A model of Taura syndrome virus (TSV) epidemics in Litopenaeus vannamei

Taura syndrome virus (TSV) is a highly virulent pathogen of Litopenaeus vannamei, has affected shrimp aquaculture throughout the world, and threatens wild populations. Despite its importance, little work has been done on the pathogen's formal epidemiology. Therefore we developed a compartment model for epidemics of TSV in closed populations of L. vannamei. The model includes five compartments, uninfected susceptible, prepatently infected, acutely infected, chronically infected, and dead infected shrimp. The transmission coefficients, patency coefficient, virulence coefficients, and removal coefficient (disappearance of dead infected shrimp) control the dynamics of the model. We estimated the coefficients in laboratory studies and inserted the estimates in the model to characterize TSV epidemics and to estimate the basic reproduction ratio R(0) and threshold density for TSV epidemics in L. vannamei. Further we examined through computer simulation the effect of varying the coefficients on R(0). Decreases in transmission decrease R(0), decreases in virulence increase R(0), increases in patency do not affect R(0), and increases in recovery most likely increase R(0) but under some conditions might decrease it.     

Seasonal dynamics and thresholds governing recurrent epidemics

Driven by seasonality, many common recurrent infectious diseases are characterized by strong annual, biennial and sometimes irregular oscillations in the absence of vaccination programs. Using the seasonally forced SIR epidemic model, we are able to provide new insights into the dynamics of recurrent diseases and, in some cases, specific predictions about individual outbreaks. The analysis reveals a new threshold effect that gives clear conditions for the triggering of future disease outbreaks or their absence. The threshold depends critically on the susceptibility S ₀ of the population after an outbreak. We show that in the presence of seasonality, forecasts based on the susceptibility S ₀ are more reliable than those based on the classical reproductive number R ₀ from the conventional theory.      

Comparing methods to quantify experimental transmission of infectious agents

Transmission of an infectious agent can be quantified from experimental data using the transient-state (TS) algorithm. The TS algorithm is based on the stochastic SIR model and provides a time-dependent probability distribution over the number of infected individuals during an epidemic, with no need for the experiment to end in final-size (e.g., where no more infections can occur). Because of numerical limitations, the application of the TS algorithm is limited to populations with only a few individuals. We investigated the error of using the easily applicable, time-independent final-size (FS) algorithm knowing that the FS situation was not reached. We conclude that the methods based on the FS algorithm: (i) underestimate R(0), (ii) are liberal when testing H(0):R(0)1 against H(1):R(0)<1, (iii) are conservative when testing H(0):R(0)1 against H(1):R(0)>1, and (iv) are conservative when testing H(0):R(control)=R(treatment) against H(1):R(control)>R(treatment). Furthermore, a new method is presented to find a difference in transmission between two treatment groups (MaxDiff test). The MaxDiff test is compared to tests based on FS and TS algorithms. The TS test and the MaxDiff test were most powerful (approximately equally powerful) in finding a difference, whereas the FS test was less powerful (especially, when both R(control) and R(treatment) are >1).     

Notions of synergy for combinations of interventions against infectious diseases in heterogeneously mixing populations

In public health programmes interventions are frequently combined with hoped for ‘synergies’ [22]. However, there is not yet a precise definition for synergy between interventions that captures the idea that there is added benefit at the population-level in using them together. To explore the synergy between interventions in the context of endemic disease, we consider a general model of infection spread in a heterogeneously mixing population. We consider interventions which may alter individuals’ infectiousness, susceptibility, profile of infectiousness through time and survival while infected. Allowing general patterns of overlap and targeting in those receiving the interventions, we show how to compute changes to epidemiological indices such as R₀, and introduce a simple technique for calculating equilibrium prevalences and incidences via an iterated map. We argue for a particular definition of synergy and investigate its behaviour, both analytically and numerically, concluding that it is easiest to achieve synergy between interventions which perform poorly in isolation; implementation strategies that minimize the overlap of different interventions in the population tend to achieve more synergy; and that in populations with heterogeneous risk, interventions that are redundant when universally targeted can regain substantial synergy when applied in a targeted manner.     

