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[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.

Adolescent↗

[Current aspects of the short-term prognosis of meningococcal infection morbidity for the sake of epidemiological surveillance].

The short-term prognosis of the epidemic situation requires the establishment of the system of constant surveillance, which takes into account the data on morbidity rates for several years, both total and in various age groups, the data on the morbidity level and its changes, induced by meningococci of the epidemic group, in the IV quarter of the year, the data on the level of carriership among the indicator groups of the population in this period, as well as the data on changes in antibody titers in the sera of donor blood samples taken in summer and in December.

Age Factors↗

Properdin deficiency in a family with fulminant meningococcal infections.

Three males in a large family showed a selective deficiency of properdin (P). One of the P deficient individuals died from a fulminant infection with Neisseria meningitidis group C. The family history revealed three previous cases of similar infections with a fatal outcome. The deficiency did not appear to be associated with repeated bacterial infections. The pattern of inheritance suggested an X-linked mode of transmittance. However, heterozygous carriers were not clearly distinguished in the family. P deficient serum supported immune haemolysis in a normal fashion. Alternative pathway functions, such as the activation of C3 by inulin or zymosan, lysis of guinea-pig erythrocytes in agarose gel and opsonization of endotoxin coated oil particles, were grossly impaired in P deficient serum while efficient C3 activation was produced by addition of cobra venom factor.

Adolescent↗

Epidemiology of invasive meningococcal infections of children in Slovenia during 1993-1999.

Invasive strains of Neisseria meningitidis isolated from sterile body fluids of children aged 0-14 years were intentionally collected in nine Slovenian laboratories, and sent to the laboratory of the National Institute of Public Health, Ljubljana for final evaluation. From 1993-1999 we collected 53 invasive strains from children presented in this study. The incidence rate of invasive diseases in children shows that there is a rapid fall from 4.74/100,000 in 1993 to 0.90/100,000 in 1999. Invasive diseases predominated in children in the age group 0-1 year (19.6 cases per 100,000 children); followed by the age groups 2-4 years, 5-9 years and 10-14 years. The results of serogrouping indicate that the largest proportion of meningococci isolated (90%) were group B, while 8% of isolates were group C and only 2% group Y. The serotype/serosubtype distribution shows that the most frequent serotype (excluding 19 non-typable NT strains) was serotype 22, which was expressed in 9 strains and the most frequent serosubtype (excluding 11 NST strains) was P1.5,2 found in 7 strains. The most frequently isolated strains (excluding NT/NST strains) were B:22:P1.14; B:NT:P1.5 and B:NT:P1.16. Thirty-one strains collected during 1993-1995 were analysed by multilocus enzyme electrophoresis (MEE). There were 25 electrophoretic types (ETs) among 31 strains; the strains were very heterogeneous with only four ETs being represented by more than one strain. Study shows that meningococcal disease is still endemic in Slovenia.

Adolescent↗

[Humoral immunity aspects of meningococcal infection. I. A method of performing and the characteristics of the immune bacteriolysis reaction].

Immune bacteriolysis test with meningococcus, group A, was used for the purpose of serum antibody study. Meningococcus cultures with a bright orange fluorescence of the colonies in oblique illumination (the I type) proved to possess the greatest lysability. Guinea pig serum sorbed with meningococcus suspension was found to be the best source of the complement. Sera obtained after 1 to 3 days of rabbit immunization, containing mostly IgM antibodies, had the greatest bactericidal capacity. Only those fractions which contained IgM possessed bactericidal activity in the hyperimmune rabbit sera with a high IgG antibody concentration. No lytic activity was displayed against meningococcus by unfractionated hyperimmune sera.

Animals↗

[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.

Adolescent↗

Outer membrane vesicles (OMVs) and detoxified lipooligosaccharide (dLOS) obtained from Brazilian prevalent N. meningitidis serogroup B strains protect mice against homologous and heterologous meningococcal infection and septic shock.

Neisseria meningitidis (N. meningitidis) is a serious bacterial pathogen that causes life-threatening invasive bacterial infections especially in children below 2 years of age, teenagers and young adults. We have investigated the protective potential of outer membrane vesicles (OMVs) and detoxified lipooligosaccharide (dLOS) obtained from Brazilian prevalent N. meningitidis serogroup B strains. Swiss mice were immunized with different combinations of OMV and dLOS from N. meningitidis serogroup B strains compared to a reference vaccine (VA-MENGOC-BC), Cuba). The OMVs + dLOS from Brazilian prevalent strains induced higher bactericidal antibody titers against homologous and heterologous target strains and stronger inhibition of thrombocytopenia as compared to the reference vaccine. When the challenge was performed with the B strain, all immunogens tested showed similar survival rates (80%) significantly higher than the control group. Bacterial clearance against the group B strain was comparable for animals immunized with the tested immunogen and the reference vaccine. Inclusion of dLOS from the B strain with the OMV, induced a similar clearance of C strain bacteria as compared to VA-MENGOC-BC. The immunogens, as well as the reference vaccine drastically inhibited increases in TNF-alpha and IL-6 plasma levels after challenge. In conclusion, the OMV/dLOS formulation obtained from Brazilian prevalent strains of N. meningitidis has a remarkable performance protecting mice against the lethal effects of meningococcal challenge showing a good potential as a vaccine and should be considered for clinical evaluation.

