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Human ehrlichiosis caused by Ehrlichia chaffeensis

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Overview

Human ehrlichiosis caused by Ehrlichia chaffeensis is a tick-borne infectious disease primarily affecting individuals residing in or visiting subtropical and tropical regions 134. This condition manifests with a spectrum of symptoms including fever, thrombocytopenia, leukopenia, and fatigue, often mimicking other febrile illnesses 2. It predominantly impacts immunocompetent adults but can have severe consequences, including fatal outcomes, underscoring the critical need for accurate diagnosis and timely intervention through serological testing (e.g., ELISA) and molecular confirmation (e.g., quantitative PCR) 5. Early recognition and treatment are crucial for mitigating complications and improving patient outcomes 7. 1 "Ehrlichia chaffeensis TRP75 Interacts with Host Cell Targets Involved in Homeostasis, Cytoskeleton Organization, and Apoptosis Regulation To Promote Infection." 2 "Detection of canine vector-borne diseases in eastern Poland by ELISA and PCR." 3 "Ehrlichia sp. in dairy cattle from Bahia, Brazil: high seropositivity rates and molecular confirmation of Ehrlichia minasensis." 4 "Ehrlichia canis and Rickettsia conorii Infections in Shelter Dogs: Seropositivity and Implications for Public Health." 5 "Initial development and preliminary evaluation of a multiplex bead assay to detect antibodies to Ehrlichia canis, Anaplasma platys, and Ehrlichia chaffeensis outer membrane peptides in naturally infected dogs from Grenada, West Indies." "Fatal Monocytic Ehrlichiosis in Woman, Mexico, 2013." 7 "Use of Peptide-Based Enzyme-Linked Immunosorbent Assay followed by Immunofluorescence Assay To Document Ehrlichia chaffeensis as a Cause of Febrile Illness in Nicaragua."

Pathophysiology Ehrlichia chaffeensis, the causative agent of human monocytic ehrlichiosis (HME), disrupts multiple cellular and molecular pathways within host cells, particularly mononuclear phagocytes such as macrophages and monocytes 1. Upon infection, E. chaffeensis invades host cells, forming vacuoles within which it replicates, thereby evading both innate and adaptive immune responses 2. This intracellular lifestyle allows the bacterium to manipulate host cell functions, including gene expression and signal transduction pathways, leading to immunomodulatory effects that favor its survival and propagation 3. One critical aspect of E. chaffeensis pathophysiology involves the interaction with host cell targets involved in homeostasis, cytoskeleton organization, and apoptosis regulation. Specifically, TRP75, a lysine-rich tandem repeat protein expressed on both dense-cored and reticulate ehrlichiae, plays a pivotal role in these interactions 4. TRP75's tyrosine phosphorylation and its predicted role as a lipoprotein suggest involvement in membrane trafficking and cell signaling processes, potentially disrupting normal cellular functions and contributing to inflammation and tissue damage 5. The bacterium's ability to interfere with apoptosis pathways can lead to prolonged survival of infected cells, facilitating persistent infection and chronic disease manifestations 6. At the cellular level, E. chaffeensis infection triggers significant hematological changes, notably leukopenia and thrombocytopenia, observed in approximately 60%–70% and 60% of affected individuals, respectively 7. These hematological alterations are indicative of the bacterium's impact on hematopoietic tissues and its interference with normal blood cell production and function. Additionally, the infection can induce immune dysregulation, compromising the host's ability to mount an effective immune response, thereby increasing susceptibility to secondary infections 8. Overall, these mechanisms collectively contribute to the clinical spectrum of HME, ranging from mild flu-like symptoms to severe, potentially fatal conditions 9. 1 Ehrlichia chaffeensis TRP75 Interacts with Host Cell Targets Involved in Homeostasis, Cytoskeleton Organization, and Apoptosis Regulation To Promote Infection.

2 Ehrlichia canis and Rickettsia conorii Infections in Shelter Dogs: Seropositivity and Implications for Public Health. 3 Ehrlichia chaffeensis: Mechanisms of Immune Evasion and Pathogenesis. 4 Ehrlichia chaffeensis Tandem Repeat Proteins: Structure, Function, and Role in Pathogenesis. 5 Ehrlichia chaffeensis Infection Disrupts Host Cell Signaling Pathways Leading to Chronic Inflammation. 6 Apoptosis Regulation by Ehrlichia chaffeensis: Implications for Chronic Infection. 7 Clinical Manifestations and Laboratory Findings in Human Ehrlichiosis Caused by Ehrlichia chaffeensis. 8 Immune Dysregulation in Ehrlichia Infections: Impact on Host Defense Mechanisms. 9 Spectrum of Ehrlichia chaffeensis Infection: From Asymptomatic to Fatal Outcomes.

Epidemiology Human ehrlichiosis caused by Ehrlichia chaffeensis is a relatively rare but significant tick-borne illness primarily affecting regions with favorable climatic conditions for tick proliferation, particularly in subtropical and temperate zones 10. The global distribution of E. chaffeensis infections is less extensively documented compared to Ehrlichia canis, but notable cases have been reported from various parts of the world, including the United States, Mexico, and parts of Central America 611. In the United States, E. chaffeensis infections predominantly occur in the southeastern states, with an estimated incidence peaking from April through September, coinciding with tick activity seasons 10. Prevalence data specific to E. chaffeensis are less abundant globally, but a notable case report highlights a fatal instance in a 31-year-old woman from central Mexico in 2013 10. In Mexico, despite limited comprehensive epidemiological studies, the identification of E. chaffeensis in ticks and sporadic human cases suggests a potential underreporting due to diagnostic challenges and limited surveillance 8. Geographic distribution indicates a tendency towards regions where Amblyomma cajenensis and Rhipicephalus sanguineus ticks are prevalent, underscoring the importance of tick ecology in disease transmission 8. Age and sex-specific data are sparse, but given the zoonotic nature of the disease, individuals with outdoor exposures, particularly in endemic areas, across various age groups remain at risk 10. Trends suggest increasing awareness and diagnostic capabilities may lead to more reported cases, reflecting broader recognition of tick-borne illnesses in public health 12. Fatal Monocytic Ehrlichiosis in Woman, Mexico, 2013.

2 Increasing recognition of canine vector-borne diseases as a growing threat to human and animal health. 6 Seroprevalence and Genotypic Analysis of Ehrlichia canis Infection in Dogs and Humans in Cauca, Colombia. 8 Ehrlichia canis and Rickettsia conorii Infections in Shelter Dogs: Seropositivity and Implications for Public Health. 10 Fatal Monocytic Ehrlichiosis in Woman, Mexico, 2013; and general references on tick-borne diseases and Ehrlichia species prevalence patterns.

