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.     

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.     

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.     

Study of platelet function by quantitative determination of the fluorescence intensity of 5HT-organelles

Assay of the fluorescence intensity of 5HT-organelles was performed to examine the functional properties of platelets from patients with meningococcal infection. Platelets were found to have a higher capacity for endocytosis at the height of the disease, tending to its normalization with treatment and convalescence. Incubation of donor's plasma rich in platelets with meningococcal lipopolysaccharide was discovered to lead to an appreciable increase in the absorption capacity of platelets. It is suggested that endotoxinemia is one of the factors responsible for the impairment of platelet function.     

Immunological factors in the evolution of the epidemic process in meningococcal infection

The results obtained in 1987 in the study of the immunostructure of the population of Yaroslavl with respect to meningococcal polysaccharides, groups, A, B, C, and lipopolysaccharide are presented in comparison with earlier results obtained in 1976. The regulating role of the immunological factor in the evolution of the epidemic process of meningococcal infection has been confirmed. The level of antibodies to meningococcal polysaccharides, groups A and B, has been found to reflect the intensity of the circulation of the infective agent among the population. The comparison of the results of investigations carried out in 1976 and 1987 has revealed the essential role of the lipopolysaccharide antigen in the formation of the postinfection immunity of the population to meningococcal infection, irrespective of the group of the infective agent.     

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.     

Distribution of HLA antigens in patients with meningococcal infection at different times of year

The character of the distribution of the antigens of the HLA system at different seasons has been studied in 160 patients with generalized forms of meningococcal infection. The occurrence of HLA-Bw16 (the marker of the population gene of susceptibility to meningococcal infection) has proved to be inversely correlated with the seasonal morbidity level.     

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.     

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.     

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 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.     

Relationship of eicosanoids to cellular and humoral immunity factors in meningococcal infection

The dynamics of the content of thromboxane B2, 6-keto-prostaglandin F1 alpha, T- and B-lymphocytes and titers of antibodies to group polysaccharides of meningococci, groups A, B and C, have been studied in 44 patients with generalized forms of meningococcal infection. As shown in this study, in patients with the clinical course of moderate severity a decrease in the number of T-lymphocytes in the first days of infection correlates with a decrease in the concentration of thromboxane B2. In some cases the concentration of thromboxane B2 and 6-keto-prostaglandin F1 alpha has been found to correlate with the titers of antibodies to group polysaccharide of group A meningococci. The severe course of meningococcal infection is characterized by the absence of correlation between eicosanoids and the immunity factors under study.     

Neisseria meningitidis Differentially Controls Host Cell Motility through PilC1 and PilC2 Components of Type IV Pili

Neisseria meningitidis is a strictly human pathogen that has two facets since asymptomatic carriage can unpredictably turn into fulminant forms of infection. Meningococcal pathogenesis relies on the ability of the bacteria to break host epithelial or endothelial cellular barriers. Highly restrictive, yet poorly understood, mechanisms allow meningococcal adhesion to cells of only human origin. Adhesion of encapsulated and virulent meningococci to human cells relies on the expression of bacterial type four pili (T4P) that trigger intense host cell signalling. Among the components of the meningococcal T4P, the concomitantly expressed PilC1 and PilC2 proteins regulate pili exposure at the bacterial surface, and until now, PilC1 was believed to be specifically responsible for T4P-mediated meningococcal adhesion to human cells. Contrary to previous reports, we show that, like PilC1, the meningococcal PilC2 component is capable of mediating adhesion to human ME180 epithelial cells, with cortical plaque formation and F-actin condensation. However, PilC1 and PilC2 promote different effects on infected cells. Cellular tracking analysis revealed that PilC1-expressing meningococci caused a severe reduction in the motility of infected cells, which was not the case when cells were infected with PilC2-expressing strains. The amount of both total and phosphorylated forms of EGFR was dramatically reduced in cells upon PilC1-mediated infection. In contrast, PilC2-mediated infection did not notably affect the EGFR pathway, and these specificities were shared among unrelated meningococcal strains. These results suggest that meningococci have evolved a highly discriminative tool for differential adhesion in specific microenvironments where different cell types are present. Moreover, the fine-tuning of cellular control through the combined action of two concomitantly expressed, but distinctly regulated, T4P-associated variants of the same molecule (i.e. PilC1 and PilC2) brings a new model to light for the analysis of the interplay between pathogenic bacteria and human host cells.     

A field trial with the liquid multicomponent meningococcal vaccine ABC

The morbidity rates of generalized forms of meningococcal infection in persons immunized with different doses of liquid meningococcal vaccine ABC were compared. The vaccine was introduced subcutaneously by means of a jet injector. Altogether 3,920 males aged 18 years and older were immunized. 1,966 vaccinees received this vaccine in a dose of 200 micrograms and 1,954 vaccinees, in a dose of 400 micrograms. Meningococcal multicomponent vaccine ABC used in these doses showed moderate reactogenicity and did not prevent the development of generalized forms of meningococcal infection.     

