COVID-19 associated mucormycosis (CAM) in Kashan, Iran: clinical presentations, risk factors, management, and outcomes.

BACKGROUND: This study aimed to estimate the disease burden and describe the clinical presentation, risk factors, and outcome of CAM in a single centre in Iran. METHODS: A case of mucormycosis was defined as one that had clinical and radiological features consistent with mucormycosis along with demonstration of the fungus in tissue via KOH mount/culture/histopathological and molecular examination. RESULTS: We report 30 cases of COVID-19 associated mucormycosis (CAM). The results of this study showed the affected age group in the range of 40-79 years (median = 65.5; IQR = 5) with women (16/30, 53%) affected more than men (14/30, 47%). Among the fungi recovered, Rhizopus oryzae had the highest frequency (79%). Out of the 30 patients, 28 (93%) patients were diabetic with 24 (80%) patients having other co-morbidities. Headache followed by retro-orbital pain, proptosis/ptosis and rapid diminution of vision was a common sequence of symptoms reported by the majority of cases. Use of mechanical ventilation (58% vs. 6%, p = 0.003), O2 required (92% vs. 50%, p = 0.024), and development of renal dysfunction during hospital stay (17% vs. 0%, p = 0.041) was significantly higher in non-survivors than survivors. Temperature (C°), PR (pulse rate), mean levels of serum creatinine, BUN, troponin, and neutrophils were significantly higher in non-survivors (p < 0.05). Besides, Albumin and PO2 were also significantly higher in survivors than non-survivors. CONCLUSION: Despite medical and surgical treatment, the mortality rate among CAM patients is still high. Thus, concerted efforts of revamping surveillance, diagnosis and management, along with public awareness and patient education, are the requisites for managing COVID-19 and mucormycosis.

Antileishmanial effects and drugability characteristics of a heterocyclic copper complex: An in silico, in vitro and molecular study.

Leishmaniasis caused by the protozoan Leishmania presents a severe illness, principally in tropical and subtropical areas. Antileishmanial metal complexes, like Glucantime®ï¸ with proven activity, are routinely studied to probe their potency. We investigated the effects of a Cu (II) homoleptic complex coordinated by two dimethyl-bipyridine ligands against Leishmania major stages in silico and in vitro. The affinity of this heterocyclic Cu (II) complex (CuDMBP) towards a parasitic metacaspase was studied by molecular docking. Key pharmacokinetic and pharmacodynamic properties of the complex were predicted using three web-based tools. CuDMBP was tested for in vitro antileishmanial activities using MTT assay, model murine macrophages, flow cytometry, and quantitative real-time polymerase chain reaction (qPCR). Molecular docking confirmed the tendency between the target macromolecule and the complex. ADMET evaluations highlighted CuDMBP's key pharmacological features, including P-glycoprotein-associated GI absorption and lack of trans-BBB permeability. MTT showed significant inhibitory effects against promastigotes. CuDMBP significantly increased the level of cellular IL-12 expression (p < 0.05), while the upregulation observed in the expression of iNOS was considered not significant (p > 0.05). It decreased the expression of IL-10 significantly (p < 0.05). Findings demonstrated that CuDMBP deserves to be introduced as a leishmanicidal candidate provided further studies are carried out.

COVID-19-associated pulmonary aspergillosis (CAPA) in Iranian patients admitted with severe COVID-19 pneumonia.

