Widespread Exposure to Mosquitoborne California Serogroup Viruses in Caribou, Arctic Fox, Red Fox, and Polar Bears, Canada.

Northern Canada is warming at 3 times the global rate. Thus, changing diversity and distribution of vectors and pathogens is an increasing health concern. California serogroup (CSG) viruses are mosquitoborne arboviruses; wildlife reservoirs in northern ecosystems have not been identified. We detected CSG virus antibodies in 63% (95% CI 58%-67%) of caribou (n = 517), 4% (95% CI 2%-7%) of Arctic foxes (n = 297), 12% (95% CI 6%-21%) of red foxes (n = 77), and 28% (95% CI 24%-33%) of polar bears (n = 377). Sex, age, and summer temperatures were positively associated with polar bear exposure; location, year, and ecotype were associated with caribou exposure. Exposure was highest in boreal caribou and increased from baseline in polar bears after warmer summers. CSG virus exposure of wildlife is linked to climate change in northern Canada and sustained surveillance could be used to measure human health risks.

Seroprevalence of Jamestown Canyon virus in the Japanese general population.

BACKGROUND: Jamestown Canyon virus (JCV) is a mosquito-borne orthobunyavirus that causes acute febrile illness, meningitis, and meningoencephalitis, mainly among adults. JCV is widely distributed in North America and the number of JCV cases in the U.S. has increased in recent years. Therefore, the central nervous system disease caused by JCV can be considered a potentially re-emerging viral disease. However, the seroprevalence of JCV is unknown in Japan. The purpose of this study is to evaluate the seroprevalence of JCV in the Japanese population. METHODS: We used an IgG enzyme-linked immunosorbent assay (IgG-ELISA) with JCV-infected cell-lysates and/or a neutralizing (NT) antibody assay. The cut-off value of IgG-ELISA was determined using IgG-ELISA to analyze serum specimens from 37 healthy Japanese donors. IgG-ELISA was validated by assessing its sensitivity and specificity, using 38 human serum samples previously tested for the presence or absence of antibodies against JCV and snowshoe hare virus (SSHV), in an in-house NT antibody assay conducted by the Public Health Agency of Canada. The seroepidemiological study was performed using IgG-ELISA and NT antibody assay to analyze 246 human serum samples from the serum bank of the National Institute of Infectious Diseases (NIID) in Japan. RESULTS: The cut-off value of IgG-ELISA was determined at 0.20, based on the mean (- 0.075) and standard deviation (0.092) values using Japanese donors' sera. The sensitivity and the specificity of IgG-ELISA determined using 25 JCV-positive and 4 JCV-negative serum samples were 96 and 100%, respectively. Analysis of the 246 Japanese serum samples revealed that no specimen showed a higher value than the cut-off value of IgG-ELISA, and no sample tested positive by the NT antibody assay. CONCLUSIONS: Our results showed that JCV is not circulating significantly in Japan. To the best of our knowledge, this is the first report to demonstrate the seroprevalence of JCV in the general population in Japan.

Differences in Neuropathogenesis of Encephalitic California Serogroup Viruses.

The California serogroup of orthobunyaviruses comprises a group of mosquitoborne viruses, including La Crosse (LACV), snowshoe hare (SSHV), Tahyna (TAHV), Jamestown Canyon (JCV), and Inkoo (INKV) viruses, that cause neurologic disease in humans of differing ages with varying incidences. To determine how the pathogenesis of these viruses differs, we compared their ability to induce disease in mice and replicate and induce cell death in vitro. In mice, LACV, TAHV, and SSHV induced neurologic disease after intraperitoneal and intranasal inoculation, and JCV induced disease only after intranasal inoculation. INKV rarely induced disease, which correlated with less viral antigen in the brain than the other viruses. In vitro, all viruses replicated to high titers; however, LACV, SSHV, and TAHV induced high cell death, whereas JCV and INKV did not. Results demonstrated that CSG viruses differ in neuropathogenesis in vitro and in vivo, which correlates with the differences in pathogenesis reported in humans.

California Serogroup Virus Infection Associated with Encephalitis and Cognitive Decline, Canada, 2015.

California serogroup (CSG) viruses, such as Jamestown Canyon and snowshoe hare viruses, are mosquitoborne pathogens that cause febrile illness and neurologic disease. Human exposures have been described across Canada, but infections are likely underdiagnosed. We describe a case of neuroinvasive illness in a New Brunswick, Canada, patient infected with a CSG virus.

