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Despite important implications for biological conservation and public health, the potential generality of a prophylactic effect of biodiversity on zoonotic pathogen transmission (e.g., dilution effect) remains hotly debated, potentially because existing studies focus on different kinds of analyses as well as different spatial scales. Here, we test if changing the spatial scale of analysis can affect the detection of a relationship between hantavirus infection prevalence and rodent species richness throughout the World. We found that these relationships are always negative, whatever the spatial scale. Nevertheless, the dilution effect magnitude decreases if larger spatial scales are considered. These results, which remain consistent for all regions, highlight that the dilution effect should be a general phenomenon for hantaviruses, but that its detection can be hampered by the spatial scale considered. Finally, we discuss the mechanisms that can hinder the observation of a dilution effect and the necessity to consider other host-pathogen systems.

Hantaviruses (Family: Hantaviridae, genus: Orthohantavirus) and their associated human diseases occur globally and differ according to their geographic distribution. The structure of small mammal assemblages and phylogenetic relatedness among host species are suggested as strong drivers for the maintenance and spread of hantavirus infections in small mammals. We developed predictive models for hantavirus infection prevalence in rodent assemblages using defined ecological correlates from our current knowledge of hantavirus-host distributions to provide predictive models at the global and continental scale. We utilized data from published research between 1971&ndash, 2014 and determined the biological and ecological characteristics of small mammal assemblages to predict the prevalence of hantavirus infections. These models are useful in predicting hantavirus disease outbreaks based on environmental and biological information obtained through the surveillance of rodents.

The global burden of infectious diseases and the increased attention to natural, accidental, and deliberate biological threats has resulted in significant investment in infectious disease research. Translating the results of these studies to inform prevention, detection, and response efforts often can be challenging, especially if prior relationships and communications have not been established with decision-makers. Whatever scientific information is shared with decision-makers before, during, and after public health emergencies is highly dependent on the individuals or organizations who are communicating with policy-makers. This article briefly describes the landscape of stakeholders involved in information-sharing before and during emergencies. We identify critical gaps in translation of scientific expertise and results, and biosafety and biosecurity measures to public health policy and practice with a focus on One Health and zoonotic diseases. Finally, we conclude by exploring ways of improving communication and funding, both of which help to address the identified gaps. By leveraging existing scientific information (from both the natural and social sciences) in the public health decision-making process, large-scale outbreaks may be averted even in low-income countries.

In this era of unprecedented biodiversity loss and increased zoonotic disease emergence, it is imperative to understand the effects of biodiversity on zoonotic pathogen dynamics in wildlife. Whether increasing biodiversity should lead to a decrease or increase in infection prevalence, termed the dilution and amplification effects, respectively, has been hotly debated in disease ecology. Sin Nombre hantavirus, which has an ∼35% mortality rate when it spills over into humans, occurs at a lower prevalence in the reservoir host, the North American deermouse, in areas with higher small mammal diversity-a dilution effect. However, the mechanism driving this relationship is not understood. Using a mechanistic mathematical model of infection dynamics and a unique long-term, high-resolution, multisite dataset, it appears that the observed dilution effect is a result of increasing small-mammal diversity leading to decreased deermouse population density and, subsequently, prevalence (a result of density-dependent transmission). However, once density is taken into account, there is an increase in the transmission rate at sites with higher diversity-a component amplification effect. Therefore, dilution and amplification are occurring at the same time in the same host-pathogen system; there is a component amplification effect (increase in transmission rate), but overall a net dilution because the effect of diversity on reservoir host population density is stronger. These results suggest we should focus on how biodiversity affects individual mechanisms that drive prevalence and their relative strengths if we want to make generalizable predictions across host-pathogen systems.

Rodents represent 42% of the world's mammalian biodiversity encompassing 2,277 species populating every continent (except Antarctica) and are reservoir hosts for a wide diversity of disease agents. Thus, knowing the identity, diversity, host-pathogen relationships, and geographic distribution of rodent-borne zoonotic pathogens, is essential for predicting and mitigating zoonotic disease outbreaks. Hantaviruses are hosted by numerous rodent reservoirs. However, the diversity of rodents harboring hantaviruses is likely unknown because research is biased toward specific reservoir hosts and viruses. An up-to-date, systematic review covering all known rodent hosts is lacking. Herein, we document gaps in our knowledge of the diversity and distribution of rodent species that host hantaviruses. Of the currently recognized 681 cricetid, 730 murid, 61 nesomyid, and 278 sciurid species, we determined that 11.3, 2.1, 1.6, and 1.1%, respectively, have known associations with hantaviruses. The diversity of hantaviruses hosted by rodents and their distribution among host species supports a reassessment of the paradigm that each virus is associated with a single-host species. We examine these host-virus associations on a global taxonomic and geographical scale with emphasis on the rodent host diversity and distribution. Previous reviews have been centered on the viruses and not the mammalian hosts. Thus, we provide a perspective not previously addressed.

Predicting outbreaks of zoonotic infections in reservoir hosts that live in highly fluctuating environments, such as Sin Nombre virus (SNV) in deer mice, is particularly challenging because host populations vary widely in response to environmental conditions and the relationship between field infection rates and abundance often appears to contradict conventional theory. Using a stage-structured host-pathogen model parameterized and cross-validated from a unique 15-year data set, we show how stochastic population fluctuations can lead to predictable dynamics of SNV in deer mice. Significant variation in host abundance and the basic reproductive number of the virus results in intermittent crossing of the critical host population density necessary for SNV endemicity and frequent local extinctions. When environmental conditions favor growth of the host population above the threshold, host–pathogen interactions lead to delayed density dependence in reservoir prevalence. The resultant ecological delay may provi...

