Biomedical subjects

P A Nuttall

Publications and source records attributed to P A Nuttall.

At least 19 recordsLinked to original sources

PubMed2006

Impact of climate change on health: what is required of climate modellers?

The potential impacts of climate change on human health are significant, ranging from direct effects such as heat stress and flooding, to indirect influences including changes in disease transmission and malnutrition in response to increased competition for crop and water resources. Development agencies and policy makers tasked with implementing adaptive strategies recognize the need to plan for these impacts. However at present there is little guidance on how to prioritize their funding to best improve the resilience of vulnerable communities. Here we address this issue by arguing that closer collaboration between the climate modelling and health communities is required to provide the focused information necessary to best inform policy makers. The immediate requirement is to create multidisciplinary research teams bringing together skills in both climate and health modelling. This will enable considerable information exchange, and closer collaboration will highlight current uncertainties and hopefully routes to their reduction. We recognize that climate is only one aspect influencing the highly complex behaviour of health and disease issues. However we are optimistic that climate-health model simulations, including uncertainty bounds, will provide much needed estimates of the likely impacts of climate change on human health.

Environmental Health↗

PubMed2006

Exposed and concealed antigens as vaccine targets for controlling ticks and tick-borne diseases.

Tick vaccines derived from Bm86, a midgut membrane-bound protein of the cattle tick, Boophilus microplus, are currently the only commercially available ectoparasite vaccines. Despite its introduction to the market in 1994, and the recognized need for alternatives to chemical pesticides, progress in developing effective antitick vaccines (and ectoparasite vaccines in general) is slow. The primary rate-limiting step is the identification of suitable antigenic targets for vaccine development. Two sources of candidate vaccine antigens have been identified: 'exposed' antigens that are secreted in tick saliva during attachment and feeding on a host and 'concealed' antigens that are normally hidden from the host. Recently, a third group of antigens has been distinguished that combines the properties of both exposed and concealed antigens. This latter group offers the prospect of a broad-spectrum vaccine effective against both adults and immature stages of a wide variety of tick species. It also shows transmission-blocking and protective activity against a tick-borne pathogen. With the proliferation of molecular techniques and their application to vaccine development, there are high hopes for new and effective antitick vaccines that also control tick-borne diseases.

Animals↗

PubMed2005

Tick-borne Great Island Virus: (I) Identification of seabird host and evidence for co-feeding and viraemic transmission.

Great Island Virus (GIV) is an arbovirus present in the tick Ixodes uriae, a common ectoparasite of nesting seabirds. Common guillemot (Uria aalge) and black-legged kittiwake (Rissa tridactyla) are the preferred and most abundant hosts of I. uriae on the Isle of May, Scotland. As part of a study to understand the epidemiology of GIV, the ability of guillemot and kittiwake to support tick-borne transmission of GIV was examined. GIV was present in ticks feeding in isolated guillemot colonies and guillemots had virus-specific neutralizing antibodies demonstrating previous GIV infection. By contrast, only uninfected ticks were found in colonies inhabited solely by kittiwakes. GIV was isolated from kittiwake ticks in colonies which also contained breeding guillemots but no virus-specific neutralizing antibodies were present in blood samples of kittiwake on which infected ticks were feeding. Thus guillemots are the main vertebrate hosts of GIV on the Isle of May whereas kittiwakes do not appear to be susceptible to infection. Virus infection of adult ticks feeding on guillemots was highly efficient and may involve both viraemic transmission and transmission from infected to uninfected ticks feeding together on birds that do not develop a patent viraemia.

Animals↗

PubMed2005

Tick-borne Great Island Virus: (II) Impact of age-related acquired immunity on transmission in a natural seabird host.

Tick-borne pathogen transmission is dependent upon tick number per host and the physical and temporal distribution of each feeding stage. Age-related acquired immunity to tick and pathogen may also be important but has received less attention. In this study we evaluate which of these parameters has the greatest impact on Great Island Virus (GIV) transmission between Ixodes uriae ticks and common guillemots (Uria aalge). The study system is well suited to investigate age-related effects because the guillemot population is naturally divided into 2 groups, older breeding and younger pre-breeding adult birds. The physical distribution and timing of adult and nymphal tick feeding was similar for both guillemot age groups. However, breeding birds were parasitized by significantly more ticks (mainly nymphs). Calculations based on tick number predict virus prevalence should be higher in ticks that have fed on breeding rather than pre-breeding birds. However, empirical evidence indicates the reverse. Protective acquired immunity to GIV infection may be the reason why GIV prevalence is actually significantly lower in ticks that have fed on breeders. Far more breeding (74%) than pre-breeding (12%) guillemots had antibodies that neutralized 1 or more GIV strains. Estimates of the force of infection support the view that pre-breeding birds experience higher rates of virus infection than breeding birds. The results indicate age-related acquired immunity is a key factor in GIV transmission and highlight the need to consider age-related effects and host immunity when undertaking quantitative studies of tick-borne pathogen transmission.

