DIROFILARIASIS: CURRENT ASPECTS OF STUDIES.

The review touches upon the main directions and some of the most important results of an investigation of dirofilariasis the species of the genus Dirofilaria, their spread, and hosts. It describes cases of human infection with Candidatus Dirofilaria hongkongensis, a study of the prevalence of filariasis using a geographic information system, data on the contamination of Dirofilaria in Europe, and current views on the endosymbiotic relations of Dirofilaria with the Wolbachia bacterium.

[XENOMONITORING OF THE DIROFILARIASIS IN THE SOUTH AND NORTH-WEST OF THE RUSSIAN FEDERATION].

Xenomonitoring (detection of filarial larvae in mosquitoes) of vectors of dirofilariasis was performed in 2009­2013 in vectors collected in southern and northwestern regions of the Russian Federation. In Rostov, Astrakhan, Krasnodar, and Novgorod Provinces and in the Republic of Adygea the degree of infestation of mosquito larvae with Dirofilaria constituted 1.8 ± 0.2 % (66/3590), 0.9 ± 0.4 % (4/470), 0.8 ± 0.2 % (11/1382), 0.7 ± 0.4 % (3/438), and 0.5 ± 0.5 % (1/190), respectively. Total degree of infestation of mosquitoes with larvae of Dirofilaria spp. constituted 2.3 ± 0.3 % (45/1936), 1.9 ± 0.4 % (25/1334), and 0.6 ± 0.1 % (15/2713) in Aedes (Meigen, 1818), Culex (Linnaeus, 1758), and Anopheles (Meigen, 1818). No microfilariae were found in Culiseta (Felt, 1904) (0/87).

[Results of studies of human dirofilariasis in Russia].

Human dirofilariasis is a pressing health problem in Russia. By 2014, there have been as many as 850 Dirofilaria repens-infested people living in 42 subjects of the Russian Federation. One of the favorable factors for circulation and spread of invasion is a temperature of above +20-24 degrees C; when the latter is maintained during at least 20 days there may be 1.-1.5 circulations of invasion in the carrier and a 2.8-fold increase in transmission intensity. The border ofa dirofilariasis area with a temperate climate is southward to 58 degrees N in European Russia and West Siberia and southward to 50 degrees N in the Far East. The conditions in the human body have been found to be more favorable for the development of Dirofilaria than considered before and allow the helminth to achieve sexual maturity and to propagate. If man has microfilaremia, he may be a source of invasion. It is necessary to examine venous blood by the enrichment method and, if possible, polymerase chain reaction and enzyme immunoassay, which make it possible to establish a diagnosis in occult invasion and to identify a pathogen species.

[Entomological monitoring of an area to assess Dirofilaria transmission risk].

As the basis for entomological monitoring, the authors first propose to investigate the structure of a season of D. repens invasion transmission in the carrier in relation to the ambient temperature, such as onset of a transmission season, terminaton of mosquito infection, the number of invasion circulations. A calculating procedure has been developed. It is shown that there is a need for entomological monitoring of each specific area irrespective of the latitude to study a risk for local dirofilariasis cases.

Geo-environmental model for the prediction of potential transmission risk of Dirofilaria in an area with dry climate and extensive irrigated crops. The case of Spain.

Zoonotic filarioses caused by Dirofilaria immitis and Dirofilaria repens are transmitted by culicid mosquitoes. Therefore Dirofilaria transmission depends on climatic factors like temperature and humidity. In spite of the dry climate of most of the Spanish territory, there are extensive irrigated crops areas providing moist habitats favourable for mosquito breeding. A GIS model to predict the risk of Dirofilaria transmission in Spain, based on temperatures and rainfall data as well as in the distribution of irrigated crops areas, is constructed. The model predicts that potential risk of Dirofilaria transmission exists in all the Spanish territory. Highest transmission risk exists in several areas of Andalucía, Extremadura, Castilla-La Mancha, Murcia, Valencia, Aragón and Cataluña, where moderate/high temperatures coincide with extensive irrigated crops. High risk in Balearic Islands and in some points of Canary Islands, is also predicted. The lowest risk is predicted in Northern cold and scarcely or non-irrigated dry Southeastern areas. The existence of irrigations locally increases transmission risk in low rainfall areas of the Spanish territory. The model can contribute to implement rational preventive therapy guidelines in accordance with the transmission characteristics of each local area. Moreover, the use of humidity-related factors could be of interest in future predictions to be performed in countries with similar environmental characteristics.

Human intraocular filariasis caused by Dirofilaria sp. nematode, Brazil.

