The Prevalence of Autism Spectrum Disorders in the Russian Federation: A Retrospective Study.

BACKGROUND: There has been an increase in the prevalence of autism spectrum disorders (ASD) worldwide over the past decades. Studies have shown that the number of confirmed diagnoses correlates with the awareness of the disorder among the general public and the professional community, in particular, as well as the availability of formalized screening procedures and modern medical and educational tools for families raising children with ASD in regional population centers. Thus, comparing autism prevalence rates in regions of the same country helps identify regions with limited access to diagnostic services and adequate medical care. AIM: To estimate the overall number of individuals meeting the diagnostic criteria for ASD in Russia and determine the differences in the number of registered individuals with established diagnosis in the constituent territories of the Russian Federation. METHODS: We conducted a retrospective, observational study and analyzed data from official statistical reports (form 12 "Information on the Number of Diseases Registered in Patients Residing in the Service Area of a Healthcare Institution" for 2020-2021). RESULTS: A steady upward trend in the number of individuals with autism has been observed since 2014 in the Russian Federation as a whole and in the federal districts, although the prevalence rates differ from the global median prevalence of ASD (all-Russian figure by almost 40 times). In addition, regional differences (by 104.5 times) in the frequency of the diagnosis have been revealed: from a minimum of 1.7 to a maximum of 177.7 per 100,000 population. The percentile distribution of the number of individuals with ASD that are followed-up at healthcare facilities in the constituent territories of the Russian Federation was in the interquartile range (25-75th percentile), below the 25th percentile, and above the 75th percentile in 38, 26 and 21 regions, respectively. CONCLUSION: The study has shown significant differences in the ASD diagnosis rates by regions in the country against a backdrop of a low (compared to international data) number of registered cases of autism. The presented data suggest that, due to the lack of proper diagnosis, a significant number of individuals with ASD do not receive adequate medical care, nor do they receive social, psychological, or pedagogical support. Possible reasons for this probably include low awareness of new diagnostic approaches among psychiatrists; low level of involvement of pediatrics professionals in screening activities; and fear of stigmatization because of a psychiatric diagnosis in the absence of a developed medical care infrastructure that encompasses a social, psychological, and pedagogical support system for people with ASD.

Multicenter study of serotype distribution of Streptococcus pneumoniae nasopharyngeal isolates from healthy children in the Russian Federation after introduction of PCV13 into the National Vaccination Calendar.

Russia introduced PCV13 in 2014. We studied the serotype composition of S. pneumoniae isolated from the nasopharynx of healthy children younger than 6 years in St. Petersburg, Smolensk, Perm, Krasnoyarsk, Khanty-Mansiysk and Khabarovsk, between 2016 and 2018. 2.4% of children had completed a 3-dose course of PCV13, while 25.6% had received 1 or 2 doses. Pneumococcal DNA detection by PCR demonstrated S. pneumoniae in 37.2% of samples with regional variation between sites (27.3 to 56.9%). There was little difference between vaccinated, partially vaccinated and un-vaccinated children. Children who had received at least 1 dose of PCV13 had lower carriage rates of vaccine serotypes than their unvaccinated peers (49.9 vs. 61.4%; p < 0.001). Children who had received at least 1 dose of PCV13 showed increased carriage rates of non-vaccine serotypes (50 vs 38.6%; P < 0.001). Especially serogroup 15AF was more prevalent among fully immunized children than among their peers (12.5 vs 2.7%; P < 0.05).

Bacterial etiology of acute otitis media and characterization of pneumococcal serotypes and genotypes among children in Moscow, Russia.

BACKGROUND: 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. METHODS: 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. RESULTS: 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%. CONCLUSIONS: 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.

Safety and immunogenicity of meningococcal ACWY CRM197-conjugate vaccine in children, adolescents and adults in Russia.

Neisseria meningitidis is the leading cause of bacterial invasive infections in people aged <15 years in the Russian Federation. The aim of this phase III, multicenter, open-label study was to assess the immunogenicity and safety of the quadrivalent meningococcal CRM197-conjugate vaccine MenACWY when administered to healthy Russian subjects aged 2 years and above. A total of 197 subjects were immunized with a single dose of the vaccine, and serogroup-specific serum bactericidal activity was measured pre and 1-month post-vaccination with human complement (hSBA) serum titers. Regardless of baseline serostatus, 1 month after a single dose of MenACWY-CRM197 85% (95%CI, 79-90%) of subjects showed serologic response against serogroup A, 74% (67-80%) against serogroup C, 60% (53-67%) against serogroup W, and 83% (77-88%) against serogroup Y. The percentage of subjects with hSBA titers ≥ 1:8 1 month after vaccination was 89% (83-93%) against serogroup A, 84% (78-89%) against serogroup C, 97% (93-99%) against serogroup W, and 88% (82-92%) against serogroup Y. Comparable results were obtained across all subjects: children (2 to 10 years), adolescents (11 to 17 years), and adults (≥18 years). The MenACWY-CRM197 vaccine showed an acceptable safety profile and was well tolerated across all age groups, with no serious adverse events or deaths reported during the study. In conclusion, a single dose of meningococcal MenACWY-CRM197 vaccine is immunogenic and has an acceptable safety profile, provides a broad protection against the most frequent epidemic serogroups, and is a suitable alternative to currently available unconjugated monovalent or bivalent polysaccharide vaccines in Russia.

Molecular characteristics of patients with glycosaminoglycan storage disorders in Russia.

BACKGROUND: 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). METHODS: 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. RESULTS: 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 was <1% 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. CONCLUSIONS: These data further enrich our knowledge of the genetic background of MPSs.

Genetic analysis of 17 children with Hunter syndrome: identification and functional characterization of four novel mutations in the iduronate-2-sulfatase gene.

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.

Awareness and utilization of reporting pathways for adverse events following immunization: online survey among pediatricians in Russia and Germany.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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 < 0.05 level. CONCLUSION: Pediatricians play a key role in the post-marketing surveillance of vaccine safety. The lack of training represents a missed opportunity. There may be a role for professional societies to improve vaccine safety training.

Serotypes and antibiotic resistance of non-invasive Streptococcus pneumoniae circulating in pediatric hospitals in Moscow, Russia.

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.

Streptococcus pneumoniae serotype distribution in children in the Russian Federation before the introduction of pneumococcal conjugate vaccines into the National Immunization Program.

WHO recommends the inclusion of PCVs in childhood vaccination programs world-wide. Many countries including the Russian Federation are currently planning the inclusion of PCVs in their National Immunization Programs and, therefore, data on the pneumococcal serotype distribution is important to estimate the potential disease impact. Here we review eight recent epidemiological studies on the pneumococcal serotype distribution from Russia. Across all studies, serotypes 6B, 14, 19F and 23F were the most prevalent. Interestingly, serotype 3 was relatively common. Serotype 19A was prevalent among AOM, CAP and nasopharyngeal isolates and among antibiotic resistant isolates in all age groups. The differences in serotype coverage between PCV10 and PCV13 were up to 26%. Based on the current data on serotype distribution, a wide use of PCVs in Russia may lead to a significant reduction of the pneumococcal disease burden.