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Canine babesiosis has been increasingly diagnosed in various regions of Germany such as north-eastern Germany in recent years. A dog with several relapses of Babesia canis infection after treatment with imidocarb is described. A 9-year-old male Magyar Viszla with B. canis infection was referred after two treatments with imidocarb (dosage 2.1 mg/kg SC) because of lethargy, fever and pancytopenia (additional treatments with prednisolone and doxycycline). Merozoites were detected in the blood smear and imidocarb treatment was repeated. Clinical signs, pancytopenia and a positive B. canis PCR occurred after the 3rd (6 mg/kg SC), 4th (7.7 mg/kg SC) and 5th (7.5 mg/kg SC and doxycycline for 4 weeks in addition) imidocarb injection and thorough tick prevention with isoxazoline and permethrin products. 12 days after the 5th injection, the PCR was negative for the first time. The dog was again presented with fever 35 days after the 5th injection. The B. canis PCR was positive and laboratory examination revealed pancytopenia. Treatment with atovaquone/azithromycin for 18 days was performed and no further relapse occurred for 32 weeks. In the case of suspected imidocarb resistance in B. canis infection, treatment with atovaquone/azithromycin can be an alternative., Competing Interests: Declaration of competing interest C. Weingart and B. Kohn declare that they have held lectures for veterinary pharmaceutical and diagnostic companies. B. Kohn declares that she has acted as consultant for veterinary pharmaceutical and diagnostic companies and had research collaborations with various companies. J. Krücken declares no conflicts of interest., (Copyright © 2024. Published by Elsevier GmbH.)

Babesia venatorum was isolated from a captive reindeer calf in Switzerland. The clinical signs consistent with acute babesiosis included hemolytic anemia and hemoglobinuria. The diagnosis was made based on visualization of intraerythrocytic parasites in the stained blood smears and confirmed by PCR analysis of the 18S rRNA gene, with subsequent species identification within Babesia confirmed by sequencing. The reindeer calf was initially treated with supportive care and an antiprotozoal drug (imidocarb dipropionate) but died a few days after hospitalization. Babesia venatorum is also known as Babesia sp. EU1 and can infect different mammalian species, including humans. The current case report aims to increase awareness among veterinarians and reindeer owners about the presence and the associated risk of this zoonotic pathogen. Considering the high morbidity and possible mortality associated with acute babesiosis, captive reindeer should receive tick prevention measures and be tested for subclinical infections in endemic area., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Certain countries including the United States remain non-endemic for particular infectious diseases such as equine piroplasmosis through import restrictions and surveillance. Endemic regions often employ premunition as the primary method to control disease, however in non-endemic countries, chemosterilization combined with methods to confirm parasite elimination are required to maintain disease-free status. The ability of imidocarb diproprionate (ID) to clear persistent Theileria equi infection from infected horses has been shown through the inability of treated horses to transmit via blood transfer. However, the common lengthy persistence of anti-T. equi antibody causes regulatory tests such as cELISA or IFA to remain positive for extended periods. Persistence of positive testing creates challenges for regulatory veterinary medicine and international trade. Concordance between nested polymerase chain reaction (nPCR) targeting the ema1 gene and immunoblotting (IB) measuring declination in anti-EMA1 and anti-EMA2 antibody were used to verify clearance of T. equi from 179 ID-treated horses. These data support the use of IB to demonstrate declining anti-EMA1 and EMA2 titers in T. equi-infected horses subsequent to successful ID treatment. Such data provide concordant support to a negative nPCR and allow for a more timely determination of effective ID clearance of T. equi. The post ID treatment results indicate that while nPCR was consistently negative by 14 days and cELISA generally remained positive after 1 year, immunoblot was on average negative after 4 months and 100% in agreement with nPCR., (Copyright © 2017 Elsevier GmbH. All rights reserved.)

Background: Classification of Babesia parasites has traditionally relied on morphological differentiation based on piroplasm size and shape. Molecular typing has subsequently revealed a more complex taxonomy for these piroplasms than previously thought. To evaluate the factors that influence the morphology of Babesia species upon microscopic examination and hence, their taxonomic classification, we performed detailed characterizations of piroplasms from archival and prospective collections of cytological samples of dogs with piroplasmosis before and after death. Merozoite morphology and time of parasite disappearance following imidocarb dipropionate was also investigated., Methods: The study was divided into a (i) review of archived cytological slides from confirmed cases of canine piroplasmosis, and (ii) a prospective study of smears and tissue imprints from 15 recently necropsied dogs. The latter group could be further sub-divided into a non-treated group and an imidocarb dipropionate-treated group. Exact times of treatment before death were reviewed. Additional blood smears prepared from the live dogs and taken before therapy were also evaluated in the latter group. Parasite burden per each slide was determined in both studies. The shape and size of merozoites were described from blood smears taken while the dogs were alive and from different organs during necropsy. The results of all measurements were statistically analyzed., Results: The morphology and size of merozoites from live dogs corresponded to that of previously described 'large' Babesia. The morphology and size of merozoites were significantly different (P < 0.001) in postmortem samples, however, and more consistent in shape and size with piroplasm cells previously referred to as 'small' Babesia. PCR and sequencing confirmed B. canis as the causative agent of disease in all investigated dogs, including in postmortem negative tissue imprints from dogs treated at least 24 h before death., Conclusions: Changes in the morphology of 'large' B. canis to 'small'-like Babesia observed by light microscopy appear to represent a common postmortem change. Classification of Babesia parasites into 'large' and 'small' Babesia using only microscopy of postmortem slides should be treated with caution. PCR-based methodologies for detection and molecular typing of Babesia spp. may prove valuable for investigating suspected cases of babesiosis following necropsy.

