[Review of current and future directions of antiviral therapy of influenza and acute respiratory viral infections in Russia].

AIM: to determine the perspectives for the use of drugs with combined antiviral, anti - inflammatory and immunomodulatory activity on the basis of medical studies of existing antiviral drugs for the treatment of influenza and acute respiratory viral infections in Russia. MATERIALS AND METHODS: A brief review of the antiviral drugs used in Russia for the treatment of influenza and acute respiratory viral infections was conducted on the basis of 37 articles published in Scopus, Web of Science (WoS), and RSCI databases in the period from 1997 to 2018. RESULTS: Resistance to neuraminidase inhibitors (oseltamivir, zanamivir), is slowly developing due to the mutations of the neuraminidase gene H275Y and Q136K. Most influenza A viruses remain resistant to adamantane antivirals. Repeated use of immunomodulators with indirect antiviral action leads to a hyporeactivity of the immune system and, subsequently, to a decrease in their effectiveness. Positive clinical and laboratory data in clinical trials were obtained using Enisamium iodide, a drug with combined action - direct antiviral, and immunomodulatory. CONCLUSION: According to the WHO strategy, the results of the review demonstrate the need for continued research of medications with combined antiviral and pathogenetic effects on the infectious process caused by influenza and acute respiratory viral infections.

Clinical efficacy of umifenovir in influenza and ARVI (study ARBITR).

AIM: The aim of the study is to obtain additional data on safety and therapeutic efficacy of the antiviral drug Arbidol (umifenovir) in patients with a diagnosis of influenza and common cold. MATERIALS AND METHODS: Double-blind, randomized, placebo-controlled clinical study investigating efficacy and safety of Arbidol (umifenovir) in Treatment and Prophylaxis of Influenza and Common Cold (ARBITR) IV phase started in November 2011 and completed in April 2016 on the basis of 15 research centers in various regions of the Russian Federation. A total of 359 patients, aged 18 to 65 years with influenza or acute respiratory tract infection, of no more than 36 hours' duration were enrolled in the study. Patients were randomized into two groups: a group of patients (therapy group) treated by Arbidol (umifenovir) at a dosage of 800 mg/day (2 capsules) for 5 days (n=181), and a group of patients receiving placebo 4 times a day for 5 days (n=178). The primary outcome measures of the study were the duration of clinical illness among patients with common cold and influenza/ARVI, the duration and severity of the main symptoms. Number of clinical complications associated with influenza and common cold was assessed as a secondary outcome. Safety was assessed by analyzing number of adverse events that are probably or definitely related to Arbidol, assessing vital signs, examining the physical condition of patients and general clinical laboratory parameters. RESULTS: In the group treated by umifenovir, the number of full recover patients on the 4th day from the disease onset were significantly differed from the number of such cases in the placebo group. The number of cases of complete recovery after 96 hours was 98 patients (54.1%) and 77 (43.3%), p<0.05, and after 108 hours - 117 (64.6%) and 98 (55.1%), p<0.05. Duration of intoxication was reduced with umifenovir compared to placebo, amounted to 77.76 and 88.91 hours, respectively, p=0.013. The duration of all intoxication syndrome symptoms was also lower in the group receiving umifenovir. Thus, in the therapy group and placebo group, these parameters were respectively: fever duration - 67.96 and 75.32 hours (p=0.037), muscle pain - 52.23 and 59.08 hours (p=0.023), headache - 52.78 and 63.28 hours (p=0.013), weakness - 76.90 and 88.89 hours (p=0.008). The incidence of complications in the umifenovir group was 3.8%, in the placebo group 5.62%. Cases of acute tracheobronchitis was an increase in the placebo group (p<0.02). Umifenovir and placebo were well tolerated. A total of 42 cases of adverse events were registered in 11 patients in the treatment group and in 18 patients in the placebo group, which were not associated with umifenovir or placebo. CONCLUSION: The results of this study indicate umifenovir safety and confirm its effectiveness to the treatment of influenza and other acute respiratory viral infections in adult patients. It was found that effect of umifenovir in the treatment of influenza in adults is most pronounced in the acute stage of the disease and appears in the reduction of time to resolution of all symptoms of the disease, reducing the severity of symptoms of the disease.

