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Wiadomosci
Lekarskie
Czasopismo Polskiego Towarzystwa Lekarskiego
ClPami^ci
1rFikSl y dra Wtadystawa
Biegariskiego
TOM LXXII, 2019, Nr 7, lipiec Rok zatozenia 1928
Aluna Publishing
© Wydawnictwo Aluna Wiadomosci Lekarskie 2019, tom LXXII, nr 7
I CONTENS / SPIS TRESCI
EDITORIAL ARTICLE / ARTYKUt REDAKCYJNY
Ewa Kucharska, Aleksandra Kucharska, AleksanderSieron, Mariusz Nowakowski, KarolinaSierori
MODERN METHODS OFTREATMENT IN PALLIATIVE CARE
ORIGINAL ARTICLES / PRACE ORYGINALNE
Svitlana V.Vozianova, OlenaO. Dyadyk, Inna I. Horda,YaroslavS. Radkevich
MORPHOLOGICAL AND IMMUNOHISTOCHEMICAL FEATURES OFTISSUE HOMEOSTASIS IN PATIENTSWITH ALOPECIA AREATA
INTHE CHRONIC STAGEASSOCIATEDWITH METABOLIC SYNDROME ANDTHE NON-BURDENED COURSE OFTHE DISEASE
DariuszJagielski, DorotaZysko, Klaudiusz Nadolny,JoannaWizowska, Bartosz Biel,Waldemar Banasiak, PiotrPonikowski
PREDICTORS OF INAPPROPRIATE SHOCKS FROM IMPLANTABLE CARDIOVERTER-DEFIBRILLATORS
OlegY.Kanikovskyi,YaroslavV. Karyi,YuraV.Babiichuk,YevhenV.Shaprynskyi
COMPARATIVE ASSESSMENT OF BILE DUCT DECOMPRESSION METHODS IN PATIENTSWITH OBSTRUCTIVEJAUNDICE OF NON-TUMOR GENESIS
IliaG. Fomenko,ViktoriiaYu. Harbuzova,OlhaA.Obukhova,VladislavV.Pohmura, InnaA. Plakhtiienko, Svitlana N. Piven
THE ASSOCIATION OFAPAI-POLYMORPHISM OFVITAMIN D RECEPTORGENE (VDR)WITH DEVELOPMENT OF GENERALIZED PARODONTITIS IN UKRAINIAN POPULATION 1253
Iryna I.Sokolova,Svitlana I.German,TetianaV.Tomilina,Yuliia O.Slynko,AnatoliyM. Potapchuk, KarynaV.Skydan, Nataliia M.Udovychenko
POSSIBILITIES OFMODERN X-RAY EXAMINATION METHODS FORDIAGNOSTICS OF HIDDEN DENTAL CARIES OFAPPROXIMAL LOCALIZATION
ValeriyA. Kapustnik, OlgaV. Istomina
THE RELATIONSHIPOFVIP LEVELWITH CARDIOPULMONARYPARAMETERS IN PATIENTSWITH CHRONIC OBSTRUCTIVE PULMONARYDISEASE INCOMBINATIONWITH HYPERTENSION 1265
Ivan I.Topchii,AlexanderN. Kirienko, DenisA. Kirienko, Iryna I.Yakovtsova,Alla A.Gavriluk, Svitlana V. Danyliuk, IgorV. Ivakhno,Vira D.Tovazhnianska
FEATURES OF ENDOTHELIUM MORPHOLOGICAL STRUCTURE IN KIDNEYVESSELS, CORONARYARTERIES AND AORTA DURING CHRONIC KIDNEY DISEASE 12
Serhii O.Soloviov,HennadiyA. Mokhort, Olena P.Trokhimenko, HlebV.Zahoriy,ViktorV.Trokhymchuk, Iryna P.Kolesnikova,IrynaV. Dziublyk
PHARMACOECONOMIC AND EPIDEMIOLOGICAL BASES OFOPTIMAL ROTAVIRUSVACCINE SUPPLYFOR UKRAINIAN POPULATION
Veronika Dudnyk,Olha Zborovska,YuiliaVyzhga, Kateryna Khromykh,Ganna Zvenigorodska,Vladymyr Popov,Valentyn Bakhnivskyi
INSTRUMENTAL ASSESSMENT OFMYOCARDIAL FUNCTION BY DOPPLERTISSUE IMAGING IN CHILDRENWITH CONGENITAL HEART DEFECTS AFTERSURGICALCORRECTION
AND ITS CORRELATIONWITH GALECTIN-3 AMOUNTAS BIOLOGICAL MARKEROFCARDIAC FIBROSIS
Jolanta Piskorz,GustawWojcik,Wtodzimierz Bulikowski, Dorota Kozak-Putowska
ASSESSMENT OFCHANGES OFSKIN MOISTURE IN PATIENTS SUBJECTTOGENERAL ANESTHESIAWITH NEUROLOGICAL DISEASES IN AN INTERVIEW
Oleg A. Bychkov,Vitalii E. Kondratiuk, Nina G. Bychkova, ZemfiraV.Morozova, Svetlana A. Bychkova,Alina P.Tarasiuk
ROLEOF IMMUNE SYSTEM IN DEVELOPMENT AND PROGRESS OFCOMBINED ARTERIAL HYPERTENSION AND GOUT
Svetlana Chuhray,Viktoria Lavrynenko,RostyslavKaminsky,Olena Ustymenko, Iryna Dzevulska, Ruzhena Matkivska,Oleksandr Kovalchuk,Olena Holubchenko, Liudmyla Sokurenko
THE INFLUENCE OF DRUGTREATMENT ONCARDIO-VASCULARSYSTEM OFTHE RATSWITH CONGENITAL HYPOTHYROIDISM
Uljana Fedorova,OrysyaSyzon, IgorGajduchok, Kostjantyn Ischejkin, Marianna Dashko
CLINICALAND METABOLICANALYSIS OF DISORDERS IN PSORIATIC PATIENTS
IrynaV.Balaniuk, ElenaV.Myronyk,YuriyO. Randiuk, AndriyV.Andruschak
GENERAL IMMUNOLOGICAL REACTIVITYOFPATIENT'S ORGANISMWITH CHRONIC HEPATITIS C
ViktorV.Kovalenko,Iryna M.Tkachenko, ZoryanaY.Nazarenko, NataliaM. Brailko,Julia G. Romanova,OlgaV.Sheshukova,YaroslavV.Vodoriz
THE STUDYOFORAL FLUID DYNAMIC PARAMETERS ONTHE BACKGROUND OFPATHOLOGICAL AND PHYSIOLOGICAL DENTAL ABRASION
OleksandrI.Smiyan, Kateryna O.Smiian-Horbunova,Tetiana P.Bynda,Andrij M. Loboda,SergijV.Popov, IhorYu.Vysotsky,OleksandrP.Moshchych,OlenaG.Vasylieva,
Yuliia A. Manko,Olena L.Ovsianko, MariiaV.Kolesnikova, Natalia O.Dolgova,Tatiana O.Aleksakhina, Bara'Al-Rawashdeh
OPTIMIZATION OFTHETREATMENT OF ROTAVIRUS INFECTION INCHILDREN BY USING BACILLUSCLAUSII
1227
Wiadomosci Lekarskie 2019, tom LXXII, nr 7 © Wydawnictwo Aluna
PRACA ORYGINALNA
ORIGINAL ARTICLE
I OPTIMIZATION OF THE TREATMENT OF ROTAVIRUS INFECTION
IN CHILDREN BY USING BACILLUS CLAUSII
Oleksandr I. Smiyan1, Kateryna O. Smiian-Horbunova1, Tetiana P. Bynda1, Andrij M. Loboda1, Sergij V. Popov1,
Ihor Yu. Vysotsky1, Oleksandr P. Moshchych2, Olena G. Vasylieva1, Yuliia A. Manko1, Olena L. Ovsianko1,
Mariia V. Kolesnikova1, Natalia O. Dolgova1, Tatiana O. Aleksakhina1, Bara'Al-Rawashdeh1
1SUMY STATE UNIVERSITY, SUMY, UKRAINE
2NATIONAL MEDICAL ACADEMY OF POSTGRADUATE EDUCATION, KIEV, UKRAINE
ABSTRACT
Introduction: Rotavirus infection is a leading place in the structure ofacute intestinal infections in children. Rotavirus is excreted in 40-60 % ofchildren hospitalized with
gastroenteritis all over the world. Every year, 2 million patients are hospitalized with a severe form of RVI, 25 million need medical help from a doctor and 111 million cases
are treated at home.
