{"id":18089,"date":"2017-12-21T10:00:31","date_gmt":"2017-12-21T10:00:31","guid":{"rendered":"http:\/\/biomedpharmajournal.org\/?p=18089"},"modified":"2018-11-06T06:29:27","modified_gmt":"2018-11-06T06:29:27","slug":"rri-children-preventive-vaccination-issues","status":"publish","type":"post","link":"https:\/\/biomedpharmajournal.org\/staging\/vol10no4\/rri-children-preventive-vaccination-issues\/","title":{"rendered":"RRI Children: Preventive Vaccination Issues"},"content":{"rendered":"

Introduction<\/strong><\/p>\n

Based on the many-year experience of contagious disease immunological prophylaxis, it is found that only healthy children should be subject to preventive vaccination. Children with changed reactivity should be vaccinated only when specific requirements are met. Moreover, vaccination calendar cannot be stable.1<\/sup>\u00a0The effectiveness of immunological prophylaxis largely depends on well-chosen age for preimmunization and optimum time between vaccinations. The issue of contra-indications of preventive vaccination is relevant and difficult. There\u2019s a category of children for whom the complete schedule of immunization provided for healthy children is intolerable.2<\/sup>\u00a0Contra-indication of some or other vaccination is defined not only based on medical case history data but also on the clinical research. The ability to respond or ignore any particular antigen, as well as the height of immune response, are genetically coded.3<\/sup>\u00a0One of the most important factors, which have a significant impact on the children development, is their morbidity, especially during first three years of their life. Implementing extensive immunization depends on this factor. About 10% of children aren\u2019t timely vaccinated because of temporary medical contra-indications.4<\/sup><\/p>\n

A group of sick children sent from the suburban area and city children’s hospitals with different pathologies was examined in the city centre of infantile infection immunological prophylaxis of Nizhni Tagil of the Sverdlovsk Region to solve the problem of carrying out preventive vaccination and making the individual schedule of specific immunological prophylaxis.5<\/sup>\u00a0Among them, a group of children who suffered the laboratory confirmed condition of the depression of the secretion of immunoglobulins of the humoral component of immunity conditionally defined as immunoglobulins syndrome was distinguished. The antiinfective profile of sick children was studied to determine what an effect preventive vaccinations have on the immune system of the children of early age with disimmunoglobulinemia syndrome, to elaborate recommendations on implementing preventive vaccinations and possibilities of using them in case of \u201cabsolute\u201d contra-indications involving assessing the level of specific immunity tension against some vaccine-preventable infections (diphtheria, tetanus, measles).6<\/sup><\/p>\n

Materials and Methods<\/strong><\/p>\n

1127 children aged from 8 months to 5 years with a clinical syndrome of antiinfective protection violation in the form of recurrent diseases of viral and bacterial etiology, in whom the decrease in one or several isotypes of immunoglobulins in the serum had been found, were observed. Among them, a group with disimmunoglobulinemia syndrome of 280 patients was distinguished. This group was chosen for a deeper and more detailed examination.<\/p>\n

A special method developed by Altukhov Y.P. and Kurbatova O.L. based on the children distribution by weight and body length to give proper characteristics of the latter group of children was used.7<\/sup>\u00a0Each child, depending on his indicators at birth, was subsequently assigned to one of 9 groups, i.e. with average, low and high characteristic values, with low and high values of body weight at an average length, with low and high values of body length at an average mass, as well as with a low body length at a large mass and with a low mass at a large body length. The average conditional \u041c was determined. The method enabled the analysis of compared groups by the number of children included in different areas, the analysis of the structure of their morbidity and providing corresponding characteristics.8<\/sup><\/p>\n

