Harvey Artsob

Dengue: a continuing global threat

Dengue fever and dengue haemorrhagic fever are important arthropod-borne viral diseases. Each year, there are ∼50 million dengue infections and ∼500,000 individuals are hospitalized with dengue haemorrhagic fever, mainly in Southeast Asia, the Pacific and the Americas. Illness is produced by any of the four dengue virus serotypes. A global strategy aimed at increasing the capacity for surveillance and outbreak response, changing behaviours and reducing the disease burden using integrated vector management in conjunction with early and accurate diagnosis has been advocated. Antiviral drugs and vaccines that are currently under development could also make an important contribution to dengue control in the future.

Evaluation of diagnostic tests: dengue

Dengue is an arthropod-borne flavivirus that comprises four distinct serotypes (DEN-1, DEN-2, DEN-3 and DEN-4) that constitute an antigenic complex of the genus flavivirus, family Flaviviridae. Infection by one serotype induces life-long immunity against reinfection by the same serotype, but only transient and partial protection against infection with the other serotypes1,2. Dengue virus infections can result in a range of clinical manifestations from asymp tomatic infection to dengue fever (DF) and the severe disease dengue haemorrhagic fever/dengue shock syndrome (DHF/ DSS). Most dengue infections are asymptomatic or cause mild symptoms, which are characterized by undifferentiated fever with or without rash. Typical DF is characterized by high fever, severe headache, myalgia, arthralgia, retro-orbital pain and maculopapular rash. Some patients show petechiae, bruising or thrombocytopenia. The clinical presentation of acute dengue infection is non-specific but 5–10% of patients progress to severe DHF/DSS, which can result in death if it is not managed appropriately. Plasma extravasation is the main pathophysiological finding of DHF/ DSS, which differentiates it from DF. DHF/ DSS is characterized by high fever, bleeding, thrombocytopenia and haemoconcentration (an increase in the concentration of blood cells as a result of fluid loss). Approximately 3–4 days after the onset of fever, patients can present with petechiae, rash, epistaxis, and gingival and gastrointestinal bleeding. Pleural effusion and ascites are common. Some patients develop circulatory failure (DSS), presenting with a weak and fast pulse, narrowing of pulse pressure or hypotension, cold and moist skin and altered mental state. Although there are no specific antiviral treatments for dengue infection, patients usually recover when the need for fluid management is identified early and electrolytes are administered3. It has been proposed that the classification of dengue disease should be simplified as severe and non-severe dengue. This simplified classification would make patient management and surveillance easier4. There is a need for specific, inexpensive dengue diagnostic tests that can be used for clinical management, surveillance and outbreak investigations and would permit early intervention to treat patients and prevent or control epidemics. Progress is being made in primary prevention, with several candidate dengue vaccines in late phases of development as well as improved vector control measures. Additionally, new techniques for the early detection of severe disease such as the use of biomarkers have the potential to decrease morbidity and

Evaluation of Commercially Available Anti–Dengue Virus Immunoglobulin M Tests

Anti–dengue virus immunoglobulin M kits were evaluated. Test sensitivities were 21%–99% and specificities were 77%–98% compared with reference ELISAs. False-positive results were found for patients with malaria or past dengue infections. Three ELISAs showing strong agreement with reference ELISAs will be included in the World Health Organization Bulk Procurement Scheme.

The emergence of Lyme disease in Canada

Lyme disease, caused by the bacterium Borrelia burgdorferi and transmitted by tick vectors, is the most commonly reported vector-borne disease in the temperate zone. [1][1] More than 20 000 cases are recorded annually in the United States. [2][2] In about 80% of cases, early Lyme disease is

Landscape structure influences continental distribution of hantavirus in deer mice

