Host lifespan and the evolution of resistance to multiple parasites.

Published onlineJournal ArticleThis is the author accepted manuscript. The final version is available from Wiley via the DOI in this record.Hosts are typically challenged by multiple parasites, but to date theory on the evolution of resistance has mainly focused on single infections. We develop a series of models that examine the impact of multiple parasites on the evolution of resistance under the assumption that parasites coexist at the host population scale as a consequence of superinfection. In this way, we are able to explicitly examine the impact of ecological dynamics on the evolutionary outcome. We use our models to address a key question of how host lifespan affects investment in resistance to multiple parasites. We show that investment in costly resistance depends on the specificity of the immune response and on whether or not the focal parasite leads to more acute infection than the co-circulating parasite. A key finding is that investment in resistance always increases as the immune response becomes more general independently of whether it is the focal or the co-circulating parasite that exploits the host most aggressively. Long-lived hosts always invest more than short-lived hosts in both general resistance and resistance that is specific to relatively acute focal parasites. However, for specific resistance to parasites that are less acute than co-circulating parasites it is the short-lived hosts that are predicted to invest most. We show that these results apply whatever the mode of defence, that is whether it is through avoidance or through increased recovery, with or without acquired immunity, or through acquired immunity itself. As a whole, our results emphasize the importance of considering multiple parasites in determining optimal immune investment in eco-evolutionary systems.NERC. Grant Number: NE=K014617=

How specificity and epidemiology drive the coevolution of static trait diversity in hosts and parasites

This is the final version of the article. Available from the publisher via the DOI in this record.There is typically considerable variation in the level of infectivity of parasites and the degree of resistance of hosts within populations. This trait variation is critical not only to the evolutionary dynamics but also to the epidemiology, and potentially the control of infectious disease. However, we lack an understanding of the processes that generate and maintain this trait diversity. We examine theoretically how epidemiological feedbacks and the characteristics of the interaction between host types and parasites strains determine the coevolution of host-parasite diversity. The interactions include continuous characterizations of the key phenotypic features of classic gene-for-gene and matching allele models. We show that when there are costs to resistance in the hosts and infectivity in the parasite, epidemiological feedbacks may generate diversity but this is limited to dimorphism, often of extreme types, in a broad range of realistic infection scenarios. For trait polymorphism, there needs to be both specificity of infection between host types and parasite strains as well as incompatibility between particular strains and types. We emphasize that although the high specificity is well known to promote temporal "Red Queen" diversity, it is costs and combinations of hosts and parasites that cannot infect that will promote static trait diversity.MB was a fellow of the Wissenschaftskolleg zu Berlin 2010–2011 during the writing of this article, and we acknowledge the support from the Natural Environment Research Council (grant NE/K014617/1) to MB and AB

Viral antibody dynamics in a chiropteran host

1. Bats host many viruses that are significant for human and domestic animal health, but the dynamics of these infections in their natural reservoir hosts remain poorly elucidated.<p></p> 2. In these, and other, systems, there is evidence that seasonal life-cycle events drive infection dynamics, directly impacting the risk of exposure to spillover hosts. Understanding these dynamics improves our ability to predict zoonotic spillover from the reservoir hosts.<p></p> 3. To this end, we followed henipavirus antibody levels of >100 individual E. helvum in a closed, captive, breeding population over a 30-month period, using a powerful novel antibody quantitation method.<p></p> 4. We demonstrate the presence of maternal antibodies in this system and accurately determine their longevity. We also present evidence of population-level persistence of viral infection and demonstrate periods of increased horizontal virus transmission associated with the pregnancy/lactation period.<p></p> 5.The novel findings of infection persistence and the effect of pregnancy on viral transmission, as well as an accurate quantitation of chiropteran maternal antiviral antibody half-life, provide fundamental baseline data for the continued study of viral infections in these important reservoir hosts

