Ehrlichia spp. and Ehrlichioses: Diversity, Distribution, Zoonotic Potential, and Challenges for Surveillance from a One Health Perspective

1. Introduction

Tick-borne diseases represent a relevant and growing challenge to both public and animal health because of the wide distribution of these vectors, the diversity of infectious agents they transmit, and the involvement of domestic and wild animals in maintaining the epidemiological cycles [1,2]. Climatic and environmental changes, including rising temperatures, land use and land cover changes, habitat fragmentation, and urbanization, directly influence the geographic distribution, population abundance, and seasonal dynamics of ticks. These factors affect host availability and community composition, thereby modifying the risk of exposure of animals and humans to pathogens transmitted by these vectors [3,4]. The complexity of these interactions complicates the surveillance and control of tick-borne diseases, reinforcing the need to integrate information on vectors, pathogens, hosts, and the environment within the One Health framework [1,5].

Within this context, bacteria of the genus Ehrlichia, which belong to the family Anaplasmataceae and the order Rickettsiales, are of particular importance. These microorganisms are gram-negative, pleomorphic, obligate intracellular bacteria transmitted primarily by ticks and capable of infecting hematopoietic cells of different vertebrate hosts [6,7]. Within host cells, the bacteria multiply in membrane-bound vacuoles, forming microcolonies known as morulae, a characteristic morphological feature associated with infections caused by these agents [6]. Species within the genus exhibit distinct cellular tropisms and host ranges and are associated with diseases of medical and veterinary importance in humans, domestic animals, and wildlife [7,8].

The diversity within the genus Ehrlichia includes species with distinct epidemiological profiles and varying degrees of relevance to human and animal health. Ehrlichia chaffeensis, Ehrlichia ewingii, and Ehrlichia muris subsp. eauclairensis are recognized as causative agents of human ehrlichiosis, whereas Ehrlichia canis and Ehrlichia ruminantium are well-established veterinary pathogens [8,9,10]. More recently, Ehrlichia minasensis has emerged as a species of increasing interest, particularly because of its association with cattle and the tick Rhipicephalus microplus. Initially described from an isolate obtained from Rhipicephalus (Boophilus) microplus in Brazil [11], the species was subsequently detected molecularly in cattle in the state of Bahia [12,13] and in horses [14], while serological evidence suggests exposure of dogs to this agent [15]. Despite these findings, several aspects related to its geographic distribution, genetic diversity, host range, transmission dynamics, pathogenicity, and possible relevance to public health remain poorly understood.

The progressive identification of Ehrlichia species and genotypes has expanded knowledge of the genus; however, the available evidence remains unevenly distributed across geographic regions and host types. Nonspecific clinical manifestations, serological cross-reactivity, and variation in molecular diagnostic sensitivity according to the stage of infection complicate etiological confirmation [16,17,21]. In Brazil, the circulation of Ehrlichia spp. in animals and ticks is well documented, whereas evidence of human infection remains largely based on serological findings without definitive species-level identification [18,19]. Therefore, this review was structured to address five main questions: which species cause human infection and disease; which tick species are confirmed vectors; which vertebrates act as reservoirs, infected hosts, or sentinels; why the widespread circulation of Ehrlichia in animals in Latin America contrasts with the small number of confirmed human cases; and which components of integrated surveillance may help reduce this uncertainty. The objective was to critically analyze the available evidence on diversity, epidemiology, transmission, zoonotic potential, and surveillance, while distinguishing conclusions supported by current data from hypotheses that still require confirmation.

2. Review Methodology

2.1. Search Strategy

A critical narrative review was conducted using a structured search in PubMed/MEDLINE and SciELO, complemented by searches in the CAPES Journal Portal, Google Scholar, and indexing and citation records available through the Scopus and Web of Science databases. The final update, conducted in September 2026, included targeted searches addressing human epidemiology, diagnostic and surveillance criteria, Brazilian notification policies, One Health implementation, and backward and forward citation tracking of the key studies. No initial publication year restriction was applied because historical studies were necessary to describe taxonomic developments, demonstrate transmission, and document the earliest reported cases.

Search terms in English, Portuguese, and Spanish were combined using the Boolean operators AND and OR. The main search strategies covered were as follows: (1) Ehrlichia, ehrlichiosis, or ehrlichioses in association with public health, zoonoses, and One Health; (2) epidemiology, distribution, and surveillance; (3) ticks, vectors, and vector competence; (4) hosts and reservoirs; and (5) Brazil and Latin America. Complementary searches included diagnosis, PCR, paired serology, case definitions, notification, clinical manifestations, treatment, emerging species, and publications from 2024 to 2026. Institutional sources included documents from the Centers for Disease Control and Prevention, the Brazilian Ministry of Health, and the Quadripartite collaboration composed of the FAO, UNEP, WHO, and WOAH. Search expressions were adapted to the available fields and specific characteristics of each source.

Records retrieved from PubMed and SciELO were exported and compared using unique identifiers within the respective databases. Records with the same identifier were considered duplicates and counted only once.

In PubMed, English-language terms were searched in the title and abstract fields (Title/Abstract). The five search strategies retrieved 866, 909, 52, 398, and 279 records, respectively. The combined searches yielded 2,504 records. The comparison of unique identifiers identified 709 duplicate occurrences across the search strategies, which were counted only once, resulting in 1,795 unique publications.

In SciELO, equivalent terms in English, Portuguese, and Spanish were searched across all indexes of the database. The five search strategies retrieved 31, 35, 114, 25, and 77 records, respectively, for a total of 282 records. A comparison of record identifiers identified 100 duplicate occurrences among the search strategies. After removing duplicates, 182 unique publications remained in the database.

In the CAPES Journal Portal, thematic combinations were searched across all fields, with the document type restricted to journal articles. The five searches returned 687, 1,457, 4,386, 1,078, and 376 results. Because the portal aggregates records from multiple databases and has limitations regarding the simultaneous export of all retrieved results, these searches were used as complementary sources. The totals obtained from the different strategies were not combined because of the substantial overlap among the retrieved records.

