Pangloss revisited: a critique of the dilution effect and the biodiversity-buffers-disease paradigm.

The twin concepts of zooprophylaxis and the dilution effect originated with vector-borne diseases (malaria), were driven forward by studies on Lyme borreliosis and have now developed into the mantra "biodiversity protects against disease". The basic idea is that by diluting the assemblage of transmission-competent hosts with non-competent hosts, the probability of vectors feeding on transmission-competent hosts is reduced and so the abundance of infected vectors is lowered. The same principle has recently been applied to other infectious disease systems--tick-borne, insect-borne, indirectly transmitted via intermediate hosts, directly transmitted. It is claimed that the presence of extra species of various sorts, acting through a variety of distinct mechanisms, causes the prevalence of infectious agents to decrease. Examination of the theoretical and empirical evidence for this hypothesis reveals that it applies only in certain circumstances even amongst tick-borne diseases, and even less often if considering the correct metric--abundance rather than prevalence of infected vectors. Whether dilution or amplification occurs depends more on specific community composition than on biodiversity per se. We warn against raising a straw man, an untenable argument easily dismantled and dismissed. The intrinsic value of protecting biodiversity and ecosystem function outweighs this questionable utilitarian justification.

Human activities predominate in determining changing incidence of tick-borne encephalitis in Europe.

Explanations for the dynamics of tick-borne disease systems usually focus on changes in the transmission potential in natural enzootic cycles. These are undoubtedly important, but recent analyses reveal that they may not be quantitatively the most significant side of the interaction between infected ticks and humans. Variation in human activities that may impact inadvertently but positively on both the enzootic cycles and the degree of human exposure to those cycles, provide more robust explanations for recent upsurges in tick-borne encephalitis in Europe. This can account for long-term increases in incidence that coincided with post-soviet political independence, for small-scales spatial variation in incidence within a country, and for short-scale fluctuations such as annual spikes in incidence. The patterns of relevant human activities, typically those related to the use of forest resources, are evidently driven and/or constrained by the cultural and socio-economic circumstances of each population, resulting in contrasting national epidemiological outcomes.

Tick-borne disease systems emerge from the shadows: the beauty lies in molecular detail, the message in epidemiology.

This review focuses on some of the more ground-shifting advances of recent decades, particularly those at the molecular and cellular level that illuminate mechanisms underpinning the natural ecology of tick-host-pathogen interactions and the consequent epidemiology of zoonotic infections in humans. Knowledge of components of tick saliva, now recognized as the central pillar in the tick's ability to complete its blood meal and the pathogen's differential ability to use particular hosts for transmission, has burgeoned with new molecular techniques. Functional studies have linked a few of them to saliva-assisted transmission of non-systemic infections between co-feeding ticks, the quantitative key to persistent cycles of the most significant tick-borne pathogen in Europe. Human activities, however, may be equally important in determining dynamic patterns of infection incidence in humans.

Dynamics of tick-borne disease systems: minor role of recent climate change.

Tick-borne disease systems are very sensitive to climate through the impact of temperature and moisture stress on rates of the demographic processes of ticks. There is no a priori reason, however, to expect tick abundance or seasonal activity patterns to respond to climate change in ways that inevitably increase the risk of infection by the transmitted pathogens. Changing host availability may be more important than climate in determining tick abundance. The credibility of any (inherently untestable) predictions of future system-specific changes will be strengthened if based on satisfactory explanations of the past. Tick-borne encephalitis (TBE) in Europe is presented as a case study: observed patterns of climate change are too similar within and between countries to provide the sole explanation for the extreme spatio-temporal heterogeneity of the marked upsurges in TBE incidence over the past two decades. Instead, a nexus of interacting factors affecting both the risk of infection and exposure of humans to that risk, and each differing in force in space and time, is a more powerful model. Many of these factors are driven by socio-economic changes, and include climate, land cover, wildlife, agricultural practices, industrial activities, (un)employment and income. The same principle may apply to the periodic epidemics of Crimean-Congo haemorrhagic fever.

Trends in ixodid tick abundance and distribution in Great Britain.

