Historical review and insights on the livestock tick-borne disease research of a developing country: The Philippine scenario

Tick-borne diseases (TBDs) remain to be a global animal health threat. Developing countries like the Philippines is not exempt to this. Despite the potential impact TBDs can give to these countries, local government initiatives and researches remain to be limited. In the Philippines, most epidemiological studies were confined only to specific areas, and predominantly in the Northern Area. Due to its unique geography and limited studies, the current nationwide status of most TBDs could not be clearly established. This review mainly covered published studies and presented challenges in the conduct of TBD research in the Philippines, which may be similar to other Southeast Asian or developing countries. To date, reported livestock TBD pathogens in the Philippines include Anaplasma, Babesia, Theileria, and Mycoplasma spp. With the ubiquitous presence of the Rhipicephalus microplus ticks in the country, it is highly probable that other pathogens transmitted by these vectors could be present. Despite studies on different TBDs in the livestock sector, the Philippine government has not yet heightened its efforts to implement tick control measures as part of the routine animal health program for local farmers. Further studies might be needed to determine the nationwide prevalence of TBDs and the presence of other possible tick species and TBD pathogens. The Philippine scenario may present situations that are similar to other developing countries.     

Tick-borne haemoparasitic diseases in small ruminants in Pakistan: Current knowledge and future perspectives

Livestock industry is an essential part of Pakistan’s economy, and a variety of ruminants (including sheep and goats) are reared for the increasing demand of milk, meat and hide products. Haemoparasitic illnesses such as theileriosis, anaplasmosis, and babesiosis are a significant health risk for small ruminants in our country. Information regarding distribution patterns, the tick species involved and effective strategies to control tick-borne diseases (TBD) in goats and sheep of Pakistan is limited. To this end, it is required to assess the present rank of TBDs in small ruminants of Pakistan with a note on their vector ticks in order to control and identify the gaps in the knowledge of TBDs. This will recommend areas for future research and will add to the understanding of these diseases and will draw attention to the need for better-quality tools for the diagnosis and control of TBDs in small ruminants of Pakistan.     

Experimental study of micro-habitat selection by ixodid ticks feeding on avian hosts

Mechanisms of on-host habitat selection of parasites are important to the understanding of host-parasite interactions and evolution. To this end, it is important to separate the factors driving parasite micro-habitat selection from those resulting from host anti-parasite behaviour. We experimentally investigated whether tick infestation patterns on songbirds are the result of an active choice by the ticks themselves, or the outcome of songbird grooming behaviour. Attachment patterns of three ixodid tick species with different ecologies and host specificities were studied on avian hosts. Ixodes arboricola, Ixodes ricinus and Ixodes frontalis were put on the head, belly and back of adult great tits (Parus major) and adult domestic canaries (Serinus canaria domestica) which were either restricted or not in their grooming capabilities. Without exception, ticks were eventually found on a bird’s head. When we gave ticks full opportunities to attach on other body parts – in the absence of host grooming – they showed lower attachment success. Moreover, ticks moved from these other body parts to the host's head when given the opportunity. This study provides evidence that the commonly observed pattern of ticks feeding on songbirds’ heads is the result of an adaptive behavioural strategy. Experimental data on a novel host species, the domestic canary, and a consistent number of published field observations, strongly support this hypothesis. We address some proximate and ultimate causes that may explain parasite preference for this body part in songbirds. The link found between parasite micro-habitat preference and host anti-parasite behaviour provides further insight into the mechanisms driving ectoparasite aggregation, which is important for the population dynamics of hosts, ectoparasites and the micro-pathogens for which they are vectors.     

On the relevance of abundance and spatial pattern for interpretations of host-parasite association data

The quantification of host-parasite associations from field data is a fundamental step towards understanding host-parasite and host-parasite-pathogen dynamics. For parasites that are not rigid host specialists, exemplified in this paper by ticks, the interpretation of host-parasite association data is difficult. Interpretations of tick collection records have largely assumed that off-host collection records offer a valid basis from which to make claims about the host specificity or generality of tick species. A simple simulation analysis of rudimentary tick-host interactions in a hypothetical 50 x 50-cell habitat demonstrates that perceptions of tick-host relationships can be strongly biased by spatial patterns. Regardless of their true level of host specificity or generality, it seems that: (i) more abundant ticks will be perceived as generalists, while rarer species will be considered specialists; and (ii) tick species that have patchy, strongly aggregated distributions will be more likely to be perceived as host specialists than species that have more dispersed or uniform distributions. Since all available evidence suggests that abundances and spatial patterns vary between tick species, there is no way of assessing the true validity of claims about host specificity without first undertaking detailed research on the relative abundances and spatial and temporal patterns of both tick and host distributions.     

