Research progress on emerging and important Tick-Borne pathogens

Abstract

Ticks are important vector arthropods, which can carry and transmit a variety of pathogenic microorganisms, and pose a serious threat to global public health. This study reviews the research progress of the main and emerging tick-borne pathogens, such as Lyme disease related Borrelia, Rickettsia, Babesia, Thrombocytopenia Syndrome Virus (SFTSV), Tick-borne Encephalitis Virus (TBEV), Alongshan virus (ALSV), etc., focuses on their genomic diversity, pathogenicity, transmission and immune escape, co- infection. In addition, the application of new detection technology [Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), metagenomic next-generation sequencing (mNGS), microfluidics] in Tick-Borne pathogens is summarized.It highlights current research limitations, including delayed vaccine development and inadequate surveillance systems. Finally, future research directions are prospected, providing theoretical references for the prevention and control of tick-borne diseases.

1. Introduction

Ticks, as obligate blood-sucking arthropods, can invade a wide range of vertebrate hosts and are the vector of a large number of pathogens. As the second largest vector of human infectious diseases after mosquitoes, Ticks are also the main vector for pathogen transmission between livestock and wild animals. Ticks carry a variety of pathogenic pathogens, which can cause Lyme disease, tick-borne encephalitis, Rickettsia disease and other diseases. Some of these diseases have a high mortality, which can lead to serious complications and even death. Such diseases not only pose a serious threat to human health, but also seriously hinder the development of animal husbandry and cause a heavy social and economic burden (De la Fuente et al., 2008; Boulanger et al., 2019).

Under the influence of global climate change and human activities, the epidemic pattern of tick-Borne diseases has changed significantly. Global warming has promoted the continuous expansion of tick habitats. Tick species that were originally only distributed in specific areas have achieved cross-regional diffusion by means of migratory birds migration, livestock and poultry transportation, etc., colonizing the new ecological environment and forming effective vector populations (Backus et al., 2022; Narvaez et al., 2024; Chitimia-Dobler et al., 2018; Ning et al., 2017; Drehmann et al., 2019). The development and utilization of the natural environment and the increase of outdoor leisure activities further improve the contact probability between people and ticks and epidemic focus. In addition, pathogenic microorganisms continue to undergo gene recombination and mutation in the process of evolution, and new Tick-Borne pathogens continue to be found. Some new pathogens have strong pathogenicity and transmission ability, which aggravates the risk of outbreak of Tick-Borne diseases, and puts forward higher requirements for prevention and control.

Although existing studies have initially revealed the diversity and transmission characteristics of Tick-Borne pathogens, most studies focus on a single pathogen or local area, and lack of integrated analysis of pathogen spectrum at the global scale; Molecular analyses of pathogen–vector–host interactions remain superficial, which is difficult to support the accurate prediction of cross regional transmission risk; At the same time, the transformation efficiency of basic research results into prevention and control technologies such as diagnosis, vaccines and drugs is low, and there is a significant gap with the actual prevention and control needs. Based on this, combined with the research results of Tick-Borne pathogens at home and abroad in recent years, this paper systematically summarizes the diversity, evolution and transmission characteristics of major Tick-Borne pathogens, analyzes the research status of new Tick-Borne pathogens, and points out the deficiencies and controversial points of existing research, so as to provide theoretical support and improvement direction for Tick-Borne disease prevention and control and related scientific research work.

2. Methods

This study systematically searched PubMed database and collected the original literatures and reviews related to tick-borne diseases published in English before April 21, 2026. The search terms of major Tick-Borne pathogens were: (Tick-Borne pathogens OR Borrelia OR Rickettsia OR Anaplasma OR Babesia OR SFTS virus OR Tick-Borne Encephalitis Virus) AND (molecular mechanism OR pathogenesis OR genome). For emerging tick-borne pathogens, the search terms were: (emerging tick-borne pathogens OR novel tick-borne virus OR new Tick-Borne bacteria) AND (Ticks OR Ixodidae). Detection technologies were searched using: tick-borne disease AND microfluidics, tick-borne disease AND metagenomic next-generation sequencing, and tick-borne disease AND Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) AND diagnosis. Inclusion criteria: English literature, covering the diversity, evolution, pathogenesis, detection technology and control progress of Tick-Borne pathogens. Exclusion criteria: letters, comments, short communications, non-English literature and unrelated literature. All articles were imported into EndNote for management, yielding 2,036 records. After removing duplicates and preliminary screening by title and abstract, 261 articles underwent full-text evaluation, with 133 ultimately included for this review.

3. Diversity, evolution, and research advances of major Tick-Borne pathogens

3.1. Lyme disease-related Borrelia

Borrelia burgdorferi sensu lato complex represent the most prevalent Tick-Borne pathogenic group in temperate regions of the Northern Hemisphere. Their evolution and transmission are governed by multiple factors, including species divergence, vector distribution, host-pathogen interactions, and environmental cues, rendering this pathogen group a key focus of global public health concern (Mead, 2022). Pronounced intercontinental differentiation exists in the species diversity of this complex: Borrelia burgdorferi sensu stricto dominates in North America, while Borrelia afzelii and Borrelia garinii are the predominant species in Europe, with pathogenic species such as Borrelia miyamotoi also detected in certain regions. This heterogeneity directly contributes to distinct clinical manifestations of Lyme disease between Europe and North America (Marques et al., 2021; Gray et al., 2024; Cialini et al., 2025). In parts of Asia (South Korea), CO infection transmission of Borrelia burgdorferi and Anaplasma phagocytophilium has been confirmed (Ma et al., 2024).

