Tick vaccines and the transmission of tick-borne pathogens

Ticks transmit pathogens that cause diseases which greatly impact both human and animal health. Vaccines developed against Boophilus spp. using Bm86 and Bm95 tick gut antigens demonstrated the feasibility of using vaccines for control of tick infestations. These vaccines also reduced transmission of tick-borne pathogens by decreasing exposure of susceptible hosts to ticks. The recently discovered tick antigens, 64P putative cement protein and subolesin involved in the regulation of tick feeding and reproduction, were also shown to reduce tick infestations. These antigens, together with the TROSPA receptor for Burrelia burgdorferi OspA were effective against tick-borne pathogens by reducing the infection levels in ticks and/or the transmission of the pathogen. Development of a vaccine targeted at both the tick vector and pathogen would contribute greatly to the control of tick infestations and the transmission of tick-borne diseases. These results have demonstrated that tick vaccines can be developed for control tick infestations and show promise for the prevention of the transmission of tick-borne pathogens.     

Targeting the Tick/Pathogen Interface for Developing New Anaplasmosis Vaccine Strategies

Bovine anaplasmosis is a tick-borne hemolytic disease of cattle that occurs worldwide caused by the intraerythrocytic rickettsiae Anaplasma marginale. Control measures, including use of acaricides, administration of antibiotics and vaccines, have varied with geographic location. Our research is focused on the tick-pathogen interface for development of new vaccine strategies with the goal of reducing anaplasmosis, tick infestations and the vectorial capacity of ticks. Toward this approach, we have targeted (1) development of an A. marginale cell culture system to provide a non-bovine antigen source, (2) characterization of an A. marginale adhesion protein, and (3) identification of key tick protective antigens for reduction of tick infestations. A cell culture system for propagation of A. marginale was developed and provided a non-bovine source of A. marginale vaccine antigen. The A. marginale adhesion protein, MSP1a, was characterized and use of recombinant MSP1a in vaccine formulations reduced clinical anaplasmosis and infection levels in ticks that acquired infection on immunized cattle. Most recently, we identified a tick-protective antigen, subolesin, that reduced tick infestations, as well as the vectorial capacity of ticks for acquisition and transmission of A marginale. This integrated approach to vaccine development shows promise for developing new strategies for control of bovine anaplasmosis.     

A ten-year review of commercial vaccine performance for control of tick infestations on cattle

Ticks are important ectoparasites of domestic and wild animals, and tick infestations economically impact cattle production worldwide. Control of cattle tick infestations has been primarily by application of acaricides which has resulted in selection of resistant ticks and environmental pollution. Herein we discuss data from tick vaccine application in Australia, Cuba, Mexico and other Latin American countries. Commercial tick vaccines for cattle based on the Boophilus microplus Bm86 gut antigen have proven to be a feasible tick control method that offers a cost-effective, environmentally friendly alternative to the use of acaricides. Commercial tick vaccines reduced tick infestations on cattle and the intensity of acaricide usage, as well as increasing animal production and reducing transmission of some tick-borne pathogens. Although commercialization of tick vaccines has been difficult owing to previous constraints of antigen discovery, the expense of testing vaccines in cattle, and company restructuring, the success of these vaccines over the past decade has clearly demonstrated their potential as an improved method of tick control for cattle. Development of improved vaccines in the future will be greatly enhanced by new and efficient molecular technologies for antigen discovery and the urgent need for a tick control method to reduce or replace the use of acaricides, especially in regions where extensive tick resistance has occurred.     

Functional genomics and evolution of tick–Anaplasma interactions and vaccine development

The genus Anaplasma (Rickettsiales: Anaplasmataceae) includes several tick-transmitted pathogens that impact veterinary and human health. Tick-borne pathogens cycle between tick vectors and vertebrate hosts and their interaction is mediated by molecular mechanisms at the tick–pathogen interface. These mechanisms have evolved characteristics that involve traits from both the tick vector and the pathogen to insure their mutual survival. Herein, we review the information obtained from functional genomics and genetic studies to characterize the tick–Anaplasma interface and evolution of A. marginale and A. phagocytophilum. Anaplasma and tick genes and proteins involved in tick–pathogen interactions were characterized. The results of these studies demonstrated that common and Anaplasma species-specific molecular mechanism occur by which pathogen and tick cell gene expression mediates or limits Anaplasma developmental cycle and trafficking through ticks. These results have advanced our understanding of the biology of tick–Anaplasma interactions and have opened new avenues for the development of improved methods for the control of tick infestations and the transmission of tick-borne pathogens.     

