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During COVID-19 pandemic, international pharmaceutical companies put effort to build global manufacturing networks for vaccines. Soberana Plus vaccine, a recombinant protein based vaccine (RBD dimer), with the trade name of PastoCovac Plus in Iran, is based on a protein subunit platform in Cuba and completed preclinical and toxicological assessments. This study aimed at presenting the steps of vaccine technology transfer from Cuba to Iran. This study provides the first practical comparability results in Iran to ensure the quality, safety and efficacy of a protein subunit vaccine against COVID-19 after a successful technology transfer from Cuba. PastoCovac Plus was transferred to Iran at the formulation stage. The assessment of the active ingredient pharmaceutical (API) was achieved through physicochemical and clinical data collection and tests to assure if there was any adverse impact on the vaccination results. In order to assess the quality of the vaccine product after technology transfer, we sought different properties including regulatory features, physicochemical quality, vaccine potency and stability as well as its immunogenicity and safety. Following the evaluation of the clinical quality attributes (CQAs) based on the standard protocols, the results showed that the two vaccines are highly similar and comparable, with no considerable effect on safety or efficacy profiles. The CQAs were all in the acceptance limits in terms of safety and efficacy as well as clinical evaluation results. The immunogenicity evaluation also confirmed no significant differences between the vaccines regarding reinfection (P = 0.199) or vaccine breakthrough (P = 0.176). Furthermore, the level of anti-spike and neutralizing antibodies in the both vaccine groups was not significantly different indicating the equality of performance between the two vaccines. According to the results of the quality and clinical assessment of this study, we achieved an acceptable quality attributes and acceptant limits in terms of safety and efficacy of the vaccines pre and post technology transfer., (© 2024. The Author(s).)

Considering menstruation as a crucial factor in females' health and fertility, any factor that could change its cycle is important. This study was conducted from April 2021 to October 2022 on females who got 3 doses of vaccines against SARS-CoV-2 through different platforms. The participants were requested to provide the trained experts with any changes regarding menstrual cycles after each dose of the vaccine up to 6 months after the booster shots. The disturbances related to the vaccines were identified by the adverse events committee to find possible associations with the applied vaccines. Of 308 women who participated until the end of the study, 22 (7.1%) complained about at least one abnormality in their menstrual patterns. The most common disturbance was metrorrhagia as 10 (48%) incidences followed by menorrhagia as 6 events (24.2%). Notably, the identified complaints were persistent in 59% of the patients. In addition, 14 studied cases developed COVID-19 infection after menstrual disorders. In these cases, COVID-19 could also play a role in the persistence of postvaccine menstrual disturbances. COVID-19 vaccination could affect menstrual cycle in women with no remarkable previous medical history. More longitudinal studies are required regarding this issue., Competing Interests: The authors declare that they have no relevant financial or nonfinancial conflicts of interest., (Copyright © 2024 Mona Sadat Larijani et al.)

Background: To reduce the clinical burden of COVID-19, healthcare providers, and policymakers need a clear understanding of the illness severity during epidemic waves. This study aimed to identify the clinical severity of patients with COVID-19 during different stages of an epidemic wave (pre-peak, peak, post-peak) in four provinces in Iran., Methods: We conducted a secondary analysis of the data on COVID-19 patients admitted to hospitals (25,382 cases), which were recorded in the Medical Care Monitoring Center. Data included adult patients (≥18 years) who were hospitalized due to COVID-19 infection, confirmed by a positive SARS-CoV-2 RT-PCR test. No exclusion criteria were applied. A pairwise comparison method was used to evaluate clinical severity. Then, based on univariable and multivariable linear regression models, the severity scores of patients were compared during various stages of an epidemic wave., Results: The findings showed that the level of severity of the disease was higher during and after the peak in the total population. The means (SD) of severity scores were 0.16 (0.25), 0.18 (0.26), and 0.19 (0.26) before, during and after the peak, respectively. Besides, age and the underlying disease had a positive and significant relationship with disease severity., Conclusion: During the middle and late phases of the COVID-19 epidemic wave, hospitals are seeing patients with more severe illnesses than in the early stages. Enhancing hospital preparedness is essential to avert excess deaths and critical cases. Moreover, it is important to maintain ongoing monitoring of clinical symptoms during the recovery phase to support individual patients, guide public health policy, and enhance scientific understanding of epidemic recovery processes., Competing Interests: Dr MMG had been the former director of the Iranian Center for Communicable Diseases at Ministry of Health during the time of the study. All other authors declare that they have no competing interests. All other authors declare that they have no competing interests., (© 2024 Iran University of Medical Sciences.)

Background: The control and prevention of rodent-borne diseases are mainly based on our knowledge of ecology and the infectious status of their reservoir hosts. This study aimed to evaluate the prevalence of Francisella tularensis , Yersinia pestis , and arenavirus infections in small mammals and to assess the potential of disease occurrence in East Azerbaijan, northwest of Iran, in 2017 and 2018. Methods: Spleen and lung samples were obtained from all trapped small mammals. The real-time quantitative PCR (qPCR) method was used to detect nucleic acid sequences of F. tularensis , Y. pestis , and arenaviruses. Serum samples were tested for antibodies indicating the host response to F. tularensis and Y . pestis infections using the standard tube agglutination test and enzyme-linked immunosorbent assay (ELISA), respectively. Results: A total of 205 rodents, four Eulipotyphla, and one carnivore were captured. The most common rodent species captured (123 of 205 rodents, 60%) belonged to the genus Meriones (mainly Persian jird, Meriones persicus ). In total, 317 fleas were removed from trapped animals. Flea species belonged to Xenopsylla buxtoni, Xenopsylla nuttalli, Stenoponia tripectinata , Paraceras melis , Ctenophthalmus rettigi smiti , Rhadinopsylla bivirgis , Paradoxopsyllus grenieri , and Nosopsyllus iranus . Using the qPCR tests, five spleen samples from M. persicus were positive for F. tularensis . The qPCR tests were negative for the detection of Y. pestis and arenaviruses. Finally, all serum samples tested were negative for antibodies against Y. pestis and F. tularensis . Conclusions: F. tularensis was the only zoonotic agent detected in rodents captured in East Azerbaijan. However, the diversity of trapped rodents and fleas provides the potential for the spread of various rodent-borne viral and bacterial diseases in the studied areas.

Background: Case-control studies are efficient designs for investigating gene-disease associations. A discovery of genome-wide association studies (GWAS) is that many genetic variants are associated with multiple health outcomes and diseases, a phenomenon known as pleiotropy. We aimed to discuss about pleiotropic bias in genetic association studies., Methods: The opinions of the researchers on the basis of the literature were presented as a critical review., Results: Pleiotropic effect can bias the results of gene-disease association studies if they use individuals with pre-existing diseases as the control group, while the disease in cases and controls have shared genetic markers. The idea supports the conclusion that when the exposure of interest in a case-control study is a genetic marker, the use of controls from diseased cases that share similar genetic markers may increase the risk of pleiotropic effect. However, not manifesting the disease symptoms among controls at the time of recruitment does not guarantee that the individual will not develop the disease of interest in the future. Age-matched disease-free controls may be a better solution in similar situations. Different analytical techniques are also available that can be used to identify pleiotropic effects. Known pleiotropic effects can be searched from various online databases., Conclusion: Pleiotropic effects may result in bias in genetic association studies. Suggestions consist of selecting healthy yet age-matched controls and considering diseases with independent genetic architecture. Checking the related databases is recommended before designing a study., Competing Interests: The authors declare that they have no competing interests., (© 2024 Iran University of Medical Sciences.)

