Efficacy of single-dose and double-dose ivermectin early treatment in preventing progression to hospitalization in mild COVID-19: A multi-arm, parallel-group randomized, double-blind, placebo-controlled trial.

BACKGROUND AND OBJECTIVE: Ivermectin is a known anti-parasitic agent that has been investigated as an antiviral agent against coronavirus disease 2019 (COVID-19). This study aimed to evaluate the efficacy of ivermectin in mild COVID-19 patients. METHODS: In this multi-arm randomized clinical trial conducted between 9 April 2021 and 20 May 2021, a total of 393 patients with reverse transcription-PCR-confirmed COVID-19 infection and mild symptoms were enrolled. Subjects were randomized in a 1:1:1 ratio to receive single-dose ivermectin (12 mg), double-dose ivermectin (24 mg) or placebo. The primary outcome was need for hospitalization. RESULTS: There was no significant difference in the proportion of subjects who required hospitalization between the placebo and single-dose ivermectin groups (absolute difference in the proportions: -2.3 [95% CI = -8.5, 4.1]) and between the placebo and double-dose ivermectin groups (absolute difference in the proportions: -3.9 [95% CI = -9.8, 2.2]). The odds of differences in mean change in severity score between single-dose ivermectin and placebo groups (ORdifference  = 1.005 [95% CI: 0.972, 1.040]; p = 0.762) and double-dose ivermectin and placebo groups (ORdifference  = 1.010 [95% CI: 0.974, 1.046]; p = 0.598) were not statistically significant. None of the six adverse events (including mild dermatitis, tachycardia and hypertension) were serious and required extra action. CONCLUSION: Single-dose and double-dose ivermectin early treatment were not superior to the placebo in preventing progression to hospitalization and improving clinical course in mild COVID-19.

Spatiotemporal Study of COVID-19 in Fars Province, Iran, October-November 2020: Establishment of Early Warning System.

Background: Using time series and spatiotemporal analyses, this study aimed to establish an Early Warning System (EWS) for COVID-19 in Fars province Iran. Methods: A EWS was conducted on (i) daily basis city-level time series data including 53 554 cases recorded during 18 February-30 September 2020, which were applied to forecast COVID-19 cases during 1 October-14 November 2020, and (ii) the spatiotemporal analysis, which was conducted on the forecasted cases to predict spatiotemporal outbreaks of COVID-19. Results: A total of 55 369 cases were forecasted during 1 October-14 November 2020, most of which (26.9%) occurred in Shiraz. In addition, 65.80% and 34.20% of the cases occurred in October and November, respectively. Four significant spatiotemporal outbreaks were predicted, with the Most Likely Cluster (MLC) occurring in ten cities during 2-22 October (P < 0.001 for all). Moreover, subgroup analysis demonstrated that Zarrindasht was the canon of the epidemic on 6 October (P=0.04). As a part of EWS, the epidemic was triggered from Jahrom, involving the MLC districts in the center, west, and south parts of the province. Then, it showed a tendency to move towards Zarrindasht in the south and progress to Lar in the southernmost part. Afterwards, it simultaneously progressed to Fasa and Sepidan in the central and northwestern parts of the province, respectively. Conclusion: EWS, which was established based on the current protocol, alarmed policymakers and health managers on the progression of the epidemic and on where and when to implement medical facilities. These findings can be used to tailor province-level policies to servile the ongoing epidemic in the area; however, governmental level effort is needed to control the epidemic at a larger scale in the future.

Epidemiological and clinical features of 2019 novel coronavirus diseases (COVID-19) in the South of Iran.

BACKGROUND: In March 2020, the WHO declared the novel coronavirus (COVID-19) outbreak a global pandemic. Although the number of infected cases is increasing, information about its clinical characteristics in the Middle East, especially in Iran, a country which is considered to be one of the most important focal points of the disease in the world, is lacking. To date, there is no available literature on the clinical data on COVID-19 patients in Iran. METHODS: In this multicenter retrospective study, 113 hospitalized confirmed cases of COVID-19 admitted to university affiliated hospitals in Shiraz, Iran from February 20 to March 20 were entered in the study. RESULTS: The mean age was 53.75 years and 71 (62.8%) were males. The most common symptoms at onset were fatigue (75: 66.4%), cough (73: 64.6%), and fever (67: 59.3%). Laboratory data revealed significant correlation between lymphocyte count (P value = 0.003), partial thromboplastin time (P value = 0.000), international normalized ratio (P value = 0.000) with the severity of the disease. The most common abnormality in chest CT scans was ground-glass opacity (77: 93.9%), followed by consolidation (48: 58.5%). Our results revealed an overall 8% (9 out of 113 cases) mortality rate among patients, in which the majority was among patients admitted to the ICU (5: 55.6%). CONCLUSION: Evaluating the clinical data of COVID-19 patients and finding the source of infection and studying the behavior of the disease is crucial for understanding the pandemic.

