Zubair Khalid

Virologist/Molecular Biologist | Veterinarian | Bioinformatician

Conventional & Molecular Virology • Vaccine Development • Computational Biology

Dr. Zubair Khalid is a veterinarian and virologist specializing in conventional and molecular virology, vaccine development, and computational biology. Dedicated to advancing animal health through innovative research and multi-omics approaches.

Dr. Zubair Khalid - Veterinarian, Virologist, and Vaccine Development Researcher specializing in Computational Biology, Multi-omics, Animal Health, and Infectious Disease Research

Section: Livestock Bacteria

[Anaplasma phagocytophilum](/knowledge/bacteria/Equine Granulocytic Anaplasmosis/anaplasma-phagocytophilum-equine-granulocytic-anaplasmosis-tick) in Livestock and Companion Animals: Diagnostics and Tick-Borne Epidemiology

Close-up of a Holstein cow inside a barn, showcasing its distinctive black and white pattern
Photo by Top5Way Agency on Pexels.

Introduction

[Anaplasma phagocytophilum](/knowledge/bacteria/Equine Granulocytic Anaplasmosis/anaplasma-phagocytophilum-equine-granulocytic-anaplasmosis-tick) is an obligate intracellular, Gram-negative bacterium belonging to the family Anaplasmataceae, order Rickettsiales. It is the etiological agent of granulocytic anaplasmosis in many mammalian hosts, including livestock species such as cattle, sheep, goats, and horses, as well as companion animals, especially dogs and cats [1, 2]. The bacterium preferentially infects neutrophils and, to a lesser extent, eosinophils and basophils, where it survives within membrane-bound vacuoles (morulae) by subverting host cell apoptosis and innate immune responses [3]. Although the pathogen is recognized as a zoonotic agent, this review focuses exclusively on its impact on livestock and companion animals.

The global distribution of A. phagocytophilum is intimately linked to its tick vectors, primarily members of the Ixodes ricinus complex [1, 4]. The pathogen has been detected on nearly every continent, with prevalence varying by geographic region, host species, and tick population dynamics [5, 6, 7]. Understanding the epidemiological patterns and refining diagnostic approaches are essential for effective veterinary management and control.

Pathogen Biology and Host Cell Interactions

A. phagocytophilum enters the host through the bite of an infected ixodid tick. During feeding, the bacterium is transmitted via tick saliva and subsequently targets peripheral blood neutrophils. The adhesion to neutrophils is mediated by bacterial surface proteins, such as major surface protein 2 (Msp2) and outer membrane protein A (OmpA), which bind to P-selectin glycoprotein ligand-1 and other receptors on the neutrophil surface [3]. Following internalization, the bacterium resides within a host-derived vacuole that resists phagolysosomal fusion. Replication occurs within morulae, which can be visualized microscopically as intracytoplasmic inclusions [3, 6]. The infection induces a state of immune dysregulation, including impaired neutrophil oxidative burst and delayed apoptosis, which facilitates bacterial persistence and dissemination.

In livestock, A. phagocytophilum infection can lead to fever, lethargy, anorexia, and in pregnant animals, abortion and perinatal mortality [8]. The detection of the pathogen in fetal and placental tissues of bovine abortions has been documented, supporting a role in reproductive failure in cattle [8]. In small ruminants, co-infections with other tick-borne pathogens such as Theileria species are common, potentially complicating clinical diagnosis and disease progression [9, 10]. In companion animals, particularly dogs, infection manifests as fever, depression, polyarthritis, thrombocytopenia, and lameness. Subclinical infections are also frequent, as demonstrated by seroprevalence surveys in clinically healthy outdoor dogs [2, 11, 12]. Cats are less commonly diagnosed but can present with similar febrile and musculoskeletal signs [12].