PURPOSE: Bacterial or virus co-infections with SARS-CoV-2 have been reported in many studies; however, the knowledge on Aspergillus co-infection among patients with COVID-19 was limited. This study was conducted to identify and isolate fungal agents and to evaluate the prevalence of pulmonary aspergillosis (CAPA) as well as antifungal susceptibility patterns of Aspergillus species in patients with COVID-19 admitted to Shahid Beheshti Hospital, Kashan, Iran. METHODS: The study involved 119 patients with severe COVID-19 pneumonia referred to the Shahid Beheshti Hospital, Kashan, Iran. A total of 17 Aspergillus spp. that were isolated from COVID-19 patients suspected of CAPA were enrolled in the study. CAPA was defined using ECMM/ISHAM consensus criteria. The PCR amplification of the ß-tubulin gene was used to identify the species. The antifungal activities of fluconazole, itraconazole, voriconazole, amphotericin B against Aspergillus spp. were evaluated according to the Clinical and Laboratory Standards Institute manual (M38-A3). RESULTS: From the 119 patients with severe COVID-19 pneumonia, CAPA was confirmed in 17 cases (14.3%). Of these, 12 (70.6%) were males and 5 (29.4%) were females; the mean age at presentation was 73.8 years (range: 45-88 years; median = 77; IQR = 18). Aspergillus fumigatus (9/17; 52.9%), Aspergillus flavus (5/17; 29.4%), Aspergillus oryzae (3/17, 17.6%), were identified as etiologic agents of CAPA, using the molecular techniques. Voriconazole and amphotericin B showed more activity against all isolates. Moreover, the MIC of fluconazole, itraconazole varied with the tested isolates. For 3 clinical isolates of A. fumigatus, 2 isolate of A. flavus and 3 A. oryzae, the MIC of fluconazole and itraconazole were ≥ 16 µg/mL. CONCLUSIONS: We observed a high incidence (14.3%) of probable aspergillosis in 119 patients with COVID-19, which might indicate the risk for developing IPA in COVID-19 patients. When comparing patients with and without CAPA regarding baseline characteristics, CAPA patients were older (p =0 .024), had received more frequent systemic corticosteroids (p = 0.024), and had a higher mortality rate (p = 0.018). The outcome of CAPA is usually poor, thus emphasis shall be given to screening and/or prophylaxis in COVID-19 patients with any risk of developing CAPA.

Anti-biofilm properties of eucalyptol in combination with antifungals against Candida albicans isolates in patients with hematological malignancy.

Oral candidiasis is a fungal infection caused mainly by Candida albicans and it is a major problem among hematologic malignancy patients. Biofilm formation is an attributable factor to both virulence and drug resistance of Candida species. The aim of the study was to evaluate the biofilm-producing ability of oral C. albicans isolates and to evaluate the inhibitory activity of eucalyptol on Candida biofilm, alone and in combination with antifungal agents. Samples were collected from the oral cavity of 106 patients with hematologic malignancy. The isolated yeasts were identified by PCR-sequencing. Then C. albicans isolates were analyzed for their biofilm-producing ability by crystal violet staining and MTT assay. The minimum biofilm inhibition concentrations (MBIC) of eucalyptol, amphotericin B, itraconazole, and nystatin and the in vitro interaction of eucalyptol with these drugs were tested according to CLSI-M-27-A3 protocol and checkerboard methods, respectively. From 106 patients, 50 (47.2%) were confirmed for oral candidiasis [mean ± SD age 39 ± 14 years; female 31 (62%) and male 19 (38%)]. C. albicans was isolated from 40 of 50 (80%) patients. From 40 C. albicans isolates, 24 (60%) and 16 (40%) were moderate and weak biofilm producer, respectively. The geometric mean MBIC of amphotericin B, itraconazole, nystatin and eucalyptol were 3.93 µg/mL, 12.55 µg/mL, 0.75 µg/mL and 798 µg/mL, respectively. Eucalyptol interacted synergistically with amphotericin B, itraconazole and nystatin against 12.5, 10, and 22.5% of isolates, respectively. Eucalyptol demonstrated promising activity against biofilm of C. albicans when tested alone or combined with antifungal drugs.

Changes in the expression of miR-103a and miR-21: a functional diagnosis of toxocariasis in rats.

Introduction. Toxocariasis is a zoonotic parasitic disease caused by migrating nematode worms, Toxocara species larvae, within tissues. MicroRNAs (miRNAs) are small RNA molecules that regulate gene expression at a post-transcriptional level.Hypothesis/Gap Statement. miRNA-based diagnostic biomarkers for toxocariasis are emerging, but there is limited information about the role of many miRNAs and a more detailed diagnostic evaluation of miRNA expression patterns is needed to understand their immunobiological function.Aim. We investigated the expression levels of circulating miRNA 21 and miRNA 103a as potential biomarkers for the prediction and diagnosis of toxocariasis in Wistar rats infected with Toxocara canis.Methodology. Thirty Wistar rats were inoculated orally with 2500 T. canis embryonated eggs via gavage. Serum samples were collected from infected animals and were tested against T. canis antigens for 60 days post-infection. The plasma samples were isolated for quantitative real-time PCR (qPCR) assays and qPCR was used to assess transcription levels of miRNA 21 and miRNA 103a.Results. The prevalence of anti-Toxocara IgG was detected in 7/30 (23.3 %) infected rats. Molecular analysis of miRNAs 21 and 103a showed that expression levels of miRNAs in both groups of Toxocara-positive and negative samples were the same without significant association. The ratio of housekeeping gene expression (U6) to gene expression of miRNAs 21 and 103a indicated the rate of change (1/1.38 ≈ 0.75 and 1/0.751 ≈ 1.3, respectively).Conclusion. Our study revealed that miRNAs 21 and 103a might play fundamental roles as biomarkers and diagnostic tools for toxocariasis. However, the changes in expression of these miRNAs were not adequate to be used as biomarkers in diagnosis.

