RESUMO
Outbreaks and spread of infectious diseases are often associated with seasonality and environmental changes, including global warming. Free-living stages of soil-transmitted helminths are highly susceptible to climatic drivers; however, how multiple climatic variables affect helminth species, and the long-term consequences of these interactions, is poorly understood. We used experiments on nine trichostrongylid species of herbivores to develop a temperature- and humidity-dependent model of infection hazard, which was then implemented at the European scale under climate change scenarios. Intestinal and stomach helminths exhibited contrasting climatic responses, with the former group strongly affected by temperature while the latter primarily impacted by humidity. Among the demographic traits, larval survival heavily modulated the infection hazard. According to the specific climatic responses of the two groups, climate change is expected to generate differences in the seasonal and spatial shifts of the infection hazard and group co-circulation. In the future, an intensification of these trends could create new opportunities for species range expansion and co-occurrence at European central-northern latitudes.
Assuntos
Mudança Climática , Helmintos , Animais , Aquecimento Global , LarvaRESUMO
To characterize the ongoing evolution of myxoma virus in Australian rabbits, we used experimental infections of laboratory rabbits to determine the virulence and disease phenotypes of recent virus isolates. The viruses, collected between 2012 and 2015, fell into three lineages, one of which, lineage c, experienced a punctuated increase in evolutionary rate. All viruses were capable of causing acute death with aspects of neutropenic septicemia, characterized by minimal signs of myxomatosis, the occurrence of pulmonary edema and bacteria invasions throughout internal organs, but with no inflammatory response. For the viruses of highest virulence all rabbits usually died at this point. In more attenuated viruses, some rabbits died acutely, while others developed an amyxomatous phenotype. Rabbits that survived for longer periods developed greatly swollen cutaneous tissues with very high virus titers. This was particularly true of lineage c viruses. Unexpectedly, we identified a line of laboratory rabbits with some innate resistance to myxomatosis and used these in direct comparisons with the fully susceptible rabbit line. Importantly, the same disease phenotype occurred in both susceptible and resistant rabbits, although virulence was shifted toward more attenuated grades in resistant animals. We propose that selection against inflammation at cutaneous sites prolongs virus replication and enhances transmission, leading to the amyxomatous phenotype. In some virus backgrounds this creates an immunosuppressive state that predisposes to high virulence and acute death. The alterations in disease pathogenesis, particularly the overwhelming bacterial invasions that characterize the modern viruses, suggest that their virulence grades are not directly comparable with earlier studies. IMPORTANCE The evolution of the myxoma virus (MYXV) following its release as a biological control for European rabbits in Australia is the textbook example of the coevolution of virus virulence and host resistance. However, most of our knowledge of MYXV evolution only covers the first few decades of its spread in Australia and often with little direct connection between how changes in virus phenotype relate to those in the underlying virus genotype. By conducting detailed experimental infections of recent isolates of MYXV in different lines of laboratory rabbits, we examined the ongoing evolution of MYXV disease phenotypes. Our results reveal a wide range of phenotypes, including an amyxomatous type, as well as the impact of invasive bacteria, that in part depended on the level of rabbit host resistance. These results provide a unique insight into the complex virus and host factors that combine to shape disease phenotype and viral evolution.
Assuntos
Myxoma virus , Mixomatose Infecciosa , Animais , Coelhos , Virulência/genética , Austrália , Fenótipo , Genótipo , Mixomatose Infecciosa/genéticaRESUMO
The conceptual understanding of immune-mediated interactions between parasites is rooted in the theory of community ecology. One of the limitations of this approach is that most of the theory and empirical evidence has focused on resource or immune-mediated competition between parasites and yet there is ample evidence of positive interactions that could be generated by immune-mediated facilitation. We developed an immuno-epidemiological model and applied it to long-term data of two gastrointestinal helminths in two rabbit populations to investigate, through model testing, how immune-mediated mechanisms of parasite regulation could explain the higher intensities of both helminths in rabbits with dual than single infections. The model framework was selected and calibrated on rabbit population A and then validated on the nearby rabbit population B to confirm the consistency of the findings and the generality of the mechanisms. Simulations suggested that the higher intensities in rabbits with dual infections could be explained by a weakened or low species-specific IgA response and an asymmetric IgA cross-reaction. Simulations also indicated that rabbits with dual infections shed more free-living stages that survived for longer in the environment, implying greater transmission than stages from hosts with single infections. Temperature and humidity selectively affected the free-living stages of the two helminths. These patterns were comparable in the two rabbit populations and support the hypothesis that immune-mediated facilitation can contribute to greater parasite fitness and local persistence.