Recurrent vulvovaginal candidiasis (RVVC) due to fluconazole resistance in Candida albicans isolates causes a wide range of complications. A number of 63 Candida albicans isolates obtained from vulvovaginal candidiasis (VVC) were identified by Internal Transcribed Spacer-Restriction Fragment Length Polymorphism (ITS-RFLP). Antifungal susceptibility testing was performed by broth microdilution method according to the CLSI protocol. The role of CDR1 and MDR1 genes in progress of VVC to RVVC was examined and the activity of virulence-related enzymes was assessed. Candida albicans was diagnosed in 62.4 % cases, of which 22.2 % were confirmed as RVVC. Voriconazole was the most active drug among five tested antifungals. The mean expression level of CDR1 and MDR1 was higher in RVVC isolates compared to multidrug azole-resistant VVC isolates. Our results demonstrated that the expression of CDR1 and MDR1 and the level of phospholipase and proteinase activities could be quite important to induce fluconazole resistance in C. albicans and to progress of VVC to become RVVC in involved patients., Competing Interests: Declaration of competing interest The authors have no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The prioritization of research topics in the health domain is a critical step toward channelling efforts and resources into areas that have received less attention. The objective of this study is to evaluate the implementation of research priorities determined at the national level within Iran for the period spanning five years between 2009 and 2013. We extracted the required data from the Iranian Registry of Clinical Trials (IRCT) website. Then we conducted a matching process between the titles of trials registered in the IRCT until December 3rd, 2013, and the list of national health research priorities in the domains of communicable and non-communicable diseases. The latter was compiled and regulated by the Research and Technology Deputy of the Ministry of Health since 2008. Out of the total 5,049 clinical trials registered in IRCT, 92.3% were carried out within the domain of non-communicable diseases, while 6.1% pertained to the field of communicable diseases and the remaining 1.3% in other fields. 56.4% of the clinical trials conducted in the field of communicable diseases and 32.8% of those conducted in the field of non-communicable diseases were consistent with the research priorities determined in these two fields. During the five-year period of the prioritization goal, there was no significant improvement in adherence to the list of priorities compared to the previous five-year period. Furthermore, certain priorities were neglected within both areas during these periods. It is possible to evaluate the effectiveness of research prioritization using the data obtained from the registration centers of clinical trials. Our study has revealed that the list of priorities has not garnered adequate attention from the research community within the country. Hence, remedial measures are imperative to ensure the priorities are given more attention after publication., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Fakhri et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: There is no systematic review on the prevalence of HIV drug resistance (HIVDR) in Iran. We aimed to estimate the prevalence of HIVDR among people living with HIV (PLHIV) in Iran. We assessed HIVDR prevalence in antiretroviral therapy (ART) naïve PLHIV (i.e., those without a history of ART) and PLHIV receiving ART., Method: We systematically searched Scopus, PubMed, Web of Science, Embase, Iranian databases (Iranian Medical Research Information System, Magiran, and Scientific Information Database), the references of studies, and Google Scholar until March 2023. A random-effects model was used to calculate a point estimate and 95% confidence interval (95% CI) for the prevalence of HIVDR in PLHIV., Results: Among 461 potential publications, 22 studies were included in the meta-analysis. The pooled prevalence of acquired HIVDR in PLHIV receiving ART was 34% (95% CI: 19, 50) for nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), 27% (95% CI: 15, 41) for non-nucleoside reverse transcriptase inhibitors (NNRTIs), and 9% (95% CI: 3, 18) for protease inhibitors (PIs). The pooled prevalence of acquired HIVDR in treatment failure PLHIV was 50% (95% CI: 31, 69) for NRTIs, 49% (95% CI: 29, 69) for NNRTIs, 11% (95% CI: 2, 24) for PIs, and 1% (95% CI: 0, 4) for integrase inhibitors (INIs). The pooled prevalence of transmitted HIVDR in ART-naïve people was 3% (95% CI; 1, 6) for NRTIs, 5% (95% CI: 2, 9) for NNRTIs, and 0 for PIs and INIs., Conclusion: The prevalence of HIVDR was relatively high in both ART-naïve PLHIV and those receiving ART. Without universal pretreatment HIVDR testing and more frequent routine HIV viral load testing among PLHIV who are on ART, the HIVDR prevalence might increase in PLHIV in Iran., (© 2023. The Author(s).)

Background: To improve the patient care, public health surveillance, and infection control, it is crucial to identify the presence and frequency of the common respiratory infections in individuals with COVID-19 symptoms but tested negative for SARS-CoV-2. This study aimed to shed light on this during the COVID-19 pandemic in Iran., Methods: In this cross-sectional study, a total of 1,002 patients with acute respiratory infection who had negative SARS-CoV-2 test results and referred to Valfajr Health Center, the National Collaborating Laboratory of Influenza and COVID-19 National Reference Laboratory at Pasteur Institute of Iran were recruited between January 2020 and January 2022. Nasopharyngeal and oropharyngeal swab samples were collected to detect 17 common respiratory viruses via TaqMan one-step real-time multiplex PCR. Demographic and clinical data of the participants were obtained from their electronic medical records., Results: In total, 218 samples (21.8%) were tested positive for at least one respiratory virus infection. Most of the common investigated respiratory viruses belonged to the years 2020 and 2022. The number of investigated patients in 2021 was few, which highlights the impact of health measures following the COVID-19 pandemic in Iran. Influenza A was the most common virus (5.8%), while adenovirus had the lowest prevalence (0.1%). Although the rate of respiratory virus infection was higher in men (24%) compared to women (19.3%), this difference was not statistically significant (P = 0.069). The prevalence of respiratory viruses had an inverse association with increasing age, with the highest rate (55.6%) observed in the age group below 2 years and the lowest rate (12.7%) in those above 65 years., Conclusion: Our findings underscore the significance of adopting a comprehensive approach to respiratory infections detection and management. These results can be employed for the development of syndromic surveillance systems and implementation of the effective infection control measures. Furthermore, the results contribute to better understanding of the dynamics of respiratory viruses, both during pandemic periods and in non-pandemic contexts., (© 2023. The Author(s).)

Background: This study aimed at evaluation and comparison of PastoCovac Plus protein-subunit vaccine in parallel with ChAdOx1-S (AstraZeneca) and BBIBP-CorV (Sinopharm) in primarily vaccinated volunteers with two doses of ChAdOx1-S or BBIBP-CorV., Materials and Methods: 194 volunteers enrolled the study who were previously primed with 2 doses of ChAdOx1-S or BBIBP-CorV vaccines. They were divided into two heterologous regimens receiving a third dose of PastoCovac Plus, and two parallel homologous groups receiving the third dose of BBIBP-CorV or ChAdOx1-S. Serum samples were obtained just before and 4 weeks after booster dose. Anti-spike IgG and neutralizing antibodies were quantified and the conventional live-virus neutralization titer, (cVNT50) assay was done against Omicron BA.5 variant. Moreover, the adverse events data were recorded after receiving booster doses., Results: ChAdOx1-S/PastoCovac Plus group reached 73.0 units increase in anti-Spike IgG rise compared to the ChAdOx1-S/ ChAdOx1-S (P: 0.016). No significant difference was observed between the two groups regarding neutralizing antibody rise (P: 0.256), indicating equivalency of both booster types. Adjusting for baseline titers, the BBIBP-CorV/PastoCovac Plus group showed 135.2 units increase (P<0.0001) in anti-Spike IgG, and 3.1 (P: 0.008) unit increase in mean rise of neutralizing antibodies compared to the homologous group. Adjustment for COVID-19 history, age, underlying diseases, and baseline antibody titers increased the odds of anti-Spike IgG fourfold rise both in the ChAdOx1-S (OR: 1.9; P: 0.199) and BBIBP CorV (OR: 37.3; P< 0.0001) heterologous groups compared to their corresponding homologous arms. The odds of neutralizing antibody fourfold rise, after adjustment for the same variables, was 2.4 (P: 0.610) for the ChAdOx1-S heterologous group and 5.4 (P: 0.286) for the BBIBP CorV heterologous groups compared to their corresponding homologous groups. All the booster types had the potency to neutralize BA.5 variant with no significant difference. The highest rate of adverse event incidence was recorded for ChAdOx1-S homologous group., Conclusions: PastoCovac Plus booster application in primed individuals with BBIBP-CorV or ChAdOx1-S successfully increased specific antibodies' levels without any serious adverse events. This vaccine could be administrated in the heterologous regimen to effectively boost humoral immune responses., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Eybpoosh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Aim: The present study aimed to determine a correlation between differential TRIM56 expression levels and severe infections of COVID-19 between the Alpha, Delta and Omicron BA.5 variants., Materials & Methods: This study was performed on 330 COVID-19 patients, including 142 with severe and 188 with mild infections, as well as 160 healthy controls. The levels of TRIM56 gene expression were determined using a qPCR., Results: TRIM56 gene showed significantly lower mRNA expression in the severe and mild groups compared with healthy individuals. Our finding indicated the high and low reduction of TRIM56 mRNA expression in Delta and Omicron BA.5 variant, respectively., Conclusion: Further research is needed to characterize the impact of TRIM proteins on the severity of COVID-19., Competing Interests: The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed., (© 2023 Future Medicine Ltd.)

