Efficacy of milbemycin oxime in chemoprophylaxis of dirofilariasis in cats.

Although cats are less susceptible to infection with Dirofilaria immitis than are dogs, the possibility of severe consequences from infection or adulticidal treatment renders preventive treatment a desirable alternative in endemic areas. To evaluate the efficacy of milbemycin oxime as a chemoprophylactic agent in cats, 48 cats were inoculated with infective D immitis larvae. Single oral treatment with 2.3 mg of milbemycin oxime (0.5 to 0.9 mg/kg of body weight) at 30 or 60 days after inoculation with infective larvae gave strong but incomplete protection. Treatment at 60, as well as 90, days after inoculation with infective larvae was completely effective in preventing development of infection. A control group of inoculated, but untreated, cats was monitored biweekly for hematologic changes and for changes in parasite-specific serum antigen and antibody concentrations. Pronounced increases in total leukocyte counts and eosinophil numbers were associated with the estimated time of in vivo molting from fourth- to fifth-stage larvae. Antibody reactivity correlated with infection status, but serum antigen concentrations through 161 days after inoculation were undetectable.     

Indirect fluorescent antibody test in occult dirofilariasis.

Indirect fluorescent antibody titers to Dirofilaria immitis microfilaria (IFA-mf) and peripheral eosinophilia were recorded from 15 to 52 months in ten experimentally infected dogs with occult dirofilariasis (heartworm infection without microfilaremia). Five dogs which were experimentally sensitized with D immitis microfilaria did not exhibit microfilaremia after inoculation with infective-stage larvae. In three other dogs, microfilaremia suddenly ceased after 4 to 7 months. In these three dogs, antimicrofilarial antibodies were detectable by IFA-mf test as soon as microfilaremia ended. In the remaining two dogs, which exhibited spontaneous occult dirofilariasis, antibodies were detected at the end of the prepatent period of 6 months. The presence of adult worms was confirmed by angiocardiography. Significant IFA=mf titers (greater than or equal to 1:8) persisted after successful treatment with an adulticide. Reinfection of treated dogs reestablished occult dirofilarasis. Eosinophilia was present in all dogs and peaked at about 3, 6, and 9 months after they were inoculated with infective-stage larvae. At necropsy, the ten dogs harbored gravid, reproducing adult worms in the heart and pulmonary arteries.     

RADIOGRAPHIC AND ANGIOGRAPHIC EVALUATIONS OF FERRETS EXPERIMENTALLY INFECTED WITH DIROFILARIA IMMITIS

Five ferrets of each sex were each inoculated with 15 third-stage infective larvae of Dirofilaria immitis to study radiographic and angiographic changes in the cardiopulmonary system following heartworm infection; 5 additional ferrets of each sex served as noninfected controls. Prior to inoculation and every 8 weeks thereafter until 40 weeks, the infected and noninfected ferrets were radiographed; angiographic examinations were done prior to necropsy. At necropsy, the worms in the heart, lungs, and associated vessels were counted, and lung histosections were prepared and examined for changes. Radiographic changes were seen in the right side of the heart and associated vessels of infected ferrets as compared with the noninfected ferrets, but changes were less prominent than those seen in heartworm-infected dogs and cats. The changes were primarily an increase in the size of the right side of the heart, especially the right atrium. Radiographically, no changes could be visualized in the pulmonary vascular system. Worms in the enlarged cranial vena cava, azygous vein, and left caudal lobar pulmonary artery of infected animals were delineated by angiography. Histologically, no changes were seen in the pulmonary vascular tissues.     

