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.     

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.     

The etiological structure of acute bacterial meningitis in different regions]

In 1985-1989 the etiological structure of acute bacterial meningitides (ABM) in children was studied in 4 largest industrial cities in different regions of the European part of the former USSR, as well as in 2 industrial cities of western Siberia. Due to the common methodological approach used in all investigations, comparable data were obtained in all cities. These investigations revealed that meningococci caused 53.0-86.7% of all cases of ABM in children, which corresponded to moderately increased morbidity rate in meningococcal infection (3.9-11.0 cases per 100,000 of the population, mostly 5.0-7.0 cases) in these cities with its progressive decrease during 3-4 years of observation. The gradual change of meningococci from group A, prevailing in the '70s and early '80s, to group B and in some cases the appearance of group C meningococci, accompanied by a decrease in morbidity rate, were noted. In St. Petersburg the indices of ABM morbidity in children aged up to 5 years for 1987 and 1988, caused by Haemophilus influenzae (0.74 and 4.13) and pneumococci (3.23 and 4.86), could be calculated. A great number of ABM cases of unclear etiology (15.9-33.3%) suggests that the number of ABM cases caused by these two infective agents was underestimated.     

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.     

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 role and place of serologic research in the system of epidemiologic surveillance of meningococcal infection

The results of serological surveys, carried out with a view to the detection of capsular meningococcal polysaccharides in the passive hemagglutination (PHA) test and covering 1,289 patients with systemic meningococcal infection, 221 patients with bacteriologically confirmed meningococcal nasopharyngitis, 2,820 persons in organized groups of children and adults with different epidemiological situation (including 650 carriers) and 4,050 residents of 8 cities with different morbidity levels, were analyzed. The patients, the carriers and the members of organized groups underwent multiple surveys. As shown in this study, the confirmation of the meningococcal etiology of the systemic forms of meningococcal infection (meningitis, meningococcemia) in all cases with the exception of children under 1 year of age, as well as the determination of the groups of meningococci, could be achieved in the PHA test twice as frequently, i.e. in 60-70% of cases, as with the use of the bacteriological method. The same regularities were observed in nasopharyngitis. The conclusion was made on the possibility of using the PHA test for more exact determination of the group of meningococci, prevailing at the initial stage of diseases, this determination playing an essential role in the epidemiological surveillance. The data obtained as the result of serological surveys in organized groups may lead to conclusions on the circulation of meningococci and their group composition, thus showing the necessity of profound epidemiological study with ensuring epidemic-control measures. The selective serological study of some hundreds of donor sera is not expedient in big cities, as it provides no data on the circulation of meningococci there.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

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.     

Microanalytical methods: latex agglutination and immunoenzyme analysis in the diagnosis of meningococcal infection

Modified polystyrene latexes with high adsorption capacity, comparable to that of latexes produced by Difco Laboratories (USA), have been developed in the USSR. Diagnostic latex preparations for the detection of meningococci of serogroups A, C, Y and Haemophilus influenza, type b, prepared on the basis of these new latexes, have shown high specificity and sensitivity in experimental and clinical tests.The latex preparations for the detection of serogroup B meningococci requires further improvement. The use of latex preparations, together with other laboratory methods, in the diagnosis of meningococcal infection has promoted the etiological confirmation of the disease in 84% of cases; this method has proved to be 1.5 times more effective than the bacteriological one and not less sensitive than the enzyme immunoassay, while being more specific.     

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.     

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.     

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.     

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).     

Prevention of secondary cases of meningococcal disease in household contacts by vaccination.

Household contacts of patients with group A meningococcal infection were vaccinated with either meningococcal vaccine or tetanus toxoid. Five of the 523 subjects who received tetanus toxoid developed meningococcal meningitis and another four probably had meningococcal disease. Only one possible case of meningococcal infection occurred among 520 contacts vaccinated with meningococcal vaccine. Vaccination had no effect on nasopharyngeal carriage of meningococci. Vaccination of household contacts of patients with group A meningococcal infections is an effective way of using limited supplies of meningococcal vaccine, though its value would be limited in an epidemic. Secondary cases of meningococcal infection often occur within a few days of the index case, and, although vaccine alone seemed to provide adequate prophylaxis in these Nigerian subjects, additional chemoprophylaxis may be needed to cover this critical period.     

