Vol 7, No 3 (2017)



Nesterova I.V., Kolesnikova N.V., Chudilova G.A., Lomtatidze L.V., Kovaleva S.V., Evglevsky A.A., Nguyen T.L.


Numerous modern basic research done undeniable fact that neutrophilic granulocytes (NG) are key effector and regulatory circuits both innate and adaptive immunity, and play a crucial role in the pathogenesis of a wide range of diseases. NG have potent receptor repertoire, providing a connection between them, cells of the immune system, as well as communication with endothelial cells, epithelial and other tissues. NG inducing stimuli activate and promote the translocation of cytoplasmic granules and vesicles surface molecules on the cytoplasmic membrane the secretion of a large spectrum of pro-and anti-inf lammatory, immunoregulatory cytokines, colony, angiogenic factors and fibrogenic, TNF superfamily members, chemokines, regulatory protein, etc. Chromatin nuclei NG capable of restructuring under the influence of inducing stimuli, which is associated with the expression of multiple cytokine genes. NG receiving complex cytokine inf luence not only acquire new features, but also in various stages of activation and differentiation processes involved in intracellular intraphagosomalis degranulation and killing of implementing elimination microorganisms and extracellular neutrophil degranulation in the formation neutrophil extracellular traps (NET), while this dying through NETosis. Features NG phenotype and their functional properties, demonstrate the existence of subpopulations of NG with different capabilities: equipment of different receptor, the ability to restructure chromatin expressing cytokine genes and secrete cytokines to implement the contents of the granular system, produce reactive oxygen species, implement cytotoxicity form NET. In our opinion, there subpopulation NG: regulatory; suppressor; proinf lammatory — initiating an inf lammatory response; inf lammation with a positive potential microbicidal (antibacterial, antiviral, antifungal); inf lammatory cytotoxic potential of the negative  — “aggressive”; anti-inf lammation regulating regression; antitumoral — TAN1; pro-tumoral — TAN2; hybrid, combining the characteristics of NG and dendritic cells. The absence of adequate response, or hyperactivation blockade NG functions leads to the development of low-intensity infectious and inf lammatory diseases, do not respond to conventional therapy of autoimmune diseases/chronic immune-dependent processes. Remodeling dysfunctions NG — the key to new immunotherapeutic strategies.

Russian Journal of Infection and Immunity. 2017;7(3):219-230
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Vaganova A.N.


Human mycoplasma pathogens are resistant to many types of antibiotics because of the lack of a cell wall. Macrolides are most often used for the treatment of mycoplasmosis, but the spread of forms resistant to these antibiotics requires the use of alternative treatment regimens, in particular, the administration of f luoroquinolones and tetracyclines. Of the existing antimicrobial compounds, only f luoroquinolones have a bactericidal effect against mycoplasmas, so use of these antimicrobials is preferable for the treatment of immunosuppressed patients. The limitation of the f luoroquinolones is the resistance of the causative agent to these antimicrobials. Mutations leading to amino acid substitutions in the composition of the targets of f luoroquinolones, gyrase and topoisomerase IV are the most common cause of resistance to f luoroquinolones both in mycoplasms and in other bacteria. It was noted that for mycoplasmas belonging to different species have different patterns of substitutions in the subunits of gyrase and topoisomerase IV. The differences of the structure of these proteins, ref lected in the natural susceptibility to f luoroquinolones in mycoplasmas, may be a reason of this heterogeneity. A number of studies indicate the existence of additional resistance mechanisms, which, first of all, include multiple-resistance systems. Such systems belonging to the ABC-transporter group were also found in mycoplasmas. They are described in Mycoplasma hominis and M. pneumoniae, in M. hominis, their ability to excrete f luoroquinolones from the cells was observed, and in M. pneumoniae the ability of multiple-resistance systems to export macrolides also was noted. Genes encoding components of multiple resistance systems have been found in genomes of other species, including M. genitalium and mycoplasmas, causing animal diseases. Also, in the non-pathogenic for human mycoplasmas Acholeplasma laidlawii, the ability to export proteins and genetic material associated with resistance to f luoroquinolones was found. Understanding the role of the mutations, the activity of transports and their cumulative effect in the development of resistance to f luoroquinolones is particularly important in the context of the determination of resistance to f luoroquinolones in difficult to culture pathogens M. genitalium and M. pneumoniae. Molecular methods for determining the resistance to antimicrobials are now included in clinical practice, but the lack of information about the molecular bases of mycoplasma resistance makes the result insufficiently informative for the pathogens of this group. In the review, the features of the development of resistance to f luoroquinolones in various species of human pathogenic mycoplasmas and their mechanisms at molecular level will be described.