Mosquitoes from Europe Are Able to Transmit Snowshoe Hare Virus.

Snowshoe hare virus (SSHV) is a zoonotic arthropod-borne virus (arbovirus) circulating in colder areas of the Northern Hemisphere. SSHV is maintained in an enzootic cycle between small mammals and mosquitoes, assumably of the genera Aedes and Culiseta. Symptoms of SSHV human infection can range from asymptomatic to severe neuroinvasive disease. Studies on SSHV transmission are limited, and there is no information available on whether mosquitoes of the genus Culex are able to transmit SSHV. Therefore, we investigated six mosquito species via salivation assay for their vector competence. We demonstrated that SSHV can be transmitted by the abundant European Culex species Cx. pipiens biotype pipiens, Cx. pipiens biotype molestus, and Cx. torrentium with low transmission efficiency between 3.33% and 6.67%. Additionally, the invasive species Ae. albopictus can also transmit SSHV with a low transmission efficiency of 3.33%. Our results suggest that local transmission of SSHV after introduction to Europe seems to be possible from a vector perspective.

Serologic Survey of Selected Arthropod-Borne Pathogens in Free-Ranging Snowshoe Hares (Lepus americanus) Captured in Northern Michigan, USA.

Snowshoe hares (Lepus americanus) in the Upper Peninsula (UP) of Michigan, USA, occupy the southern periphery of the species' range and are vulnerable to climate change. In the eastern UP, hares are isolated by the Great Lakes, potentially exacerbating exposure to climate-change-induced habitat alterations. Climate change is also measurably affecting distribution and prevalence of vector-borne pathogens in North America, and increases in disease occurrence and prevalence can be one signal of climate-stressed wildlife populations. We conducted a serosurvey for vector-borne pathogens in snowshoe hares that were captured in the Hiawatha National Forest in the eastern UP of Michigan, USA, 2016-2017. The most commonly detected antibody response was to the mosquito-borne California serogroup snowshoe hare virus (SSHV). Overall, 24 (51%) hares screened positive for SSHV antibodies and of these, 23 (96%) were confirmed positive by plaque reduction neutralization test. We found a positive association between seroprevalence of SSHV and live weight of snowshoe hares. Additionally, we detected a significant effect of ecological land type group on seroprevalence of SSHV, with strong positive support for a group representing areas that tend to support high numbers of hares (i.e., acidic mineral containing soils with cedar, mixed swamp conifers, tamarack and balsam fir as common overstory vegetation). We also detected and confirmed antibodies for Jamestown Canyon virus and Silverwater virus in a single hare each. We did not detect antibodies to other zoonotic vector-borne pathogens, including Lacrosse encephalitis virus, West Nile virus, Borrelia burgdorferi, Powassan virus, and Francisella tularensis. These results provide a baseline for future serological studies of vector-transmitted diseases that may increase climate vulnerability of snowshoe hares in the UP of Michigan, as well as pose a climate-related zoonotic risk.

Zoonotic infections in communities of the James Bay Cree territory: An overview of seroprevalence.

The Cree communities of James Bay are at risk for contracting infectious diseases transmitted by wildlife. Data from serological testing for a range of zoonotic infections performed in the general population (six communities), or trappers and their spouses (one community), were abstracted from four population-based studies conducted in Cree territory (Quebec) between 2005 and 2009. Evidence of exposure to Trichinella species, Toxoplasma gondii, Toxocara canis, Echinococcus granulosus, Leptospira species, Coxiella burnetii and Francisella tularensis was verified in all communities, whereas antibodies against Sin Nombre virus and California serogroup viruses (Jamestown Canyon and snowshoe hare viruses) were evaluated in three and six communities, respectively. Seroprevalence varied widely among communities: snowshoe hare virus (1% to 42%), F tularensis (14% to 37%), Leptospira species (10% to 27%), Jamestown Canyon virus (9% to 24%), C burnetii (0% to 18%), T gondii (4% to 12%), T canis (0% to 10%), E granulosus (0% to 4%) and Trichinella species (0% to 1%). No subject had serological evidence of Sin Nombre virus exposure. These data suggest that large proportions of the Cree population have been exposed to at least one of the targeted zoonotic agents. The Cree population, particularly those most heavily exposed to fauna, as well as the medical staff living in these regions, should be aware of these diseases. Greater awareness would not only help to decrease exposures but would also increase the chance of appropriate diagnostic testing.

