Open access peer-reviewed chapter

Oriental Theileriosis

Written By

Jerald Yam, Daniel R. Bogema and Cheryl Jenkins

Submitted: May 3rd, 2018 Reviewed: August 29th, 2018 Published: November 5th, 2018

DOI: 10.5772/intechopen.81198

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Abstract

Theileria orientalis, the causative agent of oriental theileriosis, is an apicomplexan haemoparasite and is one of several tick-borne Theileria spp. infecting cattle. Unlike the highly pathogenic transforming Theileria species (T. annulata and T. parva) which induce uncontrolled lymphocytic proliferation, T. orientalis is a non-transforming strain exerting its major pathogenic effects via erythrocyte destruction. Clinical symptoms associated with oriental theileriosis are largely consequences of the underlying anaemia. Because of its non-transforming nature, T. orientalis was previously considered a benign parasite, however, in the recent years, clinical outbreaks of T. orientalis have been increasingly observed throughout Asia and Australasia. Recent rapid spread of clinical theileriosis has been linked to a pathogenic genotype of the parasite, genotype Ikeda (Type 2). The geographic distribution of clinical outbreaks correlates to the range of the major vector tick, Haemaphysalis longicornis, although other vectors and modes of transmission are possible. This review includes discussion of T. orientalis epidemiology, transmission, pathogenesis, treatment and control and provides an update on the taxonomy of this organism which is still under debate.

Keywords

  • Theileria orientalis
  • cattle
  • taxonomy
  • epidemiology
  • transmission
  • control

1. Introduction

T. orientalishas been reported to cause mortality in up to 5% of infected cattle. Clinical outbreaks commonly occur when naïve cattle are introduced into endemic herds, when animals undergo stress through transportation or are immunosuppressed. Pregnant heifers and calves are particularly susceptible to infection, with late term abortions also commonly reported. The parasite is globally spread but countries impacted by clinical theileriosis include Australia, New Zealand, Japan, Korea, China and Vietnam [1, 2, 3]. Oriental theileriosis represents a major economic burden to cattle production. In Australia in 2010 the economic impact of the parasite was estimated at $20 million AUD per annum. However, the costs associated with disease are likely to have increased substantially since that time with the subsequent spread of bovine theileriosis into new areas of the country. In New Zealand, although the total economic impact has not been well established, clinical outbreaks were estimated to cost up to $NZ 1 million on a single large dairy farm [4]. Recently, clinical outbreaks of theileriosis were documented for the first time in dairy cattle undergoing transport stress during importation to Vietnam from Australia [3], highlighting the potential importance of this disease in the live cattle trade. In countries like Japan and China where multiple tick species have been identified as potential disease vectors, economic impacts have been significant [5, 6].

The lack of preventive measures or suitable vaccines complicates the management of T. orientalis. Currently, there are limited therapeutic options available for treatment of oriental theileriosis and no vaccines available for this disease globally. Vaccine and/or therapeutic development has been identified as a research priority for bovine theileriosis; however as in malaria studies, an understanding of the taxonomy and genetic variability within parasite populations is essential to ensure vaccine and therapeutic efficacy.

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2. Taxonomy of T. orientalis

2.1 Taxonomic history of T. orientalis

Historically, the taxonomy of T. orientalis(formerly referred to as the Theileria orientalis/sergenti/buffeligroup) has been a subject of some confusion, due to similarity in strain morphology, variability of host animals and transmission vectors, occurrence of mixed infections, parasite genetic diversity and the difficulty in extracting pure isolates for studies, especially in benign infections where parasitaemia is low [7]. Originally, these parasites were classified based on geographic origin [8, 9]. Further attempts to classify this group of parasites led to suggestions that the group should be classified into one species [1, 8, 9, 10, 11]. More recently, variations in the major piroplasm surface protein (MPSP) gene have been used to classify members of the T. orientalisgroup, separating it into 11 genotypes [1].

Members of the Theileria orientalisgroup were first identified in Australian cattle in 1910 and the organism classified as T. mutans[12] due to the morphological similarity to the previously described African species [13]. Some years later, Wenyon [14] made the first description of a similar blood parasite from sheep and named it Babesia sergenti. The morphological drawings of B. sergenti[9] corresponded to Theileriaspp. morphology and it was later found that the parasite he described was indeed a theilerial parasite of sheep [15, 16]. However, in the intervening years, a new parasite of cattle in Eastern Siberia was described and T. sergenti[17]. The sheep parasite thus has precedence with respect to the name T. sergenti,rendering this name invalid for the cattle parasite; nonetheless the name T. sergentihad been used widely for this organism in the literature. Following the initial description of “T. sergenti” in Siberian cattle, a similar cattle haemoparasite was found in the same area and the authors named it T. orientalis[18].

Serological and morphological studies [19] later revealed that the T. mutansisolate identified in Australia [12] was the same species as “T. sergenti”[17] and not the African T. mutansdescribed by [8]. Authors [15] suggested that the Australian isolate was either T. orientalis[18] or T. buffeli[20]. Serological and morphological studies conducted on Theileriastocks from Australia, Britain, Iran, Japan, USA and a higher pathogenicity stock from Korea concluded that the nomenclature of Australian Theileriashould be T. orientalis[8]. But, a few authors still propose that the name T. buffelishould be designated due to the transmission of parasite from buffalo to cattle and the fact that isolates characterised at that point of time were all infective for buffalo [11, 21, 22]. Studies in Japan suggested T. orientalisand T. buffelito be separated from T. sergentiand be classified as a different group due the serological and transmissibility differences [9, 23, 24]. Regardless of these findings, it was concluded that designation of the name T. sergentishould not be used for any blood parasite of ruminants with the exception of sheep [15, 16, 22].

2.2 Taxonomic classification using molecular techniques

As serological and morphological techniques were not suitably discriminatory for distinguishing isolates from the Theileria orientalis/sergenti/buffeligroup, molecular techniques became more prevalent. The use of the MPSP and 18S rRNA genes further clarified the relationships within this taxonomic group. Early PCR analysis of the MPSP gene revealed four major genotypes, Ikeda, Chitose and Buffeli and Thai type [25, 26]. The Buffeli genotype type was also separated into sub-genotypes B1 and B2 due to variability observed between these isolates [25]. Genotyping of the V4 variable region with the 18S rRNA gene which was previously shown to enable classification of Theileriaspp. [27] revealed seven genotypes (Genotypes A to G) [28]. Subsequent examinations of Theileria orientalis/sergenti/buffeligroup taxonomy utilised MPSP sequences due to greater observed sequence variation, producing stronger branch support in phylogenetic analyses [29, 30]. By 2010, eight MPSP genotypes (1–8) were classified including the unclassified genotype from Brisbane, Australia (T. buffeliWarwick) [29, 30, 31]. MPSP genotype 6 found in cattle and yak was reclassified and the taxonomic name Theileria sinensiswas suggested to reflect divergence from the other members of the Theileria orientalis/sergenti/buffeligroup [6, 32]. Three new genotypes from sheep, water buffalo and cattle were further identified [33] in Vietnam (N1, N2 and N3 respectively) bringing to current number of classified MPSP genotypes to 11 (Types 1–8 and N1–N3). Retrospective analysis of the genotypes previously identified with the 18S rRNA gene [28] against the current MPSP genotyping scheme shows that genotype A corresponds to Chitose while genotypes B and E correspond to Ikeda. 18S rRNA Genotypes C and D correspond to the Buffeli and Type 6 MPSP genotypes respectively. Further analysis revealed the 18S rRNA genotypes F and G identical to Theileria cervia species found in elk. Buffeli sub-genotypes B1 and B2 identified in [25] correspond to the MPSP buffeli genotype and Type 4 respectively.

Molecular examinations have considerably clarified the taxonomy of T. orientalis. Asian isolates previously referred to as T. sergentiwere found to be a mix of MPSP genotypes that were also commonly found in T. buffeliand T. orientalisisolates. Both Types 1 (Chitose) and 3 (Buffeli) were commonly found in both Australia and East Asia, with Type 3 spread globally. Hence more recent studies have begun to refer to this group by the common name T. orientalis[1, 34, 35].

Great efforts have been made by researchers to genetically characterise T. orientalis. However, current genetic characterisation methods utilise relatively few molecular markers. It has been well established that the primary mechanism driving genetic diversity in apicomplexans is through the sexual recombination; in the case of Theileriaparasites, this occurs within the tick vector. Recombination has been relatively poorly studied in T. orientalis, however it has been suggested that recombination between MPSP genotypes is unlikely due to the low sequence identities between types [33] and high sequence identities within each clade [1, 31, 36, 37].

2.3 Current taxonomic state of T. orientalis

Genetic diversity within and between the MPSP genotypes should be further investigated as it has the potential to resolve the controversy surrounding the taxonomic classification of T. orientalis,elucidate virulence factors driving differential pathogenicity, and has implications for vaccine design. A complete genome of T. orientalis(Ikeda) has now been sequenced and annotated and is available for further research [34], and whole genome sequencing of large numbers of isolates is now feasible. A recent study which presented draft genomes of Australian isolates of Ikeda, Chitose and Buffeli genotypes confirmed the MPSP phylogenies indicating that the apathogenic Chitose and Buffeli genotypes are more closely related to each other than to the pathogenic Ikeda genotype [37]. That study further suggested that T. orientalismay indeed encompass multiple species and subspecies. The average nucleotide identity (ANI) between the Ikeda genome and those of the Chitose and Buffeli genotypes (82%) was comparable to that of T. annulataand T. parva(80%). While sequencing of additional representatives of these genotypes is desirable, the evidence from the ANIs combined with the differential pathogenicity of these genotypes suggests that T. orientalisIkeda is a separate species to T. orientalisChitose and T. orientalisBuffeli. Moreover, the ANI between T. orientalisChitose and T. orientalisBuffeli (86%) was comparable to that of the murine Plasmodiumspp. suggesting that there may be further species or subspecies-level diversity within T. orientalisgenotypes. [37]. Whole genome sequencing of additional T. orientalisgenotypes is warranted to determine whether a new species designation should be applied to T. orientalisIkeda and whether this may extend to include the phylogenetically related Type 7 which has also been associated with clinical disease [38]. Additional genome-wide studies will also enable researchers to formulate vaccine strategies by characterising possible vaccine targets and allow genetic diversity investigations within parasite populations [1]. Current efforts to understand the recombination mechanisms of other species of Theileriathat lead to genetic diversity and taxonomic uncertainties [39, 40, 41] have been fruitful and it warrants researchers to conduct further investigations to answer the taxonomic questions surrounding T. orientalis.

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3. Epidemiology

T. orientalisis a cosmopolitan parasite of cattle that also affects buffaloes and yaks [8]. T. orientalisinfections have been globally reported in Australia [42, 43, 44, 45], New Zealand [46], Southeast Asia [3, 33, 47, 48, 49, 50] East Asia [6, 29, 30, 31, 36], South Asia [38, 51, 52, 53], Middle East [54, 55, 56], Africa [57, 58, 59], Europe [8, 60, 61, 62, 63, 64, 65] and the Americas [1, 10, 66]. The distribution of Theileriaspecies is dependent on the availability and competence of suitable tick vectors [7]. The principle vector of T. orientalis, H. longicornis,can be found in most of the countries where disease outbreaks have been reported (Table 1). In countries where distribution of H. longicornisis sparse or where the species is not known to occur, other Haemaphysalisspp. or other genera of ixodid ticks (Table 1) have been identified to be capable of transmitting the parasite, although the comparative competency of these species is unclear. The significance of these ticks as vectors of T. orientaliswarrants further investigation.

