Examining Seasonal Anthrax Risk in Wildlife: Comparing Home Ranges and Site Fidelity in Sero-Positive and Sero-Negative Ungulates

Anthrax is frequently reported from wildlife and livestock in the US.  While useful in reducing risk in livestock, vaccination, the primary method of prevention, is untenable for free-ranging wildlife. Because of this, accurate surveillance and carcass clean-up are the most efficacious control measures for wildlife.  However, surveillance is expensive and requires significant personnel across large landscapes. Likewise, the transmission pathways are poorly understood in most species. Wildlife telemetry improves our understanding of movement patterns during risk periods. At the same time, serological surveys provide data on host exposure. Such data allow us to test hypotheses about host/pathogen interactions on the landscape. Starting in 2010, we initiated GPS telemetry and sero-prevalence studies for managed bison, Bison bison bison, and free-range elk (Cervus elaphus) in Montana. Here we will evaluate summertime home ranges in bulls from both species in western Montana. We compared home ranges and site fidelity metrics in sero-positive and sero-negative animals. Serological tests indicated that ~30% of bull elk and ~27% of unvaccinated bison were sero-positive for anthrax exposure, suggesting that low-level exposure is frequent on this landscape. Seasonal ranges can be useful for defining areas where animals may have increased likelihood of anthrax, comparing ranges to niche-based estimates of B. anthracis. Fidelity metrics suggest both species spent considerable time in niche-based high risk areas. Inter-annual data from elk suggest long-term range fidelity and overlap with high risk areas. These data can be used to prioritize surveillance efforts in those areas to maximize disease control, while managing search costs

Population Density and Seasonality Effects on Sin Nombre Virus Transmission in North American Deermice (Peromyscus maniculatus) in Outdoor Enclosures

Surveys of wildlife host-pathogen systems often document clear seasonal variation in transmission; conclusions concerning the relationship between host population density and transmission vary. In the field, effects of seasonality and population density on natural disease cycles are challenging to measure independently, but laboratory experiments may poorly reflect what happens in nature. Outdoor manipulative experiments are an alternative that controls for some variables in a relatively natural environment. Using outdoor enclosures, we tested effects of North American deermouse (Peromyscus maniculatus) population density and season on transmission dynamics of Sin Nombre hantavirus. In early summer, mid-summer, late summer, and fall 2007–2008, predetermined numbers of infected and uninfected adult wild deermice were released into enclosures and trapped weekly or bi-weekly. We documented 18 transmission events and observed significant seasonal effects on transmission, wounding frequency, and host breeding condition. Apparent differences in transmission incidence or wounding frequency between high- and low-density treatments were not statistically significant. However, high host density was associated with a lower proportion of males with scrotal testes. Seasonality may have a stronger influence on disease transmission dynamics than host population density, and density effects cannot be considered independent of seasonality

Heterogeneity in enterotoxigenic Escherichia coli and shigella infections in children under 5 years of age from 11 African countries: a subnational approach quantifying risk, mortality, morbidity, and stunting.

BACKGROUND: Diarrhoea, a global cause of child mortality and morbidity, is linked to adverse consequences including childhood stunting and death from other diseases. Few studies explore how diarrhoeal mortality varies subnationally, especially by cause, which is important for targeting investments. Even fewer examine indirect effects of diarrhoeal morbidity on child mortality. We estimated the subnational distribution of mortality, morbidity, and childhood stunting attributable to enterotoxigenic Escherichia coli (ETEC) and shigella infection in children younger than 5 years from 11 eastern and central African countries. These pathogens are leading causes of diarrhoea in young children and have been linked to increased childhood stunting. METHODS: We combined proxy indicators of morbidity and mortality risk from the most recent Demographic and Health Surveys with published relative risks to estimate the potential distribution of diarrhoeal disease risk. To estimate subnational burden, we used country-specific or WHO region-specific morbidity and mortality estimates and distributed them subnationally by three indices that integrate relevant individual characteristics (ie, underweight, probability of receiving oral rehydration treatment of diarrhoea, and receiving vitamin A supplementation) and household characteristics (ie, type of drinking water and sanitation facilities). FINDINGS: Characterising ETEC and shigella subnational estimates of indirect morbidity (infection-attributable stunting) and indirect mortality (stunting-related deaths from other infectious diseases) identified high-risk areas that could be missed by traditional metrics. Burundi and Democratic Republic of the Congo had the highest ETEC-associated and shigella-associated mortality and stunting rates. Mozambique, Democratic Republic of the Congo, and Zimbabwe had the greatest subnational heterogeneity in most ETEC and shigella mortality measures. Inclusion of indirect ETEC and shigella mortality in burden estimates resulted in a 20-30% increase in total ETEC and shigella mortality rates in some subnational areas. INTERPRETATION: Understanding the indirect mortality and morbidity of diarrhoeal pathogens on a subnational level will strengthen disease control strategies and could have important implications for the relative impact and cost-effectiveness of new enteric vaccines. Because our methods rely on publicly available data, they could be employed for national planning. FUNDING: Bill & Melinda Gates Foundation

