Int.J.Curr.Microbiol.App.Sci (2015) 4(7): 938-953

International Journal of Current Microbiology and Applied Sciences ISSN: 2319-7706 Volume 4 Number 7 (2015) pp. 938-953 http://www.ijcmas.com

Review Article

Zoonotic significance and Prophylactic Measure against babesiosis

Faryal Saad, Kalimullah Khan, Shandana Ali and Noor ul Akbar*

Department of Zoology, Kohat University of Science and Technology, Kohat, Khyber Pakhtunkhwa, Pakistan *Corresponding author

ABSTRACT

Babesiosis is a borne disease by the different species of genus ,

affecting a large no of mammals worldwide. Babesiosis has zoonotic significance all over the world, causing huge loss to livestock industry and health hazards in human population. The primary zoonotic vector of babesia is . Keywo rd s Different species have different virulence, infectivity and pathogenicity. Literature

was collected from the individual researchers published papers. Table was made in Babesiosis , the MS excel. The present study review for the current knowledge about the Prophylactic, babesia species ecology, host specificity, life cycle and pathogenesis with an borne, emphasis on the zoonotic significance and prophylactic measures against Vector, Babesiosis. Prophylactic measure against Babesiosis in early times was hindered . but due to advancement in research, the anti babesial drugs and vaccines have been developed. This review emphasizes on the awareness of public sector, rural

communities, owners of animal husbandry and health department about the risk of

infection in KPK and control measure should be implemented. Vaccines of less price tag should be designed to prevent the infection of cattles and human population.

Introduction

Babesiosis is a tick transmitted disease, At specie level there is considerable infecting a wide variety of wild and confusion about the true number of zoonotic domestic animals, as well as humans. species. Recent studies indicate that Babesia Babesiosis is also called tick , Texas microti is a species complex together with at fever, red water and piroplasmosis caused least four named species (US, Munich, by different Babesia species found in Kobe, and Hobetsu) and unknown number tropical and temperate regions of the world of other strains (Goethert et al., 2006; Tsuji (Criado-Fornelio et al., 2004). Babesiosis is et al., 2006; Nakajima et al., 2009). an emerging zoonotic disease having Babesiosis may be asymptomatic estimating different reservoir host for zoonotic Babesia that about a third of patients remain species. B. microti, other asymptomatic (Krause et al., 2003) While in like species and B. divergens have zoonotic symptomatic cases clinical signs of human significance. Babesiosis are persistent non-periodic high

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Int.J.Curr.Microbiol.App.Sci (2015) 4(7): 938-953 fever (40–41°C) , severe sweats, the last suggesting preventive and headaches, , and lumbar and prophylactic measures in order to minimize abdominal pain. due to high level the transmission of vectors to humans and of haemolysis, and diarrhea may animals. Prophylactic measures are also also occur. Respiratory, cardiac, renal, or recommended against tick vectors, to reduce hepatic failure may be present due to release the economic loss to livestock industries in of toxins during haemolysis and because of KPK. host immune response (Zintl et al., 2003; Telford et al., 2006; Hunfeld et al., 2008). It Historical background is possible that single Babesia specie can infect more than one vertebrate host as For centuries Babesiosis was known to be a Babesia microti ( and men). serious hemolytic disease of wild and Babesiosis is transmitted biologically by a domesticated animals, chiefly cattles. Victor vector tick Ixoded species but biting of flies Babes, a Romanian scientist who 1st and fomites may also involve in the reported this disease in the Romania in mechanical transmission of Babesiosis from 1888, by describing the symptoms of infected to clinically susceptible animals haemolysis in the cattle and sheep (Ristic (Ristic and Levy, 1981). and Levy, 1981). In 1893 Americans and Fred Kilborne At the beginning of twentieth century vector recognized the parasite as the causal agent borne diseases resulting in the worldwide of this disease, they also describe that ticks epidemics affecting thousands of people are instrumental in the Babesiosis (Gubler, 1998). Zoonosis emerges in the transmission. They reported Babesiosis as populations due to the immigration of the first tick-transmitted disease. Hutcheon humans and livestock, lack of public in in 1896 describes the attentiveness and health resources, poverty presence of canine babesiosis. and changes in the climate (Sumilo et al., 2008). Pakistan being economic country Epidemiology and pathogenesis having large rural and developing urban population is also endemic to a large variety The genus Babesia causes Babesiosis which of tick vector and insect species (Reisen and is an intraerythrocytic protozoan. There are Boreham, 1979; Ghosh et al., 2007). In about more than 100 Babesia species in Pakistan more than 70% population of KPK which some are pathogenic to the humans depend on the livestock for their survival. for example Babesia microti is causative Due to restricted use of tick control measure agent of human Babesiosis in North and denied access to vaccines, the vector America while in the borne diseases in the people and livestock Europe also four to five Babesia species are industries are common in KPK and FATA reported in other human cases (Oliver Jr et regions of the Pakistan. These vectors borne al., 1993). Babesia bigemina and Babesia diseases cause morbidity and mortality from bovis cause bovine Babesiosis (Mehlhorn the animals acting as a reservoir of zoonotic, and Kakoma, 1994). Babesia argentina is vector borne agents (Irwin and Jefferies, mostly found in the South America (Levine, 2004; Otranto et al., 2009). 1985). Out of 20 Babesia species, 5 species are more important in the cattle’s. Babesia The review intended to discuss the zoonotic berbera found in the North America and significance and prophylactic measure Babesia major is slightly smaller than against Babesiosis in KPK Pakistan and in Babesia bigemina and transmitted by 939