CountryT. orientalisMPSP genotypesHost speciesVectorsReferences
Australia1, 2, 3, 5CattleH. longicornis[1, 42, 44]
New Zealand1, 2, 3, 5CattleH. longicornis[46, 67]
Japan1, 2, 3, 4, 5, 7, 8CattleH. longicornis, H. mageshimaensis, H. douglasi, I. persulcatus, I. ovatus[5, 29, 34, 36, 68, 69, 70]
Korea1, 2, 3, 4, 5, 8CattleH. longicornis[30, 71, 72, 73, 74]
Taiwan3CattleH. longicornis[31]
Vietnam1, 2, 3, 5, 7, N3CattleRhipicephalus microplus[3, 33, 49]
5, N1, N2Water buffaloUnspecified
N1SheepUnspecified
Indonesia7CattleUnspecified[48]
Thailand1, 3, 5, 6, 7, N3CattleUnspecified[10, 47, 75]
1, 3, 4, 5, 7, N2, N3Water buffaloUnspecified
Cambodia1, 3CattleUnspecified[49]
Myanmar1, 3, 4, 5, 7, N3CattleR. microplus, Haemaphysalisspp.[50]
PhilippinesUnspecified, but possible Type 1 and/or Type 3CattleUnspecified[76, 77]
India1, 3, 7CattleH. bispinosa, R. microplus[38, 52]
N2Water buffaloR. microplus[53]
Sri Lanka1, 3, 5, 7CattleUnspecified[1, 51]
N1, N2Water buffaloUnspecified
China1, 2, 3, 5, 6, 8CattleH. longicornis, H. qinghaiensis[6, 32, 78, 79, 80]
3Water buffaloH. longicornis
6YakH. qinghaiensis
Mongolia1, 3, 5, 7, N3CattleDermacentor nuttalli[36]
Russia1CattleH. longicornis[60]
Egypt1, 2CattleUnspecified[56]
2Water buffaloUnspecified
Kenya3, 5CattleUnspecified[58]
United Kingdom3CattleH. punctata[1, 8]
Italy1, 3CattleR. bursa[62]
HungaryUnspecified, PCR of 18S rRNA was done to identify presence of T. orientalisCattleH. punctata[65]
PortugalUnspecified, RLB assay was done to identify presence of T. orientalisCattleH. punctata[64, 81]
SpainUnspecified, RLB assay was done to identify presence of T. orientalisCattleHaemaphysalisspp.[63]
GreeceUnspecified, IFAT—Indirect fluorescent antibody test for T. orientalisantigensCattleH. punctata[61]
Brazil1, 2, 3, 4, 5, 7, N2 ,N3CattleR. microplus[1]
UnspecifiedWater buffaloR. microplus[66]
USA6CattleUnspecified[1, 10]
Ethiopia1, 2, 3, 5CattleUnspecified, but T. orientalisDNA found in Amblyommaand Rhipicephalusspecies[59]
IranUnspecifiedCattleH. punctata, H. longicornis[55, 82]
Turkey1, 3CattleHyalomma excavatum, R. annulatus[54, 62]
Central AfricaUnspecifiedCattleA. variegatum[57]

Table 1.

The global distribution of T. orientalisMPSP genotypes reported in four different host species and the possible transmission vectors.

Majority of the unspecified vectors were suggested to be Haemaphysalisspp. MPSP genotypes Type 1 = Chitose, Type 2 = Ikeda, Type 3 = Buffeli. The other eight genotypes (4–8 and N1–N3) have yet to be named.

3.1 Clinical disease outbreaks: Japan, Australia, New Zealand

In Japan, T. orientalissourced from grazing cattle in Hokkaido was reported to cause 0.1% and approximately 2.5% of mortality and morbidity respectively [83]. In 2009, PCR analysis of the MPSP and p23 gene of T. orientalisrevealed the presence of at least four genotypes (1, 2, 4 and 5) [29]. Further analysis [68] revealed Type 3 (Chitose) to be present in Japan and with earlier studies the authors suggested a total of seven genotypes (1–3, 4, 5, 7 and 8) to be present [69, 84]. Studies conducted over a number of years implicated T. orientalisIkeda (Type 2) as being linked to clinical disease [42, 83, 85].

In recent years, outbreaks of oriental theileriosis have been increasingly observed in a number of different countries and are usually identified as being associated with MPSP genotype Ikeda (Type 2) [29, 45, 46, 68]. Australia and New Zealand recently experienced major disease incursions linked to T. orientalisIkeda despite other genotypes of the parasite being present in these countries for many years.

T. orientaliswas first observed in Australian herds in 1910, and the introduction was linked to the importation of T. orientalisinfected H. longicornisticks on cattle from Japan [86, 87]. Surveys of cattle in New South Wales (NSW, Australia) performed in the mid-20th century revealed the presence of T. orientalisin 60% of examined blood smears [42, 86] and later studies found herd and individual animal seroprevalence of 75% and 41% respectively in endemic parts of Queensland [42, 87]. The parasite was considered to be relatively benign as it caused only mild anaemia [42]. Prior to 2006, reports of clinical theileriosis in Australia were rare and experimental transmission studies were unable to establish clinical infection in test animals, suggesting that Australian strains of T. orientaliswere of the benign Buffeli genotype [8, 22, 42, 88]. Samples from cattle imported into Japan from Australia were shown to be positive for the Chitose genotype by MPSP restriction fragment length polymorphism (RFLP), showing evidence that Chitose was present in Australia prior to 1998 [31]. However, since 2006, there was a large increase in clinical T. orientalisoutbreaks in coastal and highlands regions of NSW [44, 89] and other parts of Australia such as Queensland [43], Victoria [90, 91], Western Australia [92] and South Australia [93, 94] (Figure 1A). Most clinical theileriosis outbreaks were linked to the movement of periparturient cattle from inland areas to the coast and the introduction of naïve cattle into endemic areas and/or introduction of infected cattle to T. orientalisnon-endemic areas [2, 42, 89]. Large scale surveillance efforts identified the Ikeda genotype as the sole infecting type or as a mixed infection with other genotypes in all herds examined [43, 44, 45, 90].

Figure 1.

Map of Australia (A) and New Zealand (B) showing the extent of spread of theileriosis during the recent disease incursions in each respective country. The areas in whichT. orientalisIkeda is enzootic closely mirrors the distribution of the vector tickH. longicornis.

T. orientaliswas first reported in New Zealand in 1982 [95] with suggestions that the parasite could have been introduced through the importation of cattle from Britain or Australia where the parasite was prevalent. Prior to 2012, the Ikeda genotype was not associated with clinical theileriosis in New Zealand. Since then outbreaks of T. orientalisof the Ikeda genotype have been reported in beef and dairy cattle herds in multiple regions of the North Island [96, 97]. In 2012, genotyping tests conducted on affected cattle herds of T. orientalisoutbreaks further revealed three other genotypes present, Chitose, Buffeli and Type 5 [97]. Of the four genotypes, Ikeda was identified to be more pathogenic than Chitose and Buffeli in New Zealand [67]. Prevalence and spatial distribution studies showed T. orientalisIkeda to predominantly occur in the Northland (33 out of 35 herds; 94%) and Auckland and Waikato regions (63 out of 191 herds; 33%) where the transmission vector, H. longicornisis known to occur [96, 98] (Figure 1B). Only 2 out of 204 (1%) herds tested positive for T. orientalisIkeda in the South Island of New Zealand where the distribution of H. longicornisis sparse and less common [96, 98].

3.2 Global distribution of T. orientalis

The geographic distribution of T. orientalisMPSP genotypes was previously reviewed by [1]. Since then, new clinical cases have been reported in Ethiopia [59] where T. orientaliswas not known to occur, Type 5 was identified in cattle in Kenya [58], Type 2 Ikeda was recently identified in Vietnam via cattle imported from Australia [3], and studies in Kerala, India, revealed for the first time that MPSP genotype N2 to cause clinical theileriosis in Asian water buffaloes [53]. The majority of molecular distribution studies are based on the genetic characterisation of the T. orientalisMPSP gene. Some studies utilise other molecular markers such as the ITS 1, ITS 2, COX III and 18S rRNA genes to identify or characterise the parasite [46, 66, 99]. Studies based on molecular markers other than MPSP could not accurately classify MPSP genotypes, therefore, the identity of the MPSP genotypes found in some studies remain unclear [1].

As described above, most studies have implicated T. orientalisIkeda (Type 2) in oriental theileriosis outbreaks [29, 43, 46, 68]. However, some studies have suggested MPSP genotypes Chitose (Type 1) [46, 74] and 7 [38] to be associated with clinical disease. The clinical relevance of these genotypes cannot be confirmed as COX III and 18S rRNA genes were used to characterise the samples instead of the MPSP gene in one study [46] or the possibility of mixed infections with Ikeda genotype was not investigated [1, 38, 74]. Nonetheless, Type 7 is phylogenetically related to the Ikeda genotype [1], and may indeed represent a pathogenic genotype and should be the subject of further study. MPSP genotype N2 seems to be predominant among water buffalo populations although it has also been reported in cattle in Brazil. Type N2 was identified to cause fatal oriental theileriosis in Asian water buffaloes [53] but its virulence against cattle and other animals is unclear. Further distribution studies are required in order to determine host specificity of type N2. Cross-infection profiles between host animals in different countries may vary. For example, in India, Types 1, 3 and 7 are found in cattle and only type N2 is found in water buffaloes. But, in Thailand, Types 1, 3, 5, 7 and N3 can be found in both cattle and water buffaloes [47, 75]. This suggests that the tick vectors of a specific region may display host specificity limiting transmission to the preferred host or the tick vectors may have different preference for different genotypes. Previously, studies on T. parvahave demonstrated that different tick populations have different preference for particular genotypes [39]. Whether this holds true for T. orientalisremains unclear, and warrants further investigation.

3.3 Vectors of T. orientalis

Although, the ixodid tick, Haemaphysalis longicornis, is considered to be the principal vector of T. orientalis[5, 67, 89, 94], the parasite has been detected in other arthropods such as mosquitoes [100] and lice [94, 101, 102]. Several studies have also revealed several possible tick vectors other than H. longicornis(Table 1). Prior to the recent Australian T. orientalisoutbreak, H. bancroftiand H. humerosa[103, 104, 105, 106] were found to be more competent and efficient vectors compared to H. longicornisunder experimental conditions, although it is noted that the H. humerosaused in these studies were latterly believed to be H. bremneri[106, 107]. These studies employed the ‘Warwick stock’ of T. orientaliswhich is of the Buffeli genotype. Interestingly, the extent of spread of clinical theileriosis in Australia (Figure 1A) caused by T. orientalisIkeda corresponds very well to the known range of H. longicornisrather than to that of H. bremneri, H. bancroftior indeed, H. humerosaFurthermore, studies on a range of tick species collected from the Gippsland region of Victoria, within the theileriosis endemic zone, only detected the presence of T. orientalisin H. longicornis[94]. Similarly, in New Zealand, disease is only detected within the known range of H. longicornis(Figure 1B) and indeed, H. longicornisis the only Haemaphysalistick present in that country [98]. In parts of Australia, T. orientalisBuffeli and Chitose are known to occur outside the areas in which disease in enzootic and outside the known range of H. longicornis.Together, these findings suggest that different ticks transmit different genotypes of T. orientaliswith different efficiencies or that the tick species displays variable selection for the different genotypes. In T. parva, particular genotypes have been shown to be favoured when passaged through different tick clones, suggesting that these genotypes are selected for in tick vectors [39]. Also in China, T. sinensisis limited to the surrounding regions of the Tibetan plateau [108] as the vector H. qinghaiensisis limited to this region [6]. Indeed, recent genome sequencing studies revealed that the Ikeda, Chitose and Buffeli genotypes are sufficiently divergent to be considered different species or subspecies [37] and therefore may be adapted to different tick hosts. Vector competency for the different genotypes aside from T. orientalisBuffeli [87, 104, 105] have not yet been investigated in detail.

Currently, information on tick species transmitting disease is somewhat confounded because the vector competency for the different genotypes has not been thoroughly investigated. In Japan, H. megaspinosa, H. douglasi, I. persulcatusand I. ovatushave been identified as other potential vectors of T. orientalis[5]. Additionally, these four ticks were found to preferentially transmit the pathogenic T. orientalisIkeda [42]. In Europe, H. punctataseems to be the predominant tick vector to transmit T. orientalis[8, 61, 64, 65, 81], but in other geographical locations such as East Asia [5, 6], Australia [94] and New Zealand [98], H. longicornisis identified as the predominant tick vector. Although only limited molecular surveys have been undertaken in Europe, T. orientalisIkeda has not been identified in this region. The specific relationship between type Ikeda and H. longicornis,in Japan [5], China [6], Australia [94] and New Zealand [98] where the Ikeda genotype is limited to H. longicornisdistribution, combined with the absence or sparse distribution of H. longicornisin Europe [109], suggests that the Ikeda genotype may have a specific relationship with H. longicornis.