Semi-stochastic models for Salmonella infection within finishing pig units in the UK

A multi-group semi-stochastic model is formulated to describe Salmonella   dynamics on a pig herd within the UK and assess whether farm structure has any effect on the dynamics. The models include both direct transmission and indirect (via free-living infectious units in the environment and airborne infection). The basic reproduction number _R0$R_0$ is also investigated. The models estimate approximately 24.6% and 25.4% of pigs at slaughter weight will be infected with Salmonella within a slatted-floored and solid-floored unit respectively, which corresponds to values found in previous abattoir and farm studies, suggesting that the model has reasonable validity. Analysis of the models identified the shedding rate to be of particular importance in the control of Salmonella   spread, a finding also evident in an increase in the _R0$R_0$ value.     

Estimation and inference of R0 of an infectious pathogen by a removal method

The basic reproductive ratio, R0, is a central quantity in the investigation and management of infectious pathogens. The standard model for describing stochastic epidemics is the continuous time epidemic birth-and-death process. The incidence data used to fit this model tend to be collected in discrete units (days, weeks, etc.), which makes model fitting, and estimation of R0 difficult. Discrete time epidemic models better match the time scale of data collection but make simplistic assumptions about the stochastic epidemic process. By investigating the nature of the assumptions of a discrete time epidemic model, we derive a bias corrected maximum likelihood estimate of R0 based on the chain binomial model. The resulting 'removal' estimators provide estimates of R0 and the initial susceptible population size from time series of infectious case counts. We illustrate the performance of the estimators on both simulated data and real epidemics. Lastly, we discuss methods to address data collected with observation error.     

Explaining the geographical origins of seasonal influenza A (H3N2)

Most antigenically novel and evolutionarily successful strains of seasonal influenza A (H3N2) originate in East, South and Southeast Asia. To understand this pattern, we simulated the ecological and evolutionary dynamics of influenza in a host metapopulation representing the temperate north, tropics and temperate south. Although seasonality and air traffic are frequently used to explain global migratory patterns of influenza, we find that other factors may have a comparable or greater impact. Notably, a region''s basic reproductive number (R₀) strongly affects the antigenic evolution of its viral population and the probability that its strains will spread and fix globally: a 17–28% higher R₀ in one region can explain the observed patterns. Seasonality, in contrast, increases the probability that a tropical (less seasonal) population will export evolutionarily successful strains but alone does not predict that these strains will be antigenically advanced. The relative sizes of different host populations, their birth and death rates, and the region in which H3N2 first appears affect influenza''s phylogeography in different but relatively minor ways. These results suggest general principles that dictate the spatial dynamics of antigenically evolving pathogens and offer predictions for how changes in human ecology might affect influenza evolution.     

A theoretical framework for biological control of soil-borne plant pathogens: Identifying effective strategies

We develop and analyse a flexible compartmental model of the interaction between a plant host, a soil-borne pathogen and a microbial antagonist, for use in optimising biological control. By extracting invasion and persistence thresholds of host, pathogen and biological control agent, performing an equilibrium analysis, and numerical investigation of sensitivity to parameters and initial conditions, we determine criteria for successful biological control. We identify conditions for biological control (i) to prevent a pathogen entering a system, (ii) to eradicate a pathogen that is already present and, if that is not possible, (iii) to reduce the density of the pathogen. Control depends upon the epidemiology of the pathogen and how efficiently the antagonist can colonise particular habitats (i.e. healthy tissue, infected tissue and/or soil-borne inoculum). A sharp transition between totally effective control (i.e. eradication of the pathogen) and totally ineffective control can follow slight changes in biologically interpretable parameters or to the initial amounts of pathogen and biological control agent present. Effective biological control requires careful matching of antagonists to pathosystems. For preventative/eradicative control, antagonists must colonise susceptible hosts. However, for reduction in disease prevalence, the range of habitat is less important than the antagonist's bulking-up efficiency.     

