Canine and Feline Dirofilariasis Currently Spreads in Indonesia Damaging Pulmonary Arteries and Lungs: A Literature Review

Dirofilariasis, caused by Dirofilaria immitis, mostly known as heartworm disease, is an important mosquito-borne nematode zoonosis that naturally infects canids and other species such as cats, ferrets, and humans. There have been reports of heartworm infection from many countries in worldwide. Researchers have reported D. immitis is widely distributed in Southeast Asia because this parasitic zoonosis disease lives in temperate, tropical, and subtropical areas and can be found in colder regions. Therefore, the authors intended to provide an overview of Dirofilariasis cases in Indonesia from a global perspective. The published articles of dirofilariasis were collected and retrieved by an electronic literature search of three databases, including Google Scholar, PubMed, and Science Direct. The literature presented is intended to enhance our current understanding of the overview of D. immitis infection and its prevalence in Indonesia from a global perspective. D. immitis infection can cause caval syndrome in dogs as well as a cardiopulmonary syndrome known as Heartworm-Associated Respiratory Diseases (HARD), which can become fatal as the number of worms infecting the host increases. Whereas in cats, although the number of worms in the host are very few (one to six worms) they can cause pathological changes in the pulmonary arteries which result in a more serious infection than in dogs and endanger life.

Infection risk varies within urbanized landscapes: the case of coyotes and heartworm

Background Urbanization can have profound effects on ecological interactions. For host–pathogen interactions, differences have been detected between urban and non-urban landscapes. However, host–pathogen interactions may also differ within highly heterogeneous, urbanized landscapes. Methods We investigated differences in infection risk (i.e., probability of infection) within urbanized landscapes using the coyote (Canis latrans) and mosquito-borne nematode, Dirofilaria immitis (the causative agent for canine heartworm), as a case study. We focused on a coyote population in Chicago for which extensive behavioral and heartworm infection data has been collected between 2001 and 2016. Our objectives were to: (i) determine how onset and duration of the heartworm transmission season varied over the 16-year period and across the urban–suburban gradient; and (ii) investigate how heartworm infection risk in coyotes varied over the years, across the urban–suburban gradient, by coyote characteristics (e.g., age, sex, resident status), and coyote use of the urbanized landscape (e.g., use of urban areas, mosquito habitats). Results While onset of the heartworm transmission season differed neither by year nor across the urban–suburban gradient, it was longer closer to the core of Chicago. Of the 315 coyotes sampled, 31.1% were infected with D. immitis. Older coyotes and coyotes sampled in later years (i.e., 2012–2016) were more likely to have heartworm. While coyote location in the urban–suburban gradient was not a significant predictor of infection, the proportion of urban land in coyote home ranges was. Importantly, the size and direction of this association varied by age class. For adults and pups, infection risk declined with urbanization, whereas for subadults it increased. Further, models had a higher predictive power when focusing on resident coyotes (and excluding transient coyotes). The proportion of mosquito habitat in coyote home ranges was not a significant predictor of infection. Conclusions Our findings suggest that urbanization may affect host exposure to vectors of D. immitis, that risk of infection can vary within urbanized landscapes, and that urbanization–wildlife infection associations may only be detected for animals with certain characteristics (e.g., age class and resident status). Graphical abstract

An Accessible Alternative to Melarsomine: “Moxi-Doxy” for Treatment of Adult Heartworm Infection in Dogs

Canine heartworm infection, caused by the filarial parasite Dirofilaria immitis, represents a serious and expanding animal welfare concern that is expected to increase due to the effects of climate change and the COVID-19 pandemic. A body of evidence has emerged to support the use of a non-arsenical adulticide treatment protocol, using moxidectin and doxycycline to kill adult heartworms over a prolonged period. While a three-dose protocol using the arsenical drug melarsomine is currently the safest and most effective treatment for heartworm infection, this drug is not available in some countries and is inaccessible for many owners and animal shelters. Moxidectin-doxycycline (moxi-doxy) provides a viable alternative to no treatment at all, in cases where arsenical treatment is not possible. Based on current evidence, the most effective non-arsenical treatment regimen is doxycycline 10 mg/kg PO q 12 or 24 h for 28 days, combined with topical moxidectin at label dose. Moxidectin is repeated monthly until no antigen detected (NAD) status is confirmed. Sustained release injectable moxidectin, in combination with doxycycline, may provide an alternative in remote regions or in settings where significant compliance or accessibility concerns exist, but more studies are needed. In moxi-doxy protocols, doxycycline should be repeated annually until NAD. This review summarizes the safety and efficacy of moxi-doxy, addresses controversies surrounding this treatment approach, and provides detailed recommendations for treatment regimens and post-treatment testing.