The epidemiology of T. orientalisis important as it enables researchers to understand distribution patterns and set up appropriate biosecurity measures. It is clear that there are gaps in the current knowledge of T. orientalistransmission and distribution. Further research is essential to identify potential tick vectors that may preferentially transmit certain MPSP genotypes of T. orientalis. Molecular characterisation and investigations of the MPSP genotypes coupled with whole genome studies could provide insights on the pathogenicity and genetic diversity, therefore enabling the implementation of efficient control strategies against this emerging disease agent.

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4. Lifecycle and transmission

Evidence suggests that H. longicornisis a major vector of T. orientalis. This species is a three host tick meaning that each life stage of the tick will feed on a different host before each moult. H. longicornisparasitises cattle and other domestic ruminants [98, 110] and it undergoes obligate parthenogenesis to reproduce, as the adult female is able to lay fertile eggs in the absence of a male [111]. The three host lifecycle of H. longicornishas four life stages, an egg, larvae, nymphal and adult stage. Eggs hatch 30–90 days after being laid. The hatched larvae begin questing for its blood meal by climbing vertically on blades of grass to seek a host. H. longicornishave enhanced survivability as they are not specific in feeding even though they have a preference for cattle. Each engorgement occurs for 3–4 days before the tick falls to the ground and moults to the next stage.

In the tick vector, the Theilerialifecycle begins with blood engorgement on a mammalian host during which infected erythrocytes containing piroplasms are ingested by the tick. These piroplasms differentiate into gametocytes in the midgut of the tick and undergo a brief sexual stage to form zygotes that enter the gut epithelial cells. Motile kinetes are developed by meiotic division within the gut epithelial cells. Following meiosis, the parasite escapes into the haemolymph during the tick moulting phase and migrates to the salivary glands where sporogony occurs. Theileriakinetes invade salivary cells, develop into sporoblasts, and then into infectious sporozoites which are injected into the mammalian host when the moulted tick feeds again [112]. Sporozoites are inoculated into the mammalian host through the hypostome of the feeding tick. In T. parvaand T. annulata, sporozoites invade the mammalian host leukocytes to develop multinucleate syncytial schizonts. At this point Theileriaspp. can be separated into two evolutionary groups based on their ability to transform host leukocytes leading to clonal expansion of infected lymphoid cells [113]. Unlike T. parvaand T. annulata, T. orientalisdoes not transform the invaded leukocytes. The schizonts undergo merogony to develop merozoites and rupture the leukocytes to invade the erythrocytes and form piroplasms [114]. When the tick feeds on the infected mammalian host, the T. orientalislifecycle is completed.

Transmission of T. orientalisin the tick is transstadial, as the parasite can be transmitted from one instar to the next. Ticks that ingest erythrocytes infected with piroplasms transmit the parasite when they moult to the next instar [115]. Transovarial transmission, parasite transmission from adult female to the next generation of eggs, has yet to be scientifically demonstrated [103] by any transmission studies although some researchers have speculated that Theileriamight involve transovarial transmission in ticks [116, 117].

Interestingly, T. orientalisinfection dynamics varies depending on the genotype transmitted. A study on T. orientalistemporal dynamics in 10 animals revealed that Ikeda was detected first when naïve animals are exposed to herds infected with a mix of Ikeda, Chitose and Buffeli genotypes [35]. Thus the Ikeda genotype possesses a shorter pre-patent period than the other two genotypes, which may be due to a faster growth rate, out-competition of the other genotypes, or perhaps more efficient transmission by the tick vector [35]. Similar observations were made in temporal monitoring of mixed Ikeda and Chitose infections in experimentally infected cattle in Japan [25, 118].

Transplacental parasite transfer from pregnant cattle to offspring through the placenta has been confirmed through molecular and serological methods for a range of Theileriaspp. This mode of transmission has been demonstrated in species such as T. annulata[119] T. equi[120, 121], and T. lestoquardi[122]. Transplacental transmission also occurs in T. orientalisinfection [71, 123, 124]. Early studies [123] used blood film examination to demonstrate that transplacental transmission occurs in calves but at a low rate of 5% (5/100 calves that are 1–2 days old). The authors also determined the parasitaemia of newborn calves and post-grazing calves to be similar and suggested the low levels of parasitaemia in newborn calves to be ineffective in producing immunity against T. orientalis[123]. In contrast, 100% of the calves (n = 5) from experimentally infected dams were demonstrated to be T. orientalispositive and infected dams sometimes aborted the calves (two out of five dams) at approximately 6–7 months of gestation [71]. However, the dams in the study had an extremely high tick burden of approximately 200 ticks which had been artificially fed on cows with high parasitaemia [71]. In contrast, another recent study in New Zealand [125] did not detect transplacental transmission despite using sensitive molecular techniques. Recently, an Australian study [124] used molecular methods to confirm transplacental transmission of T. orientalisin field-affected cattle, but at low rate of approximately 2% (2/98 calves) similar to the study of [123]. In that study, abortion did not appear to correlate with transplacental transmission of T. orientalis, instead the authors posited that, abortion may occur due to hypoxia in the foetal calves due to maternal anaemia, placental insufficiency, or other factors related to maternal pathology [123].

In addition to ticks, T. orientaliscan also transmit mechanically through the inoculation of infected blood [8, 101] or via other biting arthropods such as the sucking louse (Linognathus vituli) [102, 126] and potentially the horse flies (Tabanus trigeminus) and stable flies (Stomoxys calcitrans). These biting arthropods have been hypothesised to be able to mechanically transmit T. orientalisthrough the proboscis of the biting flies or regurgitation of blood into the animal host [101, 102, 126]. In Australia, TheileriaDNA was not detected in March flies (Dasybasissp.) collected in outbreak regions in Gippsland, Victoria [94]; however, T. orientaliswas detected in mosquitoes collected from the same area. In addition, a xenosurveillance study in the United Kingdom has revealed T. orientalisin 16 out of 105 (15.2%) blood meals in mosquitoes [100]. The risk of transmission by mechanical vectors is likely to be dependent on the parasitaemia of the infected blood being transferred by these biting arthropods [101].

Mechanical transmission through routine husbandry practices is another potential method of T. orientalistransmission. A recent Australian study showed that T. orientaliscould be mechanically transmitted with volumes as low as 0.1 mL of blood and persist for at least 5 months in the infected bovine after blood inoculation [101]. Thus, injuries sustained during yarding and transport of cattle, or routine husbandry procedures such as vaccination, blood transfusion, castration or ear notching performed where contaminated instruments are re-used can result in iatrogenic transfer of T. orientalisinfection. Aside from blood transmission, there is potential for mechanical transfer of the parasite via the oral route. Dam to calf transfer of the apicomplexan Neospora caninumhas been suggested to occur via the colostrum with pathogen entry via the oral mucosa. Recent findings that T. orientalisis present in colostrum raise the possibility that a similar mode of transfer may be possible by this species in calves, although this is yet to be confirmed [101].

Although there is now clear evidence from a number of studies that T. orientaliscan be transmitted mechanically, including by haematophagous arthropods, this mode of transmission would not be expected to maintain the parasite life cycle. Mechanical transfer bypasses the sexual stage of the lifecycle where genetic recombination occurs. The direct transfer of haploid stage piroplasms from one host to another may result in reduced genetic diversity, a feature of apicomplexans which facilitates immune evasion [127, 128, 129]. Thus, mechanical transmission of T. orientalismay allow the organism to persist in the herd when tick numbers are low, but passage through the tick is likely to be important for the overall survivability of the parasite [101].

Although different forms of T. orientalistransmission have been identified, more research is required in order to increase awareness and formulate efficient control and preventive strategies to reduce disease incidence and stress on livestock.

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5. Pathogenesis

Unlike T. parvaand T. annulatathat transform host leukocytes leading to fatal lymphoproliferation [130, 131, 132], the major pathogenic effect caused by T. orientalisis through the destruction of host erythrocytes and subsequent anaemia. Schizonts can be detected transiently in the lymph nodes, spleen and liver of infected cattle approximately 10 days post-inoculation with sporozoites [132]. However, schizonts in T. orientalisare rarely associated with major pathogenic effects as the schizont-infected cells are not commonly found in the peripheral blood [132]. Piroplasms can be detected in the host erythrocytes approximately 10 days post-inoculation and anaemia develops approximately 10 days later following detection of piroplasms when parasite load and serological response peaks [133]. Host animals sometimes also experience transient pyrexia and reduction in white blood cell count as anaemia develops [132, 134]. Animals that have been immunologically exposed to T. orientalishave lower parasitaemias and recover from infections earlier and with less morbidity. However, the haemoparasites can persist in the host, potentially until death, and can cause relapse through the resumption of piroplasm proliferation when animals face stress from pregnancy, lactation or rapid changes of environmental or rearing conditions [3, 132].

The pathogenic effects of anaemia consequent to infection although not well established [135]; have been studied extensively. Splenic capture of erythrocytes is likely the primary cause of anaemia rather direct lysis of erythrocytes by the pathogen [133]. In malaria infection, splenic clearance of both infected and uninfected erythrocytes is known to occur and may be the consequence of activation of splenic macrophages or altered red pulp resulting in an increase in mechanical erythrocyte retention [136]. Yagi et al. [137] demonstrated that survival of both infected and uninfected erythrocytes decreased in T. orientalisinfected calves and suggested that denaturation of blood plasma may play a role in this reduced survivability as reported for other protozoan infections [138, 139, 140]. Studies of T. annulatahave demonstrated that anaemia might be an immune-mediated process as indicated by the presence of a haemagglutinin [141]. However, in T. orientalisinfection the destruction of erythrocytes can occur in the absence of immunoglobulin or the involvement of complement [142]. Oxygen radicals released from the lysed erythrocytes may also play a role in pathogenesis as observed for Plasmodiuminfections [140]. Indeed, [143] demonstrated the development of anaemia in association with elevated levels of methemoglobin, a product of haemoglobin oxidation. Oxidative damage of erythrocytes occurs when superoxide radicals are released simultaneously to the increased levels of methemoglobin which may result in their removal from circulation by the reticuloendothelial (mononuclear phagocyte) system [132, 143].

As described in detail in Section 3, the pathogenicity of T. orientalisis genotype-dependent unlike the transforming theilerias T. parvaand T. annulata[1]. However this may reflect the fact that the T. orientalisgenotypes display species-level divergence [37] and pathogenicity of T. orientalisIkeda may be driven by as-yet unidentified virulence factors.

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6. Clinical disease, infection dynamics and the immune response

In the early stages of clinical oriental theileriosis, signs of muscle weakness, ataxia, and abortion are observed in infected animals. A variety of clinical findings such as the lack of appetite, pyrexia, elevated heart rate, abnormal breathing, pale mucous membranes and jaundice have been reported [89]. Aggression in clinically affected animals has occasionally been observed and may be caused by the alteration of mentation as a result of cerebral hypoxia [89]. All of these symptoms are a result of the anaemia in the host animal. Identification of anaemia can be achieved by measuring haematocrit (packed cell volume), which in severely infected cattle can be as low as 8% [144]. In T. annulatainfections, bovine cerebral theileriosis associated with aggression was identified as a result of lymphocytic proliferation and blood vessel inflammation [145].

In T. orientalisboth clinical and subclinical infections are known to frequently occur as a combination of genotypes [29, 42, 44, 146]. In Japan and Australia, T. orientalisIkeda occurs with Chitose genotypes at high frequency with or without the presence of benign genotypes [45, 90, 147] and surveys from the Eastern coast of Australia have revealed genotypes Buffeli and Chitose occur in most subclinical infections [43]. The Ikeda genotype has been linked with higher parasite load and is evident in 100% of the samples that are clinically infected with Ikeda only or a mixture of Ikeda and Chitose [146]. In the clinically mixed infections, semiquantitative data revealed Ikeda to be the dominant genotype (58%) [146]. Within the genotype Chitose, there are two subtypes, Chitose A and Chitose B [35, 146]. In clinical samples from Australia, Chitose A was been noted to commonly occur with Ikeda at a high frequency (approximately 95% of cases examined) and is often detected at high parasite loads, while Chitose B occurs with Ikeda at a lower frequency [35]. Whether Chitose A is contributing to pathogenesis remains unclear. Although, the genotype Chitose was suggested to be able to solely establish a clinical infection in New Zealand cattle [46], the cytochrome oxidase III and 18S rRNA genes rather than the MPSP gene were used to characterise the samples, therefore the genotype of the parasite involved in that study remains unconfirmed. Nonetheless, if the cattle were naïve to Chitose genotype it is possible that this may have led to clinical disease. Regardless, the Ikeda genotype has been associated with recent clinical outbreaks in New Zealand [67, 96, 97]. Another Korean study [74] also suggested Chitose to independently establish clinical infection in cattle, but mixed infections were not accounted for in the study.

