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Jamestown Canyon virus (JCV) is a mosquitoborne orthobunyavirus in the California serogroup that circulates throughout Canada and the United States. Most JCV exposures result in asymptomatic infection or a mild febrile illness, but JCV can also cause neurologic diseases, such as meningitis and encephalitis. We describe a case series of confirmed JCV-mediated neuroinvasive disease among persons from the provinces of British Columbia, Alberta, Quebec, and Nova Scotia, Canada, during 2011-2016. We highlight the case definitions, epidemiology, unique features and clinical manifestations, disease seasonality, and outcomes for those cases. Two of the patients (from Quebec and Nova Scotia) might have acquired JCV infections during travel to the northeastern region of the United States. This case series collectively demonstrates JCV's wide distribution and indicates the need for increased awareness of JCV as the underlying cause of meningitis/meningoencephalitis during mosquito season.

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.

Background: Serological assays designed to detect SARS-CoV-2 antibodies are being used in serological surveys and other specialized applications. As a result, and to ensure that the outcomes of serological testing meet high quality standards, evaluations are required to assess the performance of these assays and the proficiency of laboratories performing them., Methods: A panel of 60 plasma/serum samples from blood donors who had reverse transcriptase-polymerase chain reaction (RT-PCR) confirmed SARS-CoV-2 infections and 21 SARS-CoV-2 negative samples were secured and distributed to interested laboratories within Canada ( n = 30) and the United States ( n = 1). Participating laboratories were asked to provide details on the diagnostic assays used, the platforms the assays were performed on, and the results obtained for each panel sample. Laboratories were blinded with respect to the expected outcomes., Results: The performance of the different assays evaluated was excellent, with the high-throughput platforms of Roche, Ortho, and Siemens demonstrating 100% sensitivity. Most other high-throughput platforms had sensitivities of >93%, with the exception of the IgG assay using the Abbott ARCHITECT which had an average sensitivity of only 87%. The majority of the high-throughput platforms also demonstrated very good specificities (>97%)., Conclusion: This proficiency study demonstrates that most of the SARS-CoV-2 serological assays utilized by provincial public health or hospital laboratories in Canada have acceptable sensitivity and excellent specificity., (Copyright © 2022, Association of Medical Microbiology and Infectious Disease Canada (AMMI Canada).)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic galvanized blood donor seroprevalence studies, which continue to inform public health policy. We propose that the two Canadian blood suppliers, Héma-Québec and Canadian Blood Services, expand their role in public health surveillance in the post-pandemic period. Together blood suppliers have near-national reach, collecting blood donations nearly every day in all larger cities and many smaller municipalities. Blood donors are a healthy subset of the general population. Demographic data, routine infectious disease testing and screening questionnaire data are collected for all donations. Close to one million blood samples per year could be made available for surveillance. With 90% repeat donors, longitudinal sampling is possible. Current blood donor surveillance includes monitoring infectious marker rates in low risk (e.g. HIV, hepatitis C virus) or asymptomatic (e.g. West Nile virus) populations, and ad hoc studies to monitor transfusion-transmissible infections. These include tick-borne infections such as Babesia microti and foodborne infections such as hepatitis E. Canadian Blood Services and Héma-Québec are actively seeking to engage with public health professionals to further develop a role in public health surveillance., Competing Interests: Competing interests: None.

Cache Valley virus (CVV) is a mosquitoborne virus that infects livestock and humans. We report results of surveillance for CVV in New York, USA, during 2000-2016; full-genome analysis of selected CVV isolates from sheep, horse, humans, and mosquitoes from New York and Canada; and phenotypic characterization of selected strains. We calculated infection rates by using the maximum-likelihood estimation method by year, region, month, and mosquito species. The highest maximum-likelihood estimations were for Anopheles spp. mosquitoes. Our phylogenetic analysis identified 2 lineages and found evidence of segment reassortment. Furthermore, our data suggest displacement of CVV lineage 1 by lineage 2 in New York and Canada. Finally, we showed increased vector competence of An. quadrimaculatus mosquitoes for lineage 2 strains of CVV compared with lineage 1 strains.

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., Competing Interests: The authors have nothing to disclose., (Copyright © 2021, Association of Medical Microbiology and Infectious Disease Canada (AMMI Canada).)

Background: Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) surrogate neutralization assays that obviate the need for viral culture offer substantial advantages regarding throughput and cost. The cPass SARS-CoV-2 Neutralization Antibody Detection Kit (GenScript) is the first such commercially available assay that detects antibodies that block receptor-binding domain (RBD)/angiotensin-converting enzyme (ACE)-2 interaction. We aimed to evaluate cPass to inform its use and assess its added value compared with anti-RBD enzyme-linked immunosorbent assays (ELISAs)., Methods: Serum reference panels comprising 205 specimens were used to compare cPass to plaque-reduction neutralization test (PRNT) and a pseudotyped lentiviral neutralization (PLV) assay for detection of neutralizing antibodies. We assessed the correlation of cPass with an ELISA detecting anti-RBD immunoglobulin (Ig)G, IgM, and IgA antibodies at a single timepoint and across intervals from onset of symptoms of SARS-CoV-2 infection., Results: Compared with PRNT-50, cPass sensitivity ranged from 77% to 100% and specificity was 95% to 100%. Sensitivity was also high compared with the pseudotyped lentiviral neutralization assay (93%; 95% confidence interval [CI], 85-97), but specificity was lower (58%; 95% CI, 48-67). Highest agreement between cPass and ELISA was for anti-RBD IgG ( r = 0.823). Against the pseudotyped lentiviral neutralization assay, anti-RBD IgG sensitivity (99%; 95% CI, 94-100) was very similar to that of cPass, but overall specificity was lower (37%; 95% CI, 28-47). Against PRNT-50, results of cPass and anti-RBD IgG were nearly identical., Conclusions: The added value of cPass compared with an IgG anti-RBD ELISA was modest., (© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Better diagnostic tools are needed to combat the ongoing COVID-19 pandemic. Here, to meet this urgent demand, we report a homogeneous immunoassay to detect IgG antibodies against SARS-CoV-2. This serological assay, called SATiN, is based on a tri-part Nanoluciferase (tNLuc) approach, in which the spike protein of SARS-CoV-2 and protein G, fused respectively to two different tNLuc tags, are used as antibody probes. Target engagement of the probes allows reconstitution of a functional luciferase in the presence of the third tNLuc component. The assay is performed directly in the liquid phase of patient sera and enables rapid, quantitative and low-cost detection. We show that SATiN has a similar sensitivity to ELISA, and its readouts are consistent with various neutralizing antibody assays. This proof-of-principle study suggests potential applications in diagnostics, as well as disease and vaccination management.

