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Background. Cytomegalovirus infection (CMVI) is the reason of high mortality in perinatal period, disability in children from risk groups with further development of congenital malformations and chronic diseases. Clear understanding of epidemiology and determination of focus population groups is crucial for development of measures and algorithms of congenital CMVI prevention.Objective. The aim of the study is to study CMVI seroprevalence among immunocompetent adolescents in Russian Federation with reference to the gender, regional, social and economic, and age factors.Methods. We have used for our study data from the survey of senior schoolchildren from 7 municipalities representing various regions of Russian Federation: group 1 (10–12 years old) and group 2 (14–16 years old). The study of CMVI seroprevalence and immune response was performed via the analysis of the level of IgG antibodies to cytomegalovirus (CMV) in blood serum. The social and economic well-being of the region was determined by "RIA Rating" experts.Results. Serological prevalence of CMVI in the study group of adolescents (n = 1403) was 70.6% (n = 990). There were no statistically significant gender differences in the distribution of seropositive children in regions (p = 0.525). Infection in boys (72.6%; n = 455; median age — 12.9 (11.0; 14.9)) did not prevail over the infection in girls (68.8%; n = 535; median age — 13.1 (11.0; 14,9)); p = 0,117. The overall prevalence of CMVI increased statistically significant with age — from 68% (n = 486) in group 1 to 73% (n = 504) in group 2 (p = 0.036). The prevalence of CMVI varied statistically significant by region (p = 0.003). There was no correlation between the regional seropositive level and the social and economic situation in the region (r = 0.034, p = 0.192). Immune response intensity did not differ by age, gender, and region with the antibody median of 88.9 CU/ml.Conclusion. More than half of adolescents (by the age of 10) in Russian Federation are infected, and infection increases with approaching to childbearing age, however, age is not the only aspect associated with serological status. Factors affecting immune response intensity require further study. Understanding of the CMV prevalence among children is crucial for determining future prevention approaches in target groups.

There has been developed and validated the technology for massive parallel sequencing for the purpose of molecular genetic diagnosis of hereditary glycogen storage diseases. Among 96 patients aged of from 15 months up to 18 years, the diagnosis was verified in 89 (92.6%) children. Glycogen storage disease (GSD) type IX appeared to be the most frequent form of glycogenosis in children, diagnosed in 29.3% of cases, GSD type IV, verified in 1.1% of cases, was a rare form of glycogenesis. In 39 (43.8%) out of 89 genetically confirmed children, there were revealed 35 (44.3%) of the previously undescribed mutations from 79 pathogenic variants found in 9 (45%) of different genes of 20 examined cases, indicating to a significant heterogeneity of genetic factors of the development of GSD in the Russian population. Mutations c.247C>T of the G6PC gene, c.1042_1043del of the SLC37A4 gene, c.3980G>A and c.1423+1G>A of the AGL gene, c.-32-13T>G of the GAA gene, and c.884G>A of the PHKA2 gene were been established to be characteristic for the Russian population of GSD children. There was shown the high sensitivity and specificity of the massive parallel sequencing for the search for single nucleotide substitutions in coding and adjacent intron regions, as well as small deletions and duplications of genes, mutations in which lead to the development of GSD. Massive parallel sequencing is necessary for the rapid diagnosis of GSD, timely appointment of the adequate treatment, prevention of complications, which will improve the quality of the life of GSD patients.

The aim of the study was the improvement and gain in the efficiency of preventive medical examinations of minors. There were studied the information and statistical materials of the dispanserization of the children population of the Russian Federation in 2014 concerning the health of various age groups in terms of Federal districts and subjects. There were analyzed indices of the coverage of the children’s population with preventive routine medical examination; level and structure of the revealed general and primary prevalence; frequency of the dispensary registration; neediness in additional consultations, examinations and treatment in the conditions of out-patient clinic, a day hospital, a hospital of the round-the-clock stay, the sanatorium organizations, as well as the coverage by these medical services. There was recorded the high level of the coverage of minors by routine medical examinations. The ration of healthy children's population was more than one third from all cases who passed medical examination. The revealed general and primary prevalence rate of the children's population in large part (more than one third) subjects has level above the Russian one. The main reasons of children’s morbidity are diseases of respiratory organs, bone and muscular and nervous systems while teenagers mostly have diseases of bone and muscular system, an eye, appendages of the eye and respiratory organs. The high prevalence of chronic diseases among the children’s population in preventive medical examinations failed to be followed by recommendations for treatment and rehabilitation in sufficient volume. Regional features of results of medical examination allowed to identify the most disadvantaged areas, to identify defects in its organization and the lack of continuity between medical institutions providing this type of services.

