Epidemiology and aetiology of encephalitis in Canada, 1994-2008: a case for undiagnosed arboviral agents?

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.

Spotted fever group rickettsiae: a brief review and a Canadian perspective.

Spotted fever group rickettsioses (SFGR) are infections caused by established and emerging human pathogens worldwide. These rickettsial agents are transmitted to humans via arthropods and may result in mild to severe and potentially fatal diseases. Spotted fever group rickettsioses are characterized by similar clinical features, including fever, rash, headache and myalgias, with the development of an inoculation eschar in many, but not all cases. Endemic rickettsial infections do occur but are infrequent in Canada, in contrast to the United States, where these infections are far more prevalent. Travel-associated rickettsioses, however, are being diagnosed with increasing frequency in Canadian travellers returning from international trips abroad, in particular in travellers returning from Africa. The diagnosis of rickettsial infections can be challenging owing to the non-specific nature of the clinical symptoms and the requirement for specialized testing. Serology cannot distinguish between the approximately 20 spotted fever group rickettsial species currently known or suspected to be capable of causing human infection. Molecular testing is required to determine the rickettsial species responsible for infection, but requires greater effort on the part of the clinician to collect appropriate samples, including cutaneous skin swabs from under the eschar or skin punch biopsies of the eschar or rash. Infections with spotted fever group rickettsiae likely occur more commonly than currently recognized and should be considered in patients with appropriate symptoms and exposure histories.

Flexibility of mobile laboratory unit in support of patient management during the 2007 Ebola-Zaire outbreak in the Democratic Republic of Congo.

The mobile laboratory provides a safe, rapid and flexible platform to provide effective diagnosis of Ebola virus as well as additional differential diagnostic agents in remote settings of equatorial Africa. During the 2007 Democratic Republic of Congo outbreak of Ebola-Zaire, the mobile laboratory was set up in two different locations by two separate teams within a day of equipment arriving in each location. The first location was in Mweka where our laboratory took over the diagnostic laboratory space of the local hospital, whereas the second location, approximately 50 km south near Kampungu at the epicentre of the outbreak, required local labour to fabricate a tent structure as a suitable pre-existing structure was not available. In both settings, the laboratory was able to quickly set up, providing accurate and efficient molecular diagnostics (within 3 h of receiving samples) for 67 individuals, including four cases of Ebola, seven cases of Shigella and 13 cases of malaria. This rapid turn-around time provides an important role in the support of patient management and epidemiological surveillance.

West Nile Virus in the New World: trends in the spread and proliferation of West Nile Virus in the Western Hemisphere.

The observed patterns and variations in the ecology, epidemiology, distribution and prevalence of the West Nile Virus (WNV) in different areas of the Western Hemisphere make this pathogen of particular importance as a model for understanding the potential risk factors associated with emerging pathogens worldwide, particularly those involving zoonotic pathogens whose epidemiology involves the potential for vertical transmission in arthropod vector species, and horizontal and vertical transmission within and among vertebrate host species. Record numbers of human WNV cases were recorded in Canada during 2007, with >50% more cases than documented in any previous year. Although overall numbers of human infections recorded in the United States were not exceptionally high during 2007 relative to epidemic levels reported in 2002 and 2003, the state of Oklahoma reported that the highest-ever number of human WNV cases and the numbers of human cases recorded in Canada were 50% higher than previous record levels recorded in 2003. The record and near-record numbers of human WNV infections recorded in several regions of North America during 2007 have important implications for the future management and surveillance of WNV vectors and reservoirs in North America. The spatiotemporal distribution of WNV infections in humans and animals recorded during 2007 in North America and South America have important implications for the surveillance and management of public health threats from WNV in the Western Hemisphere. Serological surveys conducted in areas of intense WNV transmission in the United States have reported low prevalence of antibodies to WNV in human s populations, indicating that additional epidemic outbreaks of human disease from WNV can be expected in the future.

Ixodes scapularis ticks collected by passive surveillance in Canada: analysis of geographic distribution and infection with Lyme borreliosis agent Borrelia burgdorferi.