Biodiversity is of critical value to human societies, but recent evidence that biodiversity may mitigate infectious-disease risk has sparked controversy among researchers. The majority of work on this topic has focused on direct assessments of the relationship between biodiversity and endemic-pathogen prevalence, without disentangling intervening mechanisms; thus study outcomes often differ, fuelling more debate. Here, we suggest two critical changes to the approach researchers take to understanding relationships between infectious disease, both endemic and emerging, and biodiversity that may help clarify sources of controversy. First, the distinct concepts of hazards versus risks need to be separated to determine how biodiversity and its drivers may act differently on each. This distinction is particularly important since it illustrates that disease emergence drivers in humans could be quite different to the general relationship between biodiversity and transmission of endemic pathogens. Second, the interactive relationship among biodiversity, anthropogenic change and zoonotic disease risk, including both direct and indirect effects, needs to be recognized and accounted for. By carefully disentangling these interactions between humans' activities and pathogen circulation in wildlife, we suggest that conservation efforts could mitigate disease risks and hazards in novel ways that complement more typical disease control efforts. This article is part of the themed issue ‘Conservation, biodiversity and infectious disease: scientific evidence and policy implications’.

Hantaviruses are widespread emergent zoonotic agents that cause unapparent or limited disease in their rodent hosts, yet cause acute, often fatal pulmonary or renal infections in humans. Previous laboratory experiments with rodent reservoir hosts indicate that hantaviruses can be cleared from host blood early in the infection cycle, while sequestered long term in various host organs. Field studies of North American deer mice (Peromyscus maniculatus), the natural reservoir of Sin Nombre hantavirus, have shown that viral RNA can be transiently detected well past the early acute infection stage, but only in the minority of infected mice. Here, using a non-degenerate RT-PCR assay optimized for SNV strains known to circulate in Montana, USA, we show that viral RNA can be repeatedly detected on a monthly basis in up to 75% of antibody positive deer mice for periods up to 3–6 months. More importantly, our data show that antibody positive male deer mice are more than twice as likely to have detectable SNV RNA in their blood as antibody positive females, suggesting that SNV-infected male deer mice are more likely to shed virus and for longer periods of time.

International audience; Parasites and pathogens are increasingly recognized as significant drivers of ecological and evolutionary change in natural ecosystems. Concurrently, transmission of infectious agents among human, livestock, and wildlife populations represents a growing threat to veterinary and human health. In light of these trends and the scarcity of long‐term time series data on infection rates among vectors and reservoirs, the National Ecological Observatory Network (NEON) will collect measurements and samples of a suite of tick‐, mosquito‐, and rodent‐borne parasites through a continental‐scale surveillance program. Here, we describe the sampling designs for these efforts, highlighting sampling priorities, field and analytical methods, and the data as well as archived samples to be made available to the research community. Insights generated by this sampling will advance current understanding of and ability to predict changes in infection and disease dynamics in novel, interdisciplinary, and collaborative ways.

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 Nino) 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.

Understanding the ecology of environmentally acquired and multi-host pathogens affecting humans and wildlife has been elusive in part because fluctuations in the abundance of host and pathogen species may feed back onto pathogen transmission. Complexity of pathogen-host dynamics emerges from processes driving local extinction of the pathogen, its hosts and non-hosts. While the extinction of species may entail losses in pathogen-host interactions and decrease the proportion of hosts infected by a pathogen (prevalence), some studies suggest the opposite pattern. Niche-based extinction, based on the species tolerance to environmental conditions, may increase prevalence of infection because the pathogen and its hosts persist, while other species go extinct. Hence, understanding prevalence of infection requires disentangling random-and niche-based extinction processes occurring simultaneously. To contribute to this exercise, we analysed the prevalence of an environmentally acquired, multi-host pathogen, Mycobacterium ulcerans (MU), in a unique dataset of 16 communities of freshwater animals, surveyed during 12 months in Akonolinga, Cameroon in equatorial Africa. Two different ecosystems were identified: rivers (lotic) and swamps and flooded areas (lentic). Increased prevalence of MU infection was correlated with niche-based extinction of aquatic host invertebrates and vertebrates in the lentic ecosystems, whereas decreased prevalence was associated with random disassembly of the lotic ecosystems. This finding suggests that random and niche-based extinction of host taxa are key to assessing the effect of local extinction of species on the ecology of environmentally acquired and multi-host pathogens.

Thirteen hantavirus genotypes, associated with at least 12 sigmodontine reservoir rodents, have been recognized in the four countries that represent the Southern Cone of South America. Host-virus relationships are not as well defined as in North America; several Southern Cone hantaviruses appear to share a common host and some viruses do not occur throughout the range of their host. Although hantavirus-host relationships in the Southern Cone are less strictly concordant with the single-host-single-virus pattern reported elsewhere, recent studies suggest that much of the ambiguity may result from an incomplete understanding of host and hantavirus systematics. Although some Southern Cone host species are habitat generalists, some sympatric species are habitat specialists, helping to explain how some strict host-virus pairings may be maintained. In some cases, host population densities were higher in peridomestic habitats and prevalence of hantavirus infection was higher in host populations in peridomestic habitats. Seasonal and multiyear patterns in climate and human disturbance affect host population densities, prevalence of infection, and disease risk to humans. Unusually high hantavirus antibody prevalence in indigenous human populations may be associated with frequent and close contact with host rodents. Ongoing studies are improving our understanding of hantavirus-host ecology and providing tools that may predict human risk.