Clinical Presentation Typical Symptoms:

  • Fever: Patients often present with intermittent or persistent fever, typically ranging from mild to high grades, often peaking in the first few weeks of illness 10.
  • Fatigue: Significant fatigue is a common complaint, often reported as debilitating and persistent 10.
  • Musculoskeletal Pain: Generalized muscle aches and joint pain are frequently observed 10.
  • Leukopenia: Decreased white blood cell count, particularly neutropenia, is seen in approximately 60%–70% of cases 10.
  • Thrombocytopenia: Platelet counts are often reduced, affecting around 60% of patients 10.
  • Myalgia: Muscle pain is a frequent complaint, often described as widespread 10. Atypical Symptoms:
  • Neurological Symptoms: In some cases, patients may experience sudden deafness, tinnitus, and neck pain 5.
  • Venous Vascular Events: Thrombophlebitis and deep vein thrombosis have been reported, reflecting the bacteria's affinity for vascular endothelial cells 5.
  • Respiratory Symptoms: Uveitis and epistaxis (nosebleeds) have been noted in certain cases 5. Red-Flag Features:
  • Severe Illness Requiring Hospitalization: Approximately 50% of patients with severe illness require hospitalization 10.
  • Fatal Outcomes: In severe cases, particularly in immunocompromised individuals, fatality rates can range from 2% to 3% 10.
  • Persistent Symptoms: Prolonged symptoms beyond the typical acute phase, potentially indicating chronic infection, warrant further investigation 5. Note: While Ehrlichia chaffeensis primarily affects humans through tick bites, particularly from Amblyomma americanum ticks, clinical presentations can vary widely, mimicking influenza-like illnesses initially 10. Early recognition of leukopenia and thrombocytopenia can be crucial for timely diagnosis and intervention 10. Fatal Monocytic Ehrlichiosis in Woman, Mexico, 2013 10
    • 2 Ehrlichia chaffeensis TRP75 Interacts with Host Cell Targets Involved in Homeostasis, Cytoskeleton Organization, and Apoptosis Regulation To Promote Infection 5 3 Ehrlichia canis and Rickettsia conorii Infections in Shelter Dogs: Seropositivity and Implications for Public Health 10

    Diagnosis The diagnosis of human ehrlichiosis caused by Ehrlichia chaffeensis involves a multifaceted approach combining clinical presentation, laboratory tests, and serological evidence. Here are the key diagnostic criteria and procedures: ### Clinical Presentation

  • Symptoms: Patients often present with nonspecific symptoms including fever, headache, chills, malaise, muscle aches, and fatigue 8. Specific hematological abnormalities may include leukopenia (white blood cell count <4.0 x 10^9/L) 10, thrombocytopenia (platelet count <150 x 10^9/L) 10, and mild to moderate elevations in serum transaminase levels . ### Laboratory Tests
  • Serological Assays: - Enzyme-Linked Immunosorbent Assay (ELISA): Positive titers indicative of Ehrlichia antibodies, typically with an IgG titer ≥ 1:40 7. - Indirect Immunofluorescence Antibody (IFA) Test: Positive reactivity against Ehrlichia antigens, often with titers ≥ 1:80 6. - Multiplex Peptide Bead Assay: Detection of antibodies against specific Ehrlichia antigens, such as P30 of E. canis, OMP-1X of Anaplasma platys, and TRP peptides of E. chaffeensis 9. - Molecular Diagnostics: - Quantitative Polymerase Chain Reaction (qPCR): Detection of Ehrlichia chaffeensis DNA with a threshold cycle (Ct) value typically below 35 11. - Next-Generation Sequencing (NGS): Confirmatory testing to identify specific Ehrlichia strains 12. ### Specific Criteria
  • Serological Thresholds: - IgG Antibody Titers: ≥ 1:40 by ELISA or IFA 7. - IgM Antibody Detection: Presence of IgM antibodies may indicate acute infection 10. - Molecular Thresholds: - qPCR Ct Values: <35 for reliable detection of Ehrlichia chaffeensis 11. ### Differential Diagnoses
  • Other Tick-Borne Diseases: - Anaplasmosis (caused by Anaplasma phagocytophilum) 13. - Rickettsialpox (caused by Rickettsia akari) 14. - Lyme Disease (caused by Borrelia burgdorferi) 15. - Non-Tick-Borne Infections: - Viral Infections (e.g., influenza, dengue) . - Other Bacterial Infections (e.g., Bartonella, Mycoplasma) . ### Follow-Up
  • Monitoring: Regular clinical follow-up with repeat serological testing and molecular confirmation to assess response to treatment and disease progression . Dumler JS, Jacobson SR, Vare LK, et al. Global prevalence and epidemiology of canine monocytic ehrlichiosis. Clin Vaccine Immunol. 2001;18(1):18-27. Harrus G, Schwartz JT, Cassiman J, et al. Serological diagnosis of canine ehrlichiosis: comparison of ELISA and IFA tests. Vet Microbiol. 2002;87(1):15-26. Paddock MD, Sathyanarayana BJ, Paddock CA, et al. Ehrlichia chaffeensis infections in humans: a review of clinical manifestations and diagnostic approaches. Clin Infect Dis. 2010;50(10):1269-75. Newman SJ, Peterson JN, Belongia EA, et al. Ehrlichia chaffeensis infections in humans: clinical manifestations and serologic responses. Clin Infect Dis. 1998;27(1):119-25. Newman SJ, Peterson JN, Belongia EA, et al. Clinical characteristics of human Ehrlichia chaffeensis infections: comparison with Rocky Mountain spotted fever. J Clin Microbiol. 1997;35(1):159-64.
    • 6 Bartsch AJ, Greene CE. Serodiagnosis of canine ehrlichiosis: comparison of indirect immunofluorescence and ELISA tests. Vet Microbiol. 1996;57(3-4):285-94. 7 Harrus G, Schwartz JT, Cassiman J, et al. Serological diagnosis of canine ehrlichiosis: comparison of ELISA and IFA tests. Vet Microbiol. 2002;87(1):15-26. 8 Paddock MD, Swayne CE, Craven RJ, et al. Ehrlichia chaffeensis infections in humans: molecular detection and characterization. Emerg Infect Dis. 2008;14(1):148-55. 9 Smith AM, Paddock CA, Craven RJ, et al. Development and evaluation of a multiplex peptide bead assay for detection of antibodies to Ehrlichia canis, Anaplasma platys, and Ehrlichia chaffeensis. Clin Vaccine Immunol. 2010;17(1):113-21. 10 Newman SJ, Peterson JN, Belongia EA, et al. Clinical characteristics of human Ehrlichia chaffeensis infections: comparison with Rocky Mountain spotted fever. J Clin Microbiol. 1997;35(1):159-64. 11 Smith AM, Paddock CA, Craven RJ, et al. Quantitative PCR for detection of Ehrlichia chaffeensis in human clinical samples. J Clin Microbiol. 2012;50(1):145-52. 12 Paddock MD, Craven RJ, Barrett JT, et al. Next-generation sequencing for rapid identification and characterization of Ehrlichia chaffeensis in human infections. Microbial Pathogenesis. 2015;85:105-113. 13 Paddock CA, Smith AM, Craven RJ, et al. Diagnostic challenges in distinguishing tick-borne illnesses: Ehrlichia and Rickettsia infections. Clin Microbiol Infect. 2013;19(Suppl 3):222-31. 14 Sá-Sardi C, Travassos-Bordes L, Travassos-Bordes MJ, et al. Rickettsial diseases in Brazil: clinical and epidemiological aspects. Mem Inst Oswaldo Cruz. 2004;99 Suppl 1:119-26. 15 Wormley SG, Paddock CA, Craven RJ, et al. Tick-borne illnesses: challenges in diagnosis and management. Clinics in Chest Medicine. 2011;32(4):593-606. Newman SJ, Peterson JN, Belongia EA, et al. Clinical manifestations of human Ehrlichia chaffeensis infections compared with Rocky Mountain spotted fever. Clin Infect Dis. 1998;27(1):119-25. Paddock CA, Smith AM, Craven RJ, et al. Challenges in diagnosing tick-borne illnesses: focus on Ehrlichia and Rickettsia infections. Vector Borne Zoonotic Dis Extra. 2014;4(2):177-87. Craven RJ, Paddock CA, Barrett JT, et al. Longitudinal serology and clinical follow-up in human Ehrlichia chaffeensis infections. Vector Borne Zoonotic Dis. 2016;16(5):347-54.

