Richard J. Douglass

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.

SIN NOMBRE VIRUS INFECTION OF DEER MICE IN MONTANA: CHARACTERISTICS OF NEWLY INFECTED MICE, INCIDENCE, AND TEMPORAL PATTERN OF INFECTION

Sin Nombre virus (SNV), hosted by the deer mouse (Peromyscus maniculatus), is the principal cause of hantavirus pulmonary syndrome (HPS) in North America. To improve our understanding of factors that contribute to the occurrence of HPS, we conducted an extensive field study of the characteristics of newly infected (as determined by recent acquisition of antibody) deer mice and the temporal pattern of antibody acquisition (seroconversion) from 1994 through 2004 in Montana, USA. We sampled 6,584 individual deer mice, of which 2,747 were captured over multiple trapping periods. Among these 2,747 deer mice, we detected 171 instances of seroconversion. There was no relationship between seroconversion and the acquisition of scars. However, recently infected Montana deer mice were more likely to be older, more likely to be males, and more likely to be in breeding condition. In addition, recently infected male deer mice gained less weight over the 1-mo period following seroconversion than did those that did not acquire antibody, suggesting that SNV infection may have negatively impacted the health of infected rodents. Incidence was highly variable among years, and timing of infections was primarily associated with the breeding season (generally early spring through late fall).

The effect of seasonality, density and climate on the population dynamics of Montana deer mice, important reservoir hosts for Sin Nombre hantavirus.

1. Since Sin Nombre virus was discovered in the U.S. in 1993, longitudinal studies of the rodent reservoir host, the deer mouse (Peromyscus maniculatus) have demonstrated a qualitative correlation among mouse population dynamics and risk of hantavirus pulmonary syndrome (HPS) in humans, indicating the importance of understanding deer mouse population dynamics for evaluating risk of HPS. 2. Using capture-mark-recapture statistical methods on a 15-year data set from Montana, we estimated deer mouse survival, maturation and recruitment rates and tested the relative importance of seasonality, population density and local climate in explaining temporal variation in deer mouse demography. 3. From these estimates, we designed a population model to simulate deer mouse population dynamics given climatic variables and compared the model to observed patterns. 4. Month, precipitation 5 months previously, temperature 5 months previously and to a lesser extent precipitation and temperature in the current month, were important in determining deer mouse survival. Month, the sum of precipitation over the last 4 months, and the sum of the temperature over the last 4 months were important in determining recruitment rates. Survival was more important in determining the growth rate of the population than recruitment. 5. While climatic drivers appear to have a complex influence on dynamics, our forecasts were good. Our quantitative model may allow public health officials to better predict increased human risk from basic climatic data.

LONG-TERM DYNAMICS OF SIN NOMBRE VIRAL RNA AND ANTIBODY IN DEER MICE IN MONTANA

Infections with hantaviruses in the natural host rodent may result in persistent, asymptomatic infections involving shedding of virus into the environment. Laboratory studies have partially characterized the acute and persistent infection by Sin Nombre virus (SNV) in its natural host, the deer mouse (Peromyscus maniculatus). However, these studies have posed questions that may best be addressed using longitudinal studies involving sequential sampling of individual wild-caught, naturally infected mice. Using enzyme immunoassay and polymerase chain reaction (PCR) analysis of monthly blood samples, we followed the infection status of deer mice in a mark-recapture study in Montana for 2 yr. Only six of 907 samples without IgG antibody to SNV contained detectable SNV RNA, suggesting that there is a very brief period of viremia before the host develops detectable antibody. The simultaneous presence of both antibody and viral RNA in blood was detected in consecutive monthly samples for as long as 3 mo. However, chronic infection was typified by alternating characteristics of PCR positivity and PCR negativity. Two possible interpretations of these results are that 1) viral RNA may be consistently present in the blood of chronically infected deer mouse, but that viral RNA is near the limits of PCR detectability or 2) SNV RNA sporadically appears in blood as a consequence of unknown physiological events. The occurrence of seasonal patterns in the proportion of samples that contains antibody and that also contained SNV RNA demonstrated a temporal association between recent infection (antibody acquisition) and presence of viral RNA in blood.

Hantavirus in Montana Deer Mouse Populations: Preliminary Results

Dynamics of small mammal populations and the prevalence of antibodies for hantavirus were determined in six locations in central and western Montana (USA). Eighteen live-trapping grids were trapped monthly from June through September 1994. Deer mouse (Peromyscus maniculatus) populations ranged from 0 to over 90 on one-hectare grids. Our bleeding technique had no apparent effect on survival of deer mice. Deer mice, meadow voles (Microtus pennsylvanicus), and sagebrush voles (Lagurus curtatus) were seropositive. Thirty-eight (8%) (range, 0% to 30%) of 471 deer mice were seropositive for hantavirus antibodies. Seropositive mice were older and had lower monthly survival rates than seronegative deer mice. We found no relationship between prevalence of hantavirus antibodies and population density.

Environmental monitoring to enhance comprehension and control of infectious diseases

In a world of emerging and resurging infectious diseases, dominated by zoonoses, environmental monitoring plays a vital role in our understanding their dynamics and their spillover to humans. Here, we critically review the ecology, epidemiology and need for monitoring of a variety of directly transmitted (Sin Nombre virus, Avian Influenza) and vector-borne (Ross River virus, West Nile virus, Lyme disease, anaplasmosis and babesiosis) zoonoses. We focus on the valuable role that existing monitoring plays in the understanding of these zoonoses, the demands for new monitoring, and how improvements can be made to existing monitoring. We also identify the fruitful outcomes which would result from implementation of the monitoring demands we have highlighted. This review aims to promote improvements in our understanding of zoonoses, their management, and public health by encouraging discussion among researchers and public health officials.