Secretory microRNA Profiles of Third- and Fourth-Stage Dirofilaria immitis Larvae with Different Macrocyclic Lactone Susceptibility: In Search of Biomarkers for Early Detection of Infection

The canine heartworm, Dirofilaria immitis, is among the most important parasites of dogs in the United States and worldwide, and may cause severe and potentially fatal disease. Current diagnostic recommendations rely on serological detection of an adult female antigen, and visualization of microfilariae in the blood. Therefore, a reliable diagnosis can be only performed approximately six months post-infection. There is a growing need to characterize novel diagnostic markers that are capable of detecting the early stages of heartworm infection, in special markers associated with third-stage larvae (L3) and fourth-stage larvae (L4). The early detection of infection would guide medical interventions that could impede the development of patent infections and further parasite transmission. We cultured D. immitis L3 and L4 of two laboratorial strains with different susceptibility statuses to macrocyclic lactone drugs in vitro. Excretory/secretory microRNAs were sequenced and analyzed. We identified two miRNA novel candidates secreted abundantly by both L3 and L4 of both strains. These candidates were previously detected in the secretions of other D. immitis stages and one of them was found in the blood of D. immitis-infected dogs. These miRNAs have not been found in the secretions of other nematodes and could be D. immitis-specific diagnostic biomarkers, which could allow for the early detection of infection.

Detection of heartworm antigen without cross-reactivity to helminths and protozoa following heat treatment of canine serum

Background Detection of Dirofilaria immitis, or heartworm, through antigen in sera is the primary means of diagnosing infections in dogs. In recent years, the practice of heat-treating serum prior to antigen testing has demonstrated improved detection of heartworm infection. While the practice of heat-treating serum has resulted in earlier detection and improved sensitivity for heartworm infections, it has been suggested that heat treatment may cause cross reactivity with A. reconditum and intestinal helminth infections of dogs. No studies have assessed the potential cross-reactivity of these parasites with heartworm tests before and after heat treatment using blood products and an appropriate gold standard reference. Methods Canine sera (n=163) was used to evaluate a heartworm antigen-ELISA (DiroCHEK®) and potential cross-reactivity with common parasitic infections. The heartworm status and additional parasite infections were confirmed by necropsy and adult helminth species verified morphologically or by PCR, and feces evaluated by centrifugal fecal flotation. Results Intestinal parasites were confirmed in 140 of the dogs by necropsy, and 130 by fecal flotation. Acanthocheilonema reconditum microfilariae were confirmed in 22 dogs. Prevalence of heartworm infection confirmed by necropsy was 35.6% (58/163). In the 105 dogs without heartworms, specificity remained unchanged at 100% both before and after heat treatment despite confirmed infections with A. reconditum, Ancylostoma caninum, Ancylostoma brasiliense, Trichuris vulpis, Toxocara canis, Dipylidium caninum, Spirometra mansonoides, Macracanthorynchus ingens, Cystoisospora sp., Giardia sp., and Sarcocystis sp. Conclusions These findings suggest that the use of heat treatment improves sensitivity of heartworm tests and is unlikely to cause false positive antigen results due to Acanthocheilonema reconditum, intestinal helminths, and protozoal parasites in dogs. Graphic abstract

Dirofilaria immitis Could Be a Risk Factor for the Development of Allergic Diseases in Humans

The Canary Islands are hyperendemic for canine heartworm and the risk of zoonotic infection is high. Additionally, there is evidence of development of allergies due to nematode infections in animals and humans. Since the population of the Canary Islands presents high prevalence of allergic comorbidities, and previous studies have shown a possible relationship between allergies and seropositivity to heartworm, the aim was to evaluate whether exposure to heartworm may contribute to the development of allergies in the human population. First, an epidemiological study was conducted on 248 owners of dogs with/without heartworm infection in the Canary Islands. Secondly, a serological analysis of the presence of total IgE and specific IgE against heartworm was conducted in 66 samples of inhabitants of the Canary Islands. The survey showed that allergic owners had heartworm-positive dogs more frequently (p < 0.01). Of the analyzed human samples, 43.9% were seropositive to heartworm and Wolbachia. Total IgE concentrations were increased in 34.5% seropositive samples and 8.1% seronegative samples. Specific IgE against heartworm was only found in human seropositive samples (17.2%). Contact with heartworm may be a risk factor for the development of allergic diseases, although further studies to elucidate the relationship between heartworm and allergies should be carried out.

