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Use of an antigen detection assay to determine mortality of Dirofilaria immitis after thiacetarsamide therapy.

The use of an antigen detection enzyme immunoassay (EIA) to determine the post-treatment infection status of 16 dogs naturally infected with Dirofilaria immitis was investigated. Dogs were treated with thiacetarsamide at a dose rate of 12mg/4.5kg twice daily for 2 days, bled at regular intervals and necropsied 9 weeks later. The infection status of all dogs at necropsy was compared to the ratios of optical density (OD) values from the EIA using fresh plasma samples (day 60/day 0 = R60) and dogs were divided into 2 groups. Using the R60 ratios, those dogs with fewer than 2 live adult worms or immature worms at necropsy ("cleared" dogs) could be differentiated with 95% confidence from those dogs with more than 1 live adult worm ("non-cleared" dogs). Changes in the average OD values from the plasma of "cleared" dogs and "non-cleared" dogs were similar up to 46 days after treatment but diverged significantly thereafter. The efficacy of thiacetarsamide was 50% if all worms were considered and 75% if the presence of immature worms was ignored. The benefits of antigen detection assays for diagnosis and improved patient assessment and the use of an R60 ratio to assess the efficacy of adulticides such as thiacetarsamide are discussed in relation to their practical significance for clinicians.

Animals↗

Systemic arterial dirofilariasis in five dogs.

Systemic arterial dirofilariasis is an unusual manifestation of heartworm disease of dogs that results from aberrant migration of Dirofilaria immitis into the peripheral arterial circulation. To expand the clinical characterization of systemic arterial dirofilariasis, 5 dogs evaluated at the North Carolina State University's College of Veterinary Medicine were reviewed. Common clinical presentations included hindlimb lameness, paresthesia of hindlimbs, and interdigital ischemic necrosis resulting from thromboembolic disease. Visualization of heartworms with angiography or ultrasonography confirmed the diagnosis in all cases. All 5 dogs were treated with an adulticide; 3 dogs were treated with thiacetasamide sodium and 2 with melarsomine dihydrochloride. Four of the 5 dogs survived the initial treatment period; 1 dog died of severe thromboembolic complications after thiacatarsamide sodium therapy. The treatment of systemic arterial dirofilariasis creates a therapeutic challenge because of multiple potential complications resulting from thromboembolic disease.

Animals↗

Clinical and laboratory observations in 91 dogs infected with Dirofilaria immitis in northern Greece.

The medical records of 91 dogs with heartworm (Dirofilaria immitis) infection were reviewed, and diagnoses were established by using parasitological and immunological methods. Twenty-one animals were asymptomatic (stage I), 57 had mild to moderate clinical signs (stage II), and 13 had the severe form of the disease including right congestive heart failure and the caval syndrome (stage III). Thoracic radiography revealed right ventricular enlargement in 38 of the dogs, pulmonary vascular enlargement in 43, and parenchymal lesions in 27. Only the cardiac and vascular changes were correlated positively with the clinical stages. D. immitis microfilaraemia was detected in 75 of 85 dogs. Occult infection occurred only in eight stage II and two stage III dogs. Thirty-two of the dogs were treated with thiacetarsamide and 39 were treated with melarsomine, and no differences were found in terms of drug efficacy or complication rate; nine stage II dogs suffered pulmonary thromboembolism and one suffered acute liver disease and there were six fatalities. The 50 treated dogs in stages II and III which were followed up for six months all recovered completely. The performance of 38 of 61 working dogs was completely restored, and the performance of another four was partially restored.

Animals↗

Immunological anomalies and thrombocytopenia in 117 dogs and cats diagnosed with chronic fatigue syndrome (CFS).

Retrospective analysis of immune dysfunctions found in 55 dogs and 62 cats diagnosed with Chronic Fatigue Syndrome (CFS), revealed leukopenia in 11% of dogs (n = 6) and 22.5% of cats (n = 14), lymphopenia in 14.5% of dogs (n = 8) and 10% of cats (n = 6), hypogammaglobulinaemia in 9% of dogs (n = 5) and 13% of cats (n = 8) and thrombocytopenia in 20% of dogs (n = 11) and 68% of cats (n = 42). All patients had creatine kinase enzyme levels above the normal range (CK = 5-100 IU/L) and carried micrococcus-like organisms on erythrocytes. Blood cultures proved positive for Staphylococcus spp. in 16 cases. After low-dosage arsenic-based therapy (thiacetarsamide sodium) all animals experienced complete clinical remission. Subsequent controls demonstrated immune restoration in 4 representative FIV-FeLV negative cats, previously diagnosed with CFS associated with leukopenia, lymphopenia, hypogammaglobulinaemia and thrombocytopenia. The main conclusion is that a CFS-like disease in dogs and cats, characterised by the common hallmarks of high CK levels, absence of known causes of chronic fatigue in animals and presence of micrococcus-like organisms in the blood, can be associated with humoral and/or cellular immune deficiencies in 9-22.5% of cases and with thrombocytopenia in 20-68% of cases. Considerations are made on the possible role of micrococci in the aetiology of the condition and on the similarities with CFS in humans.