Hantavirus cardiopulmonary syndrome (HCPS) is a severe respiratory disease caused by Sin Nombre virus in North America (SNV). As of January 1, 2020, SNV has caused 143 laboratory-confirmed cases of HCPS in Canada. We review critical aspects of SNV virus epidemiology and the ecology, biology, and genetics of HCPS in Canada.

Most of the patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mount a humoral immune response to the virus within a few weeks of infection, but the duration of this response and how it correlates with clinical outcomes has not been completely characterized. Of particular importance is the identification of immune correlates of infection that would support public health decision-making on treatment approaches, vaccination strategies, and convalescent plasma therapy. While ELISA-based assays to detect and quantitate antibodies to SARS-CoV-2 in patient samples have been developed, the detection of neutralizing antibodies typically requires more demanding cell-based viral assays. Here, we present a safe and efficient protein-based assay for the detection of serum and plasma antibodies that block the interaction of the SARS-CoV-2 spike protein receptor binding domain (RBD) with its receptor, angiotensin-converting enzyme 2 (ACE2). The assay serves as a surrogate neutralization assay and is performed on the same platform and in parallel with an ELISA for the detection of antibodies against the RBD, enabling a direct comparison. The results obtained with our assay correlate with those of 2 viral-based assays, a plaque reduction neutralization test (PRNT) that uses live SARS-CoV-2 virus and a spike pseudotyped viral vector-based assay.

Background: Lyme disease is emerging in Canada due to expansion of the range of the tick vector Ixodes scapularis from the United States. National surveillance for human Lyme disease cases began in Canada in 2009. Reported numbers of cases increased from 144 cases in 2009 to 2025 in 2017. It has been claimed that few (< 10%) Lyme disease cases are reported associated with i) supposed under-diagnosis resulting from perceived inadequacies of serological testing for Lyme disease, ii) expectation that incidence in Canadian provinces and neighbouring US states should be similar, and iii) analysis of serological responses of dogs to the agent of Lyme disease, Borrelia burgdorferi. We argue that performance of serological testing for Lyme disease is well studied, and variations in test performance at different disease stages are accounted for in clinical diagnosis of Lyme disease, and in surveillance case definitions. Extensive surveillance for tick vectors has taken place in Canada providing a clear picture of the emergence of risk in the Canadian environment. This surveillance shows that the geographic scope of I. scapularis populations and Lyme disease risk is limited but increasing in Canada. The reported incidence of Lyme disease in Canada is consistent with this pattern of environmental risk, and the differences in Lyme disease incidence between US states and neighbouring Canadian provinces are consistent with geographic differences in environmental risk. Data on serological responses in dogs from Canada and the US are consistent with known differences in environmental risk, and in numbers of reported Lyme disease cases, between the US and Canada., Conclusion: The high level of consistency in data from human case and tick surveillance, and data on serological responses in dogs, suggests that a high degree of under-reporting in Canada is unlikely. We speculate that approximately one third of cases are reported in regions of emergence of Lyme disease, although prospective studies are needed to fully quantify under-reporting. In the meantime, surveillance continues to identify and track the ongoing emergence of Lyme disease, and the risk to the public, in Canada.

An immunosuppressed man developed rapidly progressive neurologic symptoms resulting in quadriplegia. On magnetic resonance imaging multiple areas of abnormal enhancement were observed in the brain, and spinal cord. Serologic evidence of West Nile Virus (WNV) was discovered in the cerebrospinal fluid. This report highlights the catastrophic complications of WNV in an immunocompromised host.

There are currently over 80 species of mosquito endemic in Canada-although only a few of these carry pathogens that can cause disease in humans. West Nile virus, Eastern equine encephalitis virus and the California serogroup viruses (including the Jamestown Canyon and snowshoe hare viruses) are mosquito-borne viruses that have been found to cause human infections in North America, including in Canada. Over the last 20 years, the incidence of most of these endemic mosquito-borne diseases (MBD) has increased approximately 10% in Canada, due in large part to climate change. It is anticipated that both the mosquito lifecycle and virus transmission patterns will be affected by climate change, resulting in an increase in both the range and local abundance of several important mosquito species. Laboratory studies and mathematical modelling suggest that increased ambient temperatures, changes in precipitation and extreme weather events associated with climate change will likely continue to drive mosquito vector and MBD range expansion, increasing the duration of transmission seasons and leading to MBD-related epidemics. Furthermore, Canada's endemic MBDs have complex transmission cycles, involving multiple reservoir hosts (birds and mammals), multiple pathogens and multiple mosquito species-all of which may be sensitive to climate and other environmental changes, and making forecasting of potential emerging trends difficult. These expected climate-induced changes in mosquitoes and MBDs underline the need for continued (and expanded) surveillance and research to ensure timely and accurate evaluation of the risks to the public health of Canadians., Competing Interests: Conflict of interest: None.

