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Small Animal Medicine - Online Learning Programme Canine In ectious Diseases l...

Small Animal Medicine - Online Learning Programme Canine In ectious Diseases l na tio na Week o t er In e ov Aut or Simon a in pr Im MA VetMB CertSAM Di ECVIM-CA RCVS Note: Copyright on these notes is jointly owned between the Course Speaker and Improve International Ltd and the material must not be copied or distributed without prior permission/authorization from either party. Improve International Ltd has taken every effort to ensure that the information in these notes and in other taught material is accurate but it cannot take any responsibility for any problems arising from errors therein. 01793 759159 [email protected] www.improveinternational.com Copyright 2022 Improve International Ltd. All commercial copying or reproduction constitutes an infringement of copyright and is prohibited. Learning Objectives 1. Explain the aetiology of canine endemic diseases: Distemper Parvovirus Infectious Hepatitis Kennel Cough 2. Recall the clinical signs associated with these conditions 3. Outline diagnosis of these conditions 4. Appraise the treatment options for these infections 5. Compare options for prevention of these diseases 6. Explain why ticks are good vectors for disease using knowledge about their life cycles 7. Recall the clinical signs associated with Borrelia (Lyme disease) 8. Outline how to make a diagnosis of Borrelia infection 9. Consider the treatments options for Borrelia infection and the preventative options available 10. Reflect on the PET travel scheme and its impact on imported diseases 11. Explain the life cycle of the tick borne diseases caused by Babesia and Rickettsia species l na 12. Recall the clinical signs associated with infection 13. Discuss how to make a diagnosis of these conditions 14. Consider the treatment options for Babesiosis and Rickettsial disease io 15. Outline the preventative strategies available at rn te In e ov pr Im Distemper The canine distemper virus is a large enveloped single stranded RNA virus that belongs to the genus morbillivirus and is closely related to the measles virus. The incidence of distemper has reduced dramatically from the most fatal infectious disease of dogs to very low levels since the introduction of modified lives vaccines in the 1960s. In recent years cases in the USA and mainland Europe (but not the UK) have slightly increased due to a decrease in the proportion of dogs vaccinated and vaccine breakdown. There is only one serotype of distemper, although different strains have been identified with small antigenic variations which vary markedly in there pathogenicity. Distemper is readily inactivated by heat, light and disinfectant and does not survive long outside the body. Most terrestrial carnivores are susceptible to distemper; this includes dogs, foxes, ferrets, mink, otter, badgers, raccoons and large cats (lions, tigers and leopards). Distemper contributed to the near-extinction of the black-footed ferret and played a role in the extinction of the Tasmanian tiger. In the early nineties, lion number in the Serengeti reduced by 20% as a result of the infection. The disease has mutated to form phocid distemper which affects seals. l na Distemper can affect dogs of all ages but is most common in dogs less than one year of age infection; usually after maternal antibodies have waned. Disease is most commonly seen in areas of low vaccination io rates and high density areas such as rescue centres tend to perpetuate the infection. There is no zoonotic risk although an association with Paget’s disease in man has been postulated. at rn Transmission is usually by inhalation and direct dog to dog transmission, spread by fomites or the wind te over short distances is also possible. Shedding from the respiratory tract starts seven days post-infection and may last several weeks. Recovered dogs generally have lifelong immunity and do not shed the virus. In There is no carrier status, although the virus can remain in the CNS for long periods of time. e ov Distemper can replicate in macrophages, lymphoid cells, epithelial cells and neurons. Macrophages and lymphoid cells are most susceptible, with multiplication in respiratory tract macrophages leads to the pr local lymph nodes being affected. Viraemia develops about two days post-infection which is followed by spread to other lymphoid tissue over a 5-7 day period. Viral multiplication leads to lymphocytolysis and Im reduced lymphocyte numbers allowing the virus to be carried by migrating mononuclear cells to epithelial tissues throughout the body. Immunosuppression allowing multiplication in macrophages and lymphoid tissue is vital for the virus to affect epithelial tissue. The degree of epithelial and nervous involvement, and therefore the clinical signs see, varies markedly from case to case. This is related to the tissues in which the virus is most active, the stage of disease and the susceptibility of the individual. Strain variation and the ability to produce immunosuppression may also have an effect. The T-cell cytotoxic response is important in allowing recovery and elimination of the virus. Dogs showing minimal clinical signs recover quickly due to the production of high levels of neutralising antibody that persists for many years. Some dogs recover quickly despite low neutralising antibody levels and other dogs recover eventually despite never raising a high antibody titre. This response is modulated by the T-cell response and may explain breed sensitivities for example Rottweiler’s appear more susceptible to Distemper than other breeds. Dogs with subacute or chronic CNS signs usually developed antibodies within the CSF. Clinical signs very widely and infection may be subclinical in some cases. Mild pyrexia, inappetence and depression with a serious or mucopurulent ocular and/or nasal discharge can progressing gastrointestinal signs and lower respiratory tract disease. CNS signs may follow in some cases, as can more chronic signs such as hyperkeratosis (‘hard pad’) and marked weight loss. In growing animals hypoplasia of the tooth enamel may also be seen. Secondary bacterial infection especially those involved in kennel cough can occur and carry up a poorer prognosis. Other opportunistic infections such as nocardiosis, toxoplasmosis and generalised demodecosis have also been reported. CNS signs maybe delayed for months to years and result in encephalitis in the mature or older dog, sometimes without a history of pre-existing signs of distemper. This occurs when a virus remains present in the CNS for long periods despite elimination from the rest of the body. Distemper has been isolated from dogs with metaphyseal osteopathy although a causal relationship has not been documented. Transplacental infection with CDV may be associated with infertility, stillbirth and abortion; puppies can be born with neurological signs that develop at 4 to 6 weeks of age. l na Gross post-mortem changes are variable and often inconclusive. Histopathological diagnosis is possible if eosinophilic intracytoplasmic inclusion bodies can be documented in epithelial tissue. The respiratory and