Feline panleukopenia virus DNA shedding following modified live virus vaccination in a shelter setting.

This study assessed the frequency and timing of feline panleukopenia virus (FPV) shedding in feces following administration of a modified live FPV vaccine. Feces were collected from 37 shelter cats that did not meet clinical criteria for panleukopenia on the day of vaccination or on days 3, 7, 14, and 21 post-vaccination (NCL group). A commercial quantitative PCR (qPCR) fecal pathogen panel and a canine parvovirus point-of-care antigen test were performed. FPV DNA copy numbers from a concurrent study of 39 cats with panleukopenia (CL group) were compared with the NCL group. Of the 165 samples from the NCL group, one had a weak positive antigen test result on day 7, while nine samples (5.5%) from eight cats (21.6%) produced positive FPV qPCR test results, one on day 3 and eight on day 7. There were no day 21-positive qPCR results in the 11 cats that were revaccinated on day 14. There was no association between the number of additional fecal pathogens identified and a positive FPV qPCR result. Of the cats with positive results, FPV DNA copy numbers differed between NCL group and CL group (median 1.13 × 107 and 5.01 × 108 copies/g feces, respectively; P < 0.001). The FPV qPCR cannot differentiate subclinical infection from vaccine virus shedding. To avoid unnecessary isolation and euthanasia, shelters should therefore limit FPV PCR testing to cats with a high index of suspicion of panleukopenia. The timing of recent vaccination should also be considered when interpreting test results.

Comparison of effects of uncomplicated canine babesiosis and canine normovolaemic anaemia on abdominal splanchnic Doppler characteristics--a preliminary investigation.

A preliminary study was conducted to compare uncomplicated canine babesiosis (CB) and experimentally induced normovolaemic anaemia (EA) using Doppler ultrasonography of abdominal splanchnic vessels. Fourteen dogs with uncomplicated CB were investigated together with 11 healthy Beagles during severe EA, moderate EA and the physiological state as a control group. Canine babesiosis was compared with severe EA, moderate EA and the physiological state using Doppler variables of the abdominal aorta, cranial mesenteric artery (CMA), coeliac, left renal and interlobar, and hilar splenic arteries, and the main portal vein. Patterns of haemodynamic changes during CB and EA were broadly similar and were characterised by elevations in velocities and reductions in resistance indices in all vessels except the renal arteries when compared with the physiological state. Aortic and CMA peak systolic velocities and CMA end diastolic and time-averaged mean velocities in CB were significantly lower (P < 0.023) than those in severe EA. Patterns of renal haemodynamic changes during CB and EA were similar. However, the renal patterns differed from those of aortic and gastrointestinal arteries, having elevations in vascular resistance indices, a reduction in end diastolic velocity and unchanged time-averaged mean velocity. The left renal artery resistive index in CB was significantly higher (P < 0.025) than those in EA and the physiological state. Renal interlobar artery resistive and pulsatility indices in CB were significantly higher (P < 0.016) than those of moderate EA and the physiological state. The similar haemodynamic patterns in CB and EA are attributable to anaemia, while significant differences may additionally be attributed to pathophysiological factors peculiar to CB.

The pharmacokinetics of diminazene aceturate after intramuscular administration in healthy dogs.

The pharmacokinetics of diminazene aceturate following intramuscular (i.m.) administration at 4.2 mg/kg was evaluated in 8 healthy German Shepherd dogs. Blood samples were collected at 19 intervals over a period of 21 days. Diminazene plasma concentrations were measured using a validated HPLC method with UV detection and a sensitivity of 25 ng/ml. The in vitro and in vivo binding of diminazene to blood elements was additionally determined. Diminazene pharmacokinetics showed a large inter-individual variation after i.m. administration. It had a short absorption half-life (K01-HL of 0.11 +/- 0.18 h), resulting in a C(max) of 1849 +/- 268.7 ng/ml at T(max) of 0.37 h and a mean overall elimination half-life (T1/2beta) of 5.31 +/- 3.89 h. A terminal half-life of 27.5 +/- 25.0 h was measured. At 1 h after i.m. injection, 75% of the diminazene in whole blood was in the plasma fraction. The results of this study indicate that diminazene is rapidly distributed and sequestered into the liver, followed by a slower terminal phase during which diminazene is both redistributed to the peripheral tissues and/or renally excreted. It is recommended that diminazene administered i.m. at 4.2 mg/kg should not be repeated within a 21-day period.