Proteomic Analysis of Cattle Tick Rhipicephalus (Boophilus) microplus Saliva: A Comparison between Partially and Fully Engorged Females

The cattle tick Rhipicephalus (Boophilus) microplus is one of the most harmful parasites affecting bovines. Similarly to other hematophagous ectoparasites, R. microplus saliva contains a collection of bioactive compounds that inhibit host defenses against tick feeding activity. Thus, the study of tick salivary components offers opportunities for the development of immunological based tick control methods and medicinal applications. So far, only a few proteins have been identified in cattle tick saliva. The aim of this work was to identify proteins present in R. microplus female tick saliva at different feeding stages. Proteomic analysis of R. microplus saliva allowed identifying peptides corresponding to 187 and 68 tick and bovine proteins, respectively. Our data confirm that (i) R. microplus saliva is complex, and (ii) that there are remarkable differences in saliva composition between partially engorged and fully engorged female ticks. R. microplus saliva is rich mainly in (i) hemelipoproteins and other transporter proteins, (ii) secreted cross-tick species conserved proteins, (iii) lipocalins, (iv) peptidase inhibitors, (v) antimicrobial peptides, (vii) glycine-rich proteins, (viii) housekeeping proteins and (ix) host proteins. This investigation represents the first proteomic study about R. microplus saliva, and reports the most comprehensive Ixodidae tick saliva proteome published to date. Our results improve the understanding of tick salivary modulators of host defense to tick feeding, and provide novel information on the tick-host relationship.     

Assessment of the efficacy of parasiticides for the control of tick infection in dogs under field conditions: what's new?

For their biological and ecological characteristics, ticks are vectors of the widest variety of pathogens causing tick-borne diseases (TBDs). Little information is available about the ways in which time spent by ticks to feed on hosts, transmission times and TBD prevention are related and it is exclusively limited to laboratory reports on adult stages. In particular, the time required by immature stages to transmit pathogens has not been determined for most TBDs. Considering their importance for animal and human health, effective control of immature ticks is advisable to reduce the damage ticks cause. Recently, the efficacy of a combination of imidacloprid 10%/permethrin 50% was compared with that of fipronil 10%/S-methoprene 9% against ticks when administered to naturally infected dogs. A semi-quantitative method was used to assess the methodological parameters to calculate drug efficacy on immature stages. On adult ticks, the efficacy of both products was high and overall very similar, whereas for the immature stages the combination of imidacloprid 10% and permethrin 50% had a higher efficacy than fipronil 10% and methoprene 9% throughout the observation period (statistically significant difference on day + 28 only). The semi-quantitative method proposed for the evaluation of immature stages can be considered a useful tool for calculating the efficacy of a drug in the field. Due the important role of immatures in the spread of TBDs, the immature tick load should be calculated to assess the efficacy of acaricidal products both under laboratory and field conditions.     

Local host-tick coextinction in neotropical forest fragments

Ticks are obligatory parasites with complex life cycles that often depend on larger bodied vertebrates as final hosts. These traits make them particularly sensitive to local coextinction with their host. Loss of wildlife abundance and diversity should thus lead to loss of tick abundance and diversity to the point where only generalist tick species remain. However, direct empirical tests of these hypotheses are lacking, despite their relevance to our understanding of tick-borne disease emergence in disturbed environments. Here, we compare vertebrate and tick communities across 12 forest islands and peninsulas in the Panama Canal that ranged 1000-fold in size (2.6–2811.3?ha). We used drag sampling and camera trapping to directly assess the abundance and diversity of communities of questing ticks and vertebrate hosts. We found that the abundance and species richness of ticks were positively related to those of wildlife. Specialist tick species were only present in fragments where their final hosts were found. Further, less diverse tick communities had a higher relative abundance of the generalist tick species Amblyomma oblongoguttatum, a potential vector of spotted fever group rickettsiosis. These findings support the host-parasite coextinction hypothesis, and indicate that loss of wildlife can indeed have cascading effects on tick communities. Our results also imply that opportunities for pathogen transmission via generalist ticks may be higher in habitats with degraded tick communities. If these patterns are general, then tick identities and abundances serve as useful bioindicators of ecosystem health, with low tick diversity reflecting low wildlife diversity and a potentially elevated risk of interspecific disease transmission via remaining host species and generalist ticks.     