bladder mucosa are the best sites. Changes in the lymphoid tissue and respiratory tract may also be io helpful. Immunofluorescence tests for antigen in lymphoid tissue, lung and brain can also be useful. at rn In the live animal diagnosis can be difficult. CVD is readily isolated in cell culture and cytopathic effects are normally seen within 24 hours; unfortunately diagnostically virus isolation is fairly impractical. PCR is te the most sensitive test using mononuclear cells in the buffy coat, conjunctival smears or bronchial In washes. Immunocytochemistry may also help improve diagnosis on cytological samples. CSF analysis in cases with neurological signs reveals increases in protein and mononuclear cells. Antigen may be detected by PCR in acute cases; the presence of antibody is diagnostic in animals with an intact blood e brain barrier. Serology may be difficult to interpret as immunosuppression may prevent a rising antibody ov titre, although fourfold increase in antibody in a not recently vaccinated dog, is diagnostic for distemper. It can also be useful to look at IgM as this remains elevated for three months after infection but only pr three weeks after vaccination. Im In the absence of specific anti-viral treatments, therapy is largely supportive and symptomatic, with the aim of controlling the clinical signs for each patient. Non-specific supportive therapy includes antibiotic therapy (broad spectrum therapy to protect again the effects of immunosuppression) fluid therapy and careful nursing. Sedatives and anticonvulsants can be used in neurological cases, however the prognosis in these cases is poor and where progressive signs are present, euthanasia should be considered. Vaccination programs using modified life vaccines have greatly reduced the prevalence of distemper in the UK. These are either derived from avian cell culture (Ondestepoort strains) or canine cell culture (Rockborn strain). The Rockborn strain produces a more rapid response, however is associated with higher levels of post vaccine encephalitis (especially in miniature schnauzers) and is therefore no longer used in the UK. Live vaccines can also be fatal in certain zoo animals such as red pandas and black-footed ferrets. Historically measles vaccines (canine products not the human counterpart) have been used to provide protection against distemper to puppies with high maternally derived antibody, with fair success. In a kennel or rescue centre situation management and disinfectant machines can be extremely effective in control as the virus does not survive well outside the body and is very sensitive to disinfectant. The duration of immunity is generally long lived with UK vaccines being licensed with a 3 yearly interval. In the UK pet ferrets are frequently vaccinated against distemper. Canine Parvovirus Canine parvovirus (CPV) is a significant worldwide pathogen and is still the most common cause of viral enteritis in dogs in the UK. Since the virus was first discovered in 1978 it has evolved and there are now three known strains which can cause enteritis; CPV-2a, b and c. In experimentally infected dogs, mortality without treatment is as high as 91%. Although no definitive treatment has been reported, survival rates with intensive therapy can be up to 90%, however, survival rates in tertiary, referral hospitals have been shown to be higher than those in first opinion practice. Parvoviruses are small, non-enveloped, single-stranded DNA viruses. CPV emerged as a clinical problem in 1978 and is thought to have arisen as a mutation of the feline panleukopenia virus. Between 1979 and 1985, CPV-2 was largely replaced by two more virulent strains of parvovirus, CPV-2a and CPV-2b. The original CPV-2 strain no longer appears resident in the dog population, although it is still present in some live vaccines. Current studies in the United Kingdom suggest co-circulation of types 2a and 2b. In 2000, a third strain of the virus, CPV-2c, was discovered in Italy. CPV-2c is now predominant in Italy, Germany and l Spain and is also widely distributed in Portugal, France and Belgium. Sporadic isolates of CPV-2c have na been documented in the United Kingdom. Despite some anecdotal reports claiming a higher pathogenicity of CPV-2c, there is no evidence for different virulence between the strains. io at Infection mainly occurs via the faecal-oro route; rare transplacental infection is also reported. After rn infection, viral replication occurs within lymphoid tissue, spreading quickly to rapidly dividing cells. Most infections are subclinical with most older puppies and adult dogs undergoing seroconversion, without te evidence of clinical disease. Puppies with severe infections are usually under twelve weeks of age at the time of infection. The virus replicates within intestinal crypt epithelium, bone marrow and myocardium. In Animals initially become febrile and lethargic, with anorexia, vomiting and diarrhoea generally following 2-3 days later. Viral destruction of intestinal crypts results in villous collapse, intestinal bleeding and e subsequent bacterial invasion, especially with enteric gram-negative bacteria. Large volumes of foul- ov smelling and bloody diarrhoea are commonly seen, and patients are often severely dehydrated on presentation. Intestinal protein loss may occur secondary to inflammation, causing hypoalbuminaemia. pr Damage to bone marrow progenitors can lead to neutropenia, furthering increasing the risk of intestinal translocation and serious bacterial infection. Puppies that are infected in utero or before eight weeks of Im age may develop myocarditis, due to damage as the result of viral replication in the myocardium. Modified live CPV vaccines are available in the UK and these are based on CPV type 2 or 2b subtypes. Several studies have shown vaccines containing CPV-2 confer adequate short-term immunity against all CPV-2b and CPV-2c subtypes, however, there are currently no studies to show long term protection against these subtypes. The current vaccination recommendations for CPV from the World Small Animal Veterinary Association are for initial vaccination at eight to nine weeks of age followed by a second vaccination three to four weeks later, and a third vaccination given between fourteen to sixteen weeks of age; all dogs should receive a booster twelve months after the completion of the primary vaccination course. Thereafter recommendations for revaccination range from one to four years. Infection with CPV confers lifelong immunity in the majority of cases. The duration of immunity is generally shorter, but can quite durable. In a study of 144 pet dogs from the United Kingdom that had not been vaccinated for periods of three to fifteen years, 95% had protective CPV titres. Non-vaccinated dogs are at highest risk of infection with CPV, although vaccinated puppies are frequently infected with the virus. The clinical signs of CPV enteritis depend on the size of the inoculum, the age of the pup, the host’s defences and the presence of other enteric pathogens. Maternally-derived antibodies to CPV are protective during the first several weeks of life. The amount of antibody available in colostrum depends on the immune status and disease