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Flaviviruses such as dengue virus (DENV), Zika virus (ZIKV), and yellow fever virus (YFV) are spread by mosquitoes and cause human disease and mortality in tropical areas. In contrast, Powassan virus (POWV), which causes severe neurologic illness, is a flavivirus transmitted by ticks in temperate regions of the Northern hemisphere. We find serologic neutralizing activity against POWV in individuals living in Mexico and Brazil. Monoclonal antibodies P002 and P003, which were derived from a resident of Mexico (where POWV is not reported), neutralize POWV lineage I by recognizing an epitope on the virus envelope domain III (EDIII) that is shared with a broad range of tick- and mosquito-borne flaviviruses. Our findings raise the possibility that POWV, or a flavivirus closely related to it, infects humans in the tropics., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The One Health approach, which integrates the health of humans, animals, plants, and ecosystems at various levels, is crucial for addressing interconnected health threats. This is complemented by the advent of mRNA vaccines, which have revolutionized disease prevention. They offer broad-spectrum effectiveness and can be rapidly customized to target specific pathogens. Their utility extends beyond human medicine, showing potential in veterinary practices to control diseases and reduce the risk of zoonotic transmissions. This review place mRNA vaccines and One Health in the context of tick-borne diseases. The potential of these vaccines to confer cross-species immunity is significant, potentially disrupting zoonotic disease transmission cycles and protecting the health of both humans and animals, while reducing tick populations, infestations and circulation of pathogens. The development and application of mRNA vaccines for tick and tick-borne pathogens represent a comprehensive strategy in global health, fostering a healthier ecosystem for all species in our interconnected world., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 González-Cueto, de la Fuente and López-Camacho.)

The recent recognition of a syndrome of tick-acquired mammalian meat allergy has transformed the previously held view that mammalian meat is an uncommon allergen. The syndrome, mediated by IgE antibodies against the oligosaccharide galactose-alpha-1,3-galactose (alpha-gal), can also involve reactions to visceral organs, dairy, gelatin and other products, including medications sourced from non-primate mammals. Thus, fittingly, this allergic disorder is now called the alpha-gal syndrome (AGS). The syndrome is strikingly regional, reflecting the important role of tick bites in sensitization, and is more common in demographic groups at risk of tick exposure. Reactions in AGS are delayed, often by 2-6 h after ingestion of mammalian meat. In addition to classic allergic symptomatology such as urticaria and anaphylaxis, AGS is increasingly recognized as a cause of isolated gastrointestinal morbidity and alpha-gal sensitization has also been linked with cardiovascular disease. The unusual link with tick bites may be explained by the fact that allergic cells and mediators are mobilized to the site of tick bites and play a role in resistance against ticks and tick-borne infections. IgE directed to alpha-gal is likely an incidental consequence of what is otherwise an adaptive immune strategy for host defense against endo- and ectoparasites, including ticks., (© 2024 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: IgE to galactose alpha-1,3 galactose (alpha-gal) causes alpha-gal syndrome (delayed anaphylaxis after ingestion of mammalian meat). Development of sensitization has been attributed to tick bites; however, the possible role of other parasites has not been well studied., Objective: Our aims were to assess the presence, relative abundances, and site of localization of alpha-gal-containing proteins in common ectoparasites and endoparasites endemic in an area of high prevalence of alpha-gal syndrome, as well as to investigate the ability of ascaris antigens to elicit a reaction in a humanized rat basophil in vitro sensitization model., Methods: Levels of total IgE, Ascaris-specific IgE, and alpha-gal IgE were measured in sera from patients with challenge-proven alpha-gal syndrome and from controls without allergy. The presence, concentration, and localization of alpha-gal in parasites were assessed by ELISA, Western blotting, and immunohistochemistry. The ability of Ascaris lumbricoides antigen to elicit IgE-dependent reactivity was demonstrated by using the RS-ATL8 basophil reporter system., Results: Alpha-gal IgE level correlated with A lumbricoides-specific IgE level. Alpha-gal protein at 70 to 130 kDa was detected in A lumbricoides at concentrations higher than those found in Rhipicephalus evertsi and Amblyomma hebraeum ticks. Immunohistochemistry was used to localize alpha-gal in tick salivary acini and the helminth gut. Non-alpha-gal-containing A lumbricoides antigens activated RS-ATL8 basophils primed with serum from subjects with alpha-gal syndrome., Conclusion: We demonstrated the presence, relative abundances, and site of localization of alpha-gal-containing proteins in parasites. The activation of RS-ATL8 IgE reporter cells primed with serum from subjects with alpha-gal syndrome on exposure to non-alpha-gal-containing A lumbricoides proteins indicates a possible role of exposure to A lumbricoides in alpha-gal sensitization and clinical reactivity., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Dromedaries are an important livestock, used as beasts of burden and for meat and milk production. However, they can act as an intermediate source or vector for transmitting zoonotic viruses to humans, such as the Middle East respiratory syndrome coronavirus (MERS-CoV) or Crimean-Congo hemorrhagic fever virus (CCHFV). After several outbreaks of CCHFV in the Arabian Peninsula, recent studies have demonstrated that CCHFV is endemic in dromedaries and camel ticks in the United Arab Emirates (UAE). There is no apparent disease in dromedaries after the bite of infected ticks; in contrast, fever, myalgia, lymphadenopathy, and petechial hemorrhaging are common symptoms in humans, with a case fatality ratio of up to 40%. We used the in-solution hybridization capture of 100 annotated immune genes to genotype 121 dromedaries from the UAE tested for seropositivity to CCHFV. Through univariate linear regression analysis, we identified two candidate genes belonging to the innate immune system: FCAR and CLEC2B. These genes have important functions in the host defense against viral infections and in stimulating natural killer cells, respectively. This study opens doors for future research into immune defense mechanisms in an enzootic host against an important zoonotic disease.

An anti-tick mRNA cocktail vaccine promotes tick detachment and prevents transmission of tick-borne infection in guinea pigs (Sajid et al. ).