The breed prevalence of dog erythrocyte antigen 1.1 in the Onderstepoort area of South Africa and its significance in selection of canine blood donors.

The blood group antigen Dog Erythrocyte Antigen (DEA) 1.1 is clinically the most important canine blood group as DEA 1.1 antibodies are capable of causing acute haemolytic, potentially life-threatening transfusion reactions. Dogs do not have naturally occurring antibodies to DEA 1.1 but are rapidly sensitised by the first incompatible transfusion. The prevalence of DEA 1.1 in the general dog population is estimated at 42-46%. Canine blood donors registered with the Onderstepoort Animal Blood Bank (n = 93) as well as potential donors (n = 140) were typed for DEA 1.1 using a monoclonal antibody card kit. All dogs came from the Onderstepoort area, near Pretoria, Gauteng province, South Africa. Overall prevalence of DEA 1.1 was 47%. Prevalence was 47% in purebred dogs and 48% in mongrels. Distinct breed differences were noted with less than 20% of German shepherd dogs and Boxers and greater than 75% of Rottweilers, Great Danes, St Bernards and Dalmations testing DEA 1.1 positive. Knowledge of local breed differences will increase effectiveness of blood donor recruitment.

Diagnosis and medical treatment of otitis externa in the dog and cat.

Otitis externa is no longer viewed as an isolated disease of the ear canal, but is a syndrome that is often a reflection of underlying dermatological disease. Causes are classified as predisposing (increase the risk of otitis); primary (directly induce otitis), secondary (contribute to otitis only in an abnormal ear or in conjunction with predisposing factors) and perpetuating (result from inflammation and pathology in ear, prevent resolution of otitis). Common primary causes include foreign bodies, hypersensitivity (particularly atopy and food allergy), keratinisation disorders (most commonly primary idiopathic seborrhoea and hypothyroidism) and earmites, particularly in cats. A systematic diagnostic procedure is required to identify causes and contributing factors. This should include history, clinical examination, otoscopy and cytology in all cases and culture and sensitivity as well as otitis media assessment and biopsy in severe and recurrent cases. Ancillary tests may be required depending on the underlying cause. Treatment consists of identifying and addressing predisposing and primary factors; cleaning the ear canal; topical therapy; systemic therapy where necessary; client education; follow-up; and preventive and maintenance therapy as required.

The mixed acid-base disturbances of severe canine babesiosis.

Thirty-four dogs suffering from severe babesiosis caused by Babesia canis rossi were included in this study to evaluate acid-base imbalances with the quantitative clinical approach proposed by Stewart. All but 3 dogs were severely anemic (hematocrit <12%). Arterial pH varied from severe acidemia to alkalemia. Most animals (31 of 34; 91%) had inappropriate hypocapnia with the partial pressure of CO2 < 10 mm Hg in 12 of 34 dogs (35%). All dogs had a negative base excess (BE; mean of - 16.5 mEq/L) and it was below the lower normal limit in 25. Hypoxemia was present in 3 dogs. Most dogs (28 of 34; 82%) were hyperlactatemic. Seventy percent of dogs (23 of 33) were hypoalbuminemic. Anion gap (AG) was widely distributed, being high in 15, low in 12, and normal in 6 of the 33 dogs. The strong ion difference (SID; difference between the sodium and chloride concentrations) was low in 20 of 33 dogs, chiefly because of hyperchloremia. Dilutional acidosis was present in 23 of 34 dogs. Hypoalbuminemic alkalosis was present in all dogs. Increase in unmeasured strong anions resulted in a negative BE in all dogs. Concurrent metabolic acidosis and respiratory alkalosis was identified in 31 of 34 dogs. A high AG metabolic acidosis was present in 15 of 33 dogs. The lack of an AG increase in the remaining dogs was attributed to concurrent hypoalbuminemia, which is common in this disease. Significant contributors to BE were the SID, free water abnormalities, and AG (all with P < .01). Mixed metabolic and respiratory acid-base imbalances are common in severe canine babesiosis, and resemble imbalances described in canine endotoxemia and human malaria.