Deer mice (Peromyscus maniculatus) are the main reservoir host for Sin Nombre virus, the primary etiologic agent of hantavirus pulmonary syndrome in North America. Sequential changes in weather and plant productivity (trophic cascades) have been noted as likely catalysts of deer mouse population irruptions, and monitoring and modeling of these phenomena may allow for development of early-warning systems for disease risk. Relationships among weather variables, satellite-derived vegetation productivity, and deer mouse populations were examined for a grassland site east of the Continental Divide and a sage-steppe site west of the Continental Divide in Montana, USA. We acquired monthly deer mouse population data for mid-1994 through 2007 from long-term study sites maintained for monitoring changes in hantavirus reservoir populations, and we compared these with monthly bioclimatology data from the same period and gross primary productivity data from the Moderate Resolution Imaging Spectroradiometer sensor for 2000–06. We used the Random Forests statistical learning technique to fit a series of predictive models based on temperature, precipitation, and vegetation productivity variables. Although we attempted several iterations of models, including incorporating lag effects and classifying rodent density by seasonal thresholds, our results showed no ability to predict rodent populations using vegetation productivity or weather data. We concluded that trophic cascade connections to rodent population levels may be weaker than originally supposed, may be specific to only certain climatic regions, or may not be detectable using remotely sensed vegetation productivity measures, although weather patterns and vegetation dynamics were positively correlated.

SummaryHantavirus pulmonary syndrome (HPS) is an often fatal rodent-borne zoonosis caused by any of at least 20 hantavirus genotypes distributed throughout the Americas. Although HPS has been documented in several bordering countries, it has not been reported in Colombia. Here we report seroconversion to a hantavirus in paired samples from a hospitalized patient with symptoms compatible with HPS from Montería, Córdoba Department, north-western Colombia. Tests for regionally endemic agents including Plasmodium, Leptospira, Salmonella, dengue virus, Brucella, Rickettsia, human immunodeficiency virus and hepatitis viruses were negative. Because the patient was enrolled in a clinical trial for hemorrhagic fevers conducted by the University of Córdoba, serum samples were collected on admission and at discharge. Testing using Sin Nombre virus ELISA showed IgG and IgM seroconversion between samples. The eventual finding of this first clinical case of hantavirus infection in Colombia is consistent with the high prevalence of hantavirus antibodies in humans in the region and the likely exposure of the patient to rodents. The clinical presentation was similar to that found in neighbouring Panama.

The effect of intermittently occurring, non-reservoir host species on pathogen transmission and prevalence in a reservoir population is poorly understood. We investigated whether voles, Microtus spp., which occur intermittently, influenced estimated standing antibody prevalence (ESAP) to Sin Nombre hantavirus (SNV, Bunyaviridae: Hantavirus) among deer mice, Peromyscus maniculatus, whose populations are persistent. We used 14 years of data from central Montana to investigate whether ESAP among deer mice was related to vole presence or abundance while controlling for the relationship between deer mouse abundance and ESAP. We found a reduction in deer mouse ESAP associated with the presence of voles, independent of vole abundance. A number of studies have documented that geographic locations which support a higher host diversity can be associated with reductions in pathogen prevalence by a hypothesized dilution effect. We suggest a dilution effect may also occur in a temporal dimension at sites where host richness fluctuates. Preservation of host diversity and optimization of environmental conditions which promote occurrence of ephemeral species, such as voles, may result in a decreased ESAP to hantaviruses among reservoir hosts. Our results may extend to other zoonotic infectious diseases.

Background Because of complex interactions of climate variables at the levels of the pathogen, vector, and host, the potential influence of climate change on vector-borne and zoonotic diseases (VBZDs) is poorly understood and difficult to predict. Climate effects on the nonvector-borne zoonotic diseases are especially obscure and have received scant treatment. Objective We described known and potential effects of climate change on VBZDs and proposed specific studies to increase our understanding of these effects. The nonvector-borne zoonotic diseases have received scant treatment and are emphasized in this paper. Data sources and synthesis We used a review of the existing literature and extrapolations from observations of short-term climate variation to suggest potential impacts of climate change on VBZDs. Using public health priorities on climate change, published by the Centers for Disease Control and Prevention, we developed six specific goals for increasing understanding of the interaction between climate and VBZDs and for improving capacity for predicting climate change effects on incidence and distribution of VBZDs. Conclusions Climate change may affect the incidence of VBZDs through its effect on four principal characteristics of host and vector populations that relate to pathogen transmission to humans: geographic distribution, population density, prevalence of infection by zoonotic pathogens, and the pathogen load in individual hosts and vectors. These mechanisms may interact with each other and with other factors such as anthropogenic disturbance to produce varying effects on pathogen transmission within host and vector populations and to humans. Because climate change effects on most VBZDs act through wildlife hosts and vectors, understanding these effects will require multidisciplinary teams to conduct and interpret ecosystem-based studies of VBZD pathogens in host and vector populations and to identify the hosts, vectors, and pathogens with the greatest potential to affect human populations under climate change scenarios.

Reports of novel emerging and resurging wildlife and zoonotic diseases have increased. Consequently, integration of pathogen sampling into wildlife monitoring programs has grown. Sampling frequency influences interpretations of coupled host–pathogen dynamics, with direct implication to human exposure risk, but has received little empirical attention. To address this, a 15-year study, based on monthly sampling, of deer mouse (Peromyscus maniculatus) populations and Sin Nombre virus (SNV; a virulent disease in humans) dynamics was evaluated. Estimates of deer mouse abundance, number infected with SNV, and SNV prevalence from sampling less frequently than each month (achieved by deletion of months and recalculation of these parameters) were compared to monthly sampling frequencies. Deer mouse abundance was underestimated (10%–20%), SNV prevalence was overestimated when prevalence was high (>15%), and fewer annual extremes of abundance and infection were detected when sampling frequency was less than monthly. Effort necessary to detect temporal dynamics of SNV differed from effort to detect demographic patterns in deer mouse abundance. Findings here are applicable to sampling strategies for other host–pathogen dynamics and have direct implications for allocation of public health resources and intervention programs.