Background: Piroplasmosis caused by the Babesia microti-like piroplasm (Bml) is increasingly being detected in dogs in Europe. Sick dogs show acute disease with severe anaemia associated with thrombocytopenia with a poor response to current available drugs. This study assesses the safety and tolerance of three treatments and compares their efficacy over a full year of follow up in dogs naturally infected with Bml., Methods: Fifty-nine dogs naturally infected with Bml were randomly assigned to a treatment group: imidocarb dipropionate (5 mg/kg SC, 2 doses 14 d apart) (IMI); atovaquone (13.3 mg/kg PO q 8 h, 10 d)/azithromycin (10 mg/kg PO q 24 h, 10 d) (ATO); or buparvaquone (5 mg/kg IM, 2 d apart)/azithromycin (same dosage) (BUP). Before and after treatment (days 15, 45, 90 and 360), all dogs underwent a physical exam, blood tests and parasite detection (blood cytology and PCR). Clinical efficacy was assessed by grading 24 clinical and 8 clinicopathological signs from low to high severity., Results: Before treatment, most dogs had severe regenerative anaemia (88.13%) and thrombocytopenia (71.4%). On treatment Day 45, clinical signs were mostly reduced in all dogs, and by Day 90, practically all dogs under the ATO or BUP regimen were clinically healthy (76.4 and 88%, respectively). Highest percentage reductions in laboratory abnormalities (82.04%) were detected in animals treated with ATO. Over the year, clinical relapse of Bml was observed in 8 dogs (8/17) treated with IMI. However, on Day 360, these animals had recovered clinically, though clinicopathological abnormalities were still present in some of them. Parasitaemia was PCR-confirmed on Days 90 and 360 in 47.05 and 50% of dogs treated with ATO, 68 and 60.08% with BUP, and 94.1 and 73.3% with IMI, respectively. Even after 360 days, 13.3% of the dogs treated with IMI returned a positive blood cytology result., Conclusions: IMI showed the worse clinical and parasitological, efficacy such that its use to treat Bml infection in dogs is not recommended. The treatments ATO and BUP showed better efficacy, though they were still incapable to completely eliminate PCR-proven infection at the recommended dose. All three treatments showed good tolerance and safety with scarce adverse events observed.

Background: The apicomplexan hemoparasite Theileria equi is a causative agent of equine piroplasmosis, eradicated from the United States in 1988. However, recent outbreaks have sparked renewed interest in treatment options for infected horses. Imidocarb dipropionate is the current drug of choice, however variation in clinical response to therapy has been observed., Methods: We quantified the in vitro susceptibility of two T. equi isolates and a lab generated variant to both imidocarb dipropionate and a bumped kinase inhibitor compound 1294. We also evaluated the capacity of in vitro imidocarb dipropionate exposure to decrease susceptibility to that drug. The efficacy of imidocarb dipropionate for clearing infection in four T. equi infected ponies was also assessed., Results: We observed an almost four-fold difference in imidocarb dipropionate susceptibility between two distinct isolates of T. equi. Four ponies infected with the less susceptible USDA Florida strain failed to clear the parasite despite two rounds of treatment. Importantly, a further 15-fold decrease in susceptibility was produced in this strain by continuous in vitro imidocarb dipropionate exposure. Despite a demonstrated difference in imidocarb dipropionate susceptibility, there was no difference in the susceptibility of two T. equi isolates to bumped kinase inhibitor 1294., Conclusions: The observed variation in imidocarb dipropionate susceptibility, further reduction in susceptibility caused by drug exposure in vitro, and failure to clear T. equi infection in vivo, raises concern for the emergence of drug resistance in clinical cases undergoing treatment. Bumped kinase inhibitors may be effective as alternative drugs for the treatment of resistant T. equi parasites.

