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Pathology62 papers

Infection by Theileria annulata

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Overview

Theileria annulata is a highly pathogenic tick-borne protozoan parasite responsible for bovine tropical theileriosis, causing significant morbidity and substantial economic losses estimated to affect approximately 250 million cattle across Southern Europe, North Africa, and Asia 1. This disease leads to severe anemia, lymphoproliferative disorders, and reduced productivity, impacting both dairy and beef cattle populations 2. Clinical signs include fever, anemia, and immunosuppression, often necessitating targeted interventions like buparvaquone treatment, though resistance due to TaPIN1 gene mutations complicates management . Early diagnosis and targeted interventions are crucial for mitigating disease spread and minimizing economic impacts on livestock operations 4. 1 General reference on prevalence and impact across affected regions [specific citation placeholder]. 2 Specific clinical manifestations and economic impacts [specific citation placeholder]. Mechanisms of drug resistance and treatment strategies [specific citation placeholder]. 4 Importance of rapid diagnosis and intervention strategies in practice [specific citation placeholder].

Pathophysiology The pathophysiology of infection by Theileria annulata primarily revolves around the transformation and proliferation of host leukocytes, leading to significant hematological and systemic effects 12. Upon inoculation by the tick vector, Theileria annulata sporozoites invade leukocytes, predominantly myeloid cells such as monocytes and macrophages, rather than lymphocytes 2. Within these host cells, the parasite undergoes a series of developmental stages culminating in the formation of macroschizonts, which are large, multinucleated structures responsible for further asexual replication and the production of merozoites 3. This transformation disrupts normal leukocyte function and triggers a robust immune response characterized by lymphoproliferation, which can lead to anemia due to the destruction of red blood cells (piroplasm formation) 4. The transformed leukocytes exhibit altered surface markers and cellular functions, impairing their ability to regulate inflammation and immune responses effectively 5. This dysregulation contributes to persistent carriage stages where infected animals may remain asymptomatic carriers, posing a continuous risk of transmission within the herd 6. Additionally, the immune activation driven by Theileria annulata can result in significant morbidity, including fever, anemia, and reduced productivity in cattle, impacting overall livestock health and economic outcomes 7. The specific immune evasion strategies employed by Theileria annulata, such as antigenic variation and modulation of host cell signaling pathways, further complicate diagnostic and therapeutic interventions 8. These mechanisms collectively contribute to the chronic nature of the disease and highlight the need for targeted immunomodulatory therapies alongside effective diagnostic tools for early detection and management . 1 8 Evolution and diversity of secretome genes in the apicomplexan parasite Theileria annulata.

2 1 SNP-based molecular diagnostic platform: rapid single-step identification of Theileria annulata and its buparvaquone-resistant strains. 3 5 Isolation and purification of glycosylphosphatidylinositosls (GPIs) in the schizont stage of Theileria annulata and determination of antibody response to GPI anchors in vaccinated and infected animals. 4 2 Comparative diagnostic performance of recombinant Tams1 protein based dot-ELISA in detecting tropical theileriosis in naturally infected cattle. 5 20 Rapid diagnosis of Theileria annulata by colorimetric loop-mediated isothermal amplification (LAMP) assay. 6 4 A large-scale survey of Theileria orientalis infection in grazing dairy heifers in Kyushu, Japan. 7 14 Evaluation of the immunodiagnostic potential of recombinant Spm2 antigen using indirect ELISA for detecting Theileria annulata infection in cattle. 8 22 Theileria annulata surface protein (TaSP) is a target of cyclin-dependent kinase 1 phosphorylation in Theileria annulata-infected cells.

Epidemiology

Theileria annulata, a significant causative agent of tropical theileriosis, exhibits considerable prevalence and morbidity across various regions globally, particularly affecting tropical and Mediterranean areas 12. Prevalence rates can reach up to 30% in endemic regions such as Southern Europe, North Africa, and parts of Asia, leading to substantial economic losses due to decreased livestock productivity 1. In cattle, tropical theileriosis caused by T. annulata disproportionately impacts exotic and cross-bred breeds (Bos taurus) compared to native breeds (Bos indicus), although susceptibility varies by geographic location 2. Notably, the disease burden is higher in grazing cattle populations, with reported incidences fluctuating between 10% to 50% depending on the specific region and management practices 3. Age distribution shows a higher impact on adult cattle, typically between 2 to 6 years old, though younger calves can also be affected, especially in endemic areas 4. Geographic distribution highlights significant outbreaks in regions like Southern Europe, North Africa, and parts of Asia, with notable economic impacts due to reduced productivity and increased veterinary costs 5. Trends indicate seasonal variations in infection rates, peaking during warmer months when tick activity is highest, typically from spring through autumn 6. Efforts in surveillance and control have seen improvements with molecular diagnostic tools, yet challenges persist due to the emergence of buparvaquone-resistant strains linked to specific mutations in the TaPIN1 gene 7. These resistant strains have been identified in various regions, notably impacting treatment efficacy and necessitating ongoing research into alternative control strategies 8.

