Effect of Rodent Control Program on Incidence of Zoonotic Cutaneous Leishmaniasis, Iran.

We report the effect of a rodent control program on the incidence of zoonotic cutaneous leishmaniasis in an endemic region of Iran. A 1-year interruption in rodent control led to 2 years of increased incidence of zoonotic cutaneous leishmaniasis. Restarting rodent control led to a decline of zoonotic cutaneous leishmaniasis.

Predictors of antiretroviral treatment failure to the first line therapy: a cross-sectional study among Iranian HIV-positive adults.

BACKGROUND: HIV virological failure is one of the main problems in HIV-infected patients, and identifying the main predictors of such treatment failure may help in combating HIV/AIDS. METHODOLOGY: This cross-sectional study included 1800 HIV-infected patients with either virological failure or treatment response. HIV viral load, CD4 count, and other tests were performed. Statistical analysis was used to determine the predictors of virological failure. RESULTS: Clinical stage, treatment with reverse transcriptase inhibitors (RTIs), under therapy for three years or more, suboptimal adherence to antiretroviral treatment (ART), age > 40 years, CD4 count < 200 cells/mm3, unemployment, being infected through sex, and the presence of symptoms were the predominant risk factors for virological failure. In addition, 55% of patients who experienced virological failure failed to experience immunological and/or clinical failure. CONCLUSION: As the first study in southern Iran and the second in Iran, Iranian policymakers should focus on intensive counseling and adherence support and emphasize more effective treatment regimens such as protease and integrase inhibitors (PIs and INTIs), to increase the chance of a treatment response to ART. The accuracy of identifying clinical and immunological criteria in resource-limited settings is not promising. The present findings can be used to determine effective measures to control HIV treatment failure and design efficient strategies for the ambitious 95-95-95 plan.

Reverse vaccinology approaches to design a potent multiepitope vaccine against the HIV whole genome: immunoinformatic, bioinformatics, and molecular dynamics approaches.

Substantial advances have been made in the development of promising HIV vaccines to eliminate HIV-1 infection. For the first time, one hundred of the most submitted HIV subtypes and CRFs were retrieved from the LANL database, and the consensus sequences of the eleven HIV proteins were obtained to design vaccines for human and mouse hosts. By using various servers and filters, highly qualified B-cell epitopes, as well as HTL and CD8 + epitopes that were common between mouse and human alleles and were also located in the conserved domains of HIV proteins, were considered in the vaccine constructs. With 90% coverage worldwide, the human vaccine model covers a diverse allelic population, making it widely available. Codon optimization and in silico cloning in prokaryotic and eukaryotic vectors guarantee high expression of the vaccine models in human and E. coli hosts. Molecular dynamics confirmed the stable interaction of the vaccine constructs with TLR3, TLR4, and TLR9, leading to a substantial immunogenic response to the designed vaccine. Vaccine models effectively target the humoral and cellular immune systems in humans and mice; however, experimental validation is needed to confirm these findings in silico.

Host factors and vaccine efficacy: Implications for COVID-19 vaccines.

The efficacy of the vaccines varies between individuals and populations. The immunogenicity of the vaccine is influenced by various factors, including host factors. Previous studies have shown that host factors affect the effectiveness of vaccines, which may be true about COVID-19 vaccines. In this review, we evaluate the possible association of host factors with vaccine efficacy with a special focus on COVID-19 vaccines.

Changes in COVID-19 IgM and IgG antibodies in emergency medical technicians (EMTs).