Since the 1993 discovery of a highly pathogenic hantavirus associated with the North American deer mouse (Peromyscus maniculatus), intensive ecological studies have led to many advances in our understanding of the natural history of New World hantaviruses as it relates to human disease. Seventeen named hantaviruses have been identified in North America. Field and laboratory studies of Sin Nombre and other hantaviruses have delineated host associations, geographical distributions, mechanisms of transmission, temporal infection dynamics of these viruses in host populations, and environmental factors that influence these dynamics. Using data from these studies, preliminary predictive models of the risk of hantavirus infection to humans have been developed. Improved models using satellite-derived data are under development. Multidisciplinary collaboration, integration of field and laboratory studies, and establishment and maintenance of long-term monitoring studies will be critical to continued advancement in the understanding of hantavirus-host ecology and disease prevention in humans.

Canine distemper virus (CDV), Leptospira interrogans, and Toxoplasma gondii are potentially lethal pathogens associated with decline in marine mammal populations. The Caspian Sea is home for the endangered Caspian seal (Pusa caspica). In the late 1990s and early 2000s, CDV caused a series of mortality events involving at least several thousand Caspian seals. To assess current infection status in Caspian seals, we surveyed for antibodies to three pathogens with potential to cause mortality in marine mammals. During 2015-2017, we tested serum samples from 36, apparently healthy, Caspian seals, accidentally caught in fishing nets in the Caspian Sea off Northern Iran, for antibodies to CDV, L. interrogans, and T. gondii, by virus neutralization, microscopic agglutination, and modified agglutination, respectively. Twelve (33%), 6 (17%), and 30 (83%) samples were positive for CDV, L. interrogans and T. gondii antibodies, respectively. The highest titers of CDV, L. interrogans, and T. gondii antibodies were 16, 400, and 50, respectively. Frequencies of antibody to these pathogens were higher in seals >1 year old compared to seals

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.

Habitat fragmentation and diversity loss due to increased conversion of natural habitats to agricultural uses influence the distribution and abundance of wildlife species and thus may change the ecology of pathogen transmission. We used hantaviruses in Panama as a research model to determine whether anthropogenic environmental change is associated with changes in the dynamics of viral transmission. Specifically, we wanted to determine whether hantavirus infection was correlated with spatial attributes of the landscape at both large and small scales or whether these changes are mediated by changes in community composition. When analyzed at coarse spatial scales, hantavirus reservoirs were more commonly found in disturbed habitats and edge habitats than in forested areas. At local scales, reservoir species dominance was significantly correlated with the slope of the terrain. To evaluate the effect of small-mammal diversity loss on infection dynamics, we implemented an experiment with selective species removal at experimental sites. Seroprevalence of hantavirus was higher in the community of small mammals and increased through time in the experimental sites. The higher seroprevalence in experimental plots suggests that greater diversity likely reduces encounter rates between infected and susceptible hosts. Our studies suggest that habitat loss and fragmentation and species diversity loss are altering hantavirus infection dynamics in Panama. Our work represents a multidisciplinary approach toward disease research that includes biodiversity concerns such as environmental change and degradation, human settlement patterns, and the ecology of host and nonhost species, work that may be especially important in tropical countries.

We predicted that more-fragmented habitats are associated with lower diversity of small mammals and higher densities of populations of rodents that are hosts of hantaviruses. We compared diversity and distribution of small mammals that are either hosts or nonhosts of hantaviruses in 6 Panamanian national parks and adjacent areas with varying degree of human impacts. We sampled forest, edge, and anthropogenically disturbed habitats. The generalist rodents Oligoryzomys fulvescens (reservoir of Choclo virus) and Zygodontomys brevicauda (reservoir of Calabazo virus) were more abundant in disturbed habitats, especially in smaller and more isolated patches, where population density and diversity of other rodent species was lowest. In contrast, these 2 species had lower abundances in larger forested areas with more nonreservoir species of small mammals. Our results suggest that the change in the natural environment resulting from tropical deforestation is increasing the abundance and distribution of species that are reservoirs for hantaviruses. Therefore, it is likely that forest fragmentation has contributed to recent outbreaks of hantavirus pulmonary syndrome in tropical areas. Conservation of natural resources becomes all the more imperative, not only for protecting fauna and flora but also for human health.

Patients in Goalando were likely infected by direct contact with fruit bats or their secretions, rather than through contact with an intermediate host., Nipah virus (NiV) is a paramyxovirus that causes severe encephalitis in humans. During January 2004, twelve patients with NiV encephalitis (NiVE) were identified in west-central Bangladesh. A case–control study was conducted to identify factors associated with NiV infection. NiVE patients from the outbreak were enrolled in a matched case-control study. Exact odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by using a matched analysis. Climbing trees (83% of cases vs. 51% of controls, OR 8.2, 95% CI 1.25–∞) and contact with another NiVE patient (67% of cases vs. 9% of controls, OR 21.4, 95% CI 2.78–966.1) were associated with infection. We did not identify an increased risk for NiV infection among persons who had contact with a potential intermediate host. Although we cannot rule out person-to-person transmission, case-patients were likely infected from contact with fruit bats or their secretions.

We monitored Limestone Canyon hantavirus (LSCV) antibody prevalence, host (brush mouse, Peromyscus boylii) abundance, and environmental variables (temperature and rainfall) in brush mice captured on three trapping webs in southern Arizona for 5 yr. Although seasonal patterns were subtle, we observed large multiyear variation in population abundance and antibody prevalence. Limestone Canyon hantavirus infection in brush mouse populations varied over time with prevalence ranging from 0% to 33%. At all trapping webs, evidence of infection disappeared completely for an extended period (up to 2 yr) and eventually reappeared, suggesting that dispersal may play a role in maintaining infection in brush mouse metapopulations. Weather during the study period was drier and warmer than average and these conditions, especially during spring through fall, may have contributed to low brush mouse population density and the local extinction of LSCV during the second year of the study. Nevertheless, population growth was associated with relatively warm, dry conditions during winter periods and a cool, wet spring and summer period in the fifth year of the study. After prolonged absence, LSCV infection was consistently detected only when brush mouse population abundance reached relatively high levels during that fifth year. Comparison of our results to similar studies suggests that stochastic events resulting in the loss or survival of a few infected mice in low-density host populations may result in local extinction of virus; reestablishment of infection may occur via immigration of infected individuals from adjacent populations, but may be successful only when populations are of sufficient density to support frequent rodent-to-rodent interactions and virus transmission.