The \u201cdisimmunoglobulinemia syndrome\u201d condition was identified if the immunoassay of children aged from 8 months to 5 years revealed a recurrent decrease in one or several isotypes of immunoglobulins in the serum: Ig G less than 5 g\/l, Ig \u0410 less than 0,2 g\/l, Ig \u041c less than 0,4 g\/l coupled with a low or high concentration of cortisol (less than 100 nmol\/l or more than 500 nmol\/l). We have already established the close correlation relationship between the low levels of immunoglobulins and serum cortisol in the previous researches; which indicates the role of the stress-induced depression of the level of secretion of immunoglobulins of immunity humoral component.7<\/sup><\/p>\n

To obtain consistent results we determined generalized dispersion B2<\/sup>, generalized variation coefficient (\u0421v<\/sub> and \u0421v<\/sub>\u2019), generalized bonding strength \u0440, generalized factor impact rw<\/sub> and factor impact isotropy indicator rI<\/sub>, population couples\u2019 resemblance indexesr.9<\/sup><\/p>\n

Registration documents \u201cregistration cards\u201d and \u201cchild\u2019s disease diaries\u201d were specially developed. They feature data from the case history of both mother and father, delivery data, gestation course, the features of the neonatal period, morbidity, infant feeding pattern, examination data, immunization history.10<\/sup>\u00a0The following indicators were analyzed: sex ratio, mass and height indicators of children at birth, the level of \u0410, \u041c and G serum immunoglobulins content, sub-populations of T-lymphocytes, ACTH and pituitary-hypothalamic area, determining sensitivity in vitro to immune response modifiers, the activity of transferases, the condition of antidiphtheritic antitoxic immunity, titers of anti-measles antibodies and antibodies to the poliomyelitis virus of 3 types with due account for case history and morbidity. The control group consisted of 426 relatively healthy children selected by the method of defining the \u201cadaptive norm\u201d of this city population11<\/sup>.<\/p>\n

All patients were examined at different stages of inflammatory process activity: acute stage, the period of early convalescence, the stage of late convalescence, the period of non-stable remission, the period of stable remission of the main pathological process. None of the patients experienced the persistent low-intense process.12<\/sup>\u00a0The absence of the clinical manifestation of diseases for more than one year, as well as the complex of laboratory, including immunologic parameters indicating the absence of pathological process activity, were criteria determining the remission persistence.13<\/sup><\/p>\n

The analysis of antidiphtheritic immunity based on the data of antidiphtheritic antitoxic immunity in passive hemagglutination test (PHT) according to Persistent Erythrocytic Diagnostic Preparations Usage Manual approved by the USSR Ministry of Healthcare 23.06.81 was carried out.14<\/sup>\u00a0Hungarian-made microtitrator Takachi <\/em>was used for PHT. Persistent erythrocytic diphtherial diagnostic preparations produced by Mechnikov Moscow Research Institute of Vaccinations and Sera were used as antigens. To determine the sensitivity of diagnostic preparations the test was carried out in each set of tests with standard antitoxic antidiphtheric serum containing 10ME in 1 ml produced by State Control Institute Medical Biological Preparations. The last dilutions of standard sera with positive results were considered the sensitivity index, which was used to translate hemagglutination units into antitoxic ones. The tests of the serum in PHT were carried out by macromethod in 10 dilutions, titers 1:160 were considered reliable, 1:20 \u2013 1:80 \u2013 conditionally protective, 1:10 and antibody-negative \u2013 non-protective.15-20<\/sup><\/p>\n

Anti-measles antibodies\u2019 titers in hemagglutination-inhibition test (HAIT) with sera treatment with kaolin and erythrocytes to get rid of spontaneous haemagglutinins were detected; to obtain more active haemagglutinin the culture was treated according to the Nornby method. The titer of hemagglutinating antigen was identified with a 0,5% monkey erythrocyte suspension at room temperature. Detecting the fourfold and greater rising of antibody titer in the second serum had a diagnostic significance.21<\/sup><\/p>\n