Targeting arthropod subolesin/akirin for the development of a universal vaccine for control of vector infestations and pathogen transmission

Diseases caused by arthropod-borne pathogens greatly impact on human and animal health. Recent research has provided evidence that tick protective antigens can be used for development of vaccines with the dual target of controlling arthropod infestations and reducing their vector capacity for pathogens. As reviewed herein, protective antigens such as subolesin/akirin, which are highly conserved across vector species, show promise for use in development of a universal vaccine for the control of arthropod infestations and the reduction of pathogen transmission. However, further research is needed in critical areas towards achieving this goal.     

Targeting the tick/pathogen interface for developing new anaplasmosis vaccine strategies

Bovine anaplasmosis is a tick-borne hemolytic disease of cattle that occurs worldwide caused by the intraerythrocytic rickettsiae Anaplasma marginale. Control measures, including use of acaricides, administration of antibiotics and vaccines, have varied with geographic location. Our research is focused on the tick-pathogen interface for development of new vaccine strategies with the goal of reducing anaplasmosis, tick infestations and the vectorial capacity of ticks. Toward this approach, we have targeted (1) development of an A. marginale cell culture system to provide a non-bovine antigen source, (2) characterization of an A. marginale adhesion protein, and (3) identification of key tick protective antigens for reduction of tick infestations. A cell culture system for propagation of A. marginale was developed and provided a non-bovine source of A. marginale vaccine antigen. The A. marginale adhesion protein, MSP1a, was characterized and use of recombinant MSP1a in vaccine formulations reduced clinical anaplasmosis and infection levels in ticks that acquired infection on immunized cattle. Most recently, we identified a tick-protective antigen, subolesin, that reduced tick infestations, as well as the vectorial capacity of ticks for acquisition and transmission of A marginale. This integrated approach to vaccine development shows promise for developing new strategies for control of bovine anaplasmosis.     

An <Emphasis Type="Italic">in-vivo</Emphasis> study of the efficacy and safety of ethno-veterinary remedies used to control cattle ticks by rural farmers in the Eastern Cape Province of South Africa

Ticks feed on blood, are vectors of tick-borne diseases and cause considerable skin damage to livestock. They are commonly controlled using commercial acaricides, which are expensive to the rural farmers, causing them to resort to alternative tick control methods. The objective of this study was to assess the acaricidal properties and safety of some materials (Ptaeroxylon obliquum, Aloe ferox, Lantana camara, Tagetes minuta, Used engine oil and Jeyes fluid, used by rural farmers to control cattle ticks in the Eastern Cape Province, South Africa. A total of 52 cattle were divided into 13 experimental groups with 4 cattle in each. Jeyes fluid at 76.8% concentration and Used engine oil had an efficacy that was almost similar to that of the positive control Ektoban® (Cymiazol 17.5 and cypermethrin 2.5%). Extracts of L. camara at 40% concentration had an efficacy of 57% while A. ferox, P. obliquum and T. minuta were not effective. The test materials had no irritation effect on rats. The study revealed that the materials rural farmers use as acaricides vary in their efficacy in controlling ticks.     

Disease at the wildlife-livestock interface: Acaricide use on domestic cattle does not prevent transmission of a tick-borne pathogen with multiple hosts

Several prominent and economically important diseases of livestock in East Africa are caused by multi-host pathogens that also infect wildlife species, but management strategies are generally livestock focused and models of these diseases tend to ignore the role of wildlife. We investigate the dynamics of a multi-host tick-borne disease in order to assess the efficacy of tick control from an ecological perspective. We examined the efficacy of a widespread measure of tick control and developed a model to explore how changes in the population of ticks due to control measures on cattle impact dynamics of Theileria parva infection in a system with two primary host species, cattle and Cape buffalo (Syncerus caffer). We show that the frequency of acaricide application has a significant impact on the tick population both on the host and in the environment, which can greatly reduce the pathogen load in cattle. We also demonstrate that reducing the tick population through cattle-related control measures is not sufficient to diminish disease transmission in buffalo. Our results suggest that under current control strategies, which target ticks on cattle only, T. parva is likely to remain a significant problem in East Africa, and require the continued use of acaricides, which has significant economic and ecological consequences.     