American hantaviruses cause a severe respiratory disease known as hantavirus pulmonary syndrome (HPS). In the United States, Sin Nombre virus (SNV), carried by the deer mouse ( Peromyscus maniculatus), is the etiologic agent in the majority of HPS cases. The relationship between deer mouse population density and SNV infection prevalence in deer mice is poorly understood. Our purpose was to clarify this relationship by demonstrating the existence of delayed-density-dependent prevalence of SNV infection in populations of wild deer mice. We also explored the relationship between SNV infection in deer mouse populations and the incidence of human HPS. The study population was 3,616 deer mice captured on 10 mark-recapture grids in Montana during May and September, 1994-2004. Using multivariate logistic regression analysis, we found a strong association between deer mouse population density in fall (September) and SNV antibody prevalence in deer mice the following spring (May). Other characteristics associated with SNV infection in deer mice in spring were: (1) presence of at least one infected deer mouse in the population the previous fall, (2) male gender, (3) adult age class, (4) presence of scars, (5) grassland and logged habitats, and (6) elevations below 1,300 m. There was a strong association between concurrently measured SNV antibody prevalence in deer mice and probable exposure of human HPS cases during the same time period. Human cases were more likely to occur during seasons when SNV antibody prevalence was at least 10% in deer mouse populations. These findings suggest that fall rodent population parameters could be used to help guide prevention efforts the following spring.

Prevalence of antibody reactive with Sin Nombre hantavirus (SNV) was evaluated from rodents captured over 31 months (March 1988 to September 1990) from six mark-recapture grids on the central Argentine Pampa. The most frequently infected rodents were: Akodon azarae (31/459), Necromys benefactus (8/141), and Oligoryzomys flavescens (10/281), which are known hosts of Pergamino, Maciel, and Lechiguanas hantaviruses, respectively. Relative population density and antibody prevalence varied seasonally and from year to year, population densities were highest in fall and prevalences were highest in spring. A positive association between antibody prevalence and body weight corroborated findings from other studies suggesting that hantaviruses are maintained in reservoir populations by horizontal transmission. In two of three host species, transmission was more frequent among male than among female mice. We found no evidence for a detrimental effect of hantavirus infection on host body weight, growth, longevity, movement, or reproductive preparedness. This analysis, based on cryopreserved specimens, represents the earliest conducted longitudinal, mark-recapture study of the dynamics of infection of autochthonous American hantaviruses in their sigmodontine host populations.

Hantavirus pulmonary syndrome (HPS) is caused by an infection with viruses of the genus Hantavirus in the western hemisphere. Rodent hosts of hantaviruses are present throughout the United States. In July 2004, two HPS case-patients were identified in Randolph County, WV: a wildlife science graduate student working locally and a Randolph County resident. We interviewed family members and colleagues, reviewed medical records, and conducted environmental studies at likely exposure sites. Small mammals were trapped, and blood, urine, and tissue samples were submitted to the Centers for Disease Control and Prevention for laboratory analyses. These analyses confirmed that both patients were infected with Monongahela virus, a Sin Nombre hantavirus variant hosted by the Cloudland deer mouse, Peromyscus maniculatus nubiterrae. Other than one retrospectively diagnosed case in 1981, these are the first HPS cases reported in West Virginia. These cases emphasize the need to educate the public throughout the United States regarding risks and prevention measures for hantavirus infection.

Bats are natural reservoirs of several important emerging viruses. Cross‐species transmission appears to be quite common among bats, which may contribute to their unique reservoir potential. Therefore, understanding the importance of bats as reservoirs requires examining them in a community context rather than concentrating on individual species. Here, we use a network approach to identify ecological and biological correlates of cross‐species virus transmission in bats and rodents, another important host group. We show that given our current knowledge the bat viral sharing network is more connected than the rodent network, suggesting viruses may pass more easily between bat species. We identify host traits associated with important reservoir species: gregarious bats are more likely to share more viruses and bats which migrate regionally are important for spreading viruses through the network. We identify multiple communities of viral sharing within bats and rodents and highlight potential species traits that can help guide studies of novel pathogen emergence.

International audience; The potential for disease transmission at the interface of wildlife, domestic animals and humans has become a major concern for public health and conservation biology. Research in this subject is commonly conducted at local scales while the regional context is neglected. We argue that prevalence of infection at local and regional levels is influenced by three mechanisms occurring at the landscape level in a metacommunity context. First, (1) dispersal, colonization, and extinction of pathogens, reservoir or vector hosts, and nonreservoir hosts, may be due to stochastic and niche‐based processes, thus determining distribution of all species, and then their potential interactions, across local communities (metacommunity structure). Second, (2) anthropogenic processes may drive environmental filtering of hosts, nonhosts, and pathogens. Finally, (3) phylogenetic diversity relative to reservoir or vector host(s), within and between local communities may facilitate pathogen persistence and circulation. Using a metacommunity approach, public heath scientists may better evaluate the factors that predispose certain times and places for the origin and emergence of infectious diseases. The multidisciplinary approach we describe fits within a comprehensive One Health and Ecohealth framework addressing zoonotic infectious disease outbreaks and their relationship to their hosts, other animals, humans, and the environment.

