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OBJECTIVE: To describe the clinical presentation, diagnostic findings, and medical management of the first suspected autochthonous case of a dog in the US diagnosed with Angiostrongylus vasorum, the French heartworm. ANIMAL: A 10-month-old Goldendoodle born in Oregon and residing in Washington State. CLINICAL PRESENTATION, PROGRESSION, AND PROCEDURES: The dog presented for evaluation of intermittent vomiting and diarrhea. Bloodwork revealed leukocytosis with mild lymphocytosis, monocytosis, eosinophilia, and basophilia. Larvae were detected on a fecal flotation, and fecal PCR confirmed A vasorum. TREATMENT AND OUTCOME: Administration of milbemycin oxime PO once a week for 4 weeks was initiated with recommendation to continue monthly treatment at label dose. The patient improved over the course of treatment. CLINICAL RELEVANCE: This case highlights the clinical and diagnostic findings and medical management of A vasorum, also known as the French heartworm, in a dog in the US. Few cases of A vasorum have been reported in wild foxes in North America, mostly in eastern Canada and 1 within the eastern US. Here we report for the first time an autochthonous case of A vasorum in a domestic dog in the US and the first report of any canid in the western US. This case highlights the importance of considering A vasorum as a differential for respiratory disease, gastrointestinal disease, or inexplicable eosinophilia in canine veterinary patients in the US and raises awareness for veterinary practitioners to incorporate appropriate preventative and diagnostic measures for their canine patients.
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An 8-year-old neutered male Maltese dog presented with a month-long history of progressive nonambulatory tetraparesis. MRI revealed a well-defined, centrally nonenhanced, T1-weighted hypointense, extradural structure located in the vertebral canal at the level of the C5 vertebral body. CT demonstrated a hypoattenuating, space-occupying structure in the same area. Surgery revealed a long, narrow parasite in the epidural space. An adult Dirofilaria immitis was confirmed by multiplex polymerase chain reaction (PCR) assay. This is a novel report describing the MRI and CT features of cervical epidural dirofilariasis in a dog.
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Macrocyclic lactones (MLs) are the only drug class currently licensed for heartworm disease prophylaxis. Macrocyclic lactones kill third- and fourth-stage larvae of Dirofilaria immitis, thus preventing the development of adult worms in dogs, which are responsible for heartworm disease, a potentially life-threatening condition. Despite considerable overlap in terms of endectocide spectrum, several important differences distinguish moxidectin from other MLs. Moxidectin has beneficial pharmacokinetic characteristics, such as a longer half-life and greater tissue distribution compared to ivermectin. Additionally, moxidectin has a greater margin of safety compared to ivermectin in dogs with ABCB1 (previously MDR1) gene-defect, which is commonly recognized in collies and other breeds. Multiple laboratory studies have shown that moxidectin is more effective than other commonly used heartworm preventives against resistant strains of D. immitis. This improved efficacy benefits individual dogs and helps reduce the risk of spreading resistant strains within the community. Despite the presence of proven resistant strains in the United States, non-compliance with preventive measures remains a major factor contributing to the diagnosis of heartworm disease in dogs. In retrospective analyses, the oral moxidectin combination product Simparica Trio® (sarolaner, moxidectin, and pyrantel) was associated with increased compliance, resulting in more time of protection compared to dogs receiving flea/tick and heartworm preventive products separately. Compliance with the extended-release moxidectin injectables ProHeart® 6 and ProHeart® 12 was higher than with monthly heartworm preventives, as they provide 6 months or a full year of protection with one single injection, respectively, and revenues remain in the veterinary clinics as injectable moxidectin cannot be sourced through online retailers.