In Google Scholar, combinations of terms related to Ehrlichia, ehrlichiosis, and ehrlichioses with public health, zoonoses, and One Health returned approximately 25,600 results. Because the number displayed by the platform is only an estimate, duplicate versions are common, and multiple document types are included, Google Scholar was used as a complementary source to identify relevant publications and obtain full-text articles. Therefore, its search output was not incorporated into the quantitative totals of the structured databases.

During the preparation of this review, Consensus was also used as a complementary tool to identify potentially relevant literature. Publications suggested by the platform were considered only after independent verification of their bibliographic information, access to the original source, and critical appraisal of their content by the authors.

2.2. Selection Criteria

Original research articles, brief communications, case reports, reviews, and official technical documents published in Portuguese, English, or Spanish were considered. The selection prioritized studies that allowed assessment of taxonomy, geographic distribution, epidemiology, vectors, transstadial or transovarial transmission, hosts, reservoirs, human or animal infection, diagnosis, zoonotic potential, surveillance, and One Health concepts. For key questions, priority was given to primary studies involving molecular confirmation, isolation, sequencing, longitudinal designs, or experimental demonstration; review articles were used primarily for the contextualization and identification of seminal studies.

No initial publication-date restriction was applied because older studies considered fundamental for species description, experimental demonstration of transmission, vector identification, or documentation of the earliest cases were necessary for historical and epidemiological contextualization. Studies based exclusively on serological evidence were retained when relevant, but their findings were interpreted cautiously, considering the possibility of cross-reactivity and the inability of antibody detection alone to confirm active infection.

Duplicate records, publications unrelated to the main questions of the review, documents lacking sufficient methodological information, and studies in which agent identification did not support the proposed conclusions were excluded. Negative findings were retained when they contributed to assessing the consistency, frequency, or limitations of the available evidence on transmission and human infection.

Study selection was purposeful and guided by the contribution of each publication to the critical questions addressed in this review. Updated searches were conducted to identify recent publications, studies reporting divergent findings, and relevant regulatory or policy documents. In total, 75 documents were included in this synthesis. The number of records retrieved reflects the initial breadth of the searches but does not represent a systematic study selection flow; therefore, these figures should not be interpreted as evidence of exhaustive retrieval.

2.3. Data Extraction and Synthesis

The following information was extracted: taxon investigated, year, geographic location, host, tick species, diagnostic method, type of evidence, and relevance to human, animal, or environmental health. Interpretation followed an explicit hierarchy of evidence: seroreactivity was considered indicative of probable exposure but not necessarily species-specific; molecular detection demonstrated the presence of pathogen DNA in the sample but did not establish disease, vector competence, or reservoir competence; multilocus sequencing and isolation increased confidence in taxonomic identification; a clinical association supported by a direct diagnostic method strengthened evidence of causality; and experimental transmission demonstrated vector or reservoir competence. For human cases, PCR or another molecular assay, isolation followed by molecular confirmation, immunohistochemistry, or a fourfold increase in IgG titer between paired serum samples were considered confirmatory evidence, in accordance with the CDC surveillance case definition [61].

Data were organized thematically and analyzed qualitatively. The synthesis compared concordant, divergent, and negative findings and avoided equating detection in ticks with vector competence, a positive PCR result in an animal with reservoir competence, or circulation in animals with zoonotic potential. The classification of each taxon was based on the convergence of molecular evidence, clinical disease, vector involvement, host associations, and geographic distribution, as well as on the remaining knowledge gaps that precluded stronger conclusions.

3. Characterization of the Genus Ehrlichia

3.1. Taxonomic and Biological Aspects

The genus Ehrlichia belongs to the order Rickettsiales and family Anaplasmataceae and comprises pleomorphic, obligate intracellular bacteria [6,7,22]. The classification of organisms currently included in this family has changed significantly over time. Initially, morphological characteristics, cellular tropism, hosts, and vectors were widely used to differentiate them; however, these criteria did not always accurately reflect their evolutionary relationships. Phylogenetic analyses based primarily on the 16S rRNA gene sequences and the groESL operon demonstrated genetically distinct clusters and led to a broad taxonomic reorganization [22]. Consequently, some species previously classified within the genus Ehrlichia were transferred to the genera Anaplasma and Neorickettsia, whereas Cowdria ruminantium was incorporated into the genus Ehrlichia as Ehrlichia ruminantium [22]. These changes should be considered when interpreting older literature because obsolete nomenclature can hinder comparisons among studies and delineation of diversity currently attributed to the genus Ehrlichia.

From a biological perspective, these microorganisms multiply within membrane-bound cytoplasmic vacuoles. Within these compartments, they form characteristic bacterial aggregates known as morulae, which can be visualized in infected cells during certain stages of infection [6,7,23]. The intracellular developmental cycle involves dense-cored cells, which are infectious and adapted for adhesion to and entry into host cells, and reticulate cells, which are metabolically active and responsible for bacterial replication. After successive cycles of replication, reticulate cells differentiate back into dense-cored forms, enabling the dissemination of the infection to other cells [7,23].

Although they share this intracellular developmental strategy, Ehrlichia species differ in cellular tropism. Ehrlichia chaffeensis and E. canis predominantly infect cells of the mononuclear phagocyte system, particularly monocytes and macrophages, whereas E. ewingii has greater tropism for granulocytes, especially neutrophils [6,7,8]. In contrast, E. ruminantium replicates mainly in endothelial cells of blood vessels in vertebrate hosts [10]. Available evidence also supports the tropism of E. minasensis for bovine monocytes, because bacterial morulae were observed in these cells during primary culture established from peripheral blood of a naturally infected calf from a farm in the state of Mato Grosso, Brazil. An isolate subsequently designated the Cuiabá strain was obtained from this animal [12]. Differences in cellular tropism contribute to variation in pathogenesis and the clinical and hematologic manifestations associated with the different species.

