Вирусные диареи у детей в узбекистане: клинические, диагностические и молекулярногенетические особенности

Аннотация

Topicality and demand of the subject of dissertation. Acute diarrheal diseases nowadays remain as one of the most important problem of pediatric infectious pathology due to high morbidity, high frequency of moderate and severe forms, potential complications and high mortality, especially among infants. According to World Health Organization (WHO), there are 2.5 billion of diarrhea cases are registered annually worldwide, up to 70% are children before 14 years. In 2008 acute diarrhea was a cause of 15% of all deaths in age <5 year in the globe, with only pneumonia leading (18%). Etiologic patterns of acute diarrhea in recent years have significantly changed worldwide. If in earlier year’s bacteria, currently 50-80% of all cases of acute diarrhea are caused by viruses. The incidence of acute gastroenteritis caused by astroviruses and caliciviruses have sufficiently grown, and it becomes obvious that viral diarrhea is no longer pediatric problem only. The level of incidence in children of different age groups varies (from 10% to 90%). The highest incidence is reported in children before 2 year of age. In opinion of pediatricians and neonatologists, the rotovirus infection is number one cause in acute diarrhea in children of first year of age, consisting up to 50-80% of all cases. In recent years in Europe there were annually, 72 to 77 thousands children <5 у admitted to hospitals with rotovirus diarrhea, so for every thousand children there were 3 cases of hospitalization. 21% of children had nosocomial route of infection. Mcanwile, the real incidence of rotovirus infection is still not clear. 30-55% of children with acute intestinal infection, the rotovirus infection is a cause of hospitalization. It is worth to mention, several patterns and mechanisms are not fully investigated. The data on clinical features of viral diarrhea of varying etiology is still lacking in literature. Along with that, investigation of features, specific for each form of viral diarrhea, allows to define differential-diagnostic criteria that help early diagnosis and timely treatment. At the moment the diagnostics of viral gastroenteritis is sufficient enough, so high proportion of acute intestinal infections remain unidentified. Also, the data on prevalence genotype patterns of viral diarrhea in children in Uzbekistan and its clinical significance is lacking. There is no data in literature, on specific therapy of viral diarrhea that calls for appropriateness of development of early cthiotropic therapy with use of most effective medications. In the Republic of Uzbekistan, the issues of introduction and improvement of diagnosis of viral diarrhea, clinical-laboratory and epidemiological features remain actual, as well as development of therapy of viral diarrhea. The presented data indicate to actuality of problem, in general, and in particular for Uzbekistan, that is the justification the current study. Purpose of research is to detect incidence of viral diarrhea in the structure of viral diarrhea, to detect clinical features of viral diarrhea, to outline molecular-genetic charachteristics of roto-, noroviruses and to identify social-econonic aspects of diarrhea in children. To develop diagnostic algorithm and scientifically based, differentiated treatment approaches for children with viral diarrhea. Scientific novelty of dissertational research consists in the following: for the first time we have identified prevalence of acute viral diarrhea in children in Uzbekistan, which in turn suggests optimization of diagnostic search to specify etiology of acute diarrheal diseases; we detected proportional distribution of rota-, noro-, adeno- and astroviral infection in etiological structure of diarrhea in children and proved leading role of rotaviruses in morbidity of younger age children; we detected seasonality of viral diarrheas, and that in each season has its specific leading viral diarrheal disease; we identified factors that affect progress of diarrheal disease in children; for the first time we identified regional peculiarities of clinical course of rota-, noro-, adeno- and astroviral monoinfections in children of different age groups; for the first we provided comparative characteristics and detected differential diagnostic differences of rota-, noro-, adeno- and astroviral diarrhea in children; for the first time we detected molecular-genetic structure of rota- and norovirus diarrhea cases in children in Uzbekistan; we developed diagnostic algorithm of viral diarrhea in children; we have proven effectiveness of antiviral Anaferon Pediatric in children with viral diarrhea. CONCLUSION 1. Acute diarrhea in Uzbekistan in 77.5% of cases has viral origin. In 62.1% of cases it is monoifection. Etiologic structure of monovirus diarrhea in children: rotovirus infection consists consists - 21.0%, norovirus infection - 17.0%, adenovirus infection - 14.0% and astrovirus infection - 10.0%. 2.Seasonality is typical for viral diarrhea and it is more common for colder seasons. The different viruses dominate in different seasons throughout the year. The morbidity spike of rotovirus infection is observed in winter and spring (January-May), norovirus infection - December through March, adenovirus infection - September through February (autumn-winter), and astrovirus infection - from October through December. 3. Thc prevalence of viral diarrhea varies by age groups. In the age group <1 year, rotovirus infection prevails among identified viruses (32,1%). Rotovirus and adenovurs infection is the most frequent among children of 1-3 year (56.1% and 62.6% respectively), astrovirus and norovirus infection - children above 3 year (53.3% and 59.2% respectively). 4. Clinical presentation of viral diarrhea has age-specific features. Children <1 year of age suffer from more sever acute viral intestinal infections. The younger the child, the more intense and long are the clinical symptoms. The viral diarrhea of children >3 year are mild with shorter duration of fever and diarrheal syndrome. 5.In majority of cases the roto-, noro-, adeno- and astrovirus infections are moderate severity (73.8%, 75.4%, 74.8% and 82.8% respectively). Acute intestinal infections of viral etiology have similar clinical features but can be distinguished from each other by prevalence, severity and lengths of general infectious syndrome and damage of gastro-intestinal tract. In this case PCR and immunoenzyme diagnostics can be crucial. 6.1n the territory of Uzbekistan norovirus genotype GII is the most spread. The clinical presentation of the norovirus infection does not depend on virus genotype. Phylogenic analysis had shown that the norovirus strains that were circulating in the territory of Uzbekistan have South-Eastern origin. The detected strain has emerged due to recombination of Vietnamese and Japanese strains. 7. Among rotavirus infection cases the most common G genotype is GI (56.3%), GII is detected in 21.7% and Gill in 10.8% cases. Among P genotypes, the most frequent is P8 (69.8%). In combination of rotavirus genotypes, in 49.8% of cases G1P8 was identified. 8. Administration of Anaferon pediatric in complex therapy of children with viral diarrhea improves virus elimination, reduce virus excretion time, enhance host sanation thus decreasing incidence rate of single cases and outbreaks of viral diarrhea in hospitals and childcare facilities. 9. Socio-hygienic, medico-biologic and medico-organizational factors have complex impact to the clinical course of acute diarrheal diseases and complications. 10. Use of preliminary testing in acute diarrhea in children according to Markov model decreases current burden of disease from 6.4% to 13.7%.