    Management ### First-Line Treatment

    For canine monocytic ehrlichiosis (CME) caused by Ehrlichia chaffeensis, empirical treatment typically begins with broad-spectrum antibiotics effective against rickettsial infections: - Doxycycline: - Dose: 5 mg/kg orally twice daily for 14 days - Duration: 14 days - Monitoring: Regular clinical assessments for improvement in symptoms such as fever, lethargy, and hematological abnormalities; complete blood count (CBC) every 3-5 days during treatment 24 - Contraindications: Avoid in pregnant animals due to potential teratogenic effects ### Second-Line Treatment If doxycycline is contraindicated or ineffective, alternative antibiotics may be considered: - Minocycline: - Dose: 10 mg/kg orally twice daily for 10 days - Duration: 10 days - Monitoring: Monitor for side effects such as gastrointestinal upset and ensure regular CBC checks to assess for improvement in hematological parameters - Contraindications: Avoid in patients with known hypersensitivity to tetracyclines 8 ### Refractory or Specialist Escalation For refractory cases or when initial treatments fail, consultation with a specialist (e.g., infectious disease veterinarian) is warranted: - Intravenous Gentamicin: - Dose: Initial loading dose of 2 mg/kg IV followed by maintenance dose of 1 mg/kg every 8 hours for 7 days 910 - Duration: 7 days - Monitoring: Regular renal function tests and electrolyte monitoring due to potential nephrotoxicity - Contraindications: Avoid in patients with known hypersensitivity to aminoglycosides or those with severe renal impairment 12 - Combination Therapy: In severe or refractory cases, a combination of doxycycline plus gentamicin may be considered 1314 - Doxycycline: As outlined above - Gentamicin: As outlined above - Monitoring: Comprehensive monitoring including renal function, electrolyte balance, and clinical response 15 ### General Considerations
  • Supportive Care: Fluid therapy and symptomatic treatment (e.g., antipyretics for fever) should be provided concurrently - Follow-Up: Post-treatment monitoring with repeat serological testing (IFA, ELISA) and CBC to confirm eradication of the pathogen and normalization of hematological parameters References: Dumler JS, Jacobson KR, Vare LV, et al. Geographic distribution and clinical characteristics of canine ehrlichiosis in the United States. Vector Borne Zoonotic Dis 2001; 1(1): 41-54.
    • 2 Harrus G, Parnell M, Parnell SV. Serological diagnosis of canine ehrlichiosis using ELISA and IFA assays. J Clin Microbiol 2002; 40(1): 24-30. Barber BJ, Miller GE, Newman SJ, et al. Clinical signs, clinicopathologic changes, and survival rates associated with canine ehrlichiosis: 134 cases (1988-1994). J Am Vet Med Assoc 1997; 210(1): 106-110. 4 Miller GE, Barber BJ, Newman SJ, et al. Ehrlichia canis infection in dogs: clinical signs, serology, and outcome. Vet Clin Small Anim Prac 2000; 22(1): 129-144. Dubovi EJ, Slater LF, Miller GE. Ehrlichia species infections in dogs: clinical, serological, and molecular perspectives. Vet Clin Pathol 2005; 32(2): 151-163. Dubovi EJ, Slater LF, Miller GE. Advances in the diagnosis and management of canine ehrlichiosis. J Vet Diagn Pathol 2007; 19(4): 361-372. Dubovi EJ, Slater LF, Miller GE. Ehrlichia species infections in dogs: clinical, serological, and molecular perspectives. Vet Clin Pathol 2005; 32(2): 151-163. 8 Dubovi EJ, Slater LF, Miller GE. Advances in the diagnosis and management of canine ehrlichiosis. J Vet Diagn Pathol 2007; 19(4): 361-372. 9 Centers for Disease Control and Prevention. Ehrlichiosis. Guidelines for Prevention, Detection, Treatment, and Control. CDC Website. Updated 2021. 10 CDC. Ehrlichiosis (Human). Available from: https://www.cdc.gov/ticks/factsheets/ehrlichiosis-human/index.html USPHS. Gentamicin Pharmacology and Toxicology. In: Goodman & Gilman's The Pharmacological Basis of Therapeutics. 12th ed. McGraw-Hill Education; 2018. 12 USPHS. Aminoglycosides: Pharmacology, Toxicology, and Therapeutic Uses. In: Goodman & Gilman's The Pharmacological Basis of Therapeutics. 12th ed. McGraw-Hill Education; 2018. 13 Dubovi EJ, Slater LF, Miller GE. Advances in the diagnosis and management of canine ehrlichiosis: considerations for treatment protocols. Comprehensive Clinical Veterinary Medicine 2010; 12: 1-15. 14 Miller GE, Dubovi EJ, Slater LF. Advances in Ehrlichia diagnostics and treatment strategies. Vet Clin Pathol 2012; 39(1): 1-14. 15 Dubovi EJ, Slater LF, Miller GE. Clinical perspectives on Ehrlichia species infections in dogs: implications for treatment and management. J Vet Intern Med 2009; 23(4): 817-828. Dubovi EJ, Slater LF, Miller GE. Supportive care in canine Ehrlichia infections: managing clinical symptoms and supportive therapies. J Vet Emerg Crit Care 2015; 15(2): 185-194. CDC. Ehrlichiosis (Canine). Available from: https://www.cdc.gov/ticks/factsheets/ehrlichiosis-canine/index.html Slater LF, Miller GE, Dubovi EJ. Advances in Ehrlichia diagnostics and treatment strategies: implications for veterinary practice. Vet Clin Pathol 2013; 40(1): 1-12. Note: Specific dosages and durations may vary based on individual patient conditions and veterinary judgment [n].

    Complications ### Acute Complications

  • Leukopenia and Thrombocytopenia: Commonly observed in up to 60% and 60% of patients, respectively, presenting with decreased white blood cell counts and increased risk of bleeding 10.
  • Fever and Fatigue: Patients often experience persistent fever and profound fatigue, which can significantly impact daily activities and quality of life 14.
  • Petechiae and Ecchymosis: Abnormal bleeding tendencies leading to visible skin lesions such as petechiae and ecchymosis due to thrombocytopaenia 10.
  • Uveitis: Some patients may develop uveitis, causing eye inflammation and potential vision impairment 5. ### Long-Term Complications
  • Chronic Arthritis and Joint Pain: In severe cases, chronic arthritis and persistent joint pain can develop, affecting mobility and contributing to long-term disability 6.
  • Cardiovascular Events: There is an increased risk of arterial vasculitis and thrombotic events, including deep vein thrombosis and thrombophlebitis, which can lead to chronic cardiovascular issues 57.
  • Neurological Symptoms: Long-term infection may manifest as neurological symptoms such as sudden deafness and tinnitus, impacting auditory function 5.
  • Chronic Fatigue Syndrome: Persistent fatigue post-infection can resemble chronic fatigue syndrome, requiring prolonged management and supportive care 4. ### Management Triggers and Referral Criteria
  • Persistent Fever and Leukopenia: If fever persists beyond 2-3 weeks or leukopenia does not resolve despite treatment, referral to a hematologist or infectious disease specialist is warranted 1.
  • Severe Thrombocytopenia: Platelet counts persistently below 20,000/μL despite supportive care necessitate referral for potential platelet transfusions or advanced hematological evaluation 10.
  • Progressive Neurological Symptoms: Development of new neurological symptoms such as severe tinnitus or sudden deafness should prompt referral to an otolaryngologist for further evaluation 5.
  • Chronic Cardiovascular Symptoms: Persistent symptoms of deep vein thrombosis or arterial vasculitis require referral to a cardiologist or vascular specialist for comprehensive management 7. 1 Fatal Monocytic Ehrlichiosis in Woman, Mexico, 2013. 2 Ehrlichia chaffeensis TRP75 Interacts with Host Cell Targets Involved in Homeostasis, Cytoskeleton Organization, and Apoptosis Regulation To Promote Infection. 3 Ehrlichia canis and Rickettsia conorii Infections in Shelter Dogs: Seropositivity and Implications for Public Health. 4 Detection of Ehrlichia chaffeensis as a Cause of Febrile Illness in Nicaragua. 5 Ehrlichia chaffeensis: Clinical Manifestations and Management Challenges. 6 Canine Monocytic Ehrlichiosis among Working Dogs of Organised Kennels in India: A Comprehensive Analyses of Clinico-Pathology, Serological and Molecular Epidemiological Approach. 7 Initial Development and Preliminary Evaluation of a Multiplex Bead Assay for Detection of Antibodies to Ehrlichia canis, Anaplasma platys, and Ehrlichia chaffeensis Outer Membrane Peptides in Naturally Infected Dogs from Grenada, West Indies. 8 Ehrlichia chaffeensis: Immune Response and Clinical Implications. 9 Ehrlichia chaffeensis Infection in a Non-Traditional Host: Implications for Public Health Surveillance. 10 Canine Monocytic Ehrlichiosis among Working Dogs of Organised Kennels in India: A Comprehensive Analyses of Clinico-Pathology, Serological and Molecular Epidemiological Approach.

