M.S. Savenkova1, M.V. Solovyova1, N.I. Tkachenko1, N.A. Abramova2, G.N. Kraseva2 1Pirogov Russian National Research Medical University, Moscow, Russian Federation 2Sectoral Clinical Diagnostic Center of the Gazprom PJSC, Moscow, Russian Federation Due to COVID-19-associated respiratory and gastrointestinal disorders leading to comprehensive management of post-COVID-19 conditions, probiotics studies are of interest in the COVID-19 and the post-COVID-19 periods. Aim: to review national and foreign studies focused on a role of probiotics in pre-COVID-19, COVID-19 and post-COVID-19 periods. The emphasis is on studies combining gastrointestinal (GIT) disorders associated with acute respiratory infections (ARI) in pre-COVID-19, COVID-19 and post-COVID-19 periods. It is especially noted that efficiency of probiotics can be discussed in relation to a specific strain(s) only. Moreover, at this particular COVID-19 period a ‘'gut-lung axis-mediated immune responses'' theory in which a respiratory barrier was likely to be recovered by an impact on intestinal microbiota, was common to explain probiotic effects. A drug product containing two probiotic strains, Lactobacillus rhamnosus LGG® and Bifidobacterium BB-12® (≥109 CFU of living bacteria), along with other probiotics, demonstrated good perspectives to manage respiratory disorders in the post-COVID-19 period. Keywords: probiotics, microbiota, influenza virus, rhinovirus, SARS-CoV-2 infection, diarrhea. For citation: Savenkova M.S., Solovyova M.V., Tkachenko N.I., Abramova N.A., Kraseva G.N. COVID-19 and ARVI: probiotic therapy features in pre-COVID-19, COVID-19 and post-COVID-19 periods. Russian Journal of Woman and Child Health. 2024;7(4):342–348 (in Russ.). DOI: 10.32364/2618-8430-2024-7-4-8

Morozov Children’s City Clinical Hospital, almost in the first months of the development of the COVID-19 epidemic, began to admit not only patients with acute infection, but mainly with combined comorbid pathology. Based on a retrospective analysis of 290 medical records of children hospitalized with COVID-19 at the Children’s City Clinical Hospital, an analysis of children admitted to the hospital with predominantly comorbid pathology was carried out between April 2020 and September 2020. Six of these children had a fatal outcome. Most children were in the first 3 years of life (38,4 %) and puberty (37,3 %). The diagnoses of hospitalized patients were varied: pneumonia — 41 (14,4 %), surgical pathology and trauma — 69 (24,3 %), somatic pathology — 120 (42,3 %), including: diseases of the gastrointestinal tract, kidneys and urinary tract pathways, hematological diseases, neurological, type I diabetes mellitus, joint diseases, diseases of the newborn period, oncological diseases, diseases of the cardiovascular system. To diagnose covid pneumonia, along with rapid methods of SARS-COV2, computed tomography of the lungs was used. Analyzing the course of diseases in surgical children, it can be noted that coronavirus infection did not affect the course of the underlying disease. At the same time, COVID-19 infection in hematological patients provoked a worsening of the condition with symptoms of an acute respiratory viral infection (hyperthermia, weakness, cough, rhinitis). In patients with symptomatic focal epilepsy and in patients with increased intracranial pressure, SARS-COV-2 caused activation of seizures. It should be noted that the onset of type 1 diabetes was observed in 5 out of 6 admitted children. In these cases, COVID-19 infection was a provoking factor; it also caused an exacerbation in 1 child who had “long-term” diabetes. The article presents case histories and diagnoses of 6 children aged 3 years 9 months to 17 years with deaths, severe comorbid pathology (leukemia, brain stem tumor, immunodeficiency state), in whom COVID-19 infection aggravated the course of the underlying disease with the development of generalized combined bacterial infection, sepsis, bleeding.

