Immunity indices during the vaccinal therapy of protracted forms of dysentery in children

The results obtained in the study of the dynamics of systemic and local immunity characteristics in children with prolonged and chronic dysentery under the influence of vaccinal therapy are presented. The vaccine, containing soluble antigenic complexes isolated from Shigella sonnei cells by disintegration with hydroxylamine, was introduced intrarectally in doses of 2-4 mg. The course of treatment consisted of 5-6 administrations. The vaccinal therapy resulted in an increase in the level of immunoglobulins and the titer of specific antibodies, particularly IgA, in sera and fecal filtrates. These data coincided with an increase in the number of IgA-producing cells in bioptic samples of the mucous membrane of the large intestine. The vaccinal therapy contributed to the cessation of the release of bacteria in 82.5% of the patients.     

Immunoglobulin and antibody content in the blood serum, coprofiltrate and saliva of patients with Sonne dysentery]

The authors studied the immunoglobulin and specific antibodies content of various classes in the serum, coprofiltrates and the saliva of 68 patients suffering from Sonne dysentery and in 48 healthy adult persons. Mancini's test demonstrated a significant elevation of IgG and IgM content in the blood of dysentery patients in comparison with that in healthy persons, and the absence of any changes in the IgA content. The titres of specific IgG-, IgA- and IgM-antibodies in determination in the modified Coombs' test increased consideerably during dysentery infection and were found in high titres during the first week of the disease; they reached the maximum during the second week and persisted at this level for 3 weeks. The greatest antibody elevation was in the IgA-class. Antibodies revealed in the coprofiltrates and the saliva of dysentery patients belonged to IgA- and IgG-class. There proved to be a correlation of the antibody changes in these two secretions.     

Results of treatment of dysentery patients with streptomycin-dependent vaccine in comparison with other methods of treatment]

Comparative study of various methods of treatment was carried out on 777 patients suffering from acute dysentery with a bacteriologically confirmed diagnosis. To assess the therapeutic efficacy, along with consideration of clinical signs of the disease, immunoglobulin level was examined in the blood and coprofiltrates; also the state of reparative processes in the mucosa was appreciated by the histological examination of the biopsy material. Results of the work carried out indicated the inexpediency of the treatment of this disease with a combination of levomycetin and phthalazol. The use of live streptomycin-dependent dysentery vaccine was indicated in protracted torpid dysentery and was of no avail in acute form of the disease. A good therapeutic effect was observed with the application of pathogenetic therapy alone.     

Cellular immunity factors in dysentery]

Cellular immune response was studied in 89 adult patients suffering from various clinical forms of acute dysentery, with the use of the lymphocyte blast-cell transformation reaction under the action of a specific antigen (dysenterin) and a nonspecific mitogen (phitohemagglutinin). Functional value of T-lymphocytes proved to be retained in patients with acute dysentery; there was also lymphocyte stimulation by a specific antigen in patients with moderately severe and severe forms of dysentery during the first week of the disease. Specificity of blast-cell transformation of sensitized lymphocytes under the action of dysenterin was shown. Patients with a high percentage of the lymphocyte blast forms displayed a more rapid positive progress of the main clinical indices at the height of the disease than analogous patients with a low blast percentage in the blood. The expediency of using the blast-cell transformation reaction for differential diagnosis and prognosis of moderately severe and severe forms of acute dysentery is discussed.     

Immunoglobulins and antibodies of various classes in children immunized with live oral Shigella sonnei vaccine from the spontaneous mutant]

The authors determined the immunoglobulin and specific antibodies level in the blood serum of 17 children aged from 7 to 10 years during the immunization with live dysentery Some vaccine. Mancini's test demonstrated the absence of any differences in the amount of IgA and IgG in children of the given age group and in adults before the immunization; in comparison with adults, IgM was increased in children. 14 to 20 days after the immunization in children there was a significant elevation of the IgG only, whereas in adults the immunoglobulin level of all the 3 classes increased significantly. The titres of specific antibodies of the IgA-, IgG-classes and of hemagglutinins before the immunization detected by Coombs' test failed to differ in children from the titres of antibodies of these classes in adults; the level of IgM antibodies was much greater in children than in adults. The changes and accumulation of antibodies of various classes in children and adults during the enteral immunization with live dysentery vaccine differed significantly: in children the vaccine stimulated the IgA- and the IgM-antibody synthesis, whereas adults responded to the immunization by increased production of all the 3 antibody classes. On the basis of the noted immunological shifts a conclusions was drawn on a marked local immunization activity of the live enteral Sonne dysentery vaccine from the spontaneous mutant in children.     

