Tackle Ticks: Babesiosis

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Vet Times The website for the veterinary profession https://www.vettimes.co.

1 Vet Times The website for the veterinary profession Tackle Ticks: Babesiosis Author : Simon Tappin Categories : Canine, Companion animal, Feline, General, Practical, RVNs, Species, Vets Date : July 19, 2016 Image: Starover Sibiriak/Shutterstock.com Simon Tappin MA VetMB CertSAM DipECVIM-CA MRCVS European and RCVS recognised specialist in Veterinary Internal Medicine Medicine Consultant, Dick White Referrals, Six Mile Bottom, Cambridgeshire, UK Hon. Assoc. Professor of Small Animal Medicine, University of Nottingham Introduction Canine babesiosis is an endemic disease in many parts of the world, including southern Europe. Dogs with babesiosis seen in the United Kingdom are usually the result of overseas travel; however, recently cases have occurred in the Essex area without a history of travel due to exposure to a pocket of infected Dermacentor reticulatus ticks. Worldwide there are several species of Babesia, with Babesia canis most commonly seen in Europe. 1 / 11

Infection generally leads to pyrexia and a systemic inflammatory response, with moderate to severe anaemia, resulting in associated signs of lethargy and possible collapse.

2 Infection generally leads to pyrexia and a systemic inflammatory response, with moderate to severe anaemia, resulting in associated signs of lethargy and possible collapse. Diagnosis is based on identifying the parasite on peripheral blood films and/or PCR, which will also allow speciation. Definitive treatment with imidocarb will clear parasites; however, its anticholinesterase activity can lead to excessive salivation, lacrimation, nausea and vomiting. Supportive therapy with fluids and symptomatic therapy are often needed. Prevention is based on preventative acaricide treatments and prompt tick removal. Key words: Babesiosis, Babesia, ticks, haemolytic anaemia, imidocarb Babesiosis is a tick-borne parasitic disease which leads to infection of erythrocytes and can result in severe and life-threatening anaemia in dogs. It s particularly prevalent in France, due to Babesia canis, with increasing incidence in the south (particularly south of the Loire valley). However, tick vectors are widespread and the disease is endemic in most of southern Europe. 2 / 11

3 Table 1: Common Babesia species, their vectors and distributions (click to zoom). In early 2016 both the media and veterinary press (Cook and others 2016, Phipps and others 2016) reported several cases of Babesia canis infection in dogs from the Essex area that had not travelled outside the United Kingdom. These cases, combined with a fatal case of Babesia vogeli infection in an untravelled dog from Kent (Holm and others, 2006) and unpublished reports of Babesia in untravelled dogs identified by the Acarus Laboratory in Bristol (Cook and Swann 2016), suggest that canine babesiosis is becoming established within specific areas of the United Kingdom. Aetiology The first reports of babesiosis in dogs were made in Africa in the 1890s. Since then at least nine genetically distinct intra-erythrocytic piroplasm parasites, including Babesia and closely related Theileria and Cytauxzoon species have been identified. Babesia species are divided morphologically into the large (3-7?m in length) and small (1-3?m in length) species, with the species of Babesia seen varying by geographic region, largely as a result of the tick vectors present (Table 1). Babesia canis (previously called B canis canis) is transmitted by Dermacentor reticulatus (the ornate cow or marsh tick) and to a lesser degree by Rhipicephalus sanguineus (the brown dog tick). Figure 1: Dermacentor reticulatus ticks feeding (male: yellow arrow, female: red arrow). Dermacentor reticulatus (Figure 1) has historically been found in the southern parts of Europe, with 45-70% of French practices reporting confirmed infection each year. 3 / 11

