Reducing spillover of zoonotic pathogens is an appealing approach to preventing human disease and minimizing the risk of future epidemics and pandemics. Although the immediate human health benefit of reducing spillover is clear, over time, spillover reduction could lead to counterintuitive negative consequences for human health. Here, we use mathematical models and computer simulations to explore the conditions under which unanticipated consequences of spillover reduction can occur in systems where the severity of disease increases with age at infection.
View Article and Find Full Text PDFIntroduction: Transmissible vaccines offer a novel approach to suppressing viruses in wildlife populations, with possible applications against viruses that infect humans as zoonoses - Lassa, Ebola, rabies. To ensure safety, current designs propose a recombinant vector platform in which the vector is isolated from the target wildlife population. Because using an endemic vector creates the potential for preexisting immunity to block vaccine transmission, these designs focus on vector viruses capable of superinfection, spreading throughout the host population following vaccination of few individuals.
View Article and Find Full Text PDFZoonotic diseases threaten human health worldwide and are often associated with anthropogenic disturbance. Predicting how disturbance influences spillover risk is critical for effective disease intervention but difficult to achieve at fine spatial scales. Here, we develop a method that learns the spatial distribution of a reservoir species from aerial imagery.
View Article and Find Full Text PDFZoonotic pathogens spread by wildlife continue to spill into human populations and threaten human lives. A potential way to reduce this threat is by vaccinating wildlife species that harbor pathogens that are infectious to humans. Unfortunately, even in cases where vaccines can be distributed en masse as edible baits, achieving levels of vaccine coverage sufficient for pathogen elimination is rare.
View Article and Find Full Text PDFRespiratory viral infections are a leading global cause of disease with multiple viruses detected in 20-30% of cases, and several viruses simultaneously circulating. Some infections with unique viral copathogens result in reduced pathogenicity, while other viral pairings can worsen disease. The mechanisms driving these dichotomous outcomes are likely variable and have only begun to be examined in the laboratory and clinic.
View Article and Find Full Text PDFRespiratory virus infections are a leading cause of disease worldwide with multiple viruses detected in 20-30% of cases and several viruses simultaneously circulating. Some infections with viral copathogens have been shown to result in reduced pathogenicity while other virus pairings can worsen disease. The mechanisms driving these dichotomous outcomes are likely variable and have only begun to be examined in the laboratory and clinic.
View Article and Find Full Text PDF[This corrects the article DOI: 10.1371/journal.pgen.
View Article and Find Full Text PDFThe rate at which zoonotic viruses spill over into the human population varies significantly over space and time. Remarkably, we do not yet know how much of this variation is attributable to genetic variation within viral populations. This gap in understanding arises because we lack methods of genetic analysis that can be easily applied to zoonotic viruses, where the number of available viral sequences is often limited, and opportunistic sampling introduces significant population stratification.
View Article and Find Full Text PDFThe ecology and life history of wild animals influences their potential to harbour infectious disease. This observation has motivated studies identifying empirical relationships between traits of wild animals and historical patterns of spillover and emergence into humans. Although these studies have identified compelling broad-scale patterns, they are generally agnostic with respect to underlying mechanisms.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2022
Transmissible vaccines have the potential to revolutionize how zoonotic pathogens are controlled within wildlife reservoirs. A key challenge that must be overcome is identifying viral vectors that can rapidly spread immunity through a reservoir population. Because they are broadly distributed taxonomically, species specific, and stable to genetic manipulation, betaherpesviruses are leading candidates for use as transmissible vaccine vectors.
View Article and Find Full Text PDFPopulation dynamic models can be used in conjunction with time series of species abundances to infer interactions. Understanding microbial interactions is a prerequisite for numerous goals in microbiome research, including predicting how populations change over time, determining how manipulations of microbiomes affect dynamics and designing synthetic microbiomes to perform tasks. As such, there is great interest in adapting population dynamic theory for microbial systems.
View Article and Find Full Text PDFEvol Med Public Health
December 2020
Background And Objectives: Genetic engineering and similar technologies offer promising new approaches to controlling human diseases by blocking transmission from vectors. However, in spatially structured populations, imperfect coverage of the vector will leave pockets in which the parasite may persist. Movement by humans may disrupt this local persistence and facilitate eradication when these pockets are small, spreading parasite reproduction outside unprotected areas and into areas that block its reproduction.