history of the mother, and the amount absorbed varies between individuals in the litter according to how much colostrum is taken in. Maternally-derived antibodies have a half-life of ten days and puppies have a titre that is 50% of the dam. Thus there is a window of susceptibility to CPV infection between six weeks and six months of age, when declining maternal antibody levels interfere with a vaccine-induced humeral response, but cannot protect against infection. Rottweilers, Doberman pinschers, and Staffordshire bull terriers have been found to be at increased risk of CPV infection. This is thought to be due to a poor humoral response to vaccination in these breeds and l persistence of maternal antibody past the age at which the primary vaccination course would normally be na completed. Intact male dogs are infected disproportionately to their population. Climate may also be a risk factor, with an increase in cases reported between the months of July and September in temperate io climates. at rn Diagnosis of CPV infection can often be tentatively made on history and clinical findings. Leukopenia is commonly associated with parvoviral infection. Lymphocytolysis is usually the direct result of viral te replication at the time of initial infection and lymphocyte numbers usually rapidly rebound. Profound neutropenia typically develops at the onset of gastrointestinal signs as a result of peripheral neutrophil In consumption (especially in the gastrointestinal tract) and destruction of progenitor cells with the bone marrow. Although neutropenia is very suggestive of CPV enteritis, Salmonellosis, or any other e overwhelming infection can cause similar haematological findings. ov pr Parvoviral ELISA antigen snap tests are readily available in-practice tests to detect CPV in faeces of infected dogs. The specificity of these tests is excellent (one study found the percentage of positive in- Im house tests was 80.4%, 78.0% and 77.0% for CPV types 2a, 2b and 2c, respectively, confirming the ability of the tests to detect the strains of the virus currently present in the UK). ELISA results may be negative if the assay is performed early in the disease course as viral shedding is low at this stage and tests should be repeated in dogs that show signs and maintain a clinical suspicion of CPV enteritis. Vaccination with a modified live CPV vaccination may cause a weak positive result for 5 to 15 days post-vaccination. The period of shedding in clinical cases is relatively short, and may be undetectable 10 to 14 days after infection. Furthermore, ELISA snap tests are limited in their sensitivity when compared to PCR or electron microscopy (when compared with PCR or electron microscopy, sensitivity is 15.8–26.3% and 50–60% respectively), if a clinical suspicion of CPV remains in a patient testing negative on the in-house tests, negative results should be confirmed by PCR-based methods. PCR tests have higher sensitivities and specificities than conventional methods of viral antigen determination in faeces. The high sensitivity of real-time PCR allows for identification of dogs shedding low titres of CPV in their faeces. Serology (using haemagglutination inhibition) can also be used to document an immune response to CPV, documenting a current or previous infection. Antibodies to CPV become detectable when clinical signs are first seen, and titres increase rapidly and remain elevated for many years. As 25–90% of healthy unvaccinated dogs can be seropositive secondary to previous, potentially subclinical, infection, a single positive serology is not diagnostic for active CPV infection. Diagnosis of current CPV infection by serology requires consistent clinical signs and the detection of anti-CPV IgM or a rising IgG titre. If a puppy presenting with signs of acute gastroenteritis is negative on serology for anti-CPV antibodies, then this result alone is usually sufficient to exclude CPV as the cause. Other methods of detecting CPV in faeces include electron microscopy, viral isolation, latex agglutination, and immunoelectrophoresis. If the patient dies or is euthanised, post mortem examination can be used to confirm a diagnosis of CPV. Typical histologic changes are seen in the villus crypts of the jejunum and ileum and mesenteric lymph nodes. Immunohistochemistry can be used to establish the presence of CPV. l Treatment of parvoviral enteritis is primarily symptomatic and supportive. Fluid and electrolyte therapy is na crucial to treat signs of vasodilatory shock, combined with antimicrobial therapy to treat signs of secondary bacterial sepsis. Any patient being treated for CPV should be barrier nursed to prevent spread io of infection within the hospital. The virus can persist in the environment for many months to years, so careful cleaning of the environment is essential. CPV is very sensitive to hypochlorite solutions and steam cleaning. at rn te The aim of fluid therapy is to treat shock and improve perfusion, correct dehydration and to anticipate loss from on-going diarrhoea and vomiting. In patients presenting in shock, as a result of hypovolaemia In and sepsis then aggressive intravenous crystalloid administration should be given to help improve perfusion. A bolus of 10-20ml/kg of a balanced electrolyte solution (e.g. lactated Ringers solution) should e be given by rapid infusion (over 10-20 minutes). This should lead to improved peripheral perfusion ov documented by improvement in peripheral pulse quality, a reduction of heart rate and improved demeanour. If there is no change, boluses can be repeated up to 60-90ml/kg before moving onto colloid pr administration (see below). If venous access is not possible due to circulatory collapse, an intramedullary catheter is an alternative route of fluid administration. Im Once hypovolaemia is corrected, fluid deficit as a result of dehydration can be corrected. Maintenance requirements (50ml/kg/day, dogs less than 5kg may require slightly more) and an estimation of the fluid deficit (calculated by multiplying percentage dehydration x body weight in kilograms) should be calculated and fluids administered to correct the deficit over a period of 6–24 hours, depending on its severity. Subcutaneous and intraperitoneal fluids are not recommended if dehydration is severe as there will be inadequate fluid distribution secondary to peripheral vasoconstriction. Patients may present with severe hypoproteinaemia due to protein loss from gastrointestinal inflammation. Aggressive crystalloid administration should be avoided and volume resuscitation should be based on judicious crystalloid administration and colloid administered in slow 5ml/kg intravenous boluses. In hypoalbuminaemic patients colloidal support can be administered as a constant rate infusion with typical rates of 10 to 20 ml/kg/day. When colloids are administered the concurrent crystalloid rate is typically decreased by 50%. Vomiting and anorexia often result in hypokalaemia, so fluids should be supplemented with potassium chloride. Potassium chloride can be added safely at a rate of 5mmol per 250ml fluid when potassium cannot be measured or to provide maintenance potassium in anorexic patients. The infusion rate of potassium