Sarcocystosis

Sarcocystis infections of animals are commonplace and of worldwide distribution. Some species can be severely pathogenic to farm animals, causing anorexia, weight-loss, abortion and even death. But perhaps because sarcocysts are so common they have frequently been regarded as innocuous. Even in the USA and UK, many cases of abortion in farm animals go undiagnosed, and it is only now that sarcocystosis is being implicated as potentially of economic importance to the farm industry. In many cases however, the major effect is likely to be subclinical, seen in farm animals only as a reduction in liveweight gain. As this review shows, the history of research on Sarcocystis has been marked by confusion and neglect, although enormous progress has been made in the last decade. But until their economic importance is fully recognized, these widespread infections seem likely to continue unchallenged.     

State of the art and challenges in sequence based T-cell epitope prediction

Sequence based T-cell epitope predictions have improved immensely in the last decade. From predictions of peptide binding to major histocompatibility complex molecules with moderate accuracy, limited allele coverage, and no good estimates of the other events in the antigen-processing pathway, the field has evolved significantly. Methods have now been developed that produce highly accurate binding predictions for many alleles and integrate both proteasomal cleavage and transport events. Moreover have so-called pan-specific methods been developed, which allow for prediction of peptide binding to MHC alleles characterized by limited or no peptide binding data. Most of the developed methods are publicly available, and have proven to be very useful as a shortcut in epitope discovery. Here, we will go through some of the history of sequence-based predictions of helper as well as cytotoxic T cell epitopes. We will focus on some of the most accurate methods and their basic background.     

Virulence and community dynamics of fungal species with vertical and horizontal transmission on a plant with multiple infections

The virulence evolution of multiple infections of parasites from the same species has been modeled widely in evolution theory. However, experimental studies on this topic remain scarce, particularly regarding multiple infections by different parasite species. Here, we characterized the virulence and community dynamics of fungal pathogens on the invasive plant Ageratina adenophora to verify the predictions made by the model. We observed that A. adenophora was highly susceptible to diverse foliar pathogens with mixed vertical and horizontal transmission within leaf spots. The transmission mode mainly determined the pathogen community structure at the leaf spot level. Over time, the pathogen community within a leaf spot showed decreased Shannon diversity; moreover, the vertically transmitted pathogens exhibited decreased virulence to the host A. adenophora, but the horizontally transmitted pathogens exhibited increased virulence to the host. Our results demonstrate that the predictions of classical models for the virulence evolution of multiple infections are still valid in a complex realistic environment and highlight the impact of transmission mode on disease epidemics of foliar fungal pathogens. We also propose that seedborne fungi play an important role in structuring the foliar pathogen community from multiple infections within a leaf spot.     

Theoretical models of adaptive energy management in small wintering birds

Many small passerines are resident in forests with very cold winters. Considering their size and the adverse conditions, this is a remarkable feat that requires optimal energy management in several respects, for example regulation of body fat reserves, food hoarding and night-time hypothermia. Besides their beneficial effect on survival, these behaviours also entail various costs. The scenario is complex with many potentially important factors, and this has made 'the little bird in winter' a popular topic for theoretic modellers. Many predictions could have been made intuitively, but models have been especially important when many factors interact. Predictions that hardly could have been made without models include: (i) the minimum mortality occurs at the fat level where the marginal values of starvation risk and predation risk are equal; (ii) starvation risk may also decrease when food requirement increases; (iii) mortality from starvation may correlate positively with fat reserves; (iv) the existence of food stores can increase fitness substantially even if the food is not eaten; (v) environmental changes may induce increases or decreases in the level of reserves depending on whether changes are temporary or permanent; and (vi) hoarding can also evolve under seemingly group-selectionistic conditions.     

The contribution of vaccination to global health: past,present and future

Vaccination has made an enormous contribution to global health. Two major infections, smallpox and rinderpest, have been eradicated. Global coverage of vaccination against many important infectious diseases of childhood has been enhanced dramatically since the creation of WHO''s Expanded Programme of Immunization in 1974 and of the Global Alliance for Vaccination and Immunization in 2000. Polio has almost been eradicated and success in controlling measles makes this infection another potential target for eradication. Despite these successes, approximately 6.6 million children still die each year and about a half of these deaths are caused by infections, including pneumonia and diarrhoea, which could be prevented by vaccination. Enhanced deployment of recently developed pneumococcal conjugate and rotavirus vaccines should, therefore, result in a further decline in childhood mortality. Development of vaccines against more complex infections, such as malaria, tuberculosis and HIV, has been challenging and achievements so far have been modest. Final success against these infections may require combination vaccinations, each component stimulating a different arm of the immune system. In the longer term, vaccines are likely to be used to prevent or modulate the course of some non-infectious diseases. Progress has already been made with therapeutic cancer vaccines and future potential targets include addiction, diabetes, hypertension and Alzheimer''s disease.     