Assuntos
Helmintos , Parasitos , Animais , Coelhos , Helmintos/fisiologia , Trato Gastrointestinal , Imunoglobulina A , Interações Hospedeiro-ParasitaRESUMO
Research Highlight: Lunn, T. J., Peel, A. J., Eby, P., Brooks, R., Plowright, R. K., Kessler, M. K., & McCallum, H. (2021). Counterintuitive scaling between population abundance and local density: Implications for modelling transmission of infectious diseases in bat populations. Journal of Animal Ecology, https://doi.org/10.1111/1365-2656.13634. Quantifying the transmission of an infectious disease is often difficult and for natural animal systems it can be a major challenge. Animals move over time and space changing their degree of aggregation and rate of contact, which, in turn, affects the risk of infection and the onward spread of the pathogen. Capturing the fundamentals of these processes requires the identification of both the correct spatial scale at which the processes take place and what constitutes a meaningful host population unit. Lunn et al. collected data on the gregarious Pteropus (flying foxes) bats from roost sites in Australia and investigated whether total bat abundance at the roost level, the spatial scale commonly used to model pathogen spread in bat populations, was representative of bat measurements at the tree level, the scale at which pathogen transmission between bats most likely occurs. Their findings showed that bat population measurements at the sub-plot level were strong predictors for potential transmission at the tree scale, while roost-level measurements were less robust. This study suggests that bat abundance at roost is inadequate to capture the gregarious structure of bat populations and the fundamental processes of transmission at lower scale.
Assuntos
Quirópteros , Animais , Austrália , ÁrvoresRESUMO
Variation in the intensity and duration of infections is often driven by variation in the network and strength of host immune responses. While many of the immune mechanisms and components are known for parasitic helminths, how these relationships change from single to multiple infections and impact helminth dynamics remains largely unclear. Here, we used laboratory data from a rabbit-helminth system and developed a within-host model of infection to investigate different scenarios of immune regulation in rabbits infected with one or two helminth species. Model selection suggests that the immunological pathways activated against Trichostrongylus retortaeformis and Graphidium strigosum are similar. However, differences in the strength of these immune signals lead to the contrasting dynamics of infections, where the first parasite is rapidly cleared and the latter persists with high intensities. In addition to the reactions identified in single infections, rabbits with both helminths also activate new pathways that asymmetrically affect the dynamics of the two species. These new signals alter the intensities but not the general trend of the infections. The type of interactions described can be expected in many other host-helminth systems. Our immune framework is flexible enough to capture different mechanisms and their complexity, and provides essential insights to the understanding of multi-helminth infections.
Assuntos
Interações Hospedeiro-Parasita/imunologia , Modelos Imunológicos , Tricostrongiloidíase/imunologia , Tricostrongilose/imunologia , Animais , Coinfecção/imunologia , Coinfecção/parasitologia , Biologia Computacional , Simulação por Computador , Modelos Animais de Doenças , Modelos Lineares , Probabilidade , Coelhos , Especificidade da Espécie , Trichostrongyloidea/imunologia , Trichostrongyloidea/parasitologia , Tricostrongiloidíase/complicações , Tricostrongiloidíase/parasitologia , Tricostrongilose/complicações , Tricostrongilose/parasitologia , Trichostrongylus/imunologia , Trichostrongylus/parasitologiaRESUMO
In host-pathogen arms races, increases in host resistance prompt counteradaptation by pathogens, but the nature of that counteradaptation is seldom directly observed outside of laboratory models. The best-documented field example is the coevolution of myxoma virus (MYXV) in European rabbits. To understand how MYXV in Australia has continued to evolve in wild rabbits under intense selection for genetic resistance to myxomatosis, we compared the phenotypes of the progenitor MYXV and viral isolates from the 1950s and the 1990s in laboratory rabbits with no resistance. Strikingly, and unlike their 1950s counterparts, most virus isolates from the 1990s induced a highly lethal immune collapse syndrome similar to septic shock. Thus, the next step in this canonical case of coevolution after a species jump has been further escalation by the virus in the face of widespread host resistance.
