moxidectin and Dirofilariasis

Heartworm (Dirofilaria immitis) disease continues to increase and spread, remaining one of the most important and pathogenic parasitic diseases of dogs, despite the regular use of macrocyclic lactones (MLs) in preventive products. Dogs harboring strains of D. immitis resistant to MLs, the only drug class available for heartworm prevention in the United States, have been documented and proven. As no new products are available utilizing a novel drug class for the prevention of this disease, the only options for combating ML resistance include increasing the dose and/or changing the dosage regime of current MLs, or by optimizing the formulations of MLs currently available. Moxidectin provides a unique opportunity for optimization of the dose and formulation, which may provide improved efficacy against ML-resistant strains. Currently there are oral, topical, and injectable moxidectin products approved for heartworm prevention in the USA. Two new products (ProHeart

Topics: Animals; Dirofilaria immitis; Dirofilariasis; Dog Diseases; Dogs; Lactones; Macrolides; United States

The history of an 18-month-old English bulldog with a painful lump in the skin on its thigh is described. After opening the nodule a few Dirofilaria repens nematodes were found. Oval-shaped transparent eggs with moving larvae were seen microscopically. The dog was treated with milbemycin and made a complete recovery. The dog had never been abroad, but 6 months earlier in early May had been on a campsite in the middle of the Netherlands where many mosquitoes were present. This is the first described case of an autochthonous D. repens infection of a dog in the Netherlands.

Topics: Animals; Antinematodal Agents; Culicidae; Dirofilaria; Dirofilariasis; Dog Diseases; Dogs; Female; Insect Vectors; Life Cycle Stages; Macrolides; Netherlands; Treatment Outcome; Zoonoses

Assessment of the safety of heartworm preventatives in dogs with pre-existing patent heartworm (Dirofilaria immitis) infections is necessary because rapid adult worm and microfilarial death can lead to severe clinical complications, including thromboembolism and anaphylactic shock in dogs. The aim of this study was to determine the clinical safety of Simparica Trio. Twenty-four laboratory Beagle dogs were implanted with 10 male and 10 female D. immitis (ZoeKY isolate), and once infection was patent, they were randomized equally among three groups to receive no treatment, 1× or 3× the maximum recommended label dose of Simparica Trio. Dogs in the treated groups received Simparica Trio on days 0, 28 and 56. In-life assessments included body weight, physical examinations, clinical observations, daily general health observations, a quantitative estimate of food consumption and blood collections for pharmacokinetic (PK) analysis, microfilariae (MF) counts and D. immitis antigen testing. At the end of the study the heart, lungs and pleural and peritoneal cavities were examined for adult D. immitis worms.. Simparica Trio was generally well tolerated. Emesis occurred at low frequency in all groups including control. Abnormal stool occurred occasionally in the 1× and 3× groups throughout the 3-month study. Fever (> 104 °F/40 °C) was recorded in one 1× and one 3× dog 1 day after the first dose and resolved by the following day. No severe hypersensitivity reactions occurred. The mean number of circulating microfilariae (MF) counts in the control group increased from 12,000/ml at study start (Day 0) to > 20,000/ml at Day 28 and remained > 20,000/ml for the duration of the study. The least squares means of circulating MF were reduced by 69.8% on Day 1 and 97.4% on Day 7 for the 1× group and remained at > 99% lower than the control group for the remainder of the study. Similarly, least squares means of circulating MF were reduced by 85.3% on Day 1 and 93.9% on Day 7 for the 3× group and remained > 98% lower than the control group for the remainder of the study. At the end of the study, the mean number of implanted adult worms recovered was < 10 per sex in all groups with 90%, 85% and 75% of live adult heartworms recovered in control, 1× and 3× treatment groups, respectively. Low numbers of dead adult worms were recovered in 1× and 3×, with none in control. Following each dose, the moxidectin and sarolaner AUC and C. This study demonstrated that Simparica Trio (sarolaner, pyrantel, moxidectin) was well tolerated when administered to heartworm-positive dogs at 1× and 3× the maximum recommended dose at 28-day intervals for 3 consecutive months. Simparica Trio significantly reduced microfilaria counts in both treatment groups, without significant clinical consequences. At the doses administered, Simparica Trio had minor adulticidal activity but resulted in no clinical sequelae.

Topics: Administration, Oral; Animals; Dirofilaria immitis; Dirofilariasis; Dog Diseases; Dogs; Female; Macrolides; Male; Microfilariae; Pyrantel; Treatment Outcome

The current studies compared ProHeart. In two studies, each using 24 adult beagles, dogs were allocated to four treatment groups (n = 6): placebo-treated control; ProHeart 12 as per label (0.5 mg/kg moxidectin); Heartgard Plus (HGP) as per label (minimum 6 µg/kg ivermectin); and Interceptor Plus (INP) as per label (minimum 0.5 mg/kg milbemycin oxime). In both studies, ProHeart 12 was administered as a single subcutaneous dose on day 0, and HGP and INP were administered orally on days 0, 30, 60, 90, 120 and 150. In Studies 1 and 2, dogs were inoculated with 50 third-stage heartworm larvae (JYD-34 strain) on days -30 and 165, respectively. In Study 2, treatment for both HGP and INP was continued on days 180, 210, 240, 270, 300 and 330. Adult heartworm recoveries were performed on day 185 in Study 1 and on day 360 in Study 2.. In Studies 1 and 2, all placebo-treated dogs developed adult heartworm infections (geometric mean, 29.9 and 34.9 worms/dog, respectively). A single dose of ProHeart 12 was 100% effective in preventing the development of adult JYD-34 heartworms when treatment was initiated 30 days after heartworm inoculation, while six consecutive monthly doses of HGP and INP were only 10.5% and 14.6% effective, respectively. The mean worm count for the ProHeart 12-treated group was significantly lower (P < 0.0001) than that for the placebo control, HGP- and INP-treated groups. In Study 2, the dogs treated with ProHeart 12 had an efficacy of 98.3%. All dogs treated with HGP and INP for 12 consecutive months had adult heartworms with efficacies of 37.7% and 34.9%, respectively. The mean worm count for the ProHeart 12-treated dogs was significantly lower (P < 0.0001) than those for the control group, HGP- and INP-treated groups.. A single administration of ProHeart 12 was 98-100% effective in preventing the development of the ML-resistant JYD-34 heartworm strain and was significantly better than multiple consecutive monthly doses of either Heartgard Plus or Interceptor Plus in both studies.

Topics: Animals; Dirofilaria immitis; Dirofilariasis; Dog Diseases; Dogs; Drug Resistance; Female; Filaricides; Ivermectin; Macrolides; Male; Single-Blind Method

Administration of moxidectin topically and doxycycline PO has been utilized experimentally as an alternative treatment for heartworm disease. However, clinical effects of this protocol remain poorly characterized.. To evaluate the clinical and postmortem findings associated with administration of doxycycline and monthly 10% imidacloprid + 2.5% moxidectin (IMD + MOX, Advantage Multi/Advocate) to Dirofilaria immitis-experimentally infected as compared to nontreated control dogs.. Sixteen purpose-bred, female, Beagle dogs.. Prospective, blinded, experimental study. Animals with surgically transplanted adult heartworms were randomized into 2 study groups of equal size: a nontreated control group (n = 8) and an IMD + MOX and doxycycline-treated group (n = 8). Randomization was performed using a complete block design according to circulating microfilarial concentrations, measured before treatment. Serum biochemical profiles, CBCs, thoracic radiographs and echocardiograms were performed prior to and 3 weeks after transplantation, and monthly for 10 months. Postmortem gross and histopathologic evaluations were performed.. Compared to control animals, mean ± SD serum alanine aminotransferase (181 ± 203 U/L vs 33 ± 7 U/L; P < .0001) and alkaline phosphatase (246 ± 258 U/L vs 58 ± 19 U/L; P < .0001) activities were significantly higher in the treated group on day 28. Radiographic and echocardiographic evidence of heartworm disease was observed in both groups; however, no significant differences in these variables were noted between groups. Mean ± SD pulmonary arterial thrombus score was significantly higher in the treated vs nontreated group (3.9 ± 0.4 and 1.5 ± 2.1, respectively; P = .01).. The treatment protocol was well-tolerated with no clinically relevant adverse effects for any variable evaluated during the observational period.

Topics: Animals; Dirofilaria immitis; Dirofilariasis; Dog Diseases; Dogs; Doxycycline; Drug Therapy, Combination; Female; Macrolides; Neonicotinoids; Nitro Compounds; Prospective Studies

Heartworm infection (also known as dirofilariosis due to Dirofilaria immitis) in dogs causes chronic pulmonary disease that, if left untreated, can lead to right-side congestive heart failure. Currently, the only registered drug for adulticide therapy in dogs with heartworm disease (HWD) is melarsomine dihydrochloride. The recent targeting of the bacterial endosymbiont Wolbachia, through antibiotic therapy of the infected host, has offered an interesting alternative for the treatment of HWD. Recent reports of the adulticide activity of an ivermectin/doxycycline combination protocol has lead the American Heartworm Society (AHS) to include in its guidelines that, in cases where arsenical therapy is not possible or is contraindicated, a monthly heartworm preventive along with doxycycline for a 4-week period might be considered. In the present study, 20 dogs with confirmed natural D. immitis infection were included following owner consent. Fourteen dogs were treated with a topical formulation containing 10% w/v imidacloprid and 2.5% w/v moxidectin (Advocate®, Advantage Multi®, Bayer), monthly for nine months, associated to doxycycline (10 mg/kg/BID) for the first 30 days. Six dogs were treated with melarsomine (Immiticide®, Merial) (2.5 mg/kg) at enrollment, followed one month later by two injections 24 h apart. The presence of circulating antigens and the number of microfilariae (mf) were evaluated at the moment of enrollment and then at 1, 2, 3, 4, 5, 6, 7, 8, 12, 18, 24 months post enrollment. Echocardiogram and radiographs were performed at month 0, 6, 12, 18, 24. Monthly moxidectin combined with 30 days of doxycycline eliminated circulating microfilariae within one month, thus breaking the transmission cycle very quickly. Furthermore, dogs treated with the combination protocol started to become negative for circulating antigens at 4 months from the beginning of treatment and all except one were antigen negative at 9 months. All dogs treated with melarsomine were antigen negative by 5 months from the beginning of the treatment. No dogs showed worsening of pulmonary patterns or criteria indicative of pulmonary hypertension 12 to 24 months after. For the criteria mf concentration, antigen concentration, radiography and echocardiography at 12, 18 and 24 months the non-inferiority for the moxidectin group could be proven for a non-inferiority margin of 15% for the rate difference. Dogs treated with moxidectin and doxycycline became negative for microfilariae

Topics: Animals; Antigens, Helminth; Arsenicals; Dirofilaria immitis; Dirofilariasis; Dog Diseases; Dogs; Doxycycline; Drug Therapy, Combination; Female; Filaricides; Macrolides; Male; Neonicotinoids; Nitro Compounds; Time Factors; Treatment Outcome; Triazines

Dirofilaria immitis is a filarial parasite of dogs that can cause serious or fatal cardiopulmonary disease. Three studies were conducted to evaluate the efficacy and safety of monthly treatment with moxidectin in a chewable tablet product in combination with sarolaner and pyrantel to prevent heartworm disease in dogs after experimental challenge and in a clinical field study in the USA.. In two laboratory studies, dogs (8 per group) that had been inoculated 30 days prior with 50 third-stage D. immitis larvae were randomized to treatment on Day 0 with placebo or combination product, at the minimum dose of 24 µg/kg moxidectin, 2 mg/kg sarolaner and 5 mg/kg pyrantel (as pamoate salt). Study 2 also included groups treated with tablets containing moxidectin-alone (24 µg/kg) or sarolaner-alone (2 mg/kg). Efficacy was evaluated ~ 5 months after inoculation by adult heartworm counts at necropsy. In the field study, 410 dogs ≥ 8 weeks-old from 23 USA veterinary clinics were treated for 11 months with either combination product at 24-48 µg/kg moxidectin, 2-4 mg/kg sarolaner and 5-10 mg/kg pyrantel (n = 272) or Heartgard® Plus (ivermectin/pyrantel) at the label recommended dose rate (n = 138). Efficacy was evaluated on Day 330 using antigen and microfilaria testing to assess adult heartworm infection.. In the laboratory studies, there were no heartworms recovered from any dog treated with the combination product or moxidectin alone and all dogs treated with placebo or sarolaner-alone were infected with 20-44 adult heartworms. In the field study, all dogs treated with the combination product tested negative for heartworm infection on Day 330, whereas two dogs treated with Heartgard® Plus tested positive. The Heartgard® Plus-treated dogs that tested heartworm positive were from the lower Mississippi River Valley region, where heartworm resistance has been confirmed to occur. The combination product was well tolerated in all studies.. In laboratory studies, no heartworms were recovered from dogs treated with a single dose of the novel combination product containing moxidectin, sarolaner and pyrantel. Additionally, in the field study no dog tested positive for adult heartworm infection when dosed with the combination product monthly for 11 months, while two dogs treated with Heartgard® Plus tested positive.

