Theileria - available
Control ToolsDiagnostics availabilityIFA, ELISA and PCR can be used. ELISA’s have been successfully developed for the detection of antibodies to T. annulata and have shown that they can detect antibodies for a longer period in affected animals but are not commercially available. (OIE October 2009). GAPS:
None for the moment. None. The OIE refers to the use of IFA, ELISA and PCR with Giemsa stained smears from blood or lymph node biopsies being used for diagnosis. Unlikely. With the potential development of suitable sub-unit vaccines it may be necessary to develop a DIVA test, but currently there is not one available. N/A. Vaccines availabilityDespite the fact that vaccination with the cell culture vaccine against T. annulata has been available for more than three decades the use of this vaccine has been limited. The concern about the introduction of vaccine related parasites into the field tick population has led to countries developing vaccines from local isolates. On this basis therefore there does not appear to be a universally commercialised vaccine or standard method of production. The sub-unit vaccines are still in development. GAP: Little work is being undertaken on subunit vaccines against T. annulata in the EU. None. None. None. The current live attenuated vaccines carry risks associated with the breakdown of the cold chain, disease due to immunisation and the possibility of introducing other contaminating pathogens due to inadequate quality control during preparation. There is currently a limited market in Europe for vaccines against theileriosis caused by T. annulata. There is a potential market in Turkey. There is currently no regulatory or policy challenge to approval of vaccines against Theileriosis. Whilst it is feasible, the commercial viability of developing such a vaccine would depend on uptake and therefore whether the investment in research and development would be repaid in later sales. This is not considered to be a possibility in the current situation. Identification of protective antigens and delivery strategies associated with induction of protective immunity. Development of a per os delivery method of an anti-tick vaccine using plant expressed concealed tick antigen(s). GAP: Per os immunisation methodology resulting in good humoral protective responses. Pharmaceutical availabilityTheilericides such as buparvaquone are marketed for therapeutic use and are effective if given in the early stages of the disease although they are less effective if treatment is delayed. However, animals that recover following treatment often remain unproductive for months. Recently drug resistant parasites have been noted which suggests that this method of control may become less effective over time. There are currently no curative drugs registered in EU countries. GAP: No “legal” curative therapy in Europe. New theilericides may be developed in the future and it may be possible to develop compounds that could be continuously available in the blood of the cattle, (by administering via the feed for example), such that when ticks feed, the sporozoietes are neutralised before having the chance to infect. This will inhibit expansion of infected cells thereby enhancing control by the immune response. GAPS:
The current level of infection in Europe would suggest that there is limited commercial potential in Europe. Yet, some areas in Europe might have an evident need of the drugs. The use of buparvaquone for Theileria equi piroplasmosis could also justify its registration in some European countries. There is currently no regulatory or policy challenge to approval of therapeutic theilericides. Yet, buparvaquone has not been registered in any European country in spite of its need in Spain for instance. It can be used in Menorca with a special authorization of AEM (Spanish Drug Agency) but complex application and delay of several months constrain effectiveness. Treated animals and their milk and meat are not allowed to be sold anymore. Buparvaquone is available on the Africa, Asia and Middle-East markets. The main costs are related to the registration procedure and this could be too high in the EU in respect of the currently limited market potential, due to the sporadic nature of the disease in Europe. New theilericides may be developed in the future and it may be possible to develop compounds that could be continuously available in the blood of the cattle, (by administering via the feed for example), such that when ticks feed, the sporozoietes are neutralised before having the chance to infect. This will inhibit expansion of infected cells thereby enhancing control by the immune response. New developments for diagnostic testsWith the development of subunit vaccines for the surface/CD8 T cell antigens it may be possible to develop marker vaccines and thus there would be a requirement to develop diagnostics that can differentiate vaccinated and naturally infected animals. This should not be a problem using recombinant DNA technology. The detection of carrier animals remains a challenge: they present with low parasitaemias that are difficult to detect using parasitological and even molecular methods. They do not always carry specific antibodies. GAP: Specific and sensitive tests to detect carrier animals and possibly also quantify parasite loads. This could be significant depending on what is