Theaim:The purpose ofour study was to optimize the treatment ofrotavirus infection in children by usingBacillusclausii.
Materialsandmethods:There were 65 children with a rotavirus infection under supervision.The control group was consisted of28 practically healthy children.The study of
humoral immunity was carried outon the basisofdetermining the serum contentofimmunoglobulin G, immunoglobulin M, immunoglobulin A, and secretory immunoglobulin
A in coprofiltrate. In the process of treatment, the children were divided into two groups: the first received standard treatment, the second group were added to standard
treatment with a probiotic drug(Bacillusclausii).
Results: In children with RVI with modified treatment main symptoms were reduced compared with the children receiving standard treatment, (p <0.001). In patients with
rotavirus infection in the acute period ofthe disease, a decrease in the concentration of IgA (p < 0.001) and an increase in IgM (p < 0.001) in serum and a decrease in sIgA
(p < 0.001) in coprofiltrate was observed in comparison with children in control group. In the period of reconvalescence in children after the traditional treatment, it wasn't
revealed normalization of the immunoglobulins. Patients receiving a probiotic drug in addition to traditional treatment it was revealed normalization of the parameters of
serum immunoglobulins A, M, Gand sIgA in coprofiltrate.
Conclusions: So, the probiotic drug containingBacillusclausii has a positive effect on the humoral immune system in children with rotavirus infection.
KEYWORDS: rotavirus, humoral immunity, children, IgA, sIgA, IgM, IgG
INTRODUCTION
Rotavirus infection (RVI) is an urgent problem, because
it is extremely widespread, especially among young chil­
dren, is characterized by the severity of the course and
the frequency of adverse outcomes and consequences
[1]. Rotavirus infection is a leading place in the structure
of acute intestinal infections in children [2]. Rotavirus is
excreted in 40-60 % of children hospitalized with gastro­
enteritis all over the world. Every year, 2 million patients
are hospitalized with a severe form of RVI, 25 million
need medical help from a doctor and 111 million cases are
treated at home [3, 4]. The most severe illness occurs in
children at the age of4-36 months life. Annually, rotavirus
infection causes more than 600,000 deaths in children
under the age of 5 who die from severe dehydration and
electrolyte imbalance [5, 6]. Almost every young child is
infected with rotavirus regardless ofplace of residence and
socio-economic status [7].
Infection of the intestine with rotavirus depends on
many factors: such as pH of the gastric juice, the presence
of trypsin in the secretion of the duodenum, the level of
Wiad Lek 2019, 72, 7, 1320-1323
secretory IgA and the features of the morphology of the
mucous membrane. The virus is tropical to the cells of the
cylindrical epithelium, located on the villi ofthe duodenum
and in the upper parts ofthe small intestine [8]. Protection
of the human body from the rotavirus is ensured by the
components of cellular and humoral immunity [9]. Anti­
bodies protect not only from the development of clinical
manifestations of RVI, but also from infection. This protec­
tion depends on the level of antibodies: high-titers children
are completely protected from rotavirus infection [10, 11].
These facts determine the need for effective therapeutic and
prophylactic measures against rotavirus gastroenteritis.
THE AIM
The purpose of our study was to optimize the treatment
of rotavirus infection in children by using Bacillus clausii.
MATERIALS AND METHODS
Under observation, there were 65 children with RVI from
6 months to 5 years old (main group) who were treated at
1320
OPTIMIZATION OF THE TREATMENT OF ROTAVIRUS INFECTION IN CHILDREN BY USING BACILLUS CLAUSII
the Communal Nonprofit Enterprise “Children’s Clinical
Hospital of St. Zinaida” of Sumy City Council.
All children were enrolled in the study after informed
consent from their parents or guardians. Ethical approval
was obtained from Institutional research ethics commit­
tees.
Criteria for inclusion:
• age from 6 months to 5 years;
• rotavirus infection;
• hospitalization in acute phase of the disease;
• informed consent from children’s parents or guardians;
• the absence of comorbidity in patients;
• children didn’t take drugs, which were contributed to
the change in the amount of trace elements.
Criteria for exclusion:
• age less than 6 months, or more than 5 years;
• Acute intestinal infection of another viral or bacterial
etiology, as well as mixed variants of rotavirus infection
(with other viruses or bacteria).
• hospitalization in mild phase of the disease;
• parents or guardians of children didn’t give informed
consent;
• presence of comorbidity in children.
