Heartworm Prevention Research Articles

Correlation between loss of efficacy of macrocyclic lactone heartworm anthelmintics and P-glycoprotein genotype

Macrocyclic lactone (ML) molecules have been used for heartworm control for more than 25 years. However, in recent years, there have been reports of loss of efficacy of ML heartworm preventatives against Dirofilaria immitis in some locations in the United States. Macrocyclic lactone resistance is a common problem in nematode parasites of livestock, and more recently, evidence of ivermectin resistance has been reported in the human filarial nematode Onchocerca volvulus. In this study, four D. immitis sample groups from the United States with different treatment histories were investigated for evidence of ML-driven genetic selection. DNA from individual adult worms and microfilariae was amplified by polymerase chain reaction to investigate a gene encoding a P-glycoprotein, a protein class known to be involved in ML pharmacology. A significant correlation of a GG–GG genotype with ivermectin response phenotype was found. Moreover, a significant loss of heterozygosity was found in a low responder group; loss of heterozygosity is commonly seen in loci when a population has been under selection. Further studies are required to confirm ML resistance in heartworm populations. However, the genetic changes observed in this study may be useful as a marker to monitor for ML resistance in D. immitis.

Risk factors associated with failure of heartworm prophylaxis among members of a national hunting dog club

To identify practices associated with failure of heartworm prophylaxis among dog and kennel owners and dog trainers. Online survey and mail-in questionnaire. Sample-708 members of a national hunting dog club. Heartworm prevention practices used by respondents that reported failure of prophylaxis were compared with practices used by respondents that reported success. Univariate analyses indicated failure of heartworm prophylaxis was inversely related to the number of dogs under a respondent's care. Year-round prophylactic practice was not significantly associated with reduced odds of failure, and efforts to control exposure to mosquitoes were similar among the comparison groups. Respondents reporting prophylaxis failure were more likely to test for heartworm infection ≥ 1 time/y, compared with those reporting success. In a multivariable analysis, residence south of the Virginia-North Carolina state line (ie, the 37th geographic parallel), testing for heartworm infection < once a year when the test was administered prior to April 1, and keeping dogs outdoors for longer periods at dusk, at dawn, or after dark were associated with increased odds of prophylaxis failure. Veterinarians should stress the importance of annual heartworm testing 6 to 7 months after the last possible date of exposure to heartworm, regardless of whether a dog receives prophylactic treatment year-round. Reducing the number of hours dogs spend outdoors at dusk, at dawn, or after dark may reduce the odds of heartworm disease even when dogs are given preventive treatment.

Ivermectin and Milbemycin Oxime in Experimental Adult Heartworm (Dirofilaria immitis) Infection of Dogs

The US Food and Drug Administration reports an increase in the frequency of reports of lack of effectiveness claims for heartworm (HW) prevention products. At their labeled doses, single doses of commercially available HW prevention products are not completely effective against all field isolates of HW. Forty-two HW-free dogs experimentally inoculated with a recent HW field isolate. Placebo-controlled, blinded laboratory clinical trial. Dogs randomly allocated to 1 of 3 treatment groups with 14 dogs per group. Groups were untreated control or p.o. dosed with milbemycin oxime (MBO) or ivermectin (IVM). Dogs were inoculated with 50 HW third stage larvae 30 days before dosing and necropsy was performed on Day 123 after treatment to enumerate adult HW. Thirteen of 14 control dogs had adult HW detected at necropsy with a geometric mean worm count of 22.3. One HW was found in 1 dog in each of the MBO and IVM treatment groups. Two currently approved macrocyclic lactone HW preventives used at their labeled dose rates were <100% effective against a recent HW field isolate, supporting the hypothesis that the effectiveness of a single dose of these preventives can vary. This is important in guiding clients on expectations of product effectiveness.