The popular, but rarely documented, view in Britain is that ticks have increased in distribution and abundance over recent years. To assess this, we gathered evidence for changes in tick distribution and abundance by distributing a survey questionnaire throughout Britain and by analysing trends in the prevalence of tick infestation on red grouse chicks Lagopus lagopus scoticus Latham (Galliformes: Tetranoidae), gathered over 19 years at three Scottish sites, and on deer (Cetartiodactyla: Cervidae) culled over 11 years on 26 Ministry of Defence (MoD) estates. Based on the survey, the current known distribution of Ixodes ricinus Linnaeus (Acari: Ixodidae) has expanded by 17% in comparison with the previously known distribution. The survey indicated that people perceive there to be more ticks today than in the past at 73% of locations throughout Britain. Reported increases in tick numbers coincided spatially with perceived increases in deer numbers. At locations where both tick and deer numbers were reported to have increased, these perceived changes occurred at similar times, raising the possibility of a causal link. At other locations, tick numbers were perceived to have increased despite reported declines in deer numbers. The perceptions revealed by the survey were corroborated by quantitative data from red grouse chicks and culled deer. Tick infestation prevalence increased over time on all grouse moors and 77% of MoD estates and decreased at six locations.

The basic reproduction number for complex disease systems: defining R(0) for tick-borne infections.

Characterizing the basic reproduction number, R(0), for many wildlife disease systems can seem a complex problem because several species are involved, because there are different epidemiological reactions to the infectious agent at different life-history stages, or because there are multiple transmission routes. Tick-borne diseases are an important example where all these complexities are brought together as a result of the peculiarities of the tick life cycle and the multiple transmission routes that occur. We show here that one can overcome these complexities by separating the host population into epidemiologically different types of individuals and constructing a matrix of reproduction numbers, the so-called next-generation matrix. Each matrix element is an expected number of infectious individuals of one type produced by a single infectious individual of a second type. The largest eigenvalue of the matrix characterizes the initial exponential growth or decline in numbers of infected individuals. Values below 1 therefore imply that the infection cannot establish. The biological interpretation closely matches that of R(0) for disease systems with only one type of individual and where infection is directly transmitted. The parameters defining each matrix element have a clear biological meaning. We illustrate the usefulness and power of the approach with a detailed examination of tick-borne diseases, and we use field and experimental data to parameterize the next-generation matrix for Lyme disease and tick-borne encephalitis. Sensitivity and elasticity analyses of the matrices, at the element and individual parameter levels, allow direct comparison of the two etiological agents. This provides further support that transmission between cofeeding ticks is critically important for the establishment of tick-borne encephalitis.

Tick-borne disease systems: mapping geographic and phylogenetic space.

Evidence is presented that the evolution of the tick-borne flaviviruses is driven by biotic factors, principally the exploitation of new hosts as transmission routes. Because vector-borne diseases are limited by climatic conditions, however, abiotic factors have the potential to direct and constrain the evolutionary pathways. This idea is explored by testing the hypothesis that closely related viruses occupy more similar eco-climatic spaces than do more distantly related viruses. A statistical comparison of the conventional phylogenetic tree derived from molecular distances and a novel phenetic tree derived from distances between the climatic spaces within which each virus circulates, indicates that these trees match each other more closely than would be expected at random. This suggests that these viruses are indeed limited in the degree to which they can evolve into new environmental conditions.

Climate change and vector-borne diseases.

In this review we examine formally the conditions under which vector-borne diseases are likely to change, and the directions of those changes, under various scenarios of climate change. We specify the criteria that must be met in order to conclude that climate change is having an effect on vector-borne diseases. We then take several examples from the literature and show how some of them meet these criteria, while others do not. For those that do not, there are alternative explanations that involve much more plausible drivers of the recorded changes in the diseases concerned.

Tick ecology: processes and patterns behind the epidemiological risk posed by ixodid ticks as vectors.

The population ecology of ticks is fundamental to the spatial and temporal variation in the risk of infection by tick-borne pathogens. Tick population dynamics can only be fully understood by quantifying the rates of the demographic processes, which are influenced by both abiotic (climatic) factors acting on the free-living tick stages and biotic (host) responses to the tick as a parasite. Within the framework of a population model, I review methods and results of attempts to quantify (1) rates of tick development and the probability of diapause, (2) the probability of questing for hosts by unfed ticks, (3) the probability of ticks attaching to a host, and (4) tick mortality rates. Biologically, these processes involve the physiological and behavioural response of ticks to temperature, moisture stress and day length that result in specific patterns of seasonal population dynamics and host relationships. Temperate and tropical patterns will be illustrated with reference mostly to Ixodes ricinus and Rhipicephalus appendiculatus, respectively.

Testosterone increases the transmission potential of tick-borne parasites.