4 Recent work has shown the tick vector has become established more northerly in Europe with Dermacentor reticulatus reported in Poland, Belgium and Germany, where milder winters are reducing tick mortality, leading to increasing tick numbers (Wall 2012). Several studies have also documented pockets of Dermacentor reticulatus within the United Kingdom, mainly in west Wales, parts of Essex and coastal areas of both north and south Devon although until recently they were not thought to harbour Babesia species (Hansforth and others 2016). The geographic incidence of Babesia canis infection largely mirrors the distribution of its tick vector, with outbreaks of babesiosis seen in Polish sled dogs (Welc-Faleciak and others 2009). These outbreaks, together with the recent cases in the UK and Norway, reflect a northerly increase in its geographic range (Oines and others 2010). Rhipicephalus sanguineus is a vector for both Babesia canis and Babesia vogeli. It has a worldwide distribution in warm and humid areas that reflect the geographic distribution of Babesia vogeli infection. Rhipicephalus sanguineus is occasionally found within the United Kingdom in association with imported animals, but is unlikely to become endemic as climatic conditions are too cold. Defra, however, acknowledges a risk of establishment within dwellings (Toth and Roberts 2011, Jameson and others 2010). Babesia gibsoni is a small form Babesia often associated with chronic or insidious disease and is present throughout most parts of the world, although it s rarely reported in Europe. It s transmitted by Haemaphysalis species and possibly Rhipicephalus sanguineus. Interestingly, a recent PCR study of 742 ticks collected from areas throughout the United Kingdom found Babesia gibsoni DNA in 11 fed Ixodes ricinus ticks (Smith and others 2013). Ixodes species are not known vectors for Babesia gibsoni and its presence in the UK is a surprising find as it has not previously been documented within the UK tick population. Given its previous rare documentation in Europe, it has been suggested that its range is expanding, with two clinical cases of Babesia gibsoni recently reported in Germany (Hartelt and others 2007). In the United States, where competent vectors are not endemic, Babesia gibsoni can be passed by direct dog-to-dog transmission through fighting and perinatal transmission. Clinical reports of Babesia rossi infection are mainly limited to South Africa, where it affects over 10% of dogs evaluated in veterinary hospitals. It s transmitted by the yellow dog tick, Haemaphysalis elliptica (previously called H. leachi) and leads to particularly virulent clinical signs. It is most commonly seen in the summer months and bull terrier breeds have a worse prognosis. Feline disease 4 / 11

5 Feline babesiosis is rare and has not been studied as extensively as the canine disease. In the domestic cat, clinical disease is predominately reported in South Africa and Sudan due to Babesia felis (Penzhorn and others 2004). A variety of other Babesia species have been identified in wild cats, such as Babesia leo which was isolated from lions in Kruger National Park although at present the relationship between wild and domestic felids is unknown (Bosman 2006). Clinical signs are generally more subtle and cats rarely develop a haemolytic crisis. Affected animals are generally young (Mycoplasma haemofelis, leads to clinical disease (Moik and Gothe 1997). Life cycle Babesiosis is transmitted as a result of high numbers of Babesia sporozoites being passed to the host circulation within tick saliva during feeding. This happens relatively late after attachment, with the tick needing to be attached for hours for transmission to occur. These infectious sporozoites infect erythrocytes, allowing differentiation into merozoites, in turn allowing reproduction and production of more infectious merozoites. These either infect further erythrocytes or infecting ticks complete the life cycle during feeding. After feeding, the organisms appear in the tick gut about 10 hours later and differentiate into gametes, which penetrate the tick gut and undergo sexual reproduction fusing to form zygotes. Zygotes then penetrate the tick salivary gland allowing infection of the host on feeding and the ovary, transforming to infectious merozoites within eggs produced by the tick. As female ticks can produce many eggs over their lifetime (for example a fully fed Rhipicephalus sanguineus tick can lay over 5,000 eggs), one infected tick may quickly become an infected population. Clinical signs 5 / 11

Figure 2: Urine from a dog with Babesia canis infection revealing gross discolouration due to haemoglobinuria at presentation, compared to normal urine passed immediately prior to discharge four days

