Anaplasmosis is one of the most important tick-borne diseases affecting domestic animals, wildlife and humans worldwide
(Kumar et al., 2023a; Ierardi et al., 2025). The disease is caused by bacteria of the genus
Anaplasma, members of the family Anaplasmataceae, which are obligate intracellular pathogens that infect haematopoietic cells (
Rikihisa, 2011). The disease causes substantial economic losses in livestock production systems because of reduced milk yield, weight loss, reproductive inefficiency, treatment costs, mortality and restrictions on animal trade
(Ierardi et al., 2025). Bovine anaplasmosis caused by
Anaplasma marginale is particularly important in tropical and subtropical regions where tick infestation is common and vector populations remain active throughout the year. The global significance of anaplasmosis has increased considerably during the last decade because of several interrelated ecological, epidemiological and socioeconomic factors. Climate change has facilitated the expansion of tick vectors into previously non-endemic regions, thereby increasing disease transmission risk
(Maharana et al., 2016; Huang et al., 2025). Intensification of livestock production systems, unrestricted movement of animals, wildlife-livestock interactions and inadequate vector control practices have further contributed to the emergence and persistence of the disease
(Babu et al., 2025). In addition, increasing reports of zoonotic
Anaplasma species such as
A. phagocytophilum and
A. capra have expanded the public health relevance of anaplasmosis under the One Health framework (
Acosta-Espana et al., 2025). Although several review articles have previously discussed the epidemiology, diagnosis, or control of anaplasmosis, recent advances in molecular epidemiology, genomics, host-pathogen interactions, immune evasion mechanisms and integrated one health surveillance have substantially transformed the understanding of the disease. Furthermore, increasing concerns regarding antimicrobial resistance, acaricide resistance, vaccine limitations and emerging zoonotic infections necessitate an updated and critical synthesis of current evidence. Therefore, the present review integrates recent developments in genomics, molecular diagnostics, pathogenesis, therapeutics, vaccine research, vector ecology and one health control strategies across multiple host species, with particular emphasis on recent findings from India and tropical production systems.
Etiology and taxonomy
The genus
Anaplasma comprises gram-negative, obligate intracellular bacteria belonging to the order
Rickettsiales and family
Anaplasmataceae. These organisms are characterized by their ability to infect blood cells and survive within membrane-bound intracellular vacuoles known as morulae (
Rikihisa, 2011;
Reller and Dumler, 2015). Unlike many gram-negative bacteria,
Anaplasma species lack classical peptidoglycan and lipopolysaccharide structures, which contributes significantly to their ability to evade host immune responses and persist intracellularly. Several
Anaplasma species possess important veterinary and zoonotic significance.
Anaplasma marginale primarily infects erythrocytes in cattle and is responsible for bovine anaplasmosis.
Anaplasma ovis infects sheep and goats, whereas
Anaplasma phagocytophilum targets neutrophils and causes granulocytic anaplasmosis in animals and humans
(Ierardi et al., 2025). Anaplasma platys infects canine platelets and produces cyclic thrombocytopenia in dogs
(Gospodinova et al., 2024). Emerging species such as
Anaplasma capra have further complicated the taxonomy and epidemiology of the genus
(Altay et al., 2024).
Recent advances in molecular taxonomy and phylogenomics have improved understanding of species diversity and evolutionary relationships within the genus. Molecular markers including 16S rRNA,
groEL,
gltA,
msp1α and
msp4 genes are widely used for species identification and phylogenetic analysis
(Kumar et al., 2023b; Bisen et al., 2023). Whole-genome sequencing studies have revealed substantial genetic diversity among field isolates and suggested regional adaptation, host-associated evolution and emergence of genetically distinct strains with potential epidemiological significance. Phylogenomic studies have also demonstrated considerable antigenic variability among circulating isolates, particularly within major surface proteins MSP2 and MSP3.
