Rodrigo Morchón

Human and Animal Dirofilariasis: the Emergence of a Zoonotic Mosaic

SUMMARY Dirofilariasis represents a zoonotic mosaic, which includes two main filarial species (Dirofilaria immitis and D. repens) that have adapted to canine, feline, and human hosts with distinct biological and clinical implications. At the same time, both D. immitis and D. repens are themselves hosts to symbiotic bacteria of the genus Wolbachia, 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 of D. immitis and D. repens and 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 of Dirofilaria species; 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.

What is new about animal and human dirofilariosis

Dirofilaria immitis and D. repens, the causal agents of cardiopulmonary and subcutaneous dirofilariosis, respectively, affect canine, feline and human populations with an increasing incidence in temperate and tropical areas of the world. In the past decade outstanding advances in the knowledge of dirofilariosis have been achieved. Nevertheless, questions such as the impact of climate change in the transmission and distribution of dirofilariosis, as well as a profound evaluation of both the role of Dirofilaria and Wolbachia and the proteins produced by them in the parasite-host relationship have not been fully addressed; therefore there must be milestones in dirofilariosis research in order to design new strategies and tools for the control of this disease.

Heartworm Disease (Dirofilaria immitis) and Their Vectors in Europe - New Distribution Trends.

Cardiopulmonary dirofilariasis is a cosmopolitan disease caused by Dirofilaria immitis, which affects mainly canids and felids. Moreover, it causes zoonotic infections, producing pulmonary dirofilariasis in humans. Heartworm disease is a vector-borne transmitted disease, thus transmission depends on the presence of competent mosquito species, which is directly related to favorable climate conditions for its development and survival. Cardiopulmonary dirofilariasis is mainly located in countries with temperate and tropical climates. Europe is one of the continents where animal dirofilariasis has been studied more extensively. In this article we review the current prevalence of canine and feline cardiopulmonary dirofilariasis in the European continent, the transmission vectors, the current changes in the distribution and the possible causes, though the analysis of the epidemiological studies carried out until 2001 and between 2002 and 2011. The highest prevalences have been observed in the southern European countries, which are considered historically endemic/hyperendemic countries. Studies carried out in the last 10 years suggest an expansion of cardiopulmonary dirofilariasis in dogs toward central and northern Europe. Several factors can exert an influence on the spreading of the disease, such as movement of infected animals, the introduction of new species of mosquitoes able to act as vectors, the climate change caused by the global warming, and development of human activity in new areas. Veterinary controls to prevent the spreading of this disease, programs of control of vectors, and adequate protocols of prevention of dirofilariasis in the susceptible species should be carried out.

Human Subcutaneous Dirofilariasis, Russia

We report 14 cases of human subcutaneous dirofilariasis caused by Dirofilaria repens, diagnosed from February 2003 through July 2004, in patients from Rostov-on-Don, Russia. Serologic analysis showed evidence of high risk of exposure to D. repens. Surveillance studies on prevalence and prevention effectiveness of canine infection are needed to control this emerging zoonosis.

Current prevalence of Dirofilaria immitis in dogs, cats and humans from the island of Gran Canaria, Spain.

The island of Gran Canaria is a hyperendemic area for canine dirofilariasis. The aim of the present study was to provide data on Dirofilaria immitis in dogs, cats, and humans on this island in 2010. The data confirms the prevalence in the overall canine population (19%), with a considerably higher prevalence (43%) in the autochthonous breed of Canarian Warren hound. The prevalence in the feline population (33%) is higher than that of the canine population, and the existence of specific D. immitis antibodies in the inhabitants of the island of Gran Canaria (12%) is confirmed. In both cats and humans, the prevalence, according to the different climate areas on the island, is related to the prevalence of D. immitis in dogs in the same area, which shows the key epidemiological role played by the canine host with regard to the transmission to other hosts of D. immitis.

Immunopathology of Dirofilaria immitis Infection

Heartworm disease caused by Dirofilaria immitis affects canine and feline hosts, with infections occasionally being reported in humans. Studies have shown that both dirofilarial antigens and those derived from its bacterial endosymbiont Wolbachia, interact with the host organism during canine, feline and human infections and participate in the development of the pathology and in the regulation of the host’s immune response. Both innate and acquired immune responses are observed and the development of the acquired response may depend on the host and, or on its parasitological status. This review aims at illustrating current research on the role of both D. immitis and Wolbachia, in the immunology and immunopathology of dirofilariosis.

Excretory/secretory antigens from Dirofilaria immitis adult worms interact with the host fibrinolytic system involving the vascular endothelium.