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Chemoprophylactic prevention of veterinary heartworm disease in companion animals, caused by the vector-borne nematode parasite Dirofilaria immitis, is a multi-billion-dollar global market. Experimental use of cats and dogs in preclinical heartworm drug testing is increasing due to evolving drug-resistance to frontline macrocyclic lactones and renewed investment in alternative preventative drug research. We and others recently published data demonstrating proof-of-concept of utilising lymphopenic severe-combined immunodeficient (SCID) or Recombination Activating Gene (RAG)2 deficient mice with additional knockout of the IL-2/7 receptor gamma chain (γc) as alternative preventative drug screening research models of dirofilariasis. Here we summarise the current knowledge of candidate immunodeficient mouse models tested, including a comparison of susceptibility using different background strains of mice, different D. immitis isolates, following use of anti-inflammatory treatments to further suppress residual innate immunity, and efficacies achieved against different reference anthelmintics. We supplement this precis with new data on treatment response to the veterinary anthelmintic, oxfendazole, and initial evaluation of D. immitis susceptibility in CB.17 SCID and C57BL/6 RAG2 -/-γc -/- mice. We conclude that in addition to NSG and NXG mice, RAG2 -/-γc -/- mice on either a BALB/c or C57BL/6 background offer an alternative screening model option, widening access to academic and commercial laboratories wishing to pursue initial rapid in vivo drug screening whilst avoiding potentially unnecessary cat or dog testing.
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Dirofilariose , Modelos Animais de Doenças , Camundongos SCID , Animais , Cães , Gatos , Camundongos , Dirofilariose/prevenção & controle , Dirofilariose/tratamento farmacológico , Dirofilaria immitis/efeitos dos fármacos , Dirofilaria immitis/imunologia , Doenças do Gato/prevenção & controle , Doenças do Gato/parasitologia , Doenças do Gato/tratamento farmacológico , Doenças do Gato/imunologia , Doenças do Cão/prevenção & controle , Doenças do Cão/parasitologia , Doenças do Cão/tratamento farmacológico , Anti-Helmínticos/uso terapêutico , Avaliação Pré-Clínica de MedicamentosRESUMO
A bioassay-guided chemical investigation of a bacterium, Streptomyces sp. CMB-MRB032, isolated from sheep feces collected near Bathurst, Victoria, Australia, yielded the known polyketide antimycins A4a (1) and A2a (2) as potent inhibitors of Dirofilaria immitis (heartworm) microfilaria (mf) motility (EC50 0.0013-0.0021 µg/mL), along with the octapeptide surugamide A (3) and the new N-methylated analog surugamide K (4). With biological data suggesting surugamides may also exhibit activity against D. immitis, a GNPS molecular network analysis of a library of microbes sourced from geographically diverse Australian ecosystems identified a further five taxonomically and chemically distinct surugamide producers. Scaled-up cultivation of one such producer, Streptomyces sp. CMB-M0112 isolated from a marine sediment collected at Shorncliff, Qld, Australia, yielded 3 along with the new acyl-surugamides A1-A4 (5-8). Solid-phase peptide synthesis provided additional synthetic analogs, surugamides S1-S3 (9-11), while derivatization of 3 returned the semi-synthetic surugamide S4 (12) and acyl-surugamides AS1-AS3 (13-15). The natural acyl-surugamide A3 (7) and semi-synthetic acyl-surugamide AS3 (15) were shown to selectively inhibit D. immitis mf motility (EC50 3.3-3.4 µg/mL), however, unlike antimycins 1 and 2, were inactive against the gastrointestinal nematode Haemonchus contortus L1-L3 larvae (EC50 > 25 µg/mL) and were not cytotoxic to mammalian cells (human colorectal carcinoma SW620, IC50 > 30 µg/mL). A structure-activity relationship (SAR) study on the surugamides 3-15 revealed that selective acylation of the Lys3-ε-NH2 correlates with anthelmintic activity.
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Dirofilaria immitis , Streptomyces , Animais , Streptomyces/química , Dirofilaria immitis/efeitos dos fármacos , Austrália , Ovinos , Fezes/parasitologia , Fezes/microbiologiaRESUMO
Dirofilaria immitis is a filarial parasitic nematode of veterinary significance. With the emergence of drug-resistant isolates in the USA, it is imperative to determine the likelihood of resistance occurring in other regions of the world. One approach is to conduct population genetic studies across an extensive geographical range, and to sequence the genomes of individual worms to understand genome-wide genetic variation associated with resistance. The immature life stages of D. immitis found in the host blood are more accessible and less invasive to sample compared to extracting adult stages from the host heart. To assess the use of immature life stages for population genetic analyses, we have performed whole genome amplification and whole-genome sequencing on nine (n = 9) individual D. immitis microfilaria samples isolated from dog blood. On average, less than 1% of mapped reads aligned to each D. immitis genome (nuclear, mitochondrial, and Wolbachia endosymbiont). For the dog genome, an average of over 99% of mapped reads aligned to the nuclear genome and less than 1% aligned to the mitochondrial genome. The average coverage for all D. immitis genomes and the dog nuclear genome was less than 1, while the dog mitochondrial genome had an average coverage of 2.87. The overwhelming proportion of sequencing reads mapping to the dog host genome can be attributed to residual dog blood cells in the microfilariae samples. These results demonstrate the challenges of conducting genome-wide studies on individual immature parasite life stages, particularly in the presence of extraneous host DNA.