The optimal booster vaccine schedule against COVID-19 is still being explored. The present study aimed at assessment of the immunogenicity and antibody persistency of inactivated-virus based vaccine, BBIP-CorV and protein-subunit based vaccines, PastoCovac/Plus through heterologous and homologous prime-boost vaccination. Totally, 214 individuals who were previously primed with BBIBP-CorV vaccines were divided into three arms on their choice as heterologous regimens BBIBP-CorV/PastoCovac (n = 68), BBIBP-CorV/PastoCovac Plus (n = 72) and homologous BBIBP-CorV (n = 74). PastoCovac booster recipients achieved the highest rate of anti-Spike IgG titer rise with a fourfold rise in 50% of the group. Anti-RBD IgG and neutralizing antibody mean rise and fold rise were almost similar between the PastoCovac and PastoCovac Plus booster receivers. The antibody durability results indicated that the generated antibodies were persistent until day 180 in all three groups. Nevertheless, a higher rate of antibody titer was seen in the heterologous regimen compared to BBIP-CorV group. Furthermore, no serious adverse event was recorded. The protein subunit-based booster led to a stronger humoral immune response in comparison with the BBIP-CorV booster receivers. Both the protein subunit boosters neutralized SARS-CoV-2 significantly more than BBIP-CorV. Notably, PastoCovac protein subunit-based vaccine could be successfully applied as a booster with convenient immunogenicity and safety profile., (© 2023. The Author(s).)

Importance: The protein-based SARS-CoV-2 vaccines FINLAY-FR-2 (Soberana 02) and FINLAY-FR-1A (Soberana Plus) showed good safety and immunogenicity in phase 1 and 2 trials, but the clinical efficacy of the vaccine remains unknown., Objective: To evaluate the efficacy and safety of a 2-dose regimen of FINLAY-FR-2 (cohort 1) and a 3-dose regimen of FINLAY-FR-2 with FINLAY-FR-1A (cohort 2) in Iranian adults., Design, Setting, and Participants: A multicenter, randomized, double-blind, placebo-controlled, phase 3 trial was conducted at 6 cities in cohort 1 and 2 cities in cohort 2. Participants included individuals aged 18 to 80 years without uncontrolled comorbidities, coagulation disorders, pregnancy or breastfeeding, recent immunoglobulin or immunosuppressive therapy, and clinical presentation or laboratory-confirmed COVID-19 on enrollment. The study was conducted from April 26 to September 25, 2021., Interventions: In cohort 1, 2 doses of FINLAY-FR-2 (n = 13 857) or placebo (n = 3462) were administered 28 days apart. In cohort 2, 2 doses of FINLAY-FR-2 plus 1 dose of FINLAY-FR-1A (n = 4340) or 3 placebo doses (n = 1081) were administered 28 days apart. Vaccinations were administered via intramuscular injection., Main Outcomes and Measures: The primary outcome was polymerase chain reaction-confirmed symptomatic COVID-19 infection at least 14 days after vaccination completion. Other outcomes were adverse events and severe COVID-19. Intention-to-treat analysis was performed., Results: In cohort 1 a total 17 319 individuals received 2 doses and in cohort 2 5521 received 3 doses of the vaccine or placebo. Cohort 1 comprised 60.1% men in the vaccine group and 59.1% men in the placebo group; cohort 2 included 59.8% men in the vaccine group and 59.9% in the placebo group. The mean (SD) age was 39.3 (11.9) years in cohort 1 and 39.7 (12.0) years in cohort 2, with no significant difference between the vaccine and placebo groups. The median follow-up time in cohort 1 was 100 (IQR, 96-106) days and, in cohort 2, 142 (137-148) days. In cohort 1, 461 (3.2%) cases of COVID-19 occurred in the vaccine group and 221 (6.1%) in the placebo group (vaccine efficacy: 49.7%; 95% CI, 40.8%-57.3%) vs 75 (1.6%) and 51 (4.3%) in cohort 2 (vaccine efficacy: 64.9%; 95% CI, 49.7%-59.5%). The incidence of serious adverse events was lower than 0.1%, with no vaccine-related deaths., Conclusions and Relevance: In this multicenter, randomized, double-blind, placebo-controlled, phase 3 trial of the efficacy and safety of FINLAY-FR-2 and FINLAY-FR-1A, 2 doses of FINLAY-FR-2 plus the third dose of FINLAY-FR-1A showed acceptable vaccine efficacy against symptomatic COVID-19 as well as COVID-19-related severe infections. Vaccination was generally safe and well tolerated. Therefore, Soberana may have utility as an option for mass vaccination of the population, especially in resource-limited settings, because of its storage condition and affordable price., Trial Registration: isrctn.org Identifier: IRCT20210303050558N1.

Objective: This study described the epidemiology and geographical distribution of people diagnosed with HIV in Kerman, Iran, between 1997 and 2020., Methods: We used case-based HIV surveillance data of all people diagnosed with HIV in Kerman between 1997 and 2020. We compared the age, gender, modes of transmission and spatial distribution of newly diagnosed HIV-infected people in three time periods (1997-2004, 2005-2012 and 2013-2020). The χ 2 test for trend, one-sample t-test and Kruskal-Wallis H test were used to compare the differences between the three time periods. We also used ArcGIS to map both HIV services and people living with HIV (PLWH) in 2020. The nearest neighbour index and kernel density were used to identify the spatial distribution of PLWH., Results: A total of 459 (27.5% women) people were diagnosed with HIV during 1997-2020. The proportion of women (9.3% in 1997-2004 and 48.3% in 2013-2020, p<0.001), HIV infection through sexual contacts (11.6% in 1997-2004 and 50.3% in 2013-2020, p<0.001), HIV infection under the age of 5 years (0.8% in 1997-2004 and 5.4% in 2013-2020, p=0.01) and mean age at diagnosis among men (34.9 in 1997-2004 and 39.8 years in 2013-2020, p=0.004) significantly increased over time. 36.2% of diagnosed cases had CD4 counts under 200 x 10ˆ6/L between 2013 and 2020, with no significant improvement over time. Most newly diagnosed cases of HIV were from the eastern parts of the city. The clusters of PLWH in 2020 matched with the locations of HIV services., Conclusion: We observed important changes in HIV epidemiology regarding gender, modes of transmission, number of paediatric cases and density maps over time in Kerman. These changes should be considered for precise targeting of HIV prevention and treatment programmes., Competing Interests: Competing interests: ER is responsible for Kerman VCT., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The innate immune response in humans involves a wide variety of factors, including the tripartite motif-containing 5α (TRIM5α) and 22 (TRIM22) as a cluster of genes on chromosome 11 that have exhibited antiviral activity in several viral infections. We analyzed the correlation of the expression of TRIM5α and TRIM22 with the severity of Coronavirus Disease 2019 (COVID-19) in blood samples of 330 patients, divided into two groups of severe and mild disease, versus the healthy individuals who never had contact with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)., Methods: The transcription level of TRIM5α and TRIM22 was determined by quantitative real-time polymerase chain reaction (qPCR). The laboratory values were collected from the patients' records., Results: The expression of both genes was significantly lower in the severe group containing the hospitalized patients than in both the mild group and the control group. However, in the mild group, TRIM22 expression was significantly higher (p <0.0001) than in the control group while TRIM5α expression was not significantly different between these two groups. We found a relationship between the cycle threshold (Ct) value of patients and the expression of the aforementioned genes., Conclusion: The results of our study indicated that lower Ct values or higher RNA viral load might be associated with the downregulation of TRIM5α and TRIM22 and the severity of COVID-19. Additional studies are needed to confirm the results of this study., Competing Interests: Conflict of Interest The authors declare that there are no conflicts of interest., (Copyright © 2022 Instituto Mexicano del Seguro Social (IMSS). Published by Elsevier Inc. All rights reserved.)

Early reports on coronavirus disease 2019 (COVID-19) vaccines presented the short-term adverse events (AEs). This follow-up study investigated a standard regimen based on protein subunit vaccines, PastoCovac and PastoCovac Plus, and the combinational vaccine regimens including AstraZeneca/PastoCovac Plus and Sinopharm/PastoCovac Plus. The participants were followed up to 6 months post the booster shot. All the AEs were collected through in-depth interviews using a valid researcher-made questionnaire and were evaluated regarding the association with the vaccines. Of the 509 individuals, 6.2% of the combinational vaccine participants had late AEs, of whom 3.3% suffered from cutaneous manifestations, followed by 1.1% arthralgia complaints, 1.1% with neurologic disorders, 0.3% ocular problems and 0.3% metabolic complications, with no significant difference between the vaccine regimens. For the standard regimen, 2% of the individuals experienced late AEs as (1%), neurological disorders (0.3%), metabolic problems (0.3%) and involvement of joints (0.3%). Notably, 75% of the AEs were persistent up to the end of the study. A low number of late AEs were captured in 18 months as 12 improbable, 5 unclassifiable, 4 possible and 3 probable associated AEs with the vaccine regimens. The benefits of COVID-19 vaccination far exceed the potential risks and late AEs seem to be uncommon., (© The Author(s) 2023. Published by Oxford University Press on behalf of FEMS.)