Passive surveillance for the occurrence of the tick Ixodes scapularis Say (1821) and their infection with the Lyme borreliosis spirochaetes Borrelia burgdorferi s.l. has taken place in Canada since early 1990. Ticks have been submitted from members of the public, veterinarians, and medical practitioners to provincial, federal, and university laboratories for identification, and the data have been collated and B. burgdorferi detected at the National Microbiology Laboratory. The locations of collection of 2,319 submitted I. scapularis were mapped, and we investigated potential risk factors for I. scapularis occurrence (in Quebec as a case study) by using regression analysis and spatial statistics. Ticks were submitted from all provinces east of Alberta, most from areas where resident I. scapularis populations are unknown. Most were adult ticks and were collected in spring and autumn. In southern Québec, risk factors for tick occurrence were lower latitude and remote-sensed indices for land cover with woodland. B. burgdorferi infection, identified by conventional and molecular methods, was detected in 12.5% of 1,816 ticks, including 10.1% of the 256 ticks that were collected from humans and tested. Our study suggests that B. burgdorferi-infected I. scapularis can be found over a wide geographic range in Canada, although most may be adventitious ticks carried from endemic areas in the United States and Canada by migrating birds. The risk of Lyme borreliosis in Canada may therefore be mostly low but more geographically widespread than previously suspected.

The role of reverse genetics systems in determining filovirus pathogenicity.

The family Filoviridae is comprised of two genera: Marburgvirus and Ebolavirus. To date minigenome systems have been developed for two Ebola viruses (Reston ebolavirus and Zaire ebolavirus [ZEBOV]) as well as for Lake Victoria marburgvirus, the sole member of the Marburgvirus genus. The use of these minigenome systems has helped characterize functions for many viral proteins in both genera and have provided valuable insight towards the development of an infectious clone system in the case of ZEBOV. The recent development of two such infectious clone systems for ZEBOV now allow effective strategies for experimental mutagenesis to study the biology and pathogenesis of one of the most lethal human pathogens.

Genomic sequencing of deer tick virus and phylogeny of powassan-related viruses of North America.

Powassan (POW) virus is responsible for central nervous system infection in humans in North America and the eastern parts of Russia. Recently, a new flavivirus, deer tick (DT) virus, related to POW virus was isolated in the United States, but neither its pathogenic potential in human nor the taxonomic relationship with POW virus has been elucidated. In this study, we obtained the near-full-length genomic sequence of the DT virus and complete sequences of 3 genomic regions of 15 strains of POW-related virus strains. The phylogeny revealed 2 lineages, one of which had the prototype POW virus and the other DT virus. Both lineages can cause central nervous system infection in humans. By use of the combination of molecular definition of virus species within the genus Flavivirus and serological distinction in a 2-way cross-neutralization test, the lineage of DT virus is classified as a distinct genotype of POW virus.

Genetic and serotypic characterization of Sin Nombre-like viruses in Canadian Peromyscus maniculatus mice.

In Canada, hantavirus infected deer mice (Peromyscus maniculatus) have been collected from British Columbia to Newfoundland. Partial sequencing of G1 and N protein encoding regions from Canadian Peromyscus maniculatus-borne hantaviruses demonstrated the existence of significant genotypic divergence among strains. Phylogenetic analysis showed that Sin Nombre (SN)-like viruses from eastern and western Canadian deer mice can be divided into at least two broad-based genogroups. Sequencing of mitochondrial DNA from infected deer mice originating from various eastern and western provinces showed that SN-like virus genogroups appeared to be associated with distinct haplotypes of mice. Sera from deer mice infected with eastern and western viral genotypes neutralized the Sin Nombre virus strain, Convict Creek 107, but not the New York 1 hantavirus. Despite the genetic heterogeneity of Canadian SN-like strains these hantaviruses do not appear to define unique hantavirus serotypes.

A serological survey of rural dogs and cats on the southwestern Canadian prairie for zoonotic pathogens.

A survey for antibodies against agents of plague, tularemia, and Rocky Mountain spotted fever (RMSF), and against Sin Nombre hantavirus (SNV), Bartonella henselae and B. clarridgeiae was conducted in the summer of 1995 using serum from rural dogs and cats living in the vicinity of four public parks in southeastern Alberta and southwestern Saskatchewan. Antibodies to all pathogens were detected in all survey areas. Overall prevalence rates were 0.075 for Yersinia pestis, 0.089 for Francisella tularensis, 0.025 for Rickettsia rickettsii (dogs only), and 0.029, 0.178 and 0.186 for SNV, B. henselae and B. clarridgeiae, respectively (cats only). This serological survey of rural dogs and cats was more sensitive and efficient than previous surveys based on collection and culture of rodents and ectoparasites. All six pathogens appear endemic to the region. Surveillance for plague, tularemia, RMSF and SNV, and management of associated public risks should be done in endemic regions.

