Specific prophylaxis of shigellosis

A high level of shigellosis morbidity requires new approaches to the control of bacterial dysentery. According to modern concepts, the outbreaks of Shigella infections are linked both with less intensive epidemic control measures and the objective cyclic character of the epidemic process. In this connection great importance is attached to the development of vaccines for the immunization of high risk groups in territories with unfavorable epidemic conditions and in zones of military conflicts, as well as children of school and pre-school age, who mostly determine seasonal rises of shigellosis morbidity. In this article the data describing new approaches to the creation of new live enteric vaccines on the basis of the knowledge of the genetic control of microbial pathogenicity and the regulation of its expression are presented. Attenuated Shigella mutants, created by different authors and having good prospects to be used for the development of vaccines, are characterized.     

The results of a seroepidemiologic study of Newcastle dysentery

Differences in the monthly distribution in the number of seropositive individuals among children and adults in years with different intensity of the epidemic process have been revealed. Immunity in cases of dysentery caused by S. newcastle reflects the yearly and seasonal activation of the epidemic process in this Shigella infection both in children and adults, the seroconversion characteristics observed in the year of a high morbidity level being a more objective criterion indicating the beginning of the activation of the epidemic process in dysentery caused by S. newcastle in comparison with the commonly registered morbidity level.     

Nature of the epidemic process in Sonne and Flexner dysenteries and the causes of its induction

A comparative study of the epidemic process in Sh. sonnei and Sh. flexneri dysentery in different regions of the USSR revealed that the morbidity level of Sh. sonnei dysentery changed simultaneously in the regions under study at intervals of 2-3 years. Sh. flexneri dysentery showed morbidity rises occurring at intervals 6-8 years, and their occurrence did not coincide with the periods of elevated morbidity in Sh. sonnei dysentery. The data obtained in the cohort analysis and in the study of recurrent morbidity suggest that Sh. flexneri dysentery produces more pronounced postinfection immunity than Sh. sonnei dysentery, and the immunological factor probably affects the dynamics of the epidemic of these Shigella infections.     

The possibility of using the demonstration of Shigella antigens in the study of the epidemic process in dysentery

The detection of Shigella antigens in feces in accordance with the results of the passive hemagglutination test is more effective than the bacteriological method for finding out persons infected with Shigella, especially in the absence of pronounced clinical manifestations of dysentery, and can be used in the study of the mechanism of the epidemic process. The examination of two groups, each consisting of permanent and temporary members, has revealed that the use of this method for detection of the antigen makes it possible to perform the epidemiological analysis of morbidity and, in particular, to determine the source(s) of infection.     

The structure of the population morbidity with specific intestinal infections in areas with different intensities in the development of the epidemic process and an evaluation of its manifestations]

The authors analyze the morbidity structure in five enteric infections (typhoid fever, dysentery caused by Shigella flexneri and Shigella sonnei, hepatitis A, and hepatitis E (non A, non B) with the fecal/oral mechanism of the agent transmission) in three towns of Turkmenia and in the town of Novomoskovsk, Tula Province. The incidence of S. sonnei dysentery was found higher in Novomoskovsk and that of the rest enteric infections under study in Turkmenia. The incidence of typhoid fever and hepatitis E was the highest among schoolchildren and adults, whereas preschool children suffered mostly from hepatitis A and S. sonnei dysentery. The authors discuss the specific features of the epidemic process manifestation in enteric infections.     

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.     

The formulation of epidemiological hypotheses by using the methods of multivariate statistical analysis

The work demonstrates the main approaches to the use of the methods of multidimensional analysis for the creation of a hypothesis on the mechanism of the epidemiological process of dysentery in organized groups. The main risk factors have been established, and their role in the formation of annual, all-the-year-round and seasonal dysentery morbidity has been quantitatively evaluated. The results of analysis show the existence of diverse variants of the alimentary route of the transmission of infection, maintaining the epidemic process of dysentery, and the necessity of differentiating measures for the prophylaxis of all-the-year-round and seasonal morbidity.     