Tick antigens recognized by serum from a guinea pig resistant to infestation with the tick Rhipicephalus appendiculatus

Immune resistance to infestation by an ixodid tick, Rhipicephalus appendiculatus, the vector of the cattle disease East Coast Fever, was induced in a guinea pig by repeated tick infestation. This resistance is expressed as the ability of the host to interfere with tick feeding. Resistance to ixodid tick feeding is an acquired response mediated by host antibody. We report the use of antibodies from a resistant host animal, in immunoblotting, to characterize the tick antigens recognized. The major tick antigens identified had molecular weights of 120,000, 94,000, 88,000, 77,000, 58,000, 46,000, 35,000, 31,000, 28,000, 25,000, 20,000 and 16,000. Most of these antigens were found in tick salivary glands. The presence and concentration of many tick salivary antigens appeared to vary with relation to the tick feeding cycle. Many of the antigens present in salivary glands were also detected in tick cement. Tick gut extract, although a poorer source of antigens, contained more of the 31,000 dalton antigen than salivary glands. Larval and nymphal tick extract lacked many of the antigens present in adult ticks. The data suggest that tick resistance is a complex phenomenon probably elicited by several different tick antigens.     

The influence of host competition and predation on tick densities and management implications

Host community composition and biodiversity can limit and regulate tick abundance which can have profound impacts on the incidence and severity of tick-borne diseases. Our understanding of the relationship between host community composition and tick abundance is still very limited. Here, we present a novel mathematical model of a stage-structured tick population to study the influence of host behaviour and competition in the presence of heterospecifics and the influence of host predation on tick densities. We examine the influence of specific changes in biodiversity that modify the competition among and the predation on small and large host populations. We find that increasing biodiversity will not always reduce tick populations, but depends on changes in species composition affecting the degree and type competition among hosts, and the host the predation is acting on. With indirect competition, tick densities are not regulated by increasing biodiversity; however, with direct competition, increased biodiversity will regulate tick densities. Generally, we find that biodiversity will regulate tick densities when it affects tick-host encounter rates. We also find that predation on small hosts have a limited influence on reducing tick populations, but when the predation was on large hosts this increased the magnitude of tick population oscillations. Our results have tick-management implications: while controlling large host populations (e.g. deer) and adult ticks will decrease tick densities, measures that directly control the nymph ticks could also be effective.     

Spatial proximity and asynchronous refuge sharing networks both explain patterns of tick genetic relatedness among lizards,but in different years

A major question for understanding the ecology of parasite infections and diseases in wildlife populations concerns the transmission pathways among hosts. Network models are increasingly used to model the transmission of infections among hosts – however, few studies have integrated host behaviour and genetic relatedness of the parasites transmitted between hosts. In a study of the Australian sleepy lizard Tiliqua rugosa and its three‐host ixodid tick (Bothriocroton hydrosauri), we asked if patterns of genetic relatedness among ticks were best explained by spatial proximity or the host transmission network. Using synchronous GPS locations of over 50 adult lizards at 10 min intervals across the three‐month activity period, over 2 years, we developed two alternative parasite transmission networks. One alternative was based on the spatial proximity of lizards (at the centre of their home ranges), and the other was based on the frequency of asynchronous shared refuge use between pairs of lizards. In each year, adult ticks were removed from lizards and their genotypes were determined at four polymorphic microsatellite loci. Adult ticks collected from the same host were more related to each other than ticks from different hosts. Similarly, adult ticks collected from different lizards had a higher relatedness if those lizards had a shorter path length connecting them on each of the two networks we explored. The predictors of tick relatedness differed between years. In the first year, the asynchronous shared refuges network was the stronger predictor of tick relatedness, whereas in year two, the spatial proximity‐based network was the stronger predictor of tick relatedness. We speculate on how changing environmental conditions might change the relative importance of alternative processes driving the transmission of parasites.     

Vector-host interactions in disease transmission

Tick-borne spirochetes include borreliae that cause Lyme disease and relapsing fever in humans. They survive in a triangle of parasitic interactions between the spirochete and its vertebrate host, the spirochete and its tick vector, and the host and the tick. Until recently, the significance of vector-host interactions in the transmission of arthropod-borne disease agents has been overlooked. However, there is now compelling evidence that the pharmacological activity of tick saliva can have a profound effect on pathogen transmission both from infected tick to uninfected host, and from infected host to uninfected tick. The salivary glands of ticks provide a pharmacopoeia of anti-inflammatory, anti-haemostatic and anti-immune molecules. These include bioactive proteins that control histamine, bind immunoglobulins, and inhibit the alternative complement cascade. The effect of these molecules is to provide a privileged site at the tick-host interface in which borreliae and other tick-borne pathogens are sheltered from the normal innate and acquired host immune mechanisms that combat infections. Understanding the key events at the tick vector-host interface, that promote spirochete infection and transmission, will provide a better understanding of the epidemiology and ecology of these important human pathogens.     