Tick Vectors and Transmission Ecology

The primary vectors of A. phagocytophilum are ticks of the Ixodes ricinus complex. In Europe, I. ricinus is the dominant vector, while in North America, I. scapularis and I. pacificus are the principal species [1, 5, 7]. The bacterium is maintained in enzootic cycles involving tick vectors and a variety of reservoir hosts, including small rodents, deer, and livestock. Ticks acquire the infection during blood feeding on bacteremic hosts. Transstadial transmission (from larva to nymph to adult) occurs, but transovarial transmission is inefficient or absent. Therefore, the maintenance of A. phagocytophilum in nature depends on the continuous availability of infected reservoir hosts [1, 4].

Urban and peri-urban areas present unique epidemiological contexts. A study in Kosovo detected A. phagocytophilum in I. ricinus ticks collected from both urban and peri-urban environments, indicating that the pathogen circulates in close proximity to human and domestic animal populations [1]. In North America, the expanding range of I. scapularis has been associated with emerging anaplasmosis in both livestock and companion animals, particularly in Canada and the northern United States [7]. Similarly, in East Asia, surveillance in China and South Korea has identified I. persulcatus and related species as vectors, with prevalence rates in livestock varying by region [12, 5, 4].

Table 1 summarizes key geographical regions and reported tick vector species associated with A. phagocytophilum.

Table 1. Selected geographic regions and principal Ixodes vectors for A. phagocytophilum.

Region Principal Tick Vector Representative Hosts Key References
Europe Ixodes ricinus Cattle, sheep, goats, dogs [1, 9]
North America Ixodes scapularis, I. pacificus Dogs, horses, cattle [3, 7]
Asia (China, South Korea) Ixodes persulcatus Sheep, goats, cattle, dogs [12, 5, 4]
South America (Brazil) Amblyomma spp. (suspected) Sheep [10]

In addition to Ixodes ticks, other tick genera may play a role in certain regions. For example, in Brazil, while Ixodes species are less common, Amblyomma ticks are prevalent and have been associated with A. phagocytophilum infections in sheep [10]. The complex interactions between tick species, host availability, and environmental conditions influence the local epidemiology of the pathogen.

Clinical Manifestations in Livestock and Companion Animals

Livestock

In cattle, A. phagocytophilum infection is often referred to as tick-borne fever. Clinical signs include acute onset of high fever (up to 42 degrees Celsius), depression, reduced milk yield, and respiratory signs. The most significant reproductive consequence is abortion, which can occur in late gestation [8]. Diagnosis of A. phagocytophilum in aborted bovine fetuses and placentas using real-time PCR has confirmed the pathogen as a cause of abortion and perinatal mortality [8]. In sheep and goats, the disease can present similarly, with fever, anorexia, and weight loss. Co-infections with Theileria species are common and may exacerbate clinical severity [9, 10]. In sheep, A. phagocytophilum infection has been reported in meat-producing flocks, and its impact on production parameters is an area of ongoing research [10]. Horses infected with A. phagocytophilum develop [equine granulocytic anaplasmosis](/knowledge/bacteria/Equine Granulocytic Anaplasmosis/anaplasma-phagocytophilum-equine-granulocytic-anaplasmosis-tick), characterized by fever, limb edema, petechiation, and ataxia.

Companion Animals

Dogs are the most frequently diagnosed companion animal host. Canine granulocytic anaplasmosis typically presents with fever, lethargy, anorexia, polyarthritis (manifesting as joint pain and stiffness), and lameness. Hematological abnormalities include thrombocytopenia, lymphopenia, and mild anemia. In a serological and molecular survey of clinically healthy outdoor dogs in Serbia, seroprevalence to A. phagocytophilum reached 42.8%, while PCR positivity was lower at 4.2%, indicating that many infections are subclinical or that the rickettsemia is transient [2]. Similarly, surveys in Thailand and China have detected A. phagocytophilum DNA in clinically healthy dogs, emphasizing the importance of latent carriers in endemic areas [11, 12]. Cats from China also harbored the pathogen, albeit at lower prevalence rates [12]. The role of cats as competent reservoirs remains uncertain.