3.2. Species Diversity and Medical and Veterinary Relevance

The currently recognized diversity of the genus Ehrlichia includes seven tick-borne species with validly published names: Ehrlichia canis, E. chaffeensis, E. ewingii, E. muris, E. ruminantium, E. minasensis, and E. japonica [6,7,11,24,25]. The latter, formerly designated Ehrlichia sp. HF, was originally isolated from Ixodes ovatus ticks in Japan and recognized as a distinct species based on genomic comparisons, with its name validated in 2022 [24,25]. Although it is highly pathogenic to mice under experimental conditions and is used as a model for studying severe forms of human ehrlichiosis, its relevance as an agent of natural infection in humans or domestic animals remains undetermined [24]. However, the diversity of the genus is not limited to formally recognized species because different genotypes and provisional taxa have been identified in ticks and vertebrate hosts, many of which have not yet been isolated or fully characterized biologically.

Ehrlichia chaffeensis, E. ewingii, and E. muris subsp. eauclairensis have the most consistent body of evidence as human pathogens, including molecular confirmation and clinical association [8,9,17,26]. E. chaffeensis is the principal agent of human monocytic ehrlichiosis and can cause severe multisystem disease, particularly when treatment is delayed or immunosuppression is present. E. ewingii, initially recognized in dogs, also causes human granulocytic ehrlichiosis. E. muris subsp. eauclairensis was defined from cases and isolates in the upper midwestern United States. The medical relevance of E. muris subsp. muris remains less clearly defined. Collectively, these agents show that the classification of a cycle as veterinary or wildlife-associated does not preclude human infection when the vector also feeds on humans.

Panola Mountain Ehrlichia broadens this spectrum. DNA from the agent was sequenced from the blood of a patient after a bite from Amblyomma americanum, providing molecular evidence of infection associated with febrile illness [60]. A subsequent longitudinal study detected natural infection in cattle, including outside the peak vector activity period, suggesting a broader animal cycle than that indicated by the isolated human report [59]. These findings support further investigation but do not permit the estimation of human incidence, population-level pathogenicity, or the role of cattle as reservoirs.

In veterinary medicine, E. canis and E. ruminantium are prominent agents of important diseases in companion and production animals, respectively. Ehrlichia canis is the etiologic agent of canine monocytic ehrlichiosis, a globally distributed disease that may follow an acute, subclinical, or chronic course and cause important hematologic abnormalities, particularly thrombocytopenia, anemia, and, in the most severe cases, pancytopenia [6,8]. Although its importance is established primarily in animal health, molecular reports of human infection, including the detection of identical agent sequences in a patient and in a tick removed from that patient in Italy, indicate that its zoonotic potential should not be disregarded, even though its epidemiologic magnitude remains uncertain [27]. Ehrlichia ruminantium, in turn, causes heartwater, also known as cowdriosis, a potentially fatal disease of domestic and wild ruminants. Its occurrence is concentrated across much of sub-Saharan Africa and islands near the African continent, with records also from some Caribbean islands, where it represents an important animal-health constraint on livestock production [10,28]. These species illustrate the broad veterinary relevance of the genus, encompassing both clinical care of companion animals and herd health, as well as economic losses associated with tick-borne diseases.

In addition to these species of veterinary importance, E. minasensis is a more recently recognized agent in the context of bovine ehrlichiosis. Formally described from an isolate obtained from R. microplus in Brazil, the species has been recorded in countries in the Americas, Africa, Asia, and Europe, indicating a broader geographic distribution than initially recognized [11,12]. Its animal-health relevance is supported by evidence from natural and experimental infections in cattle, in which manifestations compatible with ehrlichiosis were observed, including fever, depression, lethargy, and thrombocytopenia, along with morulae in peripheral-blood monocytes [12,29]. Molecular or serologic detection of the agent in other vertebrate hosts, including cervids, horses, and dogs, raises additional questions regarding its ecology and host range [12,14,15]. Despite these advances, the frequency of infection, vector competence of the different tick species involved, and the clinical and production consequences for herds remain poorly understood, limiting the assessment of the importance of E. minasensis to cattle health.

However, from a public health perspective, currently available evidence is insufficient to classify E. minasensis as a zoonotic agent because its ability to infect and cause disease in humans remains undetermined [30]. Molecular detection of the bacterium in ticks alone does not establish vector competence, and its occurrence in different animal hosts does not demonstrate the ability to transmit to humans [12,14,15,30]. Nevertheless, the circulation of E. minasensis at the interface among cattle, ticks, other vertebrate hosts, and potentially exposed human populations warrants investigation within a One Health framework. Accordingly, its inclusion in public health discussions should be as a species of still-undetermined zoonotic relevance rather than as an established zoonotic agent.

Table 1 summarizes the medical and veterinary relevance of the main taxa and explicitly presents the current strength of the evidence and the principal gap limiting interpretation of the data.

4. Geographic Distribution, Vectors, and Hosts

4.1. Geographic Distribution and Epidemiologic Overview

The epidemiology of infections caused by Ehrlichia species results from interactions among tick vectors, vertebrate hosts, and environmental conditions that favor the maintenance of transmission cycles. The distribution of these agents is heterogeneous; some occur predominantly in specific regions, whereas others have been reported on different continents [6,8,10,12]. However, interpretation of geographic records must consider that the identification of a species also depends on the sampling effort, populations investigated, and diagnostic methods used. The limited use of molecular testing and the absence of specific surveillance systems may contribute to underdetection and produce an incomplete picture of Ehrlichia circulation in certain regions [17,21]. Thus, the distribution described in the literature reflects current knowledge but does not necessarily represent the true geographic limits of each agent.

