Hemodynamics of heartworm infection.

To determine the hemodynamic responsiveness of dogs testing positive for heartworms (direct blood smear), we compared the response of control and heartworm-infected animals to stellate stimulation (SS). Using the anesthetized, open-chest model, twenty dogs (10 control and 10 heartworm-positive) were instrumented to measure left ventricular pressure (LVP), arterial pressure (AP), and coronary flow velocity (CFV) of the left circumflex coronary artery. CFV was converted to flow per gram tissue (CBFG) by weighing the perfusion area of the circumflex artery. The average wet weight of the worm mass infecting the dogs was 1.0 +/- 0.1 g, which represented an average of 5% of the right ventricular free wall weight. Overall heart size and right ventricular weights were greater in the heartworm-positive animals, as well as heart weight to body weight ratios. Prior to SS, LVP was the same for both groups. However, dP/dt and CBFG were 21% and 19% lower, respectively, in the heartworm-positive animals. Stellate stimulation sufficient to produce a 30-mmHg rise in AP led to 25%, 13%, and 40% increases in LVP, dP/dt, and CBFG, respectively, in the control animals. Increases of 22%, 10%, and 52% in the same parameters were observed in the heartworm-positive animals. Although control dP/dt and CBFG in the heartworm-positive animals were lower than in the heartworm-negative animals, heartworm infection at this level did not hinder myocardial responsiveness to SS.

Salivary mucocele associated with dirofilariasis in a dog.

Salivary mucocele associated with dirofilariasis was diagnosed in a dog with a mass in the cranioventral cervical region. The diagnosis was based on the finding of microfilariae in fluid aspirated from the mucocele, immunoassay confirmation of circulating Dirofilaria immitis antigen, and the finding of an adult filariid within the mucocele. Drainage of the mucocele and treatment of the D immitis infection resulted in resolution of the mucocele and dirofilariasis.

Alternative treatment of heartworm disease.

Conventional adulticidal therapy may cause acute death due to embolism in major pulmonary arteries resulting in severe infarction of the lung. To avoid this problem removing a significant number of worms with flexible alligator forceps prior to adulticidal therapy is recommended. Before surgery, an accurate diagnosis and critical evaluation of the patient is mandated for proper choice and sequence of treatment.

Prevalence of Dirofilaria immitis and Dipetalonema reconditum infection in dogs: 805 cases (1980-1989).

Clinical records of 6,977 dogs examined at the small animal clinic of the University of Tennessee College of Veterinary Medicine from January 1980 through December 1989 were analyzed to determine the prevalence and changing frequency of Dirofilaria immitis and Dipetalonema reconditum infection. Using the Knott's test on these dogs, 805 (11.54%) tested positive for microfilariae, with D immitis in 430 dogs (6.16%), and Dip reconditum in 375 dogs (5.37%). Statistical analysis confirmed that the prevalence of D immitis and that of Dip reconditum were essentially equal in the population of dogs included in this study. There was a slight decrease in the prevalence of D immitis over the 10 years examined, but the prevalence of Dip reconditum remained constant. The results were not affected by year-to-year variability in the number of examinations performed. On the basis of our findings, in eastern Tennessee, those veterinarians who diagnose heartworm infection by the presence of microfilariae without differentiating the species involved, risk misdiagnosing 50% of the cases. If the patterns of prevalence seen in recent years continue, the chances of error may actually increase.

The susceptibility of the mosquitoes Aedes notoscriptus and Culex annulirostris to infection with dog heartworm Dirofilaria immitis and their vector efficiency.

The mosquitoes Aedes notoscriptus (Skuse) and Culex annulirostris Skuse were fed on a dog infected with Dirofilaria immitis (Leidy) and a blood parasite count of approximately 5000 microfilaria per ml. Cx annulirostris ingested almost 4 times as much blood and almost 4 times as many microfilariae as Ae.notoscriptus (mean 26.0 compared to 6.6). Attrition of the filarial numbers occurred primarily within the midgut during the first 24 h following ingestion and was greater in Cx annulirostris than Ae.notoscriptus. Aedes notoscriptus sustained development of almost 8 times as many third-stage infective larvae as Cx annulirostris (mean of 3.8 compared to 0.5), and thus had a vector efficiency index of 57.6 compared to 1.9 for Cx annulirostris. In a series of investigations Ae.notoscriptus has now been shown to be an important vector for dog heartworm in southern Australia and may be a significant factor in the apparent burgeoning of the disease.