The creation of the system of early prophylaxis of children disability and support of families bringing up disabled children and children with limited opportunities of health are among the main priorities of the state social policy of the Russian Federation. The search for literature sources was performed in the Scientific Online Library (eLIBRARY.RU) and PubMed. The dynamics of children’s disability in our country is characterized by the process of stagnation. Among risk factors for the formations of the disability the most discussed are achievements of perinatology leading to the improvement of nursing of prematurely born and small for date newborns, and wide uses of auxiliary reproductive technologies. An important part of all preventive measures aimed at the decline of the genetic load of population is the prenatal and preimplantation diagnosis. It seems appropriate to extend the screening for congenital and hereditary metabolic diseases in neonatal period, including the most common nosological forms of rare illnesses. In the solution of problems of the prevention of the childhood disability a priority should be given to the development of services of family planning, improvement of the antenatal and perinatal care, the preventive work with healthy children with deviations in the development, the development of medical genetic services, implementation of programs of different types of pathology screening.

Relevance of research was determined by need of enhancement and increase of efficiency of routine medical examinations of minors of the Russian Federation. The information and statistical materials of medical examination of the children’s population of 2014 concerning health of various age groups in a section of federal districts and subjects were studied. The following indicators were studied: coverage of the children’s population by routine medical examination; level and structure of the revealed general and primary incidence; frequency of dispensary registration; neediness in additional consultations, researches and treatment in the conditions of out-patient clinic, a day hospital, a hospital of the round-the-clock stay, the sanatorium organizations, as well as coverage by these medical services. The high level of coverage of minors by routine medical examinations was registered. The share of healthy children’s population more than one third from all passed medical examination. The revealed general and primary incidence of the children’s population in large part (more than one third) subjects has level above Russian. The leading reasons of children’s incidence are diseases of respiratory organs, bone and muscular and nervous systems while teenagers mostly have diseases of bone and muscular system, an eye and its additional device and respiratory organs. Despite the high prevalence of chronic diseases among the children’s population, recommendations for treatment and rehabilitation at routine medical examinations were given insufficient. Regional characteristics of the results of medical examination which allowed to identify the most disadvantaged areas, to identify defects in its organization and the lack of continuity between medical institutions providing this type of service had been established.

Relevance. Allergic pathology in particular, a hay fever, can lead to decrease in cognitive functions at children. Earlier it was established that antihistamine preparations of I generation influence cognitive functions of patients. Тhe patients with this nosology receive for a longtime courses of antihistamine preparations of II generation, so the analysis of influence of different AH preparations of II generation on cognitive activity of children with a hay fever is necessary. Purpose. Studying of influence of II generation antihistamine preparations in a complex with the specific allergen immunotherapy on cognitive functions at children with a hay fever. Patients and methods. Using the psychophysiological computer complex «Psihomat» the condition of cognitive functions was established. In total the 81 child with a hey fever were investigated. The persons under consideration were divided on subgroups depending on antihistamine which they received. For the patients in the main group of investigation the cognitive functions have been studied in 3 points. Results. The patients had changes in the attention and psychomotor activity more often, than in other conitive activity. It is not obtained distinct data on characteristic contribution of antihistamine preparations of a second generation in improvement of cognitive activity as a whole at complex treatment of hay fever with specific allergen immunotherapy. Antihistamine preparations (desloratidine and cetirizine) are improved by indexes of visual and space perception at children with a hay fever. From the 3 antihistamine preparations the cetirizine has the most carried out positive effect concerning the psiho-motoric activity in the combined ASIT. Conclusion. Padding express researches in the field are necessary for receiving the definite answers to problem questions.

We aimed to describe bacterial etiology of acute otitis media (AOM) and characterize resistance, serotypes and genotype profiles of AOM-causing pneumococci recovered in Moscow children.Children with AOM and an available middle ear fluid specimen were prospectively enrolled in this study. Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus influenzae and Moraxella catarrhalis were considered as true otopathogens. All pneumococcal isolates were serotyped using the Quellung reaction; multidrug-resistant (MDR) pneumococci underwent multilocus sequence typing.In 172 of 541 enrolled AOM patients (32%) at least 1 otopathogen was recovered, with S. pneumoniae having the highest rate of 63% (109/172). When adjusted for antibiotic treatment before sampling, in untreated patients the rate of culture-positive AOM was 35% (124/352), S. pneumoniae had a prevalence of 69% (86/124), S. pyogenes 19% (24/124), H. influenzae 13% (16/124) and M. catarrhalis 9% (11/124). Among 107 examined pneumococci, 45% were penicillin-nonsusceptible, 34 and 30% were resistant to erythromycin and clindamycin, respectively; 30% had an MDR phenotype, but no amoxicillin-resistant isolates were found. Ten of 32 (31%) MDR pneumococci related to clonal complex 320, the remaining isolates belonged to 7 different clonal complex. Six leading serotypes were 19F (27%), 3 (12%), 6B (11%), 14 (11%), 19A (9%) and 23F (8%); overall polysaccharide conjugate vaccine13 coverage was 93%.S. pneumoniae, the leading bacterial AOM pathogen in Moscow children, is characterized by a substantial rate of antibiotic nonsusceptibility and clonality. A polysaccharide conjugate vaccine with expanded coverage seems to fit the current AOM pneumococcal serotype distribution in Russia better.