Agammaglobulinemia↗

Effect of thioarsenite formation on arsenic(III) toxicity.

Soluble arsenic(III)-sulfide complexes (thioarsenites) play a significant role in the chemistry of arsenic in reducing, sulfidic environments at circumneutral pH. Chemical equilibrium calculations using thioarsenite thermodynamic data from the literature indicate that the formation of a dithioarsenite complex, AsS(OH)(SH)(-1), reduces the concentration of the uncomplexed inorganic As(III) species present (defined sigma H3AsO3, where sigma H3AsO3 = AsO3(-3) + HAsO3(-2) + H2AsO3(-1) + H3AsO3). With enough sulfide present, soluble As(III) is dominated by this complex. Therefore, it is of interest to examine the effect of dithioarsenite formation on As(III) toxicity. The Microtox acute toxicity test was used for this purpose. Tests performed on solutions with varying S:As ratios indicate that As(III) toxicity is a function of the uncomplexed As(III) concentration rather than the total As(III) concentration. This suggests that the dithioarsenite species is not bioavailable and that its formation reduces As(III) toxicity. Chemical equilibrium calculations and sediment pore-water field data from various sources indicate that, in many sediments, dithioarsenite formation can reduce toxicity.

Animals↗

Therapy of filariasis in Tamarins.

A regimen of thiacetarsamide sodium (0.22 ml/kg twice daily for 2 days) plus levamisole phosphate (11 mg/kg/day for 10 days) was effective in eliminating unidentified microfilariae from the blood in seven of eight tamarins. No serious side effects resulted from the treatment. All of the animals were initially freed of circulating microfilariae after treatment, and five have remained microfilaria-negative for 1 year. Two of the tamarins died of causes unrelated to filariasis and were microfilaria-negative before death. One tamarin remained microfilaria-positive after two courses of this treatment.

Animals↗

Treatment of crenosomiasis in dogs.

Dogs were infected with the lungworm Crenosoma vulpis. The efficacy of four drugs in the treatment of the disease was examined using a controlled test. Levamisole and diethylcarbamazine proved to be highly effective.

Animals↗

Thiacetarsamide (adulticide) versus melarsomine (RM 340) developed as macrofilaricide (adulticide and larvicide) to cure canine heartworm infection in dogs.

To implement a new macrofilaricide, treatment of heartworm infection or disease in dogs was checked in all the clinical situations ie from subclinical to severe disease. After preliminary toxicity and efficacy models on experimentally infected dogs, in addition, to the reference posology (2.5 mg of melarsomine (RM 340)/kg twice, 24 h apart by deep IM injection) a more practical program for vet practitioners was suggested (2.2 mg/kg twice, 3 h apart) using modelization of the pharmacokinetic data. The two treatments were equivalent as shown on models with experimental infection of dogs, critical tests on naturally infected dogs and clinical trials in veterinary practice. We advise using specific and well adapted therapeutic programs for each of the clinical classes (class 1: subclinical, class 2: moderate, class 3: severe). The safety margin is respectively x 3 or x 2.5 in contrast with thiacetarsamide which, being hepatotoxic, has no safety margin, and sometimes is nephrotoxic at the recommended dose. RM 340 is fully effective on D immitis adults (even on young ones of 7 months old) and L5 immatures (4 months old) when thiacetarsamide is poorly effective on 7 months or ineffective on 4-month-old parasites. Clinical trials in veterinary practice showed that the programs are well adapted to many clinical situations. The product is effective, relatively safe and easy to handle by IM injection. Preliminary results show its possible use as tactical treatment (2.2 mg/kg twice, 3 h apart) twice a year in mid August and December-January to prevent heartworm disease.

Animals↗

Platelet function, antithrombin-III activity, and fibrinogen concentration in heartworm-infected and heartworm-negative dogs treated with thiacetarsamide.

