Improvement of therapy for escherichiosis in children infected with Epstein-Barr virus

Background. Escherichiosis remains one of the most common intestinal infections, especially among young children. Indigestion of essential nutrients, transient fermentopathy, imbalance of the symbiotic flora, which develop in escherichiosis in combination with general intoxication and water-electrolyte disturbances, can lead to unfavorable outcomes. One of the factors influencing the course of escherichiosis can be Epstein-Barr virus (EBV) infection in the child. Purpose of the research — improvement of treatment of children with escherichiosis and EBV infection in different periods of the disease. Materials and methods. We examined 74 children aged 2–3 years, who were treated at the Regional Children’s Clinical Infectious Diseases Hospital in Kharkiv with a diagnosis of moderate-to-severe escherichiosis. A group of 36 children was selected, who received conventional therapy with early gradual restoration of nutrition according to the existing protocol, and the restoration of the qualitative and quantitative composition of food was carried out as soon as possible (first group). The second group was represented by 38 children, who received two-day prolonged gradual restoration of the diet: more gradual increasing the volume of food at each feeding and reducing the number of feedings per day. Children of the second group received drugs containing Lactobacillus, milk thistle extract and B vitamins (once daily with meals) from the first day. Ultrasound examination of the abdominal cavity was performed in all children. Results. Analysis of the main clinical, laboratory and instrumental parameters of patients in both groups during their stay in the hospital and one month after the discharge from the hospital revealed that in children of the second group, in whom rational diet therapy was applied, there was a reduction in the duration of bowel dysfunction, abdominal syndrome, flatulence; the parameters of the coprological test and the echosonoscopy of the hepatic parenchyma were normalized more quickly. Patients on the optimal diet regained their weight in a shorter period. The proposed methods of improving the therapy made it possible to prevent exacerbation of escherichiosis in children of the second group at the early convalescence stages. Conclusions. Early detection of EBV infection in children with escherichiosis, correction of therapy enable early restoration of physiological processes in the intestine and bile system, normalization of digestion and absorption of nutrients, and generally has a positive effect on the course of the underlying disease.