Indicators of spontaneous and stimulated nitroblue tetrazole test of polymorphous-nuclear leucocytes in acute dysentery patients

140 healthy individuals and 93 sick with acute dysentery were subjected to an examination by spontaneous and by bacterial preparations stimulated reaction with nitroblue tetrazole (NBT test). Indicators in healthy persons were normal in the spontaneous, and increased in the NBT test, stimulated by bacterial preparations. Indicators of the spontaneous NBT test in patients with acute dysentery were raised with a maximum in the period of early convalescence. Stimulation by a live shigella culture--the dysentery vaccine--revealed by means of Sonne diagnostic high, and when endotoxin from Serratia marcescens and dysenterin was used as an inductor, mild indicators of NBT test activity. When a polyvalent agglutinating dysentery serum was used as a stimulator, the activity increased considerably, and a simultaneous use of serum and vaccine had an inhibiting effect on the indicators of the stimulated NBT test. The obtained results testify the sufficient high reserve possibilities of leucocytes towards complete phagocytosis and the efficiency of the NBT test, stimulated by bacterial preparations for the study of functional and metabolic activity of leucocytes in the process of acute bacterial dysentery.     

A comparison of the dynamics of changes in large intestinal mucosa of acute dysentery patients with detection of a specific antigen in urine

The relationship between the elimination of shigellae from the body with urine and the dynamics of morphological changes in the mucous membrane of the large intestine of acute dysentery patients at the early convalescence period has been studied. The persistence of Shigella antigen in acute dysentery patients and its elimination with urine is, as a rule, accompanied by local immune cell reaction in the mucous membrane of the large intestine. The antigen circulating in the body is a factor contributing to the inflammatory process in the intestine, the amount of the eliminated antigen being higher in pronounced inflammations of the intestinal mucosa than in residual inflammatory phenomena. A group of patients (3 persons) releasing Shigella O-antigen with urine and having the inflammatory process in the large intestine, but showing no signs of local immune reaction in the lymphoid tissue of the large intestine, has been found. The reactivity of the lymphoid tissue of the intestine in such patients is a risk factor contributing to the development of prolonged dysentery or chronic postdysenteric colitis.     

Analysis of the seasonality of acute intestinal diseases with regard to the detection of dysentery by antigen indication

Coincidence in the seasonal changes of the registered morbidity in dysentery and in other acute intestinal diseases is observed. The occurrence of Shigella antigens, detected with the use of erythrocyte diagnostic reagents, in the excreta of patients with the clinical diagnosis of dysentery and patients with other acute intestinal disease has a seasonal character, its peak coinciding with the period of increased morbidity in bacteriologically confirmed dysentery. The correction of monthly morbidity levels in dysentery and in other acute intestinal diseases with due regard for the proportion of Shigella antigens in the findings, made in the groups of patients with the clinical diagnosis of dysentery and with the diagnosis of other acute intestinal diseases for the corresponding month, has revealed that the actual morbidity in other acute intestinal diseases has a less pronounced seasonal character in comparison with the registered morbidity. This fact substantiates the statement that in the group of patients with other acute intestinal diseases a large proportion of such diseases is, actually, of a noninfectious nature.     

Treatment of dysentery in children with a combination of monomycin and Eleutherococcus]

An acute dysentery process was studied in 100 children at the age of 1 to 14 years treated with monomycin; 54 patients (the 1st group) were treated with monomycin in combination with eleuterococcus and 46 patients (the 2nd group) were treated with monomycin alone. The dysentery process in the both groups was close. However, the increase in the levels of gamma-globulin, antidysentery antibodies and the phases of changes in the index of phagocytosis completeness during the disease were more pronounced in the patients of the 2nd group than those in the children of the 1st group. Recovery of the patients of the 1st group was registered earlier. It was concluded that eleuterococcus as an adaptagen provided recovery of the patients at lower efforts of the protection mechanisms. Wide use of eleuterococcus in combination with monomycin for the treatment of children with dysentery is recommended.     

