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Ovine babesiosis

Ovine babesiosis

Ovine babesiosis

Previous authors: I YERUHAM AND A HADANI

Current authors:
D T DE WAAL - Associate Professor, BVSc, PhD, DipDatMet, HDipUTL, DipEVPC, MRCVS, School of Veterinary Medicine, University College Dublin, Room 034, UCD Veterinary Sciences Centre, Belfield, Dublin, D04 W6F6, Ireland

GENERAL INTRODUCTION: BABESIOSES

Introduction

Ovine babesiosis is a tick-borne disease caused by the intraerythrocytic protozoan parasites Babesia ovis10, Babesia motasi70 and several uncharacterized Babesia spp.12, 33, 36, 59 The acute form of the disease is characterized by fever, progressive anaemia, icterus and bilirubinaemia. Haemoglobinuria is rare but may occur in the late stage of the disease. Pregnant animals may abort. Susceptible flocks may suffer a high rate of mortality. Recovered animals that are latently infected are usually immune for a certain period. There is no cross-immunity between the parasites.

Ovine babesiosis caused by B. ovis is of considerable economic importance in the southern part of the Palaearctic zone (Mediterranean basin, Balkans, Kazakhstan, Kirghizstan, Turkmenistan, Iraq and Iran) overlapping the distribution area of the vector tick, Rhipicephalus bursa.16 The presence of B. ovis in sheep in Madagascar97 is questionable.

Rhipicephalus bursa is widely distributed between the 31 and 45° parallels north, including the Mediterranean basin,45, 47, 55, 58, 87, 110 the Balkans,24, 69, 75 southern former USSR,81 Iraq85 and Iran.48 It has not been found in the southern hemisphere.

The geographical distribution of B. motasi is very wide and includes western and northern Europe, the Mediterranean basin, Asia (Turkey, India, China) and Africa (Somalia, Nigeria, Madagascar and southern Africa) and is transmitted mainly by Haemaphysalis spp. ticks. Babesia motasi was first reported in southern Africa in 1902,49 and subsequently ovine babesiosis was diagnosed in other countries in the African continent (Somalia, Nigeria, Madagascar).20, 26, 56, 63, 95, 97 Since the report of Hutcheon and Robertson in 1902,49 there are no other records on the occurrence of ovine babesiosis in southern Africa. Babesia motasi causes a severe disease and mortality in sheep in Asia,13, 50 Africa20 and China.12 It is regarded as a benign parasite in western Europe,21, 57, 82, 98 but occasionally causes anaemia in lambs.17

Babesiosis caused by B. ovis and B. motasi affects all breeds of sheep and, more rarely, goats, with B. ovis being the more pathogenic. It appears that some isolates of B. motasi are infective for sheep and goats while others only infect sheep.6

More recently several large Babesia strains (Babesia sp. BQ1 (Lintan), Babesia

sp. BQ1 (Ningxian), Babesia sp. Tianzhu, Babesia sp. Hebei, Babesia sp. Madang, Babesia sp. Liaoning and Babesia sp. Xinjiang) have been isolated in China with variable degree of virulence to sheep and goats.34 One isolate in particular Babesia sp. Xinjiang is morphologically very different from B. motasi and B. ovis.33 Based on the 18S rRNA gene sequences these Babesia isolates can be broadly divided into two groups – Babesia motasi-like; and a second group, consisting of Babesia sp. Xinjiang,  that falls between B. ovis and B. orientalis.33

Three other Babesia species have been reported to occur in sheep—B. sergenti,102 B. foliata84 and B. crassa42 (in Algeria, India and Iran respectively). These have a restricted local importance and their validity is still debated.

Aetiology and life cycle

Babesia ovis is a small parasite of 1,0 to 2,5 μm in length. The majority of parasites are oval or pyriform, tending to occur at the periphery of the erythrocytes.40, 93, 106 The angle between the paired pyriform parasites is obtuse. Cross-forms are uncommon112 (Figure 1). Babesia crassa, described in Iran,42 has a similar morphology.