Manifestations of angina morbidity as a reflection of the self-regulation of the epidemic process in streptococcal infection

The data on the application of the principles of the self regulation of the epidemic process for understanding the annual dynamics of angina morbidity in organized groups of adults are presented. In this case the reservation of group A streptococci occurs in chronic (resident) carriers, whose proportion was found to be 15.8 +/- 2.6%. The epidemic manifestations of morbidity are regulated mainly by the concentration of newly arrived members in the groups, i. e. by the size of the stratum providing the optimum conditions for the parasitization of the streptococcal population. The annual morbidity levels depend essentially not only on the heterogeneity of the group members with respect to their susceptibility to streptococcal infection, but also on the conditions of their accommodation, affecting the transmission of droplet infection. The role of individual risk factors in the variation of the quantitative characteristics of the angina morbidity manifestations under study is calculated.     

The determination in saliva of IgA antibodies to Shigella ribosomes for the diagnosis of dysentery

The levels of antiribosomal antibodies to Shigella ribosomes in serum and saliva samples from 38 dysentery patients (15 S. sonnei cases and 23 S. flexneri cases), 14 patients with salmonellosis and 136 healthy adults were determined in ELISA with ribosomes from S. sonnei R-mutant used as solid-phase antigen. High levels of "normal" antiribosomal IgA, IgG and IgM antibodies were revealed in the sera of healthy persons while the level of salivary IgA antibodies was very low. In dysentery infection no increase in the levels of serum IgG and IgM antibodies and only a slight increase in the level of IgA antibodies were revealed. Local immune response was manifested by the early (on days 2-4 from the onset of infection) and significant augmentation (12- to 16-fold) of salivary antiribosomal IgA antibodies. An increase in the level of these antibodies was registered in 95-100% of dysentery patients but not in patients with salmonellosis, which made it possible to recommend the method for diagnosing shigellosis. Immune response to Shigella ribosomal antigens, in contrast to the response induced by Shigella O-antigen, is almost exclusively local.     

New animal model of shigellosis in the Guinea pig: its usefulness for protective efficacy studies

It has been difficult to evaluate the protective efficacy of vaccine candidates against shigellosis, a major form of bacillary dysentery caused by Shigella spp. infection, because of the lack of suitable animal models. To develop a proper animal model representing human bacillary dysentery, guinea pigs were challenged with virulent Shigella flexneri serotype 2a (strains 2457T or YSH6000) or S. flexneri 5a (strain M90T) by the intrarectal (i.r.) route. Interestingly, all guinea pigs administered these Shigella strains developed severe and acute rectocolitis. They lost approximately 20% of their body weight and developed tenesmus by 24 h after Shigella infection. Shigella invasion and colonization of the distal colon were seen at 24 h but disappeared by 48 h following i.r. infection. Histopathological approaches demonstrated significant damage and destruction of mucosal and submucosal layers, thickened intestinal wall, edema, erosion, infiltration of neutrophils, and depletion of goblet cells in the distal colon. Furthermore, robust expression of IL-8, IL-1beta, and inducible NO synthase mRNA was detected in the colon from 6 to 24 h following Shigella infection. Most importantly, in our new shigellosis model, guinea pigs vaccinated with an attenuated S. flexneri 2a SC602 strain possessing high levels of mucosal IgA Abs showed milder symptoms of bacillary dysentery than did animals receiving PBS alone after Shigella infection. In the guinea pig, administration of Shigella by i.r. route induces acute inflammation, making this animal model useful for assessing the protective efficacy of Shigella vaccine candidates.     

Relation of the epidemiological characteristics of dysentery to the biological properties of the causative agents

The main forms of the epidemic manifestation of dysentery induced by different causative agents in 1975-1980 were revealed. During these years the cases of dysentery induced by Shigella sonnei, biovar II, were found to prevail (82.0-90.1%) both at the periods between epidemics and at the periods of the seasonal rise of morbidity. The experimental infection of white mice by intraperitoneal inoculation revealed no relationship between the seasonal rise of morbidity in dysentery and the virulence of its causative agents.     

