Microfilaremic Dirofilaria repens Infection in Patient from Serbia.

We report a case of Dirofilaria repens infection causing microfilaremia in a patient from Serbia. Serum samples tested positive for D. repens IgG by ELISA. Our findings and those of others suggest the parasite's progressive adaptation to humans. Clinicians should be aware that microfilaremia can develop during Dirofilaria spp. infections.

Prevention of Thelazia callipaeda Reinfection among Humans.

Thelazia callipaeda is a zoonotic vector-borne nematode that infects and causes eye disease among a wide range of domestic and wild mammals, including humans. We describe an unusual case of reinfection by this nematode in Serbia and call for a focus on preventive measures in endemic areas.

Population Pharmacokinetic Analysis of Bisoprolol in Patients With Acute Coronary Syndrome.

To date, many questions about the extent and cause of pharmacokinetic (PK) variability of even the most widely studied and prescribed ß1-adrenergic receptor blockers, such as metoprolol and bisoprolol, remain unanswered. Given that there are still no published population pharmacokinetic (PopPK) analyses of bisoprolol in routinely treated patients with acute coronary syndrome (ACS), the aim of this study was to determine its PK variability in 71 Serbian patients with ACS. PopPK analysis was conducted using a nonlinear mixed-effects model (NONMEM), version 7.3.0 (Icon Development Solutions). In each patient, the same formulation of bisoprolol was administered once or twice daily at a total daily dose of 0.625-7.5 mg. We separately assessed the effects of 31 covariates on the PKs of bisoprolol, and our results indicated that only 2 covariates could have possible influence on the variability of the clearance of bisoprolol: the mean daily dose of the drug and smoking habits of patients. These findings suggest that possible autoinduction of drug metabolism by higher total daily doses and induction of cytochrome P450 isoform 3A4 (CYP3A4) by cigarette smoke in liver could be the potential causes of increased total clearance of bisoprolol in patients with ACS.

Seroprevalence and Risk Factors for Toxocara canis Infection in Serbia During 2015.

We report data on the Toxocara seroprevalence evidenced in 2015 from samples of 40 children and 298 adults of the population living in different areas of Serbia, and on possible association of certain variables with infection. Detection of specific antibodies was performed using an enzyme-linked immunosorbent assay; all ambiguous results and part of the positive and negative sera were further analyzed by confirmatory Western blot test. An overall 23.5% seroprevalence was noticed, which was confirmed in 13.0% of the examined population with no significant difference regarding the age (children = 10.0%; adults = 13.4%) or by country area (East = 18.2%; North = 15.5%, Southeastern = 9.5%; p = 0.005). In contrast, the group of adult women proved more reactive than men (p = 0.001), and subjects both who spend spare time in square/parks (p = 0.041) and with positive onychophagy (p = 0.001) habit turned out more exposed to the infection. Possible reasons of these differences were analyzed, and the medical, veterinary, and economic impact of this soil-transmitted zoonosis were discussed.

Seroreactivity to Dirofilaria antigens in people from different areas of Serbia.

BACKGROUND: The Northern part of Serbia is hyperendemic-endemic for canine dirofilarioses. Considering this fact, many human dirofilarial infections could be expected, however only about 30 cases in Serbia have been described until today. Aims of this survey were to assess the people reactivity to the antigens of D. repens and D. immitis and to identify risk factors for the contact exposure. METHODS: Investigation included sera taken from 297 people (179 women and 118 men) living in different areas of Serbia (Pancevo, Novi Sad, Zajecar, Leskovac, Vranje, Nis, Pirot). Sera were analysed by means of two indirect enzyme-linked immunosorbent (ELISA) home-designed that use as antigens adult somatic/metabolic polyproteins of D. repens (DR) and D. immitis (DI), respectively. The results were elaborated using the statistical method of descriptive and quantitative analysis. RESULTS: Significant differences by area in the reactivity of human sera to dirofilarial antigens were not observed (p = 0.056). A high seroreactivity was demonstrated in people from the towns of northern Serbia (Pancevo = 27,1%; Novi Sad = 16,3%), as well as in people from Zajecar (eastern Serbia = 15,8%) and Vranje (southern Serbia = 15,1%). No differences were evidenced between people reactivity to polyproteins of the two dirofilarial species, nor differences related to the gender of examinees. Factor risks evidenced were: i) place of residence; ii) spending work time outdoors during the mosquito season; iii) spending time outdoors and nearby rivers, lakes, swamps or canals; unespectedly, iv) cat owning. CONCLUSION: The findings emerging from this investigation indicate that clinicians and public health authorities should pay greater attention to this zoonosis. Continuing education and training of physicians will greatly contribute to the knowledge of the actual impact of filarial worms on animal and public health, and allow for the planning of suitable measures to prevent the infections.