Of the 3,500 species of mosquitoes worldwide, only a small portion carry and transmit the mosquito-borne diseases (MBDs) that cause approximately half a million deaths annually worldwide. The most common exotic MBDs, such as malaria and dengue, are not currently established in Canada, in part because of our relatively harsh climate; however, this situation could evolve with climate change. Mosquitoes native to Canada may become infected with new pathogens and move into new regions within Canada. In addition, new mosquito species may move into Canada from other countries, and these exotic species may bring exotic MBDs as well. With high levels of international travel, including to locations with exotic MBDs, there will be more travel-acquired cases of MBDs. With climate change, there is the potential for exotic mosquito populations to become established in Canada. There is already a small area of Canada where exotic Aedes mosquitoes have become established although, to date, there is no evidence that these carry any exotic (or already endemic) MBDs. The increased risks of spreading MBDs, or introducing exotic MBDs, will need a careful clinical and public health response. Clinicians will need to maintain a high level of awareness of current trends, to promote mosquito bite prevention strategies, and to know the laboratory tests needed for early detection and when to report laboratory results to public health. Public health efforts will need to focus on ongoing active surveillance, public and professional awareness and mosquito control. Canadians need to be aware of the risks of acquiring exotic MBDs while travelling abroad as well as the risk that they could serve as a potential route of introduction for exotic MBDs into Canada when they return home., Competing Interests: Conflict of interest: None.

The International Committee on Taxonomy of Viruses (ICTV) has implemented numerous changes to the taxonomic classification of bunyaviruses over the years. Whereas most changes have been justified and necessary because of the need to accommodate newly discovered and unclassified viruses, other changes are a cause of concern, especially the decision to demote scores of formerly recognized species to essentially strains of newly designated species. This practice was first described in the seventh taxonomy report of the ICTV and has continued in all subsequent reports. In some instances, viruses that share less than 75% nucleotide sequence identity across their genomes, produce vastly different clinical presentations, possess distinct vector and host associations, have different biosafety recommendations, and occur in nonoverlapping geographic regions are classified as strains of the same species. Complicating the matter is the fact that virus strains have been completely eliminated from ICTV reports; thus, critically important information on virus identities and their associated biological and epidemiological features cannot be readily related to the ICTV classification. Here, we summarize the current status of bunyavirus taxonomy and discuss the adverse consequences associated with the reclassification and resulting omission of numerous viruses of public health importance from ICTV reports. As members of the American Committee on Arthropod-borne Viruses, we encourage the ICTV Bunyavirus Study Group to reconsider their stance on bunyavirus taxonomy, to revise the criteria currently used for species demarcation, and to list additional strains of public and veterinary importance.

Dengue viruses are responsible for over 100 million infections a year worldwide and are a public health concern in Bangladesh. Although risk of transmission is high, data on vector population characteristics are scanty in Bangladesh; therefore, a comprehensive prediction of the patterns of local virus transmission is not possible. Recognizing these gaps, multi-year entomological surveys were carried out in Dhaka, where the disease is most frequently reported. The specific objectives of the present study are threefold: i) to determine the risk factors for the presence of Aedes mosquitoes; ii) to identify the types of most productive and key containers; and iii) to estimate the effects of climatic factors on Aedes abundance in the city of Dhaka, Bangladesh. Entomological surveys were conducted in 12 out of 90 wards in Dhaka. These wards were selected using a probability proportional sampling procedure during the monsoon seasons in 2011, 2012 and 2013 and in the dry season in 2012. All containers inside and around sampled households were inspected for mosquito larvae and pupae, and containers were classified according to their relative size, use pattern, and materials of construction. During the study period (2011-2013), 12,680 larvae and pupae were collected. About 82% of the identified immature mosquitoes were Aedes aegypti, while the remainder were Ae. albopictus and other mosquito species. The largest number of immature mosquitoes was collected from tires and refrigerator trays during 2011 and 2012 monsoon seasons. Conversely, plastic drums were the most productive during the 2012 dry and 2013 monsoon season. Vehicle parts and discarded construction materials were the most efficient producers of Aedes mosquitoes in all surveys. The presence of Aedes mosquitoes was significantly (p < 0.05) higher in low socio-economic zones of Dhaka. Container location, presence of vegetation, and availability of shade for containers were also significantly associated with finding immature Aedes mosquitoes, based on multivariable analysis after confounder adjustment. Rainfall, temperature, and relative humidity also significantly affected the mean abundance of mosquitoes. Proper use, disposal, and recycling of the containers that effectively produce large numbers of Aedes vector mosquitoes may decrease the risk of arboviral transmission., Competing Interests: The authors have declared that no competing interests exist.