Experimental evidence for host preference in a tick parasitizing songbird nestlings

Mechanisms of host preference in ectoparasites are important to the understanding of host‐parasite interactions. Since ectoparasites negatively affect the condition of their hosts, while the hosts’ condition itself may affect the parasites’ choice, separating the factors that drive host preference from parasite impact asks for experiments. We combined the data of two choice experiments to investigate the preference of the nidicolous tick Ixodes arboricola when exposed to the nestlings of a passerine bird (Parus major). In the first experiment, in which complete broods at hatching were exposed to an ecologically relevant number of ticks, the relationship between tick loads and nestlings’ developmental status was characterized by a distribution with the highest tick loads on the more developed nestlings. Host preference became more apparent at a smaller brood size, suggesting a role for host density. In a second experiment we evaluated host choice in a pairwise choice experiment, exposing pairs of siblings with contrasting developmental status to eight ticks. In the first and the second pair, a median developed nestling was linked with the most developed and the least developed nestling, respectively. Seventy‐two h after tick exposure we measured the innate constitutive humoral immunity and haematocrit. No differences were found in innate immunity, but the least developed nestlings had on average a lower haematocrit than the median and most developed nestlings. Significantly fewer ticks attached on the least developed nestling compared to the median nestling, and this difference was more pronounced when the innate immunity of the median developed nestling was higher. No difference in tick load was found among the median and best developed nestlings. The linkage between host preference and host physiological condition provide further insight in the mechanisms driving ectoparasite aggregation, which is important for the population dynamics of host, ticks and tick‐transmitted pathogens.     

Reviewing the ecological evidence base for management of emerging tropical zoonoses: Kyasanur Forest Disease in India as a case study

Zoonoses disproportionately affect tropical communities and are associated with human modification and use of ecosystems. Effective management is hampered by poor ecological understanding of disease transmission and often focuses on human vaccination or treatment. Better ecological understanding of multi-vector and multi-host transmission, social and environmental factors altering human exposure, might enable a broader suite of management options. Options may include “ecological interventions” that target vectors or hosts and require good knowledge of underlying transmission processes, which may be more effective, economical, and long lasting than conventional approaches. New frameworks identify the hierarchical series of barriers that a pathogen needs to overcome before human spillover occurs and demonstrate how ecological interventions may strengthen these barriers and complement human-focused disease control. We extend these frameworks for vector-borne zoonoses, focusing on Kyasanur Forest Disease Virus (KFDV), a tick-borne, neglected zoonosis affecting poor forest communities in India, involving complex communities of tick and host species. We identify the hierarchical barriers to pathogen transmission targeted by existing management. We show that existing interventions mainly focus on human barriers (via personal protection and vaccination) or at barriers relating to Kyasanur Forest Disease (KFD) vectors (tick control on cattle and at the sites of host (monkey) deaths). We review the validity of existing management guidance for KFD through literature review and interviews with disease managers. Efficacy of interventions was difficult to quantify due to poor empirical understanding of KFDV–vector–host ecology, particularly the role of cattle and monkeys in the disease transmission cycle. Cattle are hypothesised to amplify tick populations. Monkeys may act as sentinels of human infection or are hypothesised to act as amplifying hosts for KFDV, but the spatial scale of risk arising from ticks infected via monkeys versus small mammal reservoirs is unclear. We identified 19 urgent research priorities for refinement of current management strategies or development of ecological interventions targeting vectors and host barriers to prevent disease spillover in the future.     

Advances in the genomics of ticks and tick-borne pathogens

Ticks and the diseases for which they are vectors engage in complex interactions with their mammalian hosts. These interactions involve the developmental processes of tick and pathogen, and interplay between the defensive responses and counter responses of host, tick and pathogen. Understanding these interactions has long been an intractable problem, but progress is now being made thanks to the flood of genomic information on host, tick and pathogen, and the attendant, novel experimental tools that have been generated. Each advance reveals new levels of complexity, but there are encouraging signs that genomics is leading to novel means of parasite control.     

