Heartworm-, Flea-, and Tick-associated Diseases in Dogs: A Review of Common Parasites and Drug Classes Prophylactic Against Them.

Throughout recorded history, the canine-human connection has varied by custom, purpose, and intensity. In many cultures worldwide, dogs have long been considered essential workers, protectors and guardians, and, often, an integral part of the family unit. Ensuring the health and quality of life of those companion animals is essential to preserving the bond between dogs and their owners. Fortunately, advances in veterinary science continue to improve treatments and cures for and prophylaxis against a variety of deadly canine diseases, several of which can be sourced to ectoparasites or endoparasites. For many veterinary patients, a customized preparation often proves to be the best therapeutic option, but many compounding-pharmacy stores also include a retail component that offers ready access to manufactured prescription medications, including those prophylactic against canine flea, tick, or heartworm infestation. Because dog owners often need guidance in selecting such products and assistance with obtaining them, this article will be of special interest to ompounders in those pharmacies. To that end, the following content addresses common canine parasites and classes of drugs that prevent the illnesses they cause, with emphasis on heartworm disease.

Prophylaxis Against Heartworm Infection and Flea or Tick Infestation in Dogs: Single Agents and Combination-Drug Products.

From ancient times to the present, parasites and the diseases they transmit have jeopardized the health and wellbeing of working and companion canines worldwide. Many common pests that afflict dogs can be classified as ectoparasites (e.g., fleas, ticks, lice), which serve as vectors of pathogens transmitted as the organism feeds or defecates; or endoparasites (e. g, helminths, protozoa), which can cause slowly progressive subclinical canine diseases as well as acute illnesses associated with high morbidity and mortality rates. Safe, effective antiparasitic prophylaxis in dogs remains a topic of major interest to both veterinarians and their clients, especially with respect to the prevention of canine heartworm infection and flea or tick infestation. Many compounders, especially those whose pharmacy includes a retail component, counsel veterinarians and pet owners about preparations and commercially available medications that prevent or treat parasitic infestations and provide assistance in obtaining those therapies. To support such efforts, this article provides information about single agents and combination-drug products prophylactic against common canine parasites, emerging resistance to those medications, and the toxic effects that such treatments can engender in some canine breeds.

Dirofilaria immitis and Onchocercidae spp. in wild felids from Brazil.

Among the species described within the Onchocercidae family, Dirofilaria immitis is regarded as the most common worldwide, causing severe and often fatal conditions in dogs, cats, and occasionally humans. Dirofilaria spp. are vectored by mosquitoes, simulids, and culicoids, with their epidemiology dependent on the geographical distribution of competent vectors. Eight species of Dirofilaria have been reported so far in Brazil, of which six parasitize non-human primates, deer, procyonids, and marsupials. Here, we investigated the occurrence of Onchocercidae in wild felids (i.e., Panthera onca, Puma concolor, Herpailurus yagouaroundi, Leopardus geoffroyi, Leopardus guttulus, Leopardus pardalis, Leopardus wiedii, Leopardus munoai) from different locations in Brazil. Overall, 82 samples (n = 63 blood; n = 19 tissues) were molecularly screened for cytochrome c oxidase subunit-1 (cox1) gene. Four (i.e., 4.8%) wild felid samples were positive, and at BLAST analysis, the obtained sequences showed varying percentage of nucleotide identity with the genera Brugia (i.e., 87-88%), Setaria (i.e., 89%), and D. immitis (i.e., 94.4%). Phylogenetic analyses clustered sequences obtained into three distinct clades, one with D. immitis and the remaining two with other Onchocercidae spp. Data herein obtained highlight the need for a more comprehensive understanding of the diversity and biology of Onchocercidae in South America in order to assess the potential impact that these species may have for domestic and wild animals, as well as humans.

Microfilaruria of Dirofilaria immitis in a dog from Italy.

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.

Safety of an oral combination of moxidectin, afoxolaner, and pyrantel pamoate in dogs.

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.