Mathematical modelling of liver regeneration after intoxication with CCl(4)

Liver regeneration is a complex process, having evolved to protect animals from the consequences of liver loss caused by food toxins. In this study, we established a mathematical spatial-temporal model of the liver lobule regenerating after CCl(4) intoxication. The aim of modelling the regeneration process by matching experimental observations with those from a mathematical model is to gain a better understanding of the process and to recognize which parameters are relevant for specific phenomena. In order to set up a realistic minimal model, we first reconstructed a schematised liver lobule after determination of: (i) the mean number of hepatocytes between the central vein and the periphery of the lobule, (ii) the mean size of the hepatocytes and (iii) the mean number of hepatocyte columns in the inner, midzonal and peripheral ring of the lobule. In a next step, we determined the time course of cell death and BrdU incorporation after intoxication of male Sprague Dawley rats with CCl(4), thereby differentiating between inner, midzonal and peripheral hepatocytes. These parameters were used to construct a model. The basic unit of this model is the individual cell. The detailed behaviour of the cells is studied, controlled by the model parameters: (1) probability of cell division at defined positions of the lobule at a given time, (2) "coordinated cell orientation", i.e., the ability of the cells to align during the regeneration process into columns towards the central vein of a liver lobule, (3) cell cycle duration, (4) the migration activity and (5) the polarity of the hepatocytes resulting in polar cell-cell adhesion between them. In a schematised lobule, the model shows that CCl(4) initially induced cell death of a pericentral ring of hepatocytes, followed by a wave of proliferation that starts in the surviving hepatocytes next to the inner ring of dead cells and continues to the peripheral hepatocytes, finally restoring the characteristic micro-architecture of the lobule in a 7-day process. This model was used to systematically analyze the influence of parameters 1-5. Interestingly, coordinated cell orientation and cell polarity were identified to be the most critical parameters. Elimination led to destruction of the characteristic micro-architecture of the lobule and to a high degree of disorder characterized by hexagonal cell structures. Our model suggests that the ability of hepatocytes to realign after cell division by a process of coordinated cell orientation (model parameter 2) in combination with cell polarity (model parameter 5) may be at least as critical as hepatocyte proliferation (model parameter 1) itself.     

Two groups of entomopathogenic bacteria, Photorhabdus and Xenorhabdus, share an inhibitory action against phospholipase A2 to induce host immunodepression

Photorhabdus and Xenorhabdus are two genera of entomopathogenic bacteria having a mutualistic relationship with their respective nematode hosts, Heterorhabditis and Steinernema. One of the pathogenic mechanisms of these bacteria includes host immunodepression, which leads to lethal septicemia. It has been known that X. nematophila inhibits phospholipase A2 (PLA2) to induce host immunodepression. Here, we tested the hypothesis of PLA2 inhibition using another bacterial species involved in other genera. P. temperata subsp. temperata is the intestinal symbiont of an entomopathogenic nematode, H. megidis. The bacteria caused potent pathogenicity in a dose-dependent manner against the fifth instar larvae of a test target insect, Spodoptera exigua, as early as 24 h after the intra-hemocoelic injection. In response to the live bacterial injection, hemocyte nodulation (a cellular immune response) and prophenoloxidase (pPO) activation were inhibited, while the injection of heat-killed bacteria significantly induced both immune reactions. The immunodepression induced by the live bacteria was reversed by the addition of arachidonic acid, the catalytic product of phospholipase A2. In contrast, the addition of dexamethasone, a specific PLA2 inhibitor to the heat-killed bacterial treatment, inhibited both immune capacities. In addition to a previously known PLA2 inhibitory action of X. nematophila, the inhibition of P. temperata temperata on PLA2 suggests that bacteria symbiotic to entomopathogenic nematodes share a common pathogenic target to result in an immunodepressive state of the infected insects. To prove this generalized hypothesis, we used other bacterial species (X. bovienni, X. poinarii, and P. luminescens) involved in these two genera. All our experiments clearly showed that these other bacteria also share their inhibitory action against PLA2 to induce host immunodepression.     