Age Factors↗

PubMed2005

Manipulation of host cytokine network by ticks: a potential gateway for pathogen transmission.

Ticks are obligatory blood-feeding arthropods that secrete various immunomodulatory molecules to antagonize host inflammatory and immune responses. Cytokines play an important role in regulating these responses. We investigated the extent to which ticks interact with the sophisticated cytokine network by comparing the effect of salivary gland extracts (SGE) of 3 ixodid tick species, Dermacentor reticulatus, Amblyomma variegatum and Ixodes ricinus, all of which are important vectors of tick-borne pathogens. Using specific ELISAs, anti-cytokine activity was demonstrated with 7 cytokines: IL-8, MCP-1, MIP-1alpha, RANTES, eotaxin, IL-2 and IL-4. The results varied between species, and between adult males and females of the same species. Relatively high activity levels were detected in saliva of female D. reticulatus, confirming that the observed anti-cytokine activities are an integral part of tick saliva secreted into the host. Results with fractionated SGE indicated that from 2 to 6 putative cytokine binding molecules are produced, depending on species and sex. Binding ability of SGE molecules was verified by cross-linking with radio-isotope labelled MIP-1alpha. By targeting different cytokines, ixodid ticks can manipulate the cytokine network, which will greatly facilitate blood-feeding and provide a gateway for tick-borne pathogens that helps explain why ticks are such efficient and effective disease vectors.

Animals↗

PubMed2004

Tick-borne viruses.

At least 38 viral species are transmitted by ticks. Virus-tick-vertebrate host relationships are highly specific and less than 10% of all tick species (Argasidae and Ixodidae) are known to play a role as vectors of arboviruses. However, a few tick species transmit several (e.g. Ixodes ricinus, Amblyomma variegatum) or many (I. uriae) tick-borne viruses. Tick-borne viruses are found in six different virus families (Asfarviridae, Reoviridae, Rhabdoviridae, Orthomyxoviridae, Bunyaviridae, Flaviviridae) and at least 9 genera. Some as yet unassigned tick-borne viruses may belong to a seventh family, the Arenaviridae. With only one exception (African swine fever virus, family Asfarviridae) all tick-borne viruses (as well as all other arboviruses) are RNA viruses. Tick-borne viruses are found in all the RNA virus families in which insect-borne members are found, with the exception of the family Togaviridae. Some tick-borne viruses pose a significant threat to the health of humans (Tick-borne encephalitis virus, Crimean-Congo haemorrhagic fever virus) or livestock (African swine fever virus, Nairobi sheep disease virus). Key challenges are to determine the molecular adaptations that allow tick-borne viruses to infect and replicate in both tick and vertebrate cells, and to identify the principal ecological determinants of tick-borne virus survival.

African Swine Fever↗

PubMed2004

Tick-host interactions: saliva-activated transmission.

The skin site at which ticks attach to their hosts to feed is the critical interface between the tick and its host, and tick-borne pathogens. This site is highly modified by the pharmacologically active molecules secreted in tick saliva. For pathogens, it is an ecologically privileged niche that many exploit. Such exploitation is referred to as saliva-activated transmission (SAT) - the indirect promotion of tick-borne pathogen transmission via the actions of bioactive tick saliva molecules on the vertebrate host. Here we review evidence for SAT and consider what are the most likely candidates for SAT factors among the tick pharmacopoeia of anti-haemostatic, anti-inflammatory and immunomodulatory molecules identified to date. SAT factors appear to differ for different pathogens and tick vector species, and possibly even depend on the vertebrate host species. Most likely we are searching for a suite of molecules that act together to overcome the redundancy in host response mechanisms. Whatever they turn out to be, the quest to identify the tick molecules that mediate SAT is an exciting one, and offers new insights to controlling ticks and tick-borne diseases.

Animals↗

PubMed2003

Dynamics of infection in tick vectors and at the tick-host interface.

