SUMMARY: Dirofilariasis represents a zoonotic mosaic, which includes two main filarial species (Dirofilaria immitisandD. repens) that have adapted to canine, feline, and human hosts with distinct biological and clinical implications. At the same time, bothD. immitisandD. repensare themselves hosts to symbiotic bacteria of the genusWolbachia, the study of which has resulted in a profound shift in the understanding of filarial biology, the mechanisms of the pathologies that they produce in their hosts, and issues related to dirofilariasis treatment. Moreover, because dirofilariasis is a vector-borne transmitted disease, their distribution and infection rates have undergone significant modifications influenced by global climate change. Despite advances in our knowledge ofD. immitisandD. repensand the pathologies that they inflict on different hosts, there are still many unknown aspects of dirofilariasis. This review is focused on human and animal dirofilariasis, including the basic morphology, biology, protein composition, and metabolism ofDirofilariaspecies; the climate and human behavioral factors that influence distribution dynamics; the disease pathology; the host-parasite relationship; the mechanisms involved in parasite survival; the immune response and pathogenesis; and the clinical management of human and animal infections.

Human dirofilariosis is a clinical entity caused by infection with nematode species of the genus Dirofilaria. The traditional picture depicts the disease as a sporadic event associated with the presence of a single immature worm causing a nodular lesion. With the aim to reassess this paradigm, establishing a more accurate picture of the disease and homogenize criteria, a scoping review was conducted by searching, screening and analysing published clinical cases of human dirofilariosis worldwide during the 21st century. After extracting data from 305 publications containing 576 case reports, results showed that human dirofilariosis is currently caused by five Dirofilaria species (mainly D. repens). Maturation was not uncommon, since 42.95% of the parasites recovered were described as mature worms, most of them females, 26.42% of which contained micofilariae in the uterus. Moreover, six microfilaremic cases have been described. The predominant clinical manifestation was the presence of a worm encapsulated within a nodule, but there is a considerable variety of accompanying symptoms depending on anatomical location and type of dirofilariosis. Parasites/nodules were found in 71 different anatomical locations, being the traditional nomenclature of human dirofilariosis unable to properly cover this complex situation. Delay in seeking medical assistance (patient perception) and the frequency of wrong clinical suspicions (doctor knowledge), strongly influenced clinical management. The initial suspicion in cases of subcutaneous and pulmonary dirofilariosis is predominantly a tumour, while in the ocular dirofilariosis a parasite (but not directly Dirofilaria) is mostly suspected. Surgery is usually applied, regardless of the use of non-invasive techniques during preoperative management and although its use is still limited, molecular approach is the most accurate technique to establish a species-level diagnosis. Accurate epidemiological, parasitological and clinical information while handling and reporting human clinical cases is a need for physicians and researchers to improve and standardize the clinical management of human dirofilariosis.

Vector-borne transmitted helminthic zoonosis affects the health and economy of both developing and developed countries. The concept of episystem includes the set of biological, environmental, and epidemiological elements of these diseases in defined geographic and temporal scales. Dirofilariasis caused by different species of the genusDirofilariais a disease affecting domestic and wild canines and felines and man, transmitted by different species of culicid mosquitoes. This complexity is increased becauseDirofilariaspecies harbor intracellular symbiontWolbachiabacteriae, which play a key role in the embryogenesis and development of dirofilariae and in the inflammatory pathology of the disease. In addition, the vector transmission makes the dirofilariasis susceptible to the influence of the climate and its variations. The present review addresses the analysis of dirofilariasis from the point of view of the episystem, analyzing the complex network of interactions established between biological components, climate, and factors related to human activity, as well as the different problems they pose. The progress of knowledge on human and animal dirofilariasis is largely due to the multidisciplinary approach. Nevertheless, different aspects of the disease need to continue being investigated and cooperation between countries and specialists involved should be intensified.