Invasion and persistence of infectious agents in fragmented host populations

One of the important questions in understanding infectious diseases and their prevention and control is how infectious agents can invade and become endemic in a host population. A ubiquitous feature of natural populations is that they are spatially fragmented, resulting in relatively homogeneous local populations inhabiting patches connected by the migration of hosts. Such fragmented population structures are studied extensively with metapopulation models. Being able to define and calculate an indicator for the success of invasion and persistence of an infectious agent is essential for obtaining general qualitative insights into infection dynamics, for the comparison of prevention and control scenarios, and for quantitative insights into specific systems. For homogeneous populations, the basic reproduction ratio R(0) plays this role. For metapopulations, defining such an 'invasion indicator' is not straightforward. Some indicators have been defined for specific situations, e.g., the household reproduction number R*. However, these existing indicators often fail to account for host demography and especially host migration. Here we show how to calculate a more broadly applicable indicator R(m) for the invasion and persistence of infectious agents in a host metapopulation of equally connected patches, for a wide range of possible epidemiological models. A strong feature of our method is that it explicitly accounts for host demography and host migration. Using a simple compartmental system as an example, we illustrate how R(m) can be calculated and expressed in terms of the key determinants of epidemiological dynamics.     

Patterns of genetic variation in populations of infectious agents

Background  

The analysis of genetic variation in populations of infectious agents may help us understand their epidemiology and evolution. Here we study a model for assessing the levels and patterns of genetic diversity in populations of infectious agents. The population is structured into many small subpopulations, which correspond to their hosts, that are connected according to a specific type of contact network. We considered different types of networks, including fully connected networks and scale free networks, which have been considered as a model that captures some properties of real contact networks. Infectious agents transmit between hosts, through migration, where they grow and mutate until elimination by the host immune system.     

Transmission as a predictor of ecological host specificity with a focus on vertical transmission of microsporidia

Consideration of vertical transmission is particularly important for understanding the life cycles of entomopathogens that are naturally occurring in invertebrate populations, are a problem in beneficial insect colonies, or are under consideration as classical biological control agents. Empirical studies generally corroborate the evolutionary hypothesis that virulence should be relatively low for pathogen species that utilize vertical transmission as one mechanism for maintenance in the host population. Nevertheless, many entomopathogens with significant effects on host populations are vertically as well as horizontally transmitted. In addition to gaining a better understanding of pathogen-host interactions and population dynamics, studies of the host range and specificity of putative biological control agents can benefit by using transmission studies to better predict ecological host specificity from physiological data. Horizontal transmission requires a tightly organized host-pathogen relationship to succeed, but still involves, albeit restricted by host behavior and pathogen dosage, the physiological susceptibility of the nontarget host. Vertical transmission studies can provide increased stringency for determining the ecological host specificity of a species and may be one very accurate predictor of the ability of a pathogen to successfully host-switch when introduced into a na?ve population.     

The importance of cryptic species and subspecific populations in classic biological control of weeds: a North American perspective

Classical biological control of weeds depends on finding agents that are highly host-specific. This requires not only correctly understanding the identity of the target plant, sometimes to subspecific levels, in order to find suitable agents, but also identifying agents that are sufficiently specific to be safe and effective. Behavioral experiments and molecular genetic tools have revealed that some arthropod species previously thought to be polyphagous really consist of multiple cryptic species, host races or biotypes, some of which are more host-specific than others. Whereas true species are reproductively isolated, individuals from subspecific populations may potentially interbreed with those of other populations if they should encounter them. Furthermore, biotypes may consist of individuals sharing a genotype that is not fixed within a monophyletic group, and thus may not be evolutionarily stable. This raises the question of how such populations should be classified, and how to confirm the identity of live arthropods before releasing them as classical biological control agents. The existence of host races or cryptic species may greatly increase the number of prospective biological control agents available. However, it may also create new challenges for governmental regulation. These issues are discussed using pertinent examples, mainly from North America.     