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DNA de Helmintos , Dirofilaria immitis , Dirofilariose , Doenças do Cão , Genoma Helmíntico , Microfilárias , Sequenciamento Completo do Genoma , Animais , Dirofilaria immitis/genética , Dirofilaria immitis/isolamento & purificação , Cães , Doenças do Cão/parasitologia , Dirofilariose/parasitologia , Microfilárias/genética , Microfilárias/isolamento & purificação , DNA de Helmintos/isolamento & purificação , DNA de Helmintos/química , Feminino , MasculinoRESUMO
Dirofilariosis is a zoonotic disease that mainly affects dogs and cats, with a high risk to public health. The island of Gran Canaria (Spain) has been shown to be a hyperendemic area of infection and, therefore, a model for studying the evolution of the disease. The objective of this study was to track the prevalence and distribution of heartworm in dogs, cats, and residents of Gran Canaria from 1994 to 2020, using published and unpublished data. Blood samples from 5841 dogs, 1203 cats, and 1604 humans were collected in the years analyzed, considering geographical and isoclimatic factors. In 1994, a prevalence of Dirofilaria immitis of 67.02% in dogs was reported, while in 2020 it was 15.81%. In cats, the seroprevalence in 2010 was 33.03%, compared to 17.20% in 2020. The incidence of D. immitis in humans in 2008 was 18.66%, while in 2020 it was 8.27%. For all study groups, temperate cold zone (TC) and temperate mild zone (TM) climates had the highest prevalence. Throughout these 20 years, the prevalence of heartworm disease has decreased. Despite this, it continues to be a hyperendemic island. This study highlights the importance of using the "One Health" perspective and the risks of contagion of the disease.
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The diagnosis of skin lesions involving the eyes can be challenging, especially when uncommon etiologies are considered. We present a case of a 52-year-old female initially diagnosed with blepharoconjunctivitis but later found to have a subcutaneous heartworm infection. The patient experienced recurrent episodes of unilateral palpebral edema, pain, pruritus, and a sensation of a foreign body in her eye. Upon examination, a vermiform structure with peristaltic movements was observed, raising suspicion of subcutaneous dirofilariasis and prompting further investigations. Serological tests confirmed the presence of anti-Dirofilaria spp. antibodies. Surgical removal of the worm led to the resolution of symptoms. This case highlights the importance of considering uncommon etiologies, such as subcutaneous heartworm infection, in patients presenting with atypical migratory skin lesions or ocular manifestations when there is no definite diagnosis and the condition does not respond to usual medical treatment.
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BACKGROUND: Dirofilaria immitis, commonly known as heartworm (HW), is a parasitic nematode transmitted by various mosquito species, leading to heartworm disease (HWD) in dogs. Diagnosis of HW typically involves antigen or microfilariae detection, or visualization of adult worms through imaging or post mortem examination. Polymerase chain reaction (PCR) and micro RNA (miRNA) detection have been explored for HW diagnosis. METHODS: Three dogs, previously experimentally infected with HW, underwent blood sampling every 4 weeks for 7 months. Samples were assessed for antigen presence after heat treatment, PCR amplification, and microfilaria examination using Giemsa-stained thick smears. Additionally, whole blood aliquots underwent miRNA deep sequencing and bioinformatic analysis. RESULTS: Heartworm antigen was detectable after heat treatment at 20 weeks post-inoculation and via PCR at 24 weeks, with microfilariae observed in peripheral blood smears at 28 weeks. However, deep miRNA sequencing revealed that the miRNA candidate sequences are not consistently expressed before 28 weeks of infection. CONCLUSIONS: While ancillary molecular methods such as PCR and miRNA sequencing may be less effective than antigen detection for detecting immature larval stages in an early stage of infection, our experimental findings demonstrate that circulating miRNAs can still be detected in 28 weeks post-infection.