Actuality The Influenza is a highly contagious viral infection, which may develops into severe inflammatory disease of the respiratory tract and other organs and systems. It caqn cause severe illness, and at times can lead to death. Children with chronic diseases, including allergic pathology, have a hard current of disease. Influenza in children with allergic diseases is often accompanied by the relapses of the disease, in patients with bronchial asthma proceeds with the development of attacks or complicated by pneumonia. The only reliable way of specific prevent of influenza is vaccination. Objective to study the portability and effectiveness of immunisation against influenza by vaccines «Influvac» (Netherlands) and «Grippol plus» (Russia) in children with allergic diseases. Materials and methods There were vaccinated 251 children and adolescents aged 3 to 17 years old with various allergic diseases. The group of comparison consisted of healthy children amounted to 80 people. There was analysed the portability of vaccination, the course of the main disease and frequency of acute respiratory infections during the year after immunisation. The specific immune response evaluated after the 1 and 6 months after vaccination. Results Local reactions to vaccines were found in 18% in healthy and 23% of children with allergic pathology, general reactions – both in 14% of healthy children and children with allergies. All the reactions were of mild or moderate severity. Significant differences in tolerability of influenza vaccine in healthy children compared with children c allergic pathology was revealed. There have been no cases of relapses of chronic allergic process, associated with influenza vaccination. The frequency of episodes of acute respiratory infections and bronchial asthma in following after the vaccination season was significantly decreased in children immunised with «Grippol plus» (in 1,5 times, at 35%), and with «Influvac» (in 1,4 times, at 30%). The rise of specific antibodies revealed almost in 3 times while using both vaccines in 1 month after vaccination in children of both groups, and 6 months after their decline in the majority of children up to the benchmarks. Conclusion Vaccination against influenza by vaccines of Russian and import production is safe and effective, doesn’t cause the relapses of allergic diseases and contributes to reduction of the acute respiratory infections in the season following vaccination.

Background and aims Congenital and hereditary diseases of respiratory system are often accompanied by nonspecific symptoms, that result in late diagnosis and time-lag therapy. In some cases, such diseases have symptoms, similar to asthma, so children are wrong diagnosed and do not receive appropriate treatment for a long time. Aim: to define the informative value of measurement of exhaled nitric oxide (FeNO) as a non-invasive screening method for patients with pathology of pulmonary system. Methods 598 children (from 4 to 17 y.o.) were examined at Scientific Centre of Children’s Health from 01.01.2012 to 11.06.2016. The level of FeNO was determined by portable hand held monitor using, unit ppb (parts per billion). Results 557 patients (93.14%) were diagnosed with asthma of different severity. Variation of level of FeNO depended on asthma severity and control. FeNO was normal or elevated (from 5 to 233 ppb). In 41 (6.8%) patients the level of FeNO was low ( Conclusions The finding data indicate the possibility of using of FeNO level evaluation as a non-invasive screening method in the complex differential diagnostics of pulmonary system pathology in children.

Background and aims Last five years more than 50 novel microdeletion and microduplication syndromes were described. Sometimes we find rare chromosome anomalies, which clinical significance is not always known. Our aim was to describe the new phenotype of rare chromosome disorders in patient with mental retardation caused by genotype combined with different microdeletion Methods Boy, 5 years old, was observed with developmental delay with the first year of life. Clinical features: upslanting palpebral fissures, epicanthal folds, short philtrum, synophrys, microstomia, low set ears, prominent forehead, high borderline of hair growth, sensorineural and conductive deafness. We used the CytoScan HD Array solution (Affymetrix) for detecting of chromosomal pathological variants lager than 50 kb. Results We detected a 7,4 Mb pathogenic deletion in chromosome region 7 p21.1–7 p15.2 and a smaller one 494 kb deletion in the chromosome region 22q12.1 spanning the genes TTC28 and CHEK2. This deletion has not been described previously. According to the literature, deletions in this chromosomal region larger than 300 kb was described in patients with mental retardation and multiple malformations including conductive deafness. Conclusions It is known that the patients with deletions in 7 p21–p14.3 chromosome region have mental retardation and facial features similar to Greig syndrome and patients with 22q12 deletions have mental retardation, hearing loss and heart disease. All of these clinical features were present in phenotype of our patient. The results of our molecular cytogenetic research allow to reveal the combination of two microdeletions which fully explain the existing phenotype of patient. The Affymetrix microarray solutions is a powerful flexible method for detection of rare chromosomal aberrations which can help to paediatricians and clinical geneticists explain and describe new phenotype in patients with rare chromosome disorders.

