Group License: 1 User active

Theileria mutans infection

Theileria mutans infection

Previous authors: J A LAWRENCE

Current authors:
J A LAWRENCE - Extraordinary Professor, DPhil, BSc, MRCVS (ret.), DTVM, Department of Paraclinical Veterinary Science, University of Zimbabwe, Harare, Zimbabwe 
C BYARUHANGA - Post-doc Fellow, BVM, MVPM, PhD, Department of Veterinary Tropical Diseases, Para-clinical Building, Faculty of Veterinary Science, University of Pretoria, 100 Old Soutpan Road, Onderstepoort, Pretoria, Gauteng, 0110,  South Africa
M OOSTHUIZEN - Parasitology, PhD, Department of Veterinary Tropical Diseases, Faculty of Veterinary Science, Private Bag X04, University of Pretoria, Pretoria, Gauteng, 0110,  South Africa
B J MANS - Principal Researcher, BSc, BSc (Hons) Biochemistry, MSc (Biochemistry), PhD (Biochemistry), Agricultural Research Council, Onderstepoort Veterinary Research, 100 Old Soutpan Road, Pretoria, Gauteng, 0110, South Africa

GENERAL INTRODUCTION: THEILERIOSES OF CATTLE

Introduction

Theileria mutans was first described as a benign parasite of the ox by Theiler,32 but its identity was inextricably confused with that of other benign species of Theileria for many years. It was assumed to be the only benign bovine Theileria in Africa until 1977, when it was demonstrated that Theileria taurotragi was also capable of causing a mild clinical reaction in cattle.41 Elsewhere in the world the benign Theileria of cattle is considered to be T. buffeli/orientalis.34 Theileria mutans is transmitted by Amblyomma ticks and is now known to be confined to eastern, western and southern Africa and to the Caribbean Islands where it was introduced in cattle from Africa. The parasite also infects the African buffalo (Syncerus caffer), in which it was first described under the name Theileria barnetti.2 Its only practical significance in southern Africa is the confusion that it causes in the differential diagnosis of Theileria parva (see below). In eastern Africa, pathogenic strains of the parasite occur, which may cause severe clinical illness and death.

Aetiology and life cycle

In African buffalo, extensive heterogeneity in the 18S rRNA gene of T. mutans is present in populations in South Africa 5, 6, 19.  On the other hand, in cattle, micro-heterogeneity of up to 2 nucleotides was observed between T. mutans sequences in Uganda and South Africa 3, 19.  Out of the five recognised genotypes of T. mutans, two (T. mutans, T. mutans MSD) infect cattle and buffalo, while the other three (T. mutans-like 1, T. mutans-like 2 and T. mutans-like 3) have so far been found only in African 4, 5, 19, 20  In addition to their significantly higher prevalence, T. mutans-like 1 to 3 genotypes also occur at higher parasitaemias than T. mutans and T. mutans MSD 18, 20 suggested that they should perhaps be assigned to a separate species on the basis of host specificity.

Theileria mutans has a typical theilerial life cycle (see East Coast fever: Figure 29.2) but unlike T. parva, T. mutans undergoes limited lymphocytic merogony; the main mode of replication occurs in the erythrocytes, and this may cause high piroplasm parasitaemia 30.

Theileria mutans is transmitted by several species of Amblyomma: A. astrion,33 A. cohaerens,40 A. gemma,28 A. hebraeum,9, 16 A. lepidum 37 and  A. variegatum.35 Amblyomma hebraeum is the principal vector south of the central watershed of Zimbabwe, and A. variegatum is the principal vector to the north (see Vectors: Ticks). Infection occurs transstadially from larva to nymph, or nymph to adult. Recovered animals remain carriers indefinitely. The piroplasm is readily transmitted by blood inoculation.32

The piroplasms of T. mutans are larger than those of T. parva and dividing forms may be seen during the acute phase of infection. The schizonts are also larger and the chromatin granules are more numerous and less uniform in size and shape than those of T. parva.2, 40 It has not yet been possible to culture T. mutans-infected lymphocytes in vitro.