Light- and seasonal-induced plasticity in leaf morphology, N partitioning and photosynthetic capacity of two temperate deciduous species

Processes involved in leaf photosynthetic acclimation to light and throughout the growing season were investigated in two hardwood species (Acer saccharum and Betula alleghaniensis), which differed in their level of shade-tolerance. For both species, variation in traits related to (i) leaf morphology (LMA, leaf mass:area ratio), (ii) leaf N content (N_A, leaf nitrogen content on an area basis and N_M, N concentration in leaf dry mass), (iii) leaf N partitioning among photosynthetic functions (P_r, N allocated to Rubisco, and P_b, N allocated to bioenergetics), and (iv) leaf photosynthetic capacity (V_cmax, maximal carboxylation rates, and J_max, maximal light-driven electron flow) were assessed at three different times during the growing season (early, mid- and late summer) and under four contrasting light regimes (40, 17, 6 and 2% of full sunlight). For both species, light-driven variation in most traits was greater than their seasonally driven variation. Furthermore, results showed for both species the pre-eminence of LMA changes in the light-driven acclimation of N_A. Importance of N_M to variation in N_A was restricted to seasonal acclimation, especially for the less shade-tolerant species, B. alleghaniensis. Similarly, for both species, light-driven acclimation of leaf photosynthetic capacities was tightly related to variation in N_A, which was related to LMA changes. However, variation in P_r and P_b better explained seasonally driven variation in V_cmax and J_max, specifically under lower light levels, where N_A was low. Thus, the great variability observed for leaf activity in response to contrasting light environments was related to efficient morphological adjustments, regardless of species level of shade-tolerance. Finally, physiological adjustments were mainly involved in fine-scale changes observed during seasonally driven acclimation of leaves, when LMA was constrained to a slight range of variation.     

Bond-valence sums for Tc-O systems from EXAFS data

Literature data for structures containing exclusively Tc-O bonds were used to calculate unit-valence parameters R₀ for Tc(VII), Tc(VI), Tc(V) (five-coordinate), Tc(V) (six-coordinate), Tc(IV) and Tc(III) as 1.909, 1.955, 1.870, 1.859, 1.841 and 1.768 Å, respectively. A second method of estimating R₀ was developed to validate the calculated values for these oxidation states because crystallographic data are limited. The method was first tested and shown to be valid using literature data for Cr, Mn, Fe and Co complexes. The validated R₀ values for Tc were used to calculate bond-valence sums (BVS) for Tc solids and aqueous solutions using EXAFS data for the bond distances and coordination numbers. The calculated BVS showed good agreement with the expected values for the assumed Tc oxidation states.     

Selection of a highly virulent fungal isolate, Metarhizium anisopliae CLO 53, for controlling Hoplia philanthus

The June beetle, Hoplia philanthus Füessly (Coleoptera: Scarabaeidae), has become a widespread and destructive insect pest of lawns, sport turf, pastures, and horticultural crops in Belgium. The virulence of 34 entomopathogenic fungal isolates from the genera Metarhizium, Beauveria, and Paecilomyces to third-instar H. philanthus was tested in bioassays by dipping larvae in 10(7)conidia/ml suspensions. Two isolates of Metarhizium anisopliae (CLO 53 and CLO 54) caused maximally 90% mortality 10 weeks post-inoculation while other isolates only caused mortalities between 10 and 62%. The virulence of M. anisopliae CLO 53 was further tested by exposing H. philanthus larvae to conidial serial concentrations of 10(4)-10(9)conidia/g sandy soil for up to 11 weeks at 15, 20 or 25 degrees C. Mortality was dependant on the fungal concentration, exposure time, and temperature. Eleven weeks after inoculation, the LC50 values for this isolate ranged from 1.3 to 4.0 x 10(6), 1.0 to 3.2 x 10(5), and 2.5 x 10(4) to 10(5)conidia/g soil at 15, 20, and 25 degrees C, respectively. The LT50 values for this isolate ranged from 3.5 to 21.7, 2.4 to 18.7, and 2.9 to 16.1 weeks at concentrations of 10(9) and 10(4)conidia/g soil at 15, 20, and 25 degrees C, respectively. In glasshouse pot experiment with perennial ryegrass (Lolium perenne L.), the isolate CLO 53 caused mortalities of 50 and 88% of H. philanthus larvae 10 weeks after application of 10(4) and 10(6)conidia/cm(2) soil surface, respectively. The present results suggest that the Belgian isolate CLO 53 has excellent potential for biological control of H. philanthus.     