In vitro protease inhibition and cytotoxicity of Aspergillus fumigatus biomolecules secreted under long-term aerated conditions.

The fatality rate of invasive aspergillosis (IA) is still very high, especially in prolonged and untreated pulmonary cases. Aspergillus fumigatus is the main causative agent of IA and investigation of its metabolites could provide valuable insight into virulence factor(s) associated with this organism. We evaluated the A. fumigatus culture filtrate (CF) products generated during short- and long-term aerated and non-aerated conditions and tested for (i) inhibition of cysteine or serine proteases and (ii) cytotoxicity. In addition, the mathematical model was determined using response surface methodology (RSM) to estimate the influence of different fermentation conditions on A. fumigatus CF characteristics, predict enzyme inhibition and make possible correlations with in vivo conditions. Biosynthesis of A. fumigatus low molecular weight proteinaceous products (from 6.4 to 15.4 kDa) was observed after 6 days of growth under aerated and alkaline conditions. Also, only these CFs showed significant reduction in cell lines survival (Caco-2 and WISH 35.6% and 54.6%, respectively). Obtained results provide solid starting point for further studies that would include: (i) detailed chemical characterization of A. fumigatus CF, (ii) activity relationships and in vivo correlation with pathogenicity of prolonged pulmonary IA and (iii) possible use of biomolecules as diagnostic or therapeutic markers.

Is Antihelminthics Necessary in Postoperative Treatment of Intraventricular Neurocysticercosis? A Systematic Review.

OBJECTIVE: Patients with intraventricular neurocysticercosis (IVNCC) may require cerebrospinal fluid diversion surgery for late-onset hydrocephalus in the postsurgical period. Controversy exists regarding cysticidal treatment. Our main objective was to compare surgically treated cases of IVNCC that received postoperative anthelmintics with those that did not regard the incidence and treatment of late-onset hydrocephalus. METHODS: We searched the Medline database and extracted the following data: age, gender, stage of development of cysticercosis, type of operation, frequency of delayed hydrocephalus, cerebrospinal fluid diversion surgery, outcome, and follow-up. RESULTS: We analyzed 130 articles on intraventricular cysticercosis and identified 117 cases of isolated IVNCC and 314 patients in the case-control series who met inclusion criteria. There was no significant difference in postoperative delayed hydrocephalus between isolated IVNCC and case-control study groups. Children under the age of 16 received anthelmintic drugs more frequently during the postoperative period. Statistical relevance was observed in all patient groups regarding the application of steroids in favor of cysticidal therapy Endoscopy was a better option than craniotomy for cases of isolated IVNCC and case-control studies. Other variables were not relevant. CONCLUSIONS: Patients who received antihelminths did not show a statistically significant reduction in delayed hydrocephalus compared to individuals who did not receive after surgical resection of the parasite. Corticosteroid therapy prevailed in people who have been treated with anthelmintics. Children under the age of 16 were administered anthelmintic drugs more frequently during the postoperative period. Endoscopy was the preferred method for all groups, but some patients with cysts in the fourth ventricle required a craniotomy.

Intraventricular Neurocysticercosis: Comparative Analysis of Different Localizations. Clinical Course and Treatment. A Systematic Review.