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Dirofilaria immitis , Dirofilariose , Doenças do Cão , MicroRNAs , Animais , Dirofilaria immitis/genética , Dirofilaria immitis/isolamento & purificação , Cães , Dirofilariose/diagnóstico , Dirofilariose/parasitologia , MicroRNAs/sangue , MicroRNAs/genética , Doenças do Cão/parasitologia , Doenças do Cão/diagnóstico , Antígenos de Helmintos/sangue , Antígenos de Helmintos/genética , Diagnóstico Precoce , Reação em Cadeia da Polimerase/métodos , Reação em Cadeia da Polimerase/veterinária , Microfilárias/isolamento & purificação , Microfilárias/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodosRESUMO
Although Dirofilaria immitis in dogs is considered enzootic in northern Greece, the available data on the occurrence of infection in southern parts of the country demonstrate its scarcity. The aim of this study was to update the current knowledge on D. immitis infection in dogs in areas of Greece previously considered non-enzootic (Central Greece, Attica, Peloponnese, North Aegean, South Aegean, Crete and the Ionian islands). In total, 1528 dog blood samples were collected from the aforementioned areas and examined by Dirochek® ELISA (Synbiotics). Additionally, data published until 2022 on the prevalence of infection in these areas were compared to the data of this study. The 'Wilson' Score interval method (Epitools) was employed. Overall, 10.8% of dogs were positive for D. immitis. In detail, the prevalence was 21.7, 13.7, 10.7, 5.4, 4.7, 6.2 and 17.0% for D. immitis, in Central Greece, Attica, Peloponnese, North Aegean, South Aegean, Crete and the Ionian islands, respectively. Infection with D. immitis is recorded for the first time in Crete. The probability of a dog becoming infected has increased 4.1 times since 2022 in previously non-enzootic areas. This study denotes the spread of D. immitis and highlights the necessity for preventive measures.
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Heartworm disease caused by the nematode Dirofilaria immitis is one of the most important parasitoses of dogs. The treatment of the infection is long, complicated, risky and expensive. Conversely, prevention is easy, safe, and effective and it is achieved by the administration of macrocyclic lactones (MLs). In recent years, D. immitis strains resistant to MLs have been described in Southern USA, raising concerns for possible emergence, or spreading in other areas of the world. The present study describes the first case of ML-resistant D. immitis in a dog in Europe. The dog arrived in Rome, Italy, from USA in 2023. Less than 6 months after its arrival in Italy, the dog tested positive for D. immitis circulating antigen and microfilariae, despite it having received monthly the ML milbemycin oxime (plus an isoxazoline) after arrival. The microfilariae suppression test suggested a resistant strain. Microfilariae DNA was examined by droplet digital PCR-based duplex assays targeting four marker positions at single nucleotide polymorphisms (SNP1, SNP2, SNP3, SNP7) which differentiate resistant from susceptible isolates. The genetic analysis showed that microfilariae had a ML-resistant genotype at SNP1 and SNP7 positions, compatible with a resistant strain. It is unlikely that the dog acquired the infection after its arrival in Europe, while it is biologically and epidemiologically plausible that the dog was already infected when imported from USA to Europe. The present report highlights the realistic risk of ML-resistant D. immitis strains being imported and possibly transmitted in Europe and other areas of the world. Monitoring dogs travelling from one area to another, especially if they originate from regions where ML-resistance is well-documented, is imperative. Scientists, practitioners, and pet owners should be aware of the risk and remain vigilant against ML-resistance, in order to monitor and reduce the spreading of resistant D. immitis.