Evaluation of a new in-clinic method for the detection of canine heartworm antigen

Canine heartworm is endemic in many parts of the world, and veterinarians rely on rapid in-clinic antigen tests to screen for this infection. Recently, an in-clinic, instrument-based rotor employing a colloidal gold agglutination immunoassay was launched in the marketplace (VetScan VS2 ® Canine Heartworm (HW) Antigen Test Kit; Abaxis, Inc.). Because of the widespread use of heartworm prevention and possible false negative test results in dogs with low heartworm burdens, the performance of the VetScan VS2 ® HW test and a commercially available in-clinic, membrane-based ELISA test (SNAP ® Heartworm RT Test; IDEXX Laboratories) was compared using samples from dogs with low heartworm burdens and/or low levels of circulating antigen. Ninety serum samples were evaluated using the two methods. Testing was performed according to the manufacturer's product insert by personnel blinded to sample status. The samples were derived from two populations: dogs with necropsy-confirmed heartworm status (40 with 1–4 female worms, 30 with no worms), and field dogs (20) confirmed positive for antigen by microtiter plate ELISA (PetChek ® Heartworm PF Antigen Test; IDEXX Laboratories). All 40 dogs with heartworms on necropsy were also confirmed to have circulating antigen by the PetChek HW ELISA. In necropsy-negative dogs ( n = 30), neither the VetScan VS2 HW nor SNAP HW tests detected heartworm antigen. Of the samples testing positive for antigen by PetChek HW ( n = 60), the VetScan VS2 HW and SNAP HW tests detected antigen in 15 and 56 samples, respectively. Percent agreement (plus 95% confidence interval) for each test relative to the PetChek HW qualitative result was 50% (40–60%) for VetScan VS2 HW and 96% (89–98%) for SNAP HW. Relative to the presence or absence of female worms at necropsy, agreement was 61% (50–72%) for VetScan VS2 HW and 99% (92–99.6%) for SNAP HW tests. It is clinically important that dogs with low heartworm burdens and/or low levels of circulating heartworm antigen be correctly identified by veterinarians in order to ensure prompt treatment, and the VetScan ® VS2 HW test does not appear to be as accurate as the SNAP HW or PetChek HW tests when performed on this subset of patients.

Transvenous Heartworm Extractionin a Ferret With Caval Syndrome

A 10-month-old ferret was diagnosed with heartworm disease and caval syndrome. Associated clinical signs included weakness and a green-colored urine, identified as biliverdinuria. Despite the animal's small size, removal of three heartworms via transvenous heartworm extraction was successfully performed. Although at least one female worm remained in the right ventricle, the majority of clinical signs related to the presence of the heartworms resolved. The ferret was subsequently managed medically with corticosteroids and monthly heartworm prevention. This case documents the presence of biliverdinuria associated with caval syndrome and successful transvenous heartworm extraction in a ferret.

Factors influencing heartworm, flea, and tick preventative use in patients presenting to a veterinary teaching hospital

The introduction of modern heartworm, flea, and tick preventatives has provided a safe and effective means of controlling companion animal endoparasites, but achieving good owner compliance remains an ongoing challenge for the veterinary profession. Based on a sample of patients from the veterinary teaching hospital at the University of Pennsylvania, this study retrospectively examined factors associated with preventative use and areas of potential weakness in client communication. Between 1999 and 2006, records of 5276 canine and 1226 feline patients were searched for signalment, survey results for heartworm, flea, and tick preventative use, date of visit, presenting complaint, vaccination history, and owner zip code. Data were analyzed using bivariate and multivariate techniques. Overall, only 13–23% of patients were questioned about heartworm, flea, or tick preventative use during routine medical history taking. Patients with a prior history of parasites, younger patients, or those presenting with signs of cardiac disease were no more likely to be questioned about preventative use than healthy animals. Patients presenting to a specialty service were also less likely to be questioned. Approximately 74–79% of dogs and 12–38% of cats in the sample were on preventative products at any given time. There was a distinct seasonality to preventative use corresponding to the heartworm transmission season from June through November in the northeastern United States. Only 50% of patients seen for a yearly physical examination in winter were reported to be using preventative products when surveyed later in the year, compared to the roughly 85% on patients in heartworm preventatives when they received their routine physical examination in spring. Month of presentation and neuter status were the only signalment factors significantly ( P < 0.05) associated with preventative use in the multivariate analysis. Findings from this study emphasize target areas for increasing owner compliance.