Design, Synthesis, Molecular Docking, and Cholinesterase Inhibitory Potential of Phthalimide-Dithiocarbamate Hybrids as New Agents for Treatment of Alzheimer's Disease.

A novel series of phthalimide-dithiocarbamate hybrids was synthesized and evaluated for in vitro inhibitory potentials against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The anti-cholinesterase results indicated that among the synthesized compounds, the compounds 7g and 7h showed the most potent anti-AChE and anti-BuChE activities, respectively. Molecular docking and dynamic studies of the compounds 7g and 7h, respectively, in the active site of AChE and BuChE revealed that these compounds as well interacted with studied cholinesterases. These compounds also possessed drug-like properties and were able to cross the BBB.

Spatial epidemiology and meteorological risk factors of COVID-19 in Fars Province, Iran.

This study aimed at detecting space-time clusters of COVID-19 cases in Fars Province, Iran and at investigating their potential association with meteorological factors, such as temperature, precipitation and wind velocity. Time-series data including 53,554 infected people recorded in 26 cities from 18 February to 30 September 2020 together with 5876 meteorological records were subjected to the analysis. Applying a significance level of P<0.05, the analysis of space-time distribution of COVID-19 resulted in nine significant outbreaks within the study period. The most likely cluster occurred from 27 March to 13 July 2020 and contained 11% of the total cases with eight additional, secondary clusters. We found that the COVID-19 incidence rate was affected by high temperature (OR=1.64; 95% CI: 1.44-1.87), while precipitation and wind velocity had less effect (OR=0.84; 95% CI: 0.75-0.89 and OR=0.27; 95% CI: 0.14-0.51), respectively.

Epidemiological Study of Infection and Death Due to COVID-19 in Fars Province, Iran, From February to September 2020.

Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has entered our lives with the fear of outbreak, death, and recurrence. Our objective in this study is to evaluate the epidemiological features of Coronavirus Disease 2019 (COVID-19) infection and death in Fars province, Iran. Methods: A cross-sectional study was conducted from February 18th to September 30th, 2020, where age, history of underlying diseases, sex, community-wide quarantine, nationality, close contact, pregnancy, medical staff job, traveling , and residency were compared between alive and deceased groups. Data were analyzed using IBM SPSS software, version 22.0, and the significance level was set at 0.05. Results: Regarding 57958 new cases of COVID-19, the basic reproduction number (R0) was estimated as 2.8, requiring a minimum of 65% immunization to reach herd immunity. Moreover, an R0=0.36 was required to reach the endemic state in the region. The incidence, mortality, fatality, and recurrence rates of COVID-19 were estimated as 1347.9 per 100,000 dwellers, 209.5 per 1000,000 dwellers, 1.6 %, and 3.1 per 100,000 dwellers, respectively. Age, history of underlying diseases, urban residency, and the male sex were significantly higher in the deceased group (OR=1.09, 5.48, 1.24, and 1.32; All Ps<0.001, <0.001, 0.005, and <0.001, respectively). In addition, the recurrence rate among positive cases was estimated as 0.23% with a median±inter-quartile range equal to 84±46.25 days. Community-wide quarantine was shown to be a protective factor for death due to COVID-19 (OR=0.58, P=0.005). Conclusion: Community-wide quarantine blocks the transmission of COVID-19 effectively. COVID-19 enjoys no solid immunity. History of underlying diseases, the male sex, urban residency, and age were among the most significant causes of death due to COVID-19. Further investigations are recommended on the genetic structure of SARS-CoV-2, treatments, and vaccination.

Assessment of cell phone effect on dental socket healing in rat.

BACKGROUND: Electromagnetic waves can cause biological effects on repair process. Due to the proximity of the jawbone and the soft tissue around it in a part of the face with which it has the closest contact during the cell phone use, this study aims to investigate the effect of mobile waves on socket healing after tooth extraction in rats. METHODS: This experimental study was conducted on 32 rats. The case group was exposed to a 900 MHz frequency electromagnetic field for 30 min/d. Sacrificed eight rats from the case group and 7 rats from the control group on day 14, and 8 rats from the case group and 7 rats from the control group were sacrificed on day 28 at the end of the radiation period and CBCT and microscopic examinations on the maxillary bones and soft tissue were performed. RESULTS: According to the findings, the healing process was significantly different in two groups in terms of the percentage of new bone formation on day 14 after the end of radiation (P=0.014). The other measured parameters including the degree of inflammation, thickness of the formed bone, number of osteoblasts and Gray Scale had no significant difference between the two groups in any of the 14-day and 28-day intervals. CONCLUSIONS: The results of this study showed that intermittent exposure to high frequency electromagnetic fields over a period of 20 hours has no significant effect on the healing process of alveolar socket after tooth extraction in rats.