Pulmonary arterial disease in cats seropositive for Dirofilaria immitis but lacking adult heartworms in the heart and lungs

OBJECTIVE: To determine the prevalence and severity of pulmonary arterial lesions in cats seropositive for heartworms (Dirofilaria immitis) but lacking adult heartworms in the heart and lungs during necropsy. ANIMALS: 630 adult cats from an animal control shelter in Florida. PROCEDURE: Cats were tested for adult heartworms in the heart and pulmonary arteries and antibody against heartworms in the serum. Histologic examination was conducted on the right caudal lung lobe of 24 heartworm- and antibody-positive cats; 24 heartworm-negative and antibody-positive cats; and 24 heartworm-, antibody-, and antigen-negative cats. Wall areas of 10 small to medium-sized pulmonary arteries of each cat were measured and expressed as a proportion of total cross-sectional area. RESULTS: Heartworm infection or seropositive status was significantly and strongly associated with seventy of medial hypertrophy of pulmonary arterial walls. Heartworm- and antibody-positive cats and heartworm-negative and antibody-positive cats had a significant increase in wall thickness, compared with wall thickness for heartworm- and antibody-negative cats. Heartworm- and antibody-positive cats had the most severe hypertrophy. The proportion with occlusive medial hypertrophy was significantly higher in heartworm- and antibody-positive cats (19/24 [79%]) and heartworm-negative and antibody-positive cats (12/24 [50%]), compared with heartworm- and antibody-negative cats (3/24 [13%]). CONCLUSIONS AND CLINICAL RELEVANCE: Cats with serologic evidence of exposure to heartworms, including those without adult heartworms in the lungs and heart, have a greater prevalence of pulmonary arterial lesions than heartworm-negative cats without serologic evidence of exposure. Additional studies are needed to define the pathogenesis, specificity, and clinical importance of these lesions.     

Echocardiographic quantification of Dirofilaria immitis in experimentally infected cats

The safety of heartworm preventives in heartworm-positive cats has traditionally been evaluated using adult Dirofilaria immitis removed from infected dogs and surgically implanted into the cats. An alternate study model uses infective larvae to establish adult infections in cats. Unfortunately, the number of adult worms resulting from the latter method varies widely from none to more than 30, both unacceptable for studies of natural heartworm infection and for studies evaluating product safety in heartworm-infected cats. We sought to determine infection severity in experimental infections via echocardiography to reduce the chances of enrolling uninfected and heavily infected cats into a study. Eighty adult cats were each inoculated with 60 infective D. immitis larvae and maintained for 8 months to allow for the development of adult worms. Antigen and antibody testing, as well as echocardiographic imaging, were performed to confirm and estimate adult worm burdens. Approximately 8 and 12 months post-infection, echocardiographic examination was performed to confirm and enumerate adult D. immitis populations in the cardiovascular system. Worm burdens were stratified as 0, 1-3, 4-11, and > 11 adults, with 0 being considered uninfected and more than 11 considered too heavily infected to be relevant for anthelmintic studies. Cats with clinically relevant infections (1-10 adults) subsequently received multiple treatments with the investigational drug, and worm burdens were confirmed by necropsy 30 days following the final treatment. Worm burden estimated with echocardiography correlated well, but not precisely, with post-mortem counts (p < 0.001, r2 = 0.67). Echocardiography under-, over-, and exactly estimated heartworm burden 53%, 27%, and 22% of the time, respectively. Although the correct category (0-4) was determined by echocardiography in only 54% of cats, positive cats were distinguished from negative cats 88% of the time and the heaviest infections (> 11) were correctly categorized 95% of the time. Both false negative and false positive results were observed. We conclude that echocardiography is useful for detecting mature experimental heartworm infections, identifying cats that have rejected mature infection, and detecting very heavy heartworm burdens, but it is only moderately accurate in classifying lesser burdens. While echocardiography cannot be relied upon to consistently determine the exact heartworm burden in experimentally infected cats, it is useful in stratifying worm burdens for anthelmintic safety studies.     

Strongylus vulgaris in the tunica media of arteries of ponies and treatment with ivermectin

A preliminary investigation was made into the effect of fourth-stage Strongylus vulgaris larvae sequestered in the tunica media of ileocolic arteries of pony foals treated with ivermectin. The foals had been reared parasite-free, inoculated with infective larvae and given orally a placebo or ivermectin paste. Two foals received subsequently one or two further inoculations with larvae and treatment with ivermectin. Arteriography was used to identify the lesions in the ileocolic artery following inoculation and their regression following treatment. At necropsy, foals were examined for lesions and larvae grossly and histologically. Ivermectin was highly effective against fourth-stage larvae and those present in the media appeared not to unduly affect the integrity of the ileocolic artery. Increased numbers of larvae were not found in the media of foals receiving repeat inoculations and repeat treatments. Larvae were not found in the media of foals treated with a placebo. The major pathological changes in the arterial wall of all foals were attributed to infection with S. vulgaris and there was no strong tendency for the damaged arteries to return to normal after the S. vulgaris were removed.     