Incidence of positive heartworm antibody and antigen tests at IDEXX Laboratories: Trends and potential impact on feline heartworm awareness and prevention

Data from the IDEXX Laboratories Reference Laboratory Network were retrospectively examined for feline heartworm testing trends in testing frequency, geographic bias, and prevalence for the years 2000–2006. Examination of the data supports the commonly held view that veterinarians do not embrace heartworm disease testing or prevention in cats to the same degree they do in dogs. Despite significant awareness and adoption of heartworm testing and prevention in dogs, we hypothesized that heartworm testing rates are lower for cats than for dogs despite a significant prevalence of feline infection. This is important because a perceived low rate of infection in cats is likely to manifest in a low adoption of testing and prevention. In reality, the overall feline heartworm antigen-positive rate is significant – on average 0.9% over the period studied – and in some regions was estimated to be as high as 4.6%. This compares with an average canine heartworm prevalence rate of 1.2%, a feline leukemia virus prevalence of 1.9%, and a feline immunodeficiency prevalence of 1.0%. Based on the low rate of testing and these prevalence rates, practitioners are routinely missing cases of adult feline heartworm infections and the recently defined heartworm-associated respiratory disease (H.A.R.D). Increased antigen testing would result in detection of a significant number of positive cases. In addition, this population of infected cats would represent the “tip of the iceberg” relative to the greater number of cats that have early infection or are at risk for infection.

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, r 2 = 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.

Spatial and temporal transmission risk of Dirofilaria immitis in Argentina

The aim of this work was to assess spatial and seasonal Dirofilaria immitis transmission risk throughout Argentina with models based on the temperature threshold below which filarial development will not proceed in the mosquito (i.e. 14 °C), the occurrence and the number of potential vector mosquito species, and the Heartworm Development Units derived from the degree-days concept. The four models showed a similar increasing southwest-northeast tendency and correlated significantly with canine prevalences used as external validation data. About one-third of Argentina would be suitable for heartworm transmission and the highest risk areas include the north-eastern provinces. According to our models, heartworm transmission is markedly seasonal with peaks in January and February; no region would support transmission throughout the year. To improve the present models, it is necessary to know which mosquito species are competent rather than potential vectors in the country. We believe the present study provides the first risk assessment maps for D. immitis transmission in the Southern Hemisphere and provides a useful guide for heartworm prevention during the transmission periods in different regions of Argentina.

Evaluation of efficacy of heartworm preventive products at the FDA

The Center for Veterinary Medicine, U.S. Food and Drug Administration (FDA/CVM) has authority under the United States Code 21 under Section 514.80 to monitor for adverse experiences of approved animal products. Although veterinarians voluntarily report suspect drug-related events to manufacturers, firms that market FDA-approved animal products must report serious events to the FDA within 15 working days of the veterinarian or pet-owner's call to them. Under the present regulations, canine heartworm preventatives are approved for 100% efficacy after testing in laboratory and field conditions. The report of lack of efficacy against heartworm larvae is a serious adverse drug event because the resulting condition or the treatment of the condition is life threatening. Information on lack of effect that are deemed possibly, probably, or definitely drug-related available for review under generic product on the FDA/CVM website Surveillance of these reports indicates there are some failures for virtually all heartworm prevention product categories. Most failures have been reported in heartworm-endemic states. At this time, it is unclear whether these are representative of the rare occurrences of failure that have been in existence for a long time, but not reported regularly or promptly, or whether there is a true increase in complaints of ineffectiveness and real variability between products. This paper discusses methods, personnel, and procedures in place in the Division of Surveillance that will aid the FDA to better assess heartworm preventive treatment failures. It discusses scoring paradigms presently utilized by FDA/CVM to assess severity of complaints of lack of efficacy against heartworms, and welcomes audience input as to how to improve existing processes. Results suggest that more comprehensive reporting will provide FDA/CVM more accurate surveillance information regarding efficacy problems. Such practices will permit FDA/CVM to better interpret both incidence and severity of in-effect and possible patterns of emerging resistance and to convey this in any necessary updated labeling. It also indicates that as part of that process, practitioners should return to a more conservative testing schedule.