required. The cost of developing new or improved diagnostics could be significant. Affordable pen-side tests could prove valuable in the field, especially in non EU endemic regions. Not applicable. However, parasite freedom in animals would be very difficult to demonstrate due to the fluctuating low parasitaemia in carrier animals. It would need repeated testing of the same animal. New developments for vaccinesThe main challenge is to stimulate cell-mediated immunity, which is presumed to be achieved using live vaccines. Live vaccines present difficulty for storage and delivery as the main constraint, but quality control and production are also issues. New vaccine developments should either focus on storage improvement or completely new vaccination type (e.g. DNA vaccine). Recent studies showing that a sporozoite antigen can provide a synergistic response with an attenuated cell line imply that the cell mediated mechanisms may not be directed against specific antigens. Antigen delivery and adjuvant development are probably required. GAP: There is a requirement to establish exactly how attenuated vaccines engender protective immunity. Variable because of research time needed. Medium to long term (>5 years). The cost could be substantial bearing in mind the animal studies that would be required for registration. The potential return on investment bearing in mind the geographical location of this disease may also influence any decision to proceed. Identification of protective antigens, identification of correlates for protective immune response read outs. GAP: Study of parasite transfer from vaccine (donor infected leukocytes) to receiver leukocytes. New developments for pharmaceuticalsBearing in mind the perceived resistance to current theilericides future pharmaceutical development would need to concentrate initially on new theilericides compounds, and there is little evidence, to date, that new therapeutic breakthroughs in other apicomplexa’s like Plasmodium or Toxoplasma will be applicable to Theileria. Variable because of research time needed and the fact that the active ingredient, once established, needs to be a compound that is produced under GMP. The cost could be substantial bearing in mind the animal studies that would be required for registration. The potential return on investment bearing in mind the geographical location of this disease may also influence any decision to proceed. Option of mining the apicoplast metabolism pathways for new therapeutics. Genes encoding apicoplast proteins were obtained for T. parva and nine potential drug targets with a match to other apicomplexan apicoplast genes identified. An in silico metabolic map of the Theileria apicoplast was generated: Lizunda et al. 2009. A range of putative apicoplast inhibitors was tested against macroschizont infected cells the results were not particularly encouraging, certainly relative to buparvaquone the standard that, ideally, all new drugs should aim for. Disease detailsDescription and characteristics.Theileriae are obligate intracellular tick-borne protozoan parasites infecting mammalian hosts. There are a number of species that infect cattle within Theileriae; however, the two most important species are T. parva and T. annulata. Theileria parva (East Coast fever) is restricted to sub-Saharan Africa whilst T. annulata (Tropical /Mediterranean theileriosis) occurs in southern Europe as well as North Africa and Asia. Theileria annulata can occur in cattle, yaks, water buffalo and camels and is transmitted by ticks of the genus Hyalomma. Tropical Theileriosis is more severe in European breeds, with a mortality rate of 40 – 90% while the mortality rate in indigenous breeds of cattle from endemic areas can be as low as 3%. In Spain, T. annulata infections are mainly restricted to the Southern and Mediterranean areas like Menorca Island, where the tick vector (Hyalomma sp.) is present. In Northern Spain, reports on the presence of Hyaloma ticks are only sporadic, as well as associated T. annulata infections. However, tick distribution might change due to changes in climatic conditions. Theileria orientalis/buffeli is widely spread around the world. Infection is generally subclinical; however, disease can occur in cattle depending on many epidemiological factors (including previous exposure to Theileriae, stress/health status, variations in the species pathogenicity, as reported recently in Australia and New Zealand). T. lestoquardi, also transmitted by Hyalomma ticks, is the only species of economic significance infecting small ruminants and it also occurs in North Africa, the Mediterranean basin and Asia. In sheep and goats the morbidity rate from T lestoquardi can approach 100% with a mortality rate of 46 – 100% in the most susceptible breeds. Theileria uilenbergi and Theileria luwenshuni are pathogenic ovine piroplasms described in northwestern China, but similar (on sequence) Theileria parasites have been found in sheep in Northern Spain and Turkey, but apparently with a low pathogenicity. GAPS:
Obligate intracellular protozoan. Can survive in ticks for several months (up to 6 months or more, depending on ecology of tick vector). Species involvedAll Theileria species give rise to a carrier status. They can infect cattle, yaks, water buffalo and camels. Once infected, assuming recovery, the animal becomes a carrier and can be infective for months or years. T lestoquardi infects small ruminants, like sheep and goats. GAP: Dynamics of the carrier state. Hyalomma can attach to humans but T. annulata and T. lestoquardi have never been recorded in humans. Human theileriosis has been diagnosed mainly in USA and is caused by T. microti, the pathogen is transmitted by ticks of the Ixodes genus and mice are the reservoirs. T. annulata is an obligate intracellular protozoan and uses ticks of the genus Hyalomma as the intermediary host in a cyclical life cycle. Hyalomma species present in Europe are 3 host ticks except for H. marginatum (2 host tick). The Haemaphysalis species of ticks (3 host tick) act as a vector for T. orientalis/buffeli. The transmission is only transstadial. All Theileria’s can be transferred iatrogenically by blood inoculation and the inadequate use of infected needles. GAP: Other tick genus involved, especially for T. lestoquardi? The reservoir for T. annulata and T. orientalis/buffeli involves infected mammalian species and infected species of the tick that act as the vector. There is no known environmental reservoir. Description of infection & disease in natural hostsT. annulata and T. lestoquardi are transmitted by ticks of the genus Hyalomma. Theileria sporozoites are transmitted to animals in the saliva of the feeding tick. Ordinarily T. annulata sporozoites only mature and enter the saliva after the tick attaches to a host; a tick must usually be attached for a few days before it becomes infective. However, if environmental temperatures are high infective sporozoites can develop in ticks on the ground and may enter the host within hours of attachment. Transovarial transmission does not occur. Inside the mammalian host the theileria sporozoites initiate a complex life cycle involving the replication of schizonts in leukocytes, production of merozoites and formation of piroplasms in erythrocytes. Ticks can remain infected on the pasture for up to 2 years depending on climatic conditions. GAPS: The molecular mechanisms that control sporozoite production (and parasite stage differentiation) are not fully understood. Blocking this event or production of piroplasm-infected erythrocytes would effectively block transmission. The schizont is recognised as the pathogenic stage, as it causes lymphoid proliferation and later induces lymphoid destruction. However, the piroplasm stage in erythrocytes may also be described as pathogenic since it is associated with causing jaundice, anaemia and in some cases haemoglobinuria. GAPS:
Clinical signs associated with infection of T. annulata are dependent on the acuteness of infection but generally include generalised lymphadenopathy, fever, anorexia and loss of condition with sometimes sudden decrease in milk yield. Petechiae and ecchymoses may be found on the conjunctiva and oral mucous membranes. Lacrimation, nasal discharge, corneal opacity and diarrhoea can also be seen. Terminally ill animals often develop pulmonary oedema, severe dyspnoea and a frothy nasal discharge. The destruction of red blood cells can cause jaundice, anaemia, and in some cases haemoglobinuria. Abortions might be the most important sign in non-milking animals. With T. orientalis/buffeli, clinical pathological changes are reflective of a haemolytic anaemia. A regenerative anaemia is generally present. In northern Spain, T. buffeli infections present a benign course with red cell parameters within normal ranges. GAP: Effects of mixed infections on disease severity. The incubation period is thought to be approximately 1 to 3 weeks. Primary infections are often fatal in highly productive European breeds of cattle in which the mortality can reach 40 – 90%. The mortality in indigenous cattle from endemic areas can be as low as 3%. GAP: Mortality figures for cattle and small ruminants in the EU. T. annulata is an obligate intracellular protozoan and therefore shedding does not occur. Carrier animals remain infective to ticks for several years. GAP: Length and dynamics of carrier state in production animals. The sporozoites of T. annulata and T. lestoquardi preferentially invade cells of myeloid lineage (monocytes/macrophages) and B cells. The parasite has the ability to transform its host cell (similar to oncogenic transformation). Signal transduction pathways are triggered leading to uncontrolled activation of a protein kinase called casein kinase II. This results in production of IL-2 and IL-2R. As a result an autocrine or paracrine loop is established where infected cells secrete IL-2 that in turn stimulate growth. It is also evident that host cell infection causes constitutive activation of factors that regulate the inflammatory response (e.g. NF-B). As the schizont stage develops within leucocytes, infected cells enlarge to form blasts and begin to proliferate. Since the parasite can divide synchronously with its host cell there is rapid clonal expansion of parasitized cells. Parasite infected cells also gain the ability to metastasize to many tissues and organs. This involves activation of AP-1, expression of cytokines, surface receptors and proteases. Pathology is mainly caused by the accumulation of parasitized leukocytes in vital organs causing severe inflammation and pyrexia. To some extent, pathology is also caused by haemolytic anaemia. The other Theilerias do not transform leukocytes (T. equi and T. orientalis) or only