Shigellosis

Shigellosis is a global human health problem. Four species of Shigella i.e. S. dysenteriae, S. flexneri, S. boydii and S. sonnei are able to cause the disease. These species are subdivided into serotypes on the basis of O-specific polysaccharide of the LPS. Shigella dysenteriae type 1 produces severe disease and may be associated with life-threatening complications. The symptoms of shigellosis include diarrhoea and/or dysentery with frequent mucoid bloody stools, abdominal cramps and tenesmus. Shigella spp. cause dysentery by invading the colonic mucosa. Shigella bacteria multiply within colonic epithelial cells, cause cell death and spread laterally to infect and kill adjacent epithelial cells, causing mucosal ulceration, inflammation and bleeding. Transmission usually occurs via contaminated food and water or through person-to-person contact. Laboratory diagnosis is made by culturing the stool samples using selective/differential agar media. Shigella spp. are highly fragile organism and considerable care must be exercised in collecting faecal specimens, transporting them to the laboratories and in using appropriate media for isolation. Antimicrobial agents are the mainstay of therapy of all cases of shigellosis. Due to the global emergence of drug resistance, the choice of antimicrobial agents for treating shigellosis is limited. Although single dose of norfloxacin and ciprofloxacin has been shown to be effective, they are currently less effective against S. dysenteriae type 1 infection. Newer quinolones, cephalosporin derivatives, and azithromycin are the drug of choice. However, fluoroquinolone-resistant S. dysenteriae type 1 infection have been reported. Currently, no vaccines against Shigella infection exist. Both live and subunit parenteral vaccine candidates are under development. Because immunity to Shigella is serotype-specific, the priority is to develop vaccine against S. dysenteriae type 1 and S. flexneri type 2a. Shigella species are important pathogens responsible for diarrhoeal diseases and dysentery occurring all over the world. The morbidity and mortality due to shigellosis are especially high among children in developing countries. A recent review of literature (Kotloff et al.,1999) concluded that, of the estimated 165 million cases of Shigella diarrhoea that occur annually, 99% occur in developing countries, and in developing countries 69% of episodes occur in children under five years of age. Moreover, of the ca.1.1 million deaths attributed to Shigella infections in developing countries, 60% of deaths occur in the under-five age group. Travellers from developed to developing regions and soldiers serving under field conditions are also at an increased risk to develop shigellosis.     

Tendencies in the epidemic process of dysentery in Ryazan

In shigellosis caused by Sh. sonnei and Sh. flexneri the epidemic process was found to have considerable difference in the tendencies and pace of its development. Shigellosis which dominated in the etiological structure at the period following 1966 was dysentery caused by Sh. sonnei; it showed the tendency towards a decrease in morbidity rate. Dysentery caused by Sh. flexneri was second in respect to the frequency of its occurrence after 1966 and showed the tendency towards increase. The simultaneous circulation of Sh. sonnei and Sh. flexneri, the differences in the epidemiology of these types of shigellosis make it imperative that they be studied separately, taking into ccount their etiological selectivity to the main routes of transmitting the infection.     

The mechanism of the development of the epidemic process in Sonne dysentery

An epidemic outbreak of Sonne dysentery has been studied. The data of epidemiological monitoring before and after the epidemic have been analyzed. The real prognostication value of controlling the biological properties of Shigella sonnei and the increase of their intrapopulation heterogeneity at the period of the activation of the epidemic process of Sonne dysentery has been established.     