[Substantion of the reference Values of SCFA in saliva in ratients without upper respiratory tract diseases.]

Biochemical indicators of saliva were studied in 47 patients of the intensive care unit and intensive care unit of a neurosurgical hospital with varying degrees of severity of the disease. The method of gas-liquid chromatography of the acidified substrate of the saliva filtrate determined the concentrations of short-chain fatty acids (SCFA) and their reference values for patients without respiratory tract diseases. The threshold values of the concentrations of SCFA and the values of their calculated indices were determined by ROC analysis with the construction of the ROC curve, calculation of the area under the curve (AUC) and the cutoff threshold CutOff. The method of determining reference values of HFA in saliva developed as a result of the study makes it possible to assess the risks of developing an unfavorable course of the disease, optimize treatment tactics and improve the prognosis of the disease.

[Pharmacoepidemiological study of the course of influenza and other acute respiratory viral infections in risk groups]. / Farmakoépidemiologicheskoe issledovanie techeniia grippa i drugikh ORVI v gruppakh riska.

AIM: To identify risk factors (RFs) for the development of bacterial complications and the prolonged course of influenza and other acute respiratory viral infections (ARVIs) among inpatients treated in Russian healthcare facilities in the post-pandemic period; to determine the clinical presentation of the disease (flu-like syndrome) in risk-group people and to evaluate the efficacy of antiviral therapy with arbidol (umifenovir). MATERIAL AND METHODS: The investigators retrospectively analyzed randomly selected medical records of inpatients with influenza and other ARVI in 88 hospitals from 50 regions of the Russian Federation: those of 3532 and 1755 patients in the 2010-2011 and 2014-2015 seasons, respectively, by applying parametric and nonparametric statistical methods. RESULTS: The built database of patients with influenza-like syndrome contained data from the histories of 2072 men and 2537 women, of whom there were 317 (12.49%) pregnant women; gender evidence was not given in the medical records for 678 patients. 382 (7.2%) were vaccinated against influenza. 1528 (28.9%) people were admitted to hospital with various complications. Information on laboratory tests was available in 1691 (31.98%) patients; of these, 1291 (76.4%) were detected to have influenza and other respiratory viruses. Influenza viruses were found in 1026 (60.7%) examinees; influenza A viruses in 712 (42.1%) people while pandemic strain of swine influenza A/H1N1 and A/H3N2 viruses was detected in 487 (28.8%) and 107 (6.3%) patients, respectively; influenza A subtype was indicated in 118 (7%) persons with laboratory-confirmed influenza virus. Influenza B viruses were found in 314 (18.6%) examinees. Other types of respiratory viruses were detected in 265 (15.7%) patients. The body mass index exceeded 30 kg/m2 in 227 (4.3%) patients. Single-factor analysis of variance revealed factors influencing the course of flu-like syndrome and identified risk groups: children younger than 2 years old and adults over 65, pregnant women, and people with chronic somatic diseases and obesity. The high-risk groups exhibited a more severe course of flu-like syndrome than did the patients outside the risk groups. The incidence of complications was higher, especially in the under 2-year-year-old children and in patients with endocrine, metabolic, or respiratory diseases, with a large proportion of complications being pneumonia. The efficacy of antiviral therapy was higher in the elderly, patients with chronic diseases, and pregnant women than in patients not at risk. In patients treated with umifenovir (provided that it was administered in the first 48 hours after disease onset), the duration of fever and frequency of complications proved to be lower than those in patients who did not receive antiviral therapy. CONCLUSION: The FRs for influenza and ARVI complications are patient's age (children under 3 years of age and adults older than 65 years), the presence of chronic somatic diseases, and pregnancy. Patients with endocrine, eating, metabolic (including obesity), circulatory, and respiratory disorders are at high risk for influenza and ARVI complications. Umifenovir therapy substantially reduces the duration of fever and risk of complications, especially in patients with laboratory-confirmed influenza infection.