A peptide from the P0 acidic ribosomal protein (pP0) of ticks conjugated to keyhole limpet hemocyanin from Megathura crenulata has shown to be effective against different tick species when used in host vaccination. Turning this peptide into a commercial anti-tick vaccine will depend on finding the appropriate, technically and economically feasible way to present it to the host immune system. Two conjugates (p64K-Cys 1 pP0 and p64K-βAla 1 pP0) were synthesized using the p64K carrier protein from Neisseria meningitidis produced in Escherichia coli, the same cross-linking reagent, and two analogues of pP0. The SDS-PAGE analysis of p64K-Cys 1 pP0 showed a heterogeneous conjugate compared to p64K-βAla 1 pP0 that was detected as a protein band at 91kDa. The pP0/p64K ratio determined by MALDI-MS for p64K-Cys 1 pP0 ranged from 1 to 8, being 3-5 the predominant ratio, while in the case of p64K-βAla 1 pP0 this ratio was 5-7. Cys 1 pP0 was partially linked to 35 out of 39 Lys residues and the N-terminal end, while βAla 1 pP0 was mostly linked to the six free cysteine residues, to the N-terminal end, and, in a lesser extent, to Lys residues. The assignment of the conjugation sites and side reactions were based on the identification of type 2 peptides. Rabbit immunizations showed the best anti-pP0 titers and the highest efficacy against Rhipicephalus sanguineus ticks when the p64K-Cys 1 pP0 was used as vaccine antigen. The presence of high molecular mass aggregates observed in the SDS-PAGE analysis of p64K-Cys 1 pP0 could be responsible for a better immune response against pP0 and consequently for its better efficacy as an anti-tick vaccine. Graphical abstract., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Disrupting transmission of Borrelia burgdorferi sensu lato complex (B. burgdorferi) from infected ticks to humans is one strategy to prevent the significant morbidity from Lyme disease. We have previously shown that an anti-OspA human mAb, 2217, prevents transmission of B. burgdorferi from infected ticks in animal models. Maintenance of a protective plasma concentration of a human mAb for tick season presents a significant challenge for a preexposure prophylaxis strategy. Here, we describe the optimization of mAb 2217 by amino acid substitutions (2217LS: M428L and N434S) in the Fc domain. The LS mutation led to a 2-fold increase in half-life in cynomolgus monkeys. In a rhesus macaque model, 2217LS protected animals from tick transmission of spirochetes at a dose of 3 mg/kg. Crystallographic analysis of Fab in complex with OspA revealed that 2217 bound an epitope that was highly conserved among the B. burgdorferi, B. garinii, and B. afzelii species. Unlike most vaccines that may require boosters to achieve protection, our work supports the development of 2217LS as an effective preexposure prophylaxis in Lyme-endemic regions, with a single dose at the beginning of tick season offering immediate protection that remains for the duration of exposure risk.

Background: Tick bites severely threaten human health because they allow the transmission of many deadly pathogens, including viruses, bacteria, protozoa, and helminths. Pruritus is a leading symptom of tick bites, but its molecular and neural bases remain elusive., Objectives: This study sought to discover potent drugs and targets for the specific prevention and treatment of tick bite-induced pruritus and arthropod-related itch., Methods: We used live-cell calcium imaging, patch-clamp recordings, and genetic ablation and evaluated mouse behavior to investigate the molecular and neural bases of tick bite-induced pruritus., Results: We found that 2 tick salivary peptides, IP defensin 1 (IPDef1) and IR defensin 2 (IRDef2), induced itch in mice. IPDef1 was further revealed to have a stronger pruritogenic potential than IRDef2 and to induce pruritus in a histamine-independent manner. IPDef1 evoked itch by activating mouse MrgprC11 and human MRGPRX1 on dorsal root ganglion neurons. IPDef1-activated MrgprC11/X1 signaling sensitized downstream ion channel TRPV1 on dorsal root ganglion neurons. Moreover, IPDef1 also activated mouse MrgprB2 and its ortholog human MRGPRX2 selectively expressed on mast cells, inducing the release of inflammatory cytokines and driving acute inflammation in mice, although mast cell activation did not contribute to oxidated IPDef1-induced itch., Conclusions: Our study identifies tick salivary peptides as a new class of pruritogens that initiate itch through MrgprC11/X1-TRPV1 signaling in pruritoceptors. Our work will provide potential drug targets for the prevention and treatment of pruritus induced by the bites or stings of tick and maybe other arthropods., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Ticks, being obligate hematophagous arthropods, are exposed to various blood-borne pathogens, including arboviruses. Consequently, their feeding behavior can readily transmit economically important viral pathogens to humans and animals. With this tightly knit vector and pathogen interaction, the replication and transmission of tick-borne viruses (TBVs) must be highly regulated by their respective tick vectors to avoid any adverse effect on the ticks' biological development and viability. Knowledge about the tick-virus interface, although gaining relevant advances in recent years, is advancing at a slower pace than the scientific developments related to mosquito-virus interactions. The unique and complicated feeding behavior of ticks, compared to that of other blood-feeding arthropods, also limits the studies that would further elaborate the antiviral immunity of ticks against TBVs. Hence, knowledge of molecular and cellular immune mechanisms at the tick-virus interface, will further elucidate the successful viral replication of TBVs in ticks and their effective transmission to human and animal hosts., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Ticks and the pathogens they transmit, including bacteria, viruses, protozoa, and helminths, constitute a growing burden for human and animal health worldwide. The ability of some animal species to acquire resistance to blood-feeding by ticks after a single or repeated infestation is known as acquired tick resistance (ATR). This resistance has been associated to tick-specific IgE response, the generation of skin-resident memory CD4+ T cells, basophil recruitment, histamine release, and epidermal hyperplasia. ATR has also been associated with protection to tick-borne tularemia through allergic klendusity, a disease-escaping ability produced by the development of hypersensitivity to an allergen. In addition to pathogen transmission, tick infestation in humans is associated with the α-Gal syndrome (AGS), a type of allergy characterized by an IgE response against the carbohydrate Galα1-3Gal (α-Gal). This glycan is present in tick salivary proteins and on the surface of tick-borne pathogens such as Borrelia burgdorferi and Anaplasma phagocytophilum, the causative agents of Lyme disease and granulocytic anaplasmosis. Most α-Gal-sensitized individuals develop IgE specific against this glycan, but only a small fraction develop the AGS. This review summarizes our current understanding of ATR and its impact on the continuum α-Gal sensitization, allergy, and the AGS. We propose that the α-Gal-specific IgE response in humans is an evolutionary adaptation associated with ATR and allergic klendusity with the trade-off of developing AGS., (© 2021 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

Ticks are the primary vector of arboviruses in temperate climates worldwide. They are both the vector of these pathogens to humans and an integral component of the viral sylvatic cycle. Understanding the tick-pathogen interaction provides information about the natural maintenance of these pathogens and informs the development of countermeasures against human infection. In this review, we discuss currently available information on tick-viral interactions within the broader scope of general tick immunology. While the tick immune response to several pathogens has been studied extensively, minimal work centres on responses to viral infection. This is largely due to the high pathogenicity of tick-borne viruses; this necessitates high-containment laboratories or low-pathogenicity substitute viruses. This has biased most research towards tick-borne flaviviruses. More work is required to fully understand the role of tick-virus interaction in sylvatic cycling and transmission of diverse tick-borne viruses., (© 2020 John Wiley & Sons Ltd.)