Among the taxa included within E. muris, E. muris subsp. muris has a predominantly Eurasian distribution, with its original isolation in Japan, whereas human cases associated with E. muris subsp. eauclairensis were initially concentrated in Minnesota and Wisconsin in the United States [9]. Subsequent molecular detection of this subspecies in I. scapularis ticks and Peromyscus leucopus rodents in Massachusetts provided evidence of enzootic circulation in the northeastern United States, expanding its previously recognized geographic distribution [32]. Nevertheless, human cases remain predominantly associated with the upper Midwestern United States, indicating that the distribution of this agent has not been fully delineated [9,32].

In South America, particularly Brazil, there is a contrast between the widespread circulation of Ehrlichia in animals and the limited characterization of human infections. E. canis is endemic to dogs in different regions, and human surveys have detected antibodies reactive to Ehrlichia spp.; however, serology alone cannot reliably identify the species or confirm active infection [18,19,33,34]. Complementing these findings, a PCR investigation of 75 febrile patients with a history of tick bites detected no Ehrlichia DNA in human samples, although E. canis was confirmed in four of five dogs examined [58]. The coexistence of human seroreactivity, widespread canine circulation, and negative human molecular results indicates uncertainty, not proven absence or established transmission. Prospective studies with early sampling, paired samples, and sequencing are needed to resolve this discrepancy.

Molecular evidence from Latin America is not uniform. In Costa Rica, five of 22 human samples yielded amplification products and sequences compatible with E. chaffeensis, providing relevant direct evidence, although the sample size and timing of collection limited estimates of frequency [68]. In the same country, detection of an E. canis genotype in blood donors supports infection or exposure but does not demonstrate clinical disease [71]. In Argentina, DNA attributed to E. chaffeensis was reported in A. parvum and marsh deer [72,73], and the agent was also detected molecularly in marsh deer in Brazil [74]. These findings support regional circulation and surveillance priorities, but DNA in a tick does not establish vector competence, and DNA in a vertebrate does not establish reservoir competence or the burden of human disease.

The extensive animal circulation underlying this scenario is particularly evident for E. canis, a globally distributed species found mainly in tropical and subtropical regions where populations of Rhipicephalus sanguineus sensu lato are established [6,18]. In Brazil, serologic and molecular studies have demonstrated the occurrence of the agent in dogs from different regions, although infection frequencies vary according to the characteristics of the populations evaluated, environmental conditions, and diagnostic methods used [18,19]. In the Northeast, an investigation conducted in municipalities in the semiarid region of Ceará detected E. canis DNA in 9.9% of dogs examined in Sobral and 5.6% of those from Alcântaras [35]. In southern Brazil, detection of antibodies against E. canis in dogs living in tick-infested households likewise demonstrated animal exposure in urban settings [19]. These records, obtained in distinct climatic and socioenvironmental contexts, confirm the broad distribution of E. canis in Brazil, but differences in sampling designs preclude direct comparison of frequencies or estimation of a national prevalence.

Unlike E. canis, E. ruminantium has a more restricted distribution, concentrated mainly in sub-Saharan Africa and selected areas of the Caribbean [10]. A recent serologic study in the Guadeloupe archipelago estimated a seroprevalence of 28% in cattle and detected seropositive goats on all major islands evaluated, including Les Saintes, demonstrating that the circulation of the agent remains epidemiologically relevant in the region [36]. To date, there is no evidence of established E. ruminantium circulation in Brazil [13,18].

Although formally described in Brazil, E. minasensis is not restricted to South America. A systematic review of microorganisms detected in R. microplus compiled molecular records of the bacterium from Thailand, the Philippines, China, Colombia, Kenya, Italy, and Panama, demonstrating its occurrence in the Americas, Africa, Asia, and Europe [37]. In 2026, the identification of an E. minasensis sequence in an adult female R. microplus collected from cattle in Costa Rica added a new sequence-confirmed record for Central America [38]. However, much of the evidence outside Brazil derives from molecular detections in ticks and surveys with limited sampling coverage. These records confirm the presence of bacterial DNA but do not determine infection frequency in cattle, vector competence of the tick species involved, or the magnitude of agent circulation in each region [37,38].

In Brazil, the available evidence is more consistent and includes the detection of E. minasensis in ticks and cattle from different regions, including the Central-West, the western Amazon, and the Northeast [11,12,13,29]. In the Pantanal, a molecular investigation of 400 beef cattle detected E. minasensis DNA in 167 of 347 samples with valid results, corresponding to 48.12%, with no association between infection and anemia or other clinical manifestations in the animals evaluated [39]. In Bahia, a study of 256 adult dairy cattle found antibodies against Ehrlichia spp. in 249 animals. Among 40 seropositive samples selected for molecular analysis, 13 were PCR-positive and six yielded sequenced products, all showing 100% identity with E. minasensis [13]. This study provides the first molecular evidence of the species in Bahia and northeastern Brazil. However, because molecular analysis was performed on a previously selected subset of seropositive animals, the proportion of 13 positive results among 40 samples should not be interpreted as infection prevalence in the study population. In addition, the concentration of published evidence on four farms in the Feira de Santana microregion shows that the distribution of E. minasensis within Bahia remains insufficiently characterized.

4.2. Vectors and Transmission Dynamics

The role of ticks in the epidemiology of ehrlichioses should be analyzed in the context of interactions among the agent, vector, vertebrate hosts, and environment. Although Ehrlichia species are primarily transmitted by ixodid ticks, agent-vector associations vary by bacterial species and may differ even among populations of the same tick species [6,8,40]. In this context, detection of bacterial DNA in a tick does not by itself demonstrate that the tick can transmit the agent, because the detected genetic material may originate from the blood of an infected host. For a tick species to be considered a competent vector, it must be shown to acquire the agent during blood feeding, maintain it within its body, and subsequently transmit it to another susceptible host [40]. This distinction is necessary to understand natural transmission cycles and evaluate how vector presence, host availability, and environmental conditions influence the risk of exposure of animals and humans.