Patterns determining the dynamics of the epidemic process in Sonne dysentery and its relation to the type of causative agent]

The results of studying the dynamics of the epidemic process of dysentery, based on the data from 3 districts of Moscow, are presented. The study revealed the periodicity of 3 years in the course of the epidemic process of dysentery, occurring against the background of a considerable predominance of Sh. sonnei, biochemical type 2. The use of the cohort method for analyzing the age structure of dysentery cases showed the possibility of using this method to find out to what extent the epidemic process repeatedly affected the same groups of population.     

Comparative study of the virulence of the Shigella isolated from bacterial carriers and from acute dysentery patients]

The authors present the results of study of the virulence of shigellae isolated from carriers and patients suffering from acute dysentery, on a continuous culture of E1 and Hep-2 cells. The virulence of shigellae isolated from carriers displayed no significant difference from the virulence of shigellae isolated from patients with a mild and moderately severe forms of dysentery. In the patient's organism shigellae were capable of retaining the initial virulence for a long time, despite the treatment and the influence of the macroorganism's protective factors. The authors believe that this was connected with the capacity of Shigellae to parasitic life in the cells of human intestinal epithelium, and, apparently, played a definite role in the formation of carrier state.     

Epidemiology of dysentery in Dagestan]

Analysis of material on bacterial dysentery and other acute intestinal infections morbidity in the Dagestan ASSR for a period of 15 years showed high morbidity level and its variations, with reduction and elevation in individual years, and the leading role played by Shigella flexneri among the causative agents of dysentery. The greatest incidence of dysentery was revealed among children aged under one year and between 1 and 2 years. A high bacterial dysentery incidence was recorded in Dagestan throughout the whole year. However analysis of the seasonal dysentery curve showed the beginning of elevation in July, reaching the maximum in August, and lasting four months with a decline beginning in October. The persisting activity of the water route of dysentery transmission in the Dagestan ASSR requires particular attention to the organization of good-quality water-supply to the population of the republic.     

Isolation and characteristics of Shigella antigens during the course of dysentery

In 2,436 fecal samples and 1,272 urinary samples taken from 633 patients with dysentery caused by S. flexneri, S. newcastle and S. sonnei, Shigella antigens were detected by means of the passive hemagglutination test with antibody diagnostic agents and the antibody neutralization test. The antigen-binding activity of shigellae in urine dynamically increased in the course of dysentery. The comparison of the parallel results of both serological tests made it possible to evaluate the dispersion of the released antigen: it dynamically increased in the course of the disease, this increase being particularly high in feces. The dispersion of Shigella antigens in urine was greater than in feces over the entire course of the disease. These regularities in the release of the antigens and especially the specific features of the serological tests determined the scheme of the serological diagnosis of dysentery by the indication of Shigella antigens.     

Protection of monkeys against experimental shigellosis with a living attenuated oral polyvalent dysentery vaccine

Formal, Samuel B. (Walter Reed Army Institute of Research, Washington, D.C.), T. H. Kent, H. C. May, A. Palmer, and E. H. LaBrec. Protection of monkeys against experimental challenge with a living attenuated oral polyvalent dysentery vaccine. J. Bacteriol. 91:17-22. 1966.-Virulent strains of Shigella flexneri 1b, S. flexneri 3, and S. sonnei I were mated with an Hfr strain of Escherichia coli K-12, and hybrids were selected for the xylose marker. One hybrid strain of each of the serotypes was chosen for study of their biological characteristics. Their capacity to cause a fatal enteric infection in starved guinea pigs was reduced, they failed to cause dysentery when fed to monkeys, they caused keratoconjunctivitis in the guinea pig eye, and they penetrated HeLa cells. Two doses of a polyvalent oral vaccine composed of S. flexneri 1b, 2a, and 3, and S. sonnei I hybrid strains were fed to groups of monkeys at an interval of 4 to 7 days, and they, together with controls, were challenged 10 days after the last dose with one or another of the virulent parent dysentery strains. A significant degree of protection was afforded in all vaccinated groups with the exception of one group challenged with S. flexneri 6, a component not included in the vaccine. When animals were challenged with virulent S. flexneri 2a 1 month after oral vaccination, they were also protected. The vaccine produced a rise in serum antibody, but we were not able to detect coproantibody in saline extracts of feces from animals which received the vaccine.     