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Haemaphysalis punctata and prevalent in the United Kingdom and northern Europe Pakistan economically depends on the (Pumell, 1981). Babesia equi and Babesia livestock sector, having contribution in 2008 caballi are distributed globally and cause and 2009 to agricultural value (51.8%) and equine babesiosis. Both species can be also to national gross domestic product transmitted by Boophilus, Hyalomma, (11.3%) (Mustafa, 2008). From , and species of epidemiological studies, it is revealed that tick (Levine, 1985; Friedhoff, 1988). Babesiosis in sheep is the third most and Babesia gibsoni are the important disease in Pakistan (Morris, causal agents of dog piroplasmosis and 2009). Babesiosis in Pakistan causes huge transmitted by or economic loss to the livestock industries. Dermacentor reticulatus ticks (Levine, Ticks are cosmopolitan in distribution in 1985). tropical and sub-tropical areas. Pakistan is tropical country having rich fauna of tick in Babesia jakimovi is large specie and it is the the number of genera and species, Because causal agent of Siberian piroplasmosis in of most favorable climatic conditions for the cattle. It can also infect the tartarean roe tick’s growth and reproduction (Rasul and deer, Asian elk and reindeer. The symptoms Akhtar, 1975). of Babesia jakimovi disease are similar to Babesia bigemina (Pumell, 1981). Babesia In Pakistan Hyalomma tick have highest ovate is reported in the and it is prevalence rate followed by Boophilus, slightly pathogenic and it is serologically Haemaphysalis and Rhipicephalus in district different from Babesia bigemina and Kasur (Durrani and Kamal, 2008). In the transmitted by the larvae of Haemaphysalis Khyber Pakhtunkhwa province of Pakistan longicornis (Minami and Ishihara, 1980). vector borne diseases is most prevalent due Babesia bigemina and are two to favourable climatic conditions and economically most important species to the poverty (Irwin and Jefferies, 2004; Otranto livestock industry in tropical and sub- et al., 2009). tropical areas of the world and transmitted by the same tick vector Rhipicephalus also Host specificity and life cycle called Boophilus microplus (Callow, 1984a,b; Hove et al., 1998). Babesiosis in Babesias are apicomplexan parasites of the the dogs is caused by Babesia canis first suborder Piroplasmidea of family babesiidae time reported in Itly. Babesiosis in case of due to their specific invasion in the Babesia bovis characterized by anemia, erythrocytes, multiplication by budding fever up to 42°C, jaundice, ataxia, , rather than schizogony. The life cycle of all increased respiratory rate, muscle weakness, Babesia species is approximately similar but and difficult to move. While in slight difference exists because in some Babesiosis due to Babesia bigemina, cattle species transovarial transmission occur do not seem to be as sick as those with (Babesia spp sensu stricto) while not in Babesia bovis, but haemoglobinuria occurs other species (Babesia microti). Almost all again and again, anemia and jaundice occurs the Babesia species are transmitted by the very frequently and death may occur infected tick bite. The major difference silently. Babesiosis also causes abortion in between Babesia and is that in cattle’s and reduces the fertility rate of bulls Babesia during tick infestations the approximately six to eight weeks (Callow, sporozoites directly infect the red blood cells 1984b). while in Theileria they do not readily infect 940