Among the species associated with human ehrlichiosis, E. chaffeensis and E. ewingii are transmitted primarily by A. americanum in the United States [8,17,26]. This tick uses different vertebrate hosts throughout its life cycle and also feeds on humans. The white-tailed deer (Odocoileus virginianus) plays an important role in this cycle, serving as a major host for different stages of A. americanum and as a reservoir for E. chaffeensis [17]. E. muris subsp. eauclairensis, in turn, is associated with transmission by I. scapularis, particularly in the upper midwestern United States [9,32]. These cycles demonstrate how maintenance of the bacteria in ticks and wildlife, combined with the ability of the vectors to also feed on humans, favors human infection and highlights the interdependence of human, animal, and environmental health.

From a veterinary perspective, ticks of the R. sanguineus group, which are closely associated with dogs and household and peridomestic environments, are recognized as the principal vectors of E. canis [6,8,19]. In northeastern Brazil, different investigations have demonstrated the frequent circulation of the agent in canine populations. In Ituberá, Bahia, a study of 379 dogs found 25.6% positivity by PCR and 32.7% by serology, while 46.9% of animals were positive by at least one of the diagnostic methods used [42]. In Ceará, molecular detection of E. canis in dogs from Sobral and Alcântaras, together with the high frequency of R. sanguineus infestation in these municipalities, confirmed maintenance of the agent in urban areas of the northeastern semiarid region [35]. The infection remains relevant despite differences in vector competence observed among R. sanguineus populations, as demonstrated experimentally for South American populations [41]. These findings indicate that the transmission risk varies among regions but reinforce the need for continuous surveillance, appropriate diagnosis, and tick control in dogs and their environments.

Although E. canis cycle is mainly associated with dogs, ticks of the R. sanguineus group, and household and peridomestic environments, transmission of E. ruminantium occurs in a distinct epidemiologic context involving domestic and wild ruminants and ticks of the genus Amblyomma. Among recognized vectors, Amblyomma variegatum and Amblyomma hebraeum play important roles in the maintenance and transmission of the agent [10]. A. hebraeum occurs predominantly in southern Africa, whereas A. variegatum has a broader distribution in Africa and is also present on some Caribbean islands. The movement of infected animals and ticks may contribute to the maintenance and spread of E. ruminantium in endemic areas [10,36]. Although the species is not recognized as an agent of human infection, its cycle illustrates the interdependence of herd health, wildlife, vectors, and environmental conditions.

For E. minasensis, the available body of evidence supports a consistent association with R. microplus, which remains the tick most strongly linked to the circulation of the agent. The reference strain used in the formal description of the species, designated UFMG-EVᵀ, was isolated from the hemolymph of a partially engorged female R. microplus collected in Brazil, demonstrating the presence of the bacterium beyond the blood contents of the digestive tract [11]. Subsequently, detection of E. minasensis in different developmental stages of the tick provided evidence of transstadial maintenance [43]. Together with molecular records of the agent in R. microplus and cattle from different regions, these findings provide biological support for the involvement of this tick in the maintenance of the bacterium [11,12,13,37,38,43]. However, the complete cycle of acquisition of E. minasensis from infected cattle and subsequent transmission by blood feeding to susceptible cattle has not yet been demonstrated experimentally. Thus, R. microplus may be considered a potential vector of E. minasensis, although full vector competence still requires experimental confirmation [40,43].

In addition to vector identity, the way in which bacteria are maintained throughout the tick life cycle directly affects epidemiologic dynamics. In the best-studied cycles, Ehrlichia is maintained mainly through transstadial transmission, in which a tick acquires the bacterium while feeding on an infected host and retains it after molting to the next developmental stage. This process has been demonstrated for E. canis in ticks of the R. sanguineus group, whereas transstadial maintenance of E. chaffeensis has been experimentally observed in A. americanum [41,44]. Transovarial transmission has not been demonstrated for these agents, indicating that larvae of a new generation must acquire the bacterium while feeding on infected vertebrate hosts [41,44]. Thus, the maintenance of these agents results from interactions between competent ticks and infected vertebrate hosts [8,40]. The identification of infected hosts is essential for estimating epidemiologic risk and directing surveillance and control measures toward components that effectively sustain transmission.

4.3. Epidemiologic Role of Vertebrate Hosts

Vertebrate hosts play distinct roles in the Ehrlichia transmission cycle, and identifying these roles is essential for recognizing the sources of infection for vectors, interpreting epidemiological surveillance findings, and directing prevention and control measures. Some species may act as reservoir hosts, maintaining the bacterium at levels that allow transmission to ticks during blood feeding, whereas others are incidental hosts or may serve as sentinels for agent circulation [8,40]. Thus, antibody detection indicates previous exposure, and detection of bacterial DNA demonstrates the presence of genetic material of the agent; however, neither form of evidence alone establishes that an animal can infect new ticks. This ability has been demonstrated experimentally for E. muris subsp. eauclairensis in P. leucopus, where animals acquired infection through infected I. scapularis and subsequently transmitted the bacterium to initially uninfected larvae [9,45]. Distinguishing between exposure, infection, and reservoir competence allows for the interpretation of each finding according to the strength of the available evidence. While confirmed transmission links support prevention and control measures, the detection of the agent in hosts whose epidemiologic role remains uncertain should guide surveillance and stimulate further investigation of their possible involvement in transmission cycles.

Among wildlife hosts, the white-tailed deer (O. virginianus) is one of the best-characterized examples of vertebrate involvement in Ehrlichia cycles in North America. The isolation of E. chaffeensis from naturally infected animals confirmed the role of this species as a natural reservoir host of the bacterium [46]. These cervids are also important hosts for different stages of A. americanum, contributing to both tick feeding and the circulation of the agent among vectors [8,46]. Natural infection with E. ewingii has also been demonstrated in white-tailed deer, suggesting that these animals may participate in its cycle, although this role is not established with the same strength of evidence as for E. chaffeensis [47]. The presence of these agents in cervids does not represent a direct route of transmission to humans because the risk results from exposure to infected ticks that share these environments and use different hosts during development [17]. Accordingly, surveillance of cervids and ticks may help identify areas of E. chaffeensis and E. ewingii circulation and guide measures aimed at reducing human exposure to vectors.