Dirofilaria immitis in wolves recolonizing northern Italy: are wolves competent hosts?

Background Wild carnivores such as the grey wolf (Canis lupus), red fox (Vulpes vulpes) and golden jackal (Canis aureus) are recognized hosts of Dirofilaria immitis. However, few studies have focused on their actual role in the epidemiology of heartworm infection. This study describes the prevalence and distribution of D. immitis in wolves in a heartworm-endemic area in northern Italy where wolves have recently returned after long-time eradication, and investigates the fertility status of the collected adult nematodes. Methods In the frame of a long-term wolf monitoring programme in northwestern Italy, 210 wolf carcasses from four provinces were inspected for the presence of filarioid nematodes in the right heart and pulmonary arteries. Female heartworms were measured, and their uterine content analyzed according to a previously described “embryogram” technique. Results Three wolves, all originating from a single province (Alessandria), were positive for D. immitis (1.42%, 95% CI: 0.48–4.11%, in the whole study area; 13.6%, 95% CI: 4.7–33.3%, limited to the single province from which infected wolves originated). Mean intensity was 5 worms (range: 3–7) and the female worms measured 21–28 cm in length. Six out of 9 female worms harbored uterine microfilariae: 5 were classified as gravid; 1 showed a “discontinuous gradient”; and 3 were non-gravid. Conclusions The present data show that heartworm infection is already prevalent in wolves that have recolonized the known heartworm-endemic area. Based on “embryogram” results, wolves were shown suitable heartworm hosts. Interestingly, investigated wolves appeared similarly exposed to heartworm infection as sympatric unprotected dogs (owned dogs that have never received any heartworm prevention treatment) sampled at the beginning of the wolf return process.

Canine Dirofilariasis: A Case Report and Review of the Literature

Dirofilariasis is a disease of clinical importance in dogs. It is to this end that a case of a seven-year-old mongrel with dirofilariasis was presented to examine the unique features and presentation in the canine patient in question. The dog had clinical signs consistent with the disease. Further diagnostic tests were performed to establish the presence and severity of the disease and make an appropriate treatment plan. The Knott’s test revealed Dirofilaria species in the circulating blood and radiography showed right ventricular hypertrophy with pulmonary arterial enlargement and increased bronchial opacification. The treatment instituted was ivermectin therapy by subcutaneous injection every two weeks for six months, cardiac glycoside and antibiotics for 14 days. The clinical signs resolved after completion of the treatment. A general overview of heartworm infection in dogs was also done to update current knowledge of the disease. Though the risk of significant propagation of Dirofilaria immitis is considered low, with the climate change and international pet travel regulations, this emerging zoonosis remains a threat.

Prevalence of Infection With Dirofilaria Immitis in Cats in Townsville, Australia

Objective Dirofilaria immitis commonly infects Australian dogs. Studies on the prevalence of infection by this parasitic helminth in Australia cats are rare and relatively old. Data obtained from other countries would suggest a likely prevalence of 4.7–16%. The current study aimed to determine the prevalence of D. immitis in an endemic region of Australia by antigen, antibody and PCR testing. Methods 172 healthy cats over 6 months of age from the Townsville region of Australia were tested for D. immitis specific antibodies and antigen using a commercially available kit. 50 samples were subsequently retested using a second commercially available antibody kit. 48 of these samples were checked for D. immitis DNA using PCR. Results No cat tested positive on any test. The Ausvet Epitools epidemiology calculator was used to calculate prevalences. Maximum antigen (1.27%), antibody (2.1%) and PCR (2.1%) prevalences were calculated. Conclusion Our results suggest that the prevalence of heartworm infection in pet cats in this region of Australia is lower than expected based on data from other areas around the world.