International audience; High-profile epidemics such as Ebola, avian influenza, and severe acute respiratory syndrome (SARS) repeatedly thrust infectious diseases into the limelight. Because the emergence of dis-eases involves so many factors, the need for interdisciplinary approaches to studying emerging infections, particularly those originating from animals (i.e., zoonoses), is frequently discussed. However, effective integration across disciplines is challenging in practice. Ecological ideas, for example, are rarely considered in biomedical research, while insights from biomedicine are often neglected in ecological studies of infectious diseases. One practical reason for this is that researchers in these fields focus on vastly different scales of biological organization, which are difficult to bridge both intellectually and methodologically. Nevertheless, integration across biological scales is increasingly needed for solving the complex problems zoonotic diseases pose to human and animal well-being. Motivated by current events, we use Ebola virusas a case study to highlight fundamental questions about zoonoses that can be addressed by integrating insights and approaches across scales.

The relationship between biodiversity loss and emerging infectious diseases is studied in this paper using as examples the rodent-borne hemorrhagic fevers (those caused by hantaviruses and arenaviruses). Both biodiversity loss and infectious disease have taken on importance in the last two decades and both are related to human disturbance of natural systems. Intuitively, one might expect the most diverse natural habitats to support the greatest number of animal diseases that could be transmitted to humans (zoonotic diseases). Yet an examination of the circumstances surrounding outbreaks of rodent-borne hemorrhagic fevers suggests that anthropogenically disturbed, low-diversity habitats present the greatest risk. Two possible mechanisms are suggested to help explain this increased risk. First, disturbed habitats often favor opportunistic/generalist species which happen to be reservoirs for hemorrhagic fever viruses. Second, through a process called the dilution effect, in communities of lowering r...

We applied a rigorous, quantitative methodology to the analysis of local-scale spatial clustering of multiple murid mice (brush mice, Peromyscus boylii; deer mice, P. maniculatus; pinon mice, P. truei; western harvest mice, Reithrodontomys megalotis) infected or uninfected with hantaviruses. Rodents were sampled longitudinally from 1994 to 2001 on 23 trapping webs at 10 locations in the southwestern United States. This study provided an opportunity to apply meta-analysis techniques to an important ecological question. There were sufficient captures by species on 199 occasions (three consecutive nights) to compare general use of space using multi-response permutation procedures (MRPP). The MRPP results were then used in meta-analyses by species to determine if overall effects of spatial clustering of hantavirus-infected mice as well as categorical effects (elevation, season, site, and state) were present. Based on MRPP analyses, overall spatial clustering of hantavirus-infected mice was most pronounced for brush mice, followed by the deer mouse. Meta-analyses indicated significant overall effects of spatial clustering and varying categorical effects (elevation, season, site, state) of infected mice for each species compared. The overlapping space use by rodents might be an important factor affecting the local transmission of several hantaviruses.

In August 2002, two cases of hantavirus pulmonary syndrome (HPS) were confirmed in Mineros and Concepcion, within the Santa Cruz Department of Bolivia. Extensive alteration of the native ecosystem, from dense forest to pasture or sugarcane, had occurred in both regions. An ecologic assessment of reservoir species associated with the human disease identified a single hantavirus antibody-positive Oligoryzomys microtis from Mineros and three hantavirus antibody-positive Calomys callosus from Concepcion. In Mineros, the virus from the O. microtis was 90% similar to sequences published for Rio Mamore virus. Viral nucleotide sequences from two C. callosus were 87�88% similar to the sequence of Laguna Negra virus. The viral sequence from the C. callosus was 99% identical to viral sequences obtained from the HPS patient in this area, implicating C. callosus as the host and Laguna Negra virus as the agent responsible for the HPS case near Concepcion.

The first identified outbreak of hantavirus pulmonary syndrome in Central America is described., An outbreak of hantavirus pulmonary syndrome occurred in the province of Los Santos, Panama, in late 1999 and early 2000. Eleven cases were identified; 9 were confirmed by serology. Three cases were fatal; however, no confirmed case-patient died. Case-neighborhood serologic surveys resulted in an overall hantavirus antibody prevalence of 13% among household and neighborhood members from the outbreak foci. Epidemiologic investigations did not suggest person-to-person transmission of hantavirus infection. By use of Sin Nombre virus antigen, hantavirus antibodies were detected in Oligoryzomys fulvescens and Zygodontomys brevicauda cherriei. This outbreak resulted in the first documented cases of human hantavirus infections in Central America.

We used ecologic niche modeling of outbreaks and sporadic cases of filovirus-associated hemorrhagic fever (HF) to provide a large-scale perspective on the geographic and ecologic distributions of Ebola and Marburg viruses. We predicted that filovirus would occur across the Afrotropics: Ebola HF in the humid rain forests of central and western Africa, and Marburg HF in the drier and more open areas of central and eastern Africa. Most of the predicted geographic extent of Ebola HF appear to have been observed; Marburg HF has the potential to occur farther south and east. Ecologic conditions appropriate for Ebola HF are also present in Southeast Asia and the Philippines, where Ebola Reston is hypothesized to be distributed. This first large-scale ecologic analysis provides a framework for a more informed search for taxa that could constitute the natural reservoir for this virus family.