The content of ACTH in the serum (cortisol) was determined by immunoenzyme method using Biorad<\/em> assay kits, USA. The following values were considered standard: cortisol in 8-10 hours \u2013 185-500 nmol\/l or 50-230 ng\/ml.<\/p>\n

Each fifth child was randomly taken from the control group of healthy children for antiinfective profile examination. Each hundredth child was randomly taken from the group of sick children whose immune deficiency state wasn\u2019t confirmed.<\/p>\n

Results and Discussion<\/strong><\/p>\n

Children from community-based policlinics (80% of children) or hospitals (20%) with the following clinical implications were requested to see pediatrician-immunologist: recurrent frequent ARVI (40%), recurrent otopyoses (12%), thymomegaly (24%), recurrent bronchitis (8%), recurrent furunculosis (8%), digestive dysbacteriosis (4%), lymphohypoplastic diathesis (4%). Thymomegaly was identified by X-ray when examining with obstructive bronchitis and persistent low-grade fever diagnosis. Thus, the signs of inadequate infectious morbidity were the actual cause of primary immunoassay in all observed children. It should be noted that infective disease overfrequency was registered in children who had satisfactory social and living conditions and stayed at home. A part of observed children was vaccinated according to the place of their residence before the examination and treatment by pediatrician-immunologist. Vaccinations aggravated main pathological processes against the background of the organism weakened by infections causing their need to consult pediatrician-immunologist.22<\/sup><\/p>\n

The particularities of the immunization history of observed children are as follows: 28% of children are vaccinated according to their age without complications, 8% experienced minor vaccine-induced responses (temperature rise to subfebrile values, allergic rashes), 64% of children aren\u2019t vaccinated: among them 28% because of frequent infective diseases, 36% because of other related conditions (neurological deviations, digestive dysbacteriosis, thymomegaly).<\/p>\n

All observed children passed a complex of clinical-laboratory tests, the methods of functional diagnostics, which enable describing the state of different body functional systems (central nervous system, peripheral nervous system, endocrine, immune, skin, digestive, respiratory ones, etc.) and defining patients\u2019 clinical diagnosis, were used. An emphasis was put on abnormal development and dysembryogenesis stigmas. Anamnestic data paid a lot of attention to perinatal period flow, the parents\u2019 health status before the child conceiving, during pregnancy, delivery course, the neonatal period. The features of developing clinical implications of pathological processes were defined: disease onset, frequency and flow pattern, the appearance of clinical symptoms of disease, intensity and their pathomorphism.23<\/sup><\/p>\n

The diagnosis \u2013 disimmunoglobulinemia syndrome \u2013 was made if during immunoassay of children from 6 months to 5 years a decrease of one or several isotypes of immunoglobulins was recurrently found: Ig G less than 5 g\/l, Ig \u0410 less than 0,2 g\/l, Ig \u041c less than 0,4 g\/l. Laboratory characteristics of children aged from one year to three years with disimmunoglobulinemia syndrome are given in Table 1.<\/p>\n