The effectiveness of the national hepatitis B vaccination program 25 years after its introduction in Iran: a historical cohort study.

INTRODUCTION: Hepatitis B virus (HBV) is responsible for one of the most common human viral infections. An estimated 257 million people are living with chronic HBV infection worldwide, and mortality has reached 900,000 deaths in recent years. In 2001, the World Health Organization reported a prevalence of chronic hepatitis B infection in Iran between 2-7%. OBJECTIVE: To assess the effect of the national HBV mass vaccination program after 25 years. METHODS: A retrospective cohort study was conducted in vaccinated and unvaccinated people according to the year of birth. Blood samples were obtained from each enrolled person and data about demographic variables, and medical and vaccination history were collected using a standardized questionnaire. Persons were considered uninfected if they were negative for both HBsAg and anti-HBc. Also, Vaccine effectiveness was measured by calculating the risk of disease among vaccinated and unvaccinated persons and defining the percentage risk reduction of infection in the vaccinated group. RESULTS: A total of 2720 persons were interviewed. The rate of HBV breakthrough infection among the vaccinated group was significantly lower than in unvaccinated group. One hundred ninety-four cases with positive HBV markers of infection were identified. The risk ratio of HBV infection was 0.71, 95% CI: 0.54-0.94 (vaccinated/unvaccinated). The estimated vaccination effectiveness against Hepatitis B infection was 29% (95% CI: 6%-46%). CONCLUSIONS: Iran has successfully combined hepatitis B vaccination into regular immunization programs. The WHO goal of reducing HBsAg prevalence to an equivalent of 1% by 2020 has been reached. With respect to vaccination effectiveness and low prevalence of the disease in the country, catch-up hepatitis B vaccination programs for adolescents can guarantee the immunity of the population.

Monitoring of Plasmodium infection in humans and potential vectors of malaria in a newly emerged focus in southern Iran.

Despite control programs, which aim to eliminate malaria from Iran by 2025, transmission of malaria has not been removed from the country. This study aimed to monitor malaria from asymptomatic parasitaemia and clinical cases from about one year of active case surveillance and potential vectors of malaria in the newly emerged focus of Mamasani and Rostam, southern Iran during 2014-2015. Samples were collected and their DNAs were extracted for Polymerase Chain Reaction (PCR) assay using specific primers for detection of Plasmodium species. The Annual Parasite Incidence rate (API) was three cases per 1,000 population from 2,000 individuals in three villages. Parasites species were detected in 9 out of the 4,000 blood smear samples among which, 6 cases were indigenous and had no history of travels to endemic areas of malaria. Also, the prevalence rate of asymptomatic parasites was about 0.3%. Overall, 1073 Anopheles spp. were caught from 9 villages. Totally, 512 female samples were checked by PCR, which indicated that none of them was infected with Plasmodium. Despite new malaria local transmission in humans in Mamasani and Rostam districts, no infection with Plasmodium was observed in Anopheles species. Because of neighboring of the studied area to the re-emerged focus in Fars province (Kazerun) and important endemic foci of malaria in other southern provinces, such as Hormozgan and Kerman, monitoring of the vectors and reservoir hosts of Plasmodium species would be unavoidable. Application of molecular methods, such as PCR, can simplify access to the highest level of accuracy in malaria researches.

The effectiveness of the national hepatitis B vaccination program 25 years after its introduction in Iran: a historical cohort study

ABSTRACT Introduction: Hepatitis B virus (HBV) is responsible for one of the most common human viral infections. An estimated 257 million people are living with chronic HBV infection worldwide, and mortality has reached 900,000 deaths in recent years. In 2001, the World Health Organization reported a prevalence of chronic hepatitis B infection in Iran between 2-7%. Objective: To assess the effect of the national HBV mass vaccination program after 25 years. Methods: A retrospective cohort study was conducted in vaccinated and unvaccinated people according to the year of birth. Blood samples were obtained from each enrolled person and data about demographic variables, and medical and vaccination history were collected using a standardized questionnaire. Persons were considered uninfected if they were negative for both HBsAg and anti-HBc. Also, Vaccine effectiveness was measured by calculating the risk of disease among vaccinated and unvaccinated persons and defining the percentage risk reduction of infection in the vaccinated group. Results: A total of 2720 persons were interviewed. The rate of HBV breakthrough infection among the vaccinated group was significantly lower than in unvaccinated group. One hundred ninety-four cases with positive HBV markers of infection were identified. The risk ratio of HBV infection was 0.71, 95% CI: 0.54-0.94 (vaccinated/unvaccinated). The estimated vaccination effectiveness against Hepatitis B infection was 29% (95% CI: 6%-46%). Conclusions: Iran has successfully combined hepatitis B vaccination into regular immunization programs. The WHO goal of reducing HBsAg prevalence to an equivalent of 1% by 2020 has been reached. With respect to vaccination effectiveness and low prevalence of the disease in the country, catch-up hepatitis B vaccination programs for adolescents can guarantee the immunity of the population.

