Impact of Molecular Modifications on the Immunogenicity and Efficacy of Recombinant Raccoon Poxvirus-Vectored Rabies Vaccine Candidates in Mice.

Rabies is an ancient disease that is responsible for approximately 59,000 human deaths annually. Bats (Order Chiroptera) are thought to be the original hosts of rabies virus (RABV) and currently account for most rabies cases in wildlife in the Americas. Vaccination is being used to manage rabies in other wildlife reservoirs like fox and raccoon, but no rabies vaccine is available for bats. We previously developed a recombinant raccoonpox virus (RCN) vaccine candidate expressing a mosaic glycoprotein (MoG) gene that protected mice and big brown bats when challenged with RABV. In this study, we developed two new recombinant RCN candidates expressing MoG (RCN-tPA-MoG and RCN-SS-TD-MoG) with the aim of improving RCN-MoG. We assessed and compared in vitro expression, in vivo immunogenicity, and protective efficacy in vaccinated mice challenged intracerebrally with RABV. All three candidates induced significant humoral immune responses, and inoculation with RCN-tPA-MoG or RCN-MoG significantly increased survival after RABV challenge. These results demonstrate the importance of considering molecular elements in the design of vaccines, and that vaccination with either RCN-tPA-MoG or RCN-MoG confers adequate protection from rabies infection, and either may be a sufficient vaccine candidate for bats in future work.

Plague-Positive Mouse Fleas on Mice Before Plague Induced Die-Offs in Black-Tailed and White-Tailed Prairie Dogs.

Plague is a lethal zoonotic disease associated with rodents worldwide. In the western United States, plague outbreaks can decimate prairie dog (Cynomys spp.) colonies. However, it is unclear where the causative agent, Yersinia pestis, of this flea-borne disease is maintained between outbreaks, and what triggers plague-induced prairie dog die-offs. Less susceptible rodent hosts, such as mice, could serve to maintain the bacterium, transport infectious fleas across a colony, or introduce the pathogen to other colonies, possibly facilitating an outbreak. Here, we assess the potential role of two short-lived rodent species, North American deer mice (Peromyscus maniculatus) and Northern grasshopper mice (Onychomys leucogaster) in plague dynamics on prairie dog colonies. We live-trapped short-lived rodents and collected their fleas on black-tailed (Cynomys ludovicianus, Montana and South Dakota), white-tailed (Cynomys leucurus, Utah and Wyoming), and Utah prairie dog colonies (Cynomys parvidens, Utah) annually, from 2013 to 2016. Plague outbreaks occurred on colonies of all three species. In all study areas, deer mouse abundance was high the year before plague-induced prairie dog die-offs, but mouse abundance per colony was not predictive of plague die-offs in prairie dogs. We did not detect Y. pestis DNA in mouse fleas during prairie dog die-offs, but in three cases we found it beforehand. On one white-tailed prairie dog colony, we detected Y. pestis positive fleas on one grasshopper mouse and several prairie dogs live-trapped 10 days later, months before visible declines and plague-confirmed mortality of prairie dogs. On one black-tailed prairie dog colony, we detected Y. pestis positive fleas on two deer mice 3 months before evidence of plague was detected in prairie dogs or their fleas and also well before a plague-induced die-off. These observations of plague positive fleas on mice could represent early spillover events of Y. pestis from prairie dogs or an unknown reservoir, or possible movement of infectious fleas by mice.

Combining Footwear with Public Health Iconography to Prevent Soil-Transmitted Helminth Infections.

Shoes are effective for blocking soil-transmitted helminths (STHs) that penetrate the skin. Unfortunately, shoe-wearing is uncommon in many areas where STHs are prevalent, in part because local populations are unaware of the health benefits of wearing shoes. This is especially true in low-literacy populations, where information dissemination through written messages is not possible. We launched a public health intervention that combines a public health image with sandals. The image is a "lenticular image" that combines two alternating pictures to depict the efficacy of shoes for preventing STH infection. This image is adhered to the shoe, such that the message is linked directly to the primary means of prevention. To create a culturally appropriate image, we conducted five focus group discussions, each with a different gender and age combination. Results of focus group discussions reinforced the importance of refining public health messages well in advance of distribution so that cultural acceptability is strong. After the image was finalized, we deployed shoes with the image in communities in western Uganda where hookworm is prevalent. We found that the frequency of shoe-wearing was 25% higher in communities receiving the shoes than in control communities. Microscopic analyses of fecal samples for parasites showed a sustained reduction in infection intensity for parasites transmitted directly through the feet when people received shoes with a public health image. Our results show that combining culturally appropriate images with public health interventions can be effective in low-literacy populations.

Uncovering zoonoses awareness in an emerging disease 'hotspot'.

Emerging infectious diseases from animals pose significant and increasing threats to human health; places of risk are simultaneously viewed as conservation and emerging disease 'hotspots'. The One World/One Health paradigm is an 'assemblage' discipline. Extensive research from the natural and social sciences, as well as public health have contributed to designing surveillance and response policy within the One World/One Health framework. However, little research has been undertaken that considers the lives of those who experience risk in hotspots on a daily basis. As a result, policymakers and practitioners are unable to fully comprehend the social and ecological processes that catalyze cross-species pathogen exchange. This study examined local populations' comprehension of zoonotic disease. From October 2008-May 2009 we collected data from people living on the periphery of Kibale National Park, in western Uganda. We administered a survey to 72 individuals and conducted semi-structured, in-depth interviews with 14 individuals. Results from the survey showed respondents had statistically significant awareness that transmission of diseases from animals was possible compared to those who did not think such transmission was possible (x(2) = 30.68, df = 1, p < 0.05). However, individual characteristics such as gender, occupation, location, and age were not significantly predictive of awareness. Both quantitative and qualitative data show local people are aware of zoonoses and provided biomedically accurate examples of possible infections and corresponding animal sources (e.g., worm infection from pigs and Ebola from primates). Qualitative data also revealed expectations about the role of the State in managing the prevention of zoonoses from wildlife. As a result of this research, we recommend meaningful discourse with people living at the frontlines of animal contact in emerging disease and conservation hotspots in order to develop informed and relevant zoonoses prevention practices that take into account local knowledge and perceptions.