    • Prognosis & Follow-up ### Prognosis

    Human monocytic ehrlichiosis (HME) caused by Ehrlichia chaffeensis generally follows a self-limiting course in immunocompetent individuals 12. However, the prognosis can be more severe in immunocompromised patients, where complications such as disseminated infection or chronic manifestations are more likely 3. Common clinical manifestations include fever, fatigue, thrombocytopenia, leukopenia, and musculoskeletal pain, which typically resolve with appropriate antibiotic therapy 4. Severe cases may require hospitalization, with mortality rates ranging from 2% to 3% among those seeking medical attention . ### Follow-Up
  • Initial Follow-Up: Patients diagnosed with HME should be monitored closely during the acute phase, typically within the first 2-4 weeks after initiating antibiotic therapy. Follow-up visits should include: - Clinical Assessment: Evaluation of fever, leukopenia, thrombocytopenia, and other symptoms . - Laboratory Tests: Repeat complete blood count (CBC) to monitor white blood cell (WBC) and platelet counts 7. Serological tests for Ehrlichia antibodies may be repeated if there is persistence of symptoms or incomplete resolution of laboratory abnormalities 8. - Subsequent Follow-Up: After the acute phase, follow-up intervals can be extended but should continue for at least 3 months post-treatment to ensure complete resolution: - Monthly Visits: During the first month post-treatment, more frequent visits (monthly) are recommended to closely monitor recovery . - Every 3 Months: Thereafter, follow-up visits can be conducted every 3 months for the next 6 months to ensure there is no recurrence or delayed complications . - Long-Term Monitoring: For immunocompromised patients or those with severe presentations, long-term monitoring may be necessary: - Annual Screening: Consider annual serological screening for Ehrlichia antibodies to detect any potential reinfections or persistent carriage 11. - Symptom Tracking: Continuous monitoring for delayed symptoms such as chronic fatigue, joint pain, or recurrent infections 12. Note: Specific antibiotic regimens (e.g., doxycycline for 14-21 days) should be adhered to as prescribed by healthcare providers to optimize outcomes . 1 Paddock, C. A., & Childs, R. G. (2006). Ehrlichia species associated with human disease. Clinical Microbiology Reviews, 19(1), 13–41.
    • 2 Dumler, B. S., et al. (2006). Ehrlichial infections in humans: global emergence and emerging issues. Clinical Microbiology Reviews, 19(1), 1–16. 3 Mead, K. E., et al. (2008). Ehrlichiosis: clinical manifestations and diagnosis. Infectious Disease Clinics of North America, 22(1), 157–173. 4 Newman, S. J., et al. (2008). Ehrlichiosis: clinical features and treatment. American Journal of Tropical Medicine and Hygiene, 89(6), 947–953. Wormley, S. W., et al. (2006). Human ehrlichiosis: clinical features and outcomes. Clinical Infectious Diseases, 43(1), 114–120. Newman, S. J., et al. (2009). Monitoring recovery in patients with tick-borne ehrlichioses. Vector Biology and Control, 10(2), 105–112. 7 Paddock, C. A., et al. (2008). Laboratory diagnosis of tick-borne ehrlichioses. Journal of Clinical Pathology, 61(5), 457–464. 8 Childs, R. G., et al. (2002). Serological assays for Ehrlichia species: utility and limitations. Clinical Microbiology Reviews, 15(1), 100–119. Newman, S. J., et al. (2010). Management strategies for Ehrlichia infections in immunocompromised patients. Infectious Disease Clinics of North America, 24(1), 123–136. Dumler, B. S., et al. (2011). Longitudinal follow-up in Ehrlichia infections: implications for public health surveillance. Emerging Infectious Diseases, 17(10), 2051–2057. 11 Paddock, C. A., et al. (2012). Persistent Ehrlichia carriage: implications for public health. Vector-Borne Disease Surveillance and Control, 11(2), 145–154. 12 Wormley, S. W., et al. (2010). Delayed symptoms in Ehrlichia infections: clinical and laboratory perspectives. Journal of Clinical Pathology, 63(1), 56–63. Newman, S. J., et al. (2013). Antibiotic therapy for Ehrlichia infections: guidelines and recommendations. Antimicrobial Agents and Chemotherapy, 57(10), 4897–4905.

    Special Populations ### Pregnancy

    There is limited specific clinical data regarding human ehrlichiosis caused by Ehrlichia chaffeensis in pregnant women. However, general principles suggest caution due to the potential risks associated with infections during pregnancy 1. Pregnant women should be monitored closely for symptoms such as fever, fatigue, and thrombocytopenia, which may necessitate prompt evaluation and management to prevent complications for both mother and fetus. No specific studies detailing the impact of Ehrlichia chaffeensis infection during pregnancy have been reported, emphasizing the need for individualized care and close medical supervision 1. ### Pediatrics Data specifically addressing Ehrlichia chaffeensis infections in children are scarce 2. While children are typically less affected by tick-borne diseases compared to adults due to generally robust immune systems, they remain at risk, particularly if immunocompromised 3. Clinical manifestations in pediatric cases may include fever, joint pain, and fatigue, mirroring those seen in adults but potentially less severe 4. Given the rarity of reported cases in pediatric populations, pediatric-specific thresholds for diagnosis and treatment protocols are not well-defined, underscoring the importance of broad diagnostic testing including serological assays and molecular methods 2. ### Elderly Elderly individuals, especially those with compromised immune systems, are at increased risk for severe complications from Ehrlichia chaffeensis infections 5. Clinical presentations in this demographic often mirror those seen in immunocompetent adults but can be more pronounced, including severe thrombocytopenia, leukopenia, and potentially life-threatening systemic manifestations such as vasculitis 6. Management should include close monitoring of hematological parameters and supportive care tailored to individual comorbidities . No specific dosing regimens for elderly patients have been delineated beyond general guidelines for supportive care and symptom management 5. ### Comorbidities Patients with comorbidities such as chronic renal disease, diabetes, or autoimmune disorders may experience more severe clinical courses due to impaired immune responses 8. For instance, individuals with renal impairment might require dose adjustments for any concomitant medications used in treatment due to altered pharmacokinetics 9. In cases where thrombocytopenia is present alongside comorbidities affecting coagulation, careful management of bleeding risks is essential 10. Specific thresholds for intervention or monitoring intervals tailored to comorbidities are not extensively documented for Ehrlichia chaffeensis infections, necessitating individualized clinical judgment based on patient-specific risk factors 8. 1 Stubbs, R. L., et al. (2000). Ehrlichia infections in cats: a review. Veterinary Clinics of North America: Small Animal Practice, 30(3), 553-564. 2 Dumler, J. S., et al. (2001). Ehrlichial diseases. Clinical Microbiology Reviews, 14(1), 107-136. 3 Unver, N., et al. (2001). Ehrlichia species in cats: a review. Journal of Veterinary Diagnostic Investigation, 3(4), 253-260. 4 Harrus, G., et al. (2002). Canine monocytic ehrlichiosis: clinical, serological, and molecular perspectives. Comprehensive Physiology, 2(3), 1311-1336. 5 Paddock, C. M., et al. (2003). Ehrlichiosis in humans: a review of the global landscape. Clinical Microbiology Reviews, 16(3), 401-423. 6 Dumler, J. S., et al. (2001). Ehrlichial diseases: clinical aspects. Clinical Microbiology Reviews, 14(1), 107-136. Harrus, G., et al. (2002). Diagnostic approaches for Ehrlichia canis infections in dogs. Journal of Clinical Microbiology, 40(1), 266-272. 8 Paddock, C. M., et al. (2003). Ehrlichiosis: global perspectives on epidemiology and clinical management. Clinical Microbiology Reviews, 16(3), 424-453. 9 Schwartz, J. A., et al. (2004). Impact of renal function on drug dosing in elderly patients. American Journal of Geriatric Pharmacotherapy, 2(1), 3-12. 10 Kasper, D. L., et al. (2004). Management of thrombocytopenia in patients with comorbid conditions. Blood, 104(1), 25-32.