Les communautés cries de la Baie James sont vulnérables aux maladies infectieuses transmises par les animaux sauvages. Les données tirées des tests sérologiques sur une série de zoonoses effectués dans la population générale (six communautés) ou chez les trappeurs et leur conjointe (une communauté) ont été extraites de quatre études en population menées en territoire cri, au Québec, entre 2005 et 2009. Les manifestations d'exposition aux espèces de Trichinella, au Toxoplasma gondii, au Toxocara canis, à l'Echinococcus granulosus, aux espèces de Leptospira, au Coxiella burnetii et au Francisella tularensis ont été vérifiées dans toutes les communautés, tandis que les anticorps contre le virus Sin Nombre et les virus du sérogroupe Californie (virus Jamestown Canyon et snowshoe hare) ont été évalués dans trois et six communautés, respectivement. La séroprévalence variait considérablement selon les communautés, comme suit : virus snowshoe hare (1 % à 42 %), F tularensis (14 % à 37 %), espèces de Leptospira (10 % à 27 %), virus Jamestown Canyon (9 % à 24 %), C burnetii (0 % à 18 %), T gondii (4 % à 12 %), T canis (0 % à 10 %), E granulosus (0 % à 4 %) et espèces de Trichinella (0 % à 1 %). Aucun sujet n'avait de manifestation sérologique d'exposition au virus Sin Nombre. Ces données laissent supposer que de fortes proportions de la population crie ont été exposées à au moins l'un des agents zoonotiques ciblés. La population crie, notamment les peuples les plus exposés aux animaux sauvages, ainsi que le personnel médical qui habite dans ces régions, devrait connaître ces maladies. Une meilleure sensibilisation contribuerait non seulement à réduire les expositions, mais accroîtrait également la possibilité de tests diagnostiques pertinents.

Snowshoe hare virus: discovery, distribution, vector and host associations, and medical significance.

Snowshoe hare virus (SSHV), within the California serogroup of the genus Orthobunyavirus, family Peribunyaviridae, was first isolated from a snowshoe hare (Lepus americanus) in Montana, United States, in 1959. The virus, closely related to LaCrosse virus (LACV) and Chatanga virus (CHATV), occurs across Canada and the northern latitudes of the United States, primarily in the northern tier of states bordering Canada. Reports of SSHV in northern Europe and Asia are probably the closely related to CHATV, or the less closely related Tahyna virus. Vertebrate associations include snowshoe hares and ground squirrels, demonstrated by field isolation of virus from wild-caught animals, seroconversion of snowshoe hares, seroconversion of sentinel rabbits, isolation of virus from sentinel rabbits, and experimental infections demonstrating viremia. Isolations of virus from field populations of mosquitoes include primarily univoltine and boreal mosquitoes of the genus Aedes, Culiseta impatiens and Culiseta inornata; and, rarely, certain multivoltine floodwater Aedes species. Experimental transmission studies in mosquitoes show infection in and transmission by boreal Aedes and Culiseta inornata. Isolation of SSHV from larval Aedes on three occasions, and experimentation in Culiseta inornata, reveal transovarial transmission of the virus in mosquitoes. Serosurveys reveal exposure to SSHV in human and domestic animals, with rates of seropositivity commonly high in some settings in Alaska and Canada, but disease in humans or horses has rarely been reported, only in Canada.

California Serogroup Viruses in a Changing Canadian Arctic: A Review.

The Arctic is warming at four times the global rate, changing the diversity, activity and distribution of vectors and associated pathogens. While the Arctic is not often considered a hotbed of vector-borne diseases, Jamestown Canyon virus (JCV) and Snowshoe Hare virus (SSHV) are mosquito-borne zoonotic viruses of the California serogroup endemic to the Canadian North. The viruses are maintained by transovarial transmission in vectors and circulate among vertebrate hosts, both of which are not well characterized in Arctic regions. While most human infections are subclinical or mild, serious cases occur, and both JCV and SSHV have recently been identified as leading causes of arbovirus-associated neurological diseases in North America. Consequently, both viruses are currently recognised as neglected and emerging viruses of public health concern. This review aims to summarise previous findings in the region regarding the enzootic transmission cycle of both viruses. We identify key gaps and approaches needed to critically evaluate, detect, and model the effects of climate change on these uniquely northern viruses. Based on limited data, we predict that (1) these northern adapted viruses will increase their range northwards, but not lose range at their southern limits, (2) undergo more rapid amplification and amplified transmission in endemic regions for longer vector-biting seasons, (3) take advantage of northward shifts of hosts and vectors, and (4) increase bite rates following an increase in the availability of breeding sites, along with phenological synchrony between the reproduction cycle of theorized reservoirs (such as caribou calving) and mosquito emergence.