target red bloodcells (T. microti) and are therefore not transforming parasites. GAPS: The impact of host cell type on disease pathology is not fully understood but is likely to play an important role, as are host genetic differences in cellular activation and response to infection. The full complexity of how the parasite manipulates its host to cause disease is not understood. Zoonotic potentialThere is no current evidence that T. annulata or T. lestoquardi or T. buffeli/orientalis are a hazard to humans. N/A N/A N/A N/A Impact on animal welfare and biodiversityInfection by T. annulata parasites limits the movement of cattle between countries and can result in production losses and high mortality in susceptible animals. Because this disease is most severe in highly productive exotic animals, it is a significant constraint on the importation of new breeds or improved stock into endemically affected regions. T. annulata is not known to affect any of the endangered wild species. GAP: Wildlife as reservoirs of the disease and tick hosts. The compulsory slaughter of infected animals is not currently practised, however, if the disease spreads to new countries this may become the preferred method of control, especially in Europe. Compulsory slaughtering implies slaughtering all sick, recovered and immune animals. GAP: The efficacy of compulsory slaughter on preventing disease spread. Geographical distribution and spreadTheileria annulata is present from N Africa and Southern Europe through the Middle East and into Southern Asia. Sporadic cases of T. annulata are reported in northern Spain (Atlantic climate zone) where the vector (Hyalomma spp.) is not established. T. buffeli/orientalis is present in many countries of the world. GAP: Continuous monitoring of tick species distribution for early detection of changes in vector distribution. In Spain, T. annulata infections are described in the southern and Mediterranean (e.g. Minorca) areas, where climatic conditions favour the presence of the Hyalomma tick vector. The situation is very different in different parts of Spain. T. annulata is known to be endemic in the southern, western and Mediterranean areas like Extremadura, Andalucia and Minorca. Epidemics mostly occur when susceptible animals are introduced in endemic areas or carrier animals are introduced into vector free regions, but infection has been spread through use of needles (Northern Spain). Outbreaks might also be recorded at the fringes of the geographical distribution. Disease in endemically affected locations may also occur as a result of breakdown in premunity through the occurrence of unrelated disease epizootics affecting the balance between the host and the Theileria agent. Calves are at risk even in endemic areas, on a yearly basis. Theileria incidence shows a marked seasonality resulting from the vector tick activity. Thus, the spring and the end of summer are the periods with acute T. annulata infections in Menorca. This is primarily dependant on the movement of infected cattle. It also depends on the presence of vector ticks in the new areas or the concomitant introduction of vector ticks with infected cattle. The disease is primarily dependant on suitable habitat for the tick species that transmit it. Movement of infected cattle away from the area known to be inhabited by the tick will not necessarily spread the disease (unless the vector tick is concomitantly introduced) but movement within the habitat of the tick will spread the disease. Extension of tick habitat coupled to cattle movement is likely to have greatest transboundary potential. There is a danger of introduction of North-African species of Hyalomma in Europe through sheep transports. The Moroccan vector H. detritum detritum is endophylic, so a completely different (easier) control approach would be needed once introduced. GAP: Frequency of live animal transport between Europe and North Africa. Only in that the biology/activity of the vector tick itself is seasonal. The disease will follow the geographic distribution of the tick and if the climate favours spread of the tick then spread of the disease will follow. GAP: Tick population dynamics monitoring schemes to study the effects of climate change on the local distribution and abundance of ticks. Some Hyalomma vector ticks appear to be particularly abundant during extremely warm periods. Most cases appear towards the end of summer, much more than in spring. Global warming may influence the geographical distribution of the tick, the tick abundance and the tick’s vectorial capacity that in turn will affect the distribution and incidence of the disease. Hyalomma ticks are known to occur in drier biotopes compared to most other tick genera, so climate change or global warming might favour Hyalomma survival and spread. GAPS: Which climate change parameters would promote spread of the Hyalomma tick populations? How is vectorial capacity affected by climate change? Route of TransmissionT. annulata is an obligate intracellular protozoan and therefore the usual mode of transmission is via the intermediary host tick. Theileria is often introduced in a new area through the introduction of a carrier animal and will spread if tick vector is present. The inappropriate use of contaminated needles can cause transmission. The movement of infected animals (and infected vectors) and climatic conditions