Background Neurocysticercosis is significant due to its high prevalence and considerable morbidity and mortality. The intraventricular form of NCC is less common than parenchymal, may have a rapidly progressive course and it requires a corresponding therapeutic response. Despite the extensive literature dealing with NCC and intraventricular cystic lesions, no systematic reviews have addressed similar work related to the clinical course and treatment of the infestation. Our main objective was to analyze the clinical type of the disease and the management for each ventricle separately on the basis of case reports or series of patients with individual data on the course of the disease and its treatment. As a control group, we used data on signs&symptoms and treatment of patients from published series on intraventricular neurocysticercosis. Method We performed a search in the Medline database. Google Scholar was also randomly searched. We extracted the following data from the eligible case/series: age and gender, symptoms, clinical signs, diagnostic examinations and findings, localization, treatment, follow-up period, outcome, and publication year. All data are presented in the form of absolute and relative numbers. The frequency of signs and symptoms, treatment and outcomes of the observed groups were checked by the Chi-square test and Fisher's test. The hypothesis was tested with p <0.05 as statistical significance. Results We selected 160 cases of intraventricular neurocysticercosis (IVNCC) and divided them according to their localization into five categories. Hydrocephalus was recognized in 134 cases (83.4%). Patients with isolated IVNCCare are younger (P=.0264) and have a higher percentage of vesicular cysts (p <.00001). In mixed IVNCC, degenerative and multiple confluent cysts predominate (p = 0.00068). Individuals carrying fourth + third ventricular cysts (potentially obstructive form) are younger than individuals with lateral ventricles (potentially less obstructive forme) (p = .0083). The majority of patients had individual symptoms for a longer period before the acute onset of the disease (p <.00001). The predominant clinical manifestation is headache (88.7%); the proportion within the groups ranged from 100% to 75% without statistical significance (p.074214). The same was true for patients with symptoms of vomiting or nausea, who had a lower and roughly balanced percentage of 67.7% to 44.4% (p.34702). Altered level of consciousness (ranging from 21% to 60%) and focal neurological deficit (from 51.2% to 15%) are the only clinical category with statistical significance (p <0.001 and p.023948 ). Other signs and symptoms were less frequent and statistically irrelevant. Surgical resection of the parasite was the predominant type of treatment, varying from 55.5% to 87.5% (p- .02395); endoscopy (48.2%) and craniotomy (24.4%), each individually, showed statistical significance (.00001 and .000073, respectively). The difference was also relevant among patients who had CSF diversion performance with/without medical treatment (p-.002312. Postoperatively, 31.8% of patients received anthelmintics with/without anti-inflammatory or other drugs. Endoscopy, open surgery, and postoperative antiparasitic therapy showed statistical differences (p < 0.001). Favorable outcomes or regression of symptoms were recorded in 83.7%, mortality 7.5%. In the case series, the clinical signs&symptoms were as follows: headache-64%, nausea and vomiting 48.4%, focal neurological deficit 33.6% and altered level of consciousness 25%. Open surgery was the predominant form of intervention (craniotomy (57.6% or endoscopy 31.8%); with statistical significance between them (p< .00001). Conclusion. Ventricular neurocysticercosis is an alarming clinical condition. Hydrocephalus is the dominant diagnostic sign. Isolated IVNCC patients were recognized at a younger age than Mix.IVNCC individuals; poeple with cysts in the fourth and third ventricles (as a potentially more occlusive type of disease), presented their symptoms at a younger age than individuals with LVNCC. The majority of patients had long-term signs and symptoms before the acute onset of the disease. Headache, nausea& vomiting are the most common symptoms of infestation accompanied by altered sensorium and focal neurological deficits. Surgery is the best treatment option. A sudden increase in ICP due to cerebrospinal fluid obstruction with a successive cerebral hernia is the leading cause of fatal outcomes.

A case of mycotic keratitis due to Fusarium sp. with an undesirable outcome.

Fungal keratitis, an infective disease of the cornea, represents a serious diagnostic and therapeutic problem that, if not recognized on time, could lead to irreversible eye damage. Herein we report a case of fungal keratitis due to Fusarium spp. infection. The 60-year-old man was admitted to our clinic due to an atraumatic acute onset of the disease, with a decrease in the visual acuity, photophobia, redness, and severe pain in the right eye. Clinical observation revealed an ulcer that affected 1/3 of the cornea and a hypopion in the anterior chamber. After the first results of microbiological analyzes, local and systemic antifungal therapy was applied. Due to the fact that the patient voluntarily left the treatment, there was a drastic worsening of the local findings as a full thickness total corneal infiltrate with more intense anterior chamber reaction. Finally, evisceration was performed. Given the fact that fungal keratitis is more prevalent in developing countries, official protocols and available effective antifungals are crucial for adequate treatment and a favorable outcome of this infection.

