J Vet Sci.  2010 Mar;11(1):27-34. 10.4142/jvs.2010.11.1.27.

Fatal cases of Theileria annulata infection in calves in Portugal associated with neoplastic-like lymphoid cell proliferation

Affiliations
  • 1Instituto de Ciencias Agrarias e Ambientais Mediterranicas, Departamento de Medicina Veterinaria, Universidade de Evora, Polo da Mitra, Ap.94, 7002-554 Evora, Portugal. smbb@uevora.pt
  • 2University of California, Veterinary Medical Center, 10435 Sorrento Valley Road, Suite 101 San Diego, USA.
  • 3Instituto de Investigacao Cientifica Tropical, CVZ, Faculdade de Medicina Veterinaria, Avenida da Universidade Tecnica, 1300-477 Lisboa, Portugal.
  • 4Centro de Investigacao Interdisciplinar em Sanidade Animal (CIISA), Faculdade de Medicina Veterinaria, Avenida da Universidade Tecnica, 1300-477 Lisboa, Portugal.
  • 5Vet+ Servicos Veterinarios Lda., Largo Machado Santos Lote 16, 7050-125 Montemor-o-Novo, Portugal.
  • 6Cooperativa Agricola de Compra e Venda de Montemor-o-Novo, CRL (COPRAPEC), Rua 5 Outubro 76-1 degrees, 7050-355 Montemor-o-Novo, Portugal.
  • 7Centro de Investigacao em Patobiologia Molecular, Instituto Portugues de Oncologia, Rua Prof. Lima Basto, 1099-023 Lisboa, Portugal.
  • 8Laboratorio Nacional de Investigacao Veterinaria, Estrada de Benfica 701, 1549-011 Lisboa, Portugal.
  • 9Division of Infection and Immunity, Institute of Comparative Medicine, Faculty of Veterinary Medicine, University of Glasgow, Bearsden Road, Glasgow G61 1QH, Scotland.

Abstract

This study was carried out to investigate fifteen cases of acute lethal infection of calves (< or = 4 months of age) by the protozoan parasite Theileria (T.) annulata in the south of Portugal. Calves developed multifocal to coalescent nodular skin lesions, similar to multicentric malignant lymphoma. Infestation with ticks (genus Hyalomma) was intense. Theileria was seen in blood and lymph node smears, and T. annulata infection was confirmed by isolation of schizont-transformed cells and sequencing of hypervariable region 4 of the 18S rRNA gene. At necropsy, hemorrhagic nodules or nodules with a hemorrhagic halo were seen, particularly in the skin, subcutaneous tissue, skeletal and cardiac muscles, pharynx, trachea and intestinal serosa. Histologically, nodules were formed by large, round, lymphoblastoid neoplastic-like cells. Immunohistochemistry (IHC) identified these cells as mostly CD3 positive T lymphocytes and MAC387 positive macrophages. A marker for B lymphocytes (CD79alphacy) labeled very few cells. T. annulata infected cells in these nodules were also identified by IHC through the use of two monoclonal antibodies (1C7 and 1C12) which are diagnostic for the parasite. It was concluded that the pathological changes observed in the different organs and tissues were caused by proliferation of schizont-infected macrophages, which subsequently stimulate a severe uncontrolled proliferation of uninfected T lymphocytes.

Keyword

cattle; lymphoid cell proliferation; Theileria annulata; tropical theileriosis

MeSH Terms

Animals
Base Sequence
Cattle
Cattle Diseases/epidemiology/*parasitology/pathology
Cell Growth Processes/physiology
DNA, Protozoan/chemistry/genetics
Disease Outbreaks/*veterinary
Female
Immunohistochemistry/veterinary
Lymphocytes/parasitology/*pathology
Male
Molecular Sequence Data
Polymerase Chain Reaction/veterinary
Portugal/epidemiology
RNA, Ribosomal, 18S/chemistry/genetics
Sequence Analysis, DNA
Skin Diseases/epidemiology/parasitology/pathology/*veterinary
Theileria annulata/*isolation & purification
Theileriasis/epidemiology/parasitology/*pathology

Figure

  • Fig. 1 (A) Blood smear showing three ring forms of Theileria annulata piroplasms in red blood cells. (B) Lymph node smear showing a schizont in a mononuclear cell. Giemsa stain, ×1,000.

  • Fig. 2 (A) Widespread hemorrhagic nodules in subcutaneous tissue and abdominal muscles of calf (animal No.7). (B) Pale and hemorrhagic nodules are inserted in the tongue and the laryngeal and pharyngeal mucosa of calf (animal No.4).

  • Fig. 3 Lymphoid neoplastic-like cells (A) in a nodule infiltrating the skeletal muscle (H&E stain, ×100), with indistinct cell-membrane, high nuclear/cytoplasmic ratio and occasionally indented nuclei (B) (H&E stain, ×400). (C) Cells positive to CD3 (rabbit anti-CD3, streptavidin-biotin-peroxidase, Mayer's hematoxylin counterstain, ×100; Inset ×400). (D) Cells positive to MAC387 (mouse anti-human macrophages, streptavidin-biotin-peroxidase, Mayer's hematoxylin counterstain, ×100; Inset ×400).

  • Fig. 4 Staining of Theileria annulata infected cells with monoclonal antibodies 1C7 (A) and 1C12 (B). Streptavidin-biotin-peroxidase, Mayer's hematoxylin counterstain, ×400.


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