Platelet aggregation and release, platelet number, mean platelet volume, antithrombin-III activity, and fibrinogen concentration were evaluated in heartworm-negative and heartworm-infected dogs at baseline and on days 3, 10, and 21 after treatment with thiacetarsamide. Platelet reactivity was enhanced in a group of dogs naturally infected with Dirofilaria immitis, compared with 2 groups of heartworm-negative dogs, but platelet reactivity was not further enhanced after treatment with thiacetarsamide. A significant decrease in antithrombin-III activity was detected 21 days after treatment. The platelets from a group of laboratory Beagles implanted with 50 adult D immitis displayed enhanced reactivity 6 months after implantation, but by 18 months, platelet reactivity had returned to near, or less than, baseline. Platelet reactivity was enhanced after thiacetarsamide treatment in this group. Thiacetarsamide-associated changes were not observed in platelet number or size; antithrombin-III activity decreased, but the change was not significant. Fibrinogen concentration was increased significantly (P less than 0.05) on day 10. Enhanced adenosine diphosphate (ADP)-induced platelet aggregation was observed on days 3, 10, and 21 after treatment in heartworm-negative dogs. This change was not observed in 6 control Beagles not treated with thiacetarsamide. Although antithrombin-III activity was decreased on day 3 and fibrinogen concentration was increased on day 10, paralleling changes observed in the heartworm-infected dogs, the changes were not statistically significant. In this study, thiacetarsamide was procagulatory in heartworm-negative dogs and may be an important contributing factor to the thromboembolism observed with adulticidal therapy.

Animals↗

Postadulticide pulmonary hypertension of canine heartworm disease: successful treatment with oxygen and failure of antihistamines.

Postadulticide pulmonary hypertension mechanisms and treatment with antihistamines and supplemental oxygen were studied in eight dogs with heartworm disease. To ensure severe postadulticide thromboembolism, additional heartworms (either 20 or 40 into 4 dogs each) were transplanted into naturally infected dogs before thiacetarsamide treatment. During pentobarbital anesthesia, 2 pulmonary hemodynamic studies were conducted on each dog with a sequence of baseline, hypoxia with FlO2 = 10%, hyperoxia with FlO2 = 100%, a second baseline, treatment with either diphenhydramine (D) or cimetidine (C), and another hypoxia. All dogs were pulmonary hypertensive, with each dog having a mean pulmonary arterial pressure (PPA) greater than 20 mm of Hg. Mean PPA increased from baseline conditions (25.0 +/- 4.5 SD for D and 24.3 +/- 4.4 for C) to hypoxia (28.5 +/- 4.7 for D and 28.4 +/- 3.7 for C), and decreased during hyperoxia (16.9 +/- 3.0 for D and 17.4 +/- 3.0 for C), respectively. Neither antihistamine reduced PPA at normoxia. The degree of pulmonary hypertension when breathing room air increased even more during hypoxia, and this increase was not attenuated by either antihistamine. Histamine did not appear to mediate pulmonary hypertension during postadulticide thromboembolism, nor to modify the hypoxia-mediated pulmonary hypertension at this disease stage. Because baseline PO2 was low (66.6 +/- 11.7 mm of Hg for D and 69.4 +/- 14.2 for C) and because PPA decreased during administration of oxygen, the pulmonary hypertension was mostly hypoxia-induced. In addition to the arterial lesions, much of the pulmonary hypertensive mechanism was an active and reversible vasoconstriction in response to hypoxia caused by the secondary lung disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Use of parasite antigen detection to monitor the success of drug therapy in Dirofilaria immitis-infected dogs.

Recently the authors developed a monoclonal antibody-based enzyme immunoassay for circulating Dirofilaria immitis antigen and demonstrated its utility as a diagnostic tool for canine dirofilariasis. In the present study, serum parasite antigen measurements were used to monitor the success of thiacetarsamide therapy in 2 controlled trials that involved 24 naturally infected dogs. Parasite antigen levels correlated significantly with adult worm burdens in untreated control dogs. Antigen levels fell dramatically by 8 wk after treatment in successfully treated dogs and were undetectable 12 wk after treatment in dogs that were parasitologically cured. Microfilarial counts exhibited seasonal periodicity in both treated and control dogs and were not useful in monitoring the success of adulticide therapy. Parasite antigen detection is quite useful in monitoring the efficacy of adulticide therapy for dogs infected with D. immitis. This approach may lead to improved clinical use of thiacetarsamide, and it should facilitate evaluation of new drugs for this important infection.

Animals↗