Among domestic animals, dogs are of particular epidemiologic importance because they are the principal vertebrate hosts of E. canis and have a close association with ticks of the R. sanguineus group. The persistence of the bacterium in animals with subclinical infection may allow competent ticks to acquire the agent even from asymptomatic dogs [6,8,41]. In northeastern Brazil, serologic and molecular studies conducted in Bahia and Ceará demonstrated frequent circulation of E. canis in canine populations exposed to vectors [35,42]. Because dogs share household and peridomestic environments with humans and can carry ticks into these settings, infection or infestation in dogs may signal conditions favorable to human exposure to vectors [19]. This relationship does not imply direct transmission between dogs and humans and does not, by itself, establish a zoonotic role for E. canis; however, it demonstrates the usefulness of dogs as sentinels for agent circulation and tick presence in the environment. In this context, veterinary diagnosis, treatment of infected animals, and tick control on dogs and in the environment simultaneously contribute to protecting animal health and reducing household exposure to vectors [19,35,42].

Among ruminants, participation in Ehrlichia cycles varies according to the bacterial species involved. In endemic regions of Africa and the Caribbean, domestic and wild ruminants infected with E. ruminantium may develop heartwater or, after surviving infection, remain carriers capable of infecting ticks during blood feeding [10]. The existence of these carriers complicates disease surveillance and control, especially when animals move between areas where Amblyomma vector ticks are present [10,27]. For E. minasensis, cattle are the most consistently documented vertebrate hosts, with evidence of natural and experimental infection and molecular records from different regions, including the state of Bahia, Brazil [12,13,28]. In Bahia, molecular confirmation of the agent in asymptomatic adult cattle demonstrated its circulation in herds but did not determine whether these animals are capable of infecting new ticks [13]. To date, infection of R. microplus with E. minasensis while feeding on infected cattle and subsequent transmission to susceptible animals has not been demonstrated [40,43]. Molecular or serologic records of E. minasensis in cervids, horses, and dogs broaden hypotheses regarding its host range, but the role of these species in transmission remains uncertain [12,14,15]. Therefore, joint surveillance of herds and ticks is necessary to control established cycles and to clarify associations whose animal-health importance remains undefined.

Humans are considered incidental hosts in known zoonotic Ehrlichia cycles and have no recognized role in the natural maintenance of these agents among ticks [8,17]. Human infection occurs when occupational, recreational, household, or peridomestic activities favor contact with infected vectors originating from cycles involving wild or domestic animals [8,16,17]. In this context, the identification of Ehrlichia in animals or ticks does not, by itself, demonstrate transmission to humans, but it may signal shared exposure to vectors and identify areas requiring greater epidemiologic attention [8,19,40]. Effective surveillance requires the integration of investigations of human febrile syndromes, diagnosis of infection in animals, monitoring of tick populations, and assessment of environmental conditions that favor their occurrence [18,19,20,21]. Such coordination may increase molecular confirmation of cases, guide vector control, and direct measures to reduce human and animal exposure. Joint analysis of these data is essential to assess the zoonotic potential of each Ehrlichia species without disregarding emerging signals or attributing risks that are not yet supported by evidence.

5. Zoonotic Potential and Public Health Relevance

5.1. Human Ehrlichioses and Clinical Impact

Human infections caused by E. chaffeensis, E. ewingii, and E. muris subsp. eauclairensis range from self-limited febrile syndromes to severe multisystem diseases [9,16,17,26]. Fever, headache, myalgia, malaise, leukopenia, thrombocytopenia, and elevated transaminase levels are common but non-specific. Neurologic or respiratory involvement, renal injury, coagulopathy, shock, and multiorgan failure may occur, particularly in older adults, immunosuppressed individuals, and patients with delayed treatment. The available systematic review shows that current clinical knowledge still derives largely from case reports, case series, and retrospective studies, with few prospective studies, limiting the comparable estimates of risk and outcomes [16].

The clinical impact of ehrlichiosis is also related to the recognition of the infection and timely initiation of treatment. Doxycycline is considered the antimicrobial of choice for patients of all ages with suspected ehrlichiosis, and clinical improvement generally occurs within the first 24 to 48 hours after therapy is started [17]. Because confirmatory test results may not be available during the early phase of illness, treatment should not be delayed when compatible manifestations and an epidemiologic history indicating tick exposure are present [17]. Although most patients have a favorable course when treated early, severe forms may require hospitalization and intensive care, especially when neurologic, respiratory, or multiorgan involvement occurs [16,17]. Therefore, including ehrlichioses in the differential diagnosis of febrile syndromes associated with tick exposure is essential to reduce the risk of complications and death.

5.2. Epidemiologic Overview of Human Ehrlichioses

The most consistent data come from the United States, where national surveillance documents temporal trends, seasonality, geographic distribution, and age-specific incidence. A total of 1,907 cases of E. chaffeensis ehrlichiosis were reported in 2023, compared with 200 cases in 2000; the highest concentration remains in the south-central, southeastern, and mid-Atlantic states [62]. E. ewingii and E. muris subsp. eauclairensis are identified less frequently; however, this comparison depends on the use of molecular tests capable of determining the species [31,61]. In countries without specific surveillance, records are based mainly on case reports and serologic surveys. Thus, international differences reflect both vector epidemiology and the capacity to suspect, test, classify, and report cases.

In Latin America, evidence of human ehrlichiosis remains heterogeneous and fragmented. Studies conducted in Argentina and Peru have detected antibodies against E. chaffeensis in human populations, indicating exposure to the agent or to antigenically related species, but without allowing conclusive identification of the species involved [48,49]. More direct evidence was obtained in Venezuela and Mexico, where molecular detection and sequencing of E. chaffeensis DNA in symptomatic patients confirmed human infections in the region [50,51]. However, differences among the populations studied, diagnostic methods used, and availability of specific tests make comparisons among countries and determination of the true distribution of human ehrlichioses difficult. Thus, existing records demonstrate regional circulation of agents within the genus but remain insufficient to estimate their epidemiologic magnitude in Latin America.

