Vladimir Kartashev

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.

New findings in HCV genotype distribution in selected West European, Russian and Israeli regions

BACKGROUND HCV affects 185 million people worldwide and leads to death and morbidities. HCV has a high genetic diversity and is classified into seven genotypes and 67 subtypes. Novel anti-HCV drugs (Direct-Acting-Antivirals) eligibility, resistance and cure rates depend on HCV geno/subtype (GT). OBJECTIVES Analysis of epidemiological information and viral GT from patients undergoing viral genotyping in 2011-2015. STUDY DESIGN Anonymized information from 52 centers was analyzed retrospectively. RESULTS 37,839 samples were included in the study. We show that the GT distribution is similar throughout Western European countries, with some local differences. Here GTs 1 and 2 prevalences are lower and of GT4 higher than in all previous reports. Israel has a unique GT pattern and in South Russia the GT proportions are more similar to Asia. GTs 5 and 6 were detected in very low proportions. Three cases of the recombinant genotype P were reported in Munich (Germany). In addition, we observed that GT proportion was dependant on patientś gender, age and transmission route: GTs 1b and 2 were significantly more common in female, older, nosocomially-infected patients, while GTs 1a, 3 and 4 were more frequent in male, younger patients infected by tattooing, drug consume, and/or sexual practices. In infections acquired by drug consume, GTs 1a (35.0%) and 3 (28.1%) prevailed. In infections related to sexual practices lower proportion of GT3 (14.0%) and higher of GT4 (20.2%) were detected. GT4 was mostly abundant in MSM (29.6%). HIV coinfection was significantly associated with higher proportions GTs 1a and 4 (42.5% and 19.3%, respectively). CONCLUSION Genotype prevalence evolves and correlates to epidemiological factors. Continuous surveillance is necessary to better assess hepatitis C infection in Europe and to take appropriate actions.

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.

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.

Evolution of protease inhibitor resistance in the gag and pol genes of HIV subtype G isolates

OBJECTIVES To analyse HIV Gag cleavage site (CS) and non-CS mutations in HIV non-B isolates from patients failing antiretroviral therapy. PATIENTS AND METHODS Twenty-one HIV isolates were obtained from patients infected with HIV subtype G during an outbreak in Russia 20 years ago. Most patients were failing antiretroviral therapy when genotyping was performed. RESULTS HIV Gag CS mutations accumulated in protease inhibitor (PI)-resistant HIV isolates and were correlated with the presence of three or more PI resistance mutations. Only 1 of 11 HIV isolates carrying major protease mutations did not harbour treatment-associated CS mutations. Natural polymorphism 453T, often found in HIV non-B subtypes, seems to favour the selection of CS mutation 453I rather than treatment-associated CS mutation 453L. Resistance-associated non-CS mutations (123E and 200I) were also observed in PI-resistant clinical isolates. Non-CS mutations in the frameshift-regulating site, which controls the synthesis of Gag-Pol, did not affect frameshift efficiency in dual luciferase assays. Of note, one of four HIV isolates from patients failing PI therapies without protease mutations harboured Gag mutations associated with PI resistance (123E and 436R) and reverse transcriptase inhibitor mutations conferring resistance to the backbone drug. CONCLUSIONS HIV Gag CS mutations commonly occurred in HIV isolates from patients failing PI therapies and natural polymorphisms at the same position influence their emergence. Non-CS mutations previously associated with PI resistance were also observed in clinical isolates. Gag mutations might indicate the evolution of PI resistance even in the absence of protease mutations.

Plasmin in Parasitic Chronic Infections: Friend or Foe?

Plasmin is the final product of the fibrinolytic system, the physiological mechanism responsible for dissolving fibrin clots. Its broad-range proteolytic activity implies that interaction with fibrinolysis and recruitment of plasmin by blood and tissue parasites is an important mechanism that mediates the invasion and establishment of this kind of pathogen in the hosts. However, recent studies have linked an excess of plasmin generated by this interaction with serious pathological events at the vascular level, including the proliferation and migration of arterial wall cells, inflammation, and degradation of the extracellular matrix. Therefore, we present data that support the need to reconsider the role of plasmin, as well as its benefits or drawbacks, in the context of host-parasite relations.