A case of human intraocular dirofilariasis is reported from northern Brazil. The nematode was morphologically and phylogenetically related to Dirofilaria immitis but distinct from reference sequences, including those of D. immitis infesting dogs in the same area. A zoonotic Dirofilaria species infesting wild mammals in Brazil and its implications are discussed.

Dirofilarial infections in Europe.

Nematodes of the genus Dirofilaria are currently considered emerging agents of parasitic zoonoses in Europe. Climatic changes and an increase in the movement of reservoirs (mostly infected dogs) have caused an increase in the geographical range of these parasites from the traditionally endemic/hyperendemic southern regions, and the risk for human infection has increased. In the last several years, forecast models have predicted that current summer temperatures are sufficient to facilitate extrinsic incubation of Dirofilaria in many areas of Europe. The global warming projected by the Intergovernmental Panel on Climate Change suggests that warm summers suitable for Dirofilaria transmission in Europe will be the rule in the future decades, and if the actual trend of temperature increase continues, filarial infection should spread into previously infection-free areas. Dirofilaria repens is currently the filarial species that is most commonly reported as spreading from southern to northern areas. This article reviews the zoonotic aspects, effects of climate, and other global drivers on Dirofilaria infections in Europe and the possible implications on the transmission and control of these mosquito-borne nematodes.

Autochthonous foci of canine and feline infections by Dirofilaria immitis and Dirofilaria repens in central Italy.

This survey was conducted to investigate the presence of Dirofilaria immitis and Dirofilaria repens in native dogs and cats living in an area of Italy where animal and human dirofilarioses have been sporadically reported in the past few years. From May 2008 to March 2009 individual blood samples were collected from 300 native cats and 300 native dogs in the Abruzzo region of central Italy. All 600 samples were subjected to a Knott modified method, to a test for the detection of circulating D. immitis antigen and to two species-specific PCR-coupled sequencing protocols. Epidemiological data were collected and then correlated with the filarial prevalence by univariate and multivariate statistical analyses. Twenty-five dogs (8.3%) and six cats (2%) were positive for filariae in at least one diagnostic test, with an overall prevalence rate for D. immitis and D. repens of 2.3% and 5.6% in dogs and 0.3% and 1.6% in cats, respectively. Male and large sized dogs resulted more likely to be infected by Dirofilaria spp., possibly due to the fact that animals living outdoor and of large size are more exposed to mosquito bites. However these factors were not confirmed as convincing risk factors by multivariate analysis. The results are discussed, together with the origin of these new autochthonous foci in central Italy and the present expansion southward of canine and feline filariae in Italy.

[Human dirofilariasis: diagnosis and the pattern of pathogen-host relations].

Until recently, there has been no consensus of opinion as to that D.repens females can develop in the accidental host (man). The role of man is regarded as a biological dead end for Dirofilaria that are unable to develop the adult stage; human Dirofilaria migration is considered to be larval by the type of larva migrans. Studying these matters on a specific material of 140 cases of invasion by Dirofilaria that had been eliminated in patients in different seasons and the length of their bodies measured showed that the maximum number (51.4%) was mature females, 120 to 190 mm in size; 35.7 and 12.85% had a length of 70-115 and 40-65 mm, respectively, which corresponds to immature young and juvenile specimens. This suggests that Dirofilaria normally develop and achieve the adult stage in the accidental host. A correlation was found in the sizes of the body and the time of D. repens development. Thus, the human organism is not a biological dead end for Dirofllaria. The migration of adult Dirofilaria should be appraised as the imago-migrans phenomenon: As the particular diagnostic sign, it will aid a physician to establish a correct parasitiological diagnosis at the early stages of the disease. In recent years, there has been new evidence in the diagnosis of dirofilariasis that microfilaria have been detected in the skin tumor puncture specimen and blood of the patients. In this connection, it is conceivable that man may be an actual source of mosquito infection even in the presence and paucity of mature males and females.

[Biological characteristics of the causative agent of dirofilariasis in dogs in the Rostov Region].

This paper assesses the trends in the identification of different Dirofilaria species in the Rostov Region and comparatively analyzes the general clinical and biochemical blood indices in dogs with and Without helminthism. Seasonal variations in the invasion and species composition of the parasite have been established. At present, there is a gradual replacement of the species Dirofilaria repens by Dirofilaria immitis in this area. The blood general clinical and biochemical studies in ill dogs with dirofilariasis have ascertained that the pathogenic action on the animals is more pronounced with Dirofilaria immitis being parasitizing and with the mixed invasion of two helminth species.

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.

Aedes albopictus and Culex pipiens implicated as natural vectors of Dirofilaria repens in central Italy.