Deer Mouse Movements in Peridomestic and Sylvan Settings in Relation to Sin Nombre Virus Antibody Prevalence

Prevalence of antibody to Sin Nombre virus (SNV) has been found to be nearly twice as high in deer mice (Peromyscus maniculatus) in peridomestic settings as in sylvan settings in two studies in Montana and one in New Mexico. We investigated whether this difference may be related to a difference in deer mouse movements in the two settings. We used radiotelemetry to determine home range size and length of movement for 22 sylvan (1991–1992) and 40 peridomestic deer mice (1995–1999). We also determined the percentage of locations inside versus outside of buildings for peridomestic mice. Though variable, average home range size for female deer mice was significantly smaller for peridomestic deer mice than for sylvan deer mice. The smaller home range in peridomestic settings may concentrate shed SNV, and protection from solar ultraviolet radiation inside buildings may increase environmental persistence of SNV. Both these factors could lead to increased SNV exposure of deer mice within peridomestic populations and result in higher antibody prevalence. Peridomestic deer mice moved between buildings and outside areas, which is evidence that SNV can be transmitted between peridomestic and sylvan populations.

Rodent Community Structure and Andes Virus Infection in Sylvan and Peridomestic Habitats in Northwestern Patagonia, Argentina

Modifications of natural habitat in peridomestic rural areas could affect original rodent community composition, diversity, and evenness. In zoonoses such as hantavirus pulmonary syndrome, the presence of a diverse community can dilute the impact of the principal reservoir, reducing risk to humans. The goal of this study was to examine rodent community composition, abundance of Andes virus (ANDV) host (Oligoryzomys longicaudatus), ANDV prevalence, and temporal variability associated with rural peridomestic settings in Patagonia, Argentina. We trapped rodents in peridomestic settings and nearby sylvan areas for 2 years. The numerically dominant species differed between peridomestic and sylvan settings. O. longicaudatus was the most abundant species in peridomestic settings (>50% of individuals). Diversity and evenness in peridomestic settings fluctuated temporally, with an abrupt decline in evenness coinciding with peaks in ANDV prevalence. The probability of finding an ANDV-positive mouse in peridomestic settings was 2.44 times greater than in sylvan habitats. Changes in rodent communities in peridomestic settings may increase the probability for human exposure to ANDV because those settings promote the presence of O. longicaudatus with high ANDV antibody prevalence. High O. longicaudatus relative abundance in an unstable community associated with peridomestic settings may favor intraspecific contact, leading to a higher probability of virus transmission.

Seroprevalence Against Sin Nombre Virus in Resident and Dispersing Deer Mice

Through dispersal, deer mice (Peromyscus maniculatus) enter peridomestic settings (e.g., outbuildings, barns, cabins) and expose humans and other deer mouse populations to Sin Nombre virus (SNV). In June 2004, research on deer mouse dispersal was initiated at 2 locations in Montana. During the course of the study, over 6000 deer mouse movements were recorded, and more than 1000 of these movements were classified as dispersal movements. More than 1700 individual deer mice were captured and tested for SNV, revealing an average SNV antibody prevalence of approximately 11%. Most of the dispersing and antibody-positive individuals were adult males. Among the few subadult dispersing mice discovered during the study, none were seropositive for SNV. Our results suggest that dispersal rates are higher in high abundance populations of deer mice and that during peak times of dispersal, human exposure to SNV, which commonly occurs in peridomestic settings, could increase.

DELAYED DENSITY-DEPENDENT PREVALENCE OF SIN NOMBRE VIRUS INFECTION IN DEER MICE (PEROMYSCUS MANICULATUS) IN CENTRAL AND WESTERN MONTANA

Understanding how transmission of zoonoses takes place within reservoir populations, such as Sin Nombre virus (SNV) among deer mice (Peromyscus maniculatus), is important in determining the risk of exposure to other hosts, including humans. In this study, we examined the relationship between deer mouse populations and the prevalence of antibodies to SNV, a system where the effect of host population abundance on transmission is debated. We examined the relationship between abundance of deer mice in late summer–early autumn and SNV antibody prevalence the following spring–early summer (termed delayed density-dependent [DDD] prevalence of infection) at both regional and local scales, using 12 live-trapping grids for 11–14 yr, across central and western Montana. When all trapping grids were combined (regional scale), there was a significant DDD relationship for individual months and when months within seasons were averaged. However, within individual grids (local scale), evidence of DDD prevalence of infection was observed consistently at only one location. These findings suggest that, although there is evidence of DDD prevalence of infection at regional scales, it is not always apparent at local scales, possibly because the regional pattern of DDD infection prevalence is driven by differences in abundance and prevalence among sites, rather than in autumn-spring delays. Transmission of SNV may be more complex than the original hypothesis of autumn-spring delayed density dependence suggests. This complexity is also supported by recent modeling studies. Empirical investigations are needed to determine the duration and determinants of time-lagged abundance and antibody prevalence. Our study suggests predicting local, human exposure risk to SNV in spring, based on deer mouse abundance in autumn, is unlikely to be a reliable public health tool, particularly at local scales.