Whole-genome analysis of 47 global isolates reveals a clonal structure of the core Borrelia genome, whereas plasmid-encoded lipoprotein genes involved in host interactions represent recombination hotspots. Natural selection and genetic recombination jointly drive genomic diversification, laying the molecular foundation for cross-host adaptation (Akther et al., 2024). Strain diversity profoundly impacts pathogenicity and tissue tropism: different strains of Borrelia burgdorferi sensu stricto exhibit marked variations in cardiac invasiveness, Borrelia garinii is more prone to inducing neuroborreliosis, and Borrelia afzelii is frequently associated with cutaneous and articular lesions (Pfeifle et al., 2025; Baux et al., 2025). During transmission, Borrelia must breach the sequential barriers of the tick midgut, hemocoel, and salivary glands, as well as host immune defenses. Stage-specific expression of outer surface lipoproteins including OspA, OspB, and OspC plays a pivotal role in cross-host adaptation, immune evasion, and tissue colonization (Rana et al., 2023; Radolf et al., 2021; O'Bier et al., 2024).

The geographical distribution of vector tick species directly dictates the spread range of the pathogen, with Ixodes scapularis in North America and Ixodes ricinus in Europe serving as the primary transmission vectors (Gray et al., 2024; Couret et al., 2022). The infection rate of adult Ixodes scapularis ticks in northeastern North America reaches 49%–54% and continues to rise, while the infection rate of Ixodes ricinus ticks in southern Sweden is as high as 35% (Cialini et al., 2025; Price et al., 2024). Geographic expansion of tick vectors, closely linked to global warming and habitat alterations, has further broadened the transmission range of Borrelia (Wimms et al., 2023; Socarras et al., 2022).

Host communities exert dual regulatory effects on the transmission cycle: wildlife migration facilitates cross-regional pathogen dispersal, whereas hosts such as roe deer and fallow deer can eliminate Borrelia via serum activity, generating a dilution effect. Small mammals including Apodemus and voles act as the main reservoir hosts, with their population density directly modulating transmission efficiency (Cialini et al., 2025; Veinović et al., 2024). Human genetic background also influences susceptibility to infection: the P53L missense mutation in the SCGB1D2 gene impairs inhibitory activity against Borrelia, significantly elevating infection risk (Strausz et al., 2024). Furthermore, Borrelia often causes coinfections with Anaplasma phagocytophilum and Babesia species, which may exacerbate disease severity and complicate clinical diagnosis and treatment (Ma et al., 2024; Veinović et al., 2024).

Lyme disease typically presents with erythema migrans as an early hallmark; untreated cases can progress to multi-system damage involving the nervous system, joints, heart, and other organs (Baux et al., 2025). Conventional two-tiered serological testing suffers from low sensitivity in the early stage of infection, and improved algorithms coupled with novel molecular diagnostic techniques are gradually optimizing diagnostic efficacy (Guérin et al., 2023; Taylor-Salmon and Shapiro, 2024). Early infections respond favorably to antibiotics such as doxycycline, yet effective interventions for chronic infections remain lacking, with lactate dehydrogenase identified as a potential therapeutic target (Sze et al., 2025). Multivalent chimeric vaccines based on OspA and OspC exhibit promising prospects, with protective efficacy reaching 80%–90% (O'Bier et al., 2024).

Genomic analyses of Borrelia are often limited by restricted isolate collections and short-term sampling strategies, which impair the ability to resolve fine-scale evolutionary trajectories and transmission routes. While preclinical data support the potential of vaccine candidates, these formulations have not been evaluated in large-scale clinical trials, with critical gaps remaining in the assessment of cross-genotype protection and long-term safety. Mechanistic inquiries into chronic Lyme disease are largely correlational, lacking definitive in vivo validation to substantiate their clinical relevance and translational potential. Improvements in diagnostic approaches have been modest rather than paradigm-shifting, and point-of-care diagnostic modalities remain underutilized in endemic regions, thereby hindering prompt case identification and clinical management.

3.2. Rickettsia

Rickettsia are obligate intracellular Gram-negative bacteria, and spotted fever group Rickettsia (SFGR) represents the predominant pathogenic lineage within this genus. Their evolution and transmission rely on synergistic interplay between tick vectors and vertebrate hosts, characterized by distinct geographical specificity and strong adaptability to tick vectors (Kim, 2022). To date, 48 SFGR species have been identified globally, transmitted by 146 tick species and classified into five ecological clusters; among them, Rickettsia felis and Rickettsia conorii pose pervasive threats to human public health (Zhang et al., 2023b).

Obvious heterogeneity exists in species diversity and pathogenicity across regions: Ixodes ricinus and Rhipicephalus ticks serve as the primary transmission vectors. Rickettsia rickettsii in the Americas can induce fatal Rocky Mountain spotted fever, whereas Rickettsia parkeri gives rise to mild spotted fever (Rodrigues et al., 2023; Martiniano et al., 2022). The overall prevalence of SFGR in ticks collected from Ningxia, China reaches 49.4%, accompanied by the identification of a novel candidate SFGR species (Zhu et al., 2025).

As for the immune escape mechanism, Rickettsia species use specific virulence effectors to manipulate host cells. For example, Rickettsia's outer membrane protein B (OmpB) can interact with host receptor Ku70 to mediate cell invasion, while other effectors (such as Sec7) help bacterial growth by inhibiting phagosome lysosome fusion (Rana et al., 2023). Unlike the pathogenic phagocytic Anaplasma, Rickettsia buchneri had little effect on the bioenergy of ticks and could not induce significant glycolysis (Samaddar et al., 2024). Climate warming and habitat transformations have facilitated the geographical expansion of Rickettsia. Novel epidemic strains have been documented in Kazakhstan, Iran and adjacent regions, leading to a sustained elevation in cross-regional transmission risk (Dong et al., 2023; Ghavami et al., 2024).