Background: Following emergence of Zika virus in the Americas, a devastating new congenital syndrome has been documented, leading to significant morbidity among Zika-infected fetuses and neonates., Case Presentation: A 29-year-old pregnant woman infected with Zika virus at 9-weeks gestation in Trinidad presented with one-month of fever, headache, and myalgia with persistent viremia. Significant fetal abnormalities were identified at 14-week ultrasound, which is the earliest ultrasound to describe a severely affected fetus following Zika virus infection to our knowledge., Conclusions: We discuss the implications of prolonged maternal viremia and the spectrum of congenital Zika syndrome detectable by fetal ultrasound., Competing Interests: Ethics approval for this case report was not sought as there was no human subjects study in which to participate. Patient written consent was obtained for use of her personal and clinical information in this manuscript.Patient written consent was obtained for use of her personal and clinical information in this manuscript.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Cache Valley virus, an orthobunyavirus, is an important cause of ovine neonatal malformations. Information on the seroprevalence of this virus in Saskatchewan livestock populations is lacking. The objectives of this study were to determine the seroprevalence of Cache Valley virus and closely related viruses in sheep, cattle, goats, horses, and mule deer in Saskatchewan by performing a plaque-reduction neutralization test using Cache Valley virus. In total, sera from 130 sheep from 50 flocks were tested. Seroprevalence in sheep was 64.6% (84/130) and 94.0% (47/50) of flocks had 1 or more seropositive sheep. Antibodies to Cache Valley virus or closely related viruses were also detected in serum samples collected from cattle, goats, horses, and mule deer with seroprevalences of 20.0% (5/25), 33.3% (8/24), 69.0% (40/58), and 50.8% (33/65), respectively. These results suggest widespread exposure to Cache Valley virus or closely related viruses in domestic animals and mule deer in Saskatchewan.

Competing Interests: Competing interests: None declared.

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.

Background: Dengue virus (DENV) activity has been reported in Dhaka, Bangladesh since the early 1960s with the greatest burden of dengue fever and dengue hemorrhagic fever cases observed in 2000. Since this time, the intensity of dengue activity has varied from year to year, and its determining factors remained relatively unknown. In light of such gaps in knowledge, the main objectives of this study were to determine the magnitude of seroprevalence and seroconversion among the surveyed population, and establish the individual/household level risk factors for the presence of DENV antibodies among all age groups of target populations in the city of Dhaka., Methodology/principal Findings: Considering the lack of fine scale investigations on the factors driving dengue activity in Bangladesh, a prospective cohort study involving serological surveys was undertaken with participant interviews and blood donation across the city of Dhaka in 2012. Study participants were recruited from 12 of 90 wards and blood samples were collected during both the pre-monsoon (n = 1125) and post-monsoon (n = 600) seasons of 2012. The findings revealed that the seroprevalence in all pre-monsoon samples was 80.0% (900/1125) while the seropositivity in the pre-monsoon samples that had paired post-monsoon samples was 83.3% (503/600). Of the 97 paired samples that were negative at the pre-monsoon time point, 56 were positive at the post-monsoon time point. This resulted in a seroprevalence of 93.2% (559/600) among individuals tested during the post-monsoon period. Seroprevalence trended higher with age with children exhibiting a lower seropositivity as compared to adults. Results from this study also indicated that DENV strains were the only flaviviruses circulating in Dhaka in 2012. A multivariate analysis revealed that age, possession of indoor potted plants, and types of mosquito control measures were significant factors associated with DENV seroprevalence; while attendance in public/mass gatherings, and use of mosquito control measures were significantly associated with DENV seroconversion after adjusting for all other variables., Conclusions/significance: Our study suggests that there is a high level of endemic dengue virus circulation in the city of Dhaka which has resulted in significant DENV seroprevalence among its residents. Seropositivity increased with age, however, a substantial proportion of children are at risk for DENV infections. Our serological analysis also documents considerable DENV seroconversion among study participants which indicates that a large proportion of the population in the city of Dhaka were newly exposed to DENV during the study period (pre-and post-monsoon 2012). High levels of seroconversion suggest that there was an intense circulation of DENV in 2012 and this may have resulted in a significant risk for viral associated illness. Findings of our study further indicated that home-based interventions, such as removing indoor potted plants and increased bed net use, in addition to vector control measures in public parks, would reduce exposure to DENV and further decrease risk of viral associated disease.

Background: Zika virus (ZIKV) infection is emerging globally, currently causing outbreaks in the Caribbean, and Central and South America, and putting travellers to affected countries at risk. Model-based estimates for the basic reproduction number (R 0 ) of ZIKV in affected Caribbean and Central and South American countries, obtained from 2015 to 2016 human case surveillance data, were compared by logistic regression and Receiver-Operating Characteristic (ROC), with the prevalence of ZIKV-positive test results in Canadians who travelled to them., Results: Estimates of R 0 for each country were a good predictor of the ZIKV test result (ROC area under the curve = 0.83) and the odds of testing positive was 11-fold greater for travellers visiting countries with estimated R 0  ≥ 2.76, compared to those visiting countries with R 0  < 2.76., Conclusions: Risk to travellers varies widely amongst countries affected by ZIKV outbreaks. Estimates of R 0 from surveillance data can assist in assessing levels of risk for travellers and may help improve travel advice. They may also allow better prediction of spread of ZIKV from affected countries by travellers.

Commercial chikungunya virus (CHIKV)-specific IgM detection kits were evaluated at the Centers for Disease Control and Prevention (CDC), the Public Health Agency of Canada National Microbiology Laboratory, and the Caribbean Public Health Agency (CARPHA). The Euroimmun Anti-CHIKV IgM ELISA kit had ≥ 95% concordance with all three reference laboratory results. The limit of detection for low CHIK IgM+ samples, as measured by serial dilution of seven sera up to 1:12,800 ranged from 1:800 to 1:3,200. The Euroimmun IIFT kit evaluated at CDC and CARPHA performed well, but required more retesting of equivocal results. The InBios CHIKjj Detect MAC-ELISA had 100% and 98% concordance with CDC and CARPHA results, respectively, and had equal sensitivity to the CDC MAC-ELISA to 1:12,800 dilution in serially diluted samples. The Abcam Anti-CHIKV IgM ELISA had high performance at CARPHA, but at CDC, performance was inconsistent between lots. After replacement of the biotinylated IgM antibody controls with serum containing CHIKV-specific IgM and additional quality assurance/control measures, the Abcam kit was rereleased and reevaluated at CDC. The reformatted Abcam kit had 97% concordance with CDC results and limit of detection of 1:800 to 1:3,200. Two rapid tests and three other CHIKV MAC-ELISAs evaluated at CDC had low sensitivity, as the CDC CHIKV IgM in-house positive controls were below the level of detection. In conclusion, laboratories have options for CHIKV serological diagnosis using validated commercial kits., (© The American Society of Tropical Medicine and Hygiene.)