Higher susceptibility to clinical theileriosis is observed in association with cattle movements; especially where naïve cattle are newly introduced to an endemic area, and/or infected animals are introduced to a non-endemic area with competent vectors [43]. Naïve cattle become rapidly infected in the presence of infected vector ticks, with time to patency (as determined by qPCR) as early as 11 days post-introduction to an infected herd [35]. Overall parasite load peaks around 40 days post-introduction with the onset of anaemia occurring 8–10 days later, although drops in haematocrit commence at the onset of the patent period. Interestingly, in mixed infection with Ikeda and Chitose genotypes (with or without Buffeli genotype), the Ikeda genotype is detected first and also peaks first. Declines in Ikeda genotype are then followed by an increase in the Chitose suggesting a genotype switching mechanism which may be driven by the host immune response [35, 148].

Additional factors may drive disease susceptibility in cattle such as breed or the age of the animal. In Japan, beef cattle of the Wagyu breed have been reported as being less susceptible to clinical infections [149]. Although potentially a factor in disease susceptibility, the effect of age has not been well-studied. Some cases occurring in regions where adult cattle had previously been exposed T. orientalisreported calves at 6 to 14 weeks of age to have high mortality and severe morbidity [150, 151] which coincides with high parasitaemias which are consistently observed in calves from Theileria-endemic areas [124]. While MPSP antibodies are sometimes detectable in the colostrum of dams and appear to be transferred to calves [101], any passive immunity appears to be short lived, with antibodies undetectable in calves by 4 weeks of age [124]. Lack of protection from maternal antibodies likely explains the high infection intensities and clinical disease observed in calves.

In adult cattle, seroconversion to the MPSP occurs approximately 14 days after patency and humoral responses to this protein persist for at least 11 weeks post-infection [133]. However, a study of 256 T. orientalis-infected animals showed that humoral responses to the MPSP are much more frequently observed in animals experiencing clinical anaemia (89%) versus those with subclinical infections (45%). It is unsurprising therefore that seroconversion to the MPSP is also strongly correlated with both parasite load and the Ikeda genotype [133]. Another study demonstrated that humoral responses to experimental infection with T. orientalis(via mechanical transfer) are variable and only established after persistent infection [152]. The role of humoral immunity in protecting against T. orientalisinfection in adult cattle is unclear. Cell-mediated rather than humoral immunity is generally considered more important in responding to intracellular pathogens; however once established, humoral immunity may assist in preventing the pathogen from gaining cell entry, as for Babesia bovis[153]. Further work is required to determine whether animals that have experienced clinical theileriosis are immune to disease recrudescence and whether immunity against one genotype confers protection against another.

Studies of the transforming theilerias, T. parvaand T. annulata, have shown that cattle that recover from infection are able to establish immunity against homologous strains but succumb to heterologous strains suggesting that immune responses are highly specific for particular parasite epitopes [154, 155]. Immunity is mediated via cytotoxic T lymphocytes (CTL) which target parasitized lymphocytes but allow parasitized erythrocytes to persist [129]. Thus the immune pathways important in protection against non-transforming theilerias such as T. orientalismay be more akin to those of Babesiaspecies [133].

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7. Diagnosis

Oriental theileriosis can be diagnosed by various methods such as microscopy, serology, molecular techniques and xenodiagnosis. Bovine erythrocytes are anucleate, therefore those infected with piroplasms can be visualised under a light microscope using DNA stains (such as Giemsa or Diff-Quik) [156]. In carrier-state animals, erythrocyte infections are commonly observed in the low parasitaemia range of 0.02–0.03% [85, 157]. Parasitaemia in clinically affected animals suffering severe anaemia and other related clinical signs may range from >1–30% [46, 89]. Light microscopy is a quick and inexpensive method for the initial differential diagnosis of possible clinical theileriosis [89]. It has been used to describe many of the first species of Theileriaafter Koch’s [158] initial description of T. parva[159]. However, the technique is limited as a diagnostic tool as it is considerably less sensitive than PCR and does not enable the differentiation of morphologically similar piroplasms [160, 161]. The differentiation between similar piroplasms is important to distinguish the clinically important species such as T. parva; T. annulataand T. orientalisfrom other less clinically significant species such as T. taurotragiand T. mutans.Light microscopy is unable to differentiate between pathogenic and apathogenic genotypes of T. orientalis. Furthermore, light microscopy lacks the sensitivity to adequately detect clinically-benign carrier animals [45, 159].

While a number of serological tests exist for the detection of T. orientalis[29, 87, 133, 152, 162], these assays are currently not genotype-specific and in some cases also cross-react with other Theileriaspecies [152, 162]. Serological tests are of a similar sensitivity to blood smear examination and are most reliable when the animals are clinically affected, but are unsuitable for testing newly infected animals that have not yet seroconverted [133]. Currently, serological methods do not offer any advantage over molecular methods for determining whether animals have been exposed to T. orientalissince this organism establishes lifelong infections and can be detected in the blood well beyond the initial infection period.

PCR is currently the gold standard for sensitive detection of T. orientalis[133]. PCR can detect infection in cattle up to 2 weeks before the infected erythrocytes can be observed under a light microscope [29]. Conventional PCR methods have high sensitivity and have been validated for diagnostic use [43, 44, 45, 69]. However, conventional PCR assays are laborious to perform and do not provide information on parasite load making it impossible to distinguish between clinically infected animals and subclinical carriers. To address these problems, a number of real time semi-quantitative and quantitative PCRs have been developed for the detection of T. orientalis[146, 163, 164, 165, 166]. The majority of these assays have been designed to specifically detect the pathogenic Ikeda genotype [93, 146, 163, 164, 166] and in some cases several genotype specific assays have been multiplexed [146, 163, 166]. Genotype discrimination has been most successfully achieved using assays targeting the MPSP gene [146, 163] while some other molecular markers have been shown to be insufficiently discriminatory [167].

The high prevalence of subclinical carrier animals infected with clinically-relevant genotypes [43] makes accurate quantification critical to correct diagnosis, particularly in the presence of confounding factors. In order to address this, a TaqMan probe-based assay targeting the T. orientalisMPSP was used to establish clinical thresholds for disease to facilitate diagnosis [146]. Using this assay, animals with T. orientalisgene copy numbers above 300,000 are highly likely to display clinical signs; while those with gene copy numbers below 15,000 are considered subclinical carriers. Cattle with gene copy numbers between 15,000 and 300,000 are frequently clinically affected but may also be recovering from disease or in-contact with clinically affected cohorts [146].

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8. Treatment and control of T. orientalis

8.1 Chemotherapy

The increase in oriental theileriosis outbreaks in recent years highlights the need for effective treatment and control measures for this disease. Chemotherapy remains an important strategy in combating protozoan diseases [168]. Chemotherapeutics such as imidocarb, oxytetracyclines and halofuginone have been used to treat oriental theileriosis [2]. In Australia, imidocarb and oxytetracyclines are some of the registered chemicals which in some studies, appeared to have a positive response on cattle with low parasitaemia, but a poor response in severely infected cattle [169]. Menoctone, a hydroxynaphthoquinone compound was discovered to have anti-theilerial properties [170] and two active analogues, parvaquone [171] and buparvaquone [172] were developed shortly thereafter; which treated Theileriainfections in cattle with high efficacy [173]. Total elimination of T. orientalisinfection was achieved in splenectomised calves by a chemical mixture of primaquine and buparvaquone, or primaquine with halofuginone [174]. In Japan, buparvaquone was demonstrated to be effective enough to be used as a single chemical treatment [175]. A single intramuscular injection dose of 2.5 mg/kg buparvaquone was sufficient to treat the Buffeli, Chitose and Ikeda genotypes [2, 176]. In contrast, imidocarb was identified to have little effect on T. orientalisinfection [177]. Prior to 2010, buparvaquone resistance in T. annulatahas never been documented [173]. However, in P. falciparumand Toxoplasma gondii, resistance against atovaquone, a hydroxynaphthoquinone compound, was well documented to be caused by the mutation of the mitochondrial cytochrome b gene [178, 179]. The mode of action of buparvaquone in T. orientalisis not well established, but a study in coccidian parasites suggests an effect on the generation of energy [180]. While buparvaquone treats Theileriainfections with great efficacy when used in the early stages of disease, resistance observed in apicomplexan infections are a growing concern and is a problem with chemotherapeutic agents in general.

An Australian study [169] showed that treatment with buparvaquone leads to the retention of residues in cattle tissue. The tissue residues were present up to 147 days post treatment with buparvaquone and as such this chemotherapeutic has long withholding periods and has not been approved for use at all in Australia. Previously in Japan, chemicals such as pamaquine and primaquine phosphate were commonly used treat T. orientalisinfections but due to declining efficacy, its usage was discontinued [177]. This declining efficacy further revealed the inefficacy of primaquine phosphate to eliminate T. orientalisalone [174]. It requires a combination of chemicals as discussed above to successfully eliminate T. orientalisinfection. As such, chemotherapy options have been limited due to the variations of drug efficacy. The development and identification of chemical compounds suitable for the treatment of T. orientalisis important, however, drug discovery is both time consuming and expensive. There are other important preventive measures worthy of investigating such as the control of competent vectors and management of animals that can facilitate the reduction of T. orientalisoutbreaks.

8.2 Vector control and animal management

Vector control is important to reduce the rapid spread of T. orientalisoutbreaks. Restriction of grazing cattle movements may assist in reducing exposure to infected H. longicornisticks. Control of this vector can also be achieved by using acaricides such as multi-seasonal pour-on flumethrin [83]. This method has been successfully demonstrated in Japan to reduce T. orientalisinfection [83], but it is not permitted for use in Australia due to the possibility of unacceptable residues [181]. Currently, the acceptable methods of tick control in Australia are the application of synthetic pyrethroids in the form of short-acting dips and sprays that can contain amitraz, cypermethrin with chlorfenvinphos and deltamethrin with ethion [2, 181]. The usage of these cheap and common acaricides although economic (A$0.50–A$1.50 per head), might lead to resistance in the tick vectors, which in the long run will incur higher cost due to the requirement for more expensive macrocyclic lactones (approximately A$600 per treatment for a 100-cow herd) for tick control [182]. H. longicornisas described above is a three-host tick; therefore it is a challenge for these acaricides to be effective at controlling this species due to a limited host attachment period.

An alternate method to control T. orientalistransmission by ticks would be the development of a vaccine that targets exposed antigens of the tick [132]. Currently, there is a commercialised vaccine against B. microplus[183] and similar attempts have been made by utilising tick saliva proteins (p29, p34 and p35) against H. longicornisto produce a vaccine [184, 185]. The immunised animals when exposed to ticks, display interference that reduce tick growth and increase mortality of the ticks.

Besides controlling the tick vectors, proper management of animals can also reduce T. orientalisinfection or re-infection. Infected animals are susceptible to relapses when faced with stress factors as discussed above. Supportive therapy such as blood transfusion can be performed to improve the anaemic conditions in affected animals; however, these therapies are time-consuming and expensive and may only be practical to treat valuable stud animals. Animal movement should be kept to a minimum to prevent elevated blood pressure which can cause the animal to collapse [186]. Intravenous fluids and nutritional supplements may also benefit affected animals [2] and intramuscular injection with iron dextran over the course of 3 days can aid recovery of infected animals [187]. The treatment and control of T. orientalisis multi-faceted and it requires all of the different elements discussed in order to be effective.