Russian Journal of Infection and Immunity. 2017;7(3):231-244
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Kalinina O.V., Lichnaia E.V., Boiro M.Y., Totolian A.A.


Phylogeographical and philodinamic studies have shown that the hepatitis C virus began to circulate in the human population about 500–2000 years ago on the A frican continent and only in the 20th century, this virus received the ubiquitary distribution. According to WHO in the world more than 71 million people are chronically infected by the hepatitis C virus, more than half of them live in A frica and South-East Asia. At the same time, the actual prevalence of hepatitis C in most countries of sub-Saharan A frica, including the Republic of Guinea, remains poorly understood.

The aim of this study was to evaluate the occurrence of serological and molecular markers of hepatitis C on a random small selection of blood samples obtained from healthy adults of the Republic of Guinea.

Materials and methods. Serum and plasma blood samples obtained from thirty one healthy adults of 24–71 years old of the Republic of Guinea were examined. Blood samples were collected in 2015–2016 years. The serum samples were analyzed for the presence of total anti-HCV (IgG+IgM),  of specific antibodies to the core, the NS3, the NS4 and the NS5B HCV proteins, of core antigene with “DS-ELISA-ANTI-HCV-GM”, “DS-ELISA-ANTI-HCV-SPEKTRE-GM”, “DS-ELISA-HCV-Ag” detection kits (RPC “Diagnostic Systems”, Russia), respectively. RNA HCV were detected by RT-PCR with detection kit “A mpliSens HCV-FRT” (CRIE, Moscow) and by nested-PCR using the primers from 5’UTR region. HCV genotypes were determined by RT-PCR  with detection kit “A mpliSens HCV-genotype FRT” (CRIE, Moscow) and by phylogenetic analysis based on the 5’UTR region.

Results and discussion. In this pilot study, the presence of HCV markers was confirmed in 3 (9.68%, 95% CI 3.35–24.90) of 31 examined persons. Two of them had RNA HCV. Based on the phylogenetic analysis of the 5’UTR region of the HCV genome, the isolate obtained from person No. 5 belonged to genotype 1, and the isolate obtained from person No. 6 belonged to genotype 2. The obtained results together with the analyzed literature data indicate a significant burden of hepatitis C in the Republic of Guinea, and also indicate the need to develop both an algorithm of diagnostic criteria and the improvement of diagnostic test systems for mass screening of the A frican population in order to establish the proportion of persons involved in epidemic process.

Russian Journal of Infection and Immunity. 2017;7(3):245-250
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Puzyryova L.V., Konchenko V.D., Dalabayeva L.M.


Septic implications at patients aren’t a rarity, especially in surgical, pediatric and obstetric practice now. However not enough attention, despite epidemic of this disease is paid to implication of a sepsis at patients with HIV infection now. Clinical laboratory implications of a sepsis at 36 patients with HIV infection are analysed. The main group is presented by patients with a lethal outcome (n = 18), control — with a positive outcome of a stationary stage of treatment (n = 18). Work is carried out on materials of the Infectious hospital No. 1 of D.M. Dalmatov of Omsk. At HIV-positive patients the stage of secondary diseases met most more often. Anti-retrovirus therapy was accepted only by 33% of patients in control group. At the died patients the hyperthermia arose after development of complaints from organs and systems and lasted less than 15 days. Low indicators of the CD4+ lymphocytes and a high virus load of HIV in a blood of patients with a lethal outcome became perceptible. In the general blood test thrombocytopenias, eosinopenias, monocytopenias, in the biochemical analysis — augmentation of the general bilirubin, thymol turbidity test, prothrombin ratio, urea were more often taped. At a bacteriological blood analysis various microflora with prevalence of S. aureus, sometimes in combination with Gram-negative flora was taped. Symptoms of an infectious endocarditis were taped at every second dead of the HIV-positive patient. Almost at all patients radiological changes in a pulmonary tissue were taped. Thus, clinical implications at patients with HIV infection are few symptoms and not typicalness that demands further studying.