Using laboratory-bred natural rodent hosts that had been castrated and then implanted with either testosterone or inert oil, we have shown that testosterone causes prolonged and more intense infections of a tick-borne piroplasm, Babesia microti. This will result in more ticks becoming infected while feeding. Sexually active male rodents with high testosterone levels are also known to show increased locomotory activity and reduced innate and acquired resistance to tick feeding, so that more ticks are likely to be picked up and then fed successfully by these hosts. As a result, the transmission potential of B. microti is significantly increased via hosts with high rather than low testosterone levels. It is argued that testosterone helps to generate the observed aggregated distributions of parasites amongst their hosts, which also enhances parasite persistence.

The shifting landscape of tick-borne zoonoses: tick-borne encephalitis and Lyme borreliosis in Europe.

The two major vector-borne diseases of northern temperate regions, tick-borne encephalitis (TBE) and Lyme borreliosis (LB), show very different epidemiological patterns, but both have increased significantly in incidence since the 1980s. Insight into the temporal dynamics of TBE, gained from statistical analysis of spatial patterns integrated with biological explanation, suggests that the recent increases in TBE cases in Central Europe and the Baltic States may have arisen largely from changes in human behaviour that have brought more people into contact with infected ticks. Under forecast climate change scenarios, it is predicted that enzootic cycles of TBE virus may not survive along the southern edge of their present range, e.g. in Slovenia, Croatia and Hungary, where case numbers are indeed decreasing. New foci, however, are predicted and have been observed in Scandinavia. At the same time, human impact on the landscape, increasing both the habitat and wildlife hosts of ticks, has allowed tick populations to multiply significantly. This probably accounts for a genuine emergence of LB, with its high potential transmission rate, in both the USA and Europe, although the rate of emergence has been exaggerated by improved surveillance and diagnosis.

Testosterone depresses innate and acquired resistance to ticks in natural rodent hosts: a force for aggregated distributions of parasites.

The effects of testosterone on acquired resistance to ticks, Ixodes ricinus, in their natural rodent hosts (voles, Clethrionomys glareolus, and wood-mice, Apodemus sylvaticus) were investigated by manipulating testosterone levels and exposing the hosts to repeated tick infestations. Testosterone reduced both innate and acquired resistance to tick feeding. During primary infestations, attachment rates were higher on rodents with high testosterone levels than on oil-implanted controls. Successive infestations on voles were accompanied by a decrease in tick feeding success and survival, but this decrease was significantly greater in ticks fed on control voles than in those fed on voles implanted with testosterone. When reduced feeding success had been induced, either by vaccination with tick salivary gland extract or by 4 successive infestations, implantation with testosterone partially reversed the acquired resistance. These effects of testosterone will generate heterogeneities within the rodent population with respect to tick distribution and microparasite transmission. The lowest innate and acquired resistance to tick feeding occurs in that fraction of the host population, i.e., sexually active males, most actively involved in the transmission of both Babesia microti and Borrelia burgdorferi s.l.

Seasonal synchrony: the key to tick-borne encephalitis foci identified by satellite data.

A previous analysis of tick infestation patterns on rodents in Slovakia suggested that the key to the focal distribution of western-type tick-borne encephalitis virus (TBEv) in Europe is the geographically variable degree of synchrony in the seasonal activity of larval and nymphal Ixodes ricinus ticks. This prediction is here tested by examining records, from 7 different countries, of the seasonal variation in the abundance of larvae and nymphs feeding on rodents or questing on the vegetation. Larvae consistently started feeding and questing earlier in the year at sites within TBEv foci than elsewhere, so that they appeared in the spring as soon as nymphs were active. Such larval nymphal synchrony is associated with a rapid fall in ground-level temperatures from August to October as revealed by the satellite-derived index of Land Surface Temperature (LST). Likewise, of 1992 pixels sampled on a grid across Europe, the 418 that fell within TBEv foci were characterized by a higher than average rate of autumnal cooling relative to the peak midsummer LST. It is proposed that such a seasonal temperature profile may cause unfed larvae to pass the winter in quiescence, from which they emerge synchronously with nymphs in the spring.

[Satellite data and disease transmission by vectors: the creation of maps for risk prediction]. / Données satellites et maladies transmises par vecteurs: la création de cartes de prédiction du risque.

The complex set of criteria determining the reproduction rate of infection (distribution, density, dynamics of arthropod populations, temperature, humidity...) can be estimated with far greater precision by satellite than by conventional meteorological stations. By linking a) distribution modes and type of environment and b) satellite data and rates of underlying biological processes, we have been able to elaborate two super-imposed models: one for vector populations and one for pathogenic agents. We have used such models to look at, for example, trypanosomiasis, malaria and Lyme disease.