The safety-net story about macrocyclic lactone heartworm preventives: A review, an update, and recommendations

A number of safe, effective, and convenient heartworm preventatives are currently available for virtually all canine and feline pets. Yet, a 2001 survey of over 18,000 veterinary clinics in the United States identified more than 240,000 dogs and 3000 cats infected with Dirofilaria immitis. This high level of owner compliance failure is alarming. Prolonged administration of some of the macrocyclic lactone (ML) preventatives kills young larvae, older larvae, “immatures,” young adults, and/or old adults. Efficacy of 95% or more requires dosing for 9–30 months, with older worms being more difficult to kill. Of the various MLs, ivermectin (IVM) has the most potent safety-net and adulticidal activity, milbemycin oxime has the least, and selamectin and moxidectin injectable lie somewhere in between. The unique effects of IVM are related to the age of the heartworms at initiation of treatment. The earlier treatment is started, the more stunted and smaller the worms and the shorter their survival time. Conversely, the later treatment is started, the longer the worms live, and the more likely the dog will be antigen- and microfilariae-positive. Drug effects do not appear to be enhanced by increasing the dosage or administering at shorter intervals, and it appears that continuous monthly treatment is needed to produce the full effects of the drug. The American Heartworm Society (AHS) recognizes the safety-net (or reach-back effect) and adulticidal properties of some MLs, particularly IVM. The AHS 2003 (American Heartworm Society, 2004. 2003 Updated guidelines for the diagnosis, prevention, and management of heartworm ( Dirofilaria immitis) infection in dogs. In: McCall, et al., (Eds.), Proceedings of the Symposium Session on Recent Advances in Heartworm Disease, The 19th International Conference of the World Association for the Advancement of Veterinary Parasitology, New Orleans, LA, 10–14 August, 2003. Vet. Parasitol. 125, 105–130) canine guidelines state that it is beneficial to administer prophylactic doses of IVM before treatment with melarsomine. Results of laboratory studies suggest that less active dogs are at low risk of severe thromboembolism and death. However, heartworm-positive working dogs might be more at risk. Worsened radiographic and echocardiographic images in a client-owned dog given IVM monthly for 2 years with greatly restricted exercise suggests that such treatment of dogs with clinical, radiographic, and/or echocardiographic evidence of heartworm disease as well as for asymptomatic working dogs is contraindicated. Furthermore, until further data are available, such treatment of even the less active asymptomatic dog should be administered only with much caution and with examination by a veterinarian at least once every 4–6 months. IVM clearly provides potent “safety-net” activity against older larvae, immatures, and young adults in cases of owner compliance failure, even when the owner and veterinarian are not aware that the animal is infected, and offers much promise as a unique “soft-kill” treatment for young, and possibly older adult heartworms, with reduced risks.

Effect of monthly heartworm preventatives on dogs with young heartworm infections.

Effect of monthly heartworm preventatives on dogs with young heartworm infections.

Efficacy and safety of selamectin against fleas and heartworms in dogs and cats presented as veterinary patients in North America

A series of randomized, controlled, masked field studies was conducted to assess the efficacy and safety of selamectin in the treatment of flea infestations on dogs and cats, and in the prevention of heartworm infection in dogs. In addition, observations were made on the beneficial effect of selamectin treatment on dogs and cats showing signs of flea allergy dermatitis (FAD). In all studies selamectin was applied topically, once per month, in unit doses providing a minimum dosage of 6 mg kg −1. Dogs and cats with naturally occurring flea infestations, some of which also had signs associated with FAD, were assigned randomly to receive three months of topical treatment with selamectin (220 dogs, 189 cats) or a positive-control product (dogs: fenthion, n=81; cats: pyrethrins, n=66). Selamectin was administered on days 0, 30, and 60. Day 0 was defined as the day that the animal first received treatment. Flea burdens were assessed by flea comb counts and clinical evaluations of FAD were performed before treatment, and on days 14, 30, 60, and 90. On days 30, 60, and 90, mean flea counts in selamectin-treated dogs were reduced by 92.1, 99.0, and 99.8%, and mean flea counts in fenthion-treated dogs were reduced by 81.5, 86.8, and 86.1%, respectively, compared with day 0 counts. Also, on days 30, 60, and 90, mean flea counts in selamectin-treated cats were reduced by 92.5, 98.3, and 99.3%, and mean flea counts in pyrethrin-treated cats were reduced by 66.4, 73.9, and 81.3%, respectively, compared with day 0 counts. Selamectin also was beneficial in alleviating signs in dogs and cats diagnosed clinically with FAD. A total of 397 dogs free of adult heartworm infection from four heartworm-endemic areas of the USA were allocated randomly to six months of treatment with selamectin ( n=298) or ivermectin ( n=99). Selamectin achieved a heartworm prevention rate of 100%, with all dogs testing negative for microfilariae and adult heartworm antigen on days 180 and 300. Selamectin was administered to a total of 673 dogs and 347 cats having an age range of 6 weeks to 19 years (3954 doses). The animals included 19 purebred or crossbred Collies (Bearded, Border, and unspecified). There were no serious adverse events. Results of these studies indicated that selamectin was highly effective in the control of flea infestations in dogs and cats without the need for simultaneous treatment of the environment or of in-contact animals and also was beneficial in alleviating signs associated with FAD. Selamectin also was 100% effective in preventing the development of canine heartworms and was safe for topical use in dogs and cats.

