Immunoepidemiological characteristics of the duration of a meningococcal carrier state

The duration of meningococcal carriership in children and adults in the foci of infection and outside such foci and the immunological characteristics relating to group-specific meningococcal antigens A, C, X, Y and Z at different periods after the detection of the infective agent in the nasopharynx have been studied. Carrier state has been shown to last, on the average, 11 days. The duration of the release of meningococci from the nasopharynx has proved to be influenced by the epidemic situation in a given group. Differences in the time course of the immunological reorganization of the body in response to antigenic challenge in prolonged and short-term carrier state have been detected. These data suggest that rapid immune response to meningococcal antigens in the process of short-term carrier state is probably one of the factors preventing the prolonged colonization of the nasopharynx by the infective agent.     

Epidemiologic analysis morbidity with meningococcal infections in the USSR]

The authors present the analysis of the incidence of epidemic cerebrospinal meningitis in the USSR from 1937 to 1974, and of meningococcus infection from 1965 to 1974. A rise of the meningococcus infection incidence from 1969 to 1974 was recorded 28 years after the elevation of 1940-1942 and was 1.5 times below this latter rise. The rise in 1969-1974 was characterized by marked signs peculiar to the infection with the droplet transmission mechanism; among those who contracted the disease prevalence was seen among children aged under 14 years (63-72%). A marked affection of juveniles was noted. Three types of the dynamic of the meningococcus infection incidence in the republics located in different climatic-geographical zones of the USSR were noted: slow, gradual increase of the level, interrupted and explosive. Such character was determined in the dynamics of the seasonal elevations of morbidity. Antiepidemic measures including a complex of nonspecific measures could not be assessed as sufficiently effective. This finds reflection in the natural course of the epidemic process of the meningococcus infection which remains uncontrolled. From the patients with generalized form of the disease meningococci of group A were isolated in 80-100% of cases, from the number of those typed. The group-specific reference of the nasopharyngeal strains depended on the epidemic situation: strains of serological group A prevailed at the period of the morbidity elevation, and other serological groups (particularly of C and B) increased at its decline.     

Serologic pattern of meningococci in a focus of infection]

The authors present the results of typing of meningococci (isolated from the patients and carriers) by the sera of serological groups A, B, C, D, X, Y, and Z made at the Leningrad Institute of Vaccine and Sera. The causative agents of serological group A were most frequently isolated from the patients with the generalized forms of meningococcus infection. The percentage of detection of meningococci of serological group A was the greatest in the patients and much less in the carriers in and outside the foci of this infection. Many dissociated cultures were revealed among the strains isolated from the carriers. Sera of the Leningrad Institute of Vaccine and Sera have permitted typing of meningococci cultures belonging to various serological groups in accordance with the international classification.     

Incidence of meningococcal infection in the RSFSR]

The authors present characteristics of meningococcus infection epidemic process in case of sporadic cases and under epidemic conditions (1965--1976). A scheme of epidemiological analysis suggested by the authors permitted to differentiate and to record the incidence of various clinical forms of meningococcus infection, to present data on the age, seasonal characteristics, focality, etc. Comparison of intensive morbidity indices for 10 years, both at the individual administration territories and in the Republic as a whole demonstrated morbidity level of 1.5--2.0 to be one of prognostic signs of the beginning epidemic. The main features differentiating the sporadic and epidemic morbidity periods were revealed. The presence of group diseases, a greater percentage of children among those who fell ill, and marked signs of seasonality and territorial difference characterized the period of rise caused by meningococcus of serological group A.     

Characteristics of the mechanism of the development of the epidemic process in meningococcal infection in organized collectives

The specific features of the epidemiology of meningococcal infection in organized groups have been established after comprehensive (epidemiological, microbiological and immunological) studies, evaluated from the viewpoint of the law of the autoregulation of the epidemic process. The studies have revealed the phenomenon of the adaptive biological variability of meningococci with their prolonged reservation due to the transformation of typical bacterial forms of meningococci characterized by strict serogroup specificity and typical fermentative activity into serologically and biochemically undifferentiated forms, capable of prolonged persistence in human populations. The model demonstrating the development of the epidemic process in meningococcal infection in an organized group has been worked out.     

