Biology subjects

Cattadori, I. M.

Publications and source records attributed to Cattadori, I. M..

9 recordsLinked to original sources

bioRxiv2024

Modeling the dietary effects on bat viral shedding and potential consequences for pathogen spillover

Changes in the quality and quantity of food resources can affect individuals health, the way they control infections and consequently the likelihood of onward transmission of pathogens. Dietary shifts have been proposed as one of the factors driving spillovers of zoonotic viruses from bats through a bridging host to humans. While there is a general understanding of the relationship between nutrition and infection in model systems, how diet affects pathogen shedding and the risk of spillover from bats is lacking. We used a data-driven mathematical modeling approach to disentangle the relation between diet, immunity, and viral shedding of Jamaican fruit bats infected with H18N11 and fed different dietary regimes. Model selection indicates that the synergistic interaction between the metabolite citrulline and the cytokine TNF controls viral shedding in a diet-dependent manner. Bats on a sub-optimal fat diet are more successful in terminating shedding than bats on an optimal or sub-optimal sugar diet. However, when bat foraging behavior is considered, bats on the optimal diet show a lower spillover hazard, probably because of a feeding behavior less conducive to transmission. This study provides novel insights into the diet-driven mechanisms of viral shedding and how they can potentially contribute to spillover events.

ecology↗

bioRxiv2023

Helminth ecological requirements shape the impact of climate change on the hazard of infection

Outbreaks and spread of infectious diseases are often associated with seasonality and changes caused by global warming. Free-living stages of soil-transmitted helminths are highly susceptible to environmental 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 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. These differences generated seasonal changes in the timing and intensity of the infection hazard and spatial heterogeneities within and between the two groups. A future range expansion of both groups toward northern latitudes is expected to create new opportunities for the co-circulation of the studied helminth species.

ecology↗

bioRxiv2023

Temperature affects viral kinetics and vectorial capacity of Aedes aegypti mosquitoes co-infected with Mayaro and Dengue viruses

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{degrees}C) and hot (32{degrees}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. Author summaryGlobal warming is having devastating consequences for the environment, and a cause of concern is the increase in local abundance and geographic range of mosquitoes and the associated viruses they transmit. This study explores how temperature affects the mosquitos ability to survive and potentially spread two viruses, Mayaro and dengue, in single or co-infections. We found that Mayaro virus was not clearly affected by temperature or the presence of dengue infection. In contrast, dengue virus showed higher infection and potential for higher transmission in mosquitoes kept at high temperatures, and this trend was stronger in co-infections compared to single infections. Mosquito survival consistently decreased at high temperatures. We hypothesize the differences observed for dengue virus are due to the faster growth and viral activity in the mosquito at hotter temperatures, a pattern not observed for Mayaro virus. More studies under different temperature regimes are needed to clarify the role of co-infection.

microbiology↗

bioRxiv2022

Modeling the contribution of antibodies to the within-host dynamics of single and dual helminth infections in a natural system

Within-host models of infection can provide important insights into the processes that affect parasite spread and persistence in host populations. However, modeling is often limited by the availability of empirical data, a problem commonly encountered in natural systems. Here, we used six years of immune-infection observations of two gastrointestinal helminths (Trichostrongylus retortaeformis and Graphidium strigosum) from a population of European rabbits (Oryctolagus cuniculus) to develop an age-dependent, within-host mathematical model that explicitly included species-specific and cross-reacting antibody (IgA and IgG) responses to each helminth in hosts with single or dual infections. Different models of single infection were formally compared to test alternative mechanisms of parasite regulation. The two models that best described single infections of each helminth species were then coupled through antibody cross-immunity to examine how the presence of one species could alter the host immune response to, and the within-host dynamics of, the other species. For both single infections, model selection suggested that either IgA or IgG responses could equally explain the observed parasite intensities at different host age. However, the strength of this response drastically changed between the two helminths, being stronger against T. retortaeformis than against G. strigosum and causing contrasting age-intensity profiles. When the two helminths coinfect the same host, we found a decrease of the species-specific immune response to both species together with an asymmetric cross-immune response driven by IgG. Changes in the level and affinity of antibodies from single to dual infections contributed to the significant increase of both helminth abundances. By combining mathematical modeling with immuno-infection data, our work provides a model framework for disentangling some of the complexities generated by host-parasite and parasite-parasite interactions from natural systems. Our approach thus offers a tractable general tool to examine immune-infection relationships within hosts. Author summaryThe host immune response often plays a critical role in regulating parasite dynamics and transmission. We developed a mathematical model to evaluate whether and how the observed variation in host antibody responses could explain the relative differences in the abundance of two parasite species in hosts with single and dual infections from a natural rabbit population. Our results indicated that either IgA or IgG could describe the contrasting trends of the two parasites in rabbits with single infections. Specifically, antibodies appeared to control T. retortaeformis, while the effect was less clear for G. strigosum. For dual infections, we found a weaker specific antibody response against both helminths and an asymmetric cross-immunity, which could explain the significantly greater intensities observed for T. retortaeformis and, secondly, for G. strigosum. Our within-host mathematical framework provides a plausible mechanism for the mediated role of antibodies in hosts with single and dual parasite infections, and how the strength of these infection-immune interactions changes with host age. This model framework offers a way forward to our understanding of the within-host processes that generate individual variation in infection and is relatively flexible to be applied to other natural systems.