Clinical impact of Candida respiratory tract colonization and acute lung infections in critically ill patients with COVID-19 pneumonia.

Coronavirus disease 2019 (COVID-19), which is attributable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been causing a worldwide health issue. Airways colonization by Candida spp. is prevalent among patients on automatic ventilation in intensive care units (ICUs). This research aimed to ascertain the risk factors and roles of Candida spp. respiratory tract colonization, and Candida lung infection during the progression of COVID-19 pneumonia in critically ill patients. In total, Candida spp. were recovered in 69 from 100 immunosuppressed patients with COVID-19. Bronchoscopy was used to collect the Bronchoalveolar lavage (BAL) specimens. For the identification of Candida spp. PCR sequencing was done using the ITS1 and ITS4 primers. The amplification of the HWP1 gene was conducted to identify the Candida albicans complex. The antifungal activities of fluconazole, itraconazole, voriconazole, amphotericin B and caspofungin against Candida spp. were evaluated using the Clinical and Laboratory Standards Institute M60. In 63.77% of the patients, Candida respiratory colonization at D0 and D14 had no impact on the severity of COVID-19. In comparison to C. albicans strains, Candida respiratory disorder with C. glabrata had influenced the severity of COVID-19 for critically ill patients following adjustment for the risk factors of COVID-19 (P < 0.05). Amphotericin B and caspofungin showed superior activity against all Candida spp. All antifungal agents showed 100% sensitivity against the two C. africana strains. Our observation on patients who used automatic ventilation, respiratory colonization by Candida spp. was not seen to influence the infection or death caused by COVID-19. Amphotericin B and caspofungin showed superior activity against all Candida spp. and were recommended for the treatment regime of pulmonary candidiasis associated with COVID-19 infection. Although "Candida pneumonia" is rarely being reported in critically ill patients, Candida airway colonization mainly by Candida albicans is common especially among patients with diabetes, malignancies, and kidney disorders.

Therapeutic Strategies for COVID-19 Patients: An Update.

The novel coronavirus SARS-coV-2, which emerged in Wuhan in November 2019, has increasingly spread, causing a global pandemic that infected more than 444 million people, resulting in severe social and economic ramifications, and claimed more than 6,010,000 lives by March 5, 2022. The pandemic attracted global attention with consequential multiple economic, social, and clinical studies. Among causes of poor clinical outcomes of the disease are therapeutic challenges, leading to spirals of studies in search of better therapeutic alternatives. Despite the worsening circumstances of the pandemic, no drug has yet shown remarkable efficacy in the clinical management of COVID-19 patients in large-scale trials. Many potential therapeutic strategies, including the use of nucleotide analogs, chloroquine phosphate, arbidol, protease inhibitors (lopinavir/ritonavir), plasma, monoclonal antibodies, plastic antibodies based on molecularly imprinted polymers (MIPs), traditional Chinese medicine (TCM), nanomaterials, vaccine, and mesenchymal stem cells (MSCs), have emerged with various degrees of successes. Remdesivir and dexamethasone have now been licensed based on the results of randomized controlled trials. Baricitinib, the Janus kinase (JAK) 1/2 inhibitor, is also an attractive candidate due to its properties as a potent anti-inflammatory agent and its hypothesized offtarget antiviral effects against SARS-CoV-2. Besides, human plasma from recovered COVID-19 patients is theoretically expected to be safe and effective for both therapy and post-exposure prophylaxis. In light of the literature, the correlation between the reduction of C5aR1/C5aR2 and the IL6-IL6R axis, using the available anti-IL6R mAb would be crucial. Moreover, MSCs are a potential therapeutic choice for patients with COVID-19 pneumonia. The coronavirus spike (S) protein that mediates the process of the infection via binding of host cells to the virus receptor is an essential focus for vaccine development. Importantly, with the number of patients increasing daily, there is an urgent need for effective therapeutic intervention. In this review, we expatiated on several strategies deployed for the treatment of COVID-19 infection.

