Volume 26-08
15 April 2000

[Table of Contents]

HANTAVIRUS PULMONARY SYNDROME IN CANADA, 1989-1999

Introduction

Hantavirus pulmonary syndrome (HPS) was first described in 1993 in the southwestern United States. HPS is a respiratory illness associated with the inhalation of aerosolized rodent excreta (urine and feces) contaminated by hantavirus particles. Four hantavirus species have been implicated as etiological agents of HPS in North America⁽¹⁾. One species, Sin Nombre virus, has been associated with the largest proportion of HPS cases. Its primary reservoir is the deer mouse, Peromyscus maniculatus. Person-to-person transmission of HPS has not been documented in North America.

Clinical features and case definition

Upon inhalation of hantavirus contaminated excreta, an extensive infection of pulmonary endothelial cells occurs and a viremic phase is initiated. After an incubation period of 9 to 35 days, individuals usually experience fever, chills, occasional headaches, and sometimes gastrointestinal symptoms. Five days after the onset of initial symptoms, cough and shortness of breath typically develop; pulmonary edema and deterioration of cardiopulmonary function may then rapidly occur over the ensuing 24 hours. There is no proven effective antiviral therapy for HPS although clinical trials with ribavirin are in progress. Clinical management depends on careful fluid administration and ventilatory support.

Canada has adopted the HPS case definition that was initially developed by the United States Centers for Disease Control and Prevention and recommended by the Pan American Health Organization⁽¹⁾. A confirmed case is a person with clinical illness and laboratory confirmation of infection. Clinical illness is characterized by a febrile illness (> 38.3° C) with bilateral diffuse interstitial edema that may radiographically resemble acute respiratory distress syndrome and with respiratory compromise requiring supplemental oxygen and developing within 72 hours of hospitalization. Laboratory criteria for diagnosis includes any of the following:

• presence of hantavirus-specific IgM or a fourfold or greater increase in IgG antibody titres,
• positive reverse transcriptase-polymerase chain reaction (RT-PCR) amplification of viral RNA, and
• positive immunohistochemical results for hantavirus antigen in a patient's tissue.

Epidemiology in Canada

Although HPS was made a nationally notifiable disease as of 1 January 2000, provincial and territorial public-health authorities have previously reported confirmed cases. The first case of HPS recognized in Canada during active surveillance was in 1994 in British Columbia. Subsequently cases have been identified retrospectively with the earliest case dating back to 1989 in Alberta. As of 31 December 1999, 32 laboratory-confirmed cases have been reported in Canada with a case fatality rate of 38% (12/32). The average age of HPS cases has been 39 years (range: 15 to 62 years). The majority of cases (19/32, 60%) have been male. Cases have only been reported from western Canada. The majority of these have been reported from Alberta (20) with most originating in clusters southeast and northwest of Edmonton. Remaining cases have been reported from British Columbia (6), Saskatchewan (5), and Manitoba (1). The geographical distribution of Canadian HPS cases is similar to that in the United States where less densely populated western regions have experienced the greatest burden of disease.

Since 1994 when active surveillance for HPS was initiated in Canada, the number of cases per year has fluctuated from a high of eight in 1994 to two in 1999 (Figure 1). Yearly fluctuation in cases may reflect the occurrence of higher population densities of infected rodents due to mild winters and increased breeding capacity⁽²⁾. The increased prevalence of mice may lead to increased opportunities for human exposure to rodents and their excreta, and hence a higher risk of transmission of hantavirus infection to humans.

Figure 1 Number of HPS cases reported in Canada, 1994-1999*

*Three additional retrospective cases have been recognized as having occurred in 1989, 1990, and 1992 respectively. HPS cases in Canada have occurred in every month but March, with an apparent bimodal seasonal distribution of cases corresponding to the spring and late fall: 50% of the cases (16/32) occurred during the months of April, May and June (Figure 2). Although the reasons for the seasonal pattern of HPS are unclear, it is possible that a combination of human activity, rodent behavior, and ecologic factors may be responsible.