Diagnosis of acute intestinal infection of rotavirus etiology
was verified according to anamnesis, parent complaints,
subjective and objective symptoms, and the results of the
immuno-chromatographic test «CITO TEST ROTA» by
Pharmaco Ltd. The control group consisted of28 practically
healthy children. The studywas conducted during the acute
period ofthe disease (for 1-2 days) and during the reconva­
lescence period (5-6 days). During the study, the children of
the main group were divided into two groups: the I group
consisted of 34 children with RVI who received standard
treatment (symptomatic therapy, sorbents, rehydration
therapy), and the second group included 31 children with
RVI who had received standard treatment A probiotic drug
containing spores of the polysaccharide strain Bacillus
clausii - 2 x 109 and purified water (1 vial 1 time per day)
is added. The study of humoral immunity was based on
the determination of the content of immunoglobulin G
(Ig G), immunoglobulin M (Ig M) and immunoglobulin
A (Ig A) by the method of radial immunodiffusion in agar
for Mancini G [12]. The level of secretory immunoglob­
ulin A (sIg A) was determined in the excrements by the
immune enzyme with the method using the «Vector Best»
test systems (Novosibirsk, Russia). Statistical processing of
the data was carried out by generally accepted methods of
variation statistics. The following indicators were deter­
mined: arithmetic average (M), average error (m), level
of differences between the two mean values (confidence
probability - p). Calculations were made on a personal
computer using Microsoft Excel programs adapted for
medical and biological research.
RESULTS AND DISCUSSION
The main clinical symptoms in children with rotavirus
infection were: hyperthermia, vomiting and diarrhea. At
an objective examination of children with RVI patients,
reduced elasticity of the skin and turgor of soft tissues
was revealed, which is a manifestation of exclusion due
to the general dehydration of the organism. Children
with RVI with deep palpation of the abdomen noted
pain in the epigastrium and umbilical region, as well as
rumbling along the intestinal tract. Moreover, clinical
signs I and II had no significant differences (p > 0,05).
In children with RVI with modified treatment, signs of
general weakness disappeared by 1.17 days (p < 0.001)
earlier than in children receiving standard therapy. For
patients in this group, the duration of treatment was char­
acterized by a reduction in the duration of swelling and /
or abdominal pain by 0.72 days (p < 0.05) compared with
standard treatment children. In patients with modified
treatment, the raised body temperature was shorter by
0. 52 days, compared with standard treatment (p < 0.05).
In addition, patients in group II reduced the duration of
diarrhea by 1.13 days (p < 0.001), and shortened vomiting
by 0.6 days (p < 0.001) compared with children in group
1. Along with this, there was no significant difference
between the I and II groups regarding the duration of
clinical symptoms such as pallor of the skin and appetite
disturbance (p > 0.05).
In the period of the onset of the disease in patients with
rotavirus infection (the main group) it was observed a sig­
nificant reduction of IgA levels (0.58 ± 0.02) g / l compared
to the similar indicator of children in the control group
(0.82 ± 0.02) g / l (p < 0.001) (Table I). While the concen­
tration of IgM was (1.01 ± 0.02) g / l and was significantly
higher than the similar indicator ofthe control group (0.73
± 0.02) g / l (p < 0.001), and the IgG level (8,42 ± 0.18) g /
l did not differ significantly from the children in the con­
trol group (7.96 ± 0.21) g / l (p > 0.05). The secretory IgA
in coprofiltrate in patients with CVI decreased to (23.15
± 0.42) mg / l in relation to the data of virtually healthy
children (31.18 ± 0.63) mg / l (p < 0.001).
The period of reconvalescence in children of group I
after the traditional treatment was characterized by an
increase in IgA to (0.71 ± 0.02) g / l (p < 0.001) and IgG
(9.32 ± 0.19) g / l (p < 0, 05). While the concentration of
IgM before discharge from the hospital decreased and it
was (1,03 ± 0,03) g / l (p > 0,05). The level of secretory IgA
in coprofiltrate in sick children increased and amounted
to (27.10 ± 0.31) mg / l (p < 0.001).
Patients in the 2nd group, who received a probiotic drug
in addition to traditional treatment, showed normalization
of serum immunoglobulin A, M, G, and secretory immu­
noglobulin A in coprofiltrate.
The results of many studies indicate a positive effect of
probiotic drugs on the course of acute and persistent diar­
rhea [13, 14]. In the study, researchers point to a decrease
in the duration of diarrhea in children with acute intestinal
infections, which was additionally designated Bacillus
clausii [15]. Currently, the most well documented probiotic
bacteria used in human therapy are lactic acid bacteria. In
contrast, studies aimed at studying the mechanisms respon­
sible for the probiotic positive effects of Bacillus are rare.
1321
Oleksandr I. Smiyan et al.
TableI. Dynamics of indicators of humoral immunity in children suffering from rotavirus infection, depending on the performed therapy, M ± m
Main group
Im m unological index
Control group
(n=28) before treatment
after treatment
(n=65)
(n=65) 1group
(n=34)
II group
(n=31)
1 2 3 4
0,58 ± 0,02
P 12 < 0,001
0,71 ± 0,02
O, 86 ± 0,03
P , 4 > 0,05
P 2_4< 0,001
Ig A, g / l 0,82 ± 0,02 P 1-3 < 0,001
p 2-3 < 0,001
P 3-4 < 0,001
Ig G, g / l 7,96 ± 0,21
8,42 ± 0,18
p 1-2 > 0,05
9,32 ± 0,19
P 13 < 0,001
P2_3 < 0,05
9,11 ± 0,22
P ,_4 > 0,05
P2_4 > 0,05
P3-4 > 0,05
1,01 ± 0,02
P 12 < 0,001
1,03 ± 0,03
O, 79 ± 0,03
P , 4 > 0,05
P 2_4< 0,001
Ig M, g / l 0,73 ± 0,02 P 1-3 < 0,001
P2_3 > 0,05
P 3-4 < 0,001
27,10 ± 0,31
P 13 < 0,001
P 23 < 0,001
30,32 ± 0,39
sIg A, m g / l 31,18 ± 0,63
23,15 ± 0,42
p 1-2 < 0,001
P ,_4 > 0,05
P 2_4< 0,001
P 3-4 < 0,001
Notes: p1-2-the reliability of the difference between the indicators of the primary group's children before treatment and the control group; p1-3- the
reliability ofthe difference between the indicators of children in group Iaftertreatment and control group; p2-3- the reliability ofthe difference between
the indicators ofthe children ofthe main group before treatment and Group Iaftertreatment; p1-4- the reliability ofthe difference between the indicators
of children of group II after treatment and the control group; p2-4- the reliability of the difference between the indicators of the children of the main
group before treatment and the second group after treatment; p3-4- the reliability of the difference between the indices of children of the 1stand 2nd
groups after treatment.
In the work of Urdaci, M. C., Bressollier, Ph., Pinchuk,
I. (2004) evaluation of the immunomodulating properties
of probiotic strains of B. clausii was performed in vitro on
Swiss and C57 Bl / 6j mouse cells. The authors demonstrate
that these strains in their vegetative forms are able to induce
the activity of NOS II synthetase, IFN-y production and
the proliferation of CD4 + T cells [16].