Topics: Administration, Oral; Animals; Antinematodal Agents; Azetidines; Chemoprevention; Dirofilaria immitis; Dirofilariasis; Dog Diseases; Dogs; Drug Therapy, Combination; Macrolides; Placebos; Pyrantel; Spiro Compounds; Treatment Outcome; United States

Twelve purpose-bred Beagle dogs (six males and six females) were selected and randomly allocated to two groups, untreated controls and PH6-treated dogs in groups of six each. The dogs were ≥8 months old at the start of the study, and using blood samples collected on Day -7 were shown to be negative for adult heartworm antigen and microfilariae. On Day 0, the dogs in the untreated control group were administered saline subcutaneously by injection, and the dogs in the treated group were administered PH6 according to label instructions. On Day 2, each dog was inoculated in the inguinal area with 50 L3 of D. immitis. The dogs were necropsied on Day 150 (148 days post infection), and the worms were collected and counted.. All of the six control dogs were infected and harbored a range of 21 to 37 worms (geometric mean, 25.4; 10.9 males and 13.9 females). Only one of the six PH6 dogs was found to be infected, harboring a single male worm. Efficacy was 99.5% (geometric mean).. ProHeart

Topics: Animals; Blood; Delayed-Action Preparations; Dirofilaria immitis; Dirofilariasis; Dog Diseases; Dogs; Drug Evaluation; Drug Resistance; Female; Filaricides; Injections, Subcutaneous; Lactones; Macrolides; Male

This study aimed to evaluate the efficacy of imidacloprid 10 %/moxidectin 2.5 % (w/v) spot-on (Advocate®/Advantage® Multi, Bayer) against adult Dirofilaria repens in a blinded, placebo-controlled randomised laboratory study. Twenty-four Beagle dogs were experimentally infected with approximately 75 infective D. repens larvae each on study day (SD) 0. Treatment was initiated on SD 228 after patency had been confirmed in 21 dogs, using a modified Knott Test. Eleven dogs received monthly treatments with imidacloprid/moxidectin at the minimum therapeutic dose (10 mg/kg imidacloprid and 2.5 mg/kg moxidectin) for six consecutive months and 12 control dogs were treated with a placebo formulation. Approximately one month after the last treatment, all dogs were euthanised and necropsied for the detection of D. repens worms. Eleven control dogs harboured live adult D. repens (range 2-11, geometric mean 5.44). Eight of 11 imidacloprid/moxidectin-treated dogs were free of live worms. The live worm count was reduced by 96.2 % (range 0-1, geometric mean 0.21). The majority of dead worms were encapsulated and degenerated. After the first treatment, Knott Tests were negative in all imidacloprid/moxidectin-treated dogs and this status was maintained in 10 dogs until study end. One dog showed a low microfilariae count (1 and 4/mL) on four occasions but was also negative before necropsy. The treatment was well tolerated by all study animals. It is concluded that six consecutive monthly treatments with imidacloprid/moxidectin spot-on are effective and safe against adult D. repens and provide an option for preventing the further spread of this zoonotic parasite.

Topics: Animals; Dirofilaria repens; Dirofilariasis; Dog Diseases; Dogs; Double-Blind Method; Imidazoles; Larva; Macrolides; Microfilariae; Neonicotinoids; Nitro Compounds

The efficacy of imidacloprid 10 %/moxidectin 2.5 % (Advocate®, Advantage® Multi, Bayer) against experimental Dirofilaria (D.) repens infection in dogs was evaluated in a blinded, negative controlled randomised laboratory efficacy study. On SD (study day) 0, eight dogs received a spot-on treatment at a dose of 10 mg imidacloprid and 2.5 mg moxidectin per kg body weight. Another 8 dogs were left untreated. On SD 28 each dog was infected with approximately 75 infective D. repens larvae. Blood samples were collected every 4 weeks after treatment. A modified Knott test was conducted to detect mf (microfilaria). PCR analysis was performed with mf-positive blood samples. On SDs 245 and 246, all dogs were euthanised for detection of D. repens worms. Blood samples of all treated dogs were negative for mf at all sampling days. Blood samples of control dogs were positive for mf in 5 out of 8 control dogs. Individual mf counts ranged from 7 to 2800 mf/ml. In mf-positive blood samples, only D. repens was identified by PCR analysis. During necropsy D. repens worms could be detected in eight untreated control dogs (range: 3–21 worms per dog), whereas no worm could be detected in any of the treated dogs. These results indicate a 100 % preventive efficiency of a single spot-on treatment of imidacloprid 10 %/moxidectin 2.5 % in dogs against experimental infection with D. repens (L3 larvae). The product was well tolerated in all study animals, no treatment related adverse reactions were observed throughout the study.

Topics: Animals; Anthelmintics; Blood; Dirofilaria repens; Dirofilariasis; Dog Diseases; Dogs; Double-Blind Method; Drug Combinations; Imidazoles; Macrolides; Neonicotinoids; Nitro Compounds; Parasite Load; Placebos; Polymerase Chain Reaction; Treatment Outcome

Dirofilaria immitis, Dirofilaria repens, and Acanthocheilonema reconditum are the most important canine filariae. These species are expanding their distribution in both endemic regions and in previously free areas, thus enhancing the risk for single and mixed infestations in both dogs and humans. The present study evaluated the potential use of moxidectin in a spot-on formulation in preventing these dog filarioses in a confined area where the three major canine filariae live in sympatry. The trial was performed in a private shelter with a history of mixed infestations. Twenty-nine negative dogs were monthly treated with a spot-on formulation containing moxidectin 2.5%/imidacloprid 10% in spring and summer of 2010. The blood of the dogs was examined monthly with classical and molecular assays until December 2011. Twenty-six dogs completed the study, and they scored constantly negative to all diagnostic assays. Three further dogs completed the study in February 2011 until when they were filariae-negative. These results show that monthly treatment with moxidectin may potentially contribute in reducing the spreading of canine filarial diseases. The permanent negativity of treated dogs for the study period is discussed in relation to the potential use of this spot-on formulation in the prevention of single and mixed infestations of major vector-borne canine filariae.

Topics: Acanthocheilonema; Acanthocheilonemiasis; Administration, Topical; Animals; Blood; Chemoprevention; Dirofilaria immitis; Dirofilaria repens; Dirofilariasis; Dog Diseases; Dogs; Drug Therapy, Combination; Filaricides; Humans; Imidazoles; Macrolides; Neonicotinoids; Nitro Compounds; Treatment Outcome

In the past decade reports of canine subcutaneous dirofilariosis, caused by the mosquito-transmitted nematode Dirofilaria repens, increased in number in several countries in Europe, along with a rise of human cases. Given the merit to the new approaches for the control and treatment of this infection, the present study evaluated the efficacy of a single application of the spot-on formulation containing imidacloprid 10%/moxidectin 2.5% (Advocate(®), Bayer Animal Health) in the elimination of D. repens microfilariaemia in naturally infected dogs. In September 2009, 18 dogs with a natural infection by D. repens were enrolled in the study. In October 2009 all the dogs were treated once with Advocate(®) and the presence/absence of circulating MF and skin lesions after treatment was evaluated monthly until April 2010. From November 2009 to April 2010 15 dogs scored negative for D. repens while one dog remained negative till March 2010 when it died. Two dogs had a recurrence of microfilariaemia in December 2009 and January 2010 respectively. Nine infected dogs showed skin lesions at the beginning of the trial, which disappeared after treatment in 7 dogs, whereas the other two symptomatic dogs did not show any dermatological improvement until the end of the trial even though they scored negative for D. repens microfilariae. This study demonstrated that a single dermal administration of Advocate(®) is effective in eliminating microfilariae of D. repens and likely has a certain degree of activity in killing subcutaneous adult worms as well. This study demonstrates the efficacy of Advocate(®) in the treatment of dermatitis caused by D. repens. Also, these results are of importance towards further control programs aiming to reduce the number of bites infectious for mosquitoes and the risk of infection for both humans and dogs.

Topics: Administration, Topical; Animals; Dirofilaria; Dirofilariasis; Dogs; Drug Administration Schedule; Filaricides; Imidazoles; Macrolides; Neonicotinoids; Nitro Compounds; Skin Diseases, Parasitic

Three separate randomized, blinded, vehicle-controlled studies were conducted to determine the effectiveness of a single treatment and consecutive monthly treatments of a combination flavored tablet product containing spinosad and milbemycin oxime (MBO) in the prevention of the establishment of heartworm infections in dogs challenged with recent field isolates of the heartworm (HW), Dirofilaria immitis. For each study, dogs were allocated randomly based on pre-treatment body weights to treated or control groups of 10 animals each. Dogs were infected once with infective HW larvae, on Day-30, using either a Michigan isolate or a Georgia (MP3) isolate of D. immitis. Treatments of beef-flavored chewable tablets were administered in two studies one time either on Day 0 or Day 15, and in one study twice (Days 0 and 30, or Days 15 and 45) or 3 times (Days 0, 30 and 60). For the combination product groups, dosages were in the range of 30-45 mg/kg (13.6-20.5mg/lb) for spinosad and 0.5-0.75 mg/kg (0.2-0.34 mg/lb) for MBO. Necropsies for heartworm counts were completed following euthanasia on Day 120 or Day 123. A single treatment with the combination product of spinosad and MBO 30 or 45 days post-inoculation with infective HW larvae was completely effective (100%) in preventing establishment of the Michigan D. immitis isolate, but efficacy against the Georgia MP3 isolate was incomplete, with geometric mean reductions in HW counts relative to vehicle treated controls of 99% reduction of the 30 day infection and a 98.9% reduction of the 45 day old infection. Against this same MP3 isolate, 3 consecutive monthly treatments provided complete prevention (100%) against establishment of D. immitis infections. The combination product of spinosad and MBO provides effective control of canine heartworms. A single treatment at 30 days post infection showed high but incomplete effectiveness against a heartworm isolate that had been shown to be partially refractory to treatment with marketed monthly heartworm preventives. Three consecutive monthly treatments provided complete control, providing support to the recommendation that heartworm prophylaxis should be maintained year round for optimal effectiveness.

Topics: Administration, Oral; Animals; Dirofilariasis; Dog Diseases; Dogs; Drug Administration Schedule; Drug Combinations; Female; Macrolides; Male

The objective of this GCP-compliant clinical field study was to evaluate the efficacy of the combination of moxidectin (minimum dose of 2.5 mg/kg body weight) and imidacloprid (minimum dose of 10.0 mg/kg body weight) spot-on (Advocate(®)) as a preventive and therapeutic treatment of natural infection by Dirofilaria repens in dogs in the Czech Republic.There were two arms of the study, both negatively controlled. 34 animals were randomly allocated to two groups of the treatment arm; 90 negative animals were randomly allocated to the prevention arm groups. All enrolled dogs were observed physically and blood was sampled monthly for Dirofilaria repens microfilaria counts for 18 months by modified Knott test and PCR. 34 dogs were positive for microfilaria and enrolled in the treatment arm of this study (treated: 18, untreated: 16). The reduction of the log-transformed microfilaria counts was significantly higher in the treatment group on day 28 (p = 0.007), 56, 84 and 112 (p < 0.001). All animals treated were negative after a single treatment. In the untreated control group 93.75 % remained positive (p < 0.001). 87 dogs were negative for microfilaria prior to allocation to the "preventive" arm (treated: 49; untreated: 38; 3 excluded). One dog in the untreated control group became positive for Dirofliaria repens microfilaria, while none of the treated dogs became positive. Advocate(®) was effective in the treatment of dogs infected with microfilaria of Dirofilaria repens. Due to the low rate of natural infections the preventive efficacy could not be proven, but no dog treated became positive.

Topics: Animals; Dirofilaria; Dirofilariasis; Dog Diseases; Dogs; Drug Combinations; Drug Evaluation; Filaricides; Imidazoles; Macrolides; Neonicotinoids; Nitro Compounds

The purpose of this study was to assess the efficacy of moxidectin sustained release injectable for dogs (moxidectin SR, Fort Dodge Animal Health) in protecting growing puppies from experimental infection with the heartworm, Dirofilaria immitis, six months after treatment. The study involved 27 puppies, approximately 12 weeks of age at the beginning of the study, with nine puppies in each of three size classes. The small breed class included eight Pekingese and one purpose-bred small breed mongrel; the medium breed class included nine purpose-bred mongrels, and the large breed class included nine puppies with an anticipated adult weight >or=30-35 kg. Both genders were included with no attempt made to have equal numbers of male and female puppies. Puppies were blocked by weight within each size class and randomly assigned to three treatment groups of nine dogs. On Day 0, pups in two groups were injected subcutaneously with moxidectin SR, dosed to deliver 0.17 mg moxidectin/kg b.w. The third group was injected with sterile saline. Personnel making observations were blinded to the treatment status of the animals. Following treatment, puppies were observed for signs of adverse local and systemic reactions. Puppy weights and serum moxidectin levels were also monitored. On Day 180, puppies in all treatment groups were inoculated subcutaneously with 50 third-stage larvae of D. immitis. On Days 348 and 349, puppies were euthanatized and necropsied. Hearts and lungs were examined for adult heartworms. All animals in the saline control group were infected with an arithmetic mean of 39.22 adult heartworms each. Seventeen of 18 dogs in the moxidectin SR-treated groups were uninfected. One treated puppy was infected with a single adult heartworm. This infected individual was from the large breed size class and had the second highest percent increase in body weight. Based on arithmetic means, the heartworm recovery from all treated puppies represents a 99.86% reduction relative to the saline control. There were no adverse local or systemic reactions to treatment in any animal.