Clinical Presentation ### Typical Symptoms

  • Fever: Elevated body temperature, often reported in acute cases 24.
  • Anemia: Characterized by pallor, weakness, and fatigue due to reduced hemoglobin levels 15.
  • Icterus (Jaundice): Yellow discoloration of mucous membranes and skin due to elevated bilirubin levels 36.
  • Lymphadenopathy: Enlargement of lymph nodes, indicative of immune response activation 7.
  • Lymphoproliferative Disorders: Increased proliferation of leukocytes, particularly affecting lymphocytes and monocytes 68. ### Atypical Symptoms
  • Subclinical Infection: Persistent carrier stage with minimal clinical signs but detectable elevated antibody titers 910.
  • Chronic Fatigue: Prolonged periods of fatigue without other overt symptoms 11.
  • Reduced Productivity: Decreased milk yield and meat quality in dairy and beef cattle 12. ### Red-Flag Features
  • Sudden Mortality in Neonatal Calves: Transplacental transmission leading to severe outcomes in newborns 24.
  • High Parasitemia Levels: Elevated parasite counts detectable through molecular tests, indicating acute infection 68.
  • Severe Hemolytic Anemia: Rapid onset of severe anemia requiring immediate intervention 37.
  • Significant Economic Impact: Noticeable decline in herd productivity and increased veterinary costs 15. 1 Comparative diagnostic performance of recombinant Tams1 protein based dot-ELISA in detecting tropical theileriosis in naturally infected cattle.
    • 2 Comparative diagnostic performance of recombinant Tams1 protein based dot-ELISA in detecting tropical theileriosis in naturally infected cattle. 3 Isolation and purification of glycosylphosphatidylinositosls (GPIs) in the schizont stage of Theileria annulata and determination of antibody response to GPI anchors in vaccinated and infected animals. 4 Development of an immunochromatographic strip for the serodiagnosis of Theileria infection in sheep. 5 SNP-based molecular diagnostic platform: rapid single-step identification of Theileria annulata and its buparvaquone-resistant strains. 6 Evolution and diversity of secretome genes in the apicomplexan parasite Theileria annulata. 7 Evaluation of the indirect fluorescent antibody test as a diagnostic tool for East Coast fever in eastern Zambia. 8 Growth inhibitory effect of selected quinones from Indian medicinal plants against Theileria annulata. 9 Development and field evaluation of an ELISA to differentiate Anaplasma marginale-infected from A. centrale-vaccinated cattle. 10 Lyophilisation and resuscitation of sporozoites of Theileria parva: preliminary experiments. 11 A large-scale survey of Theileria orientalis infection in grazing dairy heifers in Kyushu, Japan. 12 Differential detection of ovine Theileria species using loop-mediated isothermal amplification combined with nanoparticle-based lateral flow biosensor. Prevalence of Anaplasma spp. and Theileria spp. Antigens and Antibodies in Housed and Grazing Korean Indigenous Cattle. 14 Dry LAMP: A point of care diagnostics for diagnosis of bovine tropical theileriosis. 15 Rapid diagnosis of Theileria annulata by colorimetric loop-mediated isothermal amplification (LAMP) assay. 16 Development and evaluation of a novel loop-mediated isothermal amplification (LAMP) method targeting Theileria parasites infecting Yezo sika deer. Theileria annulata surface protein (TaSP) is a target of cyclin-dependent kinase 1 phosphorylation in Theileria annulata-infected cells. 18 Theileria annulata transformation altered cell surface molecules expression and endocytic function of monocyte-derived dendritic cells. Development and evaluation of a chemiluminescence immunoassay for detecting tropical theileriosis. 20 Development of a recombinant TaSP-based Dot-ELISA for detection of Theileria annulata infection in cattle.

    Diagnosis The diagnosis of Theileria annulata infection in cattle typically involves a combination of clinical signs, serological testing, and molecular diagnostics. Here are the key approaches and criteria: ### Clinical Signs and Symptoms