In the present study, the treatment of ichthyophthiriasis with medicated feed was investigated in rainbow trout, Oncorhynchus mykiss, and chub, Leuciscus cephalus. The anti-parasitics toltrazuril and imidocarb; the antibiotics doxycycline, erythromycin and sulphadiazine and the anti-inflammatory acetylsalicylic acid were tested. In vitro experiment revealed that all tested anti-parasitics and antibiotics were effective in killing the isolated trophonts and theronts. Minimum doses for killing 100 % of the viable trophonts and for inhibiting the development of theronts were 3 mg/L for doxycycline, 30 mg/L for erythromycin, 2 mg/L for imidocarb dipropionate, 30 mg/L for sulphadiazine and 20 mg/L for toltrazuril. Acetylsalicylic acid (40 mg/kg fish/day), doxycycline (3 and 6 mg/kg/day), erythromycin (40 mg/kg/day), imidocarb dipropionate (5.0 mg/kg/day), sulphadiazine (40 mg/kg/day), toltrazuril (20 and 40 mg/kg/day) and combinations of doxycycline and toltrazuril (3 + 20 mg/kg/day, 6 + 40 mg/kg/day) were tested as medicated feed. When administered as medicated feed, only doxycycline, toltrazuril and combinations of doxycycline and toltrazuril reduced the fish mortality and infestation level. Best results were obtained by feeding a combination of 6 mg/kg/day doxycycline and 40 mg/kg/day toltrazuril. In O. mykiss, this treatment reduced the mortality rate from 100 to 50 ± 14 % after 10 days and the infestation level from grade 4 (≥100 trophonts per skin mucus sample) to 3.5 (50-100 trophonts). In L. cephalus, the mortality rate was decreased from 100 to 39 ± 5 % and the infestation level from grades 4 to 2 (ten to 50 trophonts) after 10 days.

Two young brother male free-ranging domestic shorthair cats were evaluated for diarrhea. They presented with intraerythrocytic piroplasms on blood smear evaluation. Only the first cat was anemic (mild non-regenerative anemia). A partial segment of the 18S rRNA was amplified and sequenced, revealing a homology of 99% with Cytauxzoon sp. and of 93% with Cytauxzoon felis. The first cat was treated with doxycycline and imidocarb dipropionate and monitored by serial laboratory exams, resulting negative for Cytauxzoon sp. infection after the end of the therapy (follow-up period of 175 days). The second cat received the same therapy, but doxycycline was discontinued by the owner after 1 week. He was monitored for 130 days, remaining erythroparasitemic and asymptomatic. We described cases of Cytauxzoon sp. infection in domestic cats with detailed clinical data, description of two therapeutic protocols, and follow-up after treatment with opposite parasitological responses (parasitological cure versus persistence of infection).

Theileria equi, one of the causative agents of equine piroplasmosis, is endemic in many regions of the world but is considered a 'foreign' animal disease in the USA. In an effort to prevent the importation of T. equi, stringent serological screening of horses is practiced prior to entry to the USA. Current regulatory options available where horses are found to be infected include permanent quarantine with or without chemotherapy, repatriation, or euthanasia. Chemotherapeutics that eliminate infection and subsequently transmission risk are critical in the management of infected horses. In this study, the efficacy of the drug imidocarb dipropionate against experimental T. equi infection was assessed. Of nine horses experimentally inoculated with T. equi isolated from an animal previously imported from Peru, six were treated with imidocarb dipropionate after the resolution of the acute phase of the disease. Elimination of the parasite was demonstrated in 5/6 by nested PCR, blood transfusions to naïve horses, and reversion to seronegative status. The findings support the use of this drug as a potential treatment option in controlling outbreaks of T. equi, and also suggest that 'combination testing' using both serological and PCR detection methods are necessary to demonstrate clearance of infection., (Published by Elsevier Ltd.)

Background: Imidocarb or a combination of atovaquone and azithromycin (A&A) has been suggested for treatment of cats with cytauxzoonosis, but neither has been prospectively evaluated for efficacy., Hypothesis/objectives: That survival to hospital discharge is improved by treatment with A&A as compared with imidocarb., Animals: Eighty acutely ill cats with Cytauxzoon felis infection treated at one of 18 veterinary clinics in 5 states., Methods: An open-label, randomized prospective study compared survival in cats treated with atovaquone (15 mg/kg p.o. q8h) and azithromycin (10 mg/kg p.o. q24h) or imidocarb (3.5 mg/kg i.m.). All received heparin, fluids, and supportive care. Clinical and clinicopathologic data from initial presentation were collated. Parasitemia was quantified (n = 79) and pathogens genotyped (n = 60). Logistic regression was used to determine the impact of treatment group on the primary endpoint, survival to hospital discharge or death. Covariants were analyzed by rank-sum testing., Results: Of 53 cats treated with A&A, 32 (60%) survived to discharge while only 7 of 27 cats (26%) treated with imidocarb survived (P = .0036; odds ratio 7.2, 95% CI 2.2, 24). Cats with a lower parasitemia were more likely to survive, as were cats with higher white blood cell counts and lower total bilirubin. Unique pathogen genotypes were identified from 15 cats, while genotype isolated from 21 cats had been described previously. There were multiple pathogen genotypes identified in 24 cats., Conclusions and Clinical Importance: Survival to discharge was more likely in cats treated with A&A as compared with imidocarb, although case fatality rate remained high., (Copyright © 2010 by the American College of Veterinary Internal Medicine.)