Topics: Animals; Body Weight; Delayed-Action Preparations; Dirofilaria immitis; Dirofilariasis; Dog Diseases; Dogs; Female; Filaricides; Injections, Subcutaneous; Macrolides; Male; Treatment Outcome

A study was conducted to evaluate the safety of a commercial formulation of moxidectin sustained-release injectable for dogs (ProHeart 6, Fort Dodge Animal Health) administered as a single subcutaneous dose to 10-week-old puppies. Twelve male and 12 female purpose-bred beagles 10 weeks of age were blocked by weight within gender and randomly allocated to three treatment groups. Puppies in two groups were treated with moxidectin sustained-release injectable for dogs at three or five times the labeled dose rate of 0.17 mg moxidectin/kg. The third group was treated with saline solution as controls. Physical and neurologic status, hematologic parameters, clinical chemistries, urine samples, body weight, and food consumption were evaluated before and up to 12 weeks after treatment. When compared to controls, mild depression of erythropoiesis, characterized by reduced hemoglobin, reticulocytes, erythrocytes, and hematocrit, was noted in puppies treated with five times the label dose of moxidectin sustained-release injectable. Values for these parameters remained within normal ranges and increased during the study, but at a reduced rate relative to saline-treated controls. Other parameters evaluated remained within normal limits for all treatment groups. Based on results of this study, the no observed adverse effect level for moxidectin sustained-release injectable (ProHeart 6) treatment in 10-week-old puppies was determined to be three times the recommended rate.

Topics: Animals; Delayed-Action Preparations; Dirofilaria immitis; Dirofilariasis; Dog Diseases; Dogs; Female; Filaricides; Injections, Subcutaneous; Macrolides; Male; No-Observed-Adverse-Effect Level; Safety; Treatment Outcome

A topically applied formulation containing 10% imidacloprid+1% moxidectin (Advocate/Advantage multi) has been developed for monthly application to cats for the prevention of feline heartworm (HW) disease caused by Dirofilaria immitis; and for the treatment and control of flea infestations, ear mite infestations, and intestinal nematode infections. A study model was designed to evaluate the safety of this product in cats harboring adult D. immitis infections. Eighty adult cats (40 males/40 females) were each inoculated with 60 third-stage D. immitis larvae on test day (TD) 1. On TD 243-245 echocardiographic imaging was performed on each cat to confirm and estimate the number of adult D. immitis residing in the cardiovascular system. A total of 35 cats were subsequently eligible for safety evaluation based on inclusion criteria. Four treatment groups were established and randomly selected for treatment: imidacloprid+moxidectin solution at the label dose (n=9) (group 1), imidacloprid+moxidectin solution at 5x the Iabel dose (n=9) (group 2), 6% selamectin topical solution (Revolution) at the label dose (positive control, n=8) (group 3), and topical treatment with placebo (negative control, n=9) (group 4). All cats were treated on TD 250. Treatments for groups 1, 3, and 4 were repeated on TDs 278 and 306. Group 2 cats were euthanized and examined for adult D. immitis on TD 288. All other cats were euthanized and examined for adult D. immitis on TD 334. No adverse events attributable to treatment with the test articles were observed during the study. The geometric mean numbers of adult D. immitis recovered at necropsy from treatment groups 1-4 were 2.9, 3.2., 4.0, and 2.7, respectively. There were no statistically significant differences in the comparison of adult D. immitis recovered at necropsy (ANOVA overall group effect P-value of 0.5356). The results of this study demonstrate that imidacloprid+moxidectin topical solution can be used safely in cats heavily infected with adult D. immitis.

Topics: Animals; Anthelmintics; Cat Diseases; Cats; Dirofilaria immitis; Dirofilariasis; Drug Therapy, Combination; Female; Imidazoles; Ivermectin; Macrolides; Male; Neonicotinoids; Nitro Compounds

A topically applied formulation containing 10% imidacloprid+2.5% moxidectin (Advocate/Advantage multi) has been developed for monthly application to dogs for the prevention of canine heartworm (HW) disease caused by Dirofilaria immitis; and for the treatment and control of flea infestations, mite infestations, and intestinal nematode infections. The efficacy of this formulation to prevent canine HW disease was confirmed at three study locations which included the use of 88 purpose-bred beagles 6-8 months of age. Two of these studies also evaluated the effects of post-treatment water exposure or shampooing on product performance. Each dog was infected with 50 third-stage D. immitis larvae on test days -30 to -45. Dogs were blocked according to gender and body weight on test day -1. Topically applied test articles were administered once on test day 0 as follows: 10% imidacloprid+2.5% moxidectin (52 dogs); 2.5% moxidectin mono solution (eight dogs); 10% imidacloprid mono solution (16 dogs); and placebo solution (12 dogs). Treatment dosages were applied to provide a minimum of 10 mg/kg imidacloprid and/or 2.5 mg/kg moxidectin. Subgroups of dogs were exposed to water to simulate swimming/rain exposure at designated post-treatment intervals. Additional dogs were shampooed at 90 min, 4 h, or 24 h post-treatment. All dogs were necropsied 110-119 days post-treatment for recovery of adult D. immitis. No adult D. immitis were recovered at necropsy from any of the dogs receiving 10% imidacloprid+2.5% moxidectin or 2.5% moxidectin mono solution, demonstrating 100% efficacy for prevention of D. immitis infection. A total of 701 adult D. immitis were recovered at necropsy from dogs receiving 10% imidacloprid mono solution or placebo (range of 11-40 D. immitis/dog). The efficacy of 10% imidacloprid+2.5% moxidectin treatment for the prevention of HW disease was not decreased when dogs were shampooed as early as 90 min post-treatment, or when dogs immersed in water 5 times post-treatment at weekly intervals.

Topics: Administration, Topical; Animals; Anthelmintics; Baths; Dirofilaria immitis; Dirofilariasis; Dog Diseases; Dogs; Drug Therapy, Combination; Female; Imidazoles; Macrolides; Male; Neonicotinoids; Nitro Compounds

Topics: Animals; Delayed-Action Preparations; Dirofilariasis; Dog Diseases; Dogs; Female; Filaricides; Injections, Subcutaneous; Macrolides; Male; Treatment Outcome

Topics: Administration, Topical; Animals; Cat Diseases; Cats; Dirofilaria immitis; Dirofilariasis; Drug Therapy, Combination; Ectoparasitic Infestations; Imidazoles; Insecticides; Macrolides; Neonicotinoids; Nitro Compounds; Siphonaptera; Treatment Outcome

The authors report the efficacy of an injectable, moxidectin sustained release (SR) formulation for the prevention of canine heartworm infection in endemic areas in northern and central Italy. Three field trials were carried out on a total of 324 dogs. Two hundred forty-three dogs were treated with moxidectin SR 6 months apart and 81 dogs (positive controls) with moxidectin tablets given monthly for 5 consecutive months during the risk season each year throughout the study. Results of testing for microfilariae and circulating adult female antigens were negative for all the experimentally treated dogs at the 6, 7, 11 and 19 months after the last injection. No adverse reactions to moxidectin SR were observed but a moderate pain at palpation and swelling (5-6 cm) at the injection site after the first treatment. In the study areas, prevalence of Dirofilaria immitis infection calculated by testing dogs which had no preventive treatment in the previous transmission season ranged from 33 to 63%. This study confirms the efficacy and safety of injectable, moxidectin SR formulation in the prevention of heartworm infection in dogs and demonstrates that the prophylactic efficacy lasts for the full season and strongly suggests that the product gives 1-year protection.

Topics: Administration, Oral; Animals; Anthelmintics; Anti-Bacterial Agents; Antigens, Helminth; Delayed-Action Preparations; Dirofilaria immitis; Dirofilariasis; Dog Diseases; Dogs; Endemic Diseases; Female; Injections, Subcutaneous; Italy; Macrolides; Male; Microfilariae; Microspheres

Topics: Administration, Oral; Animals; Anti-Bacterial Agents; Antinematodal Agents; Dirofilariasis; Dog Diseases; Dogs; Female; Larva; Macrolides; Male; Skin Diseases, Parasitic

The response to heartworm infection before preventative programs were started was investigated in 56 dogs. Dogs were infected with third-stage larvae of Dirofilaria immitis and started on preventative programs (monthly treatment) with ivermectin/pyrantel pamoate (IVM/PP) or milbemycin oxime (MO) 3.5, 4.5, 5.5, or 6.5 months after infection. Each time period comprised a group of six dogs treated with IVM/PP and six treated with MO. Thoracic radiographs were obtained prior to infection, at the start of preventative treatment, and at regular intervals until dogs were necropsied 1 year after the preventative was started. All dogs developed radiographic signs of heartworm disease, and all had heartworm-related arterial changes at necropsy. From Day 210 to 330, interstitial lung disease was less severe in dogs started on MO 3.5 months after infection than in dogs given IVM/PP at the same time. Arterial surfaces were more severe at necropsy in the dogs started on MO at 4.5 months than in the dogs started on IVM/PP at the same time. There was increased caudal lobar arterial and interstitial disease in the dogs treated with IVM/PP compared with dogs treated with MO; this was attributed to the death of young worms within the caudal pulmonary arteries. Dogs started on either preventative at 5.5 and 6.5 months after infection had radiographic changes and necropsy evaluations that were similar to those of untreated controls. This study reinforces the recommendation of the American Heartworm Society that mature dogs be evaluated for infection prior to starting a monthly preventative and that any dog that tests positive by a heartworm antigen test receive treatment with an adulticide prior to starting a heartworm preventative program.

Topics: Animals; Anthelmintics; Dirofilaria immitis; Dirofilariasis; Dog Diseases; Dogs; Female; Ivermectin; Lung; Macrolides; Male; Myocardium

The authors report the efficacy of orally administered moxidectin for the prevention of canine heartworm infection in two endemic areas in northern Italy. Two trials were conducted on a total of 257 dogs, including 137 treated with moxidectin (minimum dose of 3 mcg/kg body weight), 85 with ivermectin (minimum dose 6.6 mcg/kg b.w.) and 35 untreated controls. Results of testing for microfilariae and circulating adult female antigens were negative for all treated dogs at the end of both trials. No adverse reactions to moxidectin were observed. In the study areas, prevalence values for Dirofilaria immitis infection calculated on the basis of the untreated controls and testing dogs which had no preventive treatment in the previous transmission season ranged 23-65%. This study confirms the efficacy and safety of moxidectin in the prevention of adult heartworm infection in dogs.

Topics: Animals; Anti-Bacterial Agents; Antigens, Helminth; Dirofilaria immitis; Dirofilariasis; Dog Diseases; Dogs; Female; Filaricides; Italy; Ivermectin; Macrolides; Male; Microfilariae; Prevalence; Safety

A single dose (1 mg/kg) of milbemycin D was administered orally to 24 dogs with microfilaremia of Dirofilaria immitis, and the number of circulating microfilariae was counted weekly. The number was decreased by 3 to 8% of the pretreatment levels 1 week after the drug administration. The number remained relatively stable for the first 8 weeks and was gradually increased thereafter without returning to the pretreatment levels by 20 weeks. Three or 4 dogs each were euthanatized on day 1, and 1, 4, 8, 12, 16 and 20 weeks after the drug administration to examine the effects of the drug on intrauterine microfilariae and embryos of the worms. Although no intrauterine microfilariae were destroyed directly by the drug, degeneration and collapse of morular embryos and decrease in the number of intrauterine microfilariae were observed 12 after weeks the drug administration. These findings became more remarkable with time, and no intrauterine microfilariae developed in any worms by 20 weeks. The electron-microscopic findings revealed that the nucleoli of oocytes had a high density in the worms of 1, 4 and 8 week groups. Unequal size of cleavage cells and decrease of polysome number were noticed in the early-stage embryos after 8 weeks. It was assumed that the drug might have some effect on the chromosomes or genes in the germinal stem-cell of the heartworm and interfere with protein syntheses, resulting in inhibition of embryonic development. Twelve dogs were given milbemycin D (1 mg/kg) a total of 4 or 6 times monthly according to a prophylactic program.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Anthelmintics; Anti-Bacterial Agents; Blood; Cell Nucleolus; Dirofilaria immitis; Dirofilariasis; Dog Diseases; Dogs; Drug Administration Schedule; Embryo, Nonmammalian; Female; Macrolides; Oocytes; Reproduction; Uterus

Several studies in both experimentally and naturally infected dogs have reported the adulticide effect of a combination of macrocyclic lactones and doxycycline against Dirofilaria immitis, showing that these protocols can be used as an alternative to melarsomine. The present study evaluated the efficacy of oral, topical and extended-release injectable formulations of moxidectin when combined with doxycycline in dogs naturally infected with D. immitis from a shelter located in southern Italy.. Thirty dogs with naturally acquired D. immitis infection were divided in three groups (G) and treated with oral moxidectin (G1) once a month for 9 consecutive months, topical moxidectin (G2) once a month for 9 consecutive months or extended release moxidectin injectable (G3) at enrolment and again at 6 months (Day 180). All treatment groups received doxycycline for the first 30 days. Microfilarial concentrations in 1 ml (mff/ml) blood were determined monthly for 9 months with the modified Knott's test. A clinical scoring system was employed for each dog enrolled in the study based on thoracic radiography and cardiac ultrasound (CU) examinations performed at Day - 15 (before treatment) and at Day 180.. Results from the present study suggest that the majority of dogs from all treatment groups became antigen negative, as evaluated at Day 270: 9/10 dogs (90.0%) from G1, 6/10 dogs (60.0%) from G2 and 8/10 dogs (80.0%) from G3. Improvement of radiographic alterations was observed in all treatment groups, and almost all dogs were cleared of pulmonary abnormalities by 6 months from the beginning of treatment (P = 0.000). Cardiac ultrasound examination showed a progressive improvement of cardiac function in a limited number of animals (4/30).. The combination of doxycycline and three different formulations of moxidectin leads to antigen-negative status in naturally infected dogs.