Russian Journal of Infection and Immunity. 2017;7(3):251-258
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Savchenko A.A., Borisov A.G., Kudryavcev I.V., Gvozdev I.I., Moshev A.V., Cherdancev D.V., Pervova O.V.


The aim of the study was to examine the relationship of the phenotype and metabolism of neutrophils in patients with widespread purulent peritonitis (WPP) in the dynamics of the postoperative period. The study involved 27 patients with acute surgical diseases and injuries of abdominal organs complicated by WPP. Blood sampling was performed prior to surgery (pre-operative period) and at 7, 14 and 24 day post-operative period. As controls 67 respect healthy people were examined. Research blood neutrophilic granulocytes phenotype was performed by f low cytometry using a direct immunof luorescence whole peripheral blood. The levels of surface receptor expression was assessed by the mean f luorescence intensity. The NADand NADP-dependent dehydrogenases activity in the blood neutrophils studied using bioluminescence method. It was found that in patients with WPP in the preoperative period in the peripheral blood increased content of CD62L+-, HLA-DR+and CD64+-neutrophils. High levels of CD62L+-cells stored within 24 postoperative days, whereas the amount of HLA-DR+and CD64+-neutrophils on 24 postoperative day is reduced to the level of controls. The dynamics of changes in the content of CD64+-cells in the peripheral blood of patients with WPP corresponds to the expression level of CD64-receptor on the membrane of neutrophilic granulocytes. The metabolism of blood neutrophils in patients with WPP in the preand postoperative period is characterized by high intensity of the substrate stream on the citric acid cycle, low activity of NADP-dependent glutamate dehydrogenase and aerobic reaction of lactate dehydrogenase. In the preoperative period and within 14 days of the postoperative period in neutrophil granulocytes of the patients revealed high activity of anaerobic lactate dehydrogenase reaction characterized by increased activity of anaerobic glycolysis. In the late postoperative period the intensity of anaerobic energy in the neutrophils of patients with WPP was reduced to the control level. The final stage of post-operative treatment the metabolism in the blood neutrophils of patients with WPP is also characterized by the activation of the pentose phosphate cycle, low activity of malate-aspartate shunt mitochondria and high intensity of the substrate interaction between citric acid cycle and reactions of amino acid metabolism. Using correlation analysis set dysregulation between phenotype and the system of intracellular metabolism of neutrophils which can be determined by the migration of activated cells in the inf lammatory focus as well as changes in the activity of intracellular enzymes under different regulatory factors and including postoperative therapy methods peritonitis.

Russian Journal of Infection and Immunity. 2017;7(3):259-270
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Bayazitova L.T., Tyupkina O.F., Chazova T.A., Tyurin Y.A., Isaeva G.S., Zaripova A.Z., Patyashina M.А., Avdonina L.G., Yuzlibaeva L.R.