CARDIAC AND PULMONARY ARTERY MENSURATION IN FELINE HEARTWORM DISEASE

A retrospective study was undertaken to quantify thoracic radiographic changes in cats with heartworm diseases, ( Dirofilaria immitis ). Using a blinded study format, the cardiac silhouette, thoracic cavity and pulmonary arteries were measured from thoracic radiographs of 21 cats with feline heartworm disease and 30 cats without known cardiac or pulmonary vessel pathology. Measured data were normalized to the thoracic cavity or bony structures within the radiographic field of view. The measurements were compared between the two groups of cats using an unpaired, two-tailed Student's t -test, with a p value of < 0.05 being considered significant. Cats with feline heartworm disease had enlargement of the craniocaudal aspect of the cardiac silhouette and normalized cardiac:thoracic ratio (p < 0.05) on the lateral view. Also, there was significant enlargement of the central and peripheral caudal lobar pulmonary arteries and their normalized ratios (p < 0.05) in the heartworm infected cats as visualized on the ventrodorsal projection. Tortuosity of the pulmonary arteries was seen in three of the 21 infected cats. Eleven of the 21 cats with feline heartworm disease had pulmonary parenchymal changes. Based on the present study, central and peripheral pulmonary artery enlargement as viewed on the ventrodorsal radiograph was the single best radiographic indicator of feline heartworm disease.     

Histopathological comparison of pulmonary artery lesions between raccoon dogs (Nyctereutes procyonoides) and domestic dogs experimentally infected with Dirofilaria immitis

Five raccoon dogs (Nyctereutes procyonoides) and two domestic dogs (Canis familiaris) were subcutaneously infected with 100 infective larvae (L3) of Dirofilaria immitis. Two and five worms, respectively, were collected from two of three raccoon dogs. Villous endarteritis was found in the raccoon dog with five worms and two dogs at 116 days after infection. The number of recovered worms in the raccoon dogs was significantly smaller than that of the domestic dogs having 22 and 29 worms, while histopathological features and the severity of the lesions in the raccoon dogs were similar to those in the domestic dogs. The vascular lesions in two chronically-infected raccoon dogs turned into much severe at 565 and 590 days after inoculation.     

COLLATERAL PULMONARY CIRCULATION IN DOGS EXPERIMENTALLY INFECTED WITH DIROFILARIA IMMITIS: ITS ANGIOGRAPHIC EVALUATION*

Collateral pulmonary circulation was evaluated angiographically 11 months after experimental infection of dogs with either 25 or 100 infective larvae of Dirofilaria immitis. In both groups, collateral pulmonary circulation developed from bronchial arteries and esophageal branches of the left gastric artery. Of the four dogs receiving 25 larvae, one had no detectable collateral circulation, one developed collateral pulmonary circulation from the bronchial arteries only, and two had collateral pulmonary circulation from the bronchial arteries and esophageal branches of the left gastric artery. Of the three dogs receiving 100 larvae, all had collateral pulmonary circulation from the bronchial arteries and the esophageal branches of the left gastric artery. Bronchial artery collateral pulmonary circulation was more extensive in the 100-larvae dogs than in the 25-larvae dogs. Collateral pulmonary circulation from the left gastric artery esophageal branches was similar in both dog groups. Angiographically detectable collateral pulmonary circulation developed within the first year of heaertworm infection. In some respects, the extent of collateral pulmonary circulation development was related to the severity of heartworm infection.     

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.     