Topics: Animals; Dirofilaria immitis; Dirofilariasis; Dog Diseases; Dogs; Doxycycline; Drug Therapy, Combination; Filaricides; Macrolides; Neonicotinoids; Nitro Compounds

Dirofilaria immitis, the mosquito-borne agent of dirofilariosis, a chronic and sometimes fatal cardiopulmonary canine disease, is endemic in most warm and temperate regions in the world. The efficacy of an oral endectoparasiticide product (test product or TP) combining moxidectin, afoxolaner, and pyrantel pamoate was evaluated for the prevention of heartworm disease in dogs, in two laboratory and one field studies. In each laboratory study, 20 D. immitis-naïve beagle dogs were experimentally infected with D. immitis. Ten control dogs were sham-treated, and ten dogs were administered the TP targeting the minimum effective dose, six times monthly and starting 30 days post infection. At necropsy seven months after inoculations, no heartworms were found in any of the TP treated dog, whereas 19 to 42 live heartworms were found in the control dogs. In each study, treatment efficacy was 100% and the difference between treated and untreated groups was highly significant (p < 0.0001). A field study was conducted through the full transmission season in several heartworm-endemic regions of the United States. One hundred and twenty client-owned dogs that were negative for D. immitis at enrollment were administered twelve monthly oral doses of the TP at label dose. Blood tests for D. immitis antigen and modified Knott's tests for microfilariae remained negative through the full duration of the study, demonstrating that all dogs were protected from heartworm infection during the full transmission season. These studies demonstrated that TP administered monthly for at least six doses is effective at preventing dirofilariosis.

Topics: Animals; Dirofilaria immitis; Dirofilariasis; Dog Diseases; Dogs; Heart Diseases; Macrolides; Pyrantel Pamoate; United States

On Linosa Island, Italy, Dirofilaria immitis infection has been hyperendemic in dogs and seroprevalent among islanders. In 2020, we implemented a heartworm disease elimination program on Linosa Island. Of 54 dogs tested for D. immitis antigen and microfilariae, 28 had positive results and received treatment with oral doxycycline twice daily for 4 weeks plus topical imidacloprid/moxidectin monthly for 12 months. The 26 dogs with negative results received monthly topical imidacloprid/moxidectin as preventive. During month 1, the number of microfilaremic dogs was reduced by 76.5%. From month 2 on, all animals were microfilariae negative, and during months 3 to 9, the number of antigen-positive dogs decreased progressively. Treatment of positive dogs coupled with chemoprophylaxis for noninfected dogs was effective, protecting them from new infections. The elimination program reduced the risk for human infection, representing a One Health paradigm. Monitoring and chemoprophylaxis are advocated to maintain the status of heartworm disease-free area.

Topics: Animals; Dirofilaria immitis; Dirofilariasis; Dog Diseases; Dogs; Drug Therapy, Combination; Italy; Microfilariae

The aim of the current study was to understand how the canine heartworm disease preventive ProHeart® 12 (extended-release injectable moxidectin, PH 12), impacts heartworm preventive purchase compliance and veterinary practice revenue over time compared to monthly heartworm disease preventives. This was a preliminary observational purchase compliance and revenue study based on a retrospective review of transaction data from 4,615 general practices across the United States. The review period was from September 2018 to August 2020. Anonymous transaction records of over 13 million canine patients were analyzed. Of these, only 3.5 million (25.7%) patients purchased any heartworm preventive, as has been presented in other studies. Practices that implemented PH 12 demonstrated the most growth in canine heartworm prevention revenue, patients, and patient compliance levels during the 12-month observation period, compared to previous year. These practices saw year over year growth in percent patients receiving heartworm protection, as well as 10% and 15% growth in the proportion of preventive patients compliant for more than 6 months and 12 months respectively. In contrast, practices that did not bring on PH 12 and only dispensed monthly heartworm preventives saw a decline in the proportion of canine preventive patients that were compliant for more than 6 months. Similarly, PH 12 practices experienced 15% growth in preventive revenue, and practices that did not bring on PH 12 only experienced 3.9% growth in preventive revenue. PH 12 was single-handedly responsible for all growth in patients compliant for more than 6 months in this study. Growth in protection of canine patients with PH 12 proves a helpful tool where mitigation strategies have thus far failed to curb increasing canine heartworm disease prevalence in the US.

Topics: Animals; Dirofilaria immitis; Dirofilariasis; Dog Diseases; Dogs; Filaricides; Macrolides; Patient Compliance; United States

This prospective case series evaluated the adulticidal efficacy of topical 10 % moxidectin/2.5 % imidacloprid (M/I; Advantage Multi®, Bayer, Shawnee Mission, KS, USA) and doxycycline in dogs with naturally occurring heartworm infection (HWI). Twenty-two dogs with HWI whose owners declined melarsomine were treated with M/I at the preventive dosage twice monthly for 90 days then monthly thereafter and doxycycline (median [interquartile range; IQR] dosage 12.6 [12.0-16.1] mg/kg/day) for the first 15 days. Although strict activity restriction was not imposed, owners were asked to prevent their dogs from exercising strenuously. This protocol was referred to as the MOXY protocol. Antigen testing was performed every 30-60 days, until dogs had 'no antigen detected' (NAD). Twenty-one of the 22 dogs ultimately converted to NAD by 434 days (median [IQR]), 234 (179-303). One dog remained positive 701 days after MOXY initiation and was considered a treatment failure. All sera which converted to NAD on HW antigen testing were retested after heat-treatment. Twelve dogs had NAD on the heat-treated test on the same day as having their first NAD on the conventional test. Six of 9 dogs testing positive after heat-treatment were retested and all 6 had NAD on a heat-treated test within 2-3 months. Microfilaremia was cleared in all 8 dogs re-tested. Four dogs required treatment for cough, thought due to heartworm (HW) death, an average of 89 days after initiation of MOXY. This cough was most likely due to pneumonitis with heartworm-pulmonary thromboembolism. One dog required hospitalization for 24 -h and recovered fully with corticosteroid therapy and supportive care and 2 dogs were treated in an outpatient fashion with steroids. The MOXY protocol was tolerated and 96 % (21/22) of dogs converted to NAD, though 2 dogs required greater than 1 year to achieve this result. Nonaresenical-adulticide therapy may result in pneumonitis and heartworm-pulmonary thromboembolism at unpredictable times, potentially months after initiation of macrocyclic lactone therapy and exercise restriction should be considered when using a nonarsenical protocol. Although not currently recommended by the American Heartworm Society (AHS), non-arsenical strategies are in use and the goal of this study was to evaluate the efficacy, duration of therapy, and safety of an accelerated dosing protocol of M/I with doxycycline.

Topics: Animals; Antinematodal Agents; Dirofilaria immitis; Dirofilariasis; Dog Diseases; Dogs; Doxycycline; Drug Therapy, Combination; Female; Macrolides; Male; Neonicotinoids; Nitro Compounds; Prospective Studies

Topics: Animals; Anorexia; Antidepressive Agents; Cat Diseases; Cats; Dermatitis; Dirofilaria; Dirofilariasis; Doxycycline; Florida; Insecticides; Macrolides; Male; Mirtazapine; Neonicotinoids; Nitro Compounds; Phylogeny; Skin Diseases, Parasitic

Canine heartworm disease (CHD) results from infection with Dirofilaria immitis and while it is of global concern, it is most prevalent in tropical climates where conditions support the parasite and vector life cycles. Melarsomine dihydrochloride is the sole treatment for CHD recommended by the American Heartworm Society. However, in cases where cost or access to melarsomine precludes treatment of an infected dog, therapeutic alternatives are warranted. This randomized, controlled field study evaluated the adulticidal efficacy of a combination therapeutic protocol using 10 % imidacloprid + 2.5 % moxidectin spot-on and a single 28-day course of doxycycline and compared with that of a 2-dose melarsomine dihydrochloride protocol. Of 37 naturally-infected domestic dogs with class 1, 2 or early class 3 CHD enrolled in the study, 30 were evaluated for a minimum of 12 months. Seven dogs were withdrawn due to canine ehrlichiosis, non-compliance, or wrongful inclusion. Dogs were randomly assigned to a control (CP, n = 15) or investigational (IVP, n = 15) treatment group. CP dogs received two injections of melarsomine dihydrochloride (2.5 mg/kg) 24 -hs apart and maintained on monthly ivermectin/pyrantel. IVP dogs were treated with oral doxycycline (10 mg/kg twice daily for 28 days) and topical 10 % imidacloprid + 2.5 % moxidectin once monthly for 9 months. Dogs were evaluated up to 18 months - monthly for the first 9 months, then every 3 months. Parasiticidal efficacy was based on antigen status using the IDEXX PetChek® 34 Heartworm-PF Antigen test. By month 18, antigen was not detected in any study dog except one from the IVP group. One other IVP dog was persistently antigenemic and treated with melarsomine at month 12 according to the initial study protocol. Mean antigen concentration (based on optical density) decreased more rapidly in the CP group and by month 15 was 0.11 for the IVP and 0.07 for CP groups, with equivalent median concentrations (0.04) in both groups. Conversion following heat-treatment of antigen-negative samples occurred frequently and at similar rates in both treatment groups. Based on the bias of diagnostic tests towards detection of female worms, we conclude that monthly application of 10 % imidacloprid + 2.5 % moxidectin for 9 months combined with a course of doxycycline twice daily for 28 days resulted in effective therapy against female adults in CHD. This therapeutic option may be particularly useful in cases where financial constraint o

Topics: Animals; Dirofilaria immitis; Dirofilariasis; Dog Diseases; Dogs; Doxycycline; Drug Therapy, Combination; Female; Filaricides; Grenada; Macrolides; Neonicotinoids; Nitro Compounds

Dirofilaria immitis is a life-threatening nematode spreading globally. Arsenical treatment is currently recommended for removal of adult worms. However, arsenical treatment is not available in some countries, and there are dogs that cannot tolerate the rapid kill of adult worms; therefore, alternative adulticide slow-kill treatments are needed. Criticisms against the use of these alternative protocols include the potential for allowing disease to progress and for the development of ML-resistant worms.. At enrollment, all dogs were positive for D. immitis antigen and 18 were microfilaremic. On day 30, microfilaremia counts decreased, and all dogs became amicrofilaremic by day 150. On day 180, 11 dogs were antigen-negative, and 7 more became negative by day 360. The two remaining antigen-positive dogs converted to negative by day 540 or 810. All antigen tests performed 180 days after the first negative test were negative. There was no decline in cardiac performance of the dogs throughout the study. Overall, pulmonary clinical conditions, presence of worms by echocardiography, and enlargement of caudal and main pulmonary arteries improved after treatment. Physical examinations, complete blood count results, and clinical chemistry profiles were within normal reference values. Respiratory conditions were improved, no damage to the heart was observed, and the treatment protocol was well tolerated by the animals.. This alternative adulticide treatment was efficacious and well tolerated in naturally infected dogs. The injectable formulation provides the advantage of having veterinarians able to administer, monitor, and assess the efficacy and condition of the dog throughout the treatment and post-treatment periods.

Topics: Administration, Oral; Animals; Anthelmintics; Antigens, Helminth; Dirofilaria immitis; Dirofilariasis; Dog Diseases; Dogs; Doxycycline; Drug Therapy, Combination; Filaricides; Injections, Subcutaneous; Macrolides; Microfilariae

Moxidectin has previously shown limited efficacy (≤ 44.4%) against confirmed macrocyclic lactone (ML)-resistant Dirofilaria immitis strains at 3 µg/kg after single and multiple oral dosages. Three studies were conducted to evaluate higher oral moxidectin doses for efficacy against confirmed ML-resistant D. immitis strains.. Dogs were inoculated with 50 D. immitis L3 and randomly allocated to treatments. Study 1: 6 groups of dogs (n = 8) were inoculated with JYD-34 (Day - 30) and treated as follows: T01, negative control; T02-T05, moxidectin at 3, 6, 12 or 24 µg/kg, respectively, on Day 0 only; T06, moxidectin at 3 µg/kg on Days 0, 30 and 60. Study 2: 10 groups of dogs (n = 5) were inoculated (Day - 30) with either JYD-34 (T01, T03-05) or ZoeLA (T02, T06-T10) and treated as follows: T01 and T02, negative controls; T03-T05, moxidectin at 24, 40 or 60 µg/kg, respectively, on Days 0, 28 and 56; T06 and T09, moxidectin at 3 or 60 µg/kg on Day 0 only; T07, T08 and T10, moxidectin at 24, 40 or 60 µg/kg, respectively, on Days 0, 28 and 56. Study 3: 5 groups of dogs (n = 5) were inoculated with ZoeMO (Day - 28) and treated as follows: T01, negative control; T02, moxidectin at 3 µg/kg moxidectin on Day 0 only; T03-T05, moxidectin at 24, 40 or 60 µg/kg, respectively, on Days 0, 28 and 56. All dogs were necropsied for adult heartworm recovery ~ 4-5 months post-inoculation.. All moxidectin-treated dogs showed significantly lower worm counts than controls. The efficacy of moxidectin administered once at 3 µg/kg was 19% (JYD-34), 44.4% (ZoeLA) and 82.1% (ZoeMO). Increasing both the dose and the number of dosages of moxidectin improved efficacy, with 100% protection obtained using three dosages of moxidectin at either 40 µg/kg (JYD-34, ZoeMO) or 60 µg/kg (ZoeLA). Three dosages of 24 µg/kg were also highly effective, providing ≥ 98.8% efficacy for all three strains.. Increasing both the dose and number of consecutive monthly dosages of moxidectin improved the efficacy against ML-resistant heartworms. Based on these data and other technical considerations, the 24 µg/kg dose was considered the optimal dose for further commercial development.