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.     

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.     

Epidemiological analysis of hepatitis A morbidity

A retrospective epidemiological analysis of hepatitis A morbidity for many years among the population of two neighboring towns in the temperate climatic zone of the USSR has revealed the cyclic character of the epidemic process without a perceptible decrease in its extensiveness and has determined the high-risk groups, as well as the beginning of the seasonal rise of morbidity in these groups. The results of the study indicate that different levels of hepatitis A morbidity and risk groups can be observed in these two neighboring towns. At periods of a lower morbidity level the high-risk group embraces schoolchildren, and when morbidity is at a higher level the risk group includes schoolchildren and preschool children in organized groups. Among the latter the morbidity level is influenced by factors acting all the year round and among school children, by seasonal factors. The beginning of the seasonal rise of morbidity falls on August, while in organized groups of children of preschool age the seasonal rise of hepatitis A morbidity begins 1-1.5 months later. All prophylactic measures for controlling hepatitis A should be carried out with due regard to these features of the epidemic process.     

Meningococcal infection in the Uzbek SSR

The epidemiological characteristics of meningococcal infection in Uzbekistan during the period of 8 years since its last epidemic rise in 1972 is presented. Differences in the intensity of the epidemic process among the urban and rural population due to a considerable isolation of most of the rural populated localities from the district centers and the low population density in the republic have been established. The seasonal distribution of the infection had a winter-spring character in urban areas and a spring character in rural areas. 63.4% of all cases were children under 14 years. In cities a high morbidity level among adolescents and young people was determined mainly by visitors from rural areas. A high epidemiological importance of healthy carriers, predominantly schoolchildren and young people was established. The immunological studies of humoral immunity in different groups of the population indicate that the process of immunization was more rapid in cities.     

An OMV Vaccine Derived from a Capsular Group B Meningococcus with Constitutive FetA Expression: Preclinical Evaluation of Immunogenicity and Toxicity

Following the introduction of effective protein-polysaccharide conjugate vaccines against capsular group C meningococcal disease in Europe, meningococci of capsular group B remain a major cause of death and can result in debilitating sequelae. The outer membrane proteins PorA and FetA have previously been shown to induce bactericidal antibodies in humans. Despite considerable antigenic variation among PorA and FetA OMPs in meningococci, systematic molecular epidemiological studies revealed this variation is highly structured so that a limited repertoire of antigenic types is congruent with the hyperinvasive meningococcal lineages that have caused most of the meningococcal disease in Europe in recent decades. Here we describe the development of a prototype vaccine against capsular group B meningococcal infection based on a N. meningitidis isolate genetically engineered to have constitutive expression of the outer membrane protein FetA. Deoxycholate outer membrane vesicles (dOMVs) extracted from cells cultivated in modified Frantz medium contained 21.8% PorA protein, 7.7% FetA protein and 0.03 μg LPS per μg protein (3%). The antibody response to the vaccine was tested in three mouse strains and the toxicological profile of the vaccine was tested in New Zealand white rabbits. Administration of the vaccine, MenPF-1, when given by intramuscular injection on 4 occasions over a 9 week period, was well tolerated in rabbits up to 50 μg/dose, with no evidence of systemic toxicity. These data indicated that the MenPF-1 vaccine had a toxicological profile suitable for testing in a phase I clinical trial.     

The immunological status indices of monkeys inoculated with a meningococcal B vaccine

The method for the determination of bacterial antibodies to group B meningococci was worked out. The method was used for the determination of antibodies to group B meningococcal vaccine produced in the USSR. The dynamic study of antibodies to protein, polysaccharide and lipopolysaccharide antigens of group B meningococci was made by the method of the enzyme immunoassay (EIA), and the safety of the vaccine was studied by the determination of autoantibodies active against brain tissue antigens. The data thus obtained were indicative of the immunological activity of group B protein-polysaccharide vaccines, manifested by the capacity for stimulating bactericidal antibodies whose level increased 8- to 10-fold after the immunization of monkeys in 2 and 3 injections. Similarity in the dynamics of the formation of bacteriolysins and antibodies to protein antigen, as determined in EIA, was noted. The vaccine was found to stimulate no cytotoxic anticerebral antibodies in the glia migration test, which was indicative of the safety of group B meningococcal vaccine.