The efficacy of imidocarb dipropionate for the treatment of Hepatozoon canis infection was studied in three naturally infected asymptomatic dogs followed longitudinally over 8 months. Response to treatment was followed by monitoring blood counts, parasitemia levels in blood, parasite in concentrated buffy-coat smears and by PCR. The dogs were initially treated with a low dose of 3 mg/kg imidocarb dipropionate twice a month and when parasitemia persisted after five treatments, with the regular dose of 6 mg/kg. In one dog, H. canis gamonts were no longer detectable by blood and buffy-coat microscopy after 2 months of therapy with 6 mg/kg while in the two other dogs gamonts were intermittently found in blood but persistently detectable in buffy-coat smears during the whole study period. Furthermore, combined therapy with doxycycline monohydrate administered at 10 mg/kg/day PO for 4 weeks also failed to eliminate H. canis. PCR revealed that parasite DNA was present in the blood of all dogs at all sampling dates regardless of treatment refuting the effectiveness of treatment suggested by negative blood microscopy. Detection of H. canis in buffy coat was found to be twice as sensitive than by blood smear and detection by PCR was even more sensitive revealing infection in eight samples (16% of total samples) negative by blood and buffy-coat microscopy. In conclusion, imidocarb dipropionate was not effective in eliminating H. canis from dogs treated repeatedly over 8 months. Microscopical detection is not sufficient for the evaluation of treatment response in H. canis infection and follow up by molecular techniques is recommended., (Copyright 2010 Elsevier B.V. All rights reserved.)

A 10-year-old tame zebra gelding was presented after suffering from lethargy, nervousness, reported anaemia and icterus as well as a decreased appetite. These symptoms were seen over some months, with changing severity. The animal was immobilised, treated, and blood specimens were submitted for haematology and biochemistry. This report describes molecular characterisation of Theileria equi recovered from this animal, as well as the clinical findings, treatment and historical relevance of piroplasmosis in zebra in southern Africa.

Two captive reindeer (Rangifer tarandus tarandus) at a New York zoological institution were diagnosed with Babesia odocoilei. Clinical signs consistent with acute babesiosis included fever, hemoglobinuria, and hemolytic anemia. Both episodes were precipitated by stressful events that may have compromised their immunocompetence. The diagnosis was confirmed by visualization of intraerythrocytic parasites on stained blood smears, polymerase chain reaction, and speciation of the Babesia by sequencing a hypervariable region of the 18S rRNA gene. One reindeer died with gross and histopathologic lesions, including pigmentary nephrosis with severe acute tubular degeneration and necrosis secondary to intravascular hemolysis. A second reindeer was successfully treated with supportive care and an antiprotozoal, imidocarb dipropionate (Imizol, 12%, Schering-Plough Animal Health, Union, New Jersey 07083, USA) at 3 mg/kg s.c. or i.m. s.i.d. on days 1, 2, 6, 9, and 21. Two other reindeer in the exhibit tested negative for Babesia by polymerase chain reaction but were treated with imidocarb dipropionate as prophylaxis while final testing results were pending. Additionally, B. odocoilei was identified in three novel asymptomatic host species within the collection: yak (Bos grunniens), muntjac (Muntiacus reevesi), and markhor goat (Caprafalconeri). Due to the high morbidity and mortality associated with acute babesiosis, captive reindeer should receive tick prevention, be tested for subclinical infections in endemic areas, and receive aggressive treatment for acute infections when clinical babesiosis is suspected.

An Akita Inu, living in Belgium, was presented with unusual clinical manifestations of acute babesiosis that included neurological signs and pancytopenia. Diagnosis was made by identifying Babesia canis in the blood smear. Neurological signs resolved after treatment with imidocarb diproprionate. Normalization of hematological abnormalities was gradual over 5 months.