Therapeutic Status of Famotidine in COVID-19 Patients: A Review.

The novel coronavirus, SARS-coV-2, which emerged in Wuhan in November 2019, has increasingly spread worldwide. More than 272 million cases of infection have been identified. COVID-19 has affected 223 countries and territories across the world. The principal target of the SARS-CoV-2 infection is the lower respiratory tract. Series of moderate to non-specific severe clinical signs and symptoms appear two to fourteen days after exposure to SARS-CoV-2 in patients with COVID-19 disease, including cough, breath deficiency, and at least two of these symptoms: headache, fever, chills, repeated rigor, myalgia, oropharyngitis, anosmia, and ageusia. No therapeutic agents have been validated to have substantial efficacy in the clinical care of COVID-19 patients in large-scale trials, despite worsening infected rates of COVID-19. Early clinical evidence from many sources suggests that treatment with famotidine may decrease COVID-19-related morbidity and mortality. The mechanism by which famotidine could improve the outcomes of COVID-19 is currently unknown. A more recent postulated mechanism is that the effect of famotidine is mediated by histamine-2 receptor antagonism or inverse agonism, inferring that the SARS-CoV-2, resulting in COVID-19 infection, at least partially leads to the abnormal release of histamine and perhaps dysfunction of mast cells.

Allergic fungal rhinosinusitis caused by Neoscytalidium dimidiatum: A case report: Allergic fungal rhinosinusitis due to Neoscytalidium dimidiatum.

Neoscytalidium dimidiatum is a rare dematiaceous fungus that was first described in 1916 as Dothiorella mangiferae. From the standpoint of epidemiology and therapy, early detection of fungal rhinosinusitis (FRS), the causative agents, and their associated risk factors can improve the therapeutic outcome and decrease the mortality rates among patients. In this study, we report a 34-year-old Iranian female patient with allergic bronchopulmonary aspergillosis (ABPA), who presented to our facility with an 8-year history of chronic fungal sinusitis, drug-resistant asthma, pneumonia, bronchitis, post-nasal discharge, nasal obstruction, nasal polyposis, and anemia. The patient was subjected to diagnostic nasal endoscopy and computed tomography (CT) scan of paranasal sinuses, as well as routine, complementary mycological, and molecular methods, which confirmed the diagnosis of allergic fungal rhinosinusitis in patients with ABPA. Neoscytalidium dimidiatum was isolated from the sinus of the patient. Results of in vitro susceptibility tests indicated that the case isolate was susceptible to amphotericin B and itraconazole at concentrations which are commonly achieved in patients receiving recommended dosages for invasive mycoses (0.25 to 0.75 mg/kg of body weight daily for amphotericin B and 100 to 400 mg daily for itraconazole) and resistant in vitro to caspofungin, voriconazole, and posaconazole. The patient was successfully treated with amphotericin B / itraconazole + postoperative oral corticosteroids (OCS). Neoscytalidium dimidiatum infection should be considered as a possible additional factor in the etiology of AFRS, especially in immunocompromised patients.

Immobilization of Clostridium perfringens type D in calcium alginate beads: toxin production mimics free cell culture.

Background and Objectives: Cell-immobilization is used to maintain microbial culture to produce metabolites in repeated-batch or continuous fermentations, thereby reducing the time and resources spent on delivering mass production of microbe. The technique also enables shortening of the detoxification phase and the amount of formaldehyde required due to low incidence of viable bacteria in the extract. Materials and Methods: A solution of sodium alginate containing Clostridium perfringens cells was dropped into stirring CaCl solution via a sterile syringe needle. Optimizations resulted in reasonably uniform beads containing C. perfringens. Beads were externally stabilized by poly L-lysine, followed by immersion in a solution of Na-alginate to coat them with a new layer of alginate forming an alginate-PLL-alginate cortex. Results: This study proved successful in immobilizing C. perfringens cells inside uniform alginate microspheres. Cell loading and cell propagation inside the beads were measured. The cell loaded beads were cultivable in liquid media producing 550 minimum lethal doses per milliliter (MLD/ml) in a 72 h. Conclusion: The research paved the way for further investigations to optimize and establish an efficient bacterial encapsulation method. Thus, it seems possible to produce toxins from beads engulfing C. perfringens on larger scales via repeated-batch or continuous fermentation processes.