A comparative overview of clinical signs across common livestock and companion animal hosts is provided in Table 2.

Table 2. Clinical signs of A. phagocytophilum infection in domestic animals.

Host Species Common Clinical Signs References
Cattle Fever, depression, abortion, reduced milk yield [8]
Sheep/Goats Fever, anorexia, co-infection with Theileria spp. [9, 10]
Horses Fever, limb edema, ataxia, petechiae [3]
Dogs Fever, lameness, polyarthritis, thrombocytopenia [2, 11, 12]
Cats Fever, lethargy, anorexia (less documented) [12]

Diagnostic Approaches

Accurate diagnosis of A. phagocytophilum infection requires a combination of clinical evaluation, hematological analysis, and laboratory confirmation through direct or indirect detection methods. The choice of diagnostic modality depends on the stage of infection, sample type, and available resources.

Direct Detection Methods

Microscopic Examination. Examination of Giemsa- or Wright-stained blood smears can reveal intracytoplasmic morulae within neutrophils. This method is rapid and inexpensive but has low sensitivity, particularly when rickettsemia is low or during chronic infection [2, 3]. Sensitivity is highest during the acute febrile phase.

Molecular Detection. Polymerase chain reaction (PCR) and real-time PCR targeting the msp2 gene or the 16S rRNA gene are the gold standard for active infection. These assays offer high sensitivity and specificity, even in animals with low bacteremia [8, 2, 12, 9]. PCR can be performed on whole blood, buffy coat, or tissue samples (e.g., placenta, fetal liver). Real-time PCR allows quantitative measurement, which is useful for monitoring treatment response. Nested PCR and conventional PCR are also employed in epidemiological surveys [6, 4]. The comparative advantages of PCR versus traditional virus isolation (in this case, bacterial isolation) have been well documented in veterinary virology and bacteriology; for A. phagocytophilum, culture isolation is laborious and rarely performed in diagnostic settings.

Indirect Detection Methods (Serology)

Serological assays detect antibodies against A. phagocytophilum, indicating prior or current exposure. The indirect immunofluorescence assay (IFA) and various enzyme-linked immunosorbent assay (ELISA) formats are available. IFA using whole-cell antigen is considered the reference serological method, but cross-reactivity with other Anaplasmataceae (e.g., A. platys, Ehrlichia canis) can occur [2, 11]. ELISA-based tests, including those using recombinant Msp2 antigens, offer improved specificity. Seroconversion typically occurs 1 to 2 weeks after infection, and antibodies can persist for months, making serology useful for epidemiological studies rather than diagnosis of acute cases [2].

Point-of-Care Tests

Commercially available rapid immunochromatographic tests are used in veterinary practice to detect antibodies or antigens. However, these tests may have variable sensitivity and specificity compared to laboratory-based methods. As per the non-commercial guidelines, specific brand names are omitted.

Diagnostic Algorithm

The following Mermaid diagram illustrates a recommended diagnostic workflow for suspect cases of A. phagocytophilum infection in livestock and companion animals.

flowchart TD
 A["Animal with clinical signs: fever, lameness, abortion"] --> B{Acute phase?}
 B -->|Yes| C[Collect EDTA blood and/or tissue]
 B -->|No| D[Collect serum for antibody testing]
 C --> E[Blood smear for morulae detection]
 C --> F["'Real-time PCR (msp2 or 16S rRNA')"]
 D --> G[IFA or ELISA for IgG]
 E --> H{Morulae present?}
 H -->|Yes| I["Positive: confirm with PCR"]
 H -->|No| F
 F --> J{PCR positive?}
 J -->|Yes| K[Confirm active infection]
 J -->|No| L[Rule out or consider serology]
 G --> M{Seropositive?}
 M -->|Yes| N["Exposure history; consider paired serology"]
 M -->|No| O[No evidence of infection]

Table 3. Comparison of diagnostic methods for A. phagocytophilum.