8.3 Vaccine development

Vaccination is viewed as the preferred method of control for oriental theileriosis. Unfortunately no vaccines currently exist for this disease; however, live vaccines for T. parvaand T. annulatahave been successfully used to treat East Coast fever and tropical theileriosis for over 40 years. Vaccination with highly passaged macroschizont-infected cell lines is possible for T. annulatadue to the stimulation of immunity with low doses of attenuated cells which do not induce clinical disease. In contrast, for T. parva, the doses required to stimulate an immune response also induce clinical disease, therefore vaccination against T. parvainvolves simultaneous vaccination with sporozoites (homogenised ticks) and treatment with long-acting formulation of oxytetracycline to suppress disease. Because vaccination with a single strain of T. parvaleaves animals susceptible to heterologous challenge, immunisation involves a mixture of three isolates which provides broad protection against disease [188].

The vaccination strategy employed for T. annulatais not directly transferrable to T. orientalisdue to the non-transforming nature of this species and a lack of cultivation methods for this organism. The “infect and treat” method used for T. parvahas potential promise for control of T. orientalisbut is currently somewhat limited by a lack of suitable chemotherapeutic agents for parasite suppression.

Vaccination against tick fever, caused by the closely related piroplasmids, Babesia bovisand B. bigemina,also employs live attenuated organisms and is administered to calves between 3 and 9 months of age when they are less susceptible to disease. This vaccination strategy has not been attempted with T. orientalisbut unlike for tick fever, calves are highly susceptible to oriental theileriosis [150, 151]. Nonetheless, live vaccination is still considered one of the most promising approaches for control of oriental theileriosis. It has been suggested that vaccination with benign genotypes of T. orientalismay provide cross protection against the pathogenic genotypes [189]; however recent genome studies suggesting that the differences between genotypes are at the subspecies or species level make this more doubtful [37]. Furthermore, despite a relatively high seroprevalence T. orientalisin Australia (due to the presence of benign strains), extensive outbreaks caused by T. orientalisIkeda occurred across the entire range of the vector tick. Combined with data showing that infections with T. orientalisare usually of mixed genotype [45, 90, 146, 190], there is little evidence to suggest that vaccination with T. orientalisBuffeli, Chitose or other genotypes would provide cross protection against T. orientalisIkeda.

Development of a subunit vaccine is another possible avenue for control of oriental theileriosis. Early studies showed that passive immunisation of calves with an anti-MPSP monoclonal provided protection against development of disease upon challenge [191]. Therefore the MPSP was selected for use in subunit vaccine formulations consisting of recombinant baculovirus-expressed MPSP or synthetic MPSP peptides (containing KEK motifs) mixed with Freund’s adjuvant or encapsulated in mannan-coated liposomes. Following immunisation with these vaccine formulations, calves were splenectomised and challenged with Ikeda or Chitose sporozoite stocks. Animals immunised with high dose peptide or recombinant MPSP had reduced parasitaemias relative to control calves and were protected from clinical signs of oriental theileriosis [190]. Despite these promising preliminary results, a subunit vaccine for T. orientalishas not been pursued further. Subunit vaccines are generally considered problematic when working with apicomplexans due to genetic diversity among strains. Indeed, in their subunit vaccine trial Onuma et al. observed homologous rather than heterologous protection between T. orientalisMPSP genotypes [190]. Furthermore, antigens such as the MPSP which are immunogenic are also under immune pressure, resulting in genetic drift. These issues may be overcome by using multiple antigens in the subunit vaccine formulation or targeting antigens which are not normally immunogenic. A greater understanding of how the bovine immune system responds to T. orientalisis required before further work on vaccine development can meaningfully proceed. Despite the hurdles in developing a vaccine for T. orientalis, it remains a worthy goal given the ongoing burden that this disease imposes on cattle production throughout Asia and Australasia.

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9. Conclusion

T. orientalisis an apicomplexan parasite of economic significance around the world to both beef and dairy industries. This review has highlighted several knowledge gaps surrounding oriental theileriosis from taxonomic uncertainties, vector preferences and treatment and control measures. Development of effective therapeutics or prophylactic measures such as vaccines remains a priority due to recent spread of oriental theileriosis into new areas across the Asia Pacific region. Advancements in whole genome sequencing technologies promise to provide new insights into the T. orientalistaxonomy, genetic diversity and the underlying mechanisms of pathogenesis, all of which underpin successful development and implementation of efficient control strategies against this emerging parasite.