Assuntos
Myxoma virus/genética , Infecções por Poxviridae/veterinária , Coelhos/virologia , Infecções Tumorais por Vírus/veterinária , Animais , Austrália/epidemiologia , Evolução Biológica , Myxoma virus/patogenicidade , Infecções por Poxviridae/epidemiologia , Infecções por Poxviridae/patologia , Fatores de Tempo , Infecções Tumorais por Vírus/epidemiologia , Infecções Tumorais por Vírus/patologia , VirulênciaRESUMO
BACKGROUND: One of the major challenges facing investigators in the microbiome field is turning large numbers of reads generated by next-generation sequencing (NGS) platforms into biological knowledge. Effective analytical workflows that guarantee reproducibility, repeatability, and result provenance are essential requirements of modern microbiome research. For nearly a decade, several state-of-the-art bioinformatics tools have been developed for understanding microbial communities living in a given sample. However, most of these tools are built with many functions that require an in-depth understanding of their implementation and the choice of additional tools for visualizing the final output. Furthermore, microbiome analysis can be time-consuming and may even require more advanced programming skills which some investigators may be lacking. RESULTS: We have developed a wrapper named iMAP (Integrated Microbiome Analysis Pipeline) to provide the microbiome research community with a user-friendly and portable tool that integrates bioinformatics analysis and data visualization. The iMAP tool wraps functionalities for metadata profiling, quality control of reads, sequence processing and classification, and diversity analysis of operational taxonomic units. This pipeline is also capable of generating web-based progress reports for enhancing an approach referred to as review-as-you-go (RAYG). For the most part, the profiling of microbial community is done using functionalities implemented in Mothur or QIIME2 platform. Also, it uses different R packages for graphics and R-markdown for generating progress reports. We have used a case study to demonstrate the application of the iMAP pipeline. CONCLUSIONS: The iMAP pipeline integrates several functionalities for better identification of microbial communities present in a given sample. The pipeline performs in-depth quality control that guarantees high-quality results and accurate conclusions. The vibrant visuals produced by the pipeline facilitate a better understanding of the complex and multidimensional microbiome data. The integrated RAYG approach enables the generation of web-based reports, which provides the investigators with the intermediate output that can be reviewed progressively. The intensively analyzed case study set a model for microbiome data analysis.
Assuntos
Microbiota , Software , Bactérias/classificação , Bactérias/genética , Sequência de Bases , Biologia Computacional/métodos , Filogenia , RNA Ribossômico 16S/química , RNA Ribossômico 16S/classificação , RNA Ribossômico 16S/genéticaRESUMO
The co-evolution of myxoma virus (MYXV) and the European rabbit occurred independently in Australia and Europe from different progenitor viruses. Although this is the canonical study of the evolution of virulence, whether the genomic and phenotypic outcomes of MYXV evolution in Europe mirror those observed in Australia is unknown. We addressed this question using viruses isolated in the United Kingdom early in the MYXV epizootic (1954-1955) and between 2008-2013. The later UK viruses fell into three distinct lineages indicative of a long period of separation and independent evolution. Although rates of evolutionary change were almost identical to those previously described for MYXV in Australia and strongly clock-like, genome evolution in the UK and Australia showed little convergence. The phenotypes of eight UK viruses from three lineages were characterized in laboratory rabbits and compared to the progenitor (release) Lausanne strain. Inferred virulence ranged from highly virulent (grade 1) to highly attenuated (grade 5). Two broad disease types were seen: cutaneous nodular myxomatosis characterized by multiple raised secondary cutaneous lesions, or an amyxomatous phenotype with few or no secondary lesions. A novel clinical outcome was acute death with pulmonary oedema and haemorrhage, often associated with bacteria in many tissues but an absence of inflammatory cells. Notably, reading frame disruptions in genes defined as essential for virulence in the progenitor Lausanne strain were compatible with the acquisition of high virulence. Combined, these data support a model of ongoing host-pathogen co-evolution in which multiple genetic pathways can produce successful outcomes in the field that involve both different virulence grades and disease phenotypes, with alterations in tissue tropism and disease mechanisms.