Ticks and tick-borne diseases are a challenge for medical and veterinary public health and often controlled through the use of repellents and acaricides. Research on vaccination strategies to protect humans, companion animals, and livestock from ticks and tick-transmitted pathogens has accelerated through the use of proteomic and transcriptomic analyses. Comparative analyses of unfed versus engorged and uninfected versus infected ticks have provided valuable insights into candidates for anti-tick and pathogen transmission blocking vaccines. An intricate interplay between tick saliva and the host's immune system has revealed potential antigens to be used in vaccination strategies. Immunization of hosts with targeted anti-tick vaccines would ideally lead to a reduction in tick numbers and prevent transmission of tick-borne pathogens. Comprehensive control of tick-borne diseases would come from successful anti-tick vaccination, vaccination preventing transmission of tick-borne diseases or a combination. Due to the close interaction with wildlife and ticks, with wildlife reservoirs enabling propagation of pathogens between ticks, the vaccination of these reservoirs is an attractive target to reduce human contact with ticks and tick-borne diseases through a one-health approach. Wildlife vaccination presents formulation and regulatory challenges which should be considered early in the development of reservoir-targeted vaccines., (© 2021 John Wiley & Sons Ltd.)

Immune-mediated hypersensitivity reactions to ticks and other arthropods are well documented. Hypersensitivity to ixodid (hard bodied) ticks is especially important because they transmit infection to humans throughout the world and are responsible for most vector-borne diseases in the United States. The causative pathogens of these diseases are transmitted in tick saliva that is secreted into the host while taking a blood meal. Tick salivary proteins inhibit blood coagulation, block the local itch response and impair host anti-tick immune responses, which allows completion of the blood meal. Anti-tick host immune responses are heightened upon repeated tick exposure and have the potential to abrogate tick salivary protein function, interfere with the blood meal and prevent pathogen transmission. Although there have been relatively few tick bite hypersensitivity studies in humans compared with those in domestic animals and laboratory animal models, areas of human investigation have included local hypersensitivity reactions at the site of tick attachment and generalized hypersensitivity reactions. Progress in the development of anti-tick vaccines for humans has been slow due to the complexities of such vaccines but has recently accelerated. This approach holds great promise for future prevention of tick-borne diseases., (© 2021 John Wiley & Sons Ltd.)

Ticks are blood-feeding ectoparasites that transmit a variety of pathogens to host animals and humans, causing severe infectious diseases such as Lyme disease. In a certain combination of animal and tick species, tick infestation elicits acquired immunity against ticks in the host, which can reduce the ability of ticks to feed on blood and to transmit pathogens in the following tick infestations. Therefore, our understanding of the cellular and molecular mechanisms of acquired tick resistance (ATR) can advance the development of anti-tick vaccines to prevent tick infestation and tick-borne diseases. Basophils are a minor population of white blood cells circulating in the bloodstream and are rarely observed in peripheral tissues under steady-state conditions. Basophils have been reported to accumulate at tick-feeding sites during re-infestation in cattle, rabbits, guinea pigs and mice. Selective ablation of basophils resulted in a loss of ATR in guinea pigs and mice, illuminating the essential role of basophils in the manifestation of ATR. In this review, we discuss the recent advance in the elucidation of the cellular and molecular mechanisms underlying basophil recruitment to the tick-feeding site and basophil-mediated ATR., (© 2020 The Authors. Parasite Immunology published by John Wiley & Sons Ltd.)

From seminal publications in the early 1970s, the world learned that dendritic cells (DCs) are powerful and versatile antigen-presenting cells. It took a few years until the first studies expanded our understanding of the pivotal role of these immune 'soldiers' against ticks. Advances in biochemistry, molecular biology, and bioinformatics have shed light on the identification of key salivary molecules that modulate the biology of DCs in favor of tick parasitism. Here, we present a critical overview of the discoveries accumulated on the tick-host battlefield from a DC perspective. Moreover, the clinical significance of DC-targeted tick salivary components is discussed, not only as facilitators of the transmission of tick-borne pathogens or vaccine candidates, but also as potential immunobiologics to treat immune-mediated diseases., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Alpha-gal syndrome (AGS) is an emerging immunoglobulin E (IgE)-mediated allergy to galactose-alpha-1,3-galactose (alpha-gal). The geographic distribution and burden of AGS in the United States are unknown., Objective: To characterize alpha-gal IgE testing patterns and describe the trends and distribution from 2010 to 2018 in the United States., Methods: This retrospective analysis included all persons tested for alpha-gal IgE antibodies by Viracor-IBT Laboratories (Lee's Summit, Missouri), the primary site of testing in the United States. Data included age and sex of person tested, specimen state of origin, collection date, and result value; persons with at least 1 positive test result (≥0.1 kU/L) were compared with negatives. Proportions tested and with positive test results were calculated using the US Census population estimates., Results: Overall, 122,068 specimens from 105,674 persons were tested for alpha-gal IgE during July 1, 2010, to December 31, 2018. Nearly one-third (34,256, 32.4%) had at least 1 positive result. The number of persons receiving positive test results increased 6-fold from 1110 in 2011 to 7798 in 2018. Of those receiving positive test results, mean [SD] age was 46.9 (19.8) years; men were more likely to test positive than women (43.3% vs 26.0%). Arkansas, Virginia, Kentucky, Oklahoma, and Missouri had the highest number of persons who were tested and had a positive result per 100,000 population., Conclusion: More than 34,000 persons, most presumably symptomatic, have received positive test results for IgE antibodies to alpha-gal, suggesting AGS is an increasingly recognized public health problem. The geographic distribution of persons who tested positive is consistent with exposure to Amblyomma americanum ticks., (Published by Elsevier Inc.)

Ticks are ectoparasitic arthropods that necessarily feed on the blood of their vertebrate hosts. The success of blood acquisition depends on the pharmacological properties of tick saliva, which is injected into the host during tick feeding. Saliva is also used as a vehicle by several types of pathogens to be transmitted to the host, making ticks versatile vectors of several diseases for humans and other animals. When a tick feeds on an infected host, the pathogen reaches the gut of the tick and must migrate to its salivary glands via hemolymph to be successfully transmitted to a subsequent host during the next stage of feeding. In addition, some pathogens can colonize the ovaries of the tick and be transovarially transmitted to progeny. The tick immune system, as well as the immune system of other invertebrates, is more rudimentary than the immune system of vertebrates, presenting only innate immune responses. Although simpler, the large number of tick species evidences the efficiency of their immune system. The factors of their immune system act in each tick organ that interacts with pathogens; therefore, these factors are potential targets for the development of new strategies for the control of ticks and tick-borne diseases. The objective of this review is to present the prevailing knowledge on the tick immune system and to discuss the challenges of studying tick immunity, especially regarding the gaps and interconnections. To this end, we use a comparative approach of the tick immune system with the immune system of other invertebrates, focusing on various components of humoral and cellular immunity, such as signaling pathways, antimicrobial peptides, redox metabolism, complement-like molecules and regulated cell death. In addition, the role of tick microbiota in vector competence is also discussed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Fogaça, Sousa, Pavanelo, Esteves, Martins, Urbanová, Kopáček and Daffre.)