Mathematical modelling and assessment of the pH homeostasis mechanisms in Aspergillus niger while in citric acid producing conditions

In this work we introduce an extended model of the Aspergillus niger metabolism while in citrate production conditions. The model includes many recent findings related to various transport processes. It now considers a new information about the fructose uptake system and the proton and amino acids carriers between cytoplasm and the external medium. It also accounts for recent information about both the malate-citrate antiport between mitochondria and cytoplasm and the dihydrogen citrate ion excretion symport with protons. Finally, the model also accounts for new information about the glycerol-3-phosphate shuttle and pH buffering systems. Provided with this updated representation and after having assessed its quality and dynamic behaviour, we were able to explain the observed pH homoeostasis found in A. niger while in citrate producing conditions. The model also serves to enhance our comprehension of the molecular mechanisms operating in order to keep homoeostasis of pH in A. niger and other fungi, bacteria and yeast of biotechnological relevance.     

北京城区夏、秋季节短期增温对月季暗呼吸及光合参数的影响

与光呼吸不同,光对植物叶片暗呼吸具有明显抑制作用。目前,植物叶片这一生理生态现象很少受到关注,但光抑制呼吸会导致叶片日间碳损失,对植物碳平衡有重要影响。利用Li-6400(Li-Cor,USA)光合仪模拟北京城区夏、秋季增温对月季(Rosa chinensis)叶片暗呼吸及光合参数的影响。结果表明:(1)短期增温处理显著提高了蒸腾速率(Tr),降低了胞间CO2浓度(Ci),夏季增温时气孔导度(Gs)降低而秋季增温明显升高。(2)夏季增温5℃,有光暗呼吸(RL)显著高于增温2℃(P0.05),而增温2℃对RL影响不显著(P0.05);秋季增温5℃,RL显著高于增温3℃(P0.05)。4个不同短期增温处理都对无光暗呼吸(RD)影响显著(P0.05)。(3)秋季增温5℃对光抑制呼吸影响显著(P0.05);其它3个短期增温影响不显著(P0.05)。(4)秋季增温5℃,月季暗呼吸对增温敏感性显著高于增温3℃的值(P0.05)。目的为分析城市白昼气温上升导致植物叶片碳损失估计提供实验案例,是提高城市植物碳汇生态服务功能可能途径的基础。     

Interaction of media components during bioreactor sterilization: definition and importance of R0

Summary Sterilization of bioreactor media, to destroy viability of the indigenous microbial population, is normally accomplished by autoclaving, or heating with pressurized steam. However, simultaneous chemical changes in media can also be expected to result from the high temperatures. A kinetic procedure involving on-line computer calculation of heat input, designated asF ₀ values, was previously developed to estimate sterility achievement. A similar kinetic procedure, based on a general purpose Arrhenius pseudo rate equation and designated asR ₀ values, has now been designed to evaluate, and control the effects of temperature and heating time on chemical reactions occurring in the media. Data are presented indicating thatR ₀ may be a useful parameter for reducing variability in culture metabolism and scale-up when these variations result from different nutrient concentrations produced by non-standard heating during media sterilization in stirred bioreactors.     