We conducted a pilot study to evaluate the efficacy of rodent proofing continuously occupied homes as a method for lowering the risk for hantavirus pulmonary syndrome (HPS) among residents of a Native American community in northwestern New Mexico. Rodent proofing of dwellings was paired with culturally appropriate health education. Seventy homes were randomly assigned to treatment or control categories. Treatment homes were rodent-proofed by sealing openings around foundations, doors, roofs, and pipes and repairing screens and windows. Repairs to each dwelling were limited to $500 US. After repairs were completed, 15-20 snap traps were placed in each treatment and control home and checked approximately every 2 days for an average of 3-4 weeks. During 23,373 trap nights, one house mouse (Mus musculus) was captured in one treatment home, and 20 mice (16 deer mice, Peromyscus maniculatus, two Pinyon mice, Peromyscus truei, and two unidentified mice) were captured in five control homes (one house had 14 captures, two had two captures, and two had one capture). Trap success was 0.01% in treatment homes and 0.15% in controls. Intensity of infestation (mean number of mice captured per infested home) was 1 in treatment homes and 4 in controls. Observations of evidence of infestation (feces, nesting material, gnaw marks, or reports of infestation by occupant) per 100 days of observation were 1.2 in treatment homes and 3.1 in controls. Statistical power of the experiment was limited because it coincided with a period of low rodent abundance (August-November 2000). Nevertheless, these results suggest that inexpensive rodent proofing of occupied rural homes can decrease the frequency and intensity of rodent intrusion, thereby reducing the risk of HPS among rural residents in the southwestern United States.

High species diversity of the potential animal host community for a zoonotic pathogen may reduce pathogen transmission among the most competent host, a phenomenon called the "dilution effect", but the mechanisms driving this effect have been little studied. One proposed mechanism is "encounter reduction" where host species of low-competency decrease contact rates between infected and susceptible competent hosts, especially in directly transmitted diseases. We conducted an experiment in outdoor enclosures in northwestern Mexico where we manipulated rodent assemblages to assess the effect of species richness on the frequency of intra- and interspecific interactions and activity patterns of a hantavirus reservoir host (North American deermouse; Peromyscus maniculatus). Trials consisted of three treatments of rodent assemblages that differed in species richness, but had equal abundance of deermice; treatment 1 consisted of only deermice, treatment 2 included deermice and one non-competent host species, and treatment 3 included two non-competent host species in addition to deermice. To measure interactions and temporal activity, we strategically deployed foraging stations and infrared cameras. We did not find differences in the frequency of intraspecific interactions of deermice among treatments, but there were significantly more interspecific interactions between deermouse and non-competent hosts in treatment 2 than treatment 3, which is explained by the identity of the non-competent host species. In addition, there were differences in activity patterns between rodent species, and also between deermice from treatment 1 and treatment 2. These results indicate that at least at a small-scale analysis, the co-occurrence with other species in the study area does not influence the frequency of intraspecific interactions of deermice, and that deermice may be changing their activity patterns to avoid a particular non-competent host species (Dipodomys merriami). In conclusion, in this deermouse-hantavirus system a potential dilution effect would not be through intraspecific encounter reduction in the most competent hantavirus host. To identify variables of host assemblages that can influence pathogen transmission, we highlight the need to address the identity of species and the composition of assemblages, not only host species richness or diversity.

Summary The genetic variability and divergence among natural populations of Calomys musculinus and C. laucha from eastern Argentina were examined by protein electrophoresis of 24 loci. High levels of genetic variability were found in both species when compared to other rodents and mammals. Mean expected heterozygosity (He) ranged from 0.112 to 0.156, proportion of polymorphic loci (P 95% ) from 37.5% to 50% and mean number of alleles per locus (A) of 1.6-1.7 for C. musculinus . H e from 0.097 to 0.126, P 95% from 34.8 to 39.1 and A from 1.7 to 1.9 were the values for C. laucha . Populations of this last species revealed a higher degree of geographical differentiation (Θ = 0.017, P C. musculinus (Θ = 0.002, P > 0.05). These results are in agreement with the known social structure and habitat of both species. C. musculinus is an opportunistic species, with a loose social structure and a predominance of transient over resident animals, indicating a high ambulatory activity. C. laucha , on the contrary, inhabits almost exclusively cultivated fields, and evidence of social stratification has been reported for this species.

