Efficacy and safety of using Anaferon for children and Anaferon for the prevention and treatment of influenza and other acute respiratory viral infections: a systematic review and meta-analysis

Introduction

The high prevalence of acute respiratory viral infection (ARVI) in adult and pediatric populations makes it important to choose an effective and safe drug for its prevention and treatment [1].
In the absence of a unified approach to drug therapy and prevention of ARVI in the world and even in different academic schools within the same country, it seems optimal to select therapy from the standpoint of evidence-based medicine. A universal tool for assessing the weight of evidence for the effectiveness and safety of a drug is a systematic review with meta-analysis. It is this option, in contrast to a classic review article, which often reflects to a greater extent the opinion of the authors, that allows the most complete and reliable assessment of methodological, statistical and evidentiary aspects, including the risk of systematic errors. An optional, but widespread and recommended approach when conducting systematic reviews and meta-analyses is the use of the PRISMA statement (Preferred reporting items for systematic reviews and meta-analyses), updated in 2021 and involving synthesis and analysis data from randomized clinical trials (RCTs) [2]. In routine therapeutic and pediatric practice, verification of the pathogen for each episode of acute respiratory viral infection is not carried out, therefore drugs with a broad spectrum of antiviral action are most convenient. Among the many medicines, noteworthy are domestic drugs based on technologically processed (high dilutions) affinity purified antibodies (TO AT) to interferon (IFN) γ - Anaferon (OOO NPF Materia Medica Holding, Russia), used in therapeutic practice more than 15 years in patients over 18 years of age, and Anaferon for children (LLC NPF Materia Medica Holding, Russia), actively used in children aged 1 month. for more than 20 years in lozenges, and over the past 5 years - in drops for oral administration in patients from 1 month. up to 3 years inclusive [3–5]. It is worth noting that many years of experience in the use of drugs based on TOAbs to IFN-γ has been accumulated not only in Russia, but also in the CIS countries, Southeast Asia, and Mexico.

When used prophylactically and therapeutically, the drugs have immunomodulatory and antiviral effects [3–5]. Anaferon and Anaferon for children are regulatory-type drugs - they are able to target the immunopathogenesis of ARVI, regardless of the etiology. The universality of the immune-mediated antiviral effect in acute respiratory viral infections of Anaferon and Anaferon for children is realized due to the influence on IFN-γ with the subsequent involvement in the mechanism of action of the IFN system and associated cytokines to optimize the response of the immune system to viral aggression [3–7].

The effectiveness of Anaferon and Anaferon for children for the treatment and prevention of acute respiratory viral infections with a favorable safety profile has been demonstrated in clinical trials (CTs), including double-blind, placebo-controlled RCTs, involving more than 8,500 patients [8–24]. Despite the extensive evidence base of the effectiveness and safety of Anaferon and Anaferon for children in acute respiratory viral infections/influenza, a generalized analysis of the results of RCTs on drugs has not previously been carried out.

Purpose of the study:

assessment of the effectiveness and safety of the use of drugs Anaferon and Anaferon for children for the prevention and treatment of acute respiratory viral infections using meta-analysis.

The main clinical questions that were answered during the review and meta-analysis are whether Anaferon for children is effective and safe for the treatment of ARVI/influenza, and whether the use of Anaferon and Anaferon for children is effective and safe for the prevention of ARVI/influenza.

Material and methods

Data search and selection strategy

A search for information about CI in open sources (on the Internet, medical library) was carried out using the keywords “Anaferon” and “Anaferon for children.” The searches were not restricted by language, date, or publication status. The information search strategy included access to official websites - domestic and foreign CT registries and databases, electronic libraries, including: State Register of Medicines (grls.ru); US National Library of Medicine ClinicalTrials.gov (clintrials.gov); International Clinical Trials Registry Platform (ICTRP) WHO (www.who.int/ictrp/search/en), PubMed, EMBASE, MEDLINE, Cochrane Library, scientific electronic library eLIBRARY.RU, Russian Scientific Electronic Library CyberLeninka (cyberleninka.ru). To increase the representativeness of data on efficacy and safety (obtaining information as part of pharmacovigilance), reports on the results of clinical trials were requested from the manufacturer.

Criteria for selecting CTs for inclusion in meta-analysis:

study design: prospective RCT;

RCT participants:

male and female patients aged from 1 month. with a diagnosis of ARVI/influenza/ARI (acute respiratory infection of viral origin) for Anaferon for children according to the indication “treatment of ARVI/influenza”;

male and female patients aged from 1 month. for Anaferon for children and from 18 years of age for Anaferon for the indication “prevention of ARVI/flu”;

the use of the drugs Anaferon and Anaferon for children in RCTs for the prevention and/or treatment of ARVI/influenza according to the instructions for their medical use [3–5];

using the duration of the disease and/or the duration of the febrile period as one of the end points/efficacy criteria in RCTs studying the therapeutic effectiveness of Anaferon for children in ARVI/influenza;

use as one of the end points in an RCT to study the preventive effectiveness of Anaferon and Anaferon for children against ARVI/influenza of the proportion of non-sick/sick patients.

RCTs that did not meet the inclusion criteria, duplicate publications of RCT results, and studies with insufficient data for statistical analysis were not included in the meta-analysis. A risk of bias analysis was performed to assess the methodological quality of the RCTs. In accordance with Cochrane guidelines, the following criteria were considered: method of randomization, presence and type of blinding of the study, compliance of results with endpoints/efficacy criteria and completeness of reporting of results, followed by assessment of the risk of bias in the study as a whole as low, moderate, high and uncertain [ 26, 27].

This review includes:

meta-analysis of the therapeutic effectiveness of Anaferon for children in acute respiratory viral infections/influenza/ARI based on the end points “duration of the disease” and “duration of fever”. Additionally, the effect of the drug on the duration of intoxication, catarrhal symptoms (rhinitis and cough) and the dynamics of the level of IFN-γ and IFN-α was assessed;

meta-analysis of the preventive effectiveness of Anaferon and Anaferon for children against ARVI/influenza based on the end point “proportion of disease-free patients” with calculation of the effectiveness coefficient (EC) of the drug.

The safety of therapy was assessed taking into account the number and nature of adverse events (AEs), their relationship with taking the drug, and deviations in laboratory and vital signs while taking the drugs.

The review used modified/adapted elements from the PRISMA 2021 Checklist and PRISMA 2021 flow diagram for new systematic reviews, including searches of databases, registries and other sources [2, 25].

