Bovine babesiosis is a global tick-borne disease that causes important cattle losses and has potential zoonotic implications. The impact of bovine babesiosis in Turkey remains poorly characterized, but several Babesia spp., including B. bovis, B. bigemina, and B. divergens, among others and competent tick vectors, except Rhipicephalus microplus, have been recently identified in the country.
An important chapter on animal infectious diseases began in 1888 with the sudden deaths of thousands of cows in Romania . At the time, Victor Babes associated the animal deaths with an intraerythrocytic organism, which he named as “haematococcus.” These organisms were later identified as protozoan parasites, and renamed Babesia to honor its discoverer . A few years later, two researchers in the US, Smith and Kilbourne, found out that Babesia parasites were transmitted by Ixodid ticks, demonstrating for the first time transmission of a parasite by an arthropod vector . Follow up studies have characterized several species of Babesia as tick-transmitted apicomplexan protozoan hemoparasites with veterinary and human importance, and great economic impact worldwide . Babesiosis is a disease that affects many vertebrate hosts, from humans to bats, as well as farm animals, such as cattle, horses, and small ruminants, and companion animals . There are more than 100 Babesia species reported so far, with different host specificities . Here, we focus on bovine babesiosis, a disease with a particular large impact on cattle worldwide. In addition to major economic losses derived from death of animals and decreased production of meat and dairy products, there are other important costs associated with tick control, diagnosis, and treatments required to prevent the disease. Despite the importance, there is no reliable specific quantification of the impact of bovine babesiosis at the global scale, but only independent regional assessments performed in individual countries, such as Brazil, Argentina, Australia, among others, and the estimated losses are in the order of hundreds of millions of US dollars per year.
Babesia parasites have a complex life cycle that includes the development of asexual stages in mammalian hosts and sexual stages inside their definitive tick vectors. Two characteristics that define sensu stricto Babesia parasites are their ability to be transmitted transovarially by tick vectors and exclusively infect red blood cells (RBC) in their vertebrate host. These aspects are particularly important for B. bovis, B. bigemina, and B. divergens, the major causative agents of bovine babesiosis .
Growth of asexual stages of Babesia parasites inside the vertebrate host RBC causes severe intravascular hemolytic anemia, which is a pathognomonic sign of the acute disease and highly debilitating for the host. Additionally, fever, prostration, abortion, and temporary infertility are also common clinical findings during acute infection. Hemoglobinuria is also usually present at the peak of the hemolytic crisis in B. bigemina or B. divergens infection and in late stages of the disease caused by B. bovis. In addition, residues and toxic metabolites released as a result of the infection and RBC destruction can negatively affect host organ systems . Moreover, B. bovis has the unique ability to evade the cattle immune system by expressing proteins that facilitate cytoadhesion of infected RBC to capillaries, such as in the brain, causing neurological symptoms and generalized organ failure, a feature that results in increased virulence. Altogether, these pathological mechanisms frequently lead to rapid death of cattle during the acute stage of the disease, especially when affecting adult naïve animals.
Upon infection, the immune system of the host responds differentially, depending on the age of the animals. While young animals, less than seven months old, are frequently able to control severe acute babesiosis and can survive re-exposures to the parasites, older than one-year-old animals often succumb rapidly to infection. Features associated with resistance in young animals include early and strong activation of the innate and adaptive immune effectors. Briefly, the parasite expresses molecules able to bind pathogen associated molecular patterns (PAMPs) receptors expressed on the surface of dendritic cells (DC), macrophages, neutrophils, and monocytes, especially TLR9 , and an immune response is initiated. Cytokines, such as IL-1β, TNF-α, and IL-12, and nitric oxide (NO) are released from monocytes and neutrophils, and chemokines attract immature DC to the site of infection, especially at the spleen. These stimulate natural killer cells (NKs) that release early IFNγ. The mature DC migrating to the spleen presents Babesia antigens to naive T cells. Spleen macrophages are activated by IFNγ, phagocytize infected RBC, and kill the parasites by releasing reactive nitrogen and oxygen intermediates. In turn, cytokines, such as 1L-1β, IL-12, and TNF-α, released from activated macrophages may inhibit the growth of B. bovis. Activated CD4+ T cells and specific B-cell producing antibodies are also important in maintaining immunity and overcoming the infection . Despite mounting protective adaptive immune responses, animals that survive acute babesiosis develop persistent infection, which allows transmission and perpetuation of Babesia parasites in endemic areas. These areas usually have elevated prevalence of bovine babesiosis but low numbers of clinical cases due to the establishment of endemic stability, a condition of herd immunity that develops when more than 75% of the animals have acquired protective immunity by exposure to the parasite before one year of age, when animals are less susceptible to the parasites. A highly unstable state may occur, in contrast, when less than 30% of the herd is naïve for the disease .