Subdural hematomas are most common in infants and elderly adults and result from bridging veins’ tears. Subdural haemorrhage has been described in several neurometabolic diseases with cerebral atrophy, including MPS II and IIIB. Few reports describe impaired hemostasis in MPS I and II presumably due to anticoagulant activities of glycosaminoglycans. Routine brain MRI of 8-year-old boy with MPS IIIB and developmental regression revealed chronic subdural hematoma of right hemisphere and cerebral atrophy. There was no indication on preceding trauma. Three weeks later the boy presented with seizure episode, whereupon he started to have hemiparetic gait, got drowsy. Brain KT displayed acute haemorrhage in the region of the chronic subdural hematoma. Laboratory studies demonstrated fluctuating thrombocytopenia, impaired platelet aggregation to ADP and arachidonic acid, decreased level of plasma fibrinogen. The patient was treated with platelet concentrate transfusion, etamsylate, folic acid and closed external drainage of subdural hematoma was performed. Three months after subdural hematoma surgery the patient’s status remained stable. According to presented data we conclude that regular neurovisualization and coagulation tests should be included in the standard workup for patients with neuronopathic mucopolysaccharidoses, as constellation of abnormal hemostasis and progressive cerebral atrophy may present a risk of intracranial haemorrhage.

Sarcoidosis occurs in children very rare. There is not clear recommendation about dose and duration of corticosteroid therapy in children with sarcoidosis. The 11 year old male had fatigue and granuloma annulare on his legs from February 2014. He was treated by benzatin benzylpenicillin with partial effect. Enlarged mediastinal and supraclavicular lymph nodes, small focuses in both lungs with tendency to conglomeration and small focuses in the spleen were revealed on CT-scan (CT) in July 2014. TB infection was excluded. Sarcoidosis was proven by supraclavicular lymph node biopsy. Spirometry: FEF75 – was decreased, salbutamol test – negative. The boy was prescribed methylprednisolon 22 mg/day from 18.08.2014 till 4.09.14, with further gradual reduction till withdrawal on 8.09.15. Annular granuloma and fatigue were resolved to October 2014, spirometry became normal to December 2014. CT on 16.03.15 revealed reduction of mediastinal lymph nodes size and quantity of lung focuses, CT on 15.10.15, 25.03.16 and 30.01.2017 remained this positive tendency. Conclusion This is a rare case of generalised sarcoidosis in child. It demonstrates effect of methylprednisolone therapy with gradual reduction during one year.

Objective To describe ocular changes in patients with mucopolysaccharidosis of different forms. Materials and methods We analysed the results of 78 children examination (156 eyes) at the age from 1,5 to 18 years, of them 11 children-with MPS I type, 38 children- with the MPS II Hunter, 18 – with the MPS III Sanfilippo, 4 patients with IV type and 6 children with the MPS VI Maroteaux-Lamy. The ophthalmic investigation included visometry, IOP measurement ( noncontact air-puff tonometry), biomicroscopy, ophthalmoscopy, retinoscopy, ERG-method. Results 78 patients were identified with a diagnosis of mucopolysaccharidosis. The anomaly was bilateral in 78 children. The ocular management of patients with mucopolysaccharidosis of different forms were conservative because of their intellectual impairment. Vision remained stable in 10 patients. Deterioration in other 68 patients was related to progressive corneal clouding and refraction errors, amblyopia. 3 patient were diagnosed with having intraocular pressure–related optic nerve damage. 5 patients had simptoms of ocular hypertension. Other 70 patients had no previous studies of the incidence of ocular hypertension or glaucoma. Biomicroscopy in 36 children with megalocornea, the cornea diameter reached 13 mm and dilation of conjunctiva vessels and thickening of deep layers of cornea were detected. In 16 patients, marked corneal opacity bullous regeneration was seen. Minor changes in pigmentary epithelium and chorioids were detected 24 patients with scleral defect walls and edges. In 26 children, the retina vessels had dilation, wall thickening, and normal pathway. In 68 cases on retinoscopy, astigmatism was detected, high- degree hypermetropia, high-degree amblyopia. The ERG method indicates in 6 patients disfunction of the retina with normal to severe changes. Conclusion: In MPS I macrocornea, corneal clouding,conjunctiva vessels dilation, retinal dystrophy and increase in intraocular pressure were detected. In the MPS-II megalocornea, cornea opacity localising in the cornea deep layers and stroma thickening were observed.Pigmentary rethinopathy and non-recordable ERG, pappiloedema was diagnosed in 7 patients. Mucopolysaccharidosis III is characterised by hypertelorism and proptosis, no changes in retina. In the MPS-IV corneal deposits like ‘dust’, fundus changes in the form of optic disk oedema and secondary optic atrophy were seen. ERG abnormalities were reported in this type of MPS.

