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Philosophical Transactions of the Royal... Sep 2019Predicting pathogen spillover requires counting spillover events and aligning such counts with process-related covariates for each spillover event. How can we connect...
Predicting pathogen spillover requires counting spillover events and aligning such counts with process-related covariates for each spillover event. How can we connect our analysis of spillover counts to simple, mechanistic models of pathogens jumping from reservoir hosts to recipient hosts? We illustrate how the pathways to pathogen spillover can be represented as a directed graph connecting reservoir hosts and recipient hosts and the number of spillover events modelled as a percolation of infectious units along that graph. Percolation models of pathogen spillover formalize popular intuition and management concepts for pathogen spillover, such as the inextricably multilevel nature of cross-species transmission, the impact of covariance between processes such as pathogen shedding and human susceptibility on spillover risk, and the assumptions under which the effect of a management intervention targeting one process, such as persistence of vectors, will translate to an equal effect on the overall spillover risk. Percolation models also link statistical analysis of spillover event datasets with a mechanistic model of spillover. Linear models, one might construct for process-specific parameters, such as the log-rate of shedding from one of several alternative reservoirs, yield a nonlinear model of the log-rate of spillover. The resulting nonlinearity is approximately piecewise linear with major impacts on statistical inferences of the importance of process-specific covariates such as vector density. We recommend that statistical analysis of spillover datasets use piecewise linear models, such as generalized additive models, regression clustering or ensembles of linear models, to capture the piecewise linearity expected from percolation models. We discuss the implications of our findings for predictions of spillover risk beyond the range of observed covariates, a major challenge of forecasting spillover risk in the Anthropocene. This article is part of the theme issue 'Dynamic and integrative approaches to understanding pathogen spillover'.
Topics: Animals; Communicable Diseases, Emerging; Disease Reservoirs; Humans; Models, Theoretical; Zoonoses
PubMed: 31401950
DOI: 10.1098/rstb.2018.0331 -
Viruses Feb 2020Human immunodeficiency virus (HIV-1) indefinitely persists, despite effective antiretroviral therapy (ART), within a small pool of latently infected cells. These cells... (Review)
Review
Human immunodeficiency virus (HIV-1) indefinitely persists, despite effective antiretroviral therapy (ART), within a small pool of latently infected cells. These cells often display markers of immunologic memory and harbor both replication-competent and -incompetent proviruses at approximately a 1:100 ratio. Although complete HIV eradication is a highly desirable goal, this likely represents a bridge too far for our current and foreseeable technologies. A more tractable goal involves engineering a sustained viral remission in the absence of ART--a "functional cure." In this setting, HIV remains detectable during remission, but the size of the reservoir is small and the residual virus is effectively controlled by an engineered immune response or other intervention. Biological precedence for such an approach is found in the post-treatment controllers (PTCs), a rare group of HIV-infected individuals who, following ART withdrawal, do not experience viral rebound. PTCs are characterized by a small reservoir, greatly reduced inflammation, and the presence of a poorly understood immune response that limits viral rebound. Our goal is to devise a safe and effective means for replicating durable post-treatment control on a global scale. This requires devising methods to reduce the size of the reservoir and to control replication of this residual virus. In the following sections, we will review many of the approaches and tools that likely will be important for implementing such a "reduce and control" strategy and for achieving a PTC-like sustained HIV remission in the absence of ART.
Topics: Animals; Anti-Retroviral Agents; Disease Reservoirs; HIV Infections; HIV-1; Humans; Immunologic Memory; Latent Infection; Macaca mulatta; Remission Induction; Simian Acquired Immunodeficiency Syndrome; Simian Immunodeficiency Virus; Viral Load; Virus Activation; Virus Latency; Virus Replication
PubMed: 32046251
DOI: 10.3390/v12020188 -
Parasitology Feb 2023In this work we reviewed historical and recent data on spp. infection combining data collected in Turkmenistan, Uzbekistan, Kazakhstan, Kyrgyzstan, Iran, China and... (Review)
Review
In this work we reviewed historical and recent data on spp. infection combining data collected in Turkmenistan, Uzbekistan, Kazakhstan, Kyrgyzstan, Iran, China and Mongolia. We specifically focused on a complex of co-existing species (, and ) sharing the same animal reservoirs and vectors. In addition, we analysed the presence of dsRNA viruses in these species and discussed future research directions to identify species-specific traits, which may determine susceptibility of different spp. to viral infection.
Topics: Animals; Leishmaniasis, Cutaneous; Disease Reservoirs; Gerbillinae; Leishmaniasis; Leishmania major; Turkmenistan
PubMed: 36453145
DOI: 10.1017/S0031182022001640 -
Communications Biology Nov 2021Powassan virus lineage 2 (deer tick virus) is an emergent threat to American public health, causing severe neurologic disease. Its life cycle in nature remains poorly...