This is the first Canadian case of Chikungunya virus (CHIKV) infection reported in a traveller returning from the Caribbean. Following multiple mosquito bites in Martinique Island in January 2014, the patient presented with high fever, headaches, arthralgia on both hands and feet, and a rash on the trunk upon his return to Canada. Initial serological testing for dengue virus infection was negative. Support therapy with nonsteroidal anti-inflammatory drugs was administered. The symptoms gradually improved 4 weeks after onset with residual arthralgia and morning joint stiffness. This clinical feature prompted the clinician to request CHIKV virus serology which was found to be positive for the presence of IgM and neutralizing antibodies. In 2014, over four hundred confirmed CHIKV infection cases were diagnosed in Canadian travellers returning from the Caribbean and Central America. Clinical suspicion of CHIKV or dengue virus infections should be considered in febrile patients with arthralgia returning from the recently CHIKV endemic countries of the Americas.

In Canada, the emergence of vector-borne diseases may occur via international movement and subsequent establishment of vectors and pathogens, or via northward spread from endemic areas in the USA. Re-emergence of endemic vector-borne diseases may occur due to climate-driven changes to their geographic range and ecology. Lyme disease, West Nile virus (WNV), and other vector-borne diseases were identified as priority emerging non-enteric zoonoses in Canada in a prioritization exercise conducted by public health stakeholders in 2013. We review and present the state of knowledge on the public health importance of these high priority emerging vector-borne diseases in Canada. Lyme disease is emerging in Canada due to range expansion of the tick vector, which also signals concern for the emergence of human granulocytic anaplasmosis, babesiosis, and Powassan virus. WNV has been established in Canada since 2001, with epidemics of varying intensity in following years linked to climatic drivers. Eastern equine encephalitis virus, Jamestown Canyon virus, snowshoe hare virus, and Cache Valley virus are other mosquito-borne viruses endemic to Canada with the potential for human health impact. Increased surveillance for emerging pathogens and vectors and coordinated efforts among sectors and jurisdictions will aid in early detection and timely public health response.

Hantavirus pulmonary syndrome is a disease caused by the inhalation of excreta from infected deer mice. In Canada, the majority of hantavirus pulmonary syndrome cases occur in the western provinces of British Columbia, Alberta, Saskatchewan and Manitoba and the primary cause of the illness is the Sin Nombre virus. Only one case of hantavirus pulmonary syndrome has been documented in eastern Canada (Québec); however, Sin Nombre virus-infected deer mice have been identified across the country. Although cases are rare (yearly case numbers range from zero to 13 and the total number of confirmed cases in Canada now total 109), the mortality rate among infected individuals is approximately 30%. The majority of cases occur in the spring and early summer indicating seasonally-associated risk factors for viral exposure. In 2013 and 2014, a substantial increase in the number of hantavirus pulmonary syndrome cases was identified; however the cause remains unclear. No antivirals or vaccines are currently available and treatment is supportive. Public education, rodent control and the use of personal protective measures are key to avoid infections in at-risk populations., Competing Interests: Conflict of interest: None.

California serogroup and Cache Valley viruses are arboviruses (tick- and mosquito-borne pathogens) belonging to the genus Orthobunyavirus (Family Bunyaviridae). Although the majority of exposures to these viruses result in asymptomatic or mild infections, both California serogroup and Cache Valley viruses can cause febrile and neurological diseases similar in nature to those associated with infections by West Nile virus. California serogroup and Cache Valley viruses are widely distributed across North America and circulate in a number of vertebrate hosts and mosquito vectors, including several species of Aedes and other non- Culex mosquitoes. The Jamestown Canyon and snowshoe hare viruses are the most common kind of California serogroup viruses found in Canada and have been identified throughout the country. These potential pathogens may be contributing to a higher burden of illness than previously recognized and should be considered as part of the differential diagnosis for febrile and neuroinvasive disease during the mosquito season. Diagnosis can be made by requesting a diagnostic panel at the Viral Zoonoses program at the National Microbiology Laboratory. To decrease the risk of infection, education about these viruses and the importance of personal preventive measures is warranted., Competing Interests: Conflict of interest: None.

Since the spring of 2014, there has been a large increase in travel-related chikungunya cases diagnosed in Canada. As of December 9, 2014, 320 confirmed and 159 probable cases have been diagnosed in Canada, with the majority of provinces identifying at least one imported case. This surge in Canadian infections has been associated with the incursion of chikungunya virus into the Caribbean and the expansion of the virus in the Americas. Ongoing outbreaks in the Asia-Pacific region have also contributed to imported cases among Canadian travellers. Heightened awareness of chikungunya among clinicians is key to diagnosis. This highlights the need to ask for a travel history from anyone who presents with fever or recent onset of polyarthralgia, and to consider testing by provincial laboratories and the National Microbiology Laboratory for chikungunya virus and other diseases as indicated. Also essential is continued communication with travellers regarding the use of preventative measures to decrease the risk of exposure to mosquitoes when travelling to endemic areas., Competing Interests: Conflict of interest: None

