Dirofilaria immitis, commonly known as heartworm, is a parasitic nematode that causes serious health problems in dogs and cats. The disease is transmitted through mosquito bites, making it prevalent in areas with warm and humid climates. However, given climate change, heartworm is fast becoming a concern for countries where the disease has historically not been found. In this miniseries, we will discuss the life cycle, prevalence and association with climate change of D. immitis.
What is heartworm?
Francesco Birago discovered D. immitis in the 17th century in the heart of his hunting dog; however, he thought it was a migrating renal nematode, Dioctophyme renale. D. immitis, on the other hand, is a filarial worm (nematode) that infects the pulmonary arteries and heart of dogs, as well as a variety of other mammals including cats and humans. As such, it is considered a zoonotic disease. Given this zoonotic risk and the high prevalence of this disease in some regions of the world – for example, southern Europe – it is important for vets to recognise clinical signs and be familiar with its therapy and prevention.
The life cycle of heartworms
The life cycle of D. immitis involves several stages, starting with an infected mosquito. The mosquito acts as the vector for the disease, with females of the Culicidae family – which includes over 3,000 species – responsible for the transmission of D. immitis (Figure 1).
The final hosts are dogs, foxes and wolves (Canidae family). Cats, humans and a variety of other mammals (including ferrets) are incidental (or accidental) hosts, in which the parasite has a different and difficult life cycle that leads to aberrant larval migrations and the development of fewer adult worms.
When an infected mosquito bites a dog or cat, it injects infective third-stage larvae (L3) into the subcutaneous tissue of the host, where they migrate to the bloodstream and reach the pulmonary artery. Once in the pulmonary artery, the L3 larvae moult into fourth-stage larvae (L4), and then into immature adult heartworms (pre-adults or L5). The pre-adults migrate to the right side of the heart and then to the pulmonary arteries.
Adult heartworms can be found in the pulmonary artery and right side of the heart between 70 and 80 days post-infection, with the heartworms reaching sexual maturity at 120 days post-infection. Subsequently, the adult female heartworms produce microfilariae, which circulate in the bloodstream and can be ingested by a mosquito during a blood meal.
It is important to remember that only female heartworms can produce microfilariae, but in order to do so a male heartworm is required too. Further, only female heartworms produce antigens detected by diagnostic tests, which is of relevance when considering diagnosis and treatment of the disease.
Only female heartworms produce antigens detected by diagnostic tests, which is of relevance when considering diagnosis and treatment
On ingesting the microfilariae, the mosquito will become infected and will moult to L2 in eight days and to L3 after an additional three days. Mosquitos have protective mechanisms to avoid becoming infected or stop the moulting of the parasite. These include melanisation and encapsulation of L3; microfilariae becoming damaged by buccal structures (cibarial armature or cibarium); and coagulation and trapping of microfilariae in the digestive tract.
Adult D. immitis can grow up to 30cm in length and live in dogs for up to seven years and up to two years in cats. Wolbachia species are Gram-negative bacteria that infect D. immitis. All worms are positive for Wolbachia suggesting there is an obligatory symbiosis between bacteria and its host. Wolbachia play a role in the development of D. immitis larvae. If antibiotics against these bacteria are administered, the larval development stops at L3.
Prevalence and distribution of heartworm
D. immitis is widespread in many parts of the world, including Europe, Asia, Africa, Australia and the Americas. In Europe, the highest prevalence of heartworm disease is reported in southern countries, such as Italy, Spain, Portugal and Greece, but it is also present in other regions.
The prevalence of heartworm disease in dogs and cats varies widely between different regions and populations, depending on several factors, such as the presence of the mosquito vector, climate, host susceptibility and preventative measures. In countries such as Portugal, Italy (Po valley), Japan, Iran, Malaysia and Spain (Canary Islands) the prevalence of heartworm in dogs can range between 30 and 50 percent (Simón et al., 2012).
In Europe, the highest prevalence of heartworm disease is reported in southern countries, such as Italy, Spain, Portugal and Greece, but it is also present in other regions
However, the most recent data showed a marked decrease in prevalence in the last three decades in Italy, with prevalence in dogs declining from 40 percent to 18 percent (Genchi et al., 2009; Genchi and Kramer,2020), and in the Canary Islands, which has seen a decrease from 30 percent to 19 percent (Montoya-Alonso et al., 2010). This is the result of preventative measures taken by veterinarians. Conversely, the prevalence in red foxes and coyotes in Texas was reported to reach 70 percent (Custer and Pence, 1981). For this reason, wild carnivores (Canidae) are considered the reservoir of D. immitis.
The prevalence in cats is much lower as they are suboptimal hosts for the parasite, in which the worms rarely grow to the adult form. It is believed that the prevalence in cats is only 5 to 20 percent of the prevalence in dogs in the same region (Brianti et al., 2022).
In humans, the prevalence of D. immitis in Europe is very low, whereas it is higher in the Americas (Simón et al., 2012). In Europe and Russia, infections with Dirofilaria repens are more common – this is another Dirofilaria species that causes cutaneous nodules and ocular migrations and it can infect pets too.
The role of climate change in heartworm distribution
There are two factors that have had an important role in the spread of D. immitis in regions where it previously wasn’t present: human behaviour and climate factors. The first is due to import and export – for example, the Asian tiger mosquito is believed to have been introduced into the Americas and Europe by the import of old car tyres from Asia (Scholte and Schaffner, 2007). However, the latter has a more intriguing physiological explanation.
The moulting process of D. immitis is temperature sensitive. In particular, for moulting from L2 to L3 to occur a temperature above 14°C is required – anything below this and moulting may not occur. This is one of the most relevant reasons as to why northern European countries with colder weather have not been impacted by heartworm.
With warmer weather, the mosquito vector’s habitat and range may expand, increasing the likelihood of transmission of the disease to dogs and cats
However, there is evidence showing that temperature is rising in the region. For example, in England temperatures are often reaching over 14°C for most of the spring and summer, especially in the south. With warmer weather, the mosquito vector’s habitat and range may expand, increasing the likelihood of transmission of the disease to dogs and cats.
In England, heartworm disease could be an emergent disease associated with the introduction of non-native mosquito species, therefore knowing the clinical signs and prevention of this disease may be helpful for veterinarians working in the UK. This will be the topic of the second article in the miniseries.