Efficacy of ivermectin and pyrantel pamoate combined in a chewable formulation against heartworm, hookworm, and ascarid infections in dogs.

Eight trials were conducted in dogs to document the efficacy of ivermectin (6 micrograms/kg of body weight) and pyrantel pamoate (5 mg of active pyrantel/kg) in a beef-based chewable formulation against Dirofilaria immitis, Ancylostoma caninum, Uncinaria stenocephala, Toxocara canis, and Toxascaris leonina. Three studies involved induced infection with D immitis, and 5 studies involved induced or natural infection with hookworms and ascarids. In 3 intestinal parasite trials, the efficacy of the combination chewable tablet was compared with each of its components. Results indicated that 1 component did not interfere with the activity of the other. In 1 heartworm and 2 intestinal parasite trials, the efficacy of pyrantel, ivermectin/pyrantel combination, or ivermectin with pyrantel dosage of 10 mg/kg was evaluated. The ivermectin/pyrantel combination was 100% effective in preventing development of D immitis larvae. Efficacy of the combined product against T canis, Toxascaris leonina, A caninum, and U stenocephala was 90.1, 99.2, 98.5, and 98.7%, respectively. In the intestinal parasite trials, each individual component was found not to interfere with the anthelmintic action of the other. Increasing the dosage of pyrantel to 10 mg/kg (2 x that in the combination) did not interfere with the efficacy of ivermectin against heartworm or increase the activity of pyrantel against intestinal parasites.

Safety study of a beef-based chewable tablet formulation of ivermectin and pyrantel pamoate in growing dogs, pups, and breeding adult dogs.

To determine the safety of a new combination of ivermectin and pyrantel (as pamoate salt) in a novel beef-based chewable tablet formulation, 3 tolerance trials were conducted and included growing dogs, pups, and breeding adult dogs. Growing dogs, given the combination orally for 5 consecutive days at recommended dosages (5 mg of pyrantel/kg of body weight, 6 micrograms of ivermectin/kg) or at twice the pyrantel dosage in combination with the recommended dosage of ivermectin, had no adverse effects. The combination also was administered to 6-week-old pups at 1, 3, and 5 times the recommended dose on 3 successive days for 3 times in 1 month. Compared with age-matched controls, treatment had no effect on clinical status, growth rate, or gross or histologic features. Breeding male and female dogs given the combination at 3 times the recommended dose for extended periods had no adverse effects, and prevalence of abnormalities in the offspring was not greater than that in nonmedicated controls.

Analysis of body-length distribution of Dirofilaria immitis in the cardio-pulmonary blood vessel of naturally infected dogs in Shiga Prefecture, Japan.

Body-length frequencies of Dirofilaria immitis collected from the cardio-pulmonary blood vessel of the dogs were studied in Shiga Prefecture. Japan, in October 1983 and in January and May 1984. The frequencies were not distributed normally because they included the populations of shorter-bodied worms, probably the growing younger worms, whereas the distributions of the body length of worms collected in July 1983 were proved to fit the single normal distribution. From the results of body-length distribution analysis, the worms collected in different seasons were each composed of 1 to 3 groups with different mean body-lengths, standard deviations and composition rates and successive changes were observed in the distribution patterns. According to the analysis of population structures, the infective season was estimated to range from April or May to October or November in 1983 from the respective ages of shorter-bodied worm groups. The annual rates of first infection and re-infection in 1983 determined by the population of shorter-bodied females collected in January were 48% and 93% respectively and the number of newly infecting females per dog ranged from 1 to 27 with a geometric mean of 8.5. The numbers of newly infecting female worms were distributed following the negative binomial and Poisson distributions in newly infected and already infected dogs respectively.

The occurrence of Dirofilaria immitis in dogs in South Australia.

Heart, lung and samples of blood from 230 dogs were examined for infections of filarial parasites. Dirofilaria immitis worms and microfilariae were detected in one dog. Blood samples from a further 1428 dogs were examined for microfilariae and 22 were found to be infected. Eighteen dogs were infected with D immitis microfilariae and four with Dipetolonema reconditum microfilariae. The histories were available for 18 of the dogs infected with heartworm and only seven dogs had not travelled outside South Australia. It was concluded that heartworm infection was endemic in South Australia but the apparent prevalence was only about 1%.