[Clinical efficacy of arbidol (umifenovir) in the therapy of influenza in adults: preliminary results of the multicenter double-blind randomized placebo-controlled study ARBITR].

AIM: To evaluate the efficacy and safety of Arbidol (umifenovir) in adult patients with influenza. SUBJECTS AND METHODS: The analysis of the preliminary results of the multicenter double-blind randomized placebo-controlled post-marketing study ARBITR was performed. A total of 293 adults aged 18 to 65 years with influenza or acute respiratory tract infection of no more than 36 hours' duration were enrolled in the study. Individuals were randomized into 2 treatment groups: oral umifenovir 200 mg four times daily for 5 days or placebo four times daily for 5 days. The efficacy endpoints were time to resolution of all symptoms, severity of symptoms and illness, durations of virus shedding. RESULTS: The efficacy of umifenovir was evaluated in the group of 119 (40.6%) patients with influenza: 45 patients with laboratory-confirmed influenza and 74 patients whom diagnosis of influenza was made based on clinical and epidemiological data. Umifenovir had influence on the time to resolution of all symptoms. All symptoms were resolved within the first 60 hours after therapy initiation in 23.8% patients with laboratory-confirmed influenza in the umifenovir group and it was 5.7 times greater compared to placebo group (4.2%) (p < 0.05). Severity of illness, catarrhal symptoms and intoxication was reduced with umifenovir compared to placebo, reducing of severity was most evidently observed within the first 2-3 days following the therapy initiation. Umifenovir had a significant effect on viral shedding. The proportion of patients still shedding influenza virus on day 4 was significantly reduced in the umifenovir group compared to placebo (25 vs 53%, respectively; p < 0.05). CONCLUSION: It was found that the effect of umifenovir in the treatment of influenza in adults is most pronounced in the acute stage of the disease and appears in the reduction of time to resolution of all symptoms of the disease, reducing the severity of symptoms of the disease and durations of virus shedding.

Virus susceptibility and clinical effectiveness of anti-influenza drugs during the 2010-2011 influenza season in Russia.

BACKGROUND: Antiviral drugs are critical adjuncts to influenza vaccination. This study determined the in vitro susceptibilities of influenza A and B viruses isolated in the 2010-2011 season in Russia to the neuraminidase inhibitor oseltamivir and the hemagglutinin fusion inhibitor umifenovir and clinical efficacy of this antiviral drugs in this season. METHODS: The antiviral potency of these drugs against A(H1N1)pdm09 virus in mice was assessed. Importantly, the clinical effectiveness of oseltamivir and umifenovir was evaluated in a retrospective study conducted in 26 regions of Russia. RESULTS: All tested viruses (n=36) were susceptible to oseltamivir and umifenovir in vitro. Oseltamivir (10mg/kg/day) and umifenovir (60 mg/kg/day) significantly increased the survival of mice challenged with A/California/04/2009 (H1N1)pdm09 virus (p<0.05). Influenza infection was laboratory-confirmed in 442 patients among 1462 patients hospitalized with acute respiratory infections. The treatment of influenza-infected patients within 48h of symptom onset with oseltamivir and umifenovir was associated with a significant decrease in the duration of illness (2-3 days) and symptoms (p<0.001). Pneumonia was observed in none of the patients treated with oseltamivir and in 0.3% of the patients treated with umifenovir, compared to 23.7% of patients who did not receive antiviral therapy (p<0.001). CONCLUSIONS: This study provided experimental and clinical evidence of the efficacy of oseltamivir and umifenovir against influenza viruses, representatives of which have continued to circulate in post-pandemic seasons.

[Evaluation of amixine reactivity and efficacy for prophylaxis of acute respiratory tract infections]. / Otsenka reactogennykh svoistv amikcina i ego c'ffektivnosti pri profilaktike ostrykh infektsii respiratornogo trakta.

Amixine reactivity and tolerability were evaluated in controlled trial at the risk group of medical personal at the period of flu and respiratory viral infection season. Drugs safety was estimated according to anamnesis, direct observation and hemogram. High efficacy of the drug for the infections prophylaxis and treatment was demonstrated. The drug was well tolerated and had no side effects. Amixine unreactivity was proved.