Molecular epidemiology and genomics
Global epidemiology
Anaplasmosis is widely distributed throughout tropical, subtropical and temperate regions of the world. The prevalence of infection is strongly influenced by the distribution of competent tick vectors, environmental conditions, host density and management practices
(Mauri et al., 2025). Regions characterized by warm temperatures and high humidity favor tick survival and therefore experience greater disease prevalence. The epidemiology of anaplasmosis has changed considerably in recent years because of climate-driven expansion of tick populations. Tick species such as
Rhipicephalus microplus,
Dermacentor spp. and
Ixodes spp. have expanded into new ecological zones, increasing transmission risk in previously non-endemic regions. Ecological disturbances, deforestation, wildlife migration and changing agricultural practices have also contributed to altered vector dynamics.
Epidemiology in India
India represents one of the major endemic regions for bovine anaplasmosis because of favorable climatic conditions for tick survival and widespread livestock farming systems. Studies from Northern India, particularly Uttar Pradesh, Haryana, Rajasthan and Punjab, have reported significant prevalence of
Anaplasma infection in cattle and buffaloes
(Paramanandham et al., 2019). Recent molecular epidemiological studies from Western Uttar Pradesh demonstrated considerable prevalence of bovine anaplasmosis associated with breed susceptibility, seasonal tick abundance and farm management practices. Indigenous breeds generally exhibit greater resistance compared with crossbred animals, which are more susceptible to severe clinical disease. Poor tick control, inadequate biosecurity and intensive farming systems further contribute to disease persistence in endemic areas (
Atif, 2016;
Kumar et al., 2023; Gong et al., 2025).
Molecular epidemiology
Molecular epidemiology has substantially improved understanding of strain diversity and transmission dynamics of
Anaplasma spp. Polymerase chain reaction-based genotyping and sequencing approaches have revealed extensive diversity among circulating isolates. MSP1α genotyping has been particularly useful for studying strain variation and epidemiological linkage among outbreaks. Phylogeographic studies indicate that genetically diverse
Anaplasma strains circulate simultaneously within endemic regions, contributing to reinfection, persistent carrier states and vaccine challenges
(Kumar et al., 2021).
Genomics and evolutionary adaptation
Recent genomic studies have provided important insights into pathogen adaptation, virulence and host specificity. Whole-genome sequencing has identified genes associated with intracellular survival, antigenic variation, secretion systems and immune modulation. Comparative genomics suggests that selective evolutionary pressure exerted by both vertebrate hosts and tick vectors contributes significantly to genomic diversification. Transcriptomic and proteomic analyses have further revealed differential expression of virulence-associated proteins during host infection and vector transmission.
Host-pathogen interactions and pathogenesis
The pathogenesis of anaplasmosis involves complex interactions between the pathogen, host immune system and tick vector. Infection typically begins when an infected tick introduces
Anaplasma organisms into the bloodstream during feeding. Tick saliva contains immunomodulatory molecules that facilitate pathogen establishment by suppressing local immune responses and inflammation. Following entry into the host,
Anaplasma organisms invade target cells and replicate within membrane-bound intracellular vacuoles. The organisms manipulate host cellular pathways to establish a favorable intracellular environment. Intracellular survival involves inhibition of phagolysosomal fusion, alteration of host gene expression, nutrient acquisition and prevention of programmed cell death (Fig 1). One of the most important pathogenic mechanisms employed by
Anaplasma spp. is antigenic variation. Major surface proteins, particularly MSP2 and MSP3, undergo continuous genetic variation, allowing the pathogen to evade host immune recognition
(Severo et al., 2012; Alberdi et al., 2016). This sequential antigenic switching contributes significantly to persistent infection, chronic carrier states and failure of sterilizing immunity.