The Bacteriome of Bat Flies (Nycteribiidae) from the Malagasy Region: a Community Shaped by Host Ecology,Bacterial Transmission Mode,and Host-Vector Specificity

The Nycteribiidae are obligate blood-sucking Diptera (Hippoboscoidea) flies that parasitize bats. Depending on species, these wingless flies exhibit either high specialism or generalism toward their hosts, which may in turn have important consequences in terms of their associated microbial community structure. Bats have been hypothesized to be reservoirs of numerous infectious agents, some of which have recently emerged in human populations. Thus, bat flies may be important in the epidemiology and transmission of some of these bat-borne infectious diseases, acting either directly as arthropod vectors or indirectly by shaping pathogen communities among bat populations. In addition, bat flies commonly have associations with heritable bacterial endosymbionts that inhabit insect cells and depend on maternal transmission through egg cytoplasm to ensure their transmission. Some of these heritable bacteria are likely obligate mutualists required to support bat fly development, but others are facultative symbionts with unknown effects. Here, we present bacterial community profiles that were obtained from seven bat fly species, representing five genera, parasitizing bats from the Malagasy region. The observed bacterial diversity includes Rickettsia, Wolbachia, and several Arsenophonus-like organisms, as well as other members of the Enterobacteriales and a widespread association of Bartonella bacteria from bat flies of all five genera. Using the well-described host specificity of these flies and data on community structure from selected bacterial taxa with either vertical or horizontal transmission, we show that host/vector specificity and transmission mode are important drivers of bacterial community structure.     

Modelling Fungal (Neozygites cf. Floridana) Epizootics in Local Populations of Cassava Green Mites (Mononychellus Tanajoa)

The fungus, Neozygitis cf. floridana is parasitic on the cassava green mite, Mononychellus tanajoa (Bondar) (Acari: Tetranychidae) in South America and may be considered for classical biological control of cassava green mites in Africa, where cassava is an important subsistence crop, cassava green mites are an imported pest and specific natural enemies are lacking. Spider mites generally have a viscous structure of local populations, a trait that would normally hamper the spread of a fungus that is transmitted by the contact of susceptible hosts with the halo of capilliconidia surrounding an infectious host. However, if infected mites search and settle to produce capilliconidia on sites where they are surrounded by susceptible mites before becoming infectious, then the conditions for maximal transmission in a viscous host population are met. Because the ratio between spider mites and the leaf area they occupy is constant, parasite-induced host searching behaviour leads to a constant per capita transmission rate. Hence, the transmission rate only depends on the number of infectious hosts. These assumptions on parasite-induced host search and constant host density lead to a simple, analytically tractable model that can be used to estimate the maximal capacity of the fungus to decimate local populations of the cassava green mite. By estimating the parameters of this model (host density, per capita transmission rate and duration of infected and infectious state) it was shown that the fungal pathogen can reduce the population growth of M. tanajoa, but cannot drive local mite populations to extinction. Only when the initial ratio of infectious to susceptible mites exceeds unity or the effective growth rate of the mite population is sufficiently reduced by other factors than the fungus (e.g. lower food quality of the host plant, dislodgement and death by rain and wind and predation), will the fungal pathogen be capable of decimating the cassava green mite population. Under realistic field conditions, where all of these growth-reducing factors are likely to operate, there may well be room for effective control by the parasitic fungus. This revised version was published online in November 2006 with corrections to the Cover Date.     