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Dirofilaria immitis , Dirofilariose , Doenças do Cão , Resistência a Medicamentos , Animais , Dirofilaria immitis/efeitos dos fármacos , Dirofilaria immitis/genética , Cães , Dirofilariose/parasitologia , Dirofilariose/tratamento farmacológico , Doenças do Cão/parasitologia , Doenças do Cão/tratamento farmacológico , Doenças do Cão/epidemiologia , Europa (Continente) , Itália/epidemiologia , Macrolídeos/farmacologia , Macrolídeos/uso terapêutico , Lactonas/farmacologia , Microfilárias/efeitos dos fármacos , Polimorfismo de Nucleotídeo Único , Filaricidas/farmacologia , Filaricidas/uso terapêuticoRESUMO
Previous reports of macrocyclic lactone (ML) resistance in Dirofilaria immitis, the parasitic nematode which causes heartworm disease, have mainly been from the southern Mississippi Delta region. Southeast Missouri (SEMO), forming the northern boundary of this region, has not previously been well studied. The area is an ideal propagation region for heartworm infection and possibly for the spread of ML resistance. To assess whether D. immitis isolates infecting domestic canines in SEMO exhibit evidence of resistance to MLs, domestic canines, presented to veterinary facilities testing positive for heartworms through antigen and microfilariae (MF) examination, were utilized in the study. Using a descriptive epidemiological cross-sectional study, from March 2021 through February 2022, blood sample collection from 96 canines living in SEMO testing positive for heartworms were analyzed. MiSeq technology was utilized to sequence specific genetic markers associated with susceptibility/resistance for MLs in D. immitis isolates. Genomic data revealed most D. immitis isolates had genotypic profiles consistent with resistance to MLs. Of the 96 samples tested, 91 (94.8%) had a resistant genotype, 4 (4.2%) had a mixed genotype, and 1 sample (1%) genotyped as susceptible. While detailed and reliable medical histories were not available for most canines, detailed medical history from 2 canines indicated evidence of phenotypic resistance that was consistent with their genotypes. However, in vivo preventive tests are needed to confirm a high frequency of phenotypic ML resistance in D. immitis from this region. Increasing resistance patterns to MLs indicate the approach to heartworm prevention/treatment protocol should be reconsidered. New measures may be required to stop heartworm disease.
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Dirofilaria immitis , Dirofilariose , Doenças do Cão , Resistência a Medicamentos , Animais , Dirofilaria immitis/efeitos dos fármacos , Dirofilaria immitis/genética , Dirofilariose/parasitologia , Dirofilariose/epidemiologia , Cães , Doenças do Cão/parasitologia , Doenças do Cão/epidemiologia , Missouri/epidemiologia , Resistência a Medicamentos/genética , Estudos Transversais , Feminino , Lactonas/farmacologia , Masculino , Filaricidas/farmacologia , Filaricidas/uso terapêutico , GenótipoRESUMO
Dirofilaria immitis infection is routinely detected in dogs during veterinary care in tropical and subtropical regions worldwide. Parasitological tests for the detection of this infection are routinely performed only in areas with a high prevalence. Baixada Fluminense, a region in Rio de Janeiro, was considered heartworm-free until local veterinarians began to receive blood exams results indicating the presence of microfilariae (MF). A laboratory database was hence used to collect data from 2017 to 2020 to understand the extent of spread of the parasite in this area. The results of complete blood count analysis and MF or heartworm antigen detection tests conducted on canine samples sent from veterinary clinics in Baixada Fluminense (Magé, Duque de Caxias, Guapimirim, Nova Iguaçu, and São João de Meriti municipalities) were included. In total, the results of 16,314 hematological tests were considered. The overall prevalence of D. immitis was 3.4% (554/16,314), considering that only one test result was obtained per animal on the same day. This study is highly relevant because it indicates the spreading geographic distribution of the worms, heightens awareness among local health professionals and the general population, and encourages compliance with prophylactic measures to prevent further spread of parasite.