chloride should not exceed 0.5mEq/kg/hr as this may lead to thrombophlebitis and adversely affect cardiac function. Hypoglycaemia is common in young puppies and fluids can be supplemented with the addition of concentrated glucose solution to make 2.5 to 5% glucose solution, depending on the degree of hypoglycaemia. If anaemia and hypoproteinaemia are severe enough, transfusion of packed red cells, whole blood or plasma, in addition to crystalloid or colloid fluid therapy, may be warranted. Antimicrobial therapy is necessary to treat septic shock as a result of CPV replication cases damage of the gastrointestinal barrier allowing translocation of bacterial, which is worsened by severe peripheral neutropenia. If the patient is afebrile but neutropenic the parenteral administration of cephalosporin may be sufficient. In febrile cases a combination of potentiated amoxicillin or cephalosporin, with metronidazole provide excellent cover against gram negative and anaerobic bacteria that may translocate from the gut. Fluoroquinolones, such as pradofloxacin possess broad-spectrum cover; however l enrofloxacin should be avoided as it has been associated with cartilage abnormalities in growing animals. na io Severe on-going vomiting contributes to fluid and electrolyte loss and reduces enteral nutrition. Antiemetic therapy is therefore an essential part of treatment but also in improving patient comfort. at Metoclopramide is an effective centrally-acting antiemetic that also increases gastrointestinal motility; rn where possible constant-rate infusions are more effective than intermittent dosing. Maropitant is a very potent antiemetic acting at the vomiting centre to block NK-1 receptors. Care should be taken in puppies te 40˚C), shifting limb lameness and associated lethargy. In There may also be joint swelling and enlargement of the local lymph nodes. These signs appear to be most severe in younger dogs and immunocompromised animals. e ov Lameness is usually first seen in the limb closest to the site of tick attachment and is thought to be caused be the spread of spirochetes through the skin, muscle and joint. Classically, the lameness pr improves over 2-3 days at which point signs may resolve completely or appear in a different limb. In a proportion of dogs a chronic non-erosive polyarthritis may develop, this is most likely in patients with Im chronic infection which has been incompletely cleared by the immune system representing an immune-mediated polyarthritis. Diagnosis of Borrelia as the trigger can be difficult (see below), however prolonged treatment with antibiotics and in some cases descending immunosuppressive steroids will lead to improvement in most cases. Protein-losing nephropathy (PLN) has been documented in dogs with spontaneous Borrelia infection. This so called ‘Lyme nephropathy’ has not been documented in experimental models and the underlying pathophysiology is unclear. It has most commonly been reported in Northern America but has also been seen in the UK. Dogs develop glomerular nephritis, lymphocytic plasmacytic interstitial nephritis and tubular necrosis. This leads to weight loss, lethargy and anorexia as a result of the PLN leading to renal failure. About half of dogs developing Lyme nephritis have a history of lameness, with the signs of PLN being the first sign of Borrelia in many cases. In people a dramatic “bull’s eye” skin lesion called erythema chronica migrans (ECM) develops in up to 90% of people with Lyme disease. This classic bull’s eye lesion is not seen often in dogs however a reddish rash can be seen for the first week or so after tick attachment. Neurological signs due to meningitis, encephalitis and perineuritis are seen occasionally in the later stages of infection in man. Although focal meningitis and encephalitis lesions have been documented in experimental models, neurological signs secondary to Borrelia in dogs are extremely rare. Arrhythmia secondary to Borrelia- induced myocarditis has been occasionally been reported in dogs, which is similar to Lyme carditis seen in man. As described, diagnosis of Lyme disease by clinical signs alone is challenging and is based on having appropriate clinical signs, supportive laboratory data, exclusion of other possible differential diagnoses and a positive response to treatment. Haematological and biochemical changes are not pathognomonic of borreliosis, although may support the presence of an inflammatory response. Signs of leukopenia or thrombocytopenia may suggest concurrent infection with a rickettsial pathogen, such as Anaplasma phagocytophilum, as co-infection is relatively common. Regular urinalysis to monitor for PLN is suggested, with a UPC ratio being the best marker of proteinuria. Joint taps will have high numbers of non-degenerate neutrophils, with increased protein content. Joint fluid will have a reduced l viscosity and should be negative on bacterial culture. na io During infection, Borrelia organisms change their outer surface proteins (Osp) to allow transmission and increase their chances of survival in the host. Initially this is a change from the surface protein at OspA to OspC and later OspF. The production of OspC is essential for spirochete transmission and allows it to establish infection. Another outer membrane protein, known as VIsE or variable major rn protein-like sequence rapidly changes its structure after infection allowing rapidly changing antigenic variation, which leads to difficulty in the host producing antibodies which can neutralise the infection. te The constant non-variable part of the VIsE, the C6 peptide has been shown to correlate very well with the presence of B.burgdorferi infection, with measurable levels present 3-5 weeks after infection and In declining rapidly after successful treatment. Positive serology for C6 antibodies allows rapid and definitive diagnosis of canine Lyme disease. e ov Occasionally B.burgdorferi can be visualised in body fluids (e.g. synovial fluid) using dark field microscopy or in tissue after silver or immunological stains; however the spirochete density is usually pr very low making diagnosis difficult by this method. Culture of Borrelia organisms is similarly difficult and as such, not clinically applicable. Im Quantitative PCR tests such as real time PCR have revolutionised diagnostics in many areas of veterinary medicine and the same is true of canine Lyme disease. A variety of PCR tests exist however those with primers to plasmid DNA are more sensitive due to the multiple copies present within each bacterium. Although blood and joint fluid can be used for PCR, spirochetes tend to invade through tissue rather than passive dissemination through the bloodstream, thus tissue PCR is much more sensitive. In particular PCR of synovial membrane and skin has been shown to be much more sensitive, especially in the later stages of the disease.  