Detection of Malaria Parasites and Other Haemosporidia in Migratory and Native Birds in Mazandaran and Golestan Provinces, Iran.

Background: A variety of haemoprotozoa including Plasmodium, Haemoproteus and Leucocytozoon cause infections in birds and are transmitted by some known vectors. These parasites cause anemia, low appetite, weakness and ultimately death in birds. The present study was aimed to determine these parasites, in birds of Mazandaran and Golestan provinces in Iran. Methods: The project was performed on 340 live birds in 2016. The samples were collected from February to September 2016, from each bird, two thin and thick blood smears were prepared and the remaining blood about 1ml was kept in EDTA-containing tubes for molecular studies. The slides were stained with 10% Giemsa, then examined microscopically. About ten percent of the negative samples were considered for Polymerase Chain Reaction (PCR) technique, using specific primers to diagnose Plasmodium and Haemoproteus spp. Electrophoresis was done for PCR products and relevant bands to the parasites were identified based on the size. The considered birds belonged to ducks, chickens, roosters, and pigeons. Results: From 340 microscopically examined blood samples 32 (9.5%) samples were positive. Twenty-five (7.35%) of them were infected with the genus Haemoproteus. Seven samples (14%) out of 50 microscopically negative samples were found as Haemoproteus or Plasmodium spp when PCR technique was employed. Conclusion: This study revealed the existence of malaria parasites and other haemosporidia in birds in Iran. Employing molecular methods (PCR examination) could detect more infections.

Human Toxocariasis in individuals with blood disorders and cancer patients: the first seroepidemiological study in Iran.

Toxocara is one of the most prevalent nematodes in Iran, which infect humans as an intermediate host. Infection complications result from the larva migration. Human toxocariasis prevalence was various in Iran according to the area of study and population. This study was designed to evaluate the seropositivity of Toxocara IgG in patients with blood disorders and cancer patients in southwest Iran. Moreover, the study of the associated risk factors for this infection. A total of 1122 serum samples, from February 8, 2019 to August 21, 2019, including 600 healthy individuals and 522 individuals with cancer and blood disorders patients were collected. Serum samples were collected for detection of Toxocara IgG by using ELISA (Enzyme-Linked Immunosorbent Assay) kit. Sociodemographic data of all participants were collected and examined to determine their association with the infection. Out of 101 individuals with white blood cell disorders (5.94%), red blood cell disorders (7.48%) and cancer patients (11.06%) were seropositive for Toxocara IgG antibodies. The infection rate among all study population revealed that (10.76%) were positive for Toxocara IgG. This study showed the fundamental role of contact with pets and infection in groups with blood cell disorders (P-value ≤ 0.05%); while in cancer patients the association wasn't significant. Other factors such as age, location of residence, and sex showed that the association with this infection wasn't significant.

First report of chronic invasive fungal rhinosinusitis in a patient with ovarian cancer caused by Didymella pedeiae and successful treatment with voriconazole: A case report.

BACKGROUND AND PURPOSE: Didymella pedeiae is a dematiaceous fungus that belongs to the Coelomycetes class. While species within this class are known to cause human infection,  D. pedeiae had previously only been known as phytopathogens and had never been isolated from a human sample. CASE REPORT: A 51-year-old Iranian female patient with ovarian cancer was admitted with unilateral lesions in paranasal sinuses and a five-month history of nasal obstruction, headache, postnasal drainage, swelling on the left side of the face, and orbital pain. Paranasal sinus computerized tomography scan revealed a soft tissue mass that filled the left nasal cavity, ethmoid, sphenoid, and frontal sinuses with more involvement in the maxillary and ethmoid sinuses. Antifungal treatment was simultaneously initiated with itraconazole+prednisolone 15 mg/day, and levofloxacin. Due to poor clinical response, IV voriconazole and amphotericin B were added to the treatment as well. The patient recovered completely after 10 weeks of therapy. CONCLUSION: Here, we report the first case of human D. pedeiae infection in a patient with ovarian cancer.

Acute invasive fungal rhinosinusitis: Molecular identification and update in management of frozen section biopsy.