Experimental evidence that source genetic variation drives pathogen emergence

A pathogen can readily mutate to infect new host types, but this does not guarantee successful establishment in the new habitat. What factors, then, dictate emergence success? One possibility is that the pathogen population cannot sustain itself on the new host type (i.e. host is a sink), but migration from a source population allows adaptive sustainability and eventual emergence by delivering beneficial mutations sampled from the source''s standing genetic variation. This idea is relevant regardless of whether the sink host is truly novel (host shift) or whether the sink is an existing or related, similar host population thriving under conditions unfavourable to pathogen persistence (range expansion). We predicted that sink adaptation should occur faster under range expansion than during a host shift owing to the effects of source genetic variation on pathogen adaptability in the sink. Under range expansion, source migration should benefit emergence in the sink because selection acting on source and sink populations is likely to be congruent. By contrast, during host shifts, source migration is likely to disrupt emergence in the sink owing to uncorrelated selection or performance tradeoffs across host types. We tested this hypothesis by evolving bacteriophage populations on novel host bacteria under sink conditions, while manipulating emergence via host shift versus range expansion. Controls examined sink adaptation when unevolved founding genotypes served as migrants. As predicted, adaptability was fastest under range expansion, and controls did not adapt. Large, similar and similarly timed increases in fitness were observed in the host-shift populations, despite declines in mean fitness of immigrants through time. These results suggest that source populations are the origin of mutations that drive adaptive emergence at the edge of a pathogen''s ecological or geographical range.     

Genetic erosion in wild populations makes resistance to a pathogen more costly

Populations that have suffered from genetic erosion are expected to exhibit reduced average trait values or decreased variation in adaptive traits when experiencing periodic or emergent stressors such as infectious disease. Genetic erosion may consequentially modify the ability of a potential host population to cope with infectious disease emergence. We experimentally investigate this relationship between genetic variability and host response to exposure to an infectious agent both in terms of susceptibility to infection and indirect parasite-mediated responses that also impact fitness. We hypothesized that the deleterious consequences of exposure to the pathogen (Batrachochytrium dendrobatidis) would be more severe for tadpoles descended from European treefrog (Hyla arborea) populations lacking genetic variability. Although all exposed tadpoles lacked detectable infection, we detected this relationship for some indirect host responses, predominantly in genetically depleted animals, as well as an interaction between genetic variability and pathogen dose on life span during the postmetamorphic period. Lack of infection and a decreased mass and postmetamorphic life span in low genetic diversity tadpoles lead us to conclude that genetic erosion, while not affecting the ability to mount effective resistance strategies, also erodes the capacity to invest in resistance, increased tadpole growth rate, and metamorphosis relatively simultaneously.     

Epidemiology and disease control in everyday beef practice

It is important for food animal veterinarians to understand the interaction among animals, pathogens, and the environment, in order to implement herd-specific biosecurity plans. Animal factors such as the number of immunologically protected individuals influence the number of individuals that a potential pathogen is able to infect, as well as the speed of spread through a population. Pathogens differ in their virulence and contagiousness. In addition, pathogens have various methods of transmission that impact how they interact with a host population. A cattle population's environment includes its housing type, animal density, air quality, and exposure to mud or dust and other health antagonists such as parasites and stress; these environmental factors influence the innate immunity of a herd by their impact on immunosuppression. In addition, a herd's environment also dictates the "animal flow" or contact and mixing patterns of potentially infectious and susceptible animals. Biosecurity is the attempt to keep infectious agents away from a herd, state, or country, and to control the spread of infectious agents within a herd. Infectious agents (bacteria, viruses, or parasites) alone are seldom able to cause disease in cattle without contributing factors from other infectious agents and/or the cattle's environment. Therefore to develop biosecurity plans for infectious disease in cattle, veterinarians must consider the pathogen, as well as environmental and animal factors.     

The future impact of societal and cultural factors on parasitic disease -- some emerging issues

A variety of societal and cultural factors will increase host exposure or susceptibility to infectious agents, particularly parasites. Such factors have already had a major impact on the emergence of infectious diseases and the situation is likely to worsen further as we enter the new millennium. The changes that are enhancing the spread and transmission of parasitic diseases, as well as those which are adversely affecting host responsiveness, are examined with reference to specific parasites.     