Statistical methodology

Descriptive statistics methods were used for preliminary statistical processing of data. Comparisons of continuous measures (duration of symptoms) between individual studies were made using Student's t test. When performing a meta-analysis of continuous indicators using pooled estimates of means and standard deviations, a Z-test was used to calculate the weighted average effect size of Hedges' g, construct a 95% confidence interval (CI) for it, and calculate a p-value to accept/reject the hypothesis that the effect was equal to zero . The 95% CI was calculated using two approaches: without taking into account the heterogeneity of results (fixed effects model, FEM) and taking this into account (random effects model, RFE). Cochran's Q statistics were also calculated, which allows us to evaluate the degree of homogeneity of study results using statistical hypothesis testing. Fisher's exact test was used to assess differences in frequencies between individual studies; to evaluate cumulative frequency data, use the Cochran-Mantel-Haenszel (CMH) test.

When analyzing preventive effectiveness, relative risk (RR) and odds ratio (OR) indicators were calculated to compare the proportion of disease-free patients. The results are presented in the form of individual and pooled indicators (OR and RR), as well as the corresponding 95% CI (drug/placebo or drug/comparison group). Data homogeneity was assessed when calculating frequency indicators using the Breslow-Day Test.

FE (%) was also calculated using the formula:

KE=100 × (b - a) / b,

where a is the incidence among individuals who received the drug, b is the incidence among individuals who did not receive the drug.

Research results

Study selection

1297 publications were found in open sources using keywords, 2 publications in printed form, an additional 3 reports on clinical trials were provided by the sponsoring company. The meta-analysis included data from 11 RCTs (Fig. 1).

Assessing the risk of bias in studies

Data for assessing the risk of bias/bias in studies are presented in Table 1.

The randomization method was described in only 4 RCTs, allocation concealment was provided in 3 RCTs, where the randomization procedure was carried out using an automated interactive voice system, using a floating block method, randomizing patients into 2 groups. Also, in these RCTs, the quantity of study drug supplied to the study sites exceeded the number of planned participants, which further masked the allocation, since the researchers could not know in advance which of the 2 groups each individual patient would be allocated to. Nine studies were double-blinded (RCTs 1–9), 2 RCTs were open-label. All RCTs reported results according to their stated efficacy criteria. In general, the design of all studies included in the meta-analysis corresponded to the stated objectives, and the risk of bias according to the criteria considered could be assessed as low (RCTs 1, 2, 9), moderate (RCTs 5, 6) and uncertain (RCTs 3, 4, 7 , 8, 10, 11) [27]. The results of the risk of bias assessment as “uncertain” in RCTs 3, 4, 7, 8 relate mainly to the reporting of the study design: lack of detailed information on the method of randomization and allocation concealment, and in RCT 10 and RCT 11 on the method of blinding.

Brief description of studies included in the meta-analysis

The meta-analysis included data from 11 RCTs involving 3079 patients aged 1 month or older. up to 69 years of age, of which 1729 people participated in studies of the preventive effectiveness of drugs based on TO antibodies to IFN-γ and 1550 patients - the therapeutic effectiveness of these drugs. Nine RCTs were double-blind, placebo-controlled, and 2 RCTs were open-label. All studies were prospective, parallel group studies. Four studies (RCTs 1, 2, 4, 9) were multicenter, 2 of them were international: RCT 1 was conducted in 3 countries (Russian Federation (RF), Republic of Belarus and Ukraine), RCT 9 - in 2 countries (RF, Republic of Uzbekistan) (Table 2).

In RCTs 1, 3–11, the tablet form of the drugs Anaferon and Anaferon for children was used, in RCT 2, the liquid dosage form of Anaferon for children was used. The dosage regimen of the drugs in the RCT corresponded to the current instructions for their medical use: 1 tablet was recommended per dose (or 10 drops for RCT 2) [3–5]. Despite the differences in the dosage form of the drug and the target age audience, the specific mechanism of action of drugs based on TOAT to IFN-γ avoids the need to select an individual dosage regimen depending on the age and body weight of the patient. For therapeutic purposes, in RCTs 1–7, drugs were used in the first 2 hours every 30 minutes (5 doses in total), then during the first 24 hours - 3 more doses at regular intervals. From 2 days onwards until recovery (or 5–14 days depending on the severity of clinical symptoms) / up to 5 days in RCT 2 - 1 tablet or 10 drops 3 times a day. For prophylactic purposes in RCTs 5, 8–11, drugs were used 1 tablet 1 time per day for 3 months/12 weeks.

Of the 11 studies included in the meta-analysis, 2 RCTs were conducted in patients with ARI, 1 RCT - in patients with influenza, 6 RCTs assessed the effectiveness and safety of drugs based on TO antibodies to IFN-γ in relation to ARVI/influenza, and 2 studies - in ARI/ARVI with gastrointestinal syndrome (GIS), one of which included patients only with coronavirus etiology of the disease (Table 3).

In 6 RCTs involving 2143 patients, the pathogen was verified (PCR diagnostics, enzyme-linked immunosorbent assay, immunofluorescence, indirect hemagglutination test and transmission electron microscopy) [8, 10, 12, 15–17]. Among the pathogens of ARVI, influenza viruses predominated in RCTs 1 and 3, adeno-, rota-, and coronaviruses predominated in RCT 6, coronaviruses in RCT 7, rhinovirus and respiratory syncytial (RS) virus in RCTs 8 and 9. In RCT 9, episodes of coronavirus and bocavirus infections were noted only in the group of patients receiving placebo [8]. 4 studies involving 903 patients assessed the dynamics of viral load/clearance of the pathogen, 2 other RCTs were devoted to assessing the preventive effect of the drug, and this parameter was not assessed in them. In the remaining RCTs, diagnosis was made based on clinical findings.

A number of RCTs were devoted to studying the effect of drugs based on TO Abs to IFN-γ in special groups of patients. Thus, in RCT 5 and RCT 11, the preventive and therapeutic effectiveness of Anaferon and Anaferon for children, respectively, was assessed in individuals with chronic respiratory diseases. RCT 5 included patients with mild or moderate bronchial asthma (BA), and RCT 11 included patients with bronchopulmonary pathology (BA, chronic bronchitis, chronic obstructive pulmonary disease) [14, 19]. More than 45% of patients included in RCT 8, dedicated to assessing the preventive effectiveness of Anaferon for children, belonged to the group of frequently ill children (FIC) [17].

In addition to disease duration (RCTs 1–3, 5–7), duration of fever (RCTs 2–7) and proportion of disease-free patients (RCTs 5, 8–11), duration of intoxication (RCTs 3–7) was used as endpoints. the average duration of an ARVI/flu episode when it occurs against the background of prophylactic administration of the study drugs (RCTs 8, 10, 11) and a number of other parameters (Table 4).

In RCTs 8 and 10, the EC of the drug was calculated for influenza and ARVI [17, 18].