Spatial heterogeneity lowers rather than increases host-parasite specialization

Abiotic environmental heterogeneity can promote the evolution of diverse resource specialists, which in turn may increase the degree of host–parasite specialization. We coevolved Pseudomonas fluorescens and lytic phage ϕ2 in spatially structured populations, each consisting of two interconnected subpopulations evolving in the same or different nutrient media (homogeneous and heterogeneous environments, respectively). Counter to the normal expectation, host–parasite specialization was significantly lower in heterogeneous compared with homogeneous environments. This result could not be explained by dispersal homogenizing populations, as this would have resulted in the heterogeneous treatments having levels of specialization equal to or greater than that of the homogeneous environments. We argue that selection for costly generalists is greatest when the coevolving species are exposed to diverse environmental conditions and that this can provide an explanation for our results. A simple coevolutionary model of this process suggests that this can be a general mechanism by which environmental heterogeneity can reduce rather than increase host–parasite specialization

Integrating social behaviour, demography and disease dynamics in network models: applications to disease management in declining wildlife populations

This is the final version. Available on open access from the Royal Society via the DOI in this record.The emergence and spread of infections can contribute to the decline and extinction of populations, particularly in conjunction with anthropogenic environmental change. The importance of heterogeneity in processes of transmission, resistance and tolerance is increasingly well understood in theory, but empirical studies that consider both the demographic and behavioural implications of infection are scarce. Non-random mixing of host individuals can impact the demographic thresholds that determine the amplification or attenuation of disease prevalence. Risk assessment and management of disease in threatened wildlife populations must therefore consider not just host density, but also the social structure of host populations. Here we integrate the most recent developments in epidemiological research from a demographic and social network perspective and synthesise the latest developments in social network modelling for wildlife disease, to explore their applications to disease management in populations in decline and at risk of extinction. We use simulated examples to support our key points and reveal how disease-management strategies can and should exploit both behavioural and demographic information to prevent or control the spread of disease. Our synthesis highlights the importance of considering the combined impacts of demographic and behavioural processes in epidemics to successful disease management in a conservation context.Natural Environment Research Council (NERC)Animal and Plant Health AgencyUniversity of Exete

Host-parasite fluctuating selection in the absence of specificity

Fluctuating selection driven by coevolution between hosts and parasites is important for the generation of host and parasite diversity across space and time. Theory has focused primarily on infection genetics, with highly specific ‘matching allele’ frameworks more likely to generate fluctuating selection dynamics (FSD) than ‘gene-for-gene’ (generalist-specialist) frameworks. However, the environment, ecological feedbacks, and life-history characteristics may all play a role in determining when FSD occurs. Here, we develop eco- evolutionary models with explicit ecological dynamics to explore the ecological, epidemiological and host life-history drivers of FSD. Our key result is to demonstrate for the first time that specificity between hosts and parasites is not required to generate FSD. Furthermore, highly specific host-parasite interactions produce unstable, less robust stochastic fluctuations in contrast to interactions that lack specificity altogether or those that vary from generalist to specialist, which produce predictable limit cycles. Given the ubiquity of ecological feedbacks and the variation in the nature of specificity in host parasite interactions, our work emphasizes the underestimated potential for host- parasite coevolution to generate fluctuating selection

A Comparison of Miltefosine and Sodium Stibogluconate for Treatment of Visceral Leishmaniasis in an Ethiopian Population with High Prevalence of HIV Infection.