Lameness +/- Fever / Lethargy / Anorexia Painful swollen joint Pain or swelling near Inability to Rise joint Consider: Consider weakness due to: Consider: Borreliosis Metabolic disease Immune Panosteitis Cardiopulmonary mediated Osteomyelitis disease polyarthritis Hypertrophic Neurological disease Systemic Lupus osteodsytrophy erythematosis Hypertrophic Rheumatoid osteopathy arthritis Polymyositis Investigate as Degenerative Neoplasia appropriate Joint disease l na Possible investigations: io CBC, Serum biochemistry, Urinalysis at Lyme serology / PCR Joint Radiographs rn Joint taps – cytology and culture Lymph node fine needle aspirates te Rheumatoid factor / ANA analysis In e ov Early and effective antibiotic therapy has been shown to be very effective in reducing spirochete numbers, leading to rapid improvement in arthritis signs over a 24-48 hour period. Doxycycline at 10 pr mg/kg SID or BID is the drug of choice for the treatment of B.burgdorferi although a number of other antimicrobials also have efficacy. Doxycycline is lipid soluble thus has good tissue and cellular penetration. Treatment is generally used for 4 weeks, however research has shown that not all dogs Im will clear the infection within this period, and signs due to recrudescence of infection are occasionally seen. Doxycycline should not be used in growing animals due its deleterious, but mainly cosmetic, effects on skin, nails and tooth enamel. Although doxycycline is less likely to cause these effects compared to other tetracyclines, alternatives, such as amoxicillin, are suggested for growing animals. In the UK, all of these antibiotics are used under the cascade as there is not a licensed product for the treatment of canine Lyme disease. Doxycycline also has immunomodulatory and chondroprotective effects which are helpful in the treatment of polyarthritis. If proteinuria is documented (and other causes of PLN excluded) early treatment for glomerular nephritis should be instigated alongside antibiotic therapy. Angiotensin-converting enzyme (ACE) inhibitors will reduce renal protein loss though altered glomerular filtration pressure. Ultra-low aspirin therapy (0.5mg/kg/BID) is suggested to prevent thromboembolism as a result of anti-thrombin loss and platelet dysfunction. Drug Dose Route Interval Duration Indications (Hours) (Days) Doxycycline 10 mg/kg PO 12 to 24 30 Early disease, arthritis or (Ronaxan) neurological signs. Not for young animals. Always give with food or followed by water (Especially in cats) Amoxicillin 20 mg/kg PO 8 30 Young patients l na Azithromycin 25 mg/kg PO 24 10 – 20 Early disease io Penicillin G 22,000 U/kg IV 8 14 – 30 Persistent disease Ceftriaxone 25 mg/kg IV 24 at 14 – 30 Late neurologic or cardiac disease, persistent arthritis SC rn Cefotaxime 20 mg/kg IV 8 14 – 30 Neurological te manifestations In Chloramphenicol 15-25 mg/kg PO/SC 8 14 – 30 Neurological manifestations e ov The best method of reducing the risk of Lyme disease is to prevent ticks attaching, or killing and pr removing ticks quickly when they do attach. Some molecules such as permethrin have a repellent effect against ticks while others such as fipronil or the isoxazolines (e.g. afoxolaner) are fast acting Im acaricides. Regular use of an effective acaricide such as afoxolaner, fipronil and/or permethrin 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). As spirochete transmission does not occur until at least 24 hours after tick attachment, prompt removal of the ticks with in this period will stop transmission of Borrelia. 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. A vaccine (Merilym 3) is also available to provide protection against borreliosis. The aim of vaccination is to induce antibody formation to the Borrelia surface proteins, with surface proteins OspA and OspB being the main antibody targets. Vaccine-induced antibodies enter the tick during feeding, once present they are bactericidal and kill spirochetes via complement-directed activity. Although vaccination appears to be very effective, it is considered a non-core vaccine (Day and others 2016) and is generally only used in dogs in geographically at-risk areas and with a high degree of possible exposure (such as outdoor or hunting dogs). Lyme Disease References Cook M.J. (2015) Lyme borreliosis: a review of data on transmission time after tick attachment. International journal of general medicine 8, 1-8 Dandache P. & Nadelman R.B. (2008) Erythema migrans. Infectious disease clinics of North America 22, Day M.J., Horzinek M.C., Schultz R.D. & Squires R.A. (2016) WSAVA Guidelines for the Vaccination of Dogs and Cats. Journal of Small Animal Practice 57, E1–E45 Krupka I. & Straubinger R.K. (2010) Lyme borreliosis in dogs and cats: background, diagnosis, treatment and prevention of infections with Borrelia burgdorferi sensu stricto. Veterinary Clinics of North America: Small Animal Practice. 40, 1103-19 Littman M.P. (2003) Canine Borreliosis. Veterinary Clinics of North America 33, 827-862 Littman M.P., Goldstein R.E, Labato M.A, Lappin M.R. & Moore G.E. (2006) ACVIM Small Animal Consensus Statement on Lyme Disease in Dogs: Diagnosis, Treatment and Prevention. Journal of Veterinary Internal Medicine 20, 422-434 May C., Carter S.D., Barnes A., Bell S. & Bennett D. (1991) Serodiagnosis of Lyme disease in UK dogs. Journal of Small Animal Practice 32, 170-174 l na Smith F.D., Ballantyne R., Morgan E.R. & Wall R. (2012) Estimating Lyme disease risk using pet dogs as sentinels. Comparative Immunology, Microbiology and Infectious Diseases. 35, 163-167 io Yu L.P, Smith G.N, Brandt K.D, Myers S.L, O'Connor B.L. & Brandt D.A. (1992) Reduction of the at severity of canine osteoarthritis by prophylactic treatment with oral doxycycline. Arthritis & Rheumatism 35, 1150-9 rn Babesiosis te 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 is particularly prevalent in France due to Babesia In canis, with increasing incidence in the south (particularly south of the Loire valley), however tick vectors are widespread and the disease in endemic in most of Southern Europe. In early 2016, e several cases of Babesia canis infection in dogs from the Essex area were reported in both the media and veterinary press that had not travelled outside the United Kingdom (Cook and others 2016, ov Phipps and others 2016). These cases, combined with a fatal case of Babesia vogeli infection in an untraveled dog from Kent (Holm and others, 2006) and unpublished reports of Babesia in untraveled pr 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. Im The first reports of babesiosis in dogs were made in Africa in the 1890’s and since then at least nine genetically distinct intraerythrocytic piroplasm parasites, including Babesia and closely related Theileria and Cytauxzoon species have been identified. Babesia species are divided morphologically into the large (3-7µm in length) and small (1-3µm in length) species and the observed species of Babesia seen varies by geographic region, largely the result of the tick vectors present. Species Distribution Tick Vector Clinical Findings Babesia Southern & Central Rhipicephalus Moderate clinical disease canis Europe sanguineus Haemolytic anaemia Dermacentor Thrombocytopenia reticulatus Fever Babesia South Africa Heamaphysalis Very virulent haemolytic rossi eliptica anaemia Immune mediated disease Babesia Africa, Asia, Australia Rhipicephalus In affected animals fever, l na vogeli sanguineus anaemia and Central, North and thrombocytopenia South America io Often unapparent clinical Large Forms