Estimation of population at risk of infection and number of cases of Leishmaniasis

In this paper, Dick Ashford, Philippe Desjeux and Peter deRaadt attempt to estimate the total number of people at risk of acquiring disease caused by infection with Leishmania spp. In many areas a very small risk is distributed among large numbers of people so, although the number of people at risk may be large, the number of infections may be very small. An estimate of the global annual incidence of new cases has also been made. This refers to reported clinical disease and probably grossly underestimates the number of infections. The methods by which the estimates have been made are specified so that they, as well as the estimates themselves, may be criticized and modified with some degree of objectivity.     

Multiple infections and the evolution of virulence

Infections that consist of multiple parasite strains or species are common in the wild and are a major public health concern. Theory suggests that these infections have a key influence on the evolution of infectious diseases and, more specifically, on virulence evolution. However, we still lack an overall vision of the empirical support for these predictions. We argue that within‐host interactions between parasites largely determine how virulence evolves and that experimental data support model predictions. Then, we explore the main limitation of the experimental study of such ‘mixed infections’, which is that it draws conclusions on evolutionary outcomes from studies conducted at the individual level. We also discuss differences between coinfections caused by different strains of the same species or by different species. Overall, we argue that it is possible to make sense out of the complexity inherent to multiple infections and that experimental evolution settings may provide the best opportunity to further our understanding of virulence evolution.     

Towards an ecology of protective coloration

The strategies underlying different forms of protective coloration are well understood but little attention has been paid to the ecological, life-history and behavioural circumstances under which they evolve. While some comparative studies have investigated the ecological correlates of aposematism, and background matching, the latter particularly in mammals, few have examined the ecological correlates of other types of protective coloration. Here, we first outline which types of defensive coloration strategies may be exhibited by the same individual; concluding that many protective coloration mechanisms can be employed simultaneously, particularly in conjunction with background matching. Second, we review the ecological predictions that have been made for each sort of protective coloration mechanism before systematically surveying phylogenetically controlled comparative studies linking ecological and social variables to antipredator defences that involve coloration. We find that some a priori predictions based on small-scale empirical studies and logical arguments are indeed supported by comparative data, especially in relation to how illumination affects both background matching and self-shadow concealment through countershading; how body size is associated with countershading, motion dazzle, flash coloration and aposematism, although only in selected taxa; how immobility may promote background matching in ambush predators; and how mobility may facilitate motion dazzle. Examination of nearly 120 comparative tests reveals that many focus on ecological variables that have little to do with predictions derived from antipredator defence theory, and that broad-scale ecological studies of defence strategies that incorporate phylogenetics are still very much in their infancy. We close by making recommendations for future evolutionary ecological research.     

Antiparasitic antibiotics from Japan

Antibiotics are microbial secondary metabolites and they are important for the treatment of infectious diseases. Japanese researchers have made a large contribution to studies of antibiotics, and they have also been important in the discovery of antiparasitic antibiotics. Satoshi Ōmura received the Nobel Prize in 2015 for the “discoveries concerning a novel therapy against infections caused by roundworm parasites”, which means discovery of a new nematocidal antibiotic, avermectin. Here, I review the many antiparasitic antibiotics and their lead compounds that have been discovered for use in human and veterinary medicine.     

Fourth expansion and glucose perturbation of the Dictyostelium kinetic model

The kinetic model of carbohydrate metabolism has been expanded to include: (a) the accumulation of alpha and beta-cellulose, insoluble cell-wall glycogen and mucopolysaccharide; (b) the role of RNA turnover as a source of carbon for end-product synthesis and as a buffer regulating the level of uridine nucleotides in this metabolic network; and (c) the role of purine-nucleoside phosphorylase, 5'-AMP nucleotidase, nucleosidediphosphate kinase and polynucleotide phosphorylase. One of many predictions based on this model is that cells differentiating in the presence of glucose will produce sorocarps with an abnormally high trehalose to cellulose ratio. External perturbation of either the model or of developing cells by glucose increases the levels of sorocarp trehalose and glycogen, 5-fold and 6-fold respectively. Evaluation of the experimental data and the simulation analyses have allowed several predictions to be made concerning the compartmentation of metabolites and the permeability of cells to glucose during differentiation.     