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BACKGROUND: Macrocyclic lactones (MLs) are the only class of drugs currently commercially available that are effective for preventing heartworm disease. The data presented in this article provide information on the efficacy of oral moxidectin against JYD-34, a known ML-resistant Dirofilaria immitis isolate, when dogs are treated under various dosing regimens. METHODS: Fifty-two purpose-bred Beagle dogs were used in five laboratory studies. All dogs were inoculated with 50 D. immitis third-stage larvae (L3) (JYD-34 isolate) 30 days prior to the first treatment. Dogs were randomized to treatment (four to five animals in each group) with one, three, or five monthly doses of oral moxidectin ranging from 6 to 100 µg/kg body weight. In each study, control dogs were not treated. Five to 6 months after L3 inoculation, dogs were euthanized, and adult worms were counted to evaluate efficacy of the dosing regimens. RESULTS: Adult heartworms were recovered from all control dogs, with an overall geometric mean of 29.7 worms (range 15.2 to 38.0, individual counts ranged from 8 to 51). Five monthly doses of 6 µg/kg provided 83.3% and 90.2%, efficacy, and the same number of monthly doses of 9 µg/kg demonstrated 98.8% and 94.1% efficacy. Three monthly doses of 30 and 50 µg/kg demonstrated 97.9% and 99.0% efficacy, respectively, while a single dose of 100 µg/kg demonstrated 91.1% efficacy. CONCLUSIONS: Five monthly doses of 9 µg/kg provided similar or only marginally lower efficacy against JYD-34, a known ML-resistant isolate, compared to substantially higher doses administered for 3 months. This underscores the importance of duration of exposure to moxidectin when facing ML-resistant isolates. Repeated administration of lower doses of moxidectin are an alternative to higher doses in the prevention of heartworm disease associated with less susceptible or resistant isolates.
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Dirofilaria immitis , Dirofilariose , Doenças do Cão , Animais , Cães , Dirofilariose/tratamento farmacológico , Dirofilariose/prevenção & controle , Doenças do Cão/tratamento farmacológico , Doenças do Cão/prevenção & controle , Lactonas/farmacologia , MacrolídeosRESUMO
A 9-year-old dog was presented with weight loss, respiratory effort, and an enlarged abdomen. Imaging studies and exploratory surgery showed pulmonary and splenic masses and bi-cavitary effusion, later classified as hemorrhage. Cytology of the peritoneal and pleural fluids also revealed several microfilariae. Immunologic and molecular analyses confirmed Dirofilaria immitis infection and histopathology of the spleen indicated a cavernous endothelial proliferation with undefined etiology (hemangiosarcoma vs reaction to parasite infestation). The nematode larvae are speculated to have entered body cavities via erratic migration or via hemorrhage and visceral lesions to be related to parasitism. Nematode infection should be considered as a differential diagnosis for internal bleeding of undetermined origin.
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Dirofilaria immitis , Dirofilariose , Doenças do Cão , Hemorragia , Animais , Cães , Dirofilariose/diagnóstico , Dirofilariose/patologia , Doenças do Cão/parasitologia , Doenças do Cão/patologia , Doenças do Cão/diagnóstico , Dirofilaria immitis/isolamento & purificação , Hemorragia/veterinária , Hemorragia/patologia , Hemorragia/parasitologia , Masculino , Baço/patologia , Baço/parasitologia , Líquido Ascítico/parasitologiaRESUMO
Dirofilaria immitis is a mosquito-borne nematode-causing canine heartworm disease, with adult worms localized in the pulmonary arteries and right heart. In rare cases, ectopic migration might occur, and adults and blood circulating microfilariae can be found in unusual organs or fluids (e.g., eyes, abdominal cavity, bone marrow, and urine). A 17-year-old mixed-breed female dog was presented in a private veterinary clinic in Italy for hematuria and dysuria. Physical examination showed cardiac mitral murmur with marked respiratory distress and cyanotic mucous membranes after handling. Abdominal ultrasounds revealed a non-specific chronic cystopathy, while the echocardiography showed enlargement of the right heart associated with tricuspid insufficiency and mitral regurgitation, with the presence of an adult filariae in the right ventricular chamber. Circulating microfilariae were observed in the blood smear and molecularly identified as D. immitis. Unusual microfilaruria was detected in the urine sediment. Data presented raise awareness about the occurrence of microfilariae in unusual locations, such as the bladder, suggesting the need of a thorough clinical and laboratory assessment where D. immitis is endemic.
