Epidemiological significance of carriers of hyaluronidase-active meningococci

To find out the epidemiological role of the carriers of hyaluronidase-positive meningococcal strains, their spread in the foci of meningococcal infection, as well as outside these foci, was studied. For this purpose, altogether 5059 persons from 40 family foci of infection and 40 organized groups were examined. The number of carriers of hyaluronidase-active meningococci, detected among those of them who had contacts with sick persons, was 13 times greater than among the persons having no such contacts. In preschool institutions with unfavorable morbidity situation this number was 16 times greater than in those with favorable situation. In the family foci carriers of hyaluronidase-active meningococci constituted 80-88 %. The percentage of the carriers of hyaluronidase-active meningococci causing cases of the generalized form of meningococcal infection varied in different groups. According to the results obtained in this study, the threshold percentage of such carriers constituted 30 in preschool institutions, 36 in boarding schools and 50 in common school and in hostels for adults.     

The characteristics of the serological diagnosis of meningococcal infection in children in the 1st years of life

The results of clinico-immunological examination of 181 children, aged 1 month to 6 years, with generalized forms of meningococcal infection are presented. In children under observation antimeningococcal antibodies to group-specific meningococci of the main groups A, B and C were determined over the course of the disease by passive hemagglutination (PHA) test and enzyme immunoassay (EIA). The level and frequency of seroconversion were found to depend on the patient's age and the severity of the clinical course of meningococcal infection. Antibody level was found to increase simultaneously with respect to several meningococcal polysaccharides: A, B in 18.5% and A, B, C in 3.3% of cases. In the clinical interpretation of data obtained in the PHA test and EIA not only the patient's age, the form and duration of meningococcal infection, but also serotherapy should be taken into consideration, as the latter may distort the serological results.     

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.     

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 epidemiological characteristics of meningococcal infection in the USSR

The epidemiological analysis of morbidity in meningococcal infection in the USSR in the period of 1969-1987 showed that the second rise of the morbidity level occurred in 1984 and was followed by its decrease in most of the regions of the USSR. This study also revealed that the characteristic feature of the second rise of morbidity in meningococcal infection was a considerable involvement of young children (aged up to 3 years), as well as the increased etiological role of group B meningococci in cases of meningococcal infection and the circulation of these microorganisms among the population. Besides, the preservation of the etiological importance of group A meningococci in many regions of the USSR, especially among adults, was noted. In this connection, the use of Soviet group A meningococcal polysaccharide vaccine on epidemiological indications was considered to be epidemiologically substantiated.     

Evaluation of the sanative action of rifampicin on the meningococcal carrier state]

The results of the epidemiological control experiment on the efficacy of rifampicin in sanation of meningococci carriers are presented. The preliminary study of rifampicin sensitivity of 41 freshly isolated nasopharyngeal meningococcal strains showed that the MIC of the drug for 63 per cent of the isolates was 0.04--0.1 gamma/ml. Sanation was performed for 2 days; 1.2 g of the drug was used during the treatment course. The results of examination of 91 meningococci carriers showed that 4 days after the sanation the specific weight of the persons isolating no meningococci was reliably higher in the experimental group than that in the control group. The coefficient of rifampicin efficiency was 70.8 per cent. 10 days after sanation the difference in the level of the carriers isolating no meningococci in the experimental and the control groups was statistically insignificant. Therefore, the carriers treated with the drug received temporary protection from the causative agent at an average for 1 week. Later on they could become carriers again. As a result of sanation no changes in the meningococcal sensitivity to rifampicin was observed.     

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.     

Characteristics of the meningococcal carrier state in organized collectives and its role in the development of generalized forms of meningococcal infection

Complex (epidemiological and bacteriological) investigations of the level and structure of meningococcal carriership among the members of organized collective bodies differing in the epidemiological situation with respect to meningococcal infection have been carried out. The absence of differences between the total level of meningococcal carriership and the morbidity rate with respect to the generalized forms of meningococcal infection has been shown. The presence of cases of meningococcal meningitis in the groups under study has been found to depend on the intensity of the circulation of certain meningococcal serogroups. The possibility of the ecological reservation of the causative agents of meningococcal infection as polyagglutinable forms has been suggested.     

Evaluation of the role of specific antimeningococcal antibodies in the spread of meningococcal carrier states in collectives]

The results of serological, bacteriological and epidemiological studies carried out in populations with different epidemic pattern of meningococcal infection are presented. A-group specific antibody was found to have the leading role in the intensity of the spread of meningococcal infection in the populations. The presence of antibody to this antigen in 16.7% of serum samples inhibited dissemination of meningococci in the populations. Simultaneously with an increase in the herd immunity level to 34.8% the attenuation of the active meningococcal dissemination cycle was observed. Meningococci isolated in the populations with different epidemic patterns of meningococcal infection were shown to have different ecological properties.     