View Article and Find Full Text PDFGenetically engineered organisms are prone to evolve in response to the engineering. This evolution is often undesirable and can negatively affect the purpose of the engineering. Methods that maintain the stability of engineered genomes are therefore critical to the successful design and use of genetically engineered organisms.
View Article and Find Full Text PDFForecasting the risk of pathogen spillover from reservoir populations of wild or domestic animals is essential for the effective deployment of interventions such as wildlife vaccination or culling. Due to the sporadic nature of spillover events and limited availability of data, developing and validating robust, spatially explicit, predictions is challenging. Recent efforts have begun to make progress in this direction by capitalizing on machine learning methodologies.
View Article and Find Full Text PDFAcetaminophen (APAP) overdose is one of the predominant causes of drug induced acute liver injury in the U.S and U.K.
View Article and Find Full Text PDFThe obligate intracellular bacterial pathogen is reliant on a developmental cycle consisting of two cell forms, termed the elementary body (EB) and the reticulate body (RB). The EB is infectious and utilizes a type III secretion system and preformed effector proteins during invasion, but it does not replicate. The RB replicates in the host cell but is noninfectious.
View Article and Find Full Text PDFLassa virus is a significant burden on human health throughout its endemic region in West Africa, with most human infections the result of spillover from the primary rodent reservoir of the virus, the natal multimammate mouse, M. natalensis. Here we develop a Bayesian methodology for estimating epidemiological parameters of Lassa virus within its rodent reservoir and for generating probabilistic predictions for the efficacy of rodent vaccination programs.
View Article and Find Full Text PDFWhile microbiologists often make the simplifying assumption that genotype determines phenotype in a given environment, it is becoming increasingly apparent that phenotypic heterogeneity (in which one genotype generates multiple phenotypes simultaneously even in a uniform environment) is common in many microbial populations. The importance of phenotypic heterogeneity has been demonstrated in a number of model systems involving binary phenotypic states (e.g.
View Article and Find Full Text PDFGene drives may be used in two ways to curtail vectored diseases. Both involve engineering the drive to spread in the vector population. One approach uses the drive to directly depress vector numbers, possibly to extinction.
View Article and Find Full Text PDFBackground And Objectives: Genetic engineering combined with CRISPR technology has developed to the point that gene drives can, in theory, be engineered to cause extinction in countless species. Success of extinction programs now rests on the possibility of resistance evolution, which is largely unknown. Depending on the gene-drive technology, resistance may take many forms, from mutations in the nuclease target sequence (e.
View Article and Find Full Text PDFTransmissible vaccines may provide a promising solution for improving the control of infectious disease, particularly zoonotic pathogens with wildlife reservoirs. Although it is well known that heterogeneity in pathogen transmission impacts the spread of infectious disease, the effects of heterogeneity on vaccine transmission are largely unknown. Here we develop and analyze a mathematical model that quantifies the potential benefits of a transmissible vaccine in a population where transmission is heterogeneous between two subgroups.
View Article and Find Full Text PDFZoonotic pathogens such as Ebola and rabies pose a major health risk to humans. One proven approach to minimizing the impact of a pathogen relies on reducing its prevalence within animal reservoir populations using mass vaccination. However, two major challenges remain for vaccination programs that target free-ranging animal populations.
View Article and Find Full Text PDFA working group at the National Institute for Mathematical and Biological Synthesis (NIMBioS) explored the feasibility of integrating 2 complementary approaches relevant to ecological risk assessment. Adverse outcome pathway (AOP) models provide "bottom-up" mechanisms to predict specific toxicological effects that could affect an individual's ability to grow, reproduce, and/or survive from a molecular initiating event. Dynamic energy budget (DEB) models offer a "top-down" approach that reverse engineers stressor effects on growth, reproduction, and/or survival into modular characterizations related to the acquisition and processing of energy resources.
View Article and Find Full Text PDFAs the density of human and domestic animal populations increases, the threat of localized epidemics and global pandemics grows. Although effective vaccines have been developed for a number of threatening pathogens, manufacturing and disseminating vaccines in the face of a rapidly spreading epidemic or pandemic remains a formidable challenge. One potentially powerful solution to this problem is the use of transmissible vaccines.
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