Powassan virus lineage 2 (deer tick virus) is an emergent threat to American public health, causing severe neurologic disease. Its life cycle in nature remains poorly understood. We use a host-specific retrotransposon-targeted real time PCR assay to test the hypothesis that white-footed mice, considered the main eastern U.S. reservoir of the coinfecting agent of Lyme disease, is the reservoir for deer tick virus. Of 20 virus-infected host-seeking nymphal black-legged ticks 65% fed on shrews and none on mice. The proportion of ticks feeding on shrews at a site is positively associated with prevalence of viral infection, but not the Lyme disease agent. Viral RNA is detected in the brain of one shrew. We conclude that shrews are a likely reservoir host for deer tick virus and that host bloodmeal analysis can provide direct evidence to incriminate reservoir hosts, thereby promoting our understanding of the ecology of tick-borne infections.
Topics: Animals; Disease Reservoirs; Encephalitis Viruses, Tick-Borne; Encephalitis, Tick-Borne; Massachusetts; Rhode Island; Shrews
PubMed: 34811484
DOI: 10.1038/s42003-021-02828-1 -
Viruses May 2021Puumala hantavirus (PUUV), carried and spread by the bank vole (), causes a mild form of hemorrhagic fever with renal syndrome (HFRS) called nephropathia epidemica (NE).... (Review)
Review
Puumala hantavirus (PUUV), carried and spread by the bank vole (), causes a mild form of hemorrhagic fever with renal syndrome (HFRS) called nephropathia epidemica (NE). Acute high fever, acute kidney injury (AKI), thrombocytopenia, and hematuria are typical features of this syndrome. In addition, headache, blurred vision, insomnia, vertigo, and nausea are commonly associated with the disease. This review explores the mechanisms and presentations of ocular and central nervous system involvement in acute NE.
Topics: Animals; Antibodies, Viral; Arvicolinae; Central Nervous System Diseases; Disease Reservoirs; Eye Diseases; Hemorrhagic Fever with Renal Syndrome; Humans; Population Dynamics; Puumala virus
PubMed: 34072819
DOI: 10.3390/v13061040 -
EcoHealth Mar 2022In the Americas, infectious viral diseases caused by viruses of the genus Mammarenavirus have been reported since the 1960s. Such diseases have commonly been associated... (Review)
Review
In the Americas, infectious viral diseases caused by viruses of the genus Mammarenavirus have been reported since the 1960s. Such diseases have commonly been associated with land use changes, which favor abundance of generalist rodent species. In the Americas-where the rates of land use change are among the highest worldwide-at least 1326 of all 2277 known rodent species have been reported. We conducted a literature review of studies between 1960 and 2020, to establish the current and historical knowledge about genotypes of mammarenaviruses and their rodent reservoirs in the Americas. Our overall goal was to show the importance of focusing research efforts on the American continent, since the conditions exist for future viral hemorrhagic fever (VHF) outbreaks caused by rodent-borne viruses, in turn, carried by widely distributed rodents. We found 47 species identified down to the species level, and one species identified only down to the genus level (Oryzomys sp.), reported in the Americas as reservoirs of mammarenaviruses, most these are ecological generalists. These species associate with 29 genotypes of Mammarenavirus, seven of which have been linked to VHFs in humans. We also highlight the need to monitor these species, in order to prevent viral disease outbreaks in the region.
Topics: Americas; Animals; Arenaviridae; Disease Reservoirs; Hemorrhagic Fevers, Viral; Rodentia
PubMed: 35247117
DOI: 10.1007/s10393-022-01580-0 -
Current Opinion in HIV and AIDS Jul 2021Advances in antiretroviral therapy have saved numerous lives, converting a diagnosis with human immunodeficiency virus 1 (HIV-1) from a death sentence into the... (Review)
Review
PURPOSE OF REVIEW
Advances in antiretroviral therapy have saved numerous lives, converting a diagnosis with human immunodeficiency virus 1 (HIV-1) from a death sentence into the possibility for a (nearly) normal life in many instances. However, the obligation for lifelong adherence, increased risk of accumulated co-morbidities, and continued lack of uniform availability around the globe underscores the need for an HIV cure. Safe and scalable HIV cure strategies remain elusive, in large part due to the presence of viral reservoirs in which caches of infected cells remain hidden from immune elimination, primarily within tissues. Herein, we summarize some of the most exciting recent advances focused on understanding, quantifying, and ultimately targeting HIV tissue viral reservoirs.
RECENT FINDINGS
Current studies have underscored the differences between viral reservoirs in tissue compartments as compared to peripheral blood, in particular, the gastrointestinal (GI) tract. Additionally, several novel or modified techniques are showing promise in targeting the latent viral reservoir, including modifications in drug delivery platforms and techniques such as CRISPR.