Topics: Administration, Oral; Animals; Antinematodal Agents; Chemoprevention; Dirofilaria immitis; Dirofilariasis; Dog Diseases; Dogs; Dose-Response Relationship, Drug; Macrolides; Parasite Load; Treatment Outcome

Dirofilaria immitis and D. repens are vector-borne parasites of dogs and cats, with zoonotic potential, endemic in many parts of Europe, including Italy. Control and prevention of dirofilariosis are essential points to reduce their diffusion in animals and humans and veterinarians are the main subjects involved in this "battle". With the aim to better understand current practice by veterinarians, an online questionnaire on different aspects of D. immitis and D. repens was sent to companion animal veterinary facilities registered with the Italian Veterinary chamber. The overall response rate was 25%. Approximately 47% had diagnosed at least one case of Dirofilaria spp. in dogs in the last year and approximately 6% had diagnosed at least one case of Dirofilaria spp. in cats. Of the 662 facilities surveyed, 83.8% used serology to diagnose heartworm infection. For the diagnosis of D. repens infection in dogs and cats, a high percentage of facilities relied on an external laboratory. Most recommended beginning prevention of canine heartworm disease in April-May. Topical and injectable moxidectin and oral ivermectin were the two most commonly used preventives for D. immitis in dogs. The drug most commonly used for heartworm adulticide treatment in dogs was melarsomine. This study show that veterinary facilities ians working in an endemic area for D. immitis and D. repens are aware of recent developments in adulticide therapy. Results would suggest however that diagnosis is not always carried out according to what is currently recommended by international guidelines and that the timing for starting prevention may not be optimal.

Topics: Animals; Antinematodal Agents; Cat Diseases; Cats; Dirofilaria immitis; Dirofilaria repens; Dirofilariasis; Dog Diseases; Dogs; Hospitals, Animal; Italy; Ivermectin; Macrolides; Mosquito Vectors; Surveys and Questionnaires; Veterinarians

The efficacy of an extended-release injectable moxidectin (0.5 mg/kg) suspension (ProHeart® 12) (PH 12) in preventing the development of Dirofilaria immitis in dogs for 12 months was investigated in laboratory and field studies in the USA.. In each of two laboratory studies, 20 dogs ≥ 12 months of age were randomly allocated to receive a subcutaneous injection of saline or PH 12 on Day 0 and were then inoculated with 50 D. immitis third-stage larvae (L. PH 12 was 100% effective in preventing HW disease in all three of these studies. In the laboratory studies, no PH 12-treated dogs had any adult HWs, whereas all control dogs in both studies had adult HWs [geometric mean, 30.2 (range, 22-37) for Study 1 and 32.6 (22-44) for Study 2]. In the field study, all dogs treated with PH 12 tested negative for adult HW infection on all test days (Days, 365, 480 and 605), whereas four dogs receiving HG Plus (positive control) tested positive for HWs during the study (three dogs on Day 365 and one dog on Day 480). All four dogs treated with HG Plus that subsequently tested positive for HWs during the field study were from the lower Mississippi River Valley region, where HW resistance to macrocyclic lactone preventives has been confirmed to occur. PH 12 was significantly better than HG Plus in preventing heartworm disease in the field study (P = 0.0367). PH 12 was well-tolerated in both laboratory and field studies.. A single dose of ProHeart® 12 was 100% effective in preventing heartworm disease in dogs for a full year in both laboratory and field studies.

Topics: Animals; Delayed-Action Preparations; Dirofilaria immitis; Dirofilariasis; Dog Diseases; Dogs; Female; Filaricides; Hospitals, Animal; Injections, Subcutaneous; Macrolides; Male; Random Allocation; United States

Dirofilaria repens infection was diagnosed in a 5-year-old female German shepherd crossbreed, originally from Romania but brought into the UK in February 2014. The dog presented with conjunctivitis in March 2014 and then again 2 months later with additional ocular and nasal mucopurulent discharge. Bacterial cultures from the nasolacrimal duct were negative for bacterial growth. The case was referred in August 2014 for ophthalmic examination, which revealed abnormalities in both eyes, especially the left. They included mild palpebral conjunctival hyperaemia and marked follicular conjunctivitis, as well as a dorsonasal bulbar conjunctival mass. Serum biochemistry was unremarkable and a conjunctival biopsy taken from the dorsonasal bulbar conjunctival mass revealed eosinophilic/lymphoplasmacytic conjunctivitis. At re-examination, nematodes were found in the area of the previous biopsy site and in the ventral palpebral conjunctival fornix. Polymerase chain reaction and sequencing confirmed these to be D. repens. Treatment with 10% imidacloprid and 2·5% moxidectin (Advocate Spot-On) was successful, and clinical signs resolved over a 6-week period. This case report indicates that D. repens infection should be considered as a possible aetiological cause of ocular lesions in dogs in the UK, especially those with a history of foreign travel. Implications for establishment and spread of D. repens in the UK are discussed.

Topics: Animals; Antinematodal Agents; Biopsy; Conjunctival Diseases; Dirofilaria repens; Dirofilariasis; Dog Diseases; Dogs; Female; Macrolides; Neonicotinoids; Nitro Compounds; Polymerase Chain Reaction; Romania; Sequence Analysis, DNA; United Kingdom

The use of heat-treatment in canine and feline serum has been hypothesized to break the formation of antigen-antibody complexes, thereby freeing the heartworm antigen allowing for detection by commercially available heartworm antigen kits. While studies have analyzed the effect of heat-treating serum and plasma samples in the detection of heartworm antigen, these studies have not utilized necropsy verified results for validation. This study evaluated the use of heat-treating serum samples in experimentally infected dogs during adulticidal treatment in comparison with necropsy adult heartworm recovery.. As part of a primary study, a total of 16 dogs were experimentally infected with 16 sexually mature adult heartworms using surgical transplantation, allocating 8 dogs in both the control and treated group. Treated dogs received 10 months of topical administration of Advantage Multi® for Dogs (10% Imidacloprid + 2.5% Moxidectin) every 4 weeks and 30 days of 10 mg/kg doxycycline BID. Blood samples were collected from all study animals prior to surgical transplantation of adult heartworms, on study days 0, 1, 3, 7, 14, 21, 28, and every 4 weeks thereafter for the duration of this study. Concentration of heartworm antigen was tested using the DiroCHEK® heartworm antigen test kit using serum samples both pre- and post-heat-treatment. Serum samples were heat-treated at 103 °C in a dry heat block for 10 min and centrifuging at 1818× g for 20 min.. There were a total of 4 instances (days 56, 140, 224 and 252) in 3 treated dogs in which a serum sample converted from negative for the detection of heartworm antigen prior to heat-treatment to positive for the detection of heartworm antigen post-heat-treatment. At necropsy, these dogs had no adult heartworms recovered and were all negative on antigen testing prior to and after heat treatment. There was 100% accuracy in the detection of either no infection, or 1-2 adult heartworm infections using the DiroCHEK in serum samples with and without heat-treatment at the time of necropsy.. The DiroCHEK accurately diagnosed all dogs with live adults recovered at necropsy as heartworm antigen positive and all those dogs with no live adults recovered at necropsy as heartworm antigen negative without the use of heat-treatment for samples taken on the day of necropsy. Therefore, these results indicate that the use of heat-treating serum samples did not provide data of any additional value in the diagnosis of heartworm-positive dogs receiving treatment in this study. Additionally, these results may indicate that the conversion of serum samples from negative to positive for the presence of heartworm antigen with heat-treatment may not always accurately diagnose live adult heartworm infections since no adult heartworms were recovered at necropsy for those dogs in which a conversion event occurred. These conversion events may be detecting residual antigen leftover after all adult worms have died or may even be detecting off- target antigens, which have been denatured during heat-treatment. While a necropsy was not performed at the time of the conversion events, no live adult worms were recovered from any of the dogs in which a conversion event occurred earlier in treatment.

Topics: Animals; Antigens, Helminth; Dirofilaria immitis; Dirofilariasis; Dog Diseases; Dogs; Doxycycline; Drug Combinations; Drug Therapy, Combination; Female; Hot Temperature; Macrolides; Male; Neonicotinoids; Nitro Compounds

Fluralaner provides efficacy against feline ectoparasites following topical administration. Moxidectin is routinely used to treat gastrointestinal nematode infections and prevent heartworm disease caused by Dirofilaria immitis. Praziquantel is routinely used to treat feline tapeworm infections. The safety of a fluralaner plus moxidectin combination topical solution (Bravecto™ Plus, MSD Animal Health) was assessed when administered concurrently with a commercially available praziquantel topical solution (Droncit™ Spot-on, Bayer Animal Health GmbH). The highest dose rates in clinical use were tested.. Concurrent topical administration of a fluralaner plus moxidectin and a praziquantel product did not result in adverse findings. One out of ten cats receiving praziquantel only (control group), and two out of ten cats receiving fluralaner plus moxidectin and praziquantel (treatment group) had dandruff-like flakes in their coat at the application site. Two out of the ten control cats and three cats out of the ten treatment group cats had very small amounts of unidentified material (minute crusts or crumbs) at the application site which was only visible during close inspection.. The concurrent treatment of cats with fluralaner plus moxidectin and praziquantel at the maximum dose in clinical use was well tolerated.

Topics: Acaricides; Administration, Topical; Animals; Anthelmintics; Cat Diseases; Cats; Dirofilariasis; Drug Therapy, Combination; Ectoparasitic Infestations; Female; Insecticides; Isoxazoles; Macrolides; Male; Nematode Infections; Praziquantel; Random Allocation; Treatment Outcome

Considering the recent information on the increase of Dirofilaria immitis antigen detection by rapid assays in canine blood samples after heat treatment, the proposal that immune complexes block D. immitis antigen detection and that macrocyclic lactone + doxycycline (alternative protocol) might lead to increased production of those immune complexes, resulting in the erroneous diagnosis of adult worm elimination, and that there is no recommended adulticide marketed in Brazil, a study was performed to evaluate the interference of moxidectin + doxycycline (moxi-doxy) on diagnostic procedures when heartworm positive dogs are treated with this alternative protocol. Twenty-two naturally infected pet dogs were treated monthly with topical 10% imidacloprid + 2.5% moxidectin and with oral doxycycline (10 mg/kg BID/30 days) (moxi-doxy). All the dogs had their microfilaremia level determined prior to the first day of treatment, and were tested every 6 months for microfilariae (Mf) detection prior to heating, and for antigen detection prior to and after heating, the sample.. The results indicate that the treatment protocol can eliminate adult heartworms as early as 6 months after the first dose, especially in low microfilaremic dogs (< 300 Mf/ml). In this study, all dogs were free of heartworm antigen after 18-24 months of treatment. In a comparison of pre-heated samples and non-heated samples, sample pre-heating increased antigen detection sensitivity, and non-heated samples tended to be antigen-negative earlier than the pre-heated samples, especially when dogs had low microfilaremia levels. These discrepancies were not present in a subsequent sample of the same dog 6 months later.. Two negative antigen test results 6 months apart can be recommended as the criterion to consider when a dog has been cleared of infection. The initial microfilaremia level of a dog can be used to estimate the necessary time frame to end the treatment period.

Topics: Animals; Antigens, Helminth; Brazil; Dirofilariasis; Dog Diseases; Dogs; Doxycycline; Drug Therapy, Combination; Filaricides; Hot Temperature; Macrolides; Microfilariae; Neonicotinoids; Nitro Compounds; Specimen Handling; Treatment Outcome

Anecdotal reports support the position that the adulticidal heartworm treatment utilizing doxycycline and Advantage Multi®/Advocate® for Dogs (10% imidacloprid + 2.5% moxidectin) has successfully converted antigen-positive dogs to antigen-negative. To date, no controlled experimental studies have demonstrated the adulticidal efficacy of this treatment regimen. The aim of this study was to evaluate the parasitological and clinical efficacy of Advantage Multi® for Dogs (IMD + MOX) and doxycycline in heartworm-infected beagles.. This study utilized 16 dogs, 8 dogs in each of non-treated control and treated groups. A total of 16 adult Dirofilaria immitis (Missouri strain) were surgically transplanted into the jugular vein of each study dog. The treatment regimen of monthly IMD + MOX topically (per labeled dosage and administration) for 10 months and 10 mg/kg doxycycline BID orally for 30 days was initiated 30 days post-surgical transplant. Echocardiograms, radiographs, complete blood counts, clinical chemistry profiles, heartworm antigenemia and microfilaremia were evaluated every 4 weeks. Serum samples were assayed for heartworm antigen using the DiroCHEK® heartworm antigen test. The DiroCHEK® was performed according to the manufacturer's recommendations and read using a spectrophotometer at 490 nm.. All dogs tested positive for the presence of heartworm antigen post-surgical transplant and prior to treatment. Heartworm antigen levels began declining in treated dogs 3 months post-treatment. Non-treated control dogs remained antigen-positive. No microfilariae were detected in treated dogs after 21 days post-treatment. At necropsy, adult heartworms were recovered from all non-treated control dogs with a range of 10-12 adult worms/dog for an average recovery of 10.6 adult heartworms/dog. In the IMD + MOX- and doxycycline-treated dogs, the range of adult heartworms recovered was 0-2 adult worms/dog, with five dogs having no adult heartworms present. The average adult heartworm recovery was 0.6/dog in the treated group. This treatment regimen demonstrated a 95.9% efficacy in eliminating adult heartworms (P < 0.0001).. This study demonstrated that this treatment regimen successfully eliminated D. immitis microfilariae by 21 days post-treatment, reduced heartworm antigen concentration over time, and had a 95.9% efficacy in the elimination of mature adult heartworms. Based on this study, we conclude that this treatment regimen is a relatively quick, reliable and safe option to treat canine heartworm infection as compared to other treatment regimens involving macrocyclic lactones, when the approved drug melarsomine dihydrochloride is unavailable, contraindicated or declined by an owner unable to afford the more costly treatment or concerned about the potential side effects.