Figure 2 Seasonal distribution of HPS cases reported in Canada, 1989-1999

Available data on potential exposures to hantavirus prior to onset of illness suggest 70% of the cases were likely infected during domestic and farming activities (Figure 3). All cases occurred in rural settings where opportunities for exposure are greater as compared to an urban environment.

Figure 3 Potential exposure to hantavirus prior to onset of illness in Canadian cases

Rodent surveillance

In Canada, the ubiquitous deer mouse is the primary reservoir for Sin Nombre viruses. Seroprevalence and RT-PCR amplification studies carried out on over 6,000 rodents have documented the presence of hantavirus infected mice in every province except Prince Edward Island and Nova Scotia. Seropositive mice have also been found in the Yukon, but not in the Northwest Territories and Nunavut to date. However, only limited numbers of deer mice from Prince Edward Island, Nova Scotia, and the Northwest Territories have been tested; the possible occurrence of hantavirus infected mice in these areas cannot be excluded. Furthermore, the sampling of rodents for testing has been done by convenience and not systematically. The distribution of infected mice is discontinuous; some localities show no evidence of seropositive mice, whereas mice examined at various other trap sites within the same province exhibit > 30% seroprevalence. Further rodent surveillance is necessary to give a more complete picture of deer mouse seroprevalence throughout Canada.

Ongoing studies are being carried out to determine the prevalence of hantavirus in Canadian rodents other than deer mice. Recent serosurveys of Canadian meadow voles have shown that these rodents can also harbour hantaviruses. RT-PCR amplification and sequencing analysis of a hantavirus that infected a meadow vole in Ontario showed this virus to be related to Prospect Hill virus (Dr. M. Drebot: unpublished observations). This viral species has not been associated with human disease to date⁽¹⁾.

Hantavirus molecular epidemiology

Recent studies have shown a significant degree of genetic diversity among Sin Nombre-related hantaviruses across Canada⁽³⁾. Regional genetic variation among Sin Nombre-like viruses is a potential tool for carrying out molecular epidemiologic studies that may pinpoint sites of human exposure. The ability to identify mice carrying the strain of virus associated with an HPS case may assist in distinguishing among multiple sites of possible exposures. Molecular epidemiology may also improve our understanding of the factors associated with hantavirus infection. Nucleic acid sequencing of amplified hantavirus genome was carried out as part of an investigation of the first HPS case ever reported from Manitoba in 1999. Preliminary results have demonstrated genetic matches between the hantavirus strain infecting this case and Sin Nombre-like viruses infecting deer mice at sites near where the case lived.

Conclusions

Although cases of HPS have been confined to the western provinces, the presence of infected mice in eastern Canada suggests that the potential for HPS exists across the country. Prevention of this rare disease may be achieved through education of the general public on the risks associated with exposure to rodents and their excreta and adoption of appropriate preventive practices⁽⁴⁾. The combination of molecular epidemiology and descriptive epidemiology of HPS in the human population and hantavirus infection in the rodent populations shows promise as an approach to further improve HPS risk assessment.

References

1. Hantavirus in the Americas - guidelines for prevention, diagnosis, treatment, and control. Washington, DC, 1999: PAHO. PAHO Technical Paper No. 47.

2. Mills JN, Yates TL, Ksiazek et al. Long term studies of hantavirus reservoir populations in the southwestern United States: rationale, potential, and methods. Emer Infect Dis 1999;5:95-101.

3. Drebot MA, Tipples GA. Application of molecular diagnostics for the surveillance of hantavirus and measles virus in Canada. Can J Infect Dis 1998;9:71-75.

4. LCDC. Update: hantavirus pulmonary syndrome - United States. CCDR 1999;25:141-43.

Source: MA Drebot, PhD, H Artsob, PhD, Zoonotic Diseases and Special Pathogens, Bureau of Microbiology, Canadian Science Centre for Human and Animal Health, Winnipeg, Man.; D Werker, MD, Field Epidemiology Training Program, LCDC, Ottawa, Ont.

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