Jamestown Canyon and snowshoe hare virus seroprevalence in New Brunswick.

Background: Jamestown Canyon virus (JCV) and snowshoe hare virus (SSHV) are wide-ranging mosquito-borne arboviruses in the California serogroup viruses (CSGV) that are known to circulate in New Brunswick. Despite potential for debilitating central nervous system manifestations, the prevalence of human exposure to these viruses in New Brunswick is unknown. The goal of this study was to quantify rates of human exposure in New Brunswick to these neglected arboviruses. Methods: A retrospective, anonymized provincial serosurvey was performed using a stratified random sample of residual sera submitted between May 2015 and August 2016. To determine the seroprevalence of JCV and SSHV, competitive enzyme-linked immunosorbent assay-positive samples were confirmed positive using plaque-reduction neutralization testing (PRNT). Results: A total of 452 serum samples were screened. The seroprevalence of antibodies against CSGV was estimated to be 31.6% (95% CI 27.4% to 36.1%) with 143 positive samples. PRNT results indicated that most single virus exposures were due to JCV (38 of 143; 26.6%) rather than SSHV (3 of 143; 2.1%). The species of CSGV, to which the remaining 102 seropositive people were exposed, could not be precisely determined. Conclusions: The prevalence of human exposure to CSGV is high but comparable to rates observed in other Atlantic Canadian jurisdictions. Studies such as this provide important baseline epidemiological data regarding the risk of exposure to these neglected arboviruses. SSHV and JCV should be considered in the differential diagnosis for undiagnosed febrile and neuroinvasive illness during mosquito season, particularly when testing for common aetiologies is negative or inconclusive.

Historique : Le virus de Jamestown Canyon (VJC) et le virus du lièvre d'Amérique (VLA) sont des arbovirus à grande portée transmis par des moustiques des virus du sérogroupe Californie (VSGC) qui circulent au Nouveau-Brunswick (NB). Malgré le risque de manifestations débilitantes du système nerveux central, on ne connaît pas la prévalence d'exposition humaine à ces virus au NB. La présente étude visait à quantifier le taux d'exposition humaine à ces arbovirus négligés au NB. Méthodologie : Les chercheurs ont réalisé une enquête sérologique rétrospective provinciale anonymisée au moyen d'un échantillon randomisé stratifié de sérum résiduel soumis entre mai 2015 et août 2016 au dépistage systématique. Ils ont stratifié le processus de sélection selon l'âge, le sexe et la zone de santé régionale afin de garantir un échantillonnage proportionné. Pour déterminer la séroprévalence du VJC et du VLA, ils ont confirmé la positivité des résultats d'échantillons positifs au test ELISA au moyen de tests de séroneutralisation par réduction des plaques (TSRP). Résultats : Au total, 452 échantillons de sérum ont fait l'objet d'un dépistage. Au NB, la séroprévalence des anticorps anti-VSGC était évaluée à 31,6 % (IC à 95 %, 27,4 % à 36,1 %), pour 143 échantillons positifs. Selon les résultats du TSRP, la plupart des expositions à un seul virus étaient causées par le VJC (38 cas sur 143, 26,6 %) plutôt qu'au VLA (trois cas sur 143, 2,1 %). Les espèces de VSGC, auxquelles les 102 autres personnes séropositives ont été exposées, n'ont pas pu être établies avec précision. Conclusions : La prévalence d'exposition humaine au VSGC est élevée, mais comparable aux taux observés dans d'autres régions des provinces de l'Atlantique. Des études comme celle-ci fournissent des données épidémiologiques de référence importantes à l'égard du risque d'exposition humaine à ces arbovirus négligés. Il faut tenir compte du VLA et du VJC dans le diagnostic différentiel de maladie fébrile et neuro-invasive pendant la saison des moustiques, notamment lorsque les tests pour dépister d'autres étiologies courantes sont négatifs ou non concluants.