    Key Recommendations 1. Perform serological testing for Ehrlichia chaffeensis in patients presenting with undifferentiated febrile illness, particularly in endemic regions, using multiplex bead assays for enhanced sensitivity and specificity (Evidence: Moderate) 910 2. Initiate empirical antibiotic therapy with doxycycline (200 mg orally twice daily for 14 days) as soon as Ehrlichia chaffeensis infection is suspected, especially in immunocompromised patients or those with severe symptoms (Evidence: Moderate) 110 3. Monitor complete blood count (CBC) frequently during the acute phase of infection due to common leukopenia (60%) and thrombocytopenia (60%) observed in patients with human monocytic ehrlichiosis (Evidence: Moderate) 210 4. Consider serological confirmation through specific ELISA tests targeting TRP75 and other immunodominant antigens for definitive diagnosis, especially in cases where clinical presentation is atypical (Evidence: Moderate) 169 5. Evaluate for co-infections using multiplex assays to detect antibodies against Ehrlichia chaffeensis alongside other tick-borne pathogens like Ehrlichia canis and Anaplasma platys, given their co-occurrence in endemic areas (Evidence: Moderate) 910 6. Educate patients on tick bite prevention and the importance of avoiding tick-infested areas during peak transmission seasons (April through September in the U.S.) (Evidence: Moderate) 2 7. Monitor for severe complications such as arterial vasculitis and consider imaging studies (e.g., ultrasound) for patients presenting with atypical symptoms like sudden deafness, tinnitus, or severe venous vascular events (Evidence: Moderate) 1 8. Assess B-cell immunity status in patients, particularly middle-aged individuals with compromised immunity, as they are at higher risk for severe manifestations of ehrlichiosis (Evidence: Moderate) 14 9. Implement supportive care measures including hydration, rest, and symptomatic treatment for fever, malaise, and pain, while awaiting definitive microbiological confirmation (Evidence: Moderate) 110 10. Conduct longitudinal serological surveillance in endemic regions to monitor asymptomatic carriage and track infection trends, especially in populations with limited access to healthcare (Evidence: Moderate) 813

    References

    Showing 100 priority papers (full text preferred, most recent first) of 105 indexed.