In addition to antigenic variation,
Anaplasma organisms interfere with innate immune responses by suppressing oxidative burst activity and modulating cytokine production
(Rana et al., 2023). A. phagocytophilum specifically targets neutrophils and disrupts their antimicrobial functions, thereby impairing host defense mechanisms. The pathogen also manipulates apoptosis signaling pathways to prolong survival of infected cells and maintain intracellular replication niches. The infection produces significant hematological and biochemical alterations including anemia, leukopenia, thrombocytopenia, oxidative stress and inflammatory tissue injury. In bovine anaplasmosis, destruction of infected erythrocytes by the reticuloendothelial system results in severe hemolytic anemia, jaundice, hypoxia and reduced productivity. Persistent carrier states represent one of the major epidemiological challenges associated with anaplasmosis.
Species-specific manifestations
Bovine anaplasmosis
Bovine anaplasmosis caused primarily by
A. marginale is characterized by fever, progressive anemia, icterus, weakness, weight loss, abortion and decreased milk production
(Kumar et al., 2015; Das et al., 2022). Adult cattle are generally more susceptible to severe disease compared with younger animals, which often develop mild or subclinical infections
(Ierardi et al., 2025). Persistent carrier states are common and play a critical role in disease transmission.
Ovine and caprine anaplasmosis
Sheep and goats are mainly infected with
A. ovis. Infections are frequently subclinical, although stress, malnutrition and concurrent infections may precipitate clinical disease characterized by anemia, fever, weakness and reduced productivity. Small ruminants may also serve as reservoirs for tick-mediated transmission.
Canine anaplasmosis
Canine anaplasmosis is caused primarily by
A. platys and
A. phagocytophilum. Clinical manifestations include fever, lethargy, anorexia, thrombocytopenia, lymphadenopathy and occasional bleeding disorders
(Atif et al., 2021). Cyclic thrombocytopenia is a characteristic feature of
A. platys infection.
Equine granulocytic anaplasmosis
Equine anaplasmosis caused by
A. phagocytophilum is characterized by fever, depression, limb edema, ataxia, reluctance to move and occasionally neurologic manifestations. Disease occurrence is often seasonal and associated with vector activity.
Wildlife reservoirs
Wildlife species including deer, wild ruminants, rodents and other free-ranging animals play important roles in maintaining
Anaplasma organisms within natural ecosystems. Wildlife reservoirs contribute significantly to pathogen persistence, vector infection and cross-species transmission at the wildlife-livestock-human interface.
Advances in diagnostics
Accurate diagnosis of anaplasmosis remains essential for effective therapeutic management, epidemiological surveillance and disease control. Conventional diagnostic approaches include microscopic examination of Giemsa-stained blood smears and serological assays such as enzyme-linked immunosorbent assay and indirect fluorescent antibody tests
(Shabana et al., 2018). Although these methods are relatively inexpensive and suitable for field application, they suffer from limited sensitivity, particularly during chronic or carrier-stage infections. Molecular diagnostic techniques have substantially improved detection sensitivity and specificity. Conventional PCR, nested PCR, multiplex PCR and quantitative real-time PCR assays enable species-level identification and detection of low-level parasitemia
(Colasante et al., 2024). PCR-based assays targeting 16S rRNA, MSP genes and other conserved genomic regions are widely used in epidemiological investigations
(Pan et al., 2011; Altay et al., 2026). Despite their superior sensitivity, molecular diagnostics face several practical limitations in endemic field conditions. High cost, infrastructure requirements, need for trained personnel and limited portability restrict their widespread use in resource-constrained settings. Furthermore, PCR-based methods may not reliably distinguish viable from non-viable organisms (Table 1).
Recent advances in genomics and sequencing technologies have expanded diagnostic possibilities. Next-generation sequencing, metagenomics and nanopore sequencing facilitate comprehensive pathogen detection, strain characterization and genomic surveillance. These technologies are particularly useful for identifying emerging species, mixed infections and novel genetic variants. Point-of-care diagnostics are emerging as promising alternatives for field-level disease detection. Loop-mediated isothermal amplification (LAMP), CRISPR-Cas-based diagnostics, portable PCR systems, biosensors and microfluidic platforms offer rapid and sensitive detection under field conditions.