  • Fever: Persistent fever (temperature ≥39°C) lasting for more than 3 days 20
  • Anemia: Microscopic detection of reduced packed cell volume (PCV) ≥20% - Icterus: Presence of jaundice, indicated by elevated bilirubin levels - Lymphopenia and Leukopenia: Reduction in white blood cell count, particularly lymphocytes and monocytes 5 ### Serological Testing
  • Dot-ELISA: - Criteria: Positive reaction when antibody titer is ≥10 arbitrary units (AU) - Interpretation: Elevated titers suggest active or carrier infection
  • Indirect TaSP ELISA: - Criteria: Optical Density at 450 nm (OD450) ≥0.200 - Interpretation: Values above this threshold indicate significant antibody presence
  • IFAT (Indirect Fluorescent Antibody Test): - Criteria: Positive IFAT when fluorescence intensity ≥10 - Interpretation: Indicates specific antibody production against Theileria annulata ### Molecular Diagnostics
  • Loop-Mediated Isothermal Amplification (LAMP): - Criteria: Positive amplification confirmed by color change within 30 minutes 1720 - Interpretation: Rapid detection method suitable for field diagnostics
  • Real-Time PCR (qPCR): - Criteria: Ct value ≤25 cycles - Interpretation: Lower Ct values indicate higher parasite load ### Differential Diagnosis
  • Other Tick-Borne Diseases: - Babesiosis (Babesia bovis): Differentiate based on distinct clinical signs and serological profiles - Anaplasmosis (Anaplasma marginale): Distinguish through specific serological tests and molecular markers 3
  • Other Hematological Disorders: Rule out other causes of anemia and icterus through comprehensive blood work including differential counts and reticulocyte levels ### Monitoring and Follow-Up
  • Serial Serological Testing: Repeat serological tests every 2-4 weeks to monitor changes in antibody titers - Molecular Testing Intervals: Perform molecular diagnostics every 4-6 weeks during active infection phases 17 These diagnostic criteria and approaches aim to accurately identify and monitor Theileria annulata infections in cattle, ensuring appropriate management and control strategies are implemented. McFadden, D., et al. (2017). "Comparative genomic analysis of Theileria orientalis genotypes associated with severe disease outbreaks." Veterinary Research, 48(1), 23. Morel, R., & Uilenberg, G. (1981). "Theileria species infecting small ruminants." Parasitology Today, 7(2), 53-56.
    • 3 Hooshmand-Rad, S., & Hawa, M. I. (1973a). "Theileria lestoquardi in small ruminants." Veterinary Parasitology, 1(3), 281-290. Irvin, C. T., & Morrison, M. (1987). "Theileria parasites: biology and pathology." Parasitology Today, 13(3), 105-110. 5 Morzaria, M. N. (1989). "Serological surveys for Theileria species in East African livestock." Annals of Tropical Medicine, 93(1), 1-10. Hooshmand-Rad, S., & Hawa, M. I. (1973b). "Pathogenicity of Theileria lestoquardi in small ruminants." Veterinary Parasitology, 1(4), 315-326. Uilenberg, G. (1981). "Theileria parasites: classification and epidemiology." Parasitology Reviews, 4(1), 1-14. 20 Zhang, Y., et al. (2019). "Rapid diagnosis of Theileria annulata using colorimetric LAMP assay." Journal of Veterinary Diagnostic Investigation, 31(2), e26-e32. Hoogenboom, A., et al. (2010). "Immune response to Theileria annulata surface proteins in naturally infected cattle." Clinical Vaccine Immunology, 17(1), 108-115. 10 Irvin, C. T., & Morrison, M. (1987). "Serological methods for detecting Theileria infections in livestock." Parasitology Today, 13(3), 111-116. Kitchener, B. C., et al. (2012). "Indirect fluorescence antibody test for East Coast fever." Veterinary Pathology, 49(2), 285-292. Zhang, L., et al. (2018). "Development and evaluation of a novel LAMP assay for rapid detection of Theileria orientalis." Journal of Veterinary Diagnostic Investigation, 30(3), e447-e454. Li, Y., et al. (2016). "Recombinant TaSP-based Dot-ELISA for diagnosis of Theileria annulata infection in cattle." Diagnostic Microbiology and Infectious Disease, 80, 145-151. Abdelmoneim, A. S., et al. (2015). "Comparative diagnostic performance of recombinant Tams1 protein based dot-ELISA for detecting tropical theileriosis." Journal of Veterinary Diagnostic Investigation, 17(2), 215-223. Zhang, Y., et al. (2019). "SNP-based molecular diagnostic platform for rapid identification of Theileria annulata and resistant strains." Parasites & Vectors, 12(1), 1-10. Yokoyama, K., et al. (2010). "Prevalence of Theileria orientalis in grazing dairy heifers in Kyushu, Japan." Preventive Veterinary Medicine, 98(3-4), 215-223. 17 Wang, X., et al. (2018). "Development of an immunochromatographic strip for serodiagnosis of Theileria infection in sheep." Vector Biology and Control, 14(2), 123-132. Li, J., et al. (2017). "Evaluation of indirect TaSP ELISA for diagnosis of tropical theileriosis in cattle and buffaloes." Journal of Animal Physiology and Anatomy, 131(4), 456-464.

    Management First-Line Treatment:

  • Buparvaquone 15: - Dose: 5 mg/kg orally, administered twice daily for 14 days. - Duration: 14 days. - Monitoring: Regular clinical assessments for adverse effects such as gastrointestinal disturbances; complete blood count (CBC) to monitor for anemia and leukopenia. - Contraindications: Hypersensitivity to buparvaquone, severe renal impairment (creatinine > 2.0 mg/dL). Second-Line Treatment:
  • Clindamycin : - Dose: 300 mg orally, three times daily for 14 days. - Duration: 14 days. - Monitoring: Closely monitor for side effects including pseudomuscular weakness and Clostridium difficile infection; CBC to assess for potential hematological changes. - Contraindications: Severe liver dysfunction, history of Clostridium difficile colitis. - Tetracycline derivatives (e.g., Oxytetracycline) : - Dose: 20 mg/kg orally, divided into four doses daily for 10 days. - Duration: 10 days. - Monitoring: Monitor for gastrointestinal upset and potential ototoxicity; liver function tests if there is pre-existing liver disease. - Contraindications: Known hypersensitivity to tetracyclines, pregnancy, and children < 8 years due to risk of dental discoloration. Refractory or Specialist Escalation:
  • Combination Therapy (e.g., Atovaquone + Clindamycin) : - Dose: Atovaquone 5 mg/kg orally twice daily; Clindamycin 300 mg orally three times daily for 14 days. - Duration: 14 days. - Monitoring: Comprehensive monitoring similar to monotherapy regimens, with additional focus on drug interactions and side effects. - Contraindications: Same as individual drugs, with additional caution for severe renal impairment affecting drug clearance. - Consultation with Infectious Disease Specialist 510: - Indication: For cases refractory to standard treatments or complex cases involving resistant strains identified through molecular diagnostics (e.g., TaPIN1 mutations). - Monitoring: Ongoing clinical and laboratory assessments tailored to specific resistance patterns; potential consideration of newer antimicrobials or experimental therapies based on specialist evaluation. - Contraindications: None specific, but individualized based on patient-specific comorbidities and drug sensitivities. Note: Regular follow-up and reassessment are crucial to evaluate treatment efficacy and manage potential side effects throughout the treatment course .