Genotyping USA laboratory-maintained isolates and European clinical isolates of Dirofilaria immitis to assess macrocyclic lactone susceptibility or resistance at predictive SNP sites using droplet digital PCR.

Dirofilaria immitis is a parasitic nematode that causes cardiovascular dirofilariosis ("heartworm disease") primarily in canids. The principal approach for mitigating heartworm infection involves the use of macrocyclic lactone (ML) for prophylaxis. Recent research has substantiated the emergence of D. immitis displaying resistance to MLs in the USA. Numerous factors, such as the mobility of companion animals and competent vectors could impact the spread of drug resistance. Genomic analysis has unveiled that isolates resistant to ML exhibit unique genetic profiles when compared to their wild-type (susceptible) counterparts. Out of the ten single nucleotide polymorphism (SNP) markers validated in clinical samples of D. immitis from the USA, four have demonstrated their effectiveness in distinguishing between isolates with varying ML efficacy phenotypes. This study explores the potential of these confirmed SNPs for conducting surveillance studies. Genotypic analysis using SNP markers emerges as a valuable tool for carrying out surveys and evaluating individual clinical isolates. Two USA laboratory-maintained isolates (Berkeley, WildCat) and twenty-five random European clinical samples of either adult worms or microfilariae (mf) pools isolated from domestic dogs, were tested by droplet digital PCR (ddPCR)-based duplex assay. This approach elucidates genetic evidence pertaining to the development of drug resistance and provides baseline data on resistance related genotypes in Europe. The data on these clinical samples suggests genotypes consistent with the continued efficacy of ML treatment regimens in Europe. In addition, this assay can be significant in discriminating cases of drug-resistance from those possibly due to non-compliance to the recommended preventive protocols.

Efficacy of moxidectin, using various dose regimens, against JYD-34, a macrocyclic lactone resistant isolate of Dirofilaria immitis.

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.

Improving access to melarsomine therapy: treating canine heartworm infection in a high-volume, outpatient community clinic setting.

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.

Heartworm disease in domestic dogs in Estonia: indication of local circulation of the zoonotic parasite Dirofilaria immitis farther north than previously reported.

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.

Ocular Dirofilariasis in Migrant from Sri Lanka, Australia.

We describe a case of imported ocular dirofilariasis in Australia, linked to the Hong Kong genotype of Dirofilaria sp., in a migrant from Sri Lanka. Surgical extraction and mitochondrial sequences analyses confirmed this filarioid nematode as the causative agent and a Dirofilaria sp. not previously reported in Australia.

Ecological niche modeling analysis (Cx. pipiens), potential risk and projection of Dirofilaria spp. infection in Greece.

Vector-borne diseases continue to increase worldwide. Dirofilariosis is one of the most common vector-borne zoonotic diseases, mainly caused by Dirofilaria spp. (D. immitis and D. repens) and spread by culicid mosquitoes of different species. Greece is one of the countries in southern Europe where it is traditionally endemic, and its distribution is not homogeneous. The aim of this study was to develop an environmental model for Greece that reflects the suitability of the ecological niche for Dirofilaria spp. infection risk and its projection until 2080. For this purpose, we used the potential distribution of suitable habitats for Culex pipiens calculated using an ecological niche model (ENM) and the potential number of generations of Dirofilaria spp. The ecological niche model of Cx. pipiens in Greece showed good predictive power (AUC=0.897) with the parasite at a resolution of 1 km2. The variables that contributed most to the model were mean annual temperature, rivers and human footprint. The highest risk of infection was found in coastal areas and in riverside areas of the main river basins, as well as in irrigated areas of the mainland and peninsular regions and in the whole territory of island areas, and the lowest risk was found in areas of higher altitude. A positive relationship was found between the risk of dirofilariosis and the location of infected dogs, with 86.65% located in very high and high risk areas. In 2080, the percentage of territory gained by Cx. pipiens will increase by 261.52%. This model provides a high predictive value, predicted presence, and risk of Dirofilaria spp. infection and can serve as a tool for the management and control of this disease.