Beyond Lyme: aetiology of tick-borne human diseases with emphasis on the south-eastern United States

Since its emergence in the north-eastern and upper mid-western United States in the 1970s, Lyme disease, caused by Borrelia burgdorferi, has captured the public's attention as the nation's most prevalent vector-borne zoonotic disease. In contrast, recent publications on tick-pathogen systems in the eastern United States, and findings from Department of Defense investigations of ticks found biting military personnel, indicate that residents of the south-eastern United States are primarily at risk from emerging diseases caused by tick-borne pathogens other than B.?burgdorferi. The risk of contracting these diseases varies greatly among states as a consequence of regional variation in the abundance of the key vector tick species. Moreover, this risk is changing, because tick distributions are in flux. To improve health outcomes, health providers need better information and awareness regarding which tick species bite humans in each state and which zoonotic pathogens are prevalent in these ticks. Effective diagnosis, treatment, control and reporting of tick-borne disease in the south-eastern United States require that health providers think 'beyond Lyme' and consider the marked regional differences in the tick species that bite humans and in the pathogens that these ticks carry.     

Evaluation of glycoproteins purified from adult and larval camel ticks (Hyalomma dromedarii) as a candidate vaccine

In order to identify antigens that can help prevent camel tick infestations, three major glycoproteins (GLPs) about 97, 66 and 40 kDa in size were purified from adult and larval Egyptian ticks, Hyalomma (H.) dromedarii, using a single-step purification method with Con-A sepharose. The purified GLPs were evaluated as vaccines against camel tick infestation in rabbits. The rabbits received three intramuscular inoculations of GLPs (20 µg/animal) on days 0, 14, and 28. In the immunoblot analysis, Sera from the immunized rabbits recognized the native GLPs and other proteins from larval and adult H. dromedarii ticks along with those from other tick species such as Rhipicephalus sanguineus but not Ornithodoros moubata. The effects of immunity induced by these GLPs were determined by exposing rabbits to adult H. dromedarii ticks. These results demonstrated that GLP immunization led to a slightly decreased reproductive index and significantly reduced rates of egg hatchability. These results demonstrated that immunization with the purified GLPs can provide protection against infestation by H. dromedarii and some other tick species. Further studies are needed to confirm the effectiveness of immunization with GLPs against other tick species.     

Prevalence and risk factors associated with <Emphasis Type="Italic">Theileria parva</Emphasis> infection in cattle in three regions of Tanzania

Ticks and tickborne diseases (TBDs) are serious constraints to cattle production in Tanzania and other tropical and subtropical countries. Among the TBDs, East Coast fever (ECF) is the most important as it causes significant economic losses to the cattle industry in Tanzania. However, control of ECF in Tanzania has continued to be a challenge due to inadequate epidemiological information. The main objective of this study was to determine the epidemiological situation of Theileria parva infections in cattle kept under pastoral and agro-pastoral farming systems in Mara, Singida, and Mbeya regions of Tanzania. Blood samples were collected from 648 cattle in the three regions. Genomic DNA was extracted and amplified in a polymerase chain reaction (PCR) using T. parva-specific primers targeting the 104-kD antigen (P104) gene. In addition, information was collected on the possible risk factors of T. parva infection (animal age, region, animal sex, tick burden, tick control method, and frequency of acaricide application). The prevalence of T. parva across the three regions was 14.2%. There was variation in prevalence among the three regions with Mara (21.8%) having a significantly higher (p = 0.001) prevalence than the other regions. Moreover, Mbeya exhibited relatively lower prevalence (7.4%) compared to the other regions. Factors found to be significantly associated with an animal being PCR positive for T. parva were region (p = 0.001) and tick burden (p = 0.003). Other factors were not found to be significant predictors of being PCR positive for T. parva. The present study showed high variation in tick burden and T. parva prevalence across the regions. Therefore, different strategic planning and cost-effective control measures for ticks and T. parva infection should be implemented region by region in order to reduce losses caused by ticks and ECF in the study area.     

Subolesin/akirin orthologs from Ornithodoros spp. soft ticks: cloning, RNAi gene silencing and protective effect of the recombinant proteins

