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Objective To systematically review the reported cases of Creutzfeldt-Jakob disease (CJD) in Iran. Methods A comprehensive literature review of CJD cases in Iran was undertaken using the PubMed®, Scopus® and Google Scholar databases. In addition, the Iranian database MagIran was searched for Persian language reports. Case selection used the following criteria: (i) patients of Iranian origin; (ii) publication in peer-reviewed journals or reputable medical databases; (iii) a definitive diagnosis of CJD based on established diagnostic criteria. Results Thirteen cases from twelve reports were included in this systematic review. The majority of the cases were female (11 of 13; 84.6%). The mean ± SD age of patients at hospital admission was 59.38 ± 7.44 years. The findings of the case review suggested that the prevalence of CJD in Iran is not fully established. CJD may be misdiagnosed alongside other clinical signs. The most prevalent early indications of the disease were psychiatric and neurological in nature. A considerable delay in diagnosis was observed in some cases and there was a shortage of brain autopsy records. Conclusion Efforts to improve diagnostic capabilities, promote awareness and establish monitoring systems are necessary for managing the challenges of providing an early diagnosis of CJD in Iran.

The surveillance of wastewater treatment plant (WWTP) as the end point of SARS-CoV-2 shed from infected people arise a speculation on transmission of this virus of concern from WWTP in epidemic period. To this end, the present study was developed to comprehensively investigate the presence of SARS-CoV-2 in raw wastewater, effluent and air inhaled by workers and employee in the largest WWTP in Tehran for one-year study period. The monthly raw wastewater, effluent and air samples of WWTP were taken and the SARS-CoV-2 RNA were detected using QIAamp Viral RNA Mini Kit and real-time RT-PCR assay. According to results, the speculation on the presence of SARS-CoV-2 was proved in WWTP by detection this virus in raw wastewater. However, no SARS-CoV-2 was found in both effluent and air of WWTP; this presents the low or no infection for workers and employee in WWTP. Furthermore, further research are needed for detection the SARS-CoV-2 in solid and biomass produced from WWTP processes due to flaks formation, followed by sedimentation in order to better understand the wastewater-based epidemiology and preventive measurement for other epidemics probably encountered in the future.

Abstract Background Human papilloma virus (HPV) causes the most common sexually-transmitted infection especially among sexually-active individuals. The aim of study was to characterize the molecular characterization of HPV genotypes between 5176 female and male patients. Methods HPV DNA was extracted from genital swabs of the study participants and amplified by Real Time Polymerase Chain Reaction (PCR). Genotyping was performed for 2525 cases using REALQUALITY RQ-Multi HPV Detection Kit for the identification of 14 high risk (HR) and 2 low risk (LR) HPV genotypes. Demographic figures were analyzed in correlation with virological data statistically. Results Out of 5176 cases from 7 laboratories, 2727 (53%) were positive for HPV, of which. 2372(87%) women and 355 (13%) men were HPV positive. However, in an intra-gender analysis, positive rate was higher in men (355/637, 55.7%) than in women (2372/4539, 52%; P value 0.007). HPV positive patients were younger than negative individuals. Positive rate was higher among age categories 20–40. Genotyping was performed for 2525 cases. Out of 1219 (48%) patients who contained single genotypes, 566 (22%) and 653 (26%) harboured HR and LR genotypes, respectively. In females and males, 1189 (54%) and 117 (37%) contained multiple genotypes. No substantial associations were found between different age categories and HR/LR and multiple genotypes distribution. Conclusion The prevalence of HPV infection in both genders was high. However, men had a higher rate of infection. These observations highlighted the necessity for a plan for targeted education to younger population in the society as well as application of infection control measures against HPV infection, especially in terms of general population mass HPV vaccination.

A quantitative model on exposure to pathogenic viruses in air of recreational area and their corresponding health effects is necessary to provide mitigation actions in content of emergency response plans (ERP). Here, the health risk associated with exposure to two pathogenic viruses of concern: Rotavirus (RoV) and Norovirus (NoV) in air of water spray park were estimated using a quantitative microbial risk assessment (QMRA) model. To this end, real-time Reverse Transcriptase polymerase chain reaction (real-time RT-PCR) was employed to measure the concentration levels of RoV and NoV over a twelve-month period. The probability of infection, illness and diseases burden of gastrointestinal illness (GI) caused by RoV and NoV for both workers and visitors were estimated using QMRA and Monto-Carlo simulation technique. The annual mean concentration for RoV and NoV in sampling air of water spray park were 20and 1754, respectively. The %95 confidence interval (CI) calculated annual DALY indicator for RoV (Workers: 2.62 × 10−4–2.62 × 10−1, Visitors: 1.50 × 10−5–2.42 × 10−1) and NoV (Workers: 5.54 × 10−3–2.53 × 10−1; Visitors: 5.18 × 10−4–2.54 × 10−1) were significantly higher the recommended values by WHO and US EPA (10−6–10−4 DALY pppy). According to sensitivity analysis, exposure dose and disease burden per case (DBPC) were found as the most influencing factors on disease burden as a consequences of exposure to RoV and NoV, respectively. The comprehensive information on DALY and QMRA can aid authorities involved in risk assessment and recreational actions to adopt proper approach and mitigation actions to minimize the health risk.