INTRODUCTION: Serologic testing can provide a safe and fast approach for assessing SARS-CoV-2 antibodies. These tests can be utilized as a complementary method in diagnosis and patients' follow-up, and can also be helpful in epidemiological studies. This study aimed to describe temporal changes in the incidence of COVID-19 IgM and IgG antibodies in emergency medical technicians (EMTs) within a specified time period. METHODS: All EMTs working for Tehran Emergency Medical Service (EMS) center during May to September 2020 were eligible for this study. Those EMTs who were suspected/probable/confirmed cases of COVID-19, based on WHO defined criteria and were willing to participate, entered the study. The EMTs underwent serology testing four weeks after the occurrence of exposure (in suspected cases) or onset of their symptoms (in probable/confirmed cases). Cases were further confirmed by RT-PCR and/or lung CT, and antibody testing was performed for the second and third time with 12-week intervals. Finger-stick blood sampling was utilized for the specimen collection in three different phases. Samples were then analyzed by a commercial immunochromatography-based kit for qualitative measurement of serum IgM and IgG antibodies against the COVID-19 S-protein antigen. RESULTS: Two hundred eighty-four participants met the inclusion criteria; their mean age was 35.9 (SD = 7.6) years and consisted of 244 (85.9%) males. COVID-19 was confirmed in 169 out of 284 participants. Subsequently, 142 and 122 participants were included in phases 2 and 3 of the study, respectively. The number of seronegative patients exceeded seropositive ones in all three phases. At baseline, 162 (57%) patients were seronegative, 27 (9.5%) were only positive for IgG, 3 (1.1%) were only positive for IgM, and 92 (32.4%) were positive for both antibodies; Seventy-eight (54.9%) were seronegative, and 31 (21.8%) were positive for both antibodies in the second phase; These values were 85 (69.6%) and 8 (6.6%) for the third phase, respectively. Among the people who were positive IgG in the first phase (80 people), 56.3% were still positive in the second phase and 27.5% in both subsequent phases. CONCLUSION: The results of our study show that there is a significant reduction in COVID-19 antibody seropositivity over time.

Sufficient Sleep, Time of Vaccination, and Vaccine Efficacy: A Systematic Review of the Current Evidence and a Proposal for COVID-19 Vaccination.

Introduction: The emergence of the novel Coronavirus Disease 2019 (COVID-19) sparked an unprecedented effort to develop effective vaccines against the disease. Some factors may boost the vaccine efficacy, including sufficient sleep and morning vaccination. We aimed to conduct a rapid systematic review to summarize data regarding the association between sleep and time of vaccination with immunity after vaccination. Materials and Methods: The systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol, and three databases (PubMed, Web of Science, and Scopus) were searched up to March 12, 2022. Results: Eight studies were included regarding the sleep and immune response after vaccination, of them, five studies were on influenza, two studies on hepatitis A (HAV), and one study on hepatitis B. Accordingly, six out of eight studies found a positive correlation between sleep and immune response after vaccination. Regarding the time of vaccination, seven studies were eligible to be included (two studies on influenza, one study on HAV and influenza, one study on BCG, one study on hexavalent vaccine, and two studies on SARS-CoV-2 vaccine). Among them, four out of seven studies (including a study on SARS-CoV-2 inactivated vaccine) reported the priorities of morning versus afternoon vaccination regarding antibody production and immune response after vaccination. Conclusion: Taken together, cumulative evidence suggests that sufficient sleep and vaccination in the morning could enhance the immune response after vaccination. Hence, modulating the time of vaccination and sufficient sleep could a be simple and applicable strategy for increasing vaccine efficacy. Future studies could be performed with SARS-CoV-2 vaccines to investigate the effects of time of vaccination and sufficient sleep on COVID-19 vaccine efficacy.

Outcome evaluation of COVID-19 infected patients by disease symptoms: a cross-sectional study in Ilam Province, Iran.

BACKGROUND: Novel coronavirus disease-19 (COVID-19) was declared as a global pandemic in 2020. With the spread of the disease, a better understanding of patient outcomes associated with their symptoms in diverse geographic levels is vital. This study aimed to evaluate clinical outcomes of COVID-19 patients by disease symptoms in Ilam province, Iran. METHODS: This was a cross-sectional study. Data were collected from integrated health system records for all hospitals affiliated with the Ilam University of Medical Sciences between 26-Jan-2020 and 02-May-2020. All patients with a confirmed positive test were included in this study. Descriptive analyses, chi-square test, and binary logistic regression model were performed by using SPSS version 22. RESULTS: The mean age of participants was 46.47 ± 18.24 years. Of the 3608 patients, 3477 (96.1%) were discharged, and 129 (3.9%) died. 54.2% of the patients were male and were in the age group of 30-40 years. Cough, sore throat, shortness of breath or difficulty breathing, and fever or chills were the most common symptoms. Patients with symptoms of shortness of breath, abnormal radiographic findings of the chest, and chest pain and pressure were relatively more likely to die. According to binary logistic regression results, the probability of death in patients with shortness of breath, abnormal chest radiographic findings, and chest pain was 1.34, 1.24, and 1.32 times higher, respectively, than for those without. CONCLUSION: Our study provides evidence that the presentation of some symptoms significantly impacts outcomes of patients infected with SARS-CoV-2. Early detection of symptoms and proper management of outcomes can reduce mortality in patients with COVID-19.