Northern & Central disease. Europe at Young animals may have rn more severe signs Babesia USA, Asia, North & East Rhipicephalus Haemolytic anaemia te gibsoni Africa, Australia, Likely sanguineus extending through Thrombocytopenia In southern Europe Chronic subclinical infection Heamaphysalis leading to weight loss and e bispinosa progressive debilitation ov Babesia North west Spain Probably Ixodes Severe haemolytic anaemia Annea hexagonus Small Forms pr (Theileria A proportion develop renal annae) failure Im Babesia canis (previously called B canis canis) is transmitted by Dermacentor reticulates (the ornate cow or marsh tick) and to a lesser degree by Rhipicephalus sanguineus (the Brown dog tick). Dermacentor reticulatus has historically been found in the southern parts of Europe, with 45-70% of French practices reporting confirmed infection each year. Recent work has shown the tick vector has become established more northerly in Europe with Dermacentor reticulatus reported in Poland, Belgium and Germany and milder winters 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) and the recent cases in the UK and Norway reflecting 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 wide worldwide distribution in warm and humid areas which reflect the geographic distribution of Babesia vogeli infection. Rhipicephalus sanguineus is rarely 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 through most parts of the world, although rarely reported in Europe. It is transmitted by Heamaphysalis species and possibly Rhipicephalus sanguineus. Interestingly a recent PCR study of 742 ticks collected from areas thoughout the United Kingdom found Babesia gibsoni DNA in 11 fed Ixodes ricinus ticks (Smith and others 2013). Ixodes species are not a known vector for Babesia gibsoni, however its presence in the UK is a surprising finding as 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, were competent vectors are not endemic, Babesia gibsoni can be passed by direct dog to dog transmission, through fighting and l perinatal transmission. na io Clinical reports of Babesia rossi infection are mainly limited to South Africa, with over 10% of dogs evaluated in veterinary hospitals affected. It is transmitted by the yellow dog tick, Heamaphysalis at elliptica (previously called H. leachi) and leads to a particularly virulent clinical signs. It is most commonly seen in the summer months and bull terrier breeds have a worse prognosis. rn te Feline babesiosis is rare and has not been studied as extensively as canine disease. In the domestic In cat clinical disease is predominately reported in South Africa and Sudan due to Babesia felis (Penhorn 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 e relationship between wild and domestic felids is unknown (Bosman 2006). Clinical signs are generally ov more subtle and cats rarely develop a haemolytic crisis. Affected animals are generally young (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 6 pr weeks protection again reinfection (Vercammen and others 1996). Im 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). Preventing tick attachment in the first instance or killing the tick before disease transmission occurs provide the best methods of reducing the risk of canine babesiosis. A number of different topical products have been shown to have good activity in preventing tick attachment and long acting oral treatments that kill any ticks that attach over prolonged time periods. Regular use of such a product should be suggested to all owners of dogs walked regularly 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 after 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. Babesia References 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, 33-38 Cook S., English K. & Humm K. (2016), Autochthonous babesiosis in the United Kingdom. Journal of Small Animal Practice. doi: 10.1111/jsap.12487 Cook S. & Swann J.W. (2016). Canine babesiosis: autochthonous today, endemic tomorrow? Veterinary Record 178, 417-419 Hansford K.M., Medlock J.M., Swainsbury C., Phipps L.P., De Marco M.D.M.F., Hernández-Triana l L.M. & Fooks, A.R. (2016). Babesia canis infection in ticks in Essex. Veterinary Record 178, 323-323 na Hartelt K., Rieker T., Oehme R.M., Brockmann S.O., Müller W. & Dorn, N.(2007) First evidence of io Babesia gibsoni (Asian genotype) in dogs in Western Europe. Vector Borne Zoonotic Disease. 7, 163–166 at Holm L.P., Kerr M.G., Trees A.J., McGarry J.W., Munro, E.R. & Shaw S.E. (2006) Fatal babesiosis in an untravelled British dog. Veterinary Record 159, 179-80 rn Jacobson L.S. & Clark I.A. (1994). The pathophysiology of canine babesiosis: new approaches to an te old puzzle. Journal of the South African Veterinary Association 65, 134-145 In Jameson L.J., Phipps, L.P. & Medlock, J.M. (2010) Surveillance for exotic ticks on companion animals in the UK. Veterinary Record 166, 202-203 e Moik K. & Gothe R. (1997). Babesia infections of felids and a report on a case in a cat in Germany. ov Tierarztl Prax Ausg Kleintiere Heimtiere 25, 532-535 Penzhorn B.L., Schoeman T. & Jacobson L.S. (2004). Feline babesiosis in South Africa, a review. pr Ann NY Acad Sci 1026, 183-18 Im Phipps L.P., De Marco M.D.M.F., Hernández-Triana L.M., Johnson N., Swainsbury C., Medlock J.M. & Mitchell S. (2016). Babesia canis detected in dogs and associated ticks from Essex. Veterinary Record 178, 243-244 Oines O., Storli K. & Brun-Hansen H. (2010). First case of babesiosis caused by Babesia canis canis in a dog from Norway. Veterinary parasitology 171, 350-353 Toth B. & Roberts H. (2011) Risk of Incursion and Estabilshment of Certain Exotic Disease and Tick Species to the UK via International Pet Travel. Defra, London, UK Vercammen F., De Deken R. & Maes L. (1996). Prophylactic activity of imidocarb against experimental infection with Babesia canis. Veterinary parasitology 63, 195-198 Wall R. (2012) A ticking clock for tickborne disease? Veterinary Record 170, 326-328 Welc-Faleciak R., Rodo A., Siński E. & Bajer A. (2009). Babesia canis and other tick-borne infections in dogs in Central Poland. Veterinary parasitology 166, 191-198 Rickettsial Disease Rickettsiea are intracellular organisms causing disease by affecting the function of their target cells, which are mainly white cells and platelets, leading to signs associated with deficiencies and dysfunction of those cell lines. Rickettsiea are classified within α-proteobacteria and include the genera of Ehrlichia (which includes Ehrlichia canis) and Anaplasma (which includes Anaplasma phagocytophilium). Nomenclature of rickettesial disease can be confusing as recent advances in DNA sequencing allowed reclassification of the order Rickettsiales in 2001, leading to some organisms changing their names. Also historically individual organism have been named by the genus of the infectious agent, the species it affects and its predominant target cell [for example, Ehrlichia canis leading to canine monocytotrophic ehrlichiosis], whereas with the advent of molecular testing, the genus and species responsible can be much more easily defined, creating less confusion as to the responsible infectious agent. l na io at rn te In e ov pr Im  The genera of Ehrlichia