Assuntos
Evolução Molecular , Myxoma virus/genética , Myxoma virus/patogenicidade , Mixomatose Infecciosa/genética , Virulência/genética , Animais , Austrália , Genes Virais/genética , Genótipo , Fenótipo , Filogenia , Reação em Cadeia da Polimerase , Coelhos , Reino UnidoRESUMO
Understanding the mechanisms that generate complex host-parasite interactions, and how they contribute to variation between and within hosts, is important for predicting risk of infection and transmission, and for developing more effective interventions based on parasite properties. We used the T. retortaeformis (TR)-rabbit system and developed a state-space mathematical framework to capture the variation in intensity of infection and egg shedding in hosts infected weekly, then treated with an anthelminthic and subsequently re-challenged following the same infection regime. Experimental infections indicate that parasite intensity accumulates more slowly in the post-anthelminthic phase but reaches similar maximum numbers. By contrast, parasite EPG (eggs per gram of feces) shed from rabbits in the post-treatment phase is lower and less variable through time. Inference based on EPG alone suggests a decline in parasite intensity over time. Using a state-space model and incorporating all sources of cross-sectional and longitudinal data, we show that while parasite intensity remains relatively constant in both experimental phases, shedding of eggs into the environment is increasingly limited through changes in parasite growth. We suggest that host immunity directly modulates both the accumulation and the growth of the parasite, and indirectly affects transmission by limiting parasite length and thus fecundity. This study provides a better understanding of how within-host trophic interactions influence different components of a helminth population. It also suggests that heterogeneity in parasite traits should be addressed more carefully when examining and managing helminth infections in the absence of some critical data on parasite dynamics.
Assuntos
Interações Hospedeiro-Parasita/fisiologia , Trichostrongylus/parasitologia , Animais , Anti-Helmínticos , Evolução Biológica , Helmintos/parasitologia , Modelos Biológicos , Modelos Teóricos , Parasitos , CoelhosRESUMO
Global climate change is predicted to alter the distribution and dynamics of soil-transmitted helminth infections, and yet host immunity can also influence the impact of warming on host-parasite interactions and mitigate the long-term effects. We used time-series data from two helminth species of a natural herbivore and investigated the contribution of climate change and immunity on the long-term and seasonal dynamics of infection. We provide evidence that climate warming increases the availability of infective stages of both helminth species and the proportional increase in the intensity of infection for the helminth not regulated by immunity. In contrast, there is no significant long-term positive trend in the intensity for the immune-controlled helminth, as immunity reduces the net outcome of climate on parasite dynamics. Even so, hosts experienced higher infections of this helminth at an earlier age during critical months in the warmer years. Immunity can alleviate the expected long-term effect of climate on parasite infections but can also shift the seasonal peak of infection toward the younger individuals.
Assuntos
Aquecimento Global , Helmintíase Animal/imunologia , Interações Hospedeiro-Parasita/imunologia , Coelhos/parasitologia , Envelhecimento/imunologia , Distribuição Animal , Animais , Helmintíase Animal/epidemiologia , Helmintíase Animal/parasitologia , Helmintíase Animal/transmissão , Umidade , Enteropatias Parasitárias/epidemiologia , Enteropatias Parasitárias/imunologia , Enteropatias Parasitárias/parasitologia , Enteropatias Parasitárias/veterinária , Intestino Delgado/imunologia , Intestino Delgado/parasitologia , Larva/fisiologia , Estágios do Ciclo de Vida , Óvulo/fisiologia , Dinâmica Populacional , Coelhos/imunologia , Escócia/epidemiologia , Estações do Ano , Solo/parasitologia , Estômago/imunologia , Estômago/parasitologia , Gastropatias/epidemiologia , Gastropatias/imunologia , Gastropatias/parasitologia , Gastropatias/veterinária , Temperatura , Trichostrongyloidea/crescimento & desenvolvimento , Trichostrongyloidea/fisiologia , Tricostrongiloidíase/epidemiologia , Tricostrongiloidíase/imunologia , Tricostrongiloidíase/parasitologia , Tricostrongiloidíase/transmissão , Tricostrongiloidíase/veterinária , Tricostrongilose/epidemiologia , Tricostrongilose/imunologia , Tricostrongilose/parasitologia , Tricostrongilose/transmissão , Tricostrongilose/veterinária , Trichostrongylus/crescimento & desenvolvimento , Trichostrongylus/fisiologiaRESUMO