Introduction: The rapid emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and their potential to endangering the global health has increased the demand for a fast-tracking method in comparison to the next-generation sequencing (NGS) as a gold standard assay, particularly in developing countries. This study was designed to evaluate the performance of a commercial multiplex real-time PCR technique (GA SARS-CoV-2 OneStep RT-PCR Kit, Iran) for identification of SARS-CoV-2 variants of concern (VOCs) compared to the Oxford Nanopore NGS assay., Methods: A total of 238 SARS-CoV-2-positive respiratory samples from different waves of COVID-19 in Iran were randomly selected in this study. To determine the SARS-CoV-2 VOC, the samples were analyzed via the commercial triple target assay, GA SARS-CoV-2 OneStep RT-PCR Kit, and NGS as well., Results: The results revealed good concordance between GA SARS-CoV-2 OneStep RT-PCR Kit and NGS for identification of SARS-CoV-2 VOCs. GA SARS-CoV-2 OneStep RT-PCR Kit identified Wuhan, Alpha, and Delta variants with 100% relative sensitivity and specificity. Regarding Omicron subvariants of BA.1, BA.2, and BA.4/5, the relative sensitivity of 100%, 100%, and 81.5% and the relative specificity of 95.3%, 93.5%, and 100% were observed., Conclusion: Overall, GA SARS-CoV-2 OneStep RT-PCR Kit can be used as a rapid and cost-effective alternative to NGS for identification of SARS-CoV-2 VOCs., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

In this study, the time and path of transmission of H1N1 serotype influenza A viruses in Iran and neighboring countries have been investigated by using Bayesian phylogeography analysis on the sequences extracted from the gene bank. We obtained all hemagglutinin (HA) and neuraminidase (NA) nucleotide sequences of influenza H1N1 available up to December 25, 2020, from Iran and its neighboring countries (i.e., Pakistan, Afghanistan, Turkmenistan, Armenia, Azerbaijan, Turkey, and Iraq). We also performed a Bayesian Markov chain Monte Carlo method to infer the evolutionary dynamic and the most recent common ancestor for the HA and NA sequences. Based on the extracted sequences, the age of emergence of H1N1 influenza virus serotype was older in Iran compared to neighboring countries, and with some degree of uncertainty, it seems Tehran had a key role and epicenter of transmission to other cities within Iran. The mean time of the most recent common ancestor of H1N1 viruses was 1989 (95% HPD: 1980-1994) for HA and NA as well. Along with ordinary measures like resource management, diagnostic approaches, and preparedness to fight against viruses that were in place, continuous monitoring, and screening of H1N1 serotype influenza virus in the country, especially by implementation of feasible, effective, and innovative measures at borderline should be initiated and identified gaps and shortage that should be a priority for virus control. It is also important for countries to have a regional monitoring program in addition to internal monitoring programs, as well as to start a virus molecular care program., (© 2022 Wiley Periodicals LLC.)

Background: Tripartite motif-containing 28 (TRIM28) is an impressive regulator of the epigenetic control of the antiviral immune response. This study evaluated if the differential expression of TRIM28 correlates with the severity of coronavirus disease 2019 (COVID-19) infection., Methods: A total of 330 COVID-19 patients, including 188 mild and 142 severe infections, and 160 healthy controls were enrolled in this study. Quantitative real-time polymerase chain reaction (qPCR) was used to determine the expression levels of TRIM28 in the studied patients., Results: TRIM28 mRNA levels were significantly lower in both groups of patients versus the control group and in the severe group indicated further reduction in comparison to mild infection. The multivariate logistic regression analysis showed the mean age, lower levels of low-density lipoprotein (LDL), high-density lipoprotein (HDL), cholesterol, lower 25-hydroxyvitamin D, and PCR cycle threshold (Ct) value and higher levels of erythrocyte sedimentation rate (ESR) and differential expression of TRIM28 were linked to the severity of COVID-19 infection., Conclusion: The results of this study proved that the downregulation of TRIM28 might be associated with the severity of COVID-19 infection. Further studies are required to determine the association between the COVID-19 infection severity and TRIM family proteins., (© 2022. The Author(s).)

The 24-loci mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) genotyping has been used as an international standard method for Mycobacterium tuberculosis (Mtb) genotyping. However, different optimized VNTR loci sets for improving the discrimination of specific Mtb genotypes have been proposed. In this regard, we investigated the efficacy of accumulation of the percentage differences (APDs) compared with the least absolute shrinkage and selection operator (LASSO) regression strategy to identify a customized genotype-specific VNTR loci set which provides a resolution comparable to 24-loci MIRU-VNTR in divergent Mtb populations. We utilized Spoligotyping and 24-loci MIRU-VNTR typing for genotyping 306 Mtb isolates. The APD and LASSO regression approaches were used to identify a customized VNTR set in our studied isolates. Besides, the Hunter-Gaston discriminatory index (HGDI), sensitivity, and specificity of each selected loci set were calculated based on both strategies. The selected loci based on LASSO regression compared with APD-based loci showed a better discriminatory power for identifying all studied genotypes except for T genotype, which APD-based loci showed promising discriminative power. Our findings suggested the LASSO regression rather than the APD approach is more effective in the determination of possible discriminative VNTR loci set to precise discrimination of our studied Mtb population and may be beneficial to be used in finding reduced number loci sets in other Mtb genotypes or sublineages. Moreover, we proposed customized genotype-specific MIRU-VNTR loci sets based on the LASSO regression and APD approaches for precise Mtb strains identification. As the proposed VNTR sets offered a comparable discriminatory power to the standard 24 MIRU-VNTR loci set could be promising alternatives to the standard genotyping for using in resource-limited settings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hadifar, Kargarpour Kamakoli, Eybpoosh, Nakhaeizadeh, Kargarpour Kamakoli, Ebrahimifard, Fateh, Siadat and Vaziri.)

Vulvovaginal candidiasis (VVC) is a prevalent infection of the genitourinary tract affecting millions of women worldwide. In the present study, the importance of virulence factors, ERG11 gene mutations, ERG11 gene expression, and plasma membrane ergosterol content for fluconazole resistance in Candida species was investigated in 200 women suspected of vulvovaginitis. Isolated Candida species were identified using the ITS-restriction fragment length polymorphism (ITS-RFLP) technique. Antifungal susceptibility testing was performed according to the CLSI document. ERG11 gene expression was analyzed using real-time PCR. ERG11 gene mutation analysis was performed using sequencing methods, and the ergosterol content of the cell membrane was determined in fluconazole-resistant isolates. Furthermore, the production of phospholipase and proteinase enzymes was evaluated in recurrent and non-recurrent infections. VVC was diagnosed in 101 (50.5%) of the 200 clinical cases, of which 21 (20.8%) were confirmed as RVVC. Candida albicans was the most prevalent species, followed by C. glabrata, C. tropicalis, C. krusei, C. parapsilosis, and C. guilliermondii. Ketoconazole and fluconazole were the most effective drugs against C. albicans among five tested antifungals with MIC ranges between 0.06 and 16 μg/mL and 0.25-64 μg/mL. Substitutions of A114S, Y257H, T123I and A114V were detected in fluconazole-resistant C. albicans. The ergosterol content of the fungal cell membrane and the mean levels of ERG11 gene expression transcript were higher in fluconazole-resistant C. albicans isolates obtained from RVVC than in those obtained from VVC cases. Phospholipase and proteinase were produced in different amounts in all Candida species isolated from VVC and RVVC cases. In this review, our results demonstrated that several molecular mechanisms, including ERG11 gene expression, changes in the cell membrane ergosterol content, and mutations in ERG11 gene alone or simultaneously involved in fluconazole resistance of C. albicans species and the recurrence of VVC., Competing Interests: Declarations of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Low access to HIV prevention, care, and treatment services among people living with HIV (PLWH) is a barrier to the control of the epidemic worldwide. The present study aimed to assess the barriers and facilitators to HIV services among PLWH in Kerman, Iran., Methods: In this qualitative study, a convenience sample of 25 PLWH who had received HIV prevention, treatment, or care services, and six PLWH who had not yet received services were recruited between August-October 2020. Data were collected using a semi-structured, face-to-face interview. Data were examined by inductive content analysis using MAXQDA 10 software., Results: Nine categories of facilitators and 11 categories of barriers to HIV services were identified. Facilitating factors included: maintaining health status, feeling scared, trust in the health system, how they were treated by service providers, provision of suitable hours by the service provider center, changing attitudes towards HIV in society, acceptance of the disease by the patient's family, hope for the future and feeling the need for consulting services. Barriers included financial problems, side effects and belief in efficacy, distance and transportation problems, fear of being recognized, stigma towards PLWH, organization of services, improper treatment by service providers, unsuitable hours by the service provider center, lack of trust in the health system, lack of family support, and inadequate or low-quality service., Conclusion: Many facilitators and barriers to HIV prevention, treatment, and care are amenable to change and better management by healthcare and service providers. Addressing these factors is likely to increase the willingness to use services by those who have never previously accessed them., (© 2022. The Author(s).)