Tick-borne flaviviruses are common, widespread, and successfully adapted to their mode of transmission. Most tick vectors of flaviviruses are ixodid species. These ticks are characterized by a comparatively long life cycle, lasting several years, during which the infecting virus may be maintained from one developmental stage of the tick to the next. Hence ticks act as highly efficient reservoirs of flaviviruses. Many tick-borne flaviviruses are transmitted vertically, from adult to offspring, although the frequency is too low to maintain the viruses solely in the tick population. Instead, the survival of tick-borne flaviviruses is dependent on horizontal transmission, both from an infected tick to a susceptible vertebrate host and from an infected vertebrate to uninfected ticks feeding on the animal. The dynamics of transmission and infection have traditionally been considered in isolation: in the tick, following virus uptake in the infected blood meal, infection of the midgut, passage through the hemocoel to the salivary glands, and transmission via the saliva; and in the vertebrate host, virus delivery into the skin at the site of tick feeding, infection of the draining lymph nodes, and dissemination to target organs. However, there is now compelling evidence of a complex interaction between the tick vector and its vertebrate host that affects virus transmission profoundly. The feeding site in the skin is a battleground in which the hemostatic, inflammatory, and immune responses of the host are countered by antihemostatic, anti-inflammatory, and immunomodulatory molecules (mostly proteins and peptides) secreted in tick saliva. Here we speculate that exploitation of the tick pharmacopeia, rather than development of viremia, is the key step in successful tick-borne flavivirus transmission.

Animals↗

PubMed2003

Tick-borne flaviviruses.

Tick-borne encephalitis (TBE), one of the most dangerous neuroinfections in Europe and Asia, is caused by tick-borne encephalitis virus (TBEV) and currently involves approximately 11,000 human cases annually, mostly in Russia. This chapter describes the main problems associated with the epidemiology, ecology, pathogenesis, and control of this disease. We have attempted to review the factors that influence the incidence and distribution of TBE, and to discuss possible reasons for the different clinical manifestations including most commonly observed asymptomatic infections, fever forms, acute encephalitis, and the less frequently registered biphasic milk fever and chronic encephalitis. Epidemiologic data concerning the other tick-borne flaviviruses, namely Louping ill virus, Langat virus, and Powassan virus that also produce encephalitis on a smaller scale, are also presented. Here we describe the history and current epidemiological role of Omsk hemorrhagic fever virus and Kyasanur forest disease virus, two viruses that are genetically closely related to TBEV, but produce hemorrhagic fever instead of encephalitis, and provide possible explanations for these differences. The other viruses in the tick-borne flavivirus group are also included despite the fact that they do not play an essential epidemiologic role in humans. This chapter contains a brief history of vaccination against TBE including the trials with live attenuated vaccine and reviews the modern trends in development of vaccine virus strains.

Animals↗

PubMed2003

Vasodilatory activity in horsefly and deerfly salivary glands.

Salivary gland extract (SGE) of four horsefly species (Hybomitra bimaculata Macquart, Hybomitra ciureai Séguy, Tabanus bromius L., Tabanus glaucopis Meigen) and one deerfly species (Chrysops relictus Meigen) (Diptera: Tabanidae) were shown to contain vasodilatory activity. Aliquots equivalent to 1, 5 and 10 pairs of salivary glands (SG) relaxed rat femoral artery (with intact endothelium) pre-constricted with phenylephrine. Vasodilatory activity was dose-dependent. SGE of one horsefly species (Haematopota pluvialis L.) did not induce relaxation. The kinetics of vasodilation induced by SGE of four horsefly species differed from the deerfly. These results indicate that tabanid species may produce more than one type of vasodilator to aid blood feeding.

Animals↗

PubMed2002

Heterogeneity in the effect of different ixodid tick species on human natural killer cell activity.

Tick saliva plays a vital role in blood-feeding, including manipulation of the host response to tick infestation. Furthermore, a diverse number of tick-borne pathogens are transmitted to vertebrate hosts via tick saliva, some of which exploit the immunomodulatory activities of their vector's saliva. We report that salivary gland extracts (SGE) derived from Dermacentor reticulatus adult ticks induce a decrease in the natural killer (NK) activity of effector cells obtained from healthy human blood donors. The decrease was observed with SGE from both female and male D. reticulatus fed for either 3 or 5 days on mice, but no significant effect was observed with SGE from unfed ticks or ticks that had fed for 1 day. These results indicate that the tick anti-NK factor(s) is only active after blood-feeding has commenced. Microscopic examination revealed that the first step of NK activity, namely effector/target cell conjugate formation, was affected by SGE. The observed reduction in conjugate formation occurred when effector (but not target) cells were treated with SGE for 30 min, and the effect persisted after 12 h of treatment. Similar but less potent anti-NK activity was detected for SGE from Amblyomma variegatum and Haemaphysalis inermis. By contrast, SGE derived from Ixodes ricinus and Rhipicephalus appendiculatus female ticks did not decrease NK activity. The apparent absence of such activity in these two important vectors of tick-borne viruses suggests that control of NK cells does not play an important role in promoting virus transmission, at least for these particular species.