Studies have predominantly centered on virulence genes and surface antigens, yet the molecular pathways underlying pathogen-mediated metabolic and immune manipulation in tick vectors remain fragmented and incompletely characterized. Geographic surveillance studies frequently employ convenience sampling approaches and non-standardized PCR methodologies, which substantially compromise the comparability of findings across different research cohorts and regions. For the majority of novel or candidate Rickettsia species, formal pathogenicity assessments using animal models and epidemiological investigations linking these pathogens to human cases are lacking, resulting in unquantified public health risks. Additionally, the drivers of cross-regional pathogen spread are often oversimplified to climatic and habitat factors, with insufficient consideration of livestock movement, international trade, and human behavioral patterns—factors that collectively weaken the robustness and predictive capacity of current transmission models.

3.3. Anaplasma

The global infection prevalence of this bacterium in ticks is approximately 4.76%. In the northeastern United States, infection rates in adult Ixodes scapularis ticks range from 4% to 9%, and coinfection with Borrelia burgdorferi, the causative agent of Lyme disease, occurs at 8.2%. Similar to the complex strain level changes observed in its close relative Babesia, phagocytic Anaplasma also shows significant genetic diversity, thus affecting the potential and transmission dynamics of zoonoses (Price et al., 2024; Zintl et al., 2023; Karshima et al., 2022).

Anaplasma capra is an emerging species that has been reported across Asia, Europe, and Africa, with two recognized genotypes. Most human-derived isolates belong to genotype 2 (Altay et al., 2024). Establishment of A. capra infection in ticks requires the type IV secretion system effector AteA. This pathogen also modulates tick glycolytic metabolism to support its survival and colonization within the vector (Samaddar et al., 2024; Park et al., 2023).

The global prevalence estimates reported in studies show significant differences, which are closely related to variations in detection methods, tick developmental stages, and ecological settings, and no standardized meta-analytical framework has been established to date. For Anaplasma capra (A. capra), fundamental epidemiological data remain severely limited, including key information such as definitive vectors, reservoir hosts, human seroprevalence, and clinical spectrum, all of which remain unclear. Relevant mechanistic studies are only focused on the glycolytic pathway, while the specific effects of this pathogen on lipid metabolism, amino acid metabolism, and redox metabolism have not yet been explored. In addition, research on the synergy and clinical outcomes of co-infection in humans is relatively weak, which to a certain extent limits the clinical diagnosis and treatment guidance for severe cases.

3.4. Babesia

Babesia are apicomplexan protozoans, with Babesia microti representing the principal species pathogenic to humans, transmitted primarily by specific tick vectors including Ixodes ricinus (castor bean tick). To date, approximately 250 Babesia species have been described worldwide, with host associations covering 73 tick vector species and 224 vertebrate species (Fu et al., 2025; Bajer and Dwuznik-Szarek, 2021). Unlike the highly zoonotic B. microti sensu stricto, the “Munich” strain identified in Ireland is associated with limited public health risk (Zintl et al., 2023); Studies have shown that the activation of tick Toll pathway can induce the expression of defensin, which plays a key role in controlling Babesia minimus infection in the vector (Jalovecka et al., 2024). Babesia pathogens commonly establish coinfections with Rickettsia and Anaplasma species, the presence of these pathogens usually triggers up regulation of tick defensin gene expression (Szczotko et al., 2024).

Taxonomic uncertainty in studies has led to inconsistent naming of such pathogens and overestimated species diversity calculations, which affects the accuracy and comparability of research data. Mechanistic studies are limited to the Toll pathway, while other immune signaling modules and cellular responses have not yet been systematically characterized. The molecular basis of strain-specific virulence remains unclear, making it difficult to conduct effective risk stratification. Research related to coinfection mainly focuses on vector competence, with insufficient attention paid to clinical severity, treatment response, and long-term outcomes, thereby limiting its translational relevance.

3.5. Fever with Thrombocytopenia Syndrome Virus (SFTSV) and Tick-Borne Encephalitis Virus (TBEV)

Thrombocytopenia Syndrome Virus (SFTSV) and Tick-borne Encephalitis Virus (TBEV) represent the two most clinically significant tick-borne viral pathogens worldwide. Members of the Bunyaviridae and Flaviviridae families, respectively, both viruses show evolution, transmission dynamics, and genomic diversity tightly linked to host immunity, vector adaptation, and environmental shifts, establishing them as priority targets for global public health intervention (Johnson et al., 2023; Chiffi et al., 2023).

Thrombocytopenia Syndrome Virus is an emerging tick-borne bunyavirus associated with a case fatality rate of 5%–30%. Originally documented in rural and mountainous areas of East Asia, its distribution has expanded into urban settings; both the virus and its primary vector, the long-horned tick, have been detected in urban parks inside Beijing's Fifth Ring Road (Seo et al., 2021; Woo et al., 2025; Yuan et al., 2024). The virus displays extensive genomic diversity. In the Hangzhou region, five pure genotypes (A, B-2, D, E, F) and seven reassortant genotypes have been identified, with genotype E significantly associated with higher case fatality rates. Molecular dating suggests viral divergence began around 1,785, with subsequent dispersal across regions mediated by migratory birds, leading to a multicentric epidemic structure (Wen et al., 2024). Beyond tick-bite transmission, animal-to-human and human-to-human routes have been confirmed. Exposure to dogs and contact with infectious bodily fluids substantially elevate infection risk, and occasional family clusters have been reported (Woo et al., 2025).