Adolescent Scalp Dermatitis Associated with Dermatophagoides spp. (Acariformes; Pyroglyphidae) Mite.

PURPOSE: Dermatophagoides spp. (Acariformes; Pyroglyphidae), house dust-mite well known as the causative agent of atopic hypersensitivity and allergy could potentially cause severe dermatitis. Herein we report an uncommon case of scalp dermatitis associated with the presence of Dermatophagoides spp. METHODS: A 17-year old male presented with patchy alopecia on the scalp without intense peeling or itching, surround by unchanged skin and hair. Initially, superficial fungal infection was suspected; however, parasitological examination revealed the presence of live mites. RESULTS: All the anatomical measurements and parameters from the specimens were compatible with Dermatophagoides spp. CONCLUSIONS: Dermatophagoides spp. are not yet confirmed as causative agents of parasitic infestation, but the presence of these mites could have caused an allergic reaction followed by dermatitis with mild-to-moderate clinical manifestations. However, true parasitism as well as phoresy could also be considered. The clinical manifestations caused by house-dust mite cannot be easily recognized and the lack of diagnostic tools is a hindrance that often leads to misdiagnosis and inadequate therapy.

New cases of human dirofilariosis on the Balkan Peninsula - "Masked intruders" uncovered by a surgeon.

Dirofilaria spp. nematodes are accidental parasites of humans causing mild to serious, superficial or visceral infections. Superficial dirofilariosis is rather common in Europe and is typically manifested as subcutaneous form. Herein we report 46 new cases of human dirofilariosis (19 patients with subcutaneous, 18 patients with ocular, 4 patients wih genital, 2 patients with submucosal, 2 patients with pulmonary and 1 patient with intramuscular form of infection) that were recorded from the beginning of 2015 to May 2021 on the Balkan Peninsula with a goal to update the prevalence of this parasitosis and point out potential problems in diagnosis and treatment. Besides, given the high possibility of misinterpretation as tumor, our second aim was to encourage the inclusion of this pathogen in the differential diagnosis of subcutaneous nodules. Although quite common forms, subcutaneous and ocular dirofilariosis can be very often misdiagnosed in clinical practice due to the absence of specific clinical manifestations. Therefore, raising awareness of clinicians about this zoonosis is needed as well as closer collaboration between physicians and veterinarians.

Molecular Survey of Dirofilaria and Leishmania Species in Dogs from Central Balkan.

Dirofilariosis and leishmaniosis are severe parasitic diseases in dogs, and their causative agents can also be pathogenic to humans. In this study, we conducted a multicentric survey in the regions of Serbia and North Macedonia with the goal to establish an epidemiological scenario of dirofilariosis and leishmaniosis in the territory of Central Balkan. Using molecular analyses, a total of 535 dogs from Northern Serbia (NS), Southern Serbia (SS) and North Macedonia (NM) were screened for the presence of Dirofilaria spp. and Leishmania spp. We confirmed that Central Balkan is an endemic region for Dirofilaria (D.) immitis, as it was found to be the dominant species in this area, with the highest prevalence of 8.75% in NM, followed by NS (6.68%) and a significantly lower prevalence in SS (1.51%). Two dogs (2.5%) from NM were positive for Leishmania (L.) infantum infection. None of the dogs from Serbia tested positive for Leishmania spp. High prevalence and dominance of D. immitis species, and the rising threat of L. infantum spread to the territory of Serbia, suggest that preventive measures are of a great necessity to combat the spread of these vector-borne zoonoses.

Human dirofilariosis of buccal mucosa - First molecularly confirmed case and literature review.

