Toward a Mechanistic Understanding of Environmentally Forced Zoonotic Disease Emergence: Sin Nombre Hantavirus.

Understanding the environmental drivers of zoonotic reservoir and human interactions is crucial to understanding disease risk, but these drivers are poorly predicted. We propose a mechanistic understanding of human-reservoir interactions, using hantavirus pulmonary syndrome as a case study. Crucial processes underpinning the disease's incidence remain poorly studied, including the connectivity among natural and peridomestic deer mouse host activity, virus transmission, and human exposure. We found that disease cases were greatest in arid states and declined exponentially with increasing precipitation. Within arid environments, relatively rare climatic conditions (e.g., El Niño) are associated with increased rainfall and reservoir abundance, producing more frequent virus transmission and host dispersal. We suggest that deer mice increase their occupancy of peridomestic structures during spring-summer, amplifying intraspecific transmission and human infection risk. Disease incidence in arid states may increase with predicted climatic changes. Mechanistic approaches incorporating reservoir behavior, reservoir-human interactions, and pathogen spillover could enhance our understanding of global hantavirus ecology, with applications to other directly transmitted zoonoses.

Phylogenetically distinct hantaviruses in the masked shrew (Sorex cinereus) and dusky shrew (Sorex monticolus) in the United States.

A limited search for hantaviruses in lung and liver tissues of Sorex shrews (family Soricidae, subfamily Soricinae) revealed phylogenetically distinct hantaviruses in the masked shrew (Sorex cinereus) from Minnesota and in the dusky shrew (Sorex monticolus) from New Mexico and Colorado. The discovery of these shrew-borne hantaviruses, named Ash River virus and Jemez Springs virus, respectively, challenges the long-held dogma that rodents are the sole reservoir hosts and forces a re-examination of their co-evolutionary history. Also, studies now underway are aimed at clarifying the epizootiology and pathogenicity of these new members of the genus Hantavirus.

Demographic factors associated with prevalence of antibody to Sin Nombre virus in deer mice in the western United States.

We used long-term data collected for up to 10 yr (1994-2004) at 23 trapping arrays (i.e., webs and grids) in Arizona, Colorado, Montana, and New Mexico to examine demographic factors known or suspected to be associated with risk of infection with Sin Nombre virus (SNV) in its natural host, the deer mouse (Peromyscus maniculatus). Gender, age (mass), wounds or scars, season, and local relative population densities were statistically associated with the period prevalence of antibody (used as a marker of infection) to SNV in host populations. Nevertheless, antibody prevalence and some of the risk factors associated with antibody prevalence, such as relative population density, gender bias, and prevalence of wounding, varied significantly among sites and even between nearby trapping arrays at a single site. This suggests that local microsite-specific differences play an important role in determining relative risk of infection by SNV in rodents and, consequently, in humans. Deer mouse relative population density varied among sites and was positively and statistically associated with infection prevalence, an association that researchers conducting shorter-term studies failed to demonstrate. Both wounding and antibody prevalence increased with mass class in both males and females; this increase was much more pronounced in males than in females and wounding was more frequent in adult males than in adult females. Prevalence of wounding was greatest among seropositive deer mice, regardless of mass class, but many deer mice without detectable wounds or scars eventually became infected. Many of these patterns, which will be useful in the development of predictive models of disease risk to humans, were only detected through the application of data collected over a long (10-yr) period and with abundant replication.

Hantavirus in northern short-tailed shrew, United States.

Phylogenetic analyses, based on partial medium- and large-segment sequences, support an ancient evolutionary origin of a genetically distinct hantavirus detected by reverse transcription-PCR in tissues of northern short-tailed shrews (Blarina brevicauda) captured in Minnesota in August 1998. To our knowledge, this is the first evidence of hantaviruses harbored by shrews in the Americas.

Satellite imagery characterizes local animal reservoir populations of Sin Nombre virus in the southwestern United States.

The relationship between the risk of hantaviral pulmonary syndrome (HPS), as estimated from satellite imagery, and local rodent populations was examined. HPS risk, predicted before rodent sampling, was highly associated with the abundance of Peromyscus maniculatus, the reservoir of Sin Nombre virus (SNV). P. maniculatus were common in high-risk sites, and populations in high-risk areas were skewed toward adult males, the subclass most frequently infected with SNV. In the year after an El Niño Southern Oscillation (ENSO), captures of P. maniculatus increased only in high-risk areas. During 1998, few sites had infected mice, but by 1999, 1820 of the high-risk sites contained infected mice and the crude prevalence was 30.8%. Only 118 of the low-risk sites contained infected rodents, and the prevalence of infection was lower (8.3%). Satellite imagery identified environmental features associated with SNV transmission within its reservoir population, but at least 2 years of high-risk conditions were needed for SNV to reach high prevalence. Areas with persistently high-risk environmental conditions may serve as refugia for the survival of SNV in local mouse populations.