Animals↗

PubMed2002

A high affinity serotonin- and histamine-binding lipocalin from tick saliva.

To overcome the inflammatory response in its host, the cattle-feeding, brown ear tick secretes histamine-binding proteins into the feeding site. These proteins are beta-barrels with two internal binding sites: a high-affinity (H) site for histamine and a site (L) for which the natural ligand is unknown. Here we report a related protein (SHBP), secreted by a rodent- and cattle-feeding tick, that traps both histamine and serotonin. The histamine-binding H site is well conserved in SHBP, whereas residue changes in the L-like site are consistent with binding of the bulkier serotonin molecule. As histamine is a key inflammatory mediator in cattle, while serotonin takes on this role in rodents, the diversification of these tick proteins may reflect host adaptation.

Amino Acid Sequence↗

PubMed2002

Anticoagulant activities in salivary glands of tabanid flies.

Tabanid flies are telmophages (pool feeders), taking frequent and rapid bloodmeals from many different individual hosts. To investigate how they accomplish this intermittent feeding strategy, we examined the anticoagulant activities in salivary gland extracts (SGE) from 19 species representing six genera: Atylotus, Chrysops, Haematopota, Heptatoma, Hybomitra and Tabanus (Diptera: Tabanidae). Standard coagulation screen assays were used to determine thrombin time, prothrombin time and activated partial thromboplastin time. Chromogenic substrate assays were performed for thrombin and factor Xa activity. SGE of most species (except Chrysops spp.) considerably prolonged human plasma clotting time in a dose-dependent manner, and showed potent and specific antithrombin activity in the chromogenic substrate assay. Heptatoma pellucens displayed the strongest anticoagulant activity. Specific anti-factor Xa activity in tabanid SGE was not detected. Electrophoretic profiles of SGE proteins differed between genera and species. Overall, the results suggest that tabanids have evolved at least two antihaemostatic strategies.

Animals↗

PubMed2002

Vesicular stomatitis virus nucleocapsid protein production in cells treated with selected fast protein liquid chromatography fractions of tick salivary gland extracts.

A salivary gland extract (SGE) prepared from 5-days-fed Dermacentor reticulatus female ticks was fractionated by fast protein liquid chromatography (FPLC). The effect of three FPLC fractions selected on the basis of anti-interleukin 8 (anti-IL-8) activity on vesicular stomatitis virus (VSV) nucleocapsid (N) protein formation in mouse L-cells was determined. Infected 14C-labeled cells treated with the FPLC fractions were analyzed by two-dimensional (2D) electrophoresis. The yields of VSV N protein were evaluated by Imagemaster software analysis. Most noticeable was an increase in the N protein production after treatment with the fraction 39 corresponding to the major peak of the anti-IL-8 activity. The nature of the substance in SGE that was responsible for this effect remains unclear.

Animals↗

PubMed2001

Intra-stadial tick-borne Thogoto virus (Orthomyxoviridae) transmission: accelerated arbovirus transmission triggered by host death.

Haematophagous insect vectors of arthropod-borne viruses (arboviruses) feed repeatedly. Consequently, they can transmit arboviruses to more than one host during the same developmental stage (intra-stadial transmission). By contrast, ixodid ticks generally feed only once at each parasitic stage (larva, nymph, and adult) and hence they have only one opportunity for tickborne virus transmission per stadium (inter-stadial transmission). Under natural conditions, tick-infested hosts may die (from disease or other causes) before the ticks have completed their long period of engorgement. A laboratory model was used to investigate the consequences of premature host death on tick-borne virus transmission. We report intra-stadial transmission of Thogoto virus by the nymphal, male, and female ticks of Rhipicephalus appendiculatus. Tick-borne Thogoto virus infection caused viraemia and death of hamsters before the nymphal and adult ticks feeding on them had completed engorgement. The resulting partially fed ticks were allowed to continue engorgement on new, uninfected hosts (interrupted feeding). During feeding on the subsequent hosts, they transmitted the virus intra-stadially to susceptible hosts (hamsters), and to uninfected co-feeding ticks on non-susceptible hosts (guinea-pigs). Intra-stadial transmission, mediated by interrupted feeding, may help explain outbreaks of rapid and fatal tick-borne viral diseases, and the epidemiology as well as evolution of virulence, in a susceptible host population. Additionally, intra-stadial transmission provides an increased risk of tick-borne pathogen transmission to humans and domestic animals during slaughter and game hunting.