The results of our study showed a decrease in the concen­
tration of class A immunoglobulin and an increase in IgM
in children with rotavirus infection, which may indicate the
activation ofthe antibody formation in the acute period ofthe
disease, againstthebackground ofan increasedlocalresponseto
antigenicstimulationin the intestine. DecreasedIgAconcentra­
tions maybe due to immaturity ofthe immune function ofthe
intestine in young children and / or poor adhesion ofthe virus
andneutralizingability. Atthe same time, a slow“immunolog­
ical start” or transient hypogammonoglobulinemia in young
children may explain insufficient IgG and IgA levels during
the infectious process. During the treatment of children with
rotavirus diarrhea in the acute period of the probiotic prepa­
ration containing Bacillus, there was a rapid positive dynamics
ofthe course ofthe inflammatory process: the immunological
parameters reached the level of children in the control group.
So, the probiotic drug containing Bacillus clausii has a
positive effect on the humoral immune system in children
with rotavirus infection.
According to the results of our study, it was found that in
children with rotavirus infection a decrease in the level of
immunoglobulin of class A and an increase in IgM was ob­
served. A low level of IgA during the infectious process may
be due to immaturity ofthe immune function ofthe intestine
in children or a slow “immunological start” in and / or poor
adhesion of the virus and neutralizing ability. An increase in
Ig M may indicate activation of the antibody formation in
the acute period ofthe disease, against the backdrop of an in­
creased localresponse to antigenic stimulationin the intestine.
When included in the treatment of children with rotavirus
diarrhea in the acute period ofthe probiotic preparation con­
taining Bacillus clausii, there was a rapid positive dynamics of
the course of the inflammatory process: reduction of clinical
symptoms and normalization ofimmunological parameters.
Thus, the use in the complex treatment of rotavirus
infection of a probiotic drug containing Bacillus clausii,
contributed to improving the effectiveness of treatment.
CONCLUSIONS
1. The inclusion of Bacillus clausii in the treatment of chil­
dren with rotavirus infection contributed the reduction
in the duration of clinical symptoms.
2. In children with rotavirus infection in the acute period
of the disease, there was a decrease in the concentration
1322
OPTIMIZATION OF THE TREATMENT OF ROTAVIRUS INFECTION IN CHILDREN BY USING BACILLUS CLAUSII
of IgA and an increase in the level of IgM in serum and
a decrease in sIgA in coprofiltrate.
3. During the period of reconvalescence in children with
rotavirus infection after standard treatment, the hu­
moral link of the immune system was characterized by
improvement of the indicators, however, they did not
reach the level of control group children.
4. In patients with rotavirus infection, which had been
added to the traditional treatment with Bacillus clausii,
the indices of the humoral immune system reached the
level of control group children.
Prospects for further research: It will be perspective to
further studying the effects of this probiotic drug on other
parts of the immune system of children.
REFERENCES
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and norovirus infection among children inJi'nan, China.Virologyjournal.
2013; 10(1): 1. DOI: 10.1128 / JCM.02927-13.
2. John BM, Devgan A, Mitra B. Prevalence of rotavirus infection in
children below two years presenting with diarrhea. Medical journal
armed forces India. 2014; 70(2): 116-119.https://doi.org/10.10Wj.
mjafi.2014.02.008.
3. Moradi-Lakeh M, Shakerian S,Yaghoubi M et al. Rotavirus infection in
children with acute gast.roenteritis in Iran: A systematic review and
meta-analysis. International journal of preventive medicine. 2014;
5(10): 1213-1223.
4. Van Trang N, ThiBich VuH, ThiHong LeN et al. Association between
norovirus and rotavirus infection and histo-blood group antigen types
in Vietnamese children. Journal of clinical microbiology. 2014; 52(5):
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5. Troeger C, Khalil IA, Rao PC et al. Rotavirus vaccination and the
global burden of rotavirus diarrhea among children younger than
5 years. JAMA pediatrics. 2018; 172(10): 958-965. doi: 10.1001/
jamapediatrics.2018.1960.
6. Simwaka JC, Mpabalwani EM,Seheri Metal. Diversity ofrotavirusstrains
circulating in children underfive years ofage who presented with acute
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Teaching Hospital, Lusaka, Zambia, 2008-2015.Vaccine. 2018; 36(47):
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ofvirology. 2015; 90(1): 43-56. doi: 10.1128/JVI.01930-15.
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Education". 2015.
10. Maffey L, Vega CG, Mino, S et al. Anti-VP6 VHH: an experimental
treatment for rotavirus A-associated disease. PloS one. (2016); 11(9):
e0162351. https://doi.org/10.1371/journal.pone.0162351.
11. Walker LM, Burton DR. Passive immunotherapy ofviral infections:'super-
antibodies'enter the fray. Nature Reviews Immunology. (2018); 18(5):
297. https://doi.org/10.1038/nri.2017.148
12. Mancini G, Carbonare A, Harmans J. Immunochemical quantitation
of antigens by single radial diffusion. Immunochemistry. 1965; 2:
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13. Sharif MR, Kashani HH, Ardakani AT et al.The effect ofa yeast probiotic
on acute diarrhea in children. Probiotics and antimicrobial proteins.
2016; 8(4): 211-214.https://doi.org/10.1007/s12602-016-9221-2
14. Lievin-Le Moal, Servin AL. Anti-infective activities oflactobacillus strains
in the human intestinal microbiota: from probiotics to gastrointestinal
anti-infectious biotherapeutic agents. Clinical microbiology reviews.
2014; 27(2): 167-199. DOI: 10.1128/CMR.00080-13
15. Akter S, Aziz MA, Sharmin KN etal. Anti-Diarrhoeal Effects of Probiotics
on Children. Research & Reviews: AJournal ofMicrobiologyandVirology.
2018; 8(1): 15-21.
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Strains: Antimicrobial and Immunomodulatory Activities. Journal
of Clinical Gastroenterology. 2004; 38: 86-90 doi: 10.1097/01.
mcg.0000128925.06662.69.
Authors’contributions:
According to the order o f the Authorship.
Conflict of interest:
The Authors declare no conflict o f interest.