Int.J.Curr.Microbiol.App.Sci (2015) 4(7): 938-953 the red blood cells, but first they invade the basic function of this structure is gamete lymphocyte or macrophage in which they fusion (Kakoma and Mehlhorn, 1993; develop into schizont (Uilenberg, 2006). Rudzinska et al., 1983). Then epithelial cells Babesia species require two classes of host, of the tick gut are penetrated by the a vertebrate and invertebrate. All Babesia Strahlenkörper and start feeding on the species depend on both hosts for their epithelial cells after 80 hours of penetration, survival because specific tick vector must from where they move to the salivary glands feed on the vertebrate reservoir in order to of the tick with the help of haemolymph attain infectious stage. Babesia species (Rudzinska et al., 1983). generally complete their life cycle in 3- stages. The development of sporozoites complete in 3 phases in the tick salivary glands. First, 1-Gamogony (in the tick gut gametes fusion they form sporoblast that is a branching and formation) meshwork from which new sporozoites develop by budding approximately 5,000 to 2-Sporogony (in salivary glands asexual 10,000 new sporozoites can be develop in reproduction occur) the single Sporoblast (Kakoma and Mehlhorn, 1993; Karakashian et al., 1983). 3-Merogony (in the vertebrate asexual In the Second step, the specialized reproduction occur) organelles of the new developing sporozoites (micronemes, rhoptries, and Infection is directly related to the tick double membrane segments beneath the infestation time if it is prolonged then plasma membrane) will form within the infection rate will be 100 % (Piesman and meshwork when ticks host start feeding Spielman, 1982). Ixodes ticks are again. Finally, through budding process a instrumental in the transmission of mature sporozoite will form which is 2∙2 by babesiosis. Except in the Babesia meri in 0∙8µm in size and pear shaped having which a non-ixodes tick smooth endoplasmic reticulum, free erracticus acting as a vector. They feed in ribosome’s, mitochondria like structures, the fall (May through July) and in spring in interiorly located rhoptry and many nymphal stage, after which they lay eggs, micromeres (Karakashian et al., 1983). hatched in the larvae in summer (late July), During final hours of attachment and these infected larvae overwinter and moult feeding approximately several thousands of to become nymphs in the spring again. sporozoites are deposited around the tick Finally nymphs molt into adults in the fall mouth in dermis. Transmission is directly and complete the life cycle. Tick responsible related to the saliva having anti- for transmission of B. divergens to humans inflammatory or immunosuppressive is . The life cycle of I. ricinus pharmacological activity (Ribeiro, 1987). complete in 3 years, as larva in the first year, nymphs in the second, and adults in the In Babesia divergens and other large third. When tick feed on the vertebrate host Babesia species transmission is transovarian for 10 hours, the organism can be seen in the in which the zygote also called ookinete, ticks in consumed red blood cells after 46– enters in haemolymph from where they may 60 hours. Some of the gametocytes develop invade the fat bodies or nephrocytes. The in arrow head structure in the anterior region ookinete undergo second cycle of division called Strahlenkörper or ray bodies. The forming secondary ookinete which invade