B. bovis and B. bigemina, which are transmitted by Rhipicephalus ticks, are the most important causative agents of bovine babesiosis in tropical and subtropical regions worldwide. In addition, B. divergens is another important Babesia species that is transmitted by Ixodes ticks and affects cattle in Europe and North Africa. Apart from its impact on bovines, B. divergens is especially important as a zoonotic pathogen implicated in human babesiosis in Europe . Acute bovine babesiosis caused by B. bovis is often severe due to cytoadhesion of infected RBC in the lung, kidney, and brain capillaries, which leads to hypotension, respiratory stress syndrome, neurological symptoms, and death . In contrast, B. bigemina induces massive hemolytic anemia without causing the symptoms associated with cytoadhesion . Also of importance as causative agents of bovine babesiosis are B. ovata, B. major, B. occultans, and additional unclassified Babesia that are characterized by their low pathogenicity in cattle compared to B. bovis, B. bigemina, and B. divergens .
Turkey is a transcontinental country located in the Northern hemisphere with a territory spanning the Anatolian peninsula in Western Asia and a small portion on the Balkan Peninsula in Southeastern Europe. Geographic coordinates of the country lie at latitude 39 and longitude 35. It is a peninsula with a strategic position as a land connection between Europe and Asia. Considering its location, the country has been also regarded as a natural bridge for transcontinental transmission of tick species and tick-borne diseases (TBD) . Turkey covers an area of 783,582 km2 with a population of 82 million people. The country’s economy is based on modern industry, tourism, and trade, and is also heavily supported by the agricultural sector. Therefore, the presence of emerging tick populations and TBD can pose a serious risk to the cattle industry that may impact the overall economy of Turkey and neighboring countries .
Although the importance of cattle has been different in every society throughout the history of humanity, these animals have always had significant importance in several cultures and religions, and still remain an important economic asset in Turkey and worldwide. There are approximately 66 million farm animals in Turkey, and 27% of which (18 million) are cattle. In Turkey, milk production consisted of 90.5% cattle, 6.6% sheep, and 2.5% goat. As for meat production, 89.5% of the total meat produced in Turkey comes from cattle. According to a report from 2018, approximately 1.5 million live animals are imported to Turkey . Some of these animals come from countries that are endemic for cattle ticks, bovine babesiosis, and other cattle TBD, such as Brazil, from where Turkey obtains 42% of its total imported animals . Considering that cattle are a very important source of protein, especially meat and milk production, the cattle industry is a significant sector to secure food supply and sustain the economy in Turkey . Assuring constant supply of cattle milk and meat requires keeping high animal sanitary standards and rational strategies for industry development. In addition, particular attention should be placed in controlling diseases that limit cattle production and may compromise public health. This should be extended to the potential introduction of additional animal health risk factors, such as foreign pathogenic organisms. Taking into consideration the social and economic importance of cattle in Turkey, we argue that the development of a national intensive research program on TBD, specifically in bovine babesiosis, and the implementation of informed animal health policies of disease control based on the state-of-the-art knowledge should be considered issues of crucial importance for the country.
It is estimated that more than 500 million cattle are at risk of babesiosis worldwide; therefore, this disease poses a major threat to animal health and human livelihood in areas where Babesia parasites and competent tick vectors are present . As an attempt to contain such threat, a radical tick control campaign was launched in the US at the beginning of the 20th century, lasting 40 years and demanding the use of millions of taxpayer’s dollars. With this effective, but costly campaign, bovine babesiosis was eradicated in the US, and consequently approximately $3 billion US dollars annually were saved for the livestock industry . Unfortunately, the success of this approach was not reproduced in other countries that also attempted similar tick eradication schemes , and given a current scenario of increased acaricide resistance in ticks and climate change, among other factors, it is unlikely that this achievement can be duplicated elsewhere .
Annual economic losses due to bovine babesiosis and anaplasmosis in the world range from $16.9 million US dollars in Australia, $21.6 million US dollars in South Africa, and $57.2 million US dollars in China . These losses are not only due to animal mortality, but also abortion, decrease in meat and milk production, and disease control costs (e.g., spraying, vaccination, disease treatments, professional veterinary support, and others). In addition, disease-related deaths are frequently observed in naïve cattle imported to regions with enzootic stability for bovine babesiosis , a factor that causes additional economic losses and complicates the attempts to carry out genetic improvement of herds. In this way, preventing clinical cases of bovine babesiosis by strategies based on maintaining enzootic stability may also interfere with the efforts to improve productivity, such as increased weight and milk production, heavily affecting the meat and dairy industries, respectively, which increases production costs .