Table 1: Laboratory characteristics of children aged from one year to three years with <\/strong>disimmunoglobulinemia syndrome<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
Index<\/strong><\/td>\nUnits of<\/strong><\/td>\nCorrelation diagram area<\/strong><\/td>\n<\/tr>\n
\u00a0<\/strong><\/td>\nmeasurement<\/strong><\/td>\n\u041c0<\/strong><\/td>\n\u041c+<\/strong><\/td>\n\u041c-<\/strong><\/td>\nMpd<\/strong><\/td>\n<\/tr>\n
Ig A<\/td>\ng\/l<\/td>\n0,40<\/td>\n0,30*<\/td>\n1,6<\/td>\n0,66<\/td>\n<\/tr>\n
Ig M<\/td>\ng\/l<\/td>\n0,95<\/td>\n0,75<\/td>\n0,41<\/td>\n1,26<\/td>\n<\/tr>\n
Ig G<\/td>\ng\/l<\/td>\n4,0<\/td>\n4,0<\/td>\n3,6*<\/td>\n3,58*<\/td>\n<\/tr>\n
CD 3<\/td>\n%<\/td>\n48,0<\/td>\n56,0<\/td>\n68,0<\/td>\n60,0<\/td>\n<\/tr>\n
CD 4<\/td>\n%<\/td>\n15,0<\/td>\n18,0<\/td>\n48,0<\/td>\n29,0<\/td>\n<\/tr>\n
CD 8<\/td>\n%<\/td>\n36,0<\/td>\n26,0<\/td>\n12,0<\/td>\n27,5<\/td>\n<\/tr>\n
0<\/td>\n%<\/td>\n34,0<\/td>\n30,0<\/td>\n32,0<\/td>\n31,5<\/td>\n<\/tr>\n
Circulating immune complexes<\/td>\nUNITS<\/td>\n60<\/td>\n34<\/td>\n70<\/td>\n43,8<\/td>\n<\/tr>\n
Cortisol<\/td>\nnmol\/l<\/td>\n175,0<\/td>\n990,0<\/td>\n145,0<\/td>\n963,5<\/td>\n<\/tr>\n
Lactogenic hormone<\/td>\n\u043c\u041c\u0415\/l<\/td>\n253,0<\/td>\n230,4<\/td>\n443,5<\/td>\n498,5<\/td>\n<\/tr>\n
Testosterone<\/td>\nnmol\/l<\/td>\n0,9<\/td>\n0,0*<\/td>\n0,1*<\/td>\n0,6<\/td>\n<\/tr>\n
Alanine aminotransferase<\/td>\nnmol\/l<\/td>\n1,8<\/td>\n0,25<\/td>\n0,8<\/td>\n0,96<\/td>\n<\/tr>\n
AAT<\/td>\nnmol\/l<\/td>\n4,2<\/td>\n2,2<\/td>\n2,2<\/td>\n0,9<\/td>\n<\/tr>\n
Crude protein<\/td>\ng\/l<\/td>\n6,8<\/td>\n7,2<\/td>\n7,0<\/td>\n6,98<\/td>\n<\/tr>\n
Thymol test<\/td>\nUNITS<\/td>\n2,4<\/td>\n1,2<\/td>\n2,2<\/td>\n2,38<\/td>\n<\/tr>\n
Exercise tolerance test<\/td>\n<\/td>\n<\/td>\n<\/td>\n<\/td>\n<\/td>\n<\/tr>\n
with thymalin<\/td>\nIndex<\/td>\n1,0<\/td>\n1,0<\/td>\n1,0<\/td>\n1,0<\/td>\n<\/tr>\n
with tymogen<\/td>\nIndex<\/td>\n1,0<\/td>\n1,0<\/td>\n1,0<\/td>\n1,0<\/td>\n<\/tr>\n
with levamisole<\/td>\nIndex<\/td>\n1,0<\/td>\n1,0<\/td>\n1,0<\/td>\n1,0<\/td>\n<\/tr>\n
Total children<\/td>\n280<\/td>\n60<\/td>\n49<\/td>\n39<\/td>\n132<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Note:<\/em> * \u2013 data are statistically valid<\/p>\n

The predominant deficit of Ig \u0410 was observed in 45 children, Ig G \u2013 in 180, combined decrease in Ig \u0410 and Ig G \u2013 in 55 children; there were no children with a low content of Ig \u041c. The average age of children when admitted for observation was 1,6+<\/u>1,2 years. The hypogammaglobulimenia condition was first registered at the age of to 1 year in 22 children, from 1 year to 2 years \u2013 in 123 children, from 2 to 3 years \u2013 in 67, from 3 to 4 \u2013 in 56, from 4 to 5 years \u2013 in 12.<\/p>\n