Epidemiological characteristics of meningococcal infection in Cuba

The results of the epidemiological analysis of the morbidity rate in meningococcal infection for 1976-1984 are presented. The maximum rise of morbidity rate, equal to 14.4 per 100000 of population, was observed in 1983. Primarily, the rise of morbidity rate in 1979 was induced by meningococci of two serogroups: C (44.6%) and B (36.4%). The vaccinal prophylaxis of the population, carried out in 1979 with the use of polysaccharide vaccine A + C, did not affect morbidity caused by group B meningococci. The isolation rate of these organisms reached 98.7% from patients and 81.0% from carriers. The characteristic feature of the epidemic process of meningococcal infection in Cuba was a considerable increase in the number of patients under 1 year of age and the absence of seasonal fluctuations in morbidity rate.     

Adhesion in meningococcus

The adhesive activity of 113 meningococcal strains with different invasive properties and 10 Neisseria nonpathogenic strains have been studied. Adhesive properties have been revealed in 80-82% of these strains. Meningococcal strains isolated from the nasopharynx of carriers possess high hemagglutinating activity. The percentage of cells with pili in these strain was also higher than that in meningococcal strains isolated from the liquor of patients. This shows the presence of direct correlation between the number of pili in the cells (according to the data of electron microscopy) and their activity in the hemagglutination test, which makes it possible to use this test for the determination of the adhesive capacity of meningococci, associated with the presence of pili.     

Antibodies to meningococcal lipopolysaccharide in different forms of meningococcal infection

The results of the determination of antibodies to lipopolysaccharide (LPS) in 270 patients with different forms of meningococcal infection and in 816 healthy persons by means of the passive hemagglutination test are presented. The role of antibodies to LPS in the formation of humoral immunity to meningococci in sick children and adults is shown. Different forms of meningococcal infection have been found to have their specific features of the accumulation of antibodies to LPS. As revealed, the time of the sanation of liquor and the level of antibodies to LPS are unrelated, which indicates that antibodies to LPS may play some role in the pathogenesis of meningococcal infection.     

Criteria of the epidemiological surveillance of meningococcal infection

The results of studies carried out with the use of the unified, specially developed methods in eight regions of the USSR are generalized. Basing on the analysis of the results, the leading role of serogroup A meningococci in the rise of morbidity is emphasized, the relation of the morbidity level to the serogroup composition of meningococci circulating among healthy population is revealed, the necessity of carrying out selective bacteriological surveys with a view to establish the serogroups of meningococci circulating among the population is shown. The expedient criteria to be used in the system of epidemiological surveillance of meningococcal infection are presented.     

Immunochemical properties of a protective cross-reacting antigen of meningococci

The study of protective cross-reacting antigenic preparations isolated from meningococci of groups A and C in the blot immunoassay has shown the presence of a group of proteins with a molecular weight ranging from 23 to 31 KD and common for 8 tested serological groups of meningococci, gonococci and 4 nonpathogenic Neisseria species. The possible role of these structures as common Neisseria antigen in the formation of natural resistance to meningococcal infection is discussed.     

Serotypes among Neisseria meningitidis serogroups B and C strains isolated in Canada

Antisera made to prototype serogroup B strains of Neisseria meningitidis were used to serotype, by agar gel double diffusion, 262 meningococcal serogroups B and C strains isolated in Canada. The strains included 93 from patients and 169 from carriers. Serotype 2 was associated with 39 of 75 (52%) of group B strains and 14 of 18 (77.8%) of group C strains isolated from patients. The group B strains were mainly (87.2%) serotype 2b, while the majority (92.2%) of group C strains was serotype 2a. Other serotypes (including a new provisional serotype) represented 25.3 and 5.5% of groups B and C strains, respectively. The new serotype accounted for 13% of the group B strains. Approximately 23% of the strains isolated from patients were nontypable. The distribution of serotype 2, nontype 2 (other serotypes), and nontypable strains isolated from carriers was 2.1, 36.6, and 61.3%, respectively, for group B meningococci and 22.2, 29.6, and 48.25, respectively, for group C meningococci. Serotype 11 was the most prominent of the strains isolated from carriers. Approximately 7% of all the strains were multiple serotypes. Serotype 2 is an important virulence marker associated with meningococcal groups B and C disease in Canada, with serotypes 2a and 2b being markedly associated with groups C and B meningococcal disease, respectively.     