Dugbe orthonairovirus (DUGV) is a tick-borne arbovirus within the order Bunyavirales . DUGV was first isolated in Nigeria, but virus isolations in ten further African countries indicate that DUGV is widespread throughout Africa. Humans can suffer from a mild febrile illness, hence, DUGV is classified as a biosafety level (BSL) 3 agent. In contrast, no disease has been described in animals, albeit serological evidence exists that ruminants are common hosts and may play an important role in the transmission cycle of this neglected arbovirus. In this study, young sheep and calves were experimentally inoculated with DUGV in order to determine their susceptibility and to study the course of infection. Moreover, potential antibody cross-reactivities in currently available diagnostic assays for Crimean-Congo hemorrhagic fever orthonairovirus (CCHFV) were assessed as DUGV is distantly related to CCHFV. Following subcutaneous inoculation, none of the animals developed clinical signs or viremia. However, all ruminants seroconverted, as demonstrated by two DUGV neutralization test formats (micro-virus neutralization test (mVNT), plaque reduction (PRNT)), by indirect immunofluorescence assays and in bovines by a newly developed DUGV recombinant N protein ELISA. Sera did not react in commercial CCHFV ELISAs, whereas cross-reactivities were observed by immunofluorescence and immunoblot assays.

Ticks and tick transmitted infectious agents are increasing global public health threats due to increasing abundance, expanding geographic ranges of vectors and pathogens, and emerging tick-borne infectious agents. Greater understanding of tick, host, and pathogen interactions will contribute to development of novel tick control and disease prevention strategies. Tick-borne pathogens adapt in multiple ways to very different tick and vertebrate host environments and defenses. Ticks effectively pharmacomodulate by its saliva host innate and adaptive immune defenses. In this review, we examine the idea that successful synergy between tick and tick-borne pathogen results in host immune tolerance that facilitates successful tick infection and feeding, creates a favorable site for pathogen introduction, modulates cutaneous and systemic immune defenses to establish infection, and contributes to successful long-term infection. Tick, host, and pathogen elements examined here include interaction of tick innate immunity and microbiome with tick-borne pathogens; tick modulation of host cutaneous defenses prior to pathogen transmission; how tick and pathogen target vertebrate host defenses that lead to different modes of interaction and host infection status (reservoir, incompetent, resistant, clinically ill); tick saliva bioactive molecules as important factors in determining those pathogens for which the tick is a competent vector; and, the need for translational studies to advance this field of study. Gaps in our understanding of these relationships are identified, that if successfully addressed, can advance the development of strategies to successfully disrupt both tick feeding and pathogen transmission., Competing Interests: SW is Senior Science Advisor for U.S. Biologic, a biotechnology company that develops solutions for tick-borne diseases, pet health, and antimicrobial resistance in poultry and livestock through oral vaccines. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Boulanger and Wikel.)

Ticks are blood-sucking arthropods of great importance in the medical and veterinary fields worldwide. They are considered second only to mosquitos as vectors of pathogenic microorganisms that can cause serious infectious disorders, such as Lyme borreliosis and tick-borne encephalitis. Hard ( Ixodid ) ticks feed on host animals for several days and inject saliva together with pathogens to hosts during blood feeding. Some animal species can acquire resistance to blood-feeding by ticks after a single or repeated tick infestation, resulting in decreased weights and numbers of engorged ticks or the death of ticks in subsequent infestations. Importantly, this acquired tick resistance (ATR) can reduce the risk of pathogen transmission from pathogen-infected ticks to hosts. This is the basis for the development of tick antigen-targeted vaccines to forestall tick infestation and tick-borne diseases. Accumulation of basophils is detected in the tick re-infested skin lesion of animals showing ATR, and the ablation of basophils abolishes ATR in mice and guinea pigs, illustrating the critical role for basophils in the expression of ATR. In this review article, we provide a comprehensive overview of recent advances in our understanding of the cellular and molecular mechanisms responsible for the development and manifestation of ATR, with a particular focus on the role of basophils., (Copyright © 2020 Karasuyama, Miyake and Yoshikawa.)

Immunodeficiency disorders and autoimmune diseases are common, but a lack of effective targeted drugs and the side-effects of existing drugs have stimulated interest in finding therapeutic alternatives. Naturally derived substances are a recognized source of novel drugs, and tick saliva is increasingly recognized as a rich source of bioactive molecules with specific functions. Ticks use their saliva to overcome the innate and adaptive host immune systems. Their saliva is a rich cocktail of molecules including proteins, peptides, lipid derivatives, and recently discovered non-coding RNAs that inhibit or modulate vertebrate immune reactions. A number of tick saliva and/or salivary gland molecules have been characterized and shown to be promising candidates for drug development for vertebrate immune diseases. However, further validation of these molecules at the molecular, cellular, and organism levels is now required to progress lead candidates to clinical testing. In this paper, we review the data on the immuno-pharmacological aspects of tick salivary compounds characterized in vitro and/or in vivo and present recent findings on non-coding RNAs that might be exploitable as immunomodulatory therapies., (Copyright © 2020 Aounallah, Bensaoud, M’ghirbi, Faria, Chmelar̆ and Kotsyfakis.)

A total of 1,337 serum and plasma specimens (939, 393 and 15 from cattle, sheep and goats, respectively) were collected monthly for one a year from ruminant species slaughtered in three Turkish cities endemic for Crimean-Congo hemorrhagic fever virus (CCHFV), Samsun, Sivas and Tokat. The serum samples were tested by commercial indirect ELISA to detect CCHFV antibodies, and positive or equivocal samples were later confirmed by a virus neutralization test (VNT). The seroprevalence in cattle, sheep, and goats was 36.21% (340/939), 6.27% (24/383), and 6.67% (1/15), respectively. Quantitative real-time RT-PCR was employed to detect viraemic animals at slaughter time. The percentage of CCHFV-viraemic animals was 0.67% (9/1337). The virus load varied between 4.1 x 10 1 and 2.4 x 10 3 RNA equivalent copies/mL in viraemic animals. The plasma samples that were positive for CCHFV genomic RNA were collected between April and May, when Hyalomma ticks are active. This study presents quantitative CCHFV load data in ruminant species at slaughter and interprets the likelihood of transmission for employees working in slaughterhouses in CCHFV-endemic regions.