Ticks and tick-borne disease systems in space and from space.

Analyses within geographical information systems (GISs) indicate that small- and large-scale ranges of hard tick species (Ixodidae) are determined more by climate and vegetation than by host-related factors. Spatial distributions of ticks may therefore be analysed by statistical methods that seek correlations between known tick presence/absence and ground- or remotely-sensed (RS) environmental factors. In this way, local habitats of Amblyomma variegatum in the Caribbean and Ixodes ricinus in Europe have been mapped using Landsat RS imagery, while regional and continental distributions of African and temperate tick species have been predicted using multi-temporal information from the National Oceanic and Atmospheric Administration-Advanced Very High Resolution Radiometer (NOAA-AVHRR) imagery. These studies illustrate ways of maximizing statistical accuracy, whose interpretation is then discussed in a biological framework. Methods such as discriminant analysis are biologically transparent and interpretable, while others, such as logistic regression and tree-based classifications, are less so. Furthermore, the most consistently significant variable for predicting tick distributions, the RS Normalized Difference Vegetation Index (NDVI), has a sound biological basis in that it is related to moisture availability to free-living ticks and correlated with tick mortality rates. The development of biological process-based models for predicting the spatial dynamics of ticks is a top priority, especially as the risk of tick-borne infections is commonly related not simply to the vector's density, but to its seasonal population dynamics. Nevertheless, using statistical pattern-matching, the combination of RS temperature indices and NDVI successfully predicts certain temporal features essential for the transmission of tick-borne encephalitis virus, which translate into a spatial pattern of disease foci on a continental scale.

The global spread of malaria in a future, warmer world.

The frequent warnings that global climate change will allow falciparum malaria to spread into northern latitudes, including Europe and large parts of the United States, are based on biological transmission models driven principally by temperature. These models were assessed for their value in predicting present, and therefore future, malaria distribution. In an alternative statistical approach, the recorded present-day global distribution of falciparum malaria was used to establish the current multivariate climatic constraints. These results were applied to future climate scenarios to predict future distributions, which showed remarkably few changes, even under the most extreme scenarios.

Fragile transmission cycles of tick-borne encephalitis virus may be disrupted by predicted climate change.

Repeated predictions that vector-borne disease prevalence will increase with global warming are usually based on univariate models. To accommodate the full range of constraints, the present-day distribution of tick-borne encephalitis virus (TBEv) was matched statistically to current climatic variables, to provide a multivariate description of present-day areas of disease risk. This was then applied to outputs of a general circulation model that predicts how climatic variables may change in the future, and future distributions of TBEv were predicted for them. The expected summer rise in temperature and decrease in moisture appears to drive the distribution of TBEv into higher-latitude and higher-altitude regions progressively through the 2020s, 2050s and 2080s. The final toe-hold in the 2080s may be confined to a small part of Scandinavia, including new foci in southern Finland. The reason for this apparent contraction of the range of TBEv is that its transmission cycles depend on a particular pattern of tick seasonal dynamics, which may be disrupted by climate change. The observed marked increase in incidence of tick-borne encephalitis in most parts of Europe since 1993 may be due to non-biological causes, such as political and sociological changes.

Impact of microclimate on immature tick-rodent host interactions (Acari: Ixodidae): implications for parasite transmission.

Rodents play a significant role in enzootic cycles of tick-borne pathogens, notably, in the northern hemisphere, tick-borne encephalitis virus and Lyme borreliosis spirochaetes. The relative numbers of nymphal and larval ticks feeding on rodents are crucial variables in determining the probability of rodent infection and the degree of amplification of infection prevalence in the tick population. Manipulation of the microclimate within quasinatural experimental arenas revealed that under increasingly dry conditions the numbers of unfed nymphal Ixodes ricinus L. questing in upper layers of the herbage decreased, whereas the rate of fat use and the numbers of nymphs feeding on small rodents, both increased. This is consistent with nymphs descending to the moist lower vegetation layers for water replenishment, where they would come into contact with small hosts. Very few larvae quested or fed on rodents under the dry conditions, but many more did so once the humidity increased, suggesting that larvae escape desiccation by becoming quiescent. The ratio of larvae to nymphs feeding on rodents thus increases with increasing humidity, contributing to the seasonal and geographical variation in disease transmission dynamics.