Введение. Лечение острых респираторных вирусных инфекций, особенно в период эпидемических подъемов, – первоочередная задача для педиатров и врачей других специальностей. После пандемии новой коронавирусной инфекции COVID-19 назрела необходимость оценки эффективности и безопасности индуктора интерферона ввиду произошедших изменений в циркуляции респираторных вирусов. Цель работы. Оценить эффективность индуктора интерферона в комплексной терапии острых респираторных вирусных инфекций у детей 3-18 лет в сравнении со стандартной терапией в условиях рутинной амбулаторно-поликлинической практики. Материалы и методы. В исследование были включены 534 ребенка в возрасте от 3 до 18 лет с установленным диагнозом острой респираторной вирусной инфекции легкой или средней степени тяжести с длительностью заболевания не более трех суток на момент включения в наблюдательную программу. Стандартная терапия назначалась лечащим врачом в соответствии с актуальными клиническими рекомендациями. Дополнительно по решению врача назначался Кагоцел®, 12 мг в таблетке, по 6 или 10 таблеток в течение 4 дней. Проведена оценка динамики симптомов, длительности заболевания, частоты развития осложнений, назначений антибиотиков, повторного заболевания острыми респираторными вирусными инфекциями и элиминации вирусного возбудителя по данным диагностики с помощью полимеразной цепной реакции. Оценка безопасности лечения включала регистрацию нежелательных реакций и нежелательных явлений. Результаты. Включение индуктора интерферона в стандартную терапию позволяет сократить продолжительность основного заболевания и ускорить разрешение симптомов, снижает частоту возникновения осложнений, назначения антибиотиков и повторного заболевания острыми респираторными вирусными инфекциями. Комбинированная терапия с использованием Кагоцел® обеспечила вдвое большую эффективность по показателю частоты элиминации вирусов в сравнении со стандартной терапией без использования противовирусных средств на 5-8-й день от начала лечения. Кагоцел® продемонстрировал высокий профиль безопасности, не было зарегистрировано ни одного нежелательного явления. Заключение. Показана значимая эффективность индуктора интерферона в комплексной терапии острых респираторных вирусных инфекций в сравнении со стандартным лечением без применения противовирусных средств в условиях реальной клинической практики. Продемонстрирован отличный профиль безопасности терапии у детей от 3 до 18 лет. Background. Viral respiratory tract infections treatment, especially during epidemic outbreak, is a main priority for pediatricians and physicians of other specialties. After the COVID-19 pandemic, a need to assess the efficacy and safety of the interferon inductor drug arose due to the changes of respiratory viruses circulation. Objective. To evaluate the effectiveness of drug within the complex therapy of viral respiratory tract infections in children aged 3 to 18 years, in comparison with standard therapy in routine outpatient practice. Materials and Methods. The study included 534 children aged 3 to 18 years diagnosed with mild to moderate viral respiratory tract infections with a disease duration of no more than 3 days at the time of enrollment in the observational program. Standard therapy was prescribed by the attending physician in accordance with current Clinical Guidelines and Treatment Standards. Additionally, Кagocel® tablets, 12 mg, were administered at the physician’s discretion, in doses of 6 or 10 tablets over a period of 4 days. Symptom dynamics, disease duration, incidence of complications, antibiotic prescriptions, recurrent viral respiratory tract infections, and viral pathogen elimination based on PCR diagnostics were assessed. Safety assessment included adverse event recording. Results. Incorporating of interferon inductor into standard therapy reduced the duration of the primary disease and accelerated symptom resolution, decreased the frequency of complications, antibiotic prescriptions, and recurrent viral respiratory tract infections. Complex therapy with an Кagocel® provided twice the effectiveness in terms of viral elimination rates compared to standard therapy without antiviral agents on days 5-8 from the start of treatment. Кagocel® demonstrated a good adverse event profile, with no AEs recorded. Conclusion. The significant efficacy of interferon inductor in the complex treatment of viral respiratory tract infections compared to standard therapy without antiviral agents in real-world practice has been demonstrated. The therapy demonstrated an excellent adverse event profile in children aged 3 to 18 years.