Security assessment

AEs were most often assessed as safety criteria (see Table 4). The total number of reported AEs was 114 when taking drugs based on TOAB to IFN-γ and 117 when taking placebo. In RCTs 1, 2, 8 and 9, there were no statistically significant differences between the study drug group and the placebo group in terms of AEs [8–10, 17]. In the remaining RCTs, no AEs were registered while taking Anaferon and Anaferon for children. During the generalized safety assessment, it was found that from the moment of registration of the drugs to May 2021, a total of 156 AEs and adverse reactions (ARs) were identified. Most of the pediatric AEs/AEs recorded during the use of the drugs Anaferon and Anaferon are manifestations of increased individual sensitivity, information about the possibility of which is contained in the instructions for medical use of the drugs [3–5]. The remaining AEs/AEs are isolated, belong to different classes of MedDRA (Medical Dictionary for Regulatory Activities) systems and organs, and have a low level of cause-and-effect relationship with the drug. Over the entire period of circulation of drugs on the market, no safety signals or other safety problems have been identified in connection with drugs based on TOABs to IFN-γ; the benefit/risk ratio for the drugs remains positive.

Results of a meta-analysis of RCTs of the effectiveness of Anaferon for children in the treatment of ARVI/influenza

A meta-analysis of the effectiveness of Anaferon for children for the treatment of ARVI/influenza was carried out based on data from 7 double-blind, placebo-controlled RCTs (RCTs 1–7) involving 1550 patients aged 1 month or older. Patients were included in RCTs 1, 2, 5 in the first 24 hours from the onset of the disease, in RCT 3 and RCT 4 - on days 1–2, and no data were found for RCT 6 and RCT 7. In all RCTs, Anaferon for children and placebo were used against the background of standard therapy for ARVI, which included taking antipyretic drugs.

To analyze the “disease duration” indicator, data from 1245 patients from 6 RCTs (RCTs 1–3, 5–7) were taken, and “fever duration” — data from 981 patients from 6 RCTs (RCTs 2–7). Additionally, the criteria “duration of intoxication” (RCTs 3–7), “duration of rhinitis” and “duration of cough” (RCTs 3–5, 7) were assessed.

On average, the duration of ARVI/flu when taking Anaferon for children was 1.4 times shorter than when taking placebo, and was 4.71±2.53 days versus 6.37±6.23 days (p<0.001). The average duration of fever when taking Anaferon for children was 2.19±1.21 days versus 3.22±1.81 days with placebo (p<0.001). The average duration of intoxication in all studies was 2.76±1.28 days in the Anaferon children's group versus 4.23±3.14 days in the placebo group, rhinitis - 3.87±1.44 days and 5.12±2.73 days, cough - 3.71±3.10 days and 7.02±6.33 days, respectively (p<0.001).

Despite the heterogeneity of data on the criteria under consideration when testing for homogeneity and the preference for using MFE for all criteria, except for the “duration of cough” criterion, for completeness, the results obtained using MFE are given below (Table 5).

According to the results of the meta-analysis, Anaferon for children demonstrated a significant superiority in the effect on the duration of ARVI/influenza and febrile syndrome over placebo in the form of a significant reduction in the duration of both the disease and febrile syndrome. The effect size, which reflects the comparative effect normalized by the standard error of the data, according to the disease duration criterion, was largest in RCT 7 and RCT 6, 2.63 and 1.88, respectively, and smallest in RCT 1 (Fig. 2A). Effect sizes for duration of fever were largest in RCTs 3, 6, and 7, at 1.52, 1.38, and 1.27, respectively, and smallest in RCT 2 (Figure 2B).

When assessing additional effectiveness criteria, a significant advantage was shown in the use of Anaferon for children in the treatment of ARVI/influenza for faster relief of both intoxication symptoms with a maximum effect size in RCTs 6 and 7, and catarrhal syndrome (rhinitis and cough) with a maximum effect size in RCT 7 ( Table 6).

Thus, in the course of a meta-analysis of the therapeutic effectiveness of Anaferon for children in acute respiratory viral infections/influenza, convincing evidence was obtained of higher effectiveness compared to placebo according to all criteria considered.

Interferon status was analyzed separately according to 334 patients from 3 studies (RCTs 3, 6, 7). During the treatment of ARVI/influenza in 105 patients, RCT 3 examined the levels of induced production of IFN-α and IFN-γ, total serum IFN, and spontaneous IFN. In 229 patients in RCTs 6 and 7, serum levels of IFN-α and IFN-γ were additionally determined.

The meta-analysis showed a significant effect of Anaferon for children on the level of induced IFN-α and IFN-γ on days 2–3 of treatment, with the effect maintaining at the end of therapy. The weighted mean effect size for induced IFN-γ production on days 2–3 of therapy in MFE was 0.99 [95% CI 0.66; 1.33] (p<0.001, two-sided Z-test), in ITU - 1.27 [95% CI 0.06; 2.48] (p=0.039, two-sided Z-test).

Results of a meta-analysis of RCTs of the effectiveness of Anaferon and Anaferon for children for the prevention of ARVI/influenza

A meta-analysis of the preventive effectiveness of Anaferon and Anaferon for children against ARVI/influenza was carried out based on data from 5 RCTs involving 1729 patients aged 1 month or older. (for Anaferon for children in lozenges) and from 18 years of age (for Anaferon). Three RCTs were double-blind, placebo-controlled (RCTs 5, 8, 9), 2 studies were open-label (RCTs 10, 11). RCTs 5, 8, 10, 11 additionally assessed the duration of illness/symptoms when an episode of acute respiratory viral infection/influenza occurred during a preventive intervention.

In general, the proportion of patients who did not develop ARVI/influenza while taking Anaferon for children was 70.3% versus 56.3% when taking placebo (CMH=38.8; p<0.0001) with an overall EC of 32%. When taking Anaferon, on average, the proportion of patients who did not get ARVI/influenza was 60% versus 7.6% in the comparison group (CMH=81.5; p<0.0001) with EC 56.7%.

A meta-analysis of RCT data based on the criterion “proportion of disease-free patients” demonstrated the superior preventive efficacy of drugs based on TO antibodies to IFN-γ. The overall RR for Anaferon for children was 1.25 [95% CI 1.2; 1.3] with OR 2.2 [95% CI 1.7; 2.9], for Anaferon the corresponding figures were 6.7 [95% CI 3.8; 11.8] and 20.1 [95% CI 9.2; 44.0] (Fig. 3 and 4).

The results of assessing the homogeneity of the OR in the studies of Anaferon and Anaferon for children using the Breslow-Day test are presented in Table 7.

Thus, the results of a meta-analysis of the preventive effectiveness of Anaferon and Anaferon for children showed a significant superiority of their use for the prevention of influenza and other acute respiratory viral infections compared to placebo and the absence of preventive intervention.