Babesia motasi is a relatively large parasite measuring 2,2 to 3,8 μm in length by about 2,0 μm in width. It commonly appears as a pair of pear-shaped organisms, separated by an acute angle, occupying two-thirds or more of the affected erythrocyte.5, 98 Ring, oval, elongated and budding forms are less common. Babesia motasi often possesses a double nucleus, which is invariably single in B. ovis. The intraerythrocytic stages include single tropozoites, dividing forms and paired merozoites. The fine structure of the tropozoites and merozoites are apparently similar to those described for other species of Babesia.28

Babesia sp. Xinjiang is also large approx. 2.42 (±0.35) µm in length and 1.06 (±0.22) µm wide and typically occurs in most cases as single or paired pirifom bodies at an acute angle within erythrocytes. A variety of other morphological forms has also been found, including ring, trifoliate, rod- shaped and oval.33

Rhipicephalus bursa, a two-host tick,107 is the only known vector of B. ovis.106 Haemaphysalis punctata, a three-host tick, is the only proven vector of B. motasi in Europe5 while H. bispinosa and H. intermedia are the only proven ones in India.3, 50 In China the large Babesia isolates are transmitted by a number of three-host ticks including H. longicornis, Hyalomma anatolicum anatolicum  and H. qinghaiensis33, 34, 36

Markov (cited by Erashov23 and Warnecke101) reported on the transmission of B. motasi by Haemaphysalis otophila, a three-host tick. The possibility that R. bursa may be a vector of B. motasi is extremely doubtful.98 Opasina74 suggested that Amblyomma variegatum, a three-host tick, is a vector of B. motasi in goats in Nigeria.

Babesia ovis, B. motasi and the Chinese Babesia isolates all develop only in erythrocytes and multiply by binary fission into merozoites (merogony).

Figure 1  Cross-form of Babesia ovis in a blood smear

The life cycle of B. ovis in the vector R. bursa has been thoroughly studied2, 14, 27, 29, 67, 68 and consists of gametogony (sexual cycle) in the gut of engorged female ticks, which results in the formation of ookinetes (zygotes). A primary schizogony (= sporogony) produces sporokinetes. A number of schizogonic cycles occur in the gut and various tissues. Schizonts have been observed in the haemolymph, eggs and salivary glands. During the final schizogony in the salivary glands, the infective forms (merozoites) are produced. Young kinetes of B. ovis in haemolymph and eggs of R. bursa are round in shape, but subsequently become elongated and cigar-shaped (Figures 2 and 3).

Adult R. bursa ticks become infected with B. ovis during a blood meal. Transmission to a susceptible host occurs by all instars of the succeeding generation.106 Rhipicephalus bursa can be infected with B. ovis both alimentarily and vertically. Alimentary transmission gives rise to a higher rate and degree of tick infection than that following vertical transmission. Eggs infected with B. ovis appear earlier in horizontally (alimentary) infected ticks than in vertically infected ones.108

Infection rates in ticks can be estimated by examining their haemolymph 7 to 12 days after their detachment, and those of eggs 5 to 10 days after the commencement of oviposition.104 In the salivary glands, infective particles can be observed and are transmitted to the host during a blood meal.

Babesia ovis infection in sheep has been observed 11 to 12 days post-infestation by the tick vector.64 It is readily transmitted by inoculation of infected blood.105 Successive serial passages of infected blood in splenectomized lambs result in a decrease in the degree of parasitaemia and apparent attenuation of the parasite; this feature has been employed in the production of a blood-based vaccine.96, 99, 105 Intra-uterine infection of the foetus in pregnant sheep by B. ovis also occurs.92

Transmission of B. ovis by R. bursa109 and of B. motasi by H. punctata is transovarial as well as transstadial.5, 14, 106 All instars of H. punctata are capable of transmitting B. motasi parasites.5 Little is know about the Chinese Babesia spp. and the transmission of them have only been studied in a few instances. Transmission is transovarial in H. longicornis, Hy. a. anatolicum and H. qinghaiensis  with larvae, nymphs and adults being able to transmit the parasite to sheep, although, the ability of adult H. longicornis to transmit Babesia still needs to be confirmed.12, 33, 36 The life cycle of Babesia sp. Xinjiang in its vector Hy. a. anatolicum has also been studied.33

Epidemiology

The larvae, nymphs and adults of R. bursa, a two-host tick, parasitize the same animal species, and their natural hosts are wild sheep and goats.48 This tick is one of the most important species in endemically infected countries (Cyprus, Syria, Israel, the Balkans, Turkey)1, 8, 51, 55, 75, 77, 105, 110 and favours a habitat characterized by rendzinas and terra rossa soils, low average precipitation and a long, dry summer.46 It has a strictly seasonal life cycle with one generation annually. Larvae are found on the pasture, and larvae and nymphs on the animals during the winter period (October to February) in the northern hemisphere, with a peak prevalence in November to December. The adult ticks first appear in April, their numbers reaching a peak in May, and persist in the field and on the animals until July.111