Genetic diversity of Dirofilaria spp. isolated from subcutaneous and ocular lesions of human patients in Ukraine

This short communication describes the phylogenetic analysis of 48 Dirofilaria worms isolated from human patients in Ukraine. 102 cases were both of subcutaneous (47; 46.1%) and ocular (54; 52.9%) locations. Worms from 44 patients (15 subcutaneous and 29 ocular) were subjected to DNA extraction and amplification of a specific fragment of the 12S rRNA subunit, and sequences were used for phylogenetic analysis. Results showed that 13.8% of the ocular cases analyzed at molecular level were caused by Dirofilaria immitis. Very few cases of ocular human dirofilariosis due to D. immitis have been described in the literature to date, majority of them attributed to Dirofilaria repens. Our results show that ocular dirofilariosis cannot be excluded in areas of low endemicity for D. repens were D. immitis is also present.

Human subcutaneous/ocular dirofilariasis in the Russian Federation and Belarus, 1997–2013

OBJECTIVES This study was performed to determine the yearly frequency, trends in spread, and clinical-epidemiological characteristics of human subcutaneous/ocular dirofilariasis (HSOD) in the Russian Federation and Belarus. METHODS The surveillance data of HSOD cases occurring between January 1997 and June 2013, obtained from the regional health administrations of the Russian Federation and Belarus, were analyzed. The spatial distribution of cases was assessed using a GIS map, and the clinical-epidemiological characteristics were defined using 719 cases for which information on anatomical location, age, sex, and area of residence was available. The statistical analysis was performed using the Chi-square test. RESULTS One thousand two hundred and seventy-two clinical cases of HSOD were identified, the majority of them reported in the south-western regions of the Russian Federation. The disease has spread into northern areas, changing its limit from latitude 45°N in 1997 to latitude 61°N in 2013. The statistical analysis of the data showed that the disease is more frequent in the ocular location, in women, in patients aged between 41 and 60 years, and in patients living in urban areas. CONCLUSIONS Alternative sources to the scientific literature could be necessary to assess the epidemiological situation regarding HSOD in some areas where it has become an emerging condition. There is an urgent need for uniform criteria for reporting and retrieving human cases of dirofilariasis.