Prevalence estimate of pneumococcus carrier in preschool age children (medically fragile children with respiratory diseases and practically healthy organized children) have been carried out; microbiological features of clinical isolates S. pneumoniae have been studied. 511 S. pneumoniae strains isolated from medically fragile children with respiratory diseases aged between 6 months to 7 years during the period 2009–2016 and 47 isolates isolated from 200 practically healthy children attending preschool institutions of Kazan (2016) have been included in the research. Among 343 strains, 76 isolates were isolated during the period of 2009–2011; 82 strains — in 2012–2013; 87 strains — in 2014; 98 strains — in 2015; 168 strains — in 2016. Analysis of microbiocenosis of nasopharynx in medically fragile children showed that S. pneumoniae was sowed in 32.9% cases. In 58.4% of children it was as a monoculture (degree of colonization is 104–106  CFU/ml). S. pneumoniae contaminated nasopharynx in bacterial associations with other respiratory pathogens (S. aureus, Moraxella spp., Haemophilus spp.) in 41.6% of children. The analysis of microbiocenosis character of nasopharynx in children aged between 2.5–7 years attending preschool institutions in Kazan (n = 200) have showed that contamination S. pneumoniae (23.5%) was observed in 47 children. Pneumococcus have been isolated in monoculture in 82.9% of children; the contamination degree made 103–106 CFU/ml. According to serotyping data, nasopharynx of often and long-term ill children living in Kazan is colonized by serotypes of pneumococcus which are covered with 13 valence conjugated serum. The obtained data on the dynamics of strain S. pneumoniae antibiotic sensitivity among medically fragile children with respiratory diseases in Kazan during 2009–2015 showed high activity of β-lactams antibiotics (from 96 to 90.8% sensitive isolates) and clyndamicin (94.7–91.8% sensitive straines). Macrolides (azytromicin, clarytromicin) and phtorchinolons (ciprof loxacin) are less active in regard to isolates S. рneumoniae. S. pneumoniae with multiple antibiotic resistance were detected in children nasopharynx: 3.8–9.95 in medically fragile children and 8.5% in organized children-bactericides. Identification of the carrier level S. pneumoniae and monitoring the dynamics on antibiotic resistance and serotyping composition of nasopharyngeal pneumococcus will optimize prevention and treatment of infections S. pneumoniae in preschool children.


Russian Journal of Infection and Immunity. 2017;7(3):271-278
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Smirnova V.S., Petlenkoa S.V., Savelyeva S.A., Redlichb G., Stukana N.I.


Aim. To evaluate the efficacy and safety of the generic drug Wartocid® (Imiquimod cream 5% for external use) in patients with external anogenital (venereal) warts (AGW).

Materials and methods. The single-blind comparative, randomized, placebo-controlled clinical trial included 50 women aged 18 to 60 with an established clinical diagnosis of AGW in the vulva and perianal region. Patients in group 1 received placebo cream for external use, while patients in group 2 received therapy with Wartoсid in a daily dose of 10 mg cream/cm2  of skin area. The drug was applied every other day until the complete disappearance of AGW, but in any case, not more than 16 weeks. A follow-up was carried out for 4 more weeks. The study evaluated the dynamics of subjective and objective symptoms, the presence and the frequency of relapses, and the percentage of full treatment of AGW.

Main results. Treatment with Wartoсid resulted in a complete cure of AGW in 16% of patients, and a reduction in the focus area of AGW in 36% of patients. Against the background of the placebo no dynamics of the disease were reached. Neither serious adverse events nor clinically significant changes in blood tests, urine or serum biochemical parameters in any of the patients who received treatment with Wartoсid were observed.

Conclusion. The generic drug Wartocid has been proved to be effective and safe for AGW treatment and its effectiveness is similar to the original drug Aldara® (Imiquimod cream 5% for external use).

Russian Journal of Infection and Immunity. 2017;7(3):279-284
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Lyamin A.V., Ismatullin D.D., Zhestkov A.V., Kovalyov A.M., Baryshnikova L.A., Nenjajkin S.S.