The coevolution of myxoma virus (MYXV) and wild European rabbits in Australia and Europe is a paradigm for the evolution of a pathogen in a new host species. Genomic analyses have identified the mutations that have characterized this evolutionary process, but defining causal mutations in the pathways from virulence to attenuation and back to virulence has not been possible. Using reverse genetics, we examined the roles of six selected mutations found in Australian field isolates of MYXV that fall in known or potential virulence genes. Several of these mutations occurred in genes previously identified as virulence genes in whole-gene knockout studies. Strikingly, no single or double mutation among the mutations tested had an appreciable impact on virulence. This suggests either that virulence evolution was defined by amino acid changes other than those analyzed here or that combinations of multiple mutations, possibly involving epistatic interactions or noncoding sequences, have been critical in the ongoing evolution of MYXV virulence. In sum, our results show that single-gene knockout studies of a progenitor virus can have little power to predict the impact of individual mutations seen in the field. The genetic determinants responsible for this canonical case of virulence evolution remain to be determined.IMPORTANCE The species jump of myxoma virus (MYXV) from the South American tapeti to the European rabbit populations of Australia and Europe is a canonical example of host-pathogen coevolution. Detailed molecular studies have identified multiple genes in MYXV that are critical for virulence, and genome sequencing has revealed the evolutionary history of MYXV in Australia and Europe. However, it has not been possible to categorically identify the key mutations responsible for the attenuation of or reversion to virulence during this evolutionary process. Here we use reverse genetics to examine the role of mutations in viruses isolated early and late in the Australian radiation of MYXV. Surprisingly, none of the candidate mutations that we identified as likely having roles in attenuation proved to be important for virulence. This indicates that considerable caution is warranted when interpreting the possible role of individual mutations during virulence evolution.
Assuntos
Genoma Viral , Mutação , Myxoma virus/genética , Myxoma virus/patogenicidade , Genética Reversa , Fatores de Virulência/genética , Animais , Austrália , Evolução Molecular , Técnicas de Inativação de Genes , Genômica , Myxoma virus/classificação , Myxoma virus/isolamento & purificação , Filogenia , Coelhos , VirulênciaRESUMO
Myxomatosis is a rapidly lethal disease of European rabbits that is caused by myxoma virus (MYXV). The introduction of a South American strain of MYXV into the European rabbit population of Australia is the classic case of host-pathogen coevolution following cross-species transmission. The most virulent strains of MYXV for European rabbits are the Californian viruses, found in the Pacific states of the United States and the Baja Peninsula, Mexico. The natural host of Californian MYXV is the brush rabbit, Sylvilagus bachmani. We determined the complete sequence of the MSW strain of Californian MYXV and performed a comparative analysis with other MYXV genomes. The MSW genome is larger than that of the South American Lausanne (type) strain of MYXV due to an expansion of the terminal inverted repeats (TIRs) of the genome, with duplication of the M156R, M154L, M153R, M152R, and M151R genes and part of the M150R gene from the right-hand (RH) end of the genome at the left-hand (LH) TIR. Despite the extreme virulence of MSW, no novel genes were identified; five genes were disrupted by multiple indels or mutations to the ATG start codon, including two genes, M008.1L/R and M152R, with major virulence functions in European rabbits, and a sixth gene, M000.5L/R, was absent. The loss of these gene functions suggests that S. bachmani is a relatively recent host for MYXV and that duplication of virulence genes in the TIRs, gene loss, or sequence variation in other genes can compensate for the loss of M008.1L/R and M152R in infections of European rabbits.