immunology↗

bioRxiv2022

Divergent Evolutionary Pathways of Myxoma Virus in Australia: Virulence Phenotypes in Susceptible and Partially Resistant Rabbits Indicate Possible Selection for Transmissibility

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 2012-2015, 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 septicaemia, characterized by minimal signs of myxomatosis, the occurrence of pulmonary oedema 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 titres. 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 towards 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. IMPORTANCEThe evolution of the myxoma virus (MYXV) following its release as a biological control for European rabbits in Australia is the textbook example of the co-evolution 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.

microbiology↗

bioRxiv2021

The Enemy of my Enemy is my Friend: Immune-Mediated Facilitation Contributes to Fitness of Co-Infecting Helminths

Our 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 parasite competition and yet, there is ample evidence of positive interactions between species that could be generated by immune-mediated facilitation. Here, we develop an immuno-epidemiological framework and apply it to longitudinal infection data of two gastrointestinal helminths that infect a population of free-living rabbits to investigate, through model testing, the mechanisms of immune-mediated facilitation in dual infections. Simulations show that weakened, species-specific IgA antibody responses and unequal, albeit low, IgA cross-reactions explain higher parasite intensities in dual compared to single infections, for both helminths. Simulations also show that rabbits with dual infections shed more free-living stages that survive fort longer in the environment, implying greater onward transmission than hosts with single infections. These findings support the hypothesis that the two helminths interact through immune-mediated facilitation which contributes to greater fitness and the long-term co-circulation of both species in the host population.

ecology↗

bioRxiv2021

Gastrointestinal Helminths Increase Bordetella bronchiseptica Shedding and Host Variation in Supershedding

Multi-species infections have been suggested to facilitate pathogen transmission and the emergence of supershedding events. However, how the interactions between co-infecting pathogens affect their dynamics of shedding, and how this is related to the host immune response, remains largely unclear. We used laboratory experiments and a modeling approach to examine temporal variations in the shedding of the respiratory bacterium Bordetella bronchiseptica in rabbits challenged with one or two gastrointestinal helminth species. Experimental data showed that rabbits co-infected with one or both helminths shed significantly more B. bronchiseptica by direct contact with an agar petri dish than rabbits with bacteria alone. There was also evidence of synergistic effects when both helminth species were present (triple infection). Co-infected hosts generated supershedding events of higher intensity and more frequently than hosts with no helminths. Model simulations revealed that the two helminths affected the relative contribution of neutrophils and specific IgA and IgG to B. bronchiseptica neutralization in the respiratory tract. In turn, these changes led to differences in the magnitude and duration of shedding among the various types of infection. However, the rapid variation in individual shedding, including supershedding, could not be explained by the interactions between infection and immune response at the scale of analysis that we used. We suggest that local rapid changes at the level of respiratory tissue probably played a more important role. This study provides novel insight into the role of helminths to the dynamics of respiratory infections and offers a quantitative explanation for the differences generated by two helminth species. Author summaryThe dynamics of bacterial infections can be facilitated by the presence of gastrointestinal helminths. Understanding the immunological processes that underline the pathogen-parasite interactions, and how they affect the dynamics of shedding, is important particularly for infections where control of the parasite maybe more effective than trying to reduce the bacterial infection. In this study, we examined the role of two gastrointestinal helminth species on the shedding of the respiratory Bordetella bronchiseptica using laboratory experiments of rabbits together with mathematical modeling. Hosts infected with helminths shed significantly more bacteria with evidence of supershedding, than hosts with only B. bronchiseptica. Simulations showed that by altering the relative contribution of neutrophils, specific IgA and IgG, helminths affected the control of bacterial infection in the respiratory tract. These interactions altered the intensity and duration of bacterial shedding, including the frequency and intensity of supershedding events. However, at the host level our model did not explain the rapid variation in shedding observed, suggesting that local processes in the respiratory tissue are critical for the prediction of the daily shed in the environment. This study advances our understanding of the dynamics of shedding in bacteria-helminth co-infections and provides insight that can be used to control disease spread.