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Int.J.Curr.Microbiol.App.Sci (2015) 4(7): 938-953 the ovaries and insure transovarial database of already known sequence which transmission (Telford et al., 1993). In the enables the identification of the infecting vertebrate hosts the sporozoites first go to organism. So patients are parasitemic which lymphocytes forming multinucleate have known Babesial DNA. DNA presence schizonts in Theileria and in some Babesia is an indication of an active infection most species (Meldrum et al., 1992). Schizonts studies shown that microbial DNA is cleared undergo the budding process forming from blood in absence of microbial merozoites which lyses the host cell. The replication (Kain et al., 1993; Nocton et al., merozoites or sporozoites of Babesia species 1994; Krause et al., 1998). without forming pre-erythrocytic stage penetrate the erythrocytes and form Prophylactic measures parasitophorous vacuole. This vacuole will later on disintegrate exposing the parasite Chemophylaxis with single membrane which is different from the species having host Drugs against trypanosomes are also used membrane along with its own (Rudzinska, for babesiosis. Infection in cattle’s can be 1976). In the host red blood cells the controlled by regular treatment with merozoites change in trophozoites, these tickicide. Imidocarb is the drug of choice in trophozoites form a large number of bovine babesiosis. Acarcicides are also merozoites which destroy host red blood frequently use drug against bovine cells, causing haemoglobinuria and at this Babesiosis (Levine, 1973). First successful time four parasites can shape Maltese cross treatment against Babesia bigemina was form. The trophozoites have the capacity to trypan blue to indicate the type of infection. form gametocytes but at that time trophozoites do not reproduce but only grow They recommend treatment for Babesia in size (Mehlhorn et al., 1980; Rudzinska et divergens is and oral in al., 1979). The gametocytes change to order to resist hemolysis and to prevent gametes in the tick gut prior to leave the red renal failure while for Babesia microti blood cells. infections drugs such as hydroxynapthoquinone derivatives Laboratory analysis (), , tetracycline, , and For the diagnosis two methods are used are recommended (Rowin et al., 1982). microscopy and PCR. Thin blood smears stained with giemsa in which organisms are In humans Imidocarb has not approved. darkly stained ring like with light blue and cotrimoxazole are also cytoplasm. The organism may be seen in used for Babesia divergens treatment different forms that are simple rings (Farwell et al., 1982). For Babesia (annular), paired or pyriform, single pear bigemina, Babesia bovis, Babesia jakimovi shaped trophozoites but rarely in Maltese and Babesia ovate diminazene diaceturate cross (tetrad form). Patients with mild (3-5 mg/kg), Imidocarb (1-3 mg/kg), infections are not diagnosed microscopically amicarbalide (5-10 mg/kg) and quinuronium so remain untreated, for such low grade are used. Drugs used for the infections more sensitive techniques are and Babesia equi Imidocarb is used in required, such as PCR which is a molecular different dosage for example 2 mg/kg twice technique. In this sequence of amplified a day and 4 mg/kg four times at interval of fragments is analyzed and then compare to a 72 hours, respectively (Kuttler, 1981). 942

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parasite of the genus Babesia, gaining the Vaccine world attention as an emerging zoonosis (Kakoma and Mehlhorn, 1993). Babesiosis Vaccines comprising live, attenuated strains has a cosmopolitan distribution, mostly of Babesia bovis, Babesia divergens and endemic to tropical and subtropical regions Babesia bigemina are formed from the of the world and affecting a large variety of infected animal’s blood or from in vitro mammals and a small no of bird species. culture. Vaccines are provided either in chill Transmission route is by the infected ixodes or frozen form. Live Babesia vaccines are tick bite, other routes might be not completely safe. A single dose can transplacental, intrauterine, blood provide lifelong immunity against transfusion and organ transplant (Phipps and Babesiosis (Barriga, 1994; Callow et al., Otter, 2004). All Babesia species replicate in 1997; Palmer and McElwain, 1995). In 1964 the vertebrate red blood cells and called as by adaptation in splenactomized calves piroplasmosis due to the pear shape attenuated strain vaccine for Babesia bovis structure. Babesia parasite requires two was prepared (Callow, 1971), but attenuated proficient hosts, a vertebrate and non- vaccines are most problematic, including the vertebrate for transmission (Kakoma and transmission of bovine leukosis virus an Mehlhorn, 1993). Human Babesiosis is enzootic agent (Wright, 1991). caused by one of the species of Babesia having distinctive geographical distribution Recombinant vaccines BM86 and BM95 are depending on the competent hosts. In North also prepared to compensate the problems America first human case was diagnosed created by the use of attenuated vaccines. In from California (USA) in 1966 (Scholtens et early history living parasites are used in al., 1968), but the causal organism similar to livestock management for Babesiosis for a the Babesia duncani or Babesia specie CA- long period of time (Callow, 1971, 1979). type, but in Massachusetts (USA) in 1969 Recombinant vaccines are also developing Babesia microti was diagnosed as the most from surface antigens of sporozoites in familiar parasite responsible for human which apical complex proteins are important Babesiosis in North America (Western et al., so these antigens are protective in 1970), transmitted by the . Babesiosis infection (Palmer and McElwain, Babesia microti is a borne piroplasm 1995; Wright et al., 1992). The scenario for which intermittently transmitted by the other recombinant vaccine is still challenging newly documented species of Babesia called (Brown et al., 2006). SBm7462 is a WA1 piroplasm. The primary reservoir of synthetic anti-Boophilus microplus vaccine Babesia microti is white-footed mouse derived from the tick intestinal protein. (Peromyscus leucopus) but this disease is SBm7462 is 43 amino acid residues are also caused by the similar Babesia species, derived from the BM86 protein structure. A in short tailed shrews, Eastern cottontail killed vaccine for B. divergens has been rabbits and Eastern chipmunks (Anderson et prepared from the blood of infected calves al., 1991; Stafford et al., 1999; Telford and (Zintl et al., 2003). Still no Commercial Spielman, 1993). subunit vaccine is prepared. Within the last decade, cases of human Discussion Babesiosis have increased (Persing et al., 1995). Babesia microti is the primary cause Babesiosis caused by the intraerythrocytic of human Babesiosis in North America, but