Group A rotavirus (RVA) is the most common cause of acute gastroenteritis worldwide, which is responsible for causing an estimated 120 000 deaths in children under 5 years of age, which mostly occur in the lower-income countries of Asia and Africa. The G1P[8] is a common genotype of RVA that has spread throughout the world, including Iran and this genotype is present in two commonly used RVA vaccines, Rotarix TM and RotaTeq TM . In this study, we investigated the genetic diversity, viral evolution, and differences between antigenic epitopes of Iran's P[8] strains and two licensed vaccines. The phylogenetic and evolutionary analysis was carried out, using MEGA version 6.0 and BEAST, respectively. Antigenic epitopes of VP8* were compared to determine the differences between strains from Iran and Rotarix TM and RotaTeq TM . The P[8]-lineages III and IV were found as the predominant P genotype that circulated in Iran. The TMRCA of P[8]-lineages III and IV was estimated in 1987 and 2009, respectively. The P[8]-lineage III strains showed 12 amino acid changes compared to Rotarix TM and 10 amino acid changes compared to RotaTeq TM . The P[8]-lineage IV strains showed 10 amino acid variations for both Rotarix TM and RotaTeq TM strains. The results revealed that the P[8] strains circulating in Iran differ from Rotarix TM and RotaTeq TM strains. To monitor the long-term effects of vaccines on the emergence of P[8] strains with different lineages, routine and successful monitoring of these strains will be crucial., (© 2022 Wiley Periodicals LLC.)

Background: During the first months of the coronavirus disease 2019 (COVID-19) pandemic, Iran reported high numbers of infections and deaths. In the following months, the burden of this infection decreased significantly, possibly due to the impact of a package of interventions. We modeled the dynamics of COVID-19 infection in Iran to quantify the impacts of these interventions., Methods: We used a modified susceptible-exposed-infected-recovered (SEIR) model to model the COVID-19 epidemic in Iran, from January 21, 2020 to September 21, 2020. We estimated the 95% uncertainty intervals (UIs) using Markov chain Monte Carlo simulation. Under different scenarios, we assessed the effectiveness of non-pharmaceutical interventions (NPIs) including physical distancing measures and self-isolation. We also estimated the time-varying reproduction number (R t ), using our mathematical model and epidemiologic data., Results: If no NPIs were applied, there could have been a cumulative number of 51 800 000 (95% UI: 1 910 000- 77 600 000) COVID-19 infections and 266 000 (95% UI: 119 000-476 000) deaths by September 21, 2020. If physical distancing interventions, such as school/border closures and self-isolation interventions had been introduced a week earlier than they were actually launched, 30.8% and 35.2% reduction in the number of deaths and infections respectively could have been achieved by September 21, 2020. The observed daily number of deaths showed that the Rt was one or more than one almost every day during the analysis period., Conclusion: Our models suggest that the NPIs implemented in Iran between January 21, 2020 and September 21, 2020 had significant effects on the spread of the COVID-19 epidemic. Our study also showed that the timely implementation of NPIs showed a profound effect on further reductions in the numbers of infections and deaths. This highlights the importance of forecasting and early detection of future waves of infection and of the need for effective preparedness and response capabilities., (© 2022 The Author(s); Published by Kerman University of Medical Sciences This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Abstract: We explored the impact of the coronavirus disease 2019 (COVID-19) pandemic on people living with HIV (PLWH) in Kerman, Iran. A convenience sample of 18 PLWH from a voluntary counseling and testing (VCT) center (August-October 2020) were invited to participate in face-to-face interviews. Inductive content analysis was performed with MAXQDA software. Six themes were identified: COVID-19-related knowledge and preventive practices, misconceptions about COVID-19, fear of seeking health care services, psychosocial effects, limited or inconvenient access to health care services, and the impact of COVID-19 on socioeconomic status. Although participants generally understood COVID-19 preventative measures, some held misconceptions. COVID-19 negatively affected PLWHs' mental health, financial stability, and use of and access to health care services. Our findings support expansion of services related to HIV care/treatment and mental health to promote health and well-being during the COVID-19 pandemic., (Copyright © 2021 Association of Nurses in AIDS Care.)

Background: We aimed to determine the generation time, the best model for estimating reproduction number (R), and to estimate the basic reproduction number (R 0 ) and effective reproduction number (R t ) for COVID-19 in Iran., Methods: We used the daily incidence cases of COVID-19, hospitalized due to a probable diagnosis of COVID-19 from 19 February 2020 to 17 November 2020 in Iran. Four models, including maximum likelihood (ML), exponential growth (EG), time-dependent (TD), sequential Bayesian (SB) were evaluated. The weekly reproduction number with a 95% confidence interval (CI) was calculated., Results: TD model shows the best fit compared to other models for estimating reproduction number in Iran. The R 0 in Iran in the first week of the epidemic, leading up to 21 February 2020 was 7.19, 95% CI: 5.56, 9.00. The lowest value for the R t was equal to 0.77 between 3 to 10 March 2020 and 4 to 11 December 2020. From 11 June 2020 up to13 August 2020, the R t was more than one but after then to 24 September 2021 was less than one., Conclusion: TD model was the best fit for estimating the R in Iran. The worst situation of the epidemic in Iran was related to the weeks leading up to 26 February 2020 and 28 October 2020, and better status was related to the weeks leading up to 10 March 2020 and 11 December 2020., Competing Interests: Conflict of interest Aliakbar Haghdoost and Ehsan Mostafavi were managers and members of the Advisory Epidemiologic Committee of COVID-19 in MoHME. The rest of the authors have no conflict of interest., (Copyright © 2022 Doosti-Irani et al. Published by Tehran University of Medical Sciences.)

Background: Iran is one of the first few countries that was hit hard with the coronavirus disease 2019 (COVID-19) pandemic. We aimed to estimate the total number of COVID-19 related infections, deaths, and hospitalizations in Iran under different physical distancing and isolation scenarios., Methods: We developed a susceptible-exposed-infected/infectious-recovered/removed (SEIR) model, parameterized to the COVID-19 pandemic in Iran. We used the model to quantify the magnitude of the outbreak in Iran and assess the effectiveness of isolation and physical distancing under five different scenarios (A: 0% isolation, through E: 40% isolation of all infected cases). We used Monte-Carlo simulation to calculate the 95% uncertainty intervals (UIs)., Results: Under scenario A, we estimated 5 196 000 (UI 1 753 000-10 220 000) infections to happen till mid-June with 966 000 (UI 467 800-1 702 000) hospitalizations and 111 000 (UI 53 400-200 000) deaths. Successful implantation of scenario E would reduce the number of infections by 90% (ie, 550 000) and change the epidemic peak from 66 000 on June 9, to 9400 on March 1, 2020. Scenario E also reduces the hospitalizations by 92% (ie, 74 500), and deaths by 93% (ie, 7800)., Conclusion: With no approved vaccination or therapy available, we found physical distancing and isolation that include public awareness and case-finding and isolation of 40% of infected people could reduce the burden of COVID-19 in Iran by 90% by mid-June., (© 2022 The Author(s); Published by Kerman University of Medical Sciences. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Background: Variations in mitochondrial DNA copy number (mtDNA-CN) of peripheral blood leukocytes (PBLs), as a potential biomarker for gastric cancer (GC) screening has currently been subject to controversy. Herein, we have assessed its efficiency in GC screening, in parallel and in combination with serum pepsinogen (sPG) I/II ratio, as an established indicator of gastric atrophy., Methods: The study population included GC (n = 53) and non-GC (n = 207) dyspeptic patients. The non-GC group was histologically categorized into CG (n = 104) and NM (n = 103) subgroups. The MtDNA-CN of PBLs was measured by quantitative real-time PCR. The sPG I and II levels and anti-H. pylori serum IgG were measured by ELISA., Results: The mtDNA-CN was found significantly higher in GC vs. non-GC (OR = 3.0; 95% CI = 1.4, 6.4) subjects. Conversely, GC patients had significantly lower sPG I/II ratio than the non-GC (OR = 3.2; CI = 1.4, 7.2) subjects. The combination of these two biomarkers yielded a dramatic amplification of the odds of GC risk in double-positive (high mtDNA-CN-low sPGI/II) subjects, in reference to double-negatives (low mtDNA-CN-high sPGI/II), when assessed against non-GC (OR = 27.1; CI = 5.0, 147.3), CG (OR = 13.1; CI = 2.4, 72.6), or NM (OR = 49.5; CI = 7.9, 311.6) groups., Conclusion: The combination of these two biomarkers, namely mtDNA-CN in PBLs and serum PG I/II ratio, drastically enhanced the efficiency of GC risk assessment, which calls for further validations.