and Anaplasma are tick borne diseases and limited to the geographic location of the vector. Ehrlichia canis is the most common of the rickettsial disease seen in Southern Europe, but is not currently considered endemic in the United Kingdom. Whereas Anaplasma phagocytophilium has been isolated in Ixodes ticks within the United Kingdom and rarely associated with clinical disease. Species Distribution Cells infected Tick Vector Disease reservoir Ehrlichia canis Temperate and Monocytes & Rhipicephalus Wild & domestic tropical areas Macrophages sanguineus canids worldwide, except (Canine monocytotropic Australia ehrlichiosis) Ehrlichia chaffeensis Southern parts of Monocytes, Numerous ticks White-tailed deer, the United States Macrophages, including coyotes, racoons, Neutrophils & Amblyomma voles l na (Human monocytotropic Lymphocytes americanum ehrlichiosis) io Ehrlichia ewingi Midwest and at Granuloctyes Amblyomma Wild & domestic Southern United americanum canids rn States te (Granulocytotropic ehlichiosis) In Anaplasma Worldwide, mainly Granulocytes Idoxes spp. White-tailed deer, e phagocytophilum temperate and mice, voles & ov northern areas migratory birds pr (Granulocytotropic anaplasmosis) Im Anaplasma platys Worldwide Thrombocytes Likely: Canids & small Rhipicephalus ruminants sanguineus (Thrombocytotrophic anaplasmosis) Ehrlichia canis Ehrlichia canis, the causal agent of canine monocytotrophic ehrlichiosis, is a small, pleomorphic gram negative intracellular rickettsial parasite, which appear as round intracytoplasmic inclusions with in monocytes and macrophages. Ehrlichia canis infects dogs and wild canids, including the jackal, fox and coyote. It was first described in Algeria in 1935, but did not gain prominence until the Vietnam War when many American service German shepherd dogs, which are highly susceptible to Ehrlichia Canis infection [or tropical canine pancytopenia as it was known at the time], died as a result of the disease. It also received publicity when confused as the cause of human monocytotrophic ehrlichiosis in the late 1980’s until Ehrlichia chaffeensis was discovered as the cause. Ehrlichia canis infection is found worldwide in temperate and tropical areas, with the exception of Australia. The areas where canine Ehrlichia canis infection are reported mirrors the geographic distribution of its vector Rhipicephalus sanguineus (the brown dog tick). In Europe, accurate information on the disease prevalence is not available; however cases are particularly concentrated around the south coast of France, Corsica, Greece and the southern half of Italy. Although Ehrlichia canis is not currently considered endemic in the United Kingdom, dogs are occasionally imported with l na the disease and a recent cases in an untraveled dogs have been reported (Wilson and others, 2013). The route of infection in these dogs is unknown; neither had knowingly mixed with dogs that had travelled abroad or had recent history of tick attachment. Rhipicephalus sanguineus is not endemic to io the United Kingdom as climatic conditions are too cold, however numbers are increasing due to importation and Defra acknowledges a risk of establishment within houses (Toth and Roberts 2011, at Jameson and others 2010). There has also been suggestion that Ehrlichia could become established in other tick species, for example Argas vespertilionis which is a tick associated with bats in Europe rn (Socolovschi and others 2012). te In The reservoir for Ehrlichia canis infection is in wild and domestic dogs. Its vector Rhipicephalus sanguineus has a single host preference and feeds on dogs at all three stages of its life cycle. Experimentally the American dog tick Dermocentor variabilis has also been shown to transmit e infection. Ehrlichia canis is passed to the next stage but is not passed on transovarially in the tick so ov unexposed ticks must feed on an infected dog in the acute phase to become infected. After attachment Ehrlichia transmission may be rapid, with experimental studies showing this can occur as early as 3 hours post exposure (Fourie and others 2013). pr Im Once infected the incubation period is reported as 8-20 days and the organism spreads throughout the body multiplying in macrophages. Three phases of ehrlichoisis are seen; acute, subclinical and chronic. The acute phase usually lasts 1-4 weeks and most dogs recover with appropriate treatment. Typically non-specific signs such as fever, anorexia and lymphadenomegaly are reported. Haematology results usually reveal thrombocytopenia, leucopenia and anaemia. Untreated dogs or those that do not fully clear the organism may enter a subclinical state where they are become asymptomatic carriers for months to years. Persistently infected dogs may spontaneously clear Ehrlichia, however some dogs the organism persists leading to chronic infection. Not all dogs develop the signs of chronic disease and why this occurs is not clear, but appears more common in German shepherd dogs. The spleen and its mononuclear phagocytic system appears important in determining pathogenesis and in experimental animals splenectomised dogs show less severe clinical signs. Chronic infection leads to bone marrow hypoplasia and resultant pancytopenia. Thrombocytopenia and platelet dysfunction leads to severe bleeding in some cases (sub-mucosal haemorrhage and epistaxis). The prognosis associated with chronic Ehrlichia canis infection is very guarded. In this phase biochemistry will usually reveal a marked increase in globulins. This increase in globulins is usually polyclonal, although occasional monoclonal increases have been reported and hyperviscosity associated with clinical signs such as retinal detachment have been occasionally seen. Identification of Ehrlichia morulae in leucocytes is diagnostic, but can be difficult and is time consuming. Blood collected from a peripheral capillary vessel, for example form the ear margin, or buffy coat analysis are most rewarding. Morulae have also been reported within macropahges within lymph node and lung aspirates. Serology is widely used, with immunofluorescence antibody titres >40 to 80 considered evidence of exposure. Using serology, a rising titre of a fourfold increase over a two l week period confirms active infection. Several commercial ELISA tests are also available and are na useful for patient side use, cross reaction and therefore false positive results can occur to if there is exposure to less pathogenic rickettsiae, however this is much less of a problem in Europe than in the io United States. Diagnosis can be made on the basis of PCR which is very sensitive and is effective at confirming that animals have cleared the infection after treatment. at rn Doxycycline is the treatment of choice (5mg/kg q12hrs po or 10mg/kg q24hrs for 21 days) and generally leads to a clinical improvement within 1-3 days. Imidocarb has been suggested for use in te resistant infections, however experimental work has shown it to be infective at clearing Ehrlichia canis infection (Eddlestone and others, 2006). Chloramphenicol should be used in these instances (25- In 50mg/kg q8hrs po for 21-28 days). Chloramphenicol has also been suggested in puppies younger than 5 months