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Int.J.Curr.Microbiol.App.Sci (2015) 4(7): 938-953 four other species have been reported The primary cause of human Babesiosis in responsible for human Babesiosis including Europe is Babesia divergens and its related Babesia duncani, Babesia sp. CA-type, zoonotic species called EUI, also known as Babesia sp. MO1, and Babesia sp, TN1 Babesia venatorum reported in Europe. In from a patient in Tennessee (64, 65and 66). Asia approximately four zoonotic Babesia Babesiosis is the most common disease species with rare infection have been which is frequently transmitted by the blood identified in Korea, Korea, Japan, Taiwan, transfusion (Young et al., 2012). In Canada India and China (Wei et al., 2001; Arai et no infection has reported transmitted by the al., 2003; Marathe et al., 2005; Kim et al., tick fauna, but transfusion transmitted cases 2000). Cattles are the natural host for of Babesia microti are diagnosed. Blood Babesia divergens their infection have been transfusion is responsible for the sporadic prevalent in Europe and possibly in North cases in the non-endemic areas as in the Africa (Kim et al., 2000). In 1992 a Babesia Texas, California, Washington, and Georgia divergens like species have been identified (Kain et al., 2001). Probably from 1980 to from the Canary Islands, Spain (Olmeda et 2010, 70–100 infections are transmitted al., 1997). In 1998 another human pathogen through transfusion in the United States was reported and diagnosed as EUI (Leiby, 2011). (European union-1) in Itly and Austria. The most familiar vector for Babesia species Transovarial transmission for Babesia EU1 is Ixodes ricinus (Herwaldt et al., microti has not been reported while large 2003). Babesia species, for example Babesia divergens transovarially transmitted. A In Africa a number of Babesia species have Babesia species formally called Babesia been reported from domestic and wild duncani was morphologically similar to the animals but due to deficiency of human Babesia microti identified in Washington Babesiosis cases sequence analysis, no and California in 1990s (Conrad et al., reservoir for zoonotic Babesiosis is known 2006). Important cases have been reported in Africa (Mazyad et al., 2010). in immunocompromised, splenectomized and acquired individuals Bovine Babesiosis is caused by the two most (Herwaldt et al., 2011). From the prevalent Babesia species (Babesia Phylogenetic analysis, it is evident that it is bigemina and Babesia bovis) in the tropics a separate clade from other Babesia species and subtropics of the world. Bovine (Charles et al., 2012). For Babesia duncani Babesiosis causes most serious economic yet no reservoir and tick vector is identified loss to the livestock industry, endangering (Persing et al., 1995). In 1992, a rare case of half a billion cattle across the world. human Babesiosis caused by new specie Babesia bigemina and Babesia bovis are MO1 was reported in in primarily transmitted by Boophilus splenectomized patient. The natural host for microplus, also transmitted by the principal MO1 is lagomorphs and a vector is Ixodes vectors such as Boophilus annulatus and dentatus. Phylogenetic analysis on the Boophilus decoloratus. Babesia bigemina is fragment of an 18s rRNA fragment to a large pear shaped body jointed at acute indicate that this parasite was initially angle in mature infected . resemble to the Babesia divergens but While the Babesia bovis is a small subsequent analysis showed that MO1 is pleomorphic Babesia rounded single body distinct from the Babesia divergens or pear shaped jointed at obtuse angle. (Holman et al., 2005; Holman, 2006). Transmission is by the feeding of the 944