Abstract In this pandemic SARS-CoV-2 crisis, any attempt to contain and eliminate the virus will also stop its spread and consequently decrease the risk of severe illness and death. While ozone treatment has been suggested as an effective disinfection process, no precise mechanism of action has been previously reported. This study aimed to further investigate the effect of ozone treatment on SARS-CoV-2. Therefore, virus collected from nasopharyngeal and oropharyngeal swab and sputum samples from symptomatic patients was exposed to ozone for different exposure times. The virus morphology and structure were monitored and analyzed through Atomic Force Microscopy (AFM), Transmission Electron Microscopy (TEM), Atomic Absorption Spectroscopy (AAS), and ATR-FTIR. The obtained results showed that ozone treatment not only unsettles the virus morphology but also alters the virus proteins’ structure and conformation through amino acid disturbance and Zn ion release from the virus non-structural proteins. These results could provide a clearer pathway for virus elimination and therapeutics preparation.

Background: Detection of Leishmania RNA virus (LRV) in Old World Leishmania species and their possible role in the disease prognosis requires sensitive and specific methods, preferably independent of the viral genome. We aimed to develop an indirect immunofluorescence antibody (IFA) assay to detect LRV in the Old World Leishmania parasites. Methods: Clinical samples were collected from 86 cutaneous leishmaniasis (CL) patients in different endemic areas of CL in Iran, during 2017-2019. For antibody preparation, the viruses were obtained from sediment of an LRV-infected L. major culture-using freeze and thaw cycles followed by gradient cesium chloride centrifugation. The purified viruses were used to immunize a male 3-4 months rabbit. Various dilutions of the LRV-immunized rabbit's serum and a conjugated antibody were deployed to detect LRV in 48 isolates by IFA assay. Results: LRV virus was detected in four of the 48 CL cases using IFA method. Amplification of a partial fragment of RNA-dependent RNA polymerase (RdRp) gene from the isolates confirmed the IFA results. In phylogeny, the generated RdRp sequences from four isolates were grouped with the other Old World LRVs, but separate from L. aethiopica LRVs, which appeared as a highly supported distinct clade. Conclusion: Further optimization of this approach to detect the LRV directly in lesion scrapings can make it a more reliable tool for field studies and disclosing the virus's possible role in disseminating and unusual clinical features.

Meningitis is defined as an inflammation of the meninges, which are the protective membranes surrounding the brain and spinal cord. Aseptic meningitis is the term used to describe all forms of meningitis that are not caused by pyogenic bacteria. Aseptic meningitis can be caused by a variety of etiological agents. Infectious agents include viruses, fungi, and parasites. Viruses are regarded as a significant etiological agent of aseptic meningitis. The viral etiology of this disease exhibits variability across different age groups and countries. This study aimed to examine the prevalence of different viruses (enterovirus, mumps virus, and HSV-1) in cerebrospinal fluid (CSF) samples of children diagnosed with aseptic meningitis. A total of 58 cerebrospinal fluid (CSF) samples were obtained from patients suspected of having meningitis and admitted to Ali Asghar Hospital in Tehran during the 2019-2020 period. Nucleic acid extraction was conducted, and polymerase chain reaction (PCR) testing was performed to investigate the presence of various meningitis-causative viruses. A total of 32 patients (24 males and 8 females) were found to be infected with viruses. The most prevalent meningitis virus identified was enterovirus, accounting for 25.9% of cases (n=15). The mumps virus and herpes simplex virus (HSV) were identified in 11 (19%) and six (10.3%) patients, respectively. The most common clinical manifestations observed in children with aseptic meningitis were fever and vomiting. A statistically significant correlation was identified between term week and the occurrence of viral meningitis among patients infected with HSV and mumps (p-value = 0.04). Furthermore, a borderline relationship was observed between a history of surgery and viral meningitis. Enteroviruses represent a significant etiological agent of aseptic meningitis across a range of age groups. An accurate diagnosis of meningitis viruses, such as enteroviruses, will facilitate the implementation of appropriate and life-saving antiviral therapies, while reducing the overuse of antibiotics. [ABSTRACT FROM AUTHOR]

