Iran's research prioritization: Are we meeting the goals? A study based on clinical trial registry data.

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.

Up-regulation of CDR1 and MDR1 efflux pump genes and fluconazole resistance are involved in recurrence in Candida albicans-induced vulvovaginal candidiasis.

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.

Prevalence of acquired and transmitted HIV drug resistance in Iran: a systematic review and meta-analysis.

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.

Expression of TRIM56 gene in SARS-CoV-2 variants and its relationship with progression of COVID-19.

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.

Scientists looked at a protein called TRIM that helps fight viruses to see if a specific TRIM protein, TRIM56, was linked to how poorly people became with COVID-19. The study looked at the blood samples of 330 patients and found that COVID-19 patients had less TRIM56 than healthy people, especially those who were particularly ill.

Epidemiological surveillance of respiratory viral infections in SARS-CoV-2-negative samples during COVID-19 pandemic in Iran.

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.

Immunogenicity and safety of heterologous boost immunization with PastoCovac Plus against COVID-19 in ChAdOx1-S or BBIBP-CorV primed individuals.

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.

Comparison of a Multiplex Real-Time PCR Technique with Oxford Nanopore Technologies Next-Generation Sequencing for Identification of SARS-CoV-2 Variants of Concern.

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.

Efficacy and Safety of a Protein-Based SARS-CoV-2 Vaccine: A Randomized Clinical Trial.

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.

PastoCovac and PastoCovac Plus as protein subunit COVID-19 vaccines led to great humoral immune responses in BBIP-CorV immunized individuals.

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.

Assessment of long-term adverse events regarding different COVID-19 vaccine regimens within an 18-month follow-up study.

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.

Impact of TRIM5α and TRIM22 Genes Expression on the Clinical Course of Coronavirus Disease 2019.

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.

Epidemiology and spatial distribution of people diagnosed with HIV between 1997 and 2020 in Kerman, Iran.

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 χ2 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.

Comparing the expression levels of tripartite motif containing 28 in mild and severe COVID-19 infection.

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.

The shortcut of mycobacterial interspersed repetitive unit-variable number tandem repeat typing for Mycobacterium tuberculosis differentiation.

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.

Reconstruction of molecular evolution of human influenza A H1N1/2009 virus in Iran and neighboring countries.

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.

The Dynamic Effective Reproductive Number of COVID-19 during the Epidemic in Iran.

Background: We aimed to determine the generation time, the best model for estimating reproduction number (R), and to estimate the basic reproduction number (R0) and effective reproduction number (Rt) 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 R0 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 Rt 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 Rt 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.

Molecular epidemiology, antifungal susceptibility, and ERG11 gene mutation of Candida species isolated from vulvovaginal candidiasis: Comparison between recurrent and non-recurrent infections.

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.

Barriers and facilitators of access to HIV prevention, care, and treatment services among people living with HIV in Kerman, Iran: a qualitative study.

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.

Exploration of the Impact of Coronavirus Disease 2019 on People Living With HIV in Kerman, Iran: A Qualitative Study.

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.