A theoretical investigation of the effect of predators on foraging behaviour and energy reserves

Data show that when small birds are exposed to a model of a predator, their body mass may either increase or decrease. Although attempts have been made to explain the data using previous models, these models are based on a constant level of predation and hence are not appropriate for making predictions about the response of a bird to the sight of a predator. We have developed a novel model that includes encounters between a bird and potential predators. We show that, depending on the biology of the predator, optimal body mass may either increase or decrease. The model also makes predictions about the foraging behaviour of the bird after it has seen a predator.     

New understanding of the group A Streptococcus pathogenesis cycle

Group A Streptococcus (GAS) has long been recognized as a human pathogen causing an exceptionally broad range of infections. Despite intense research, however, the molecular mechanisms of GAS disease remain unclear. Recently, many important discoveries have been made that shed light on GAS pathogenesis and open exciting avenues for future research. Advances in genome sequencing, microarray technology and proteomic analysis, in combination with the development of more suitable animal models, have markedly increased our knowledge of the mechanisms underlying GAS pathogenesis. The information gained from these studies will translate into improved diagnostics and new targets for therapeutic drugs and vaccines.     

Epidemic predictions in an imperfect world: modelling disease spread with partial data

‘Big-data’ epidemic models are being increasingly used to influence government policy to help with control and eradication of infectious diseases. In the case of livestock, detailed movement records have been used to parametrize realistic transmission models. While livestock movement data are readily available in the UK and other countries in the EU, in many countries around the world, such detailed data are not available. By using a comprehensive database of the UK cattle trade network, we implement various sampling strategies to determine the quantity of network data required to give accurate epidemiological predictions. It is found that by targeting nodes with the highest number of movements, accurate predictions on the size and spatial spread of epidemics can be made. This work has implications for countries such as the USA, where access to data is limited, and developing countries that may lack the resources to collect a full dataset on livestock movements.     

Genic capture and resolving the lek paradox

The genic capture hypothesis offers a resolution to the question of how genetic variation in male sexually selected traits is maintained in the face of strong female preferences. The hypothesis is that male display traits are costly to produce and hence depend upon overall condition, which itself is dependent upon genes at many loci. Few attempts have been made to test the assumptions and predictions of the genic capture hypothesis rigorously and, in particular, little attention has been paid to determining the genetic basis of condition. Such tests are crucial to our understanding of the maintenance of genetic variation and in the evaluation of recent models that propose a role for sexual selection in the maintenance of sex. Here, we review approaches to testing the link between genetically determined condition and levels of sexual trait expression and consider the probable importance of deleterious mutations.     