Imidocarb treatment of horses infected with Babesia caballi is supposed to eliminate the infection, but data on the efficacy of this treatment is scarce. The study presented here concerns four Paso Fino horses, which were imported into the island of Curacao on the basis of a piroplasmosis negative complement fixation test (CFT). Upon re-testing with an indirect fluorescent antibody test immediately after arrival in Curacao, two horses appeared to have antibodies to B. caballi and all horses had antibodies to Theileria equi. Subsequent testing with polymerase chain reaction combined with a reverse line blot yielded positive results for both agents in all four horses. Treatment with five consecutive doses of imidocarb dipropionate (4.7 mg/kg BW im q 72 h), temporarily resulted in negative results, but B. caballi and T. equi were detected again in the samples taken at 6 and 18 weeks after completion of the treatment. These results confirm that the CFT is not a suitable test for pre-import testing and that even high dose treatment with imidocarb may not be capable of eliminating B. caballi and T. equi infections from healthy carriers.

Histological and electron microscopic examinations of the kidneys of 8 dogs suffering from fatal, naturally acquired Babesia canis infection and nephropathy are presented. Seven animals were treated with imidocarb dipropionate on average 4.5 days prior to death. Severe anaemia was present only in 2 cases. Degenerative histological changes observed mostly in the proximal convoluted tubules included vacuolar-hydropic degeneration, necrosis and detachment of renal tubular epithelial (RTE) cells from the basement membrane. Necrotic debris occasionally formed acidophilic casts within the tubules. In some cases, necrosis of the whole tubule was observed. Haemoglobin casts in the tubules and haemoglobin droplets in RTE cells seldom appeared. No significant histological changes were seen in the glomeruli. Ultrastructural lesions in RTE cells included nuclear membrane hyperchromatosis, karyopyknosis, karyolysis, swelling or collapse of mitochondria with fragmentation of cristae and vacuolar-hydropic degeneration in the endoplasmic reticulum and microvilli. Nuclear oedema was also observed. Many RTE cells exhibiting necrosis collapsed. Vacuolar-hydropic degeneration and necrosis were also observed in the glomerular and interstitial capillary endothelium. The severe acute tubular necrosis described in this study is probably the result of hypoxic renal injury. Systemic hypotension leading to vasoconstriction in the kidneys might be the most important cause of renal hypoxia in B. canis infections, but anaemia may also contribute to inadequate oxygenation. Imidocarb should be applied with caution in patients with possible renal involvement until further data become available on its potential nephrotoxicity in dogs.

The objective of this study was to evaluate the therapeutic and prophylactic efficacy of imidocarb dipropionate (IMDP) against babesiosis and to determine specific antibodies against Babesia ovis in experimentally infected lambs. Thirty-six 6-month-old splenectomized lambs were used. The lambs were randomly divided into six groups with six animals each, and were intravenously inoculated with 50 mL B. ovis-infected erythrocytes as follows: group I (therapy group) was treated with IMDP (1.2 mg/kg body weight) starting on the day of onset of clinical signs of babesiosis after the inoculation; group II (untreated control animals) was not treated with any therapeutic treatment after the inoculation; groups III, IV, V and VI (prophylaxis groups) were administered IMDP (2.4 mg/kg body weight) 1, 2, 3 and 4 weeks before the inoculation, respectively. The animals were housed in a tick-proof room with water and food ad libitum up to the 30th day post-inoculation (PI). The lambs were monitored from the first day PI by recording the manifestation of clinical disease, rectal temperature, and the degree of parasitaemia. All the lambs became infected with B. ovis, except five animals from group III, which were treated 1 week prior to experimental infection. Other animals showed signs of acute clinical babesiosis. The animals treated with IMDP (group I) were able to clear the parasite from the blood circulation after 48 h post-treatment. The recrudescence of B. ovis was observed in two lambs 7 days after treatment, and they were treated with the second similar dose of the drug. Six lambs (1, 1, 2 and 2 lambs in group III, IV, V and VI, respectively) from the prophylaxis groups died within 7-17 days after showing high parasitaemia and clinical symptoms of the disease. Regardless of the clinical symptoms, 83.30% and 66.66% of the lambs which were administered IMDP 1-2 and 3-4 weeks before, were determined to be protected against the virulent field strain of B. ovis.

Canine babesiosis caused by Babesia gibsoni was diagnosed in a 3-month-old Pit-bull pup during a routine clinical examination. Diagnosis was confirmed by way of smear examination, PCR, Reverse Line Blot (RLB) and sequence analysis which showed 100% homology with B. gibsoni (Japan AB118032) and Babesia sp. (Oklahoma) (AF205636). Haematology showed moderate anaemia and severe thrombocytopenia. Treatment was initiated with diminazene aceturate (Berenil RTU) followed by 2 doses of imidocarb diproprionate (Forray-65) 3 days and 14 days later, respectively. Babesia gibsoni DNA was still detectable 2 weeks post-treatment on the PCR/RLB test. A 10-day course of combination drug therapy using atovaquone and azithromycin was initiated. Blood samples taken on Day 1 and Day 40 after completion of treatment were negative for B. gibsoni DNA on PCR/RLB test. The implications of a possible introduction of B. gibsoni into South Africa are discussed.