BACKGROUND: Antimonials are the mainstay of visceral leishmaniasis (VL) treatment in Africa. The increasing incidence of human immunodeficiency virus (HIV) coinfection requires alternative safe and effective drug regimens. Oral miltefosine has been proven to be safe and effective in the treatment of Indian VL but has not been studied in Africa or in persons with HIV and VL coinfection. METHODS: We compared the efficacy of miltefosine and sodium stibogluconate (SSG) in the treatment of VL in persons in Ethiopia. A total of 580 men with parasitologically and/or serologically confirmed VL were randomized to receive either oral miltefosine (100 mg per day for 28 days) or intramuscular SSG (20 mg/kg per day for 30 days). RESULTS: The initial cure rate was 88% in both treatment groups. Mortality during treatment was 2% in the miltefosine group, compared with 10% in the SSG group. Initial treatment failure was 8% in the miltefosine group, compared with 1% in the SSG group. Among the 375 patients (65%) who agreed to HIV testing, HIV seroprevalence was 29%. Among patients not infected with HIV, initial cure, mortality, and initial treatment failure rates were not significantly different (94% vs. 95%, 1% vs. 3%, and 5% vs. 1% for the miltefosine and SSG groups, respectively). Initial treatment failure with miltefosine occurred in 18% of HIV-coinfected patients, compared with treatment failure in 5% of non-HIV-infected patients. At 6 months after treatment, 174 (60%) of the 290 miltefosine recipients and 189 (65%) of the 290 SSG recipients experienced cure; 30 (10%) of 290 in the miltefosine group and 7 (2%) of 290 in the SSG group experienced relapse, and the mortality rate was 6% in the miltefosine group, compared with 12% in the SSG group. HIV-infected patients had higher rates of relapse (16 [25%] of 63 patients), compared with non-HIV-infected patients (5 [5%] of 131). CONCLUSIONS: Treatment with miltefosine is equally effective as standard SSG treatment in non-HIV-infected men with VL. Among HIV-coinfected patients, miltefosine is safer but less effective than SSG

A privileged intraphagocyte niche is responsible for disseminated infection ofStaphylococcus aureusin a zebrafish model

The innate immune system is the primary defence against the versatile pathogen, Staphylococcus aureus. How this organism is able to avoid immune killing and cause infections is poorly understood. Using an established larval zebrafish infection model, we have shown that overwhelming infection is due to subversion of phagocytes by staphylococci, allowing bacteria to evade killing and found foci of disease. Larval zebrafish coinfected with two S. aureus strains carrying different fluorescent reporter gene fusions (but otherwise isogenic) had bacterial lesions, at the time of host death, containing predominantly one strain. Quantitative data using two marked strains revealed that the strain ratios, during overwhelming infection, were often skewed towards the extremes, with one strain predominating. Infection with passaged bacterial clones revealed the phenomenon not to be due to adventitious mutations acquired by the pathogen. After infection of the host, all bacteria are internalized by phagocytes and the skewing of population ratios is absolutely dependent on the presence of phagocytes. Mathematical modelling of pathogen population dynamics revealed the data patterns are consistent with the hypothesis that a small number of infected phagocytes serve as an intracellular reservoir for S. aureus, which upon release leads to disseminated infection. Strategies to specifically alter neutrophil/macrophage numbers were used to map the potential subpopulation of phagocytes acting as a pathogen reservoir, revealing neutrophils as the likely ‘niche’. Subsequently in a murine sepsis model, S. aureus abscesses in kidneys were also found to be predominantly clonal, therefore likely founded by an individual cell, suggesting a potential mechanism analogous to the zebrafish model with few protected niches. These findings add credence to the argument that S. aureus control regimes should recognize both the intracellular as well as extracellular facets of the S. aureus life cycle

Coexistence of hexatic and isotropic phases in two-dimensional Yukawa systems

We have performed Brownian dynamics simulations on melting of two-dimensional colloidal crystal in which particles interact with Yukawa potential. The pair correlation function and bond-orientational correlation function was calculated in the Yukawa system. An algebraic decay of the bond orientational correlation function was observed. By ruling out the coexistence region, only a unstable hexatic phase was found in the Yukawa systems. But our work shows that the melting of the Yukawa systems is a two-stage melting not consist with the KTHNY theory and the isotropic liquid and the hexatic phase coexistence region was found. Also we have studied point defects in two-dimensional Yukawa systems.Comment: 9 pages, 8 figures. any comments are welcom