Recently there has been a significant increase in the incidence of mycobacteriosis, which is due to an increase in the proportion of immunosuppressed patients, the presence of these various comorbid conditions, as well as the improvement of diagnostic methods. Selecting the most accurate method of identification is extremely important in determining treatment strategy of patients. The aim of the study was to conduct a comparative analysis of modern methods of identification NTMB isolated from clinical specimens in 2015 in the Samara region. The work was carried out identification of 78 strains of microorganisms. Laboratory diagnosis was carried out using the DNA hybridization method and MALDI-ToF mass spectrometry. When microbial identification using MALDI-ToF mass spectrometry was isolated 16 strains (20.5%) M. kansasii; 11 strains (14.1%) M. avium and M. fortuitum; 9 strains (11.5%) M. gordonae; strain 3 (3.8%) M. peregrinum, M. szulgai, M. chimera intracellulare group, strain 2 (2.6%) M. abscessus, M. septicum, M. paragordonae, M. senegalence, 1 strain (1.3%) M. chelonae, M. frederiksbergense, M. monacense, M. lentiflavum. By using mass spectrometry, it was identified 15 types NTMB compared with 9 types — by DNA hybridization. Full match identification results was observed only in 45 (57.7%) strains of divergent strains were found in 16 (20.5%). Most often when using the DNA hybridization method, discrepancy was detected in slow-growing cultures (9 strains) with a predominance of microorganisms identified as M. gordonae. Among the representatives of fast-growing NTMB, seven investigations were identified in the identification, more often among representatives of the M. fortuitum and M. peregrinum groups. Particular attention should be paid to the identification of the M. kansasii strain by a molecular genetic method, which mass spectrometry was defined as M. bovis. Both cultures of M. tuberculosis complex, which were identified by MALDI-ToF spectrometry, DNA hybridization were not determined to species. 17 (21.8%) of microbial strains which have been identified using the method of DNA hybridization, identified by spectrometry, including slow-growing microorganisms, non-mycobacteria strains seven (9.0%): Gordonia rubriperticta, Nocardia forcinica, Tsukumurella spp., Rhodotorula mucilaginosa. Accurate species identification NTMB is fundamental to determine the tactics of treatment of patients with mycobacteriosis. Due to this rather limited possibility of identification of non-tuberculous mycobacteria, using a DNA-hybridization method is inadequate to date. The introduction of new techniques, such as MALDI-ToF spectrometry, can identify a greater number of species of nontuberculous mycobacteria, as well as other types of slow-growing microorganisms having similarities with mycobacteria on cultural and morphological properties, which significantly increases the diagnostic capabilities of laboratories.

Russian Journal of Infection and Immunity. 2017;7(3):285-291
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Fadeev A.V., Zhilinskaya I.N.


This paper describes results of comparison of genetic sequences of inf luenza viruses obtained from clinical samples (nasopharyngeal swabs) and viruses isolated on MDCK cells and in developing chick embryos. The obtained data shows that 1–2x fold passaging of inf luenza viruses in MDCK cells does not lead to additional mutations in the genome of the inf luenza virus, and the genetic material of this virus is identical to the genetic material from the clinical sample. When passaging viruses in chick embryos within 1–2 passages, the genetic material of the virus differs from the genetic material from the clinical sample, because of mutations in the receptor region of hemagglutinin, leading to aminoacid substitution Q223R. The mutation Q223R changes the receptor specificity of hemagglutinin from human-type receptors (α-2.6-sialic acids) to avian receptors (α-2.3-sialic acids). The data obtained coincide with the data of Japanese researchers who showed that a similar substitution in the hemagglutinin gene was detected in Japanese strains of inf luenza virus subtype A (H1N1) pdm09, passaged in chick embryos for 1–2 passages. With their further passaging in chick embryos, the number of acquired mutations in the surface proteins of these viruses increases. Thus, we have shown that for the genetic analysis of epidemic-relevant strains of inf luenza viruses for routine epidemiological surveillance tasks, the use of direct sequencing of clinical samples containing the genetic material of viruses makes it possible to obtain the most reliable data, to increase their efficiency, since it saves time normally spent on virus isolation procedure. If preliminary isolation of viruses is necessary, for example, if it is not possible to carry out full genome amplification from a clinical sample (low content of the material, presence of polymerase chain reaction inhibitors), virus isolation on MDCK cells with a minimal amount of passage is optimal, which is used in practice of epidemiological surveillance.

Russian Journal of Infection and Immunity. 2017;7(3):292-296
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Aleksanina N.V., Moiseyeva O.V.