During the first immunoassay the average level of Ig G in 235 children with Ig G deficit (isolated or combined with Ig \u0410 deficit) made 4,1+<\/u>0,78 g\/l, but only 11 of them had the Ig G level less than 3 g\/l. The average level of Ig \u0410 in 101 children with Ig \u0410 deficit (isolated or combined with Ig G deficit) was 0,15+<\/u>0,03 g\/l and varied from 0,09 g\/l to 0,19 g\/l.<\/p>\n

For a comparative study of antiinfective profile with assessing the tension level of specific immunity against some vaccine-preventable diseases (diphtheria, tetanus, measles) in the groups of children with the depression of the secretion of immunoglobulins of the humoral component of immunity the sick children with disimmunoglobulinemia syndrome were divided into two large groups:<\/p>\n

With a low content of immunoglobulins and cortisol in the serum;<\/p>\n

With a low level of immunoglobulins and a high content of cortisol.<\/p>\n

Each of examined groups was further divided into two groups:<\/p>\n

Children vaccinated according to the place of their residence before the admission under the care of pediatrician-immunologist;<\/p>\n

Children not vaccinated for some reason and requested to consult pediatrician-immunologist to address the preventive vaccination issue, as a result, these children were vaccinated after examination and treatment. The rate of antibody-negative children when vaccinated against vaccine-preventable diseases in the groups of children with disimmunoglobulinemia followed up by pediatrician-immunologist is given in Table 2.<\/p>\n

It turned out that among the rate of antibody-negative children vaccinated with antitoxins and live vaccines before treatment was notably higher in all studied groups as compared to the control group.<\/p>\n

Following the first diphtheria vaccination, the rate of antibody-negative children vaccinated before treatment made up 62-63%, and 43% in the control group. Following the second diphtheria vaccination, the rate of antibody-negative children in studied groups made up 18-19%, in the control group of healthy children \u2013 10%. After diphtheria revaccination, the rate of antibody-negative children in studied groups made up 6,7%, and there were no diphtheria antibody-negative children in the control group.<\/p>\n