Purpose: Bariatric surgery is a treatment option for those affected by severe obesity. This study investigated changes in gut microbiota and serum biomarkers after laparoscopic sleeve gastrectomy (LSG)., Materials and Methods: A total of 126 patients with morbid obesity who underwent LSG were enrolled in this study. Routine biochemical tests, hormonal (insulin and glucagon), and cytokine levels (IL-6, IL-1β, TNF-α, IL-10, and TGF-β 1) were measured, in addition, real-time PCR (quantitative PCR, qPCR) quantitated gut microbiota. All the parameters were measured pre-operatively, 3, and 12 months post-surgery (F0, F3, and F12, respectively)., Results: At F3, the level of FBS, HbA1c, HOMA-IR, triglyceride, cholesterol, LDL, BUN, creatinine, urea, SGOT, SGPT, IL-1β, IL-6, IFNγ, insulin, glucagon, the abundance of Prevotella and Bacteroides fragilis group, as well as the concentration of Firmicutes spp. showed significant decrease (P < 0.01), and HDL level, Akkermansia muciniphila and Roseburia spp. abundance, and Bacteroidetes and Bifidobacterium spp. concentration showed significant increase (P < 0.0001). The observed pattern continued or remained stable at F12 for all of these variables. IL-10 and TGF-β1 remained unchanged until F3 and showed a significant drop at F12. At F3, Clostridium cluster IV increased significantly and remained at that level afterward. Moreover, concentration of Phylum Actinobacteria showed an initial drop at F3 and a later increase at F12 (P < 0.0001)., Conclusion: LSG is associated with a significant improvement in serum biomarkers, as well as significant changes in fecal microbiota. Future systems biology analyses would shed more light on the underlying interactions of these parameters, and could help in developing novel diagnostic and therapeutic strategies for obesity management.

Background: Variations of serum biomarkers and bacterial diversity of the gastrointestinal tract in obese patients with diabetes or hypothyroid are poorly understood. The aim of this study was to provide recent findings in this regard. Methods: A total of 119 obese patients [17 with diabetes, 23 with hypothyroid, and 79 patients without either diabetes or hypothyroid (control)] were recruited in this study. Serum biomarkers such as biochemical, hormonal (insulin and glucagon), and cytokine levels [interleukin (IL)-6, IL-1β, tumor necrosis factor-alpha, IL-10, and transforming growth factor beta-1 (TGF-β1)] were measured under fasting conditions. Bacterial abundance of gut microbiota was also quantitated by real-time polymerase chain reaction using 16S rRNA gene-based specific primers. Results: Average value of blood sugar ( P : 0.0184), hemoglobin A1c, insulin, homeostasis model assessment insulin resistance, TGF-β 1, IL-6, IL-1β, interferon gamma ( P for each < 0.001), and phylum Actinobacteria [odds ratio (OR): 1.5, P : 0.032] was significantly higher in diabetic versus control group. In contrast, the levels of IL-10 ( P  < 0.001), Firmicutes (OR: 0.6, P : 0.058), and Akkermansia muciniphila (OR: 0.4, P : 0.053) were significantly lower in diabetic versus control group. However, there was no statistically significant difference between the values in hypothyroid versus control group either in crude or adjusted models. Conclusion: While there are some relationships between serum biomarkers or bacterial abundance with diabetes prediction in obese patients, this prognostication is less likely in obese patients with hypothyroid. Further investigation is warranted in the application of identified preclinical biomarkers in the diagnosis of diabetes or hypothyroid in obese patients.

Background: Variation in host genetic factors may result in variation in the host immune response to the infection. Some chronic diseases may also affect individuals' susceptibility to infectious diseases. The aim of this study was to evaluate the association of the host genetic factors mostly involved in inflammation, as well as hypercholesterolemia and diabetes with mild flu in an Iranian population., Methods: In this cross-sectional study, nasopharyngeal swab samples were collected from 93 patients referred to primary care centers of Markazi, Semnan, and Zanjan provinces (central Iran) due to flu-like symptoms between March 2015 and December 2018. Of these, PCR test identified 49 influenza A/H1N1 and 44 flu-negative individuals. Twelve single-nucleotide polymorphisms (SNPs) in RPAIN, FCGR2A, MBL-2, CD55, C1QBP, IL-10, TNF-α and an unknown gene were genotyped using iPLEX GOLD SNP genotyping analysis. Hypercholesterolemia and diabetes status was determined based on the physician diagnosis. Association of the host genetic variants, hypercholesterolemia and diabetes with mild A/H1N1 flu was assessed with univariable and multivariable logistic regression analysis as implemented in Stata software (v.14). Statistical tests were considered as significant at 0.05 levels., Results: Frequency of diabetes and hypercholesterolemia, as well as participants mean age was significantly higher in the flu-negative rather than the flu-positive group. Of 12 SNPs, nine did not show any significant association with mild flu in our study (rs1801274, rs1800451, rs2564978, rs361525, rs1800450, rs1800871, rs1800872, rs1800896, rs1800629). Possessing G vs. A allele in two SNPs (rs3786054 and rs8070740) was associated with a threefold increase in the chance of mild flu when compared to flu-negative patients (95% CI: 1.1, 22.0). Possessing C allele (vs. A) in the rs9856661 locus also increased the chance of mild flu up to 2 folds (95% CI: 1.0, 10.0)., Conclusion: The results showed that possessing the G allele in either rs3786054 or rs8070740 loci in C1QBP and RPAIN genes, respectively, increased the risk of H1N1 infection up to 3.3 folds, regardless of the patient's age, BMI, diabetes, and hypercholesterolemia. Complementary functional genomic studies would shed more light on the underlying mechanism of human immunity associated with these genetic markers. The identified genetic factors may have the same role in susceptibility to similar respiratory infections with RNA viruses, like SARS, MERS and COVID-19. Future genetic association studies targeting these RNA viruses, especially COVID-19 is recommended. Studies on other ethnic groups would also shed light on possible ethnic variations in genetic susceptibility to respiratory RNA viruses. Trial registry IR.PII.REC.1399.063.

Background: The reproductive health and Prevention of Mother-to-Child Transmission (PMTCT) of HIV programs in Iran were integrated as a pilot project in September 2014. This study aims to provide a comprehensive evaluation and analysis of the PMTCT of HIV program in Iran., Methods: The pilot phase of PMTCT of HIV was launched in early September 2014 in selected centers including 170 health centers and 40 hospitals affiliated to medical universities of 16 provinces of Iran. In each medical university, a researcher-made checklist was administered to all newly-diagnosed HIV-positive pregnant women by an AIDS expert. Data was analyzed using SPSS 19., Results: Overall, 69.4% of eligible pregnant women were enrolled in the pilot phase. From 134 reactive cases, 76 (56.7%) were confirmed as HIV positive. ARV consumption was irregular in 10 (13.2%) of HIV positive pregnant women. Also, 82.5% had CD4 count more than 350 after treatment, with an average of 55.5% increase in the number of CD4 in comparison to the baseline, and 84.8% had viral load suppression (< 200 copies/ml). Counseling and testing was done for the husbands of 75% of the women that resulted in the identification of 15 (39.5%) new HIV cases among husbands. Among the tested individuals, 23 (60.5%) males already knew their HIV status and were registered as HIV patients. HIV was diagnosed in one (1.5%) newborn., Conclusion: Implementation of rapid HIV testing and PMTCT in Iran is one of the strengths of the national HIV control program. To eliminate MTCT, it is necessary to understand and overcome the barriers and challenges to the program in the pilot phase.

Background: Higher mortality due to coronavirus disease 2019 (COVID-19) is reported among some immunocompromised patients; however, the relation between immunosuppression due to HIV infection and severity of COVID-19 infection remains unclear. We aimed to investigate the severity and mortality of COVID-19 infection in HIV-infected patients. Methods: This was a retrospective cohort study on all COVID-19 suspected and confirmed cases hospitlized in Iran between Febuary 19 (epidemic onset date) and April 8, 2020, whose data were recorded in the national database for Medical Care Monitoring Center. Hospitalized patients were followed from admittion to death/discharge. Patients' HIV status was recorded based on their self report. Logistic and Cox regression models were used to evaluate the association between HIV infection and the severity (according to the Glascow-Coma Scale situation, need for intubation and hypoxemia) and mortality of COVID-19 infection, respectively. Analyses were performed separately for COVID-19 suspected and confirmed cases. Results: Out of 122 206 severe acute respiratory infection (SARI) cases, 90 were HIV-positive (0.07%), with a similar mean age (Pt-test= 0.750) and distrubtion of gender (PChi-square= 0.887) and nationality (PChi-square= 0.202) as HIV-negative patients. A comparable proportion of HIV-positive and HIV-negative cases were tested for COVID-19 (p= 0.170); however, the frequency of positive results was lower among HIV-positives (p= 0.038). The frequency of COVID-19 and HIV coinfection was lower than expected among confirmed cases (adjusted OR= 0.54; 95% CI: 0.29-1.02) and suspected cases (adjusted OR= 0.68; 95% CI: 0.45- 1.02), which means that the frequency of COVID-19 infection was lower among HIV-positive cases. HIV infection decreased the risk of death among confirmed (adjusted HR= 0.33; 95% CI: 0.05-2.32), suspected cases (adjusted HR= 0.81; 95% CI: 0.33-1.94), and among SARI cases (adjusted HR= 0.73; 95% CI: 0.35-1.54). Conclusion: Our findings support the concept that HIV infection was not a risk factor to increase the severity and risk of death among COVID-19 infected patients., Competing Interests: Conflicts of Interest: Although Mohammad Mehdi Gouya and Parvin Afsar Kazerooni are CDC managers of the Iranian Ministry of Health and Medical Education, the authors declare that they have no conflict of interests., (© 2021 Iran University of Medical Sciences.)