Identification of Dirofilaria immitis-infected dogs with a coagglutination assay.

The presence of Dirofilaria immitis excretory-secretory (ES) products was detected in the urine of infected dogs using a coagglutination assay. Urine samples from 30 naturally infected dogs were positive. Seventeen of them were microfilaremic, whereas 13 had become amicrofilaremic after receiving 2 courses of diethylcarbamazine. Urine samples from 20 dogs infected with other parasites, Dipetalonema reconditum (7), Toxocara canis (5), and Ancylostoma caninum (8), and urine samples from 20 healthy dogs were negative. The assay detected 200 ng/ml or more of ES products. This assay is simple, easy to perform with minimum training, and requires no equipment. Therefore it should be useful to detect canine filariasis under field conditions.

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.

Diagnóstico de dirofilariose oculta pelo teste de ELISA, em cäes do Estado de Säo Paulo / Diagnosis of canine dirofilariasis, by ELISA test, in the State of Säo Paulo

A dirofilariose oculta constitui-se num grande problema diagnóstico e pode estar relacionada a: a) infecçöes pré-patentes; b) infecçöes causadas por vermes de um único sexo; c) esterilidade dos parasitas devido à idade ou induzida por açäo de drogas; d) resposta imune mediada. Avaliou-se, no presente trabalho, a prevalência de dirofilariose em cäes do Estado de Säo Paulo, através do teste de ELISA (CITER Semi-QuantTM Canine Heartworm Antigen Test Kit), bem como se tentou caracterizar a causa da ausência de microfilaremia circulante, com auxílio de exames subsidiários. De 244 soros examinados, 35 (14,34//) mostraram-se positivos. Destes, 20 apresentaram, além do teste de ELISA positivo, uma ou mais alteraçöes (radiográficas/eletrocardiográficas), compatíveis com o diagnóstico de dirofilariose canina; e, nos demais 15 animais, assintomáticos, também soropositivos pelo teste de ELISA, descartou-se a forma de infecçäo pré-patente, pois haviam sido expostos ao risco da infecçäo há mais de 6 meses, e também a esterilidade dos parasitas conseqüentemente à açäo de drogas

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.

Effects of treatment with aspirin or aspirin/dipyridamole combination in heartworm-negative, heartworm-infected, and embolized heartworm-infected dogs.

To determine the drug dose required to inhibit platelet reactivity by at least 50%, 2 drug regimens were evaluated in heartworm-negative, heartworm-infected, and heartworm-infected dogs embolized with dead heartworms. Aspirin, or a combination of aspirin and dipyridamole, were administered to 2 groups of Beagles (n = 5 each) for 5 to 9 days; a third group of 5 Beagles served as nontreated controls. For heartworm-negative dogs, mean (+/- SD) aspirin dosage that inhibited collagen-induced platelet reactivity by at least 50% was 6 (+/- 2) mg/kg of body weight given once daily. The aspirin/diphridamole combination dosage was 1 mg of each drug/kg given every 12 hours. All dogs (n = 15) were implanted with 7 adult heartworms each and remedicated (or not treated) beginning at 21 days after heartworm implantation. In heartworm-infected dogs, mean aspirin dosage required to inhibit collagen-induced platelet reactivity greater than or equal to 50% was 10 (+/- 6) mg/kg. Mean dosage of aspirin/dipyridamole combination was 1.6 +/- (0.5) mg of each drug/kg given every 12 hours. When platelet reactivity in response to collagen was determined to be inhibited by at least 50% in all medicated dogs, each dog (n = 15) was embolized with 7 dead adult heartworms to mimic heartworm adulticidal treatment. Platelet reactivity was monitored for 21 days after treatment, and drug dose was adjusted to maintain platelet inhibition by at least 50%. In embolized dogs, mean aspirin dosage was 17 (+/- 14) mg/kg given once daily. Mean dosage of the aspirin/dipyridamole combination was 2.8 (+/- 1.3) mg of each drug/kg given every 12 hours. All dogs (n = 15) were euthanatized 21 days after heartworm embolization. Each lung lobe was evaluated for severity of lesions and presence of organized or fibrinous thrombi. Lesion severity in the aspirin- and aspirin/dipyridamole-treated dogs was not significantly different from that in control dogs.