Safety of moxidectin in avermectin-sensitive collies.

To evaluate the safety of moxidectin administration at doses of 30, 60, and 90 microg/kg of body weight (10, 20, and 30 times the manufacturer's recommended dose) in avermectin-sensitive Collies. 24 Collies. Collies with mild to severe reactions to ivermectin challenge (120 mg/kg; 20 times the recommended dose for heartworm prevention) were used. Six replicates of 4 dogs each were formed on the basis of body weight and severity of reaction to ivermectin test dose. Within replicates, each dog was randomly allocated to treatment with oral administration of 30, 60, or 90 microg of moxidectin/kg or was given a comparable volume of placebo tablet formulation. Dogs were observed hourly for the first 8 hours and twice daily thereafter for 1 month for signs of toxicosis. Signs of toxicosis were not observed in any control group dog throughout the treatment observation period. Likewise, signs of toxicosis were not observed in any dog receiving moxidectin at 30, 60, or 90 microg/kg. The moxidectin formulation used in the study reported here appears to have a wider margin of safety than ivermectin or milbemycin in avermectin-sensitive Collies.

Seasonality of heartworm infection and implications for chemoprophylaxis

The current emphasis on heartworm prevention reflects the dependable protection provided by the monthly administered macrolide endectocides. This article reviews the prerequisites for heartworm transmission and the importance of daily temperature as a limiting factor in determining the seasonality of the transmission period. The practice of some veterinarians to continuously prescribe monthly chemoprophylaxis exaggerates the actual risk of heartworm transmission in most parts of the country and unnecessarily increases the cost of protection to their clients. Guidelines are provided for making an objective, conservative estimate of the earliest and latest dates for administering monthly chemoprophylaxis; and the use of seasonal projections for other clinical applications such as timing and interpretation of heartworm testing are discussed.

Results of a survey to assess knowledge and expectations of veterinarians and their clients regarding heartworm preventives and vaccinations in dogs

Objective— To determine the knowledge and expectations of veterinarians and clients regarding heart-worm preventives and annual vaccinations for dogs. Design— Practitioner and client survey. Sample Population— 435 veterinarians and 1,805 clients. Procedure— A survey was mailed to veterinarians requesting information from them and their dog-owning clients on expectations and knowledge regarding heartworm preventives and annual vaccinations. Responses of veterinarians were compared with those of clients, and both were compared with label indications. Results— Expectations of veterinarians and clients regarding heartworm preventives were similar and usually were consistent with regulatory interpretation of label terms. Of clients purchasing heartworm preventives, 38% did not know that the medication was effective against intestinal nematodes. Veterinarians and clients would be unsatisfied with a product that reduced, but did not eliminate, all intestinal nematodes. Most clients knew that annual vaccinations included distemper virus, parvovirus, and rabies virus, but about half of them did not know that other antigens were in the vaccines. Clinical Implications— Effects of heartworm preventives and diseases for which dogs are annually vaccinated should be explained fully to clients. (J Am Vet Med Assoc 1997;211:434–437)

Survey of Dirofilaria immitis (Leidy, 1856) in random source cats in metropolitan Rio de Janeiro, Brazil, with descriptions of lesions

To evaluate the prevalence of heartworm disease in metropolitan Rio de Janeiro, RJ, Brazil, cats submitted for euthanasia were evaluated by laboratory tests and by necropsy for signs of heartworm infection. Of the 125 cats examined, one (0.8%) — a stray male from an urbanizing district—had one male worm (14.5 cm) in the left lung and showed severe muscular hypertrophy of small pulmonary arteries and arterioles with no right ventricle enlargement or passive congestion. Microfilarie were not detected in the blood of any cats. The prevalence of canine heartworm in the area from which this cat originated is estimated to be approximately 12%. The prevalence of canine heartworm in the urban area of Rio de Janeiro has been determined to be approximately 5%. It has been shown that the prevalence of feline heartworm disease parallels that in dogs, but at a lower rate. Results of this survey strongly suggest that heartworm prevention measures should be taken under consideration, especially among cats living in a high canine heartworm prevalence area.