Animals↗

[Group specific antibodies in generalized forms of meningococcal infection].

Seroconversion was revealed in the indirect hemagglutination test with a stable erythrocytic diagnostic agent containing meningococcus antigen of serogroup A in 93.4% of patients with generalized forms of meningococcus infection. A study of the sera obtained at various periods of the disease from 168 patients showed that the antibodies increased sharply during the first days, reaching the maximum (1:2560--1:10240) on the 5th--10th day of the disease; then the titres decreased somewhat becoming stabilizaed at the same level up to recovery. In 75--92% of the persons of control group (patients with meningites of nonmeningococcal etiology, healthy persons and those suffering from gonorrhea) the antibody titre was not over 1:20--1:40; no dynamic increase in its level was noted. The diagnostic value of the reaction for differentiation of meningococcus etiology from other meningites is emphasized.

Adolescent↗

[The enzyme diagnosis of liver involvement in meningococcal infection].

A complex of blood enzymes (AST, ALT, AP, GTT) was studied in 84 patients with generalized forms of MI. The study showed that signs of liver involvement were noted in 15.4% of the patients on the 1st day of disease. Laboratory signs of cytolysis and cholestasis were revealed in most examinees on the 7th-15th day of disease during a dynamic follow-up. The most noticeable syndromes were revealed in young patients (30 persons) with brain edema (42.2%). Primary liver involvement (i. e. noted on admission to hospital) in 6 patients was associated with MI toxic effects, in 7 patients--with a severe concomitant pathology of the pulmonary and cardiovascular system. Delayed liver involvement was detected in 55.3% of the young patients and in half of the elderly patients. It was established that a course of disease was accompanied by the affection of many organs from the first days complicating the interpretation of enzymological data therefore requiring combined enzymological investigations.

Adolescent↗

[Group-specific antibodies to meningococcus of serogroup A in different forms of meningococcal infection].

The authors present analysis of the data obtained in titration in the passive hemagglutination test of the sera obtained from 2498 persons with erythrocytes sensitized with specific polysaccharide of group A meningococcus. It appeared that in children aged under one year, even in those suffering from a generalized form of meningococcus infection, antibodies almost failed to be produced, whereas in older children the mean geometrical of the titre on the 5th-14th days of the disease constituted 1:343. The mean titres in the localized forms (nasopharyngitis and carriership) constituted 1:29.5 and 1:15.1, respectively; in the case of detection in the nasopharynx of meningococcus of group A the mean titre was 1:61. One to two months after sustaining any form of the infection the antibodies disappeared almost completely. Thus, the detected antibodies served as the indices of a recent meningococcus infection, including the asymptomatic one. From 12 to 49% of the persons with antibodies to meningococcus A in titres of 1:20 and over were found in the collective bodies in which meningitis patients were present. No antibodies were revealed in the donor sera collected in the localities with complete absence of meningitis, but in the localities with the recorded meningitis morbidity the sera contained antibodies to meningococcus of group A, the percentage varying from 1.5 to 40 depending on the epidemic curve level. A conclusion was drawn that detection in the collective bodies of over 10% of the persons reacting positively in the passive hemagglutination test with polysaccharide of group A meningococcus pointed to the threatening epidemic situation, despite the seeming welfare.

Adult↗

[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.

Hemagglutination Tests↗

Experimental meningococcal infection in mice: a model for mucosal invasion.

A more complete understanding of meningococcal disease has been hampered by the lack of an appropriate animal model. Previous models have utilized injections of meningococci, which precludes the study of nasopharyngeal colonization and invasion. We have developed a model for meningococcal disease in which litters of 5-day-old mice are challenged intranasally with 10(7) viable meningococci. Bacteremia is monitored by jugular venous blood cultures, and cerebrospinal fluid is sampled by cisternal punctures. Human disease-associated and carrier strains were compared; nasopharyngeal colonization was similar for these bacteria, but the case-associated strains were much more frequently invasive and caused bacteremia. Twenty-one percent of bacteremic animals had meningitis. There was an age-related susceptibility to infection which correlated inversely with the levels of serum complement. Preinjection of iron dextran increased the number of animals which were bacteremic, the concentration of bacteria in blood, and nasopharyngeal colonization. Noncapsular variants of virulent meningococci did not colonize nasopharyngeal tissue in vivo, and they were not invasive. This neonatal mouse model mimics meningococcal disease as seen in humans and may be useful in studying the initial events in the pathogenesis of meningococcal disease.