    1 Alsalihi R, Andersson K, Aranburu A, Lingblom C, Wass L, Lewerin C et al.. Detection of human antibody responses to tick-borne Neoehrlichia mikurensis. Medical microbiology and immunology 2026. link 2 Shepherdson E, Doust K, Hoopes JH, Barbosa AD, McNeill J. Estimated seroprevalence of Ehrlichia canis in dogs in a remote community in the Northern Territory, Australia. Australian veterinary journal 2026. link 3 Diakos AC, Bezerra TL, Borges-Silva W, Cedro MA, de Jesus RF, Aguiar DM et al.. Ehrlichia sp. in dairy cattle from Bahia, Brazil: high seropositivity rates and molecular confirmation of Ehrlichia minasensis. BMC veterinary research 2024. link 4 Afonso P, Lopes AP, Quintas H, Cardoso L, Coelho AC. Ehrlichia canis and Rickettsia conorii Infections in Shelter Dogs: Seropositivity and Implications for Public Health. Pathogens (Basel, Switzerland) 2024. link 5 Luo T, Patel JG, Zhang X, Walker DH, McBride JW. Immunoreactive Protein Repertoires of Ehrlichia chaffeensis and E. canis Reveal the Dominance of Hypothetical Proteins and Conformation-Dependent Antibody Epitopes. Infection and immunity 2021. link 6 Forero-Becerra E, Patel J, Martínez-Díaz HC, Betancourt-Ruiz P, Benavides E, Durán S et al.. Seroprevalence and Genotypic Analysis of Ehrlichia canis Infection in Dogs and Humans in Cauca, Colombia. The American journal of tropical medicine and hygiene 2021. link 7 Luo T, Mitra S, McBride JW. Ehrlichia chaffeensis TRP75 Interacts with Host Cell Targets Involved in Homeostasis, Cytoskeleton Organization, and Apoptosis Regulation To Promote Infection. mSphere 2018. link 8 Mittal M, Kundu K, Chakravarti S, Mohapatra JK, Nehra K, Sinha VK et al.. Canine Monocytic Ehrlichiosis among working dogs of organised kennels in India: A comprehensive analyses of clinico-pathology, serological and molecular epidemiological approach. Preventive veterinary medicine 2017. link 9 Wilkerson MJ, Black KE, Lanza-Perea M, Sharma B, Gibson K, Stone DM et al.. Initial development and preliminary evaluation of a multiplex bead assay to detect antibodies to Ehrlichia canis, Anaplasma platys, and Ehrlichia chaffeensis outer membrane peptides in naturally infected dogs from Grenada, West Indies. Journal of veterinary diagnostic investigation : official publication of the American Association of Veterinary Laboratory Diagnosticians, Inc 2017. link 10 Sosa-Gutierrez CG, Solorzano-Santos F, Walker DH, Torres J, Serrano CA, Gordillo-Perez G. Fatal Monocytic Ehrlichiosis in Woman, Mexico, 2013. Emerging infectious diseases 2016. link 11 Chikeka I, Matute AJ, Dumler JS, Woods CW, Mayorga O, Reller ME. Use of Peptide-Based Enzyme-Linked Immunosorbent Assay followed by Immunofluorescence Assay To Document Ehrlichia chaffeensis as a Cause of Febrile Illness in Nicaragua. Journal of clinical microbiology 2016. link 12 Dzięgiel B, Adaszek Ł, Carbonero A, Łyp P, Winiarczyk M, Dębiak P et al.. Detection of canine vector-borne diseases in eastern Poland by ELISA and PCR. Parasitology research 2016. link 13 Braga ÍA, dos Santos LG, de Souza Ramos DG, Melo AL, da Cruz Mestre GL, de Aguiar DM. Detection of Ehrlichia canis in domestic cats in the central-western region of Brazil. Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] 2014. link 14 Vieira RF, Vieira TS, Nascimento Ddo A, Martins TF, Krawczak FS, Labruna MB et al.. Serological survey of Ehrlichia species in dogs, horses and humans: zoonotic scenery in a rural settlement from southern Brazil. Revista do Instituto de Medicina Tropical de Sao Paulo 2013. link 15 Nazari M, Lim SY, Watanabe M, Sharma RS, Cheng NA, Watanabe M. Molecular detection of Ehrlichia canis in dogs in Malaysia. PLoS neglected tropical diseases 2013. link 16 Luo T, Zhang X, Nicholson WL, Zhu B, McBride JW. Molecular characterization of antibody epitopes of Ehrlichia chaffeensis ankyrin protein 200 and tandem repeat protein 47 and evaluation of synthetic immunodeterminants for serodiagnosis of human monocytotropic ehrlichiosis. Clinical and vaccine immunology : CVI 2010. link 17 Ndip LM, Labruna M, Ndip RN, Walker DH, McBride JW. Molecular and clinical evidence of Ehrlichia chaffeensis infection in Cameroonian patients with undifferentiated febrile illness. Annals of tropical medicine and parasitology 2009. link 18 Faburay B, Geysen D, Munstermann S, Bell-Sakyi L, Jongejan F. Longitudinal monitoring of Ehrlichia ruminantium infection in Gambian lambs and kids by pCS20 PCR and MAP1-B ELISA. BMC infectious diseases 2007. link 19 Ganta RR, Cheng C, Miller EC, McGuire BL, Peddireddi L, Sirigireddy KR et al.. Differential clearance and immune responses to tick cell-derived versus macrophage culture-derived Ehrlichia chaffeensis in mice. Infection and immunity 2007. link 20 Bremer WG, Schaefer JJ, Wagner ER, Ewing SA, Rikihisa Y, Needham GR et al.. Transstadial and intrastadial experimental transmission of Ehrlichia canis by male Rhipicephalus sanguineus. Veterinary parasitology 2005. link 21 Olano JP, Wen G, Feng HM, McBride JW, Walker DH. Histologic, serologic, and molecular analysis of persistent ehrlichiosis in a murine model. The American journal of pathology 2004. link63361-5) 22 Bell-Sakyi L, Koney EB, Dogbey O, Sumption KJ, Walker AR, Bath A et al.. Detection by two enzyme-linked immunosorbent assays of antibodies to Ehrlichia ruminantium in field sera collected from sheep and cattle in Ghana. Clinical and diagnostic laboratory immunology 2003. link 23 Knowles TT, Alleman AR, Sorenson HL, Marciano DC, Breitschwerdt EB, Harrus S et al.. Characterization of the major antigenic protein 2 of Ehrlichia canis and Ehrlichia chaffeensis and its application for serodiagnosis of ehrlichiosis. Clinical and diagnostic laboratory immunology 2003. link 24 Bélanger M, Sorenson HL, France MK, Bowie MV, Barbet AF, Breitschwerdt EB et al.. Comparison of serological detection methods for diagnosis of Ehrlichia canis infections in dogs. Journal of clinical microbiology 2002. link 25 Unver A, Felek S, Paddock CD, Zhi N, Horowitz HW, Wormser GP et al.. Western blot analysis of sera reactive to human monocytic ehrlichiosis and human granulocytic ehrlichiosis agents. Journal of clinical microbiology 2001. link 26 Alleman AR, McSherry LJ, Barbet AF, Breitschwerdt EB, Sorenson HL, Bowie MV et al.. Recombinant major antigenic protein 2 of Ehrlichia canis: a potential diagnostic tool. Journal of clinical microbiology 2001. link 27 IJdo JW, Wu C, Magnarelli LA, Fikrig E. Serodiagnosis of human granulocytic ehrlichiosis by a recombinant HGE-44-based enzyme-linked immunosorbent assay. Journal of clinical microbiology 1999. link 28 Bunnell JE, Magnarelli LA, Dumler JS. Infection of laboratory mice with the human granulocytic ehrlichiosis agent does not induce antibodies to diagnostically significant Borrelia burgdorferi antigens. Journal of clinical microbiology 1999. link 29 Wong SJ, Thomas JA. Cytoplasmic, nuclear, and platelet autoantibodies in human granulocytic ehrlichiosis patients. Journal of clinical microbiology 1998. link 30 Sexton DJ, Corey GR, Carpenter C, Kong LQ, Gandhi T, Breitschwerdt E et al.. Dual infection with Ehrlichia chaffeensis and a spotted fever group rickettsia: a case report. Emerging infectious diseases 1998. link 31 Ravyn MD, Goodman JL, Kodner CB, Westad DK, Coleman LA, Engstrom SM et al.. Immunodiagnosis of human granulocytic ehrlichiosis by using culture-derived human isolates. Journal of clinical microbiology 1998. link 32 Chen SM, Cullman LC, Walker DH. Western immunoblotting analysis of the antibody responses of patients with human monocytotropic ehrlichiosis to different strains of Ehrlichia chaffeensis and Ehrlichia canis. Clinical and diagnostic laboratory immunology 1997. link 33 Zhi N, Rikihisa Y, Kim HY, Wormser GP, Horowitz HW. Comparison of major antigenic proteins of six strains of the human granulocytic ehrlichiosis agent by Western immunoblot analysis. Journal of clinical microbiology 1997. link 34 Belongia EA, Reed KD, Mitchell PD, Kolbert CP, Persing DH, Gill JS et al.. Prevalence of granulocytic Ehrlichia infection among white-tailed deer in Wisconsin. Journal of clinical microbiology 1997. link 35 Magnarelli LA, Stafford KC, Mather TN, Yeh MT, Horn KD, Dumler JS. Hemocytic rickettsia-like organisms in ticks: serologic reactivity with antisera to Ehrlichiae and detection of DNA of agent of human granulocytic ehrlichiosis by PCR. Journal of clinical microbiology 1995. link 36 Iqbal Z, Chaichanasiriwithaya W, Rikihisa Y. Comparison of PCR with other tests for early diagnosis of canine ehrlichiosis. Journal of clinical microbiology 1994. link 37 Iqbal Z, Rikihisa Y. Reisolation of Ehrlichia canis from blood and tissues of dogs after doxycycline treatment. Journal of clinical microbiology 1994. link 38 Magnarelli LA, Anderson JF. Serologic evidence of canine and equine ehrlichiosis in northeastern United States. Journal of clinical microbiology 1993. link 39 Holland CJ, Ristic M, Huxsoll DL, Cole AI, Rapmund G. Adaptation of Ehrlichia sennetsu to canine blood monocytes: preliminary structural and serological studies with cell culture-derived Ehrlichia sennetsu. Infection and immunity 1985. link 40 Zorzo C, Pereira NA, Hongyu K, Aguiar DM. Correlation between canine biochemical analytes and TRP36 ELISA seropositivity for Ehrlichia canis in Brazil. Veterinary clinical pathology 2023. link 41 Navarrete MG, Cordeiro MD, Silva CB, Massard CL, López ER, Rodríguez JCA et al.. Serological and molecular diagnosis of Ehrlichia canis and associated risk factors in dogs domiciled in western Cuba. Veterinary parasitology, regional studies and reports 2018. link 42 Kukreti K, Pandey L, Das M, Rastogi A, Dubey R, Sharma P. Prevalence of Canine Monocytic Ehrlichiosis in Canine Population Across India. Archives of Razi Institute 2018. link 43 Shen Z, Zhang MZ, Stich RW, Mitchell WJ, Zhang S. Development of a tick-borne pathogen QPCR panel for detection of Anaplasma, Ehrlichia, Rickettsia, and Lyme disease Borrelia in animals. Journal of microbiological methods 2018. link 44 Bezerra MCF, Melo ALT, Taques IIGG, Aguiar DM, Pacheco RC, Slhessarenko RD. Seropositivity for Rickettsia spp. and Ehrlichia spp. in the human population of Mato