To the Editor: The ≈20 recognized arenaviruses in the Americas are hosted by rodents of the family Cricetidae; 1 exception may be hosted by a bat (genus Artibeus, family Phyllostomidae) (1). Pichinde virus, hosted by Oryzomys albigularis, was described from animals in the Pichinde Valley near Cali, Colombia (2), and antibody reactive to Pichinde virus was found in 2 of 82 serum samples from humans in the same area. No studies of arenavirus infection in rodents or humans have been conducted in Colombia since 1971. Although Pichinde virus is not associated with human disease, Guanarito virus, which is hosted by Zygodontomys brevicauda, the short-tailed cane mouse (3,4), causes Venezuelan hemorrhagic fever in the Venezuelan state of Portuguesa (5). This state borders on Colombia, and Z. brevicauda is a common species in Caribbean Colombia. Our aim was to determine the prevalence of antibody to arenaviruses among wild rodents in this region. During November 1, 2008–June 10, 2009, we trapped 322 rodents in 3 rural localities in the Department of Cordoba, Colombia (Monteria, Vereda El Escondido, 8°34.183′N, 75°42.776′W; Sahagun, Vereda Las Llanadas, 8°56.533′N, 75°20.909′W; and Lorica, Colegio Instituto Tecnico Agricola, 9°24.067′N, 075°75.707′W). The landscape at the study sites is dominated by tropical savanna, small patches of forest, and cultivated land. Live-capture traps were set in a variety of habitats at each locality, and captured rodents were processed according to methods by Mills et al. (6). Rodents were anesthetized, and blood (by cardiac puncture) and tissue (liver, lung, spleen, hearty, kidney) samples were collected into individual cryovials, placed in liquid nitrogen in the field, and transferred to freezers and stored at –80°C at the Instituto de Investigaciones Biologicas del Tropico, Universidad de Cordoba, Monteria, Colombia. Rodent species were identified on the basis of morphologic analyses of formalin-fixed carcasses; chromosomal data and mitochondrial DNA sequencing of the cytochrome b gene were used to confirm identification of most antibody-positive animals. Alcohol-preserved voucher specimens are archived at the Museum of Texas Tech University (Lubbock, TX, USA). Blood samples were tested for arenavirus immunoglobulin (Ig) G by indirect immunofluorescent antibody assays. Guanarito and Pichinde virus–infected Vero E6 cells were used as antigens on spot slides. The secondary antibody was a fluorescein-conjugated goat, antimouse IgG. Serum samples were screened at a dilution of 1:10 and endpoint titers were measured by using serial 2-fold dilutions (1:10–1:320) (7). Attempts to amplify viral RNA in tissues by reverse transcription PCR were unsuccessful. We collected 210 sigmodontine rodents of 3 species: 181 Z. brevicauda, 28 Oligoryzomys fulvescens, and 1 Oecomys concolor. Eleven serum samples, 10 from Z. brevicauda and 1 from O. fulvescens rodents, had detectable arenavirus antibody. Three Z. brevicauda rodent samples had antibody reactive to both Pichinde and Guanarito virus, and 7 more were positive for either Pichinde or Guanarito arenaviruses (Table). Table Comparison of PICHV and GTOV antibody titers in rodents after serologic screening of 210 sigmodontine rodents, Cordoba, Colombia, November 1, 2008–June 10, 2009* We used only 2 viral antigens in our screening belonging to the 2 viruses that are either known to occur in Colombia (Pichinde virus) or known to be hosted by species that we captured (Guanarito virus). Among the 10 Z. brevicauda samples with detectable antibody, 5 reacted only to Pichinde virus antigen or their antibody titer to Pichinde virus was at least 4-fold higher than their titer to Guanarito virus (Table), suggesting those rodents were infected with Pichinde or a closely related virus. Additional studies, including isolation and sequencing are needed to definitively identify this virus. Surprisingly, only 2 Z. brevicauda rodents (1.1%) had antibody only to Guanarito virus or had a 4-fold greater titer to Guanarito virus, much lower than the 15% antibody prevalence in the same species in the Venezuelan hemorrhagic fever–endemic area, Portuguesa State, Venezuela (5). Our testing protocols differed from the earlier study, and we have not definitively identified Guanarito virus in those 3 rodents; nevertheless, this low prevalence might help explain the absence of Venezuelan hemorrhagic fever in Colombia, although inadequate surveillance is a second possible explanation. The single antibody-positive O. fulvescens rodent had a low antibody titer only to Pichinde virus. This apparent 4% antibody prevalence is based on only 28 mice. The significance of this finding is not clear but may represent spillover or an undescribed arenavirus specific to the species O. fulvescens. Again, additional studies are needed. Our results demonstrate the presence of >1 arenaviruses circulating among common rodent hosts in Caribbean Colombia. We emphasize that many New World arenaviruses are likely cross-reactive to the antigens we used; recovery and sequencing of viral RNA will be essential to fully characterize these viruses. Hemorrhagic fever of arenaviral origin should be included in the differential diagnosis of tropical fevers, at least in our study region. As the human population of the rural Department of Cordoba and adjacent areas of the Caribbean coast of Colombia continues to increase, the potential for arenavirus-related disease could become a public health concern.

Arenaviruses are single-stranded RNA viruses that are grouped taxonomically into Old World/lymphocytic choriomeningitis (i.e., Africa, Europe, Asia, and Oceania) and New World/Tacaribe (i.e., the Americas) complexes. Over 40 arenaviruses have been identified to date, although a minority are recognized human pathogens. Arenaviruses are maintained in nature by chronic infection in rodents of the Muridae and Cricetidae families. There is a tight reservoir rodent–virus species pairing that limits the endemic area of each arenavirus to the geographic distribution of its specific reservoir. The geographic distribution of infected rodents is usually considerably restricted relative to the entire range of the species. Since most rodent reservoirs inhabit rural sylvatic niches, primary arenavirus infection in humans occurs almost exclusively in rural and often remote settings. The incidence of human infection may vary considerably with variations in rodent population densities that may relate to climatic and seasonal weather changes and human-induced habitat perturbation, especially agricultural expansion converting forest to cultivated fields. Infected rodents shed virus in urine, feces, and saliva and primary human infection occurs through contact with these biological substances. Secondary human-to-human transmission may occur, especially with viruses of the Old World complex, through contact with bodily fluids, most often to those caring for sick persons at home or in healthcare centers. However, secondary attack rates are generally low as long as strict barrier nursing practices are observed. Large outbreaks are almost always fueled by nosocomial transmission, usually in resource-poor regions where barrier nursing practices may not be maintained. Arenaviruses classically cause two distinct syndromes in humans—central nervous system disease (lymphocytic choriomeningitis and Dandenong viruses) and hemorrhagic fever (Lassa and Lujo viruses in Africa and Junin, Machupo, Guanarito, Sabia, and Chapare viruses in South America)—although many arenavirus infections may be asymptomatic or result in a nonspecific febrile illness. Treatment options include the antiviral drug ribavirin and convalescent immune plasma. Some arenaviruses are considered “Select Agents” that could possibly be used as bioweapons. The nonspecific clinical presentation and general lack of readily available laboratory testing for arenavirus infection pose significant challenges to diagnosis. The remote and geographically restricted endemic areas, often in resource-poor countries, apparent rarity of most arenaviral infections in humans, and challenges to diagnosis make surveillance and reliable estimates of infection and disease difficult. Control methods generally involve integrated pest management strategies to limit human contact with rodent excreta and the use of appropriate personal protective materials for those at occupational risk through patient care, laboratory exposure, or fieldwork. During outbreaks, intensive rodent trapping in villages, as well as aggressive case identification, patient isolation, and contact tracing may all be needed. Vaccines are generally in the development stages. Further research and public health advances are needed to understand the complex epizoologic, epidemiologic, and ecologic interplay of arenaviruses that result in human disease, with the ultimate goal being the capacity to predict the emergence of these viruses and thus take steps to prevent human infections.