Clinical observations of Babesia canis infection in 63 dogs during a 1-year period are summarised, demonstrating the pathogenicity of the Babesia strain endemic in Hungary. Most patients had babesiosis in the spring and autumn, correlating with the seasonal activity of ticks. Male animals appeared in higher numbers, probably due to an overrepresentation of outdoor dogs. Uncomplicated babesiosis was diagnosed in 32 cases. The disease affected dogs of any age in this study. Symptoms were similar to those published from other parts of the world: lethargy, fever, splenomegaly, pallor, icterus, haemoglobinuria and presence of ticks were the most common observations. Thrombocytopenia, lymphopenia and neutropenia were frequent haemogram changes. Imidocarb appeared to be highly effective in eliminating the Babesia infection. Thirty-one animals demonstrated babesiosis with complications. Most Rottweilers (7/9) developed complicated disease. Old age was a risk factor for multiple complications. Multiple organ manifestations had poor prognosis. Hepatopathy (44%), pancreatitis (33%), acute renal failure (ARF; 31%) and disseminated intravascular coagulation (DIC; 24%) were frequent complications, while immune-mediated haemolytic anaemia (IMHA; 10%), acute respiratory distress syndrome (ARDS; 6%) and cerebral babesiosis (3%) were rarely observed. There was a significant difference between the mean age of dogs having uncomplicated disease, babesiosis with a single complication and babesiosis with multiple complications (3.4, 4.8 and 8.6 years, respectively, p < 0.001). The recovery rate (78, 68 and 25%, respectively, p = 0.005) and mortality rate (3, 21 and 67%, respectively, p < 0.001) also tended to differ significantly in these groups. Systemic inflammatory response syndrome (SIRS) and DIC are two possible pathways leading to multiple organ dysfunction syndrome (MODS) in babesiosis. DIC was found to predict MODS more sensitively in this study than SIRS: there were 6 animals developing MODS out of 11 identified with DIC, while only 5 dogs developed MODS out of 22 having SIRS.

In this study one spleen-intact dog (A) and two splenectomised dogs (BSE, CSE) were infected with Babesia canis. All animals developed an acute disease characterised by fever, haemoglobinuria and anaemia, the latter being more severe in the splenectomised dogs. Fever and parasitised red blood cells were detected for three days after imidocarb treatment in the splenectomised animals. Haematological abnormalities included regenerative anaemia, thrombocytopenia and leukopenia (due to neutropenia and lymphopenia) in the acute phase, soon followed by leukocytosis, neutrophilia and left shift a few days later. Acute hepatopathy was detected in all dogs with elevated ALT activity, which was more seriously altered in the splenectomised dogs. Diffuse changes in liver structure and hepatomegaly were seen by ultrasonography. Liver biopsy and histology revealed acute, non-purulent hepatitis in the splenectomised dogs. Both splenectomised dogs were successfully cured after collection of 400 ml highly parasitised blood, proving that large-amount antigen production is possible with rescuing the experimental animals. Whole blood transfusion, imidocarb and supportive care with infusions, antipyretics, glucocorticoids and diuretics were applied. The spleen-intact dog clinically recovered after receiving supportive treatment, with no imidocarb therapy. Microbial infections developed in both splenectomised animals (BSE: haemobartonellosis, CSE: osteomyelitis caused by Escherichia coli), probably as a consequence of immunosuppression after splenectomy and glucocorticoid therapy.

Piroplasmosis, a disease endemic to most tropical and subtropical areas, appears to be spreading to more temperate zones. This article gives a review of equine piroplasmosis and describes an acute case of infection with Babesia caballi in a Dutch Standard bred foal after a short stay at a stud in Normandy (France). A 3-month-old stallion foal was presented with lethargy, fever of 41 degrees C, and pale mucosal membranes. Haematology revealed a low packed cell volume (14 l/l) leucytosis (25 G/l) and a high blood urea nitrogen concentration (20.1mmol/l). Infection with B. caballi was diagnosed on the basis of Giemsa staining blood smears and was confirmed by polymerase chain reaction in combination with RLB. Treatment with imidocarb dipropionate and a blood transfusion resolved the haemolytic crisis.