Table 2:<\/strong> The rate of antibody-negative children vaccinated against vaccination-preventable infections in the groups of children with disimmunoglobulinemia syndrome (per 100 children of this group)<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
\u00a0<\/strong><\/td>\nChildren\u00a0suffering\u00a0disimmunoglobulinemia\u00a0syndrome<\/strong><\/td>\nControl<\/strong><\/td>\n<\/tr>\n
\u00a0<\/strong><\/td>\nwith a low level of<\/strong><\/td>\nwith a low level of Ig and<\/strong><\/td>\ngroup of<\/strong><\/td>\n<\/tr>\n
Vaccination<\/strong><\/td>\nIg and\u00a0cortisol<\/strong><\/td>\na high level of cortisol<\/strong><\/td>\nhealthy<\/strong><\/td>\n<\/tr>\n
\u00a0<\/strong><\/td>\nvaccinated\u00a0before<\/strong><\/td>\nvaccinated\u00a0after<\/strong><\/td>\nvaccinated\u00a0before<\/strong><\/td>\nvaccinated\u00a0after<\/strong><\/td>\nchildren<\/strong><\/td>\n<\/tr>\n
\u00a0<\/strong><\/td>\ntreatment<\/strong><\/td>\ntreatment<\/strong><\/td>\ntreatment<\/strong><\/td>\ntreatment<\/strong><\/td>\n\u00a0<\/strong><\/td>\n<\/tr>\n
<\/td>\nn<\/td>\np<\/td>\nn<\/td>\np<\/td>\nn<\/td>\np<\/td>\nn<\/td>\np<\/td>\nn<\/td>\np<\/td>\n<\/tr>\n
Diphtheria\u00a0vaccination 1st<\/sup><\/td>\n23<\/td>\n62,16*<\/td>\n29<\/td>\n46,77<\/td>\n40<\/td>\n63,49*<\/td>\n57<\/td>\n48,31<\/td>\n37<\/td>\n43,53<\/td>\n<\/tr>\n
Diphtheria\u00a0vaccination 2nd<\/sup><\/td>\n7<\/td>\n18,92*<\/td>\n6<\/td>\n9,68<\/td>\n12<\/td>\n19,05*<\/td>\n13<\/td>\n11,02<\/td>\n9<\/td>\n10,59<\/td>\n<\/tr>\n
Diphtheria\u00a0revaccination<\/td>\n3<\/td>\n8,12*<\/td>\n0<\/td>\n0,0<\/td>\n5<\/td>\n7,94*<\/td>\n0<\/td>\n0,0<\/td>\n0<\/td>\n0,0<\/td>\n<\/tr>\n
Tetanus\u00a0vaccination 1st<\/sup><\/td>\n14<\/td>\n37,84*<\/td>\n13<\/td>\n20,97<\/td>\n23<\/td>\n36,51*<\/td>\n23<\/td>\n19,49<\/td>\n13<\/td>\n15,29<\/td>\n<\/tr>\n
Tetanus\u00a0vaccination 2nd<\/sup><\/td>\n3<\/td>\n8,12<\/td>\n5<\/td>\n8,06<\/td>\n5<\/td>\n7,94<\/td>\n9<\/td>\n7,63<\/td>\n6<\/td>\n7,06<\/td>\n<\/tr>\n
Tetanus\u00a0revaccination<\/td>\n2<\/td>\n5,41*<\/td>\n0<\/td>\n0,0<\/td>\n4<\/td>\n6,35*<\/td>\n0<\/td>\n0,0<\/td>\n0<\/td>\n0,0<\/td>\n<\/tr>\n
Measles\u00a0vaccination<\/td>\n14<\/td>\n37,84*<\/td>\n13<\/td>\n20,97*<\/td>\n22<\/td>\n34,92*<\/td>\n25<\/td>\n21,19*<\/td>\n9<\/td>\n10,59<\/td>\n<\/tr>\n
Total children<\/td>\n37<\/td>\n<\/td>\n62<\/td>\n<\/td>\n63<\/td>\n<\/td>\n118<\/td>\n<\/td>\n85<\/td>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Note<\/em>: n \u2013 actual frequency<\/p>\n

p \u2013 relative frequency<\/p>\n

* \u2013 the difference of data with the control group of healthy children is statistically valid<\/p>\n

Following the first tetanus vaccination, the rate of antibody-negative children in the groups vaccinated before treatment made up 36-37%, in the control group of healthy children \u2013 15%. Following the second tetanus vaccination, the rate of antibody-negative children made up 7-8% \u2013 the same as in the control group. After tetanus revaccination, there were 5% of antibody-negative children in studied groups, and there were no such children in the control group.<\/p>\n

Following the vaccination of children with a vaccine against measles, the rate of antibody-negative children in the groups vaccinated before treatment made up 34-36%, in the control group of healthy children \u2013 only 10.4%.<\/p>\n

233 children were vaccinated after examination and treatment, among them 180 of children with disimmunoglobulinemia syndrome (62 children with a low content of immunoglobulins and cortisol in the serum and 118 children with a low content of immunoglobulins and a high level of cortisol).<\/p>\n

It turned out that there were no more antibody-negative children in these groups of children after vaccination with antitoxins than in the control group of healthy children. Thus, after the first diphtheria vaccination, their rate made up 47-48%, after the second diphtheria vaccination \u2013 9-10%, after diphtheria revaccination \u2013 0,0%; after the first tetanus vaccination \u2013 19-20%, after the second tetanus vaccination \u2013 7-8%, after tetanus revaccination \u2013 0,0%.<\/p>\n

After live vaccination against measles in the children groups vaccinated after treatment, the rate of antibody-negative patients made up 20% among patients with disimmunoglobulinemia syndrome, 14% \u2013 among children, whose disimmunoglobulinemia diagnosis wasn\u2019t confirmed, in the control group of healthy children \u2013 10%.<\/p>\n