ecology↗

bioRxiv2020

Relationship between Anti-Spike Protein Antibody Titers and SARS-CoV-2 In Vitro Virus Neutralization in Convalescent Plasma

Newly emerged pathogens such as SARS-CoV-2 highlight the urgent need for assays that detect levels of neutralizing antibodies that may be protective. We studied the relationship between anti-spike ectodomain (ECD) and anti-receptor binding domain (RBD) IgG titers, and SARS-CoV-2 virus neutralization (VN) titers generated by two different in vitro assays using convalescent plasma samples obtained from 68 COVID-19 patients, including 13 who donated plasma multiple times. Only 23% (16/68) of donors had been hospitalized. We also studied 16 samples from subjects found to have anti-spike protein IgG during surveillance screening of asymptomatic individuals. We report a strong positive correlation between both plasma anti-RBD and anti-ECD IgG titers, and in vitro VN titer. Anti-RBD plasma IgG correlated slightly better than anti-ECD IgG titer with VN titer. The probability of a VN titer [≥]160 was 80% or greater with anti-RBD or anti-ECD titers of [≥]1:1350. Thirty-seven percent (25/68) of convalescent plasma donors lacked VN titers [≥]160, the FDA-recommended level for convalescent plasma used for COVID-19 treatment. Dyspnea, hospitalization, and disease severity were significantly associated with higher VN titer. Frequent donation of convalescent plasma did not significantly decrease either VN or IgG titers. Analysis of 2,814 asymptomatic adults found 27 individuals with anti-RBD or anti-ECD IgG titers of [≥]1:1350, and evidence of VN [≥]1:160. Taken together, we conclude that anti-RBD or anti-ECD IgG titers can serve as a surrogate for VN titers to identify suitable plasma donors. Plasma anti-RBD or anti-ECD titer of [≥]1:1350 may provide critical information about protection against COVID-19 disease.

immunology↗

bioRxiv2019

Identifying age cohorts responsible for Peste des petits ruminants virus transmission among sheep, goats, and cattle in northern Tanzania

Peste des petits ruminants virus (PPRV) causes a contagious disease of high morbidity and mortality in global sheep and goat populations and leads to approximately $2 billion USD in global annual losses. PPRV is currently targeted by the Food and Agricultural Organization and World Animal Health Organization for global eradication by 2030. To better control this disease and inform eradication strategies, an improved understanding of how PPRV risk varies by age is needed. Our study used a piece-wise catalytic model to estimate the age-specific force of infection (FOI, per capita infection rate of susceptible hosts) among sheep, goats, and cattle from a cross-sectional serosurvey dataset collected in 2016 in Tanzania. Apparent seroprevalence rose with age, as would be expected if PPRV is a fully-immunizing infection, reaching 53.6%, 46.8%, and 11.6% (true seroprevalence: 52.7%, 52.8%, 39.2%) for sheep, goats, and cattle, respectively. Seroprevalence was significantly higher among pastoral animals than agropastoral animals across all ages, with pastoral sheep and goat seroprevalence approaching 70% and 80%, respectively, suggesting endemicity in pastoral settings. The best fitting piece-wise catalytic models included merged age groups: two age groups for sheep, three age groups for goats, and four age groups for cattle. However, the signal of these age heterogeneities was weak, with overlapping confidence intervals around force of infection estimates from most models with the exception of a significant FOI peak among 2.5-3.5 year old pastoral cattle. Pastoral animals had a higher force of infection overall, and across a wider range of ages than agropastoral animals. The subtle age-specific force of infection heterogeneities identified in this study among sheep, goats, and cattle suggest that targeting control efforts by age may not be as effective as targeting by other risk factors, such as management system type. Further research should investigate how specific husbandry practices affect PPRV transmission. Author SummaryAge differences in transmission are important for many infections, and can help target control programs. We used an age-structured serosurvey of Tanzanian sheep, goats, and cattle to explore peste des petits ruminants virus transmission. We estimated rate at which susceptibles acquire infection (force of infection) to determine which age group(s) had the highest transmission rates. We hypothesized that an age-varying model with multiple age groups would better fit the data than an age constant model and that the highest transmission rates would appear in the youngest age groups. Furthermore, we hypothesized evidence of immunity would increase with age. The data supported our hypothesis at the species level and the best fitting models merged age groups: two, three, and four age group models were best for sheep, goats, and cattle, respectively. The highest rates occurred among younger age groups and evidence of immunity rose with age for all species. In most models, confidence interval estimates overlapped, but there was a significant FOI peak among 2.3-3.5 year old pastoral cattle. Importantly, these data indicate that there is not sufficient evidence to support targeted control by age group, and that targeted control based on production system should be more effective.

ecology↗