In Brazil, the first suspected cases and subsequent case series were defined by clinical manifestations and seroreactivity to E. chaffeensis, without molecular confirmation of the species [52,53]. Other surveys detected antibodies against E. chaffeensis, E. canis, or Ehrlichia spp. in Minas Gerais, Paraná, and Mato Grosso; however, cross-reactions prevented reliable etiologic attribution [33,34,54]. In contrast, PCR testing of 75 febrile patients exposed to ticks was negative despite detection of E. canis in dogs from the same study [58]. These positive and negative results should be interpreted together: they support the plausibility of circulation but do not define its magnitude, distribution, or the species responsible for human disease. In addition, human ehrlichiosis is not listed as a specific condition in Brazil's National List of Compulsorily Notifiable Diseases in force in 2026 [63]. The Brazilian problem therefore involves underdiagnosis, absence of specific surveillance, underrecording, and possible classification of cases as other febrile syndromes, rather than merely undernotification of a disease with its own national reporting pathway.

5.3. Emerging Species and Gaps in the Assessment of Zoonotic Potential

E. canis illustrates the distinction between demonstrating human infection and defining population-level importance. Its DNA was detected and sequenced in six Venezuelan patients with manifestations compatible with monocytic ehrlichiosis [55]. In Italy, identical 16S rRNA and groEL gene sequences were obtained from the blood of a patient and from a Haemaphysalis punctata tick attached to that patient [27]. These studies confirm that E. canis can infect humans. In Costa Rica, an E. canis genotype was also detected molecularly in samples from blood bank donors, demonstrating infection or exposure but not clinical disease [71]. The small number of reports does not define frequency, clinical spectrum, principal vectors, or disease burden. The most recent species-specific review reached the same conclusion and emphasized that serology does not distinguish E. canis from other Ehrlichia species, making molecular confirmation essential [57]. Therefore, the most appropriate classification is that of a rare or underdetected human pathogen whose epidemiologic relevance remains undetermined.

Other more recently recognized species present gaps in the assessment of their public health importance. Ehrlichia japonica, formerly designated Ehrlichia sp. HF, can cause severe and fatal infection in experimental mice but has not yet been associated with natural infection in humans [24,25]. E. minasensis has been identified in different vertebrate hosts and tick species across distinct geographic regions, without confirmed human infections [11,12,13,14,15,29]. These examples demonstrate that pathogenicity observed in experimental models or widespread circulation of an agent among animals and ticks is not, by itself, sufficient to establish zoonotic relevance. Clarifying this potential requires studies that combine clinical and epidemiologic data with molecular detection and characterization of the agent in humans, especially in populations frequently exposed to ticks. Including these species in investigations of febrile syndromes of undetermined etiology may help generate the necessary evidence while avoiding both premature attribution of a zoonotic role and dismissal of that possibility solely because confirmed cases have not yet been identified.

In addition to formally recognized species, molecular tools have enabled the identification of Ehrlichia genotypes and provisional taxa, whose biological and health significance still requires clarification. In southern Brazil, sequences of the 16S rRNA, sodB, and groEL genes obtained from capybaras supported the identification of a potentially new species, provisionally designated "Candidatus Ehrlichia hydrochoerus," although its vector, host range, and ability to cause disease remain unknown [56]. These findings demonstrate the importance of molecular techniques for recognizing poorly known agents, characterizing their genetic diversity, and identifying the hosts and regions in which they circulate. A broader understanding of their epidemiological relevance can be complemented by isolation, genomic characterization, host and vector studies, and investigation of possible disease associations. Integrating these approaches into the surveillance of domestic animals, wildlife, ticks, and exposed human populations is essential for distinguishing agents restricted to animal cycles from those that may represent emerging public health threats.

The diversity of potentially relevant lineages has also increased. In French Guiana, an analysis of 1,919 samples from humans, wildlife, and ticks described "Candidatus Ehrlichia cajennense" in A. cajennense, with phylogenetic proximity to E. ewingii and homologs of virulence-associated factors [66]. In northern Chile, a genospecies related to the clade containing agents of human monocytic ehrlichiosis was characterized at multiple loci in one of 90 Ixodes ticks examined [67]. Phylogenetic proximity, candidate virulence genes, and detection in putative vectors are signals for research prioritization and not demonstrations of human infection, pathogenicity, or vector competence.

6. Challenges in Diagnosis and Epidemiologic Surveillance

6.1. Diagnostic Limitations in Humans and Animals

The value of each method depends on the stage of infection and the epidemiologic question being addressed. Microscopic detection of morulae is rapid but has low sensitivity and does not reliably identify the species. PCR or another nucleic acid amplification test provides direct evidence and is most useful before or shortly after treatment begins, when circulating DNA is present. Serology is useful for retrospective confirmation and surveys, but an early sample may be negative, and a single titer may reflect past exposure or cross-reactivity. Under the CDC surveillance case definition, PCR, isolation with molecular confirmation, immunohistochemistry, or a fourfold increase in IgG in paired sera constitute confirmatory evidence; a single elevated IgG titer and microscopic identification of morulae are considered presumptive evidence. Species-level classification requires a molecular method because serology does not reliably distinguish related Ehrlichia species [61]. This hierarchy should guide both clinical confirmation and comparisons among studies, in accordance with recent laboratory recommendations [69].

In humans, these limitations are compounded by low clinical suspicion and restricted availability of specific tests, particularly in regions where ehrlichioses are not routinely investigated. Late sample collection, initiation of treatment before PCR, and absence of a second serum sample during convalescence may prevent etiologic confirmation, leaving some infections classified only by clinical and serologic criteria [16,17,21]. In animals, subclinical infections, persistence of antibodies after exposure, and differences among molecular and serologic protocols complicate the distinction between previous exposure and active infection [2,18,19]. These features must be considered when interpreting results so that seropositivity, detection of bacterial DNA, and clinical disease are not treated as equivalent forms of evidence.