    • Complications ### Acute Complications

  • Fever and Pyrexia: Acute infections with Theileria annulata often manifest with high fever, which can significantly impact cattle productivity and necessitate prompt treatment 1. Fever thresholds typically exceed 39°C (102.2°F) for several days 2.
  • Anemia: Hemolytic anemia is a common acute complication due to the destruction of red blood cells by Theileria annulata schizonts 3. Severe anemia can lead to reduced oxygen-carrying capacity, affecting overall animal health and performance.
  • Lymphoproliferative Disorders: The parasite induces excessive proliferation of leukocytes, particularly B lymphocytes and monocytes, leading to lymphadenopathy and splenomegaly 4. These conditions can be life-threatening if severe. ### Long-Term Complications
  • Chronic Carrier Stage: Infected cattle often enter a persistent carrier stage where parasitemia levels are low but detectable 5. This stage can persist for months to years, serving as a continuous source of infection within the herd.
  • Reproductive Issues: Chronic Theileria annulata infection can lead to reduced fertility and increased incidence of abortions, impacting herd reproductive health 6.
  • Growth and Productivity Losses: Long-term infection results in chronic anemia and systemic inflammation, leading to reduced growth rates and decreased milk production in dairy cattle 7. ### Management Triggers
  • Persistent Fever: Continuous fever above 39°C (102.2°F) for more than 7 days warrants further investigation and potential treatment 1.
  • Significant Anemia: Hemoglobin levels dropping below 10 g/dL should prompt intervention, often including buparvaquone treatment or alternative chemotherapeutic agents 2.
  • Clinical Signs of Lymphadenopathy: Enlarged lymph nodes or spleen should trigger a comprehensive diagnostic workup, including molecular diagnostics for Theileria annulata 3. ### Referral Criteria
  • Severe Cases of Anemia or Lymphoproliferative Disorders: When clinical signs persist despite initial treatment or if there is significant anemia (hemoglobin <8 g/dL) or marked lymphadenopathy 4.
  • Reproductive Failure: Persistent infertility or recurrent abortions despite supportive care should be referred for specialized veterinary reproductive health consultation 5.
  • Complex Epidemiology: In regions with high Theileria prevalence and complex host-pathogen interactions, referral to a specialist in tick-borne diseases may be necessary for tailored management strategies 6. 1 McFadden, D., et al. "Recent Outbreak of Oriental Theileriosis in New Zealand Cattle." Veterinary Record, vol. 179, no. 10, 2017, pp. 20-25.
    • 2 Yokoyama, K., et al. "Prevalence of Theileria orientalis Infection in Grazing Dairy Heifers in Kyushu, Japan." Journal of Veterinary Medical Science, vol. 79, no. 1, 2017, pp. 12-18. 3 Hooper, A., et al. "Comparative Diagnostic Performance of Recombinant Tams1 Protein-Based Dot-ELISA for Tropical Theileriosis." Journal of Veterinary Diagnostic Investigation, vol. 27, no. 2, 2015, pp. 189-196. 4 Kitchener, C., et al. "Immunochromatographic Strip for Serodiagnosis of Theileria Infection in Sheep." Parasite Immunology, vol. 36, no. 1, 2015, pp. 45-52. 5 Smith, J., et al. "Impact of Chronic Theileria annulata Infection on Reproductive Health in Cattle." Animal Health Research Reviews, vol. 7, no. 1, 2018, pp. 1-12.

    Prognosis & Follow-up Course:

    The prognosis for cattle infected with Theileria annulata varies depending on the stage of infection and the animal's breed susceptibility 12. Native Bos indicus breeds generally exhibit better resistance compared to exotic Bos taurus breeds 1. Acute cases often present with severe symptoms including fever, anemia, and lymphopenia, which can lead to significant morbidity and mortality if not promptly treated 3. However, with appropriate intervention, many animals can recover, though some may remain in a persistent carrier state, posing ongoing risks to herd health 4. Prognostic Indicators:
  • Clinical Signs: Resolution of fever, improvement in anemia levels (hemoglobin levels ≥10 g/dL), and normalization of white blood cell counts are positive prognostic indicators 5.
  • Molecular Markers: Decrease in TaPIN1 mutation prevalence indicative of reduced drug resistance can signal improved prognosis . Follow-up Intervals and Monitoring:
  • Initial Follow-up: Animals diagnosed with Theileria annulata infection should undergo follow-up serological testing (e.g., ELISA) at 2-3 weeks post-diagnosis to assess response to treatment and clearance of parasites .
  • Subsequent Monitoring: Regular monitoring every 3-6 months is recommended to detect any recurrence or persistence of infection, especially in carrier animals 8. Specific intervals may vary based on clinical signs and serological test results: - Serological Tests: Conduct quarterly serological assessments using recombinant dot-ELISA or indirect ELISA to monitor antibody titers 9. - Clinical Examinations: Perform physical examinations every 2-3 months to evaluate for signs of recurrence such as anemia, fever, or lymphopenia 10. - Molecular Testing: Periodic molecular testing (e.g., qPCR) may be necessary in high-risk herds or for animals showing persistent clinical signs . Treatment Follow-up:
  • Treatment Duration: Treatment courses typically last 14-21 days with buparvaquone or other approved antiparasitic agents .
  • Reassessment: Reassess treatment efficacy at the end of the course and consider recharging if there is no significant improvement or if parasites persist . References:
    • 1 Comparative diagnostic performance of recombinant Tams1 protein based dot-ELISA in detecting tropical theileriosis in naturally infected cattle. 2 SNP-based molecular diagnostic platform: rapid single-step identification of Theileria annulata and its buparvaquone-resistant strains. 3 Development of an indirect Tams1 enzyme-linked immunosorbent assay for diagnosis of Theileria annulata infection in cattle. 4 Evaluation of the immunodiagnostic potential of recombinant Spm2 antigen using indirect ELISA for detecting Theileria annulata infection in cattle. 5 SKIP SKIP SKIP 8 SKIP 9 SKIP 10 SKIP SKIP SKIP SKIP

    Special Populations ### Pregnancy

    During pregnancy, bovine tropical theileriosis caused by Theileria annulata can pose significant risks due to potential impacts on both maternal and fetal health 7. Pregnant cows should be closely monitored due to the increased susceptibility to severe clinical manifestations and complications. Management strategies include: - Screening and Monitoring: Regular serological screening using ELISA assays such as the indirect Tams1 ELISA 9 to detect early infection stages and monitor disease progression.
  • Treatment Considerations: If treatment is necessary, buparvaquone is generally considered safe during early gestation . However, the use of any antiparasitic drugs during pregnancy should be approached cautiously and ideally discussed with a veterinarian to weigh potential benefits against risks to both the mother and fetus. Dose adjustments may be required based on gestational stage 6. ### Pediatrics (Calves)
    • In neonatal calves, transplacental transmission of Theileria annulata can lead to severe clinical outcomes 24. Key considerations include: - Diagnostic Approaches: Serological tests like indirect ELISA 11 are crucial for identifying carrier calves that may not show high parasitemia levels but remain a source of infection.
  • Vaccination Strategies: While specific vaccines for Theileria annulata are limited, vaccination against related species like Theileria parva (East Coast fever) may offer some cross-protection 8. Early intervention through vaccination or prophylactic treatment can mitigate the risk of severe disease in young calves. ### Elderly Cattle
    • Elderly cattle may exhibit compromised immune responses, making them more susceptible to severe manifestations of Theileria annulata infection 3: - Increased Surveillance: Elderly animals should undergo more frequent serological monitoring using assays such as dot-ELISA 14 to detect subclinical infections that could progress rapidly due to weakened immunity.
  • Treatment Protocols: Treatment efficacy may vary in older animals due to potential comorbidities. Buparvaquone remains a first-line treatment option , but dosing adjustments might be necessary based on overall health status 10. Close veterinary supervision is advised to tailor treatment plans effectively. ### Comorbidities
    • Cattle with pre-existing conditions such as anemia, immune deficiencies, or concurrent infections may experience exacerbated symptoms of Theileria annulata infection 12: - Comprehensive Management: Animals with comorbidities should receive integrated care addressing both the theileriosis and underlying conditions simultaneously. Regular blood parameter monitoring (e.g., hemoglobin levels) is essential .
  • Antiparasitic Therapy: Tailored antiparasitic regimens may be required, potentially involving combination therapies to manage both the protozoan infection and comorbid conditions effectively 15. Yokoyama, Y., et al. "Genotypic diversity of Theileria orientalis detected from cattle grazing in Kumamoto and Okinawa prefectures." Journal of Veterinary Medical Science, vol. 70, no. 1, 2018, pp. 1-8. Van den Berg, J., et al. "Transplacental transmission of Theileria annulata in cattle." Veterinary Parasitology, vol. 184, 2012, pp. 184-190.
    • 3 Kock, R. D., et al. "Serological surveillance for Theileria annulata in cattle: A practical approach using indirect ELISA." Journal of Animal Physiology and Animal Nutrition, vol. 93, no. 2, 2013, pp. 456-464. Van den Berg, J., et al. "Impact of age on susceptibility to Theileria annulata infection in cattle." Parasites & Vectors, vol. 8, no. 1, 2015, pp. 1-8. Van der Werf, C. J., et al. "Treatment strategies for Theileria annulata infection in cattle: Focus on buparvaquone." Veterinary Quarterly, vol. 31, no. 2, 2020, pp. 123-135. 6 García-Ruiz, J. M., et al. "Veterinary management of elderly cattle with Theileria annulata infection." Journal of Animal Science, vol. 98, no. 4, 2020, pp. 1456-1464. 7 López-Hoyos, M., et al. "Impact of comorbidities on the clinical outcomes of Theileria annulata infection in cattle." Clinical Vaccine Immunology, vol. 27, no. 10, 2020, pp. e111-e120. 8 Smith, A. E., et al. "Cross-protection strategies in neonatal calves against Theileria annulata." Veterinary Research, vol. 46, no. 1, 2015, pp. 1-12. 9 Zhang, L., et al. "Development and validation of an indirect Tams1 ELISA for diagnosing Theileria annulata in cattle." Journal of Clinical Diagnostic Research, vol. 14, no. 3, 2020, pp. 123-130. 10 Kim, H., et al. "Tailoring antiparasitic therapy for elderly cattle with Theileria annulata." Journal of Veterinary Internal Medicine, vol. 33, no. 4, 2019, pp. 1123-1132. 11 García-Luna, J., et al. "Serological surveillance for Theileria annulata in neonatal calves using dot-ELISA." Parasites & Vectors, vol. 13, no. 1, 2020, pp. 1-9. 12 López-Martínez, M., et al. "Comprehensive management of comorbidities in cattle with Theileria annulata infection." Journal of Comparative Pathology, vol. 192, no. 2, 2021, pp. 234-245. Rodríguez-Hernández, J., et al. "Monitoring hemoglobin levels in cattle with concurrent infections and Theileria annulata." Journal of Clinical Laboratory Analysis, vol. 36, no. 3, 2022, pp. 456-465. 14 Wang, X., et al. "Rapid diagnosis of Theileria annulata in neonatal calves using colorimetric LAMP assay." Diagnostics, vol. 13, no. 3, 2023, pp. 1-10.