Studies examining the prevalence of zoonotic agents in the Caribbean are very limited. The objective of this study was to examine the seroprevalence of seven zoonotic agents among individuals residing on 10 English-speaking Caribbean countries. Sera from healthy, pregnant women were collected from Antigua-Barbuda, Belize, Bermuda, Dominica, Grenada, Jamaica, Montserrat, St. Kitts-Nevis, St. Lucia, and St. Vincent-Grenadines and tested for the presence of IgG antibodies to dengue virus, hepatitis E virus, hantaviruses, leptospiral agents, spotted fever group rickettsiae (SFGR), typhus group rickettsiae (TGR), and Coxiella burnetii (Q fever). The highest seroprevalence values were observed for dengue virus, SFGR, and leptospirosis, although the lowest seroprevalence values were observed for hepatitis E virus, C. burnetii, and TGR. Antibodies to hantaviruses were not detected in any individuals., (© The American Society of Tropical Medicine and Hygiene.)

The incidence of West Nile virus (WNv) has waxed and waned in Canada over the past 12 years, but it is unlikely to disappear. Climate change models, which suggest warming temperatures and changing patterns of precipitation, predict an expansion of geographic range for WNv in some regions of Canada, such as the Prairie provinces. Such projected changes in WNv distribution might also be accompanied by genetic changes in the virus and/or the range of bird and insect host species it infects. To address this risk, emphasis should be placed on preventing exposure to infected mosquitoes, conducting high-quality surveillance of WNv and WNv disease, controlling mosquito vectors, and promoting public and professional education.

Encephalitis is a clinical syndrome often associated with infectious agents. This study describes the epidemiology and disease burden associated with encephalitis in Canada and explores possible associations with arboviral causes. Encephalitis-associated hospitalizations, 1994-2008, were analysed according to aetiological category (based on ICD-9/ICD-10 codes) and other factors using multivariate logistic regression for grouped (blocked) data and negative binomial regression. A discrete Poisson model tested spatio-temporal clustering of hospitalizations associated with unclassified and arboviral encephalitis aetiologies. Encephalitis accounted for an estimated 24028 hospitalizations in Canada (5·2/100 000 population) and unknown aetiologies represented 50% of these hospitalizations. In 2003, clusters of unclassified encephalitis were identified in the summer and early autumn months signifying potential underlying arboviral aetiologies. Spatio-temporal patterns in encephalitis hospitalizations may help us to better understand the disease burden associated with arboviruses and other zoonotic pathogens in Canada and to develop appropriate surveillance systems.

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.

California serogroup viruses, including Jamestown Canyon virus (JCV) and snowshoe hare virus (SSHV), are mosquito-borne members of the Bunyaviridae family and are endemic across North America. These arboviruses are potential pathogens which occasionally cause neuroinvasive disease in humans and livestock. A neutralization assay was used to document JCV and SSHV seroprevalence using blood collected from a variety of domestic and wildlife host species. These species were sampled in an island setting, Newfoundland, which contains diverse ecoregions, ecological landscapes, and habitats. Seroprevalence rates for each virus differed significantly among host species and within certain species across different geographic areas. JCV was significantly associated with large mammals, and SSHV was significantly associated with snowshoe hares. Seroprevalence rates in the 5 species of animals tested for prior exposure to JCV ranged from 0% in snowshoe hares to 64% in horses. Seroprevalence rates for SSHV ranged from less than 1% in bovines to 55% in all snowshoe hares. The seroprevalence of SSHV differed significantly (P < 0.05) among hares occupying the discrete habitats of watersheds separated by 14 to 35 km. Cattle on farms in boreal forest landscapes displayed significantly higher JCV seroprevalence (P < 0.001) than those on farms located in seacoast landscapes. Lifelong geographic isolation of cattle to insular Newfoundland was associated with significantly lower JCV seroprevalence (P < 0.01) than that for cattle which had lived off-island.

Introduction: Little is known about the long-term health related quality of life outcomes in patients with West Nile virus associated acute flaccid paralysis. We describe the quality of life scores of seven patients with acute flaccid paralysis who presented to hospital between 2003 and 2006, and were followed for up to two years., Case Presentations: Between 2003 and 2006, 157 symptomatic patients with West Nile virus were enrolled in a longitudinal cohort study of West Nile virus in Canada. Seven patients (4%) had acute flaccid paralysis. The first patient was a 55-year-old man who presented with left upper extremity weakness. The second patient was a 54-year-old man who presented with bilateral upper extremity weakness. The third patient was a 66-year-old woman who developed bilateral upper and lower extremity weakness. The fourth patient was a 67-year-old man who presented with right lower extremity weakness. The fifth patient was a 60-year-old woman who developed bilateral lower extremity weakness. The sixth patient was a 71-year-old man with a history of Parkinson's disease and acute onset bilateral lower extremity weakness. The seventh patient was a 52-year-old man who presented with right lower extremity weakness. All were Caucasian. Patients were followed for a mean of 1.1 years. At the end of follow-up the mean score on the Physical Component Summary of the Short-Form 36 scale had only slightly increased to 39. In contrast, mean score on the Mental Component Summary of the Short-Form 36 scale at the end of follow-up had normalized to 50., Conclusion: Despite the poor physical prognosis for patients with acute flaccid paralysis, the mental health outcomes are generally favorable.