CORRESPONDING AUTHOR
OleksandrI.Smiyan
Department of Pediatrics,
Sumy State University,
28 Troytska Str., 40022 Sumy, Ukraine
tel: +380506316005
e-mail: smiyana@ukr.net
Received: 17.02.2019
Accepted: 18.06.2019
1323

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OPTIMIZATION OF THE TREATMENT OF ROTAVIRUS INFECTION IN CHILDREN BY USING BACILLUS CLAUSII

  • 1. Wiadomosci Lekarskie Czasopismo Polskiego Towarzystwa Lekarskiego ClPami^ci 1rFikSl y dra Wtadystawa Biegariskiego TOM LXXII, 2019, Nr 7, lipiec Rok zatozenia 1928 Aluna Publishing
  • 2. © Wydawnictwo Aluna Wiadomosci Lekarskie 2019, tom LXXII, nr 7 I CONTENS / SPIS TRESCI EDITORIAL ARTICLE / ARTYKUt REDAKCYJNY Ewa Kucharska, Aleksandra Kucharska, AleksanderSieron, Mariusz Nowakowski, KarolinaSierori MODERN METHODS OFTREATMENT IN PALLIATIVE CARE ORIGINAL ARTICLES / PRACE ORYGINALNE Svitlana V.Vozianova, OlenaO. Dyadyk, Inna I. Horda,YaroslavS. Radkevich MORPHOLOGICAL AND IMMUNOHISTOCHEMICAL FEATURES OFTISSUE HOMEOSTASIS IN PATIENTSWITH ALOPECIA AREATA INTHE CHRONIC STAGEASSOCIATEDWITH METABOLIC SYNDROME ANDTHE NON-BURDENED COURSE OFTHE DISEASE DariuszJagielski, DorotaZysko, Klaudiusz Nadolny,JoannaWizowska, Bartosz Biel,Waldemar Banasiak, PiotrPonikowski PREDICTORS OF INAPPROPRIATE SHOCKS FROM IMPLANTABLE CARDIOVERTER-DEFIBRILLATORS OlegY.Kanikovskyi,YaroslavV. Karyi,YuraV.Babiichuk,YevhenV.Shaprynskyi COMPARATIVE ASSESSMENT OF BILE DUCT DECOMPRESSION METHODS IN PATIENTSWITH OBSTRUCTIVEJAUNDICE OF NON-TUMOR GENESIS IliaG. Fomenko,ViktoriiaYu. Harbuzova,OlhaA.Obukhova,VladislavV.Pohmura, InnaA. Plakhtiienko, Svitlana N. Piven THE ASSOCIATION OFAPAI-POLYMORPHISM OFVITAMIN D RECEPTORGENE (VDR)WITH DEVELOPMENT OF GENERALIZED PARODONTITIS IN UKRAINIAN POPULATION 1253 Iryna I.Sokolova,Svitlana I.German,TetianaV.Tomilina,Yuliia O.Slynko,AnatoliyM. Potapchuk, KarynaV.Skydan, Nataliia M.Udovychenko POSSIBILITIES OFMODERN X-RAY EXAMINATION METHODS FORDIAGNOSTICS OF HIDDEN DENTAL CARIES OFAPPROXIMAL LOCALIZATION ValeriyA. Kapustnik, OlgaV. Istomina THE RELATIONSHIPOFVIP LEVELWITH CARDIOPULMONARYPARAMETERS IN PATIENTSWITH CHRONIC OBSTRUCTIVE PULMONARYDISEASE INCOMBINATIONWITH HYPERTENSION 1265 Ivan I.Topchii,AlexanderN. Kirienko, DenisA. Kirienko, Iryna I.Yakovtsova,Alla A.Gavriluk, Svitlana V. Danyliuk, IgorV. Ivakhno,Vira D.Tovazhnianska FEATURES OF ENDOTHELIUM MORPHOLOGICAL STRUCTURE IN KIDNEYVESSELS, CORONARYARTERIES AND AORTA DURING CHRONIC KIDNEY DISEASE 12 Serhii O.Soloviov,HennadiyA. Mokhort, Olena P.Trokhimenko, HlebV.Zahoriy,ViktorV.Trokhymchuk, Iryna P.Kolesnikova,IrynaV. Dziublyk PHARMACOECONOMIC AND EPIDEMIOLOGICAL BASES OFOPTIMAL ROTAVIRUSVACCINE SUPPLYFOR UKRAINIAN POPULATION Veronika Dudnyk,Olha Zborovska,YuiliaVyzhga, Kateryna Khromykh,Ganna Zvenigorodska,Vladymyr Popov,Valentyn Bakhnivskyi INSTRUMENTAL ASSESSMENT OFMYOCARDIAL FUNCTION BY DOPPLERTISSUE IMAGING IN CHILDRENWITH CONGENITAL HEART DEFECTS AFTERSURGICALCORRECTION AND ITS CORRELATIONWITH GALECTIN-3 AMOUNTAS BIOLOGICAL MARKEROFCARDIAC FIBROSIS Jolanta Piskorz,GustawWojcik,Wtodzimierz Bulikowski, Dorota Kozak-Putowska ASSESSMENT OFCHANGES OFSKIN MOISTURE IN PATIENTS SUBJECTTOGENERAL ANESTHESIAWITH NEUROLOGICAL DISEASES IN AN INTERVIEW Oleg A. Bychkov,Vitalii E. Kondratiuk, Nina G. Bychkova, ZemfiraV.Morozova, Svetlana A. Bychkova,Alina P.Tarasiuk ROLEOF IMMUNE SYSTEM IN DEVELOPMENT AND PROGRESS OFCOMBINED ARTERIAL HYPERTENSION AND GOUT Svetlana Chuhray,Viktoria Lavrynenko,RostyslavKaminsky,Olena Ustymenko, Iryna Dzevulska, Ruzhena Matkivska,Oleksandr Kovalchuk,Olena Holubchenko, Liudmyla Sokurenko THE INFLUENCE OF DRUGTREATMENT ONCARDIO-VASCULARSYSTEM OFTHE RATSWITH CONGENITAL HYPOTHYROIDISM Uljana Fedorova,OrysyaSyzon, IgorGajduchok, Kostjantyn Ischejkin, Marianna Dashko CLINICALAND METABOLICANALYSIS OF DISORDERS IN PSORIATIC PATIENTS IrynaV.Balaniuk, ElenaV.Myronyk,YuriyO. Randiuk, AndriyV.Andruschak GENERAL IMMUNOLOGICAL REACTIVITYOFPATIENT'S ORGANISMWITH CHRONIC HEPATITIS C ViktorV.Kovalenko,Iryna M.Tkachenko, ZoryanaY.Nazarenko, NataliaM. Brailko,Julia G. Romanova,OlgaV.Sheshukova,YaroslavV.Vodoriz THE STUDYOFORAL FLUID DYNAMIC PARAMETERS ONTHE BACKGROUND OFPATHOLOGICAL AND PHYSIOLOGICAL DENTAL ABRASION OleksandrI.Smiyan, Kateryna O.Smiian-Horbunova,Tetiana P.Bynda,Andrij M. Loboda,SergijV.Popov, IhorYu.Vysotsky,OleksandrP.Moshchych,OlenaG.Vasylieva, Yuliia A. Manko,Olena L.Ovsianko, MariiaV.Kolesnikova, Natalia O.Dolgova,Tatiana O.Aleksakhina, Bara'Al-Rawashdeh OPTIMIZATION OFTHETREATMENT OF ROTAVIRUS INFECTION INCHILDREN BY USING BACILLUSCLAUSII 1227
  • 3. Wiadomosci Lekarskie 2019, tom LXXII, nr 7 © Wydawnictwo Aluna PRACA ORYGINALNA ORIGINAL ARTICLE I OPTIMIZATION OF THE TREATMENT OF ROTAVIRUS INFECTION IN CHILDREN BY USING BACILLUS CLAUSII Oleksandr I. Smiyan1, Kateryna O. Smiian-Horbunova1, Tetiana P. Bynda1, Andrij M. Loboda1, Sergij V. Popov1, Ihor Yu. Vysotsky1, Oleksandr P. Moshchych2, Olena G. Vasylieva1, Yuliia A. Manko1, Olena L. Ovsianko1, Mariia V. Kolesnikova1, Natalia O. Dolgova1, Tatiana O. Aleksakhina1, Bara'Al-Rawashdeh1 1SUMY STATE UNIVERSITY, SUMY, UKRAINE 2NATIONAL MEDICAL ACADEMY OF POSTGRADUATE EDUCATION, KIEV, UKRAINE ABSTRACT Introduction: Rotavirus infection is a leading place in the structure ofacute intestinal infections in children. Rotavirus is excreted in 40-60 % ofchildren hospitalized with gastroenteritis all over the world. Every year, 2 million patients are hospitalized with a severe form of RVI, 25 million need medical help from a doctor and 111 million cases are treated at home. Theaim:The purpose ofour study was to optimize the treatment ofrotavirus infection in children by usingBacillusclausii. Materialsandmethods:There were 65 children with a rotavirus infection under supervision.The control group was consisted of28 practically healthy children.The study of humoral immunity was carried outon the basisofdetermining the serum contentofimmunoglobulin G, immunoglobulin M, immunoglobulin A, and secretory immunoglobulin A in coprofiltrate. In the process of treatment, the children were divided into two groups: the first received standard treatment, the second group were added to standard