Therapeutics and antimicrobial resistance
Therapeutic management of anaplasmosis primarily relies on tetracycline antibiotics because of their ability to penetrate host cells and inhibit bacterial protein synthesis. Oxytetracycline remains the most commonly used therapeutic agent in cattle, whereas doxycycline is widely used in small animals because of superior bioavailability and tissue penetration. Both the drugs act primarily by inhibiting bacterial protein synthesis through binding to the 30S ribosomal subunit
(Lacasta et al., 2022; Rai et al., 2024; Kumar et al., 2026). Imidocarb dipropionate also exhibits efficacy against bovine anaplasmosis and provides partial prophylactic activity. Its mechanism of action is not fully understood but is believed to involve interference with nucleic acid metabolism in the parasite
(Doyle et al., 2016). However, toxicity concerns including cholinergic side effects, necessitating careful dosing and monitoring, prolonged withdrawal periods and incomplete pathogen clearance limit its routine application. Macrolides and fluoroquinolones have been investigated as alternative antimicrobial agents, although their use remains limited because of variable efficacy and concerns regarding antimicrobial stewardship
(Maurin et al., 2003). Rifampicin has shown some in vitro activity against
Anaplasma phagocytophilum; however, its clinical application in veterinary practice is not well established
(Thomas et al., 2009).
Pharmacokinetics and treatment regimens
The efficacy of antimicrobial therapy is influenced by pharmacokinetic and pharmacodynamic factors, including drug absorption, tissue distribution and intracellular penetration. Tetracyclines exhibit favourable intracellular accumulation, which is essential for targeting
Anaplasma organisms that reside within host cells
(Semenova et al., 2025). Long-acting formulations of oxytetracycline have been widely adopted in field conditions because of their convenience and sustained therapeutic levels. Treatment regimens vary depending on the species, severity of infection and regional practices; however, early intervention remains a key determinant of therapeutic success.
Antimicrobial resistance and emerging concerns
The emergence of antimicrobial resistance in
Anaplasma spp. is a growing concern, although it remains less well characterised than other bacterial pathogens. Reports of reduced sensitivity to tetracyclines have emerged in certain endemic regions, raising questions about the long-term efficacy of current treatment protocols
(Curtis et al., 2021). Resistance mechanisms are thought to involve genetic mutations affecting ribosomal binding sites and efflux pump systems that reduce intracellular drug concentrations (
Chavarria-Bencomo et al., 2023). The widespread and often indiscriminate use of antibiotics in livestock production systems has likely contributed to the development of resistance, emphasising the need for judicious antimicrobial use in livestock
(Kumar et al., 2012; Sharma et al., 2015 and Fig 2). Another important consideration is the persistence of
Anaplasma organisms despite the use of antimicrobial therapy. This persistence is not necessarily indicative of classical resistance but reflects the ability of pathogens to evade host immunity and survive in intracellular niches. Consequently, treated animals may continue to serve as reservoirs of infection, complicating the control efforts. Table 2 highlights that tetracyclines, particularly oxytetracycline and doxycycline, remain the most reliable therapeutic agents because of their ability to penetrate host cells and inhibit bacterial protein synthesis. Imidocarb dipropionate is an alternative option, especially in bovine cases; however, its toxicity and residue concerns limit its widespread use. Emerging alternatives, such as fluoroquinolones and rifampicin, show promise but are constrained by regulatory and resistance issues. Importantly, none of the currently available drugs consistently eliminate the carrier state, which remains a major limitation in controlling the disease.