Does animal behavior underlie covariation between hosts' exposure to infectious agents and susceptibility to infection? Implications for disease dynamics

Animal behavior is unique in influencing both components of the process of transmission of disease: exposure to infectious agents, and susceptibility to infection once exposed. To date, the influence of behavior on exposure versus susceptibility has largely been considered separately. Here, we ask whether these two key mechanisms act in concert in natural populations, whereby individuals who are most exposed to infectious agents or have the most contact with conspecifics are also the most susceptible or infectious. We propose three mechanisms that can generate covariation between these two key elements of the transmission of disease within and among hosts, and we provide empirical examples of each. We then use a mathematical model to examine the effect of this covariation on the dynamics of disease at the population level. First, we show that the empirical mechanisms generating covariation between behavioral and physiological components of disease transmission are widespread and include endocrine mediators of behavior, mate choice, group size, sickness behaviors, and behavioral avoidance of infectious conspecifics. The diversity of these empirical mechanisms underscores the potential importance and breadth of covariation in the disease process. Second, we show mathematically that the variability in hosts' exposure to infectious agents and susceptibility or infectiousness, and how tightly they are coupled, strongly influences the ability of a disease to invade a host population. Overall, we propose that covariation between behavioral and physiological components of transmission is likely widespread in natural populations, and can have important consequences for the dynamics of disease at the population level as well as for our understanding of sexual selection, social behavior, and animal communication.     

The mathematical modelling of tumour angiogenesis and invasion

In order to accomplish the transition from avascular to vascular growth, solid tumours secrete a diffusible substance known as tumour angiogenesis factor (TAF) into the surrounding tissue. Endothelial cells which form the lining of neighbouring blood vessels respond to this chemotactic stimulus in a well-ordered sequence of events comprising, at minimum, of a degradation of their basement membrane, migration and proliferation. Capillary sprouts are formed which migrate towards the tumour eventually penetrating it and permitting vascular growth to take place. It is during this stage of growth that the insidious process of invasion of surrounding tissues can and does take place. A model mechanism for angiogenesis is presented which includes the diffusion of the TAF into the surrounding host tissue and the response of the endothelial cells to the chemotactic stimulus. Numerical simulations of the model are shown to compare very well with experimental observations. The subsequent vascular growth of the tumour is discussed with regard to a classical reaction-diffusion pre-pattern model.     

Biology and distribution of microbe-associated thelytokous populations of aphid parasitoids (Hym., Braconidae, Aphidiinae)

Abstract: Some phenomena of the biology and ecology of the microbe ( Wolbachia )-associated thelytokous populations of aphid parasitoids are presented for the first time. Thelytokous virgin females were found to refuse the mating attempts by males of biparental populations, although males occurred quite rarely among the offspring. The host range was found to be about identical in conspecific biparental and thelytokous populations, whereas the association of solely biparental populations with a certain host group might be considered as a marker of the presence of sibling species in the area. The relative frequency of conspecific biparental and thelytokous populations varied, depending upon the area and host species. The microbe-induced thelytokous populations were confirmed in three species of the genus Lysiphlebus Foerst. ( Lysiphlebus cardui Marsh., Lysiphlebus confusus Tremblay and Eady, Lysiphlebus fabarum Marsh.) and probably some other, as yet undescribed, species only in the West Palearctic subregion, whereas the other known congeneric species in the subregion as well as in the Nearctic and the Neotropical regions were determined as strictly biparental species. Microbe-induced thelytokous populations did not change due to host species alternation and/or distribution area (purposeful introductions as biocontrol agents).     

Chemokines and chemokine receptors in infectious diseases

Today, 10 years after the discovery of IL-8, chemokines (chemotactic cytokines) are seen as the stimuli that largely control leucocyte migration. Chemokines are low molecular weight chemoattractant cytokines secreted by a variety of cells, including leucocytes, epithelial cells, endothelial cells, fibroblasts and numerous other cell types. They are produced in response to exogenous stimuli, such as viruses and bacterial LPS, and endogenous stimuli, such as IL-1, TNF and IFN. These factors mediate chemotaxis and leucocyte activation. They also regulate leucocyte extravasation from the blood and/or lymph vessel luminal surface to the tissue space, the site of inflammation. There is no doubt that chemokines and chemokine receptors are critical for defence against infectious pathogens. It is also clear that these pathogens have evolved to accommodate the workings of the host immune system. Survival of these infectious agents appears dependent upon strategies that can evade, suppress, counteract or otherwise confound the constellation of host responses to invading pathogens. In this regard, the chemokines and their receptors are a major target. Reviewed in the present paper are several examples in which microbial pathogens have usurped the mammalian chemokine system to subvert the host immune response.     