treatment with a probiotic drug(Bacillusclausii). Results: In children with RVI with modified treatment main symptoms were reduced compared with the children receiving standard treatment, (p <0.001). In patients with rotavirus infection in the acute period ofthe disease, a decrease in the concentration of IgA (p < 0.001) and an increase in IgM (p < 0.001) in serum and a decrease in sIgA (p < 0.001) in coprofiltrate was observed in comparison with children in control group. In the period of reconvalescence in children after the traditional treatment, it wasn't revealed normalization of the immunoglobulins. Patients receiving a probiotic drug in addition to traditional treatment it was revealed normalization of the parameters of serum immunoglobulins A, M, Gand sIgA in coprofiltrate. Conclusions: So, the probiotic drug containingBacillusclausii has a positive effect on the humoral immune system in children with rotavirus infection. KEYWORDS: rotavirus, humoral immunity, children, IgA, sIgA, IgM, IgG INTRODUCTION Rotavirus infection (RVI) is an urgent problem, because it is extremely widespread, especially among young chil­ dren, is characterized by the severity of the course and the frequency of adverse outcomes and consequences [1]. Rotavirus infection is a leading place in the structure of acute intestinal infections in children [2]. Rotavirus is excreted in 40-60 % of children hospitalized with gastro­ enteritis all over the world. Every year, 2 million patients are hospitalized with a severe form of RVI, 25 million need medical help from a doctor and 111 million cases are treated at home [3, 4]. The most severe illness occurs in children at the age of4-36 months life. Annually, rotavirus infection causes more than 600,000 deaths in children under the age of 5 who die from severe dehydration and electrolyte imbalance [5, 6]. Almost every young child is infected with rotavirus regardless ofplace of residence and socio-economic status [7]. Infection of the intestine with rotavirus depends on many factors: such as pH of the gastric juice, the presence of trypsin in the secretion of the duodenum, the level of Wiad Lek 2019, 72, 7, 1320-1323 secretory IgA and the features of the morphology of the mucous membrane. The virus is tropical to the cells of the cylindrical epithelium, located on the villi ofthe duodenum and in the upper parts ofthe small intestine [8]. Protection of the human body from the rotavirus is ensured by the components of cellular and humoral immunity [9]. Anti­ bodies protect not only from the development of clinical manifestations of RVI, but also from infection. This protec­ tion depends on the level of antibodies: high-titers children are completely protected from rotavirus infection [10, 11]. These facts determine the need for effective therapeutic and prophylactic measures against rotavirus gastroenteritis. THE AIM The purpose of our study was to optimize the treatment of rotavirus infection in children by using Bacillus clausii. MATERIALS AND METHODS Under observation, there were 65 children with RVI from 6 months to 5 years old (main group) who were treated at 1320
  • 4. OPTIMIZATION OF THE TREATMENT OF ROTAVIRUS INFECTION IN CHILDREN BY USING BACILLUS CLAUSII the Communal Nonprofit Enterprise “Children’s Clinical Hospital of St. Zinaida” of Sumy City Council. All children were enrolled in the study after informed consent from their parents or guardians. Ethical approval was obtained from Institutional research ethics commit­ tees. Criteria for inclusion: • age from 6 months to 5 years; • rotavirus infection; • hospitalization in acute phase of the disease; • informed consent from children’s parents or guardians; • the absence of comorbidity in patients; • children didn’t take drugs, which were contributed to the change in the amount of trace elements. Criteria for exclusion: • age less than 6 months, or more than 5 years; • Acute intestinal infection of another viral or bacterial etiology, as well as mixed variants of rotavirus infection (with other viruses or bacteria). • hospitalization in mild phase of the disease; • parents or guardians of children didn’t give informed consent; • presence of comorbidity in children. Diagnosis of acute intestinal infection of rotavirus etiology was verified according to anamnesis, parent complaints, subjective and objective symptoms, and the results of the immuno-chromatographic test «CITO TEST ROTA» by Pharmaco Ltd. The control group consisted of28 practically healthy children. The studywas conducted during the acute period ofthe disease (for 1-2 days) and during the reconva­ lescence period (5-6 days). During the study, the children of the main group were divided into two groups: the I group consisted of 34 children with RVI who received standard treatment (symptomatic therapy, sorbents, rehydration therapy), and the second group included 31 children with RVI who had received standard treatment A probiotic drug containing spores of the polysaccharide strain Bacillus clausii - 2 x 109 and purified water (1 vial 1 time per day) is added. The study of humoral immunity was based on the determination of the content of immunoglobulin G (Ig G), immunoglobulin M (Ig M) and immunoglobulin A (Ig A) by the method of radial immunodiffusion in agar for Mancini G [12]. The level of secretory immunoglob­ ulin A (sIg A) was determined in the excrements by the immune enzyme with the method using the «Vector Best» test systems (Novosibirsk, Russia). Statistical processing of the data was carried out by generally accepted methods of variation statistics. The following indicators were deter­ mined: arithmetic average (M), average error (m), level of differences between the two mean values (confidence probability - p). Calculations were made on a personal computer using Microsoft Excel programs adapted for medical and biological research. RESULTS AND DISCUSSION The main clinical symptoms in children with rotavirus infection were: hyperthermia, vomiting and diarrhea. At an objective examination of children with RVI patients, reduced elasticity of the skin and turgor of soft tissues was revealed, which is a manifestation of exclusion due to the general dehydration of the organism. Children with RVI with deep palpation of the abdomen noted pain in the epigastrium and umbilical region, as well as rumbling along the intestinal tract. Moreover, clinical signs I and II had no significant differences (p > 0,05). In children with RVI with modified treatment, signs of general weakness disappeared by 1.17 days (p < 0.001) earlier than in children receiving standard therapy. For patients in this group, the duration of treatment was char­ acterized by a reduction in the duration of swelling and / or abdominal pain by 0.72 days (p < 0.05) compared with standard treatment children. In patients with modified treatment, the raised body temperature was shorter by 0. 