References

  1. 1. Sivakumar T, Hayashida K, Sugimoto C, Yokoyama N. Evolution and genetic diversity ofTheileria. Infection, Genetics and Evolution: Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases. 2014;27:250-263
  2. 2. Watts JG, Playford MC, Hickey KL.Theileria orientalis: A review. New Zealand Veterinary Journal. 2016;64(1):3-9
  3. 3. Gebrekidan H, Nelson L, Smith G, Gasser RB, Jabbar A. An outbreak of oriental theileriosis in dairy cattle imported to Vietnam from Australia. Parasitology. 2017;144(6):738-746
  4. 4. Ministry for Primary Industries, New Zealand.TheileriaVeterinary Handbook 2 [Internet]. 2015. Available from:http://www.mpi.govt.nz/dmsdocument/9518-theileria-veterinary-handbook-2-august-2015[Accessed: Jul 13, 2018]
  5. 5. Yokoyama N, Sivakumar T, Ota N, et al. Genetic diversity ofTheileria orientalisin tick vectors detected in Hokkaido and Okinawa, Japan. Infection, Genetics and Evolution. 2012;12(8):1669-1675
  6. 6. Liu A, Liu Z, Liu J, et al. Detecting and differentiatingTheileria sergentiandTheileria sinensisin cattle and yaks by PCR based on major piroplasm surface protein (MPSP). Experimental Parasitology. 2010;126(4):476-481
  7. 7. Chae JS, Allsopp BA, Waghela SD, et al. A study of the systematics ofTheileriaspp. based upon small-subunit ribosomal RNA gene sequences. Parasitology Research. 1999;85(11):877-883
  8. 8. 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;38(3):352
  9. 9. Fujisaki K, Kawazu S, Kamio T. The taxonomy of the bovineTheileriaspp. Parasitology Today. 1994;10(1):31-33
  10. 10. Kakuda T, Shiki M, Kubota S, et al. Phylogeny of benignTheileriaspecies from cattle in Thailand, China and the U.S.A. based on the major piroplasm surface protein and small subunit ribosomal RNA genes. International Journal for Parasitology. 1998;28(8):1261
  11. 11. Gubbels MJ, Hong Y, Van Der Weide M, et al. Molecular characterisation of theTheileria buffeli/orientalisgroup. International Journal for Parasitology. 2000;30(8):943-952
  12. 12. Dodd S. Piroplasmosis of cattle in Queensland. Journal of Comparative Pathology and Therapeutics. 1910;23:141-160
  13. 13. Theiler A.Piroplasma mutans(n. spec.) of South African cattle. Journal of Comparative Pathology and Therapeutics. 1906;19:292-300
  14. 14. Wenyon CM. Protozoology. A Manual for Medical Men, Veterinarians and Zoologists. Vol. 2. New York: Hafner Publishing Company. 1926
  15. 15. Morel PC, Uilenberg G. Sur la nomenclature de quelquesTheileria(Sporozoa, Babesioidea) des ruminants domestiques. Revue d’élevage et de médecine vétérinaire des pays tropicaux. 1981;34(2):139-143
  16. 16. Uilenberg G.Theileria sergenti. Veterinary Parasitology. 2011;175(3-4):386
  17. 17. Yakimoff W, Dekhtereff N. Zur frage über die Theileriose in Ostsibirien. Archiv für Protistenkunde. 1930;72:176-189
  18. 18. Yakimoff W, Soudatschenkoff W. Zur frage der piroplasmiden der rinder in Ost-Sibirien. Archiv für Protistenkunde. 1931;75:179-190
  19. 19. Uilenberg G, Mpangala C, McGregor W, Callow L. Biological differences between AfricanTheileria mutans(Theiler 1906) and two benign species ofTheileriaof cattle in Australia and Britain. Australian Veterinary Journal. 1977;53(6):271-273
  20. 20. Neveu-Lemaire M. GenreTheileriaou piroplasmes bacilliformes. In: Parasitologie des animaux domestiques. Paris: J Lamarre et Cie; 1912. pp. 286-291
  21. 21. Callow LL. Animal health in Australia. In: Protozoal and Rickettsial Diseases. Vol. 5. Canberra, ACT, Australia: Australian Government Publishing Service; 1984
  22. 22. Stewart NP, Uilenberg G, de Vos AJ. Review of Australian species ofTheileria, with special reference toTheileria buffeliof cattle. Tropical Animal Health and Production. 1996;28(1):81
  23. 23. Kawazu S, Sugimoto C, Kamio T, Fujisaki K. Analysis of the genes encoding immunodominant piroplasm surface proteins ofTheileria sergentiandTheileria buffeliby nucleotide sequencing and polymerase chain reaction. Molecular and Biochemical Parasitology. 1992;56(1):169-175
  24. 24. Fujisaki K. A review of the taxonomy ofTheileria sergenti/buffeli/orientalisgroup parasites in cattle. The Journal of Protozoology. 1992;2(3):87-96
  25. 25. Kubota S, Sugimoto C, Kakuda T, Onuma M. Analysis of immunodominant piroplasm surface antigen alleles in mixed populations ofTheileria sergentiandT. buffeli. International Journal for Parasitology. 1996;26(7):741-747
  26. 26. Sarataphan N, Nilwarangkoon S, Tananyutthawongese C, Kakuda T, Onuma M, Chansiri K. Genetic diversity of major piroplasm surface protein genes and their allelic variants ofTheileriaparasites in Thai cattle. Journal of Veterinary Medical Science. 1999;61(9):991-994
  27. 27. Allsopp B, Baylis H, Allsoppi M, et al. Discrimination between six species ofTheileriausing oligonucleotide probes which detect small subunit ribosomal RNA sequences. Parasitology. 1993;107(02):157-165
  28. 28. Chae JS, Lee JM, Kwon OD, Holman PJ, Waghela SD, Wagner GG. Nucleotide sequence heterogeneity in the small subunit ribosomal RNA gene variable (V4) region among and within geographic isolates ofTheileriafrom cattle, elk and white-tailed deer. Veterinary Parasitology. 1998;75(1):41-52
  29. 29. Ota N, Mizuno D, Kuboki N, et al. Epidemiological survey ofTheileria orientalisinfection in grazing cattle in the eastern part of Hokkaido, Japan. The Japanese Society of Veterinary Science. 2009;71(7):937-944
  30. 30. Jeong W, Yoon SH, An DJ, Cho SH, Lee KK, Kim JY. A molecular phylogeny of the benignTheileriaparasites based on major piroplasm surface protein (MPSP) gene sequences. Parasitology. 2010;137(2):241-249
  31. 31. Kim SJ, Tsuji M, Kubota S, Wei Q , Lee JM, Ishihara C, et al. Sequence analysis of the major piroplasm surface protein gene of benign bovineTheileriaparasites in East Asia. International Journal for Parasitology. 1998;28(8):1219
  32. 32. Bai Q , Liu G, Yin H, et al. Theileria sinensis sp nov: A new species of bovineTheileria—Molecular taxonomic studies. Acta Veterinaria et Zootechnica Sinica. 2002;33(2):185-190
  33. 33. Khukhuu A, Lan DT, Long PT, et al. Molecular epidemiological survey ofTheileria orientalisin Thua Thien Hue province, Vietnam. Journal of Veterinary Medical Science. 2011;73(5):701-705
  34. 34. Hayashida K, Hara Y, Abe T, et al. Comparative genome analysis of three eukaryotic parasites with differing abilities to transform leukocytes reveals key mediators ofTheileria-induced leukocyte transformation. MBio. 2012;3(5):e00204-e00212
  35. 35. Jenkins C, Micallef M, Alex SM, Collins D, Djordjevic SP, Bogema DR. Temporal dynamics and subpopulation analysis ofTheileria orientalisgenotypes in cattle. Infection, Genetics and Evolution: Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases. 2015;32:199-207
  36. 36. Altangerel K, Battsetseg B, Battur B, et al. The first survey ofTheileria orientalisinfection in Mongolian cattle. Veterinary Parasitology. 2011;182(2-4):343
  37. 37. Bogema DR, Micallef ML, Liu M, et al. Analysis ofTheileria orientalisdraft genome sequences reveals potential species-level divergence of the Ikeda, Chitose and Buffeli genotypes. BMC Genomics. 2018;19(1):298
  38. 38. Aparna M, Ravindran R, Vimalkumar MB, et al. Molecular characterization ofTheileria orientaliscausing fatal infection in crossbred adult bovines of South India. Parasitology International. 2011;60(4):524
  39. 39. Katzer F, Ngugi D, Oura C, et al. Extensive genotypic diversity in a recombining population of the apicomplexan parasiteTheileria parva. Infection and Immunity. 2006;74(10):5456-5464
  40. 40. Weir W, Ben-Miled L, Karagenç T, et al. Genetic exchange and sub-structuring inTheileria annulatapopulations. Molecular and Biochemical Parasitology. 2007;154(2):170-180
  41. 41. Henson S, Bishop RP, Morzaria S, et al. High-resolution genotyping and mapping of recombination and gene conversion in the protozoanTheileria parvausing whole genome sequencing. BMC Genomics. 2012;13(1):1-15
  42. 42. Kamau J, de Vos AJ, Playford M, Salim B, Kinyanjui P, Sugimoto C. Emergence of new types ofTheileria orientalisin Australian cattle and possible cause of theileriosis outbreaks. Parasites & Vectors. 2011;4(1):22
  43. 43. Eamens GJ, Bailey G, Gonsalves JR, Jenkins C. Distribution and temporal prevalence ofTheileria orientalismajor piroplasm surface protein types in eastern Australian cattle herds. Australian Veterinary Journal. 2013;91(8):332-340
  44. 44. Eamens GJ, Bailey G, Jenkins C, Gonsalves JR. Significance ofTheileria orientalistypes in individual affected beef herds in New South Wales based on clinical, smear and PCR findings. Veterinary Parasitology. 2013;196(1-2):96-105
  45. 45. Eamens GJ, Gonsalves JR, Jenkins C, Collins D, Bailey G.Theileria orientalisMPSP types in Australian cattle herds associated with outbreaks of clinical disease and their association with clinical pathology findings. Veterinary Parasitology. 2013;191(3-4):209-217
  46. 46. McFadden AMJ, Rawdon TG, Meyer J, et al. An outbreak of haemolytic anaemia associated with infection ofTheileria orientalisin naïve cattle. New Zealand Veterinary Journal. 2011;59(2):79
  47. 47. Sarataphan N, Kakuda T, Chansiri K, Onuma M. Survey of benignTheileriaparasites of cattle and buffaloes in Thailand using allele-specific polymerase chain reaction of major piroplasm surface protein gene. Journal of Veterinary Medical Science. 2003;65(1):133-135
  48. 48. Govaerts M, Verhaert P, Jongejan F, Goddeeris BM. Characterisation of the 33 kDa piroplasm surface antigen ofTheileria orientalis/sergenti/buffeliisolates from West Java, Indonesia. Veterinary Parasitology. 2002;104(2):103-117
  49. 49. Inoue M, Van Nguyen D, Meas S, et al. Survey ofTheileriaparasite infection in cattle in Cambodia and Vietnam using piroplasm surface protein gene-specific polymerase chain reaction. The Japanese Society of Veterinary Science. 2001;63(10):1155-1157
  50. 50. Bawm S, Shimizu K, Hirota JI, et al. Molecular prevalence and genetic diversity of bovineTheileria orientalisin Myanmar. Parasitology International. 2014;63(4):640-645
  51. 51. Sivakumar T, Yoshinari T, Igarashi I, et al. Genetic diversity withinTheileria orientalisparasites detected in Sri Lankan cattle. Ticks and Tick-borne Diseases. 2013;4(3):235-241
  52. 52. Kakati P, Sarmah P, Bhattacharjee K, et al. Emergence of oriental theileriosis in cattle and its transmission throughRhipicephalus(Boophilus)microplusin Assam, India. Veterinary World. 2015;8(9):1099-1104
  53. 53. Vinodkumar K, Shyma V, Justin DK, et al. FatalTheileria orientalisN2 genotype infection among Asian water buffaloes (Bubalus bubalis) in a commercial dairy farm in Kerala, India. Parasitology. 2016;143(1):69-74
  54. 54. Aktas M, Altay K, Dumanli N. A molecular survey of bovineTheileriaparasites among apparently healthy cattle and with a note on the distribution of ticks in eastern Turkey. Veterinary Parasitology. 2006;138(3):179-185
  55. 55. Ghaemi P, Hoghooghi-Rad N, Shayan P, Eckert B. Detection ofTheileria orientalisin Iran by semi-nested PCR. Parasitology Research. 2012;110(2):527-531
  56. 56. Elsify A, Sivakumar T, Nayel M, et al. An epidemiological survey of bovineBabesiaandTheileriaparasites in cattle, buffaloes, and sheep in Egypt. Parasitology International. 2015;64(1):79-85
  57. 57. Kiltz H, Uilenberg G, Franssen F, Perié N.Theileria orientalisoccurs in Central Africa. Research in Veterinary Science. 1986;40(2):197-200
  58. 58. Adjou Moumouni PF, Aboge GO, Terkawi MA, et al. Molecular detection and characterization ofBabesia bovis,Babesia bigemina,Theileriaspecies and Anaplasma marginale isolated from cattle in Kenya. Parasites & Vectors. 2015;8(1):496
  59. 59. Gebrekidan H, Gasser RB, Baneth G, et al. Molecular characterization ofTheileria orientalisfrom cattle in Ethiopia. Ticks and Tick-borne Diseases. 2016;7(5):742-747
  60. 60. Minami T, Fujinaga T, Furuya K, Ishihara T. Clinico-hematologic and serological comparison of Japanese and Russian strains ofTheileria sergenti. National Institute of Animal Health Quarterly. 1980;20(2):44-52
  61. 61. Papadopoulos B, Perié NM, Uilenberg G. Piroplasms of domestic animals in the Macedonia region of Greece 1. Serological cross-reactions. Veterinary Parasitology. 1996;63(1-2):41-56
  62. 62. Savini G, Onuma M, Scaramozzino P, Kakuda T, Semproni G, Langella V. First report ofTheileria sergentiandT. buffeli/orientalisin cattle in Italy. Annals of the New York Academy of Sciences. 1998;849(1):404-407
  63. 63. García-Sanmartín J, Nagore D, García-Pérez AL, Juste RA, Hurtado A. Molecular diagnosis ofTheileriaandBabesiaspecies infecting cattle in northern Spain using reverse line blot macroarrays. BMC Veterinary Research. 2006;2(1):16
  64. 64. Gomes J, Soares R, Santos M, et al. Detection ofTheileriaandBabesiainfections amongst asymptomatic cattle in Portugal. Ticks and Tick-borne Diseases. 2013;4(1):148-151