Introduction
In the structure of acute bacterial intestinal infections (II) in infants one of the most common is еscherichiosis.Pathogenic E. coli can cause not only inflammation of the gastrointestinal tract, but also leads to the generalized forms with urinary tract lesions (widespread use of diapers in children under one year contributes to this now), biliary system disorders and sepsis [1,2].Especially dangerous are enterohemorrhagic E. coli, which, in comparison with other strains, are more often as a factor of development of severe forms, lethal outcomes [3].
The main factors that lead to disruption of digestion and absorption of the main nutrients in bacterial II are the occurrence of an inflammatory process with damage of intestinal enterocytes and mucus secretion, disruption of the acid medium, enzymatic balance and motor function of the gastrointestinal tract, development of imbalance of symbiotic microflora [4][5][6].The intensification of these pathological changes by fever, refusal to eat or loss of appetite, repeated vomiting and/or regurgitation, the phenomena of water-electrolyte disorders inherent in children with еscherichiosis, contributes to the de-Íà äîïîìîãó ïåä³àòðó / To Help the Pediatrician ® velopment of prolonged bowel dysfunction, anemia and hypovitaminosis, irritable bowel syndrome, progressive weight loss [7].
The course of еscherichiosis largely depends on the child's age, pathogenic properties of the pathogen, the state of the immune system, the presence of concomitant diseases.In recent decades, the herpes-viral infection (Epstein-Barr virus (EBV) among the young children) has a leading role in the socioeconomic importance, impact on the level and quality of life, prevalence among the population [8,9].Presence of persistent EBV infection with periodic activation and exacerbation of the process leads to suppression of the cellular immune response, expressed immunosuppressive state of the organism.As is known, one of the largest organs of the immune system, consisting of Peyer's plaques, lymphatic follicles, mesenteric lymph nodes, is the GALT-system (gut associated lymphoid tissue), whose main function is the recognition and elimination of antigens or the formation of immunological tolerance to them [10,11].Therefore, the development of bacterial inflammatory process in the mucosa of the gastrointestinal tract in children infected with EBV infection can enhance the dysfunction of immune-competent cells of the body, deepen immune disorders.Simultaneously with inflammatory process of the gastrointestinal tract, disorders of the main antigen-presented dendritic cells of the GALT system may occur, causing a breach of oral tolerance, formation of allergic sensitization, which enhances and supports bowel dysfunction [12,13].Diarrheal syndrome at еscherichiosis in children with EBV can be prolong by such factors as a violation of the functional state of the liver, dysfunction of the biliary system, the development of secondary pancreatic insufficiency, which together are the main components of the formation of malabsorption syndrome [14].
Considering all the above, it is clear the importance of following a rational diet in the treatment of еscherichiosis in children with EBV, improving the diet of children at different stages of the disease and timely correction of the diet depending on the severity and activity of pathological process [15][16][17].The importance of diet in combination with rehydration therapy in the treatment of еscherichiosis increases due to the prevalence of resistance of Enterobacteriaceae pathogens to antibiotics despite the success of the pharmaceutical industry [18,19].In the sources available to us, we did not find work devoted to the features of dietary therapy of еscherichiosis in children infected by EBV.Earlier research conducted by us revealed the peculiarities of еscherichiosis in children with EBV, which include prolonged fever, oropharyngeal hyperemia, lymphadenopathy, hepatomegaly, signs of liver parenchymal reaction, longer disease course, extension of dyspeptic phenomena, signs of hepatomegaly [20].In our opinion, it is possible to improve the therapy of such children by improving of dietary therapy.It is rational for all parameters of nutrition (according to age, activity of persistent herpes-viral infection, severity of the main disease, disorders of liver function and bileexcreting system) will facilitate rapid regression of diar-rheal syndrome, improve the general condition of the child, and shorten the stay in the hospital.
Purpose of the research -improvement of treatment of children with еscherichiosis and infected with EBV in different periods of the disease.

Materials and methods
Under our supervision there were 74 children of twothree years who were treated at the Regional Children's Clinical Infectious Disease Hospital in Kharkov with a diagnosis of moderate-severe forms of еscherichiosis.An additional examination of children revealed the presence of a persistent EBV infection in them.The diagnosis of еscherichiosis was established based on the clinical, epidemiological, bacteriological and serological studies.Persistent EBV infection was diagnosed when the patient had high titers of antibodies to the capsid antigen (EBV CA) IgG class in the dynamics of the disease (latent form).The results of studies of patients for other herpes viruses were negative.Medical treatment of children was carried out in accordance with approved clinical protocols (Order N 354 of 09.07.2004 "On the approval of protocols for the diagnosis and treatment of infectious diseases in children").In the acute phase the daily amount of food was reduced on 1/3-1/4 of the physiological norm with increasing frequency rate to 7-10 feedings per day.
All children were divided into two groups.The first group included 36 children who received conventional therapy with early gradual restoration of nutrition, while the restoration of the qualitative and quantitative composition of food was carried out as soon as possible (in accordance with the existing protocol).The second group was represented by 38 children, who received two days prolonged gradual restoration of diet: more gradual increasing the volume of food at each feeding and reducing the number of feedings per day.Children of the second group received drugs containing Lactobacillus, Milk thistle extract and Vitamins group B (once daily along with meals) from the first day.The choice of this drug is due to the prevention of the intestinal dysbiosis resulting from the antibiotics therapy as well as the protection of liver cells.The liver's damage is possible as a result of acute еscherichiosis and/or persistent EBV-infection.The use of drugs of combined effect is less expensive.It was recommended for parents of second group children to feed them more frequently, in small portions for two weeks in the period of early rehabilitation: up to 6 times a day not more than 150 ml depending on the age and nutritional value of products.
Statistical processing of the obtained data was carried out by means of Excel and Statistica 7.0 applications.The significance of differences between groups was determined using the t-test (Student's test).