Evaluation of the effectiveness of anaferon for children in the nonspecific prevention of ARVI in primary schoolchildren

According to the Federal Service for Surveillance on Consumer Rights Protection and Human Welfare for 2005, about 16.5 million cases of acute respiratory viral diseases (ARVI) were registered among children under the age of 14 years, of which the share of cases of confirmed influenza amounted to 2.3% - more than 370 thousand [1].

Respiratory pathology is caused by about 300 types of pathogens. This is a large group of microorganisms, which includes not only viruses (influenza A and B viruses, adenovirus, parainfluenza virus, RS virus, rhino- and reoviruses, coronavirus and picornaviruses, etc.) - about 200 species, but also other pathogens : opportunistic infections, bacteria and fungi [2, 3].

Currently, there are three main ways to control ARVI and influenza: vaccination, chemotherapy and nonspecific prophylaxis [4]. Vaccination against influenza viruses, while providing a stable and long-lasting protective effect, unfortunately has a narrow focus. In addition, the constantly changing antigenic properties of the influenza virus, associated with its high variability, significantly complicate the implementation of complete vaccine prevention [5].

Chemotherapy involves the use of synthetic and natural substances that affect the reproduction of viruses. However, the rather narrow spectrum of action and the possibility of rapid development of viral resistance to drugs of this class limits their use [5].

In this regard, it is now quite natural to focus attention on nonspecific prevention of acute respiratory viral infections and influenza, associated primarily with an increase in the activity of natural anti-infective defense mechanisms.

Particular importance in programs for seasonal nonspecific prevention of influenza and ARVI is given to immunomodulatory agents and inducers of endogenous interferons [5]. Currently, an interesting drug is one of the representatives of this group - anaferon for children.

It contains affinity-purified antibodies to human γ-interferon (γ-INF): a mixture of homeopathic dilutions C12, C30 and C50. According to numerous literature data, anaferon for children has immunomodulatory and antiviral effects [6, 7, 8].

It is known that the production of interferons is an important component of a complete immune response to a viral infection and largely determines the nature of the course of the disease [9]. Anaferon has a versatile modulating effect on all parts of the immune system and interferon status [6, 8, 10]. Thus, anaferon induces and modulates the formation of endogenous “early” interferons α, β and, most importantly, γ-INF. Interferons suppress virus replication and prevent infection of other cells. Under the influence of anaferon, the functional activity of macrophages and NK cells (cytotoxic lymphocytes), which lyse already infected cells, also increases. All these processes underlie the relatively rapid antiviral effect of anaferon [6, 8, 10].

In addition, anaferon affects the production of endogenous cytokines, restores their activity and modulates functionally associated processes. Anaferon is an inducer of both cellular (through Th-1) and humoral (through Th-2) immune response: it increases the production of Th-1 cytokines (γ-IFN and interleukin (IL)-2) and Th-2 (IL-2). 4, IL-10). In addition, anaferon regulates the ratio of Th-1 and Th-2 activities and increases the production of antibodies (including secretory immunoglobulin A) [6].

Due to the use of special production technology, the active substance in the drug is contained in ultra-low doses. In this regard, anaferon is highly safe and can be widely used as a means of nonspecific prevention of influenza and ARVI during an epidemically dangerous period in organized children's groups [11]. Anaferon for children is indicated for healthy children for the prevention of acute respiratory viral infections and influenza, as well as for children belonging to the group of people who are often and long-term ill [12, 13, 14].

In January–February 2005, to study the effectiveness of children's Anaferon in the prevention of acute respiratory viral infections and influenza, we conducted a comprehensive study at a secondary school of a healthy child.

For prophylactic use, Anaferon for children was used during an epidemic period, 1 tablet per day for 40 days, sublingually. This scheme has proven itself on the positive side; it is simple and convenient to use in mass children’s groups [11, 12, 13, 14].

The study involved 200 children in 1st and 2nd grades aged 7 to 8 years. When forming the main and control groups, randomization (a simple method) was used, which ensured the homogeneity of the groups. The children who made up the main group (100 children) received anaferon for children for nonspecific prevention of ARVI. The control group (100 children) included children who did not receive nonspecific prevention of ARVI and influenza. As a result of randomization, children from both the main and control groups were present in each class. Analyzing the effectiveness of preventing influenza and ARVI with the drug Anaferon for children, it should be noted that during the epidemic, only 13% of children receiving this drug fell ill, while in the group of schoolchildren who did not receive non-specific means of preventing ARVI, 58% fell ill (Fig. 1).

The security indicator was about 77.6%. Significance was assessed using two-sided Fisher's test (p < 0.001).

According to the objectives, the features of the course of ARVI, in particular, the severity of the disease, were separately analyzed.

Only 6 children from the main group had a severe course of ARVI, while in the control group 28 children suffered a severe acute respiratory disease. These differences are also significant according to the two-sided Fisher test (p < 0.001) (Fig. 2).

When assessing pharmacoeconomic effectiveness, we used data from I. L. Shakhanina [15]. The cost of nonspecific prevention of ARVI with anaferon for children was 24,500 rubles. The cost of treating cases of ARVI is 74,200 rubles. Thus, the total costs in the main group amounted to 98,700 rubles. An assessment of the preventive effect showed that the use of Anaferon for children prevented 45 cases of ARVI, including 23 episodes of complications from ARVI. At the same time, the prevented economic damage amounted to 270,900 rubles. When comparing the costs of nonspecific prevention of ARVI with anaferon for children with the amount of prevented economic damage, it turned out that the economic benefit from the use of anaferon for children in junior high school per 100 children amounted to 172,200 rubles.

Based on the results of our study, the following conclusions can be drawn:

• anaferon for children has shown high effectiveness as a means for nonspecific prevention of acute respiratory viral infections in children in secondary schools in relation to influenza and acute respiratory viral infections during an epidemically dangerous period, during the winter season of 2004-2005;
• the absence of contraindications, as well as the absence of side effects, a convenient method (sublingual tablet) and a regimen of use (1 tablet once a day, daily for 40 days) allow the widespread use of Anaferon for children in mass children's groups;
• anaferon for children can be successfully used for mass prevention of influenza and ARVI, as well as their complications in school groups during seasonal diseases of the respiratory tract;
• The economic efficiency of using anaferon for children among primary school students, as studies have shown, is quite high.