Int.J.Curr.Microbiol.App.Sci (2015) 4(7): 938-953 nymphal and adult ticks. Calves are virtually high prevalence. Babesia felis is mostly resistant to the Babesia. Babesia bovis prevalent in the domestic cats of India and causes more severe clinical signs as Africa. In feline Babesiosis younger cats are compared to Babesia bigemina (Riek, 1968). more susceptible as compared to the adults For bovine babesiosis, Imidocarb are the due to low immunity and a cat which is free drug of choice which can prevent clinical roaming in nature are also more susceptible infection up to 2 months, but dosage are (Ghosh et al., 2007). Feline Babesiosis is different for different species depending on more prevalent in the humid seasons (July- the status of infected host (Kuttler, 1981). August) and different seasons have different Some Babesia species are nonpathogenic concentrations of ticks. The concentration of while some causes mild clinical infections, disease is equal in both male and female for example Babesia major is nonpathogenic while in the Babesia canis the disease in nature but can lead to death in the susceptibility is different in male and splenectomized calves while Babesia ovate females. Canine Babesiosis is caused by two is mildly pathogenic in nature and have important species having differential size; similar chemophylaxis as Babesia bigemina Babesia gibsoni is small in size than (Minami and Ishihara, 1980). Babesia canis. In case of canine Babesiosis males are more susceptible to the disease Babesia ovis, is a small Babesia specie of than females because male dogs are goat and sheeps causing mild infection involved in organized fighting, while other mostly inconsiderable but the symptoms of studies reported that susceptibility sex ratio infection are just like of Babesia bigemina. is same (Martinod et al., 1986). The In swine Babesiosis is caused by the two zoonotic significance of the parasitic important species, the large one is called infection is dependent on the availability of Babesia trautmanni and a small one Babesia accurate and significant diagnostic perroncitol having no resemblance in the techniques. sign of disease to cattle. In Africa their reservoir are wild pigs (Bush pigs and Molecular techniques, significantly PCR warthogs) but these species are frequently (polymerase chain reaction) play an nonpathogenic so they are often ignored important role in the diagnostic, (Kuttler, 1981). In wild canids and dogs characterization of parasites and in the piroplasmosis is caused by Babesia gibsoni, control measure of the zoonosis. Common the disease is characterized by the method used for the diagnosis is microscopy intermittent fever, haemoglobinuria, anemia but in case of low parasitemia this method is and ultimately death. Vaccination is done botched. In order to detect low parasitemic against canine babesiosis; most commonly cases more accurately molecular diagnostic used recombinant vaccine rP50t is effective methods PCR and ELISA (Enzyme Linked to create protective immunity (Fukumoto et Immunosorbent Assay) are used. Several al., 2003). prophylactic measures have been adopted including chemophylaxis and vaccines for Feline vector borne diseases have been the treatment of babesiosis. Vaccines are emerged in the recent years and attain used in order to provide lifelong immunity worldwide geographical distribution. Feline because a single dose of an effective vaccine Babesiosis is less common than the canine can induce both innate and acquired Babesiosis and little work is done. Climatic protective immunity. factors, especially temperature leading to its

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Table.1 Recognized Babesia species in the world of the domestic animals