Thus, the effectiveness of specific immunization against vaccine-preventable infections (diphtheria, tetanus, measles) in RRI children with antiinfective protection violation and the laboratory confirmed condition of disimmunoglobulinemia coupled with a high or low content of adaptive ACTH in the serum substantially increases after their treatment and normalization of clinical and laboratory indicators.24-<\/sup>25<\/sup><\/p>\n

Conclusions<\/strong><\/p>\n

The findings allow us to claim that disimmunoglobulinemia syndrome in children with laboratory-confirmed hypogammaglobulimenia and dyshormonosis is not a contra-indication to preventive immunization after patient\u2019s pre-treatment. The level of specific immunity tension in children who were adequately treated in line with their pathological process was no different from those in healthy children after laboratory indicators\u2019 stabilization. RRI children with laboratory-confirmed disimmunoglobulinemia syndrome before planned immunization are, therefore, subject to pharmaceutical treatment with the provisional arrangement of comfortable nutrition and care conditions.<\/p>\n

Acknowledgement<\/strong><\/p>\n

The author expresses gratitude to the Director of Health of Nizhny Tagil Dmitry Sergeevich Malakhov for the provided opportunity to use city immunologic laboratory\u2019s equipment.<\/p>\n

References<\/strong><\/p>\n

    \n
  1. Kozhevnikova O. A. The effectiveness of immunological prophylaxis in toddler patients with disimmunoglobulinemia, Pediatrics. The Journal named after Speransky G.N.\u00a0<\/em>2000;79:7.<\/li>\n
  2. Konovalov I. V., Shamsheva O. V and Elshina G. A. Safety and immunological effectiveness of the combined immunization of children aged 6-7 years with vaccines of the national calendar of preventive vaccinations.\u00a0\u00a0Children’s Infections.<\/em>\u00a02013;1:14-17.<\/li>\n
  3. Barycheva L. Y., Golubeva M. V and Germanova O. N. Specific and non-specific ARI prevention in children. The Medical Herald of North Caucasus.<\/em>\u00a02010;17:64-76.<\/li>\n
  4. Shamsheva O. V. Ways to implement the national vaccination calendar, Pediatrics. The Journal named after Speransky G.N.\u00a0<\/em>\u00a02016;95:83-90.<\/li>\n
  5. Pomitkina T. E. Coverage of preventive vaccinations of the attached population of the polyclinic. Multidisciplinary hospital: interdisciplinary aspects of medicine. Materials of the XIX All-Russian Scientific and Practical Conference.\u00a0<\/em>2015;214.<\/li>\n
  6. Fridman I. V., Nedorova E. P and Goleva O. V. Vaccination of often ill children in the calendar of vaccinations and extra-calendar vaccines. 2013;506-523.<\/li>\n
  7. Altukhov Y. P., Kurbatova O. L. Human\u2019s heredity and environment. Nauka.\u00a0<\/em>\u00a01994;7-35.<\/li>\n
  8. Kulichenko T. V., Dymshits M. N and Lazareva M. A. Violation of the vaccination prevention calendar for children the view of doctors and parents on the problem. Pediatric Pharmacology.\u00a0<\/em>2015;3:330-334.
    \nCrossRef<\/a><\/li>\n
  9. Kozhevnikova O. A. Stress-induced disorders of immune mechanisms. In the World of Scientific Discoveries.<\/em>\u00a02010;2:149-151.<\/li>\n
  10. National calendar of preventive vaccinations and a calendar of preventive vaccinations for epidemiological indications. Epidemiology and Vaccine Prevention.<\/em>\u00a02008;1:36-39.<\/li>\n
  11. Kovalev E. V., Nenadskaya S and Miroshnichenko G. A. On the urgent issues of immunization of infectious diseases. Chief Physician of the South of Russia.\u00a0<\/em>2017;1:5-7.<\/li>\n
  12. Kudryashova E. M., Kopytova V. A Immunization first experiments and successes. The Bulletin of Medical Internet Conferences.\u00a0<\/em>2016;5:441.<\/li>\n