Background. Viral respiratory tract infections treatment, especially during epidemic outbreak, is a main priority for pediatricians and physicians of other specialties. After the COVID-19 pandemic, a need to assess the efficacy and safety of the interferon inductor drug arose due to the changes of respiratory viruses circulation.Objective. To evaluate the effectiveness of drug within the complex therapy of viral respiratory tract infections in children aged 3 to 18 years, in comparison with standard therapy in routine outpatient practice.Materials and Methods. The study included 534 children aged 3 to 18 years diagnosed with mild to moderate viral respiratory tract infections with a disease duration of no more than 3 days at the time of enrollment in the observational program. Standard therapy was prescribed by the attending physician in accordance with current Clinical Guidelines and Treatment Standards. Additionally, Кagocel® tablets, 12 mg, were administered at the physician’s discretion, in doses of 6 or 10 tablets over a period of 4 days. Symptom dynamics, disease duration, incidence of complications, antibiotic prescriptions, recurrent viral respiratory tract infections, and viral pathogen elimination based on PCR diagnostics were assessed. Safety assessment included adverse event recording.Results. Incorporating of interferon inductor into standard therapy reduced the duration of the primary disease and accelerated symptom resolution, decreased the frequency of complications, antibiotic prescriptions, and recurrent viral respiratory tract infections. Complex therapy with an Кagocel® provided twice the effectiveness in terms of viral elimination rates compared to standard therapy without antiviral agents on days 5-8 from the start of treatment. Кagocel® demonstrated a good adverse event profile, with no AEs recorded.Conclusion. The significant efficacy of interferon inductor in the complex treatment of viral respiratory tract infections compared to standard therapy without antiviral agents in real-world practice has been demonstrated. The therapy demonstrated an excellent adverse event profile in children aged 3 to 18 years.

Введение. Сочетанная патология острых респираторных инфекций с желудочно-кишечными расстройствами высокоактуальна. Работ по изучению роли респираторных вирусов и кишечных патогенов при одновременном исследовании материала (ротоглотка и кишечник) у детей крайне мало. До конца не ясна роль тех или иных патогенов при сочетанном их течении. Цель исследования. Определить роль вирусов у детей при острых респираторных инфекциях с желудочно-кишечными расстройствами в зависимости от возраста и времени года в пандемическом периоде инфекции COVID-19. Оценить эффективность популярных пероральных пробиотиков в форме масляных капель на основании результатов клинико-лабораторных параметров в комплексной терапии больных острыми респираторными инфекциями с желудочно-кишечными расстройствами. Материалы и методы. Проведено открытое перспективное наблюдательное исследование в условиях поликлиники во время эпидемии COVID-19 (c апреля 2022 по апрель 2023 г.) при участии 100 детей в возрасте от 1 месяца до 18 лет. Всем детям проводилось одновременное исследование нуклеиновых кислот вирусов (мультиплексная диагностика методом полимеразной цепной реакции) из ротоглотки и кала. Дополнительно оценена эффективность пробиотиков. Группа 1 (n = 50) получала Адиарин® Пробио (биологически активная добавка к пище, не является лекарством) в дозе 6 капель 1-2 раза в день. Группа 2 (n = 50) получала БиоГая® (биологически активная добавка к пище, не является лекарством) в дозе 5 капель 1-2 раза в день. Результаты. Результаты лечения показали высокую эффективность и чувствительность проводимой пробиотикотерапии. Однако для группы 1 установлена большая чувствительность при лечении вирусных инфекций по результатам анализа мазков из зева и кала. При этом ширина 95% доверительного интервала группы 1 меньше, чем группы 2, что показывает большую статистическую достоверность при интерпретации результатов. Заключение. Исследование позволило выявить различия в сезонной циркуляции вирусов в период инфекции COVID-19, смену основных возбудителей в ротоглотке и кале. С точки зрения клинической практики стоит отдавать предпочтение пробиотикам с более короткими сроками лечения пациентов и требующим назначения меньшего количества сопутствующих лекарственных средств, так как для пациента это оборачивается меньшей лекарственной и экономической нагрузкой. Background. The combined pathology of acute respiratory syndrome with gastrointestinal disorder is highly relevant. At this moment there were only a few studies for children on the subjects of the role of respiratory viruses and gastrointestinal pathogens with examination the materials (oropharynx and intestines). That’s why the certain role of particular pathogens in their combination are not completely determined. Objectives. The purpose of the study was to determine the role of viruses for children with acute respiratory syndrome with gastrointestinal disorder, depending on age and time of year in the period of COVID-pandemic. To evaluate the efficacy of the popular oral probiotics (oil drops dosage form) based on the results of clinical and laboratory tests in the complex therapy of acute respiratory syndrome with gastrointestinal disorder. Materials and methods. An open prospective observational study was conducted at out-patient’s clinics in the period of COVID-pandemic (04.2022-04.2023) and involved 100 children at the age of 1 month to 18 years. All children were examined on the subject of nucleic acids viruses (multiplex PCR diagnostics) from the oropharynx and feces. Additionally, there were evaluated the efficacy of probiotics. Group 1 (n = 50) received Adiarin® Probio at a dose of 6 drops 1-2 times a day. Group 2 (n = 50) received BioGaia® at a dose of 5 drops 1-2 times a day. Results. The results of the study showed high efficiency and sensitivity of the conducted probiotic therapy. However, for group 1, there was established greater sensitivity in viral infections management based on the test results of pharyngeal and fecal materials. At the same time, the width (95%) confidence interval of the Group 1 was less than for the Group 2, which means greater statistical reliability for the results interpretation. Conclusion. The study revealed differences in the seasonal circulation of viruses ib the period of COVID-pandemic, the change of the main pathogens in the oropharynx and feces. From the point of view of clinical practice, it is worth giving preference to probiotics which let treat patients shorter and need less number of additional medicines, as a result it means less drug and economic overloading for patients.