The lethal and sub-lethal consequences of entomopathogenic nematode infestation and exposure for adult pine weevils, Hylobius abietis (Coleoptera: Curculionidae)

Entomopathogenic nematodes (EPN) frequently kill their host within 1-2 days, and interest in EPN focuses mainly on their lethality. However, insects may take longer to die, or may fail to die despite being infected, but little is known about the effects of EPN infection on insects, other than death. Here we investigate both lethal and sub-lethal effects of infection by two EPN species, Steinernema carpocapsae and Heterorhabditis downesi, on adults of the large pine weevil, Hylobius abietis. Following 12 h nematode-weevil contact in peat, S. carpocapsae killed a significantly higher proportion of weevils (87-93%) than H. downesi (43-57%) at all concentrations tested. Less than 10% of weevils were dead within 2 days, and weevils continued to die for up to 10 days after exposure (LT₅₀ of 3 days or more). In a separate experiment, live weevils dissected 6 days after a 24 h exposure to nematodes on filter paper harbored encapsulated and dead nematodes, showing that weevils could defend themselves against infection. Some live weevils also harbored live nematodes 6 days after they had been removed from the nematode infested medium. Feeding by weevils was not affected by infection with, or exposure to, either species of EPN. We discuss these results in relation to the use of EPN in biological control against H. abietis.     

Effects of temperature on fecundity in vitro, egg hatching and reproductive development of Benedenia seriolae and Zeuxapta seriolae (Monogenea) parasitic on yellowtail kingfish Seriola lalandi

Globally, aquaculture industries involved with commercial culture of kingfish (Seriola spp.) experience outbreaks of monogenean parasites, which can cause heavy stock losses. In Australia and New Zealand, aquaculturists of kingfish Seriola lalandi incur financial losses caused by two monogenean species: Benedenia seriolae and Zeuxapta seriolae which parasitise the skin and gills, respectively. This study provides information on some basic temperature-dependent life-cycle parameters of these problematic monogeneans on S. lalandi. Hatching times and age at maturity were inversely related to water temperature within the range experienced by wild kingfish in New Zealand (13-21 degrees C). Mature B. seriolae in vitro laid on average 37 eggs/day that hatched over approximately 4 days; peak hatching occurred 9, 11 and 22 days post-deposition at temperatures of 21, 17.5 and 13+/-1.0 degrees C, respectively. Z. seriolae in vitro laid on average 246 eggs/day that hatched over 2 days; peak hatching occurred 7, 9 and 15 days post-deposition at these respective temperatures. B. seriolae matured within 20, 25 and 48 days p.i. at 21, 18 and 13 degrees C. Z. seriolae matured within 25, 37 and >52 days p.i. at the same temperatures. This research describes stages in the reproductive development of B. seriolae and Z. seriolae and discusses the inclusion of basic parasitic life-cycle parameters into management strategies designed to maximise treatment efficacy and limit monogenean epizootics in sea-cage kingfish culture.     

Evidence for an increasing presence of Echinococcus multilocularis in foxes in The Netherlands

Echinococcus multilocularis, a tapeworm causing alveolar echinococcosis which is considered a serious zoonosis known to affect humans, appears to be expanding its geographical range in Europe. We studied the emergence of the parasite in the European westernmost edge of its geographical distribution, based on two consecutive parasitological examinations of red foxes (Vulpes vulpes) sampled between 1996 and 2003 in The Netherlands. The average worm count increased from 2.6 worms per fox in the first surveillance to 16.6 worms per fox in the second. Using a mathematical model for a spatially spreading parasite, we found a strong indication that the parasite population is increasing in number and is spreading northward at the speed of 2.7 km per year. The reproduction number (R0), reflecting the parasite's transmission process, is estimated from the surveillance data and it is likely to be more than 1 but not exceeding a value of 4. We analysed a parasite control strategy by estimating the critical fox density for parasite elimination. We conclude that E. multilocularis is an emerging parasite in The Netherlands and thus in the western part of Europe. Control will be very difficult given the current high fox population density.