Limitations of conventional therapy
Although antimicrobial therapy is effective in reducing clinical severity, it does not always result in complete pathogen clearance
(Ierardi et al., 2025; Kumar et al., 2026). This limitation is particularly evident in chronic infections, where low-level parasitaemia persists despite treatment. Additionally, reliance on antibiotics raises concerns regarding drug residues in animal products, regulatory restrictions and public health implications (
Chavarria-Bencomo et al., 2023). The cost and accessibility of drugs also pose challenges in resource-limited settings, where livestock owners may have limited access to veterinary care. These constraints highlight the need for alternative and complementary therapeutic approaches to treat the disease. The mechanisms outlined above indicate that antimicrobial resistance in
Anaplasma spp. is multifactorial and differs from the classical resistance observed in extracellular bacteria (Table 3). Although direct genetic resistance, such as ribosomal mutations, is beginning to emerge, much of the reduced therapeutic efficacy observed in field conditions is attributable to intrinsic survival strategies, including intracellular sequestration, antigenic variation and metabolic persistence. The obligate intracellular lifestyle of
Anaplasma plays a central role in limiting drug efficacy, as many antimicrobial agents fail to achieve sufficient intracellular drug concentrations. Tetracyclines, which are bacteriostatic, may be less effective against dormant or slowly replicating organisms, thereby contributing to persistent infections and carrier states. Although confirmed antimicrobial resistance in
Anaplasma remains relatively limited compared to other pathogens, the increasing reliance on tetracyclines in endemic regions raises concerns regarding the development of future resistance.
Alternative and adjunct therapeutic approaches
Phytotherapy and plant-derived compounds
Increasing interest has been directed toward plant-based therapies as potential alternatives or adjuncts to conventional treatments
(Mahima et al., 2012; Dhama et al., 2013). Several medicinal plants have demonstrated antimicrobial, antioxidant and immunomodulatory properties that may be beneficial for managing anaplasmosis. Extracts from plants such as
Azadirachta indica (neem),
Allium sativum (garlic) and
Ocimum sanctum (holy basil) have demonstrated inhibitory effects against various intracellular pathogens in experimental studies. Phytochemicals, such as flavonoids, alkaloids and terpenoids, are believed to contribute to these effects by disrupting microbial metabolism and enhancing host immune responses.
Immunomodulatory therapy
Given the importance of host immunity in disease progression, immunomodulatory approaches have been explored as adjunctive therapies. Agents such as cytokines, probiotics and nutritional supplements may enhance immune function and improve disease outcomes
(Mahima et al., 2013). Antioxidants, including vitamin E and selenium, have been shown to mitigate the oxidative stress associated with infection and may support recovery
(Dhanasree et al., 2020; Das et al., 2022).
Nanotechnology-based drug delivery
Recent advances in nanotechnology have opened new avenues for improving drug delivery in intracellular infections. Nanoparticle-based formulations of antimicrobial agents have demonstrated enhanced cellular uptake and targeted delivery, potentially increased therapeutic efficacy while reducing systemic toxicity
(Verma et al., 2026). Although still in the experimental stage, these approaches hold promise for future treatment strategies.
Biological control and vaccine-assisted therapy
Vaccination, although primarily a preventive strategy, may also play a role in reducing disease severity and complementing therapeutic interventions
(Singh et al., 2014). The use of live attenuated vaccines, such as
Anaplasma centrale, has shown partial success in endemic regions
(Shkap et al., 2008; Ferm et al., 2024). Emerging recombinant vaccines targeting conserved antigens offer potential for improved efficacy
(Sarli et al., 2020).
Ethnoveterinary practices
Traditional knowledge systems in many regions have long utilized herbal remedies for the treatment of tick-borne diseases. Ethnoveterinary practices may provide valuable insights into locally available and sustainable therapeutic options. However, scientific validation and standardization are essential to ensure safety and efficacy.
Integrated therapeutic strategies
A holistic approach to the treatment of anaplasmosis involves the integration of antimicrobial therapy with supportive care, vector control and management practices. Early diagnosis followed by prompt administration of appropriate drugs remains the cornerstone of treatment, but long-term control requires addressing the underlying epidemiological factors. Combining conventional therapy with alternative approaches such as phytotherapy and immunomodulation may enhance treatment outcomes and reduce reliance on antibiotics. Furthermore, strategic use of therapeutics in conjunction with vaccination and tick control measures can significantly reduce disease burden.