Measles outbreak in South of iran, where vaccine coverage was high: a case-series study.

BACKGROUND: Measles is a highly contagious viral disease that remains an important cause of mortality among children despite the availability of a safe and effective vaccine around the world. We aimed this study to show a measles out-break occurring. METHODS: In early 2012, a report of measles outbreak was recorded on center for disease control (CDC) of Fars province, south of Iran. With this case-series study, characteristics of cases and network transition model were described. RESULTS: The primary case was an Afghan refugee who is likely to carry the measles virus from its country or from anywhere in Iran to Koordeh, a small village in south of Iran. Followed by the Afghan case, 6 secondary and tertiary cases including rural health worker, were occurred. Except a case of 35 year old, in which her vaccination status was unknown, all cases has had adherence to vaccination protocol. CONCLUSION: More immunologic and vaccine quality investigations are needed to find the main cause of the outbreak. Nonetheless, due to the warm weather, probable bad temperature management of cold chain and technical problem in vaccination are the main suspicious reasons of the outbreak.

Synthesis, characterization and structural determination of some nickel(II) complexes containing imido Schiff bases and substituted phosphine ligands.

Some new tridentate ONN Schiff base complexes of [NiL(PR3)] (where L=Salicylidene2-amino4-nitrobenzene (L(1)), 5-BrSalicylidene2-amino4-nitrobenzene (L(2)), 5-NO2Salicylidene2-amino4-nitrobenzene (L(3)), 5-MeOSalicylidene2-amino4-nitrobenzene (L(4)) and 3-MeOSalicylidene2-amino4-nitrobenzene (L(5)), R=Bu and Ph (with L(1))) were synthesised and characterized by IR, UV-Vis, (1)H NMR spectroscopy and elemental analysis. The geometry of [NiL(1)(PPh3)] was determined by X-ray crystallography. It indicated that the complex had a planar structure and four coordinates in the solid state. The thermogravimetry (TG) and differential thermoanalysis (DTA) of the synthesized complexes were carried out in the range of 20-600°C, leading to the decomposition of L(1)-L(3) type in three stages and of L(4)-L(5) and [NiL(1)(PPh3)] type in four stages. Thermal decomposition of the complexes was closely the dependent upon the nature of the Schiff base ligands and proceeded via the first order kinetics.

High titers of hemagglutination inhibition antibodies against 2009 H1N1 influenza virus in Southern Iran.

BACKGROUND: Pandemic flu had at least two waves in Iran. Knowing how many of the general population were already exposed to this infection has a major impact on national preventive measures. As of December 30, 2009, a total of 3672 confirmed cases of human infection with a novel Influenza A (2009 H1N1) virus had been reported in Iran with 140 deaths. OBJECTIVE: In this study we aim to measure, as a pilot study, the seroprevalence of positive antibody titer (humoral immunity) against 2009 H1N1 virus in Iranian population in Shiraz, Southern Iran. METHODS: Through cluster random sampling of families residing in Shiraz, 2553 subjects were selected and after a medical interview blood samples were taken and checked for polyclonal antibody against 2009 H1N1 antigen using hemagglutination inhibition assay. An antibody titer of more than 1:40 dilution was considered positive. Data were analyzed considering the demographic characteristics of the population and were compared among different age groups. RESULTS: 1504 (58.91%) samples were tested positive for the presence of polyclonal antibody against 2009 H1N1 virus. The prevalence of positive titers were significantly higher in 60 to 64 years old group and significantly lower in 20 to 24 years old group (p<0.05). Data did not differ based on other demographic characteristics or the history of flu like illnesses in the past 6 months. CONCLUSION: High seroprevalence of antibody against 2009 H1N1 in the sera of our subjects describes either a high level of pre-existing immunity against H1N1 in Iranian population or a high rate of asymptomatic infection in our area compared to other countries.