The clinical diagnosis of Acute Invasive Fungal Rhinosinusitis (AIFRS) is technically difficult because it presents with non-exclusive and nonspecific clinical symptoms. Laboratory confirmation (usually via histopathologic techniques such as formalin-fixed paraffin-embedded (FFPE)) is necessary but it is time-consuming, despite the urgent need for timely diagnosis of AIFRS for effective management. This study aimed to investigate the sensitivity and specificity of the GMS frozen-section biopsy in the diagnosis of AIFRS and compare the same with that of different tissue staining methods to provide valid decision-grounds that may guide clinicians in prompt diagnosis of acute fungal invasive rhinosinusitis. A cross-sectional study was conducted in the Medical Mycology Laboratory, Faculty of Medicine, Iran University of Medical Sciences between 2018 and 2020 on 200 patients with suspected AIFRS referred to Baqiyatallah and Imam Khomeini Hospital, Tehran. All patients were subjected to diagnostic nasal endoscopy and computed tomography (CT) scan of paranasal sinuses. Magnetic resonance imaging (MRI) was done in cases of suspected intracranial extension. After screening by routine mycological examination, the diagnosis was confirmed using complementary molecular methods. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the frozen-section biopsy were also compared with FFPE. Of the 200 suspect patients, 47 cases (23.5%) met the criteria for AIFRS. Species of the genus Aspergillus were the predominant 27 (57.4%) followed by Mucorales species 10 (21.3%), and Fusarium spp 3 (6.4%). Also, 3 cases (6.4%) of co-infection due to Aspergillus/Rhizopus were reported. The accuracy, sensitivity, specificity, PPV, and NPV of frozen section assessments were 99.5%, 97.9%, 100%, 100% and 99.3%, respectively. For GMS frozen-section alone, sensitivity, specificity, NPV, and PPV was 100%. Overall, the calculated accuracy of FFPE was 98.5%, sensitivity was 94%, specificity was 100%, PPV was 100%, and NPV was 98.1%. Examination of the frozen-section biopsy is a highly predictive tool for a rapid and effective diagnosis of patients with suspected AIFRS. We observed that GMS frozen-section is a fast and reliable exam to confirm the diagnosis of fungal invasion, with good accuracy, sensitivity, and specificity compared to the gold-standard FFPE biopsy.

Parasite-derived microRNAs as a diagnostic biomarker: potential roles, characteristics, and limitations.

MicroRNAs (miRNAs), a subclass of small regulatory RNAs that present from ancient unicellular protozoans to parasitic helminths and parasitic arthropods. MiRNAs' mode of action has attracted wide attention as a result of their unique functional importance. MiRNAs play a role in diverse physiological and pathological processes ranging from organ development, immune function to apoptosis and cancer at the post-transcription gene expression. Thus, miRNAs are known to be targets for clinical treatment and therapy. The discovery of the high stability of circulating miRNA in various types of host body fluids, such as whole blood, serum, plasma, saliva, and urine has increased great interest among researchers in the potential of circulating miRNA as a prognosis/diagnosis of infectious. Some circulating miRNAs biomarkers advanced to clinical applications related to human diseases. However, this idea starts to come only in the fields of infectious disease. The goal of this review is to enhance the current understanding of these molecules and their applicability in the field of medicine. A detailed review of the available literature consulting tools performed in online repositories such as NCBI, PubMed, Medline, ScienceDirect, and UpToDate. This review summarizes an overview of preclinical studies using circulating miRNAs biomarkers against infectious diseases affecting humans. The use of miRNA as a safe and potential tool is encouraging news, considering that until now, guidelines for the use of miRNA in clinical practice are still lacking.

Molecular identification and clinical features of fungal rhinosinusitis: A 3-year experience with 108 patients.

This study aimed to determine the prevalence, the causative agents, clinical features, and the risk factors associated with the fungal rhinosinusitis in a tertiary health center with a view to providing valid grounds that may guide healthcare professionals to effectively prevent, control, and treat fungal infections. All patients were subjected to diagnostic nasal endoscopy and CT scan of paranasal sinuses and FRS were confirmed by routine and complementary mycological and molecular methods. The inclusion criteria for invasive FRS were: confirmed diagnosis of IFRS according to the guidelines of the EORTC/MSG criteria (i.e., clinical, microbiological, and histological evidence of invasive fungal infection). From a total of 512 suspected patients, FRS was confirmed in 108 cases (21.1%). Our results showed FB (38/108; 35.2%) is the most common form of FRS followed by AIFRS (33/108; 30.6%), AFS (32/108; 29.6%), and CIFRS (5/108; 4.6%). A. flavus and Rhizopus oryzae were the most common causes of infection in AFS, FB, CIFRS, and AIFRS, respectively. Univariate analysis of variables predictive of AIFRS revealed 3 variables significantly associated with AIFRS. These included mucosal abnormalities of the middle turbinate and septum, and specifically, necrosis of the middle turbinate (P < .0001). Microbiological cultures, although useful for mycological speciation, are less sensitive. Furthermore, we used molecular methods to confirm the identity of some isolates that were not detectable using routine methods. Our data showed that the molecular methods and histologic diagnosis in all patients were more sensitive than the unenhanced sinus CT scan, and conventional microbiological methods.