Effects of treatment with ticlopidine in heartworm-negative, heartworm-infected, and embolized heartworm-infected dogs.

Ticlopidine hydrochloride was evaluated for its effectiveness in inhibiting platelet aggregation and serotonin release in 5 laboratory Beagles before and after heartworm implantation with 7 adult Dirofilaria immitis, and after embolization with 7 dead heartworms to mimic what happens after heartworm adulticide treatment. Five other laboratory Beagles, similarly implanted and embolized with heartworms, were used as nonmedicated controls. During the heartworm-negative stage, the dosage of ticlopidine that inhibited adenosine diphosphate (ADP)-induced platelet aggregation in 5 dogs by at least 50% after 5 days of treatment was 62 mg/kg of body weight once a day. In the same dogs implanted with 7 adult heartworms 21 days previously, mean (+/- SD) ticlopidine dosage required to obtain similar results was 71 (+/- 13) mg/kg given once daily. During the 21 days after dead heartworms were implanted in heartworm-infected dogs, mean ticlopidine dosage was 108 (+/- 35) mg/kg (range, 62 to 150 mg/kg). Ticlopidine treatment was associated with increased platelet numbers in all 5 dogs during the heartworm-negative stage and in 4 of 5 dogs during the heartworm implantation and heartworm embolization stages. Mean platelet volume tended to decrease as platelet numbers increased. At necropsy, gross and histologic pulmonary lesions were less severe in ticlopidine-treated dogs than in nonmedicated control dogs.

Chemoprophylactic effects of milbemycin oxime against larvae of Dirofilaria immitis during prepatent development.

Three studies were conducted to determine the efficacy of milbemycin oxime in the prevention of Dirofilaria immitis infection in dogs. Dogs were given single or multiple experimental inoculations with infective third-stage D immitis larvae and were treated with milbemycin oxime at a target dosage of 0.5 mg/kg of body weight either once or at monthly intervals at various times after inoculation. The compound was effective in preventing infection when 1 dose was administered 30 or 45 days after inoculation. Significant, but incomplete, protection was achieved when single treatments were administered 60 or 90 days after inoculation. Multiple monthly treatments beginning 60 days after inoculation appeared to provide additive effects that resulted in restoration of complete efficacy.

The humoral response in natural Dirofilaria immitis infections in dogs.

Plasma samples from dogs with infections of Dirofilaria immitis were assessed using ELISA and Western blotting techniques. These results were then assessed in relation to age and sex of the host, and to the numbers of microfilariae and adult filariae. Dogs with microfilariae tended to have lower levels of infection. In infected dogs, mean ELISA titres increased directly with the degree of infection. Dogs that were either young or mildly infected, showed a preferential antibody reactivity to antigens in the high molecular weight regions of the immunoblots. With increasing age and/or the extent of infection, an antibody response to antigens in the low molecular weight regions was apparent.

Efficacy of ivermectin chewable tablets and two new ivermectin tablet formulations against Dirofilaria immitis larvae in dogs.

One hundred four heartworm-free Beagles less than 1 year old were studied to determine the efficacy of ivermectin chewable tablets and of 2 other ivermectin tablet formulations against heartworm larvae. At 30 days after SC inoculation of dogs with infective Dirofilaria immitis larvae, all ivermectin formulations were given orally at dosage of 6 micrograms/kg of body weight. The ivermectin chewable tablets also were given orally at dosage of 2 and 6 micrograms/kg at 30 and 45 days, respectively, after injection of larvae. Replicates of 6 or 8 dogs in each study were formed on the basis of gender and body weight and, within replicates, were randomly allocated to treatment groups. At 30 days after injection of larvae, the additional dogs (in replicates of 8) were assigned to the control group and to the group given ivermectin chewable tablets at dosage of 6 micrograms/kg. All dogs were housed individually. Necropsy was performed approximately 5 or 6 months after larvae were administered. In both trials, all control dogs had heartworms at necropsy (University of Illinois--geometric mean, 35.0; Florida--geometric mean, 26.1). In both trials, the ivermectin chewable tablet (6 micrograms/kg) and both tablet formulations (6 micrograms/kg) given at 30 days after larval injection, and the chewable formulation (6 micrograms/kg) given at 45 days after larval injection were 100% effective (P less than 0.01) in preventing development of induced infection with D immitis.(ABSTRACT TRUNCATED AT 250 WORDS)