Introduction: Alpha-gal Syndrome (AGS) is a unique allergy to non-primate mammalian meat (and derived-products) that is associated with tick bites and is due to a specific IgE antibody to the oligosaccharide galactose-α-1,3-galactose (alpha-gal). AGS has many novel features that broaden the paradigm of food allergy, including that reactions are delayed 3-6 hours after exposure and patients have frequently tolerated red meat for many years prior to the development of allergic reactions. Due to the ubiquitous inclusion of mammal-derived materials in foods, medications, personal products and stabilizing compounds, full avoidance is difficult to achieve., Areas Covered: This review describes the author's experience with diagnosis, management, and design of appropriate avoidance for patients with AGS and provides clinicians with practical advice for care of these patients., Expert Opinion: The number of patients with AGS is rising and may have exceeded awareness of the diagnosis amongst healthcare providers. In summarizing experience gained to thus far, we hope to create a resource for identifying and managing this unique allergic syndrome.

We characterized the antibody response to decorin-binding protein A (DbpA) or DbpB from immune serum samples collected from 27 dogs infected with Borrelia burgdorferi by Ixodes scapularis ticks. Immunoglobulin M (IgM) antibodies to DbpA or DbpB were rarely detected, but high levels of IgG antibodies to DbpA were detected in 16 of 27 of the immune sera collected 1 mo after infection, 20 of 25 of the sera collected after 2 mo, and each of the 23, 17, or 11 serum samples evaluated after 3, 4, or 5 mo, respectively. In addition, IgG antibodies to DbpB were detected in 22 of 27 ( p  = 0.005) tested dogs after 1 mo, and the frequency of detecting the antibodies thereafter closely mimicked the antibody responses to DbpA. Moreover, antibodies to DbpA or DbpB were not produced by dogs vaccinated with a whole-cell B. burgdorferi bacterin; removing the antibodies to DbpA by adsorption to recombinant DbpA (rDbpA) did not affect the reactivity detected by a rDbpB ELISA. Therefore, the findings from our preliminary study showed that antigenically distinct antibodies to DbpA or DbpB are produced reliably during canine infection with B. burgdorferi , and the response is not confounded by vaccination with a Lyme disease bacterin. Larger studies are warranted to more critically evaluate whether detecting the antibody responses can improve serodiagnostic confirmation of canine Lyme disease.

Ticks are major parasites of domestic livestock, wildlife, and humans. After a tick bite, diverse cutaneous manifestations initially occur in the bitten area in the host. In this study, a label-free proteomics approach was applied to identify the differentially ubiquitinated proteins (DUPs) induced by tick-bitten in the skin. In total, 113 proteins were ubiquitinated in rabbit skin during tick bitten period, among which the ubiquitination levels of 43 proteins were altered. These DUPs in skin subjected to tick-bitten were enriched in metabolic processes, immune processes, and protein degradation processes. Bioinformatic analysis suggested that tick bitten may regulate the glycolysis pathway in host skin via differential ubiquitination of GAPDH, HK1 and TPI1, while regulate the ubiquitin-proteasome system, the MHC-I and MHC-II antigen-presenting pathways, and the HIF-1 signaling pathway via differential ubiquitination of MEK1, PSMC3, PSMA6, MHC-II and PSMD1. Moreover, PSMC3, PSMA6, PSMD1 and MEK1 were demonstrated as novel targets of ubiquitination. This study provides the first overview of ubiquitination in host skin affected by tick bitten and broadens our knowledge of the molecular mechanism involved in tick bitten., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The spirochete Borrelia miyamotoi has recently been shown to cause relapsing fever. Like the Lyme disease agent, Borrelia burgdorferi, B. miyamotoi is transmitted through the bite of infected ticks; however, little is known about the response of the immune system upon infection. Dendritic cells (DCs) play a central role in the early immune response against B. burgdorferi We investigated the response of DCs to two different strains of B. miyamotoi using in vitro and ex vivo models and compared this to the response elicited by B. burgdorferi. Our findings show that B. miyamotoi is phagocytosed by monocyte-derived DCs, causing upregulation of activation markers and production of proinflammatory cytokines in a similar manner to B. burgdorferi. Recognition of B. miyamotoi was demonstrated to be partially mediated by TLR2. DCs migrated out of human skin explants upon inoculation of the skin with B. miyamotoi. Finally, we showed that B. miyamotoi -stimulated DCs induced proliferation of naive CD4 + and CD8 + T cells to a larger extent than B. burgdorferi. In conclusion, we show in this study that DCs respond to and mount an immune response against B. miyamotoi that is similar to the response to B. burgdorferi and is able to induce T cell proliferation., (Copyright © 2020 by The American Association of Immunologists, Inc.)

Background: Alpha-gal syndrome is a complex allergy with high clinical relevance regarding mammalian-derived food and drugs and is characterized by the presence of IgE antibodies directed at the carbohydrate galactose-α-1,3-galactose. As not all alpha-gal sIgE-positive individuals pre-sent clinical symptoms upon consumption of mammalian meat, the diagnostic value of alpha-gal sIgE has yet to be clarified., Objective: To investigate the prevalence of alpha-gal-sIgE positivity among allergy patients, examine the impact of tick bites as associated risk factors and determine the diagnostic value of alpha-gal-sIgE positivity., Methods: A retrospective cross-sectional study evaluating patients in the Allergy Unit was performed. Alpha-gal-sIgE levels were assessed by ImmunoCAP assay. Exposure to tick bites was assessed by a questionnaire. A receiver operating characteristics (ROC) curve analysis was performed to determine the diagnostic value of alpha-gal sIgE for the diagnosis of alpha-gal syndrome., Results: In the study population (n = 1369), the overall prevalence of alpha-gal-sIgE-positive (≥0.10 kUA/L) individuals was 19.9%, and the highest prevalence (30.2%) was found in patients with insect venom allergies. A reported tick bite within the 12 months prior to blood sampling significantly increased the risk of alpha-gal-sIgE positivity (OR 2.084). The ROC curve analysis indicated alpha-gal sIgE ≥0.54 kUA/L as the optimal cutoff point for assessing the diagnostic value of alpha-gal syndrome in allergy patients., Conclusions: In allergy care settings, alpha-gal-sIgE positivity is a common finding. Alpha-gal sIgE is a sensitive marker in the diagnosis of alpha-gal syndrome but has limited predictive value for the characteristics or severity of this allergy., (© 2019 S. Karger AG, Basel.)