The evolution of meningococcal infection in Mongolia]

On the basis of the generalization and analysis of the results of bacteriological and immunological investigations the epidemic process of meningococcal infection (MI) in Mongolia was found to undergo definite changes during the last 20 years. Group A meningococci prevailing in the etiology of MI were replaced by strains belonging to group B affecting mainly young children (aged up to 3 years). MI morbidity rate caused by group B meningococci was found to be higher in Mongolia than in other countries of the world. These data substantiate the necessity of using more effective remedies for the control of this infection and, in particular, specific immunization with vaccines against group B meningococci; profound study of the properties of the circulating meningococcal strains is to be carried out.     

Characterization of the foci of meningococcal infection in closed groups of males

A total of 257 foci of meningococcal infection in groups of servicemen were selectively examined in 1982-2002. From these groups 353 patients with generalized forms of the disease underwent hospitalization. Most of the foci had a single infection, the proportion of foci with 10-40 patients was 82.6%. The meningococcal infection rate among humans in the foci was 25-37%, group A meningococci playing the leading role. In the structure of meningococcal infection generalized forms of infection constituted 16%, localized forms constituted 25% and inapparent forms (carriers)--59%. The formation of the morbidity structure was influenced by the type of the focus (with a single or multiple infection) and the character of morbidity for many years (during epidemic or at the period between epidemics). No absolute dependence of the level of meningococcal carrier state in the groups of servicemen on the appearance of the generalized forms of meningococcal infection was noted. Thus, both during epidemic and at the period between epidemics the population of meningococci, heterogeneous in its serological structure and differing in its clinical and epidemiological importance, constantly circulated with the leading role played by group A meningococci.     

Antagonistic and bacteriocinogenic activity of Meningococci]

Antagonistic and bacteriocinogenic activity was studied in 169 strains of meningococci of various serological groups and with different localization in the human organism at the time of isolation. Bacteriocinogenic activity was revealed in all the meningococcus strains (by delayed antagonism method), and, in addition, antagonistic activity was found in 100 strains. The inhibitory activity was the greatest in meningococci isolated from the cerebrospinal fluid. The data obtained suggest an important inhibitory activity of meningococci, along with their resistance to the antagonistic activity of the nasopharyngeal microorganisms, in the manifestation of pathogenic properties in them.     

Types of meningococci isolated from carriers and patients in a non-epidemic period in the netherlands

In a non-epidemic period the carrier rate of meningococci among 60 members of the laboratory staff during a long-term observation period of 1.5 years was 38%.In a children's home only a few children were carriers. The meningococci practically did not spread.In 161 recruits observed for periods of at most eight weeks the percentage of positives was 39.1 on the day of joining up and reached its maximum of 80.1 in the course of the period of observation.Among the strains isolated from patients and from carriers, type B predominated. In patients, type C was second in frequency; in carriers, type Y. Type A was found very rarely in carriers and somewhat more frequently in patients.The high carrier rate of type B in adults, together with its low aggressiveness for persons older than ten, may explain the relatively high frequency of the disease in the younger age groups.     

Detection of the etiologic structure of generalized and localized forms of meningococcal infection using the passive hemagglutination test

Preparations of formalin-treated erythrocytes sensitized with meningococcus polysaccharides of serological groups A, C, X, Y, and Z were used for the purpose of examination of patients with meningococcus infection; these preparations were highly specific in the tests of precipitation, hemagglutination and hemagglutination inhibition. Indirect hemagglutination test with the sera of 99 patients suffering from generalized forms of meningococcus infection was conducted with the mentioned preparations in Moscow and Novosibirsk in 1974--1975 when a stable morbidity decline was noted in these towns after an epidemic rise. The diagnostic value of this test was confirmed: it permitted to diagnose meningococcus etiology beginning from the 5th day of the disease and to decipher it from the aspect of individual serological groups. As shown, the incidence of cases caused by serological group A, reaching 87% at the height of the epidemic rise, fell to 49.5% at the stage of decline. Cases caused by group Y which was not encountered formerly were revealed in 16.2% of the patients. Among 127 patients with miningitis of nonmeningococcus etiology meningococcus antibodies to groups A and Y were revealed with the same frequency (in titres of not over 1 : 20--1 : 80), but the leading role of serological group A in the etiology of the manifest forms permitted to draw a conclusion on the presence of a higher invasiveness in the strains of group A.     