Epidemiology

Theileria mutans is widespread throughout the range of its tick vectors in sub-Saharan Africa and on some Caribbean islands. The pathogen was confirmed using reverse line blot (RLB) hybridisation assay in cattle in Uganda 1, 3, 17, 23 25, 27, Kenya 24, Nigeria 17, and South Africa 19, and in African buffalo in Uganda 26, Botswana 12 and South Africa 7, 19. The prevalence of T. mutans varies, depending on the geographical area and the different genotypes being detected; it can reach 100% in adult cattle, with most calves becoming infected by five to six months of age 1, 21.  High prevalence of T. mutans in Uganda has been attributed to high tick infestation of cattle with A. lepidum and A. variegatum 3, and to the long carrier state at high levels after infection 1 Amblyomma cohaerens, which is commonly found on African buffalo and cattle and develops high infection rates with T. mutans, is also likely to promote high levels of T. mutans transmission where buffalo and cattle come into contact.2

Fatal infections due to T. mutans have been described 14 often in situations where animals have been exposed to T. mutans infection after immunization against T. parva with a reduction in tick control.29, 31.  It is probable that stress caused by poor nutrition, intercurrent disease or other factors predisposes cattle to anaemia when infected with T. mutans. On the other hand, a protective effect of benign T. mutans and T. velifera co-infections against T. parva infection may occur. A study in Kenya showed that concurrent infections with the less pathogenic theileria’s at first infection with T. parva were associated with a reduction (89%) in mortality associated with T. parva in a population of East African Short-horn Zebu cattle 38. Field and experimental evidence suggests that strains of T. mutans derived from buffalo may be more pathogenic to cattle than those derived from cattle.13, 21

Clinical signs

Infection with T. mutans following tick transmission usually results in a mild febrile reaction and slight swelling of lymph nodes commencing after an incubation period of 20 to 30 days from the time of attachment of the ticks, and lasting for two to five days. Pathogenic strains in eastern Africa cause severe anaemia and icterus and sometimes death.28, 31.  The parasite may also cause stunting in young calves.22 It is unlikely that the clinical disease described in 1937 at Tzaneen in the Limpopo Province of South Africa 8 was, in fact, caused by T. mutans. There is no evidence that T. mutans causes cerebral theileriosis and reports of cerebral theileriosis in South Africa attributed to T. mutans should be ascribed to T. taurotragi.10

Pathogenesis and pathology

The pathogenic effects of T. mutans result from the invasion and proliferation of piroplasms in circulating erythrocytes. Pathogenic strains in eastern Africa are presumed to cause intravascular haemolysis associated with a heavy piroplasm parasitaemia resulting in anaemia and icterus.14 The degree of anaemia observed in an animal correlates closely with the level of piroplasm parasitaemia 42.

Diagnosis

Theileria mutans infection may be suspected when a mild febrile reaction occurs in cattle exposed to Amblyomma spp. and when theilerial piroplasms are demonstrated in blood smears. Schizonts, although larger than those of other species of Theileria, are very scanty and are present for only a short period. They are therefore rarely detected. The presence of large numbers of piroplasms in animals showing anaemia and icterus may rouse suspicion of infection with a pathogenic strain of T. mutans, if no other cause can be demonstrated. Confirmation of diagnosis is possible using various methods 18. Detection of antibodies is possible using an enzyme-linked immunosorbent assay (ELISA) based on a T. mutans-specific piroplasm antigen, or by indirect immunofluorescence using piroplasm antigen. These tests provide a specific retrospective diagnosis and are also useful in epidemiological studies. Detection of antigen can be achieved by polymerase chain reaction (PCR) and reverse line blot (RLB) techniques, based on the 18S rRNA gene, and Pan-FRET real-time PCR targeting the Cox III gene; RLB does not detect the T. mutans-like 1 to 3 genotypes 5. Sequence and phylogenetic analyses based upon small-subunit rRNA gene can be used to reveal the relationships between gene variants 3, 4, 5, 19, 20. A quantitative real-time PCR (qPCR) assay based on the cytochrome oxidase subunit (cox) III gene enables the simultaneous detection and differentiation of T. mutans and five other Theileria species (T. annulata, T. velifera, T. taurotragi, T. buffeli and T. parva) in buffalo and cattle blood samples, using melting curve analysis 6, 15.

Differential diagnosis

Differentiation of infection with T. mutans from infection with T. parva has been discussed in relation to East Coast fever (see East Coast fever). The pathogenic form of T. mutans infection seen in eastern Africa must be differentiated from other haemoparasitic infections, notably babesiosis, anaplasmosis and trypanosomosis, by demonstration of the piroplasms in blood smears.

Control

As T. mutans is usually a benign parasite, there are seldom indications for its treatment or control under normal conditions. The virulence of field infections with pathogenic strains may be reduced by inoculation of blood containing piroplasms of the local strain, prior to exposure. Parasitaemia is reduced after exposure and the resulting anaemia is less severe. 36, 39. The piroplasms are destroyed by treatment with a number of 8-aminoquinoline compounds (including primaquin), parvaquone 11 and buparvaquone.