Disease and the dynamics of extinction

Invading infectious diseases can, in theory, lead to the extinction of host populations, particularly if reservoir species are present or if disease transmission is frequency-dependent. The number of historic or prehistoric extinctions that can unequivocally be attributed to infectious disease is relatively small, but gathering firm evidence in retrospect is extremely difficult. Amphibian chytridiomycosis and Tasmanian devil facial tumour disease (DFTD) are two very different infectious diseases that are currently threatening to cause extinctions in Australia. These provide an unusual opportunity to investigate the processes of disease-induced extinction and possible management strategies. Both diseases are apparently recent in origin. Tasmanian DFTD is entirely host-specific but potentially able to cause extinction because transmission depends weakly, if at all, on host density. Amphibian chytridiomycosis has a broad host range but is highly pathogenic only to some populations of some species. At present, both diseases can only be managed by attempting to isolate individuals or populations from disease. Management options to accelerate the process of evolution of host resistance or tolerance are being investigated in both cases. Anthropogenic changes including movement of diseases and hosts, habitat destruction and fragmentation and climate change are likely to increase emerging disease threats to biodiversity and it is critical to further develop strategies to manage these threats.     

Local adaptation, resistance, and virulence in a hemiparasitic plant-host plant interaction

Abstract.— Coevolution may lead to local adaptation of parasites to their sympatric hosts. Locally adapted parasites are, on average, more infectious to sympatric hosts than to allopatric hosts of the same species or their fitness on the sympatric hosts is superior to that on allopatric hosts. We tested local adaptation of a hemiparasitic plant, Rhinanthus serotinus (Scrophulariaceae), to its host plant, the grass Agrostis capillaris . Using a reciprocal cross-infection experiment, we exposed host plants from four sites to hemiparasites originating from the same four sites in a common environment. The parasites were equally able to establish haustorial connections to sympatric and allopatric hosts, and their performance was similar on both host types. Therefore, these results do not indicate local adaptation of the parasites to their sympatric hosts. However, the parasite populations differed in average biomass and number of flowers per plant and in their effect on host biomass. These results indicate that the virulence of the parasite varied among populations, suggesting genetic variation. Theoretical models suggest that local adaptation is likely to be detected if the host and the parasite have different evolutionary potentials, different migration rates, and the parasite is highly virulent. In the interaction between R. serotinus and A. capillaris all the theoretical prerequisites for local adaptation may not be fulfilled.     

Models of epidemics and endemicity in genetically variable host populations

A discrete time genetics model is developed for populations that are undergoing selection due to infectious disease. It is assumed that the generation time of the host and infectious agent are non-synchronous and that only the host population is evolving. Two classes of epidemic processes are considered. The first class is for infectious agents that confer immunity following infection, while the second class is for those that do not confer immunity. The necessary and sufficient conditions are found in order for the disease to persist in a stable polymorphic host population. These conditions are shown to depend on the density of susceptibles, the selection coefficients, and the severity and class of the disease process.     