2007年重庆市流脑流行季节前健康人群抗体水平和带菌率调查

为了解重庆市流脑流行季节前健康人群免疫水平和带菌状况,预测发病趋势,提出新的免疫策略,提供有效的预防措施。按照全国流脑监测方案并结合重庆市2006年流脑疫情情况,选择重庆市北碚区、长寿区和万盛区为2007年流脑监测点,采集0~、5~、10~、15~、25~、35~及45岁以上共7个年龄组人群的静脉血和咽拭子,分别进行抗体水平和带菌率检测。结果显示,重庆市健康人群A群流脑IgG抗体的阳性率为76.02%(485/638),C群流脑IgG抗体的阳性率为47.65%(304/638),健康人群脑膜炎奈瑟菌(简称Nm)带菌率为0.47%(3/638)。重庆市健康人群A群流脑IgG抗体阳性率维持在较高水平,而C群流脑IgG抗体的阳性率较低,提示该市大部分人群对A群流脑有免疫作用,但C群抗体水平较低,有引起局部流脑爆发的风险。     

Antibody response to capsular polysaccharide antigen in an infection caused by meningococcus serogroup B in children

The continuous synchronous cultivation of serogroup B meningococci and the use of the selected clones of producer strains has made it possible to obtain the serologically active preparation of the group-specific antigen from the culture in the exponential phase. The erythrocyte diagnosticum produced on the basis of this preparation has permitted the detection of group-specific antibodies in the sera of immunized rabbits and children with generalized infection caused by serogroup B meningococci. The intensity of immune response depends on the age of children. This new technique of the passive hemagglutination test is recommended for the confirmation of generalized infection caused by serogroup B meningococci.     

Specific activity of colored variants of N. meningitidis colonies

The character of fluorescence of the colonies formed by serogroup A meningococci (229 strains) in oblique light and their activity in the agglutination test with group specific S and RD antisera to the meningococcal dissociant of the same serogroup were studied. Orange and orange-green colonies were found to have pronounced group-specific activity, and faint gray colonies changed the character of their agglutination with the group-specific antiserum up to the loss of agglutinability; and simultaneously their capacity for agglutination with the antiserum to the dissociant was revealed. The study of the character of fluorescence and the group-specific activity of meningococcal colonies belonging to other serogroups provided similar results.     

Pathogenesis of diphtheria carrier state from the immunological point of view.

Results of a comparative investigation of diphtheria antitoxin and type-specific antibacterial antibodes in 264 carriers of diphtherial bacteria, 41 diphtheria patients and 263 non-infected subjects are presented. A high level of antitoxin did not prevent the development of toxigenic-strain carrier state. A basically similar immunological antibacterial response was observed in patients with manifest forms of diphtheria and in carriers of toxigenic strains; such a response could not as yet be detected in carriers of non-toxigenic strains. It has been suggested that the infectious process in the toxigenic-strain carrier state is due to factors of the virulence responsible for infectivity and invasiveness of the diphtherial microbe. The toxin plays no pathogenic role in carrier state.     

Interaction of Neisseria meningitidis with eukaryotic cells in a mixed infection in vitro

To study the adhesion of meningococci under the conditions of a monoinfection and mixed infection (in association with influenza virus), the experimental model of mixed influenzal and meningococcal infection has been created in the culture of epithelial cells HEp-2. On this model in increase in the intensity of the adhesion of meningococci to eukaryotic cells, as well as in the intensity of the meningococcal colonization of such cells, after their preliminary infection with influenza virus has been observed. The study has revealed that in mixed infection the adsorption of extracellular virions onto the surface of bacteria occurs. During this adsorption viral processes directly interact with the microcapsule of the meningococcus.     