References

  1. ASIIMWE, B.B., WEIR, W., TAIT, A., LUBEGA, G.W. & OURA, C.A.L., 2013. Haemoparasite infection kinetics and the population structure of Theileria parva on a single farm in Uganda. Veterinary Parasitology,193, 8-14.
  2. BROCKLESBY, D.W., 1965. A new theilerial parasite of the African buffalo (Syncerus caffer). Bulletin of Epizootic Diseases of Africa, 13, 325–330.
  3. BYARUHANGA, C., COLLINS, N.E., KNOBEL, D., CHAISI, M.E., VORSTER, I., STEYN, H.C. & OOSTHUIZEN, M.C., 2016. Molecular investigation of tick-borne haemoparasite infections among transhumant zebu cattle in Karamoja Region, Uganda. Veterinary Parasitology: Regional Studies and Reports, 3-4, 27-35.
  4. CHAE, J., ALLSOPP, B.A., WAGHELA, S.D., PARK, J., KAKUDA, T., SUGIMOTO, C., ALLSOPP, M.T.E.P., WAGNER, G.G. & HOLMAN, P.J., 1999. A study of the systematics of Theileria spp. based upon small-subunit ribosomal RNA gene sequences. Parasitology Research, 85, 877-883.
  5. CHAISI, M.E., COLLINS, N.E., POTGIETER, F.T. & OOSTHUIZEN, M.C., 2013a. Sequence variation identified in the 18S rRNA gene of Theileria mutans and Theileria velifera from the African buffalo (Syncerus caffer). Veterinary Parasitology, 191, 132-137.
  6. CHAISI, M.E., JANSSENS, M.E., VERMEIREN, L., OOSTHUIZEN, M.C., COLLINS, N.E. & GEYSEN, D., 2013b. Evaluation of a real-time PCR test for the detection and discrimination of Theileria species in the African buffalo (Syncerus caffer). PLoS ONE 8 (10): e75827.doi:10.1371/journal.pone.0075827.
  7. CHAISI, M.E., SIBEKO, K.P., COLLINS, N.E., POTGIETER, F.T. & OOSTHUIZEN, M.C., 2011. Identification of Theileria parva and Theileria sp. (buffalo) 18S rRNA gene sequence variants in the African buffalo (Syncerus caffer) in southern Africa. Veterinary Parasitology, 182, 150-162.
  8. DE KOCK, G., VAN HEERDEN, C.J., DU TOIT, R. & NEITZ, W.O., 1937. Bovine theileriasis in South Africa with special reference to Theileria mutans. Onderstepoort Journal of Veterinary Science, 8, 9–125.
  9. DE VOS, A.J. & ROOS, J.A., 1981. Observations on the transmission of Theileria mutans in South Africa. Onderstepoort Journal of Veterinary Research, 48, 1–6.
  10. DE VOS, A.J., BESSENGER, R. & BANTING, L.F., 1981. Theileria ? taurotragi: A probable agent of bovine cerebral theileriosis. Onderstepoort Journal of Veterinary Research, 48, 177–178.
  11. DOLAN, T.T., 1981. Progress in the chemotherapy of theileriosis. In: IRVIN, A.D., CUNNINGHAM, M.P. & YOUNG, A.S., (eds). Advances in the Control of Theileriosis. The Hague, Boston, London: Martinus Nijhoff Publishers.
  12. EYGELAAR, D., JORI, F., MOKOPASETSO, M., SIBEKO, K.P., COLLINS, N.E., VORSTER, I., TROSKIE, M. & OOSTHUIZEN, M.C., 2015. Tick-borne haemoparasites in African buffalo (Syncerus caffer) from two wildlife areas in Northern Botswana. Parasites & Vectors, 8, 26.
  13. GROOTENHUIS, J.G. & YOUNG, A.S., 1981. The involvement of wildlife in Theileria infections of domestic animals in East Africa. In: IRVIN, A.D., CUNNINGHAM, M.P. & YOUNG, A.S. (eds). Advances in the Control of Theileriosis: Proceedings of an International Conference Held at ILRAD, Nairobi, 9–13 February 1981. The Hague: Martinus Nijhoff Publishers, pp. 71–73.
  14. IRVIN, A.D., BROWN, C.G.D., BURRIDGE, M.J., CUNNINGHAM, M.P., MUSOKE, A.J., PIERCE, M.A., PURNELL, R.E. & RADLEY, D.E., 1972. A pathogenic theilerial syndrome of cattle in the Narok District of Kenya. 1. Transmission studies. Tropical Animal Health and Production, 4, 220–229.