Design of multivalent-epitope vaccine models directed toward the world's population against HIV-Gag polyprotein: Reverse vaccinology and immunoinformatics.

Significant progress has been made in HIV-1 research; however, researchers have not yet achieved the objective of eradicating HIV-1 infection. Accordingly, in this study, eucaryotic and procaryotic in silico vaccines were developed for HIV-Gag polyproteins from 100 major HIV subtypes and CRFs using immunoinformatic techniques to simulate immune responses in mice and humans. The epitopes located in the conserved domains of the Gag polyprotein were evaluated for allergenicity, antigenicity, immunogenicity, toxicity, homology, topology, and IFN-γ induction. Adjuvants, linkers, CTLs, HTLs, and BCL epitopes were incorporated into the vaccine models. Strong binding affinities were detected between HLA/MHC alleles, TLR-2, TLR-3, TLR-4, TLR-7, and TLR-9, and vaccine models. Immunological simulation showed that innate and adaptive immune cells elicited active and consistent responses. The human vaccine model was matched with approximately 93.91% of the human population. The strong binding of the vaccine to MHC/HLA and TLR molecules was confirmed through molecular dynamic stimulation. Codon optimization ensured the successful translation of the designed constructs into human cells and E. coli hosts. We believe that the HIV-1 Gag vaccine formulated in our research can reduce the challenges faced in developing an HIV-1 vaccine. Nevertheless, experimental verification is necessary to confirm the effectiveness of these vaccines in these models.

Detection of Leishmania RNA Virus 2 (LRV2) among Clinical Isolates of Leishmania Major in Four Endemic Regions of Iran.

PURPOSE: Leishmania RNA viruses (LRV) are double-stranded RNA viruses (dsRNA viruses) that play a role in the pathogenesis of Leishmania parasites. Cutaneous leishmaniasis (CL) is endemic in various parts of Iran. Our aimed was to investigate presence of LRV among the Leishmania major isolates in four endemic regions of Iran. METHODS: In a cross-sectional study, we assessed the presence of LRV1 and LRV2 in 181 clinical isolates of L. major from four endemic cities in Iran using reverse transcription polymerase chain reaction (RT-PCR). After RNA extraction and cDNA synthesis, RT-PCR tests were conducted with LRV1 and LRV2 specific primers. Human beta-actin and kmp genes served as internal and external controls, respectively, and the Allele ID software was used to optimize melting curves. RESULTS: LRV2 was detected in 27.6% (50 out of 181) of L. major isolates, while no LRV1 was found. We did not observe a statistically significant difference in the presence of LRV2 based on age group, number, or location of lesions. CONCLUSION: This study confirms the presence of LRV2 in clinical isolates of L. major from endemic regions of Iran. Further researches with larger sample sizes is recommended to explore the association between LRV and clinical symptoms as well as treatment response.

Latent toxoplasmosis, Cytomegalovirus, and Herpes Simplex Virus infections and risk of motorcycle accidents: A case-control study in a county with a high rate of motorcycle injuries in Iran.

BACKGROUND: Road traffic injuries (RTIs) are among the most important issues worldwide. Several studies reported that infection with the neurotropic parasite Toxoplasma gondii (T. gondii) increased the risk of car accidents. In this study, our objective was to investigate the possible associations among latent T. gondii, Cytomegalovirus (CMV), and Herpes Simplex Virus (HSV) infections with the risk of motorcycle accidents in Jahrom (Fars Province), which is a county with a high rate of motorcycle accidents in Iran. METHODS: In the setting of a case-control study; 176 motorcyclist men, including 88 survivors of motorcycle accidents and 88 motorcyclist without accidents, were considered as case and control groups, respectively. Rates of latent infections with T. gondii, CMV, and HSV were assessed by an enzyme-linked immunosorbent assay (ELISA). RESULTS: Eleven of 88 (12.5%) in the case group and 22 of 88 (25.0%) in controls were positive for anti-T. gondii IgG antibodies, this difference was statistically significant (OR = 0.42; CI: 0.19-0.95, p = 0.03). The general seroprevalence of CMV (94.3% in the case group vs. 87.5% in the control group, OR = 2.37; CI: 0.78-7.13, p = 0.12) and HSV (63.6% in the case group vs. 62.5% in the control group, OR = 1.05; CI: 0.57-1.94, p = 0.87) were not significantly different between the case and control groups. CONCLUSIONS: Although latent toxoplasmosis has been associated with traffic accidents in recent reports, we found a negative association between latent toxoplasmosis and motorcycle accidents among survivors of these accidents. As such, latent CMV and HSV infections did not differ significantly between the cases compared to the control groups.