Mites and ticks are associated with many human diseases including allergic diseases and scabies. With the recent advances in the high throughput DNA sequencing technology, many mitochondrial nuclear genomes of these species have been sequenced and the resulting genomic resources will certainly provide novel insights for the future investigation of the functionally important proteins and peptides in these species. In this mini-review, the current situation of mite and tick genomes is described and the future perspectives for the application of the genomic resources are discussed, especially including the novel identification and structural analysis of allergens., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The blood-feeding behavior of ticks has resulted in them becoming one of the most important vectors of disease-causing pathogens. Ticks possess a well-developed innate immune system to counter invading pathogens. However, the coevolution of ticks with tick-borne pathogens has adapted these pathogens to the tick's physiology and immune response through several mechanisms including transcriptional regulation. The recent development in tick and tick-borne disease research greatly involved the "omics" approach. The omics approach takes a look en masse at the different genes, proteins, metabolomes, and the microbiome of the ticks that could be differentiated during pathogen infection. Data from this approach revealed that oxidative stress-related molecules in ticks are differentiated and possibly being exploited by the pathogens to evade the tick's immune response. In this study, we review and discuss transcriptomic and proteomic data for some oxidative stress molecules differentially expressed during pathogen infection. We also discuss metabolomics and microbiome data as well as functional genomics in order to provide insight into the tick-pathogen interaction., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Ticks are a growing concern to human and animal health worldwide and they are leading vectors of arthropod-borne pathogens in the United States. Ticks are pool blood feeders that can attach to the host skin for days to weeks using their saliva to counteract the host defenses. Tick saliva, as in other hematophagous arthropods, contains pharmacological and immunological active compounds, which modulate local and systemic immune responses and induce antibody production. In the present study, we explore differences in the salivary gland extract (SGE) protein content of Amblyomma americanum ticks raised in a laboratory colony (CT) vs. those collected in the field (FT). First, we measured the IgG antibody levels against SGE in healthy volunteers residing in Kansas. ELISA test showed higher IgG antibody levels when using the SGE from CT as antigen. Interestingly, antibody levels against both, CT-SGE and FT-SGE, were high in the warm months (May-June) and decreased in the cold months (September-November). Immunoblot testing revealed a set of different immunogenic bands for each group of ticks and mass spectrometry data revealed differences in at 19 proteins specifically identified in the CT-SGE group and 20 from the FT-SGE group. Our results suggest that differences in the salivary proteins between CT-SGE and FT-SGE may explain the differential immune responses observed in this study.

Tick-borne allergies are a growing public health concern and have been associated with the induction of IgE-mediated food allergy to red meat. However, despite the increasing prevalence of tick bite-induced allergies, the mechanisms by which cutaneous exposure to ticks leads to sensitization and the production of IgE Abs are poorly understood. To address this question, an in vivo approach was used to characterize the IgE response to lone star tick proteins administered through the skin of mice. The results demonstrated that tick sensitization and challenge induced a robust production of IgE Abs and supported a role for IgE-mediated hypersensitivity reactions in sensitized animals following oral administration of meat. The induction of IgE responses was dependent on cognate CD4 + T cell help during both the sensitization phase and challenge phase with cutaneous tick exposure. In addition, IgE production was dependent on B cell-intrinsic MyD88 expression, suggesting an important role for TLR signaling in B cells to induce IgE responses to tick proteins. This model of tick-induced IgE responses could be used to study the factors within tick bites that cause allergies and to investigate how sensitization to food Ags occurs through the skin that leads to IgE production., (Copyright © 2019 by The American Association of Immunologists, Inc.)

The α-Gal syndrome is a tick-associated and emerging IgE-mediated hypersensitivity reaction directed against the carbohydrate Galα1-3Galβ1-(3)4GlcNAc-R (α-Gal) epitope after red meat intake. Herein, we describe a clinical case of a 44-year-old French patient who suffered from recurrent anaphylactic reactions after mammalian meat consumption for five years before the final diagnosis of the α-Gal syndrome was established in 2018. The patient also reported multiple tick bites prior to symptom onset. This unique type of allergy has increasingly been reported across the world, but it is still unknown in many European countries. Therefore, the present clinical case should increase awareness among primary care practitioners and further improve the early diagnosis of the α-Gal syndrome in affected individuals., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

Objective: To review published studies on galactose α-1,3-galactose (α-gal), a carbohydrate epitope found on proteins and lipids in nonprimate mammals and present in foods (particularly organ or fat-rich red meat) and medications, where it causes delayed-onset and immediate-onset anaphylaxis., Data Sources: A literature search for the terms galactose α-1,3-galactose and α-gal using PubMed and Embase was performed., Study Selections: Studies on α-gal were included in this review., Results: Several species of ticks contain α-gal epitopes and possibly salivary adjuvants that promote high titer sensitization and clinical reactivity. Risk factors for α-gal syndrome include exposure to ticks of particular species. Age and sex differences seen in various cohorts possibly reflect the prevalence of these exposures that vary according to setting., Conclusion: The reason and mechanisms for delayed onset of food-related anaphylaxis and the preponderance of abdominal reactions are not clear but may involve the kinetics of allergen digestion and processing or immunologic presentation via a different mechanism from usual immediate-type food allergy., (Copyright © 2019 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Rickettsia bacteria are responsible for diseases in humans and animals around the world, however few details are available regarding its ecology and circulation among wild animals and human populations at high transmission risk in Brazil. The aim of this study was to investigate the occurrence of ticks and Rickettsia spp. in wild boars, corresponding hunting dogs and hunters., Methods: Serum samples and ticks were collected from 80 free-range wild boars, 170 hunting dogs and 34 hunters from southern and central-western Brazil, from the Atlantic Forest and Cerrado biomes, respectively, between 2016 and 2018. Serum samples were tested by indirect immunofluorescent-antibody assay (IFA) to detect IgG antibodies against Rickettsia rickettsii, Rickettsia parkeri, Rickettsia bellii, Rickettsia rhipicephali and Rickettsia amblyommatis. Tick species were identified by morphological taxonomic keys, as previously described. A total of 164 ticks including A. sculptum, A. brasiliense and A. aureolatum were tested in PCR assays for Spotted Fever Group (SFG) Rickettsia spp., Results: A total of 58/80 (72.5%) wild boars, 24/170 (14.1%) hunting dogs and 5/34 (14.7%) hunters were positive (titers ≥ 64) to at least one Rickettsia species. A total of 669/1,584 (42.2%) ticks from wild boars were identified as Amblyomma sculptum, 910/1,584 (57.4%) as Amblyomma brasiliense, 4/1,584(0.24%) larvae of Amblyomma spp. and 1/1,584 (0.06%) nymph as Amblyolmma dubitatum. All 9 ticks found on hunting dogs were identified as Amblyomma aureolatum and all 22 ticks on hunters as A. sculptum. No tested tick was positive by standard PCR to SFG Rickettsia spp., Conclusions: The present study was the concomitant report of wild boar, hunting dog and hunter exposure to SFG rickettsiae agents, performed in two different Brazilian biomes. Wild boar hunting may increase the risk of human exposure and consequently tick-borne disease Wild boars may be carrying and spreading capybara ticks from their original habitats to other ecosystems. Further studies can be required to explore the ability of wild boars to infecting ticks and be part of transmission cycle of Rickettsia spp., Competing Interests: The authors have declared that no competing interests exist.