Method Target Sensitivity Specificity Time to Result Use Case References
Blood smear microscopy Morulae Low to moderate High (if typical morulae) <1 hour Acute phase [2, 3]
Real-time PCR DNA (msp2 or 16S rRNA) High High 2-4 hours Active infection, abortion, tissues [8, 2, 12]
Conventional PCR DNA Moderate High 4-8 hours Epidemiological surveys [6, 4]
IFA Antibodies (IgG) High Moderate (cross-reactivity) 2-4 hours Seroprevalence, chronic cases [2, 11]
ELISA (recombinant Msp2) Antibodies High High 2-4 hours Seroprevalence, large-scale testing [2]

Epidemiology in Livestock and Companion Animals

The prevalence of A. phagocytophilum varies widely. In cattle, seroprevalence in endemic areas can exceed 50%, but active infection rates are lower. A study on bovine abortions in Europe found that 6.5% of investigated abortion cases involved A. phagocytophilum DNA in fetal or placental tissues [8]. In small ruminants, a survey in Portugal reported A. phagocytophilum DNA in 4.8% of sheep and goats, often alongside Theileria species [9]. Brazilian sheep flocks showed evidence of exposure through PCR detection [10]. In India, molecular surveys in bovines and canines have documented A. phagocytophilum in multiple states [6].

For companion animals, canine seroprevalence can be substantial. In Serbia, seropositivity was 42.8% among outdoor dogs, while PCR positivity was only 4.2%, highlighting the endemicity and the frequent subclinical carrier state [2]. In Thailand, PCR detection in stray dogs was 1.7% in companion dogs and 5.3% in stray dogs [11]. In China, pet dogs and cats from mainland China had A. phagocytophilum detection rates of 3.2% and 1.8%, respectively [12]. The discrepancy between serological and molecular results is partly due to the transient nature of bacteremia and the persistence of antibodies after clearance.

Geographic expansion of Ixodes ticks has been documented in Canada, leading to emergence of anaplasmosis in both humans and animals [7]. Similarly, South Korea has reported increasing environmental risk [5]. Livestock-associated ticks in northwestern China harbor A. phagocytophilum DNA, indicating a risk to grazing animals [4].

Risk Factors

Risk factors include: (i) grazing on pastures with high tick density, (ii) lack of tick control, (iii) co-grazing with wildlife reservoirs (e.g., deer), (iv) outdoor access for companion animals, and (v) living in or near wooded or peri-urban habitats [1, 11, 5, 7].

Prevention and Control

Integrated tick management is the cornerstone of prevention. For livestock, acaricide treatment, pasture rotation, and breeding resistance to ticks can reduce exposure. Vaccines are not commercially available for A. phagocytophilum in animals, although research continues. For companion animals, regular use of acaricidal products (collars, spot-ons, oral formulations) and avoiding tick habitats are recommended. Prompt removal of ticks and monitoring for signs of illness are essential. Diagnosis and treatment with appropriate antibiotics (e.g., doxycycline) under veterinary supervision are effective.

Conclusion

[Anaplasma phagocytophilum](/knowledge/bacteria/Equine Granulocytic Anaplasmosis/anaplasma-phagocytophilum-equine-granulocytic-anaplasmosis-tick) remains a significant tick-borne pathogen affecting livestock and companion animals worldwide. Its epidemiology is tightly linked to the distribution of Ixodes ticks and the presence of competent reservoir hosts. Accurate diagnosis requires molecular methods for acute cases and serology for exposure history. Ongoing surveillance, as reported from diverse regions including Kosovo, Serbia, Thailand, China, India, Brazil, Portugal, and Canada, is critical for understanding changing risk patterns [1, 2, 11, 12, 9, 10, 6, 4, 7]. Improved point-of-care tests and enhanced tick control strategies are needed to mitigate the impact of this pathogen on animal health and production.