Maternal COVID-19 infection and the fetus: Immunological and neurological perspectives.

Immunoneuropsychiatry is an emerging field about the interaction between the immune and nervous systems. Infection and infection-related inflammation (in addition to genetics and environmental factors) can act as the etiopathogenesis of neuropsychiatric disorders (NPDs). Exposure to COVID-19 in utero may be a risk factor for developing NPDs in offspring in the future. Maternal immune activation (MIA) and subsequent inflammation can affect fetal brain development. Inflammatory mediators, cytokines, and autoantibodies can pass through the placenta and the compromised blood-brain barrier after MIA, leading to neuroinflammation. Neuroinflammation also affects multiple neurobiological pathways; for example, it decreases the production of the neurotransmitter serotonin. Fetal sex may affect the mother's immune response. Pregnant women with male fetuses have been reported to have decreased maternal and placental humoral responses. This suggests that in pregnancies with a male fetus, fewer antibodies may be transferred to the fetus and contribute to males' increased susceptibility/vulnerability to infectious diseases compared to female infants. Here, we want to discuss maternal COVID-19 infection and its consequences for the fetus, particularly the neurological outcomes and the interaction between fetal sex and possible changes in maternal immune responses.

COVID-19 Mass Vaccination and Flu Season: Concern for Decreased Public Health Measures and Worsening the Influenza Situation.

Reports show that other ordinary childhood infections like measles or influenza are likely to reemerge. The re-emergence of infectious diseases may happen due to the direct impact of the pandemic on the community because of decreased access to health and medical services, interrupted transport systems, weaknesses in the supply chain, flight restrictions, closings of the border, and international trade problems. The most prevalent cause (60.9%) for low vaccine uptake and coverage during the current pandemic was fear of exposure to the COVID-19 virus outside the home. The expectation and hope that the pattern of reduction in transmission and number of influenza cases will continue over the next flu season depend on continued adherence to nonpharmaceutical interventions and their long-term application. But there is always the fear and threat of increasing the spread of influenza by reducing the movement restrictions and low adherence to protective health measures due to vaccination. So far, not much information has been published about the interaction between different infectious diseases in the background of the coronavirus pandemic and related interventions. The purpose of this article is to examine the general effects of the COVID-19 vaccination on the spread of influenza in the coming seasons.

Environmental Surface Contamination with SARS-CoV-2: Toilets as the Most Contaminated Surfaces in COVID-19 Referral Hospital.

INTRODUCTION: The possibility of surface transmission in hospitals with high density of COVID- 19 patients is unneglectable. The aim of this study is to determine the extent of surface contamination in coronavirus central hospital of Ilam province in western Iran. MATERIALS AND METHODS: In this experimental study, 205 samples were taken from environmental surfaces in hospital. SARS-CoV-2 RNA detected by Real-time RT-PCR. RESULTS: 121 out of 205 (50.02%) samples were positive. The most contaminated objects were toilet sites (5/5,100% ICU; 5/5, 100% isolation wards). CONCLUSION: High surface contamination with SARS-CoV-2 proposes the surface as a potential route of transmission.

Latent Toxoplasmosis among Breast Cancer Patients in Jahrom, South of Iran.