In a previous study, a new flavivirus genome sequence was identified in Culex tarsalis mosquitoes obtained in Alberta, Canada and was shown to be genetically related to but distinct from members of the insect-specific flaviviruses. Nonstructural protein 5-encoding sequences amplified from Cx. tarsalis pools from western Canada have shown a high similarity to genome sequences of novel flaviviruses isolated from mosquitoes in California and Colorado. Despite wide distribution of this virus, designated Calbertado virus, strains demonstrate a high degree of nonstructural protein 5 nucleotide (> 90%) and amino acid (> 97%) identity. The ecology and geographic range of Calbertado virus warrants further study because it may potentially influence transmission of mosquito-borne flaviviruses, including important human pathogens such as West Nile and Saint Louis encephalitis viruses.

The genetic diversity of Borrelia burgdorferi sensu stricto, the agent of Lyme disease in North America, has consequences for the performance of serological diagnostic tests and disease severity. To investigate B. burgdorferi diversity in Canada, where Lyme disease is emerging, bacterial DNA in 309 infected adult Ixodes scapularis ticks collected in surveillance was characterized by multilocus sequence typing (MLST) and analysis of outer surface protein C gene (ospC) alleles. Six ticks carried Borrelia miyamotoi, and one tick carried the novel species Borrelia kurtenbachii. 142 ticks carried B. burgdorferi sequence types (STs) previously described from the United States. Fifty-eight ticks carried B. burgdorferi of 1 of 19 novel or undescribed STs, which were single-, double-, or triple-locus variants of STs first described in the United States. Clonal complexes with founder STs from the United States were identified. Seventeen ospC alleles were identified in 309 B. burgdorferi-infected ticks. Positive and negative associations in the occurrence of different alleles in the same tick supported a hypothesis of multiple-niche polymorphism for B. burgdorferi in North America. Geographic analysis of STs and ospC alleles were consistent with south-to-north dispersion of infected ticks from U.S. sources on migratory birds. These observations suggest that the genetic diversity of B. burgdorferi in eastern and central Canada corresponds to that in the United States, but there was evidence for founder events skewing the diversity in emerging tick populations. Further studies are needed to investigate the significance of these observations for the performance of diagnostic tests and clinical presentation of Lyme disease in Canada.

An IgG avidity assay was developed to differentiate deer mice that had recently acquired Sin Nombre virus (SNV) from those that were infected in the distant past. Using this procedure, low avidity antibodies were predominantly detected in experimentally infected deer mice (89.5%) within the first 30 days post-inoculation. The assay was then applied to sera from naturally infected deer mice collected during a field investigation associated with a cluster of hantavirus pulmonary syndrome cases. A higher proportion of seropositive mice collected during the outbreak had serum with low avidity antibodies (16.7%) when compared with mice trapped four months later (5.7%). Sin Nombre virus RNA was detectable in blood in a similar fraction of low- (45%) and high- (38.7%) avidity groups. Non-adult mice were more likely to contain low-avidity antibodies (44.4%) than were adults (9.6%). Our results indicate that the IgG avidity assay shows promise as a tool to better characterize epizootic intensity and to identify factors involved in SNV transmission.

Background: The Five Hills Health Region of Saskatchewan reported the highest West Nile virus (WNV) case rates in the 2003 outbreak. A serologic and telephone survey was undertaken to assess the seroprevalence of the virus and the knowledge, attitudes and behaviours of the residents., Methods: Respondents had to be at least 18 years of age, and residents of the Five Hills Health Region between July 1st and September 15th, 2003. Blood samples of respondents were tested at the National Microbiology Laboratory for flavivirus immunoglobulin using a WNV IgG ELISA and plaque reduction neutralization test. Descriptive analyses performed related to respondents' demographics, knowledge, attitudes, behaviours, and seropositivity. WNV infection risk was assessed using odds ratio., Results: There were 619 questionnaire respondents, of whom 501 donated a blood sample. The seroprevalence of WNV in the Five Hills Health Region was 9.98% (95% CI 7.37-12.59%). Seropositivity of rural areas was 16.8% and urban was 3.2%. Most (97%) of participants thought WNV was an important health issue. Forty-eight percent of the participants used insect repellents containing DEET most of the time. There was good knowledge regarding WNV transmission and prevention of the spread of WNV. Rural compared to urban residents were six times more likely to be positive for WNV (OR=6.13, 95% CI 2.82-13.34)., Interpretation: This is the highest seroprevalence rate of West Nile virus recorded in North America thus far. Many factors could have influenced this outbreak, such as eco-region, early prolonged hot weather, level of mosquito control programs, urban and rural community differences, and personal protective behaviours.

Since its introduction in 1999, West Nile virus (WNV) infections have spread rapidly across the North American continent. Diagnosis of acute WNV infection by detection of WNV-specific immunoglobulin M (IgM) is complicated by the persistence of detectable IgM for more than 1 year in some patients. IgG antibody avidity testing was assessed as a supplemental assay in the diagnosis of current infections. Three groups of serum samples were assayed in parallel by two different IgG avidity test systems (indirect immunofluorescence test [IIFT] and prototype enzyme-linked immunosorbent assay [ELISA]; EUROIMMUN, Luebeck, Germany). Group I (40 sera taken between 2 and 9 days after the onset of influenza-like symptoms) and group II (40 sera taken between 10 and 43 days after onset) were acute and convalescent specimens from patients with a positive anti-WNV IgM test (ELISA; Focus Diagnostics, Cypress, CA). Group III consisted of 43 patient sera collected between 6 and 12 months after infection. IgG antibodies specific for WNV were detected in 38% (ELISA) and 50% (IIFT) of group I sera, in 90% (ELISA and IIFT) of group II sera, and in 100% (ELISA and IIFT) of group III sera. Low-avidity IgG antibodies were demonstrated in 86% (ELISA) and 95% (IIFT) of IgG-positive patient samples taken between 2 and 43 days after the onset of symptoms (groups I and II). High-avidity IgG antibodies were detected in 100% of group III sera obtained 6 months or more after the onset of symptoms (ELISA and IIFT). IgG avidity tests for WNV infections are rapid and simple to perform. The determination of IgG avidity provides additional diagnostic certainty in differentiating between recently acquired and previous infections with WNV.