  15. JANSSENS, M.E., 2009. Molecular biological tools for the immunization and diagnosis of Theileria parva. PhD Thesis. Faculteit Wetenschappen, Universiteit Anwerpen, Belgium.
  16. LAWRENCE, J.A., MACKENZIE, P.K.I. & NORVAL, R.A.I., 1981. Isolation of Theileria mutans in Zimbabwe. Zimbabwe Veterinary Journal, 12, 27–30.
  17. LORUSSO, V., WIJNVELD, M., MAJEKODUNMI, A.O., DONGKUM, C., FAJINMI, A., DOGO, A.G., THRUSFIELD, M., MUGEYI, A., VAUMOURIN, E., IGWEH, A.C., JONGEJAN, F., WELBURN, S.C. & PICOZZI, K., 2016. Tick-borne pathogens of zoonotic and veterinary importance in Nigerian cattle. Parasites & Vectors, 9, 217.
  18. MANS, B.J., PIENAAR, R. & LATIF, A.A., 2015. A review of Theileria diagnostics and epidemiology. International Journal for Parasitology: Parasites and Wildlife, 4, 104-118.
  19. MANS, B.J., PIENAAR, R., LATIF, A.A. & POTGIETER, F.T., 2011. Diversity in the 18S SSU rRNA V4 hyper-variable region of Theileria spp. in Cape buffalo (Syncerus caffer) and cattle from southern Africa. Parasitology,138, 766-779.
  20. MANS, B.J., PIENAAR, R., RATABANE, J., PULE, B. & LATIF, A.A., 2016. Investigating the diversity of the 18S SSU rRNA hyper-variable region of Theileria in cattle and Cape buffalo (Syncerus caffer) from southern Africa using a next generation sequencing approach. Ticks and Tick Borne Diseases 7, 869-879.
  21. MOLL, G., LOHDING, A. & YOUNG, A.S., 1984. Epidemiology of theileriosis in the Trans-Mara Division, Kenya. Husbandry and disease background and preliminary investigations on theilerioses in calves. Preventive Veterinary Medicine, 2, 801–832.
  22. MOLL, G., LOHDING, A., YOUNG, A.S. & LEITCH, B.L., 1986. Epidemiology of theileriosis in calves in an endemic area of Kenya. Veterinary Parasitology, 19, 255–274.
  23. MUHANGUZI, D., MATOVU, E. & WAISWA, C., 2010. Prevalence and characterization of Theileria and Babesia species in cattle under different husbandry systems in western Uganda. International Journal of Animal and Veterinary Advances, 2, 51-58.
  24. NJIIRI, N.E., BRONSVOORT, B.M., COLLINS, N.E., STEYN, H.C., TROSKIE, M., VORSTER, I., THUMBI, S.M., SIBEKO, K.P., JENNINGS, A., VAN WYK, I.C., MBOLE-KARIUKI, M., KIARA, H., POOLE, E.J., HANOTTE, O., COETZER, K., OOSTHUIZEN, M.C., WOOLHOUSE, M. & TOYE, P., 2015. The epidemiology of tick-borne haemoparasites as determined by the reverse line blot hybridisation assay in an intensively studied cohort of calves in western Kenya. Veterinary Parasitology, 210, 69-76.
  25. OURA, C.A.L., BISHOP, R.P., WAMPANDE, E.M., LUBEGA, G.W. & TAIT, A., 2004. Application of a reverse line blot assay to the study of haemoparasites in cattle in Uganda. International Journal for Parasitology, 34, 603-613.
  26. OURA, C.A.L., TAIT, A., ASIIMWE, B., LUBEGA, G.W. & WEIR, W., 2011a. Haemoparasite prevalence and Theileria parva strain diversity in Cape buffalo (Syncerus caffer) in Uganda. Veterinary Parasitology,175 , 212-219.
  27. OURA, C.A.L., TAIT, A., ASIIMWE, B., LUBEGA, G.W. & WEIR, W., 2011b. Theileria parva genetic diversity and haemoparasite prevalence in cattle and wildlife in and around Lake Mburo National Park in Uganda. Parasitology Research, 108, 1365-1374.
  28. PALING, R.W., GROOTENHUIS, J.G. & YOUNG, A.S., 1981. Isolation of Theileria mutans from Kenyan buffalo, and transmission by Amblyomma gemma. Veterinary Parasitology, 8, 31–37.