SUMMARY
Elimination of tissue viral reservoirs is likely the key to generation of an effective HIV cure. Exciting studies have come out recently that reveal crucial insights into topics ranging from the basic biology of reservoir seeding to effective drug targeting. However, there are still many outstanding questions in the field about the relative importance of specific reservoirs, such as the GI tract, that may alter the final strategy pursued.
Topics: CD4-Positive T-Lymphocytes; Disease Reservoirs; HIV Infections; HIV-1; Humans; Virus Latency
PubMed: 34039843
DOI: 10.1097/COH.0000000000000688 -
Viruses Jul 2021Rodents (order Rodentia), followed by bats (order Chiroptera), comprise the largest percentage of living mammals on earth. Thus, it is not surprising that these two... (Review)
Review
Rodents (order Rodentia), followed by bats (order Chiroptera), comprise the largest percentage of living mammals on earth. Thus, it is not surprising that these two orders account for many of the reservoirs of the zoonotic RNA viruses discovered to date. The spillover of these viruses from wildlife to human do not typically result in pandemics but rather geographically confined outbreaks of human infection and disease. While limited geographically, these viruses cause thousands of cases of human disease each year. In this review, we focus on three questions regarding zoonotic viruses that originate in bats and rodents. First, what biological strategies have evolved that allow RNA viruses to reside in bats and rodents? Second, what are the environmental and ecological causes that drive viral spillover? Third, how does virus spillover occur from bats and rodents to humans?
Topics: Animals; Chiroptera; Disease Outbreaks; Disease Reservoirs; Humans; Rodentia; Virus Diseases; Zoonoses
PubMed: 34452374
DOI: 10.3390/v13081509 -
Zoonoses and Public Health Mar 2021Salmonellosis is a major global public health issue; its most common infection, gastroenteritis, accounts for approximately 90 million illnesses and 150,000 mortalities...
Salmonellosis is a major global public health issue; its most common infection, gastroenteritis, accounts for approximately 90 million illnesses and 150,000 mortalities per year. Eradicating salmonellosis requires surveillance, prevention and treatment, entailing large expenditures. However, it is difficult to control Salmonella transmission because it occurs via multiple routes; exotic reptiles are a reservoir of Salmonella and comprise one such route. As the popularity of exotic pets and animal exhibition has increased, human encounters with reptiles have also increased. As a result, reptile-associated salmonellosis (RAS) has been recognized as an emerging disease. The development of antimicrobial resistance in RAS-causing Salmonella sp. requires alternatives to antibiotics. In this study, bacteriophages have been established as an alternative to antibiotics because only target bacteria are lysed; thus, they are promising biocontrol agents. Here, bacteriophage pSal-SNUABM-02, which infects and lyses reptile Salmonella isolates, was isolated and characterized. The morphology, host range, growth traits and stability of the phage were investigated. The phage was assigned to Myoviridae and was stable in the following conditions: pH 5-9, 4-37°C, and ultravioletA/ultravioletB (UVA/UVB) exposure. Salmonella clearance efficacy was tested using planktonic cell lysis activity and biofilm degradation on polystyrene 96-well plates and reptile skin fragments. The phage exhibited vigorous lysis activity against planktonic cells. In in vitro biofilm degradation tests on reptile skin and polystyrene plates, both low- and high-concentration phage treatments lowered bacterial cell viability by approximately 2.5-3 log colony-forming units and also decreased biomass. Thus, bacteriophages are a promising alternative to antibiotics for the prevention and eradication of RAS.
Topics: Animals; Biofilms; Disease Reservoirs; Humans; Pets; Reptiles; Salmonella Infections; Salmonella Phages; Zoonoses
PubMed: 33455089
DOI: 10.1111/zph.12804 -
Ecology Letters Nov 2023Zoonotic diseases threaten human health worldwide and are often associated with anthropogenic disturbance. Predicting how disturbance influences spillover risk is...
Zoonotic 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. Our approach uses neural networks to extract features of known or hypothesized importance from images. The spatial distribution of these features is then summarized and linked to spatially explicit reservoir presence/absence data using boosted regression trees. We demonstrate the utility of our method by applying it to the reservoir of Lassa virus, Mastomys natalensis, within the West African nations of Sierra Leone and Guinea. We show that, when trained using reservoir trapping data and publicly available aerial imagery, our framework learns relationships between environmental features and reservoir occurrence and accurately ranks areas according to the likelihood of reservoir presence.
Topics: Animals; Humans; Lassa Fever; Disease Reservoirs; Zoonoses; Lassa virus; Guinea; Murinae
PubMed: 37737493
DOI: 10.1111/ele.14307