52 days, compared with standard treatment (p < 0.05). In addition, patients in group II reduced the duration of diarrhea by 1.13 days (p < 0.001), and shortened vomiting by 0.6 days (p < 0.001) compared with children in group 1. Along with this, there was no significant difference between the I and II groups regarding the duration of clinical symptoms such as pallor of the skin and appetite disturbance (p > 0.05). In the period of the onset of the disease in patients with rotavirus infection (the main group) it was observed a sig­ nificant reduction of IgA levels (0.58 ± 0.02) g / l compared to the similar indicator of children in the control group (0.82 ± 0.02) g / l (p < 0.001) (Table I). While the concen­ tration of IgM was (1.01 ± 0.02) g / l and was significantly higher than the similar indicator ofthe control group (0.73 ± 0.02) g / l (p < 0.001), and the IgG level (8,42 ± 0.18) g / l did not differ significantly from the children in the con­ trol group (7.96 ± 0.21) g / l (p > 0.05). The secretory IgA in coprofiltrate in patients with CVI decreased to (23.15 ± 0.42) mg / l in relation to the data of virtually healthy children (31.18 ± 0.63) mg / l (p < 0.001). The period of reconvalescence in children of group I after the traditional treatment was characterized by an increase in IgA to (0.71 ± 0.02) g / l (p < 0.001) and IgG (9.32 ± 0.19) g / l (p < 0, 05). While the concentration of IgM before discharge from the hospital decreased and it was (1,03 ± 0,03) g / l (p > 0,05). The level of secretory IgA in coprofiltrate in sick children increased and amounted to (27.10 ± 0.31) mg / l (p < 0.001). Patients in the 2nd group, who received a probiotic drug in addition to traditional treatment, showed normalization of serum immunoglobulin A, M, G, and secretory immu­ noglobulin A in coprofiltrate. The results of many studies indicate a positive effect of probiotic drugs on the course of acute and persistent diar­ rhea [13, 14]. In the study, researchers point to a decrease in the duration of diarrhea in children with acute intestinal infections, which was additionally designated Bacillus clausii [15]. Currently, the most well documented probiotic bacteria used in human therapy are lactic acid bacteria. In contrast, studies aimed at studying the mechanisms respon­ sible for the probiotic positive effects of Bacillus are rare. 1321
  • 5. Oleksandr I. Smiyan et al. TableI. Dynamics of indicators of humoral immunity in children suffering from rotavirus infection, depending on the performed therapy, M ± m Main group Im m unological index Control group (n=28) before treatment after treatment (n=65) (n=65) 1group (n=34) II group (n=31) 1 2 3 4 0,58 ± 0,02 P 12 < 0,001 0,71 ± 0,02 O, 86 ± 0,03 P , 4 > 0,05 P 2_4< 0,001 Ig A, g / l 0,82 ± 0,02 P 1-3 < 0,001 p 2-3 < 0,001 P 3-4 < 0,001 Ig G, g / l 7,96 ± 0,21 8,42 ± 0,18 p 1-2 > 0,05 9,32 ± 0,19 P 13 < 0,001 P2_3 < 0,05 9,11 ± 0,22 P ,_4 > 0,05 P2_4 > 0,05 P3-4 > 0,05 1,01 ± 0,02 P 12 < 0,001 1,03 ± 0,03 O, 79 ± 0,03 P , 4 > 0,05 P 2_4< 0,001 Ig M, g / l 0,73 ± 0,02 P 1-3 < 0,001 P2_3 > 0,05 P 3-4 < 0,001 27,10 ± 0,31 P 13 < 0,001 P 23 < 0,001 30,32 ± 0,39 sIg A, m g / l 31,18 ± 0,63 23,15 ± 0,42 p 1-2 < 0,001 P ,_4 > 0,05 P 2_4< 0,001 P 3-4 < 0,001 Notes: p1-2-the reliability of the difference between the indicators of the primary group's children before treatment and the control group; p1-3- the reliability ofthe difference between the indicators of children in group Iaftertreatment and control group; p2-3- the reliability ofthe difference between the indicators ofthe children ofthe main group before treatment and Group Iaftertreatment; p1-4- the reliability ofthe difference between the indicators of children of group II after treatment and the control group; p2-4- the reliability of the difference between the indicators of the children of the main group before treatment and the second group after treatment; p3-4- the reliability of the difference between the indices of children of the 1stand 2nd groups after treatment. In the work of Urdaci, M. C., Bressollier, Ph., Pinchuk, I. (2004) evaluation of the immunomodulating properties of probiotic strains of B. clausii was performed in vitro on Swiss and C57 Bl / 6j mouse cells. The authors demonstrate that these strains in their vegetative forms are able to induce the activity of NOS II synthetase, IFN-y production and the proliferation of CD4 + T cells [16]. The results of our study showed a decrease in the concen­ tration of class A immunoglobulin and an increase in IgM in children with rotavirus infection, which may indicate the activation ofthe antibody formation in the acute period ofthe disease, againstthebackground ofan increasedlocalresponseto antigenicstimulationin the intestine. DecreasedIgAconcentra­ tions maybe due to immaturity ofthe immune function ofthe intestine in young children and / or poor adhesion ofthe virus andneutralizingability. Atthe same time, a slow“immunolog­ ical start” or transient hypogammonoglobulinemia in young children may explain insufficient IgG and IgA levels during the infectious process. During the treatment of children with rotavirus diarrhea in the acute period of the probiotic prepa­ ration containing Bacillus, there was a rapid positive dynamics ofthe course ofthe inflammatory process: the immunological parameters reached the level of children in the control group. So, the probiotic drug containing