Dirofilaria immitis is the causative agent of canine and feline heartworm disease. The parasite can survive for long periods of time (7 years or more) in the circulatory system of immunocompetent reservoirs, producing usually a chronic inflammatory vascular disease. In addition, the simultaneous death of groups of adult worms can trigger an acute disease characterized by the exacerbation of inflammatory reactions and the emergence of serious thromboembolic events. In the context of the D. immitis/host relationships, the aim of this study was to investigate the interaction between the excretory/secretory antigens from D. immitis adult worms (DiES) and the fibrinolytic system of the host. Using an enzyme-linked immunosorbent assay we showed that DiES extract is able to bind plasminogen and generate plasmin, although this fact requires the presence of the tissue plasminogen activator (t-PA). Moreover, we established that DiES extract enhances t-PA expression in cultured vascular endothelial cells. Additionally, 10 plasminogen-binding proteins from DiES extract were identified by mass spectrometry (HSP60, actin-1/3, actin, actin 4, transglutaminase, GAPDH, Ov87, LOAG_14743, galectin and P22U). The data suggest that DiES antigens interact with the environment of the parasite regulating the activation of the fibrinolytic system of the host with involvement of the vascular endothelium in the process.

Canine and Human Dirofilariosis in the Rostov Region (Southern Russia)

Epidemiological data on canine and human dirofilariosis in the Rostov Region (Southern Russia) are presented. Prevalence of Dirofilaria spp. infections in 795 autochthonous dogs, assessed by the Knott test, was 20.25%. The highest prevalence was found in Novocherkassk (38.3%) and Rostov-on-Don (18.5%), while prevalences were lower in other points of the region. Prevalence of D. repens was 44.7%, prevalence of D. immitis was 30.3%, and coinfections were observed in 25.0% of the dog population. A case finding study carried out during 9 years (2000–2009) revealed 131 cases of human dirofilariosis in the Rostov Region, 129 of subcutaneous dirofilariosis and 2 of pulmonary dirofilariosis. Seroprevalence among 317 healthy blood donors from the Rostov Region was 10.4%, while seroprevalence in policemen living in Rostov city and working in training dogs was 19%. These data show high infection rates of Dirofilaria spp. in both human and dog populations of Rostov, probably because of the existence of favorable conditions for the transmission in this region.

Surface associated antigens of Dirofilaria immitis adult worms activate the host fibrinolytic system

Cardiopulmonary dirofilariosis (Dirofilaria immitis) is characterized by apparent contradictory events, like the long-term survival of adult worms in the circulatory system of the infected hosts and the development of life-threatening events like thromboembolisms and others. Thus parasite mechanisms, like the activation of fibrinolytic system, are key to the survival of both the worms and the host. The aim of this study was to investigate the interaction between D. immitis adult worms surface-associated antigens (DiSAA) and the fibrinolytic system of the host. We demonstrate that DiSAA extract is able to bind plasminogen and generate plasmin, with the latter occurring in a tissue plasminogen activator (t-PA) dependent manner. Additionally, 11 plasminogen-binding proteins from DiSAA extract were identified by proteomics and mass spectrometry (MS) (actin-5C, actin-1, enolase, fructose-bisphosphate aldolase, GAPDH, MSP domain protein, MSP 2, beta-galactosidase-binding-lectin, galectin, immunoglobulin I-set domain-containing protein and cyclophilin Ovcyp-2). Because in a previous work we have shown the positive interaction between the excretory/secretory antigens of D. immitis (DiES) and the host fibrinolytic system and many of the molecules identified here are shared by both antigens, we hypothesize that DiSAA cooperate in host fibrinolytic system activation promoting the fibrin clot lysis.

Canine dirofilariosis caused by Dirofilaria immitis is a risk factor for the human population on the island of Gran Canaria, Canary Islands, Spain

The aim of the present study was compare the prevalence of D. immitis in dogs and seroprevalence in humans of Gran Canaria (Canary Islands, Spain) taking into consideration the four isoclimatic areas of the island. A close relationship between the prevalence of Dirofilaria immitis in dogs and the seroprevalence in humans, in each isoclimatic area, was observed. The highest seroprevalence of infection in both canine and human hosts were found in a strip of mid-range altitude with 25.47% and 30.4% in dogs and 25.66% and 29.73% in humans, respectively. The coastal zone and the highest part of the island have prevalences significantly lower. These results demonstrate that the risk of infection by D. immitis in the human population in each area is tied to the prevalence in the canine population. Physicians should be alerted to the possibility of finding cases of human pulmonary dirofilariosis amongst the inhabitants of the island.