6 Figure 2: Urine from a dog with Babesia canis infection revealing gross discolouration due to haemoglobinuria at presentation, compared to normal urine passed immediately prior to discharge four days later. Babesia infection results in an array of clinical signs, which vary between the infecting strain and species. However, host factors such as age and the immunogenic response generated against the parasite and/or its tick vector play a role. Most signs result from anaemia or the systemic inflammatory response this generates, leading to tissue dysfunction and resulting in eventual multiple organ failure. Antigens from the parasite become incorporated into the erythrocyte surface, and soluble antigens can also adhere to platelets and erythrocytes that are not infected with parasites. Host antibodies focus on these antigens, leading to the removal of infected erythrocytes by the splenic mononuclear-phagocytic system. In addition, antibodies against normal erythrocyte and platelet targets can also be produced, leading to immune-mediated haemolytic anaemia and/or thrombocytopenia, which doesn t correlate to the number of parasites present. Presenting clinical complaints are very variable and may be compounded by concurrent disease also transmitted by the tick vector, for example Ehrlichia canis. Acute illness, with pyrexia, pallor and splenomegaly is frequently noted with Babesia canis infection, with progression to signs of collapse in severe cases. Haemoglobinuria and bilirubinuria can also be reported secondary to 6 / 11

7 excessive red cell breakdown (Figure 2). The systemic inflammatory response caused can lead to organ dysfunction and a more severe syndrome often referred to as "complicated babesiosis", which includes acute kidney injury, hepatic dysfunction, acute lung injury, cerebral dysfunction and coagulation defects, secondary to disseminated intravascular coagulation and immune-mediated thrombocytopenia. These signs are also frequently associated with Babesia rossi infection. Compared to Babesia canis, Babesia vogeli infections are usually milder and rarely complicated. They may also be subclinical, without significant haematological abnormalities. Diagnosis Figure 3: A blood film revealing Babesia canis merozoites within erythrocytes (green arrows). Diagnosis of canine Babesia is most convincingly made by demonstrating the presence of organisms within infected erythrocytes, with Babesia canis usually forming pairs of pyriform organisms (Figure 3). The level of parasitism is often low, especially in chronic cases, which can make detection difficult. Collecting blood from peripheral capillary beds with lower flow rates (e.g. the ear tip or nail bed) can yield a higher number of infected cells. Yield can also be improved by examining cells from spun microhaematocrit tubes, taken from just below the buffy coat, as the parasite is present in higher numbers in immature red cells. PCR on EDTA anticoagulated blood is the most sensitive and specific way of diagnosing infection, 7 / 11