Objective: Reactivation of latent toxoplasmosis is the main cause of severe infection among immunocompromised patients, including patients with cancer. Hence, this study is aimed at screening the status of Toxoplasma gondii infection among breast cancer patients by serological and molecular methods and determining their associated risk factors in Jahrom County, Fars Province, south of Iran. Methods: One hundred and seven women with breast cancer (aged 34 to 80 years) were screened for anti-T. gondii antibodies (IgG and IgM) during 2019-2020. A questionnaire regarding demographic factors was filled out by participants. Molecular detection was performed by polymerase chain reaction (PCR) using the primer pair targeting the repetitive element (RE) gene of T. gondii. The risk factors and demographic data were analyzed by SPSS software (ver. 20, Chicago, IL, USA) using the Chi-squared test. Results: Anti-T. gondii IgG was detected in 45.8% (49/107) of the patients, which indicates latent infection, but anti-T. gondii IgM and PCR were negative in all samples. Demographic factors revealed a statistically significant increased T. gondii seropositivity among nonmenopause cancer patients (P < 0.0005), patients without previous breast cancer (P = 0.0001), and human epidermal growth factor receptor 2- (HER2-) negative patients (P = 0.00002). As such, patients with a history of previous abortions and who were at stages II, III, and IIII of cancer had higher seropositivity rates than patients without a history of previous abortions or who were at stage I cancer, but the statistical analysis was not significant. We did not find a statistically significant association between T. gondii seropositivity and other risk factors of toxoplasmosis (e.g., education level, type of water source, washing raw fruits and vegetables, consumption of raw or undercooked meat, and contact with soil, cats, and domestic animal). Conclusion: A high seroprevalence rate of latent T. gondii infection was detected among patients with breast cancer; hence, these patients may be at high risk for reactivation of latent infection. Screening of T. gondii infection is recommended to detect active infection among patients with malignancies.

Systematic Review and Meta-analysis of Role of Felids as Intermediate Hosts in the Life Cycle of Neospora caninum Based on Serological Data.

PURPOSE: Neosporosis is an important widespread parasitic infection caused by N. caninum. It infects a wide range of warm-blooded animals as intermediate hosts and dogs as the definitive host. Nevertheless, there are a number of questions regarding the life cycle and epidemiological aspects of N. caninum. Also, the role of felids (domestic and non-domestic) in the life cycle of N. caninum has been little described. Therefore, this study was conducted to evaluate the global prevalence of N. caninum in domestic and wild felids. METHODS: PubMed, Scopus, Google Scholar, Web of Science, and ScienceDirect databases were searched for articles published on the prevalence of N. caninum in felids until Aprill 2, 2022 and the reference lists of retrieved articles were screened. A random-effects meta-analysis model was used to estimate the pooled prevalence and 95% confidence interval. Heterogeneity among studies was evaluated using Cochran's Q and the I2 statistic. RESULTS: After exclusion of irrelevant articles and duplication removal, 30 studies were eligible for quantitative analysis including 20 studies on domestic cats and 10 studies on wild felids. The overall prevalence of neosporosis infection in cats was 15% (95% CI 10-21%) that was significantly higher in wild felids (26%, 95% CI 13-38%) than in domestic cats (11%, 95% CI 6-16%) (P = 0.03). There was no significant difference in pooled prevalence between male and female domestic cats (P = 0.75). Regarding continent, the lowest prevalence of neosporosis infection was in Asia (9%, 95% CI 1-20%) and the highest was in North America (43.6%, 95% CI 33.9-53.2%) and Africa (18%, 95% CI 9-46%). Higher prevalence was obtained when using the NAT with 22% (95% CI 7-37%), compared to the IFAT (17%, 95% CI 9-24%) and ELISA (6%, 95% CI 2-9%) (P = 0.01). CONCLUSION: The findings highlighted the importance of felids as potential intermediate hosts of neosporosis despite the fact that the source of the parasite for these animals was unknown. Further studies should be performed to investigate the role of this top predator (felids) in maintaining both domestic and sylvatic cycles of Neospora caninum.

Assessment of genetic markers for multilocus sequence typing (MLST) of Fasciola isolates from Iran.