6.2. Underdiagnosis, Absence of Specific Surveillance, and Data Integration

Underdiagnosis, under recording, and underreporting are not equivalent. Underdiagnosis occurs when an infection is not recognized or confirmed; under recording refers to the loss of clinical or laboratory information; and underreporting presupposes the existence of an applicable notification pathway. In the United States, standardized case definitions allow cases to be classified and compared, although the limited use of molecular testing reduces species-level identification [21,61]. In Brazil, the current national list does not include human ehrlichiosis as a specific notifiable condition [63]. Therefore, the small number of national records may simultaneously result from low clinical suspicion, limited access to diagnosis, absence of specific surveillance, and classification as other febrile syndromes.

Fragmentation among human clinical data, veterinary diagnoses, tick records, and environmental variables prevents the assessment of whether these events coincide in space and time [5,20]. Integration requires compatible definitions, species-level agent identification, time and location metadata, sampling protocols, and regular data-sharing mechanisms. Without these elements, a high frequency in dogs or ticks may be inappropriately used as a surrogate for human risk, while febrile cases lacking early sample collection remain etiologically unresolved.

7. One Health, Prevention, Control, and Future Perspectives

7.1. Integrated Surveillance and Prevention and Control Measures

An operational One Health approach to ehrlichiosis should begin with the exposure event. In a patient with a febrile syndrome and a history of tick contact, early collection of whole blood for PCR, acute- and convalescent-phase serum, and standardized recording of the likely location and date of exposure are recommended. When relevant, dogs and other animals in the household or on the property should be evaluated using molecular and serologic methods, and collected ticks should be identified and tested with sequencing confirmation. These data should be linked to environmental and geospatial information within the same investigation. The outcome is not merely an inventory of positive results; it is the ability to assess concordance among agent, vector, host, time, and place and to target tick control, clinical guidance, and surveillance to demonstrated exposures [8,19]. A multidimensional investigation of urban dogs in Iquitos illustrates the value of combining animal, owner, and environmental variables, although its cross-sectional design and dependence on qPCR thresholds do not permit direct inference of human risk [70].

Environmental factors should be incorporated into surveillance by monitoring climatic variables, land-use changes, habitat fragmentation, and the population dynamics of tick species present in each region [3,4,5]. Understanding the variation in abundance, seasonal activity, developmental stages, and host use is essential for identifying periods and locations with greater vector activity and a higher likelihood of human and animal exposure. These parameters can be influenced by environmental conditions and alter opportunities for contact among vectors, hosts, and agents. However, their effects vary according to the region and epidemiologic cycle under analysis [3,4]. Joint analysis of records of human and animal infections, the locations where they occurred, tick population data, and environmental information may help identify risk areas and changes in agent circulation. Continuous monitoring systems are therefore needed to distinguish sporadic detections from consistent epidemiologic changes and to direct investigations and preventive measures toward populations that are actually exposed [5,20].

The implementation of this model depends on governance, funding, data interoperability, the participation of exposed communities, and workforce training. These components are included in recent recommendations for translating One Health into coordinated action, and the implementation period of the One Health Joint Plan of Action has been extended to 2029 [64,65]. For ehrlichiosis, practical application requires defining responsibilities for joint investigations, reference laboratories, a minimum data set, a results communication workflow, and performance indicators, such as the proportion of febrile cases tested before treatment and the proportion of detections identified at the species level.

7.2. Knowledge Gaps and Research Priorities

Priorities should be defined by the gaps that prevent inference. For human diseases in Latin America, prospective studies of febrile syndromes with sampling before treatment, PCR, sequencing, and paired serology are needed. For tick-agent associations, the priority is to demonstrate acquisition, maintenance, and transmission to a susceptible host, rather than merely expanding surveys of DNA in ticks. For reservoirs, the duration and intensity of bacteremia and the ability to infect infection-free larvae or nymphs should be evaluated. For emerging agents, isolation, genomics, and multi-locus characterization reduce identification errors and allow strain comparisons among humans, animals, and vectors.

For E. canis, the central question is to quantify molecularly confirmed human infections and define their clinical and vector spectra [57]. For E. minasensis, it remains necessary to demonstrate the complete acquisition and transmission cycle involving R. microplus, measure clinical and production effects, and investigate highly exposed human populations without presuming zoonosis. For Panola Mountain Ehrlichia, findings in humans and cattle justify studies on reservoirs, seasonality, and incidence [59,60]. E. japonica and "Candidatus Ehrlichia hydrochoerus" require evidence of natural infection, vector involvement, and clinical association. Negative studies, when appropriately designed and timed for sample collection, should also be published because they help delineate frequency and prevent conclusions based solely on positive results.

8. Conclusions

The strength of the evidence varies substantially among Ehrlichia taxa. E. chaffeensis, E. ewingii, and E. muris subsp. eauclairensis are established human pathogens. E. canis has well-established veterinary importance and a demonstrated ability to infect humans; however, its burden of human disease remains unknown. E. ruminantium is an important veterinary pathogen with no established relevance to human health. For E. minasensis, E. japonica, and provisional taxa, detection in animals or ticks has not yet demonstrated zoonosis. Interpretation should continue to distinguish between exposure, infection, disease, vector competence, and reservoir competence.

In Brazil, widespread animal circulation contrasts with the scarcity of confirmed human cases; however, this discrepancy does not allow conclusions of either absence or high occurrence. Current evidence is limited by the predominance of serology, scarce human molecular findings, absence of specific surveillance, and fragmented data. Progress depends on prospective studies, early sample collection, molecular confirmation, and operational integration among health services, veterinary laboratories, tick surveillance, and environmental information. This framework will help distinguish true risk from failures of detection and prioritize prevention and control measures supported by the strength of the evidence.