Development of specific IgE antibodies to the oligosaccharide galactose-α-1, 3-galactose (α-gal) following tick bites has been shown to be the source of red meat allergy. In this study, we investigated the presence of α-gal in four tick species: the lone-star tick ( Amblyomma americanum ), the Gulf-Coast tick ( Amblyomma maculatum ), the American dog tick ( Dermacentor variabilis ), and the black-legged tick ( Ixodes scapularis ) by using a combination of immunoproteomic approach and, carbohydrate analysis. Anti-α-gal antibodies identified α-gal in the salivary glands of both Am. americanum and Ix. scapularis , while Am. maculatum and De. variabilis appeared to lack the carbohydrate. PNGase F treatment confirmed the deglycosylation of N-linked α-gal-containing proteins in tick salivary glands. Immunolocalization of α-gal moieties to the salivary secretory vesicles of the salivary acini also confirmed the secretory nature of α-gal-containing antigens in ticks. Am. americanum ticks were fed on human blood (lacks α-gal) using a silicone membrane system to determine the source of the α-gal. N-linked glycan analysis revealed that Am. americanum and Ix. scapularis have α-gal in their saliva and salivary glands, but Am. maculatum contains no detectable quantity. Consistent with the glycan analysis, salivary samples from Am. americanum and Ix. scapularis stimulated activation of basophils primed with plasma from α-gal allergic subjects. Together, these data support the idea that bites from certain tick species may specifically create a risk for the development of α-gal-specific IgE and hypersensitivity reactions in humans. Alpha-Gal syndrome challenges the current food allergy paradigm and broadens opportunities for future research.

Background: Ticks, as blood-feeding arthropod vectors, have evolved their own unique mechanism to suppress host immune responses and evade immune defenses in order to complete blood-feeding. The immunoregulatory effect of tick bioactive molecules on hosts has been widely reported, and the cystatin family has been identified as one of the major immunomodulators. In previous studies, we obtained a novel tick salivary bioactive protein named RHcyst-1, which belongs to the type 1 cystatin family. Here, we demonstrated the effects of RHcyst-1 on the host immune response mainly on dendritic cell (DC) function. Understanding the function of tick-derived bioactive molecule may help to clarify the mechanisms of how ticks escape the host immune response and help to control ticks and tick-borne disease transmission., Methods: Bone marrow-derived DCs (BMDCs) were generated and induced by GM-CSF and IL-4 with or without RHcyst-1 addition. Flow cytometry was used to analyze the differentiation and maturation of BMDCs and T cell cytokine production. Quantitative real-time PCR (qRT-PCR) and western blot were used to measure changes in expression within STAT and p38 MAPK signaling pathways., Results: Flow cytometry analysis revealed that RHcyst-1 inhibited the differentiation of BMDCs, but had no effect on the maturation of BMDCs. T cells co-cultured with DCs treated with RHcyst-1 produced significantly less TNF-α, IFN-γ and IL-2 than the control group. Further analysis showed that the mRNA level and phosphorylation of p38, ERK and STAT were significantly changed after RHcyst-1 added to bone marrow monocytes during the differentiation stage., Conclusions: Our results suggest that RHcyst-1 is one of the major immunosuppressive proteins of BMDC function from blood-feeding ticks.

Ixodid ticks are acknowledged as one of the most important hematophagous arthropods because of their ability in transmitting a variety of tick-borne diseases. Mathematical models have been developed, based on emerging knowledge about tick ecology, pathogen epidemiology and their interface, to understand tick population dynamics and tick-borne diseases spread patterns. However, no serious effort has been made to model and assess the impact of host immunity triggered by tick feeding on the distribution of the tick population according to tick stages and on tick population extinction and persistence. Here, we construct a novel mathematical model taking into account the effect of host immunity status on tick population dynamics, and analyze the long-term behaviours of the model solutions. Two threshold values, [Formula: see text] and [Formula: see text], are introduced to measure the reproduction ratios for the tick-host interaction in the absence and presence of host immunity. We then show that these two thresholds (sometimes under additional conditions) can be used to predict whether the tick population goes extinct ([Formula: see text]) and the tick population grows without bound ([Formula: see text]). We also prove tick permanence (persistence and boundedness of the tick population) and the existence of a tick persistence equilibrium if [Formula: see text]. As the host species adjust their immunity to tick infestation levels, they form for the tick population an environment with a carrying capacity very much like that in logistic growth. Numerical results show that the host immune reactions decrease the size of the tick population at equilibrium and apparently reduce the tick-borne infection risk.