There is a striking seasonal incidence of ovine babesiosis caused by B. ovis. The disease occurs annually in R. bursa infested areas during the activity period of the adult ticks.106 The prevalence of babesiosis reaches a peak in May, corresponding to a peak in the infestation rate of R. bursa on the animals. It thereafter decreases and, by the end of July, disappears.1, 11, 51, 58, 69, 75, 89, 106 Ovine babesiosis occurs two weeks after the first appearance of the R. bursa adult ticks on pasture.113 The disease may reappear annually in the same flocks in endemic areas. This epidemiological pattern differs from the state of enzootic stability known to develop in bovine babesiosis.62 Sporadic clinical cases of ovine babesiosis may occur outside the main season of adult R. bursa activity, concurrently with the rare appearance of few adult ticks.89 Relapses of chronic latent cases due to stress factors, such as heat, food shortage and helminthosis, may also occur in the autumn months.

Figure 2 Kinetes of Babesia ovis in a smear of the haemolymph of a tick

The incidence of babesiosis in 6- to 12-month-old sheep in their first grazing season may be almost double (10 per cent) that of ewes (5,1 per cent).83, 106 The average rate of parasitaemia in lambs and hoggets (7,5 per cent) may be somewhat higher than in ewes (5,6 per cent).112 These rates are rather low when compared to those recorded in endemic areas of bovine babesiosis.18, 80

It appears that a certain percentage of sheep are not exposed annually to infection and consequently remain susceptible. Endemic stability in bovine babesiosis depends on regular exposure to the parasite, and is influenced by climatic conditions, animal management, and dipping. It appears that endemic stability in ovine babesiosis in R. bursa-infested areas is rarely established.

Figure 3 Kinetes of Babesia ovis in a tick-egg smear

In general, unstable endemic situations accompanied by outbreaks of ovine babesiosis depend to a large extent on four factors: transhumance (animals are moved to endemic areas), health management (tick control and chemotherapy), especially unfavourable climatic conditions, and chemoprophylaxis. Intensive tick control should be avoided to maintain endemic stability.91

Recovered animals remain patent or latent carriers of B. ovis for varying periods. The parasites persist in the blood of infected sheep for two years37 and ticks feeding on the animals during this period may become infected. The presence of parasites in the circulating blood maintains a state of premunity.88

High annual rates of seroconversion have been observed in both hoggets and ewes (84,5 per cent and 89 per cent, respectively). The ‘autumn-winter rise’ in serological reactions observed in young animals might be caused by larval and nymphal infestations.106

In young animals, immunity to babesiosis may be conferred by colostral antibodies and exposure to immature and/or adult R. bursa ticks. Morbidity in flocks grazing in endemic areas can be attributed to the fact that only 75 per cent of the colostrum samples of the hoggets and 67,5 per cent of those of the ewes may contain maternal antibodies to B. ovis, and these may persist for only three months in lambs,37, 113 as compared to the longer period of resistance known in B. bovis in cattle.86 It therefore appears that lambs must be exposed to B. ovis infection up to the age of three months in order to maintain an immune state. Lambs infested with R. bursa larvae may develop antibody titres after a relatively long post-infestation period (39 days on average) and may suffer from only mild clinical reactions when subsequently challenged with infected R. bursa adult ticks.113 The delay in the serological reaction and the fact that only 85 per cent of the lambs may become serologically positive are probably due to the low B. ovis infection rate of the preimaginal stages of the tick.109

The relationship between antibody levels and the degree of immunity to babesiosis is not clear. Serologically positive animals, when challenged, may develop clinical babesiosis. A similar situation has been reported in bovine babesiosis.15, 31 In addition to the climatic and husbandry factors mentioned above, the precarious enzootic stability in ovine babesiosis caused by B. ovis might be due to the fact that the active period of R. bursa adults is short, resulting in low levels of colostral antibodies, as well as the short lifespan of these antibodies in lambs. The transmission of B. ovis by the pre-imaginal stages during the autumn and winter months, causing seroconversion, might play a major role in pre-immunizing and boosting the immunity in sheep against infections which occur during the spring to summer months.106