Background and aims The purpose of the study was to assess the quality of preventive medical examinations of minors. Methods The official data of Federal state statistics service for children health were analysed. Results The study resulted in the development of a method for assessing the quality of preventive medical examinations of minors, and recommendations for improving those examinations. On the whole, the quality of preventive medical examinations is rate as satisfactory. At the same time, morbidity underestimation patterns were identified. In order to improve the quality of preventive medical examinations of minors, it is necessary to ensure implementation of a set of measures: improve the quality of detection of the reproductive system diseases; improve the quality of detection of allergic diseases and of adequate treatment and preventive interventions; improve the quality of detection of the endocrine system diseases. Conclusions The priority directions for minors health improving are: - to extend the National calendar of vaccinations; - The Russian public health authorities in the regions of the RF should ensure comprehensive preventive medical examinations of minors.

Aim To examine the status of blood coagulation factors in patients with mucopolysaccharidosis (MPS) type II. To diagnose of polymorphism in the genes of coagulation in this pathology. Materials and methods We observed 16 boys with MPS II type. The deficiency of XII factor (Hageman factor) was detected in half of patients; meanwhile we found the combined deficiency of XII factor with deficiency of other factors of blood coagulation: two patients had combined deficiency of IX and VIII factors; one patient had deficiency of VII and VIII factors; a single case – the deficiency of IX factor. One patient had a deficiency of VIII, VII, IX factors. However, the deficiency of von Willebrand factor (VWF) was found only in 1 case, but without the deficiency of XII factor. We found polymorphisms in genes of coagulation. It was discovered carriage of modified alleles in the genes encoding the enzymes involved in homocysteine metabolism: MTHFR (methylentetrahydrofolate) and MTRR (methionine-synthase-reductase) and plasminogen activator inhibitor PLANH1 5G. The gene polymorphism of ???FR found almost half of the cases. The heterozygous state of MTHFR C677C/T gene identified in 37.5% of cases; homozygous state C667 T/T in 12%. Heterozygous carriers of the MTRR A66G met at −56,25% of the patients, and homozygous MTRR G66G – 31,25% of patients. The polymorphism −675 4G/5G (5G->4G) of plasminogen activator inhibitor PLANH1 5G (−675)4G was found in 31% patients. Discussion The results of the study suggest that in children with MPS high probability of a deficiency of Hageman factor, not only in isolation but also in combination with a deficiency of certain other blood coagulation factors. The presence of polymorphisms in genes of coagulation responsible for the exchange of the folate cycle and methionine can play the role of trigger factors in the development of thrombosis, thromboembolism, especially in combination with a deficiency of the Hageman factor. Conclusion The investigation of these parameters plays a prognostic role in the development of possible complications of the hemostatic system in children with chronic diseases of the cardiovascular system.

The mucopolysaccharidoses (MPSs) are rare genetic disorders caused by mutations in lysosomal enzymes involved in the degradation of glycosaminoglycans (GAGs). In this study, we analyzed a total of 48 patients including MPSI (n=6), MPSII (n=18), MPSIIIA (n=11), MPSIVA (n=3), and MPSVI (n=10).In MPS patients, urinary GAGs were colorimetrically assayed. Enzyme activity was quantified by colorimetric and fluorimetric assays. To find mutations, all IDUA, IDS, SGSH, GALNS, and ARSB exons and intronic flanks were sequenced. New mutations were functionally assessed by reconstructing mutant alleles with site-directed mutagenesis followed with expression of wild-type and mutant genetic variants in CHO cells, measuring enzymatic activity, and Western blot analysis of protein expression of normal and mutated enzymes in cell lysates.A total of five novel mutations were found including p.Asn348Lys (IDUA) in MPSI, p.Tyr240Cys (GALNS) in MPSIVA, and three ARSB mutations (p.Gln110*, p.Asn262Lysfs*14, and pArg315*) in MPSVI patients. In case of mutations p.Asn348Lys, p.Asn262Lysfs*14, and p.Gln110*, no mutant protein was detected while activity of the mutant protein was1% of that of the normal enzyme. For p.Tyr240Cys, a trace of mutant protein was observed with a remnant activity of 3.6% of the wild-type GALNS activity. For pArg315*, a truncated 30-kDa protein that had 7.9% of activity of the normal ARSB was detected.These data further enrich our knowledge of the genetic background of MPSs.

Vaccine safety surveillance is highly dependent on accurate reporting of adverse events following immunization (AEFI). An online survey was conducted to assess the utilization of AEFI reporting standards and pathways among pediatricians in Germany, and in Russia where pediatric specialization begins in medical school. In May 2011, a 31-item online questionnaire was sent to members of the German Professional Association for Pediatricians (BVKJ) and the Union of Pediatricians of Russia (UPR), capturing information on vaccine safety training, awareness of AEFI reporting pathways, and use of standardized case definitions for the ascertainment of AEFI. A convenience sample of 1,632 completed online surveys was analyzed. Participating pediatricians reported spending approximately 50 min per 8-hour workday on vaccine safety consultations, but only 42 % (56 % UPR, 26 % BVKJ) have ever received any formal vaccine safety training. Two-thirds reported having observed AEFI in their practice, but only one-third utilized standardized case definitions for case ascertainment. Only 35 % of participants named accurate AEFI reporting pathways. Every second pediatrician would report AEFI to institutions that are not primarily in charge of vaccine safety surveillance; the remaining reports would either be lost or delayed. Pediatricians who had received formal vaccine safety training were significantly more likely to apply international safety standards and to report adequately, both at the p