When presented in unusual manner, human dirofilariosis is hard to recognize and often leads to misdiagnosis and unjustified use of various medications. Herein, we report a rare case of Dirofilaria infection localized in buccal mucosa. A 45-year-old male, residing in the Central Serbia, developed striking edema of buccal mucosa followed by leucocytosis, with both neutrophylia and eosinophylia. Thirty days after first symptoms occurred, nodule was formed along the lateral edge of right maxilla. Therefore, patient underwent surgical extirpation and subsequent histopathological analysis of the specimen revealed the presence of a nematode. Based on morphological characteristics of detected parasite, the diagnosis of submucosal Dirofilaria repens-like infection was made. The diagnosis was confirmed, being the first case in the world analyzed by molecular methods. So far, only 13 such cases have been reported worldwide and our paper brings attention to rare form of this zoonosis and updates the data about human dirofilariosis in buccal mucosa.

Manifestations of Lyme carditis.

The first data of Lyme carditis, a relatively rare manifestation of Lyme disease, were published in eighties of the last century. Clinical manifestations include syncope, light-headedness, fainting, shortness of breath, palpitations, and/or chest pain. Atrioventricular (AV) electrical block of varying severity presents the most common conduction disorder in Lyme carditis. Although is usually mild, AV block can fluctuates rapidly and progress from a prolonged P-R interval to a His-Purkinje block within minutes to hours and days. Rarely, Lyme disease may be the cause of endocarditis, while some studies and reports, based on serological and/or molecular investigations, have suggested possible influence of Borrelia burgdorferi on degenerative cardiac valvular disease. Myocarditis, pericarditis, pancarditis, dilated cardiomyopathy, and heart failure have also been described as possible manifestations of Lyme carditis. The clinical course of Lyme carditis is generally mild, short term, and in most cases, completely reversible after adequate antibiotic treatment.

Eyeworm infections in dogs and in a human patient in Serbia: A One Health approach is needed.

Thelazia callipaeda eyeworm has been frequently reported parasitizing humans in Asia. In Europe, the parasite is endemic in wild and domestic carnivores and only eight cases have been reported in humans so far. We describe the first case of human thelaziosis in Serbia, along with two cases in dogs from the same area. A One Health approach, based on cooperation amongst veterinarians and physicians, is strongly advised for this emerging infection in order to assess the risk for and prevent of the zoonotic infection.

Canine and human Dirofilaria infections in the Balkan Peninsula.

Dirofilaria immitis and Dirofilaria repens infections are mosquito-borne diseases, mainly of dogs. Both parasites are zoonotic, and they sometimes cause serious infections in humans. The aim of this short review was to examine the situation in the Balkan Peninsula, from where it is not always easy to obtain suitable data, often reported in journals and other publications difficult to be retrieved and with poor or no visibility. The review included data from international and regional literature, doctoral theses, and conference proceedings.

Canine Dirofilaria infections in two uninvestigated areas of Serbia: epidemiological and genetic aspects.

In 2009 canine filarial infections were investigated in two northern areas of Serbia (Pancevo and Veliko Gradiste), applying morphometry, biochemical staining, and immunological kit to detect Dirofilaria immitis antigens, and two home-made ELISAs to detect antibodies to D. repens and D. immitis somatic/metabolic polyproteins. Moreover, molecular tools were applied to analyze the phylogenetic relationships of the isolates. The microfilariae detected in 21/122 dogs (17.2%) were identified as D. repens (n=21) and D. immitis (n=2). D. immitis antigens were found in another 13 animals with occult infection. All of the 15 heartworm-positive dogs also had antibodies to this parasite, which were detected in another 13 subjects, indicating an overall D. immitis seroprevalence rate of 22.9%. Serology for D. repens revealed evidence of antibodies in 42.6% of the dogs, but was negative for 4 microfilaremic dogs. As for the two different areas, the prevalence of microfilariae and/or D. immitis antigens, mainly due to D. repens microfilaremic animals, was not significantly higher in Veliko Gradiste (33.3%) than in Pancevo (22%). However, serology showed a different epidemiological picture. Heartworm infection occurred more often in both areas, and antibodies to dirofilarial nematodes were detected in 72.9% of dogs living in Pancevo, a rate higher than in those living in Veliko Gradiste (57.1%). No risk factors for infection were found, confirming the uselessness of prophylactic drugs against D. repens, and suggesting the presence in these areas of sunrise- or sunset-biting mosquitoes as important vectors. The results indicate the need for both appropriate entomological studies and further research on the intra-species variability shown by D. repens.