8 and also allows determination of the species present. Serology is possible and can support exposure however, PCR and direct identification of the parasite are preferred. General haematology results will typically reveal a normocytic normochromic anaemia, which becomes regenerative a few days after infection. Autoagglutination is seen in around 20% of cases, with 85% reported to have positive Coombs test results (Jacobson and Clark 1994). Thrombocytopenia is usually not particularly severe and overt signs of bleeding are uncommon. Concurrent infection with Ehrlichia canis may worsen the risk of bleeding due to platelet dysfunction. A leucocytosis with neutrophilia and left shift is usually present, although a moderate neutropenia has been reported in Babesia canis cases. Biochemistry results are not specific and include elevated bilirubin, globulins and liver enzymes, with hypoglycaemia, azotaemia and marked acid-base imbalances associated with Babesia rossi infection. Treatment Treatment for babesiosis is based on providing symptomatic supportive care and parasite clearance. Supportive care usually consists of cautious intravenous fluid therapy with balanced crystalloid solutions to correct fluid balance, support renal function and improve acid-base imbalances. Symptomatic treatment of specific clinical signs such as vomiting may require specific antiemetic therapy. In cases of severe anaemia blood transfusions can be required. The decision to perform a transfusion is made on an individual patient basis, with it being strongly considered in any patient with a haematocrit less than 0.15l/l or showing clinical signs associated with poor oxygen carriage and delivery (tachypnoea, tachycardia, systemic weakness etc). Steroid use is controversial and usually avoided unless signs of severe agglutination or immunemediated thrombocytopenia are present in these circumstances therapy can often be tapered rapidly over days. The monocytemacrophage system is important in removing the Babesia parasites and usually does so quickly after definitive treatments have been given. Inhibiting its action through immunosuppression can result in a more severe parasitaemia post administration. In general, imidocarb dipropionate is suggested as the most effective drug for clearance of Babesia canis. Imidocarb is used off label, under the cascade, as there is no licensed product for the treatment of canine babesiosis available in the UK but it is readily available in injectable format as a treatment for Babesia divergens, which causes redwater fever in cattle. If imidocarb is not immediately available, high dose clindamycin (25 mg/kg q12h po) is suggested until definitive treatment can be given. Various dose regimes have been reported but two treatments of imidocarb (5mg/kg) given intramuscularly 14 days apart is most commonly recommended. In general, improvement is normally seen within 24 to 72 hours of treatment, but some dogs can respond more slowly taking up to seven days to respond. Imidocarb is an aromatic diamidine derivative and interferes with parasite DNA metabolism and aerobic glycolysis. It also has anticholinesterase activity, which leads to commonly seen side 8 / 11

9 effects relating to stimulation of muscarinic cholinergic receptors. These include excessive salivation and/or lacrimation, nausea and vomiting, tachycardia, diarrhoea and unsettled or agitated behaviour. Premedication with atropine ( mg/kg i/m) is suggested to prevent these signs occurring, or an alternative strategy is to monitor closely and administer atropine (0.02mg/kg) intravenously should side effects be noted. Pain at the injection site is also commonly reported. Transient increases in liver enzymes will be seen post administration. Acute hepatic and renal tubular necrosis are rarely reported with high doses (>10mg/kg). It is suggested that dose reductions should be made in animals with hepatic or renal insufficiency. As imidocarb is excreted slowly, it persists in tissues, providing up to six weeks protection against reinfection (Vercammen and others 1996). Treatment for feline babesiosis is more difficult as imidocarb is not effective and treatment options have not been as critically evaluated. Currently primaquine phosphate is the treatment of choice. However, care needs to be taken as its effective dose (0.5mg/kg given once orally) is very close to its lethal dose (1mg/kg). Prevention Preventing tick attachment in the first instance, or killing the tick before disease transmission occurs, provides the best methods of reducing the risk of canine babesiosis. There are several different molecules licensed. Some, such as permethrin and flumethrin, have a repellent effect against ticks, while others, such as the isoxazolines (afoxolaner, fluralaner and sarolaner), are fast acting acaricides. Regular use of an effective tick product should be suggested to all owners of dogs walked in areas with high tick numbers, especially at high risk times of the year (autumn and spring) and in areas with a risk of possible canine babesiosis. As transmission of Babesia species classically does not occur until 48 hours after tick attachment, prompt removal of the ticks will limit transmission. Owners in high-risk areas should examine their animals regularly as any acaricide will not be 100% effective in preventing tick attachment. Owner vigilance and prompt tick removal using a tick hook will further reduce risks. In general, canine and feline Babesia species do not appear to pose a zoonotic risk. However, rare cases of human babesiosis have been reported in immunosuppressed, elderly and splenectomised patients. Immunosuppressed or splenectomised individuals should therefore exercise caution in removing ticks and handling blood samples from animals infected with Babesia species. Find out more about NexGard Spectra. Brought to you by Merial Animal Health, manufacturers of: 9 / 11

Merilym 3 contains inactivated Borrelia burgdorferi sensu lato: Borrelia garinii, Borrelia afzelii, Borrelia burgdorferi sensu stricto. Legal category: POM- V (UK); POM (Ireland).