Renal involvement in dogs with babesiosis.

Proteinuria, and renal tubular casts and epithelial cells in urine sediment, are commonly observed in both complicated and uncomplicated babesiosis, but do not necessarily reflect or predict renal failure. This study investigated the presence and degree of renal damage in canine babesiosis. Renal function and integrity were evaluated using serum urea and creatinine, serum electrolytes (sodium and potassium), fractional clearance of sodium (FcNa) and potassium (FcK), urine enzyme activity of gamma-glutamyl transpeptidase and alkaline phosphatase, urine protein:creatinine ratio, and urinalysis. One control group (n = 10) and 3 groups of babesiosis cases were studied: mild uncomplicated (n = 10), severe uncomplicated (n = 11), and complicated (n = 9). All babesiosis groups showed well-concentrated urine. Mean serum urea was elevated in the severe and complicated groups, and was significantly different from the control group. There was no statistically significant difference between the groups for creatinine, although the complicated group had a mean value above the normal reference range. Hypokalaemia was uncommon in all the groups. Hyperkalaemia was present in only 2 dogs in the complicated group. Marginal hyponatraemia was present in a minority of dogs in all groups. The serum electrolytes were not significantly different between groups. There was no overall elevation, nor any statistically significant difference in both the FcNa and FcK between the groups. Only 1 dog, in the complicated group, showed marked enzymuria. Proteinuria was a common finding and was significantly different between the severe and complicated groups and the control group. Some dogs in all groups had renal tubular epithelial cells in the urinary sediment, which increased in severity from the mild to the complicated groups and was significantly different from the control group. This study demonstrated that minimal renal damage occurs more often in canine babesiosis than significant damage or acute renal failure.

Feline babesiosis: signalment, clinical pathology and concurrent infections.

Fifty-six cats with naturally occurring Babesia felis infection were studied. No breed or sex predilection could be identified, but there was an apparent predilection for young adult cats less than 3 years of age. Macrocytic, hypochromic, regenerative anaemia was present in 57% of the cats and in-saline agglutination tests were positive in 16%. No characteristic changes were observed in total or differential leukocyte counts. Thrombocyte counts were variable and thrombocytopaenia was an inconsistent finding. Hepatic cytosol enzyme activity and total bilirubin concentrations were elevated in the majority of cats. Serum protein values were mostly normal, but increased values were occasionally observed and polyclonal gammopathies were observed in all cats with increased total globulin concentrations. No remarkable changes in renal parameters were observed. A variety of electrolyte abnormalities occurred in a number of cats, but no consistent pattern of change could be identified. A close correlation was evident between peripheral and central parasite counts. Concurrent infections with Haemobartonella felis, feline immunodeficiency virus and/or feline leukemia virus were identified in a number of cats.

Systemic inflammatory response syndrome and multiple-organ damage/dysfunction in complicated canine babesiosis.

This study was designed to document the systemic inflammatory response syndrome (SIRS) and multiple-organ dysfunction syndrome (MODS) in dogs with complicated babesiosis, and to assess their impact on outcome. Ninety-one cases were evaluated retrospectively for SIRS and 56 for MODS. The liver, kidneys, lungs, central nervous system and musculature were assessed. Eighty-seven percent of cases were SIRS-positive. Fifty-two percent of the cases assessed for organ damage had single-organ damage and 48 % had MODS. Outcome was not significantly affected by either SIRS or MODS, but involvement of specific organs had a profound effect. Central nervous system involvement resulted in a 57 times greater chance of death and renal involvement in a 5-fold increased risk compared to all other complications. Lung involvement could not be statistically evaluated owing to co-linearity with other organs, but was associated with high mortality. Liver and muscle damage were common, but did not significantly affect outcome. There are many similarities between the observations in this study and previous human and animal studies in related fields, lending additional support to the body of evidence for shared underlying pathophysiological mechanisms in systemic inflammatory states.