  13. Order of the Ministry of Health and Social Development of Russia from 31.01.2011 # 51\u041d “On the approval of the national calendar of preventive vaccinations and the calendar of preventive vaccinations for epidemiological indications. pediatric pharmacology.<\/em> 2011;1:130-136.<\/li>\n
  14. Nikolaeva A. U., Shamsheva O. Ways to optimize the immune response to vaccination in children who are often ill. Children’s Infections.\u00a0<\/em>2004;4:38-40.<\/li>\n
  15. Zakharova L. I., Pechkurov D. V and Koltsova N. S.\u00a0 The formation of the immune system of the newborn and the child of the first year of life. Modern adaptation of the national calendar of preventive vaccinations of children of the first year of life. Outpatient Neonatology.<\/em>\u00a02014;108-113.<\/li>\n
  16. Kovalev E. V., Nenadskaya S and Miroshnichenko G. A. On the urgent issues of immunization of infectious diseases. Chief Physician of the South of Russia.\u00a0 \u00a0 \u00a0\u00a0<\/em>2017;1:5-7.<\/li>\n
  17. Lakotkina E. A., Harit S. M and Mironova Z. G. Vaccination of children with disrupted health. 2000;87-106.<\/li>\n
  18. Nikityuk N. F., Glushchenko V. A and Panin I. V. Organization of immunoprophylaxis of persons with disabilities in the state of health. Biopreparations.\u00a0<\/em>2014;1:35-42.<\/li>\n
  19. Leshchenko M. V., Derinova E. A. Reactions and complications after vaccination of children. Justification of fears. Preschool Education.\u00a0<\/em>2017;2:52-57.<\/li>\n
  20. Kozhukhov P., Vechkotov N. The problem of vaccination in modern society. Bulletin of Medical Internet Conferences.\u00a0<\/em>2017;1:223-224.<\/li>\n
  21. Onishchenko G. G., Ezhlova E. B and Melnikova A. A.\u00a0 Actual problems of vaccine prophylaxis in the Russian Federation. Journal of Microbiology, Epidemiology and Immunobiology.\u00a0<\/em>2014;1:9-19.<\/li>\n
  22. Malakhov A. B., Harit S. M. The main directions of improving the vaccine prevention of controlled infections in children and adolescents. Doctor Ru.\u00a0<\/em>2010;5:32-38.<\/li>\n
  23. V.K. The National Immunoprophylaxis Calendar is the present and the future. Biopreparations.\u00a0<\/em>2010;1:25-30.<\/li>\n
  24. Iosefovich O. Vaccine prophylaxis of infectious diseases: what’s new? Deputy Chief Physician.<\/em>\u00a02014;12:6-15.<\/li>\n
  25. Kharit S. M., Chernyaeva T. V and Lakotkina E. A. Principles of working with parents while vaccinating children in medical and preventive institutions (a new medical technology). Modern approaches to diagnosis, therapy and prevention of infectious diseases in children. Scientific works. Collection of methodical recommendations (new medical technology), manuals for doctors (advanced medical technology) and teaching aids.<\/em>\u00a02011;30-47.<\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"

    Introduction Based on the many-year experience of contagious disease immunological […]<\/p>\n","protected":false},"author":9,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[53],"tags":[],"class_list":["post-18089","post","type-post","status-publish","format-standard","hentry","category-vol10no4"],"_links":{"self":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts\/18089","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/users\/9"}],"replies":[{"embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/comments?post=18089"}],"version-history":[{"count":12,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts\/18089\/revisions"}],"predecessor-version":[{"id":23903,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts\/18089\/revisions\/23903"}],"wp:attachment":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/media?parent=18089"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/categories?post=18089"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/tags?post=18089"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}