The therapeutic efficacy of imidocarb, artesunate, arteether, buparvaquone and arteether+buparvaquone combination was evaluated against Babesia equi of Indian origin in splenectomised donkeys with experimentally induced acute infection. Efficacies of these drugs were tested by administering each drug or drug combination to groups of donkeys (having three donkeys each group). One group of donkey was kept as untreated control for comparing the results. Parasitaemia, haematology (WBC, RBC, PCV, granulocytes and haemoglobin), biochemical parameters (SAST, SALT, alkaline phosphatase, albumin/globulin ratio) were monitored at regular intervals. Individually, arteether and buparvaquone were found to have no parasite clearing efficacy and the treated animals died within 5-6 days after showing high parasitaemia and clinical symptoms of the disease. However, artesunate treated animals were able to restrict the parasite multiplication but only during the treatment period. Animals treated with imidocarb and arteether+buparvaquone combination were able to clear the parasite from the blood circulation after 2-5 days post-treatment (PT). After 55-58 days PT, recrudescence of B. equi parasite was observed in both these groups and a mean survival period of 66 days and 69 days, respectively, was recorded in these groups. Results of haemato-biochemical parameters had shown that imidocarb had deleterious effect on the liver function while on the other hand arteether+buparvaquone combination was found to be safe. This limited study indicates that arteether+buparvaquone combination could be a better choice than imidocarb for treating B. equi infection, but further trials are required in detail.

It is proposed that the chronic asymptomatic carrier state produced by Babesia canis infection could make dogs more resistant against subsequent infections. This suggests that treatment with imidocarb dipropionate, which removes the organism, can make dogs more susceptible to reinfection in a short period of time. Ten male and female dogs of approximately 4-5 months of age were inoculated with B. canis. Half of them received treatment with imidocarb dipropionate (7 mg/kg) on days 15 and 27 post-infection and the other half were untreated. All the animals were examined using clinical and laboratory methods (CBC, platelet counts and serological study by indirect immunofluorescence test) for a 6-month period. Antibodies were first detected on day 7 post-injection and remained at high levels (1:2560) over the period in the non-treated group. This result was significantly different (P<0.001) from the treated group in which antibodies titers declined after day 34 post-infection. Six months later, after a homologous challenge infection only the dogs of treated group showed parasitaemia, thrombocytopenia and splenomegaly, which was significantly different (P<0.05) from the non-treated group. The sterilizing treatment with imidocarb dipropionate was effective in clearing the infection, but inhibited the maintenance of protective antibodies, making the animals more susceptible to reinfection.

This paper reports the clinicopathologic responses of 93 dogs with spontaneously occurring ehrlichiosis to 3 different treatment protocols. Thirty-two dogs were treated with doxycycline (10 mg/kg/day for 28 days), 31 were treated with imidocarb dipropionate (5 mg/kg given 15 days apart in 2 separate injections), and 30 were treated with both drugs simultaneously, at the doses as specified. The dogs underwent clinicopathologic evaluation before and after treatment, and were examined periodically during the 24-month period after the treatment. No differences were found in the clinical responses among the dogs in the 3 treatment groups. As for the clinicopathologic response, in spite of the fact that at the end of the study the results obtained with the 3 protocols were similar, the platelet count and serum protein electrophoresis results returned to normal more slowly in dogs that received imidocarb dipropionate as compared to those given the other 2 treatments.

Bobcats (Lynx rufus) are the reservoir hosts for Cytauxzoon felis, the causative agent of cytauxzoonosis. Cytauxzoonosis is a highly fatal tickborne blood protozoal disease of domestic and exotic cats. Treatment of clinically affected cats has generally been unrewarding. In our report, 6 of 7 cats had signs of illness and laboratory findings indicative of cytauxzoonosis and were successfully treated with 2 i.m. injections of diminazene aceturate or imidocarb dipropionate (2 mg/kg [0.9 mg/lb] of body weight, each). One cat died after the first injection of diminazene. Additional treatment with isotonic fluids i.v. and heparin s.c. were used as supportive care for dehydration and disseminated intravascular coagulation that were detected by laboratory testing between diminazene or imidocarb treatments. Atropine was effective in recovery and preventing adverse reactions associated with imidocarb treatment of 1 cat.

The hydroxynaphthoquinone, atovaquone (Wellvone, Glaxo-Wellcome Ltd.) was found to have significant activity against Babesia microti, the main cause of human babesiosis in the U.S.A. This activity compares well with that of the most effective babesicide currently available for use in animals, imidocarb dipropionate, that unlike atovaquone is not licensed for use in humans. Treatment with well tolerated doses of atovaquone results in a rapid reduction in parasitemias and an early disappearance of parasites from blood smears. However, in common with all the other babesicides tested, atovaquone did not sterilize gerbils of infection, even at very high daily doses administered for up to 10 days. A combination of atovaquone and clindamycin was more effective than atovaquone alone in the treatment of both acute and chronic infections but failed to eliminate parasites completely.

Treatment of pregnant mares to prevent abortions due to equine piroplasmosis is a novel idea practised empirically at some Thoroughbred studs in South Africa. This paper presents the results of an investigation to ascertain whether imidocarb dipropionate crosses the equine placenta. Three pregnant mares were injected intramuscularly with imidocarb and their foetuses were mechanically aborted at varying time intervals thereafter. Imidocarb was found in foetal blood at a level similar to that in the dam's blood, suggesting that imidocarb administered to the dam would be available for anti-parasitic activity in the foetal circulation. Uncertainty concerning the time of treatment to achieve the desired effect currently makes this a questionable exercise.