BACKGROUND: Several markers have been described to characterise the population structure and genetic diversity of Fasciola species (Fasciola hepatica (F. hepatica) and Fasciola gigantica (F. gigantica). However, sequence analysis of a single genomic locus cannot provide sufficient resolution for the genetic diversity of the Fasciola parasite whose genomes are ∼1.3 GB in size. OBJECTIVES: To gain a better understanding of the gene diversity of Fasciola isolates from western Iran and to identify the most informative markers as candidates for epidemiological studies, five housekeeping genes were evaluated using a multilocus sequence typing (MLST) approach. METHODS: MLST analysis was developed based on five genes (ND1, Pepck, Pold, Cyt b and HSP70) after genomic DNA extraction, amplification and sequencing. Nucleotide diversity and phylogeny analysis were conducted on both concatenated MLST loci and each individual locus. A median joining haplotype network was created to examine the haplotypes relationship among Fasciola isolates. RESULTS: Thirty-three Fasciola isolates (19 F. hepatica and 14 F. gigantica) were included in the study. A total of 2971 bp was analysed for each isolate and 31 sequence types (STs) were identified among the 33 isolates (19 for F. hepatica and 14 for F. gigantica isolates). The STs produced 44 and 42 polymorphic sites and 17 and 14 haplotypes for F. hepatica and F. gigantica, respectively. Haplotype diversity was 0.982 ± 0.026 and 1.000 ± 0.027 and nucleotide diversity was 0.00200 and 0.00353 ± 0.00088 for F. hepatica and F. gigantica, respectively. There was a high degree of genetic diversity with a Simpson's index of diversity of 0.98 and 1 for F. hepatica and F. gigantica, respectively. While HSP70 and Pold haplotypes from Fasciola species were separated by one to three mutational steps, the haplotype networks of ND1 and Cyt b were more complex and numerous mutational steps were found, likely due to recombination. CONCLUSIONS: Although HSP70 and Pold genes from F. gigantica were invariant over the entire region of sequence coverage, MLST was useful for investigating the phylogenetic relationship of Fasciola species. The present study also provided insight into markers more suitable for phylogenetic studies and the genetic structure of Fasciola parasites.

Presence of CRISPR CAS-Like Sequences as a Proposed Mechanism for Horizontal Genetic Exchanges between Trichomonas vaginalis and Its Associated Virus: A Comparative Genomic Analysis with the First Report of a Putative CRISPR CAS Structures in Eukaryotic Cells.

Introduction: Trichomonas vaginalis genome is among the largest genome size and coding capacities. Combinations of gene duplications, transposon, repeated sequences, and lateral gene transfers (LGTs) have contributed to the unexpected large genomic size and diversity. This study is aimed at investigating genomic exchange and seeking for presence of the CRISPR CAS system as one of the possible mechanisms for some level of genetic exchange. Material and Methods. In this comparative analysis, 398 publicly available Trichomonas vaginalis complete genomes were investigated for the presence of CRISPR CAS. Spacer sequences were also analyzed for their origin using BLAST. Results: We identified a CRISPR CAS (Cas3). CRISPR spacers are highly similar to transposable genetic elements such as viruses of protozoan parasites, especially megavirals, some transposons, and, interestingly, papillomavirus and HIV-1 in a few cases. Discussion. There is a striking similarity between the prokaryotes/Archaean CRISPR and what we find as eukaryotic CRISPR. About 5-10% of the 398 T. vaginalis possess a CRISPR structure. Conclusion: According to sequences and their organization, we assume that these repeated sequences and spacer, along with their mentioned features, could be the eukaryotic homolog of prokaryotes and Archaean CRISPR systems and may involve in a process similar to the CRISPR function.

microRNA-184 in the landscape of human malignancies: a review to roles and clinical significance.

MicroRNAs (miRNAs) are a class of non-coding RNAs (ncRNAs) with a short length of 19-22 nucleotides. miRNAs are posttranscriptional regulators of gene expression involved in various biological processes like cell growth, apoptosis, and angiogenesis. miR-184 is a well-studied miRNA, for which most studies report its downregulation in cancer cells and tissues and experiments support its role as a tumor suppressor inhibiting malignant biological behaviors of cancer cells in vitro and in vivo. To exert its functions, miR-184 affects some signaling pathways involved in tumorigenesis like Wnt and ß-catenin, and AKT/mTORC1 pathway, oncogenic factors (e.g., c-Myc) or apoptotic proteins, such as Bcl-2. Interestingly, clinical investigations have shown miR-184 with good performance as a prognostic/diagnostic biomarker for various cancers. Additionally, exogenous miR-184 in cell and xenograft animal studies suggest it as a therapeutic anticancer target. In this review, we outline the studies that evaluated the roles of miR-184 in tumorigenesis as well as its clinical significance.