Bacillus clausii has a positive effect on the humoral immune system in children with rotavirus infection. According to the results of our study, it was found that in children with rotavirus infection a decrease in the level of immunoglobulin of class A and an increase in IgM was ob­ served. A low level of IgA during the infectious process may be due to immaturity ofthe immune function ofthe intestine in children or a slow “immunological start” in and / or poor adhesion of the virus and neutralizing ability. An increase in Ig M may indicate activation of the antibody formation in the acute period ofthe disease, against the backdrop of an in­ creased localresponse to antigenic stimulationin the intestine. When included in the treatment of children with rotavirus diarrhea in the acute period ofthe probiotic preparation con­ taining Bacillus clausii, there was a rapid positive dynamics of the course of the inflammatory process: reduction of clinical symptoms and normalization ofimmunological parameters. Thus, the use in the complex treatment of rotavirus infection of a probiotic drug containing Bacillus clausii, contributed to improving the effectiveness of treatment. CONCLUSIONS 1. The inclusion of Bacillus clausii in the treatment of chil­ dren with rotavirus infection contributed the reduction in the duration of clinical symptoms. 2. In children with rotavirus infection in the acute period of the disease, there was a decrease in the concentration 1322
  • 6. OPTIMIZATION OF THE TREATMENT OF ROTAVIRUS INFECTION IN CHILDREN BY USING BACILLUS CLAUSII of IgA and an increase in the level of IgM in serum and a decrease in sIgA in coprofiltrate. 3. During the period of reconvalescence in children with rotavirus infection after standard treatment, the hu­ moral link of the immune system was characterized by improvement of the indicators, however, they did not reach the level of control group children. 4. In patients with rotavirus infection, which had been added to the traditional treatment with Bacillus clausii, the indices of the humoral immune system reached the level of control group children. Prospects for further research: It will be perspective to further studying the effects of this probiotic drug on other parts of the immune system of children. REFERENCES 1. Sai L, Sun J, Shao L et al. Epidemiology and clinical features of rotavirus and norovirus infection among children inJi'nan, China.Virologyjournal. 2013; 10(1): 1. DOI: 10.1128 / JCM.02927-13. 2. John BM, Devgan A, Mitra B. Prevalence of rotavirus infection in children below two years presenting with diarrhea. Medical journal armed forces India. 2014; 70(2): 116-119.https://doi.org/10.10Wj. mjafi.2014.02.008. 3. Moradi-Lakeh M, Shakerian S,Yaghoubi M et al. Rotavirus infection in children with acute gast.roenteritis in Iran: A systematic review and meta-analysis. International journal of preventive medicine. 2014; 5(10): 1213-1223. 4. Van Trang N, ThiBich VuH, ThiHong LeN et al. Association between norovirus and rotavirus infection and histo-blood group antigen types in Vietnamese children. Journal of clinical microbiology. 2014; 52(5): 1366-1374. doi: 10.1128/JCM.02927-13. 5. Troeger C, Khalil IA, Rao PC et al. Rotavirus vaccination and the global burden of rotavirus diarrhea among children younger than 5 years. JAMA pediatrics. 2018; 172(10): 958-965. doi: 10.1001/ jamapediatrics.2018.1960. 6. Simwaka JC, Mpabalwani EM,Seheri Metal. Diversity ofrotavirusstrains circulating in children underfive years ofage who presented with acute gastroenteritis beforeand after rotavirusvaccine introduction, University Teaching Hospital, Lusaka, Zambia, 2008-2015.Vaccine. 2018; 36(47): 7243-7247.https://doi.org/10.10Wj.vaccine.2018.03.035. 7. Mchaile DN, Philemon RN, Kabika S et al. Prevalence and genotypes of Rotavirus among children under 5 years presenting with diarrhoea in Moshi, Tanzania: a hospital based cross sectional study. BMC research notes. 2017; 10(1): 542. doi: 10.1186/s13104-017-2883-3. 8. Saxena K,BluttSE,EttayebiKetal.Human intestinalenteroids:anewmodelto studyhuman rotavirusinfection,hostrestrictionand pathophysiology.Journal ofvirology. 2015; 90(1): 43-56. doi: 10.1128/JVI.01930-15. 9. Mazankova LN, Gorbunov SG, Shishkina AA. Features ofthe course and prevention of rotavirus infection in children of early age: studying. Method manual; HBOU DPO"Russian Medical Academy ofPostgraduate Education". 2015. 10. Maffey L, Vega CG, Mino, S et al. Anti-VP6 VHH: an experimental treatment for rotavirus A-associated disease. PloS one. (2016); 11(9): e0162351. https://doi.org/10.1371/journal.pone.0162351. 11. Walker LM, Burton DR. Passive immunotherapy ofviral infections:'super- antibodies'enter the fray. Nature Reviews Immunology. (2018); 18(5): 297. https://doi.org/10.1038/nri.2017.148 12. Mancini G, Carbonare A, Harmans J. Immunochemical quantitation of antigens by single radial diffusion. Immunochemistry. 1965; 2: 235-239. 13. Sharif MR, Kashani HH, Ardakani AT et al.The effect ofa yeast probiotic on acute diarrhea in children. Probiotics and antimicrobial proteins. 2016; 8(4): 211-214.https://doi.org/10.1007/s12602-016-9221-2 14. Lievin-Le Moal, Servin AL. Anti-infective activities oflactobacillus strains in the human intestinal microbiota: from probiotics to gastrointestinal anti-infectious biotherapeutic agents. Clinical microbiology reviews. 2014; 27(2): 167-199. DOI: 10.1128/CMR.00080-13 15. Akter S, Aziz MA, Sharmin KN etal. Anti-Diarrhoeal Effects of Probiotics on Children. Research & Reviews: AJournal ofMicrobiologyandVirology. 2018; 8(1): 15-21. 16. Urdaci MC, Bressollier Ph, Pinchuk I.Bacillus clausii Probiotic Strains: Antimicrobial and Immunomodulatory Activities. Journal of Clinical Gastroenterology. 2004; 38: 86-90 doi: 10.1097/01. mcg.0000128925.06662.69. Authors’contributions: According to the order o f the Authorship. Conflict of interest: The Authors declare no conflict o f interest. CORRESPONDING AUTHOR OleksandrI.Smiyan Department of Pediatrics, Sumy State University, 28 Troytska Str., 40022 Sumy, Ukraine tel: +380506316005 e-mail: smiyana@ukr.net Received: 17.02.2019 Accepted: 18.06.2019 1323