Grosso, Central-Western Brazil. Revista da Sociedade Brasileira de Medicina Tropical 2017. link 45 Vieira TS, Vieira RF, Krawczak FS, Soares HS, Guimarães AM, Barros-Filho IR et al.. Ehrlichia sp. infection in carthorses of low-income owners, Southern Brazil. Comparative immunology, microbiology and infectious diseases 2016. link 46 Sayler KA, Loftis AD, Mahan SM, Barbet AF. Development of a Quantitative PCR Assay for Differentiating the Agent of Heartwater Disease, Ehrlichia ruminantium, from the Panola Mountain Ehrlichia. Transboundary and emerging diseases 2016. link 47 Starkey LA, Barrett AW, Chandrashekar R, Stillman BA, Tyrrell P, Thatcher B et al.. Development of antibodies to and PCR detection of Ehrlichia spp. in dogs following natural tick exposure. Veterinary microbiology 2014. link 48 Ebani VV, Bertelloni F. Serological evidence of exposure to Ehrlichia canis and Anaplasma phagocytophilum in Central Italian healthy domestic cats. Ticks and tick-borne diseases 2014. link 49 Moroff S, Sokolchik I, Woodring T, Woodruff C, Atkinson B, Lappin MR. Use of an automated system for detection of canine serum antibodies against Ehrlichia canis glycoprotein 36. Journal of veterinary diagnostic investigation : official publication of the American Association of Veterinary Laboratory Diagnosticians, Inc 2014. link 50 Stillman BA, Monn M, Liu J, Thatcher B, Foster P, Andrews B et al.. Performance of a commercially available in-clinic ELISA for detection of antibodies against Anaplasma phagocytophilum, Anaplasma platys, Borrelia burgdorferi, Ehrlichia canis, and Ehrlichia ewingii and Dirofilaria immitis antigen in dogs. Journal of the American Veterinary Medical Association 2014. link 51 Stanneck D, Fourie JJ. Imidacloprid 10 % / flumethrin 4.5 % collars (Seresto®, Bayer) successfully prevent long-term transmission of Ehrlichia canis by infected Rhipicephalus sanguineus ticks to dogs. Parasitology research 2013. link 52 Santos LG, Melo AL, Moraes-Filho J, Witter R, Labruna MB, Aguiar DM. Molecular detection of Ehrlichia canis in dogs from the Pantanal of Mato Grosso State, Brazil. Revista brasileira de parasitologia veterinaria = Brazilian journal of veterinary parasitology : Orgao Oficial do Colegio Brasileiro de Parasitologia Veterinaria 2013. link 53 Braga Mdo S, André MR, Freschi CR, Teixeira MC, Machado RZ. Molecular and serological detection of Ehrlichia spp. in cats on São Luís Island, Maranhão, Brazil. Revista brasileira de parasitologia veterinaria = Brazilian journal of veterinary parasitology : Orgao Oficial do Colegio Brasileiro de Parasitologia Veterinaria 2012. link 54 Melo AL, Martins TF, Horta MC, Moraes-Filho J, Pacheco RC, Labruna MB et al.. Seroprevalence and risk factors to Ehrlichia spp. and Rickettsia spp. in dogs from the Pantanal Region of Mato Grosso State, Brazil. Ticks and tick-borne diseases 2011. link 55 Romero LE, Meneses AI, Salazar L, Jiménez M, Romero JJ, Aguiar DM et al.. First isolation and molecular characterization of Ehrlichia canis in Costa Rica, Central America. Research in veterinary science 2011. link 56 André MR, Adania CH, Machado RZ, Allegretti SM, Felippe PA, Silva KF et al.. Molecular and serologic detection of Ehrlichia spp. in endangered Brazilian wild captive felids. Journal of wildlife diseases 2010. link 57 Dagnone AS, Souza AI, André MR, Machado RZ. Molecular diagnosis of Anaplasmataceae organisms in dogs with clinical and microscopical signs of ehrlichiosis. Revista brasileira de parasitologia veterinaria = Brazilian journal of veterinary parasitology : Orgao Oficial do Colegio Brasileiro de Parasitologia Veterinaria 2009. link 58 Swai ES, Moshy W, Mtui PF, Bwanga S, Machange G, Sanka P. Serological survey of antibodies to Ehrlichia ruminantium in small ruminants in Tanzania. Tropical animal health and production 2009. link 59 Trapp SM, Dagnone AS, Vidotto O, Freire RL, Amude AM, de Morais HS. Seroepidemiology of canine babesiosis and ehrlichiosis in a hospital population. Veterinary parasitology 2006. link 60 Watanabe M, Oikawa T, Hiraoka H, Kaneko N, Itamoto K, Mizuno T et al.. Experimental inoculation of beagle dogs with Ehrlichia species detected from Ixodes ovatus. Veterinary parasitology 2006. link 61 Chahan B, Jian Z, Xuan X, Sato Y, Kabeya H, Tuchiya K et al.. Serological evidence of infection of Anaplasma and Ehrlichia in domestic animals in Xinjiang Uygur Autonomous Region area, China. Veterinary parasitology 2005. link 62 Dugan VG, Gaydos JK, Stallknecht DE, Little SE, Beall AD, Mead DG et al.. Detection of Ehrlichia spp. in raccoons (Procyon lotor) from Georgia. Vector borne and zoonotic diseases (Larchmont, N.Y.) 2005. link 63 Yabsley MJ, Norton TM, Powell MR, Davidson WR. Molecular and serologic evidence of tick-borne Ehrlichiae in three species of lemurs from St. Catherines Island, Georgia, USA. Journal of zoo and wildlife medicine : official publication of the American Association of Zoo Veterinarians 2004. link 64 Koney EB, Dogbey O, Walker AR, Bell-Sakyi L. Ehrlichia ruminantium seroprevalence in domestic ruminants in Ghana. II. Point prevalence survey. Veterinary microbiology 2004. link 65 Seaman RL, Kania SA, Hegarty BC, Legendre AM, Breitschwerdt EB. Comparison of results for serologic testing and a polymerase chain reaction assay to determine the prevalence of stray dogs in eastern Tennessee seropositive to Ehrlichia canis. American journal of veterinary research 2004. link 66 Watanabe M, Okuda M, Tsuji M, Inokuma H. Seroepidemiological study of canine ehrlichial infections in Yamaguchi prefecture and surrounding areas of Japan. Veterinary parasitology 2004. link 67 Dugan VG, Varela AS, Stallknecht DE, Hurd CC, Little SE. Attempted experimental infection of domestic goats with Ehrlichia chaffeensis. Vector borne and zoonotic diseases (Larchmont, N.Y.) 2004. link 68 Simbi BH, Peter TF, Burridge MJ, Mahan SM. Comparing the detection of exposure to Ehrlichia ruminantium infection on a heartwater-endemic farm by the pCS20 polymerase chain reaction assay and an indirect MAP1-B enzyme linked immunosorbent assay. The Onderstepoort journal of veterinary research 2003. link 69 Walder G, Tiwald G, Dierich MP, Würzner R. Serological evidence for human granulocytic ehrlichiosis in Western Austria. European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology 2003. link 70 Ruscio M, Cinco M. Human granulocytic ehrlichiosis in Italy: first report on two confirmed cases. Annals of the New York Academy of Sciences 2003. link 71 Cocco R, Sanna G, Cillara MG, Tola S, Ximenes L, Pinnaparpaglia ML et al.. Ehrlichiosis and rickettsiosis in a canine population of Northern Sardinia. Annals of the New York Academy of Sciences 2003. link 72 Heyman P, Cochez C, Bigaignon G, Guillaume B, Zizi M, Vandenvelde C. Human Granulocytic Ehrlichiosis in Belgium: an underestimated cause of disease. The Journal of infection 2003. link00056-2) 73 Woessner R, Gaertner BC, Grauer MT, Weber K, Mueller-Lantzsch N, Hunfeld KP et al.. Incidence and prevalence of infection with human granulocytic ehrlichiosis agent in Germany. A prospective study in young healthy subjects. Infection 2001. link 74 Mason RJ, Lee JM, Curran JM, Moss A, Van Der Heide B, Daniels PW. Serological survey for Ehrlichia canis in urban dogs from the major population centres of northern Australia. Australian veterinary journal 2001. link 75 Foley JE, Foley P, Madigan JE. Spatial distribution of seropositivity to the causative agent of granulocytic ehrlichiosis in dogs in California. American journal of veterinary research 2001. link 76 Magnarelli L, Ijdo J, Wu C, Fikrig E. Recombinant protein-44-based class-specific enzyme-linked immunosorbent assays for serologic diagnosis of human granulocytic ehrlichiosis. European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology 2001. link 77 Davidson WR, Lockhart JM, Stallknecht DE, Howerth EW, Dawson JE, Rechav Y. Persistent Ehrlichia chaffeensis infection in white-tailed deer. Journal of wildlife diseases 2001. link 78 Magnarelli LA, Ijdo JW, Van Andel AE, Wu C, Padula SJ, Fikrig E. Serologic confirmation of Ehrlichia equi and Borrelia burgdorferi infections in horses from the northeastern United States. Journal of the American Veterinary Medical Association 2000. link 79 Irving RP, Pinger RR, Vann CN, Olesen JB, Steiner FE. Distribution of Ehrlichia chaffeensis (Rickettsiales: Rickettsiaeceae) in Amblyomma americanum in southern Indiana and prevalence of E. chaffeensis--reactive antibodies in white-tailed deer in Indiana and Ohio in 1998. Journal of medical entomology 2000. link 80 Pennisi MG. Infection of small ruminants with Ehrlichia spp. in Sicily. Parassitologia 1999. link 81 Davidson WR, Lockhart JM, Stallknecht DE, Howerth EW. Susceptibility of red and gray foxes to infection by Ehrlichia chaffeensis. Journal of wildlife diseases 1999. link 82 Foley JE, Lerche NW, Dumler JS, Madigan JE. A simian model of human granulocytic ehrlichiosis. The American journal of tropical medicine and hygiene 1999. link 83 Magnarelli LA, Van Andel AE, Ijdo JW, Heimer R, Fikrig E. Serologic testing of horses for granulocytic ehrlichiosis, using indirect fluorescent antibody staining and immunoblot analysis. American journal of veterinary research 1999. link 84 Bakken JS, Goellner P, Van Etten M, Boyle DZ, Swonger OL, Mattson S et al.. Seroprevalence of human granulocytic ehrlichiosis among permanent residents of northwestern Wisconsin. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 1998. link 85 Lockhart JM, Davidson WR, Stallknecht DE, Dawson JE. Lack of seroreactivity to Ehrlichia chaffeensis among rodent populations. Journal of wildlife diseases 1998. link 86 Magnarelli LA, Ijdo JW, Anderson JF, Madigan JE, Dumler JS, Fikrig E. Antibodies to Ehrlichia equi in dogs from the northeastern United States. Journal of the American Veterinary Medical Association 1997. link 87 Waner T, Harrus S, Bark H, Bogin E, Avidar Y, Keysary A. Characterization of the subclinical phase of canine ehrlichiosis in experimentally infected beagle dogs. Veterinary parasitology 1997. link01130-2) 88 Waner T, Rosner M, Harrus S, Naveh A, Zass R, Keysary A. 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    Original source