Ovine babesiosis caused by B. motasi has not been studied in detail. It has been suggested that Nigerian sheep are resistant to infection with B. motasi.56 Furthermore, certain isolates of B. motasi might be of lower pathogenicity, while others are known to cause severe disease and even death in sheep in India50 and in Somalia.20 It has been proposed that the virulence of different isolates of B. motasi and the severity of the disease might be greatly affected by the tick vector.20, 50 Although B. motasi may be a significant pathogen on its own, it seems more probable that disease in certain regions may be complicated by other tick-borne pathogens, such as Theileria spp., Ehrlichia spp.,60 and Nairobi sheep disease virus.20

Over the last three decades at least seven large Babesia spp. have been isolates from sheep in China. Based on 18S rRNA gene phylogeny it has been shown that six of these isolates (Babesia sp. BQ1 (Lintan), Babesia sp. BQ1 (Ningxian), Babesia sp. (Tianzhu), Babesia sp. (Hebei), Babesia sp. (Madang) and Babesia sp. (Liaoning)) all had a 88-98 per cent identity to the European isolates of B. motasi 59 and referred to as Babesia motasi-like. Although it is still debated if these represent one or more subspecies. The seventh isolate, Babesia sp. Xinjiang, is morphologically different, less pathogenic, less than 82 per cent similarity with other ovine Babesia spp. and forms a sister clade with B. ovis, B. bovis, B. orientalis and B. occultans 53

From recent large scale sero-surveys in China it would appear that these Babesia spp. are widespread throughout China with seroprevalence ranging between 30 – 44 per cent32, 71, 100

In goats, clinical babesiosis cases are rare.78 It seems that the local breeds possess a certain degree of natural resistance to babesiosis.

In the absence of non-ovine susceptible hosts, the tick might serve as a reservoir of B. ovis.65 Babesia ovis and B. motasi have been reported to occur in unusual hosts22 and ticks9, 73 but the role of these, as asymptomatic carriers or true vectors, is still unknown.

Pathogenesis

Upon infection of a susceptible sheep with B. ovis or B. motasi, multiplication of the organisms occurs in erythrocytes with the development of a clinically detectable anaemia which results in hypoxia of tissues that may cause the death of the host. Organs, particularly those with high metabolic activity, such as the liver and kidneys,44 are the most severely affected in ovine babesiosis.39, 41, 55, 94, 104

Severe anaemia may occur in sheep harbouring a low parasitaemia, which implies that additional factors are involved in its pathogenesis. Erythrophagocytosis of both parasitized and non-parasitized erythrocytes has been observed in cases of B. ovis infection. A similar finding has been recorded in infections with other species of Babesia.44, 61

The anaemia following infections with Babesia spp. is considered to be caused by:

  • mechanical damage of red blood cells by invading organisms;
  • autoimmune phenomena; and
  • adsorption of antigens onto normal erythrocytes followed by the formation of immune complexes and the activation of the classical complement pathway resulting in their destruction.6

The pathogenic mechanisms of B. ovis are broadly similar to those of B. bovis, provoking lesions characteristic of a hypovolaemic and endotoxic shock process. The latter is probably the result of a massive release of catabolites from the lysis of erythrocytes and necrosis of tissues.39 The lesions observed generally arise from vascular alterations, such as vasodilation and vascular stasis, leading to hypoxia of the tissues.39 Apart from the changes in the brain, other findings are similar to those reported in B. bovis infection of cattle.103

Clinical signs

Ovine babesiosis, in general, is an acute disease particularly in susceptible animals. Morbidity and mortality due to ovine babesiosis in flocks in endemic areas occur annually. Babesia ovis infections may cause 10 per cent morbidity with 2 per cent mortality,110 but a mortality rate as high as 25 per cent has been reported.83

The clinical signs of ovine babesiosis caused by either B. ovis or B. motasi are similar. In general, the signs observed are typical of those due to an anaemia. An incubation period, generally ranging from seven to nine days, is followed by a febrile period of several days during which inappetence and depression are evident. The febrile response in babesiosis caused by B. ovis precedes a detectable parasitaemia by at least 24 hours.109

Initially, visible mucous membranes are reddened and the urine is normal in colour, but as the disease progresses visible mucous membranes become pale and icteric. Haemoglobinuria is uncommon. Constipation may occur, and faecal pellets may contain blood and be covered by mucus. Respiration and pulse rates are increased. Weakness and prostration develop together with muscular tremors, lachrymation and salivation. The parasitaemia in B. ovis infections is usually low (less than 1 per cent).109

Death may occur at any time after the onset of the clinical signs depending on the virulence of the Babesia strain and the susceptibility of the animal.