Delayed Diagnosis of Dirofilariasis and Complex Ocular Surgery,Russia

To the Editor: Dirofilaria repens is a vector-borne, zoonotic, filarial nematode that infects dogs, cats, and humans. In humans, D. repens worms cause subcutaneous dirofilariasis, characterized by the development of benign subcutaneous nodules that mimic skin carcinomas (1), and ocular dirofilariasis in orbital, eyelid, conjunctival, retroocular, and intraocular locations (2). Intraocular and retroocular dirofiliariasis causes considerable damage and discomfort in patients from the presence of the worms and from their surgical removal (3). Here, we report a retroocular D. repens nematode infection in a patient in Russia that illustrates the difficulties in clinical management and the inherent risks of surgical procedures to remove the worms. A 20-year-old woman living in Rostov-na-Donu in southwestern Russia who had never traveled outside the city sought ophthalmologic consultation for pain and skin redness and swelling in the inner corner of the upper left eyelid. Swelling migrated successively to the temporal area, the lower eyelid, and the inner corner of the lower eyelid. The patient had no other ocular signs or symptoms, and her general condition was otherwise good. Results of ophthalmologic examination and routine laboratory tests were within normal limits. Four days of treatment with cefotaxime resulted in the remission of signs and symptoms. Approximately 2 months later, swelling in the inner corner of the upper eyelid appeared again, affecting the whole upper eyelid, without itching or tenderness. Allergies were diagnosed; cetirizine was administered for 4 days, and the signs remitted at the third day of treatment. One month later, marked upper left eyelid swelling occurred, resulting in ptosis. Cetirizine was prescribed again; edema subsided after 4 days of treatment but relapsed in the following 3–4 days. At least 4 subsequent relapses occurred; thus, a computed tomographic scan of the paranasal sinuses and orbits was performed, 4 months after signs and symptoms began (Figure, ​,panel A).panel A). The scan detected a soft tissue structure, 12 × 13 × 14 mm, behind the left eyeball, adjacent to and medially dislodging the optic nerve. No other abnormalities were found in the visible area of the brain and sinuses. Magnetic resonance imaging (MRI) performed 1 month later (Figure, panel B) corroborated the presence of a cyst-like structure with an irregular, rounded shape and clear, smooth borders closely adhered to the eyeball and optic nerve. T2-weighted images showed that the lesion had a high-density core but the surrounding tissue was low density. Adjacent to the lesion, the retrobulbar tissue was slightly swollen, the optic nerve was displaced medially and downward, and the adjacent upper muscle was displaced medially and upward. The diagnosis was evidence of a retroocular cystic lesion in the left orbit with a well-defined capsule and high-density but heterogeneous core structure. Figure Retroocular nodule of a Dirofilaria repens worm detected in a 20-year-old woman, Rostov-na-Donu, Russia. The cyst (arrows) is shown by computed tomography scan (A) and magnetic resonance imaging (B). Ultrasonography images (C) show a worm-like structure ... High-resolution ultrasound examination (Figure, panel C) revealed a well-defined, 3-mm, cyst-like wall containing fluid and dense, coiled-twisted linear internal structures that appeared to be actively moving (Video 1). Color Doppler examination (Figure, panel D; Video 2) revealed blood vessels in the wall but not inside the cystic structure. These additional examinations led to a diagnosis of a retroocular parasitic cyst in the left orbit, most likely a Dirofilaria spp. parasite. The parasitic cystic nodule was removed during a transpalpebral orbitotomy. A live, adult roundworm, 87 × 0.6 mm, was discharged from the cyst. Conventional PCR identified the roundworm as D. repens (data not shown). Video 1 High-resolution ultrasound examination images showing a Dirofilaria repens worm actively moving inside retroocular nodule in a 20-year-old woman, Rostov-na-Donu, Russia. Video 2 Color Doppler examination images showing the blood flow only outside the retroocular nodule in which the movement of a Dirofilaria repens worm is detected in a 20-year-old woman, Rostov-na-Donu, Russia. Although human subcutaneous Dirofilaria spp. nodules are benign, their detection may raise suspicion for a malignant tumor; thus, differential diagnosis is the key point in the management of human dirofilariasis (4). The case we described illustrates the difficulties of diagnosis when worms are in deep locations and patients experience unspecific and even unusual signs. These confounders resulted in a lengthy diagnostic procedure, with consequent detrimental physical and psychological effects on the patient. Even though the final diagnosis determined that the nodule was nonmalignant, its anatomic location required aggressive surgical intervention to remove it. D. repens nematodes are spreading in Europe from the south toward the north and east (5–7) as a consequence of global warming, and prediction models have suggested incidence is increasing among animal and human hosts (3). Consequently, human ocular dirofilariasis will probably be found with increasing frequency in the future. Our experience illustrates that dirofilariasis should be included in the differential diagnosis of any nodule, independent of its anatomic location and the signs and symptoms shown by the patient. Moreover, ultrasonography represents a noninvasive technique that enables rapid preoperative identification of the parasitic origin of the nodules, thus avoiding unnecessary diagnostic delays. This technique is used for the diagnosis of cardiopulmonary dirofilariasis in animals (8) but has been used only sporadically for human dirofilariasis (9,10), which is habitually diagnosed postoperatively, after the surgical removal of the nodules or worms (1).

Thirty cases of human subcutaneous dirofilariasis reported in Rostov-on-Don (Southwestern Russian Federation)

INTRODUCTION Different species of the genus Dirofilaria, mainly D. immitis and D. repens, are responsible for emergent vector borne transmitted zoonotic diseases in the Old World. Human D. repens infections are characterized by the appearance of benign subcutaneous nodules that mimic skin malignant tumors or due to live worms in the ocular area. METHODS Thirty patients presenting superficial or deep nodules were treated at the Rostov Regional Diagnostic Center (Southwestern Russian Federation). Anatomical characteristics of the nodules were studied by non-invasive ultrasound and color and power Doppler techniques. Worms were surgically removed from every nodule and their DNA analyzed by polymerase chain reaction (PCR). RESULTS Twenty-four out of the 30 nodules were located in the hypodermis, two in a retro-ocular location and four in scrotal location. Image techniques allowed the identification of the helminthic origin of all nodules, based on their oval and regular shape, peripheral vasculature, and the existence of internal linear winding hyperechoic structures with or without movements, indicating the presence of live or dead worms, respectively. Specific adscription to D. repens was achieved by the PCR analysis. CONCLUSION The series described in the present paper confirms the increasing risk of infection by D. repens in humans living in endemic areas of Eastern Europe. The use of non-invasive ultrasounds and Doppler techniques can contribute to an appropriate management of human dirofilariasis. Moreover, awareness of the medical community in the endemic areas influences the report of cases, and consequently the current epidemiological picture of human dirofilariasis.