The adhesive activity of diphtheritic strains in relation to the characteristics of the infectious process they induce]

The degree of adhesiveness of 602 C. diphtheriae strains isolated from patients with different forms of diphtheria was studied on trypsinized sheep red blood cells (SRBC) used as an experimental model. The titer of bacterial suspension, i.e. its highest dilution ensuring the agglutination of 50% of SRBC, was assumed to be the index of adhesive activity. The toxigenic strains were more homogeneous with respect to the degree of their activity and proved to be moderately and highly adhesive, while among the nontoxigenic strains faintly and moderately adhesive ones prevailed. The degree of adhesiveness was not linked with the cultural biological strains variants, but depended on the form of C. diphtheriae infection. The toxigenic strains isolated from diphtheria patients were essentially more active than those isolated from carriers. Both toxigenic and nontoxigenic strains isolated in cases of prolonged carrier state (more than 4 weeks) did not differ in the degree of their adhesiveness and were essentially more active than the strains isolated from short-term carriers. The strains circulating in 10 closed groups with a high proportion of pronounced cases of carrier state (70.6% to 86.7%) were essentially more active than those circulating in 10 similar groups, but having a low proportion of pronounced cases of carrier state (6.7% to 23.8%). The conclusion was made that the degree of adhesiveness proved to be an important factor of C. diphtheriae pathogenicity, responsible for the formation of carrier state. Along with pathogenicity, this factor should be taken into consideration in the evaluation of the epidemiological importance of different sources of infection.     

Epidemiological evaluation of the serological grouping of meningococci]

Use of the precipitation and hemagglutination inhibition tests to determine the serological group of 114 meningococcus strains which cannot be grouped by agglutination slide permitted to establish the serological group of 56% of the strains, this pointing to the greater diagnostic value of these tests. Nevertheless, 70% of 307 strains isolated from carriers could not be referred to any of the determinable groups (A, C, X, Y, and Z). Strains (417) isolated from the cerebrospinal fluid of patients with meningitis were grouped depending on the epidemic curve: only half of the cultures could be classified in sporadic cases, but from 80 to 100% of the strains were classified at the "peak" of the meningitis incidence rise. This rise was connected with increase of the incidence of cases caused by meningococcus, group A; at the decline these strains were eliminated, and cases due to the rarely encountered serological groups and nongrouping strains occurred. Marking meningococc by serological groups proved to be of no use for detection of epidemiological relations between the infected persons.     

Makeup and properties of a polycomponent meningococcal vaccine]

The polycomponent meningococcae vaccine represented a preparation of the high-molecular fraction of meningococcus cell wall substances. Meningococcae strains for the vaccine preparation were chosen in such a way that the end preparation contained antigens of group specificity A, B, C and also other antigens detected in the cell wall of strains of epidemiological significance. Protein, group polysaccharides., lipopolysaccharides and nucleic acids were included into the vaccine composition. In doses used inhumans the vaccine was safe for mice causing no retardation in weight gain. In immunization of mice the vaccine produced formation of antigbodies to the antigens of group specificity A, B, and C, and protected them from infection with the srtrain isolated from the patient's cerebrospinal fluid. THE VACCINE PRODUCED NO HARMFUL ACTION IN ADMINISTRATION TO MAN. Antibodies to antigens of group specificity A, B, C and also to proteins and lipopolysaccharides of the meningococcus cell wall formed in the vaccinated persons. Sera of the vaccinated individuals lysed meningococci of groups A, B, and C.     

Hemagglutination Inhibition for Serogrouping of Neisseria meningitidis

A hemagglutination inhibition (HI) test has been studied as an alternative to bacterial agglutination (BA) for serogrouping strains of Neisseria meningitidis isolated from clinical specimens. The HI test consists of polysaccharide antigens adsorbed to sheep red blood cells which were then agglutinated by group-specific antisera. Supernatant fluids from suspensions of meningococci were used to inhibit the agglutination. Results of the two tests agreed for 381 (80%) carrier strains. Of the remaining 95 strains, 82 (86%) were identified by HI although they were nongroupable by BA. Thus, the HI test has been shown to be more highly specific and sensitive and to be more economical of reagents and time than the BA test.     

Hyaluronidase in meningococcus]

A total of 204 meningococcus strains were tested for the presence of hyaluronidase, and 45.5% of the strains were found to contain it. Strains penetrating into the cerebrospinal fluid were the ones which largely produced the enzyme (in 83% of the cases). The enzyme was revealed only in 25.5% of the strains habituating on the nasopharyngeal mucosa. Hyaluronidase was mostly found in the meningococcus strains referred to the serological group A; strains of other serological groups and ungrouped strains produced the enzyme in 23.7% of the case only. There was no correlation between the capacity to form hyaluronidase and the virulence determinable in intraperitoneal infection of mice.