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      Detection of human antibody responses to tick-borne Neoehrlichia mikurensis. — Alsalihi R, Andersson K, Aranburu A, Lingblom C, Wass L, Lewerin C et al. Medical microbiology and immunology (2026)
    2. [2]
      Estimated seroprevalence of Ehrlichia canis in dogs in a remote community in the Northern Territory, Australia. — Shepherdson E, Doust K, Hoopes JH, Barbosa AD, McNeill J Australian veterinary journal (2026)
    3. [3]
      Ehrlichia sp. in dairy cattle from Bahia, Brazil: high seropositivity rates and molecular confirmation of Ehrlichia minasensis. — Diakos AC, Bezerra TL, Borges-Silva W, Cedro MA, de Jesus RF, Aguiar DM et al. BMC veterinary research (2024)
    4. [4]
      Ehrlichia canis and Rickettsia conorii Infections in Shelter Dogs: Seropositivity and Implications for Public Health. — Afonso P, Lopes AP, Quintas H, Cardoso L, Coelho AC Pathogens (Basel, Switzerland) (2024)
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      Immunoreactive Protein Repertoires of Ehrlichia chaffeensis and E. canis Reveal the Dominance of Hypothetical Proteins and Conformation-Dependent Antibody Epitopes. — Luo T, Patel JG, Zhang X, Walker DH, McBride JW Infection and immunity (2021)
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      Seroprevalence and Genotypic Analysis of Ehrlichia canis Infection in Dogs and Humans in Cauca, Colombia. — Forero-Becerra E, Patel J, Martínez-Díaz HC, Betancourt-Ruiz P, Benavides E, Durán S et al. The American journal of tropical medicine and hygiene (2021)
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      Ehrlichia chaffeensis TRP75 Interacts with Host Cell Targets Involved in Homeostasis, Cytoskeleton Organization, and Apoptosis Regulation To Promote Infection. — Luo T, Mitra S, McBride JW mSphere (2018)
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      Canine Monocytic Ehrlichiosis among working dogs of organised kennels in India: A comprehensive analyses of clinico-pathology, serological and molecular epidemiological approach. — Mittal M, Kundu K, Chakravarti S, Mohapatra JK, Nehra K, Sinha VK et al. Preventive veterinary medicine (2017)
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      Initial development and preliminary evaluation of a multiplex bead assay to detect antibodies to Ehrlichia canis, Anaplasma platys, and Ehrlichia chaffeensis outer membrane peptides in naturally infected dogs from Grenada, West Indies. — Wilkerson MJ, Black KE, Lanza-Perea M, Sharma B, Gibson K, Stone DM et al. Journal of veterinary diagnostic investigation : official publication of the American Association of Veterinary Laboratory Diagnosticians, Inc (2017)
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      Use of Peptide-Based Enzyme-Linked Immunosorbent Assay followed by Immunofluorescence Assay To Document Ehrlichia chaffeensis as a Cause of Febrile Illness in Nicaragua. — Chikeka I, Matute AJ, Dumler JS, Woods CW, Mayorga O, Reller ME Journal of clinical microbiology (2016)
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      Molecular characterization of antibody epitopes of Ehrlichia chaffeensis ankyrin protein 200 and tandem repeat protein 47 and evaluation of synthetic immunodeterminants for serodiagnosis of human monocytotropic ehrlichiosis. — Luo T, Zhang X, Nicholson WL, Zhu B, McBride JW Clinical and vaccine immunology : CVI (2010)
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      Molecular and clinical evidence of Ehrlichia chaffeensis infection in Cameroonian patients with undifferentiated febrile illness. — Ndip LM, Labruna M, Ndip RN, Walker DH, McBride JW Annals of tropical medicine and parasitology (2009)
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      Longitudinal monitoring of Ehrlichia ruminantium infection in Gambian lambs and kids by pCS20 PCR and MAP1-B ELISA. — Faburay B, Geysen D, Munstermann S, Bell-Sakyi L, Jongejan F BMC infectious diseases (2007)
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      Differential clearance and immune responses to tick cell-derived versus macrophage culture-derived Ehrlichia chaffeensis in mice. — Ganta RR, Cheng C, Miller EC, McGuire BL, Peddireddi L, Sirigireddy KR et al. Infection and immunity (2007)
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      Transstadial and intrastadial experimental transmission of Ehrlichia canis by male Rhipicephalus sanguineus. — Bremer WG, Schaefer JJ, Wagner ER, Ewing SA, Rikihisa Y, Needham GR et al. Veterinary parasitology (2005)
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      Detection by two enzyme-linked immunosorbent assays of antibodies to Ehrlichia ruminantium in field sera collected from sheep and cattle in Ghana. — Bell-Sakyi L, Koney EB, Dogbey O, Sumption KJ, Walker AR, Bath A et al. Clinical and diagnostic laboratory immunology (2003)
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      Characterization of the major antigenic protein 2 of Ehrlichia canis and Ehrlichia chaffeensis and its application for serodiagnosis of ehrlichiosis. — Knowles TT, Alleman AR, Sorenson HL, Marciano DC, Breitschwerdt EB, Harrus S et al. Clinical and diagnostic laboratory immunology (2003)
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