Effects of parasites on fish behaviour: a review and evolutionary perspective

Fish serve as hosts to a range of parasites that are taxonomically diverse and that exhibit a wide variety of life cycle strategies. Whereas many of these parasites are passed directly between ultimate hosts, others need to navigate through a series of intermediate hosts before reaching a host in (or on) which they can attain sexual maturity. The realisation that parasites need not have evolved to minimise their impact on hosts to be successful, and in many cases may even have a requirement for their hosts to be eaten by specific predators to ensure transmission, has renewed interest in the evolutionary basis of infection-associated host behaviour. Fishes have proved popular models for the experimental examination of such hypotheses, and parasitic infections have been demonstrated to have consequences for almost every aspect of fish behaviour. Despite a scarcity of knowledge regarding the mechanistic basis of such behaviour changes in most cases, and an even lower understanding of their ecological consequences, there can be little doubt that infection-associated behaviour changes have the potential to impact severely on the ecology of infected fishes. Changes in foraging efficiency, time budget, habitat selection, competitive ability, predator-prey relationships, swimming performance and sexual behaviour and mate choice have all been associated with – and in some cases been shown to be a result of – parasite infections, and are reviewed here in some detail. Since the behavioural consequences of infections are exposed to evolutionary selection pressures in the same way as are other phenotypic traits, few behavioural changes will be evolutionarily neutral and host behaviour changes that facilitate transmission should be expected. Despite this expectation, we have found little conclusive evidence for the Parasite Increased Trophic Transmission (PITT) hypothesis in fishes, though recent studies suggest it is likely to be an important mechanism. Additionally, since the fitness consequences of the many behavioural changes described have rarely been quantified, their evolutionary and ecological significance is effectively unknown.Potential hosts may also change their behaviour in the presence of infective parasite stages, if they adopt tactics to reduce exposure risk. Such `behavioural resistance', which may take the form of habitat avoidance, prey selectivity or avoidance of infected individuals, can be viewed as behavioural change associated with the threat of being parasitised, and so is included here. Actually harbouring infections may also stimulate fishes to perform certain types of simple or complex behaviours aimed at removing parasites, such as substrate scraping or the visitation of cleaning stations, although the efficacy of the latter as a parasite removal strategy is currently subject to a good deal of debate.The effects parasites have on shoaling behaviour of host fish have attracted a good deal of attention from researchers, and we have provided a case study to summarise the current state of knowledge. Parasites have been shown to affect most of the antipredator effects of shoaling (such as vigilance, co-ordinated evasion and predator confusion) and can also impair an individual's foraging ability. It therefore seems unsurprising that, in a number of species avoidance of parasitised individuals has evolved which may explain the occurrence of parasite-assorted shoals in the field. Parasitised fish are found more often in peripheral shoal positions and show a reduced tendency for shoaling in some fish species. Given the array of host behaviours that may be changed, the fitness consequences of shoal membership for parasitised hosts and their parasites are not always easy to predict, yet an understanding of these is important before we can make predictions regarding the ecological impact of infections on host fish populations.Clearly, there remain many gaps in our knowledge regarding the effects of parasites on the behaviour of host fish. We believe that a much greater understanding of the importance of infection-associated behaviour changes in fish could be gained from high quality research in comparatively few areas. We have completed our review by highlighting the key research topics that we believe should attract new research in this field.     

Molecular genetics and pathogenesis of Clostridium perfringens.

Clostridium perfringens is the causative agent of a number of human diseases, such as gas gangrene and food poisoning, and many diseases of animals. Recently significant advances have been made in the development of C. perfringens genetics. Studies on bacteriocin plasmids and conjugative R plasmids have led to the cloning and analysis of many C. perfringens genes and the construction of shuttle plasmids. The relationship of antibiotic resistance genes to similar genes from other bacteria has been elucidated. A detailed physical map of the C. perfringens chromosome has been prepared, and numerous genes have been located on that map. Reproducible transformation methods for the introduction of plasmids into C. perfringens have been developed, and several genes coding for the production of extracellular toxins and enzymes have been cloned. Now that it is possible to freely move genetic information back and forth between C. perfringens and Escherichia coli, it will be possible to apply modern molecular methods to studies on the pathogenesis of C. perfringens infections.     

Why Was the 2009 Influenza Pandemic in England So Small?

The "Swine flu" pandemic of 2009 caused world-wide infections and deaths. Early efforts to understand its rate of spread were used to predict the probable future number of cases, but by the end of 2009 it was clear that these predictions had substantially overestimated the pandemic's eventual impact. In England, the Health Protection Agency made announcements of the number of cases of disease, which turned out to be surprisingly low for an influenza pandemic. The agency also carried out a serological survey half-way through the English epidemic. In this study, we use a mathematical model to reconcile early estimates of the rate of spread of infection, weekly data on the number of cases in the 2009 epidemic in England and the serological status of the English population at the end of the first pandemic wave. Our results reveal that if there are around 19 infections (i.e., seroconverters) for every reported case then the three data-sets are entirely consistent with each other. We go on to discuss when in the epidemic such a high ratio of seroconverters to cases of disease might have been detected, either through patterns in the case reports or through even earlier serological surveys.     

Deciphering the timescales and mechanisms of protein folding using minimal off-lattice models.

Considerable insights into the mechanisms and timescales of protein folding have been obtained from detailed studies of minimal off-lattice models. These models are coarse-grained representations of polypeptide chains. Many novel predictions of the mechanisms and timescales of the folding of proteins have been made using simulations of off-lattice models. The concepts derived from these simulations have been used to analyze the recent experiments and simulations of proteins and peptides.