Assuntos
Adaptação Fisiológica/genética , Genoma Viral , Myxoma virus/genética , Mixomatose Infecciosa/virologia , Infecções Tumorais por Vírus/virologia , Proteínas Virais/genética , Virulência/genética , Animais , Sequência de Bases , Evolução Biológica , California , Europa (Continente) , México , Dados de Sequência Molecular , Myxoma virus/classificação , Myxoma virus/patogenicidade , Mixomatose Infecciosa/genética , Filogenia , Coelhos , Homologia de Sequência do Ácido Nucleico , Sequências Repetidas Terminais/genética , Infecções Tumorais por Vírus/genética , Replicação ViralRESUMO
The evolutionary interplay between myxoma virus (MYXV) and the European rabbit (Oryctolagus cuniculus) following release of the virus in Australia in 1950 as a biological control is a classic example of host-pathogen coevolution. We present a detailed genomic and phylogeographic analysis of 30 strains of MYXV, including the Australian progenitor strain Standard Laboratory Strain (SLS), 24 Australian viruses isolated from 1951 to 1999, and three isolates from the early radiation in Britain from 1954 and 1955. We show that in Australia MYXV has spread rapidly on a spatial scale, with multiple lineages cocirculating within individual localities, and that both highly virulent and attenuated viruses were still present in the field through the 1990s. In addition, the detection of closely related virus lineages at sites 1,000 km apart suggests that MYXV moves freely in geographic space, with mosquitoes, fleas, and rabbit migration all providing means of transport. Strikingly, despite multiple introductions, all modern viruses appear to be ultimately derived from the original introductions of SLS. The rapidity of MYXV evolution was also apparent at the genomic scale, with gene duplications documented in a number of viruses. Duplication of potential virulence genes may be important in increasing the expression of virulence proteins and provides the basis for the evolution of novel functions. Mutations leading to loss of open reading frames were surprisingly frequent and in some cases may explain attenuation, but no common mutations that correlated with virulence or attenuation were identified.
Assuntos
Evolução Molecular , Genoma Viral , Interações Hospedeiro-Patógeno , Myxoma virus/genética , Infecções por Poxviridae/veterinária , Coelhos/virologia , Adaptação Fisiológica , Animais , Dados de Sequência Molecular , Myxoma virus/isolamento & purificação , Myxoma virus/patogenicidade , Myxoma virus/fisiologia , Filogenia , Filogeografia , Infecções por Poxviridae/transmissão , Infecções por Poxviridae/virologia , VirulênciaRESUMO
The attenuation of myxoma virus (MYXV) following its introduction as a biological control into the European rabbit populations of Australia and Europe is the canonical study of the evolution of virulence. However, the evolutionary genetics of this profound change in host-pathogen relationship is unknown. We describe the genome-scale evolution of MYXV covering a range of virulence grades sampled over 49 years from the parallel Australian and European epidemics, including the high-virulence progenitor strains released in the early 1950s. MYXV evolved rapidly over the sampling period, exhibiting one of the highest nucleotide substitution rates ever reported for a double-stranded DNA virus, and indicative of a relatively high mutation rate and/or a continually changing selective environment. Our comparative sequence data reveal that changes in virulence involved multiple genes, likely losses of gene function due to insertion-deletion events, and no mutations common to specific virulence grades. Hence, despite the similarity in selection pressures there are multiple genetic routes to attain either highly virulent or attenuated phenotypes in MYXV, resulting in convergence for phenotype but not genotype.
Assuntos
Evolução Molecular , Genoma Viral , Myxoma virus/genética , Myxoma virus/patogenicidade , Mixomatose Infecciosa/virologia , Animais , Austrália , Sequência de Bases , Evolução Biológica , DNA Viral/genética , Europa (Continente) , Dados de Sequência Molecular , Taxa de Mutação , Filogenia , Coelhos , Análise de Sequência de DNARESUMO
Given the health and economic burden associated with the widespread occurrence of co-infections in humans and agricultural animals, understanding how coinfections contribute to host heterogeneity to infection and transmission is critical if we are to assess risk of infection based on host characteristics. Here, we examine whether host heterogeneity to infection leads to similar heterogeneity in transmission in a population of rabbits single and co-infected with two helminths and monitored monthly for eight years. Compared to single infections, co-infected rabbits carried higher Trichostrongylus retortaeformis intensities, shorter worms with fewer eggs in utero, and shed similar numbers of parasite eggs. In contrast, the same co-infected rabbits harbored fewer Graphidium strigosum with longer bodies and more eggs in utero, and shed more eggs of this helminth. A positive density-dependent relationship between fecundity and intensity was found for T. retortaeformis but not G. strigosum in co-infected rabbits. Juvenile rabbits contributed to most of the infection and shedding of T. retortaeformis, while adult hosts were more important for G. strigosum dynamics of infection and transmission, and this pattern was consistent in single and co-infected individuals. This host-parasite system suggests that we cannot predict the pattern of parasite shedding during co-infections based on intensity of infection alone. We suggest that a mismatching between susceptibility and infectiousness should be expected in helminth coinfections and should not be overlooked.