  29. ROBSON, J., PEDERSEN, V., ODEKE, G.M., KAMYA, E.P. & BROWN, C.G.D., 1977. East Coast fever immunization trials in Uganda: Field exposure of Zebu cattle immunized with three isolates of Theileria parva. Tropical Animal Health and Production, 9, 219–231.
  30. SIVAKUMAR, T., HAYASHIDA, K., SUGIMOTO, C. & YOKOYAMA, N., 2014. Evolution and genetic diversity of Theileria. Infection, Genetics and Evolution, 27, 250-263.
  31. SNODGRASS, D.R., TREES, A.J., BOWYER, W.A., BERGMAN, J.R., DAFT, J. & WALL, A.E., 1972. East Coast fever: Field challenge of cattle immunized against Theileria parva (Muguga). Tropical Animal Health and Production, 4, 142–151.
  32. THEILER, A., 1906. Piroplasma mutans (n. spec.) of South African cattle. Journal of Comparative Pathology and Therapeutics, 19, 292–300.
  33. UILENBERG, G., 1983. Acquisitions nouvelles dans la connaisance du rôle vecteur de tiques du genre Amblyomma (Ixodidae). Revue d’Élevage et de Médecine Vétérinaire des Pays Tropicaux, 36, 61–66.
  34. UILENBERG, G., PERIÉ, N.M., SPANJER, A.A.M. & FRANSSEN, F.F.J., 1985. Theileria orientalis, A cosmopolitan blood parasite of cattle: Demonstration of the schizont stage. Research in Veterinary Science, 38, 352–357.
  35. UILENBERG, G., ROBSON, J. & PEDERSEN, V., 1974. Some experiments on the transmission of Theileria mutans (Theiler 1906) and Theileria parva (Theiler 1904) by the ticks Amblyomma variegatum (Fabricius 1794) and Rhipicephalus appendiculatus Neumann 1901, in Uganda. Zeitschrift für Tropenmedizin und Parasitologie, 25, 207–216.
  36. UILENBERG, G., SILAYO, R.S., MPANGALA, C., TONDEUR, W., TATCHELL, R.J. & SANGA, H.J.N., 1977. Studies on Theileriidae (Sporozoa) in Tanzania. X. A large-scale field trial on immunization against cattle theileriosis. Tropenmedizin und Parasitologie, 28, 499–506.
  37. WALKER, A.R., BOUATTOUR, A., CAMICAS, J.-L., ESTRADA-PEÑA, A., HORAK, I.G., LATIF, A.A., PEGRAM, R.G. & PRESTON, P.M., 2013. Ticks of domestic animals in Africa: a guide to identification of species. Bioscience Reports, Edinburgh Scotland,U.K.
  38. WOOLHOUSE, M.E.J., THUMBI, S.M., JENNINGS, A., CHASE-TOPPING, M., CALLABY, R., KIARA, H., OOSTHUIZEN, M.C., MBOLE-KARIUKI, M.N., CONRADIE, I., HANDEL, I.G., POOLE, E.J., NJIIRI, E., COLLINS, N.E., MURRAY, G., TAPIO, M., AUGUET, O.T., WEIR, W., MORRISON, W.I., KRUUK, L.E.B., BRONSVOORT, B.M.C., HANOTTE, O., COETZER, K. & TOYE, P.G., 2015. Co-infections determine patterns of mortality in a population exposed to parasite infection. Science Advances, 1, e1400026. Doi: 10.1126/sciadv.1400026.
  39. YOUNG, A.S., 1985. Immunization of cattle against theileriosis in the Trans-Mara division of Kenya. A comparison of trials under traditional Maasai management with trials on a ranch development. In: IRVIN, A.D., (ed.). Immunization against Theileriosis in Africa. Nairobi: International Laboratory for Research on Animal Diseases.
  40. YOUNG, A.S., BURRIDGE, M.J. & PAYNE, R.C., 1977. Transmission of a Theileria species to cattle by the ixodid tick, Amblyomma cohaerens (Donitz 1909). Tropical Animal Health and Production, 9, 37–45.
  41. YOUNG, A.S., GROOTENHUIS, J.G., KIMBER, C.D., KANHAI, G.K. & STAGG, D.A., 1977. Isolation of a Theileria species from eland (Taurotragus oryx) infective for cattle. Tropenmedizin und Parasitologie, 28, 185–194.
  42. YOUNG, A.S., PURNELL, R.E., PAYNE, R.C., BROWN, C.G.D. & KANHAI, G.K., 1978. Studies on the transmission and course of infection of a Kenyan strain of Theileria mutans. Parasitology, 67, 99-115.