Blood pressure changes in dogs with babesiosis.

Systemic arterial blood pressures were measured in 30 dogs with acute babesiosis, 10 each with mild uncomplicated, severe uncomplicated and complicated disease. Ten healthy dogs were used as controls. Hypotension was defined as more than 3 standard deviations below the control mean. Normal mean pressures (+/-SD) were: systolic arterial pressure 151 (+/-11) mm Hg, diastolic arterial pressure 89 (+/-8) mm Hg and mean arterial pressure 107 (+/-10) mm Hg. Hypotension was the most frequent abnormality, and increased strikingly in incidence as disease severity increased, with 5/10 dogs in the complicated group being hypotensive for systolic, diastolic and mean arterial pressures, compared with 2/10 in the severe uncomplicated group and 0/10 in the mild uncomplicated group. Systolic, diastolic and mean arterial pressures in the complicated group and severe uncomplicated group, and systolic pressure in the mild uncomplicated group, were significantly lower than in the controls. There were no significant relationships between arterial pressures and age, pulse rate, respiratory rate, temperature, mucous membrane colour or haematocrit. There was a significant negative correlation between arterial pressures and white cell and immature neutrophil counts. Arterial pressures differed significantly between dogs that were clinically collapsed and those that were not, but not between survivors and non-survivors. Pulse pressure (systolic-diastolic) was low in 7/10 complicated, 1/10 mild uncomplicated, and 1/10 severe uncomplicated cases, and differed significantly between the complicated and control groups. The high incidence of hypotension in clinically severe babesiosis has important implications for therapy.

A survey of feline babesiosis in South Africa.

South Africa appears to be the only country where feline babesiosis is a significant clinical entity in domestic cats. Little is known about its epidemiology or the clinical challenges facing practitioners. A questionnaire posted to 1760 South African veterinarians was returned by 16%, representing approximately 40% of practices. Just over half reported seeing feline babesiosis, with most cases occurring in the coastal areas of the Western Cape, Eastern Cape and KwaZulu-Natal Provinces. Overall incidence is highest in summer, but seasonality is less pronounced in non-seasonal and winter rainfall areas. No age, breed or sex predisposition was identified. Weight loss, weakness, anaemia, fever and icterus are common clinical findings. Complications include hepatopathy, renal failure, pulmonary oedema, cerebral signs, immune-mediated haemolytic anaemia and concurrent infections. The antibabesial drug of choice is primaquine phosphate. Response to therapy is generally good, but recurrence and chronic infections were identified as problems. The average mortality rate was 15%. Approximately 3000 cases are seen annually by the respondents, at an estimated cost of R750 000 to the owners. Feline babesiosis is a significant problem in South Africa, and further investigations of taxonomic status, concurrent infections, chemotherapy, complications and management of refractory cases are warranted.

Do babesiosis and malaria share a common disease process?

Clinical Confusion between human babesiosis and malaria is often reported in the literature. Headache, fever, chills, nausea, vomiting, myalgia, altered mental status, disseminated intravascular coagulation, anaemia with dyserythropoiesis, hypotension, respiratory distress, and renal insufficiency are common to both diseases. This remarkable similarity is not restricted to the human host. In the mouse, for example, the histological changes wrought by fatal malaria (Plasmodium vinckei) and babesiosis (Babesia rhodaini) are identical, and parasites of both genera cross-protect. Malarial disease pathogenesis is now generally associated with excessive production of pro-inflammatory cytokines , such as tumour necrosis factor. While this concept has not yet been examined in babesiosis, indirect evidence arises from noting the parasite density at which illness occurs in primary infections caused by either organism. Naive mice tolerate high loads of malarial or babesial parasites before they become ill, and are also tolerant to endotoxicity, which is mediated by these same cytokines. In contrast, humans require very much smaller loads of Plasmodium or Babesia spp. before becoming ill, and likewise are very sensitive to endotoxin, the harmful effects of which are mediated by the pro-inflammatory cytokines. For these reasons, as discussed in this review, the diseases caused by these two genera of intra-erythrocytic protozoan parasites will probably prove to be conceptually identical.