Molecular Characterization and Phylogeny of Taenia hydatigena and Echinococcus granulosus from Iranian Sheep and Cattle Based on COX1 Gene.

Hydatid cyst, the larval stage of Echinococcus granulosus, and Cysticercus tenuicollis, the larval stage of Taenia hydatigena, are prevalent in domestic, livestock, and wild ruminants. The main goal of this research was to identify the isolates of E. granulosus and C. tenuicollis by partial sequencing with PCR amplification of the cytochrome C oxidase 1 (COX1) gene. During a routine veterinary inspection at a Chabahar city slaughterhouse, two samples of hydatid cysts from sheep's liver and cattle's lung and two samples of C. tenuicollis from sheep's liver were collected. After DNA extraction, the fragment of the COX1 gene was amplified by the PCR method. Sample sequences were modified and synchronized by Chromas and CLC genomic workbench 11 software. Sequence analysis was carried out by BLAST algorithms and GenBank databases. Phylogenetic trees were performed using MEGA 7 software and the neighbor-joining and maximum likelihood method for T. hydatigena and E. granulousus. The result indicated that the main genotype of parasites and the amplified fragment size were G1 and approximately 455 bp, respectively. The analysis of phylogenetic trees based on nucleic acid for four samples showed that there was a common ancestor. However, the shift in nucleotides in the two isolates in E. granulosus and the two isolates of T. hydatigena were non-synonymous type and synonymous type, respectively. The present study showed that the dominant genotype in all isolates was G1 and this report was similar to other studies in Iran and the world. Also, the partial COX1 gene sequence was matched with T. hydatigena.

Spatial analysis of Toxocara spp. eggs in soil as a potential for serious human infection.

Toxocara spp. cause one of the most widespread soil-transmitted helminthic infections worldwide. In both developed and developing countries, soil contamination with Toxocara eggs is considered as a major threat to public health. A total of 515 soil samples from 89 sampling sites were collected from different locations of public health such as Wastelands and Streets, public parks, and marginal areas. The soil samples were examined for Toxocara eggs using a centrifugal-floatation technique utilizing a saturated sodium nitrate solution. centralization of positive soil samples in the province was studied by Spatial Statistics Techniques such as Average Nearest Neighbors and Spatial Autocorrelation and Kernel Density Function Toxocara spp. eggs were found in 94 (18.25 %) out of 515 samples collected from the studied areas. According to the results obtained, marginal areas are often contaminated with eggs of Toxocara. Consequently, preventive measures including health education should be implemented to reduce the potential risk of this parasitic infection.

New foci of zoonotic cutaneous leishmaniosis due to Leishmania major in the northeastern Iran cities of Sabzevar and Neghaab.

Cutaneous leishmaniosis (CL) is a major public health challenge in Iran. Overall, 18 provinces out of 31 of the country's provinces are in the endemic areas. The objective of the present study was to determine the presence of CL species in Sabzevar and Neghaab cities, Khorasan Razavi province, northeastern Iran. Overall, 280 samples were taken from suspected individuals referred to Sabzevar's and Neghaab's health centers during 2014-2016. Smear preparation, case detection and further identification by partial amplification of 7SL RNA and high-resolution melting curve analysis were done for all samples, followed by randomly polymerase chain reaction (PCR)-sequencing confirmation. Based on findings, the most infection rate was found in males with the age groups of 20-30 in both districts. All samples were characterized as Leishmania major, except one isolate in Neghaab closely related to Leishmania tropica. Various risk factors play roles in creating new foci of zoonotic CL (ZCL) caused by L. major in Sabzevar and Neghaab in northeastern Iran. Reports of the prevalence of CL in new foci make serious concerns about the incidence of cases and expansion of disease to the neighboring areas. Further measures are essential to control the disease in the regions.