Non-effectiveness of Ivermectin on Inpatients and Outpatients With COVID-19; Results of Two Randomized, Double-Blinded, Placebo-Controlled Clinical Trials.

Background: Ivermectin which was widely considered as a potential treatment for COVID-19, showed uncertain clinical benefit in many clinical trials. Performing large-scale clinical trials to evaluate the effectiveness of this drug in the midst of the pandemic, while difficult, has been urgently needed. Methods: We performed two large multicenter randomized, double-blind, placebo-controlled clinical trials evaluating the effectiveness of ivermectin in treating inpatients and outpatients with COVID-19 infection. The intervention group received ivermectin, 0.4mg/kg of body weight per day for 3 days. In the control group, placebo tablets were used for 3 days. Results: Data for 609 inpatients and 549 outpatients were analyzed. In hospitalized patients, complete recovery was significantly higher in the ivermectin group (37%) compared to placebo group (28%; RR, 1.32 [95% CI, 1.04-1.66]; p-value = 0.02). On the other hand, the length of hospital stay was significantly longer in the ivermectin group with a mean of 7.98 ± 4.4 days compared to the placebo receiving group with a mean of 7.16 ± 3.2 days (RR, 0.80 [95% CI, 0.15-1.45]; p-value = 0.02). In outpatients, the mean duration of fever was significantly shorter (2.02 ± 0.11 days) in the ivermectin group versus (2.41 ± 0.13 days) placebo group with p value = 0.020. On the day seventh of treatment, fever (p-value = 0.040), cough (p-value = 0.019), and weakness (p-value = 0.002) were significantly higher in the placebo group compared to the ivermectin group. Among all outpatients, 7% in ivermectin group and 5% in placebo group needed to be hospitalized (RR, 1.36 [95% CI, 0.65-2.84]; p-value = 0.41). Also, the result of RT-PCR on day five after treatment was negative for 26% of patients in the ivermectin group versus 32% in the placebo group (RR, 0.81 [95% CI, 0.60-1.09]; p-value = 0.16). Conclusion: Our data showed, ivermectin, compared with placebo, did not have a significant potential effect on clinical improvement, reduced admission in ICU, need for invasive ventilation, and death in hospitalized patients; likewise, no evidence was found to support the prescription of ivermectin on recovery, reduced hospitalization and increased negative RT-PCR assay for SARS-CoV-2 5 days after treatment in outpatients. Our findings do not support the use of ivermectin to treat mild to severe forms of COVID-19. Clinical Trial Registration: www.irct.ir IRCT20111224008507N5 and IRCT20111224008507N4.

Seroepidemiology of HBV, HCV, HIV, HTLV, and CMV in Pregnant Women Referring to Sari Birth Cohort.

Background: Congenital infections are among the most important conditions threatening human fetal health, the majority of which are caused by viral agents. Screening pregnant women for viral infections is essential because such infections can cause serious consequences for both the mother and the infant. So, this study aimed to serologically investigate sexually transmitted viral infections in pregnant women and also find the association between the prevalence of viral infections and epidemiological parameters in pregnant women of Sari, Iran. Materials and Methods: This descriptive, observational study was performed in pregnant women referring to Sari Birth Cohort Center between 2018 and 2020. A total of 1092 blood samples were investigated for hepatitis B (HBV), hepatitis C (HCV), human immunodeficiency virus (HIV), human T-lymphotropic virus (HTLV), and cytomegalovirus (CMV) serological markers by enzyme-linked immunosorbent assay (ELISA). Results: The prevalence of HBsAg positivity, HCV, HIV, and HTLV was 0.2%, 0.09%, 0.09%, and 0.2%, respectively. The percentage of participants with CMV-IgM and -IgG antibody titers above normal was 0.2% and 91.8%, respectively. Pregnant women whose educational level was bachelor's degree or lower, those who did not use a male condom before pregnancy, or those with a family history of infectious disease were found to be more likely to have HBV, HCV, HIV, HTLV, and CMV infections. Conclusion: Family history, maternal age, pregnancy stage, and not using a male condom are among the risk factors for sexually transmitted viral infections in pregnant women in Sari.

Immunogenicity and Complications of the Pentavalent Vaccine in Iranian Children.

Objective: Vaccination is one of the most convenient and safe preventive care measures available for children. The Pentavalent vaccine which protects against five major infections including diphtheria, tetanus, pertussis, hepatitis B(HepB) and Haemophilus influenzae type b(Hib) was added to the Iranian national immunization program in November 2014. This study aimed to determine the Pentavalent vaccine adverse events and immunogenicity in an Iranian children population in Sari, northern Iran. Method: In this descriptive-analytical study, children who were vaccinated with three doses of the Pentavalent vaccine were studied. Two venous blood samples were obtained before the first dose and 4 weeks following the last booster dose. Possible local and systemic complications of the vaccine were recorded until 7 days following vaccination. Antibody titers were measured by quantitative ELISA kits and geometric mean titer(GMT) was calculated for each vaccine component before and after 3 doses of vaccine. Statistical analysis was performed by SPSS 20.0 software and Chi-square and Fisher's exact tests were used for analysis. Results: Immunogenicity of the Pentavalent vaccine for tetanus was 100%(GMT:2.52 Eu/mL, 95%CI: 2.22-2.88), Hib 98.7%(GMT:2.44 Eu/mL, 95%CI: 2.06-2.89), HepB 98.7%(GMT:153.54 Eu/mL, 95%CI: 133.73-176.29), diphtheria 93.1%(GMT:0.43 Eu/mL, 95%CI:0.37-0.51) and pertussis were 63.7% (GMT:19.44 Eu/mL, 95%CI:16.42-23.03). The most common systemic complication after vaccination was fever. Also, one infant cried for more than 3 hours after the second dose. Other serious side effects were not observed. Conclusion: The Pentavalent vaccine used in Iran can cause adequate antibody response against diphtheria, tetanus, pertussis, Hib and hepatitis B in most cases with minimal side effects. The immunogenicity of this vaccine is significantly lower for pertussis. In this study, no severe complication leading to contraindication to subsequent injections was reported. So, the present policy in replacing triple DTP vaccine with Pentavalent vaccine should be continued in Iran.

Comparing Watchful Waiting Approach vs. Antibiotic Therapy in Children with Nonsevere Acute Otitis Media: A Randomized Clinical Trial.

OBJECTIVE: To compare both approaches for the treatment of nonsevere acute otitis media (AOM) in Iran. METHODS: This randomized clinical trial was performed at a pediatric infectious diseases clinic in Buali tertiary hospital in Sari, north of Iran, from 2016 to 2018. All participants in this study were previously healthy children with AOM diagnosis, who were 6 months to 6 years old. The patients were randomly assigned into two groups: the intervention (80 mg/kg/day amoxicillin for 7-10 days) and the control group (watchful waiting approach). AOM recovery and adverse drug reactions were evaluated after 72 hours, and the patients were followed for the frequency of AOM and middle ear effusion 1 and 3 months' postintervention. RESULTS: A total of 396 children have participated in this study. AOM recovery was significantly different in the two groups (73% vs. 44% in the intervention and control groups, respectively). Recurrence of AOM and middle ear effusion (MEE) persistence, one month following the intervention, have not shown any significant differences between the two groups. However, the AOM recurrence between 1 and 3 months was more frequent in the control group. The frequency of diarrhea was also higher in the intervention group compared to the control but no significant difference was found between the two groups regarding vomiting and skin rash. CONCLUSION: The faster recovery from AOM is achieved when an antibiotic treatment regimen is applied, although the risk of potential side effects should be considered.