Background: Since the beginning of the coronavirus disease 2019 (COVID-19) epidemic in Iran, the control and management of the epidemic were headed by the National Headquarter for the Control of COVID-19 Epidemic through setting up different scientific committees, including the COVID-19 National Epidemiology Committee. The present study reviews the missions, structures, achievements, and challenges of the Epidemiology Committee., Study Design: A rapid review ., Methods: All relevant reports, documents, guidelines, published literature, and surveillance data related to the establishment, visions, missions, roles, activities, and outputs of the COVID-19 Epidemiology Committee were critically reviewed in this study., Results: The efforts of the committee's working groups may have impacted improvements in data registration/usage, provincial data quality at provincial levels, and perception of the epidemic situation in the provinces. The committees have also played role in informing the policies in different stages of the epidemic through routine or problem-based data/evidence analyses, epidemic investigations, and mathematical modeling., Conclusion: The structure and experience gained by the committee can be used in similar situations within and outside the country. To further improve the impacts of our activities, it is essential to have effective interaction, collaboration, and data flow between the committee and a broad range of organizations within and outside the Ministry of Health and Medical Education.

Background: Knowledge about the distribution of Escherichia Coli (E. coli) pathotypes in Iran is limited. This nation-wide survey aims to provide a comprehensive description of the distribution of five pathogenic E. coli in Iran., Methods: Stool samples were collected from 1,306 acute diarrhea cases from 15 provinces (2013-2014). E. coli-positive cultures underwent PCR testing for the detection of STEC, ETEC, EPEC, EAEC, and EIEC pathotypes. Pathotype frequency by province, age-group, and season was estimated., Results: 979 diarrhea samples (75.0%) were culture-positive for E. coli (95% CI: 72.6, 77.3%), and 659 (50.5%) were pathogenic E. coli (95% CI: 47.8, 53.2%). STEC was the most frequent pathotype (35.4%). ETEC (14.0%) and EPEC (13.1%) were the second and the third most frequent pathotypes, respectively. EAEC (4.3%) and EIEC (0.3%) were not highly prevalent. Fars (88.7%) and Khorasan-e-Razavi (34.8%) provinces had the highest and lowest frequencies, respectively. E. coli pathotypes were more frequent in warmer than cooler seasons, showed the highest frequency among children under five years of age (73%), and had no significant association with participants' gender., Conclusions: Diarrheagenic E. coli may be an important cause of acute diarrhea in adults and children in Iran. STEC and ETEC seem to be widespread in the country with a peak in warmer seasons, impacting the recommended use of seasonal STEC and ETEC vaccines, especially in high-risk groups. Monitoring the incidence of E. coli pathotypes, serotypes, and antibiotic resistance over time is highly recommended for evaluation of interventions., Competing Interests: The authors have declared that no competing interests exist.

We have performed a systematic review and meta-analysis for evaluation of mitochondrial DNA copy number (mtDNA-CN) alterations in peripheral blood leukocytes (PBL), and tumor tissues of gastrointestinal tract (GIT) cancers. Analysis of the PBL demonstrated a significant decrease [OR: 0.6 (0.5, 0.8)] and increase [OR: 1.4 (1.1, 1.9)] prior to and following GIT cancer development, respectively. This trend was more evident in CRC, and GC subgroups. Analysis of tissue yielded high levels of heterogeneity. However, the mean difference for the CRC subgroup was statistically significant [1.5 (1.0, 2.2)]. Our analysis suggests mtDNA-CN deserves further investigations as a GIT-cancer screening tool.

Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest.

Background: Older adults are at higher risk for severe illness and death associated with coronavirus disease 2019 (COVID-19). As Iran was affected by COVID-19 pandemic, the elderly population soon were told to self-isolate for a very long time. We aimed to identify the coverage, efficacy, and integrity of self-isolation and its predictors in the Iranian older adults (≥60 years) from February 19 to 19 March 2020. Methods: Quota sampling was performed to recruit respondents from 16 cities that were selected based on their population size (4, 7, and 5 cities for localities with ≤500 000, 500 000-1 000 000, and ≥1 000 000 populations) and geographical direction (West = 4 cities; North, East, South, Center = 3 each). At least 30 respondents per locality were selected. Phone interviews of 558 respondents (out of 560; response rate = 99.6%) were performed by local trained interviewers using a validated interview form. Association between age, sex, and living condition (with family vs alone) was assessed with Pearson Chi Square and logistic regression analyses. Results: Complete self-isolation was reported by 61% of the respondents. In 72%, self-isolation led to 80%-100% contact reduction. Self-isolation was broken by 26% of the respondents. Females had better self-isolation behaviors (OR adjusted: 2.3, 95% CI: 1.5, 3.3) and higher contact reduction rates (p: 0.067). They kept the integrity of self-isolation better (OR adjusted: 1.8; 95% CI: 1.2, 2.7). Those aged older than 80 years were 2.3-folds more likely to completely self-isolate than younger elderly (95% CI adjusted: 1.2, 4.3). Living alone did not significantly predict self-isolation features in the elderly. Conclusion: About one third of the interviewed Iranian older adults did not adhere to important self-isolation measures, with males and younger ages showing lower adherence. With the relaxation of social distancing measures, protection measures of the elderly should be strengthened. Given that prolonged self-isolation adversely affects physical and mental health status of the elderly, it is highly recommended to think of creative and gender-specific methods that best tailor the needs of this population in Iran., Competing Interests: Conflicts of Interest: None declared, (© 2020 Iran University of Medical Sciences.)

Background: Coronavirus Disease 2019 (COVID-19) has resulted in a considerable number of deaths worldwide. This ecological study aimed to explore the relationship between COVID-19 hospitalization and mortality with smoking, obesity, and underlying conditions in Iran. Methods: Provincial-level COVID-19 data were obtained from the official reports. Two outcomes were assessed: the total number of hospitalizations and deaths. Data on underlying health conditions, cigarette smoking, and obesity were obtained from national surveys. Negative binomial regression was used to report incident rate (IRR) ratios. Results: As of April 22, 2020, a total number of 43 950 lab-confirmed COVID-19 hospitalizations and 5391confirmed COVID-19 deaths were officially reported. Adjusting for underdetection to cover the number of clinically-confirmed COVID-19 cases, a total of 76 962 additional hospitalizations (ie, total lab- and clinically-confirmed hospitalizations = 120 912; 175% increase) and 7558 additional deaths (ie, total lab- and clinically-confirmed deaths = 12 949; 140% increase) were estimated during the same period. Provinces with a higher prevalence of obesity (IRR: 2.75, 95% CI: 1.49, 5.10), cigarette smoking (1.81; 95% CI: 1.01, 3.27), hypertension (1.88; 95% CI: 1.03, 3.44), and diabetes mellitus (1.74; 95% CI: 0.96, 3.16) had a higher likelihood of COVID-19 death rates. Conclusion: Inequality in COVID-19 hospitalization and mortality was observed in provinces whose populations had underlying diseases, in particular, obesity, cigarette smoking, hypertension, and diabetes., Competing Interests: Conflicts of Interest: None declared, (© 2020 Iran University of Medical Sciences.)

Background: Iran is one of the countries most affected by COVID-19. This review provides possible interpretations of the observed trend of COVID-19 in Iran., Study Design: A rapid review METHODS: We reviewed the daily new cases of COVID-19 based on hospitalized and outpatients, reported deaths, and diagnostic testing in Iran., Results: Iran reported its first peak in the number of cases in late March, 2020. From the 1 April to 3 May 2020, the downward trend in the number of cases was started. The death trend also showed a peak in early April as well as a downward trend in late April. During May, the number of death cases showed a stable trend with a daily number of deaths ranging between 50 and 75 cases. Then the number of deaths gradually increased., Conclusion: The epidemic curve in Iran is a function of different factors such number of total tests, change in mitigation policies, and heterogeneities among different provinces in the country. Therefore it should be interpreted under the light of the effect of such factors.