Mucopolysaccharidosis type II (MPS II) is a rare X-linked disorder caused by alterations in the iduronate-2-sulfatase (IDS) gene. In this study, IDS activity in peripheral mononuclear blood monocytes (PMBCs) was measured with a fluorimetric enzyme assay. Urinary glycosaminoglycans (GAGs) were quantified using a colorimetric assay. All IDS exons and intronic flanks were bidirectionally sequenced. A total of 15 mutations (all exonic region) were found in 17 MPS II patients. In this cohort of MPS II patients, all alterations in the IDS gene were caused by point nucleotide substitutions or small deletions. Mutations p.Arg88His and p.Arg172* occurred twice. All mutations were inherited except for p.Gly489Alafs*7, a germline mutation. We found four new mutations (p.Ser142Phe, p.Arg233Gly, p.Glu430*, and p.Ile360Tyrfs*31). In Epstein-Barr virus (EBV)-immortalized PMBCs derived from the MPS II patients, no IDS protein was detected in case of the p.Ser142Phe and p.Ile360Tyrfs*31 mutants. For p.Arg233Gly and p.Glu430*, we observed a residual expression of IDS. The p.Arg233Gly and p.Glu430* mutants had a residuary enzymatic activity that was lowered by 14.3 and 76-fold, respectively, compared with healthy controls. This observation may help explain the mild disease phenotype in MPS II patients who had these two mutations whereas the p.Ser142Phe and p.Ile360Tyrfs*31 mutations caused the severe disease manifestation.

Summary Background Pneumococcal infections remain a major medical problem associated with high morbidity and mortality. Moreover, the resistance of Streptococcus pneumoniae to conventional antibiotics is constantly growing. The implementation of pneumococcal conjugate vaccines (PCVs) in the last decade has dramatically reduced the incidence of the vaccine type-associated invasive pneumococcal diseases in many countries. However, information on the seroepidemiology of S. pneumoniae in Russia is limited. Methods We report the results of serotyping and antibiotic susceptibility testing performed on 863 non-invasive pneumococcal isolates collected prospectively in 2009–2013 from children (median age 3.5 years) who sought medical care at five pediatric hospitals in Moscow. The isolates were recovered from the nasopharynx (71.2%), middle ear fluid (14.3%), and lower respiratory tract specimens (13.6%). Results In total, we identified 45 different serotypes. The six leading serotypes (prevalence >5%) included 19F (21.7%), 6B (12.8%), 23F (10.1%), 14 (9.0%), 6A (8.4%), and 3 (7.5%). Serotype 19A isolates had a prevalence of 2.3%. The proportion of PCV-13 serotypes was 78%; the coverage by PCV-7 was 58.2% and was similar to that of PCV-10 (59.8%). The rate of multidrug-resistant pneumococci (i.e., resistant to ≥3 antimicrobials) was 22%. The majority of the multidrug-resistant isolates were serotype 6B, 14, 19A, and 19F. Penicillin non-susceptibility was displayed by 28% of the isolates. The resistance rate to erythromycin was 26%. Among the examined erythromycin-resistant strains, 54% had the erm(B) gene and 13% had the mef gene as a single resistance determinant, whereas both determinants were found in 31% of these strains. Conclusions Our data predict a good coverage of the circulating S. pneumoniae by the PCVs and could be useful for evaluating the serotype distribution in support of the introduction of PCV in Russia. In addition, the antimicrobial resistance rate of S. pneumoniae in Russia is substantial, and the emergence of pneumococcal strains with a dual macrolide resistance mechanism is alarming.

The article is dedicated to food allergies. There still is no accurate estimate of the socioeconomic burden of food allergies and its impact upon the healthcare budget despite increasing prevalence thereof and lack of clear prognostic criteria. The authors present a modern classification of predominant clinical manifestations based on pathogenetic mechanisms of development. They describe therapeutic approaches, propose recommendations on diet broadening for both patients with food allergy manifestations and risk group children, define cross-sensitization and discuss a problem of non-immune reactions to foods. Keywords: food allergy, tolerance, food allergens, cow milk protein, therapeutic formulae, panallergens, cross-sensitization, risk group children, elimination diet, supplementary feeding, diet, tolerance window.