References

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[2] Kovačević Filipović MM, Beletić AD, Ilić Božović AV, et al. Molecular and Serological Prevalence of Anaplasma phagocytophilum, A. platys, Ehrlichia canis, E. chaffeenses, E. ewingii, Borrelia burgdorferi, Babesia canis, B. gibsoni and B. vogeli among Clinically Healthy Outdoor Dogs in Serbia. Vet Parasitol Reg Stud Reports. 2018. URL: https://pubmed.ncbi.nlm.nih.gov/31014716/

[3] Thomas RJ, Dumler JS, Carlyon JA. Current management of human granulocytic anaplasmosis, human monocytic ehrlichiosis and Ehrlichia ewingii ehrlichiosis. Expert Rev Anti Infect Ther. 2009. URL: https://pubmed.ncbi.nlm.nih.gov/19681699/

[4] Tan H, Dong X, Kang J, et al. Molecular characterization of livestock-associated ticks and tick-borne bacteria in Xinjiang, northwestern China. Parasit Vectors. 2025. URL: https://pubmed.ncbi.nlm.nih.gov/41331487/

[5] Oh HS. Emerging risk of tick-borne diseases in South Korea: Lyme disease, anaplasmosis, and babesiosis. Clin Exp Vaccine Res. 2026. URL: https://pubmed.ncbi.nlm.nih.gov/41660214/

[6] Ravindran R, Kumar KGA, Deepa CK, et al. Molecular epidemiology of tick-borne infections of bovines and canines of India - Current status. Parasitol Int. 2026. URL: https://pubmed.ncbi.nlm.nih.gov/41651013/

[7] Ngo C, Koubaesh C, MacFadden D, et al. Anaplasmosis: Emerging threat in Canada. Can Fam Physician. 2025. URL: https://pubmed.ncbi.nlm.nih.gov/41087130/ *** Disclaimer: This article is for educational and informational purposes only. It is not intended to substitute for professional veterinary advice, diagnosis, treatment, or regulatory guidance. Always consult a licensed veterinarian or qualified specialist regarding animal health, disease diagnosis, and therapeutic decisions.

[8] Van Loo H, Pascottini OB, Hooyberghs J, et al. Detection of Anaplasma phagocytophilum in fetal and placental tissue of bovine abortions and perinatal mortalities. Vet Rec. 2023. URL: https://pubmed.ncbi.nlm.nih.gov/37012899/

[9] Muñoz-Hernández C, Moraga-Fernández A, Sánchez-Sánchez M, et al. Molecular evidence of co-infections with Anaplasma and Theileria species in domestic sheep and goats from Alentejo, Portugal. Vet Parasitol Reg Stud Reports. 2026. URL: https://pubmed.ncbi.nlm.nih.gov/42276661/

[10] Balaro MFA, Cordeiro MD, Magalhães IFB, et al. Tick-borne pathogens in meat sheep from Brazil: first report of Theileria ovis in sheep in Latin America. Parasitol Res. 2026. URL: https://pubmed.ncbi.nlm.nih.gov/41770286/

[11] Pham BX, Phoosangwalthong P, Inkaew T, et al. The Comparative Study for Detection of Canine Vector-Borne Pathogens Between Companion and Stray Dogs in Bangkok and Vicinities, Thailand. Pathogens. 2026. URL: https://pubmed.ncbi.nlm.nih.gov/42198653/

[12] Ye Q, Zhang G, Wang R, et al. Survey of tick species and tick-borne pathogens in pet dogs and cats in mainland China. Vet Parasitol. 2026. URL: https://pubmed.ncbi.nlm.nih.gov/42155156/

[13] Hing M, Van Den Bossche D, Lernout T, et al. Prevalence of Anaplasma phagocytophilum in humans in Belgium for the period 2013-2016. Acta Clin Belg. 2019. URL: https://pubmed.ncbi.nlm.nih.gov/30029581/