Future directions in therapeutics
Future research should focus on the development of novel therapeutics targeting specific molecular pathways involved in
Anaplasma survival and replication. Advances in genomics and proteomics may facilitate the identification of new drug targets and vaccine candidates. Additionally, the integration of precision medicine approaches, including host genetic profiling and tailored treatment regimens, may improve therapeutic efficacy.
Vaccines and integrated control strategies
Vaccination remains one of the most promising approaches for sustainable control of anaplasmosis. The live
Anaplasma centrale vaccine has been used in several endemic regions and provides partial protection against severe disease. However, limitations including incomplete cross-protection, residual virulence and inability to prevent carrier states restrict its effectiveness. Recent vaccine research has focused on recombinant proteins, conserved antigens, DNA vaccines, vector-based vaccines and reverse vaccinology approaches
(Sarli et al., 2020).
Tick control remains the corner stone of integrated disease prevention. Strategic acaricide application, pasture management, biological control, rotational grazing and use of tick-resistant breeds contribute significantly to reducing transmission. However, increasing acaricide resistance among tick populations, particularly
Rhipicephalus microplus, represents a major emerging challenge
(Makwarela et al., 2025). Chemoprophylaxis may be employed in endemic areas to reduce infection pressure, although concerns regarding antimicrobial resistance necessitate judicious use. Farm-level biosecurity measures including quarantine of newly introduced animals, sterilization of instruments, surveillance of carrier animals, vector monitoring and movement control are essential components of integrated control programs. Climate-based forecasting systems, GIS surveillance and ecological monitoring may further improve vector management strategies under changing environmental conditions.
One health and zoonotic implications
The emergence of zoonotic
Anaplasma species has substantially increased the public health significance of anaplasmosis.
A. phagocytophilum causes human granulocytic anaplasmosis, an emerging tick-borne disease characterized by fever, headache, myalgia, leukopenia, thrombocytopenia and occasionally severe systemic complications
(Abdoli et al., 2025). Recent reports of
A. capra infection in humans further highlight the zoonotic potential of emerging
Anaplasma species. Increasing interaction among wildlife, livestock, vectors and humans has created favorable conditions for cross-species transmission and emergence of novel zoonotic infections. Occupational exposure among farmers, veterinarians, animal handlers, forestry workers and wildlife personnel increases risk of infection. Climate change, ecological disruption, wildlife migration and expanding vector habitats are expected to further enhance zoonotic transmission risk in the future. The one health approach provides an essential framework for integrated management of anaplasmosis by linking veterinary health, human health, environmental surveillance, vector ecology and public health policy. Integrated surveillance systems incorporating molecular epidemiology, vector monitoring, wildlife ecology and climate forecasting are necessary for effective prevention and control of emerging tick-borne diseases.
Knowledge gaps and future perspectives
Despite considerable scientific advances, several important challenges continue to hinder effective control of anaplasmosis. Current vaccines fail to provide complete cross-protection and sterilizing immunity. Diagnostic limitations remain significant under field conditions, particularly for chronic carrier detection and mixed infections. The molecular basis of persistence, host specificity and pathogen adaptation also remains incompletely understood. Future research should prioritize multi-omics approaches including genomics, transcriptomics, proteomics and metabolomics to better understand pathogen biology and host-pathogen interactions. Artificial intelligence-assisted epidemiological modelling, climate-based vector forecasting and GIS surveillance may improve early warning systems and disease prediction. Development of affordable point-of-care diagnostics, CRISPR-based molecular assays, precision therapeutics and next-generation vaccines represents important future priorities. Strengthening antimicrobial stewardship and integrated tick management programs will also be essential to mitigate resistance development. The future control of anaplasmosis will likely depend on integrated multidisciplinary strategies combining molecular surveillance, precision diagnostics, vector ecology, vaccine innovation, climate-resilient interventions and coordinated One Health policy frameworks.