Objective: Leishmania RNA virus (LRV) is a double-stranded RNA (dsRNA) virus that circulates within many species of the Leishmania parasite. In this study, we aimed to investigate the presence of LRV2 circulating in Leishmania isolates in an old focus of ZCL located in northeastern of Iran. Methods: Leishmania isolates were collected from 85 patients that confirmed to have cutaneous leishmaniasis (CL) based on parasitological examination. To identify the Leishmania isolates, species-specific primer sets were applied for molecular identification. The presence of LRV2 was performed by RdRp-semi nested-PCR. The genetic diversity were calculated using MEGA and DnaSP. To assess haplotype diversity, 31 LRV2 strains in different regions were surveyed using analysis a 292-bp section of the RdRp sequences. Results: Out of 85 patients, 83 (97.6 %) were diagnosed with L. major and 2 (2.4 %) with L. tropica. LRV2 virus was detected in 59 (69.4%) of the CL cases. For the first time, LRV2 was reported in one L. tropica strain in Iran. The current LRV2 sequences indicated the highest similarities to an Old World LRV2. Moreover, 10 unique haplotypes were identified based on the analyzed sequences of the RdRp gene. Conclusions: Our results indicated the highest occurrence of Leishmania/LRV2 co-circulation in this known ZCL focus from northeastern Iran. Phylogenetic analyses of LRV2 sequences confirmed that these isolates belong to the order of LRV2 from the Old World. This study offered an insight into LRV2 haplotype that the informative issue can be used for genetic research of LRV2 in other regions.

Abstract Hepatitis B virus (HBV), along with Hepatitis C virus chronic infection, represents a major risk factor for hepatocellular carcinoma (HCC) development. However, molecular mechanisms involved in the development of HCC are not yet completely understood. Recent studies have indicated that mutations in CTNNB1 gene encoding for β-catenin protein lead to aberrant activation of the Wnt/ β-catenin pathway. The mutations in turn activate several downstream genes, including c-Myc, promoting the neoplastic process. The present study evaluated the mutational profile of the CTNNB1 gene and expression levels of CTNNB1 and c-Myc genes in HBV-related HCC, as well as in cirrhotic and control tissues. Mutational analysis of the β-catenin gene and HBV genotyping were conducted by direct sequencing. Expression of β-catenin and c-Myc genes was assessed using real-time PCR. Among the HCC cases, 18.1% showed missense point mutation in exon 3 of CTNNB1, more frequently in codons 32, 33, 38 and 45. The frequency of mutation in the hotspots of exon 3 was significantly higher in non-viral HCCs (29.4%) rather than HBV-related cases (12.7%, P = 0.021). The expression of β-catenin and c-Myc genes was found upregulated in cirrhotic tissues in association with HBV infection. Mutations at both phosphorylation and neighboring sites were associated with increased activity of the Wnt pathway. The results demonstrated that mutated β-catenin caused activation of the Wnt pathway, but the rate of CTNNB1 gene mutations was not related to HBV infection. HBV factors may deregulate the Wnt pathway by causing epigenetic alterations in the HBV-related HCC.

Abstract Background Currently available anti-influenza drugs are often associated with limitations such as toxicity and the appearance of drug-resistant strains. Therefore, there is a pressing need for the development of novel, safe and more efficient antiviral agents. In this study, we evaluated the antiviral activity of zinc oxide nanoparticles (ZnO-NPs) and PEGylated zinc oxide nanoparticles against H1N1 influenza virus. Methods The nanoparticles were characterized using the inductively coupled plasma mass spectrometry, x-ray diffraction analysis, and electron microscopy. MTT assay was applied to assess the cytotoxicity of the nanoparticles, and anti-influenza activity was determined by TCID50 and quantitative Real-Time PCR assays. To study the inhibitory impact of nanoparticles on the expression of viral antigens, an indirect immunofluorescence assay was also performed. Results Post-exposure of influenza virus with PEGylated ZnO-NPs and bare ZnO-NPs at the highest non-toxic concentrations could be led to 2.8 and 1.2 log10 TCID50 reduction in virus titer when compared to the virus control, respectively (P