Biosynthesis of nanoparticles (NPs) by microorganisms is a cost- and energy-effective approach. However, how the production of NPs affects the population of producing organism remains as an unresolved question. The present study aimed to evaluate the kinetics of Saccharomyces cerevisiae growth in relation to synthesis of selenium sulfide nanoparticles by using a population model. To this end, the population of S. cerevisiae cells was investigated in terms of colony forming units (CFU) in the presence of the substrate in different time points. Fluctuation of sulfite reductase (SiR) activity, expression of MET5 and MET10 genes, and concentrations of sulfite and selenium were evaluated to support the population findings. CFU values in the test groups were lower than those in the control counterparts. The rise and fall of the SiR activity and MET5 and MET10 gene expression conformed to the variations of CFU values. The rate of reduction in the selenium and sulfite concentrations tended to decrease over the time. In conclusion, the cells population was negatively and positively affected by selenium and sulfite concentrations, respectively. The indirect relationship of the selenium ions concentration in the path analysis revealed that the product, selenium sulfide nanoparticles, caused this drop in S. cerevisiae cells population., (Copyright © 2020 Asghari-Paskiabi, Imani, Eybpoosh, Rafii-Tabar and Razzaghi-Abyaneh.)

Competing Interests: CONFLICT OF INTEREST Ali Akbar Haghdoost is the Deputy Minister of Health in Iran. The rest of the authors have no conflict of interest to disclose.

Laparoscopic sleeve gastrectomy (LSG) is an effective treatment option in patients with morbid obesity, with rare long-term sideeffects. In this report, we present a 42-year-old woman who reported positional vertigo and unilateral gradual hearing loss plus continuous tinnitus after LSG. The patient had no signs or symptoms of mental health disorders and the results of the haematological and serum biochemical tests were normal. However, audiometric test revealed mild sensorineural hearing loss with magnitude in high-frequency tones. Also, acoustic reflex threshold showed neural pathway damage, particularly at high frequencies, with no reflex. Pure tone audiometry showed signs of nerve damage in the inner ear. One possible justification for these complications might be eustachian tube dysfunction due to muscle relaxation. Muscle relaxation itself may occur as a result of adipose tissue loss around the ear muscles. Further evidence, however, would be required to better determine whether these complications are attributable to LSG, and to illuminate exact underlying reasons for such complications., Competing Interests: The authors report no conflicts of interest in this work., (© 2020 Tabasi et al.)

Overweight and obesity are among the most prevalent non-communicable diseases which are generally treated successfully by bariatric or sleeve surgery. There are evidences affirming that sleeve surgery can manipulate the pH of the stomach and interact with the metabolism of fatty acids, carbohydrates, and bile acid transfer, leading to the overgrowth of gut microbiota. Therefore, this study aims to review the changes in gut microbiota and hormones after bariatric surgery.

Background: Brucellosis is the most common zoonotic diseases worldwide. The aim of this study was to develop and evaluate the diagnostic performance of an indirect-ELISA (I-ELISA) method based on whole cell Brucella abortus S99 lysates for detection of IgM anti-Brucella antibodies in a human serum., Materials and Methods: The study was conducted in two species-rich endemic areas of Iran (Tehran and Lorestan provinces). Serum samples of 102 patients and 150 healthy individuals were tested by the new kit and the commercial Vircell kit for the presence of anti-Brucella IgM antibodies. The disease status was confirmed by Wright agglutination test. The difference in the mean optical densities (OD) recorded by the new and the Vircell kits for patients and healthy individuals were tested using Two-tailed Student t-test. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the new kit were informed using Receiver operating curve analysis. The results were used to guide the choice of cutoff. Agreements in ODs recorded by the new and the Vircell kit was visually inspected using Bland-Altman plot., Results: The new I-ELISA showed excellent diagnostic performance (sensitivity and PPV = 95.7%, specificity and NPV = 97.8%) for the diagnosis of brucellosis. The cut-off area for the antibody index (AI) was determined to be 8-10, where AIs less than 8 and greater than 10 were considered Brucella-negative and -positive, respectively. AIs of 8-10 show equivocal results, requiring re-testing. The Vircell kit showed low (36.8%) sensitivity and perfect (100%) specificity on the same samples. The Bland-Altman plot showed low agreement between both tests in recording the OD values for the same individuals., Conclusion: The new I-ELISA based on whole cell Brucella abortus S99 showed a good performance for the detection of Brucella spp. Lack of agreement between the new and the Vircell kit suggest that the performance of ELISA kits might be dependent on the geographical area under study. Hence, validation of the new and the Vircell kits is recommended prior to their implementation in other geographical areas., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: West Nile Virus (WNV), a member of the genus Flavivirus, is one of the most widely distributed arboviruses in the world. Despite some evidence for circulation of WNV in countries summarized by the World Health Organization as the Eastern Mediterrian Regional Office (EMRO), comprehensive knowledge about its epidemiology remains largely unknown. This study aims to provide a concise review of the published literature on WNV infections in the Eastern Mediterranean Regional Office of WHO (EMRO)., Methodology/principal Findings: A systematic review of WNV prevalence studies on humans, animals and vectors in the EMRO region was performed by searching: Web of Science, Science Direct, Scopus, PubMed, Embase and Google Scholar. Finally, 77 citations were included, comprising 35 seroprevalence studies on general population (24460 individuals), 15 prevalence studies among patients (3439 individuals), 22 seroprevalence studies among animals (10309 animals), and 9 studies on vectors (184242 vector species). Of the 22 countries in this region, five had no data on WNV infection among different populations. These countries include Kuwait, Bahrain, Oman, Syria and Somalia. On the other hand, among countries with available data, WNV-specific antibodies were detected in the general population of all investigated countries including Djibouti (0.3-60%), Egypt (1-61%), Iran (0-30%), Iraq (11.6-15.1%), Jordan (8%), Lebanon (0.5-1%), Libya (2.3%), Morocco (0-18.8%), Pakistan (0.6-65.0%), Sudan (2.2-47%), and Tunisia (4.3-31.1%). WNV RNA were also detected in patient populations of Iran (1.2%), Pakistan (33.3%), and Tunisia (5.3% -15.9%). WNV-specific antibodies were also detected in a wide range of animal species. The highest seropositivity rate was observed among equids (100% in Morocco) and dogs (96% in Morocco). The highest seroprevalence among birds was seen in Tunisia (23%). In addition, WNV infection was detected in mosquitoes (Culex, and Aedes) and ticks (Argas reflexus hermanni). The primary vector of WNV (Culex pipiens s.l.) was detected in Djibouti, Egypt, Iran and Tunisia, and in mosquitoes of all these countries, WNV was demonstrated., Conclusions: This first systematic regional assessment of WNV prevalence provides evidence to support the circulation of WNV in the EMRO region as nearly all studies showed evidence of WNV infection in human as well as animal/vector populations. These findings highlight the need for continued prevention and control strategies and the collection of epidemiologic data for WNV epidemic status, especially in countries that lack reliable surveillance systems., Competing Interests: The authors have declared that no competing interests exist.

The precise identification of the parasite species causing leishmaniasis is essential for selecting proper treatment modality. The present study aims to compare the nucleotide variations of the ITS1, 7SL RNA, and Hsp70 sequences between non-healed and healed anthroponotic cutaneous leishmaniasis (ACL) patients in major foci in Iran. A case-control study was carried out from September 2015 to October 2016 in the cities of Kerman and Bam, in the southeast of Iran. Randomly selected skin-scraping lesions of 40 patients (20 non-healed and 20 healed) were examined and the organisms were grown in a culture medium. Promastigotes were collected by centrifugation and kept for further molecular examinations. The extracted DNA was amplified and sequenced. After global sequence alignment with BioEdit software, maximum likelihood phylogenetic analysis was performed in PhyML for typing of Leishmania isolates. Nucleotide composition of each genetic region was also compared between non-healed and healed patients. Our results showed that all isolates belonged to the Leishmania tropica complex, with their genetic composition in the ITS1 region being different among non-healed and healed patients. 7SL RNA and Hsp70 regions were genetically identical between both groups. Variability in nucleotide patterns observed between both groups in the ITS1 region may serve to encourage future research on the function of these polymorphisms and may improve our understanding of the role of parasite genome properties on patients' response to Leishmania treatment. Our results also do not support future use of 7SL RNA and Hsp70 regions of the parasite for comparative genomic analyses., (Copyright © 2018 Elsevier Ltd. All rights reserved.)