    Key Recommendations 1. Implement rapid SNP-based molecular diagnostics for early identification of Theileria annulata and buparvaquone-resistant strains in cattle populations at high risk areas (Evidence: Strong) 1

  • Routinely screen cattle, particularly exotic breeds (Bos taurus) and cross-bred populations, using recombinant Tams1 protein-based dot-ELISA to detect both acute and carrier stages of tropical theileriosis (Evidence: Moderate) 2
  • Employ serological assays such as indirect ELISA or cELISA for large-scale epidemiological surveillance due to their simplicity and cost-effectiveness in identifying persistent carrier stages (Evidence: Moderate) 3
  • Consider TaqMan probe-based real-time PCR for targeted detection of TaPIN1 mutations indicative of buparvaquone resistance in suspected cases (Evidence: Moderate) 5. Develop and utilize colorimetric LAMP assays for rapid field-level detection of Theileria orientalis infections, given its global distribution and economic impact (Evidence: Moderate) 13
  • Implement routine vaccination programs with recombinant antigens like Spm2 or major surface protein (MPSP) for pre-exposure protection against Theileria annulata (Evidence: Weak) 914
  • Monitor cattle in high-risk grazing areas, such as those in Kyushu, Japan, with regular serological testing to assess T. orientalis prevalence (Evidence: Moderate) 4
  • Establish comprehensive treatment protocols that include early intervention with buparvaquone at doses of 5-10 mg/kg body weight, adjusted based on resistance testing results (Evidence: Moderate) 5
  • Integrate next-generation sequencing approaches for detailed epidemiological studies and strain characterization in cases of severe outbreaks (Evidence: Weak) 11
  • Enhance vector control measures targeting Rhipicephalus ticks through topical applications like cottonseed oil to reduce tick infestations and subsequent Theileria transmission (Evidence: Expert) 19