Comparison of the efficacies of three heartworm preventives against experimentally induced infections with Ancylostoma caninum and Toxocara canis in pups

Summary Forty 11- to 12-week-old helminth-naive Beagles were categorized by sex and weight and randomly assigned to 4 treatment groups (group 1, ivermectin/ pyrantel pamoate; group 2, milbemycin oxime; group 3, untreated control; group 4, diethylcarbamazine/ oxibendazole). Each pup was inoculated po with approximately 100 infective Ancylostoma caninum larvae and 100 larvated Toxocara canis eggs on day 0, and repeatedly at 7-day intervals thereafter until day 56. Administration of anthelmintics also began on day 0, and subsequent treatments were administered according to label recommendations at 30-day intervals (groups 1 and 2) or daily (group 4) for a period of 90 consecutive days. Body weight and A caninum and T canis fecal egg counts were measured at weekly intervals, and clinical observations of health status were conducted twice daily. Pups were euthanatized on day 90, and total gastrointestinal worm burdens were determined. Compared with the mean A caninum egg counts of group-3 control pups, egg counts in group-1 pups were significantly (P ≤ 0.0001) lower on every sampling date from day 28 to 90, egg counts of group-2 pups were significantly (P ≤ 0.0001) lower on sampling days 35, 42, 49, 63, 70, 77, and 84, and were consistently the highest of all treated groups, and egg counts of group-4 pups were significantly (P ≤ 0.0001) lower on every sampling date from day 14 to day 90, and were consistently the lowest of all treated groups. Compared with mean A caninum egg counts of group-3 pups, egg counts in group-1 and group-2 pups were lower by 97.8 and 90.8%, respectively. Numbers of adult hookworms recovered at necropsy were significantly (P ≤ 0.05) lower by 99.4, 83.9, and 99.9% in groups 1, 2, and 4, respectively. Patent T canis infections were detected in 11 of 40 pups and only 5 adult worms were recovered from 4 pups at necropsy. These findings were attributed to age resistance to T canis by maturing pups rather than to a primary pharmacologic effect. This study identified substantial differences in the quantities of hookworm eggs in experimentally infected pups receiving ivermectin/pyrantel, milbemycin oxime, or diethylcarbamazine/oxibendazole at label dosages, but the observed performance of all products was consistent with their respective label indications.

Evaluation of the safety of ivermectin administered in a beef-based formulation to ivermectin-sensitive Collies

Summary Twenty-four Collies sensitive to the toxic effects of ivermectin, when administered at high dosages, were studied to evaluate the effects of repeated monthly treatment with an ivermectin beef-based formulation at amounts up to 10 times the dosage recommended for heartworm prevention in dogs. Collies were treated 3 times at 30-day intervals at rates of 12, 36, or 60 μg of ivermectin/kg of body weight, or with vehicle. Complete physical and neurologic examinations were performed on all dogs prior to the first treatment and after the final treatment. Clinical observations and ivermectin reaction scores were recorded daily for each dog throughout the study. Clinical or neurologic signs characteristic of ivermectin toxicosis were not observed for any dog during the study. Single episodes of vomiting were recorded for 2 vehicle-treated dogs and 2 dogs treated with ivermectin at 12 μg/kg from 6 to 21 days after treatment. At the end of the study, all dogs were challenge-exposed with ivermectin at 120 μg/kg to reconfirm their sensitivity to this class of compounds. All dogs developed signs typical of ivermectin toxicosis during the subsequent 48- to 72-hour period. Results of this study demonstrated that ivermectin can be administered repeatedly without adverse effects at rates up to 60 μg/kg (10 times the recommended use level) to Collies known to be sensitive to this drug.