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Biomedical subjects

S E Randolph

Publications and source records attributed to S E Randolph.

At least 19 recordsLinked to original sources

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.

Animals↗

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.

Animals↗

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.

Adaptation, Physiological↗

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.

Animals↗

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.

Animals↗

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.

Animals↗

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.

Animals↗

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.

Animals↗

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.

Animals↗

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.

Animals↗

[Satellite data and disease transmission by vectors: the creation of maps for risk prediction].

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.

Animals↗

Ixodes ticks: serum species sensitivity of anticomplement activity.

Ixodid ticks feed for extended periods of up to 2 weeks or more. To complete engorgement, they must overcome their host's innate immune mechanisms of which the complement system is a major component. Using in vitro assays, salivary gland extracts of the ixodid ticks, Ixodes ricinus, I. hexagonus, and I. uriae, were shown to inhibit activity of the alternative pathway of complement. The ability of the different Ixodes species to inhibit complement activity varied with the animal species used as a complement serum source. Serum species sensitivity correlates to the reported host range of the tick species tested.

Animals↗

Survival strategy of tick-borne encephalitis virus: cellular basis and environmental determinants.

Although TBE virus can be transmitted in the laboratory by a wide variety of ixodid tick species to a wide variety of vertebrate host species, nevertheless in nature endemic cycles of TBE virus depend principally on just two tick species, Ixodes ricinus in the western and I. persulcatus in the eastern Palaearctic. A complete transmission cycle, from tick to tick via vertebrates, occurs most efficiently between co-feeding ticks in the absence of a systemic viraemia. This non-systemic route depends on TBE virus replication within particular immunocompetent cells in the skin, and only certain vertebrate species, notably Apodemus mice, are susceptible to this. Amongst the potential tick vectors in Europe, only I. ricinus has the correct host relationships and appropriate natural life cycle to support such non-systemic transmission cycles. Within the wide European distribution of this tick-host relationship, only in certain places do larval and nymphal ticks feed together on the same hosts with sufficient coincidence to ensure TBE virus survival. The environmental factors that determine this seasonal coincidence are being identified with the help of remotely-sensed meteorological satellite imagery to create predictive risk maps of TBE foci.

Animals↗

Incidence from coincidence: patterns of tick infestations on rodents facilitate transmission of tick-borne encephalitis virus.

Tick-borne encephalitis (TBE) virus has a highly focal distribution through Eurasia. Endemic cycles appear to depend on the transmission of non-systemic infections between ticks co-feeding on the same rodent hosts. The particular features of seasonal dynamics and infestation patterns of larval and nymphal Ixodes ricinus, but not Dermacentor reticulatus, from 4 regions within TBE foci in Slovakia, are such as to promote TBE virus transmission. The distributions of larvae and nymphs on their principal rodent hosts are highly aggregated and, rather than being independent, the distributions of each stage are coincident so that the same ca. 20% of hosts feed about three-quarters of both larvae and nymphs. This results in twice the number of infectible larvae feeding alongside potentially infected nymphs compared with the null hypothesis of independent distributions. Overall, co-feeding transmission under these circumstances brings the reproductive number (R0) for TBE virus to a level that accounts quantitatively for maintained endemic cycles. Essential for coincident aggregated distributions of larvae and nymphs is their synchronous seasonal activity. Preliminary comparisons support the prediction of a greater degree of coincident seasonality within recorded TBE foci than outside. This identifies the particular climatic factors that permit such patterns of tick seasonal dynamics as the primary predictors for the focal distribution of TBE.

Animals↗

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.

Animals↗

Ticks are not Insects: Consequences of Contrasting Vector Biology for Transmission Potential.

Quantitative analyses of vector-borne parasite systems are dominated by insect systems. In attempts to formulate general statements concerning vectors and their indirectly transmitted parasites, ticks are usually ignored or they are implicitly or explicitly assumed to obey the same rules as insects. Here, Sarah Randolph shows that contrasting biological attributes of these two different arthropod classes (ticks and insects) directly affect their performance as vectors. The equations for estimating their respective potential to transmit parasites differ in important respects, as does the relative impact of each factor on these estimates. These conclusions direct attention towards the empirical field data most appropriate for quantifying the spatially and temporally variable risk of infection from these contrasting vector-borne parasite systems.

Journal Article↗

Competence of pheasants as reservoirs for Lyme disease spirochetes.

Pheasants, Phasianus colchicus L., constitute a major part of the ground-feeding avifauna of England and Wales and are important hosts to immature stages of Ixodes ricinus L., the principal tick vector of Lyme borreliosis spirochetes in Europe. Therefore, their competence as hosts for Borrelia burgdorferi Johnson, Schmid, Steigerwalt & Brenner sensu lato was investigated. One group of pheasants was inoculated by needle with 1 x 10(6) cultured B. burgdorferi s.s. organisms, and a 2nd group of birds was infested with I. ricinus nymphs collected from a focus of Lyme borreliosis in southern England. Both bird groups were subjected to xenodiagnoses using uninfected I. ricinus nymphs. All recovered engorged ticks, as well as pheasant skin biopsies, were analyzed by a nested polymerase chain reaction targeting the 5S-23S rRNA genes of B. burgdorferi s.l. Both groups proved to be infective for ticks. The birds that were infected by tick bites proved to be significantly more infective for ticks (23% of the xenodiagnostic ticks positive) than those infected by needle (5%). The results show that pheasants can be infected experimentally with B. burgdorferi s.l., that they can pass the spirochetes to ticks and that their infectivity for ticks may persist as long as 3 mo. We conclude that pheasants are reservoir competent for Lyme borreliosis spirochetes and potentially play an important role in the maintenance of B. burgdorferi s.l. in England and Wales.

Animals↗