To identify the natural vectors of Dirofilaria repens Railliet et Henry, entomological samplings were carried out in four sites within the Lazio region, foci of canine subcutaneous dirofilariasis. Collections were made in 2002-2003 by means of dog-baited and miniature Centers for Disease Control and Prevention traps as well as on humans. Microscopy identified 1576 attracted mosquito females as belonging to six species, but molecular diagnostics detected filarial DNA only in Culex pipiens L. and Aedes albopictus (Skuse, 1894). Dirofilaria immitis Leidy DNA, D. repens DNA, or both were found in the head and thorax of both mosquitoes. The simultaneous presence of vectors showing diurnal and nocturnal activity patterns is of concern for animal and human health. The finding of D. immitis DNA in mosquitoes in areas where only D. repens was been recovered in dogs also demonstrates that this filarial parasite circulates among carnivores (wild or domesticated pets).

[Dirofilariasis in the practice of an ophthalmologist]. / Dirofiliarioz v praktike glaznogo vracha.

A youth aged 16 was hospitalized in ophthalmological department for surgical treatment of the lower eyelid chalazion of the left eye. No helminths were diagnosed before surgery. Opening of the chalazion resulted in release of a thread-shaped helminth into the wound; the helminth was identified as immature Dirofilaria repens female. A solid connective tissue capsule formed round the parasite. Routes of Dirofilarias infection, its vectors, permanent, intermediate, and accidental hosts, and prevalence are discussed.

Relaxing and contracting activities of heartworm extract on isolated canine abdominal aorta.

Effect of adult heartworm (HW) crude extract on isolated canine abdominal aortic strips precontracted with noradrenaline was examined by recording isometric changes in tension. HW extract caused contraction of the aortic strip at a low concentration (LC) and its relaxation at a high concentration (HC). In aortic strips without endothelium, LC extract elicited a contraction similar to that in the strips with endothelium, whereas HC extract failed to produce any relaxation but instead produced a contraction. The relaxing effect of HC extract was blocked after treatment with 300 microM NG-nitro-L-arginine methyl ester hydrochloride, with reversal by additional treatment with 3 mM L-arginine. It was also markedly reduced or abolished after treatment with 3 microM oxyhemoglobin or 1 microM methylene blue. Fractionation of HW extract by high-performance liquid chromatography revealed that the relaxing and contracting activities are due to different substances in the extract. The results indicate that HW extract contains 2 different vasoactive substances, 1 causing contraction of canine abdominal aorta via a direct action on the smooth muscle, and the other its relaxation indirectly by releasing nitric oxide from endothelial cells. These vasoactive substances might play a role in HW extract-induced shock in dogs, and in the pathogenesis of HW infection.

[Two clinical cases of zoonotic filariasis probably caused by Dirofilaria repens: I. Passage of the nematode under the bulbar conjunctiva. II. Subcutaneous abscessed nodule]. / Due casi clinici di filariasi zoonotica da probabile Dirofilaria repens: I. Passaggio del nematode sotto la congiuntiva bulbare. II. Nodulo sottocutaneo ascessuato.

Two new human cases of zoonotic filariasis are reported, one subconjunctival and the other subcutaneous, occurred both in 67 and 73 year-old women, respectively, living in the provinces of Alexandria and Pavia (Northern Italy). The morphology of the nematodes could not be examined. Nevertheless, the anamnesis, the course of infection, the symptomatology and the geographic area where the cases occurred, suggested that they were associated with Dirofilaria repens.

Heartworm migration toward right atrium following artificial pulmonary arterial embolism or injection of heartworm body fluid.

Heartworms harboring in the pulmonary arteries migrated toward the right atrium following insertion of dead heartworms or heartworm-like silicone tubes, or intravenous injection of body fluid extract of a female heartworm. The migration occurred within 3 hr (early group) or 1 to 7 days (late group) after insertion of dead worms, 1 to 11 days after insertion of silicone tubes, and immediately after infusion of heartworm-body fluid. The cardiac output decreased to an unmeasurably low level, and the pulmonary arterial pressure was also reduced in the early group. Although the output decreased, the pulmonary arterial pressure and the total pulmonary resistance increased gradually in the late group. In dogs with heartworm migration, in which silicone tubes had been inserted, the changes in cardiopulmonary values were the same as those in dogs of the late group. In dogs to which the body fluid had been administered intravenously, the changes in cardiopulmonary values were well accord with those in the early group. The systemic blood pressure also fell immediately after the administration with the shock-like state. These results suggest that the death of a part of the heartworms may be closely associated with the migration of heartworms toward the right atrium through the pulmonary arterial embolism and/or shock-like reaction by heartworm body fluid.