Literature

1. Infectious disease incidence in the Russian Federation for January-December 2005. Reference information of the Federal Service for Surveillance in the Sphere of Protection of Consumer Rights and Human Welfare of the Federal State Health Institution, “Federal Center for Hygiene and Epidemiology.”
2. Evstropov A. N. Pathogens of acute respiratory viral infections in humans // Clinical antimicrobial chemotherapy. 2001. T. 3. No. 1-2. pp. 38-41.
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4. Drinevsky V. P., Osidak L. V., Tsybalova L. M. Acute respiratory infections in children and adolescents: a practical guide / ed. O. I. Kiseleva. St. Petersburg: SpetsLit, 2003. P. 181.
5. Ershov F.I., Kasyanova N.V., Polonsky V.O. Is rational pharmacotherapy of influenza and other acute respiratory viral infections possible? // Consilium Medicum. 2003. T. 5. No. 6. P. 129-135.
6. Osidak L.V., Afanasyeva O.I., Drinevsky V.P. Anaferon for children. A new remedy in the treatment and prevention of influenza and acute respiratory infections in children: a method. manual for doctors. St. Petersburg, 2003. P. 25.
7. Chuvirov G. N., Markova T. P. Antiviral therapy in the treatment of influenza // Russian Medical Journal. 2004. T. 12. No. 21. P. 1216-1226.
8. Uchaikin V.F., Epshtein O.I., Sergeeva S.A., Orlova T.G., Kharlamova F.S. et al. Anaferon for children. Domestic immunocorrector with antiviral activity: a manual for pediatricians and infectious disease specialists / ed. V. F. Uchaikina. M., 2003. P. 35.
9. Ershov F.I. The interferon system in normal conditions and in pathology. M.: Medicine, 1996. P. 240.
10. Martyushev-Poklad A. V. Mechanisms of antiviral and immunomodulatory effects of ultra-low doses of antibodies to interferon gamma: dis. ...cand. honey. Sci. Tomsk, 2003. 119 p.
11. Timchenko V. N., Chernova T. M. Modern methods of influenza prevention // Terra Medica. 2005. No. 4. P. 14-18.
12. New opportunities for the prevention and treatment of acute respiratory viral infections in children: effectiveness and safety: Based on materials from the scientific and practical conference “Pharmacotherapy in Pediatrics” 2005 // Polyclinic. 2006. No. 1. P. 10-11.
13. Lytkina I. N., Volkova N. A. Experience in the use of some modern drugs during nonspecific prevention of ARVI in children's organized groups // Children's infections. 2004. No. 4. P. 49-54.
14. Kuprina N. P., Kokoreva S. P., Semenchenko L. V., Shishlova S. A., Ragozina V. N. Clinical and laboratory effectiveness of the use of “Anaferon for children” in the complex therapy of frequently ill children. // Childhood diseases. 2005. No. 3. P.54-58.
15. Shakhanina I. L., Osipova L. A. Economic losses from infectious diseases in Russia: values ​​and trends // Epidemiology and infectious diseases. 2005. No. 4. pp. 19-21.

T. I. Garashchenko, Doctor of Medical Sciences, Professor L. I. Ilyenko, Doctor of Medical Sciences, Professor M. V. Garashchenko Russian State Medical University, Moscow

Discussion

The rational use of drugs for the treatment and prevention of acute respiratory viral infections/influenza is based on the preferential use of drugs with a strong evidence base. This meta-analysis demonstrates convincing advantages of the effectiveness and safety of the use of the drugs Anaferon and Anaferon for children for the prevention and treatment of ARVI.

A meta-analysis of the therapeutic effectiveness of Anaferon for children in ARVI/influenza according to the criteria “duration of the disease” and “duration of fever” with an additional assessment of the effect of the drug on the duration of intoxication, catarrhal symptoms (rhinitis and cough) and the dynamics of the level of IFN-γ and IFN-α showed a significant decrease in the duration disease and duration of individual symptoms. Anaferon for children demonstrated statistically significantly better effectiveness compared to placebo in all considered indicators. Thus, for one of the key endpoints - “disease duration” - the weighted average effect size was 1.05 [95% CI 0.44; 1.67], according to another - “duration of fever” - 0.97 [95% CI 0.61; 1.33] (p<0.001, p-value of two-sided Z-test; ITU). The therapeutic effectiveness of Anaferon for children did not depend on the pathogen of ARVI, nor on the clinical picture, including ARVI with combined damage to the respiratory tract and GIS, nor on the presence of comorbidity (BA). The data obtained on the effect of Anaferon for children on the level of induced production of IFN-γ and IFN-α indicate its ability to activate key cytokines of the immune system - IFN, which allows the natural factors of antiviral immune defense to more fully realize their potential while taking the drug.

A clear preventative intervention for influenza is vaccination. According to the US Centers for Disease Control and Prevention, the effectiveness of influenza vaccination for all types of vaccines in the 2019/2020 season in patients over 18 years of age was 26–45% [28]. The EC for ARVI/influenza was 32% for Anaferon for children and 56.7% for Anaferon. A meta-analysis of the preventive effectiveness of Anaferon for children and Anaferon for ARVI/influenza according to the criterion “proportion of patients who did not get sick” demonstrated significant preventive effectiveness of the drugs - for Anaferon for children, the RR was 1.2 [95% CI 1.2; 1.3] with OR 2.2 [95% CI 1.7; 2.9], for Anaferon - 6.7 [95% CI 3.8; 11.8] and 20.1 [95% CI 9.2; 44.0] respectively. At the same time, the proportion of patients who did not get ARVI/influenza when taking Anaferon was almost 8 times higher than in the absence of preventive intervention, and when taking Anaferon for children - 1.3 times compared to placebo. The preventive effectiveness of the drugs did not depend on the presence of concomitant bronchopulmonary pathology or whether the child belonged to the CBD group.

An assessment of the safety of the use of Anaferon and Anaferon for children, taking into account the number and nature of AEs, their connection with taking the drug, deviations in laboratory and vital signs while taking the drugs, confirmed their favorable safety profile.

The limitations and strengths of this meta-analysis should be highlighted separately. Of course, the strengths of the analysis are the absence of restrictions on gender, age and concomitant ARVI/influenza pathology, which makes it possible to interpolate the calculated data to the conditions of real clinical practice as much as possible.

Limitations of the meta-analysis regarding the treatment of ARVI/influenza include the assessment of the effectiveness of the study drug against the background of the use of basic therapy, which included the use of antipyretic drugs. However, this problem in any RCT is of an ethical nature. A relative limitation can be considered the heterogeneity of RCTs in terms of effectiveness criteria, which does not contradict the criteria for inclusion in the meta-analysis - only 6 out of 7 RCTs analyzed the duration of the disease and the duration of fever. Data on additional criteria were presented in 5 studies - on the duration of intoxication and in 4 RCTs - on the duration of rhinitis and cough.

The strength of the meta-analysis of the effectiveness of Anaferon for children for the treatment of acute respiratory viral infections/influenza is, of course, the design of RCTs - all studies included in the analysis were double-blind, placebo-controlled. However, in one RCT the placebo control group was less than 30 people and when assessing the risk of bias, a number of RCTs, due to insufficient information about the randomization procedure and allocation masking, were classified as RCTs with uncertain risk, which can also be attributed to the limitations of this meta-analysis and several reduce the quality of evidence.