Subolesin/akirin is a well characterized protective antigen highly conserved across vector species and thus potentially useful for the development of a broad-spectrum vaccine for the control of arthropod infestations including hard ticks, mosquitoes, sand flies and the poultry red mite Dermanyssus gallinae. Soft ticks could be also targeted by this vaccine if proved that the soft tick subolesin orthologs are conserved and induce protective immune responses too. However, to date no soft tick subolesin orthologs have been fully characterized nor tested as recombinant antigens in vaccination trials. The objectives of the present work were to clone and characterize the subolesin orthologs from two important vector species of soft ticks as Ornithodoros erraticus and O. moubata, to evaluate the effect of subolesin gene silencing by RNAi, and to test the protective value of the recombinant antigens in vaccination trials. The obtained results demonstrate that both soft tick subolesins are highly conserved showing more than 69% and 74% identity with those of hard ticks in their nucleotide and amino acid sequences, respectively. Additionally, we demonstrate that both soft ticks possess fully operative RNAi machinery, and that subolesin gene silencing by dsRNA injection inhibits oviposition indicating the involvement of subolesin in tick reproduction. Finally, vaccination with the recombinant soft tick subolesins induced a partial protective effect resulting in the reduction of the oviposition rate. These preliminary results encourage further studies on the use of recombinant subolesins as vaccines for the control of soft tick infestations, either alone or in combination with other specific molecules.     

蜱半胱氨酸蛋白酶抑制分子研究进展

蜱是以吸血为生的体外寄生虫,能传播多种病原体。控制蜱的传统方法是使用杀虫剂,但会产生药物残留等问题。为了找到控制蜱及蜱传病的新方法,必须在分子水平上了解蜱的相关生理过程。蜱半胱氨酸蛋白酶抑制分子是一类抗蛋白酶分子,主要作用于半胱氨酸蛋白酶的抑制调控。论文介绍了蜱半胱氨酸蛋白酶抑制分子的结构和分类,以及在蜱的吸血、血液消化、蜱的先天免疫及对宿主免疫调节等生理过程的重要作用,同时也综述了半胱氨酸蛋白酶抑制分子具有抗寄生虫和抗癌的作用,为全面了解蜱半胱氨酸蛋白酶抑制分子提供参考。     

Molecular identification of tick-borne pathogens in Nigerian ticks

A molecular epidemiology investigation was undertaken in two Nigerian states (Plateau and Nassarawa) to determine the prevalence of pathogens of veterinary and public health importance associated with ticks collected from cattle and dogs using PCR, cloning and sequencing or reverse line blot techniques. A total of 218 tick samples, Amblyomma variegatum (N=153), Rhipicephalus (Boophilus) decoloratus (N=45), and Rhipicephalus sanguineus (N=20) were sampled. Pathogens identified in ticks included piroplasmids (Babesia spp., Babesia bigemina and Babesia divergens), Anaplasma marginale and Rickettsia africae. Piroplasmids were identified in A. variegatum, A. marginale was found in R. decoloratus, while R. africae was detected in all tick species examined. Ehrlichia spp. and Theileria spp. were not identified in any of the ticks examined. Of the 218 ticks examined, 33 (15.1%) contained pathogen DNA, with the presence of B. divergens and R. africae that are zoonotic pathogens of public health and veterinary importance. The variety of tick-borne pathogens identified in this study suggests a risk for the emergence of tick-borne diseases in domestic animals and humans, especially amongst the Fulani pastoralists in Plateau and Nassarawa states of Nigeria.     

Modelling bovine babesiosis: a tool to simulate scenarios for pathogen spread and to test control measures for the disease

Tick-borne diseases are of increasing concern in many countries, particularly as a consequence of changes in land use and climate. Ticks are vectors of numerous pathogens (viruses, bacteria, protozoa) that can be harmful to humans and animals. In the context of animal health, bovine babesiosis poses a recurrent threat to cattle herds. In this study, we use a modeling approach to investigate the spread of babesiosis and evaluate control measures. A previously developed tick population dynamics model (here, Ixodes ricinus) is coupled with a pathogen spread model (here, the protozoan Babesia divergens), which describes pathogen spread in a dairy herd through the following processes: transmission, acquisition, transovarial transmission, transstadial persistence, and clearance of the pathogen. An assessment of the simulated B. divergens prevalence levels in ticks and cattle in the context of existing knowledge and data suggested that the model provides a realistic representation of pathogen spread. The model was then used to evaluate the influence of host density and the effect of acaricides on B. divergens prevalence in cattle. Increasing deer density results in an increase in prevalence in cattle whereas increasing cattle stocking rate results in a slight decrease. A potential increase in deer density would thus have an amplification effect on disease spread due to the increase in the number of infected ticks. Regular use of acaricides produces a reduction in pathogen prevalence in cattle. This model could be adapted to other tick-borne diseases.     