Assuntos
Coinfecção/veterinária , Fezes/parasitologia , Helmintíase Animal/parasitologia , Helmintos/classificação , Coelhos/parasitologia , Animais , Helmintos/fisiologiaRESUMO
BACKGROUND: Increasing global temperatures and unpredictable climatic extremes have contributed to the spread of vector-borne diseases. The mosquito Aedes aegypti is the main vector of multiple arboviruses that negatively impact human health, mostly in low socioeconomic areas of the world. Co-circulation and co-infection of these viruses in humans have been increasingly reported; however, how vectors contribute to this alarming trend remains unclear. METHODS: Here, we examine single and co-infection of Mayaro virus (D strain, Alphavirus) and dengue virus (serotype 2, Flavivirus) in Ae. aegypti adults and cell lines at two constant temperatures, moderate (27 °C) and hot (32 °C), to quantify vector competence and the effect of temperature on infection, dissemination and transmission, including on the degree of interaction between the two viruses. RESULTS: Both viruses were primarily affected by temperature but there was a partial interaction with co-infection. Dengue virus quickly replicates in adult mosquitoes with a tendency for higher titers in co-infected mosquitoes at both temperatures, and mosquito mortality was more severe at higher temperatures in all conditions. For dengue, and to a lesser extent Mayaro, vector competence and vectorial capacity were higher at hotter temperature in co- vs. single infections and was more evident at earlier time points (7 vs. 14 days post infection) for Mayaro. The temperature-dependent phenotype was confirmed in vitro by faster cellular infection and initial replication at higher temperatures for dengue but not for Mayaro virus. CONCLUSIONS: Our study suggests that contrasting kinetics of the two viruses could be related to their intrinsic thermal requirements, where alphaviruses thrive better at lower temperatures compared to flaviviruses. However, more studies are necessary to clarify the role of co-infection at different temperature regimes, including under more natural temperature settings.
Assuntos
Aedes , Alphavirus , Coinfecção , Vírus da Dengue , Dengue , Flavivirus , Animais , Humanos , Temperatura , Mosquitos Vetores , Alphavirus/genética , Flavivirus/genéticaRESUMO
Peste des petits ruminants virus (PPRV) is a multi-host pathogen with sheep and goats as main hosts. To investigate the role of cattle in the epidemiology of PPR, we simulated conditions similar to East African zero-grazing husbandry practices in a series of trials with local Zebu cattle (Bos taurus indicus) co-housed with goats (Capra aegagrus hircus). Furthermore, we developed a mathematical model to assess the impact of PPRV-transmission from cattle to goats. Of the 32 cattle intranasally infected with the locally endemic lineage IV strain PPRV/Ethiopia/Habru/2014 none transmitted PPRV to 32 co-housed goats. However, these cattle or cattle co-housed with PPRV-infected goats seroconverted. The results confirm previous studies that cattle currently play a negligible role in PPRV-transmission and small ruminant vaccination is sufficient for eradication. However, the possible emergence of PPRV strains more virulent for cattle may impact eradication. Therefore, continued monitoring of PPRV circulation and evolution is recommended.
Assuntos
Doenças das Cabras , Cabras , Peste dos Pequenos Ruminantes , Vírus da Peste dos Pequenos Ruminantes , Animais , Peste dos Pequenos Ruminantes/transmissão , Peste dos Pequenos Ruminantes/virologia , Peste dos Pequenos Ruminantes/epidemiologia , Bovinos , Vírus da Peste dos Pequenos Ruminantes/imunologia , Vírus da Peste dos Pequenos Ruminantes/fisiologia , Cabras/virologia , Doenças das Cabras/virologia , Doenças das Cabras/transmissão , Doenças dos Bovinos/transmissão , Doenças dos Bovinos/virologia , Doenças dos Bovinos/epidemiologia , Erradicação de Doenças/métodosRESUMO
Co-infections alter the host immune response but how the systemic and local processes at the site of infection interact is still unclear. The majority of studies on co-infections concentrate on one of the infecting species, an immune function or group of cells and often focus on the initial phase of the infection. Here, we used a combination of experiments and mathematical modelling to investigate the network of immune responses against single and co-infections with the respiratory bacterium Bordetella bronchiseptica and the gastrointestinal helminth Trichostrongylus retortaeformis. Our goal was to identify representative mediators and functions that could capture the essence of the host immune response as a whole, and to assess how their relative contribution dynamically changed over time and between single and co-infected individuals. Network-based discrete dynamic models of single infections were built using current knowledge of bacterial and helminth immunology; the two single infection models were combined into a co-infection model that was then verified by our empirical findings. Simulations showed that a T helper cell mediated antibody and neutrophil response led to phagocytosis and clearance of B. bronchiseptica from the lungs. This was consistent in single and co-infection with no significant delay induced by the helminth. In contrast, T. retortaeformis intensity decreased faster when co-infected with the bacterium. Simulations suggested that the robust recruitment of neutrophils in the co-infection, added to the activation of IgG and eosinophil driven reduction of larvae, which also played an important role in single infection, contributed to this fast clearance. Perturbation analysis of the models, through the knockout of individual nodes (immune cells), identified the cells critical to parasite persistence and clearance both in single and co-infections. Our integrated approach captured the within-host immuno-dynamics of bacteria-helminth infection and identified key components that can be crucial for explaining individual variability between single and co-infections in natural populations.