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Dirofilaria immitis , Dirofilariose , Doenças do Cão , Microfilárias , Animais , Dirofilariose/parasitologia , Dirofilariose/diagnóstico , Cães , Dirofilaria immitis/isolamento & purificação , Doenças do Cão/parasitologia , Doenças do Cão/diagnóstico , Itália , Feminino , Microfilárias/isolamento & purificação , Urina/parasitologiaRESUMO
NexGard®PLUS (moxidectin, afoxolaner, and pyrantel pamoate), is an oral combination product for dogs indicated for the prevention of heartworm disease, the treatment and prevention of flea and tick infestations, and the treatment of gastro-intestinal nematode infections. The safety of this product in dogs was evaluated in three studies. Study #1 was a margin-of-safety study conducted in puppies, dosed six times at 28-day intervals at 1X, 3X, or 5X multiples of the maximum exposure dose (equivalent to 24 µg/kg moxidectin, 5 mg/kg afoxolaner, and 10 mg/kg pyrantel). In Study #2, the product was administered to ABCB1-deficient collie dogs at a 1X dose twice at a 28-day interval, and at a 3X or 5X dose once. Study #3 evaluated the safety of the product at 1X and 3X doses administered three times at 4-week intervals, to dogs harboring adult Dirofilaria immitis. In the three studies, the safety was evaluated on the basis of multiple clinical observations and physical examinations, including a complete assessment of toxicity to macrocyclic lactones, and on comprehensive clinical and anatomical pathology evaluations in Study #1. No clinically significant combination product-related effects were observed in any of the three studies. No signs of macrocyclic lactone toxicity were observed in the ABCB1-deficient collie dogs. Some mild and self-resolving instances of emesis or diarrhea were occasionally observed in the 3X and 5X dosed dogs. NexGard® PLUS was demonstrated to be safe following multiple administrations in puppies, in ABCB1-deficient collie dogs, and in microfilaremic dogs infected with adult D. immitis.
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Doenças do Cão , Combinação de Medicamentos , Macrolídeos , Pamoato de Pirantel , Animais , Cães , Macrolídeos/administração & dosagem , Macrolídeos/uso terapêutico , Macrolídeos/efeitos adversos , Masculino , Feminino , Doenças do Cão/tratamento farmacológico , Pamoato de Pirantel/administração & dosagem , Pamoato de Pirantel/uso terapêutico , Pamoato de Pirantel/efeitos adversos , Isoxazóis/administração & dosagem , Isoxazóis/uso terapêutico , Administração Oral , Dirofilariose/tratamento farmacológico , Dirofilaria immitis/efeitos dos fármacos , Naftalenos/administração & dosagemRESUMO
BACKGROUND: Models that provide high-quality veterinary care for more affordable prices are emerging, but not well documented outside of wellness and preventative care. Effective treatment guidelines for heartworm disease have been developed by the American Heartworm Society; however, not all owners are able to access treatment due to the high costs associated with sick and emergency care services. METHODS: To increase access to high-quality adulticidal treatment of canine heartworm disease, we developed and implemented a technician-leveraged heartworm treatment protocol for high-volume, outpatient community clinic settings based on the American Heartworm Society guidelines. Modifications were few and included limited pre-treatment blood work, pre-injection sedation, post-injection pain medication, and a reduced exercise restriction period. We monitored retention rates for 556 dogs throughout treatment, evaluated treatment success (defined as no antigen detection 9 months post treatment) for patients that returned for post-treatment antigen testing, and reported on adverse reactions and therapy adherence throughout treatment. RESULTS: Of the patients that began adulticide therapy, 539/556 (97%) successfully completed the three-injection series. No microfilariae were detected in 99% (428/433) of those who returned for post-injection microfilaria testing. Among those that returned for or reported the results of post-injection antigen testing, no antigen was detected for 99% (245/248) and no microfilariae were detected for 99.5% (200/201). During the course of treatment, 483/539 (90%) of patients experienced at least one adverse reaction, with the most frequently reported types being behavioral and injection site reactions. 25/539 (4.6%) of owners sought additional medical care for adverse reactions at some point during the treatment course. The overall mortality rate was 1.3% (7/556). CONCLUSIONS: This study represents the first evaluation of a heartworm treatment protocol optimized for implementation in a high-volume, outpatient community clinic setting. Our findings align with those previously reported in private practice or tertiary referral centers, illustrating that through the inclusion of pre-treatment blood work, employing short-acting or reversible sedatives, ensuring proper analgesia, minimizing the use of ancillary diagnostics, reducing the duration of in-clinic monitoring while focusing on outpatient care, and maximizing technician involvement, we can deliver effective and safe melarsomine therapy at a more affordable cost to pet owners.