Currently, there are about 37 million people worldwide living with human immunodeficiency virus (HIV) /AIDS, with an estimated two million new cases per year globally. According to estimates from the World Health Organization (WHO), only 75% of the population with HIV know their status. Initially, HIV infection was associated with significantly increased rates of mortality and morbidity. However, the rapid advances in treatment and the advent of different classes of antiretroviral drugs over time have led to change the face of HIV/AIDS from a deadly infection to chronic and manageable disease. There is strong evidence that HIV-infected patients undergoing antiretroviral therapy have longer lives and are less likely to transmit infection to their sexual partners. Since the introduction of zidovudine in 1987 as the first antiretroviral drug, significant strides have been made in antiretroviral therapy. The introduction of potent antiretroviral drugs for the treatment of HIV infection has been one of the significant events in the evolution of modern medicine. Antiretroviral therapy refers to the use of drugs in the treatment of HIV. Generally, these drugs are categorized based on the steps of the HIV life cycle suppressed by them. There are six main classes of antiretroviral agents including nucleoside/ nucleotide reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, fusion inhibitors, co-receptor inhibitors, and integrase inhibitors. Combination antiretroviral therapy should be considered for HIV patients to achieve the highest viral suppression rate, and to reduce the risk of resistance development and morbidity and mortality associated with AIDS. Achieving and maintaining HIV viral load suppression among treated patients has remarkably increased over the last years due to the development of potent and well-tolerated agents which can be co-formulated as a once-daily single-tablet or fixed-dose combination for simplification. However, there are some limitations preventing patients to benefit from this treatment. The main goals of HIV therapy in the future are to overcome the limitations of current treatment, including side effects. This review will provide an overview of advances in the current antiretroviral drugs by focusing on their pharmacokinetics, mechanism of action, dosing recommendations, and adverse events for each drug class.

Background Rotavirus is the most prevalent cause of severe gastroenteritis, hospitalizations, and deaths among infants and young children, globally. No specific antiviral drug is available against rotavirus infection. Objective The current study aimed to assess the antiviral effect of human cathelicidin antimicrobial peptide LL-37 on rotavirus infection in vitro. Methods This study was conducted in the laboratory conditions of Iran University of Medical Sciences, in Tehran City, Iran. The neutral red assay was performed to assess the cytotoxicity of different concentrations of the peptide on the MA-104 cell line, and its antiviral activity was determined by TCID50 (50% tissue culture infective dose) assay. Findings According to the cytotoxicity results, viability maintained more than 90% up to the concentration of 50 μg/mL of LL-37 peptide. The antiviral assays results revealed that the concentration of 50 μg/mL LL-37 peptide could significantly reduce (3.36 log10 TCID50) the production of rotavirus progeny when administered before virus exposure (P= 0.0001). However, no inhibitory effect was detected after cell exposure to virus. Conclusion The obtained data suggested that LL-37 can be considered as a new antiviral agent for protecting infants and young children against gastroenteritis caused by rotaviruses. However, further in vivo investigations are required to confirm this finding.

Introduction: Glycoprotein B (gB) is the major antigen for induction of humoral responses against human cytomegalovirus (HCMV) making it an attractive candidate for immune prophylaxis. In the present study, the humoral immune response of BALB/c mice to a truncated HCMV gB protein fused with GFP was evaluated. Methods: The truncated gB coding sequence was synthesized and cloned in pEGFPN1 eukaryotic expression vector and expressed in HEK 293T cell line. After optimization, expression of the recombinant truncated HCMV gB was verified using HRP-conjugated polyclonal antibody specific for HCMV gB.The level of humoral immune responses was assessed in mice using DNA/DNA, peptide/peptide, and DNA/ peptide (prime-boost) immunization strategies. Results: Cloning of the truncated gB coding sequence in the pEGFPN1 was verified by restriction enzyme analysis and sequencing. After optimizing the transfection procedure the number of the GFP positive cells reached 32%. Western blot analysis confirmed the in vitro expression of the truncated HCMV gB protein with an apparent molecular weight of approximately 70 kDa. In vivo prime-boost immunization using HCMV gB DNA/peptide regimen showed significantly higher humoral immune responses compared to the control groups. Conclusion: This study demonstrated that the pEGFPN1 eukaryotic expression vector could be used to optimize and evaluate the expression of this truncated protein.The results also showed that the DNA/peptide vaccination could induce a significant antibody response in animal model.

Background and Objectives: The viruses are the most common cause of eye infection. The most common viruses in conjunctivitis infection include Herpes simplex virus, Adeno virus and Entrovirus. It has been estimated that HSV1 causes 60-90% conjunctival infectionsin adults. Recurrent infection by HSV1 results in Herpes keratitis that is the most common cause for blindness in developing countries. Therefore, a prompt laboratory diagnosis is often very useful. Theaim of this study was to evaluate the prevalence of conjunctivitis infection by HSV-1 Hospital affiliated to Iran University of Medical Sciences (IUMS) in 2009.Methods: This descriptive cross-sectional study was doneon 100 tear film and eye swabs specimens from patient with symptoms of viral conjunctivitis. All samples werecollected in viral transport media (VTM) and inoculated in Vero cell line. Viral cytopatic effect was compared with control sample. HSV1 DNA wasdetected by polymerase chain reaction (PCR). Chi-square test was used to for data analysis (p