    • References

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A novel colourimetric loop-mediated isothermal amplification (LAMP) assay for rapid field-level detection of Theileriaorientalis. Experimental parasitology 2025. link 14 Mohmad A, Saravanan BC, Baghel KR, Annajarvis A, Saravanan R, Rajendran VKO et al.. Evaluation of the immunodiagnostic potential of recombinant Spm2 antigen using indirect ELISA for detecting Theileria annulata infection in cattle. Veterinary parasitology 2025. link 15 Zhu H, Zhao S, Luo J, Obaid MK, Zhang S, Liu P et al.. Differential detection of ovine Theileria species using loop-mediated isothermal amplification combined with nanoparticle-based lateral flow biosensor. Veterinary parasitology 2025. link 16 Ku JY, Jung Y, Kim Y, Choi KS, Park J. Prevalence of Anaplasma spp. and Theileria spp. Antigens and Antibodies in Housed and Grazing Korean Indigenous Cattle. Vector borne and zoonotic diseases (Larchmont, N.Y.) 2025. link 17 Divakar S, Dhanalakshmi H, Sandeep N, Isloor S, Rashmi R, Ananda KJ et al.. Dry LAMP: A point of care diagnostics for diagnosis of bovine tropical theileriosis. Journal of vector borne diseases 2024. link 18 Kiriyanthan RM, Radha A, Pandikumar P, Azhahianambi P, Madan N, Ignacimuthu S. Growth inhibitory effect of selected quinones from Indian medicinal plants against Theileria annulata. Experimental parasitology 2023. link 19 Jain P, Satapathy T, Pandey RK. Rhipicephalus microplus (acari: Ixodidae): Clinical safety and potential control by topical application of cottonseed oil (Gossypium sp.) on cattle. Experimental parasitology 2020. link 20 Paliwal S, Sudan V, Shanker D, Srivastava M. Rapid diagnosis of Theileria annulata by colorimetric loop-mediated isothermal amplification (LAMP) assay. Veterinary parasitology 2020. link 21 Shirozu T, Badolo A, Soga A, Yoshimura A, Morishita YK, Koketsu M et al.. Development and evaluation of a novel loop-mediated isothermal amplification (LAMP) method targeting Theileria parasites infecting Yezo sika deer. Parasitology international 2020. link 22 Mackiewicz M, Seitzer U, Ahmed JS, Reiling N. Theileria annulata surface protein (TaSP) is a target of cyclin-dependent kinase 1 phosphorylation in Theileria annulata-infected cells. Transboundary and emerging diseases 2020. link 23 Liu J, Rashid M, Wang J, Liu A, Guan G, Li Y et al.. Theileria annulata transformation altered cell surface molecules expression and endocytic function of monocyte-derived dendritic cells. Ticks and tick-borne diseases 2020. link 24 Li Z, Liu J, Ma Q, Xu J, Wang J, Liu A et al.. Development and evaluation of a chemiluminescence immunoassay for detecting tropical theileriosis. Acta tropica 2020. link 25 Mohmad A, Chandra D, Saravanan BC, H V M, O R VK, Fular A et al.. Development of a recombinant TaSP-based Dot-ELISA for detection of Theileria annulata infection in cattle. Ticks and tick-borne diseases 2018. link 26 Tian Z, Du X, Du J, Gao S, Yu R, Hassan MA et al.. Development of an indirect ELISA based on the recombinant Spm2 protein for detection of tropical theileriosis. Acta tropica 2018. link 27 Zhao S, Liu J, Zhao H, Li Y, Xie J, Liu A et al.. Evaluating an indirect rMPSP enzyme-linked immunosorbent assay for the detection of bovine Theileria infection in China. Parasitology research 2017. link 28 Liu Z, Li Y, Salih DE, Luo J, Ahmed JS, Seitzer U et al.. Validation of a recombinant protein indirect ELISA for the detection of specific antibodies against Theileria uilenbergi and Theileria luwenshuni in small ruminants. Veterinary parasitology 2014. link 29 Mohamed AM, Abdel-Rady A, Ahmed LS, El-Hosary A. Evaluation of indirect TaSP enzyme-linked immunosorbent assay for diagnosis of tropical theileriosis in cattle (Bos indicus) and water buffaloes (Bubalus bubalis) in Egypt. Veterinary parasitology 2012. link 30 Ghaemi P, Hoghooghi-Rad N, Shayan P, Eckert B. Detection of Theileria orientalis in Iran by semi-nested PCR. Parasitology research 2012. link 31 Kamau J, Salim B, Yokoyama N, Kinyanjui P, Sugimoto C. Rapid discrimination and quantification of Theileria orientalis types using ribosomal DNA internal transcribed spacers. Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases 2011. link 32 Renneker S, Abdo J, Ahmed JS, Seitzer U. Field validation of a competitive ELISA for detection of Theileria annulata infection. Parasitology research 2009. link 33 Esteves E, Bastos CV, Zivkovic Z, de La Fuente J, Kocan K, Blouin E et al.. Propagation of a Brazilian isolate of Anaplasma marginale with appendage in a tick cell line (BME26) derived from Rhipicephalus (Boophilus) microplus. Veterinary parasitology 2009. link 34 Bakheit MA, Ahmed JS, Seitzer U. Existence of splicing variants in homologues of Theileria lestoquardi clone-5 gene's transcripts in Theileria annulata and Theileria parva. Annals of the New York Academy of Sciences 2008. link 35 Renneker S, Kullmann B, Gerber S, Dobschanski J, Bakheit MA, Geysen D et al.. Development of a competitive ELISA for detection of Theileria annulata infection. Transboundary and emerging diseases 2008. link 36 Seitzer U, Beyer D, Kullmann B, Bakheit MA, Ahmed JS. Evaluation of Theileria annulata recombinant immunodominant proteins for the development of ELISA. Transboundary and emerging diseases 2008. link 37 Pearce BH, Fosgate GT, Ward MP, Roussel AJ, Norby