Assuntos
Coinfecção/parasitologia , Modelos Teóricos , Animais , Infecções por Bordetella/microbiologia , Bordetella bronchiseptica/patogenicidade , Coinfecção/imunologia , Helmintos , Sistema Respiratório/parasitologia , Trichostrongylus/patogenicidadeRESUMO
The migration of infective nematode larvae into the tissues of their hosts has been proposed as a mechanism of reducing larval mortality and increase parasite lifetime reproductive success. Given that individual hosts differ in the level of exposure, strength of immune response and physiological conditions we may expect the number of larvae in tissue to vary both between and within hosts. We used 2 gastrointestinal nematode species common in the European rabbit (Oryctolagus cuniculus) and examined how the number of larvae in the tissue changed with the immune response, parasite intensity-dependent constraints in the lumen and seasonal weather factors, in rabbits of different age, sex and breeding status. For both nematode species, larvae from the gastrointestinal tissue exhibited strong seasonal and host age-related patterns with fewer larvae recovered in summer compared to winter and more in adults than in juveniles. The number of larvae of the 2 nematodes was positively associated with intensity of parasite infection in the lumen and antibody responses while it was negatively related with air temperature and rainfall. Host sex, reproductive status and co-infection with the second parasite species contributed to increase variability between hosts. We concluded that heterogeneities in host conditions are a significant cause of variability of larval abundance in the gastrointestinal tissues. These findings can have important consequences for the dynamics of nematode infections and how parasite's life-history strategies adjust to host changes.
Assuntos
Trato Gastrointestinal/parasitologia , Nematoides/fisiologia , Infecções por Nematoides/veterinária , Coelhos/parasitologia , Envelhecimento , Animais , Animais Selvagens , Feminino , Larva/fisiologia , Masculino , Infecções por Nematoides/parasitologia , Tempo (Meteorologia)RESUMO
Increasing global temperatures and unpredictable climatic extremes have contributed to the spread of vector-borne diseases. The mosquito Aedes aegypti is the main vector of multiple arboviruses that negatively impact human health, mostly in low socioeconomic areas of the world. Co-circulation and co-infection of these viruses in humans have been increasingly reported; however, how vectors contribute to this alarming trend remains unclear. Here, we examine single and co-infection of Mayaro virus (-D strain, Alphavirus) and dengue virus (serotype 2, Flavivirus) in Ae. aegypti adults and cell lines at two constant temperatures, moderate (27°C) and hot (32°C), to quantify vector competence and the effect of temperature on infection, dissemination and transmission, including on the degree of interaction between the two viruses. Both viruses were primarily affected by temperature but there was a partial interaction with co-infection. Dengue virus quickly replicates in adult mosquitoes, with a tendency for higher titers in co-infected mosquitoes at both temperatures and mosquito mortality was more severe at higher temperatures in all conditions. For dengue, and to a lesser extent Mayaro, vector competence and vectorial capacity were higher at hotter temperature in co- vs single infections and was more evident at earlier timepoints (7 vs 14 days post infection). The temperature-dependent phenotype was confirmed in vitro by faster cellular infection and initial replication at higher temperatures for dengue but not for Mayaro virus. Our study suggests that contrasting kinetics of the two viruses could be related to their intrinsic thermal requirements, where alphaviruses thrive better at lower temperatures compared to flaviviruses, but further studies are necessary to clarify the role of co-infection at different and variable temperature regimes.