Topics: Administration, Topical; Animals; Antigens, Helminth; Dirofilaria immitis; Dirofilariasis; Dog Diseases; Dogs; Doxycycline; Drug Therapy, Combination; Filaricides; Macrolides; Microfilariae; Neonicotinoids; Nitro Compounds; Treatment Outcome

Monthly topical and sustained-release injectable formulations of moxidectin are currently marketed; however, an oral formulation, while approved at a dose of 3 μg/kg, is not currently marketed in the United States. Although resistance of heartworms to all macrocyclic lactone (ML) heartworm preventives (ivermectin, milbemycin, selamectin and moxidectin) has been demonstrated, to date no data have been reported on the effectiveness of oral moxidectin against recent isolates of Dirofilaria immitis.. A total of nine studies were conducted to determine the efficacy of moxidectin against a range of older and recently sourced heartworm isolates. Dogs (groups of three to eight) were inoculated with 50 D. immitis infective larvae (L3) from nine different isolates (MP3, Michigan, JYD-34, ZoeMO-2012, ZoeKy-2013, ZoeLA-2013, GCFL-2014, AMAL-2014 and ZoeAL-2015) and treated 28-30 days later with single oral doses of 3 μg/kg of moxidectin. Additionally, one group of dogs that was inoculated with JYD-34 was treated monthly for 3 consecutive months beginning 30 days post inoculation. Dogs were held for approximately 4 months after the initial (or only) treatment and then necropsied for recovery of adult heartworms.. A single dose of 3 μg/kg of moxidectin was 100% effective in preventing the development of five of nine heartworm isolates (MP3, Michigan, ZoeKy, GCFL and ZoeAL isolates), confirming their susceptibility to oral moxidectin at this dose. MP3 and Michigan are isolates sourced from the field more than 9 years ago, while ZoeKy, ZoeAL and GCFL were isolated from the field within the past 2 to 3 years. Against JYD-34, ZoeMO, ZoeLA and AMAL isolates, a single dose of 3 μg/kg of moxidectin was not completely effective, with efficacies of 19%, 82%, 54% and 62%, respectively, demonstrating resistance of these heartworm isolates to oral moxidectin at this dosage. Three consecutive monthly doses of 3 μg/kg of moxidectin were also incompletely effective against the JYD-34 isolate, with an efficacy of 44%. JYD-34 was originally isolated in 2010, while ZoeMO, ZoeLA and AMAL were isolated within the past 2 to 3 years.. A single oral dose (3 μg/mg) of moxidectin was 100% effective in preventing the development of ML-susceptible heartworm isolates while being incompletely effective against ML-resistant isolates.

Topics: Animals; Dirofilaria immitis; Dirofilariasis; Dog Diseases; Dogs; Drug Evaluation; Drug Resistance; Filaricides; Macrolides

Initial studies of heartworm preventive drugs all yielded an observed efficacy of 100% with a single dose, and based on these data the US Food and Drug Administration (FDA) required all products to meet this standard for approval. Those initial studies, however, were based on just a few strains of parasites, and therefore were not representative of the full assortment of circulating biotypes. This issue has come to light in recent years, where it has become common for studies to yield less than 100% efficacy. This has changed the landscape for the testing of new products because heartworm efficacy studies lack the statistical power to conclude that finding zero worms is different from finding a few worms.. To address this issue, we developed a novel statistical model, based on a hierarchical modeling and parametric bootstrap approach that provides new insights to assess multiple sources of variability encountered in heartworm drug efficacy studies. Using the newly established metrics we performed both data simulations and analyzed actual experimental data.. Our results suggest that an important source of modeling variability arises from variability in the parasite establishment rate between dogs; not accounting for this can overestimate the efficacy in more than 40% of cases. We provide strong evidence that ZoeMo-2012 and JYD-34, which both were established from the same source dog, have differing levels of susceptibility to moxidectin. In addition, we provide strong evidence that the differences in efficacy seen in two published studies using the MP3 strain were not due to randomness, and thus must be biological in nature.. Our results demonstrate how statistical modeling can improve the interpretation of data from heartworm efficacy studies by providing a means to identify the true efficacy range based on the observed data. Importantly, these new insights should help to inform regulators on how to move forward in establishing new statistically and scientifically valid requirements for efficacy in the registration of new heartworm preventative products. Furthermore, our results provide strong evidence that heartworm 'strains' can change their susceptibility phenotype over short periods of time, providing further evidence that a wide diversity of susceptibility phenotypes exists among naturally circulating biotypes of D. immitis.

Topics: Animals; Biometry; Dirofilaria immitis; Dirofilariasis; Dog Diseases; Dogs; Drug Evaluation; Filaricides; Macrolides; Treatment Outcome

Prior work has shown that the levels of moxidectin in dogs treated with Advantage Multi® for Dogs (Bayer Animal Health) remain at a high plasma concentration for the full month after application. The objective of this study was to demonstrate the efficacy of 10% imidacloprid + 2.5% moxidectin topical solution (Advantage Multi® for Dogs, also known as Advocate® for Dogs) for the prevention of heartworm infection and disease 30 days after just one application.. Two groups of eight dogs each were included. Dogs in Group 1 received the product (Advantage Multi® for Dogs) while those in Group 2 remained as nontreated controls. All dogs entering the study completed a physical examination including examination for Dirofilaria immitis antigen and circulating microfilariae. Dogs in Group 1 were treated on Study Day (SD) -30 as per the label recommendation. Thirty days later (SD 0) dogs in Groups 1 and 2 were subcutaneously infected in the inguinal region with approximately 50 infective third-stage D. immitis larvae ("Missouri" isolate). Blood was collected on SDs 120 and 147 for examination for D. immitis antigen and circulating microfilariae. On SD 148, all animals were euthanized and necropsied for recovery of adult heartworms. All procedures were performed in accordance with the VICH GL9 guidelines.. Examination and worm counts made at necropsy showed no heartworms in the treated dogs (Group 1) compared with six of eight nontreated dogs (Group 2) with heartworms (range of 2-33). The treated dogs (Group 1) had significantly fewer heartworms (p < 0.05) compared with the nontreated controls (Group 2).. The results demonstrated that 10% imidacloprid + 2.5% moxidectin topical solution (Advantage Multi® for Dogs) is efficacious for the prevention of heartworm infection and disease all month long with no observation of treatment-related adverse events.

Topics: Animals; Dirofilaria immitis; Dirofilariasis; Dog Diseases; Dogs; Female; Filaricides; Macrolides; Male; Neonicotinoids; Nitro Compounds; Time Factors

Monthly heartworm preventives are designed to protect dogs by killing heartworms acquired the month prior to their administration, and after treatment with most products, the drug levels rapidly dissipate to very low levels. Work with Advantage Multi® for Dogs (imidacloprid + moxidectin) topical solution showed protection against hookworm infection throughout the month after administration of several monthly doses suggesting that similar protection might occur with heartworms. This study assessed the amount of protection afforded to dogs by the administration of four monthly doses of Advantage Multi for Dogs prior to infection with third-stage heartworm larvae (Dirofilaria immitis) 28 days after the last (fourth) treatment.. There were 16 purpose-bred mongrel dogs in the study that were divided into two groups, 8 control and 8 treated dogs. Dogs were housed in a manner preventing contact between animals and groups, and personal protective gear worn by staff minimised the chance spread of the topically applied product between runs. The dogs in the treated group received monthly applications of Advantage Multi for Dogs as per label instructions on Study Days 0, 28, 56, and 84. On Study Day 112, all 16 dogs received 50 third-stage larvae of D. immitis ("Missouri" isolate) via subcutaneous inoculation in the inguinal region. The study was terminated on Day 264, and the number of heartworms per dog was determined at necropsy.. Moxidectin levels after 4 treatments 28 days apart were near steady state on Study Day 112 when the dogs were inoculated with D. immitis third-stage larvae. At necropsy, 152 days after infection, all the control dogs had adult worms in their pulmonary arteries (geometric mean = 33.9; range 25-41), and none of the dogs treated four times prior to infection, with the last treatment 30 days prior to infection, harbored worms at necropsy.. The efficacy of prevention was 100% when the dogs were infected 28 days after the last monthly treatment. When dogs receive consecutive doses of Advantage Multi for Dogs as prescribed, heartworm infections will be prevented throughout the monthly dosing interval after administration of several monthly doses.

Topics: Animals; Anthelmintics; Dirofilaria immitis; Dirofilariasis; Dog Diseases; Dogs; Drug Therapy, Combination; Female; Imidazoles; Macrolides; Male; Neonicotinoids; Nitro Compounds

Topics: Animals; Anthelmintics; Biopsy, Fine-Needle; Delayed-Action Preparations; Diagnosis, Differential; Dirofilariasis; Dog Diseases; Dogs; Female; Inflammation; Injections, Subcutaneous; Macrolides; Microspheres; Skin Neoplasms

The present study evaluated the microfilaricidal efficacy of a single application of the spot-on containing imidacloprid 10%/moxidectin 2.5% (Advocate(®), Bayer Animal Health) in dogs naturally infected either by Dirofilaria immitis or Dirofilaria repens. Dogs living in north-eastern and central-southern Italy, endemic for D. immitis and D. repens respectively, were randomly screened. Sixteen animals, eight infected with D. immitis and eight with D. repens, and fulfilling inclusion criteria were enrolled. Dogs infected with D. immitis received an adulticide treatment prior to the study and Advocate(®) 3 weeks after. The animals were divided in blocks of two (1:1, T1:T2) animals each, where Day 0 (D0) had an interval of 15days to compare T2 vs. T1 dogs during the first fortnight of examination (i.e. T2 dogs acted as control animals at each examination). At baseline (Days -15 and 0 for T2 and T1 dogs, respectively) the animals had a range of microfilaraemia of 180-99.700mff/ml (D. immitis) and 60-750 mff/ml (D. repens). All animals received a topical administration of Advocate(®) at D0 and were examined for microfilariae with microscopic and molecular tests at D15, D30, D60 and D90. All animals scored negative for mff at the first control post-treatment and throughout the study, with the exception of two D. immitis- infected animals that had a 2 mff/ml count at D15, and then become negative from Day 30 onwards. No adverse events were observed. The present study demonstrates the safety and the high microfilaricidal efficacy (99.97% and 100% for D. immitis and D. repens, respectively) of a single dose of moxidectin contained in Advocate(®) in naturally infected dogs.

Topics: Animals; Antinematodal Agents; Dirofilaria immitis; Dirofilaria repens; Dirofilariasis; Dog Diseases; Dogs; Drug Combinations; Imidazoles; Insecticides; Macrolides; Neonicotinoids; Nitro Compounds

Infection of cats with Dirofilaria immitis causes seroconversion on antibody tests and pulmonary pathology, often without subsequent development of adult heartworms. Consistent administration of topical 10% imidacloprid-1% moxidectin has been shown to result in sustained plasma levels of moxidectin in cats after three to five treatments, a pharmacokinetic behavior known as "steady state".. To evaluate the ability of moxidectin at "steady state" to protect cats from subsequent infection with D. immitis, cats (n = 10) were treated with the labeled dose of topical 10% imidacloprid-1% moxidectin for four monthly treatments. Each cat was inoculated with 25 third-stage larvae of D. immitis 7, 14, 21, and 28 days after the last treatment; non-treated cats (n = 9) were inoculated on the same days, serving as infection controls. Blood samples were collected from each cat from 1 month prior to treatment until 7 months after the final inoculation and tested for antibody to, and antigen and microfilaria of, D. immitis.. Measurement of serum levels of moxidectin confirmed steady state in treated cats. Cats treated with topical 10% imidacloprid-1% moxidectin prior to trickle inoculation of D. immitis L3 larvae throughout the 28 day post-treatment period remained negative on antibody and antigen tests throughout the study and did not develop gross or histologic lesions characteristic of heartworm infection. A majority of non-treated cats tested antibody positive by 3-4 months post infection (6/9) and, after heat treatment, tested antigen positive by 6-7 months post-infection (5/9). Histologic lesions characteristic of D. immitis infection, including intimal and medial thickening of the pulmonary artery, were present in every cat with D. immitis antibodies (6/6), although adult D. immitis were confirmed in only 5/6 antibody-positive cats at necropsy. Microfilariae were not detected at any time.. Taken together, these data indicate that prior treatment with 10% imidacloprid-1% moxidectin protected cats from subsequent infection with D. immitis for 28 days, preventing both formation of a detectable antibody response and development of pulmonary lesions by either immature stages of D. immitis or young adult heartworms.

Topics: Administration, Topical; Animals; Anthelmintics; Antibodies, Helminth; Antigens, Helminth; Cat Diseases; Cats; Chemoprevention; Dirofilaria immitis; Dirofilariasis; Macrolides; Plasma; Treatment Outcome

Macrocyclic lactone (ML) endectocides are used as chemoprophylaxis for heartworm infection (Dirofilaria immitis) in dogs and cats. Claims of loss of efficacy (LOE) of ML heartworm preventives have become common in some locations in the USA. We directly tested whether resistance to MLs exists in LOE isolates of D. immitis and identified genetic markers that are correlated with, and therefore can predict ML resistance. ML controlled studies showed that LOE strains of D. immitis established infections in dogs despite chemoprophylaxis with oral ivermectin or injectable moxidectin. A whole genome approach was used to search for loci associated with the resistance phenotype. Many loci showed highly significant differences between pools of susceptible and LOE D. immitis. Based on 186 potential marker loci, Sequenom(®) SNP frequency analyses were conducted on 663 individual parasites (adult worms and microfilariae) which were phenotypically characterized as susceptible (SUS), confirmed ML treatment survivors/resistant (RES), or suspected resistant/loss of efficacy (LOE) parasites. There was a subset of SNP loci which appears to be promising markers for predicting ML resistance, including SNPs in some genes that have been associated with ML resistance in other parasites. These data provide unequivocal proof of ML resistance in D. immitis and identify genetic markers that could be used to monitor for ML resistance in heartworms.