Assuntos
Arsenicais , Dirofilaria immitis , Dirofilariose , Doenças do Cão , Filaricidas , Triazinas , Cães , Humanos , Animais , Dirofilariose/diagnóstico , Pacientes Ambulatoriais , Doenças do Cão/tratamento farmacológicoRESUMO
BACKGROUND: Veterinary knowledge regarding feline heartworm has been increasing significantly over the past two decades. Necropsy surveys of shelter cats have shown feline adult heartworm infection prevalence to be 5-20% of the rate in unprotected dogs; however, other studies have shown feline heartworm antibody prevalence up to 33%, reflecting higher exposure rates and potential immature adult infections. Thus, the true prevalence of feline heartworm infection is likely underestimated due to the limitations of current diagnostic techniques, inadequate testing protocols, and the high likelihood of cats exhibiting transient clinical signs or dying without confirmation of infection. Diagnosing Feline Heartworm Disease (FHWD), also referred to as Heartworm Associated Respiratory Disease (HARD), is one of the conundrums of veterinary medicine. The purpose of this study was to evaluate and characterize the occurrence of Heartworm Associated Respiratory Disease [HARD] in shelter cats, naturally-infected with D.immitis. METHODS: Fifty shelter cats slated for euthanasia between December 2009 and June 2010 were investigated by gross necropsy, radiography, serology, and lung histopathology using techniques that have been established in experimental models of cat heartworm infection. The relationship between pulmonary vascular disease and serological markers for heartworm was also examined using correlations and statistical modeling. Serology included standard heartworm antigen test and a commonly used heartworm antibody test. Also included were heat-treated heartworm antigen test and two additional heartworm antibody tests previously evaluated on experimentally-infected cats. RESULTS: None of the cats were heartworm antibody (HW Ab) positive on a commonly used HW Ab test used by many reference laboratories even though 20% of the study cats were heartworm antigen (HW Ag) positive on heat-treated samples. Two additional HW Ab test were positive on 26% and 22% of the study cats. The combination of heat-treated HW Ag, HW Ab tests, and histopathology indicated 34% of the study cats had HARD. CONCLUSIONS: Utilizing both, the above tests, and thoracic radiographs, enhanced the ability to predict vascular disease, possibly caused by infection with immature and adult heartworms and supported the premise that cats develop heartworm disease at the same rate as dogs.
Assuntos
Doenças do Gato , Dirofilaria immitis , Dirofilariose , Doenças Vasculares , Animais , Gatos , Alabama , Anticorpos Anti-Helmínticos , Doenças do Gato/diagnóstico , Doenças do Gato/epidemiologia , Doenças do Gato/patologia , Dirofilariose/diagnóstico , Dirofilariose/epidemiologia , Dirofilariose/patologia , Pulmão/patologia , Doenças Vasculares/patologiaRESUMO
BACKGROUND: The mosquito-borne zoonotic parasite Dirofilaria immitis continues to spread northwards in Europe. This parasite can cause potentially life-threatening heartworm disease in dogs and pulmonary dirofilariasis in humans and is, therefore, a major health concern in both the veterinary medicine and human medical fields. This is the first report of D. immitis infections and heartworm disease in the Baltic country Estonia. METHODS: Data on canine D. immitis infections and heartworm disease were collected from the electronic patient records database of the Small Animal Clinic of Estonian University of Life Sciences, the only university clinic in Estonia. The patient records of dogs with confirmed diagnosis of D. immitis infection or heartworm disease were reviewed and summarised. RESULTS: Six dogs had been diagnosed with confirmed D. immitis infection or heartworm disease at the university clinic in 2021-2022. The confirmed diagnoses had been reached following international guidelines, based on a combination of different tests. Molecular confirmation of the parasite species had not been performed. Two of the dogs had been imported while four had no travel history outside of the country. CONCLUSIONS: Four of the dogs with a confirmed D. immitis infection or heartworm disease had no history of being imported or travelling outside of the country, indicating autochthonous infections and, consequently, local circulation of the parasite in Estonia. These findings represent the new northernmost autochthonous cases of D. immitis infection and canine heartworm disease reported in the European Union.