Development of a new guinea-pig model of shigellosis

Shigellosis is a major form of bacillary dysentery caused by Shigella spp. To date, there is no suitable animal model to evaluate the protective efficacy of vaccine candidates against this pathogen. Here, we describe a successful experimental shigellosis in the guinea-pig model, which has shown the characteristic features of human shigellosis. This model yielded reproducible results without any preparatory treatment besides cecal ligation. In this study, guinea-pigs were discretely infected with virulent Shigella dysenteriae type 1 and Shigella flexneri type 2a into the cecocolic junction after ligation of the distal cecum. All the experimental animals lost ～10% of their body weight and developed typical dysentery within 24-h postinfection. In the histological analysis, distal colon showed edema, hemorrhage, exudation and inflammatory infiltrations in the lamina propria. Orally immunized animals with heat-killed S. dysenteriae type 1 and S. flexneri type 2a strains showed high levels of serum immunoglobulin G (IgG) and mucosal IgA antibodies and conferred significant homologous protective immunity against subsequent challenges with the live strains. The direct administration of shigellae into the cecocolic junction induces acute inflammation, making this animal model useful for assessing shigellosis and evaluating the protective immunity of Shigella vaccine candidates.     

Assessment of the effectiveness of inactivated influenza vaccines for adults

In 9 controlled epidemiological observations (1977-1984) the effectiveness of modern Soviet whole-virion vaccines was studied in organized groups of adults and at industrial enterprises. During the epidemic outbreaks of influenza of different etiology and intensity morbidity rate in influenza and acute respiratory diseases was shown to decrease 1.1-2.2 times among the vaccinees, depending on the correspondence of epidemic and vaccine influenza strains. The absence of influenza virus B in inactivated influenza vaccines was the reason for their low effectiveness during influenza outbreaks of mixed etiology B + A (H1N1).     

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.     

Seeding efficiency of the causative agent of dysentery as an index of the intensity of the epidemiologic process]

A study was made of the character and extent of interrelationship between the indices of dysentery morbidity and the indices of the seeding efficiency of dysentery bacilli persons who did not apply for medical aid. Establishment of such interrelationship permitted the authors to suggest the use of a more objective index of the seeding efficiency of dysentery bacilli, along with morbidity indices, for the assessment of the intensity of the epidemic process in this infection. On the basis of investigations carried out the authors came to the conclusion that a tendency to the increase of dysentery incidence the last few years chiefly bore a "statistical" character and was due to the improved detection of patients and carriers.     

A large-scale epidemic of diphtheria in Moscow in recent years: patterns of development

Data on the dynamics of diphtheria morbidity in Moscow in 1958-1999 are presented. The last epidemic which started at the end of the 1980s and reached its peak in 1994, giving a 59-fold rise in morbidity in comparison with the pre-epidemic period, is characterized in detail. During the epidemic 12,267 persons fell ill, 454 of them died (mortality rate was 4%). Having started in Moscow, the epidemic gradually spread not only over the territory of Russia, but also over some other republics of the former Soviet Union (Ukraine, Belarus, etc.). Possible causes of this epidemic emergency are considered. The ever increasing share of adult population among persons affected by the epidemic (75%) is noted. The infection adults is characterized by severity of clinical manifestations and increased morbidity among adults, is shown. Under complicated social and economic conditions (crisis situation) the increase of groups of high risk which included unemployed adults of working age, retirees as well as socially non-adapted persons, was registered. Mainly these groups determined tense epidemiological situation in diphtheria in Moscow.     

112株志贺菌菌群分布和药敏特点分析

目的研究本地区2001年至2005年志贺菌菌群分布及其药敏特点,以指导临床合理抗菌治疗。方法经大便培养筛选志贺菌,用生化和血清学方法鉴定菌群和血清型,采用K-B法检测病原菌耐药性。结果在112例细菌性痢疾患者中,男女比例相似,年龄分布以婴幼儿最高,临床表现不典型者较多,菌群分布以福氏志贺菌最多,F2b为优势血清型,对抗菌药物敏感性差异有显著性。结论近5年来本地区细菌性痢疾患者发病特点有年龄差异,菌群仍以福氏志贺菌为主,血清型以F2b为主,第3代头孢菌素是治疗细菌性痢疾最佳的抗菌药物。