At the pathogenic level, SFTSV enters host cells through its Gn/Gc glycoproteins, while the non-structural protein NSs suppresses host innate immune signaling. The virus replicates in platelets and stimulates hyperactivation, triggering coagulation disorders that culminate in thrombocytopenia and multiple organ failure (Sun et al., 2025; Fang et al., 2023). N6-methyladenosine (m6A) RNA modification critically supports infection: the viral nucleoprotein sequesters host m6A regulatory factors to enhance mRNA translation and genome stability. This modification is highly conserved in tick cells, providing a molecular mechanism for cross-species transmission (Chen et al., 2024c). The host factor IFITM3 binds the viral Gc protein to block cellular entry, while Akkermansia-derived hamalin mitigates systemic inflammation, highlighting novel therapeutic targets (Du et al., 2024; Xie et al., 2023). Currently, there are no licensed vaccines for SFTSV, and clinical care remains highly supportive. Although neutralizing antibodies and favipiravir show preliminary promise, large-scale clinical validation is still lacking (Zhang et al., 2025; Yu et al., 2026).

Tick-borne Encephalitis Virus is the dominant tick-borne encephalitic virus across Eurasia, with a geographic range that continues to expand. Endemic in many European countries and Heilongjiang Province, China, its spread is driven primarily by climate warming (Chiffi et al., 2023; Chen et al., 2024a). In addition to transmission by tick bite, food-borne infection has emerged as an important secondary route; consumption of unpasteurized cow's or goat's milk can cause household clusters, with children at elevated risk (Ličková et al., 2021; Buczek et al., 2022). TBEV is a positive-sense single-stranded RNA virus encoding three structural and seven non-structural proteins. The envelope (E) protein mediates viral attachment and membrane fusion, whereas NS5 interacts with SIRT1 to inhibit DNA damage repair, thereby worsening neurological injury (Pulkkinen et al., 2022; Sui et al., 2024). LRP8 has been identified as a key receptor for central nervous system entry; soluble receptor decoys targeting LRP8 effectively neutralize the virus, supporting a novel strategy for antiviral development (Li et al., 2025).

Tick-borne Encephalitis Virus infection typically follows a biphasic clinical course, and 40%–50% of patients develop long-term neurological sequelae. Severe illness and cognitive impairment are also well-documented in pediatric cases (Chiffi et al., 2023; Parfut et al., 2023). Distinct transcriptional responses in neurons, astrocytes, and microglia offer insights into the neuropathogenic mechanisms of TBEV (Rosendal et al., 2024). Licensed vaccines in Europe confer >92% protection and strongly reduce infection risk. However, no specific antiviral therapies are available, and nucleoside analogs and other candidates remain in preclinical or early clinical development (Angulo et al., 2023).

Transmission of both viruses displays strong seasonal and geographic patterns. Range expansion of tick vectors, host migration, viral mutation, and immune evasion together drive the growing global burden of tick-borne viral diseases, representing a central challenge for control programs. Future strategies will require strengthened surveillance, improved diagnostic platforms, and the development of next-generation vaccines and therapeutics based on newly identified molecular targets.

For SFTSV, Bird-mediated dispersal has been hypothesized, but direct tracking evidence and genomic phylogeographic data are still lacking. m6A, IFITM3, and hamalin findings are limited to in vitro or mouse models; human relevance is unconfirmed. Favipiravir and neutralizing antibody trials are small, non-randomized, and short–term, limiting clinical adoption. For TBEV, foodborne risk is understudied globally with limited dairy monitoring. Neurological sequelae mechanisms are poorly defined, hindering rehabilitation strategies. Antiviral development is slow, with poorly characterized off–target effects. Coinfections and interactions with other pathogens are entirely unstudied, preventing full epidemiological modeling.

3.6. Comparative analysis of major Tick-Borne pathogens

A comparative analysis of major Tick-Borne pathogens, ncluding their transmission cycles, pathogenic mechanisms, immune evasion strategies, and control measures is presented in Table 1.

Table 1.

Comparative analysis of major Tick-Borne pathogens.

Pathogen	Transmission cycle	Pathogenesis	Immune evasion strategies	Control measures
Borrelia	Ixodes-borne; The host community has dual regulatory effects on transmission; Co infection.	Significant differences in tissue tropism among different genospecies.	stage-specific expression of OspA, OspB and OspC; plasmid-encoded lipoprotein genes serve as recombination hotspots.	Doxycycline; multivalent vaccines.
Rickettsia	Ixodes-borne; synergistic interactions between ticks and vertebrate hosts.	Regulate tick metabolic and immune pathways to improve transmission adaptability; Virulence effectors mediate cytoskeletal rearrangement.	Plasmid-encoded surface protein gene recombination leads to antigen variation and immune evasion;unclear molecular pathway mechanism.	vector surveillance;Ecological environment management.
Anaplasma	Studies show that the tick carriage averages 4.76%; co infections with Borrelia.	Type IV effector AteA mediates infection; modulate tick glycolysis for colonization.	Modulates tick metabolism to adapt to the vector and sustain transmission.	Weak research on metabolism and mixed infection.
Babesia	Ixodes ricinus-borne.	Pathogenicity difference of different strains.	Activates tick Toll pathway; modulates defensin expression.	Insufficient research on clinical diagnosis and treatment of mixed infection.
SFTSV	Main vector Haemaphysalis longicornis; animal/human-to-human spread.	Invades host cells via envelope glycoproteins Gn/Gc, causing coagulation disorders.	NSs suppresses innate immunity; m6A modification enhances replication.	Supportive treatment; favipiravir;neutralizing antibody.
TBEV	Tick bite; food-borne via unpasteurized milk.	Neuroinvasion via LRP8; neuronal injury; long-term sequelae.	Envelope-mediated escape; NS5 inhibits DNA repair.	Licensed vaccines; symptomatic treatment.

Data compiled from cited references.

3.7. Coinfection of Tick-Borne pathogens

In tick-borne diseases, Borrelia burgdorferi, Rickettsia, Anaplasma, Babesia and some new pathogens are often co-infected. The coexistence of multiple pathogens can significantly change the disease process and have an important impact on clinical symptoms, diagnosis and treatment (Cutler et al., 2021).