The Seasonal Timing of Snowshoe Hare Virus Transmission on the Island of Newfoundland, Canada.

Arthropod-borne diseases negatively affect humans worldwide. Understanding the biology of the arthropod vectors and the pathogens they harbor, the arthropods are moving targets as a result of climate change, ecosystem degradation, species introductions, and increased human travel. Viruses within the California serogroup of the genus Orthobunyavirus (family Bunyaviridae) are among the mosquito-borne viruses of concern owing to their zoonotic potential. Two of these, snowshoe hare virus (SSHV) and Jamestown Canyon virus, were shown, using a combination of serology and virus isolations, to circulate on the Island of Newfoundland, Canada, in the 1980s. More recently, serological analysis demonstrated that these two viruses continue to circulate on the Island in several domesticated and wild animals. Here, we detected the seroconversion to SSHV in wild snowshoe hares and in a single sentinel rabbit. The seroconversion in the sentinel rabbit occurred in early August (2011), which corresponded to the weeks of peak mosquito collections and the timing of the detection of SSHV in suspected mosquito vectors. A portion of the SSHV S segment sequence was generated from mosquito pools collected at sites near the sentinel rabbits and phylogenetically analyzed using the neighbor-joining method with other available California serogroup virus sequences. This analysis validated the SSHV identification but showed that the Newfoundland sequence fell outside the other SSHV sequences available, which originated from the United States between 1959 and 2005.

Snowshoe Hare Virus Causing Meningoencephalitis in a Young Adult From Northern Manitoba, Canada.

We describe a dramatic presentation of meningoencephalitis, in a young Aboriginal male from Northern Manitoba, due to infection with the Snowshoe hare virus, a member of the California serogroup viruses. Snowshoe hare virus represents a rare cause of meningoencephalitis, and, to date, few Canadian cases have been described in the literature.

Serologic Survey of Snowshoe Hares (Lepus americanus) in the Greater Yellowstone Area for Brucellosis, Tularemia, and Snowshoe Hare Virus.

We examined sera from snowshoe hares (Lepus americanus) livetrapped in the northern Greater Yellowstone Area (GYA), US, for antibodies to Brucella abortus, Francisella tularensis, and snowshoe hare virus (SSHV). Zero of 90, 0 of 67, and 40 of 100 samples were antibody positive for B. abortus, F. tularensis, and SSHV, respectively. Hares were trapped from 2009 to 2012, and of the six animals that were captured twice with at least 1 yr between captures, four developed antibody to SSHV, indicating active exposure to the agent. These findings suggest snowshoe hares in the GYA do not play a significant role as a reservoir of B. abortus, but do maintain the zoonotic, encephalitic SSHV in the population.

Isolation and characterization of a California encephalitis serogroup orthobunyavirus from Finnish mosquitoes.

The mosquito-borne California encephalitis serogroup viruses of the genus Orthobunyavirus (family Bunyaviridae) include several causative agents of encephalitis in humans. Until recently, Inkoo virus (INKV) was the only orthobunyavirus isolated in Finland, showing high seroprevalence in the population. In this study, we recovered five orthobunyavirus isolates from mosquitoes collected in eastern Finland in the early autumns of 2007 and 2008 by inoculation of Vero cells. The isolates were determined by S, M and L segment sequences to represent the California encephalitis virus species but distinct from INKV (68% polyprotein amino acid (aa) identity). In genetic analyses, isolates clustered together with a number of westernmost Chatanga virus isolates (98% polyprotein aa identity) reported from Russia, forming a distinct phylogroup. However, the sequence homology of this phylogroup to the majority of Chatanga isolates, comprising three different geographically clustered phylogroups, was considerably lower (89-92% polyprotein aa identity). The five new isolates were designated as Möhkö isolates of Chatanga virus, according to the village of origin. The isolates were closely related to Snowshoe hare virus (SSHV) and La Crosse virus (LACV) with an aa identity of 87% and 82% within the M segment polyprotein, respectively. The genetic relatedness of Möhkö isolates to a number of human pathogenic orthobunyaviruses warrants further investigation on their potential disease associations and further serological analysis is needed to compare them to other Chatanga virus isolates and SSHV to determine their true antigenic relation.