Canine babesiosis in South Africa: more than one disease. Does this serve as a model for falciparum malaria?

South African canine babesiosis is caused by the virulent Babesia canis rossi. In recent years, this common disease has been detected in 12% of dogs presented at the outpatients' division of the University of Pretoria's (Onderstepoort) Veterinary Academic Hospital, and 31% of the affected dogs have been hospitalized as seriously ill. Of these hospitalized cases, 50% had severe anaemia at presentation, 32% had moderate anaemia and 18% were non-anaemic (often polycythaemic), frequently with central-nervous-system signs or multiple organ failure. A retrospective survey of 662 hospitalized cases revealed that the haematology, clinical biochemistry and patient profile (signalment) of the severely anaemic dogs were distinct from those of the non-anaemic, indicating that the babesiosis in these two groups of dogs should be viewed as two different disease in terms of the postulated, underlying, 'pathomechanisms'. The severely anaemic dogs exhibited hypoxic hepatic disease and an increase in serum urea (without a concomitant increase in creatinine), seldom had profound electrolyte imbalances and tended to have a much more profound leucocytosis, consisting of a left-shifted inflammatory leucogram, with higher numbers of circulating metamyelocytes, lymphocytosis and monocytosis. In contrast, the non-anaemic dogs exhibited severe azotaemia (which could be of renal or pre-renal origin) and often showed a marked electrolyte disturbance (reflecting acid-base abnormalities) and a very mild leucocyte response; such dogs often presented as leucopenic, many being lymphocytopenic. These results indicate that the severely anaemic dogs had developed haemolytic disease (possibly immune-mediated), whereas the non-anaemic dogs had developed an acute and overwhelming inflammatory response. The mean age of the non-anaemic dogs (2.66 years) was less than the dogs in the 'severe anaemia group' (0.83 years). Dogs belonging to the traditional fighting breeds (bull terriers, pit bull terriers and Staffordshire bull terriers) were noticeably over-represented in the non-survivors of the acute inflammatory response, possibly indicating an underlying genetic basis for the different presentations. It is evident that the inflammatory-response disease presentation, which is similar to complicated falciparum malaria in humans, amy serve as an animal model for the disease.

The biological basis of malarial disease.

In this review we summarise the arguments that inflammatory cytokines, triggered by material released from the parasite at schizogony (malarial toxin), might induce the illness and pathology seen in malaria. These pro-inflammatory cytokines can generate inducible nitric oxide synthase and cause nitric oxide to be released, as can low concentrations of malarial toxin itself provided interferon-gamma, which has only low activity in the absence of malarial toxin, is present. We suggest here that recently described hypermetabolic functions of these mediators provide a much more plausible explanation for malarial hyperlactataemia and hypoglycaemia, the chief prognostic indicators in falciparum malaria, than does hypoxia secondary to mechanical blockage of vessels by sequestering parasites, which is the dominant current theory. We also review the arguments that rationalise, through these mediators, the reversibility of the coma of cerebral malaria. Although not yet tested at a cellular level, the proposal that nitric oxide generated in cerebral vascular walls contributes to this coma continues to gather indirect support. In addition, new evidence incriminating nitric oxide in the mechanism of tolerance to endotoxin rationalises the raised nitric oxide generation seen in malarial tolerance.

Suspected primary immunodeficiency syndrome in three related Irish wolfhounds.