The article is dedicated to the issues of organization of long-term follow-up monitoring of the patient population in real clinical practice. Every medical intervention is analyzed from the position of positive evidence of its effectiveness, safety and clinical-economic benefits. Although randomized clinical trials (RCTs) are the gold standard of evidence-based medicine, they feature a range of drawbacks; in some cases, such trials are infeasible are extremely complicated to perform due to certain aspects. Along with that, results of RCTs may not completely correlate with clinical practice. Thus, a register – a system of long-term clinical monitoring of a patient population – is a significant source of information on effectiveness and safety of medical interventions. This tool of follow-up observation of a patient’s condition is irreplaceable in medicine, particularly, in allergology both for epidemiological purposes and to assess effectiveness and safety of therapeutic interventions: e.g., use of IgE antibodies – biopharmaceutical omalizumab. Keywords: register, long-term follow-up monitoring system, effectiveness, safety, uncontrolled severe persisting bronchial asthma, omalizumab, children.

The paper is devoted to neuropsychology — the science that studies dysfunction, degree of formation of the higher mental functions, allows not only to describe symptoms of their disorders, but also to identify mechanisms, to develop adequate tactics of the patient treatment. The authors emphasize that in recent years the interest of psychologists, teachers, and pathopsychologists to this area due to the increasing number of children with difficulties in adaptation, underachieving in education. The character of neuropsychological examination of a child, which must be structurally dynamic is described. Refinement of the individual characteristics of the child, the necessary motivation formed by physician permits the effective correctional work. Key words: neuropsychology, the founders, the higher mental functions, neuropsychological investigation, correctional work, children. (Pediatric pharmacology. — 2011; 8 (6): 83–87).

The epidemiologic data on RSV infection prevalence in the Russian Federation and its impact on respiratory morbidity in the pediatric population are limited. This article provides the analysis of results of a prospective, multicenter, observational cohort study. The study was conducted in 9 centers in the Russian Federation — in Moscow, St. Petersburg, and Tomsk. Children less than 2 years of age were included. It was found that during the season of high RSV morbidity RSV is found in 38 % of children hospitalized for lower respiratory tract infections; mean hospitalisation duration in children with severe RSV infection was over 1 week. Usually the duration of hospitalization was associated with disease severity and requirements for healthcare resources and oxygen supplementation. Moreover, in the Russian Federation the hospital length of stay in patients with RSV infection depended on the type of medical insurance. It was demonstrated that RSV infection caused severe respiratory failure in some infants less than 1 year of age and, therefore, was a substantial burden for the system of hospital medical care in the Russian Federation. Prophylaxis of severe RSV infection in high-risk groups of children during the might reduce the need for hospitalization. Key words: respiratory syncytial virus infection, bronchiolitis, risk factors, prophylaxis, epidemiology, children. (Pediatric pharmacology. — 2011; 8 (6): 61–66).

Varicella — is a common viral infection that can cause complications and adverse outcome not only in children at risk, but also in healthy children and adults. Socio-economic burden of disease due to both-direct health care, costs — to seek medical care and treatment, and indirect — social. The introduction of immunization after the development of live attenuated vaccine has shown impressive results provided high coverage of morbidity and mortality associated with chickenpox declined sharply. However, the development of infection in vaccinated patients — a breakthrough varicella may be related with the deterioration of post-vaccinal immunity with time, and the primary tolerance and inability to induce an effective immune response. Despite the undeniable progress in the prevention of chicken pox since the early 2000s. the world’s a discussion about the need to move to the two-dose vaccination scheme in national immunization programs has been started. Key words: vaccination, children, chickenpox, varicella, breakout. (Pediatric pharmacology. — 2011; 8 (6): 18–22).

In recent years in expanding diagnostic capabilities and improved knowledge level diseases that were previously considered rare become increasingly identified. Along with the achievements of the pharmaceutical industry, timely diagnosis and adequate therapy appointment can often save the life of the child and delay the progression of the disease. This article focuses on a rare, genetically determined, pathology of lysosomal diseases group, inherited autosomal recessively — NPD type C. Different versions of the clinical course and diagnostic methods are showed in details. Take account of the existing in our country hypo diagnostics of this disease, the authors propose to put into practice a diagnostic algorithm «index of suspicion of the disease NP-C» in order to improve detection and timely initiation of pathogenetic therapy. Key words: rare diseases, storage diseases, lysosomal diseases, Niemann-Pick disease type C, diagnostics, clinical course, treatment, children. (Pediatric pharmacology. — 2011; 8 (6): 114–118).

The paper is devoted to one of the rare genetically determined diseases — mucopolysaccharidosis. Despite the great achievement of science — the development of the pathogenetic enzyme replacement therapy, many challenges remain. Among them — the lack of timely diagnosis, causing delayed treatment and disease progression, the lack of a national register of patients with common approaches to treatment and rehabilitation of these patients. Objective and subjective obstacles to resolving these problems are demonstrated. The authors developed and represent an efficient system for providing high quality medical care for children with MPS which consists of hospital and rehabilitation phases to colleagues. In addition, the article highlights the issues and postinfuzional reactions during enzyme replacement therapy. Key words: mucopolysaccharidosis, the organization of medical care, diagnosis, treatment, enzyme replacement therapy, the organization of infusion, rehabilitation, supervision, children. (Pediatric Pharmacology. — 2011; 8 (5): 6–12.)