Adhesiveness↗

Control of meningococcal infection in the African meningitis belt by selective vaccination.

During an outbreak of group-A meningococcal meningitis, information was collected on the distribution of cases of this infection in an area in northern Nigeria. More than 1 case was recorded in all but 3 of 23 affected villages. Members of 9 villages, with a population of about 10 000, in which there had been 2 cases of meningococcal disease were vaccinated with 50 microgram of group-A and group-C meningococcal polysaccharide vaccine. There were subsequently 10 cases of meningococcal disease in these villages but only 2 of these patients had been vaccinated. In contrast there were 38 cases of meningococcal disease in 7 control villages with a similar population. Until we have more information on the duration of immunity after meningococcal vaccination, selective vaccination may be a more cost-effective means of controlling meningococcal disease in the African meningitis belt than routine mass immunisation.

Adolescent↗

Meningococcal infections in England and Wales: 1994.

One thousand one hundred and twenty-nine isolates of Neisseria meningitidis from cases of invasive disease were submitted to the PHLS Meningococcal Reference Unit in 1994, a fall of 13% from the total of 1297 in 1993. One hundred and seventy-four cases were diagnosed serologically, making 1303 laboratory ascertained cases, compared with 1368 in 1993. The overall fall of 4% was similar to the 5% fall in notifications to the Office of Population Censuses and Surveys. The seasonal increase between the third and fourth quarters of the year was less apparent than usual in 1994, when a higher proportion of cases occurred during the summer months. Regional rates of infection varied, notably in the proportions of group C infections, which were highest in the south east. DNA based typing techniques have clarified the characterisation of previously non-typable organisms. B4PI.4 has been identified as a recently emergent strain, which is now responsible for a quarter of all group B infections. Considerable regional variation was observed in the use of serodiagnosis. The monthly distribution of cases diagnosed serologically was similar to that of cases confirmed by isolation, but the age profile was skewed towards older patients.

Adolescent↗

Experimental meningococcal infection in neonatal animals: models for mucosal invasiveness.

A more complete understanding of meningococcal disease has been hampered by lack of an appropriate animal model. We subjected 5-day-old guinea pigs, rats, and mice to intranasal challenge with meningococci and we measured rates of bacteremia as a marker of mucosal invasion. After a single intranasal instillation of 10(7) serotype 2 meningococci, positive blood cultures were found in 0% of guinea pigs, 16% of rats, and 39% of mice, and so mice were used for further studies. Death occurred in 4% of mice and was associated with a purulent leptomeningitis and ventriculitis. Forty percent of mice had nasopharyngeal colonization which increased to 65% with repeated injections. Carrier strains were avirulent, a nonserotype 2 disease strain had low invasiveness, and serotype 2 strains were most virulent. Iron dextran increased rates of bacteremia after challenge with serotype 2 strains. Adult animals were not susceptible to bacteremia after intranasal challenge. The neonatal mouse model fulfills most of the criteria for an appropriate experimental model of meningococcal disease.

Animals↗

[Preventive and therapeutic action of sera to the Re mutant of Salmonella minnesota in experimental generalized meningococcal infection].

The preparations of the blood plasma of humans and the sera of animals immunized with enterobacterial vaccine proved to have elevated titers of antibodies to deep determinants of the core of the gram-negative bacterial endotoxin molecule (to glycolipid of chemotype Re) and protected animals from infection with live cultures or serogroup A, B, or C meningococcal endotoxins. Sera from nonimmunized animals and normal donor blood plasma showed no protective activity. In experiments carried out on different models immune plasma possessed both a pronounced protective activity and a curative effect. The efficacy of protection depended not on the serogroup of the infective agent, but on the virulence of the strain used in the experiment, being statistically significant in all cases.

Animals↗

Bacterial meningitis and meningococcal infection.

Now that invasive disease caused by Haemophilus influenzae type b has been largely controlled in the developed world, the principal bacterial pathogen causing meningitis in most countries is the meningococcus. Serogroup B and C strains predominate in most industrialised countries in contrast to the situation in sub-Saharan Africa, where serogroup A meningococcal disease is periodically a problem of massive epidemic proportions. This review focuses on developments in our understanding of the diagnosis and treatment of meningococcal disease, of host factors important in susceptibility to, and severity of, this infection, and on advances which may eventually lead to its prevention.

Child↗