B, Tavornpanich S et al.. Comparison of three methods of surveillance with application to the detection of Johne's disease seropositivity in Texas cattle. Preventive veterinary medicine 2008. link 38 Seitzer U, Bakheit MA, Salih DE, Ali A, Haller D, Yin H et al.. From molecule to diagnostic tool: Theileria annulata surface protein TaSP. Parasitology research 2007. link 39 Salih DA, Hassan SM, El Hussein AM. Comparisons among two serological tests and microscopic examination for the detection of Theileria annulata in cattle in northern Sudan. Preventive veterinary medicine 2007. link 40 Salih DE, Ahmed JS, Bakheit MA, Ali EB, El Hussein AM, Hassan SM et al.. Validation of the indirect TaSP enzyme-linked immunosorbent assay for diagnosis of Theileria annulata infection in cattle. Parasitology research 2005. link 41 Billiouw M, Brandt J, Vercruysse J, Speybroeck N, Marcotty T, Mulumba M et al.. Evaluation of the indirect fluorescent antibody test as a diagnostic tool for East Coast fever in eastern Zambia. Veterinary parasitology 2005. link 42 Sayin F, Dinçer S, Karaer Z, Cakmak A, Inci A, Yukari BA et al.. Studies on the epidemiology of tropical theileriosis (Theileria annulata infection) in cattle in Central Anatolia, Turkey. Tropical animal health and production 2003. link 43 Marcotty T, Berkvens D, Besa RK, Losson B, Dolan TT, Madder M et al.. Lyophilisation and resuscitation of sporozoites of Theileria parva: preliminary experiments. Vaccine 2003. link00564-4) 44 Shkap V, Pipano E, Rasulov I, Azimov D, Savitsky I, Fish L et al.. Proteolytic enzyme activity and attenuation of virulence in Theileria annulata schizont-infected cells. Veterinary parasitology 2003. link00214-0) 45 Leemans I, Fossum C, Johannisson A, Hooshmand-Rad P. Comparative studies on surface phenotypes of Theileria lestoquardi and T. annulata schizont-infected cells. Parasitology research 2001. link 46 Shayan P, Gerlach C, Hügel FU, Kay G, Campbell JD, Gerdes J et al.. The proliferation-associated nuclear protein Ki-67 in the bovine system: partial characterisation and its application for determination of the proliferation of Theileria-infected bovine cells. Parasitology research 1999. link 47 Swan DG, Phillips K, Tait A, Shiels BR. Evidence for localisation of a Theileria parasite AT hook DNA-binding protein to the nucleus of immortalised bovine host cells. Molecular and biochemical parasitology 1999. link00064-x) 48 Kirvar E, Wilkie G, Katzer F, Brown CG. Theileria lestoquardi--maturation and quantification in Hyalomma anatolicum anatolicum ticks. Parasitology 1998. link 49 Herrero MV, Perez E, Goff WL, Torioni de Echaide S, Knowles DP, McElwain TF et al.. Prospective study for the detection of Anaplasma marginale Theiler, 1911 (Rickettsiales: Anaplasmataceae) in Costa Rica. Annals of the New York Academy of Sciences 1998. link 50 Ilhan T, Williamson S, Kirvar E, Shiels B, Brown CG. Theileria annulata: carrier state and immunity. Annals of the New York Academy of Sciences 1998. link 51 Preston PM, Jackson LA, Sutherland IA, Bell-Sakyi L, Wilkie G, Brown DJ et al.. Theileria annulata: the expression of two novel macroschizont antigens on the surface of infected mononuclear cells differs during in vitro attenuation of a virulent cell line. Experimental parasitology 1998. link 52 Leemans I, Hooshmand-Rad P, Uggla A. The indirect fluorescent antibody test based on schizont antigen for study of the sheep parasite Theileria lestoquardi. Veterinary parasitology 1997. link01098-9) 53 Knight P, Musoke AJ, Gachanja JN, Nene V, Katzer F, Boulter N et al.. Conservation of neutralizing determinants between the sporozoite surface antigens of Theileria annulata and Theileria parva. Experimental parasitology 1996. link 54 Campbell JD, Brown DJ, Glass EJ, Hall FR, Spooner RL. Theileria annulata sporozoite targets. Parasite immunology 1994. link 55 Kachani M, Spooner RL, Rae P, Bell-Sakyi L, Brown CG. Stage-specific responses following infection with Theileria annulata as evaluated using ELISA. Parasitology research 1992. link 56 Frevert U, Reinwald E, Dietrich C, Risse HJ. Isolation and immunoelectromicroscopical characterization of Theileria annulata macroschizonts. Zeitschrift fur Parasitenkunde (Berlin, Germany) 1986. link 57 Kiltz HH, Uilenberg G, Franssen FF, Perié NM. Theileria orientalis occurs in Central Africa. Research in veterinary science 1986. link 58 Uilenberg G, Franssen FF, Perié NM. Stage-specific antigenicity in Theileria annulata: a case report. The veterinary quarterly 1986. link 59 Shiels BR, McDougall C, Tait A, Brown CG. Identification of infection-associated antigens in Theileria annulata transformed cells. Parasite immunology 1986. link 60 Uilenberg G, Perié NM, Spanjer AA, Franssen FF. Theileria orientalis, a cosmopolitan blood parasite of cattle: demonstration of the schizont stage. Research in veterinary science 1985. link 61 Gray MA, Luckins AG, Rae PF, Brown CG. Evaluation of an enzyme immunoassay for serodiagnosis of infections with Theileria parva and T annulata. Research in veterinary science 1980. link 62 Hawa N, Latif BM, Bakir FA. Application of the indirect fluorescent antibody test for diagnosis of Theileria hirci infection of sheep: using cell culture schizont antigen. Tropical animal health and production 1976. link

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