Etiology of suppurative bacterial meningitis

The results of the laboratory examination of 2034 patients with meningococcal infection and purulent meningitides, hospitalized during the period of June 1980 to October 1983, revealed that three main etiological agents were responsible for these diseases: meningococci, pneumococci and Haemophilus influenzae. The susceptibility of the patients to different etiological agents was found to depend on their age. Children aged up to 3 years constituted 75% of the patients with meningitis caused by H. influenzae; 50% of the patients with meningococcal infection were children aged up to 5 years; pneumococcal meningitis occurred more frequently in adults. Serogroup A meningococci were found to prevail in patients with meningococcal infection. Besides, in children serogroup C meningococci could be isolated in 24% of cases. Since 1983 the cases of the isolation of strains belonging to serogroup B increased in number. Among the pneumococci responsible for the disease serotypes 1, 19, 6 and in children serotype 12 occurred most frequently.     

Detection of IgG and IgM to meningococcal outer membrane proteins in relation to carriage of Neisseria meningitidis or Neisseria lactamica

Carriage of non-serogroupable Neisseria meningitidis or Neisseria lactamica induces antibodies protective against meningococcal disease. Antibodies directed against outer membrane proteins are bactericidal and the serotype and subtype outer membrane protein antigens are being examined for their value as vaccine candidates for serogroup B disease. The aim of this study was to examine the effect of carriage of these two Neisseria species among children and young adults on induction of antibodies to outer membrane components from strains causing disease in Greece. Among 53 patients with meningococcal disease, IgG or IgM antibodies were detected by ELISA in 9 of 13 (69%) from whom the bacteria were isolated and 27 of 40 (67%) who were culture-negative. For military recruits (n = 604), the proportion of carriers of meningococci with IgM or IgG to outer membrane proteins was higher than non-carriers, P < 0.05 and P = 0.000000, respectively. Among school children (n = 319), the proportion with IgM or IgG to outer membrane proteins for carriers of meningococci was higher compared with non-carriers, P = 0.000000 and P = 0000043, respectively. Carriage of N. lactamica was not associated with the presence of either IgM or IgG to the outer membrane proteins in the children. The higher proportion of children (50%) with IgM to outer membrane proteins compared with recruits (10%) might reflect more recent exposure and primary immune responses to the bacteria. The lack of association between antibodies to outer membrane proteins and carriage of N. lactamica could reflect observations that the majority of N. lactamica isolates from Greece and other countries do not react with monoclonal typing reagents. Bactericidal antibodies to meningococci associated with high levels of IgG to N. lactamica were found in a previous study; these are thought to be directed to antigens other than outer membrane proteins or capsules and imply antigens such as lipo-oligosaccharide are involved in induction of antibodies cross-reactive with meningococci.     

Detection of individuals within a group of risk for meningococcal infection morbidity in organized collectives

The survey of 2,500 persons in different educational organized groups has been carried out by the method based on the study of changes occurring in the standard population of group A meningococci due to its interaction with the surviving culture of human leukocytes. The heterogeneity of humans with regard to the individual antimeningococcal activity of their blood irrespective of their levels of humoral immunity and complement activity has been revealed. The survey has shown the possibility of detecting the groups of risk among the members of organized groups having, according to our data, a significantly higher level of morbidity in generalized meningococcal infection and meningococcal carriership (including epidemiologically important groups A, B and C).     

Epidemiological surveillance of meningococcal infection and the prediction of the development of an epidemic process

The signs necessary for the prognostication of the development of the epidemic process have been formulated on the basis of the epidemiological analysis of materials obtained in the process of trials of the system for the surveillance of meningococcal infection with the use of previously established characteristics. The data on the prevalence of meningococcal infection among different age groups and on the seasonal distribution of the infection as well as on the serogroups of meningococci isolated from patients, have been shown to be of importance for prognostication.     

Serum immunoglobulin levels in various forms of meningococcal infection and in meningococcus carriers

The levels of serum IgG, IgA and IgM were examined in 191 adults including 103 patients with various forms of meningococcal infection, 32 meningitis convalescents and 56 carriers, in order to elucidate the causes of different susceptibility to the meningococcal infection. The IgD level was determined in 54 meningitis patients as well as in convalescents and carriers. The amount of immunoglobulins was determined by radial immunodiffusion. The level of IgG at the beginning of the disease in patients with the generalized forms of meningococcal infection (meningitis, meningitis combined with meningococcaemia, meningococcaemia) was found to be considerably lower than in healthy subjects. The levels of all immunoglobulins, particularly of IgA and IgM, increased in the course of the disease. The levels of IgG, IgA and IgM in meningitis convalescents a year after recovery were found to be the same as in the controls. The levels of IgG, IgA and IgM in patients with meningococcal nasopharyngitis were significantly lower than in healthy subjects. The carriers showed a decreasd level of IgA and a considerably increased level of IgG while the levels of IgM and IgD did not differ from the control.