10 Merilym 3 contains inactivated Borrelia burgdorferi sensu lato: Borrelia garinii, Borrelia afzelii, Borrelia burgdorferi sensu stricto. Legal category: POM- V (UK); POM (Ireland). For further information refer to datasheet or contact Merial Animal Health Ltd, CM19 5TG, UK. Merial Ltd All rights reserved. Use medicines responsibly. References and further reading Bosman, A.M., Venter, E.H. & Penzhorn, B.L. (2006). Occurrence of Babesia felis and Babesia leo in various wild felid species and domestic cats in Southern Africa, based on reverse line blot analysis. Veterinary parasitology 144: Cook, S., English, K. and Humm, K. (2016). Autochthonous babesiosis in the United Kingdom. Journal of Small Animal Practice. doi: /jsap Vol 57, Issue 6: 332. Cook, S. and Swann, J.W. (2016). Canine babesiosis: autochthonous today, endemic tomorrow? Veterinary Record 178: Hansford, K.M., Medlock, J.M., Swainsbury, C., Phipps, L.P., De Marco, M.D.M.F., Hernández-Triana, L.M. and Fooks, A.R. (2016). Babesia canis infection in ticks in Essex. Veterinary Record 178: Hartelt, K., Rieker, T., Oehme, R.M., Brockmann, S.O., Müller, W. and Dorn, N.(2007) First evidence of Babesia gibsoni (Asian genotype) in dogs in Western Europe. Vector Borne Zoonotic Disease. 7: Holm, L.P., Kerr, M.G., Trees, A.J., McGarry, J.W., Munro, E.R. and Shaw, S.E. (2006). Fatal babesiosis in an untravelled British dog. Veterinary Record 159: Jacobson, L.S. and Clark, I.A. (1994). The pathophysiology of canine babesiosis: new approaches to an old puzzle. Journal of the South African Veterinary Association 65: Jameson, L.J., Phipps, L.P. and Medlock, J.M. (2010). Surveillance for exotic ticks on companion animals in the UK. Veterinary Record 166: Moik, K. and Gothe, R. (1997). Babesia infections of felids and a report on a case in a cat in Germany. Tierarztl Prax Ausg Kleintiere Heimtiere 25: / 11

11 Powered by TCPDF ( Oines, O., Storli, K. and Brun-Hansen, H. (2010). First case of babesiosis caused by Babesia canis canis in a dog from Norway. Veterinary parasitology 171: Penzhorn, B.L., Schoeman, T. and Jacobson, L.S. (2004). Feline babesiosis in South Africa, a review. Ann NY Acad Sci 1026: Phipps, L.P., De Marco, M.D.M.F., Hernández-Triana, L.M., Johnson, N., Swainsbury, C., Medlock, J.M. and Mitchell, S. (2016). Babesia canis detected in dogs and associated ticks from Essex. Veterinary Record 178: Smith, F.D. and Wall, R. (2013). Prevalence of Babesia and Anaplasma in ticks infesting dogs in Great Britain. Veterinary Parasitology 198: Toth, B. and Roberts, H. (2011). Risk of Incursion and Establishment of Certain Exotic Disease and Tick Species to the UK via International Pet Travel. Defra, London, UK. Vercammen, F., De Deken, R. and Maes, L. (1996). Prophylactic activity of imidocarb against experimental infection with Babesia canis. Veterinary parasitology 63: Wall, R. (2012). A ticking clock for tickborne disease? Veterinary Record 170: Welc-Faleciak, R., Rodo, A., Sinski, E. and Bajer, A. (2009). Babesia canis and other tickborne infections in dogs in Central Poland. Veterinary parasitology 166: // 11 / 11

Canine vector-borne diseases prevalence and prevention

Vet Times The website for the veterinary profession https://www.vettimes.co.uk Canine vector-borne diseases prevalence and prevention Author : SIMON TAPPIN Categories : Vets Date : March 3, 2014 SIMON