Aggravating Clinical Symptoms: Co-infection can significantly aggravate the disease, increase the severe rate and mortality. When Lyme disease is combined with Anaplasma phagocytophilum or Babesia infection, the risk of multiple system damage is significantly increased (Ma et al., 2024).

Increasing Diagnostic Difficulty: The clinical symptoms of co-infection are lack of specificity and are prone to misdiagnosis and missed diagnosis (Ma et al., 2024; Cutler et al., 2021). Traditional detection methods are mostly targeted at a single pathogen, which is difficult to diagnose mixed infection, increasing the difficulty of diagnosis (Price et al., 2024; Karshima et al., 2022; Cutler et al., 2021).

Decreased therapeutic effect: A single antibiotic is difficult to cover the mixed infection of bacteria and protozoa, and the curative effect is reduced. When bacteria and protozoa coexist, the lack of a unified treatment scheme increases the difficulty of clinical treatment (Ma et al., 2024; Sze et al., 2025; Cutler et al., 2021).

Poor prognosis: The severe rate and mortality rate of patients with co-infection are higher. The risk of chronic sequelae (nerve, joint, heart injury) is increased, and the rehabilitation cycle is prolonged (Baux et al., 2025; Parfut et al., 2023).

4. Emerging Tick-Borne pathogens: discovery, diversity, and public health implications

As shown in Figure 1, new Tick-Borne pathogens continue to be found. With global warming and long-distance transmission through birds, they may pose an increasingly serious threat to global public health (Figure 1).

Figure 1.

Schematic diagram of the diversity of newly emerging Tick-Borne pathogens globally and the prevention and control of their transmission. This figure was created based on information and data from previous studies (Ni et al., 2023; Tian et al., 2025; Du et al., 2025; Ergunay et al., 2024a; Gömer et al., 2024; Wang et al., 2024; Jamil et al., 2025; Altay et al., 2024; Sheng et al., 2025; Shimojima et al., 2024).

New Tick-Borne pathogens continue to emerge and spread globally, representing a growing threat to public health. These agents span diverse viral and bacterial taxa, whose evolution and transmission are tightly associated with vector adaptation, host–vector interactions, and environmental changes, resulting in pronounced regional heterogeneity and variable pathogenic potential (Ni et al., 2023; Tian et al., 2025; Ergunay et al., 2024a; Du et al., 2025).

4.1. Novel tick-borne viruses

New viruses constitute the majority of novel pathogens, with species diversity far exceeding previous understanding. A global metatranscriptomic analysis of 31 tick species recovered 1,801 RNA viral genomes in a single investigation, establishing ticks as major natural reservoirs for RNA viruses (Ni et al., 2023). In Ningxia, China, 26 novel viruses were identified across seven tick species from three genera. Viral composition displayed strong genus-specificity: 22 viruses were unique to Ixodes, 12 to Dermacentor, and 27 to Haemaphysalis, reflecting close associations with tick geographic distribution and ecological traits (Tian et al., 2025). In Mexico, seven novel viruses were detected in ticks, including members of Bunyavirales and Flaviviridae; several are distantly related to known pathogenic viruses and may represent emerging public health threats (Laredo-Tiscareño et al., 2025).

Alongshan virus (ALSV) can antagonize the host's type I interferon response. Non-structural protein (nsp1) binds and degrades human stat2 protein through autophagy, directly inhibiting the expression of interferon-stimulated gene (ISG). Nsp1 can also induce mitochondrial autophagy and inhibit mitochondrial production, further weakening the host immune response. The methyltransferase of NSP can specifically bind to the key site F175/R176 in stat2. Inhibiting mitochondrial autophagy with 3-methyladenine or promoting mitochondrial formation with pioglitazone can reverse the inhibitory effect of nsp1 on ISG, which provides a potential strategy for antiviral therapy (Zhao et al., 2024).

Among recently recognized viral pathogens, the global expansion of ALSV is especially prominent. ALSV is a tetrapartite, single-stranded positive-sense RNA virus with surface glycoproteins carrying Asian lineage-specific signatures. Transmitted by Ixodes persulcatus, this virus was detected in 2.9% of tick samples from Mongolia, and human infections have been documented across multiple Asian and European countries (Du et al., 2025; Gömer et al., 2024). ALSV was identified for the first time in tick surveys from Poland; its genome falls within the European lineage with no evidence of recombination, indicating sustained endemic circulation via tick-borne transmission (Ergunay et al., 2025).

The incubation period of human infection with ALSV is 3–7 days. The clinical symptoms include fever, persistent headache, fatigue, nausea, cervical lymphadenopathy, mild liver injury, and no death cases have been reported. ALSV can cause obvious cytopathic effect in Vero cells (Ren et al., 2025; Kholodilov et al., 2020; Zhang et al., 2020). Human infection is closely related to tick bites. The disease mainly affects field workers aged 40–60 years, and the cases are concentrated in May to July when ticks are most active. The virus infects livestock such as sheep and goats, and can also reproduce in tick cells, indicating a wide range of hosts (Kholodilov et al., 2020; Litov et al., 2024). The virus was detected in all life stages of ticks, including adults, nymphs and larvae. Vertical transmission is also recorded, allowing the virus to persist in the natural cycle (Ebert et al., 2023; Wu et al., 2023). In Northeast China and Russia, Ixodes persulcatus is the main vector, and Ixodes ricinus is dominant in Europe. ALSV is often co-infected with other Tick-Borne pathogens, which increases the difficulty of clinical diagnosis and treatment. At present, there is no vaccine or specific drug on the market. Most patients can recover within 6–8 days after symptomatic treatment (Ren et al., 2025; Wu et al., 2013; Casel et al., 2021).