Immunoblot analysis of specific antigen bands predictable for Dirofilaria immitis infection in cats

Serial sera from four mongrel cats experimentally inoculated with infectious larvae of Dirofilaria immitis were analyzed by immunoblot patterns against a phosphate buffered saline-extract of D. immitis. Antigen-specific protein bands detected indicate that the low molecular weight bands of 36, 32, 22, 19 and 14 kDa, are predictable for positive adult worm infection, suggesting diagnostic usefulness for adult D. immitis infection in cats.     

Public health aspects of dirofilariasis in the United States

Coin lesions in the human lung present significant differential diagnostic problems to the physician. There are at least 20 known causes of such lesions, including neoplastic lesions, infectious diseases, and granulomas. The human medical literature contains many misconceptions about the life cycle of Dirofilaria immitis, including the method of entry of the infective-stage larvae and the development of the young adult worm. These misconceptions have obscured the recognition of the clinical presentation of pulmonary dirofilariasis and the potential for D. immitis to lodge in many other areas of the human body besides the lung. Exposure to infective larvae of D. immitis is more common in humans than is currently recognized. Reported cases in humans reflect the prevalence in the canine population in areas of the United States. The veterinary literature provides compelling evidence that D. immitis is a vascular parasite, not an intracardiac one. Its presence in the right ventricle is a post-mortem artifact, because it has never been shown to be there by echocardiography or angiography in a living dog, even though these techniques have demonstrated adult D. immitis in the pulmonary, femoral, and hepatic arteries; posterior vena cava; and right atrium of live dogs. Physicians have taken the name "heartworm" literally, believing that the worm lives in the heart and only after it dies does it embolize to the pulmonary artery. However, the coin lesion is spherical in shape, not pyramidal, as embolic infarcts to the lung in humans are known to be. The coin lesion is an end-stage result of the parasite's death in the vascular bed of the lungs and the stimulation of a pneumonitis followed by granuloma formation. This pneumonitis phase of human pulmonary dirofilariasis is often not recognized by the radiologist because of the way pneumonitis is diagnosed and treated and because the developing nodule is obscured by the lung inflammation. Serologic methods for use in humans are needed for clinical evaluations of patients with pneumonitis living in highly enzootic D. immitis regions. As well, epidemiological surveys are needed to determine the real extent of this zoonotic infection.     

Use of echocardiography for the diagnosis of heartworm disease in cats: 43 cases (1985-1997)

OBJECTIVE: To determine the usefulness of echocardiography in the diagnosis of heartworm disease in cats and to compare this modality with other tests. DESIGN: Retrospective study. ANIMALS: 43 cats with heartworm infection that had echocardiographic examinations at 2 veterinary teaching hospitals between 1985 and 1997. Twenty-two of these 43 cats also underwent radiography of the thorax and heartworm antibody and heartworm antigen testing. PROCEDURE: Cats were determined to be infected with Dirofilaria immitis infection on the basis of 1 or more of the following findings: positive modified Knott or antigen test result, echocardiographic evidence of heartworm disease, or confirmation of the disease on postmortem examination. The percentage of echocardiographs in which heartworms were evident was compared with the percentage of radiographs in which pulmonary artery enlargement was evident and results of antigen or antibody tests in cats in which all tests were performed. RESULTS: Overall, heartworms were detectable by use of echocardiography in 17 of 43 cats, most often in the pulmonary arteries. In the 22 cats in which all tests were performed, antibody test results were positive in 18, antigen test results were positive in 12, and pulmonary artery enlargement was evident radiographically and heartworms were identifiable echocardiographically in 14. Heartworm infection was diagnosed exclusively by use of echocardiography in 5 cats in which the antigen test result was negative. CONCLUSIONS AND CLINICAL RELEVANCE: Although echocardiography was less sensitive than antigen testing, it was a useful adjunctive test in cats that had negative antigen test results in which there was a suspicion of heartworm disease. The pulmonary arteries should be evaluated carefully to increase the likelihood of detection of heartworms echocardiographically.     