  65. 65. Hornok S, Mester A, Takács N, Fernández de Mera IG, De La Fuente J, Farkas R. Re-emergence of bovine piroplasmosis in Hungary: Has the etiological role ofBabesia divergensbeen taken over byB. majorandTheileria buffeli? Parasites & Vectors. 2014;7(1):434
  66. 66. Silveira JA, de Oliveira CH, Silvestre BT, et al. Molecular assays reveal the presence ofTheileriaspp. andBabesiaspp. in Asian water buffaloes (Bubalus bubalis, Linnaeus, 1758) in the Amazon region of Brazil. Ticks and Tick-borne Diseases. 2016;7(5):1017-1023
  67. 67. McFadden A, Pulford D, Lawrence K, Frazer J, van Andel M, Donald J, et al. Epidemiology ofTheileria orientalisin cattle in New Zealand. In: Proceedings of the Society of Dairy Cattle Veterinarians Annual Conference. VetLearn Foundation. Jan 2013. pp. 207-217
  68. 68. Yokoyama N, Ueno A, Mizuno D, et al. Genotypic diversity ofTheileria orientalisdetected from cattle grazing in Kumamoto and Okinawa prefectures of Japan. Journal of Veterinary Medical Science. 2011;73(3):305-112
  69. 69. Zakimi S, Kim JY, Oshiro M, Hayashida K, Fujisaki K, Sugimoto C. Genetic diversity of benignTheileriaparasites of cattle in the Okinawa prefecture. Journal of Veterinary Medical Science. 2006;68(12):1335-1338
  70. 70. Yamane I, Koiwai M, Tsusui T, Hamaoka T. A survey ofTheileria sergentiinfection, daily weight gain and conception proportions in 85 herds of grazing heifers in Japan. Veterinary Parasitology. 2001;99(3):189-198
  71. 71. Baek BK, Soo KB, Kim JH, et al. Verification by polymerase chain reaction of vertical transmission ofTheileria sergentiin cows. Canadian Journal of Veterinary Research. 2003;67(4):278
  72. 72. Ko MS, Lee KK, Hwang KK, Kim BS, Choi GC, Yun YM. Antigenic diversity ofTheileriamajor piroplasm surface protein gene in Jeju Black cattle. Journal of Veterinary Science. 2008;9(2):155-160
  73. 73. Park J, Han YJ, Han DG, et al. Genetic characterization ofTheileria orientalisfrom cattle in the Republic of Korea. Parasitology Research. 2017;116(1):449-454
  74. 74. Kim S, Yu DH, Chae JB, et al. Pathogenic genotype of major piroplasm surface protein associated with anemia inTheileria orientalisinfection in cattle. Acta Veterinaria Scandinavica. 2017;59(1):51
  75. 75. Altangerel K, Sivakumar T, Inpankaew T, et al. Molecular prevalence of different genotypes ofTheileria orientalisdetected from cattle and water buffaloes in Thailand. Journal of Parasitology. 2011;97(6):1075-1079
  76. 76. Belotindos LP, Lazaro JV, Villanueva MA, Mingala CN. Molecular detection and characterization ofTheileriaspecies in the Philippines. Acta Parasitologica. 2014;59(3):448-453
  77. 77. Ochirkhuu N, Konnai S, Mingala CN, et al. Molecular epidemiological survey and genetic analysis of vector-borne infections of cattle in Luzon Island, the Philippines. Veterinary Parasitology. 2015;212(3-4):161-167
  78. 78. Yin H, Guan G, Ma M, et al. Haemaphysalis qinghaiensis ticks transmit at least two differentTheileriaspecies: One is infective to yaks, one is infective to sheep. Veterinary Parasitology. 2002;107(1):29-35
  79. 79. Sivakumar T, Khukhuu A, Igarashi I, et al. Phylogenetic analysis ofTheileria orientalisin cattle bred in Fujian province, China. The Journal of Protozoology Research. 2011;21(1):14-19
  80. 80. Liu M, Jia L, Cao S, et al. Molecular detection ofTheileriaspecies in Cattle from Jilin Province, China. Tropical Biomedicine. 2017;34(3):598-606
  81. 81. Estrada-Peña A, Santos-Silva MM. The distribution of ticks (Acari: Ixodidae) of domestic livestock in Portugal. Experimental & Applied Acarology. 2005;36(3):233-246
  82. 82. Uilenberg G, Hashemi-Fesharki R.Theileria orientalisin Iran. Veterinary Quarterly. 1984;6(1):1-4
  83. 83. Shimizu S, Nojiri K, Matsunaga N, Yamane I, Minami T. Reduction in tick numbers (Haemaphysalis longicornis), mortality and incidence ofTheileria sergentiinfection in field-grazed calves treated with flumethrin pour-on. Veterinary Parasitology. 2000;92(2):129-138
  84. 84. Kim JY, Yokoyama N, Kumar S, et al. Identification of a piroplasm protein ofTheileria orientalisthat binds to bovine erythrocyte band 3. Molecular and Biochemical Parasitology. 2004;137(2):193-200
  85. 85. Shimizu S, Yoshiura N, Mizomoto T, Kondou Y.Theileria sergentiinfection in dairy cattle. Journal of Veterinary Medical Science. 1992;54(2):375-377
  86. 86. Seddon HR. Diseases of Domestic Animals in Australia. Part 4. Protozoan and Viral Diseases: Service Publications. Australia: Department of Health, Veterinary Hygiene. Vol. 8. 1952
  87. 87. Stewart NP, Standfast NF, Baldock FC, Reid DJ, de Vos AJ. The distribution and prevalence ofTheileria buffeliin cattle in Queensland. Australian Veterinary Journal. 1992;69(3):59-61
  88. 88. Roberts FHS. A systematic study of the Australian species of the genus Haemaphysalis Koch (Acarina: Ixodidae). Australian Journal of Zoology. 1963;11(1):35-80
  89. 89. Izzo MM, Poe I, Horadagoda N, de Vos AJ, House JK. Haemolytic anaemia in cattle in NSW associated withTheileriainfections. Australian Veterinary Journal. 2010;88(1):45-51
  90. 90. Perera PK, Gasser RB, Anderson GA, Jeffers M, Bell CM, Jabbar A. Epidemiological survey following oriental theileriosis outbreaks in Victoria, Australia, on selected cattle farms. Veterinary Parasitology. 2013;197(3-4):509-521
  91. 91. Islam MK, Jabbar A, Campbell BE, Cantacessi C, Gasser RB. Bovine theileriosis—An emerging problem in South-Eastern Australia? Infection. Genetics and Evolution: Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases. 2011;11(8):2095-2097
  92. 92. Thomson J. Bovine Anaemia Detected in Western Australia [Internet]. 2013. Available from:https://www.agric.wa.gov.au/news/media-release/bovine-anaemia-detected-wa[Accessed: Jul 13, 2018]
  93. 93. Gebrekidan H, Gasser RB, Perera PK, et al. Investigating the first outbreak of oriental theileriosis in cattle in South Australia using multiplexed tandem PCR (MT-PCR). Ticks and Tick-borne Diseases. 2015;6(5):574-578
  94. 94. Hammer JF, Emery D, Bogema DR, Jenkins C. Detection ofTheileria orientalisgenotypes inHaemaphysalis longicornisticks from southern Australia. Parasites & Vectors. 2015;8(1):229
  95. 95. James MP, Saunders BW, Guy LA, Brookbanks EO, Charleston WAG, Uilenberg G.Theileria orientalis, a blood parasite of cattle. First report in New Zealand. New Zealand Veterinary Journal. 1984;32(9):154-156
  96. 96. McFadden AMJ, Gias E, Heuer C, Stevens McFadden FJ, Pulford DJ. Prevalence and spatial distribution of cattle herds infected withTheileria orientalisin New Zealand between 2012 and 2013. New Zealand Veterinary Journal. 2016;64(1):55
  97. 97. Pulford D, McFadden A, Hamilton J, Donald J. Investigation of the index case herd and identification of the genotypes ofTheileria orientalisassociated with outbreaks of bovine anaemia in New Zealand in 2012. New Zealand Veterinary Journal. 2016;64(1):21-28
  98. 98. Heath ACG. Biology, ecology and distribution of the tick,Haemaphysalis longicornisNeumann (Acari: Ixodidae) in New Zealand. New Zealand Veterinary Journal. 2016;64(1):10
  99. 99. Kamau J, Salim B, Yokoyama N, Kinyanjui P, Sugimoto C. Rapid discrimination and quantification ofTheileria orientalistypes using ribosomal DNA internal transcribed spacers. Infection, Genetics and Evolution. 2011;11(2):407-414
  100. 100. Fernandez De Marco M, Brugman VA, Hernandez-Triana LM, et al. Detection ofTheileria orientalisin mosquito blood meals in the United Kingdom. Veterinary Parasitology;2016(229):31-36
  101. 101. Hammer JF, Jenkins C, Bogema D, Emery D. Mechanical transfer ofTheileria orientalis: Possible roles of biting arthropods, colostrum and husbandry practices in disease transmission. Parasites & Vectors. 2016;9(1):34
  102. 102. Fujisaki K, Kamio T, Kawazu S, Shimizu S, Simura K.Theileria sergenti: Experimental transmission by the long-nosed cattle louse, Linognathus vituli. Annals of Tropical Medicine and Parasitology. 1993;87(2):217
  103. 103. Stewart NP, de Vos AJ, McGregor W, Shiels I. Haemaphysalis humerosa, notH. longicornis, is the likely vector ofTheileria buffeliin Australia. Australian Veterinary Journal. 1987;64(9):280-282
  104. 104. Stewart NP, de Vos AJ, Shiels I, McGregor W. The experimental transmission ofTheileria buffeliof cattle in Australia by Haemaphysalis humerosa. Australian Veterinary Journal. 1987;64(3):81-83
  105. 105. Stewart NP, de Vos AJ, Shiels IA, Jorgensen WK. Transmission ofTheileria buffelito cattle by Haemaphysalis bancrofti fed on artificially infected mice. Veterinary Parasitology. 1989;34(1-2):123
  106. 106. Heath ACG. Theileriosis and ticks; the role of the vector, and its control. In presentation at Australia/New Zealand workshop on bovine Theileriosis. 2015: Pan Pacific Veterinary Conference, Brisbane. Unpublished
  107. 107. Forshaw D, Cotter J, Palmer D, Roberts D. Define the Geographical Distribution ofTheileria orientalisin the Denmark Shire [Internet]. 2016. Available from:https://www.agric.wa.gov.au/sites/gateway/files/Theileria%20orientalis%20-%20Final%20Report.pdf[Accessed: Jul 13, 2018]
  108. 108. Teng KF, Jiang ZJ. Economic Insect Fauna of China Fasc 39 Acari: Ixodidae. Fauna Sinica Beijing: Science Press; 1991
  109. 109. Camicas JL. Les Tiques du monde: acarida, ixodida. Paris: Éditions de l’Orstom; 1998
  110. 110. Roberts FHS. Australian Ticks. Melbourne: Commonwealth Scientific and Industrial Research Organization; 1970
  111. 111. Bremner KC. Observations on the biology of Haemaphysalis bispinosa Neumann (Acarina: Ixodidae) with particular reference to its mode of reproduction by parthenogenesis. Australian Journal of Zoology. 1959;7(1):7-12
  112. 112. McKeever DJ. Bovine immunity—A driver for diversity inTheileriaparasites? Trends in Parasitology. 2009;25(6):269-276
  113. 113. Shaw MK.Theileriadevelopment and host cell invasion. In: Dobbelaere DAE, McKeever DJ, editors. World Class Parasites,Theileria. Vol. 3. Boston, London: Kluwer Academic Publishers; 2002. pp. 1-22
  114. 114. Mehlhorn H, Schein E, Ahmed JS.Theileria. In: Kreier JP, editor. Parasitic Protozoa. San Diego: Academic Press; 1994. pp. 217-304
  115. 115. Bishop R, Musoke A, Morzaria S, et al.Theileria: Intracellular protozoan parasites of wild and domestic ruminants transmitted by ixodid ticks. Parasitology. 2004;129(S1):S271-S283
  116. 116. Ray HN. Hereditary transmission ofTheileria annulatainfection in the tick, Hyalomma aegyptium Neum. Transactions of the Royal Society of Tropical Medicine and Hygiene. 1950;44(1):93-104
  117. 117. Dipeolu OO, Ogunji FO. The transmission ofTheileria annulatato a rabbit by the larvae of the tickHyalomma rufipes. Laboratory Animals. 1977;11(1):39-40
  118. 118. Matsuba T, Kubota H, Tanaka M, et al. Analysis of mixed parasite populations ofTheileria sergentiusing cDNA probes encoding a major piroplasm surface protein. Parasitology. 1993;107(4):369-377
  119. 119. Sudan V, Singh SK, Jaiswal AK, Parashar R, Shanker D. First molecular evidence of the transplacental transmission ofTheileria annulata. Tropical Animal Health and Production. 2015;47(6):1213-1215
  120. 120. Allsopp MT, Lewis BD, Penzhorn BL. Molecular evidence for transplacental transmission ofTheileria equifrom carrier mares to their apparently healthy foals. Veterinary Parasitology. 2007;148(2):130-136
  121. 121. Chhabra S, Ranjan R, Uppal SK, Singla LD. Transplacental transmission of Babesia equi (Theileria equi) from carrier mares to foals. Journal of Parasitic Diseases. 2012;36(1):31-33
  122. 122. Zakian A, Nouri M, Barati F, Kahroba H, Jolodar A, Rashidi F. Vertical transmission ofTheileria lestoquardiin sheep. Veterinary Parasitology. 2014;203(3-4):322-325
  123. 123. Onoe SSC, Tanaka M, Kubota S, et al. Prenatal infections withTheileria sergentiin calves. Journal of Protozoology Research. 1994;4(3):119-123
  124. 124. Swilks E, Fell SA, Hammer JF, Sales N, Krebs GL, Jenkins C. Transplacental transmission ofTheileria orientalisoccurs at a low rate in field-affected cattle: Infection in utero does not appear to be a major cause of abortion. Parasites & Vectors. 2017;10(1):227
  125. 125. Lawrence KE, Gedye K, McFadden AMJ, Pulford DJ, Pomroy WE. An observational study of the vertical transmission ofTheileria orientalis(Ikeda) in a New Zealand pastoral dairy herd. Veterinary Parasitology. 2016;218:59-65
  126. 126. Heath ACG. The role of ticks, biting flies and lice in the transmission of theileriosis. Vetscript. 2013;26(6):13-14
  127. 127. McKeever DJ.Theileria parvaand the bovine CTL response: Down but not out? Parasite Immunology. 2006;28(7):339-345
  128. 128. Walker A, Katzer F, Ngugi D, McKeever D. ClonedTheileria parvaproduces lesser infections in ticks compared to unclonedT. parvadespite similar infections in cattle. The Onderstepoort Journal of Veterinary Research. 2006;73(2):157
  129. 129. MacHugh ND, Weir W, Burrells A, et al. Extensive polymorphism and evidence of immune selection in a highly dominant antigen recognized by bovine CD8 T cells specific forTheileria annulata. Infection and Immunity. 2011;79(5):2059-2069