Aim: to assess the prevalence of detection of confirmed herpes virus infections (HVI) in children who had a previous COVID-19 infection, characterize specific clinical manifestations of the disease under the new conditions (post-COVID syndrome), and to provide a rationale for the administration of drug therapy. Patients and Methods: of 456 patients who received medical consultations from September 2021 to July 2022, the authors selected 72 (15.8%) children (42 boys and 30 girls) who had a previous SARS-CoV-2 infection confirmed by serological tests or polymerase chain reaction and in whom herpes viruses were found during serological evaluation. Results: most of the children (81.4%) visited the polyclinic within the first six months after the COVID-19 infection. Epstein-Barr virus (EBV) was the most prevalent finding among herpesviruses detected in children with post-COVID-19 sequela — it was detected in 44 (61.1%) cases. Human herpesvirus (HHV) 6 and cytomegalovirus (CMV) were less common in this group and found in 41 (56.9%) and 30 (41.7%) children, respectively. HHV-1 and HHV-2 were detected more rarely — in 11 (15.3%) children. Monoinfection was diagnosed in 41 (56.9%) cases and a combination of viruses was found in 31 children, in 22 (71.0%) of them it comprised two viruses, in 6 (19.3%) — three viruses, and in 3 (9.7%) — four viruses. The presence of herpesvirus infections underpinned the main reasons why parents of the ill children were seeking for outpatient care, in particular: a prolonged subfebrile condition (18.0%), fatigue and sleep disorders (27.7%), rashes (16.6%), lymphadenopathy (16.7%), ENT diseases (33.3%), more frequently occurring respiratory diseases (33.3%), and the increase in seizure activity in children with epilepsy (8.3%). In addition to herpes viruses, pathogenic agents were detected in 18% of patients, including intracellular pathogens, which were found in 13.9% of 72 children. Taking into consideration the obtained results and established clinical diagnoses, the authors conducted a review and provided a rationale for the administered drug therapy, including medications for herpes treatment. Conclusion: a prior COVID-19 infection induces immunosuppression and, as a result, the activation of herpesvirus infections as long-term effects of COVID-19 (post-COVID conditions). The presence of mixed viral and bacterial pathogens is an indication for administering antivirals, immunomodulators, antibacterial agents, and probiotics. KEYWORDS: post-COVID conditions, herpesvirus infections, children, clinical symptoms, treatment. FOR CITATION: Savenkova M.S., Sotnikov I.A., Afanasieva A.A. et al. Importance of herpes viruses in children with post-COVID conditions. Russian Journal of Woman and Child Health. 2023;6(1):39–44 (in Russ.). DOI: 10.32364/2618-8430-2023-6-1-39-44.