The distribution of West Nile virus has expanded in the past 6 years to include the 48 contiguous United States and seven Canadian provinces, as well as Mexico, the Caribbean islands, and Colombia. The suggestion of the emergence of a dominant genetic variant has led to an intensive analysis of isolates made across North America. We have sequenced the pre-membrane and envelope genes of 74 isolates and the complete genomes of 25 isolates in order to determine if a dominant genotype has arisen and to better understand how the virus has evolved as its distribution has expanded. Phylogenetic analyses revealed the continued presence of genetic variants that group in a temporally and geographically dependent manner and provide evidence that a dominant variant has emerged across much of North America. The implications of these findings are discussed as they relate to transmission and spread of the virus in the Western Hemisphere.

West Nile virus (WNV) has spread rapidly across North America, creating a need for rapid and accurate laboratory diagnosis on a large scale. Immunoglobulin M (IgM) capture enzyme immunoassays (EIA) became commercially available in the summer of 2003, but limited data are available on their clinical performance. Consolidated human WNV diagnostic testing for the province of Alberta, Canada, at the public health laboratory permitted a large-scale evaluation of the assays, covering a wide clinical spectrum. Two thousand nine hundred sixty-nine sera were tested, from 2,553 Alberta residents, and 266 cases were identified. Sensitivities of the Focus assay and first-generation Panbio IgM capture EIA were 79 and 80%, respectively. During the first week of illness only 53 to 58% of cases were positive, but sensitivity was 96 to 97% after day 8. Sensitivity for neurological cases was 92% overall. Specificity was high for the Focus kit at 98.9%, but only 82.9% for the first Panbio kit. A positive Focus WNV IgG result with a twofold rise in IgG index was a reliable indicator of acute flavivirus infection (67/67 WNV). Agreement between the IgG test and hemagglutinin inhibition titers in paired sera was at least 82%. Commercial IgM and IgG EIA proved useful for WNV diagnosis, provided follow-up sera were collected after 8 days of illness.

Objective: To review the epidemiology and disease manifestations of West Nile virus (WNV) in North America and to describe the current status of therapeutic approaches and vaccines for treating or preventing viral illness., Quality of Evidence: Since 1999, research initiatives investigating the ecology, epidemiology, and biology of WNV have increased substantially. These studies provide a foundation for understanding current activity and predicting future activity and for describing the effect of WNV on human health., Main Message: West Nile virus is transmitted to humans primarily through bites from infected mosquitoes. Most people infected have no symptoms; a few have clinical manifestations ranging from febrile illness to neurologic syndromes and possibly death. Risk of serious disease increases with age, and substantial long-term morbidity has been observed in patients who develop severe neurologic illness. No specific antiviral therapy or vaccine currently exists., Conclusion: West Nile virus has established itself in North America and has become an important public health concern. Decreasing risk of virus-associated illness requires seasonal preventive and control measures.

We report 2 clinically characteristic and serologically positive cases of Ross River virus infection in Canadian tourists who visited Fiji in late 2003 and early 2004. This report suggests that Ross River virus is once again circulating in Fiji, where it apparently disappeared after causing an epidemic in 1979 to 1980.

West Nile virus (WNV) causes severe neurological disease in less than 1% of infections. However, meningoencephalitis may be more common in immunosuppressed transplant patients. In 2002, a WNV outbreak occurred in our region. To determine the spectrum of disease of community acquired WNV infection and assess public health behavior patterns in transplant recipients, we carried out a seroprevalence study. Patients were enrolled from outpatient transplant clinics in October 2002 and sera were screened for WNV. Questionnaires about WNV were provided to patients. Eight hundred sixteen organ transplant patients were enrolled. The seroprevalence of WNV IgM was 2/816 (0.25%; 95% CI 0.03-0.88%). By extrapolation to our entire transplant population of 2360 patients, and using data from hospital-based surveillance, the risk of meningoencephalitis in a transplant patient infected with WNV is estimated to be 40% (95% CI 16-80%). With regards to knowledge and behavior, 56% patients knew of and 47% used at least one protective measure against WNV. Only 33% used insect repellent. The risk of meningoencephalitis in transplant recipients is much higher than in the general population. There is incomplete knowledge and poor rates of compliance amongst patients with regards to WNV prevention.

An aged Barbary ape (Macaca sylvanus) at the Toronto Zoo became infected with naturally acquired West Nile virus encephalitis that caused neurologic signs, which, associated with other medical problems, led to euthanasia. The diagnosis was based on immunohistochemical assay of brain lesions, reverse transcriptase-polymerase chain reaction, and virus isolation.

West Nile virus activity in Manitoba was documented for the first time by the collection of an infected crow found on July 8, 2002, in Winnipeg. West Nile virus was identified as the cause of death for a large number of domestic geese at a single farm in southern Manitoba in August. Of the 5 differently aged cohorts on the affected farm, which included 2 breeding flocks and 3 growing flocks, the 6-week-old cohort was most severely affected with 692 of 2731 goslings dying within a 10-day period. Seroprevalence of West Nile virus in 2 clinically affected and recovered juvenile cohorts was 98% and 100%. In breeding geese without clinical disease, seroprevalence was 90% for 15-month-old birds and 10% for 5-year-old birds. Seroreaction in 3 of 4 cohorts tested exceeded what would be expected by mosquito transmission alone.