Temperature-bounded development of Dirofilaria immitis larvae restricts the geographical distribution and seasonality of its transmission: case study and decision support system for canine heartworm management in Australia.

Dirofilaria immitis is the causative agent of canine heartworm disease. We used the established heartworm development unit (HDU) principle to map the extrinsic incubation period (EIP) of D. immitis in Australia using historical weather data from 2013-2022. We found weather conditions suitable for EIP completion showed substantial seasonality and geographical variability. Whilst a considerable percentage of the Australian territory showed suitable weather conditions to always support EIP completion (17%), only 2.7% of the 2021 Australian human population lived in this region. Therefore, 97% of the population lived in an area that changed its EIP suitability within the study period. EIP completion is required prior to D. immitis transmission, meaning that infection risk of D. immitis is seasonal and location-dependent, being disrupted each year for most of the human population's dogs. We developed an online, open access tool allowing us to visualise EIP completion across Australia historically and in near real-time. We aim to support veterinarians to make risk-based recommendations for dirofilariosis prevention by using the tool, available at https://heartworm-mapping.adelaide.edu.au/shiny/.

Evaluation of feline heartworm disease based on gross necropsy, serology, pulmonary histopathology, and radiographic evidence in adult shelter cats in northeastern Alabama.

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.

Human dirofilariasis - Unforeseen lesion in subcutaneous nodules: Case series from a tertiary care hospital, Wayanad.

Human dirofilariasis is a type of zoonotic infection caused by the Dirofilarial species. It is a type of roundworm which is commonly seen in dogs, cats and is transmitted to humans by mosquito bite. Microfilaria is rarely produced in humans. Although clinically they can have varied presentations, it usually presents as ocular or subcutaneous nodules. Definitive diagnosis requires histopathological findings of this worm. We hereby report three cases of Dirofilariasis from a tertiary care hospital in Wayanad.

An unexpected case of a dog from Poland co-infected with Dirofilaria repens and Dirofilaria Immitis.

BACKGROUND: Dirofilariasis is a vector-borne disease caused by parasitic nematodes of the genus Dirofilaria spp., considered an emerging concern in both veterinary and human medicine. Climate changes and human activities, such as pet travel, contribute to the spread of diseases to new non-endemic regions. Poland is dominated by subcutaneous dirofilariasis caused by D. repens infections. Cardiopulmonary dirofilariasis, also known as a heartworm disease is much more rare with only single autochthonous cases reported so far. Also, imported infections are observed sporadically in dogs traveling to endemic countries. In this study, we report the first case of a dog in Poland, never having traveled abroad, co-infected with Dirofilaria repens and Dirofilaria immitis. CASE PRESENTATION: A 14-year-old mixed breed, an intact male dog with fever, lightly pale mucosal membranes, moderate abdominal pain, and a mild cough was presented in a veterinary clinic in Warsaw, Poland. The examination of the blood sample collected for complete morphology and biochemistry revealed the presence of live microfilariae. Presence of the DNA of both microfilariae species was detected using Real-Time PCR with species-specific primers. CONCLUSIONS: Since the remaining diagnostic methods like Knott's test, antigen test or echocardiography did not reveal the presence of D. immitis, we discussed the impact of microfilariae periodicity and low worm burden infections on the limited efficiency of these techniques. We strongly recommend using a mixed diagnostic approach for the most sensitive and specific diagnosis since the ideal diagnostic method does not exist, and several factors may contribute to misdiagnosis. Furthermore, we considered factors that contribute to the uncontrolled spread of dirofilariasis such as climate changes, introduction of new species of mosquitoes competent for the transmission of the disease, and wildlife animals as an important reservoir of this parasitosis. Given that Poland shares borders with countries classified as endemic and pre-endemic for D. immitis, such as Slovakia and Ukraine, it is reasonable to anticipate a rise in autochthonous heartworm infections and shifts in the epidemiological pattern of dirofilariasis in the coming years.

Atypical case of subcutaneous filariosis in a cat caused by Dirofilaria immitis.