Comparative proteomic analysis of biofilm and planktonic cells of Neisseria meningitidis

Neisseria meningitidis is a commensal of the human nasopharynx occasionally causing invasive disease. In vitro biofilms have been employed to model meningococcal carriage. A proteomic analysis of meningococcal biofilms was conducted and metabolic changes related to oxygen and nutrient limitation and upregulation of proteins involved in ROS defense were observed. The upregulated MntC which protects against ROS was shown to be required for meningococcal biofilm formation, but not for planktonic growth. ROS-induced proteomic changes might train the biofilm to cope with immune effectors.     

sTNFR-II and sICAM-1 are associated with acute disease and hepatic inflammation in schistosomiasis japonica

Soluble intracellular adhesive molecule 1 (sICAM-1) and tumour necrosis factor receptors I (TNFR-1) and II (TNFR-II) have been shown to be associated with numerous liver disorders. Shedding of these membrane proteins can be triggered by the Th1 cytokines, TNF-alpha and IFN-gamma, which are associated with susceptibility or resistance to hepatic schistosomiasis, respectively. Further, TNF-alpha receptors and sICAM-1 have been implicated in periportal fibrosis in advanced human schistosomiasis mansoni and correlate with schistosome granuloma formation in the murine model. We measured serum levels of sICAM-1, TNFR-I and TNFR-II in Chinese patients with different clinically defined stages of schistosomiasis japonica and controls; these included 35 patients with acute schistosomiasis, 45 patients with chronic schistosome infections, 34 advanced patients with evidence of severe morbidity and 20 patients with no known history of exposure to infection. Markedly elevated levels of soluble TNFRs (sTNFRs) and sICAM-1 were observed in the acute and advanced patients compared with the chronic and control groups. Mean sTNFR-II levels were significantly higher in acute patients compared with advanced (P<0.00001) and chronic patients (P<0.00001) and showed the strongest association of the markers with acute disease (odds ratio (OR)=1.099). sTNFR-II and sICAM-1 levels both correlated with infection intensity and there were significant positive correlations observed between eosinophil count and infection intensity (P=0.0072) and sICAM-1 (P=0.0014). Although there were significantly higher levels of antigen-specific IgG4 and total IgG in infected individuals compared with controls, none correlated with infection intensity. Further, no differences in IgG4 and total IgG levels were observed between the acute and chronic groups. The results suggest sTNFRs and sICAM-1 are associated with liver inflammation and disease progression. Measurement of sTNFR-II and sICAM-1 levels in serum could serve as additional markers for the diagnosis of acute stage disease and the monitoring of hepatic inflammation in human schistosomiasis japonica.     

Meningococcal disease: A paradigm of type‐IV pilus dependent pathogenesis

Neisseria meningitidis (meningococcus) is a Gram‐negative bacterium responsible for two devastating forms of invasive diseases: purpura fulminans and meningitis. Interaction with both peripheral and cerebral microvascular endothelial cells is at the heart of meningococcal pathogenesis. During the last two decades, an essential role for meningococcal type IV pili in vascular colonisation and disease progression has been unravelled. This review summarises 20 years of research on meningococcal type IV pilus‐dependent virulence mechanisms, up to the identification of promising anti‐virulence compounds that target type IV pili.     

Epidemiological characteristics of meningococcal infection in a number of territories of the RSFSR (1969-1984)

In this work the dynamics and morbidity level in respect of meningococcal infection at 11 territories of the RSFSR at the period of 1969-1984 are analyzed. The study covered altogether 16 cities and 211 districts. The role of big cities as the sources of infection spreading into rural areas and further "fixation" of this infection mainly in regions with a population of 60,000 and more had been established. The data on meningococcal morbidity and carriership among different age groups are presented. The study has shown a pronounced increase in the incidence rate of meningococcal infection among children aged up to 2 years, as well as an increase in the proportion of these children among patients with meningococcal infection in recent years.     

The schistosomiasis problem in Nigeria

Schistosomiasis is endemic in Nigeria as revealed by several prevalence studies but the degree of endemicity is low. The proliferation of several irrigation projects all over the country has stabilized the infection in Northern Nigeria while in the West rapid urbanisation, supply of portable water and mass chemotherapy have combined to reduce the prevalence rates. Human infection is measured by the determination of incidence, prevalence and intensity of infection. Heavy infections can rapidly be detected by use of urinalysis reagent strips to measure haematuria and protein levels in urine. The prevalence of severe pathological forms of the disease is very low and schistosomiasis is not associated with bacteriuria or hypertension in Nigeria, although isolated cases of ectopic lesions of the genitalis and uterus have been reported. Nodular filling defects occur early during infection, while bladder calcification comes at a later stage. The severity of the disease is related to the intensity of infection. Clinical trials with metrifonate and niridazole among other drugs have been carried out, with varying results. A new drug, praziquantel has been assessed and found suitable for mass use. Three methods of control include adequate provision of safe water, selective or targeted mass chemotherapy and use of molluscicides to kill the snails. Each method has its advantages and drawbacks, but the therapeutic approach is cheap, effects quicker result and treats the infected patients.     

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.