Vertebrate S.No Parasite Tick Vector Geographical distribution host 1 Babesia bovis Cattles and Boophilus annulatus, B. Cosmopolitan/worldwide (syn deer microplus, Ixodes spp B.argentina) suspected 2 B.bigemina Cattles Boophilus annulatus, B. Cosmopolitan/worldwide microplus and B. decoratus 3 B.divergens Cattles Ixodes ricinus Northern Europe and United kingdom 4 B.ovate Cattles Haemaphysalis longicornis Japan 5 B.microti Cattles Ixodes scapularis North America 6 B.gibsoni Dogs and Rhipicephalus sanguineus or Worldwide wild canids Dermacentor reticulates 7 B.major Cattles H. punctata United kingdom and Northern Europe 8 B.jakimovi Cattles and Ixodes ricinus Siberia wild ruminants 9 B.caballi Horses Dermacentor, Hyalomma Worldwide and Rhipicephalus species 10 B.equi Horses Dermacentor and Hyalomma Worldwide 11 B.motsi Sheep and Dermacentor silvarum Sothern Europe, middle goats suspected, R. bursa and East, former soviet union, Haemophysalis spp South east Asia and Africa 12 B.ovis Sheep and Suspected Ixodes ricinus and Southern Europe and goats D. reticulatus, R. bursa middle east 13 B.trautmani Swine R. sanguineus and Soviet union, southern Dermacentor suspected, Europe and Africa Boophilus and Hyalomma 14 B.perroncitoi Swine Unknown Soviet union, southern Europe and Africa 15 B. felis Cats, lion, Haemophysalis spp Africa and India leopard 16 B. occultans Cattles Hyalomma marginatum Africa

17 B. canis Dogs and Rhipicephalus sanguineus or Worldwide wild canids Dermacentor reticulatus

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The humoral response to Babesial infections vaccines efficacy (Garcia-Garcia et al., especially to Babesia microti has limited 2000). SBm7462 is a synthetic anti- importance in protection. have a Boophilus microplus vaccine derived from short period of protection and have better the tick intestinal protein. SBm7462 is 43 effect on the free parasite then in the amino acid residues is derived from the infected red blood cells (Morgan, 2000). BM86 protein structure and encapsulated Imidocarb is administering intramuscular or synthetic Spf66 peptide was used to subcutaneously while it becomes toxic when compare with the SBm7462 because of the given intravenously, side effects include similarity in size and synthetic procedure. salivation, muscle tremor, colic and The controlled release system such as PLGA irritation at the location of inoculation microspheres allow a continuous and (Wood, 1971). Vaccination is best pulsable release of encapsulated antigens. prophylactic measure having live, SBm7462 vaccine capsulated in the 50:50 attenuated, dead whole parasite, crude PLGA microspheres promote an immune parasite extracts and recombinant vaccines. response which is better to the immune Live vaccines are not safe because the response promoted this peptide emulsified in vaccine strain can itself cause infection. In saponin. The saponin is an excellent order to lessen the virulence of live vaccine, adjuvant that gave the best response to the it should be continuously passed through the SBm7462 peptide (Igartua et al., 1988). In splenectomized calves (Taylor et al., 1983). Pakistan, especially the province KPK is endemic for the entomological vectors for Protective antigens either alone or in various diseases. The most lethal and combination are the basis of recombinant common, acquiring the attention of vaccines. Although the attenuated vaccines researchers is babesiosis, which also have are good, but due to co-transmission of other the public health significance. In KPK, a enzootic agents such as bovine leukosis major proportion of population has virus and short shelf life these attenuated residence in countryside where people life vaccines give no reliable results. So the expenses are totally reliant on the animals. recombinant vaccines are made from the The livestock in rural areas are suffering surface antigens of sporozoites particularly from different vector born diseases, from apical complex proteins due to their including Babesiosis, thelioriosis, host cell penetration capacity. The rhoptry rickettsiosis and viral hemorrhagic fever due associated proteins (RAP-1) which are to no control measures and awareness in the encoded by a multigene family. RAP-1can public sector against these diseases (Irwin induces the production of the CD+4 and Th1 and Jefferies, 2004; Otranto et al., 2009). cells to provoke partial immunity against babesiosis. Vaccines used against tick vector Conclusion and future recommendation Boophilus microplus is BM86. In case of reinfestation of the tick, the combined From the current study it is revealed that 17 therapy of Acarcicides along with BM86 is different species of Babesia are found in used while in the case of resistance to different domestic livestock (Table 1) BM86. BM95 are used along with the BM86 throughout the world. Hyalomma tick has which can protect the animals that are the highest prevalence rate in Pakistan resistant to the immunization with BM86. followed by Boophilus, Haemaphysalis and Rhipicephalus. Vaccines are available for a Antigens are also used to improve the few species of Babesia. It is highly recommended after the above 947

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