Stage-structured infection transmission and a spatial epidemic: a model for Lyme disease

A greater understanding of the rate at which emerging disease advances spatially has both ecological and applied significance. Analyzing the spread of vector-borne disease can be relatively complex when the vector's acquisition of a pathogen and subsequent transmission to a host occur in different life stages. A contemporary example is Lyme disease. A long-lived tick vector acquires infection during the larval blood meal and transmits it as a nymph. We present a reaction-diffusion model for the ecological dynamics governing the velocity of the current epidemic's spread. We find that the equilibrium density of infectious tick nymphs (hence the risk of human disease) can depend on density-independent survival interacting with biotic effects on the tick's stage structure. The local risk of infection reaches a maximum at an intermediate level of adult tick mortality and at an intermediate rate of juvenile tick attacks on mammalian hosts. If the juvenile tick attack rate is low, an increase generates both a greater density of infectious nymphs and an increased spatial velocity. However, if the juvenile attack rate is relatively high, nymph density may decline while the epidemic's velocity still increases. Velocities of simulated two-dimensional epidemics correlate with the model pathogen's basic reproductive number (R0), but calculating R0 involves parameters of both host infection dynamics and the vector's stage-structured dynamics.     

Impact of biodiversity and seasonality on Lyme-pathogen transmission

Lyme disease imposes increasing global public health challenges. To better understand the joint effects of seasonal temperature variation and host community composition on the pathogen transmission, a stage-structured periodic model is proposed by integrating seasonal tick development and activity, multiple host species and complex pathogen transmission routes between ticks and reservoirs. Two thresholds, one for tick population dynamics and the other for Lyme-pathogen transmission dynamics, are identified and shown to fully classify the long-term outcomes of the tick invasion and disease persistence. Seeding with the realistic parameters, the tick reproduction threshold and Lyme disease spread threshold are estimated to illustrate the joint effects of the climate change and host community diversity on the pattern of Lyme disease risk. It is shown that climate warming can amplify the disease risk and slightly change the seasonality of disease risk. Both the “dilution effect” and “amplification effect” are observed by feeding the model with different possible alternative hosts. Therefore, the relationship between the host community biodiversity and disease risk varies, calling for more accurate measurements on the local environment, both biotic and abiotic such as the temperature and the host community composition.     

Tick-host immunology: Significant advances and challenging opportunities

Immunological interactions at the tick-host interface involve innate and acquired host defenses against infestation and immunomodulatory countermeasures by the tick. The cellular and molecular immunological bases of these host-parasite relationships are being defined. Acquired resistance to tick infestation involves humoral and cellular immunoregulatory and effector pathways. Ticks respond by suppressing antibody production, complement, and cytokine elaboration by both antigen-presenting cells and specific T-cell subsets. Tick-borne disease-causing agents probably exploit tick suppression of host defenses during transmission and initiation of infection. Because of the public health importance of ticks and Pick-borne diseases, it is crucial that we understand these interactions and exploit them in novel immunological control strategies. Here, Stephen Wikel and Douglas Bergman discuss recent advances in understanding tick-host immunology and propose future studies.     

Simulation of climate‐tick‐host‐landscape interactions: Effects of shifts in the seasonality of host population fluctuations on tick densities

Tick vector systems are comprised of complex climate‐tick‐host‐landscape interactions that are difficult to identify and estimate from empirical observations alone. We developed a spatially‐explicit, individual‐based model, parameterized to represent ecological conditions typical of the south‐central United States, to examine effects of shifts in the seasonal occurrence of fluctuations of host densities on tick densities. Simulated shifts in the seasonal occurrence of periods of high and low host densities affected both the magnitude of unfed tick densities and the seasonality of tick development. When shifting the seasonal densities of all size classes of hosts (small, medium, and large) synchronously, densities of nymphs were affected more by smaller shifts away from the baseline host seasonality than were densities of larval and adult life stages. When shifting the seasonal densities of only a single size‐class of hosts while holding other size classes at their baseline levels, densities of larval, nymph, and adult life stages responded differently. Shifting seasonal densities of any single host‐class earlier resulted in a greater increase in adult tick density than when seasonal densities of all host classes were shifted earlier simultaneously. The mean densities of tick life stages associated with shifts in host densities resulted from system‐level interactions of host availability with tick phenology. For example, shifting the seasonality of all hosts ten weeks earlier resulted in an approximately 30% increase in the relative degree of temporal co‐occurrence of actively host‐seeking ticks and hosts compared to baseline, whereas shifting the seasonality of all hosts ten weeks later resulted in an approximately 70% decrease compared to baseline. Differences among scenarios in the overall presence of active host‐seeking ticks in the system were due primarily to the degree of co‐occurrence of periods of high densities of unfed ticks and periods of high densities of hosts.