Renal microcirculatory and correlated histologic changes associated with dirofilariasis in dogs

Nine 7-month-old Beagle dogs were inoculated with 200 third-stage larvae of Dirofilaria immitis. The development of cardiac disease secondary to heartworm infection was confirmed by thoracic radiography, echocardiography, and angiography with blood pressure measurements. The only indication of renal disease was mild-to-moderate proteinuria. The dogs were euthanatized approximately 18 months after inoculation. The mean microfilarial count in blood at the time of euthanasia was 88,700/ml, with a mean of 89 adult heartworms in the vena cavae, heart, and pulmonary arteries. The kidneys were perfused for microangiographic and correlative histologic examination of the intrarenal microvasculature and associated renal morphologic features. Angiograms of whole kidneys from 6 dogs revealed attenuation or truncation of the major renal vessels. Microangiograms of all kidney slices revealed attenuation in the microangiographic appearance of the glomerular capillaries. Histologic examination of all kidney slices revealed mild-to-intense, diffuse, chronic interstitial nephritis and generalized membranoproliferative glomerulonephritis. Microfilariae were observed within the glomerular capillaries and the medullary vessels. The microangiographic changes correlated with and were explained in part by the histologic changes in the renal parenchyma.     

Prevalence of Dirofilaria immitis infection among shelter cats

OBJECTIVE: To determine prevalence of Dirofilaria immitis infection among shelter cats. DESIGN: Cross-sectional study. ANIMALS: 239 cats euthanatized at an animal shelter in southeastern Michigan. PROCEDURE: A gross necropsy focusing on the thoracic cavity, heart, lungs, and pulmonary vessels was performed within 5 hours after cats were euthanatized. Blood was collected directly from the heart of cats found to be infected and tested, using a filter test for microfilariae. Serum was tested for D immitis antigens by use of 2 antigen detection kits and for D immitis-specific antibodies by use of 2 antibody detection kits. RESULTS: Cats ranged from approximately 4 months to 15 years old. Adult D immitis were found in 6 (2.5%) cats. Blood could not be recovered from 1 of the cats with heartworm infection. For the 5 other cats, results of the filter test were negative, and results of both antigen and both antibody tests were positive. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that cats living in an urban area in the northern part of the United States have a low prevalence of adult D immitis infection. However, this is likely to be an underestimate of the true prevalence of infection, because no attempts were made to identify cats infected with larval or juvenile stages of D immitis.     

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.     

Influence of immune treatments against Dirofilaria immitis infection in dogs

Mongrel dogs were inoculated with two kinds of antigenic substances. The first was a phosphate buffered saline extract of whole Dirofilaria immitis mixed with aluminum hydroxide gel (group 1), and the second was an orally administered live Metastrongylus apri infective larvae (L3) (group 2). Both groups were then infected with D. immitis L3. Indirect hemagglutination (IHA) tests showed that the antibody was produced by these inoculations before the infection was introduced, even in dogs inoculated with M. apri. This suggests a cross-reactivity between D. immitis and M. apri. The initial passive cutaneous anaphylaxis (PCA) antibody production was markedly delayed by about 70 days in group 2 compared with the production in the infected control dogs (group 3). The appearance of microfilaremia was also delayed by about one month in group 2 compared with that in the above control group. All dogs were sacrificed after the termination of the observation and worms recovered from the right ventricle and pulmonary arteries were counted and measured. The results indicated that immunization resulting from the homologous worm-somatic antigen might accelerate the growth of the infected larvae, whereas immunization resulting from the heterologous worm antigen, but cross-reactive to D. immitis, might disadvantageously affect the growth.     

THORACIC COMPUTED TOMOGRAPHY,ANGIOGRAPHIC COMPUTED TOMOGRAPHY,AND PATHOLOGY FINDINGS IN SIX CATS EXPERIMENTALLY INFECTED WITH AELUROSTRONGYLUS ABSTRUSUS