due to the risk of tetracycline leading to enamel staining of teeth. e ov Supportive therapy with fluid therapy and blood transfusions may be required, depending on the patient. Short term use of steroids should also be considered if there is a life threating pr thrombocytopenia as it is likely that immune mediated destruction is part of its pathogenesis. Pancytopenia (especially in the presence of severe anaemia), prolonged activated partial Im thromboplastin time and hypokalaemia have been shown to be associated with a poor prognosis (Shipov and others 2008). Anaplasma phagocytophilium Anaplasma phagocytophilium, previously named Ehrlichia phagocytophilium, Ehrlichia Equi and Cytoecetes phagocytophilia, leads to granulocytic ehrlichiosis. First reported in the Scottish sheep in the 1930’s, it was reported as the cause of pasture fever in cattle in England in the 1950’s and Finland a decade later. The first canine cases were reported in the 1980’s in Switzerland, Sweden and North America, and feline cases in Sweden in the late 1990’s. Anaplasma is transmitted by several species of Ixodes ticks with transmission of the organism thought to occur within 24-48 hours of attachment. A low prevalence (0.74%) of Anaplasma phagocytophilium has been found in Ixodes ticks in the United Kingdom (Smith and others 2013). Clinical cases are occasionally reported both in the United Kingdom (Bexfield and others, 2005) and other temporal parts of Northern Europe. Ixodes ticks that harbour Anaplasma may also co-infect with other organisms, such as Borrelia burgdorferi. Anaplasma phagocytophilium is an obligate intracellular organism and infects mainly granulocytes. Its complete pathogenesis is unknown however it appears within cytoplasmic inclusions, which can be seen in circulating neutrophils for 7-14 days post infection. Clinical signs vary between geographic strains and are usually seen after an incubation period of 4-14 days. Initial signs are usually vague, with anorexia and listlessness commonly reported. Clinical examination often revealed pyrexia, lameness, with associated joint stiffness and swelling and lymph node enlargement. Neurological signs secondary to meningitis are more commonly seen with Anaplasma infection compared to Ehrlichia. Diagnostic evaluation may reveal Anaplasma inclusion bodies within neutrophils, accompanied by mild to marked neutropenia and thrombocytopenia. PCR for Anaplasma performed on whole EDTA blood is commonly available and more sensitive than direct microscopy. Treatment with Doxycycline (10mg/kg q12hrs po for 10-21 days) is usually successful, steroidal therapy may need to be considered if immune mediated disease is present. Anaplasma platys l na Anaplasma platys (previously known as Ehrlichia platys) has a tropism for platelets and leads to canine cyclic thrombocytopenia. It was first reported in the United States in 1978 and since then has io been reported in much of the world including southern Europe and the Mediterranean basin, Southeast Asia, South America, Africa and Australia. Although its mode of transmission has not been at fully detailed, it is believed to be transmitted by Rhipicephalus sanguineus, which is supported by its rn geographical distribution and reported co-infection with Ehrlichia canis, although has not yet been definitive proven by experimental transmission studies. te In Anaplasma platys morulae appear as small round or oval inclusions with in platelets and appear at their highest concentrations around 8-15 days after experimental infection. This is followed by a period of profound thrombocytopenia, with the platelet counts often dropping below 20x109/l as a e result of direct injury to the platelets and the associated immune response, recovering to normal over ov 3-4 days. Cyclical episodes of thrombocytopenia then occur at 7-14 day intervals. The levels of parasitemia becoming less marked over time; however the thrombocytopenia is often marked pr suggesting an immune mediated mechanism during later episodes. Im There is geographic variation in strains of Anaplasma platys and there for differences in reported clinical signs by area. In the United States minimal clinical signs post infection are reported, however in Mediterranean area severe cyclical episodes of bleeding such as epistaxis have been reported. Co- infection with Babesia canis or Ehrlichia canis may lead to more pronounced clinical signs. Diagnosis is usually made by microscopic detection of the organism; however serology and PCR tests are also available. Treatment with doxycycline (10mg/kg q12hrs po for 10 days) or enrofloxacin (5mg/kg q24hrs po for 21 days) have been shown to clear infection. Prevention of Rickettsial Disease The best method of reducing the risk of rickettsial disease is to prevent ticks attaching, or killing and removing ticks quickly when they do attach. Some molecules such as permethrin have a repellent effect against ticks while others such as fipronil or the isoxazolines (e.g. afoxolaner) are fast acting acaricides. Regular use of an effective acaricide such as afoxolaner, fipronil and/or permethrin 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). 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 the risk of tick borne disease transmission. This will help reduce the risk of Anaplasma infection with is thought to take 24-48 hours to be transmitted after tick attachment, however may be less effective against Ehrlichia canis, which can occur very rapidly after tick attachment. Rickettsial Disease References Bexfield N.H., Villiers E.J. & Herrtage M.E. (2005) Immune-mediated haemolytic anaemia and thrombocytopenia associated with Anaplasma phagocytophilum in a dog. Journal of Small Animal Practice 46, 543-548 Breitschwerdt E.B., Abrams-Ogg A.C.G., Lappin M.R., et al. (2002). Molecular evidence supporting Ehrlichia canis-like infection in cats. Journal of Veterinary Internal Medicine 16, 642-649 l Eddlestone SM, Neer TM, Gaunt SD, et al. (2006) Failure of imidocarb dipropionate to clear na experimentally induced Ehrlichia canis infection in dogs. Journal of Veterinary Internal Medicine 20, 840-844 io Fourie J.J., Stanneck D., Luus H.G., Beugnet F., Wijnveld M. & Jongejan, F., (2013) Transmission of at Ehrlichia canis by Rhipicephalus sanguineus ticks feeding on dogs and on artificial membranes. Veterinary parasitology 197, 595-603 rn Shipov A, Klement E, Reuveni-Tager L, et al. (2008) Prognostic indicators for canine monocytic ehrlichiosis. Veterinary Parasitology 153,131-138 te Smith F.D., Ellse L. & Wall R. (2013) Prevalence of Babesia and Anaplasma in ticks infesting dogs in In Great Britain Veterinary Parasitology 198, 18-23 Socolovschi C., Kernif T., Raoult D. & Parola P. (2012) Borrelia, rickettsia, and ehrlichia species in bat e ticks, France, 2010. Emerging Infectious Diseases 18, 1966-75 ov Toth B. & Roberts, H. (2011) Risk of Incursion and Estabilshment of Certain Exotic Disease and Tick Species to the UK via International Pet Travel. Defra, London, UK pr Wilson H.E., Mugford A.R., Humm K.R. & Kellett-Gregory L.M. (2013) Ehrlichia canis infection in a Im dog with no history of travel outside the United Kingdom. Journal of Small Animal Practice 54, 425- 427