Topics: Animals; Chemoprevention; Dirofilaria immitis; Dirofilariasis; Dog Diseases; Dogs; Drug Resistance; Female; Filaricides; Genetic Markers; Ivermectin; Lactones; Macrolides; Male; Microfilariae; Polymorphism, Single Nucleotide

A mixed breed dog was presented with dyspnoea and fever. In the purulent thorax aspirate, a nematode larva was found during the cytological examination. Subsequent diagnostic tests revealed an infection with Dirofilaria repens, which was probably acquired autochthonously in central Germany. Moxidectin was administered every 4 weeks for 6 months and shown to be effective as indicated by subsequent blood examinations. This case report shows that infection with Dirofilaria repens is possible in Germany and can be treated successfully.

Topics: Animals; Dirofilaria repens; Dirofilariasis; Dog Diseases; Dogs; Filaricides; Germany; Macrolides

This study examined the efficacy of 10 % imidacloprid + 2.5 % moxidectin topical solution (Advantage ® Multi, Advocate®, Bayer) for the treatment of circulating microfilariae from dogs naturally infected with Dirofilaria immitis. The study included two groups of 11 dogs each that consisted of two replicates. Replicate 1 contained 12 dogs (6 treated and 6 controls) and replicate 2 contained 10 dogs (5 treated and 5 controls). Six of the 10 dogs in replicate 2 were the controls from replicate 1. All dogs entering the study completed a physical examination including chest radiographs, blood collections for examination of Dirofilaria immitis circulating microfilariae, serum chemistry, complete blood counts and urinalysis. To qualify for the study each dog was required to have a geometric mean ≥ 300 microfilariae per ml of blood from 3 consecutive samples collected during the 8 day acclimation period and a heartworm disease classification of 1 or 2. Dogs were treated on study days 0 and 28. Post-treatment microfilarial counts were performed on study days 1, 2, 3, 7, 14, 21, 28, 29, 35, and 42. Percent microfilarial reduction was determined by comparing the geometric mean number of circulating microfilaria remaining in treated dogs with those remaining in the control dogs post-treatment. Seven days after the first treatment, the geometric mean microfilarial counts in treated dogs were reduced by > 99 % compared to the control dogs. Reduction remained at > 99 % through the end of the study at 42 days after the first treatment (14 days after the second treatment). The results of this study demonstrated that Advantage® Multi for dogs is efficacious for treatment of circulating D. immitis microfilariae in naturally infected heartworm-positive dogs with no treatment-related adverse events observed.

Topics: Administration, Topical; Animals; Anthelmintics; Dirofilaria immitis; Dirofilariasis; Dog Diseases; Dogs; Drug Combinations; Female; Imidazoles; Insecticides; Macrolides; Neonicotinoids; Nitro Compounds

The frequency of canine heartworm infection in the state of Rio de Janeiro, Brazil was high before chemoprophylactic treatment was available, with one of the highest rates of infection (52.5 %) found among dogs living on the eastern shore of the state. Following the launch of a chemoprophylactic product, the rate of infection gradually decreased, and new infections were rarely reported. After 2005, outbreaks reported at the eastern shore as well as for new infections in other areas of high infection frequency were considered to possibly be related to reduced efficacy of macrocyclic lactones. Therefore, this study aimed to evaluate the efficacy of topical heartworm preventatives from different drug families at the high challenge area of the state of Rio de Janeiro.. A total of 46 dogs, including animals negative for Dirofilaria immitis microfilariae and antigen (Snap 4 Dx, IDEXX Laboratories, USA) at the initial screening were randomly allocated to two monthly treatment groups. Dogs in one group received topical moxidectin + imidacloprid and dogs in the other group received topical selamectin for eight consecutive months. Blood samples were obtained for microfilariae and antigen detection until the eleventh month after the first treatment. Dogs becoming microfilaremic or antigenemic on or before day 180 were considered to be infected prior to the first dose and were excluded from the study.. A total of 29 dogs completed the study, including 14 treated with moxidectin + imidacloprid and 15 treated with selamectin. No dogs treated with moxidectin + imidacloprid (0/14) became infected during the treatment period, whereas four dogs of the selamectin group (4/15) became infected.. Topical moxidectin + imidacloprid is 100 % effective in preventing D. immitis infections in dogs living in a high challenge natural environment.

Topics: Administration, Topical; Animals; Anthelmintics; Brazil; Chemoprevention; Dirofilaria immitis; Dirofilariasis; Dog Diseases; Dogs; Drug Therapy, Combination; Environment; Female; Imidazoles; Ivermectin; Lactones; Macrolides; Male; Microfilariae; Neonicotinoids; Nitro Compounds

To better understand the efficacy of doxycycline and 10% imidacloprid+2.5% moxidectin (Advantage Multi(®); Bayer Animal Health, Shawnee Mission, Kansas) on immature adult Dirofilaria immitis parasites and the results of antigen tests, 12 healthy, randomly selected dogs were experimentally infected with D. immitis and monitored for 407 days. Two dogs in each of three subgroups of four dogs were each infected with six (total of 6 dogs) or 12 (total of 6 dogs) D. immitis infective third-stage larvae (L3) obtained from infected mosquitoes. Doxycycline (10mg/kg per os twice daily×30 days) and 10% imidacloprid+2.5% moxidectin (1ml/kg by topical application every 30 days) treatment was initiated at 105 (Group A) and 149 (Group B) days post infection (PI) in two groups. One subgroup of two dogs given 6 L3 and one subgroup of two dogs given 12 L3 remained as untreated controls (GroupC). Serum obtained regularly throughout the study was evaluated by ELISA (PetChek(®) Heartworm-PF Antigen Test, IDEXX Laboratories, Inc.) for D. immitis adult circulating antigens. Six of the eight dogs in the treated groups had detectable antigenemia starting between 148 and 240 days post infection, but antigen was not detected in any treated dog at the end of the study. In the control subgroups, the dogs that received 6 L3 had no detectable antigen while the two dogs that received 12 L3 had detectable antigen beginning on Day 180 that persisted until the end of the study. None of the infected dogs had evidence of circulating microfilariae. At necropsy, no heartworms were recovered from the treated dogs, but all dogs in the untreated group had viable adult heartworms. These results indicate that early immature adult worms (3.5 and 5 months of age) of D. immitis were susceptible to a combined treatment regimen of doxycycline and 10% imidacloprid+2.5% moxidectin.

Topics: Animals; Antigens, Helminth; Dirofilaria immitis; Dirofilariasis; Dog Diseases; Dogs; Doxycycline; Drug Therapy, Combination; Female; Filaricides; Imidazoles; Macrolides; Male; Neonicotinoids; Nitro Compounds; Random Allocation

A controlled laboratory study was conducted to establish the safety and efficacy of 10% imidacloprid+2.5% moxidectin topical solution (Advantage Multi® for Dogs, Bayer HealthCare, Shawnee, KS) for the treatment of circulating Dirofilaria immitis microfilariae in dogs. Twenty beagles were experimentally infected with D. immitis via surgical implantation of 10 pairs of adult worms (Pepper strain, TRS Labs) from donor dogs on Day -82. Between Days -7 and -1, physical examinations were performed, chest radiographs were taken, and blood and urine samples were collected for microfilariae counts, serum chemistry, complete blood counts, and urinalysis. Each dog was required to have a mean pretreatment count of at least 300 mf/ml of blood. On Day -1, all 20 dogs were randomized by mean pretreatment microfilarial counts to two study groups (10 animals/group). Animals in Group 1 were treated on Days 0 and 28 with 10% imidacloprid+2.5% moxidectin topical solution at the minimum label dose of 0.1 ml/kg. Group 2 animals served as negative controls and were treated on Days 0 and 28 with mineral oil at an equivalent volume as for the study solution. All dogs were observed hourly for 8h after treatment, again at 12h, and then once daily on all other study days. Blood samples for microfilarial counts were collected daily for 3 days after treatment and then weekly for 6 weeks. The percentage reduction in microfilariae was determined by comparing the geometric mean number of circulating microfilariae remaining in Group 1 dogs with the mean counts remaining in control dogs. Group 1 mean microfilarial counts were reduced 93.1% three days following the first treatment and by >99% on Days 14 through 42. Group 1 had significantly fewer (p<0.05) microfilariae compared with Group 2 counts on Days 28 and 42. In addition, log-transformed geometric mean microfilarial counts were significantly different between the two groups (p<0.05) using separate repeated measures analysis of covariance for Days 2, 3, 7, 14, 21, 28, 35, and 42. No adverse events related to treatment were reported during the study. The results of this study demonstrate that 10% imidacloprid+2.5% moxidectin topical solution is efficacious for treatment of circulating D. immitis microfilariae in heartworm-positive dogs with no treatment-related adverse events observed.

Topics: Animals; Dirofilaria immitis; Dirofilariasis; Dog Diseases; Dogs; Drug Therapy, Combination; Female; Filaricides; Imidazoles; Macrolides; Male; Microfilariae; Neonicotinoids; Nitro Compounds; Random Allocation; Treatment Outcome

Adult stages of Dirofilaria repens (Nematoda, Filarioidea) reside in the subcutaneous tissues of the definitive or occasional host as dogs, other animals, and humans, and it is transmitted by mosquitoes. Canine infections with adults and circulating larvae of D. repens are often considered asymptomatic, although in some cases, the parasite causes subcutaneous nodules, diffused dermatitis, skin lesions, and itching. This report provides a complete clinical description of an unusual case of allergic diffused dermatitis caused by D. repens in a naturally infected dog and its successful treatment with the use of a spot-on solution containing imidacloprid 10%/moxidectin 2.5%. The dog presented multiple pustules and alopecic areas with lichenification, hyperpigmentation, and erythematous scaling margins without pruritus. Histological examination was compatible with allergic dermatitis. After being unsuccessfully managed for suspected food hypersensitivity, with a significantly worsening of the lesions, a Knott’s analysis detected nematode larvae in the blood. Morphological and molecular identification showed them to be D. repens. The dog was then treated with a single administration of a spot-on formulation containing imidacloprid 10%/moxidectin 2.5%, and the dermatological signs completely resolved within 2 months after treatment. The dog showed no recurrence of the lesions, and no circulating microfilariae were found upon microscopic and molecular examination for six consecutive months after treatment. This report indicates the apparent primary role of D. repens in causing hypersensitivity-like skin disease without pruritus in a dog. It also confirms, as recently shown elsewhere, the efficacy of imidacloprid 10%/moxidectin 2.5% in the treatment of dermatitis caused by D. repens.

Topics: Animals; Antinematodal Agents; Dirofilaria repens; Dirofilariasis; Dog Diseases; Dogs; Histocytochemistry; Hypersensitivity; Imidazoles; Macrolides; Male; Neonicotinoids; Nitro Compounds; Skin; Skin Diseases, Parasitic; Treatment Outcome

Elimination of microfilaria in dogs infected with zoonotic Dirofilaria repens would be desirable to reduce further spread. Moxidectin has demonstrated efficacy against microfilariae and safety in dogs infected with Dirofilaria immitis and could be an option for controlling D. repens microfilariae. A field study with 64 dogs previously confirmed positive for D. repens microfilaria was conducted in Hungary, in which a spot-on product (Advocate, Bayer) was tested. Treatments were applied to 44 dogs once a month for 3 months (five dogs) or 6 months (22 dogs), alternatively every 2 weeks for 6 months (17 dogs). Twenty dogs remained untreated. Microfilaria counts were performed once a month and for a further 6 months following the last treatment. Two weeks after the first treatment, 38 of 44 dogs were microfilaria negative. Four weeks after the initial treatment, one dog still showed a low microfilaria count. Following the second treatment, all treated dogs were negative. This status was maintained during the 6-month observation period after the last treatment. These data demonstrate the successful long-lasting elimination of microfilariae. Moreover, it may be supposed that adult D. repens were killed based on the observation that no further microfilariae were seen up to 6 months after the end of the treatment period.

Topics: Administration, Topical; Animals; Dirofilaria; Dirofilariasis; Dog Diseases; Dogs; Female; Filaricides; Hungary; Imidazoles; Macrolides; Male; Neonicotinoids; Nitro Compounds; Treatment Outcome

A study was carried out to assess the efficacy of a moxidectin microsphere sustained release (SR) injectable formulation (Guardian SR Iniettabile, Fort Dodge) for the prevention of Dirofilaria repens infection in experimentally infected dogs. On day 0, 18 Beagle dogs, 9 male dogs and 9 female dogs, weighing 12-16 kg were ranked in ascending order of body weight (b.w.) and blocked into pairs. Within each pair, dogs were allocated to Group 1 or Group 2 at random. On the same day, dogs in Group 1 were injected with 0.05 ml/kg b.w. of saline solution and dogs in Group 2 were injected with moxidectin SR at the label dose 0.17 mg/kg b.w. (0.05 ml/kg b.w.). Six months after moxidectin SR or saline injection, on day 180, each dog in the two groups was challenged with 50 infective larvae of D. repens collected from laboratory-reared, experimentally infected Aedes aegypti. Dogs were humanely euthanized on day 380 of the study, approximately 7 months from D. repens challenge. At necropsy, no worms were found in dogs treated with moxidectin SR (Group 2) while adult worms were found in saline-treated dogs (total 90; 38 males and 52 females; arithmetic mean 10, standard error 0.96, median 9, range 7-15) (Group 1 vs Group 2 P<0.001). In this experimental study, moxidectin SR injectable showed full efficacy (100%) lasting at least 6 months, and is able to prevent subcutaneous D. repens patent infection throughout the entire transmission season in Europe.