Animals↗

PubMed2001

Feeding aggregation of the tick Rhipicephalus appendiculatus (Ixodidae): benefits and costs in the contest with host responses.

Gregariousness can be advantageous in interspecific competition while intraspecific competition may favour solitude. We examined feeding behaviour of the ixodid tick, Rhipicephalus appendiculatus, in the context of interspecific (tick-host) and intraspecific (tick-tick) competition. Such competition is mediated through host rejection responses to tick infestation to which ticks respond by secreting immunodulatory saliva. We observed that group feeding adults increased their blood-feeding rate, reducing the time to mating and repletion, compared with individual feeding of paired adults. The benefits of feeding aggregation indicate direct reciprocity between ticks, most likely resulting from the shared activities of their bioactive saliva. However, fast-feeding ticks appeared to impair blood-feeding success of slow-feeding females during group feeding. This may be explained by the faster feeders exacerbating host responses on detachment that are then directed against the slower feeders. As female fecundity is generally proportional to the size of the bloodmeal, there will be a selection pressure to feed gregariously. Greater understanding of the benefits and costs of feeding aggregation may help to improve tick control strategies.

Animals↗

PubMed2001

Salivary fluid secretion in the ixodid tick Rhipicephalus appendiculatus is inhibited by Thogoto virus infection.

Adult Rhipicephatus appendiculatus ticks, infected with Thogoto (THO) virus or control, were fed on guinea pigs and removed at intervals throughout the feeding cycle. Salivary fluid secretion was measured by an in vitro technique. The salivary glands of infected, partially-fed ticks secreted fluid in vitro at about 75% the rate of controls, but the difference between infected and controls among engorged ticks was not statistically significant. Basal and DA-stimulated levels of cyclic AMP (cAMP) were determined in isolated glands and were significantly affected by THO virus infection. The differences in secretory rate among control and infected ticks could not be explained in terms of altered cAMP levels. Haemolymph volume was measured by a tracer-dilution technique using 3H-inulin. The mean haemolymph volume for both THO-infected and control groups was between 23-24% body weight throughout the feeding cycle, indicating that infection by this arbovirus did not influence salivary fluid secretion via altered haemolymph volume. The mechanism by which THO virus affects secretory activity of its tick vector remains unknown.

Animals↗

PubMed2001

Molecular individuality and adaptation of the tick Rhipicephalus appendiculatus in changed feeding environments.

The tick Rhipicephalus appendiculatus Neumann (Acari: Ixodidae) naturally infests many host species. However, the mechanisms that enable it to feed on such a wide range of hosts are unclear. One possibility is that a tick population maintains molecular (genotypic and/or phenotypic) diversity among individuals such that individuals vary in their competency in taking bloodmeals under different feeding conditions. As a first step in testing this hypothesis, we showed that the polymorphism of salivary gland proteins, previously demonstrated in unfed ticks, was maintained during feeding on guinea-pigs. We then compared feeding performance under standard laboratory rearing conditions: one instar (adults or nymphs) feeding on guinea-pigs, with three changed conditions: (1) two instars (adults and nymphs) feeding together on guinea-pigs; (2) one instar (adults or nymphs) feeding on hamsters; and (3) two instars (adults and nymphs) feeding together on hamsters. The mean engorged weight of adult females was significantly reduced under all changed conditions, indicating that most of the adult individuals were significantly challenged by the changed conditions. However, some individuals achieved successful engorgement, indicating competence to the changed condition, and demonstrating variation in adaptive ability among individuals. Engorged females produced egg masses positively correlated to the engorged weights. More interestingly, the correlation coefficient (R) increased when feeding condition was changed. This may lead to more efficient selection for population adaptation under the changed conditions. As the feeding success of ixodid ticks depends on the efficiency of the cocktail of immunomodulatory saliva, the relevance of the polymorphism of salivary gland proteins and host adaptation is discussed.

Animals↗