  130. 130. Kawamoto S, Takahashi K, Kurosawa T, Sonoda M, Onuma M. Intraerythrocytic schizogony ofTheileria sergentiin cattle. The Japanese Journal of Veterinary Science. 1990;52(6):1251-1259
  131. 131. Heussler VT.Theileriasurvival strategies and host cell transformation. In: McKeever D, Dobbelaere D, editors.Theileria. Boston, London: Kluwer Academic Publishers; 2002. pp. 69-84
  132. 132. Sugimoto C, Fujisaki K. Non-transformingTheileriaparasite of ruminants. In: McKeever D, Dobbelaere D, editors.Theileria. Boston, London: Kluwer Academic Publishers; 2002. pp. 93-106
  133. 133. Jenkins C, Bogema DR. Factors associated with seroconversion to the major piroplasm surface protein of the bovine haemoparasiteTheileria orientalis. Parasites & Vectors. 2016;9(1):106
  134. 134. Kawazu S, Niinuma S, Kamio T, et al. Changes in the proportion and number of monocytes in the peripheral blood of calves infected withTheileria sergenti. The Journal of Veterinary Medical Science. 1991;53(2):341-343
  135. 135. Stockham SL, Kjemtrup AM, Conrad PA, et al. Theileriosis in a Missouri beef herd caused byTheileria buffeli: Case report, herd investigation, ultrastructure, phylogenetic analysis, and experimental transmission. Veterinary Pathology. 2000;37(1):11-21
  136. 136. Huang S, Amaladoss A, Liu M, et al. In vivo splenic clearance corresponds with in vitro deformability of red blood cells fromPlasmodium yoeliiinfected mice. Infection and Immunity. 2014;31(IAI):01525
  137. 137. Yagi Y, Ito N, Kunugiyama I. Decrease in erythrocyte survival inTheileria sergenti-infected calves determined by non-radioactive chromium labelling method. The Japanese Society of Veterinary Science. 1991;53(3):391-394
  138. 138. Rosenberg EB, Strickland GT, Yang S, Whalen GE. IgM antibodies to red cells and autoimmune anemia in patient with malaria. American journal of Tropical Medicine and Hygiene. 1973;22(2):146-152
  139. 139. Quinn TC, Wyler DJ. Intravascular clearance of parasitized erythrocytes in rodent malaria. Journal of Clinical Investigation. 1979;63(6):1187-1194
  140. 140. Clark IA, Hunt NH, Cowden WB. Oxygen-derived free radicals in the pathogenesis of parasitic disease. Advance Parasitology. 1986;25:1-44
  141. 141. Hooshmand-Rad P. The pathogenesis of anaemia inTheileria annulatainfection. Research in Veterinary Science. 1976;20(3):324-329
  142. 142. Hagiwara K, Tsuji M, Ishihara C, Tajima M, Kurosawa T, Takahashi K. Serum fromTheileria sergenti-infected cattle accelerates the clearance of bovine erythrocytes in SCID mice. Parasitology Research. 1995;81(6):470-474
  143. 143. Shiono H, Yagi Y, Thongnoon P, et al. Acquired methemoglobinemia in anemic cattle infected withTheileria sergenti. Veterinary Parasitology. 2001;102(1):45-51
  144. 144. Irwin T. Anaemia Caused by Theileriosis [Internet]. 2013. Available from:http://www.flockandherd.net.au/cattle/reader/theileriosis-northwest.html[Accessed: Jul 13, 2018]
  145. 145. Dabak M, Dabak DO, Aktas M. Cerebral theileriosis in a Holstein calf. The Veterinary Record. 2004;154(17):533-534
  146. 146. Bogema DR, Deutscher AT, Fell S, Collins D, Eamens GJ, Jenkins C. Development and validation of a quantitative PCR assay using multiplexed hydrolysis probes for detection and quantification ofTheileria orientalisisolates and differentiation of clinically relevant subtypes. Journal of Clinical Microbiology. 2015;53(3):941-950
  147. 147. Kubota S, Sugimoto C, Onuma M. A genetic analysis of mixed population inTheileria sergentistocks and isolates using allele-specific polymerase chain reaction. Journal of Veterinary Medical Science. 1995;57(2):279-282
  148. 148. Kubota S, Sugimoto C, Onuma M. Population dynamics ofTheileria sergentiin persistently infected cattle and vector ticks analysed by a polymerase chain reaction. Parasitology. 1996;112(5):437-442
  149. 149. Higuchi M, Kurita T, Miyashita K. Resistance to theileriosis in Japanese black (Wagyu) cattle X Japanese shorthorn F1 calves. Livestock Research Bulletin, Serial No. 1229, Tohoku Agricultural Testing Station. 1997
  150. 150. Ball M.Theileriaand Pneumonia in Calves [Internet]. 2011. Available from:http://www.flockandherd.net.au/cattle/reader/theileria.html[Accessed: Jul 13, 2018]
  151. 151. Eastwood S. Benign Theileriosis in Beef Calves [Internet]. 2011. Available from:http://www.flockandherd.net.au/cattle/reader/benign-theileriosis-III.html[Accessed: Jul 13, 2018]
  152. 152. Zhao S, Liu J, Zhao H, et al. Evaluating an indirect rMPSP enzyme-linked immunosorbent assay for the detection of bovineTheileriainfection in China. Parasitology Research. 2017;116(2):667-676
  153. 153. Brown WC, Norimine J, Knowles DP, Goff WL. Immune control of Babesia bovis infection. Veterinary Parasitology. 2006;138(1-2):75-87
  154. 154. Radley DE, Brown CG, Cunningham MP, et al. East Coast fever: 3. Chemoprophylactic immunization of cattle using oxytetracycline and a combination of theilerial strains. Veterinary Parasitology. 1975;1(1):51-60
  155. 155. Preston PM, Brown CG, Bell-Sakyi L, Richardson W, Sanderson A. Tropical theileriosis inBos taurusandBos tauruscrossBos indicuscalves: Response to infection with graded doses of sporozoites ofTheileria annulata. Research in Veterinary Science. 1992;53(2):230-243
  156. 156. Biddle A, Eastwood S, Martin L, Freeman P, Druce E. A survey to determine the prevalence ofTheileriaspp. in beef cattle in the northern tablelands of New South Wales. Australian Veterinary Journal. 2013;91(10):427-431
  157. 157. Kamio T, Ito Y, Fujisaki K, Minami T. Infection rates ofTheileria sergentiinHaemaphysalis longicornisticks collected from the field in Japan. The Japanese Journal of Veterinary Science. 1990;52(1):43-48
  158. 158. Koch R. Reise-Berichte über Rinderpest, Bubonenpest in Indien und Afrika, Tsetse-oder Surrakrankheit, Texasfieber, tropische Malaria. Schwarzwasserfieber: Springer; 1898
  159. 159. Mans BJ, Pienaar R, Latif AA. A review ofTheileriadiagnostics and epidemiology. International Journal for Parasitology: Parasites and Wildlife. 2015;4(1):104-118
  160. 160. Uilenberg G. Theilerial species of domestic livestock. In: Irvin AD, Cunningham MP, Young AS, editors. Advances in the Control of Theileriosis. Current Topics in Veterinary Medicine and Animal Science. Vol. 14. Dordrecht: Springer; 1981. pp. 4-37
  161. 161. Criado-Fornelio A. A review of nucleic acid-based diagnostic tests forBabesiaandTheileria, with emphasis on bovine piroplasms. Parassitologia. 2007;49:39
  162. 162. Li Y, Liu Z, Liu J, et al. Seroprevalence of bovine theileriosis in northern China. Parasites & Vectors. 2016;9(1):591
  163. 163. Gebrekidan H, Gasser RB, Stevenson MA, Jabbar A. Multiplexed tandem PCR (MT-PCR) assay using the major piroplasm surface protein gene for the diagnosis ofTheileria orientalisinfection in cattle. Journal of Clinical Microbiology. 2018;56(3):e01661-e01617
  164. 164. Pulford DJ, Gias E, Bueno IM, McFadden AM. Developing high throughput quantitative PCR assays for diagnosing Ikeda and otherTheileria orientalistypes common to New Zealand in bovine blood samples. New Zealand Veterinary Journal. 2016;64(1):29-37
  165. 165. Yang Y, Mao Y, Kelly P, et al. A pan-TheileriaFRET-qPCR survey forTheileriaspp. in ruminants from nine provinces of China. Parasites & Vectors. 2014;7(1):413
  166. 166. Perera PK, Gasser RB, Firestone SM, Smith L, Roeber F, Jabbar A. Semiquantitative multiplexed tandem PCR for detection and differentiation of fourTheileria orientalisgenotypes in cattle. Journal of Clinical Microbiology. 2015;53(1):79-87
  167. 167. Gebrekidan H, Gasser RB, Jabbar A. Inadequate differentiation ofTheileria orientalisgenotypes buffeli and Ikeda in a multiplexed tandem PCR (MT-PCR) assay using the p 23 gene as a marker. Journal of Clinical Microbiology. 2017;55(2):641-644
  168. 168. Monzote L, Siddiq A. Drug development to protozoan diseases. The Open Medicinal Chemistry Journal. 2011;5:1
  169. 169. Bailey G. Buparvaquone Tissue Residue Study [Internet]. 2013. Available from:https://www.mla.com.au/download/finalreports?itemId=123[Accessed: Jul 13, 2018]
  170. 170. McHardy N, Haigh AJ, Dolan TT. Chemotherapy ofTheileria parvainfection. Nature. 1976;261(5562):698
  171. 171. McHardy N, Morgan DW. Treatment ofTheileria annulatainfection in calves with parvaquone. Research in Veterinary Science. 1985;39(1):1-4
  172. 172. McHardy N, Wekesa LS, Hudson AT, Randall AW. Antitheilerial activity of BW720C (buparvaquone): A comparison with parvaquone. Research in Veterinary Science. 1985;39(1):29-33
  173. 173. Mhadhbi M, Naouach A, Boumiza A, Chaabani MF, BenAbderazzak S, Darghouth MA. In vivo evidence for the resistance ofTheileria annulatato buparvaquone. Veterinary Parasitology. 2010;169(3-4):241-247
  174. 174. Stewart NP, de Vos AJ, McHardy N, Standfast NF. Elimination ofTheileria buffeliinfections from cattle by concurrent treatment with buparvaquone and primaquine phosphate. Tropical Animal Health and Production. 1990;22(2):116-122
  175. 175. Ozawa H, Nogami T, Tomita M, et al. Chemotherapy ofTheileria sergentiinfection with Buparvaquone. Journal of the Japan Veterinary Medical Association. 1988;41(1):32-35
  176. 176. Carter P. Assessment of the Efficacy of Buparvaquone for the Treatment of ‘Benign’ Bovine Theileriosis [Internet]. 2011. Available from:http://www.mla.com.au/CustomControls/PaymentGateway/ViewFile.aspx?N1+8Z+okrmT5EXqmGClwuhTuGH4gXCGZbwgHgTts+VHug4FlGztCKPHAvPZG36hd3EYMKKAfsht7d1Tnt3BqiA== [Accessed: Jul 13, 2018]
  177. 177. Minami T, Nakano T, Shimizu S, Shimura K, Fujinaga T, Ito S. Efficacy of naphthoquinones and imidocarb dipropionate onTheileria sergentiinfections in splenectomized calves. The Japanese Journal of Veterinary Science. 1985;47(2):297-300
  178. 178. Korsinczky M, Chen N, Kotecka B, Saul A, Rieckmann K, Cheng Q. Mutations inPlasmodium falciparumcytochrome b that are associated with atovaquone resistance are located at a putative drug-binding site. Antimicrobial Agents and Chemotherapy. 2000;44(8):2100-2108
  179. 179. McFadden DC, Tomavo S, Berry EA, Boothroyd JC. Characterization of cytochrome b from toxoplasma gondii and Qo domain mutations as a mechanism of atovaquone-resistance. Molecular and Biochemical Parasitology. 2000;108(1):1-12
  180. 180. Fry M, Hudson AT, Randall AW, Williams RB. Potent and selective hydroxynaphthoquinone inhibitors of mitochondrial electron transport in Eimeria tenella (Apicomplexa: Coccidia). Biochemical Pharmacology. 1984;33(13):2115-2122
  181. 181. Ottaway S, Cook L. Chemicals for Controlling Paralysis Ticks in Cattle. NSW, Australia: NSW Department of Primary Industries; 2005
  182. 182. Department of Agriculture and Fisheries. Tick Control for Dairy Cattle [Internet]. 2011. Available from:https://www.daf.qld.gov.au/animal-industries/animal-health-and-diseases/animal-disease-control/cattle-tick/tick-control-for-dairy-cattle[Accessed: Jul 13, 2018]
  183. 183. Willadsen P, Bird P, Cobon GS, Hungerford J. Commercialisation of a recombinant vaccine againstBoophilus microplus. Parasitology. 1995;110(S1):S43-S50
  184. 184. Mulenga A, Sugimoto C, Ingram G, Ohashi K, Onuma M. Molecular cloning of twoHaemaphysalis longicorniscathepsin L-like cysteine proteinase genes. Journal of Veterinary Medical Science. 1999;61(5):497-503
  185. 185. Tsuda A, Mulenga A, Sugimoto C, Nakajima M, Ohashi K, Onuma M. cDNA cloning, characterization and vaccine effect analysis ofHaemaphysalis longicornistick saliva proteins. Vaccine. 2001;19(30):4287-4296
  186. 186. Bailey G. Bovine Anaemia Caused byTheileria orientalisGroup [Internet]. 2011. Available from:http://www.dpi.nsw.gov.au/__data/assets/pdf_file/0003/404679/Bovine-anaemia-caused-by-Theileria-orientalis-group-Primefact-1110.pdf[Accessed: Jul 13, 2018]
  187. 187. Nakamura Y, Dorjee J, Muhindo JB, et al. Effects of iron dextran on anemia in calves experimentally infected withTheileria sergenti. Bulletin of the National Institute of Animal Health (Japan). 2010;(116):1-10
  188. 188. Nene V, Morrison WI. Approaches to vaccination againstTheileria parvaandTheileria annulata. Parasite Immunology. 2016;38(12):724-734
  189. 189. de Vos AJ.Theileria: Assess potential to develop a vaccine forTheileria orientalisinfection [Internet]. 2011. Available from:https://www.mla.com.au/download/finalreports?itemId=115[Accessed: Jul 13, 2018]
  190. 190. Onuma M, Kubota S, Kakuda T, et al. Control ofTheileria sergentiinfection by vaccination. Tropical Animal Health and Production. 1997;29(4):119S-123S
  191. 191. Tanaka M, Ohgitani T, Okabe T, et al. Protective effect against intraerythrocytic merozoites ofTheileria sergentiinfection in calves by passive transfer of monoclonal antibody. Japanese Journal of Veterinary Science. 1990;52(3):631-633

Written By

Jerald Yam, Daniel R. Bogema and Cheryl Jenkins

Submitted: May 3rd, 2018 Reviewed: August 29th, 2018 Published: November 5th, 2018