The wide spread of drug-resistant forms of the pathogens, complicating prevention and treatment of acute intestinal infections, determines the feasibility of using bacteriophages and immune lactoglobulins for antibacterial therapy of these diseases. The aim of this study was to investigate the antibacterial efficacy of the joint use of immune lactoglobulin and Salmonella bacteriophage in the treatment of experimental salmonellosis in mice. The experimental Salmonella infection was reproduced by means of a single intragastric administration of 2LD50 of daily agar culture of S.typhimurium. As a result, the development of Salmonella infection lasting up to 14 days was noted. The animals were divided into four groups according to the pattern of the treatment. The following preparations were used for the treatment of animals: «Lactoglobulin against opportunistic bacteria and Salmonella» dry cow, «Lactoglobulin» liquid, bacteriophage of Salmonella ABCDE groups, liquid. The preparations were daily administered to mice orally after the infection for 7 days. In the study of the joint therapeutic effect of the lactoglobulin and bacteriophage the special attention was paid to the terms of elimination of the pathogen from animal organs. Analysis of the data showed that in all four groups a positive dynamics of excretion of the pathogen of mice was revealed. In groups of animals that were treated with both drugs, the elimination of Salmonella out of organs occurred 1.5 times faster than in the control groups of mice. At the same time in the experimental groups on the third day of treatment with preparations the statistically significant decrease in the number of S.typhimurium in the contents of the large intestine of animal was revealed. The study found that immune lactoglobulin used simultaneously with Salmonella phage for 7 days reduced the severity and duration of the disease course and blocked the further development of the infectious process, promoted the efficient and rapid cleansing of animals organism of the pathogen, increased the survival of mice. The obtained data suggest the applicability of joint use of immune lactoglobulin preparations and bacteriophages in the treatment of acute intestinal infections caused by antibiotic-resistant strains of Salmonella.

Russian Journal of Infection and Immunity. 2017;7(3):297-302
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Bashketova N.S., Chkyhindzheriya I.G., Bichurina M.A., Krainova T.I., Bryanceva E.A., Lavrentieva I.N., Suhobaevskaya L.P., Degtjarev O.V., Demakova T.E.


Inf luenza and acute respiratory viral infections (ARVI) account for up to 90% of the total reported infectious morbidity annually in Russia. The economic damage from these infections reaches 86% of the economic losses associated with infectious diseases. As a result of antigenic drift or a shift, new variants of the inf luenza virus, including pandemic strains, appear. In 2009, an inf luenza pandemic arose due to the shifter version of the inf luenza A (H1N1) pdm09 virus. This virus caused epidemic rises of inf luenza in the world in subsequent years.

The aim of the study was to describe the epidemic process of inf luenza in January–March 2016 in St. Petersburg.

Materials and methods. The incidence of inf luenza and acute respiratory viral infections in St. Petersburg was recorded according to statistical coupons by age groups of the population. Examined nasopharyngeal f lushes received no later than 3–4 days from the onset of the disease, and in case of a lethal outcome — sectional material (bronchi, trachea, lungs, spleen tissues). The detection of RNA of inf luenza viruses was carried out in RT-PCR (Amplicenc Inf luenza virus A/B, Amplicenc Inf luenza virus A/H1-swine-FL, Amplicenc Inf luenza virus A типа-FL,  «Interlabservice», Moscow). Isolation of inf luenza viruses from the clinical material was carried out on culture by the MDSC cell. Isolates were typed in RTGA with diagnostic sera to reference and epidemic inf luenza viruses. Isolation of inf luenza viruses from the clinical material was carried out on culture by the MDSC cell. Isolates were typed in RTGA with diagnostic sera to reference and epidemic inf luenza viruses.

Results. In 2016, the incidence of inf luenza in St. Petersburg was 81.38 per 100 000 population and was 4.1 times higher than the incidence rate in 2015. The epidemic rise in the incidence of inf luenza and ARVI began with the 3rd calendar week, lasted 6 weeks, with a peak incidence at the 5th calendar week. In total, 398 675 people (7.6% of the population) were ill during this period, including adults — 184 658 (4%), children 0–14 years old — 214 017 or 31.5% of this age group. The greatest number of cases among children was registered in the group of 3–6 years — 87 766 (41.0%). Among the ill children, 86.2% attended pre-school children’s institutions (kindergartens). During the epidemic recovery in 2016, inf luenza viruses were detected in 297 people (46.2%): the inf luenza A (H1N1) virus pdm09 in 97.1% of cases, A (H3N2) — 0.6%, B — 2.3%. There were 102 deaths from complications after the inf luenza, including 101 cases of inf luenza A (H1N1) and A (H3N2) inf luenza A (H1N1) pdm09 confirmed by PCR. Among the dead 101 adults (including 2 pregnant women) and one child. All of them were not vaccinated against the f lu earlier. All deceased adults suffered from chronic physical illnesses.

Russian Journal of Infection and Immunity. 2017;7(3):303-308
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