Other emerging viruses, including Tacheng tick virus 1 and 2, have been detected in northwestern China and adjacent regions. Tacheng tick virus 1 was found in both Dermacentor reticulatus and Ixodes ricinus, providing the first evidence that I. ricinus may act as a competent vector (Ergunay et al., 2024b). Songling virus (SGLV) was isolated from patients with tick biting history in Heilongjiang Province, China. The virus has the typical genomic characteristics of the genus nemerovirus and forms an independent phylogenetic clade. SGLV can cause pathological changes in human liver cancer cells; It can cause febrile diseases, accompanied by headache, dizziness, discomfort and fatigue (Ma et al., 2021). Wetland virus (WELV) is a novel orthonairovirus first identified from a tick-bitten patient with fever and multiple organ dysfunction in Inner Mongolia, China, in 2019. It is closely related to the Hazara orthonairovirus genogroup, capable of inducing cytopathic effects in human cells and causing lethal infections in mice. WELV has been detected in 17 patients across northeastern China, ticks of five species, and multiple animals, with Haemaphysalis concinna possibly serving as its transovarial vector (Zhang et al., 2024b).

4.2. Novel Tick-Borne bacteria

Novel bacterial Tick-Borne pathogens are widespread and carry clear zoonotic risk. Rickettsia barbariae was first isolated from eggs of Rhipicephalus turanicus in northwestern China. Its genome carries the full set of virulence genes typical of spotted fever group rickettsiae and is closely related to the pathogenic R. parkeri, suggesting high disease potential (Wang et al., 2024). This pathogen is widely distributed and has been documented in Algeria, Israel, and Türkiye (Abdelkadir et al., 2019; Waner et al., 2014; Erol et al., 2025). Its vectors include ticks such as Rhipicephalus turanicus, Hyalomma marginatum, and Rhipicephalus bursa, while hosts also include the flea Vermipsylla alakurt, marbled polecats (Vormela peregusna), and domestic cats (Abdelkadir et al., 2019; Waner et al., 2014; Zhao et al., 2016; Liu et al., 2018; Erol et al., 2025). Although human infection has been confirmed, systematic data on its pathogenicity, infectivity, vector competence, and actual disease burden remain limited (Wang et al., 2024; Erol et al., 2025). A previously unrecognized rickettsia detected in ticks from Pakistan clusters phylogenetically with Asian R. sibirica and African R. africae, pointing to historical intercontinental transmission (Jamil et al., 2025).

Anaplasma capra has diversified into two genotypes across Asia, Europe, and Africa. Most human isolates belong to genotype 2, with a broad host range covering humans, domestic animals, and wildlife, and transmission by multiple hard tick species, making it a growing global zoonotic threat (Altay et al., 2024). Human infection presents with fever, headache, fatigue, rash and lymphadenopathy; severe cases show elevated hepatic transaminases (Li et al., 2015). Unlike other Anaplasma species, it exclusively infects erythrocytes (Peng et al., 2021a,b). Genotype 2 strains carry higher pathogenic potential and severe disease has been documented (Li et al., 2015). It is widely distributed in China, France, Spain, South Korea and Russia (Jouglin et al., 2025, 2022; Ullah et al., 2025; Altay et al., 2022; Remesar et al., 2022; Amer et al., 2019; Yang et al., 2017). Hosts include humans, goats, sheep, cattle, dogs, deer and rodents (Shi et al., 2019; Peng et al., 2018; Remesar et al., 2022; Amer et al., 2019; Yang et al., 2017; Miranda et al., 2021). Prevalence in goats ranges from 9%–78.6% in China and reaches 24% in France (Jouglin et al., 2022; Peng et al., 2018; Yang et al., 2017); in dogs it is 12.1% (Shi et al., 2019); in roe deer (Spain) 5.8% and in water deer (South Korea) 17.8% (Remesar et al., 2022; Amer et al., 2019). Confirmed vectors include Haemaphysalis longicornis, Ixodes persulcatus, Rhipicephalus microplus, Dermacentor marginatus, Haemaphysalis concinna, Rhipicephalus turanicus and Alveonasus lahorensis (Guo et al., 2019; Ullah et al., 2025; Yang et al., 2016; Tang et al., 2024; Tan et al., 2025). Pathogen detection in H. concinna salivary glands in France supports its vector competence (Jouglin et al., 2025). Tick infection rates are 1.32% (Hubei), 8%–63% (Shandong), 1.8% (Xinjiang) in China (Tang et al., 2024; Tan et al., 2025; Lu et al., 2023). Human cases are concentrated in East Asia and spreading to Europe, with a severe case rate of ~18% and fatal outcomes reported (Li et al., 2015). Coinfections with Rickettsia, Borrelia and Anaplasma phagocytophilum are common, exacerbating illness and complicating diagnosis (Guo et al., 2019; Miranda et al., 2021). Its prevalence and geographic range have expanded in recent years, making it an important emerging tick-borne zoonosis (Peng et al., 2018; Yang et al., 2017; Li et al., 2015). For comparative, the vector, geographical distribution and clinical characteristics of the key emerging Tick-Borne pathogens are summarized in Table 2.

Table 2.

Vector, distribution, and clinical significance of key emerging Tick-Borne pathogens.

Pathogen	Vector	Distribution	Clinical significance
ALSV	I. persulcatus, I. ricinus	Asia, Europe	Fever, headache, fatigue, nausea, cervical lymphadenopathy, mild liver injury, no deaths
Tacheng tick virus	D. reticulatus, I. ricinus	NW China	Potential public health threat
SGLV	Ticks	Heilongjiang, China	Fever, headache, dizziness, fatigue
WELV	H. concinna, etc	NE China	Fever, organ dysfunction
R. barbariae	R. turanicus, H. marginatum, R. sanguineus	NW China, Algeria, Israel, Türkiye	Human infection confirmed
A. capra	Multiple hard ticks	China, France, Spain, South Korea, Russia	Fever, headache, fatigue, rash, lymphadenopathy; fatal cases reported

Data compiled from cited references.