The partial lack of information in RCTs about influenza vaccination, which could additionally influence the results of the prophylactic use of Anaferon and Anaferon for children, as well as the open design of RCT 10 and RCT 11, are limitations of the meta-analysis assessing the preventive effectiveness of the drugs. In addition, some of the data come not only from double-blind, placebo-controlled studies, but also from comparative (noninferiority) studies.

Experience of using Anaferon in pediatric practice

The article reviews clinical studies on the use of the drug Anaferon. Anaferon is an antiviral agent with immunomodulatory activity, many years of experience in the use of which has proven the effectiveness and safety of the drug in the treatment and prevention of a wide range of viral and bacterial infectious diseases in children. The key mechanisms of action of Anaferon are the induction of endogenous type I and II interferons, as well as allosteric modulation of the interferon gamma receptor. The authors note that the high safety of the drug, the possibility of its use in children from 1 month of age, and the lack of addiction allow us to recommend Anaferon as the drug of choice for the treatment and prevention of infectious diseases of various etiologies.

Introduction

Infectious diseases remain the most common in childhood, among which acute respiratory diseases and acute intestinal infections occupy one of the leading places. Every year, more than a billion cases of acute respiratory diseases and the same number of acute intestinal infections are registered worldwide.

Children attending school and preschool institutions most often get sick, which is directly related to the increase in the number of contacts. First of all, we are talking about acute respiratory diseases and influenza, which a child suffers on average 8 times in the first year of visiting, 4–6 times in the second year, and 3–4 times in the third year. In total, in 2012, 28 million 423 thousand 135 people in the country suffered from acute upper respiratory tract infections, of which 67% were children under 14 years of age. The incidence rate was 19,896.3 per 100 thousand people, and in children under 14 years old - 87,391.6 per 100 thousand people. The incidence of acute intestinal infections remains high. If in 2002 635,514 cases of acute intestinal infections were registered in the country, then in 2012 there were 808,585 cases of acute intestinal infections. Among the sick, more than 60% are children, most of them under the age of 3 years.

An undoubted achievement in the field of studying acute respiratory diseases and acute intestinal infections should be considered their etiological decoding. A screening survey showed that about 60% of all diarrheal diseases are caused by viruses, most often by rotaviruses (80%), less often by astro-, calici- and adenoviruses (15%) and in 5% of cases the disease is caused by associations of viruses. About 12% of acute intestinal infections are caused by bacteria, the etiology of 28% remains unspecified.

Acute respiratory viral infections (ARVI) also predominate in the structure of acute respiratory diseases (90–95%). The share of bacterial and other acute respiratory diseases (caused by staphylococci, less commonly streptococci, Moraxella catarrhalis, Haemophilus influenzae, Mycoplasma spp

., mushrooms, etc.) account for 5–10%.

Diagnosis of ARVI

Among the reasons for the total prevalence of ARVI, one can highlight the presence of an extraordinary variety of respiratory pathogens, the formation of type-specific post-infectious immunity and the ease of transmission of pathogens. Nevertheless, the predominant tropism for one or another part of the respiratory tract, formed in the process of evolution, makes it possible to identify characteristic signs, which simplifies the differential diagnosis of the disease and allows timely prescription of etiotropic drugs.

Thus, parainfluenza is characterized by symptoms of damage to the laryngeal mucosa, which in 50% of cases manifests itself as croup syndrome. Adenovirus infection is characterized by damage to the mucous membrane of the nasopharynx with the involvement of lymphoid formations in the process with the formation of pharyngotonsillitis and pharyngitis. With respiratory syncytial infection, the pathological process begins with damage to the mucous membrane of small and medium bronchi, which is clinically manifested by expiratory shortness of breath. The initial symptom of influenza infection is tracheitis, and rhinovirus infection is rhinitis.

Thus, topical diagnosis occupies a central place in the system of clinical guidelines in ARVI. In principle, identifying a symptom pathognomonic for a given infection is a central link in the diagnosis of the disease [1]. For example, a feature of the clinical picture of all calicivirus infections is the presence of a symptom complex of damage to the upper gastrointestinal tract (GIT) in the form of nausea, vomiting and abdominal pain, while shigellosis is characterized by colitis syndrome, which is associated with the tropism of Shigella spp

. to the mucous membrane of the large intestine.

Immunotropic drugs in the treatment of ARVI

The idea of ​​the tropism of the lesion (that is, the initiation of the infectious process only if the pathogen is found, recognized and binds to a specific related receptor in the tropic organ) made it possible to determine the main principle of treating an infectious patient - etiotropic. Currently, treatment regimens have been developed based on the use of etiotropic, pathogenetic and symptomatic agents. Numerous studies have shown that in patients with ARVI, timely administration of Anaferon, Algirem or Arbidol leads to a reduction in clinical manifestations by 1.5–2 times compared to standard therapy.

A promising direction in modern therapy for such infections in children is the use of immunotropic drugs, in particular endogenous interferon inducers (IFN). Interferon inducers have a universally wide range of antiviral activity (etiotropic effect) and a pronounced immunomodulatory effect. Against the background of their use, the synthesis of endogenous interferon is balanced and controlled by the body, which prevents a number of side effects characteristic of exogenously administered interferons. A single administration of classical inducers leads to long-term, and in some cases unreasonably long, circulation of endogenous interferon (up to 120 hours or more) [2].

One of the inducers of endogenous interferons alpha and gamma, widely used in the complex therapy of viral and bacterial infections in children, is the domestic drug Anaferon for children. In the production process of this drug, technological processing of the starting substance is used, which leads to the release of a special physicochemical, biological and pharmacological activity called release activity. Thus, Anaferon for children contains affinity-purified antibodies to IFN-gamma in a release-active form [3].

Release-active antibodies to IFN-gamma have a specific modifying effect on the antigen to which they are produced [3], causing conformational (spatial) changes in the IFN-gamma molecule. In addition, it was found that release-active antibodies to IFN-gamma enhance the interaction of IFN-gamma with its receptor (increase the amount of IFN-gamma bound to the receptor) and change the affinity of the interaction of IFN-gamma with antibodies to IFN-gamma [4, 5].

In a series of preclinical studies, it was shown that when administered prophylactically and/or therapeutically, release-active antibodies to IFN-gamma have an antiviral effect against RNA and DNA viruses and immunotropic activity. The antiviral and immunotropic effect is realized due to the influence on the functional activity of natural factors of immune defense (cellular, humoral immune response, phagocytic activity of neutrophils and macrophages). The wide range of immunotropic effects of the drug is associated with the involvement of the interferon system in the implementation of pharmacological activity, in particular IFN-gamma, the induction of which is a key mechanism of its action [4–8].