Three related Irish wolfhound dogs less than one year old presented with a history of chronic nasal discharge and signs of lower respiratory tract disease. These responded well to treatment initially but were chronically recurring. Cursory evaluation of the immune system (full blood counts, globulin determination and fractionation, electrophoresis and lymphocyte blastogenesis) seemed to indicate a cell-mediated immunodeficiency which, because of the age of the patients, is strongly suspected to be primary.

Hydromyelia in the dog.

Hydromyelia is a dilation of the spinal cord central canal. In man this may be due to congenital malformations such as Dandy-Walker syndrome and Chiari malformations or may be acquired as result of infection, trauma or neoplasia. In dogs hydromyelia may be accidentally diagnosed during routine cisterna magna myelography. Hydromyelia, and its possible etiology, may be confirmed by means of computed tomography or magnetic resonance imaging. Three dogs with hydromyelia due to differing etiologies are described.

Changes in haematocrit after treatment of uncomplicated canine babesiosis: a comparison between diminazene and trypan blue, and an evaluation of the influence of parasitaemia.

It has been suggested that the antibabesial drug diminazene causes a rapid decline in haematocrit after treatment of dogs with high Babesia canis parasitaemias, compared with trypan blue. To test this, 19 dogs with clinically mild to moderate, uncomplicated babesiosis were placed in low, moderate or high parasitaemia groups, based on venous parasitaemias, and were allotted randomly to diminazene or trypan blue treatment groups. Haematocrit and parasitaemia were determined before treatment, and at 2, 6, 12, 18 and 24 hours. The drugs were compared for effects on haematocrit and parasite clearance. Changes in haematocrit after treatment were analysed. There were no significant differences between diminazene and trypan blue for haematocrit or parasite clearance. There was no correlation between initial parasitaemia and initial or post-treatment haematocrit. In all dogs, haematocrit fell following treatment. The maximum mean reduction from the baseline (0 h) was 0.046 l/l (range 0.02-0.07 l/l); this most often occurred at 6 or 12 h. The 24 h haematocrit ranged from 70.5-113.6% of baseline (mean absolute haematocrit 0.019 l/l below baseline). All dogs improved clinically during the study period. It was concluded that either diminazene or trypan blue can be safely used to treat dogs with clinically mild or moderate, uncomplicated babesiosis. Parasitaemia need not be taken into account when deciding which antibabesial drug to administer and does not appear to be related to the degree of anaemia.

Rhabdomyolysis as a complication of canine babesiosis.

Rhabdomyolysis was diagnosed in two dogs with babesiosis. The first animal presented with muscle pain and caramel-coloured urine, and had markedly elevated serum myoglobin and muscle enzymes. Acute renal failure complicated the clinical picture. The second dog exhibited muscle pain and tremors, together with neurological signs and pulmonary oedema, and died soon after admission. Muscle necrosis and haemorrhage were found at necropsy. In human malaria, a disease clinically similar to canine babesiosis, rhabdomyolysis is unusual, but clinically silent muscle damage appears to be common. Likewise, biochemical evidence of muscle damage is readily found in experimental bovine babesiosis. Muscle enzymes were mildly elevated in three dogs with severe babesiosis and pigmenturia but there was no obvious muscle damage, indicating that this might also apply to canine babesiosis. The pathogenesis of infection-associated rhabdomyolysis and acute renal failure remains unclear, but inflammatory cytokines and nitric oxide could play an important role.

Canine multiple cartilaginous exostoses: unusual manifestations and a review of the literature.

Multiple cartilaginous exostoses were diagnosed in a two-year-old Great Dane and a four-month-old border collie. Clinically, the Great Dane showed only mild discomfort, while the border collie exhibited tetraparesis due to cervicothoracic compression. Unusual features in the Great Dane were exostoses that bridged physes, with progression after skeletal maturity. The border collie puppy's exostoses resembled tumoral calcinosis radiographically. Limb exostoses in this puppy often were para-articular, and most were not attached to the underlying bone. These features resembled metachondromatosis in humans. Analysis of previously reported cases of multiple cartilaginous exostoses indicated that the prognosis is guarded to poor.