Turkey’s geographic location and climatic conditions, in addition to the country’s animal management systems, encourage the occurrence of ticks and TBD . The emergence of tick populations and TBD have increased around the globe in the recent years, including in Turkey . Estimation of the amount of TBD drugs sale per year during the disease seasons indirectly shows the importance of these diseases on animal health and in the economy of Turkey . The economic impact of topical theileriosis caused by Theileria annulata, a tick-borne apicomplexa parasite related to Babesia sp., was estimated at a total annual loss of approximately 600,000 US dollars in Turkey . However, despite being considered as a costly burden, the actual economic impact of bovine babesiosis on the cattle industry in Turkey remains largely unknown. Therefore, a well-designed national surveillance study to evaluate the real impact of the disease on the cattle industry in the country is urgently needed.
Tick vectors are essential components for the completion of the life cycle of Babesia parasites. Thus, competent ticks must provide the environment required for sexual reproduction, which occurs in their midgut, and for invasion of tick eggs by the kinete stage of parasites that circulates in the tick hemolymph, an event that ultimately guarantees transovarial transmission of Babesia. A large number of Ixodid tick species are listed as competent Babesia vectors in the literature . Of these, 22 were confirmed vectors for 18 different Babesia species that infect livestock, companion animals, and humans . Identification of pathogen DNA in adult ticks cannot be accepted alone as evidence of vector competence, and more detailed studies on tick-Babesia interactions are needed to establish the tick competence. Additionally, the presence of Babesia DNA in the salivary glands, eggs, and unfed larvae, though more convincing, also requires confirmation as a measure of tick competence . B. bovis and B. bigemina are transmitted by R. annulatus, R. microplus, and R. geigyi ticks found in tropical and temperate regions of the world. B. bigemina can also be transmitted by R. decoloratus and R. evertsi, making it the most common Babesia species infecting cattle in Africa . B. divergens are transmitted mainly by I. ricinus, which develops only in moisture-saturated microhabitats . B. occultans, B. major, B. orientalis, and B. ovata are transmitted by Hyalomma rufipes, Haemaphysalis punctata, R. haemaphysaloides, and Hae. longicornis, respectively . A summary of known competent tick vectors implicated in bovine babesiosis is shown in Table 1, where we highlight the species present in Turkey.
Table 1. Babesia spp. currently identified in cattle with proven vectors and geographical distribution.
To date, R. annulatus, R. bursa, R. turanicus, R. sanguineus, Hy. anatolicum, Hy. dromedari, Hy. detritum, Hy. excavatum, Hy. marginatum, Hy. rufipes, Hy. aegyptium, Dermacentor marginatus, D. niveus, I. ricinus, and Hae. parva ticks have been reported infesting cattle in Turkey , and some of them were associated with transmission of cattle Babesia parasites (Table 1). In a study using ticks collected from cattle in the Black Sea region, Babesia parasites were reported in Hy. marginatum, Hy. Excavatum, and R. turanicus at the rates of 3.5%, 2.3%, and 6.6%, respectively . Babesia sp. Kayseri 1, a novel parasite isolate, was identified in Hy. marginatum feeding on cattle in the Kayseri province located in Central Anatolia . B. bigemina was also reported in unfed larvae from R. annulatus in this same province . In another study in the same region, B. bigemina was found in tick populations of R. annulatus, R. turanicus, Hy. marginatum, and Hy. Anatolicum, whereas B. bovis positive samples were detected in Hy. marginatum ticks . B. occultans was reported in Hy. marginatum and R. turanicus, as well as in their eggs, and thus, these findings suggest that this later tick can also be a competent vector for B. occultans . In another study, B. occultans was identified in questing Hy. marginatum ; however, despite the findings, effective transmission of Babesia by these ticks remains to be demonstrated in Turkey.
Collectively, currently available data indicate the presence and expansion of tick populations in Turkey. In addition, most of these tick species have been shown to be competent in transmitting Babesia parasites implicated in bovine babesiosis. Considering the current environmental changes and the importance of the cattle industry in Turkey, epidemiological and entomological studies focused on ticks associated with Babesia transmission are urgently needed in the country. Given the absolute dependence of ticks for parasite survival, identifying all competent vectors for Babesia species circulating in the country and a more complete understanding of the dynamics of the Babesia-tick interactions will be essential to achieve improved control of bovine babesiosis in Turkey.