying degrees of clinical severity. The incidence of rodent and human cases of Seoul virus (SEOV) in Europe has been considered to be low, and speculated to be driven by the sporadic introduction of infected brown rats (Rattus norvegicus) via ports.MethodsBetween October 2010 and March 2012, 128 brown rats were caught at sites across the Lyon region in France.ResultsSEOV RNA was detected in the lungs of 14% (95% CI 8.01 – 20.11) of brown rats tested using a nested pan-hantavirus RT-PCR (polymerase gene). Phylogenetic analysis supports the inclusion of the Lyon SEOV within Lineage 7 with SEOV strains originating from SE Asia and the previously reported French & Belgian SEOV strains. Sequence data obtained from the recent human SEOV case (Replonges) was most similar to that obtained from one brown rat trapped in a public park in Lyon city centre. We obtained significantly improved recovery of virus genome sequence directly from SEOV infected lung material using a simple viral enrichment approach and NGS technology.ConclusionsThe detection of SEOV in two wild caught brown rats in the UK and the multiple detection of SEOV infected brown rats in the Lyon region of France, suggests that SEOV is circulating in European brown rats. Under-reporting and difficulties in identifying the hantaviruses associated with HFRS may mask the public health impact of SEOV in Europe.