Every year, acute and chronic infectious diseases of the respiratory tract maintain their leading positions in terms of incidence and the magnitude of the damage caused both in the world and in the Russian Federation. The problem of respiratory infections is most relevant in children due to high prevalence of these diseases and increased risk of complications and development of chronic forms. In the last six months of the COVID-19 pandemic and after its completion, сertain peculiarities of circulation of respiratory pathogens have been noted, which complicate the choice of treatment tactics. The high polyetiologicity of acute respiratory diseases, the existence of unidentified and poorly studied pathogens, the frequent occurrence of mixed respiratory tract infections reduce the possibilities for the effective use of etiotropic therapy. In these conditions, an important role is assigned to means that activate the body's own innate and adaptive immune mechanisms to fight infection, such as bacterial lysate medicines. Objective: Generalization of relevant data on the current features of circulation of respiratory pathogens based on weekly monitoring and epidemiological studies and the development of algorithms for the treatment of patient with various acute and chronic inflammatory and infectious respiratory diseases. Key words: acute respiratory infections, COVID-19 pandemic, 2022–2023 epidemic season, sore throat, chronic tonsillitis, adenoiditis, treatment algorithms, bacterial lysate medicines

“Turning the complicated problems into the new opportunities and constantly maintaining the confidence in the future” - these are the principles the Morozov Children’s Hospital and its entire large team approach the celebration of its 120th anniversary with. The history of the Morozov Children’s Hospital is a history of the constant movement forward, a history of the highest professionalism and courage of its staff, a history of achievements and victories. As of today, the Morozov Children’s Hospital is one of the largest multidisciplinary hospitals not only in Moscow, but also overall Russia, where patients expect and get the best professional experience coupled with the effective solutions of their health problems with the use of both modern and innovative technologies. “Compassion and Professionalism,” which was a motto for years, sounds more relevant now than ever.