favouring the habitat and proliferation of the tick will favour the spread of the disease. Detection and Immune response to infectionInnate and adaptive immune responses cooperate to protect cattle against T. annulata theileriosis. Intracellular parasites are mostly affected by cell-mediated immunity. Infection of leukocytes by T. annulata activates the release of cytokines, initiating an immune response and helping to present parasite antigen to CD4+ T cells. These cells produce interferon-γ that activates non-infected macrophages to synthesise tumour necrosis factor α and nitric oxide which destroy schizont and piroplasm infected cells. CD8+ T cells have recently been shown to recognise parasite MHC presented antigens and kill infected leukocytes. B cells produce antibody that along with nitric oxide kill extracellular merozoites and intracellular piroplasms. On the other hand overproduction of cytokines, in particular tumour necrosis factor α by macrophages generates many of the clinical signs and pathological lesions that characterise T. annulata theileriosis and the outcome of infection depends on the fine balance between protective and pathological properties of the immune system. GAP: Conclusive identification of parasite antigens that confer protective immunity. The relative importance of different arms of the immune response. The ability of the parasite to manipulate the immune response. The indirect fluorescent antibody test is the most widely used diagnostic test for T. annulata. It is easy to perform and provides adequate specificity for use in the field but has limitations for large-scale serological surveys. Serological tests based on ELISA techniques are increasingly being used for the detection of parasite specific antibodies and have been shown to detect antibodies for a longer period of time than the IFA. PCR tests have also been developed. GAP: A standardised diagnostic test that is routinely employed across endemic regions. Elisa for T. lestoquardi. Main means of prevention, detection and controlControl of the disease by the use of acaricides (mainly pour-ons) involves more or less continuous use during seasons of tick challenge and is difficult to maintain. In addition to environmental concerns, continuous use of acaricides is known to result in the selection of acaricide resistant ticks. Treatment is effective if given in the early stages of the infection, but creates a carrier status, source of infection for the vector. Slaughter might be the most effective measure to prevent spread to a new area. GAP: Effective strategies for disease eradication (if desirable). There are no effective means of mechanical control. It is conceivable that biological control of the ticks could be exercised by using a natural pathogen/predator of the tick but this does not appear to have been tried as a serious means of control to date. Keeping animals inside might not help since ticks can be found in the stable walls and in hay. Cementing walls may be effective but requires continued maintenance. GAP: Effect of different management systems on infection prevalence. Serological tests as IFA, ELISA and PCR assays, together with identification of schizonts in Giemsa-stained smears from blood or lymph node biopsies are used for diagnosis. GAP: Quick test kit for Theileria sp, Babesia sp and Anaplasma sp. Live vaccines produced by attenuating parasite-infected leukocytes have been used to vaccinate cattle against T. annulata. In more recent times subunit vaccine research has been focused on surface antigens (recombinant SPAG-1 and Tams1 surface antigens of T. annulata sporozoites and merozoites, respectively). It has been shown that SPAG-1 recombinant protein can act synergistically with live attenuated vaccine to provide increased protection against challenge. GAPS:
Chemotherapeutic compounds such as buparvaquone with theilericidal properties have been used but tend not to completely eradicate the infection thus leading to the development of carrier states. Buparvaquone is registered in Turkey but not in EU. Resistance against this drug has recently been reported for Tunisia and cases have been identified in Turkey. GAP: The extent of drug resistance, development of test for drug resistance monitoring. In the endemic areas it is unlikely that biosecurity measures would be practical but in theory it would be possible to maintain the animals in a tick free environment thus removing the threat of infection from the intermediate host stage of the disease. It is unlikely that the spread of the ticks could be controlled. On the other hand, controlling animal movement would be useful in managing the disease. Pre-movement acaricide treatment or treatment at movement nodes represents an appropriate method of control where cattle move from endemic to non-endemic disease areas. GAP: Movement patterns of cattle from affected to unaffected regions. Vaccination is an efficient prevention tool in endemic areas. Prevention could also rely on the effective use of acaricides with proper use of these compounds to avoide resistance build up among the tick population. Anti-tick vaccine development might be another approach. Not currently practised. Difficult to get financial support for epidemiological studies. Data collected through research based studies. GAP: The prevalence of disease and distribution of competent vectors within