In practical pediatrics specialists paid wrongly little attention to identification and treatment of cognitive disorders in children. At the same time it is difficult to overestimate the influence of cognitive functions on the formation of human personality and social maladjustment in this part of population. The paper is devoted to the diagnosis and treatment of cognitive impairments. In addition, the classification of this pathology, highlighting aetiopathogenetic factors, prognosis are showed. One of the important problems of early revealing of cognitive impairments and appropriate management of children with this pathology according to the authors opinion are the following: the deficiency of educational programs for training specialists in neurology, lack of knowledge concerning the possibilities of psychological-pedagogical correction, inefficient system of neurological techniques for primary care. Key words: cognitive function, mild cognitive impairment, classification, diagnosis, treatment, prognosis, social maladjustment, psychopedagogical support, children. (Pediatric Pharmacology. — 2011; 8 (5): 37–41.)

The problem of diagnosis, prevention and treatment of diseases caused by human papilloma virus (HPV), in recent years has become more urgent, not only for physicians, scientists, but also for patients. This is due to the high contagiousness of HPV, its prevalence and, of course, proved oncogenicity. Creation and introduction of preventive vaccines against the most common HPV types played a definite role in the global health, and, of course, raised the attention of doctors and the public to human papillomavirus infection and associated diseases. At the same time propaganda against vaccination blocks the widespread adoption of this disease prevention in our country. In this paper, we introduce the American experience of monitoring vaccination adverse events.Key words: human papillomavirus infection, prevention, vaccination, adverse events, monitoring, children.

To a risk group of a heavy course of the respiratory syncytial viral (RSV) infection could be ascribed preterm infants, born before the 35th week of gestation inclusive, as well as children under 2 years old with the bronchopulmonary dysplasia or hemodynamically significant congenital heart defects. World experience shows that the seasonal immunoprophylaxis against RSV-infection with palivizumab in these patients enables to reduce the frequency of hospitalization and resuscitation measures, as well as to decrease the number of deaths. The article presents authors’ clinical and laboratory data and instrumental evaluation of the efficacy and safety of palivizumab on specific clinical examples.Key words: respiratory syncytial virus, acute respiratory viral infection, prematurity, bronchopulmonary dysplasia, congenital heart defects, palivizumab.

Allergic diseases are getting more and more widespread pathology. Among them, allergic rhinitis is the most «harmless» and prognostically favorable. However, recent studies show that this disease not only significantly degrades the life quality of the children violates the cognitive function, but is a risk factor for asthma. In this connection, a special importance is attached to the adequate symptoms of allergic rhinitis control and to minimizing the adverse effects of drugs used. The article presents the results of numerous studies of the efficacy and safety of one of the drugs for the allergic rhinitis treatment, i. e. intranasal corticosteroids representative of the group — fluticasone furoate.Key words: allergic diseases, allergic rhinitis, treatment, intranasal corticosteroids, the efficacy, safety, children.

The steady increase in the prevalence of allergic diseases causes the social significance of this pathology. These statistics often do not reflect the true morbidity picture. The social and economic burden of allergy forces experts to seek new ways of preventing the beginnings and development of this pathology. The relationship between bronchiolitis caused by respiratory syncytial virus (RSV) infection in the early childhood and further development of asthma was proved by numerous randomized trials. The use of the drug for RSV monoclonal antibodies will reduce not only the incidence of the infection, prevent the development of bronchiolitis, but reduce the risk of asthma in early childhood.Key words: asthma, children, respiratory syncytial virus, prophylaxis.

The article presents a generalized 2-year Russian experience in the application of monoclonal antibodies to IgE in children and adolescents with severe, resistant to standard treatment of bronchial asthma. Data on 65 patients treated with anti-IgE therapy with omalizumab within more than 6 months period in 6 centers of the Russian Federation from 2007 to 2010 were analyzed. The results of this analysis demonstrate the safety and high clinical effectiveness of anti-IgE-therapy in children and adolescents with severe uncontrolled atopic bronchial asthma. Full control of the disease or marked improvement can be achieved in 73% patients, the effect in most cases significantly increases during the first 6 months of treatment and becomes stable in the future, providing a good quality of life and normal lung function.Key words: bronchial asthma, anti-IgE-therapy, treatment, adolescents, children, quality of life, omalizumab.

Identification of the early markers of the onset of atopic march in children remains important for the effective primary and secondary prevention of allergic diseases. The article contains results of the study of the expression of receptors for interleukin of Th2 profile (IL 4, IL 5) in infants with the formation of the atopic status. The obtained results indicate that expression of receptors is different in families with burden atopic anamnesis and/or in case of impact of certain perinatal factors.Key words: newborn, atopy, interleukin receptors, CD124, CD125, immunoglobulin E.