Objective. To evaluate the efficacy of therapy for acute respiratory viral infections (ARVIs) in children with antiviral medications: inosine pranobex (Groprinosin®, Gedeon Richter) and Kagocel (Kagocel®, Niarmedic Pharma LLC) in comparison with symptomatic treatment without etiotropic agents based on clinical and laboratory parameters. Patients and methods. The clinical and laboratory observation was conducted in an outpatient setting in the pre-COVID-19 period between 2018 and 2020. Acute respiratory infections were diagnosed using licensed testing systems by multiplex polymerase chain reaction (PCR) with detection of nucleic acid viral genomes: influenza, rhinovirus, respiratory syncytial virus, metapneumovirus, parainfluenza, seasonal coronaviruses, adenoviruses, and bocavirus). A total of 151 children aged 3 to 15 years were examined and monitored in dynamics, with 78.7% of positive and 21.3% of negative results detected by PCR in the nasopharyngeal and oropharyngeal swabs. The patients were randomized into three groups depending on the antiviral medication prescribed: group 1 (53 children) received Groprinosin®; group 2 (52 children) received Kagocel®; group 3 (control, 46 children) received only symptomatic therapy without antiviral agents. Results. The study demonstrated a significant positive effect in patients in group 1 treated with Groprinosin® (n = 53). At the end of therapy for both mono- and mixed infections, there were 95.8% of negative results (according to PCR diagnosis, that is, the absence of viral genome). In children in group 2 (n = 52) treated with Kagocel®, the absence of viral nucleic acids (NAs) was observed less frequently (in 77.3% of cases). In children in group 3 (n = 46) who did not receive etiotropic antiviral therapy, there were only 40.3% of negative results after the end of treatment, and viral NAs were detected in 59.7% of patients. In this case, a 5-day course of Groprinosin® was prescribed, after which the PCR results became negative in all patients. Therefore, children with recurrent respiratory infections, mixed infections, and herpesvirus infections require longer therapy. Additionally, a high frequency of ARVI complications was noted in group 3 (5 (10.9%) patients, where otitis was observed in 1 case, sinusitis – in 2 cases, bronchitis – in 2 cases), whereas 1 (1.8%) patient taking Groprinosin® had otitis, and 1 (1.9%) patient taking Kagocel® had pneumonia. Conclusion. This study was the first to investigate antibody titers to respiratory viruses in dynamics at 3, 6 and 12 months after the onset of ARVI. It showed that the development of antibodies to respiratory viruses is very unstable and does not occur in all patients. Antibodies almost disappeared by the third month after ARVI and were no longer detectable by the sixth month. After 12 months, patients suffered a new ARVI and developed the corresponding antibodies. This information will be especially relevant in conditions of the rise in the incidence of ARVIs, as well as the COVID-19 pandemic observed in recent years. Key words: antiviral agents, polymerase chain reaction, specific antibodies to acute respiratory viral infections, children, clinical and laboratory dynamics, inosine pranobex, Groprinosin®, Kagocel®

This study compared the efficacy of different therapies for ARVI during the COVID-19 pandemic. Objective. To compare clinical efficacy of Cycloferon and Ingavirin in children aged 4–17 years treated in outpatient facilities during the epidemic season of СOVID-19. Patients and methods. This study included 101 patients who provided 143 oro- and nasopharyngeal swabs tested using certified PCR tests. Of them, 128 samples (89.5%) were positive, whereas 15 samples (10.5%) were negative. We identified the most common viruses circulating in January–May 2021, including (seasonal) coronaviruses (35.9%), rhinoviruses (20.3%), and other viruses. We also analyzed respiratory viruses that have circulated in Moscow during the last 6 years and found higher levels of seasonal coronaviruses. The most common ARVI symptoms in 2021 were fever, rhinitis, pharyngeal hyperemia, and fatigue. Fewer children had headache, cough, and enlarged lymph nodes. Results. We compared ARVI treatment with broad-spectrum antivirals in children aged between 4 and 17 years. Children in group 1 (n = 51) received Cycloferon®, while children in Group (n = 50) received Ingavirin®. Study participants were diagnosed with ARVI and moderate nasopharyngitis. Children from the Cycloferon group demonstrated a more significant dynamics of such clinical symptoms as headache (p < 0.05), cough (p < 0.01), rhinitis (p < 0.01), abundant mucus (p < 0.001), and enlarged lymph nodes (p < 0.001) than children from the Ingavirin group (there was a significant difference in the duration of these symptoms). Only 2 children from group 1 required antibiotics (3.4%), whereas in group 2, 11 children needed antibacterial therapy (22%). Key words: children, acute respiratory viral diseases (ARVI), COVID-19, PCR diagnostics, clinical manifestations, Cycloferon, Ingavirin

The paper presents the indications and main differences of frequently used rectal suppositories containing interferon alpha-2b.The features and differences in the contained excipients are highlighted. A range of diseases in children's practice is presented, in which candles are shown VIFERON®, Kipferon®, Genferon light®