endemic and bordering regions/countries. Eradication using available control measures might be very difficult to achieve, and may be undesirable as it generates a population of highly susceptible cattle. Eradication could be an option under specific conditions of known epidemiology in areas experiencing sporadic disease or spread to new areas. Tick control and vaccination have proven their efficiency under specific conditions. GAP: Current epidemiological situation of T. annulata in EU. The cost of control may be substantial and it is conceivable that part of the reason for lack of effective control is that subsistence farmers in the endemic area are reluctant to commit sufficient resources to control the disease. It is also possible that the true cost of productive losses (subclinical losses) resulting in endemically affected indigenous cattle may not be obvious to farmers. Studies in Tunisia have indicated that sub clinical disease has most impact on economic production. GAP: The true cost of subclinical disease in indigenous breeds of cattle in endemically affecting regions/countries. Disease information from the OIEYes. http://www.oie.int/fileadmin/Home/eng/Animal_Health_in_the_World/docs/pdf/THEILERIOSIS_FINAL.pdf http://www.oie.int/index.php?id=169&L=0&htmfile=chapitre_1.11.13.htm http://www.oie.int/fileadmin/Home/eng/Health_standards/tahm/2.04.16_THEILIERIOSIS.pdf Socio-economic impactN/A N/A This can be substantial especially for subsistence farmers found throughout the affected area. Where the disease occurs in Southern Europe, high producing breeds of animal tend to suffer proportionately higher mortality. The cost of the continuous use of acaricides during the tick-feeding season can be high (per application: 0,20€ for spraying - 3,1€ for pour-on) and in fact may not be effective. Cost of chemotherapy is high and beyond subsistence farmers. Surveillance, compulsory slaughtering, production and delivery of vaccine require state/government involvement. GAP: Identification of most cost effective control strategy. The main impact is on security of the food supply for indigenous people in endemic areas, since it is unlikely that significant improvements to production through breeding can be accomplished and even infected indigenous breeds of cattle can show high levels of morbidity with loss of production of meat and milk. Over judicious use of acaricides may increase entry of chemicals into the food chain. Loss of animal draught power, animal byproducts used as fuel. Trade implicationsExports from the EU are unlikely to be affected. Exportation of live animals will be subject to restrictions. Animals from the endemic area of Southern Europe would be expected to have veterinary certificates indicating they were free of the disease and had been recently treated with an acaricide to prevent the inadvertent movement of ticks. GAP: Feasability of veterinary certification given lower than 100% efficacy of acaricide treatment and carrier status detection. Providing that the appropriate veterinary certificates are available and treatment with acaricides had been undertaken then there should be no reason to prevent national trade in live animals. Main perceived obstacles for effective prevention and controlThe main obstacle to effective prevention and control would be the difficulty in achieving eradication of the tick population from the endemic areas and/or effective vaccination. Tick control: expensive infrastructure or expensive products (pour-on), residues in milk, meat and environment. Vaccination: strain specific, live vaccine requiring storage < -80°C, good quality control and delivery. Live vaccines might import different genotypes. Iatrogenic spread through injecting pharmaceuticals without changing needles also needs to be considered. Generation and spread of drug resistance. GAP: The most effective timing/interval for acaricide treatments within age class of cattle. Main perceived facilitators for effective prevention and controlAn effective and cheap sub-unit vaccine may facilitate the control of this disease. GAP: Identification of protective antigens and delivery strategies associated with induction of protective immunity. RiskThe two most pressing potential risks are: 1. The spread of the disease to other previously uninfected areas due to expansion oftick habitat as a result of global warming. 2. Severe constraint on the ability to significantly develop/increase production capacity of indigenous stock in the currently affected areas in order to avoid food shortages resulting form human population growth. ConclusionSome 240 million cattle over a region extending from the Mediterranean basin through the Middle East and across South Asia are at risk of infection. Livestock are a key resource for the production of milk and meat as well as generating cash for an enormous number of very poor farmers in the tropical and sub-tropical regions of the world. Improvement of the standard of living and nutrition of these farmers can be achieved by improving the productivity of their livestock. It should not be overlooked that indigenous cattle from these regions have a much lower risk of mortality from T. annulata. Management level will be instrumental in choosing the appropriate approach to disease control; either low input farming with indigenous cattle, or high input farming using high productive animals. |