Babesia canis infections were apparently sterilised by a single dose of imidocarb at 7.5 mg kg-1, as well as by a single dose of diminazene at 3.5 mg kg-1, followed by a single dose of imidocarb at 6 mg kg-1 the following day. This was confirmed by subinoculation of blood from these dogs to splenectomised recipients. Sterilisation of the infection is not recommended in endemic areas; a more rational approach would be to allow a state of premunity to develop in dogs at risk to repeated infections.

Two in vivo drug resistance assays were developed using gerbils. Cross resistance, involving related babesicides as well as the chemically unrelated antibiotic, oxytetracycline, was demonstrated, but the suggestion that imidocarb may select for pathogenic strains of parasites was not supported. Limited tests of field strains did not detect resistance. It is suggested that an in vitro assay would be more appropriate for surveys through in vivo assays would be essential for confirmatory studies.

Buparvaquone, a naphthoquinone with known efficacy against Theileria parva parva in cattle, was tested for activity against Theileria cervi piroplasms in both an in vitro culture system and in vivo in experimentally infected white-tailed deer. The in vitro data showed a significant decrease in the incorporation of 3H-hypoxanthine by infected red blood cells treated with buparvaquone when compared to that seen with imidocarb and chloroquine treatment. In both intact and splenectomized deer treated with buparvaquone (2.5 mg kg-1) a gradual decrease in piroplasm parasitaemia was observed following treatment. However, in the splenectomized deer, parasitaemia levels returned to near pretreatment values after approximately 2 weeks.

It was found that surprisingly low doses of four babesicides were effective against Babesia divergens in gerbils and it was concluded that this was due to the involvement of host resistance, which may be of a non-specific nature. The efficacy of the drugs relative to each other was the same in gerbils as in cattle and this host-parasite system is evidently more suitable for the screening of babesicides than are other rodent babesia systems. The prophylactic dose of imidocarb dipropionate required to provide a similar degree of protection in gerbils as in cattle was found to be much higher and was very close to toxic levels. Challenge infections resulted in sterile immunity. Acute babesiosis in gerbils could be cured with all four drugs if parasitaemias were below approximately 45 per cent and packed cell volumes above 18 per cent at treatment.

Imidocarb dipropionate (IDP), a potent prophylactic drug against Babesia bovis infections in cattle, was tested for its effect on the infectivity and immunogenicity of a live B. bovis vaccine marketed in Australia. At the recommended prophylactic dose rate of 3 mg/kg, IDP suppressed infectivity of the vaccine for at least 6 weeks. The vaccine infected all cattle inoculated either 8 weeks after treatment with 3 mg/kg, or 4 weeks after treatment with the recommended therapeutic dose of 1.2 mg/kg. These infections were, however, partially suppressed and the level of immunity to a subsequent heterologous virulent challenge was reduced. Cattle that failed to become infected after vaccination were fully susceptible to the challenge. It is concluded that where B. bovis vaccination is contemplated, prophylactic use of IDP should be avoided.

The therapeutic efficacies of imidocarb and parvaquone were tested against Babesia equi of European origin in carrier horses and for induced acute infections in splenectomized ponies. Imidocarb, at a dosage of 4 mg/kg of body weight, given IM at 72-hour intervals 4 times, was ineffective in eliminating B equi-carrier infection in 9 mature geldings. A single IM administration of 4 mg/kg was not therapeutic in acutely infected splenectomized ponies. When given at 3 different dosages and treatment schedules, parvaquone was ineffective in clearing carrier infection. Parvaquone given IM once at a dosage of 20 mg/kg was effective for acute B equi infections in splenectomized ponies; parasitemia began to decrease within 24 hours after treatment. Infections were not eliminated however, and within 4 weeks, secondary parasitemia and anemia developed. Of 4 ponies, 3 died of acute piroplasmosis.

Live Babesia divergens derived from gerbils were used to vaccinate cattle that had previously been treated with imidocarb dipropionate. Drug doses ranged from 1 to 2 mg/kg and animals were infected subcutaneously three to seven days later. After a further 35 days, vaccinated and control animals were given a heavy heterologous intravenous challenge. This regimen was effective for both avirulent and virulent strains in 12- to 18-month-old cattle. However, at low drug doses some animals reacted to the virulent vaccine strain and at high doses animals infected with the avirulent strain failed to seroconvert although they were still resistant to challenge. The variable infectivity of vaccine strains was a minor problem which can be overcome by strain selection and optimisation of infectivity using gerbils as experimental animals. Gerbils would also be useful as a source of parasites for the further development of in vitro cultures which could ultimately produce the vaccine.