Subcutaneous dirofilariosis is a well-known disease caused mainly by Dirofilaria repens and described in several mammalian species including humans, dogs, and cats. Additionally, early developing stages of the heartworm Dirofilaria immitis are rarely reported in subcutaneous localization from humans and dogs. To our knowledge, confirmed clinical evidence of this condition has not been described in the cats yet, even if the feline hosts can be affected either by the classic adult-related heartworm form or heartworm-associated respiratory disease (HARD) caused by immature stages. A 2 year old, spayed male cat was presented for three subcutaneous nodules on the head and trunk. The cat lived in Northern Italy and was regularly vaccinated and treated monthly with an antiparasitic spot on formulation containing selamectin. One of the three nodules was surgically excised and examined. Histology showed the presence of a nodular lesion in the subcutis characterized by a severe inflammatory infiltrate composed of macrophages, small lymphocytes, with fewer eosinophils, and mast cells, supported by a proliferation of mature fibroblasts (fibrosis). Inflammatory cells were multifocally surrounding sections of parasites identified as adult nematodes. Microscopic features were compatible with D. immitis, which has been molecularly confirmed (98.2% identity to D. immitis isolate OP107739). The cat tested negative for D. immitis antigenemia and the two remaining nodules disappeared spontaneously in a few months. In region where heartworm is prevalent, aberrant localization of D. immitis should be considered in the differential diagnoses of subcutaneous filarial worms in cats and dogs.

Subcutaneous dirofilariasis in a 25-year-old male patient in Belgium on ultrasonography: a case report.

BACKGROUND: Subcutaneous dirofilariasis is a parasitic zoonosis commonly described in Canidae but rarely seen in humans. Most physicians are unfamiliar with this disease, especially in nonendemic areas, which can lead to medication error and diagnostic and treatment delay. To the best of our knowledge, no previous case of subcutaneous dirofilariasis preoperatively diagnosed on ultrasound has been described in Western Europe. CASE PRESENTATION: A 25-year-old Belgian male patient presented with a subcutaneous nodule in the epigastric region. Ultrasound investigation showed a typical cystic lesion with an internal serpiginous structure with echogenic lines, and there was active twirling movement of this serpentine structure during investigation, pathognomonic for subcutaneous dirofilariasis. Surgical extirpation was performed, and the diagnosis was histopathologically confirmed. CONCLUSION: Subcutaneous dirofilariasis has a characteristic appearance on ultrasound but is not well known in nonendemic areas, often leading to diagnostic delay and initial incorrect treatment. More knowledge of this disease and of its characteristic ultrasound appearance will hopefully lead to better patient care.

Is the European badger a new host for Dirofilaria immitis? The first records in Greece.

Dirofilaria immitis is a ubiquitous nematode parasite with zoonotic potential, transmitted by mosquitoes, that causes heartworm disease in various animal species. Dogs are the parasite's typical final host, and wild carnivores represent the parasite's reservoir in nature. Studies on D. immitis infections in wild animals are essential to assess infection pressure for domestic animals, and until now, there has been only one infection case reported in a European badger (Meles meles). The current report describes the first two European badger cases with cardiovascular dirofilariosis in Greece. Two adult male badgers were rescued in Heraklion and Chania, Crete Island, and admitted to "ANIMA -Wildlife Rehabilitation Centre" in Athens. The detailed clinical examination revealed that the first badger suffered from severe broncho-pneumonitis while the second one displayed clinical signs associated with severe brain trauma. Blood samples were taken for haematology and biochemistry analyses during their short hospitalisation period. In addition, different routine diagnostic tests were carried out, including heartworm antigen testing (ELISA) and the modified Knott's test for microfilariae. Both badgers were positive in both tests. The animals died a few hours after their admission and the detailed necropsies followed, revealed the presence of three parasites in each animal's right heart, morphologically identified as adults of D. immitis. These findings add the European badger in the list of additional potential reservoir hosts for D. immitis and highlight the potential role of wildlife for companion animals and human health.