Agent-based hantavirus transmission model incorporating host behavior and viral shedding heterogeneities derived from field transmission experiments

Behavioural and environmental heterogeneities among host populations can play an important role in hantavirus transmission. We designed an agent-based model to determine the relative role of direct and indirect transmission on Sin Nombre hantavirus (SNV) dynamics in deer mice, incorporating host heterogeneities. We parameterized the model to reproduce aggressive encounters, movement and excretions from field-based studies and lab experiments. Our model captured known properties of SNV spread and matched the outcomes of transmission experiments. Although the model was not fit to $R_0$ values, the $R_0$ distribution from our simulations was similar to values from other hantavirus models. We also found that a small per cent of mice were responsible for a high per cent of direct transmission. Our model indicated that mouse heterogeneity and environmental contamination are both important. Model extensions can explore larger ecosystem dynamics by incorporating temporal heterogeneity, to understand how changes in host characteristics and environment influence SNV transmission

Increased Detection of Sin Nombre Hantavirus RNA in Antibody-Positive Deer Mice from Montana, USA: Evidence of Male Bias in RNA Viremia

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

Effects of geographic and economic heterogeneity on the burden of rotavirus diarrhea and the impact and cost-effectiveness of vaccination in Nigeria.

Child mortality from rotavirus gastroenteritis remains high in Nigeria, representing 14% of all rotavirus deaths worldwide. Here, we examine the potential impact and cost-effectiveness of national rotavirus vaccine introduction in geographic and economic subpopulations of Nigeria. We projected the health and economic outcomes of rotavirus vaccination in children over the first five years of life using a spreadsheet-based model. We modeled child populations using national survey data on rotavirus mortality risk factors and vaccination coverage to predict burden and impact across regional and wealth quintile subpopulations within Nigeria. Our base case considered introduction of a general rotavirus vaccine, modeled to encompass characteristics of existing vaccines, versus no vaccine. Base case costs were estimated from the government perspective, assuming Gavi subsidies, over the first five years. We also present estimates from the cost of vaccination from the perspective of Gavi. We explored uncertainty in model parameters through probabilistic uncertainty, one-way sensitivity, and scenario analyses. According to our estimates, rotavirus enteritis was responsible for 47,898 [95% Uncertainty Limits: 35,361; 63,703] child deaths per year, with approximately 80% of the national burden concentrated in the three northern regions of Nigeria. Rotavirus vaccination was estimated to prevent 6,454 [3,960; 9,721] deaths, 13% [9%; 18%] of the national annual RV burden. National ICERs for rotavirus vaccination from the Nigerian government and Gavi perspectives were US$47 [$18; $105] and$62 [$29;$130] per DALY averted, respectively. General rotavirus vaccination was projected to reduce rotavirus mortality by only 6% [4%; 9%] in the North West region compared to 35% [24%; 47%] in the South East region. Base case ICERs ranged from US$25 [10; 56] per DALY averted in North West to US$64 [18; 157] per DALY averted in South South. Gavi perspective ICERs ranged from US$33 [$15; $68] in North West to US$88 [35; 191] per DALY averted in South South. According to one-way sensitivity analyses, ICERs were most sensitive to vaccine efficacy, followed by estimated administrative costs and rotavirus mortality. Disparities in mortality reduction were largely driven by inequality in vaccination coverage across regions and between socioeconomic subpopulations. Due to high, persistent, and inequitable burden of rotavirus in Nigeria, routine vaccination with any of these rotavirus vaccines would be an high impact and cost-effective strategy in reducing child mortality