Aelurostrongylus abstrusus infection is common in endemic areas and may cause severe respiratory clinical signs. Computed tomography (CT) is an important tool to diagnose pulmonary disease, because it allows detection of small lesions and discrimination of superimposed structures. The purpose of this study was to characterize by CT and angiographic CT the pulmonary lesions in six cats before, and 48 and 81 days after inoculation with 100 or 800 A. abstrusus infective larvae. Histological examination of the accessory lung lobe was performed to determine the microscopic, pathomorphologic correlate of the CT findings. The predominant CT lesion consisted of multiple nodules of varying size distributed throughout the lungs, severity depending on infectious dose. The histological correlate of the nodular lesions was multifocal dense granulomatous to mixed inflammatory cell infiltrates, including eosinophils distributed in the parenchyma and obliterating the alveoli. Marked, multifocal, dose‐dependent thickening of the bronchi and adjacent interstitial changes blurred the margins of the outer serosal surface of the bronchi and vessels. Histologically, this was due to peribronchial mixed cell inflammation. During the course of infection some of the nodular and peribronchial changes were replaced by areas of ground‐glass opacity. In addition to providing detailed depiction of pulmonary lesions resulting from an infectious cause and clearly defining lesions with respect to time and severity of infection, CT allowed quantitative assessment of bronchial thickness and lymph node size during the course of disease. Findings indicated that CT characteristics of this disease are consistent with pathologic findings.     

Renal effects of Dirofilaria immitis in experimentally and naturally infected cats

Canine heartworm infection has been associated with glomerular disease and proteinuria. We hypothesized that proteinuria, likely due to glomerular damage, would also be found in cats experimentally and naturally infected with Dirofilaria immitis. Two populations of cats were evaluated, including 80 that were each experimentally infected with 60 infective heartworm larvae as part of a drug safety study, and 31 that were naturally infected with D. immitis. Each had a control population with which to be compared. In the experimentally infected group, we evaluated urine from 64 cats. Ten of these cats were shown to have microalbuminuria 8 months post infection. No cat refractory to infection with larvae and no cats from the control group demonstrated microalbuminuria. All 10 microalbuminuric cats were shown to have significant proteinuria, as measured by the urine protein:creatinine ratio. There was a subtle, but significant, association between worm burden and proteinuria, and although the presence of adult heartworms was required for the development of proteinuria, both microfilaremic and amicrofilaremic cats were affected. Neither the presence of circulating heartworm antibodies and antigen nor the presence of antigenuria predicted the development of proteinuria. Both heavily infected cats (5-25 adult heartworms) and cats with worm burdens compatible with natural infections (1-4 adult heartworms) developed proteinuria, and the relative numbers of cats so affected were similar between heavily and more lightly infected cats. Naturally infected cats, for which only dipstick protein determinations were available, were shown to have a significantly greater incidence of proteinuria (90% vs 35%) than did those in an age- and gender-matched control population. Additionally, the proteinuria in heartworm-infected cats was 3- to 5-fold greater in severity. We conclude that cats infected with mature adult heartworms are at risk for developing proteinuria and that this is recognized relatively soon after infection. While heavier infections may predispose cats to developing proteinuria, this complication is seen in naturally infected cats and experimental cats with worm burdens similar to those seen in natural infections (i.e., "clinically appropriate" worm burdens). The clinical relevance of heartworm-associated proteinuria is yet to be determined.     

Efficacy of a single milbemycin oxime administration in combination with praziquantel against experimentally induced heartworm (Dirofilaria immitis) infection in cats

The efficacy of a combination of milbemycin oxime and praziquantel in preventing the establishment of experimentally induced heartworm (Dirofilaria immitis) infection was investigated in a study involving 24 young domestic short-hair cats. The animals were inoculated with 50 infective larvae on day 0. Subsequently they were divided into two groups of 12 animals each. The animals in group 1 were treated once with medicated tablets containing 4 mg milbemycin (minimum dose 2 mg/kg body weight) and 10 mg praziquantel (MILBEMAX) on day 30 after infection. Cats in group 2 received placebo tablets on the same day. On day 183 post-infection a blood sample was taken from each animal before euthanasia and necropsy. The blood samples were tested for the presence of microfilariae and the necropsied animals were examined for the presence of adult worms. Microfilariae were not found in any of the investigated cats. No heartworms were found in the animals in group 1 (treated with medicated tablets). Out of the 12 placebo-treated cats 1 was heartworm-free, whereas all the others were found to be infected with 1-3 adult heartworms.