Like other interferon inducers, Anaferon for children promotes the production of endogenous interferons. However, unlike classical inducers, Anaferon for children has a selective effect on the production of endogenous IFN alpha and gamma, depending on the presence of the virus in the body. The selectivity of Anaferon's action is manifested in the fact that during the acute period of a viral infection it activates all types of interferon production (spontaneous and stimulated/induced production). This results in an increase in serum concentrations of IFN alpha and gamma to levels sufficient to combat infection. As the virus is eliminated and during the convalescence period, the stimulating effect of Anaferon for children on interferonogenesis decreases. This leads to the fact that by the time the drug is finished (the treatment regimen involves taking the drug for 5–7 days), there is a decrease in the content of interferons in the serum until a normal level is reached without developing a state of hyporeactivity. During this period, the effect of Anaferon for children is manifested by higher (compared to placebo) levels of induced production of IFN alpha and gamma, reflecting the functionality of the IFN system in the event of recurrent infection. Anaferon for children has a similar effect when used prophylactically [3].

Thus, depending on whether there is contact with viruses, Anaferon for children acts differently. During infection, the drug actively stimulates the production of interferons, increases the expression and binding ability of IFN-gamma receptors. Outside of contact with viruses, the drug increases the functional reserves of the interferon system and maintains the child’s body in a state of high readiness to protect against viruses. It should be noted that the ability to influence the reception of IFN-gamma also distinguishes Anaferon for children from other inducers. Optimization of ligand-receptor interactions of IFN-gamma molecules with its receptor may underlie the physiological nature of the action of Anaferon for children. Under conditions of more complete interaction of IFN molecules with receptors, the regulatory effects of IFN-gamma are realized more quickly. On the one hand, this leads to a faster activation of the immune response, and on the other hand, stimulation of the IFN system stops faster through feedback channels [9, 10].

The described properties of Anaferon for children allow its use in repeated therapeutic and prophylactic courses without excessive stimulation of IFN, and therefore, without the risk of depletion of the immune system and the development of a stage of hyporeactivity, which is possible when using other IFN inducers. This also determines the possibility of using Anaferon for children in patients at risk, whose immune system requires a more balanced effect [9]. All of the above indicates the wide therapeutic potential of Anaferon for children, and taking into account the fact that the drug is approved for use in children aged 1 month and older, it can be considered the drug of choice in pediatric practice.

Anaferon for children in the treatment and prevention of influenza and ARVI in children

Currently, a fairly impressive number of studies have been conducted confirming the effectiveness and safety of Anaferon for children in the treatment and prevention of influenza and ARVI in children [11, 12]. Experts note that most studies were comparative, randomized and prospective. A significant part of the work involved the use of placebo control and various masking methods (simple and double blinding) [11].

As part of an expert assessment of 10 years of clinical experience in the use of Anaferon for children, presented at the XX National Congress “Man and Medicine”, Professor E.G. Kondurina noted that over the past decade, clinical studies of Anaferon took place in more than 40 cities of Russia, more than 50 research centers participated in their implementation, and the number of patient participants approached 6,000.

Anaferon for children is most widely used for the treatment and prevention of acute respiratory viral infections. This also determines the predominance of studies devoted to this topic. In the available literature sources you can find information about 27 comparative studies on the use of Anaferon for this pathology in children aged 1 month to 15 years. The vast majority of studies were randomized, and five studies were double-blind placebo-controlled [11, 12].

Thus, according to a two-center randomized placebo-controlled study, the prophylactic use of Anaferon for children in a group of more than 200 people reduced the average number of ARVI episodes by 2.3 times compared with the placebo group (p

The therapeutic effect of Anaferon for children during a multicenter, randomized, double-blind, placebo-controlled clinical trial was manifested in a reduction in the duration of the main symptoms of influenza by 24–43 hours. Thus, the duration of hyperthermia was 54 ± 3.1 hours versus 88.1 ± 2.9 hours in the placebo group (p

It should be noted that Anaferon for children is widely used for the prevention and treatment of viral infections in children at risk for the development of ARVI and complications. These groups include children with secondary immunodeficiency conditions, as well as children with concomitant pathologies that limit the possibility of using pharmacotherapeutic methods for the prevention of ARVI [11]. Research by Professor N.K. Perevoshchikova (Kemerovo) showed the feasibility of including Anaferon for children in the program for the management of frequently ill children with pathology of the lymphopharyngeal ring. It has been proven that the use of preventive courses of Anaferon for children reduces the incidence of ARVI in this category of children by 2.5 times. Moreover, the preventive effect after completion of the 3-month rehabilitation and preventive program remains for another 1.5–2 months (total observation period - 5 months). In addition to clinical effects in frequently ill children receiving Anaferon for children, elimination of microorganisms from the mucous membrane of the nasopharynx is noted. At the same time, the detection of Staphylococcus aureus decreased by 1.5 times, and positive smears for hemolytic streptococcus were detected 6 times less often than in the control group. In nasocytograms of children who received a course of Anaferon for children, there was a significant increase in the number of columnar epithelium, a decrease in sensitization of the nasopharyngeal mucosa, a decrease in the adsorption index of squamous epithelium, which indirectly confirmed a decrease in the content of microorganisms on the mucous membranes of the upper respiratory tract. When using Anaferon for children, a significant increase in lysozyme activity and an increase in the level of IgA and sIgA in nasal secretions were recorded [18–20].

Anaferon for children in the treatment and prevention of acute respiratory viral infections in children suffering from atopic diseases

Pediatricians and allergists have accumulated extensive experience in using Anaferon for children as an antiviral drug and an inducer of interferons, primarily IFN-gamma, in children suffering from atopic diseases. Randomized comparative and placebo-controlled studies were conducted at the Center for Child and Adolescent Health (Moscow), Siberian State Medical University (Tomsk), Novosibirsk State Medical University (Novosibirsk), ChelSMA (Chelyabinsk), as well as in Dnepropetrovsk [21–26]. Prophylactic use of Anaferon for children made it possible to reduce the number of children who suffered acute respiratory infections during the epidemic period by 2–2.5 times, and to reduce the incidence of ARVI by 3.5 times. In addition, under the influence of the drug, the frequency of virus-induced exacerbations of allergic diseases was reduced. For example, the average number of exacerbations of bronchial asthma in the group of children receiving Anaferon was 0.43 ± 0.08 compared to 0.88 ± 0.02 in the placebo group (p

A study of the therapeutic effectiveness of Anaferon for children in acute respiratory viral infections in children with allergic diseases demonstrated the ability of the drug to reduce the severity and duration of intoxication syndrome and catarrhal phenomena, as well as good tolerability of Anaferon. The Influenza Research Institute of the Ministry of Health of the Russian Federation showed that the inclusion of Anaferon for children in the complex therapy of 100 children aged 6 months and older with a history of dermato- and respiratory allergies and combined damage to the respiratory and gastrointestinal tract led to a significant decrease in the proportion of people with elevated body temperature already after 1 day of taking the drug, compared with the group receiving placebo. In addition, after 3 days, the number of children with persistent symptoms of intoxication and gastrointestinal manifestations significantly decreased, and after 4 days - with catarrhal phenomena in the nasopharynx and auscultatory changes in the lungs. In general, signs of acute infection were eliminated on the 5th day in the main group and on the 8th day in the placebo control group. Clinical improvement was accompanied by an increase in serum INF alpha and gamma levels on days 2–3 of illness, as well as in the levels of sIgA, CD3, and CD16. It should be emphasized that by the time of recovery, serum levels of interferons were normalized. The treatment course of Anaferon led to a statistically significant reduction in the release of viral antigens in the nasal passages of these children.