Cocktail vaccines are proposed as an attractive way to increase protection efficacy against specific tick species. Furthermore, such vaccines made with different tick antigens have the potential of cross-protecting against a broad range of tick species. However, there are still limitations to the selection of immunogen candidates. Acknowledging that glutathione S-transferases (GSTs) have been exploited as vaccines against ticks and other parasites, this study aimed to analyze a GST-cocktail vaccine as a potential broad-spectrum tick vaccine. To constitute the GST-cocktail vaccine, five tick species of economic importance for livestock industry were studied (Rhipicephalus appendiculatus, Rhipicephalus decoloratus, Rhipicephalus microplus, Amblyomma variegatum, and Haemaphysalis longicornis). Tick GST ORF sequences were cloned, and the recombinant GSTs were produced in Escherichia coli. rGSTs were purified and inoculated into rabbits, and the immunological response was characterized. The humoral response against rGST-Rd and rGST-Av showed a stronger cross-reactivity against heterologous rGSTs compared to rGST-Hl, rGST-Ra, and rGST-Rm. Therefore, rGST-Rd and rGST-Av were selected for constituting an experimental rGST-cocktail vaccine. Vaccination experiment in rabbits showed that rGST-cocktail caused 35% reduction in female numbers in a Rhipicephalus sanguineus infestation. This study brings forward an approach to selecting immunogens for cocktail vaccines, and the results highlight rGST-Rd and rGST-Av as potentially useful tools for the development of a broad-spectrum tick vaccine., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: The Infection and Treatment Method (ITM) of vaccination is the only immunization procedure currently available to protect cattle against East Coast fever (ECF), a tick-transmitted disease responsible for losses of several hundreds of millions of dollars per year in sub-Saharan Africa. The vaccine comprises a homogenized preparation of infected ticks packaged in straws and stored in liquid nitrogen. The current manufacturing protocol results in straws containing 30-40 doses (ILRI 0804), which is impractical for immunizing small herds as found in dairy and smallholder farming systems. The ILRI 0804 SD stabilate was prepared as a 1:5 dilution of the parent stabilate, with the aim of producing vaccine stabilate straws containing between four to eight doses and thus suitable for smallholder farming systems. Infectivity of the diluted stabilate was assessed and the protective efficacy of the diluted stabilate was determined by performing experimental and field immunizations., Results: Two groups of six cattle were inoculated with 1 ml of the diluted stabilate at 1:20 (equivalent to the recommended field dose for ILRI 0804, assuming no loss of sporozoite viability during thawing and refreezing) and 1:14 (assuming 30-35% loss of sporozoite viability). Schizonts were detected in all 12 animals, showing viability of sporozoites. Ten animals from the infectivity study and two control animals not previously exposed to T. parva were challenged with the parental ILRI 0804 stabilate. The results show that the two control animals displayed severe ECF reactions and were treated 14 days after challenge. Of the previously infected animals, only one underwent a severe reaction following challenge, a result in accord with the challenge experiments performed previously with the parent stabilate [Ticks Tick-Borne Dis 7:306-314, 2016]. The animal that displayed a severe reaction had no detectable schizonts and did not seroconvert following the initial inoculation with ILRI 0804 SD. In addition, 62 animals immunized under field conditions showed a mean seroconversion rate of 82%., Conclusion: The results presented in this article demonstrate that it is possible to prepare straws suitable for use in smallholder herds by thawing, diluting and refreezing already packaged vaccine.

Background: West Nile Virus (WNV), a member of the genus Flavivirus, is one of the most widely distributed arboviruses in the world. Despite some evidence for circulation of WNV in countries summarized by the World Health Organization as the Eastern Mediterrian Regional Office (EMRO), comprehensive knowledge about its epidemiology remains largely unknown. This study aims to provide a concise review of the published literature on WNV infections in the Eastern Mediterranean Regional Office of WHO (EMRO)., Methodology/principal Findings: A systematic review of WNV prevalence studies on humans, animals and vectors in the EMRO region was performed by searching: Web of Science, Science Direct, Scopus, PubMed, Embase and Google Scholar. Finally, 77 citations were included, comprising 35 seroprevalence studies on general population (24460 individuals), 15 prevalence studies among patients (3439 individuals), 22 seroprevalence studies among animals (10309 animals), and 9 studies on vectors (184242 vector species). Of the 22 countries in this region, five had no data on WNV infection among different populations. These countries include Kuwait, Bahrain, Oman, Syria and Somalia. On the other hand, among countries with available data, WNV-specific antibodies were detected in the general population of all investigated countries including Djibouti (0.3-60%), Egypt (1-61%), Iran (0-30%), Iraq (11.6-15.1%), Jordan (8%), Lebanon (0.5-1%), Libya (2.3%), Morocco (0-18.8%), Pakistan (0.6-65.0%), Sudan (2.2-47%), and Tunisia (4.3-31.1%). WNV RNA were also detected in patient populations of Iran (1.2%), Pakistan (33.3%), and Tunisia (5.3% -15.9%). WNV-specific antibodies were also detected in a wide range of animal species. The highest seropositivity rate was observed among equids (100% in Morocco) and dogs (96% in Morocco). The highest seroprevalence among birds was seen in Tunisia (23%). In addition, WNV infection was detected in mosquitoes (Culex, and Aedes) and ticks (Argas reflexus hermanni). The primary vector of WNV (Culex pipiens s.l.) was detected in Djibouti, Egypt, Iran and Tunisia, and in mosquitoes of all these countries, WNV was demonstrated., Conclusions: This first systematic regional assessment of WNV prevalence provides evidence to support the circulation of WNV in the EMRO region as nearly all studies showed evidence of WNV infection in human as well as animal/vector populations. These findings highlight the need for continued prevention and control strategies and the collection of epidemiologic data for WNV epidemic status, especially in countries that lack reliable surveillance systems., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Ticks are obligate hematophagous arthropod ectoparasites that transmit pathogens responsible for a growing number of tick-borne diseases (TBDs) throughout the world. Vaccines have been shown to be the most efficient, cost-effective, and environmentally friendly approach for the control of ticks and the prevention of TBDs. Although at its infancy, interactomics has shown the possibilities that the knowledge of the interactome offers in understanding tick biology and the molecular mechanisms involved in pathogen infection and transmission. Furthermore, interactomics has provided information for the identification of candidate vaccine protective antigens. Areas covered: In this special report, we review the different approaches used for the study of protein-protein physical and functional interactions, and summarize the application of interactomics to the characterization of tick biology and tick-host-pathogen interactions, and the possibilities that offers to vaccine development for the control of ticks and TBDs. Expert commentary: The combination of interacting proteins in antigen formulations may increase vaccine efficacy. In the near future, the combination of interactomics with other omics approaches such as transcriptomics, proteomics, metabolomics, and regulomics together with intelligent Big Data analytic techniques will improve the high throughput discovery and characterization of vaccine protective antigens for the prevention and control of TBDs.

Hydrogen peroxide (H 2 O 2 ) and hydroxyl radicals (HO·) are generated through partial reduction of oxygen. The HO· are the most reactive and have a shorter half-life than H 2 O 2 , they are produced from comparatively stable H 2 O 2 through Fenton reaction. Although controlling HO· is important and biologically advantageous for organisms, it may be difficult. Ticks are obligate hematophagous arthropods that need blood feeding for development. Ticks feed on vertebrate blood containing high levels of iron. Ticks also concentrate iron-containing host blood, leading to high levels of iron in ticks. Host-derived iron may react with oxygen in the tick body, resulting in high concentrations of H 2 O 2 . On the other hand, ticks have antioxidant enzymes, such as peroxiredoxins (Prxs), to scavenge H 2 O 2 . Gene silencing of Prxs in ticks affects their blood feeding, oviposition, and H 2 O 2 concentration. Therefore, Prxs could play important roles in ticks' blood feeding and oviposition through the regulation of the H 2 O 2 concentration. This review discusses the current knowledge of Prxs in hard ticks. Tick Prxs are also multifunctional molecules related to antioxidants and immunity like other organisms. In addition, tick Prxs play a role in regulating the host immune response for ticks' survival in the host body. Tick Prx also can induce Th2 immune response in the host. Thus, this review would contribute to the further understanding of the tick's antioxidant responses during blood feeding and the search for a candidate target for tick control.