Results and discussion
We analyzed the main clinical, laboratory and instrumental parameters of patients of both group within pathological process and for one month after discharge from the hospital.It was revealed significantly longer preservation of the local manifestation of intestinal disorders in children of the first group: diarrheal syndrome (5.83 ± ± 0.24 vs 4.55 ± 0.32 days, р < 0.05), abdominal pain (3.51 ± 0.21 vs 2.41 ± 0.15 days, p < 0.05), signs of flatulence (3.09 ± 0.22 vs 2.01 ± 0.18 days, p < 0.05, respectively in groups).The coprological test revealed a longer presence of impurities of undigested food, increased amounts of fat and fatty admixtures at patients of the first group (6.44 ± 0.27 days vs 4.29 ± 0.29, p < 0,05), which indicates a transient dysfunction of the pancreas and is grounds for early use of drugs that improve the digestion and absorption of food (enzymes) to treat the children with еscherichiosis who are infected with EBV.Rapid recovery of bowel function in children of the second group leads to positive dynamics of their body weight.The daily gain of body mass and its normalization occurred in much shorter period at patients of the second group (10.33 ± 0.45 vs 6.84 ± 0.57 days, respectively, p < 0.05).Thus, compliance with such a diet contributed to a better absorption of nutrients.
One of the features of еscherichiosis in children with EBV is hepatomegaly.We revealed preservation of hepatomegaly in all children until discharge from the hospital.However, the dynamics of liver size reduction was more significant in children of the first group, in whom the liver was reduced on 1.06 ± 0.24 cm compared to 1.85 ± ± 0,37 cm in patients of the second group, although the difference was not significant, p > 0.05.More significant changes were found by echosonoscopy of the liver.Preservation of the parenchymal reaction of the liver with an increase of its echogenicity until discharge from the hospital was noted only in 12 patients of the second group, while among the children of the first group this feature was found in 24 patients.Long-term maintenance of the main clinical symptoms in the patients of the first group resulted in the prolongation of the stay of these children in the hospital (10.89 ± 0.51 vs 8.27 ± 0.32 days, respectively, p < 0.05).
Follow-up observation for one month has shown an exacerbation in five children of the first group which were characterized by moderate bowel dysfunction on day 4.38 ± 1.34 after discharges from the hospital.Parents noticed the deterioration of stool consistency and increased its frequency rate, which required correction of therapy.There were no such manifestations among the patients of the second group.After one month of observation the echosonoscopy of liver was performed and hepatomegaly was found in 10 patients of the second group without signs of parenchymal organ reaction and in 22 patients of the first group with preservation of parenchymal liver reaction in 8 children.
Thus, our obtained data indicate that rational diet therapy remains the main component of treatment of children with еscherichiosis not only in the acute period, but also at the stages of rehabilitation.Early detection of EBV infection among children with еscherichiosis, correction of patients' therapy creates conditions for restoring physiological processes in the intestine and bile excretory system, facilitates the speedy normalization of digestion and absorption of nutrients, and generally has a positive effect on the course of the disease.

Conclusions
1. Children with еscherichiosis who are infected with EBV require long-term gradual recovery in feeding regime in the acute period.
2. Adherence to the nutritional care in combination with drugs containing Lactobacillus, Milk thistle extract and vitamins B in children with еscherichiosis and infected with EBV facilitates the restoration of their clinical, laboratory and instrumental indexes.
3. Saving of mode frequent and small portions feeding during early rehabilitation at patients with еscherichiosis and infected with EBV, prevents the development of bowel dysfunction and has positive impact on the liver restoration.
The procedure was done strictly in compliance with the Helsinki Declaration after approval from the Regional Ethical Review Board at Kharkiv National Medical University.