Hantavirus pulmonary syndrome in Manitoba.

The first confirmed case of hantavirus pulmonary syndrome in Manitoba was diagnosed in 1999. To define better the risk of exposure to hantaviruses in this area, the clinical features and epidemiological factors pertaining to this case were described, and a serological survey of rodents collected near the patient's residence was undertaken. Small mammals were collected using live traps, were anesthetized via inhalation of isoflurane and were bled. Human and mouse serologies were undertaken using an ELISA to detect hantavirus-specific immunoglobulin G and/or immunoglobulin M antibodies. In addition, a full medical and epidemiological assessment, as well as individual risk factor and exposure analysis, were conducted. A 27-year-old Manitoba woman presented with severe respiratory distress and diffuse bilateral air space disease radiologically. Despite extremely aggressive measures, including mechanical ventilation, antibiotics, fluid management and inotropic support, the patient's condition rapidly deteriorated, and she died 8 h after admission. Hantavirus pulmonary syndrome was confirmed by the detection of immunoglobulin M and immunoglobulin G antibodies to the Sin Nombre virus (SNV) in her sera and by the demonstration of SNV genomic sequences in her lung tissue. Exposure to hantavirus likely occurred in and around the home or in the rural area in which she resided. A total of 252 small mammals, primarily deer mice (Peromyscus maniculatus), were collected from 17 different sites at or near where the patient lived. Antibodies to SNV were detected in 28 of 244 (11.5%) deer mice, which were collected within 9 km of the residence of the fatal case, indicating that these rodents are a significant reservoir for SNV in this area.

Hantavirus pulmonary syndrome in northern Alberta, Canada: clinical and laboratory findings for 19 cases.

We reviewed the clinical and laboratory findings for 19 cases of hantavirus pulmonary syndrome (HPS) identified either serologically or by immunohistochemical testing of archival tissue at our tertiary care center. Fever (95%), cough (89%), and dyspnea (89%) were the most common presenting symptoms. The most prevalent presenting signs were respiratory abnormalities (95%) and tachycardia (84%). Common laboratory findings included thrombocytopenia (95%) and leukocytosis (79%). Elevated aspartate aminotransferase and lactate dehydrogenase levels were found in all patients tested. Intubation was required in 58% of the patients, and inotropic support was required in 53%. Our study confirms that serological responses appear early during clinical illness, making the enzyme immunoassay a useful tool for the diagnosis of acute HPS. The mortality (26%) and severity of disease that we observed among patients with HPS appear to be less than those reported elsewhere.

Leptospira infections in trappers from Ontario.

BACKGROUND: Four trappers presented to the Middlesex-London Health Unit in November, 1997 with similar clinical presentations. All four complained of fever, chills and headache, and three of the four had severe muscle aches. All gave histories of trapping raccoons before the onset of illness. Three of the four men exhibited diagnostic seroconversions to Leptospira grippotyphosa. OBJECTIVE: To describe the four suspected cases of leptospira infections and to determine whether raccoons might serve as a reservoir of infection using field studies. DESIGN: Raccoon serology were undertaken using the microscopic agglutination test against eight serovars of Leptospira interrogans including L grippotyphosa. Raccoons were trapped using Tomahawk live traps, anaesthetized with intramuscular injection of ketamine and acepromazine, bled by cardiac puncture and released. RESULTS: Forty-two raccoons were trapped in Middlesex (n=36) and Kent counties (n=6) from April 25 to May 2, 1998, and 10 (23.8%) of these animals had antibodies to L grippotyphosa. CONCLUSIONS: Infections due to L grippotyphosa or a closely related serovar are a risk for trappers in Ontario, and raccoons are a likely reservoir of this bacterium.

Arthropod-borne disease in Canada: A clinician's perspective from the 'Cold Zone'.

Arthropod-borne diseases do not occur commonly in Canada. Nevertheless, Canadians run the risk of contracting certain infections within the country during arthropod season, as well as when travelling abroad. Therefore, it is important that clinicians are aware of the possible occurrence of arthropod-borne diseases, and consider them in their differential diagnoses. The present review is divided into two sections: arthropod-borne diseases or disease agents documented in Canada, and imported arthropod-borne diseases. The review also provides brief overviews of these diseases.