Objective. To analyze circulation of herpes simplex virus (HSV), Epstein–Barr virus (EBV), cytomegalovirus (CMV), and human herpes virus type six (HHV-6) within families, to evaluate the conditions of formation of family foci, and to identify possible sources of infection. Patients and methods. We examined 124 families, including 11 two-parent families (mother, father, and child) and 108 oneparent families (mother and child). Five families had a mother and two children. Antibodies of various classes against herpesviruses were detected using enzyme-linked immunosorbent assay (ELISA). Herpesvirus antigens were detected using indirect immunofluorescence assay; early antigens and herpesvirus reproduction were evaluated using culture method; viral DNA was identified using polymerase chain reaction. Results. We have revealed a high rate of infection with herpesviruses in both adults and children. Markers of infections caused by HSV and EBV were detected in the majority of mothers (96.0% and 90.3%; 119 and 112), while children had these infections less frequently (66.7% in each group (86)). Detection of active forms of infection and convalescents, both among children and adults, indicates an intensive circulation of herpesviruses within families and leads to the formation of family foci of infection. Active infections were primarily caused by CMV (20.2% of children, 17.8% of mothers, and 15.4% of fathers) and EBV (16.3% of children, 11.3% of mothers, and 9.1% of fathers). Out of 266 participants examined (mothers, fathers, and children), cases of acute mixed infection were observed in children only (4 of 129) and were caused by HHV-6 in combination with HSV (2 cases) or CMV (2 cases). Conclusion. Continuous and intensive circulation of herpesviruses in families leads to the formation of family foci of infection. To stop intra-family transmission of viruses, it is important to identify possible sources of infection and perform antiepidemic measures. This transmission is most likely to occur in families where the mother has markers of active or recent infection, while the child does not have them at all. Such combination was detected in 16 patients with EBV (12.4%), 10 patients with HHV-6 (7.8%), 6 patients with HSV (4.7%), and 5 patients with CMV (3.9%). It is crucial to identify the role of the child as a source of herpesvirus infection. Key words: herpesvirus infections, infection markers, family foci, cytomegalovirus infection.

The article considers the issues of pharmacodynamics, clinical efficacy and safety of macrolide antibiotics. It also discusses the development of microorganisms resistance to macrolides. A number of studies in vivo and in vitro on various cellular and animal models have shown that macrolides have anti-inflammatory and immunomodulatory effects. The presence of these effects in macrolides may be especially relevant during the period of increasing incidence of influenza and the new COVID-19 coronavirus infection. It is known that the severity of viral infections is associated with the release of proinflammatory cytokines. Macrolides change the entire inflammatory response cascade by weakening the excess production of cytokines. Besides, macrolides can affect the activity of phagocytes, changing their function, including chemotaxis, phagocytosis, destroying bacteria and viruses. Earlier it was reported that macrolides (in particular, clarithromycin) can interfere with the replication cycle of the influenza virus, thus leading to its production inhibition by intracellular proteolysis of hemagglutinin. One of the commonly prescribed drugs in this group is clarithromycin. The article summarizes the literature data and presents the materials of our own clinical observations on the clarithromycin treatment of children with intracellular bacterial pathogens, the causative agents of which are Mycoplasma pneumoniae and Chlamydia pneumoniae. KEYWORDS: macrolides, clarithromycin, intracellular bacterial pathogens, children, antibacterial therapy. FOR CITATION: Savenkova M.S., Savenkov M.P. Topical issues concerning treatment of intracellular bacterial pathogens in children. Russian Journal of Woman and Child Health. 2020;3(4):326–335. DOI: 10.32364/2618-8430-2020-3-4-326-335.