Topics: Animals; Anthelmintics; Delayed-Action Preparations; Dirofilaria; Dirofilariasis; Dog Diseases; Dogs; Female; Macrolides; Male; Random Allocation; Statistics, Nonparametric

Topics: Animals; Anthelmintics; Culicidae; Dirofilaria; Dirofilariasis; Disease Vectors; Dog Diseases; Dogs; Female; Macrolides; Netherlands; Treatment Outcome

Throughout the end of March to beginning of May 2006, 212 owned cats and 608 owned dogs from a heavy endemic area for canine heartworm (HW) disease in northern Italy have been examined to assess HW infection prevalence. Both cats and dogs were clinically examined and blood samples were taken from each animal to be examined for HW antibody (Ab). Ab-positive cats were further examined for circulating microfilariae, HW antigens (Ag) and by echocardiography (ECHO) to assess the presence of adult worms. Dogs were clinically examined and blood samples taken from each animal were examined for circulating microfilariae and for HW Ag. Ten cats (4.7%) were found Ab positive. Of these, 6 cats were Ag positive (2.6%) and in 4 (1.8%) the worms were visualized by ECHO. HW prevalence in dogs was 36% (221/608). One hundred and seventy-six (29%) were both microfilaraemic and Ag positive, 40 (7%) had occult infections (no circulating microfilariae) and 7 (1%) were microfilaraemic but Ag negative. Upon owners' consent, 132 cats (including cats Ab and/or Ag and ECHO positive) were prophylactically treated against HW disease with an imidacloprid/moxidectin spot-on combination (10% imidacloprid/1% moxidectin) monthly administered for 6 months. Cats were re-examined for HW infection in November, 1 month after the last drug administration, and in May-June 2007, 7-8 months after the last treatment. All 122 cats found HW negative before treatment, were found negative at the two examinations at the end of study. The 4 cats Ab positive, 2 cats Ab and Ag positive and 1 Ab, Ag and ECHO positive at the beginning of treatment were found negative. Throughout the treatment, transitory hypersalivation and generic signs of annoyance were reported by owners in 6 cats (4.5%). All signs regressed spontaneously.

Topics: Animals; Cat Diseases; Cats; Dirofilaria immitis; Dirofilariasis; Drug Therapy, Combination; Female; Filaricides; Imidazoles; Macrolides; Male; Neonicotinoids; Nitro Compounds

The objective of this study was to ascertain the ability of a single subcutaneous injection of a sustained-release (SR) formulation of moxidectin to protect dogs against challenge inoculation with infective Dirofilaria immitis larvae 364 days after administration. Twenty four purpose-bred adult mixed-breed dogs were grouped into three blocks of eight based on weight and sex. Saline solution (0.9% NaCl) or a moxidectin SR formulation at volumes designed to deliver 0.17 or 0.27 mg moxidectin/kg b.w. was injected subcutaneously on day 0. Throughout the post-treatment period, injection sites of all dogs were periodically examined visually and by palpation. Palpable swellings were characterized as to size, consistency and the presence of associated pain or erythema. On day 364, each dog was inoculated subcutaneously with 50 D. immitis L3. On days 510 and 511, dogs were euthanatized, and their hearts, lungs and thoracic cavities were inspected for the presence of adult heartworms. number, sex and viability of recovered heartworms were determined. The mean number of heartworms recovered from dogs that had received the saline control injection was 35.7. No heartworms were recovered from any dog treated with either 0.17 or 0.27 mg moxidectin/kg b.w. For variable periods of time following treatment, small (1-4 mm diameter), firm, subcutaneous swellings could be palpated at the injection sites of dogs treated with 0.17 or 0.27 mg moxidectin/kg b.w. These swellings contracted progressively and eventually disappeared except for the case of one animal treated with 0.27 mg/kg, in which the swelling persisted for the entire study period. At no time during the study was pain or erythema noted at the injection site of any dog, and no dog exhibited any adverse systemic reaction related to treatment. We conclude that under conditions pertaining in this study, a single subcutaneous injection of a moxidectin SR formulation at dosing rates of either 0.17 or 0.27 mg/kg b.w. can safely protect adult dogs against experimental challenge inoculation with infective heartworm larvae for a period of 12 months.

Topics: Animals; Anthelmintics; Cohort Studies; Delayed-Action Preparations; Dirofilaria immitis; Dirofilariasis; Dog Diseases; Dogs; Female; Injections, Subcutaneous; Macrolides; Male; Random Allocation

Topics: Animals; Antinematodal Agents; Dirofilariasis; Dog Diseases; Dogs; Drug and Narcotic Control; Macrolides; Product Surveillance, Postmarketing; Safety; United States; United States Food and Drug Administration

Sixteen controlled laboratory studies, involving 420 kittens and cats, were conducted to evaluate the efficacy and safety of topically applied formulations of imidacloprid and moxidectin for the prevention of feline heartworm disease, treatment of flea infestations and treatment and control of intestinal nematodes. Unit-dose applicators and the dosing schedule used in these studies were designed to provide a minimum of 10mg imidacloprid and 1mg moxidectin/kg. Treatments were applied topically by parting the hair at the base of the skull and applying the solution on the skin. Imidacloprid treatment alone did not display activity against Dirofilaria immitis or intestinal nematodes and moxidectin treatment alone provided little or no activity against adult Ctenocephalides felis infestations. The formulation containing 10% imidacloprid and 1% moxidectin was 100% efficacious against the development of adult D. immitis infections when cats were treated 30 days after inoculation with third-stage larvae. A single treatment with this formulation also provided 88.4-100% control of adult C. felis for 35 days. Imidacloprid/moxidectin was 100% efficacious against adult Toxocara cati and 91.0-98.3% efficacious against immature adults and fourth-stage T. cati larvae. The formulation provided 98.8-100% efficacy against adult Ancylostoma and immature adults and third-stage A. tubaeforme larvae. Monthly topical application with 10% imidacloprid/1% moxidectin is convenient, efficacious and safe for the prevention of feline heartworm disease, treatment of flea infestation and for the treatment and control of intestinal nematode infections of cats.

Topics: Administration, Topical; Animals; Antinematodal Agents; Cat Diseases; Cats; Dirofilariasis; Dose-Response Relationship, Drug; Drug Administration Schedule; Ectoparasitic Infestations; Female; Filaricides; Imidazoles; Insecticides; Intestinal Diseases, Parasitic; Life Cycle Stages; Macrolides; Male; Nematode Infections; Neonicotinoids; Nitro Compounds; Treatment Outcome

To evaluate the efficacy of a single injection of a sustained-release formulation of moxidectin in preventing heartworm (Dirofilaria immitis) infection for 12 months in dogs.. 14 healthy dogs.. Group A (nontreated control dogs; n = 6) received sterile vehicle administered SC, and group B (treated dogs; n = 6) received a sustained-release formulation of moxidectin administered SC. All dogs were housed in a heartworm-endemic area for 11.5 months, and heartworm antigen and modified Knott tests were performed monthly. All dogs (including 2 additional control dogs [group C]) were then inoculated with infective-stage larvae (L3) of D. immitis, and 4.5 months later, all dogs were euthanatized and post-mortem examinations were performed. Adult D. immitis were counted and measured, and their age was estimated.. All dogs in groups A and C were infected with young (4- to 4.5-month old) adult male and female D. immitis. No dogs in group B were infected with heartworms. CONCLUSIONS AND.. The age of heartworms recovered suggests that infection was the result of experimental inoculation and not natural exposure to mosquitoes during the 11.5-month period the dogs resided in a heartworm-endemic area. A single SC injection of a sustained-release formulation of moxidectin was effective in providing protection against heartworm infection after 12 months in dogs. This formulation is a convenient method of heartworm prophylaxis that could eliminate the problem of poor owner compliance.

Topics: Aedes; Animals; Antinematodal Agents; Australia; Delayed-Action Preparations; Dirofilariasis; Dog Diseases; Dogs; Drug Evaluation; Macrolides

To test the ability of a single injection of a sustained-release formulation of moxidectin (moxidectin SR) to protect dogs against heartworm infection for 180 days after inoculation with infective third-stage larvae (L3) of Dirofilaria immitis.. 32 adult mixed-breed dogs.. Dogs were allocated to 4 groups on the basis of weight and sex. Dogs were injected SC with saline (0.9% NaCl) solution or moxidectin SR at the rate of 0.06, 0.17, or 0.5 mg/kg of body weight (day 0). Each dog was inoculated SC with 50 D immitis L3 180 days later. On days 330 and 331, dogs were euthanatized. The heart, lungs, and thoracic cavity were examined, and number and sex of heartworms were determined.. A mean of 35.9 heartworms was recovered from untreated control dogs. Fourteen worms were recovered from 1 of 8 dogs given moxidectin SR at the lowest dosage, and none of the dogs in the 2 highest moxidectin treatment groups were infected. Small barely palpable granulomas were detected at injection sites of moxidectin-treated dogs. Frequency and size of granulomas were positively correlated with dose of moxidectin administered.. A single dose of moxidectin SR at a dosage as low as 0.17 mg/kg can safely and reliably confer complete protection against infection after challenge-exposure with D. immitis L3, and protection lasts for at least 180 days. This mode of prophylactic treatment against infection with heartworms effectively eliminates failure of prophylaxis that results from erratic administration of medications designed for monthly administration.

Topics: Animals; Anti-Bacterial Agents; Delayed-Action Preparations; Dirofilaria immitis; Dirofilariasis; Dog Diseases; Dogs; Female; Granuloma; Heart; Histocytochemistry; Injections, Subcutaneous; Lung; Macrolides; Male; Microspheres; Random Allocation; Skin

Topics: Animals; Anti-Bacterial Agents; Antinematodal Agents; Dirofilariasis; Dog Diseases; Dogs; Drug Overdose; Macrolides

Starting from milbemycin D (1), milbemycin A4 (2) and milbemycin A3 (3), a series of 5-keto-5-oxime derivatives were synthesized by selective oximation at the alpha,beta-conjugated carbonyl function of the 5-ketomilbemycins (4-6). The activities of the synthesized compounds were studied in dogs naturally infested with microfilariae of Dirofilaria immitis. The 5-keto-5-oximes of milbemycin D (7), A4 (8) and A3 (9) had quite high efficacy to control the microfilariae and more potency than their parents, while the 5-O-acyl oximes (11-15) also exhibited high activity.

Topics: Animals; Anti-Bacterial Agents; Dirofilaria immitis; Dirofilariasis; Dogs; Macrolides; Microfilariae; Oximes; Structure-Activity Relationship

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.

Topics: Animals; Anthelmintics; Anti-Bacterial Agents; Dirofilaria immitis; Dirofilariasis; Dog Diseases; Dogs; Female; Larva; Macrolides; Male

Topics: Animals; Anthelmintics; Anti-Bacterial Agents; Dirofilariasis; Dog Diseases; Dogs; Female; Intestinal Diseases, Parasitic; Macrolides; Male; Nematode Infections

Some adverse reactions such as shock-like reaction and dirofilarial hemoglobinuria (caval syndrome) occasionally occurred in microfilaremic dogs following milbemycin D (Milbe) administration. This study was carried out to seek the prevention of these adverse reactions. In two groups containing 16 and 9 dogs respectively which were administered either chlorpheniramine maleate (1 mg/kg) or indomethacin (2.5 mg/kg) simultaneously with Milbe (1 mg/kg), the incidence of clinical signs such as the pale color of the visible mucous membranes, respiratory disorders, caval syndrome and shock-like reaction as well as changes in clinical parameters such as RBC and WBC counts, WBC profile and serum total protein, were almost equal to that observed in the group administered Milbe alone. In 41 dogs administered prednisolone (1 mg/kg) simultaneously with Milbe (1 mg/kg), no shock-like reaction was observed. Changes in clinical parameters were different from those in the group administered Milbe alone, whereas some clinical signs of adverse reactions, including caval syndrome, were observed. These results indicated that prednisolone was effective for prevention of the shock-like reaction in microfilaremic dogs induced by Milbe.

Topics: Animals; Anti-Bacterial Agents; Dirofilaria immitis; Dirofilariasis; Dog Diseases; Dogs; Female; Insecticides; Macrolides; Male; Prednisolone; Shock

Topics: Animals; Anthelmintics; Anti-Bacterial Agents; Dirofilaria immitis; Dirofilariasis; Dog Diseases; Dogs; Filaricides; Lactones; Macrolides

Topics: Animals; Anti-Bacterial Agents; Blood Pressure; Cardiac Output; Dirofilaria immitis; Dirofilariasis; Dog Diseases; Dogs; Female; Hemodynamics; Hemoglobinuria; Lactones; Macrolides; Male; Pulmonary Artery

Topics: Animals; Anti-Bacterial Agents; Dirofilariasis; Dog Diseases; Dogs; Female; Hemoglobinuria; Lactones; Macrolides; Male

Topics: Animals; Anti-Bacterial Agents; Dirofilariasis; Dog Diseases; Dogs; Female; Lactones; Macrolides; Male

Topics: Animals; Anti-Bacterial Agents; Dirofilariasis; Dog Diseases; Dogs; Female; Lactones; Macrolides; Male; Shock

Topics: Animals; Anti-Bacterial Agents; Dirofilariasis; Dog Diseases; Dogs; Drug Evaluation; Female; Lactones; Macrolides; Male; Neuromuscular Diseases

Topics: Animals; Anti-Bacterial Agents; Dirofilariasis; Dog Diseases; Dogs; Female; Lactones; Macrolides; Male

Topics: Animals; Anti-Bacterial Agents; Dirofilariasis; Dog Diseases; Dogs; Female; Lactones; Macrolides; Male