4.3. Transmission dynamics and control of emerging Tick-Borne diseases

Climate warming and habitat alteration are driving the geographic expansion of tick vectors. These changes support the cross-regional transmission of diverse pathogens. Migratory birds and other mobile hosts further promote the long-distance dissemination of pathogens. For example, SFTSV has formed multicenter epidemic distributions through bird-mediated dispersal (Sheng et al., 2025). Both viral and bacterial pathogens improve environmental and host adaptability via genomic recombination and mutation. In tick-borne bunyaviruses, N-glycosylation of viral glycoproteins modulates virulence and host tropism (Shimojima et al., 2024). Interactions between the host skin microbiome and Tick-Borne pathogens have drawn growing research interest. Hamalin produced by Akkermansia can dampen inflammatory responses, offering new intervention targets against emerging infections (Xie et al., 2023).

Nearly all work in studies is limited to pathogen discovery and genome sequencing, lacking systematic assessments of their pathogenicity, infectivity, host range, vector competence, and human disease burden. Metagenomic studies mostly adopt convenience sampling methods and fail to cover the vast regions of Africa, South America, and tropical Asia. Research on microbiome interactions focuses only on single strains rather than community effects, which reduces the ecological realism of the studies. The development of diagnostic methods, vaccines, and drugs for these emerging pathogens has not yet been carried out, creating a critical gap in prevention and control preparedness.

4.4. Limitations and challenges

The lack of suitable animal models for viruses such as CCHF limits the evaluation of efficacy; The protective efficacy of SFTSV vaccines in the elder remains suboptimal, and the therapeutic efficacy of drugs in the later stages of the disease is poor; Lyme disease vaccines must strike a balance between immunogenicity and safety to avoid the risk of cross-reactivity (Wang et al., 2025; Zhang et al., 2025; Strnad et al., 2020). Pathogen genetic diversity and variation pose challenges to cross-protection provided by vaccines, necessitating the development of multivalent vaccines or the design of conservative antigens to address these issues (Chen et al., 2024b). In the future, there is a need to strengthen interdisciplinary collaboration, combining structural biology and immunomics to optimize antigen design, and utilizing novel delivery systems such as LNP to enhance immunogenicity; to advance multicentre clinical trials to clarify the efficacy and safety of drugs across different populations; and to strengthen cross-regional monitoring and collaboration under the principle of One Health, ultimately achieving precise and efficient prevention and control of tick-borne diseases.

Most vaccine candidates in studies do not take into account the genetic diversity of circulating strains, posing a risk of narrow protective spectrum. Clinical trials are small in scale, conducted in single centers, and have short follow-up periods, lacking real-world effectiveness data. Animal models often fail to accurately simulate human pathogenesis, reducing their predictive value.

5. New techniques for detection of Tick-Borne pathogens

The traditional detection technology of Tick-Borne pathogens generally has the defects of low detection flux and unable to identify unknown pathogens, which makes it difficult to achieve rapid and accurate detection. In recent years, CRISPR-Cas, metagenomic next-generation sequencing (mNGS) and microfluidics, have shown great potential in breaking through the above limitations, and have a good application prospect in the detection of Tick-Borne pathogens.

In the field of CRISPR technology, some researchers have constructed CRISPR/dCas9 biosensor, which can quickly distinguish scrub typhus and severe fever with thrombocytopenia syndrome (SFTS) within 20 min. The sensitivity is 100 times higher than that of RT-PCR, and can reach the single molecule level (Koo et al., 2018). For TBEV, RT-RPA combined with CRISPR/Cas13a and lateral flow dipstick can complete the detection within 1 h. The sensitivity and specificity of clinical samples are 100%, which is suitable for grass-roots site use (Zhang et al., 2024a). Similarly, the detection method based on RPA-CRISPR/Cas12a can detect Anaplasma marginale (4 copies/μL) and SFTSV (3 copies/reaction), which has strong specificity and is suitable for rapid detection in the field (Sutipatanasomboon et al., 2024; Huang et al., 2022). In addition, a one-step CRISPR/Cas12a detection system has been established to complete the detection of SFTSV within 45 min (Shu et al., 2025). In addition, RPA-CRISPR/Cas12a can also specifically detect Ehrlichia canis and Anaplasma platys, with higher sensitivity than PCR (Paenkaew et al., 2023). CRISPR/Cas12a combined with RT-RPA has also been used to rapidly detect multiple genotypes of SFTSV (Park et al., 2022). In addition, targeted retrieval was conducted for each novel diagnostic technology to supplement key original studies, and the backward and forward citation tracking methods were used to further identify relevant literature, ensuring no omission of important research.

Metagenomic next-generation sequencing has the advantages of broad-spectrum and unbiased detection, which can identify all known and unknown viruses, bacteria, fungi and parasites in the sample at one time, and has been widely used for the detection of Tick-Borne pathogens (Jiao et al., 2021).

According to the mNGS detection of Dermacentor nuttalli and Ixodes persulcatus in Inner Mongolia, China, Candidatus Rickettsia tarasevichiae was found in Dermacentor nuttalli in China for the first time (Jiao et al., 2021). Large scale mNGS monitoring of Dermacentor ticks in Mongolia detected Rickettsia, Anaplasma, Bartonella, etc., which clarified the high prevalence of tick-borne diseases in local livestock and provided a basis for cross-border transmission risk assessment (Altantogtokh et al., 2022). Shanghai, Qingdao and other places in China have found SGLV, Hubei tick virus and other new tick-borne viruses in Haemaphysalis longicornis and Ixodes persulcatus through mNGS, expanding the knowledge of tick viromics (Zeng et al., 2025; Hu et al., 2023).