Nonhuman primate quarantine: its evolution and practice

Nonhuman primates (NHPs) are imported to the United States for use in research, domestic breeding, and propagation of endangered populations in zoological gardens. During the past 60 years, individuals responsible for NHP importation programs have observed morbidity and mortality typically associated with infectious disease outbreaks. These outbreaks have included infectious agents such as tuberculosis, Herpesvirus sp., simian hemorrhagic fever, and filovirus infections such as the Ebola and Marburg viruses. Some outbreaks have affected both animal and human populations. These epizootics are attributable to a variety of factors, including increased population density, exposure of na?ve populations to new infectious agents, and stress. The practice of quarantining animals arriving in the United States was first applied by individual research programs to improve animal health and ensure the quality of animals entering research programs. The development of government regulations for nonhuman primate quarantine accompanied the recognition that imported NHPs could pose a risk to public health. This article briefly reviews the history of US NHP importation and the factors behind the development of NHP quarantine regulations. The focus is on regulations concerned with infectious disease, public health, and the health of domestic primate colonies. These regulations have had the dual benefit of protecting public health as well as reducing animal morbidity and mortality during importation and quarantine. We review current practices and facilities for nonhuman primate quarantine and identify challenges for the future.     

Use of Exposure History to Identify Patterns of Immunity to Pneumonia in Bighorn Sheep (Ovis canadensis)

Individual host immune responses to infectious agents drive epidemic behavior and are therefore central to understanding and controlling infectious diseases. However, important features of individual immune responses, such as the strength and longevity of immunity, can be challenging to characterize, particularly if they cannot be replicated or controlled in captive environments. Our research on bighorn sheep pneumonia elucidates how individual bighorn sheep respond to infection with pneumonia pathogens by examining the relationship between exposure history and survival in situ. Pneumonia is a poorly understood disease that has impeded the recovery of bighorn sheep (Ovis canadensis) following their widespread extirpation in the 1900s. We analyzed the effects of pneumonia-exposure history on survival of 388 radio-collared adults and 753 ewe-lamb pairs. Results from Cox proportional hazards models suggested that surviving ewes develop protective immunity after exposure, but previous exposure in ewes does not protect their lambs during pneumonia outbreaks. Paradoxically, multiple exposures of ewes to pneumonia were associated with diminished survival of their offspring during pneumonia outbreaks. Although there was support for waning and boosting immunity in ewes, models with consistent immunizing exposure were similarly supported. Translocated animals that had not previously been exposed were more likely to die of pneumonia than residents. These results suggest that pneumonia in bighorn sheep can lead to aging populations of immune adults with limited recruitment. Recovery is unlikely to be enhanced by translocating naïve healthy animals into or near populations infected with pneumonia pathogens.     

Glacial refugia in pathogens: European genetic structure of anther smut pathogens on Silene latifolia and Silene dioica

Climate warming is predicted to increase the frequency of invasions by pathogens and to cause the large-scale redistribution of native host species, with dramatic consequences on the health of domesticated and wild populations of plants and animals. The study of historic range shifts in response to climate change, such as during interglacial cycles, can help in the prediction of the routes and dynamics of infectious diseases during the impending ecosystem changes. Here we studied the population structure in Europe of two Microbotryum species causing anther smut disease on the plants Silene latifolia and Silene dioica. Clustering analyses revealed the existence of genetically distinct groups for the pathogen on S. latifolia, providing a clear-cut example of European phylogeography reflecting recolonization from southern refugia after glaciation. The pathogen genetic structure was congruent with the genetic structure of its host species S. latifolia, suggesting dependence of the migration pathway of the anther smut fungus on its host. The fungus, however, appeared to have persisted in more numerous and smaller refugia than its host and to have experienced fewer events of large-scale dispersal. The anther smut pathogen on S. dioica also showed a strong phylogeographic structure that might be related to more northern glacial refugia. Differences in host ecology probably played a role in these differences in the pathogen population structure. Very high selfing rates were inferred in both fungal species, explaining the low levels of admixture between the genetic clusters. The systems studied here indicate that migration patterns caused by climate change can be expected to include pathogen invasions that follow the redistribution of their host species at continental scales, but also that the recolonization by pathogens is not simply a mirror of their hosts, even for obligate biotrophs, and that the ecology of hosts and pathogen mating systems likely affects recolonization patterns.