Emerging perspectives in the research of bovine babesiosis and anaplasmosis

The Babesia bovis and B. bigemina apicomplexan protozoa in conjunction with the rickettsia Anaplasma marginale are intraerythrocytic pathogens that are responsible for the most prevalent and costly tick borne diseases (TBD's) of cattle worldwide. These organisms are historically associated as they can cause clinically related hemolytic diseases in cattle, are all transmitted by Rhiphicephallus (Boophilus) ticks, and share an uncanny ability to evade the immune systems of the vertebrate hosts, causing persistent disease. In addition, acute babesiosis and anaplasmosis can be prevented quite effectively by combining tick control and vaccination with living attenuated organisms. However these methods of control have numerous limitations and improved approaches are needed. Importantly, immunizations of cattle with inactivated experimental Babesia and Anaplasma vaccines can elicit variable degrees of protection, indicating the feasibility for the development of inactivated or subunit vaccines. A new research toolbox that includes full genome sequencing combined with the improved ability to genetically modify the organisms is enhancing our understanding of their biology. An emerging paradigm is the use of recently developed Babesia and Anaplasma transfection methods for functional gene characterizations and for vaccine development. Promising recently identified subunit vaccine candidates are also emerging, including babesial proteases, putative rhoptry, microneme, and sexual stage antigens, as well as subdominant, conserved, A. marginale outer membrane major surface proteins. However, significant knowledge gaps on the role of key parasite molecules involved in cell invasion, adhesion, asexual and sexual reproduction, tick transmission, and evasion of the immune system, remain. A better understanding of the biology of these organisms and the protective immune responses will positively contribute toward the goal of developing improved immunological and pharmacological interventions against these elusive pathogens that are responsible for the most devastating TBD's of cattle. Importantly, the currently available research toolbox provides basic research instruments for helping close current knowledge gaps which will aid the design and production of effective vaccines and alternative pharmacological interventions.     

The effect of the bont tick (Amblyomma hebraeum) on the weight gain of Africander steers

The effects of the bont tick Amblyomma hebraeum on the productivity of cattle need to be quantified in order to design economically optimal control programs. Liveweight gains (LWGs) of three groups of Africander steers, maintained in the same pasture and exposed to zero, medium or high numbers of larvae, nymphs and adults of the tick, were measured. Larvae and nymphs had no significant effect on LWG but adults had a large, statistically significant effect (P less than 0.05). The tick-free group had an average LWG of 20 kg more than the heavily infested group after 3.5 months. No mortality was recorded from ticks or tick-borne diseases during the experiment. There was no relationship between the number of engorging adult female ticks counted and loss of LWG of individual animals. The latter suggests that exposure to ticks as well as engorgement by female ticks causes losses. The loss per adult female that completed engorgement was estimated, by relating the LWGs of individual animals to their tick infestations, to be 4 +/- 2 g per adult female tick. An alternative estimate, made by comparing the average LWG and tick infestations of each treatment group, was equal to 10 +/- 4 g. This latter estimate includes the effect of challenge (and rejection) as well as tick feeding and so was accepted as giving the best estimate. Screw-worm fly (Chrysomya bezziana) struck an average of 7.5% of the cattle infested with ticks in any week but the effects on the productivity of the cattle were minimized by immediate treatment. There was a significant, positive correlation between the incidence of screw-worm fly strike and the numbers of adult ticks counted on the experimental animals. The results provide data for calculating losses caused by A. hebraeum in different parts of its geographical range.     

Anaplasmosis in Cattle in Italy

Bovine anaplasmosis caused by Anaplasma marginale is a disease transmitted by ticks belonging to the Ixodidae family. Southern Italy is considered an endemic zone but environmental and social factors are changing the epidemiology of the disease to expand to previously anaplasmosis-free regions. The available data of published reports of anaplasmosis in Italy together with the data obtained by the National Centre of Reference for Anaplasma, Babesia, Rickettsia and Theileria (C.R.A.Ba.R.T.), allowed to report A. marginale infection in different Italian regions (Lazio, Marche, Campania, Puglia, Basilicata, Calabria, Lombardy, Tuscany, Umbria and Sicily). Cattle are also subject to infection with the related Ixodes ricinus-transmitted pathogen, Anaplasma phagocytophilum that results in reduced milk production in cattle. A. phagocytophilum infect also small ruminants, domestic and wild animals and causes the human granulocytic anaplasmosis. Different studies have been conducted on the presence of A. phagocytophilum in Italy both in the tick vectors and in the wild and domestic reservoirs. Contrary to A. marginale, the prevalence of A. phagocytophilum embraces the whole Italian territory from the Alps to the southern and insular regions.