Reactogenicity and immunologic activity of live enteric Sonne dysentery vaccine from a spontaneous mutant]

Live dysentery Sonne vaccine from a spontaneous mutant proved to be practically areactogenic and specifically harmless in oral immunization of children aged from 7 to 13 years, in doses of from 3 to 25 milliard live microbial cells and in single and triple immunization schemes. Weak reactions of the gastro-intestinal tract were noted with the same frequency (1.7%) in children immunized with the vaccine and in children given placebo (2.2%). There proved to be a significant increase in the serum of the immunized persons of the level of specific hemagglutinins, and also of the IgA-and IgM-titers in 82% of the persons vaccinated; they persisted at a high level for 2 months. The appearance of IgA-antibodies in high titres in the persons vaccinated orally pointed to a marked local and general immunological activity of the live dysentery Sonne vaccine from the spontaneous mutant processing the capacity to survive in the intestine of children for a long time.     

Course of dysentery and the specific alteration of the neutrophils in children in the use of monomycin and a diet with an increased protein content]

Acute dysentery mainly due to Shigella sonnei and dynamics of the neutrophil damage index (NDI) of the blood were studied in 80 children at the age of 1 to 14. 20 children (group 1) were treated with monomycin under conditions of a diet with an excessive content of protein (by 25% higher than the physiological norm). 60 children or 3 groups of 20 children each were not subject to such conditions and were considered as control groups. Reduction in the time of recovery (by 4 days) and bacteriological sanation (by 6 days) of the convalescents in the 1st group decreased as compared to that in the control groups. The test for the NDI of the blood was close in all the groups. It was concluded that an excessive protein content in the diet increased the efficacy of monomycin therapy in dysentery children. It is recommended that the diet with an excessive protein content be used in monomycin treatment of dysentery children.     

Experience with the diagnosis of dysentery in adults by determining antibodies to Shigella in the saliva]

Concentration of immunoglobulins and titres of antibodies to Sh. sonnei, Sh. flexneri and enteropathogenic E. coli 0111 was determined in mixed saliva and the blood serum of patients suffering from Sonne dysentery, acute intestinal diseases of unknown etiology, and healthy individuals. The sum total immunoglobulin concentration in mixed saliva proved to be 53--81 times less than in the blood serum, but in the first substrate there was 53--75, and in the second--15% of immunoglobulin A. There proved to be distinct changes in the specific IgA-antibodies in the saliva of patients with Sonne dysentery. A preponderant accumulation of IgG-antibodies was noted in the blood serum. Elevation of both types of antibodies was maximal during the second week of the disease. Sonne dysentery was diagnosed in 80% of the patients by recording the intensity of shifts in the specific antibodies in the saliva, and in 63%--in the blood. The expediency of immunological testing of saliva for the diagnosis of dysentery is substantiated.     

Effectiveness of the antibacterial therapy of patients with various forms of dysentery]

The analysis of the efficacy of various methods of antibacterial therapy in 1382 patients with obliterated, light and moderately severe forms of dysentery as compared to the patients subjected only to patholgenic therapy showed that broad spectrum antibiotics lost their role in treatment of such patients. Furazolidon proved to be one of the most active drugs. The authors suppose that treatment of patients with obliterated forms of dysentery with antibacterial drugs is not obligatory and is indicated only in cases with repeated isolation of the causative agent.     

An analysis of the dysentery epidemic process in Blagoveshchensk

The retrospective analysis of dysentery morbidity in Blagoveshchensk for the period of 1960-1987 was made. The regularities linking general natural and biological factors triggering the epidemic process with dysentery morbidity among the population are emphasized. The study revealed that under the conditions of Blagoveshchensk dairy products were of major epidemic importance among factors contributing to the transmission of dysentery. Such a factor as flies also had a definite influence on the epidemic process of dysentery. Another risk factor was drinking water which influenced the epidemic process both directly and indirectly through dairy products and, probably, other foodstuffs. Reliable correlation between dysentery morbidity among the population and the quality of dairy products, tap water and the number of flies was established.     

T-lymphocyte subpopulations and tumor necrosis factor-alpha in patients with acute Flexner's dysentery

In 41 patients aged 24-63 years with acute Flexner's dysentery T-lymphocyte subpopulations CD-3, CD-4, CD-8, IRI and the content of tumor necrosis factor alpha (TNF-alpha) in the blood serum were detected. The suppression of T-cell mediated immunity on account of the presence of CD-4 with decreased immunoregulatory index and an increased content of TNF-alpha were established. Changes in T-cell mediated immunity and TNF-alpha depended on the period and the severity of the diseases.