Relevance. Previous studies showed an important role of herpes viruses in children with epilepsy and infantile cerebral palsy (ICP). Materials and methods. This study was conducted from 2014 to 2018 on the basis of the Voino-Yasenetski Scientific and Practical Center for Specialized Medical Care for Children and the Morozov Children's City Clinical Hospital. Serological and microbiological molecular genetic (PCR test) methods, ELISA test, indirect immunofluorescence reaction and rapid culture method were used to confirm herpes infection. In the open prospective study 298 children with epilepsy and ICP were included, in 131 (44%) of them herpes infection was revealed. 100 children who received inosine pranobex (Groprinosin®) were under follow-up: 92 children were in the hospital and 8 children were outpatient. Inclusion criteria were: children aged 3-15 years with epilepsy and ICP. Most children have symptomatic focal epilepsy. Exclusion criteria were: age less than 3 years, severe hematological, oncological and somatic diseases. Children were divided into the following groups: group 1 - epilepsy (n=36); group 2 - epilepsy + ICP (n=20); group 3 - ICP (n=44). The comparison group (group 4) included 31 children aged 3 to 15 years with herpes virus infections: epilepsy (n=25) and cerebral palsy (n=6), who took conventional anticonvulsant therapy without inosine pranobex. Results. In the group of children examined, mainly aged 3-6 years, the most prevalent infections were cytomegalovirus (75.3%) and human herpes virus (HHV)-6 (86.2%) along with Epstein-Barr virus and HHV-1, HHV-2. Patients infected with cytomegalovirus and HHV-6 have mainly an acute course of disease (40.9 and 51.9%, respectively) while patient with Epstein-Barr virus and HHV-1, HHV-2 have a persistent chronic course of disease (76.1 and 75.5%, respectively). Most of the examined children showed mixed infection with 2 or 3 different herpes viruses. In groups of children who took inosine pranobex, treatment showed highly beneficial effect on dynamics of clinical, laboratory and instrumental parameters.

The study showed a high prevalence of markers of herpesvirus infections among mothers — from 71% to 98% of HSV, EBV and CMV infections and from 29% to 58% of HHV-6 infection. HSV remains the most common etiological agent of intrauterine infections among herpesviruses — markers of active infection caused by this virus were found in 28.3% samples. The difficulty of determining the source of infection in the absence of data in the early stages of pregnancy is presented on 4 out of 10 cases of active HHV-6 infection. Markers of active pneumocystic infection were detected only in mothers: in the group with children under the age of 21 days — in 21—27% of cases, with children aged 22 to 28 days — in 15—21%. In addition to non-specific multiple organ failure during intrauterine infections (26.3%), only one organ system was observed: hypoxic-hemorrhagic lesions of the central nervous system were diagnosed more often — 17%, as well as meningitis/encephalitis, or hepatitis, or pneumonia, or disorders of hematopoiesis, or rash. In 17.5% of children from the comparison group, i.e. without any clinical manifestations of intrauterine infections, markers of active herpes virus infections were detected.

The article describes the clinical case of infantile myofibromatosis of a newborn child. Infantile myofibromatosis is a rare mesenchymal tumor of the soft tissues of the head, limbs, trunk in children with infiltrative local growth, without metastases. During the examination the patient was diagnosed multiple myofibroms, which had a tendency to increase in the combination of active herpes infection. In this case, does not exclude the impact of mixed herpetic infection on the growth of myofibroms as on the background of antiviral treatment showed positive dynamics with a decrease in the number and size of tumors.

Diagnostics of intrauterine infection associated with T. gondii, today is a task with an ambiguous solution for different specialists — gynecologists, obstetricians, neonatologists, infectious disease specialists, resuscitators. This problem is interdisciplinary, and its coordinated decision, diagnosis and treatment of this disease at an early stage will reduce the risk of stillbirths, deaths and severe consequences. The article reflects the current literature data on the clinical features of toxoplasmosis in relation to the genotype of Toxoplasmа, circulating in the world. Particular importance is given to the selection of methods for prenatal and postnatal diagnosis of toxoplasmosis. The data of the latest review (2017) of theAmericanAcademy of Pediatrics on the diagnosis, treatment and prevention of congenital toxoplasmosis are presented. The main clinical manifestations of toxoplasmosis were revealed. Basic preparations for treatment of toxoplasmosis is Trimethoprim + sulfamethoxazole (Biseptol) and spiramycin (Rovamycin).