We hypothesized that landscape structure affects movement of individuals through the landscape, which affects the rate and pattern of disease transmission. Based on this hypothesis, we predicted a relationship between landscape structure and disease incidence in spatially structured populations. We tested this prediction for hantavirus incidence in deer mice (Penomysens moniculatus), using a novel index of habitat fragmentation for transect data. A series of four stepwise logistic regression analyses were conducted on serological and ecological data from 2837 mice from 101 sites across Canada. The significant variables, ranked in decreasing order of size of their effect on virus incidence were: human buildings, landscape composition (amount of deer mouse habitat in the 1-km radius landscape surrounding each site), landscape configuration (fragmentation of deer mouse habitat in the 1-km radius landscape surrounding each site), mean annual temperature, and seasonal variation. Our results suggest that epidemiological models should consider not only the demographic structure of the host population, but its spatial structure as well, as inferred from landscape structure. Landscape structure can have a greater effect on the pattern of distribution of a virus in its host population than other ecological variables such as climate and seasonal change. The usefulness of landscape data in epidemiological models depends on the use of the appropriate spatial scale, which can be determined empirically. Epidemiological models with a spatially structured host population can benefit from the explicit consideration of landscape structure.

West Nile Virus Surveillance and Diagnostic: A Canadian Perspective

A surveillance program has been in place since 2000 to detect the presence of West Nile virus (WNV) in Canada. Serological assays are most appropriate when monitoring for human disease and undertaking case investigations. Genomic amplification procedures are more commonly used for testing animal and mosquito specimens collected as part of ongoing surveillance efforts. The incursion of WNV into this country was documented for the first time in 2001 when WNV was demonstrated in 12 Ontario health units during the late summer and fall. In 2002 WNV activity was documented by avian surveillance in Ontario by mid-May with subsequent expansion of the virus throughout Ontario and into Quebec, Manitoba, Saskatchewan and Nova Scotia. Human cases were recorded in both Ontario and Quebec in 2002 with approximately 800 to 1000 probable, confirmed and suspect cases detected. The possible recurrence and further spread of WNV to other parts of Canada in 2003 must be anticipated with potential risk to public health. The continued surveillance and monitoring for WNV-associated human illness is necessary and appropriate disease prevention measures need to be in place in 2003.

Rapid Antigen-Capture Assay To Detect West Nile Virus in Dead Corvids

The utility of the VecTest antigen-capture assay to detect West Nile virus (WNV) in field-collected dead corvids was evaluated in Manitoba and Ontario, Canada, in 2001 and 2002. Swabs were taken from the oropharynx, cloaca, or both of 109 American Crows, 31 Blue Jays, 6 Common Ravens, and 4 Black-billed Magpies from Manitoba, and 255 American Crows and 28 Blue Jays from Ontario. The sensitivity and specificity of the antigen-capture assay were greatest for samples from American Crows; oropharyngeal swabs were more sensitive than cloacal swabs, and interlaboratory variation in the results was minimal. The sensitivity and specificity of the VecTest using oropharyngeal swabs from crows were 83.9% and 93.6%, respectively, for Manitoba samples and 83.3% and 95.8%, respectively, for Ontario birds. The VecTest antigen-capture assay on oropharyngeal secretions from crows is a reliable and rapid diagnostic test that appears suitable for incorporation into a WNV surveillance program.

West Nile Virus infection in humans and horses, Cuba.

A surveillance system to detect West Nile virus (WNV) was established in Cuba in 2002. WNV infection was confirmed by serologic assays in 4 asymptomatic horses and 3 humans with encephalitis in 2003 and 2004. These results are the first reported evidence of WNV activity in Cuba.

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.

Sin Nombre virus shedding patterns in naturally infected deer mice (Peromyscus maniculatus) in relation to duration of infection.

A 2-year capture-mark-recapture study was conducted in southern Manitoba, Canada, to test for an association between the duration of Sin Nombre virus (SNV) infection in deer mice (Peromyscus maniculatus) and virus shedding. Hantavirus-specific IgG antibodies were detected in 22.2% of captured deer mice, and recently infected deer mice were identified based on the detection of low-avidity IgG antibodies. SNV RNA was detected in blood samples from the majority of seropositive deer mice with no significant difference in the association of SNV RNA between the low- and high-avidity groups (57.8% and 52.1%, respectively). A small subset of seropositive mice (11.6%) had detectable SNV RNA in oropharyngeal fluids (OPF) or urine. A greater proportion of deer mice with low-avidity antibodies had SNV RNA in OPF or urine compared with rodents with high-avidity antibodies (21% versus 6.8%, respectively). This is the first study of naturally infected deer mice to provide evidence that recently infected mice are more likely to shed SNV and thus might represent a greater risk of human infection.