Anaferon for children in the treatment of acute intestinal viral infections

The wide distribution of rotavirus infection in pediatrics is explained by high natural susceptibility, especially in young children. The leading role in antiviral protection, starting from the earliest stage of penetration of rotavirus into the gastrointestinal mucosa, belongs to the interferon system. By inhibiting the processes of transcription and translation of viral templates, they are able to suppress the replication of many RNA and DNA viruses [27, 28]. The effectiveness of including Anaferon for children in the treatment of acute intestinal infections of viral (rotavirus and calicivirus infections), viral-bacterial nature, as well as the prevention and treatment of acute infections with combined damage to the respiratory and intestinal tracts has been studied and confirmed by a number of authoritative experts [12, 27–32 ]. It was shown that the inclusion of Anaferon for children in the treatment regimen for patients with ARVI with gastrointestinal lesions (adeno-, corona-, calici- and rotavirus infections) led to a reduction in fever (1.3 times), intoxication (1.9 times), catarrhal symptoms (2.5 times) and manifestations of gastrointestinal dysfunction (1.4 times), and also shortened the period of isolation of viral antigens from convalescents and led to the discharge of children at an earlier time [27, 32].

Placebo-controlled studies conducted at the Research Institute of Children's Infections of the FMBA, at the Central Research Institute of Epidemiology of Rospotrebnadzor, at the Department of Children's Infectious Diseases of Rostov State Medical University, indicate the advisability of including Anaferon for children in the complex therapy of rotavirus gastroenteritis [32]. A significant reduction in the duration of the main manifestations of the disease was demonstrated in 29 children aged 1 to 8 years. Thus, the symptoms of intoxication were relieved for 24–36 hours, fever – for 48–50 hours, and the restoration of stool character – 2.3 days earlier compared to children receiving standard therapy.

Similar data indicating the cessation of rotavirus isolation in 90% of cases on the 5th day of treatment with Anaferon were obtained by N.Kh. Tkhakushinova and N.G. Soboleva [31]. This fact is apparently due to the activating effect of the drug on antiviral resistance and the immune response, which ensures accelerated sanitation of the body from rotavirus, despite the known tendency of the latter to long-term persistence [27, 28].

The data obtained in a study conducted under the guidance of Professor A.V. deserve special attention. Gorelova [32]. The use of Anaferon for children for the treatment of rotavirus infection made it possible to prevent infection of children during their hospital stay. Thus, among children who received placebo as part of complex therapy for rotavirus infection, by the time of discharge, the number of children in whom the presence of viral-bacterial mixtures in the feces was determined by PCR method increased by 10%, while in the group of children who received Anaferon for children, No such phenomena were noted.

Thus, the interferonogenic activity of Anaferon for children in respiratory and intestinal infections of viral etiology and their combination has a positive effect on various parts of the humoral and cellular antiviral immune response. As a result of the antiviral and immunomodulatory activity of Anaferon for children in the treatment of rotavirus infection, the concentration of the virus in the affected tissues of the gastrointestinal tract decreases and the rate of its elimination increases. This is important both for a specific child and for the pediatric population as a whole, since it prevents prolonged viral shedding by convalescents and helps reduce the level of sporadic and outbreak morbidity.

The prospects for the use of Anaferon in pediatric practice are not limited only to viral infections. In a study conducted by I.V. Babachenko et al. showed that the inclusion of Anaferon for children in the treatment of pertussis infection in children contributed to a reduction in the incidence of intercurrent ARVI by 2–2.5 times compared to the control group, and a reduction in the incidence of pneumonia and bronchitis from 50 to 20% [33].

Use of Anaferon for children in other infections and immunodeficiency conditions

The presence of Anaferon for children not only has an antiviral effect, but also immunomodulatory activity, which makes it possible to effectively use it against the background of secondary immunodeficiency states, chronic infections, which are most difficult to treat due to the high variability of causative viruses and their ability to suppress the immune response. Based on the results of a double-blind, placebo-controlled, randomized clinical trial, conclusions were drawn about the effectiveness and safety of Anaferon for children in the treatment of chickenpox in children [34]. Revealed significant (p

The experience of using Anaferon in children from 4 months to 3 years with HIV infection who had perinatal contact with HIV infection (stages A1–B3) is interesting. According to V.N. Timchenko, against the background of the preventive course of the drug, there was a decrease in the incidence of ARVI, and a quarter of the children in the group did not get sick at all during the observation period, while in the control group the incidence of ARVI was one hundred percent. The proportion of children with repeated ARVI decreased by 2 times. When assessing the therapeutic effectiveness of Anaferon for children in children with HIV infection and contacts of HIV infection (the drug was used according to a standard treatment regimen), it was found that the duration of the main symptoms of ARVI is reduced by 1.5–2.3 times. The safety of using Anaferon for children in HIV-infected young children has also been shown [35].

Currently, there is data on the use of Anaferon for children in infectious mononucleosis, hemorrhagic fever with renal syndrome, pseudotuberculosis and yersiniosis, whooping cough, tubulointerstitial nephritis, enteroviral and meningococcal meningitis, as well as ARVI in children with concomitant cardiac pathology [36–39].

Conclusion

The collected evidence base, which includes registered and published clinical studies with a high level of evidence, allows us to recommend the widespread use of Anaferon for children in practical medicine, including in pediatrics. Anaferon for children occupies a special place in the treatment of influenza and ARVI, which is associated with the physiological effect of the drug on induced interferonogenesis, on the IFN-gamma system. Anaferon for children is not addictive, which allows it to be used to treat children prone to frequent respiratory infections.

A wide range of antiviral activity allows us to classify Anaferon for children as the drug of choice in the treatment of children with viral infections manifested not only by respiratory, but also by other, including gastrointestinal, symptoms. Finally, the combination of effectiveness with a high safety profile plays a special role in the treatment of viral infectious and inflammatory diseases in children with allergic and other underlying pathologies.