Pathology

Infection with either B. ovis or B. motasi leads to a macrocytic hypochromic anaemia which coincides with the peak of parasitaemia. Reticulocytosis, poikilocytosis and anisocytosis, together with hypochromasia, indicate that haemopoetic centres attempt to compensate for the anaemia. There is an initial leukocytosis, largely due to neutrophilia,6 and increased total and conjugated bilirubin levels.

The clinico-pathological findings in babesiosis due to B. motasi infection are considerably milder than those observed in B. ovis infections.6

Affected animals show a decrease in the packed cell volume (PCV), which ranges between 30 and 40 per cent.109 There is an increase in plasma transaminases, particularly aspartate aminotransferase and alanine aminotransferase, dehydrogenase, blood urea nitrogen and creatine, and a decrease in sorbitol dehydrogenase, alkaline phosphatase, total proteins and albumin.38, 66 A proteinuria occurs in the course of the disease.38

In experimental B. ovis infection in sheep39, 109 evidence of anaemia, marked icterus, splenomegaly, a grossly enlarged dark-brown degenerated liver, and nephrosis are noted. Ecchymotic haemorrhages are present in the epicardium, endocardium and subserosa of the viscera.

Erythrocytes parasitized by B. ovis have not been observed to block capillaries in the brain,109 as recorded in B. bovis infections in cattle. This explains the absence of neurological signs in acute ovine babesiosis caused by B. ovis. A disseminated intravascular coagulation syndrome has been observed in sheep suffering from B. ovis infection.39, 109

Diagnosis

Acute ovine babesiosis can be confirmed by microscopic examination of stained blood smears made from capillary blood. The parasitaemia in B. ovis infection is, however, low. Diagnosis of ovine babesiosis at necropsy is possible if decomposition is not too advanced.

Babesia parasites deform within a few hours of death, thus making their morphological identification impossible. Thin blood smears from the peripheral circulation, and impression smears of the spleen, liver and kidneys should be made.

A variety of serological tests has been used to demonstrate the presence of antibodies to B. ovis and B. motasi.7, 19, 25, 37, 52, 57, 76, 79, 98, 109 Cross-reactions have recently been reported within the genus Babesia. A high correlation is found between B. motasi and B. crassa, and a lower one between these two and B. ovis.79 No cross-reactions have been found between B. ovis antigens and B. motasi, B. crassa or Theileria ovis.40 Serological tests are used mainly in epidemiological surveys. The indirect immunofluorescence test (IFAT) is one of the simplest, most sensitive and effective techniques used for this purpose. However, as in the case with other serological techniques, the specificity of the method is not always satisfactory.79 Recombinant ELISAs have been developed for the Chinese Babesia spp.32, 35, 71, 72, 100

Differential diagnosis

Ovine babesiosis should be differentiated from infections caused by other tick-borne blood parasites such as Anaplasma ovis, Theileria ovis, Anaplasma phagocytophilum and Mycoplasma ovis. Copper poisoning resulting in an acute haemolytic crisis with icterus, should also be considered.

Control

The control of babesiosis in sheep is similar to that used for the control of bovine babesiosis (see Bovine babesiosis) and is based on a combination of strategic tick control, vaccination, chemoprophylaxis, when necessary, and chemotherapy.

Immunization can be achieved by inoculation of a whole blood vaccine containing attenuated parasites.54, 96, 99 Attenuation is achieved by serial passage of the parasites in splenectomized lambs. A crude extract of B. ovis parasites in Freund’s complete adjuvant has been also used as a vaccine.4 There is, however, no ovine babesiosis vaccine available commercially. An effective method for the control of the disease in endemic areas might be the exposure of sheep to immature stages of R. bursa in October to February before the main adult tick period in April to July.

Animals suffering from clinical babesiosis should be treated with the babesiacidal drugs used in bovine babesiosis. Diminazene aceturate (Berenil®) is used at a dosage rate of 3 to 5 mg/kg body weight subcutaneously.90, 98 Diminazene can also be used in the chemoprophylaxis of ovine babesiosis with a withdrawal period as recommended by the manufacturers.30 Imidocarb dipropionate (Imizol®) is used at a dosage rate of 1,2 mg/kg body weight intramuscularly. A second treatment may be necessary in case of recrudescence of the infection.43 Amicarbalide isethionate (Pirodia®, Diampron ®) at 5 mg/kg body weight subcutaneously has also been used with success.98

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