In clinical application, mNGS has obvious advantages for laboratory diagnosis of atypical cases such as Rickettsia, TBEV, SFTSV, etc., which can quickly identify the pathogen, especially for cases without clear epidemiological exposure history (Zhang et al., 2023a). In patients with tick-borne encephalitis virus infection, the whole genome of the virus can be directly obtained through mNGS detection of cerebrospinal fluid samples, helping to trace the source of typing (Zakotnik et al., 2022). A 4-year-old encephalitis patient was diagnosed with Powassan virus (POWV) infection in Ohio, USA through mNGS (Farrington et al., 2023).

Although mNGS has obvious advantages, there are also challenges such as high cost, complex data analysis, insufficient sensitivity of detection of low abundance pathogens, and background microbial interference (Hu et al., 2023). In the future, with technological progress and cost reduction, mNGS will play an important role in the monitoring of Tick-Borne pathogens and early warning of new pathogens, providing important technical support for the prevention and control of tick-borne diseases. In addition, targeted retrieval was conducted for each novel diagnostic technology to supplement key original studies, and the backward and forward citation tracking methods were used to further identify relevant literature, ensuring no omission of important research.

Microfluidic is an important tool for the rapid detection of Tick-Borne pathogens by virtue of its advantages of miniaturization, high throughput and rapid detection, which can realize the synchronous detection of multiple samples and pathogens (Rodino and Pritt, 2021).

High-throughput microfluidic technology has been mature for large-scale epidemiological investigation of Tick-Borne pathogens. Ninety-six samples can be detected in a single run, covering a variety of Tick-Borne pathogens such as Borrelia, Rickettsia, and Anaplasma, significantly improving the detection efficiency (Moutailler and Galon, 2024). In the study of parasitic ticks on ruminants in Senegal, 36 kinds of pathogenic microorganisms can be screened at a time by using this technology (Rodino and Pritt, 2021). In the monitoring of ticks in tropical areas, microfluidic PCR combined with network analysis can simultaneously detect a variety of pathogens, revealing the co-infection mode and interaction relationship of pathogens (Díaz-Corona et al., 2024). The microfluidic chip based on RT-LAMP-CRISPR/Cas12b can realize portable and rapid detection of SFTS.The chip is driven by manual pressure without external power supply, and the detection limit is as low as 5 copies/reaction. The sensitivity of clinical samples is 88.9% and the specificity is 100% (Long et al., 2026).

With technological iterations, microfluidic chips will further integrate nucleic acid extraction, amplification and detection processes, and play a greater role in the large-scale monitoring of Tick-Borne pathogens (Boularias et al., 2021). In addition, targeted retrieval was conducted for each novel diagnostic technology to supplement key original studies, and the backward and forward citation tracking methods were used to further identify relevant literature, ensuring no omission of important research. In addition, targeted retrieval was conducted for each novel diagnostic technology to supplement key original studies, and the backward and forward citation tracking methods were used to further identify relevant literature, ensuring no omission of important research.

6. Conclusions and outlook

Ticks are major vectors of viral, bacterial, and protozoan pathogens that cause widespread zoonotic diseases, threatening human health and livestock production. Climate warming and human activity have expanded tick ranges and driven pathogen emergence, making tick-borne disease control an urgent global challenge. Recent advances in pathogen diversity, evolution, vector–pathogen–host interactions, control strategies, and countermeasure development have strengthened the evidence base for targeted intervention.

6.1. Priorities for future research

Future research must prioritize the following aspects:

1. Conduct sustained, global, and genetically informed surveillance of emerging Tick-Borne pathogens to improve relevant databases and risk maps;

2. Carry out mechanistic studies in natural vector-host systems to clarify the causal pathways of transmission and pathogenesis;

3. Develop broadly protective, thermostable, and age-optimized vaccines and therapeutics, focusing on the elderly and coinfected patients;

4. Build an integrated One Health system that organically combines ecological management, personal protection, surveillance and early warning, and cross-border collaboration.

6.2. Conclusion

In general, the research and prevention and control of Tick-Borne pathogens is a long-term and systematic project. It is necessary to face the limitations of existing research, abandon the research mode of single dimension and local area, and strengthen interdisciplinary, cross departmental and cross regional cooperation based on basic research, with technological innovation as the core and practical application as the guidance in the future, so as to continuously improve the scientific cognition level and comprehensive prevention and control ability of Tick-Borne diseases, minimize its harm to human health and animal husbandry development, and ensure public health safety and ecological environment stability.

Funding Statement

The author(s) declared that financial support was received for this work and/or its publication. This work was supported by the Natural Science Foundation of Chongqing [grant number CSTB2024NSCQMSX0795], Chongqing public health key specialty (discipline) project, and Chongqing Medical Scientific Research Project (Joint project of Chongqing Health Commission and Science and Technology Bureau) [Grant Number 2026ZDXM016]. This work was also supported by the National Key Research and Development Program of China [Grant Number: 2024YFC2311403]. These projects provides relevant financial support for this study, and all authors agree with this modification.

Author contributions

GD: Writing – original draft, Writing – review & editing. LK: Writing – review & editing. SD: Data curation, Visualization, Writing – original draft. SN: Writing – review & editing. WG: Funding acquisition, Writing – review & editing.

Conflict of interest

The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Generative AI statement

The author(s) declared that generative AI was used in the creation of this manuscript. The creation of the illustrations was assisted by Nano Banana 2 and literature screening and sorting were assisted by Doubao, an AI assistant developed by ByteDance.

Any alternative text (alt text) provided alongside figures in this article has been generated by Frontiers with the support of artificial intelligence and reasonable efforts have been made to ensure accuracy, including review by the authors wherever possible. If you identify any issues, please contact us.

Publisher's note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.